THE EFFECTS OF VITAMIN E DEFICIENCY IN THE LAMB

By
FELIX ANTONIO BACIGALUPO

A THESIS

S u b m itte d to th e School of G raduate S tu d ie s of M ichigan
S t a t e C o l le g e o f A g r i c u l t u r e and A p p lie d S c ie n c e
in p a r t i a l f u l f i l l m e n t of the req u ire m e n ts
f o r the degree of

DOCTOR OF PHILOSOPHY
Dairy Department
Year 1952
Approved^

e.

/. t-f.

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F e lix Antonio Bacigalupo
candidate
Doctor

for

the degree

of

of Philosophy

F i n a l e x a m in a tio n , Ja n u a r y 21, 1952, 1 :0 0 P.M .,
H u s b a n d r y S e m i n a r Room, D a i r y B u i l d i n g
D issertation:
O utline

The E f f e c t s

o f V i t a m i n E D e f i c i e n c y i n t h e Lamb

of Studies

Major s u b j e c t :
Minor s u b j e c t :
Biographical
Born,

213 D a i r y

D airy Husbandry
Biochem istry

(N utrition)

Items

F e b r u a r y 21, 1927, Lima,

Peru

U ndergraduate S tu d ie s , N ational College
La M o lin a, Lim a, P e r u 1943-1948

of A g ric u ltu re

G radu ate S t u d i e s , A g r i c u l t u r a l and M echanical C o lle g e
Texas 1948-1949, M ichigan S t a te C o lle g e 1949-1951.
Experience:

of

R esearchW orker, N a tio n a l College of A g r i c u l t u r e ,
Lima, P e r u , A g r i c u l t u r a l and M e c h a n ic a l C o l le g e
of Texas.

Member o f A s o c i a c i o n P e r u a n a d e I n g e n i e r o s A g r o n o m o s ,
S o c i e t y o f Si g ma Xi

370040

ACKNOWLEDGMENTS
The w r i t e r
J.
his

M iller
stage

for

wished to e x p r e s s h i s

the

is

and Frank Thorp,

tion.

interest,

and e n c o u ra g e m e n t d u r i n g

greatly

Jr.

for

o b l i g e d t o D r s . R i c h a r d W. L u e c k e

their

inspiration,

and e n c o u r a g e m e n t t h r o u g h o u t th e
Their l o f t y

frien d s w ill

qualities

constant aid ,

course

as te a c h e r s ,

gui­

of the in v e s tig a ­

investigators

and

be a l w a y s rem em bered w i t h p r i d e .

Thankful
Duncan f o r the

a c k n o w l e d g m e n t t o D r . C. F .
many s u g g e s t i o n s

interest

and blood p r e s s u r e

and a s s i s t a n c e
studies;

H u f f m a n a n d Mr .

and v a l u a b l e

B. V. A l f r e d s o n a n d W. D. C o l l i n g s
unfailing

to Dr. E l r o y

in the Department of A g r i c u l t u r a l Chem istry.

The a u t h o r

dance

guidance,

gratitude

help;

fo r t h e i r kind

C. W.

to Drs.
guidance,

in the e le c tro c a rd io g ra p h ic

to h is e x c e l l e n t

f r i e n d and co­

w o r k e r R u d o l f C u l i k f r o m C z e c h o s l o v a k i a w i t h whom t h e a u t h o r
enjoyed p a rta k in g

the v i c is s itu d e s

The a u t h o r e x t e n d s h i s
M. G r i m e s a n d M i s s B.
the

chemical a n a ly s e s ;

for

their

Mr . M. L .

gratitude

Johnson fo r

t o Dr. E.

their

Gray f o r

J.

care.
B e n n e , Mr .

many s u g g e s t i o n s

t o M i s s e s A. M. R e d d e r a n d S .

h e l p i n t h e amino a c i d a n a l y s e s

a n d D r . R. L .

ta k in g the p i c t u r e s ;

T, Wade

of the m uscles;

to Miss J.

in

to

F. A i t k e n

Johnston for reading the m anuscript.

He d e e p l y a p p r e c i a t e s
gan S t a t e

of th e animals*

College

the

scholarships

and t h e I n s t i t u t e

p r o v i d e d by M i c h i ­

of N u t r i t i o n of t h i s

Col-

lege,

w h i c h a l l o w e d him t o

to carry

on t h i s

The a u t h o r
for

the

also

is

s t u d i e s and

i n d e b t e d t o S w i f t a n d Compa ny, C h i c a g o ,
support

given for the

to Merck & C o . ,

D i v i s i o n , A m e r i c a n C y a n a m i d Co.
used in t h i s

graduate

investigation.

financial

experim ent;

complete h i s

work.

Inc.
for

111.

accomplishment of t h i s

and L e d e rle L a b o r a t o r i e s

th e p r o v i s i o n of v ita m in s

TABLE OF CONTENTS
Page
INTRODUCTION ...................................................................................................

1

REVIEW OF LITERATURE ..............................................................................

3

Occurrence of Vitamin E D eficien cy

................................

3

R a t s ................................................................

...............................

3

R a b b i t s a n d G u i n e a P i g s ...............................................

3

D o g s .......................... .

4

Monkeys

.......................................................

.........................................................................................

5

B i r d s ...................................................................................................

5

S h e e p ...................................................................................................

6

C attle

8

..............................................................................................

H u m a n s .........................................................
Nature

of Vitamin E

9

....................................................................

S y n e r g i s t s and A n ta g o n is ts

of Vitamin E

. . . .

11

Macro a nd M i c r o p a t h o l o g i c a l A l t e r a t i o n s i n
V i t a m i n E D e f i c i e n c y ..............................................................
R e p ro d u c tiv e System

....................................................

9

13

•

14

M u s c u l a r S y s t e m .........................................................................

15

N ervous System

17

.........................................................................

C i r c u l a t o r y S y s t e m .............................................................

19

D igestive

S y s t e m ...................................................

21

Changes

22

Physiological
C reatine
Effect

...............................................................

and C r e a t i n i n e E x c r e t i o n

of Vitamin E

. . . . .

o n G r o w t h .................................

Changes i n the B lood, M ilk and C o lo stru m P r o ­
d u c e d by V i t a m i n E D e f i c i e n c y ..........................

22
23
23

P a ge
E lectrocardiogram

. . . .

.....................................................

I n t e r r e l a t i o n s h i p s ...................................................................

26
27

I n t e r r e l a t i o n s h i p of V ita m in E and th e
L i p i d s ........................................................................ . .

.

.

28

I n t e r r e l a t i o n s h i p of V itam in E and th e
N itro g en M etabolism

.

.

31

C arbohydrate M etabolism

.

33

V ita m in E and t h e

V i t a m i n E and t h e M i n e r a l M e tab o lis m
Theory of P h y s i o lo g i c a l

Functions

. . .

34

...............................

36

EXPERIMENTAL PROCEDURE.........................................................................

39

A n i m a l s U s e d .........................................................................................

39

C om position and P r e p a r a t i o n

39

of the P u r i f i e d D iet

C a r e a n d F e e d i n g .........................................................................

46

B l o o d S t u d i e s ...................................................................................

49

U r i n e S t u d i e s ...................................................................................

51

Studies

.....................................

53

...............................................................

54

o f the Gross P a th o lo g y

H istological

Studies

E lectro card io g rap h ic Studies
Studies

on t h e

..........................................

Chemical Changes of the M uscles

F ie ld Cases of Stiff-Lam b Disease

. . . . . . .

55
60
64

R E S U L T S .............................................................................................................

65

G r o w t h a n d H e a l t h .........................................................................

65

C linical

O bservations

on t h e V i t a m i n E D e f i c i e n c y 68

Gross P a t h o l o g i c a l R e s u l t s

...............................................

75

R esults

Studies

..........................

78

..........................

83

of the H i s t o l o g i c a l

R e s u l t s of Blood S t u d i e s .

. . . . .

P a ge
a)

Tocopherol

..........................................................

83

b)

B l o o d H e m o g l o b i n ...............................................................

87

c)

D ifferential

87

d)

B l o o d P r e s s u r e .......................................................................... 87

e)

The L e v e l

R esults

of Urine

Content

White

Count

..........................................

of P a n t o th e n i c A cid in th e Blood

93

...............................................................

94

Studies

a)

E f f e c t o f V i t a m i n E on t h e U r i n a r y E x c r e t i o n
o f C r e a t i n e a n d C r e a t i n i n e ......................................94

b)

E f f e c t o f V i t a m i n E on t h e U r i n a r y E x c r e t i o n
o f S o d i u m a n d P o t a s s i u m ........................................... 98

R esults
a)

of the E l e c t r o c a r d i o g r a p h i c

Studies

.

• • 101

The E l e c t r o c a r d i o g r a m o f La mb s F e d D i e t B
Supplemented w ith Alpha Tocopherol . . .

101

The H e a r t R a t e .................................................................. 101
The PR I n t e r v a l ..............................
The QRS I n t e r v a l

.........................................

103
. 103

The QT I n t e r v a l ............................................................. 1 0 4
The S y s t o l i c
The P Wave

I n d e x ........................................................1 0 4
.........................

104

The QHS C o m p l e x .............................................................1 0 5
The T Waves

..............................................1 0 5

The ST S e g m e n t .........................
The E l e c t r i c a l A x i s
b)

106
................................... 1 0 6

The E l e c t r o c a r d i o g r a m o f V i t a m i n E D e f i ­
c i e n t Lambs.
..............................................
1)

ECG-s o f V i t a m i n E D e f i c i e n t Lambs
Showing A c u te C a r d ia c I n v o lv e m e n t

106
108

Page
2)

3)

c)

d)

ECGs o f V i t a m i n E D e f i c i e n t L a m b s
Showing C h ro n ic C a r d i a c I n v o l v e ­
m e n t .................................. . . . . . . .

Ill

ECG-s o f V i t a m i n E D e f i c i e n t Lambs
No t S h o w i n g Any Sympt om o f
..........................
Cardiac Involvem ent

115

The E l e c t r o c a r d i o g r a m o f L a mb s F e d D i e t A
Sup plem ented w i t h A lp h a T o c o p h e r o l and
Cod L i v e r O i l ................................... . . . • .

116

The E l e c t r o c a r d i o g r a m o f La mb s Fed D i e t B
Supplemented w ith Alpha Tocopherol
(R e co v e ry ), P ro s tig m in e and C o r t is o n e
116

S t u d i e s o f t h e M in e ra l Changes o f t h e S k e l e t a l
Heart Muscles
due to V ita m in E D e f i c i e n c y

and
•.

118

S u l f a t e d A s h . . . . . ............. ...........................................

119

Sodium

119

..............................................................................

.

P o t a s s i u m .........................

12 2

C a l c i u m ............................................ ....... ......................... .....

.

12 6

M a g n e s i u m ...................................................................................

128

P h o s p h o r u s ...................................................................................

129

M ineral R a tio s

129

.........................................................................

S t u d i e s on t h e Ami no A c i d C h a n g e s i n t h e S k e l e t a l
and H e a r t M u s c l e s due to V i t a m i n E D e f i c i e n c y
133
1 - P r o l i n e ........................................................................................

133

1-G lycine.

137

* .............................................................................

1 - L e u c i n e ..............................

137

1-Isoleucine

...............................................................

138

D I S C U S S I O N ........................................................................................................

141

G r o w t h ......................................................................* .............................

141

Sympt oms

143

....................................................

•

P age
P a t h o l o g y ...................................................................................................

151

Blood Tocopherol

. . . . . . .

152

................................

153

Creatine
M ineral

..........................................

and C r e a t i n i n e
Changes i n

E xcretion

the Muscles

. . . . . . . . .

154

Ami no A c i d s .........................................................................................

158

Electrocardiogram

..............................................................

163

C a s e s o f S t i f f - L a m b D i s e a s e ...............................

169

Field

C oncluding Remarks . . . . . . . .

................................

172

SUMMARY AND C O N C L U S I O N S ....................................................................

173

A P P E N D I X .............................................................................................................

178

B I BLI OGRAPHY...................................................................................................

186

INTRODUCTION
Vitamin E i s
appearance

of s tr u c tu r a l

rat,

mouse,

roo,

dog,

guinea p ig ,

duckling,

In sp ite
gical

a dietary

necessary

and f u n c t i o n a l
rabbit,

turkey,

of the

factor

sim ilarity

g u i n e a p i g s and r a t s

histopathological

picture

sheep,

man

( Mason 1 9 4 4 ) .

dystrophy produced in

by v i t a m i n E d e f i c i e n c y ,

of p r o g re s s iv e

to dem onstrate with c e r t a i n t y

and th e

muscular dystrophy
it

h a s b e e n i m­

vitam in E d eficien cy

in

(Pappenheimer 1948).
In sheep,

dem onstrated,
and cure

v ita m in E d e f i c i e n c y has not been d i r e c t l y
even though a lp h a to c o p h e ro l

"stiff-lam b"

nutritional

disorder

disease.

producing p a r a ly s is

m uscles,

Sometimes i t

c a u s e s 30% m o r t a l i t y

and e v e n t u a l l y the

The i n v e s t i g a t i o n a b o u t t h i s
on ia m b s f e d n a t u r a l
whether the

rations

deficiency

capable of c a u sin g the
Th e a n s w e r t o
purified

this

was f o u n d t o p r e v e n t

T his malady i s a s p e c t a c u l a r

the s k e le ta l

able

kanga­

between th e p a t h o l o ­

a n d o t h e r m u s c u l a r d i s o r d e r s o f human b e i n g s ,
possible

goat,

c h i c k and guppy f i s h

striking

the

derangement in the

ham ster,

f in d in g s of chronic muscular

rabbits,

to p re v e n t

and,

and d e g e n e r a t i o n of
death of lambs.

i n c ro p s of young la m b s.
disease

had been c a r r i e d

therefore,

it

out

was q u e s t i o n ­

o f t o c o p h e r o l was t h e u n i q u e a g e n t

"stiff-lam b"

disease.

q u e s t i o n had been p o s s i b l e

d i e t s were f o r m u l a t e d

for

since

e x p e r i m e n t a t i o n w i t h young

- 2 lambs

( L u e c k e _et al^. 1 9 5 0 ) #

in itiated
the

to

study the e f f e c t

the presen t

identity

of

several

F irst,

o f v i t a m i n E d e f i c i e n c y on

of th e

respects,

when t h e y a r e

these

nutrition

fed n a tu ra l

anim al

fo r the

because h eart le s io n s
dystrophy,

experiment

(trial

is

v ita m in E has a s p e c i a l

of the lamb,
rations.

since

Therefore,

s tu d y of v i t a m i n E.

appeared

constantly,

an u r g e n t

need fo r b e t t e r

the experim ental r e s u l t s

of the

it

sig­

occurs even

t h e lamb s h o u l d
And s e c o n d ,

alo n g w ith m uscular

p r o g r e s s i v e m u sc u la r d y stro p h y and c a r d i a c
humans,

proved the

and v i t a m i n E d e f i c i e n c y .

i n lambs fed a v ita m in E - d e f i c i e n t

Since th e re

I)

f i n d i n g s were e x t r e m e l y i n t e r e s t i n g #

t h e y showed t h a t

in the

be an i d e a l

first

" stiff-la m b ” disease

because

nificance

the

w o r k wa s

lamb.
The r e s u l t s

In

And s o ,

diet.
knowledge

of the

diseases affectin g

first

trial

suggested

c o n t i n u a t i o n o f f u r t h e r r e s e a r c h on t h e v i t a m i n E d e f i ­

ciency

i n lambs#

T h u s t wo mor e e x p e r i m e n t s
out i n an a t t e m p t

to

a c t i o n o f v i t a m i n E.

elucidate

(trials

II

and I I I )

the p o ss ib le

we r e

carried

mechanisms o f

REVIEW OF LITERATURE
Occurrence

of Vitam in E D e fic ie n c y

R ats:
Th e e x i s t e n c e

of a vitam in n ece ssa ry

been susp ected

i n 1 9 2 0 by M a t i l l

1922 by M a t i l l

a n d i n 1 9 2 3 by S u r e

However,
w ith r a t s ,

it

called
lity

proved t h a t

certain

Soon a f t e r ,

diets

"fertility
the

before

working
factor

nutrient

as the

was

"anti-steri­

factor".

same w o r k e r s f o u n d t h a t v i t a m i n E n o t o n l y
action,

b u t was a b l e t o c u r e

symptoms o f young s u c k l i n g r a t s

m aintained,

in 1923,

lacked a n u tr itio n a l

The n e w l y d i s c o v e r e d

p o s s e s s e d an " a n t i - s t e r i l i t y "

regimen

(B icknell 1948).

v i t a m i n E a n d was named s p e c i f i c a l l y
or

in

d e a t h and r e s o r p t i o n o f embryos and

degeneration.

vitam in",

paretic

and C o n k l in and c o n firm ed

was E v a n s a n d c o - w o r k e r s who,

n e c e ssa ry to p re v e n t the
testicular

f o r r e p r o d u c t i o n had

and a f t e r l a c t a t i o n ,

whos e m o t h e r s h a d b e e n
on a v i t a m i n E d e f i c i e n t

( P a p p e n h e i m e r 1943 and 1 9 4 8 ) .

S l o w p r o g r e s s i n g m u s c u l a r d y s t r o p h y wa s r e p o r t e d b y P a p p e n ­
heimer

(1942)

to

the a d u lt white

be a n o t h e r

sympt om o f v i t a m i n E d e f i c i e n c y

in

rat.

R a b b i t s and Guinea p i g s :
Muscular dystro p h y is
deficiency

in r a b b its

th e main m a n i f e s t a t i o n

and g u in e a p i g s .

It

of v ita m in E

was f i r s t

reported

-

4 -

by G-oettsch and P a p p enh eim er
"nutritional

muscular

(1931),

dystrophy".

c o n d i t i o n s Pappenheimer e t a l .
pigs,

as in the r a t ,

resulted

who named t h e

Under c e r t a i n

(1948)

in te s tic u la r

degeneration.

dead or

the

same w o r k e r s f o u n d t h a t

in guinea

d ie ta ry vitam in E

F e t a l d e a t h was a l s o

noted to occur around the middle of the
rabbits,

experim ental

showed t h a t

a la c k of s u f f i c i e n t

disease

g estatio n period.

the

In

r o u n g may be b o r n

s u r v i v e b u t a few d a y s .

Dogs:
A n d e r s o n et_ a l .

(1940)

produced v itam in E d e fic ie n c y in

p u p s by f e e d i n g t h e m o t h e r a m i n e r a l i z e d m i l k d i e t .
lo p ed hemorrhages in the p e r i c a r d i a ,
cutaneous t i s s u e s .
to the pups,
j em et^ al^.

When t h e

nutritional

(1944)

lungs,

same m i n e r a l i z e d m i l k was g i v e n

Vitamin E d e fic ie n c y

(1941).

in the a d u lt

dog i s m a n i f e s t e d by

d e g en e ra tio n a ccordin g to Brinkhous

biliary

fistula,

s o r p t i o n o f v i t a m i n E due t o t h e
tract.

to reproduce.

They were a b l e t o p r o d u c e

by m e a n s o f a c h r o n i c

Elveh-

t h a t y o u n g p u p s wh o s e m o t h e r s

had b e en f e d a m i n e r a l i z e d m il k were u n a b le

and Warner

b r a i n s and su b ­

muscular dystrophy developed.

found l a t e r

m u s c u la r and t e s t i c u l a r

Pups d ev e­

the d e fic ie n c y

which re d u c e d th e a b ­

lack of b ile

in the i n t e s t i n a l

- 5 Monkeys:
The mo nke y
muscular

(macaca r h e s u s )

has a lso

been found to d ev elo p

d y s t r o p h y d u e t o l a c k o f v i t a m i n E (Mason 1 9 4 7 ) .

more c o m p r e h e n s i v e
opment of

chronic

study of the

vitam in E d e fic ie n c y

m a n i f e s t a t i o n s were a l t e r a t i o n
pneumocardiogram

macaca r h e s u s

(Filer

in the

A

during the d ev el­

s h o we d t h a t

the only

electrocardiogram

and

e t a l . 1949).

B irds:
Vitam in E i s
life.

Embryos,

necessary during a ll

pullets,

and a d u l t s

periods

are

of th e c h i c k e n 's

susceptible

to the

d e fi ciency.
He n s f e d a v i t a m i n E f r e e
died

at

the

fourth

f o u n d t o be t h e

disintegration

lethal

In p u lle ts ,
different

ways:

nutritional
(1940)

ring

of the b l a s t o ­

fo rm a tio n of a t y p i c a l

dense

vitam in E d eficien cy

is m anifested in th ree

exudative d ia th e s is ,

g e n e r a l i z e d e dema a n d

the

( Ma s o n 1 9 4 4 ) .

exudative

subcutaneous t i s s u e s ,

generally

The c a u s e o f d e a t h was

of blood v e s s e l s

diathesis,

by t h e a c c u m u l a t i o n o f p l a s m a - l i k e
of the

e ggs whose e m br yo s

(Adamstone 1 9 3 1 ) .

encephalom alacia

described

laid

day o f i n c u b a t i o n .

d e r m , w h i c h wa s a p p a r e n t b y t h e
ridge-like

diet

throughout

the

Crazy c h ic k d i s e a s e ,

fluid

m uscles,

B i r d and C u l to n
w h i c h was c h a r a c t e r i z e d

in lo c a liz e d areas

adipose

t i s s u e s and

connective t i s s u e s .
observed for the f i r s t

time i n 1928,

w&s. r e c o g n i z e d b y P a p p e n h e i m e r a n d G - o e t t s c h ( 1 9 3 1 )

a s one o f

- 6 nutritional

o r i g i n and a c c o r d i n g l y

phalom alcia.
of the

The s y m p t o m s w e r e m u s c u l a r

c h i c k s on t h e p e l v i c

s a u l t s or r o t a t i o n
In the a d u lt
slight

named i t

bone,

in a la te ra lly
chicken,

nutritional

ence-

incoordination,

retraction

of

resting

the head,

somer­

prone p o s i t io n .

symptoms o f v i t a m i n E d e f i c i e n c y a r e

m u s c u la r d y s t r o p h y and t e s t i c u l a r

degeneration

(Mason

1944)Pappenheimer

(1939)

reported

that

the d e fic ie n c y of v i t a ­

m i n E i n d u c k s wa s m a n i f e s t e d by d y s t r o p h y o f s k e l e t a l m u s c l e s .
In turkey p o u lts ,

however,

he d i d n o t f i n d a n y s p e c i f i c

outward

sign of the vitam in E deficiency*
Sheep:
V itam in E d e fic ie n c y has been p o s tu la te d
the

c o n d i t i o n kno wn a s

"lamb p a r a l y s i s " ,

"stiff-lam b"

"stiff-neck"

and "white muscle d is e a s e "
to

occur in d i f f e r e n t

Hagan 1 9 2 7 ; Lee 1 9 3 5 ;

(Cheng 1 9 4 5 ) .

sections

the lo s s e s

a nd Hagan 1927)
never

of t h is

S ho ll 1939;

The d i s e a s e

country

Thorp 1942)
It

is

o r e v e n 30% ( S h o l l 1 9 3 9 ) .

been r e p o r t e d a f f e c t e d

turned

"lamb r h e u m a tis m " ,

is

kn o wn

( M e tzg e r and
and i n Europe

a common d i s e a s e among

b e i n g s o m e t i m e s a s h i g h a s 10-15% ( M e t z g e r

Sympt oms o f t h e
are

cause of

(Willrnan e t a l . 1934 a n d 19 45 )

( S l a g s v o l d and L u n d - L a r s e n 1 9 3 4 ) ,
lambs,

disease,

as the

by t h i s

stiffness

o u t on p a s t u r e

appear

in the

Adult

sheep have

disease.
t h e day a f t e r

spring.

th e lambs

The l a m b s show a

- 7 disturbance

in the locom otion,

le g s , paralysis
incidence

and d e a th

of the

long w in te rs ,

stiffness

of t h e h in d and f o r e

( M e t z g e r and Hagan 1 9 2 7 ) .

appearance of the

stiff

lambs w ith u n u s u a l l y

t h e tim e o f w ean in g , and t h e

lam bs from p e n s t o

ran g e have

Th e c o ­

translocation

of

b e e n s p e c u l a t e d u p o n by many

workers.
Sholl

(1939)

year with the

previous

"stiff-lam b"

Th e e x e r c i s e
disease

the disease

same i n t e n s i t y .

and r a i n y and t h e
of the

noted t h a t

disease

Whenever t h e

s p r i n g s were c o ld

had been lo n g ,

(1929);

p ossibility

the

incidence

was h i g h e s t .

f a c t o r wa s s u g g e s t e d a s t h e

b y W e l c h e_t al_.

discarded th is

fall

did not appear every

cause of the

l a t e r Willman e t a l .

(1934)

and i n s t e a d proved t h a t t h e

"stiff-

l a m b " d i s e a s e was c o n s i s t e n t l y p r o d u c e d i n a n i m a l s f e d c e r t a i n
rations.
the

T h is work marks t h e t u r n i n g p o i n t

"stiff-lam b"

pathological
coccidiosis

disease,

o r i g i n of the

since

early

disease,

suggestions

study of
on t h e

as a secondary e f f e c t of

( J u n g h e r r and Welch 1 9 2 7 ) ,

(Marsh 1932) and th e

of the

um bilical

a c t i o n of c e r t a i n b a c t e r i a

infection
(Lee 1 9 3 5 )

w e r e s h e l v e d a n d t h e d i s e a s e a c c e p t e d a s one o f n u t r i t i o n a l
disturbance.
L a mb s r e a r e d

on o p e n r a n g e s o r u n d e r

have never been observed to develop the
Vawter

(1939)

thought th a t

sem i-range c o n d itio n s

"stiff-lam b"

disease.

such c o n d it i o n s p ro b ab ly a f f o r d a

- 8 better

opportunity

be t h e

case under r e s t r i c t e d

The o c c u r r e n c e

for

of

the

ewes t o b a l a n c e

four p a rts

Ms t i f f - l a m b "

three

parts

of o ats

ration

the

useful

in the

of c u ll

disease

ration"

study of the

The s t u d y o f S h o l l
also
the

beans,

disease

(1939)

is

parts

1936).

and i t

disease

of Michigan p o in te d

and th e

l a m b s w e r e o b s e r v e d on f l o c k s

rations:

first

cutting a lfa lfa ,

oats,

and soybean meal;

grain;

alfalfa,

clover hay,
falfa,

oats

barley,

oats

of

fed the follo w in g

bundle

silage,

alfalfa

nutrition

and o a t s ;

mixed h a y ,

cornstalks

and c o r n f o d d e r ;

tim othy hay,

ear corn,

hay a lo n e and a l f a l f a ;

clover hay,

of b a r l e y and

( W i l l m a n et_ al_. 1 9 3 9 ) .

S tiff

alfalfa,

in

h a s p r o v e d to be v e ry

ewe.

c o rn and o a t s ;

very fr e q u e n t

They c a l l e d t h i s

in the S tate

to a c o r r e l a t i o n between th e

alfalfa,

t h a n would

c o n ta in in g second c u tt i n g

three

(Willman e t . a l ,

"stiff-lam b

diet

diets.

l a m b s w h o s e dams h a v e b e e n f e d a r a t i o n
alfalfa,

their

clover,

corn,

bran,

c l o v e r h a y , no
wheat and o a t s ;

hay and b a r l e y ;

al­

and c o r n s t a l k s .

C attle:
S l a g s v o l d and L u n d - L a r s e n
heifers
of the
the
to

as well

as lambs,

fe e d in g regimen.

spring,
grass for

first

found o c c a s io n a lly

reported th at

calves,

developed m y o s itis a s a consequence
Th e d i s e a s e wa s more n o t i c e a b l e

a few d a y s a f t e r
the

(1934)

tim e.

anim als,

fed indoors,

during

were l e t

out

The same d i s t u r b a n c e s h a v e b e e n

in calves ra is e d

in farms of M ichigan

(Thorp,

- 9 Barner,

Johnston,

In adult

and Huffman,

cattle,

comm unication).

m a i n t a i n e d on a v i t a m i n E f r e e r a t i o n

fo r a prolonged p e rio d ,
was t h e

personal

t h e o n l y sympt om o f t h e

sudden d e a th of th e a n im a ls

deficiency

( G - u l l i c k s o n et_ al_. 1 9 4 6 ) .

Humans:
Sy mpt oms o f v i t a m i n E d e f i c i e n c y
been discovered*
it

Pappenheimer

must e x i s t ;

see,

a b o u t by t h i s
Man i s

nutritional
gist,

however,

n o t y e t b e e n d i s c o v e r e d i n man*

the le s io n s

that

he a l o n e

lack,

w ith the

as

s t r i k i n g and o f t e n pathognomonic*

i n many r e s p e c t s ,

but there

s h o u l d be immune t o

and i t

And y e t ,

i n many s p e c i e s o f a n i m a l s b r o u g h t

d eficien cy are

a c u rio u s animal

to th in k th a t

believes,

lfL e s i o n s w h i c h p o i n t u n e q u i v o c a l l y t o d e f i c i e n c y

o f v i t a m i n E have
we s h a l l

(1948)

i n man h a v e n o t a s y e t

is

is

the e f f e c t s

a challenging task for

no r e a s o n
of t h is

the p a th o lo ­

n e c e s s a r y a i d o f t h e b i o c h e m i s t and th e

clinician,

t o u n c o v e r t h e p a t h o l o g y o f v i t a m i n E d e f i c i e n c y ' 1*
N atu re of V itam in E
W h e a t germ o i l
p r o t e c t i o n and cure

was t h e

first

fo r anim als

product discovered to

deficient

offer

i n v i t a m i n E (Evans

and Bishop 1923).
Years l a t e r ,
isolated

the a c t iv e

principles

by c h e m i c a l p r o c e d u r e s a n d w e r e

closely related

h igher alcohols*

preventing reabsorption

o f w h e a t ge rm o i l w e r e
found t o be t h r e e

Because of t h e i r

of f e t u s e s ,

the

effect

in

c o mp o u n d s w e r e c a l l e d

10 alpha,
bear

b e t a a n d gamma t o c o p h e r o l s ,

offspring"

a G re ek word m eaning " t o

( Ma s on 1 9 4 4 ) .

T o c o p h e ro ls have been used s u c c e s s f u l l y to p r e v e n t and
cure

t h e d i s e a s e s p r o d u c e d by t h e a b s e n c e o f v i t a m i n E i n t h e

diet

( P a p p e n h e i m e r et^ al_. 1 9 3 9 a n d 1 9 4 8 ; W i l l m a n et_ a l . 1 9 4 5 ) .
A b u n d a n t e v i d e n c e h a s s h own t h a t a l p h a ,

t o c o p h e r o l s have
carried

different

biological

o u t by G - o t l i e b e t a l .

proved t h a t

Hickman and H a r r i s

(1943);

(1946),

gamma t o c o p h e r o l ,

the

co-vitam ins.

activ ities

H arris

This,

dl

compounds o f a l p h a ,

of the

electrom etric
Another

(1949)

compounds,

Sim ilar
who d e m o n s t r a t e d

of alpha,
are

b e t a and

o f t h e same

i_n v i t r o .

b e t a a n d gamma t o c o p h e r o l s .
is

comparable

to

the a n t i o x i d a n t

a s m e a s u r e d by a s p e c i a l r e d o x -

apparatus.
c ompound w i t h s p e c i f i c v i t a m i n E a c t i v i t y

p r e p a r e d by M i l h o r a t e t a l .
alpha

of th e

( 1 9 4 4 ) t o h a v e mor e p o t e n c y t h a n t h e

a c c o r d i n g t o Wachs

activity

reasoned

b e t a a n d gamma t o c o p h e r o l s w e r e f o u n d by

and c o -w o rk e rs

synthetic

(1944),

elevated tem peratures,

order as th e ir an tio x id an t potencies
N atural alp h a,

and

should r e p r e s e n t the a b i l i t y

biological
at

(1947a)

than b e ta ,

of a c t i v i t y ,

w e r e o b t a i n e d by Hove a n d Hove

the r e l a ti v e

Rats assays

Hove a n d H a r r i s

The d i f f e r e n c e

d e p le te d organism to m ethylate

that

values.

a l p h a t o c o p h e r o l was mor e a c t i v e

b e t a m o r e t h a n gamma.

results

b e t a a n d gamma

(1949).

has been

They d i s c o v e r e d t h a t

tocopherylhydroquinone reduced c r e a tin u r ia

i n human

dl

- 11 p a t i e n t s w i t h m u s c u la r d y s t r o p h y and a l s o
trophy

in standardized,

A ll

vitam in E - d e f ic ie n t r a b b its .

compounds w i t h v i t a m i n E a c t i v i t y

B o y e r , R a b i n o v i t z and L i e b e
chem ical

cured m uscular dys­

structure

vitam in E a c t i v i t y
xychromans,
be r e a d i l y

(1951)

were

i n an e f f o r t

to the vitam in E fu n c tio n .
was l i m i t e d

to

certain

or 5 - h y d r o x y c o u m a r a n s , or t o
converted

studied

to the s u b s t i t u t e d

by

to r e l a t e

the

They f o u n d t h a t

substituted

6-hydro-

compounds w h i c h c a n
6 - h y d r o x y c h r o m a n s by

hy d ro ly sis or red u ctio n .
A d m in is tr a tio n of c u r a t iv e

and p r e v e n t i v e

doses of to c o ­

p h e r o l s have been s u c c e s s f u l l y a c c o m p l i s h e d i n v a r i o u s ways.
Hove a n d H a r r i s

(1947a)

in je c te d alpha tocopheryl

i n t r a m u s c u l a r l y and found t h a t
prolonged a c tio n .

in th is

Willman and c o -w o rk ers

c u t a n e o u s l y 1 0 0 mg.

dose of disodium s a l t

pherol phosphoric acid e s te r d isso lv e d
cured E d e f i c i e n t lambs.
min E i s
the

by o r a l

rations

way i t

in

phosphate

had a slow b u t

(1946)

injected

sub-

of d l-alp h a toco­
sterile

water,

and

The m o s t common way t o s u p p l y v i t a ­

adm inistration

e i t h e r mixed w i t h o i l s o r w i t h

(Willman e t a l . 1945;

Pappenheimer e t a l . 1939).

S y n e r g i s t s and A n t a g o n i s t s of V ita m in E
S y n e r g i s m o f t h e v i t a m i n A a n d E was s u g g e s t e d by t h e w o r k
o f Quackenbush and c o l l a b o r a t o r s

(1942).

rectify

of r a t s

the vitam in A d e fic ie n c y

They were u n a b l e

to

with carotene u n less

- 12 alpha
to

tocopherol

be s p e c i f i c

wa s g i v e n a t

to vitam in E since

p y ro g a llo l, catechol

Ka c h m a r et^ a l .

(1950)

however,

T h i s a c t i o n seemed

a t the 0.02^ le v e l

v i t a m i n K,

have been r e c e n t l y r e p o r te d

by

who a n a l y z e d t h e b l o o d p l a s m a f o r v i t a m i n

v i t a m i n A, and c a r o t e n e ,

E rations

same t i m e .

and h y d roquinone were i n a c t i v e .

Opposite r e s u l t s ,

E,

the

did not impair

and concluded t h a t

the u t i l i z a t i o n

th e low v i t a m i n

o f c a r o t e n e and v i t a m i n

A.
Dam a n d G l a v i n d
unable

to r e p a ir

(1940) r e l a t e d

a faulty

t h a t v i t a m i n s K and C we re

c a p i l l a r y p e r m e a b i l i t y p r o d u c e d by

vitam in E d e fic ie n cy .
A scorbic acid,
(1935)

a c c o r d i n g t o W illm a n , M o r r i s o n and O l a f s o n

did not possess a s y n e r g is tic a c tio n

" s t i f f - l a m b 11 d i s e a s e .
ported

However,

the

same v i t a m i n h a s b e e n r e ­

r e c e n t l y b y Dam a n d c o - w o r k e r s

i n the r e d u c tio n of the
chickens.

Cystine,

had a s i m i l a r

action

incidence

(1948a)

deficiency.

It

t o be e f f e c t i v e

of e x u d ativ e d i a t h e s i s

nordihydroguairetic

of

a c i d and c h o lin e a l s o

(Dam et^ al^. 1 9 4 8 ; V i v a n c o e t a l . 1 9 4 8 ) .

X a n t h o p h y l l , when g i v e n i n m a s s i v e
G o l d h a b e r e_t al^.

in th e case of

(1950)

to p r o te c t

doses,

was s h o wn b y

c h i c k e n s from v i t a m i n E

a p p e a r e d t o them t h a t

th e p r o t e c t i o n of t o c o ­

p h e r o l s by x a n t h p h y l l w a s c o n f i n e d t o

the g a s t r o in t e s ti n a l

tract.

they thought,

T h i s mechanism o f p r o t e c t i o n ,

e n t from t h e one o f a s c o r b i c a c i d ,
p ro te c ts the

tocopherol

of the

was d i f f e r ­

sin c e v ita m in C presumably

tissues

from o x i d a t i o n .

- 13 A ntagonistic
liver

o il,

factors

to v i t a m i n E have b een found i n cod

which have been i d e n t i f i e d

T h i s w i l l be r e v i e w e d i n d e t a i l
relationship

is

under the heading of

a n t a g o n i s t r e p o r t e d up t o

the d i-O -cresy l

fed r a b b i t s

a normal

di-o-cresyl

succinate.

succinate.

diet

o f 50 mg. o f s y n t h e t i c

A less

Meunier and C henavier

(1949)

t o w h i c h t h e y a d d e d 1 0 0 - 1 6 6 mg.

of the

The r a b b i t s

first

tocopherol

to

developed d ia r r h e a ,

specific

A dm inistration

s i m il a r ly poisoned anim als

and a l l o w e d them t o r e g a i n

p r e v i o u s l y by W o o l l e y
quinone

"Inter­

the p resen t

t h e n became p a r a l y z e d and d i e d w i t h i n s e v e n d a y s .

was c u r a t i v e

fa tty acids.

o f V ita m in E and the L i p i d s " .

The m o s t s p e c i f i c
time

as unsaturated

their

former w eig h t.

v ita m in E a n t a g o n i s t had been r e p o r t e d
(1945).

He f o u n d t h a t a l p h a t o c o p h e r o l

seemed to have an a n t i v i t a m i n i c

a c tio n to both vitam ins

E a n d K.
Hove

(1948)

influencing
poisoning,

observed,

the m o r ta lity
that

on t h e a c t i v i t y

in h is
of r a t s

w o r k on t h e
after

6 methyl t h i o u r a c i l

carbon

effect

of f a c t o r s

tetrachloride

had an o b l i t e r a t i n g a c t i o n

of alpha tocopherol.

Macro an d M i c r o p a t h o l o g i c a l A l t e r a t i o n s
in Vitamin E D eficiency
"The m o s t o u t s t a n d i n g c h a r a c t e r i s t i c
min E d e f i c i e n c y ,

w h i c h h a s no p a r a l l e l

deficiency s ta te ,

is

tional

the m u l t i p l i c i t y

a lte ra tio n s exhibited

of experim ental v i t a ­

i n any o t h e r v i t a m i n

of s tr u c tu r a l

and f u n c ­

s o m e t i m e s by c l o s e l y r e l a t e d s p e c i e s ,

- 14 and the
ies."

sim ilarity

of c e rta in

changes in q u ite u n r e la te d

( Ma s o n 1 9 4 4 ) .
Structural

of the

alterations

organism.

have been ob served

H a r r i s and Kujawski

b ib lio g ra p h y to a l t e r a t i o n s

(1950)

m uscular,

central

excretory,

endocrine,

Reproductive
In the
failure

to

nervous,

in every system

referred

produced in the fo llo w in g

as a r e s u lt of vitam in E deficiency:

ture

spec­

reproductive,

circulatory,

in th e ir
systems

skeletal,

respiratory,

digestive,

s k i n and s e n s o r y o r g a n s .

System:
f e m a l e r a t M a r t i n a n d Moor e

(1939) r e p o r t e d

i n d u c e p r e g n a n c y was d u e t o a l t e r a t i o n s

of the u te rin e

w all,

as

deposited

in the

the

struc­

shown b y t h e d e g e n e r a t i o n o f t h e

smooth m uscle and a v e r y d i s t i n c t i v e
brown g r a n u l e s

that

in the

p i g m e n t a t i o n due t o y e l l o w

cytoplasm of the

smooth muscle

fibers.
I n t h e m a l e r a t P i e r a n g e l i ejt a l .
p re se n c e of f l u o r e s c e n t pigm ents,
in the

testes

of r a t s

(1949) has r e p o r t e d t h e

y e llo w or lum inous and w h i t i s h

rendered atro p h ic

by a v i t a m i n o s i s E .

This

f l u o r e s c e n t l i p o - p i g m e n t was n o t f o u n d i n n o r m a l t e s t e s .
Ma s o n ( 1 9 2 6 )

p o i n t e d o u t t h a t ma l e r a t s

o f v i t a m i n E from e a r l y l i f e
of the
but

show a n i r r e v e r s i b l e

degeneration

se m in ifero u s e p ith e liu m a t the onset of sexual m a tu rity ,

no i n j u r y

tozoa

severely depleted

show t h e

during adolescence.
first

alteration,

He a l s o
and t h e s e

found t h a t th e
are

s p e r ma -

f o l l o w e d by d e -

- 15 generative
later

ch an g es i n s p e r m a t id s and s p e r m a to g o n ia .

stages,

t h e t u b u l e s we r e f o u n d t o b e l i n e d w i t h i n d i f ­

ferent Sertoli

cells.

T h e e x p e r i m e n t s o f E s c u d e r o ejb a l .
that

the

vitam in E d e fic ie n cy

epithelium but also
Seminal v e s i c l e s
d u rin g the

In the

the

dem onstrated

damages n o t o n ly t h e

in tersticial

and p r o s t a t e

(1942)

cells

germinal

of the t e s t e s .

glands of r a t s

d ecreased in weight

s i x m o n th s on a low v i t a m i n E d i e t .

M uscular System:
The f i r s t

d e s c r i p t io n of the h i s t o l o g i c a l

m usculature of the
and Pappenheim er
stage

of the

necrosis
to

g u i n e a p i g a n d r a b b i t was d o n e by G - o e t t s c h

(1931).

Th e y o b s e r v e d t h a t a t t h e e a r l i e s t

degeneration there

of th e muscle f i b e r s .

degenerate a t the

rapidly

a l t e r a t i o n of the

degenerated.

i s a very e x te n siv e hyaline
A ll

same t i m e ' ,

the

fibers

were not

found

some r e m a i n e d n o r m a l w h i l e o t h e r s

Pappenheimer,

i n 1948,

in his lec tu re

"On C e r t a i n A s p e c t s

o f V i t a m i n E D e f i c i e n c y 11 r e v i e w e d some o f

the c h a r a c t e r i s t i c s

of n u tr itio n a l

rat,
the

m uscular dystrophy in th e

and d e s c r i b e d t h e m u s c u la r n e c r o s i s
contractile

sarcoplasm a.

The n u c l e i

selectively affecting
were l e f t w i t h t h e i r

adjacent

cytoplasm v ia b le .

He t h o u g h t t h a t t h i s

possible

t h e e x t r a o r d i n a r i l y r a p i d and s u c c e s s f u l

F ollow ing the l o s s

of s t r i a t i o n

stance,

"there

he s t a t e d ,

c h a n g e ma k e s
regeneration.

of th e c o a g u la te d muscle

sub­

occurs a s tro n g inflamm atory resp o n se,

- 16 w i t h edema a n d c e l l u l a r
24 h o u r s ,

in filtration,

polymorphonuclear le u c o c y te s

process progresses,

the

replaced

im portant fe a tu re

of the le s io n s

c h i e f l y the c o n t r a c t i l e
Th e n e c r o t i c

m aterial

portion

persists

for

it

isfc t h a t

the

not a l l

curious

com pletely a f t e r

features

of the

others ra p id ly

sp ecu lated about these

or from t h e

it

disease,

degenerate,

l a s t observations

i m m o b i l i z e d by t h e i r
histological

nutritional

muscular

dystrophy

Cheng 1 9 4 5 ;

C ulik 1951).

The o b s e r v e d h i s t o l o g i c a l
known t o

days".

some

and t h a t t h e
He

and r e a s o n e d t h a t t h e

attachm ent

or p e r h a p s a r e

to t h e muscle

sheath.

already described

in other species

a f f e c t e d by

( O l c o t t 1 9 3 8 ; D a v i s ejt al_. 1 9 3 8 ;

changes are

essentially

t h e human p a t h o l o g i s t a s h y a l i n e ,

d e g e n e ra tio n u s u a lly a s s o c ia te d with acu te
(Ma s o n 1 9 4 4 ) .

it

of th e m uscle.

changes to those

have been confirm ed elsew here

intact

he m e n t i o n e d

same t i m e ,

surface

giant

undergoes r a p i d

f i b e r may h a v e a r i c h e r b l o o d s u p p l y ,

Sim ilar

. . . . .

four or five

degenerate at the

d e g e n e ra tio n never extends to the

partially

fibers.

in which case

For t h e most p a r t ,

the f i b e r s

r e m a in e d normal w h ile

superficial

necrosis a ffe c ts

of the muscle

may become c a l c i f i e d ,

d i g e s t i o n and d is a p p e a r s

well

m o n o n u c l e a r s ............................. An

b e c o m e s s u r r o u n d e d by m u l t i n u c l e a t e

some t i m e .

Among t h e

As t h e

the polym orphonuclears

d e r i v e d e i t h e r from f u s e d h i s t i o c y t e s

young m yoblasts;

that

by l a r g e

during the f i r s t

predom inate.

e dema s u b s i d e s ,

d is a p p e a r and a re

cells,

in which,

those

waxy o r Z e n k e r ' s

infections

and f e v e r

- 17 Sometimes,

t h e most s t r i k i n g f i n d i n g s a t a u t o p s y o f g u i n e a

p i g s and lambs w ith n u t r i t i o n a l

muscular dystrophy are th e

w h i t i s h p a t c h e s and s t r e a k s o b s e r v e d s c a t t e r e d
skeletal
white
the

m uscles

(Willman e t a l . 1934;

appearance

disturbance

P a m u c k c u 1: 948)*

of th e la m b s ' m u sc le s have
as the

“w h i t e m u s c l e

throughout the

justified

The
naming

disease"*

Nervous System:
The e x p e r i m e n t s

o f P a p p e n h e im e r and G-oettsch

(1940)

in

which th e y p re v e n te d th e o c c u rre n c e of th e n u t r i t i o n a l m uscular
d y stro p h y in young r a t s ,
q u e s tio n whether
genic

disease,
Since

relation

the

by d e n e r v a t i o n ,

has given r i s e

syndrome i s p r i m a r i l y a m y o g e n i c ,

to

the

neuro­

or a co m b in atio n of both*

that

of th e

t i m e , many r e s e a r c h w o r k e r s h a v e s t u d i e d
disease

to the

central

nervous

the

system and m otor

end p l a t e s *
The c e n t r a l
in ra ts
that

depleted

nervous

i n v i t a m i n E by L i p s h u t z

g en erally the

process occurred
Other

first

and l a r g e s t

site

i n th e lumbo— s a c r a l

re p o rte d to
(1936)*
of the

part

i n v e s t i g a t o r s have a t t a c k e d

found d i f f e r e n t
no l e s i o n s

s y s t e m wa s f i r s t

of th e

the

Pappenheimer

(1943)

He s t a t e d
degeneration
spinal

cord.

same p r o b l e m a n d h a v e

d i s t r i b u t i o n and c h a r a c t e r s

at all.

be a f f e c t e d

of th e l e s i o n s ,

or

c a r e f u l l y reviewed th e

w o r k d o n e on v i t a m i n E up t o 1 9 4 3 a n d c o n c l u d e d t h a t t h e

vitam in

E deficiency

nervous

does not a l t e r

the

structure

of th e

central

- 18 system ,

and t h a t

were

due t o

lack

of adequate

results

in technique,

control

m aterial

the

wrong i n t e r p r e t a t i o n s ,

the e f f e c t s

(1949)

ra tio n for

nervous

i n d e p e n d e n t l y by L u t r e l l

system i s

actually

affected.

s h o we d e v i d e n c e

nization,

gliosis,

and d i s t o r t i o n of th e

posterior

columns and p ro x im a l p a r t s
t h o r a c i c and lumbar

This confirmed e a r l i e r

dem onstrated
L utrell

r e a r e d on a v i t a m i n E d e f i c i e n t

9-12 months c o n s i s t e n t l y

cervical,

and

(1949), designed

of v i ta m in E d e f i c i e n c y ,

found t h a t r a t s

and

fo r comparison.

r e c e n t work c o n d u c t e d

central

a n d Ma s o n

the

f o u n d by d i f f e r e n t w o r k e r s

( 1 9 4 9 ) a n d by M a l a m u d , N e l s o n a n d E v a n s

to re -e v a lu a te
that

different

variations

However,
Mason

the

axon p a t t e r n of th e

of the p o s t e r i o r r o o t s

segments of the

observations

of dem yali-

spinal

of

cord.

o f E i n a r s o n and R e i g s t e d

and o t h e r s .
Ma l a mud ejt al_.

(1949)

and doubted th e v a l i d i t y
the

case

of lesio n s

essentially

of the

criticism

of the p o s t e r io r

study,

s t a i n i n g methods y i e l d e d the

latter

and c o n t r a s t e d

control

same o b s e r v a t i o n s

of Pappenheimer i n

columns,

since,

in th eir

same p o s i t i v e p r o o f o f t h e

sh a rp ly w ith the

normal

fin d in g s in the

anim als.

The s t u d i e s
motor

made t h e

end p l a t e s

of T e lfo rd

(1941)

indicated

that

t h e damage o f

was s e c o n d a r y t o t h e d e g e n e r a t i o n o f t h e m u s c l e s .

Vi/hen t h e r e wa s a s l i g h t d e g r e e o f m u s c u l a r d e g e n e r a t i o n ,
w a s no a p p r e c i a b l e
tion

alteration

was c o n s i d e r a b l e ,

of nerve en d in g s;

t h e r e wa s a l s o

if

considerable

there

the degenera­
reduction of

- 19 the

nerve t e r m i n a l s and i f

long stan d in g ,

the

the

n e c r o s i s was w i d e s p r e a d a n d o f

n erv e t e r m i n a t i o n s were c o m p le te ly l o s t .

C i r c u l a t o r y System:
C irculatory
factor

d i s t u r b a n c e h a s b e e n f o u n d t o be t h e p r i m a r y

in the p ro d u c tio n of n u t r i t i o n a l

chicks.

Wolf and Pappenheim er

(1939)

h a v e o b s e r v e d t h a t , du e t o

n e c r o s i s wa s p r o d u c e d i n t h e
and t h a t t h e r e
dead

(1931)

and Papp enh eim er e t a l .

circulatory

cerebellum ,

was h e m o r r h a g i c

ganglion c e lls

encephalom alcia of

and g l i a l

edema,

capillary

(1947) a s a d i s t u r b a n c e o f th e

G-lavind

(1940)

vitam in £ to the
or a sc o rb ic

acid.

workers

(1951),

against

the

Ma s o n
fetuses,

diet

Dam a n d

wa s i n c r e a s e d

w h i c h c a n b e c h e c k e d by a d d i t i o n o f

offers

fragility

observed

sig n ifican t protection

p r o d u c e d by a R a d o n o i n t m e n t .

that,

prior

appeared a b n o rm a litie s

l o c a l i z e d or

turbance

there

to

the e x it u s of r a t

in the v ascu la r

d e g re e s of d i l a t a t i o n and

and d e e p e r v a s c u l a r c h a n n e l s ,

diffuse areas

system.

a n d by

of h em orrh ages.

(1949a and 1949 b) h a s d e s c r i b e d a n o t h e r v a s c u l a r
in ra ts

and

b u t n o t b y a d d i t i o n o f v i t a m i n K, c i t r i n

throm bosis of p e rip h e ra l

Hove

by Dam ( 1 9 4 4 b )

vascular w all.

conditions

T h e y w e r e c h a r a c t e r i z e d by v a r i a b l e

either

and

A c c o r d i n g t o t h e e x p e r i m e n t s o f Ames a n d c o ­

increased

there

in these

vitam in S also

(1943)

throm bosis,

elem ents.

Hepding

c a p illa ry perm eability,

ischemic

cerebrum and m e d u l l a ,

E x u d a tiv e d i a t h e s i s has been i n t e r p r e t e d

found t h a t

failure,

when d e p l e t e d o f v i t a m i n E .

dis­

W i t h i n 6 —12 w e e k s

-

75% o f th e r a t s
lobular

died

20

-

from m a s s i v e l u n g h e m o r r h a g e s ,

and sometimes e x te n s i v e

necrosis

with c e n t r i -

of the l i v e r

and d i s ­

t e n s i o n of the subcutaneous blood v e s s e l s .
The r o l e

o f v i t a m i n E i n th e p r e v e n t i o n of a r t e r i t i s

d o g s was d e m o n s t r a t e d by Hol man
vitam in E retard ed

the

( 19 4 7 a n d 1 9 4 9 )

incidence

of a r t e r i a l

which had e x p e r im e n ta lly produced r e n a l
Heart le s io n s

These l e s i o n s ,

When a n y a b n o r m a l i t y was f o u n d ,

it

again reported

ventricle.

lesions,

however,

in the

(M e tzg e r and Hagan 1 9 2 7 ) .

showed h e a r t

lesions

were i n c o n s t a n t .

of w h i t i s h p a tc h e s

right ventricle

t h a t a sm all p e r c e n t a g e of s t i f f lambs
usually

The r e p o r t s

lamb

in the

endocardium of the r i g h t

of other i n v e s tig a to r s agreed th a t

( S l a g s v o l d and L u n d - L a r s e n 1934;

S la g s v o ld and L und-L arsen
l a m b s showed e s s e n t i a l l y
vitam in E d e fic ie n cy .
gical

stu dy of h e a r t s

E deficiency.
fibers,

the

(1934)

the

in the h e a r t

Cheng 1 9 4 5 ) .

described th a t

same h e a r t a b n o r m a l i t i e s

c a l v e s and
due t o

G u l l i c k s o n et_ a l . i n 1 9 4 6 made a h i s t o l o ­
obtained

f r o m c ows t h a t

had d ied of v ita m in

He f o u n d a t r o p h y a n d s c a r r i n g o f t h e

increase

of

Y e ars l a t e r Willman e t a l .

v ita m in E d e f i c i e n c y did not always produce l e s i o n s
of the

i n dogs

insufficiency.

consisted

b e n e a th th e endocardium and u s u a l l y

(1945)

who f o u n d t h a t

have been o b s e r v e d i n lambs s u f f e r i n g from

vitam in E d e fic ie n cy .

the h e a rt

in

in c e llu la r elem ents,

c a r d i a c muscle

a n d i n some i n s t a n c e s

n o d u l e s w h i c h r e s e m b l e d t h e A s c h o f f n o d u l e s s e e n i n human e n d o ­
card itis.

- 21 Anatomical

i n j u r y of th e h e a r t has been r e p o r t e d

s p e c ie s as a r e s u l t
and Houchin

(1947)

o f f e e d i n g a d i e t low i n v i t a m i n E.
noted th a t

of c a r d i a c muscle a re

severity:

papillary

heart,

ventricular

The P u r k i n j e

w alls

fibers

the

absence

(1938).

a year

of th is

The

They n o t e d t h a t r a t s

o r more o f t h e

peculiar,

in the l e f t

D igestive

system:

As a r u l e

the

since

vitam in E d eficien cy

on t h e h e a r t

(1939)

tract

is

in vitam in
disease

can pro d uce

( Mason 1 9 4 4 ) .

severe

c h an g e s were s i m i l a r t o

the

However,

in turkey p o u lts ,

myopathy of the

the

by h y a l i n e

gizzard.

changes of s k e l e t a l
necrosis

f i b e r s w ith secondary inflamm atory r e a c tio n ;
or re g e n e ra tio n .

immune t o

even i n t h e p r e s e n c e o f s e v e r e

h a v e shown t h a t ,

m u sc le s and were c h a r a c t e r i z e d

by f i b r o s i s

of O lc o tt

t h e l e s i o n s were p r e d o m i n a n t l y

symptoms i n o t h e r o r g a n s

Pathological

which e x p la in e d

symptomatology of th e

gastro-intestinal

Pappenheimer e t a l .

s ymp­

ventricle.

of v itam in E d e fic ie n c y ,

dystrophic

in r a t s

showed t h i s

deficiency,

(1949)

out th a t the

localized

effects

found m yocardial l e s i o n s

study of B u ttu r in i

is rather

apex of

sympt om i n p r e v i o u s e x p e r i m e n t s

E deficien cy pointed
in r a t s

columnae c a r n a e ,

and s e p t u m and i n f r e q u e n t l y atfcria.

(1945)

in v ita m in E.

tom o n l y a f t e r

m uscles,

i n o r d e r of f r e q u e n c y and

appeared u n a ffe cte d .

Ma s o n a n d Emmel
deficient

Gatz

th e p o r t i o n of th e h e a r t which

shows n e c r o s i s
the

in other

this

o f t h e muscle
was f o l l o w e d

- 22 P h y s i o l o g i c a l Changes
C reatine

and C r e a t i n i n e E x c r e t i o n :

C r e a t i n u r i a has been c o n sid e re d the
of the vitam in E d eficien cy
Hummel

(1951),

in th eir

(B icknell

studies

and g l y c o c y a m in e i n r a b b i t s
that

creatinuria

lysis

but also

prece

1948).

deficient

creatinuria
all

s y mp t o m,

the v ita m in d e f i c i e n c i e s ,

of the d ise a s e

since

it

was f o u n d i n

a n d was m e r e l y t h e

to any l o s s

h y p e r c r e a t i n u r i a , he s t a t e d ,

c a n be c o r r e c t e d

vitam in d e fic ie n t

sharp

to

of vitam in E d e fic ie n c y .

chloride.

that

observed

Bauer and B erg

sh ip between c r e a t i n e
They p r o p o s e d t h a t
trophy

the

Hove

in r a t s
(1943)

t o be a l t e r e d
noted a

in creatinine

excretion,

poisoned with carbon t e t r a ­
s u g g e s te d an abnormal r e l a t i o n ­

and c r e a t i n i n e
creatinuria

on t h e

This

o n l y by a d d i n g

(1947a)

during vitam in E d e p le tio n .

of n u tr itio n a l

c o u l d be due t o h y d r a t i o n o f c r e a t i n i n e

based h is p ro p o s itio n

patholo­

in the diet*

i n c r e a s e d e x c r e t i o n and r e d u c t i o n

sim ilar

first

i n body w e i g h t .

C r e a t i n i n e e x c r e t i o n has a ls o been r e p o r t e d
as a re su lt

However,

in the urine*

was a n u n s p e c i f i c

specific

signs of p a r a ­

changes.

severity

out

c o n c lu d e d from h i s e x p e r i m e n t s t h a t h y p e r -

gical m anifestation prior

the

M e l v i l l e and

ded no t o n ly t h e e x t e r n a l

and t h e amount o f c r e a t i n e

sign

i n v i t a m i n E, p o i n t e d

any o b s e rv a b le h i s t o l o g i c a l

(1949)

clinical

on t h e m e t a b o l i s m o f c r e a t i n e

t h e y f o u n d no c o r r e l a t i o n b e t w e e n t h e

B utturini

first

fact that

to

alteration

muscular dys­
creatine.
of th e

He

normal

- 23 water balance

of t is s u e s

is

chem ic al and h i s t o l o g i c a l

a consistent

fin d in g in the

exam ination of t i s s u e s

bio­

affected

by

vitam in E d ep letio n .
Effect

o f V i t a m i n E on Grow th :

V i t a m i n E h a s n o t b e e n s h o w n t o be a g r o w t h f a c t o r
young r a t ,

Emerson and Evans

deficiency affected
month o f l i f e .
to

the

normal

diet.

the

(1937)

only a f t e r

The g r o w t h was r e e s t a b l i s h e d

growth of r a t s

the

observed th a t vitam in E

growth of r a t s

During e a r l y age,

for

the

fourth

by a d d i n g v i t a m i n E

v ita m in E does not a l t e r

the

(O lcott 1937).

I n m ice, V o g t-M /lle r

(1942)

o b ta in ed the

same g r o w t h c u r v e s

regardless

of th e p r e s e n c e or absence of v i t a m i n E i n th e r a t i o n .

In c a ttle ,

G ullickson et a l .

effect

(1949) were u n a b le

of th e v itam in E d e fic ie n c y

( 1 9 3 4 ) made t h e

interesting

th e lambs t h a t were b e t t e r

on g r o w t h .

observation th at

to d e te c t any
Willman et_ a l .

in f ie ld

cases

d e v e l o p e d w e r e mor e s u s c e p t i b l e

to

”s tif f - la m b ” d isease.
The g r o w t h o f monkeys i s
vitam in E (F ile r e t a l .
turkey poults

n o t a f f e c t e d by a l a c k o f d i e t a r y

1949);

however,

chickens,

r e q u i r e d vitam in E fo r adequate

ducks,

growth

and

(Pappen­

heim er 1939).
C h a n g e s i n t h e B l o o d , M i l k a n d C o l o s t r u m P r o d u c e d by V i t a m i n E
D eficiency:
One o f t h e f i r s t

changes noted in the com position of the

b lo o d plasm a o f lambs d e f i c i e n t

i n v i t a m i n E,

was t h e l o w

- 24 c r e a t i n i n e and high p r o t e i n n itro g e n
(1949),
gical

however,

studies,

was u n a b l e t o

blood g lu cose,

(Sholl 1939).

F iler

e_t a l .

d e t e c t any change i n h e m a to lo ­
blood n o n -p ro te in n itro g e n ,

p l a s m a p r o t e i n o f monkeys a f f e c t e d

with

and

chronic vitam in E

deficiency.
U ntil

recently

a n aly ze blood
biological
to

tion,

had been v e ry l a b o r i o u s

Ne we r p h y s i c a l

to c o p h e r o ls have g r e a t l y

i n anim al and v e g e t a b l e
Ka c h ma r eJL a l .

level

and chem ical a s s a y methods

th u s a llo w in g f o r an e x te n s i v e

failure,

m aterials

(1950)

facilitated

of l e s s

found t h a t

A n im a ls t h a t r e c e i v e d mixed t o c o p h e r o l

Ferrando

level

o f cod l i v e r

oil

micrograms p e r
oil

the

cent.

(1949)

dying of c ard ia c

had a c a l c u l a t e d

human m a t e r n a l
cord,

cows,

that

I n on e cow, w h i c h r e c e i v e d
fell

no c o d l i v e r

o n l y f r o m 3 4 8 t o 275 a n d r o s e a g a i n
of plasma d u rin g the

t h e venous and a r t e r i a l

and c o n c l u d e d t h a t

t h r o u g h t h e p l a c e n t a and i s

the blood

r e c e i v i n g 5 0 - 7 5 gm.

(1947) measured th e to c o p h e r o l
serum,

d i e t s had a

t wo m o n t h s was l o w e r e d a b o u t 1 0 0

t o 3 1 6 m i c r o g r a m s p e r 100 m l .
A thanassiu

tocopherol

of blood plasma.

in th e ir

reported

of T a ra n ta is e

daily for

tocopherol value

um bilical

cattle

o f 685 m i c r o g r a m s p e r c e n t .

and c o - w o r k e r s

plasma to c o p h e ro l le v e l

investiga­

( Ma s on 1 9 4 4 ) .

t h a n 100 m ic r o g r a m s p e r 100 ml.

tocopherol

the

determ in atio n of to co p h ero ls

due t o v i t a m i n E d e f i c i e n c y ,

calculated

and e x p e n s i v e t o

s a m p l e s f o r a l p h a t o c o p h e r o l by me a n s o f t h e

method.

determ ine

it

same p e r i o d .

co n ten t of the
blood of the

the v itam in E p asses

a b s o r b e d by t h e

fetus.

freely

- 25 W h itin g and L o o s l i

(1948b)

d u c t i o n wa s n o t s i g n i f i c a n t l y
pherol
per

or cod l i v e r

cow d a i l y ,

slightly
liver

a c t e d by t o c o p h e r o l
The e f f e c t

were

the

percentage
of f i v e

of f a t

Cod

this

c o u l d n o t be c o u n t e r ­

feeding.

of tocopherol

(1947).

f e e d i n g on t h e

It

was f o u n d t h a t

th a n the

20 m i c r o g r a m s p e r
were g iv e n d a i l y

tocopherol le v e l

latter.

the

co n ten t of the

When no t o c o p h e r o l s
tocopherol

cent.

When 0 . 5

in the ra tio n ,

level

and t h a t o f

to 1.0

the le v e l

gm. o f
of to co ­

c hanged t o 150 m ic r o g r a m s p e r c e n t i n t h e c o l o s t r u m

a n d 17 m i c r o g r a m s p e r

cent in the m ilk f a t .

t o c o p h e r o ls were g iv en d a i l y ,

the lev el

t r u m t o 489 a n d t o 3 9 m i c r o g r a m s p e r

i n sheep and g o a t s .

colostrum .

When 1 0 gm.

increased

fat

of

in the c o lo s­

cent in th e milk f a t .

S i m i l a r r e s u l t s were o b t a i n e d l a t e r

the

in the m ilk.

c o l o s t r u m f a t was 98 m i c r o g r a m s p e r c e n t ,

tocopherols

(1948b)

feeding,

o u n c e s p e r cow d a i l y d e c r e a s e d

a p p r o x i m a t e ly 11%;

i s much l a r g e r

milk f a t

pherol

toco­

of tocopherol

during w inter

g i v e n i n t h e r a t i o n o f c ows t h e a v e r a g e

in the

m ilk p ro ­

c o l o s t r u m a n d t h e e a r l y m i l k o f cows was s t u d i e d by

Parrish et al.
former

The f e e d i n g o f 1 gm.

fed a t the r a te

the f a t percentage

the t o t a l

a f f e c t e d by f e e d i n g e i t h e r

o v e r a f o u r week p e r i o d

in c re a s e d the

oil

of the

oil.

found t h a t

by W h i t i n g a n d L o o s l i

T h e i r m i l k was much l e s s

ric h than

- 26 -

E lectrocard iogram :
The e l e c t r o c a r d i o g r a p h i c
field

of animal

and S te n stro m

nutrition a l i t t l e

(1929)

used t h i s

produced in the h e a rt
Since

technique

o v e r 20 y e a r s

method t o d e t e c t

of anim als

some h e a r t l e s i o n s w e r e l a t e r

thought th a t
for

the

th e u n d e rs ta n d in g of the

flections
anim al.

discovered

(1946)

They c o n c lu d e d t h a t
of the

it

the

informa­

by a v i t a m i n E - f r e e r a t i o n .
of the v a rio u s

de­

to the d e a th of the

o f t h e h e a r t wa s a l s o

results

was

studied e le ctro ca rd io ­

wa s m o d i f i e d f o u r m o n t h s p r i o r
axis

oil.

t o be c a u s e d

d ie t of anim als,

i n c r e a s e d and t h e p o t e n t i a l

The e l e c t r i c a l

activity

the a l t e r a t io n s

disease#

changes produced in c a t t l e

Th e PR i n t e r v a l

Agduhr

e le c tro c a rd io g ra m could give v a lu a b le

G u l l i c k s o n and C a l v e r l y
graphic

ago,

f e d an e x c e s s o f cod l i v e r

by t h e a b s e n c e o f v i t a m i n E i n t h e

tion

was p u t t o u s e i n t h e

showed a d e c r e a s e d

myocardium i n t h e t e r m i n a l

changed.
functional

s ta g e s of th e

deficiency.
In r a t s ,

Ensor

(1946)

did

not fin d a d e f i n i t e

b e t w e e n a n i m a l s m a i n t a i n e d f o r a y e a r on a d i e t
32 a n d t h o s e k e p t o n t h e
that,

perhaps,

of the

free

v i t a m i n E.

o u t o f 15 r a t s ,

which

c o u l d be t h e o n l y n o t i c e a b l e

deficiency.

E - d e f i c i e n t r a b b i t s were s u b m i t t e d t o v a r i o u s
tests

of v ita m in

He r e p o r t e d

a s l i g h t w i d e n i n g o f t h e QRS c o m p l e x ,

occurred in fiv e
effect

same d i e t p l u s

difference

by Houchin and Sm ith

(1944).

functional

They found t h a t d e f i c i e n t

- 27 a n i m a l s had a g r e a t l y
tary

extract,

cardiac
L ater,

increased s e n s itiv ity

a higher resistan c e

glycosides,

and

Gatz and Houchin

that

to

the

to p o s t e r i o r p i t u i ­

toxic e ffe c t

the h e a rt probably

(1947) p o i n t e d o u t t h a t

became d i l a t e d .
rabbits

m y o c a r d i t i s p r o d u c e d by v i t a m i n E d e f i c i e n c y a l s o
EKG r e c o r d .
those

The r e c o r d s

of normal r a b b i t s

verted

potential

frequently

o f QRS

of d e f i c ie n t anim als as
showed a r i g h t a x i s
i n l e a d s 1 and 3;

compared w i t h

appeared

work o f B ragdon and L e v i n e

was n o t h i n g

(1949)

rabbits

s h o w e d e l e v a t e d ST s e g m e n t s a n d i n v e r s i o n

part

II.

(1947).

E-deficient
of the T

These changes were o n ly o b s e r v e d d u r i n g t h e

of the p e rio d of o b s e r v a tio n .

I n monkeys w i t h c h r o n i c v i t a m i n E d e f i c i e n c y ,
(1949)
of

pointed

out th a t

there

is

w ith the

results

quite

et_ a l .

He c o m p a r e d

o b t a i n e d i n v i t a m i n B1 d e f i c i e n c y

o f m o n k e y s by W a i s m a n a n d M c C a l l
were

Filer

a re d u c tio n in the amplitude

t h e R and T waves and i n v e r s i o n o f t h e T w a v es.

his re s u lts

The

d id not. f u l l y r e p r o d u c e th e

r e p o r t e d by G a t z a n d H o u c h i n

in lead

No s i g ­

i n t h e PR a n d QRS i n t e r v a l s .

results

latter

an i n ­

o c c u r r i n g i n T1 a n d T2 a n d i n v e r s i o n o f T 3 .

n ifican t variations

waves

having

gave a b n o r m a l

deviation,

there

of

(1944)

and c o n c lu d e d t h a t

they

sim ilar.

Interrelationships:
The s t u d y o f t h e e f f e c t s
chem ical

o f v i t a m i n E d e f i c i e n c y on t h e

composition of the t is s u e s

h a v e shown t h a t

it

influences

- 28 the l i p i d ,
These

protein,

changes presuppose

or in d ire c tly ,
are

far

these

carbohydrate

of the

metabolism of the

paragraphs,

they w ill

taking into

constituents.

the p re v io u s a l t e r a t i o n

from u n d e r s t a n d i n g th e

changes,

and m i n e r a l

either

tissues.

directly

A l t h o u g h we

complex mechanisms i n v o l v e d i n

be b r i e f l y

reviewed in the fo llo w in g

co n sid eratio n the

E on t h e m e t a b o l i s m o f p r o t e i n s , l i p i d s ,

influence

of v ita m in

c a r b o h y d r a t e s and

m inerals.
Interrelationship
There
the l i p i d

is

of V ita m in E and t h e L i p i d s :

no d o u b t t h a t v i t a m i n E m u s t b e c o n c e r n e d w i t h

metabolism since

and cod l i v e r

oil

certain

especially)

fatty

given in the

symptoms o f t h e v i t a m i n S d e f i c i e n c y
and,
lipid

(rancid f a t

diet precipitate

the

(Mackenzie e t a l . 1 9 4 1 ),

the v ita m in E d e f i c ie n c y produces derrangem ents of the
c o m po sitio n of the
Rancid f a t s ,

of fre e

fatty

by M a t i l l
drastic

(1938)

action

lo n g time to

tissues.

m a t e r i a l s h a v i n g a r a n k s m e ll and h i g h c o n t e n t

acids,

Excessive

1929)

m aterials

aldehydes,

t o be h i g h l y d e s t r u c t i v e

was due t o r a p i d

be d e t r i m e n t a l

dystrophy

made a n e f f o r t

to

to

oil

This

to anim als
it

h a s b e e n known f o r a
(Agduhr and S t e n s t r o m

to f a c i l i t a t e

(Davis e t a l . 1 938).

identify

v i t a m i n E.

oxidative process.

f e e d i n g o f cod l i v e r

a n d many w o r k e r s h a v e u s e d

the muscular

k e t o n e s and p e r o x i d e s were found

the fa c to rs

the

study of

The same a u t h o r s

i n cod l i v e r

oil

res­

- 29 ponsible
arsenic

for
nor

such a c t i o n .
cholesterol

Their r e s u l ts

indicated

that

neither

were c o n c e r n e d w ith th e p r o d u c t i o n o f

m uscular dystrophy.
Mor e r e c e n t
o f cod l i v e r
et

a l.

were

o il.

(1950)

the

in the

investigations
Dam ( 1 9 4 4 a ,

chicken.

factor

toxic

which c o n t r i b u t e s

to the

However,

rabbits

yet

defined.
oil

shown a n ta g o n is m
fa t also

deficiency
three

little
(I.N .

effect
104)

oil

(1948)

the

acids

in t h e cod l i v e r

oil

in dogs.

on t h e a p p a r e n t

towards vitam in E in experim ents

of th e to x ic ity

was n o t t h e

chick.

f a tty acids

fatty

development of a r t e r i t i s

to the

only f a t t y

fatty

conclusion th a t

of cod l i v e r

the

th at has

of v i ta m in E
by s e p a r a t i n g

of d i f f e r e n t

le a st unsaturated frac tio n

and gave o n ly e x u d a t e s ;

was n o t

showed t h a t hog

he f o u n d ,

acids

oil

m aterial

Dam ( 1 9 4 4 b )

Furthermore,

o f hog l i v e r

(I.N .

iodine

5) h a d

interm ediate fra c tio n

gave b o t h e x u d a t e s and e n c e p h a l o m a l a c i a , w h e re a s t h e

most u n s a t u r a t e d
severe

substances contained

to th e v ita m in E.

of the

that:

and G oldhaber

that

h a d an e f f e c t on t h e p r o d u c t i o n

fractions

number,

stated

and g u i n e a p i g s l e d

nature

Cod l i v e r

liver

constituents

for production of vitam in E d eficien cy

t h e r e v i e w of- C o r m i e r

a n t a g o n i s m o f cod l i v e r

specific

1944b and 1948)

Holman ( 19 47) a l s o

p r o b a b l y were the

the

towards o th er

thought th a t probably the u n sa tu rated

necessary

w ith r a t s ,

point

fraction

(I.N .

241)

e n c e p h a lo m a la c ia and e a r l y

caused a ra p id

death of the

onset of

anim als.

- 30 Mo r e e v i d e n c e
essential
(1946)

on t h e

unsaturated

fat

interrelation

but

and

a c i d s wa s g i v e n by Hove a n d H a r r i s

who s h o w e d t h a t E - d e f i c i e n c y

when t o c o p h e r o l

of alpha tocopherol

no e s s e n t i a l

fat

s y m p t o ms w e r e a g g r a v a t e d
was f e d t o

fat-deficient

rats.
The i n f l u e n c e

o f v i t a m i n E on t h e l i p i d

t i s s u e s wa s s t u d i e d by v a r i o u s
(1942)

found t h a t

com position of the

investigators.

in vitam in E deficiency

E s c u d e r o jet a l .

the l i p i d

content of

the adrenals

was d i m i n i s h e d a f t e r

s i x months.

The e x t e n s i v e w o r k o f Dam o n t h e v i t a m i n E d e f i c i e n c y

of chicks

r a t s were on a low E d i e t

(1 9 4 4 a, 1944b and 1949)

E deficiency

decreased

the r a t i o

in th e blood plasma of c h ic k s,

g a v e some e v i d e n c e t h a t
of phospholipid to

b u t he t h o u g h t t h a t

the

e n o u g h t o be o f d i a g n o s t i c v a l u e .

showed

t h a t the development

pose

tissue

coincided
the

of ch ick s,

with the

depot f a t .

w h i c h was a p p a r e n t
tissues.

due t o l a c k o f t o c o p h e r o l s

t i m e when p e r o x i d e s

L ater,

the p e ro x id es

These l a s t

that

meat of t u r k e y s ,

their

ration,

storage•

increased

f i n d i n g s were e s s e n t i a l l y

by C r i d d l e

and Morgan

( 1 9 4 7 ) who,

w hich were n o t

developed u n p lea sa n t

differ­
He a l s o

in the a d i ­

in the d ie t,

c o u l d be d e m o n s t r a t e d

t h r o u g h t h e brown c o l o r a t i o n

reported
the

of exudates

the

other lip id s

e n c e was n o t g r e a t
(Dam 1 9 4 8 b )

in the
of th e
the

besides,

in

tissues,
fat

same a s
observed

fed to co p h e ro ls

flavors

for

in

during prolonged

- 31 B r a t z l e r et_ a l .
depleted
acid.

in

(1950) a n a l y z e d t h e

tocopherols

the expense

of o le ic

of the

saturated

acids.

Interrelationship

of V ita m in E and the N i t r o g e n M e tab o lis m :

The i n f l u e n c e
on t h e

of

the d e f i c i e n c y of v ita m in E i n the

creatine-creatinine

been review ed.
modify the

creatine,

creatinine,

(1932)

M elville

tissues

of E d e p le te d r a b b i t s
liver

glyocyamine c o n te n t of t i s s u e s

found t h a t

muscle d e c r e a s e d ,

brain.

of the

a n d Hummel

and th e

same may be t r u e

tem porarily

store

whereas

the

the

in the l i v e r .

or

creatine
that

con­
of the

c o n ten t of c r e a t i n e

These f i n d i n g s

some s t o r a g e

some o f t h e

content

a n a l y s i s of

tim es over normal,

t h e m u s c l e wa s l o w e r t h a n n o r m a l .
is

creatine

a l s o made t h e

and found t h a t

increased five

perhaps there

the

but not in e it h e r h e art

(1951)

k i d n e y and b l o o d f o u r t i m e s ,

them t h a t

has a lr e a d y

i n v i t a m i n E.

G - o e t t s c h a n d Brown
of the r a b b i t

e x c re tio n in the urine

diet

Alpha to c o p h e ro l a ls o has been dem onstrated to

of anim als d e f i c ie n t

tent

of p ig s

and found a h ig h p e rc e n ta g e

Th e e x c e s s was p r o d u c e d a t

fatty

body f a t

in

suggested to

in the kidneys c e l l s ,
Both o r g a n s would

creatine released

from d e g e n e r a t i n g

m uscles.
Vitam in E not only has
compounds

j u s t mentioned,

p r o te in m etabolism .

interrelations

but also

with

the n itro g en o u s

w i t h t h e amino a c i d s and

- 32 Herschel

(1946)

made a t h e o r e t i c a l

alpha

tocopherol

there

m u s t be a r e l a t i o n

pecially

cystine

On t h e

study of the a c t io n

on t h e a n i m a l p h y s i o l o g y .
of vitam in E to

t h e amino a c i d s ,

o th er workers a rr iv e d

c l u s i o n s whe n i n v e s t i g a t i o n s w e r e c a r r i e d

amino a c i d s ,
specific

It

He c o n c l u d e d t h a t
es­

and i s o l e u c i n e .

o th er hand,

of c r e a t i n e .

of

was f o u n d t h a t

but e s p e c ia lly

biological

creatine

from g l y c i n e

precursors

at

s i m il a r con­

out about

the

origin

was f o r m e d f r o m s e v e r a l
and a r g i n i n e ,

of c re a tin e

the

(Sahdu 19 4 7 ; Alm-

q u i s t e t a l . 1941; B loch and Schoenheimer 1 9 4 1 ).
G - l u t a m i n e o f t h e m u s c l e was f o u n d by R o d e r u c k
reduced

in vitam in E d e fic ie n t

(1949)

t o be

muscle o f g u i n e a p i g s and r a b b i t s .

N o tw ith stan d in g the com position of the

n o n - g l u t a m i n e amino a c i d s

rem ained unchanged.
Th e p o s s i b i l i t y

t h a t v i t a m i n E m i g h t be r e l a t e d

m e t a b o l i s m h a s b e e n s u g g e s t e d by s e v e r a l
Hove 1 9 4 6 ;
(1948)

Hove a n d H a r r i s 1 9 4 7 b ; Moor e 1 9 4 8 ,

found

that

E and p r o t e i n ,
protein,
on t h e

failure

same p r o b l e m ,

the e ff ic ie n c y
adding alpha

alpha

in ra ts

and d e n t a l

Other

workers

1949).

Moor e

o f g r o w t h was m a i n l y du e t o l a c k o f

d e p ig m e n t a ti o n to l a c k of v i t a m i n E.
Hove a nd H a r r i s

tocopherol

tocopherol,

(Dam 1 9 4 4 b ;

h a v i n g a combined d e f i c i e n c y o f v i t a m i n

of u t i l i z a t i o n

studies,

to p r o te in

to

the

(1947b)

out th a t

o f p r o t e i n was n o t a f f e c t e d b y
diet.

which combined t h e e f f e c t

dem onstrated

pointed

Working

certain

of p r o t e i n and

interesting

interrelations.

- 33 The o c c u r r e n c e
ficiency

of

of h e p a t i c

sulfur

and Himsworth

fatal

injuries

et_ a L .
liver

protein

however,

the

But t o c o p h e r o l

of the l i v e r

and L o t t i n i

V ita m in E and th e

skeletal

e d some c a s e s

the form ation

therapy,

since

vitam in E is a

h a s no i n f l u e n c e

in the

m uscle,

of vitam in E to

M o s t o f t h e k n o w l e d g e on t h i s

diseases.

h e lp e d the

o b s e r v a t i o n s on t h e e f f e c t s

B utturini

(1949)

showed t h a t

f o r m a t io n and d e p o s i t of g lu c o s e

i n t h e h e a r t and i n t h e l i v e r .

of d i a b e t i s

increased

by

Carbohydrate M etabolism:

metabolism.

tocopherol

the

and d o e s n o t a c t on t h e p l a t e l e t s .

o f v i t a m i n £ on c e r t a i n

it

could not prevent

suggested th a t

m a t t e r a t p r e s e n t c o me s f r o m c l i n i c a l

that

o f w e i g h t due t o a

w o r k h a s b e e n d o n e on t h e r e l a t i o n

carbohydrate

in the

tocopherol prevented

with f a t .

(1950)

in hemophilia

form ation of f i b r i n ,

alpha

(Kemeny

t h r o m b i n f r o m p r o t h r o m b i n c o u l d be i n f l u e n c e d

factor

L ittle

feeding.

in methionine

found t h a t

a d m i n i s t r a t i o n of a lp h a to c o p h e ro l,

coagulant

the

(1949)

ration.

heavy i n f i l t r a t i o n

of the p ro te in

deficient

anaem ia and p e r s i s t e n t l o s s

deficient

Prosperi

was f o u n d by L i n d a n

could not com pletely p revent the

Y e t , Moor e

necrosis,

p r o d u c e d by a d e ­

t o b e d e l a y e d by a l p h a t o c o p h e r o l

c a u s e d by a d i e t

1949).

in r a t s ,

c o n t a i n i n g amino a c i d s ,

(1950)

Alpha to c o p h e ro l,

necrosis

m e l l i t u s w i t h v i t a m i n E,

the d iffe re n c e

between a r t e r i a l

He t r e a t ­

and found
and venous

g ly c e m ia and re d u c e d th e h y p e rg ly c em ia and g l y c o s u r i a .

He c o n -

- 34 eluded
cases

from h i s

experience

of d i a b e tis

severe

cases,

increased

the

of in su lin .

that

m ellitus

it

was p o s s i b l e

by o n l y t h e u s e

to cure mild

of v i t a m i n E.

In

he w r o t e ,

vitam in E s t i l l

was h e l p f u l

intensity

and d u r a t i o n of

the hypoglycemic e f f e c t

The mor e c o m p l e t e u t i l i z a t i o n

diabetis

was d e m o n s t r a t e d by t h e

wh e n t h e

g l y c e r n ic v a l u e s were s t i l l

since

it

of carbohydrates

disappearance

in

of g ly c o s u ria ,

over the usual renal

thres­

hold.
In c lin ica l

cases

pituitary-diencephalic
adm inistration
tory

effect
It

o f hypo and h y p e r f u n c t i o n a l
system,

Heinsen

of alpha tocopherol

on t h e

reported

that

the
the

had a n o r m a l i z i n g or r e g u l a ­

c a r b o h y d r a t e and w a t e r m e t a b o l i s m .

m u s t be a d m i t t e d ,

interrelationship

(1951)

s t a t e s of

however, th a t

critical

d a t a on t h e

of v i t a m i n E and c a r b o h y d r a t e s a r e l a c k i n g .

V ita m in E and th e M in e ral M etabolism :
The i n v e s t i g a t i o n o f F e n n a n d G - o e t t s c h
that

m ineral

changes in th e

magnesium,
rabbits.

dystrophic

indicated

com position of th e muscles o c c u rre d

in a s s o c ia tio n with n u t r it i o n a l
They fo u n d t h a t

(1937)

muscular

dystrophy of r a b b i t s .

m u sc le s had l e s s

potassium ,

less

and more sodium and c h l o r i n e t h a n m u s c l e s o f normal
When t h e m u s c l e s

calcification

s h o we d h i s t o l o g i c a l

t h e r e wa s a l s o

found,

evidence

of

by t h e c h e m i c a l m e t h o d ,

h i g h c o n c e n t r a t i o n s of c a l c i u m and p h o s p h o r u s .
C alcification
heim er

(1942)

deficiency.

of n e c ro tic

f i b e r s was o b s e r v e d by P a p p e n ­

and M o r g u l i s and J a c o b i

(1946)

in vitam in E

- 35 The p h o s p h o r u s m e t a b o l i s m was f o u n d t o be d i s t u r b e d
absence

o f v i t a m i n E by L u , E m e rso n and E v an s

noticed

that

inorganic
decrease
ester

in paralyzed r a ts

t h e r e was a s l i g h t

p h o sphorus and c r e a t i n e
of t o t a l

acid soluble

of phosphorus*

(1941),

phosphorus,

phosphorus,

However,

When t h e

rats

increase

o f 50-180/& i n

creatine

phosphorus*

Pappenheimer
ders a sso c ia te d
interpretation
is

difficult,

of

the

overall

because

of the

dystro p h ic m uscles,

erating

fibers,

tissue,

and p a t h o l o g i c

Early

to

"stiff-lam b"

containing

of v i ta m in E,

tory

in phospho-

disor­

stated that

as regard

normal,

in terstitial

calcification

the
content

in composition

n e c r o t i c and r e g e n ­
f a t and c o n n e c t i v e

of dead f i b e r s *

suspicious

t h a t an imbalance

o f c a l c i u m t o p h o s p h o r u s h a d some c o n n e c t i o n

cull

disease

(Marsh 1 9 3 2 ) .

b e an s and a l f a l f a

Willman e t a l ,
to

muscles

changes in the e l e c t r o l y t e

p h o r u s and p r o d u c e d h i g h i n c i d e n c e
ease,

calcium

muscular

complex v a r i a t i o n s

i n v e s t i g a t o r s were

ratio

the

review of the

wandering c e l l s ,

of the

in the

w h i c h was a c c o m p a n i e d by a n

in his

with d e fic ie n cy

of

and o rg a n ic

c a l c i u m a n d by a d e c r e a s e

(1943),

of the

decrease

b e c a me m a r k e d l y d y s t r o p h i c t h e

h a d a w h i t e a n d waxy a p p e a r a n c e ,

wa s

pronounced dys­

t r o p h y was n o t o b s e r v e d a n d no c h a n g e o c c u r r e d
content*

It

and a marked

pyro,

in these r a ts

by t h e

sheep,

(1946)

Since r a t i o n s

c o n t a i n e d more p h o s ­
of " s t i f f - l a m b "

fed r a t i o n s

dis­

known t o be s a t i s f a c ­

but to which enough d i b a s i c

sodium p h o s p h a te

36 wa s a d d e d ,
that

i n o r d e r t o make t h e p h o s p h o r u s

of the

"stiff-lam b

p h o s p h o r u s by i t s e l f

ration".

content

The r e s u l t s

was n o t a f a c t o r

equal

to

indicated

in the

that

vitam in E d e f i ­

c ie n c y of th e lamb.
I r o n had been used to d e s t r o y th e v ita m in E c o n te n t of
diets
were

and p r o d u c e
interested

influence

ferrous

form,

Zacharias e t a l .

t o know w h e t h e r o r n o t i r o n p e r

in the

They f o u n d t h a t

the E d e f ic ie n c y .

(1950)

s e had a n y

development of the v ita m in E d e f i c i e n c y .
t h e i n c l u s i o n o f irot> e i t h e r

h a d no e f f e c t

in the

on t h e p l a s m a l e v e l

ferric

or

of the c h i c k .

Theory of P h y s i o lo g i c a l F u n c tio n s :
The t h e o r i e s
E were re v ie w e d

about the p h y s io lo g ic a l

by Ma s on

"P h y sio lo g ic a l A ction
antioxidant
he

said,

fu n ctio n of the

reasons

the

inability

the

inverse

given to

tocopherols,

support his

of other a n tio x id a n ts

relationship

to

of h i s work:

Homologues".

may b e " ,

p o i n t of view were:
substitute

v i t a m i n E,

and b i o l o g i c a l

of to co p h e ro ls

a n d t h e nnBanner i n w h i c h c h a n g e s u n r e l a t e d
alter

"The

o f v i t a m i n E ...................... "

between a n t i o x i d a n t s

group i n th e molecule

of v ita m in

im portant as i t

the prime r o l e

lac k of a n tio x id a n t a c t i v i t i e s

ingestion,
hydroxyl

in a chapter

of V ita m in E and I t s

"cannot rep resen t

Among t h e

actions,

(1944)

functions

biological

after

to p henolic

activity

of the

tocopherol s.
"Adamstone" , c o n t i n u e d Mason,
v i t a m i n E may e x e r t a c o n t r o l l i n g

"postulated
influence

the th eo ry t h a t

over

cell p ro life ra ­

- 37 tion.

This idea

inspired

E m i g h t be n e c e s s a r y
tin

o th e r workers

either

for

the

to

suggest th at

synthesis

vitam in

of n u c le a r

or the m aintenance of the p hysico-chem ical

state

chroma­

of the

l a t t e r ."
A n u mb e r o f i n v e s t i g a t o r s p r o p o s e d
c o u ld be i n v o l v e d
m uscles.

Mason (1944 )

been deducted
tant

in the m etabolic
described

special

symptoms i n r a t s ,

ferent a b ilitie s

to

synthesize

gans or t i s s u e s a re a f f e c t e d
are

striking

interpreted

disclose

i s an impor­

by v i t a m i n E d e f i c i e n c y ,

in a v a rie ty

tim e,

fact that different

in th is

c a n be

in a s p e c if ic

of tis s u e s ,

role

have been c a r r i e d o u t

of v i t a m i n E.

by H a r r i s a n d K u j a w s k i

(1950)

In the b i b li o ­

the follow ing

enzy m es have b e e n r e p o r t e d t o h a v e a clos.e r e l a t i o n s h i p
carotene

oxidase,

coenzyme I ,

cytochrome

choline e s te ra s e ,

oxidase,

hyaluronidase, asparticglutam ic
phatase,

muscle a l k a l i n e

and p h o s p h o ry la s e s .

or

of enzymic p r o c e s s e s . "

many i n v e s t i g a t i o n s

v i t a m i n E:

or­

and t h a t

regard,

common t o a v a r i e t y

the p h y sio lo g ic a l

graphy c o l l e c t e d

"the

1) v i t a m i n E t a k e s p a r t

which i s

plays a p a rt
Since t h a t

to

arginine

a n i m a l s known t o h a v e d i f ­

species differences

i n t wo w a y s :

m etabolic process
it

that

which had

arginine.

" I n c o n c l u s i o n , " Ma s o n s t a t e d ,

2)

hypotheses,

component o f n u c l e o p r o t e i n s , and t h a t v i t a m i n E d e f i c i e n c y

produces

there

th at arginine

d y sfu n ctio n of dy stro p h ic

these

f r o m t h e known f a c t s ,

the t h e s is

phosphatase,

the

succinoxidase,

cytochrome r e d u c t a s e ,
transam inase,

to

liver

lipase,

a c id phos­

muscle a c i d p h o sp h a ta s e

- 38 T h i s e x t e n s i v e a c t i o n o f v i t a m i n E on t h e e nz yme s y s t e m
m ight i n d i c a t e
E is

played

in the

R ecently,
the
that

t h a t p e r h a p s t h e most i m p o r t a n t r o l e
enzymic p r o c e s s e s

Hickman

(1949)

highly polyfunctional

of th e animal

has p o s tu la te d

properties

organism*

a hypothesis about

o f v i t a m i n E*

v ita m in E p la y s a predominant r o l e

of vitam in

in the

He p r o p o s e d

i_n t r a n s i t u

c h e m i s t r y p e r f o r m i n g an o r g a n i c

h o u s e k e e p i n g and t i d i n e s s

w h i c h s h o u l d be

to th e a g in g problem*

closely related

job

EXPERIMENTAL PROCEDURE
A nim als Used
A total
in th is

o f 51 l a m b s w a s :

species.

used to

study vitam in E d e fic ie n c y

Most o f them we re o b t a i n e d

State

C o l l e g e ’s e x p e r i m e n t a l

farms.

The m a i n c r i t e r i o n

from t h e M ic h ig a n

f l o c k a n d some f r o m n e i g h b o r i n g

for

the

s e le c tio n of the experim ental

a n i m a l s were age and h e a l t h .
It
the

was t h o u g h t t h a t l a m b s t h r e e

most d e s i r a b l e

to use i n t h i s

to

f o u r d a y s o l d w o u l d be

experiment.

At t h i s age they

would have r e c e i v e d enough c o lo s tru m to d ev elo p n o rm a lly b u t
not q u ite

enough to

b u i l d up a g r e a t

which would have e i t h e r

increased

w o u l d h a v e n o t made p o s s i b l e
deficient

storage

the

time

of d e p le tio n ,

lambs*

t y p e o f m u tt o n and f i n e

wool.

and t w in lam bs were u sed i n t h i s

but a ll

E ssentially,
wa s s i m i l a r

to

that

their

and growth o f

the p u rifie d

belonged to

Fem ales and m ales,

single

experiment.

C o m position and P r e p a r a t i o n of the P u r i f i e d

found t h a t

or

the p ro d u c tio n of v itam in E

The l a m b s w e r e p u r e b r e d o r c r o s s b r e d ,
the

of to co p h e ro ls,

d i e t used i n t h i s

r e p o r t e d by L u e c k e e t a l .

d i e t was v e r y s a t i s f a c t o r y

the young s u c k l in g lamb.

Diet
investigation

(1950).

for

However,

They

the development
fo r the p re s e n t

- 40 work,
diet

it

was f e l t

n e c e s s a r y t o make c e r t a i n

in order to elim in ate

intestinal
of the

synthesis

the p o s s i b i l i t y

of v ita m in E,

i n many a n i m a l s *
constituted

of the lambs.

the

intestinal

only source

s hown i n T a b l e s I ,

II

synthesis

of carbohydrate

first

wa s t o a t t e m p t

t h a t perhaps the
since

to

duplicate

the

field.

acute

this

it

was t h o u g h t t h a t

of a sm a ll amount o f

was t h e r e a s o n ,

feed a vitam in E antagonist.
s e c o n d was t o u s e i n g r e d i e n t s

were s u c c e s s i v e l y

T h i s wa s n o t

then,

for production of vitam in E d e fic ie n c y .

p r e p a r a t i o n of the

I

symptoms o f v i t a m i n E

If

the

trial

has been s t a t e d ,

Therefore,

tocopherols

and the

compo­

syndrome of v i t a m i n E

of th e presence

t wo c h o i c e s

mild.

as i t

d e f i c i e n c y was t h e r e s u l t
in the d ie t.

diet

d i e t wa s n o t a b s o l u t e l y

which,

cause of p r o d u c t i o n of moderate

was t o

in the

glu­

t h e symptoms o f v i t a m i n E d e f i c i e n c y

investigation,

d e f i c i e n c y found in the

were

thus,

10 a n i m a l s o f t h e

an e x te n d e d p e r i o d were r a t h e r

aim o f t h e

of vitam ins

and I I I .

w ith the

of to c o p h e ro ls,

even a f t e r

the

the r e s u l t s

The d i e t was c a l l e d d i e t A w h i c h h a d t h e

( d i e t A) i n d i c a t e d

the

which could a l t e r

L a c t o s e was r e p l a c e d by g l u c o s e ;

The e x p e r i e n c e

free

gastro­

c o n sisted in the e lim in a tio n of l a c to s e ,

a s u g a r kno wn t o p r o m o t e t h e

sition

of e a r ly

experiment*

The m o d i f i c a t i o n

cose

changes in t h i s

liquid

employed.

diet.

there
One

a lo n g w ith th e E-low d i e t ,
freer

of to c o p h e r o ls for

Both of the a p p ro a c h e s

-

41 -

TABLE I
COMPOSITION OF THE PURIFIED DIET
D iet A
Per cent

Component
Solids

D iet B
p e r ceni

16.05

Casein

(Labco)

Glucose
Lard

(commercial)

16.05
4.80

4.80

6.08

6.08

4.16

(m olecular
distilled)

4.16

S a l t m ixture

0.96

0.96

Vitamins

0.05

0.05

D istilled

water

83.95

83.95

100.00

100.00

TABLE I I
VITAMIN CONTENT OF (THE PURIFIED DIET
Mg. p e r I t .
of a r t i f i c i a l
milk

Vitam ins

Mg. p e r I t .
of a r t i f i c i a l
milk

Vitamins

Thiamine

1.4

Inosi tol

R iboflavin

3.0

Bi o t i n

acid

4.0

Choline

Calcium p a n t o ­
thenate

5.0

0(-Tocopherol
acetate

2.00

Pyridoxine

2.0

2-Methyl naphthoquinone

0*4

N icotinic

Pteroyl
acid

glutam ic

p-Amino b e n z o i c
acid

40.00
0.04
400.00

0.2
4.0

Vi t a r n i n A

4000 I . U .

Vitamin D

500 I . U .

- 42 TABLE I I I
COMPOSITION OF THE SALT MIXTURE

Component

Per cent

NaCl

11.88

K2HP04

25.76

CaHP04

33.80

Ca l a c t a t e

Ca(C3H503)2-5H20

22.88

Mg S 04. 7H20

3.54

FeS04.7H20

1.93

KI

0.06

MnS04. H20

0.10

ZnCl2

0.02

CuS04 . 5H20

0.02

Co Cl 2

0.01

.6H20

1 0 0 .0 0

- 43 Cod l i v e r
tion

oil

was s e l e c t e d

of an tag o n istic

were a l r e a d y
trols,
tim e,

f a c t o r s to

a s the product
v i t a m i n E.

fe d a v i t a m i n E-low d i e t

which were
were d a i l y

fo r supplem enta­

Three a n im a ls,

that

f o r 40 d a y s a n d t wo c o n ­

fed a vitam in E c o n ta in in g d i e t
supplem ented w ith 5 ml.

for

the

same

o f cod l i v e r

oil

by

m o u t h f o r a p e r i o d o f 25 d a y s .
Of a l l
the

the

ingredients

only m a te ria l

quantities
attenuate

lard

syndrome.

animal

fat)

micrograms of to c o p h e r o ls per
d i e n t s remained u n a l t e r e d .

of

Thus,

the

or

commercial l a r d

by a n e q u a l a m o u n t o f a m o l e c u l a r d i s t i l l e d

(low t o c o p h e r o l

to

significant

te n d in g to delay the ap p ea ra n c e,

the E d e fic ie n c y

wa s i d e n t i c a l

c o m m e r c i a l l a r d was

su sp ec ted to c o n ta in small but

of tocopherol

wa s s u b s t i t u t e d

o f t h e d i e t A,

containing less

gram.

The r e s t

than fiv e

of the

ingre­

The new d i e t was c a l l e d B w h i c h

d ie t A in every resp ec t

except

for the

nature

the l a r d .
Some o f t h e

chemical

characteristics

of the

commercial and

m olecular d i s t i l l e d

l a r d h a v e b e e n d e t e r m i n e d by t h e D i s t i l l a t i o n
1
Production In d u s trie s
which a r e summarized i n Table IV.

^ R ochester 3,

N. Y .

D i v i s i o n o f E a s t m a n Kodak Compa ny.

-

44 -

TABLE IV
SOME CHEMICAL CHARACTERISTICS OF COMMERCIAL
AND MOLECULAR DISTILLED LARD

C haracteri s tic
Iodine

Commercial
lard

M olecular d i s ­
tille d lard

65.9

65.0

195.0

195.3

n u mb e r

S a p o n i f i c a t i o n Number
Percent U nsaponifiable

to•
o

0.3

Acid Value

0.9

0.02

Peroxide

numbe r

P e r o x i d e number a f t e r
four hour of a e r e a t i o n
a t a b o u t 98°C.
The p r e p a r a t i o n
the

to

80-S5°C.

warm w a t e r ,

23.0

361.0

418.0

of the l i q u i f i e d

f o llo w in g manner.

measured i n t o

14.0

D i s t i l l e d water

is

present

and th e
rapid

Sodium b i c a r b o n a t e

the

was

and to t h i s

( 82 g m . ) was d i s s o l v e d i n t h e

solution casein

to

sodium c a s e i n a t e ,

in the

n a tu ra l m ilk.

( 1 7 2 8 g m. ) wa s a d d e d

I n t h i s way c a s e i n wa s

which i s

the

form t h a t

The f o r m a t i o n o f t h i s

casein
c o mp o u n d

p r e p a r a t i o n o f a h o m o g e n o u s s u s p e n s i o n wa s a i d e d by

stirring.

A fter a ll

of the

p e n s i o n wa s c o n t i n u o u s l y s t i r r e d
assute

(29.5 l i t e r s )

out in

a 10 g a l l o n m i l k c a n a n d wa r me d w i t h a s t e a m c o i l

v e ry slow ly and i n sm all p o r t i o n s .
transform ed

d i e t was c a r r i e d

u n i f o r m i t y and i n c o r p o r a t e

suspension.

c a s e i n was a d d e d ,

the

sus­

f o r about 30-45 m inutes to
the

s m a ll lumps of c a s e i n t o

— 45 Then g l u c o s e
wa s r e a d y t o

( 2 1 8 9 g m . ) was a d d e d a n d t h e p r e p a r a t i o n

receive

was m e l t e d o n t h e

the

fat

s t e a m b a t h a n d 36 m l .

f o r c e d w i t h 0 . 4 mg. p e r m l .
This l i q u i f i e d
stirred

casein,

sugars and l a r d

inch in

the

second s t a g e .

At t h i s p o in t the

into

suspension of

of s a l t

m ixture.

A b o u t 50 gm. p o r t i o n

s a l t m i x t u r e was p l a c e d i n W a r i n g b l e n d o r s ^
of the

su s p e n d e d and i n c o r p o r a t e d

stirring,
into

the

contained

to

step

of the milk p r e p a r a t i o n

of s u f f i c i e n t
i n 360 m l .

quantities

salts

were

t h e b u l k o f t h e homo­

g e n iz e d p r e p a r a t i o n w ith th e a i d of e l e c t r i c a l
The l a s t

filled

c a p a c i t y w ith the homogenized p r e p a r a t i o n .

seven to t e n m inutes of f a s t

addition

the

t h i s h o m o g e n i z e d p r o d u c t was r e m o v e d t o make

a s u s p e n s i o n o f 3 4 5 gm.

finely

( V i t a m i n K ) , wa s a d d e d *

stage and 3200-2500 pounds p r e s s u r e p e r square

A p o r tio n of

A fter

rein­

The o p e r a t i o n was d one a t 600 p o u n d s p e r s q u a r e
first

one-third

o il,

stirrers*

consisted

in the

of B v i t a m i n s which were

o f a 20$ a l c o h o l

solution.

The m i x t u r e

w a s c o m p l e t e d by a n o t h e r two t o t h r e e m i n u t e s o f s t i r r i n g ,
after
into

)

was h o m o g e n i z e d i n a Ma n t o n - G- a u l i n

the

the

( 1 4 9 8 gm.

o f cod l i v e r

of menadione

preparation.

inch in

of

The l a r d

f a t m i x t u r e was s l o w l y p o u r e d

rapidly

homogenizer.

constituents.

which the p u r i f i e d
clean s t e r i l e

liquid

gallon b o ttle s .

The m i l k was s t o r e d u n d e r
use,

but

lity

of a l t e r a t i o n .

d i e t was r e a d y t o be p o u r e d

refrigeration

a t 4°C.

n e v e r f o r mor e t h a n 1 5 d a y s t o e l i m i n a t e

until

its

any p o s s i b i ­

- 46 Care and Feeding
The e x p e r i m e n t was c a r r i e d

out d u rin g the w in ter and s p r i n g

of 1951.

The l a m b s w e r e k e p t i n a c o n c r e t e - f l o o r e d room m a i n ­

tained at

60°F .

F i n e w i r e mesh f e n d e r s s u b d i v i d e d t h e r oom i n

s m a l l p e n s o f a p p r o x i m a t e l y 4x12 f e e t .
w i t h t wo b e d s made o f b u r l a p b a g s f i l l e d
o f wood s h a v i n g s .

Two o r t h r e e

E very day t h e group of a n im a ls
one,

E a c h p e n was p r o v i d e d
w ith a small q u a n t i t y

a n i m a l s were p l a c e d i n e a c h p e n .
i n o n e p e n was moved t o a c l e a n

w h ic h a l s o was p r o v i d e d w i t h c l e a n b e d d i n g .

The d i r t y

pens

were t h e n s c r u b b e d and c l e a n e d w i t h h o t w a t e r and d i s i n f e c t e d
w ith a lye

solution

Th e s l i g h t

slope

t o make t h e p l a c e a s a s e p t i c

of the flo o r

aid ed in the

c le a n i n g of the pen s.

Th e l a m b s w e r e f e d t h e p u r i f i e d m i l k d i e t
by m e a n s o f c l e a n s t e r i l e
wa s t h o r o u g h l y
that

settled

indicated

to

the

that

period.

It

m ilk

was p o u r e d i n t o
A fter

thus,

special

records

care

one o r t wo

and became

troubles

in

was t a k e n t o r e g u l a t e

milk d i e t .

of e a c h o f t h e lam bs were k e p t c o n c e r n ­

in g m ilk consumption,

growth

clinical

of t h e h e a l t h and b e h a v i o r

observations

the

P r e v i o u s e x p e r i e n c e had

o v e r f e e d i n g was one o f t h e u s u a l

consumption of the a r t i f i c i a l
Individual

The a r t i f i c i a l

t o d r i n k from t h e b o t t l e

new m e t h o d o f f e e d i n g .

r a i s i n g young lam bs;
the

storage

a n d wa r me d up t o a b o u t 8 0 ° F .

d ays th e lam bs were a b le
adjusted

nursing b o ttle s .

four times a day,

shaken to put back in su s p e n s io n the m in e r a ls

during the

nursing b o ttle s

as p o s s ib le .

(weight every th r e e

days),

and

of the a n im a l s .

- 47 The w h o l e e x p e r i m e n t was c o n d u c t e d
trials*

A total

o f 19 l a m b s wa s

in three

used d u rin g the

E l e v e n o f t h e m w e r e p l a c e d on d i e t A t o
diet

was u s e f u l

second group
the

successive

find i f

trial

I.

the liq u id

in the production of vitam in E d e fic ie n c y .

o f l a m b s was u s e d a s c o n t r o l s ;

these also receiv ed

d i e t A and i n a d d i t i o n were g i v e n o r a l l y e v e r y o t h e r

1 0 0 mg.

of d l-a lp h a

The o i l

wa s a d m i n i s t e r e d by m e a n s o f a s y r i n g e

rubber hose.
rating

the

of five

tocopherol

To t e s t

diluted

in

corn o i l

day,

(Mazola).

fitted

t h e u s e f u l n e s s o f cod l i v e r

development

A

with a

oil

in a cc ele ­

of v ita m in E d e f i c i e n c y a n o th e r group

a n i m a l s was u s e d i n t h i s

first

trial.

The t e c h n i q u e

was d e s c r i b e d a b o v e u n d e r t h e h e a d i n g o f C o m p o s i t i o n a n d P r e ­
p a r a t i o n of

the P u r i f i e d D ie t.

The s e c o n d t r i a l
The p u r p o s e o f t h i s

was c a r r i e d

second t r i a l

out with a t o t a l

was t o p r o d u c e a n a c u t e s y n ­

drome o f v i t a m i n E d e f i c i e n c y .

For t h i s

T w elv e lam bs were

the

of
the

separated for

sim ilar

B, a n d w e r e
manner a s t h e

Th e o b j e c t
graphic

supplemented with d l - a l p h a
controls

of t r i a l

also,

III

to

of th e

was t o

study the

D i e t B was a g a i n u s e d i n t h i s
controls,

group and a group

The c o n t r o l s

first

also received

tocopherol

electrocardio­
deficiency

of

recovery of E -d e fic ie n t

trial.

in

trial.

study the

c h a n g e s o f t h e l a m b s p r o d u c e d by t h e

v itam in E and,

as

r e a s o n d i e t B wa s u s e d .

deficient

f o u r l a m b s wa s k e p t a s c o n t r o l s .
diet

o f 16 a n i m a l s .

lambs.

T h r e e a n i m a l s we r e k e p t

w h i c h r e c e i v e d d l —a l p h a t o c o p h e r o l

i n an i d e n t i c a l

- 48 manner t o

the previous

controls.

T h i r t e e n lambs were p l a c e d

on t h e d e f i c i e n t

d i e t w i t h o u t any s u p p l e m e n t a t i o n .

was a t t e m p t e d

six of the

use

in

of d l-a lp h a

tocopherol

th irtee n deficient

Recovery

l a m b s by m a k i n g

acetate-®- a n d c o r t i s o n e ^ .

Two v i t a ­

m in E d e p l e t e d l a m b s were t r e a t e d w i t h p r o s t i g m i n e ^ t o
the

effect

of th is

test

d r u g on t h e v i t a m i n E d e f i c i e n c y .

Recovery w ith d l- a lp h a to co p h ero l

was t r i e d

on f o u r l a m b s .

The t h e r a p y was s t a r t e d when one o f t h e a n i m a l s was s e v e r e l y
deficient

and th e

three

o t h e r s were b e g i n n i n g to

symptoms.

The t r e a t m e n t

o f 500 mg.

of alpha tocopherol

o th er day.
in the

c o n s i s t e d i n f e e d i n g an i n i t i a l

V i t a m i n E was d i l u t e d

in corn o i l
the

and a d m i n i s t e r e d
control anim als.

The n u m b e r o f d a y s o f t h e r a p y was g r a d u a l l y
the

first

l a m b s were s a c r i f i c e d
order

animal

dose

f o l l o w e d by 1 0 0 mg. d o s e s e v e r y

same m a n n e r a s d e s c r i b e d a b o v e f o r

one day f o r

show t h e f i r s t

increased

t o 40 d a y s f o r t h e l a s t

immediately a f t e r

the therapy

from

one.

The

ended,

in

t o f o l l o w p a t h o l o g i c a l l y and c h e m i c a l l y t h e p r o c e s s o f

reco v ery of th e E - d e f i c i e n t lambs.
The e x p e r i e n c e w i t h a l p h a t o c o p h e r o l
that
the

it

is

mor e s u c c e s s f u l

s y mp t o ms w e r e n o t i c e d .

to

start

the

Therefore,

therapy indicated

m e d ic a tio n as e a r l y a s
f o u r o t h e r lambs t h a t

1 A lpha T o c o p h e r o l A c e t a t e Merck.
Merck & C o . , I n c .
N. J .
^ Cortone A c e ta te .
Merck & C o . , I n c .
R a h w a y , N. J .
^ Prostigm ine

Bromide M erck.

Merck & C o . ,

Inc.

Rahway,

R a h w a y , N.

J.

-

49

-

began to

show t h e v i t a m i n E s y mp t o ms w e r e i m m e d i a t e l y t r e a t e d

w ith the

o th e r drugs*

mine.

It

0 . 5 mg.

Two a n i m a l s w e r e t r e a t e d w i t h p r o s t i g -

wa s i n j e c t e d

s u b c u t a n e o u s l y e v e r y day i n d o s e s o f

The o t h e r t wo l a m b s w e r e a d m i n i s t e r e d

wa s i n j e c t e d

intram uscularly a t

the r a t e

cortisone,

which

o f 50 mg, p e r d a y .

Blood S t u d i e s
The m a i n o b j e c t i v e
the

progressive e ffe ct

tocopherol

and t h e

A b o u t 20 m l .

values
Then,

o f t h e v i t a m i n E d e f i c i e n c y on t h e t o t a l

c o n te n t of the blood plasma,

of the blood,

placed into

o f t h e b l o o d s t u d i e s was t o d e t e r m i n e

differential

the hemoglobin c o n te n t

white

count.

o f b l o o d were c o l l e c t e d

oxalated

of toco p h ero l

tubes and,
and o t h e r

from t h e

jugular vein,

a s soon as p o s s i b l e ,

the

in itial

c o n s t i t u e n t s were d e t e r m i n e d .

b l o o d s a m p l e s w e r e d r a w n e v e r y t e n d a y s a n d when t h e

a n i m a l s were o l d e r ,
week u n t i l

t h e b l o o d a n a l y s i s was c a r r i e d o u t e v e r y

t h e end of t h e

The p r o c e d u r e

for

b l o o d p l a s m a wa s t h e

experiment.
of to c o p h e ro ls

in the

one d e s c r i b e d by Q u a i f e a n d H a r r i s

(1944)

and Q uaife and B i e h l e r

the

determ ination

(1945).

Most of t h e

sam ples were a n a l y z e d i m m e d ia te ly a f t e r

time

the blood

collection;

however,

i n a few i n s t a n c e s e x t r a c t s o f b l o o d p l a s m a were k e p t f o r a
week u n d e r r e f r i g e r a t i o n
This,
trials

a c c o rd in g to
in th is

until

t h e a n a l y s i s was p e r f o r m e d .

the l i t e r a t u r e

laboratory,

already

cited

and p r e v i o u s

showed t h a t p e t r o l e u m e t h e r - a l c o h o l

extracts

of samples kept under r e f r i g e r a t i o n

not a l t e r

the

exact dilution
the

of a blood

optical

density

solution

total

leukocyte

was d e t e r m i n e d by m a k i n g a n

sample and d e t e r m i n i n g c o l o r i m e t r i of the

S a n f o r d P h o t e l o m e t e r " was t h e
The

20 d a y s d i d

content of tocopherols.

The h e m o g l o b i n c o n c e n t r a t i o n

cally

for

solution*

The " C e n c o - S h e a r d -

in stru m e n t used

in these an aly ses.

c o u n t was d e t e r m i n e d by u s i n g a 1%

o f 0*1 N HC1 t o w h i c h one o r t wo d r o p s o f g e n t i a n

v i o l e t were a d d e d .

A h e m o c y t o m e t e r w i t h N e u b a u e r r u l i n g was

used for

the

enumeration.

was u s e d

to

The

classify

suggested

Thus,

blood p ressu res
give

it

th a t perhaps the

to

was t h o u g h t t h a t t h e

testing

the v a li d i ty

of the vitam in E

( f e d d i e t B) c o u l d

of t h i s h y p o th e s is .

s e v e r a l methods fo r m easuring blood p r e s s u r e
way t o d e t e r m i n e t h e

b l o o d p r e s s u r e was by u s i n g a n e l e c t r o n i c

consisted

of three

oscillograph.

parts:

The s t r a i n

s y s t e m by n e e d l e

s y s t e m was

d e te rm in a tio n of

trial

was c o n c l u d e d t h a t t h e o n l y a c c u r a t e

lam bs'

on v i t a m i n E

circulatory

as a r e s u l t

i n lambs of th e t h i r d

some s u p p o r t
A fter

it

immersion o b j e c ti v e

and second t r i a l s

s y s t e m t o be a f f e c t e d

deficiency.

The o i l

the le u k o c y te s.

f i n d in g s of thef i r s t

experim ents
the f i r s t

actual

a strain

gage,

device.

an a m p l i f i e r and a n

g a g e 1 was c o n n e c t e d t o

the a r t e r i a l

p u n c tu r e and t r a n s fo r m e d the p r e s s u r e

1 S t a t h a m B lo o d P r e s s u r e S t r a i n Gage.
Los A ngeles, C a l i f o r n i a .

It

pulse

Statham L a b o r a t o r i e s ,

- 52 to

collect

fore,

in

the urine

at

some c a s e s i t

collections

wa s p o s s i b l e

under r e f r i g e r a t i o n

urine

in the

m ajority,

collections

was m e a s u r e d ,

three

were made.

filtered

f o r a b o u t 20 d a y s u n t i l

and c r e a t i n i n e

method o f P e t e r s

employed f o r m easuring th e

there

and s t o r e d

were enough

w e r e d e t e r m i n e d by u s i n g t h e
(1942).

The s p e c t r o p h o t o m e t e r

d e n s ity of the c o lo red s o lu tio n s

“Be ckman Mode l B S p e c t r o p h o t o m e t e r ” .

The

sodium and p o t a s s i u m c o n t e n t o f the u r i n e

determ ined

i n an e f f o r t

take place

due t o

the

The a n a l y s i s
carried

There­

ru n an a n a l y s i s .

C reatine

wa s t h e

anim als.

t o h a v e o n l y two u r i n e

a n d i n a few la m b s f o u r

The v o l u m e o f t h e

analytical

ages of the

d u r i n g t h e whole e x p e r i m e n t ,

collections,

samples to

definite

to

detect

changes t h a t might

vitam in E d e fic ie n cy .

of the u rin e

o u t by t h e

other

was a l s o

for

these

t wo m i n e r a l s wa s

flame p h o to m e te r method and u s i n g the

“ F l a m e P h o t o m e t e r Mode l 52 A ” o f t h e P e r k i n - E l m e r C o r p o r a t i o n .
The

“i n t e r n a l

s t a n d a r d ” m e t h o d was t h e a n a l y t i c a l

employed i n t h i s

determ ination.

It

technique

c o n s i s t s of adding to th e

s a m p l e s a n d s t a n d a r d s t h e same a m o u n t o f a known e l e m e n t
(lithium
tive

for

optical

standard.

the mentioned photometer)
density

of samples as

The p h o t o m e t e r i s

built

and m easuring th e r e l a ­

compared to t h a t

of the

t o m e a s u r e o n one t u b e t h e

a m o u n t o f l i g h t e m i t t e d by t h e c o n s t a n t a m o u n t o f l i t h i u m ,
while

other

t u b e m e a s u r e s t h e amount of l i g h t e m i t t e d by t h e

- 53 unknown e l e m e n t .
cause

The m e t h o d i s

many o f t h e v a r i a b l e s ,

such as

atom ization,

flame te m p e ra tu re ,

air

pressure

tend to a f f e c t

the

same m a n n e r .

Therefore

(The P e r k i n - E l m e r
Two m l .

added,

( a b o u t 1%)

sample v i s c o s i t y ,

foreign m aterials,

both the l it h i u m
the r a t i o

rate

of

gas and

a n d u n k n o wn i n

t e n d s t o be c o n s t a n t .

were p l a c e d

i n a 50 m l .

volum etric

flask,

o f a s o l u t i o n c o n t a i n i n g 20 0 0 ppm o f l i t h i u m was

a n d t h e m i x t u r e made up t o v o l u m e w i t h d i s t i l l e d

By t h i s

be­

C orporation 1949).

of urine

t h e n 1 .2 5 ml.

very a c c u ra te

dilution,

t h e sodium c o n t e n t o f th e

7 5 - 3 0 0 ppm a n d t h a t

sample f e l l

w ater.
between

o f t h e p o t a s s i u m b e t w e e n 5 0 - 2 0 0 ppm.

Studies

of the Gross Pathology

The l a m b s w e r e c l o s e l y e x a m i n e d o n c e a d a y t o d e t e c t t h e
changes th a t
wa s n o t i c e d

v i t a m i n E d e f i c i e n c y was i n d u c i n g .
that

was s a c r i f i c e d
necropsied.

the

d e a t h o f a l a m b was i m m i n e n t ,

by e x s a n g u i n a t i o n u n d e r e t h e r

experim ental

controls,
period to

by t h e d e f i c i e n c y ,
pherols
there
and,

to

wa s s u i t a b l e

was no e r r o r
finally,

we r e s a c r i f i c e d
find

a t t h e end o f t h e

t h e e x t e n t o f t h e da ma ge p r o d u c e d

the n u t r it i o n

containing

toco-

of th e lam bs and t h a t

in th e p ro c e ss of th e milk m an u fa ctu rin g ,

i n o r d e r t o have m a t e r i a l

of the m uscles.

t h e y were

The r e m a i n i n g a n i m a l s ,

check whether th e d i e t
for

th e animal

a n e s t h e s i a and

I n c a s e s where lam bs d i e d s u d d e n l y ,

a u t o p s i e d a s soon as t h e y were f o u n d .
in clu d in g the

Whenever i t

for

the

chemical a n a l y s i s

- 54 The c a r c a s s e s o f t h e l a m b s a n d a l l
fully
to

examined f o r

the

gross le s io n s ,

alterations

of the muscular

t a n c e was g i v e n t o
the

color

relation

of

the b i l a t e r a l

the m u sc le s,

a t t e n t i o n was p a i d t o t h i s

ly,

in the

several

F irst,

second t r i a l
prelim inary

noticed in

and t h e

the le s io n s .
the h e a r t ,

little

organ during the f i r s t

trial.

more l e s i o n s

appeared and,

s t u d i e s were s t a r t e d

on t h i s

How­

consequent­
organ.

d i a g r a m s and p h o t o g r a p h s o f t h e h e a r t were t a k e n t o

s t u d y t h e m o s t commonl y a f f e c t e d a r e a s .
injected

into

the

coronary a r t e r i e s

wa s a n y r e l a t i o n s h i p
necrotic

areas*

s a me p u r p o s e ,
0.0$

impor­

of the le s io n s ,

of exudates,

to

care­

a tt e n t i o n paid

Particular

distribution

the presence

few l e s i o n s were

special

system.

o f n e r v e s and b l o o d v e s s e l s

Since

ever,

with

t h e o r g a n s were

NaCl.

L a t e r on,

after
It

between the

in order to

find

if

there

and t h e

g e l a t i n wa s u s e d f o r

the

had b e e n p e r f u s e d w i t h i s o t o n i c

m u s t be p o i n t e d o u t t h a t

wa s a p p l i e d o n l y a f t e r

i n d i a i n k wa s

coronary a r t e r i e s

carmine

the h e a rt

Then,

this

last

technique

some s a m p l e s o f h e a r t m u s c l e s h a d a l ­

r e a d y b e en removed f o r t h e amino a c i d and m i n e r a l a n a l y s i s .
H istological
The h i s t o l o g i c a l
system ,

heart,

liver,

Studies

s t u d i e s were c o n f i n e d to
k id n e y and a d r e n a l s .

e n t m u sc le s were t a k e n ,

the s k e le ta l

S e c tio n s of d i f f e r ­

b u t w i t h more f r e q u e n c y f r o m t h e v a r i o u s

m u sc le s o f t h e r e a r and f r o n t l e g s ,

and from t n e h e a r t .

Samples

- 55 from t h e a b d o m in a l m u s c l e s ,
c o lle c te d w ith le s s
fixative
ffin

diaphragm,

frequency.

Z enker’s flu id

fo r th e m uscular t i s s u e s .

and t h e n

cut

in sections

tongue and m a s s e t e r were
was u s e d a s a

They were imbedded i n p a r a ­

of s e v e n m i c r a i n t h i c k n e s s and

sta in e d with hem atoxylin-eosin.
L iver,

k id n e y and a d r e n a l

Z e n k e r ’s f l u i d
addition,
fixed

tissues

were a l s o

fixed

and s t a i n e d w ith h e m a t o x y l i n - e o s i n .

tissues

of th e se

i n 10$ form o l

saline

organs,

and th e h e a r t ,

in

But,

in

were a l s o

a n d s t a i n e d w i t h S u d a n IV f o r

studies

on f a t .
E lectrocardiographic Studies
It

was m e n t i o n e d

in the h e a r t

in th e review of l i t e r a t u r e

that lesions

o f t h e l a m b p r o d u c e d by v i t a m i n E d e f i c i e n c y w e r e

r e p o r t e d a s s p o r a d i c by m o s t o f t h e r e s e a r c h w o r k e r s .
the

results

lesions

were r a t h e r

Therefore,
the

of the f i r s t

it

and second t r i a l s

frequent

in the p r e s e n t

However,

indicated th a t these
investigation.

w o u l d seem o f i n t e r e s t t o d e t e r m i n e by m e a n s o f

e l e c t r o c a r d i o g r a p h whether any f u n c t i o n a l

changes were a l s o

present.
Th e f i r s t
of the
until

start
the

e l e c t r o c a r d i o g r a m s were r e c o r d e d w i t h i n f i v e

days

o f t h e e x p e r i m e n t and t h e n wer e t a k e n e v e r y week

end o f t h e

experiment.

- 56 The e l e c t r o c a r d i o g r a p h u s e d i n t h e p r e s e n t
was a C a r d i o t r o n ,
leads
the

I,

II

Mo d e l P C - 1 A ^ .

and I I I

The t h r e e

front

in e le c tr ic a l

l e g and th e l e f t

f r o n t l e g and th e l e f t
left

standard dipolar

w e r e s u c c e s s i v e l y r e c o r d e d i n e a c h one o f

group of t e n anim als of the t h i r d

difference

investigation

potential

front leg;
rear leg;

f r o n t l e g and th e l e f t

rear

trial.

In lead I ,

the

i s measured between th e r i g h t
in lead I I

between th e r i g h t

and i n l e a d I I I ,

between th e

leg.

The a r e a o f a p p l i c a t i o n o f t h e e l e c t r o d e s wa s s i t u a t e d a
little
the

above

hocks i n

contact

the

knees in the

the r e a r

of the

legs.

paste

to

skin,

saturated

surface

t h e i r a p p l i c a t i o n to the s k in .

intim ate

t h e a r e a was c l i p p e d ,

A small q u a n tity of

of the e le c tr o d e s ,

So d i u m C h l o r i d e USP
P o t a s s i u m b i t a r t r a t e USP

1 5 0 0 gm.
112 gm.
18 0 0 gm.

Pumice Powdered
T r a g a c a n t h USP ( R i b b o n s )

225 gm.

G l y c e r i n e USP

360 m l .

D istilled

water

1 E lectro-P hysical L aboratories

prior

The c o m p o s i t i o n o f t h e

e l e c t r o d e p a s t e was a s f o l l o w s ;

P h e n o l l i q u i d USP

above

w ith e th y l e t h e r and

wa s r u b b e d o n t h e a r e a .

t h e p a s t e wa s p l a c e d o n t h e

and a l i t t l e

In o rd er to e s t a b l i s h

e le c tr o d e s with the

rubbed w ith a cheese c lo th
electrode

front legs,

15 m l .
70 0 0 m l .

I n c . , New Yo r k *

- 57 It

wa s p r e p a r e d , i n t h e f o l l o w i n g m a n n e r .

diluted

with h a lf

the w a t e r and h e a t e d

c a n t h was s o a k e d i n t h i s
and th e b i t a r t r a t e
added to

the

were

solution

to b o i li n g .

dissolved

i n the

rest

was

The t r a g a -

f o r 6-12 h o u rs .

s w o l l e n gum w i t h s t i r r i n g .

thoroughly u n til

The g l y c e r i n e

The s a l t s

o f the w a te r and

They were m ix e d

t h e m i x t u r e became s m o o t h .

F i n a ll y the phenol

and t h e pumice powder were added and mixed.
The f i r s t
to

take

electrocardiographic

r e c o r d i n g s were d i f f i c u l t

due to n e r v o u s n e s s of th e lam b s.

T h is happened even

t h o u g h c o n s i d e r a b l e t i m e was a l l o w e d f o r t he m t o become a c c u s ­
tomed t o t h e

e l e c t r o d e s a n d t o t h e wo o d e n b o x i n w h i c h t h e y

were p l a c e d f o r b e t t e r h a n d l i n g and f o r
ground.
taken,
it

But a f t e r
the

the f i r s t

i n s u l a t i o n from th e

two o r t h r e e r e c o r d s h a d b e e n

b e h a v i o r o f t h e a n im a l s improved c o n s i d e r a b l e

was much e a s i e r

to

o b t a i n good r e c o r d s .

The n o m e n c l a t u r e o f E i n t h o v e n

(Pardee 1936),

c ommonl y u s e d

i n h u ma n e l e c t r o c a r d i o g r a p h y was e m p l o y e d t o d e s c r i b e
electrocardiogram

and

of the lambs.

Thus,

n a me d P , Q, R, S a n d T w h i c h w e r e

the

t h e d e f l e c t i o n s were

considered p o s itiv e
when b e l o w ,

when

a p p e a r i n g above th e base l i n e ,

negative

p h a s i c whe n e v e n l y d i s t r i b u t e d

on b o t h s i d e s o f t h e b a s e l i n e .

T h e s e g m e n t s ST a n d TP w e r e r e g a r d e d a s e l e v a t e d
when t h e y d i d n o t h a v e t h e

electrocardiogram

or d e p re ss e d

same l e v e l a s t h e b a s e l i n e .

The f o l l o w i n g m e a s u r e m e n t s we re s t u d i e d
the

and d i ­

of th e lamb:

i n the a n a l y s i s

heart ra te ,

t h e PR,

QRS

of

- 58 a n d QT i n t e r v a l s ,
complex,

shape

the

systolic

and c h a r a c t e r

index,

of the

potential

deflections,

o f t h e QRS
and af^ry-

thm ias.
The s y s t o l i c
heart rate

index o r,

of the

was c a l c u l a t e d a c c o r d i n g t o

(P ardee 1936)

: K =

electrocardiogram ;
b e g in n in g of the
RR i s

the r a t i o

th e time

systole

the B a z e tt's

to

the

formula

QT
w h e r e K i s a c o n s t a n t i n t h e huma n
V*rr "~
QT i s t h e t i m e i n t e r v a l i n s e c o n d s f r o m t h e

c o m p l e x QRS t o

interval

the

end o f t h e T wave, and

i n s e c o n d s b e t w e e n t wo s u c c e s s i v e R

wave s .
Due t o

the

scarcity

of in fo rm a tio n about the e l e c t r o c a r d i o ­

g r a m o f shj eep a n d r e l a t e d

species

a true

electrical

c a l c u l a t i o n of the

such as c a t t l e

(A lfre d s o n 1942)

a x is of the lam b's h e a r t

was n o t p o s s i b l e #
Many a u t h o r s h a v e e x p e r i e n c e d
have r e s o r te d

sim ilar lim ita tio n s

but they

t o t h e k n o w l e d g e o f t h e human e l e c t r o c a r d i o g r a m

and used the methods f o r th e d e t e r m i n a t i o n of the human's
cardiac

electrical

several

species

B irds,

Sturkie

to

to estim ate

the

e le c tric a l axis

of

(B o vine, A l f r e d s o n 1942; R a t s , E nsor 1946;
1949)#

f o r m easuring the
applied

axis,

Likewise

electrical

in th is

axis

study,

one o f t h e m ethods

o f t h e human h e a r t h a s b e e n

the lam b's electrocardiogram #

Th e a p p r o x i m a t e

electrical

e s tim a te d w ith an e r r o r
The d e t e r m i n a t i o n s

a x i s of the

l a m b ' s h e a r t was

o f 3 0 ^ by t h e m e t h o d o f W i l s o n

of the e l e c t r i c a l

axes,

acco rd in g to

(1 9 o 8 )#

this

-

method,
the
to

59 -

w e r e d one by m a t c h i n g t h e

electrocardiogram s

relative

to a p a t t e r n

occur a t v a rio u s d eg rees of a x is

QRS p o t e n t i a l s

of

o f QRS-j_ , QRS g , QR$3 known
deviation

(Table V).

TABLE V
MODIFIED WILSON'S TABLE FOR THE APPROXIMATE DETERMINATION
OF THE ELECTRICAL AXIS OF THE HUMAN HEART
E l e c t r i c a l Axis
Approximate
of th e Human's
number o f
h e a r t ______________ d e g r e e s

R elative
Lead I

p o t e n t i a l s o f QRS
Lead I I

±180°

-2

-1

-150°

-1

-1

-120°

-1

-2

-1

-1

-1

-1

-2

-

90°

0#
41

D eviation

0#

O
to

42

41
41
42

41

41

41
12

0
0

0°
to
-*

41

Normal A x i s

41

D eviation

t 60°

41

4 90°

0*

0#

R ight Axis

4120°

-1

41

D e v i a t i on

4150o

-1

0

il80°

-2

-1

diphasic

41

0

- 60°
1

L e f t Axis

* E ither

Lead I I I

or z e r o p o te n t i a l .

-1
-1
0*

#

41
41

- 60 Studies

on t h e

Chemical Changes o f t h e Muscles

The t h i g h m u s c l e s a n d p a r t
h e a r t were removed a t
tightly

and k e p t

months.
pared

A fter

time o f n e c r o p s y ,

i n a deep f r e e z e r

this

tim e,

the

(-22°C.)

of the lam bs'

put into
for

jars,

t wo t o

closed

three

sa m p le s were d e f r o s t e d and p r e ­

im m ediately f o r chemical a n a l y s i s .
The c h e m i c a l

analysis

follow ing m inerals:
and sodium,
proline,

leucine

the m ineral

fre e d of

consisted

calcium ,

in the d e te r m i n a ti o n of the

phosphorus,

magnesium, p o ta s s iu m

a n d t h e d e t e r m i n a t i o n o f t h e amino a c i d s :

Th e m u s c l e
for

the

of the v e n t r i c l e s

glycine,

and i s o l e u c i n e .
sa m p le s were p r e p a r e d
analysis.

the muscular

c u t i n small p ie c e s ,

i n t h e f o l l o w i n g manner

The h e a r t a n d t h i g h m u s c l e s we r e

sheaths,

t e n d o n s and f a t .

Then t h e y were

p l a c e d on a p r e v i o u s l y w e i g h e d c r u c i b l e

a n d a s a m p l e o f a b o u t 10 gm. was w e i g h e d a c c u r a t e l y o n t h e
p re c is io n balance.
The c r u c i b l e s
hydrate

the

the

the ex p erien ce

of t h i s

of the A g r i c u l t u r a l

Institution,

sample and q u ic k foam ing,

errors

in the

quantitative

Muscle sam ples t r e a t e d
still

not

in order

samples as slo w ly as p o s s i b l e b e ca u se ,

a c c o rd in g to
laboratory

w e r e p l a c e d on a h o t p l a t e

ready for ashing,

few d r o p s o f s u l f u r i c

there

to de­

otherw ise,

Chemistry

w o u l d be s p l a t t e r i n g o f

which would i n t r o d u c e l a r g e

determ inations.
i n such a manner,
t h e y needed

however,

further

were

treatm ent.

a c i d we r e a d d e d t o e a c h s a m p l e a n d t h e

A

- 61 crucibles
burner*
fully

c a r e f u l l y heated with

the f r e e

E a c h s a m p l e was t r e a t e d

in th is

avoiding the

tendency to

flame

of a Bunsen

wa y , e a c h t i m e c a r e ­

foam w h i l e

the

organic m atter

was b e i n g o x i d i z e d .
This p ro ce ssin g l e f t
bottom of th e

crucibles,

a black,
which,

dry r e s id u e

after

cooling,

w i t h a f ew d r o p s o f c o n c e n t r a t e d n i t r i c

g i v e a maximum t e m p e r a t u r e

p revent the v o l a t i l i z a t i o n
of the

yet,

sary

get a white ash.

to

furnace,

acid.

regulated

of sodium or p o t a s s i u m

salts*

warm c r u c i b l e s w e r e p l a c e d i n a d e s i c a t o r

t h e y r e a c h e d r oom t e m p e r a t u r e a n d we r e w e i g h e d a g a i n t o
mine t h e amount o f s u l f a t e d a s h .

Then,

hydrochloric

a c i d was a d d e d t o

m inute.

s o l u t i o n s were f i l t e r e d

paper

The

into

thoroughly

50 m l .

volum etric

cleaned

water a t l e a s t

rem ained.

5 ml.

until
deter­

of concentrated

th e a s h e s and b o i l e d

f o r one

through an a s h le s s

flasks.

neces­

filter

The c r u c i b l e s w e r e

w ith the po licem an and r i n s e d w ith d i s t i l l e d

three

tim es.

a d d mo r e h y d r o c h l o r i c a c i d t o
still

Mo s t

b e f o r e a w h i t e a s h was o b ­

i n a few c a s e s t h r e e a nd f o u r a s h i n g s were

The s t i l l

The

o f 500°C* w h i c h i s l o w e n o u g h t o

s a m p l e s r e q u i r e d t wo a s h i n g s

tained;

the

were t r e a t e d

and s u l f u r i c

c r u c i b l e s were p l a c e d o v e r n i g h t i n a m u ffle
to

s t i c k i n g to

I n some c a s e s
dissolve

The s o l u t i o n s w e r e

r e a d y t o be u s e d f o r

the m ineral

it

was n e c e s s a r y t o

some o f t h e a s h t h a t

t h e n made up t o v o l u m e a n d

determ inations.

-

An a l i q u o t
determ ination,
(1922).
of the

of the

62

-

s o l u t i o n was e m p l o y e d f o r

w h i c h was done

a c c o rd in g to

The r e s i d u a r y s u p e r n a t a n t l e f t
calcium o x a la te

was u s e d f o r

the

the

calcium

th e method of Shohl

after

the p r e c i p i t a t i o n

d e t e r m i n a t i o n o f mag ­

n e s i u m w h i c h was p e r f o r m e d f o l l o w i n g t h e m e t h o d o f B r i g g s
Another

a l i q u o t was t a k e n t o make t h e d e t e r m i n a t i o n o f

p o t a s s i u m a n d s o d i u m by t h e f l a m e p h o t o m e t e r m e t h o d *
maximum s e n s i t i v i t y
is

a b o u t 3 0 0 ppm,

less

in the p resen t

t h e a l i q u o t was d i l u t e d u n t i l

s i t u a t i o n was a b o u t 100 mg.

of s o lu tio n .

have a d i l u t i o n
other cases,

Since

However,

o f 1 0 0 mg.

1 0 0 mg.

sometimes i t

it

contained

The u s u a l

of s u l f a t e d ash in
was n e c e s s a r y t o

o f a s h e d s a m p l e i n 50 m l .

o f a s h i n 200 m l .

dilution

of so lu tio n .

and,

those

described

potassium in
It

in the q u a n tita tiv e

analysis

in

The p r o ­

c e d u r e and a p p a r a t u s u se d i n t h e d e t e r m i n a t i o n were the
as

the

of t h e a p p a r a t u s f o r p o t a s s i u m and sodium

t h a n 300 ppm o f s o d i u m a n d p o t a s s i u m .

100 m l.

(1924).

same

o f sodium and

the u r i n e .

was i m p o s s i b l e

t o d e t e r m i n e p h o s p h o r u s by u s i n g t h e

p r e v i o u s l y d e s c r i b e d a s h i n g method b e c a u se of th e v o l a t i l i t y
most of the phosphorus
to

form,

at

the

before

ashing,

tem perature

I t would have been n e c e s s a r y

non-volatile

c o mpounds o f p h o s p h o r u s

o f 500°C. , which c o u ld have b e e n a c c o m p l i s h e d

by a d d i t i o n o f B a ( 0 H ) 2 .
cedure

compounds.

of

The o t h e r

c h o i c e was t h e

w h i c h was s e l e c t e d b e c a u s e t h e

from t h e a c i d h y d r o l y s a t e s

samples

wet-ash pro­

c o u l d be d r a w n

of m uscles p rep a red fo r the d e t e r ­

- 63 m i n a t i o n o f amino a c i d s ,
employed f o r

which i s

Th e p r o c e d u r e

o r 5 gm.

finely

f o r th e p r e p a r a t i o n o f the muscle

o f a b o u t 300 m l . ) .

Fifty

t i v e l y were added to th e
stirred
tissue
small

sticking

segments and the

rather

m uscle,

, we r e

c le a n e d and f r e e d from

in a small w a rrin g blen d o r
a n d 25 m l .

of d i s t i l l e d

to

Pieces

of connective

continued u n t il

t h e r e was a

homogenous s u s p e n s i o n o f t h e m uscle t i s s u e s .

a n d t o a v o l u m e o f 50 m l .
several

Im mediately a f t e r

o f s a m p le were t a k e n ,
p l a c e d i n Erlemmeyer

in the
times

this,

The method o f S t o k e s

in the

by t a k i n g

o f 6 N HC1.

into

c o n t a i n i n g 2 grams

calibrated

pippetes,

and

for hydrolysis.

et_ a l .

( 1 9 4 5 ) was u s e d f o r

the a c id

of a u t o c l a v i n g

The a m o u n t o f HC1 a c i d wa s c a l c u l a t e d

c o n sid e ra tio n the d ilu tio n

The h y d r o l y s a t e s

muscle.

t o be s u r e o f e q u a l

h y d r o l y s i s w h i c h was a c c o m p l i s h e d by e i g h t h o u r s
50 m l .

case of th ig h

case of h e art

aliquots

w ith wide t i p p e d
flasks

Then t h e

t r a n s f e r e d to a g r a d u a t e d cy­

a n d made up t o a v o l u me o f 200 m l .

dispersion.

w ith

water r e s p e c ­

t h e b l a d e s were c u t a g a i n i n t o

stirring

The c y l i n d e r was i n v e r t e d

(capacity

Wai r i ng b l e n d o r s a n d t h e m i x t u r e

s u s p e n s i o n wa s q u a n t i t a t i v e l y
linder

T w e n t y gm. o f t h i g h

f o r a b o u t t h r e e - t o- f o u r m i n u t e s .
t h a t were

samples f o r

follow s.

of h e a r t muscle

c u t and p l a c e d

one d e s ­

(1925).

t h e a s s a y o f a m i n o a c i d s was a s

fat,

The method

t h e d e t e r m i n a t i o n o f p h o s p h o r u s was t h e

c r i b e d by F i s k e and Su b b a rro w

muscle,

d e s c r ib e d below.

were f i l t e r e d ,

of t h e muscle

samples.

n e u t r a l i z e d t o pH 6 . 8 w i t h NaOH,

- 64 and s t o r e d u n d e r t o l u e n e and r e f r i g e r a t i o n #
Th e d e t e r m i n a t i o n o f t h e a m i n o a c i d s
m icrobiologically#
used fo r

were c a r r i e d

T h e m e t h o d o f S c h w e i g e r t e t a l # ( 1 9 4 4 ) was

th e d e t e r m i n a t i o n of l e u c i n e and i s o l e u c i n e ,

method of S a u b e r l i c h e t a l .
m in a tio n of p r o l i n e

out

and th e

( 1 9 4 6 ) wa s e m p l o y e d f o r t h e d e t e r ­

and g ly c in e #

F i e l d C a s e s o f S t i f f Lamb D i s e a s e
C a se s o f v i t a m i n E d e f i c i e n c y o c c u r r i n g i n lambs and i n
calves

were r e p o r t e d

wa s b e i n g c a r r i e d
to

study the

beneficial

bn f a r m s i n M i c h i g a n w h i l e

out.

tocopherol therapy.

t o s t o f t hem w e r e r a p i d l y c u r e d by t h e

a d m i n i s t r a t io n of d l- a lp h a

tocopherol,

before

t r e a t m e n t wa s e s t a b l i s h e d .

m itted

to the

same p a t h o l o g i c a l

on t h e e x p e r i m e n t a l l a m b s ,
experiment and, a ls o ,

ities

confirm the

lambs i n th e Michigan S t a t e C o lleg e F lo c k a l s o

developed s tiffn e s s #

the

experiment

gave a n o t h e r o p p o r t u n i t y

symptoms o f t h e E - d e f i c i e n c y and t o

value of the

Several

This co incidence

this

but three

o f them d i e d

They were a u t o p s i e d an d s u b ­

and chem ical s t u d i e s perform ed

in order

to

check the r e s u l t s

to f in d the s i m i l a r i t i e s

of

or d i s s i m i l a r ­

o f v i t a m i n E d e f i c i e n t l a m b s f e d two d i f f e r e n t r a t i o n s .

RESULTS
Growth and H e a l t h
Th e g r o w t h c r i t e r i o n i n t h e p r e s e n t
as

secondary,

since

many w o r k e r s

e x p e r i m e n t was r e g a r d e d

( O l c o t t and M a t i l l

1937;

E merson and Evans 1937; V o g t - M / l l e r 1948; W illman e t a l . 1934)
had d e m o n s tra te d i n s e v e r a l
not req uired for
E is

animal

species

growth o f young anim als*

re c o g n iz e d as a growth f a c t o r

et_ a3^. 1 9 4 0 ;

Even th o u g h v i t a m i n

i n some a d u l t a n i m a l s

V o g t - M / l l e r 1942) however,

th a t vitam in E is

th a t vitam in E is

(Nelson

o n l y a few h a v e f o u n d

n e c e s s a r y f o r a d eq u a te growth of young a n im a ls

( K a u n it z and Jo h n so n 1 9 4 6 ) .
For t h i s
attem pt

reason i t

to sim p lify the la b o rio u s

reducing the

on t h e

other

h a n d , wa s a l s o

results

maximum g r o w t h o f t h e

(every fiv e

justifiable

by

tim e s a day
hours)*

since

it

c a l v e s c an grow a t a normal r a t e

them m i l k o n l y t w i c e a day
the

from f i v e

t o f o u r t i m e s a day

well-known f a c t t h a t

However,

job of r e a r i n g t h e lam b s,

n umbe r o f f e e d i n g t i m e s

(every four h o u rs),
This,

was c o n s i d e r e d o p p o r t u n e t o make a n

was a
by f e e d i n g

(Warner and .S u t t o n 1 9 4 8 ) .
of th e growth d a ta su g g e ste d t h a t

l a m b s on a m i l k d i e t ,

r e g i m e n o f f e e d i n g wa s a n e c e s s i t y .

It

a five

for

t i m e s a day

wa s f o u n d t h a t

the

rate

o f g r o w t h o f a n i m a l s f e d d i e t A f o u r t i m e s a d a y was l o w , 0 . 1 6
pounds per day,

a s c o m p a r e d t o 0 . 3 6 p o u n d s p e r d a y made by

- 66 o t h e r lambs

fed an i d e n t i c a l

non-published data)*
The r a t e
lower

five

t i m e s a day ( B a c i g a l u p o ,

The g r o w t h c u r v e s a r e

shown i n F i g u r e 1 .

o f g r o w t h o f l a m b s on d i e t B was f o u n d t o be e v e n

(0 .1 0 pounds per day)*

scouring e ffe c t
feedings

diet

This,

o f d i e t B, a s w e l l

perhaps,

was d u e t o

the

a s t h e r e d u c e d number o f

( f o u r t i m e s a day)*

P n e u m o n i a wa s a g a i n t h e m o s t m a l i g n a n t d i s e a s e
young lam bs,

especially

la m b s were a l s o

those of the

deficient

of th e

groups.

Control

o b s e r v e d t o h a v e s y mp t o ms o f p n e u m o n i a ,

severely

or as

f r e q u e n t l y a s d e f i c i e n t lambs*

but

never

as

The

usual

symptoms o f p n e u m o n i a we re c o u g h i n g an d l a b o r e d r e s p i r a ­

tion,

w h i c h a l w a y s c o i n c i d e d w i t h a n i n c r e a s e d number o f l e u k o ­

cytes .
P e n i c i l l i n was s u c c e s s f u l l y u s e d t o
but

it

wa s r a r e l y a b l e t o

e r r a d i c a te the

anim al.

The a f f e c t e d l a m b s w e r e

procaine

penicillin

treatm ent

pneumonia from t h e

t r e a t e d w ith 100,000 u n i t s

by i n j e c t i o n i n t h e

neck r e g i o n .

had t o be g i v e n e v e r y o t h e r d a y u n t i l

experiment

to keep the

pneumonia.
to rea so n s

therapy,

The
end of t h e

t h r e e lambs d i e d

of

A n o t h e r e i g h t la m b s d i e d d u r i n g t h e e x p e r i m e n t due
not r e la te d

to pneumonia or to the

vitam in £ d e f i ­

The d e a t h s were d i a g n o s e d a s o v e r e a t i n g

intestinal

the

of

anim als alive*

Xnn-spite o f t h e p e n i c i l l i n

ciency.

combat t h e d i s e a s e ,

obstruction

( t wo l a m b s ) ,

( t wo l a m b s ) ,

and c o c c i d i o s i s

(£ne l a m b ) .

The c a u s e o f d e a t h o f t h e o t h e r t h r e e l a m b s was n o t i d e n t i f i e d .

-

67

20
Control lambs fed diet A
Deficient lambs fed diet A
Control lambs fed diet B

BODY

WEIGHT

IN POUNDS

Deficient lambs fed diet B

30

45

60

75

DAYS ON EXPERIMENT

Figure !•

Grow th Guryes of Lambs Fed Diets Deficient
in V itamin E (Diets A and B) and of Lambs
Fed the Same Diets Supplemented with dl~
G( “ tocopherol*

- 68 C linical
It

is

O b s e r v a t i o n s on t h e V i t a m i n E D e f i c i e n c y

im possible

to

summarize s t e p

by s t e p

o f s y m p t o m s p r o d u c e d by v i t a m i n E d e f i c i e n c y ,
c ien cy did not produce the

the

sequence

since

same s y m p t o m a t o l o g i c

the

defi­

picture

in each

one o f t h e a n i m a l s .
The f o l l o w i n g
ficant

description

Those

of the

that

description is

the

disease

syndrome

The f i r s t

and,

indications that

down m o s t o f t h e

condition,
As t h e

tim e.

in

that

this

the

several

were:

poor ap p ea ra n c e,

la c k of v ig o r,

progressed,
efforts

it

before

th e a n i m a l s were

reduced a c t i v i t y ,

small o b s t a c l e s .

the lambs d id not l o s e

disease

their

In spite

was o b s e r v e d t h a t
they

A lso,

to

straighten

th e lambs

could get up.

m u s c l e o f t h e f r o n t l e g s was a f f e c t e d
lam bs were u n a b l e

of th e ir

appetites.

t i m e b e c a me mor e i n c o o r d i n a t e d .

a consequence,
tim e.

c an be c o n s i d e r e d

t h e lambs were b e i n g a f f e c t e d

I t was a p p a r e n t t h a t

crossing

h a d t o make r e p e a t e d
walk a t

the

l e g w eakness and te n d e n c y to l a y

because of t h e i r

and d i f f i c u l t y

to

of the v ita m in E d e f i ­

absence of v ita m in E in the d i e t

abnormal

in

found i n the p r e s e n t work.

locom otor in c o o r d in a tio n ,

poor

consequently, i t

representative

signi­

be c a me d e f i c i e n t

symptoms h a v e b e e n a r r a n g e d a c c o r d i n g

severity

by t h e

a c o n d e n sa tio n of the

symptoms o b s e r v e d i n t h e la m b s t h a t

v ita m in E.

ciency

is

their

It

Their

was e v i d e n t

first
front

because
legs.

As

they adopted the k n e e lin g p o s i t i o n fo r a long

during th is

period,

three

lambs c o u ld n ot open

- 69 their

mouths,

apparently

due t o p a r a l y s i s

of the m a s tic a to ry

m uscles.
When t h e m u s c u l a r w e a k n e s s i n v o l v e d t h e
the
of

lambs were u n a b le
struggling

to

g e t up o r t o r e m a i n k n e e l i n g ,

and k i c k i n g w i t h t h e i r l e g s .

had been h e lp e d to a s t a n d i n g p o s i t i o n ,
As t h e

hind le g s to o ,

deficiency progressed,

However,

their

w hich gave them a n a p p e a r a n c e

In the
to

final

stages

s t a n d e v e n when h e l d

mass o f muscle and b on e ,
shown by p a r a l y s i s

to

wet a l l

tim e,

the

acteristicly
due t o
or

of

b a ck s a r c h e d and
typical

of

2).

of the d e p le tio n ,
(Fig.

3);

they

t h e lambs were u n a b le

seemed l i k e

e x c e p t i n on e s i n g l e

degree

of d e f ic ie n c y

perhaps

due t o u r i n e .

because
Further,

urinary excretion

or to

The d i e t A ,

a flabby

case of s t i f f n e s s

a p p e a r e d t o be

their
at

b o d i e s were

this

tim e,

a char-

which c o u ld have been

(probably in cre ased

creatine

the r e a c t i o n of such p ro d u cts with the

t h e wool

coat.

c o n t a i n i n g a commercial l a r d

p r o d u c e d i n most of t h e

matology,

their

s t r o n g o d o r was n o t i c e a b l e ,

creatinine)

fat,

this

pneumonia,

an a l t e r e d

constituents

spread,

of the locom otor m uscles.

L a mb s r e a c h i n g
susceptible

t o walk*

U sually they r e ­

th e ir legs

(Fig.

they

t h e lam bs were u n a b l e t o

mained s t a n d i n g w ith

vitam in E deficiency

after

t h e y were a b l e

s t e p mo r e t h a n a f e w t i m e s w i t h o u t f a l l i n g .

rumps l o w e r e d ,

in sp ite

as

the source

c a s e s the above d e s c r i b e d

w h i c h was c a l l e d m i l d v i t a m i n E d e f i c i e n c y .

of

sympto­
On t h e

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- 72 other

h a n d d i e t B,

duced e s s e n t i a l l y
several

other

required

the

same d i s t u r b a n c e s ,

symptoms.

Due t o

the

distilled
but

fact

and 5 5 th day,
between the

whereas

symptoms i n a p e r i o d

those

symptoms,

m u sc le s and a f t e r w a r d s
While

noticeable

the

first

d y stro p h y of the

t h e lam b s were s t i l l

stiffness

between th e 2 0 th

showed,

b esid es the

of the le g s,

thigh

o th e r locom otor muscles

able

to walk,

wobbling j o i n t s ,

there

was

dragging

When t h e s e l a m b s w e r e f o r c e d

t h e y r a n w i t h a n e x c e s s i v e l y b a l a n c i n g movement f r o m

f r o n t to

several

symp­

A n i m a l s on t h e

a r e d u c e d volume of the

and a p e c u l i a r m arc h in g g a i t .

run,

the

3 0 t h and 8 0 th day.

forem entioned

to

t i m e wa s

on d i e t A h a d become d e f i c i e n t

Lambs w i t h a c u t e v i t a m i n £ d e f i c i e n c y

as w ell.

pro­

in a d d itio n caused

that less

c a lle d acute vitam in E d eficiency.

B showed d e f i c i e n c y

feet

lard,

t o p r o d u c e v i t a m i n E d e f i c i e n c y w i t h d i e t B,

tom s were
diet

co n tain in g a m olecular

the

b a c k a n d made v e r y l i t t l e

instances

they f e l l

on t h e i r

progress.

In

k n e e s a nd were n o t a b l e

to

stand again.
A bnorm alities
tu rn around.
the

the
fell;
the

legs.
first
rear

n o t i c e d when t h e a n i m a l s t r i e d

The t u r n i n g was d i f f i c u l t

lambs r o t a t e d
A test

we r e a l s o

to measure

c o n s i s t e d of p u sh in g

o n t h e r ump t o m e a s u r e
legs,

a pivot,

since

them selves with t h e i r re a r le g s kept to g e th e r.

was d e v i s e d
It

and l i k e

to

the degree of weakness of
t h e l a m b s down u n t i l

they

th e degree of r e s i s t a n c e

and t h e n on the w i t h e r s

t o measure

the

of

resistance

- 73 of the

front legs.

T h e s e t wo m e a s u r e m e n t s w e r e c o m p a r e d t o

c o n t r o l s and a d e g re e
that

r a n from 0

(control

a v e r y weak p u s h ) .
tion

of the

of the

o f w e a k n e s s was e s t a b l i s h e d

state

This

anim als)

to four(lam bs f a l l i n g

the estim a ­

o f t h e lam b s and t h e p e r f o r m a n c e

l a m b s s h o w e d s y mpt oms o f g o o s e - s t e p p i n g a n d t wo

o th e r s r e p e a te d ly kicked the
a short period

floor,

o f t wo t o t h r e e

but in both cases for

days.

T h i s wa s r a t h e r

s u c h symptoms had n e v e r b e e n r e p o r t e d

min E d e f i c i e n c y ,
motor

for

after

a n i m a l s on r e c o v e r y .

Two o f t h e

since

on a s c a l e

c r i t e r i o n was i m p o r t a n t

of d eficien cy

the

and i t

incoordination

in the

Therefore,
diet,

it

acid

reason,

deficiency

in the v i t a ­

tim e.

Loco­

the c h a r a c t e r i s t i c

in the p ig

( L e e c k e jrfc a l .

of the

the plasma l e v e l

of

a n i m a l s and compare them w i t h t h e

d e f i c i e n t and c o n t r o l

anim als.

For t h a t

a c i d d e t e r m i n a t i o n s were r u n i n the

plasma of a l l

the

dure

by S k e g g s and W r i g h t

an aly sis are

is

wa s i m p o r t a n t t o d e t e r m i n e

pantothenic

outlined

such a s h o r t

special

e v e n t h o u g h p a n t o t h e n i c a c i d wa s s u p p l i e d

p an to th en ic acid of these
plasma le v e l

for

(goose-stepping)

s y mp t o m o f p a n t o t h e n i c
1949).

lasted

before

only

blood

experim ental anim als according to the p ro c e ­
(1944).

The r e s u l t s

summarized i n Table X I under the

of t h i s

h e a d in g of Blood

Studies.
Alpha to co p h ero l

was f o u n d v e r y e f f e c t i v e

fo r the

cure of

t wo y o u n g l a m b s s h o w i n g d e f i c i e n c y o f v i t a m i n E ( l a m b s n o s .
and 4 9 ).

T h e t h e r a p y was mor e s u c c e s s f u l

when t h e t r e a t m e n t

42

- 74 was s t a r t e d
A fter

soon a f t e r

fall

vigor

of the

no.

was s t a r t e d

50)

deficiency.

some h e l p

it

feet.

to

to

The t h e r a p y

in a th ird

lamb

(lamb
s ta g e s of

s t a n d up a n d was v e r y

wa s l i t t l e

hope,

if

any,

t h e t r e a t m e n t wa s s t a r t e d .
that

t h e l a m b was a b l e

of l e g r e s i s t a n c e

for the
I t wa s

t o g e t up w i t h

t h e t r e a t m e n t wa s s t a r t e d ,

a n d t wo d a y s
dragging

was a p p l i e d e v e r y d a y a n d

some i m p r o v e m e n t i n t h e a n i m a l ,

Thus,

be g a i n i n g

though i t

was n o t

some d a y s t h e l a m b l o o k e d v e r y w e l l a n d a p p e a r e d
strength,

leg resistan c e.

The

w a l k i n g and t u r n i n g .
that

same d e g r e e

g e t up w i t h o u t a s s i s t a n c e a n d w a l k ,

The t e s t

indicated

steady.

however,

improve­

was o f t h e

when t h e a n i m a l was i n t h e f i n a l

the day a f t e r

wa s a b l e

showed g r e a t

it

dying anim al,

amazing to f i n d ,

symptoms*

The r e s i s t a n c e

Even though t h e r e

cure of th is

first

of the l e g s .

The a n i m a l was u n a b l e t o

em aciated.

later

and s t r e n g t h

controls.

of the

t h e lambs

i n c r e a s e d d a y by d a y u n t i l

as th a t

his

appearance

a few d a y s o f t r e a t m e n t ,

ment i n g e n e r a l
to

the

y e t days l a t e r

seemed weaker and had p o o r

same t h i n g was t r u e
A fter

of the t e s t s

40 d a y s o f t r e a t m e n t ,

it

of running,
was f o u n d

t h e r e wa s some i m p r o v e m e n t o f m u s c u l a r s t r e n g t h o f t h i s

anim al,

and o f th e a b i l i t y

of em aciation of

to w alk and r u n .

However,

t h e a n i m a l was i m p r o v e d v e r y l i t t l e

the

state

by t h e

treatm ent•
The t h e r a p e u t i c
of the

use of p ro stig m in e

and c o r t i s o n e

s y m p t o m s o f v i t a m i n E d e f i c i e n c y was n o t

though these

d r u g s w e r e u s e d when t h e

deficiency

in the

successful.

cure
Even

symptoms b e g a n

to

75 -

a p p e a r , t h e l a m b s o n l y showed a t e m p o r a r y r e l i e f

appeared a f t e r
relapsed

five

to

e ig h t days.

A fterw ards,

which d i s ­

the lambs

a n d s h o w e d mo r e m a r k e d s i g n s o f v i t a m i n E d e p l e t i o n .

The f e e d i n g o f c o d l i v e r
25 d a y s d i d n o t a c c e l e r a t e

oil

to E - d e f ic ie n t

or a c c e n tu a te

the

anim als for

s ymp t o ms o f t h e

vitam in E deficien cy .
C ontrol anim als
plus

fed d ie t A plus alpha to co p h ero l,

alpha tocopherol,

cod l i v e r

oil

did not

or d i e t A plus alpha tocopherol
show a n y o f t h e

signs

diet B
plus

described above,

c a u s e d by t h e v i t a m i n E d e f i c i e n c y .
Cross P a th o lo g ic a l R e s u lts
It

was v e r y

produced e i t h e r
lam bs'
the

surprising that
consistently

color

gave th e

difference

However,
histological

The f a c t

that

im pression th a t

was n o t b e i n g p r o d u c e d .
natural

or c l e a r l y

or treatm en ts

the w h iten in g of the

m u s c l e s , a sympt om c o n s i d e r e d by many t o b e t y p i c a l

vitam in E deficiency.

a pale

none o f t h e d i e t s

of

t h e muscles had j u s t

the vitam in E d eficien cy

T h i s was c o m p l i c a t e d e v e n more by t h e

in color

shades of s k e le t a l m uscles.

a c l o s e r o b s e r v a t i o n o f t h e m u s c u l a t u r e and t h e
studies

m u sc le s were a f f e c t e d

distinctly

s howe d t h a t

most o f t h e

by t h e l a c k o f v i t a m i n E .

skeletal

The d a ma g e d

m u s c l e s o f a r e g i o n w e r e r e c o g n i z e d by t h e p a l e y e l l o w - g r a y i s h
color,

and t h e p r e s e n c e

gelatinous.

of a s t i c k y

e x u d a t e w h i c h s o m e t i m e s wa s

- 76 Both s i d e s of t h e
ficult

in a ll

body were a f f e c t e d ,

motor system .
the

In advanced

the

deficiency

the

anim al,

even the

diaphragm,

of

disease.

the l o c o ­

found d e g e n e ra t e d .

intercostal,

Two l a m b s i n t h i s

edematous m u scles,
in ethyl

same a n i m a l s a n d a n o t h e r
nerve

of th e

cases of d e fic ie n c y m uscles of the

injured.

com pletely soluble

sciatic

was v e r y d i f ­

were t h o s e

o f v i t a m i n Hi h a d p r o d u c e d t h e

m u s c l e s were a l s o

the

affected

n e c k a n d l o i n were l i k e w i s e

to have v e ry

it

cases to e s ta b lis h the b i l a t e r a l l i t y

The m u s c l e s m o s t s e v e r e l y

rump,

but

greatest

When

da ma ge t o

m a s s e te r and tongue
s t a g e were o b s e r v e d

w h i c h w e r e f o u n d t o be a l m o s t

e t h e r and w a t e r .

I t was f o u n d i n

showing g o o s e - s t e p p i n g ,

was s u r r o u n d e d b y a t h i c k f a t t y

coat,

th a t the
yellow in

color•
Heart le s io n s
than in the

w e r e mo r e common i n a n i m a l s f e d t h e

d i e t A.

wer*e o b s e r v e d

When d i e t A was f e d ,

only a f t e r

The h e a r t l e s i o n s
many r e s p e c t s .
white

or

p r o d u c e d by d i e t B w e r e o u t s t a n d i n g i n
t h e y were e a s y to o b s e r v e

from p i n p o i n t s

in size

some i n s t a n c e s
in diam eter.

due t o t h e

and t h e i r p e c u l i a r

t o r o d s and ro u n d ed a r e a s ,

f r o m o n e t o f o u r mm.

fused

of the h e a r t

a r a th e r prolonged tim e.

g ray ish c o lo r of the l e s io n s

which v a r i e d
differed

F irst,

lesions

diet B

shape,
and

These r o d s and d i s c s

t o make b i g p a t c h y s p o t s

in

o f a b o u t 12 mm.

The s e c o n d a n d n o t l e s s o u t s t a n d i n g f e a t u r e w a s t h e

location

of th e s e

th a t the

right

injured

ventricle

areas.
was t h e

E arlier

observations

indicated

o n l y p l a c e where t h e s e damaged

a r e a s were p r e s e a t .
the

left

lam bs),

ventricle
the r i g h t

Less

However,

later

on,

was a f f e c t e d a n d ,
ventricle

frequent

signs

d e f i c i e n c y were t h e
pericardial

77 -

w h i c h wa s f e d

presence

i n v e r y few i n s t a n c e s

( t wo

alteratio n

c a u s e d by t h e E

of hem orrhages and an e x c e ss of

o b s e r v a t i o n was made a t a u t o p s y o f l a m b 4 7 ,

t h e v i t a m i n E - d e f i c i e n t d i e t B.
a t the

which v a n is h e d i n a very s h o r t
T h e re were
or a d r e n a l s ,

no t y p i c a l

several

were

these

found i n

It

was a s t r o n g

time o f o p e n in g t h e c a r c a s s

time

(Less

t h a n one m i n u t e ) .

gross changes in the l i v e r ,

p r o d u c e d by v i t a m i n E d e f i c i e n c y

O ccasionally,

degrees

of f a t

kidney

in the d i e t .

in filtration

and n e c r o s i s

organs.

P n e u m o n i a was a c o m p l i c a t i n g a n d ,
the vitam in E d eficien cy .

at

tim es,

a masking f a c t o r

This happened in the

case

o f lamb

w h i c h h a d p n e u m o n i a a n d was b e i n g t r e a t e d w i t h p e n i c i l l i n .

Before

death,

respiration,
to

found t h a t

was f o u n d w i t h o u t i n j u r y .

of heart

ammoniacal odor n o t i c e a b l e

14,

wa s a l s o

fluid.

A very unusual

to

it

it

was o b s e r v e d t h a t

t h e lamb had v e r y l a b o r i o u s

p r e s u m a b l y due t o t h e p n e u m o n ia,

be t h e c a u s e

of death.

showed t h a t a c t u a l l y

N evertheless,

w h i c h was a s s u m e d

the electro ca rd io g ra m

t h e l a m b was s u f f e r i n g

from h e a r t

which e v e n t u a l l y produced the d e ath of the a n im al.
roborated
veal

T h i s was c o r ­

by t h e p o s t - m o r t e m l u n g e x a m i n a t i o n w h i c h d i d n o t r e ­

s e v e r e e n o u g h d a ma g e t o

Instead

failure,

the h e a rt

pathological

justify

s h o we d e x t e n s i v e

exam ination.

the

d e a t h of t h e a n i m a l .

damage by t h e m a c r o a n d h i s t o -

- 78 T h e r e wa s n o t h i n g c h a r a c t e r i s t i c
c o u l d be c o r r e l a t e d
lateral

to

and b i l a t e r a l

the v ita m in E d e f i c i e n c y .

Both t h e u n i ­

ty p e o f b ro n c h o -p n e u m o n ia were p r e s e n t

v a ry in g degrees of s e v e r i t y ,
control

about th e pneumonia t h a t

which were found i n d e f i c i e n t

in

and

lambs*

The m a c r o s c o p i c o b s e r v a t i o n s
lesions

to

the

circulatory

t i o n were u s u a l l y l o c a t e d
vessels

(Fig.

4).

fused w ith g a la tin
tim e and th e

in the v ic in ity

carmine i s
w ill

of

relation

s y s t e m showed t h a t

The h i s t o l o g i c a l

results

R esults

about the

areas

of degenera­

of im portant h e a rt

study of h e a rt

being c a rrie d

be r e p o r t e d

of t h e

tissu es per­

out a t

in the near

the present
future.

the H i s t o l o g i c a l S tu d ie s

The c h a n g e s p r o d u c e d by t h e v i t a m i n E d e f i c i e n c y

in skeletal

m u s c le s o f th e lamb can be summarized as a p r o c e s s i n v o l v i n g
hyaline
in

d e g e n e ra tio n of th e

the presence

of c e llu la r

The m u s c le f i b e r s
w hile

first

s a r c o p l a s m and a c o a g u l a t i o n n e c r o s i s
in filtratio n .
b e c a me s w o l l e n ,

th e c r o s s and l o n g i t u d i n a l

fibers

stained

At the
place

same t i m e

the rev erse

fibers

nuclei,

These

t h a t t h e d e g e n e r a t i v e p r o c e s s was t a k i n g

process

o f r e g e n e r a t i o n was a l s o

noticed.

by an i n c r e a s e p r o l i f e r a t i o n

of muscular

w h i c h i n d u c e d f o r m a t i o n o f new f i b e r s .

stained

m ultiple

disappeared.

deeper w ith the h e m a to x y lin - e o s in .

T h i s was c h a r a c t e r i z e d
fiber

striations

s h r u n k and f r a g m e n t e d

nuclei

fainter

The new

w i t h t h e h e m a t o x y l i n - e o s i n a n d s h o we d t h e

arranged

i n rows a t t h e

center

of the

fiber.

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79

; 1111 i i *1111 n uT
METRI C I

2

- 80 The s a r c o p l a s m o f t h e m u s c l e
v a c u o liz e d , a t the

same t i m e

fibers

that

became g r a n u l a r

the nuclei

ordinarily

then
became

pyknotic.
The f i n a l

stage

of the

degenerative process

was m a r k e d b y

d e a t h of muscle

fibers.

by i n f i l t r a t i o n

o f a few p o l y m o r p h o n u c l e a r l e u k o c y t e s ,

marcophages and g i a n t
of c learin g

the

disappeared

blasts

which tended

nuclei

cells

detritus

fibers

fibers.

The n e c r o t i c p r o c e s s wa s a c c o m p a n i e d

However,
and f i b e r s

5).

The l a t t e r

from t h e n e c r o t i c

there

was a n a c t i v e

to f i l l

at

(Fig.

t h e time

skeletal

process

started

epicardium .
picture
cells
fact

m uscles.

fibroflastic

from the

that a ll

integrity
the

characteristics

categories.

The l o w e s t

anim als,

of the Purkinje

histopathological

the

se v e re n e s s of the

state

of

same c h a n g e s a s
the d e g en e ra tiv e

the h i s t o lo g i c a l

fibers,

of giant

in spite

of the

severely affected .

s y mp t o ms w e r e c l a s s i f i e d

disease

c a t e g o r y wa s

(0)

in fiv e

f o r normal

a n d t h e h i g h e s t c a t e g o r y was

s e v e r e l y damaged t i s s u e s .
the

muscle

proliferation.

h e a r t were t h e a b s e n c e

s u r r o u n d i n g c e l l s we r e

a cc o rd in g to

by t h e m u s c l e

e n d o c a r d i u m and p r o g r e s s e d t o w a r d s t h e

Other r e l e v a n t

The d i f f e r e n t

judge

c a n be a d d e d t h a t

of a vitam in E -d e fic ie n t

and t h e

control

But i t

of f ib r o ­

re g e n e ra tio n the

Th e h e a r t m u s c l e e s s e n t i a l l y u n d e r w e n t t h e
the

As t h e m u s c l e

proliferation

of muscle

overshadowed the

had t h e r o l e

area.

the empty sp a c e l e f t

many

different
tissues

(44) f o r

of

t h e most

T h i s s y s t e m was e s p e c i a l l y h e l p f u l

o f r e c o v e r y o f lam bs on t r e a t m e n t .

to

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- 82 The r e c o v e r y

of d e f i c i e n t anim als

p h e r o l wa s a p p a r e n t
p roliferation,
cells.
in the

with alp h a to c o ­

through the in c re a s e d m uscular f i b e r

as well

as the

fibers

was t h o u g h t t o be

sarcolemma or i n th e a c t i v e l y p r o l i f e r a t i n g
the most a c t i v e

t h e ro u n d e d end o f t h e

part

m entioned,

new f i b e r s .

theless,

which were c l a s s i f i e d
therefore,

it

seemed t o

It

wa s a n i n c r e a s e d

as

the

(14).

was

h isto lo g ic a l ab­
Th e t h e r a p y a f o r e ­

tissues

40 d a y s w e r e p e r f e c t l y

n u mb e r o f c e l l

It

was o b s e r v e d t h a t wh e n t h e

have b e e n s a t i s f a c t o r y .

c a n n o t be s a i d t h a t

with vitam in E for

nuclei.

of the r e g e n e r a tin g f i b e r s

o f t h e r a p y wa s l o n g e r t h e r e w e r e l e s s e r

norm alities

nuclei

n u mb e r o f m a c r o p h a g e s a n d g i a n t

The o r i g i n o f t h e r e g e n e r a t i n g

seemed t h a t

time

treated

nuclei.

l o n g e d t r e a t m e n t would have l o w e r e d t h e

Never­

o f lambs t r e a t e d

normal,

since there

P r o b a b l y a more p r o ­
n u mb e r o f c e l l

nuclei

t o a normal v a l u e .
The s u c c e s s

of th e c o r t i s o n e

was-

very d i f f i c u l t

were

not ta k e n b e fo r e

the

in itial
Despite

lesions
m ild

state

to e s t a b l i s h because previous tis s u e
the b e ginning of

of the

this

the

factor,

it

c o u l d be

f o u n d i n p r o s t i g m i n e and c o r t i s o n e

indicated

from c o r t i s o n e

(34)

and

the p o s s i b i l i t y

and p r o s t i g m i n e

c o n c lu s io n could

therapy,

samples

to i n d ic a te

anim al.

lim iting

(2+) a s compared t o

findings

and p r o s t i g m i n e t r e a t m e n t s

n o t be d r a w n .

(44)

sa id t h a t the

treated

l a m b s we r e

of d e f i c i e n t lam bs.

of b e n e f ic ia l

treatm ent,

effects

These

derived

though a d e f i n i t e

- 83 -

Field
to

those

found in the p r e s e n t

difference
of f i e l d

c a s e s showed s i m i l a r h i s t o l o g i c a l

anim als;

Tocopherol

t h e l e s i o n s were a lw a y s

experim ental

fed d i e t B (II
Fr om t h e

(44).

of Blood S t u d i e s

levels
trial

and I I I

of the lambs fed t h e

are

blood plasma.

in itial

and t h o s e

in Table VII.

tables

quantity

The v a l u e s

d ie t A in the

summarized in Table VI,

trials)

study of these

observed in the

ml.

graded as

case

content:

The t o c o p h e r o l
first

The o n l y n o t i c e a b l e

b e t w e e n t h e m was a more p r o n o u n c e d damage i n t h e

R esults
a)

experim ent.

sig n s of d e fic ie n c y

a wide v a r i a t i o n

of t o ta l

c a n be

tocopherol

of the

r a n g e d from 0 . 0 5 9 t o 0 . 3 7 2 mg./lOO

of blood plasma.
The t o c o p h e r o l

shows a g r a d u a l

c o n t e n t o f c o n t r o l lambs i n t h e

increase

end o f th e e x p e r i m e n t .
content

increased

and in th e I I

of le v e ls
In the

from the b e g i n n i n g t o t h e

first

trial,

from 0 . 0 5 9 t o an a v e r a g e

and I I I

trials

three t r i a l s

the

total

tocopherol

o f 0 . 2 4 6 mg./lOO m l . ,

from 0 . 1 0 5 t o 0 . 2 6 1 mg./lOO m l.

of

blood plasma.
The r e v e r s e p r o c e s s
in blood plasma values

of decrease

was a p p a r e n t

of the l e v e l s of v ita m in E
i n d e f i c i e n t lambs f e d d i e t s

A a n d B.
Animals of the d e f i c i e n t
an average

initial

value

group

in t r i a l

I,

f e d d i e t A,

of 0 .2 2 6 which d im in ish e d to 0 .0 9 4

had

- 84 TABLE V I .
TOCOPHEROL CONTENT OF BLOOD PLASMA OF LAMBS FED A.
COMMERCIAL LARD DIET (DIET A) AND THE EFFECT OF COD
LIVER OIL TREATMENT ON THE LEVEL OF PLASMA TOCOPHEROLS
( A l l v a l u e s e x p r e s s e d i n mg* p e r 1 0 0 ml* o f b l o o d p l a s m a )

Diet
A

A plus
0(-Tocopherol

Lamb
No.

0-10

6
8
11
12
14
17
18
19

0.244
0.216
0.372.
--------------- 0.072

Av.

0.226

7
10
13
15
Av.

0.059

0.059

Days on e x p e r i m e n t
20-30
30-40
40-50
0.085
0.275
0.165
0.147
0.041
0.056
0.128

0.075
0.097
0.147
0.141
------- -----——
0.106
0.141
0.118

0.485
0.162
0.428
0.200

0.112#
0.399^

0.069
0.119

oil
oil

cod l i v e r

oil
0.094

0.103

oil
oil

0.246

0.319

0.063
0.088
0.081

0.147#
0.141#
0•563#

0.077

Av .

■ ^ Un e x p e c t e d v a l u e s *
c a l c u l a t i o n of the

60-70

cod l i v e r
cod l i v e r

0.281
0.212
cod l i v e r
cod l i v e r

14
A plus
cod l i v e r l 7
19
oil

A plus
13
C C- T o c o - 15
p h e r o l and
cod l i v e r Av.

0.109
0.097

50-60

0.072
0.047
0.072
0.063

0.409
0.175

0.266
0.266

0.109
0.122

0.072

0.292

0.266

0.115

0.072

They were n o t c o n s i d e r e d f o r t h e
av erag es value*

-

85 -

TABLE V I I .
TOCOPHEROL CONTENT OF BLOOD PLASMA IN LAMBS FED A
MOLECULAR DISTILLED LARD DIET (DIET B) AND THE EFFECT
OF Q(-TOCOPHEROL THERAPY ON THE LEVEL OF PLASMA TOCOPHEROL
(All

values

D iet
B

B plus
0(- Toco­
pherol
(controls)

B plus
0(- Toco­
pherol
(recovery)

Lamb
No.
22
23
24
27
29
34
38
39
42
43
44
45
46
47
48
49
50

<s x p r e s s e d

0-10
0.144
0.115
0.187
0.131
0.159

i n mg. p e r 1 0 0 m l .

o f ;p l a s m a )

D a y s on e x p e r i m e n t
20-30
30-40
40-50

50-60

60-70

0.125
0.097
0.084
0.103
0.147

0.178
0.266*
0.350*
0.054
0.109
0.228
0.084
0.097
0.156
0.097
0.134
0.050
0.250*
0.103
0.050
0*150
0.069

0.187* 0.116
0.050
0.069
0.131* 0.069
0.103
0.091
0.097
E-therapy
0.078
0.091
0.069
0.200* 0.153
0.063
0.128
0.250* 0.069
0.069
0.081
0.200*
0.119
0.069
0.097
0.050
0*E-tfc
0.097
0.806* 0.100
0.069
E-therapy
0.131
0.084
E-therapy

Av

0.122

0.111

0.092

0.080

0.088

0.083

20
21
37
40
41

0.159
0.070
0.159
0.059
0.078

0.153
0.081
0.228
0.112
0.172

0.150
0.309
0.162
0.091
0.332

0.072*
0.299
0.187
0.159

0.131
0.406
0.234
0 • 366

0.148
0.428
0.175
0.294

Av

0.105

0.149

0.209

0.215

0.284

0.261

0.084

0.162
0.040
0.127
0.116
0.097

0.097
0.134*

0.040

42
49
50

0.128

0.069

0.384
0.313
0.175

Av

0.128

0.076

0.290

■ ^ Un e x p e c t e d v a l u e s .
They were n o t c o n s i d e r e d f o r
averages values.

the c a l c u l a t i o n

of the

- 86 mS * / 1 0 0 m l .

after

B in t r i a l s

II

their
ml.
the

D e f i c i e n t lambs fed d i e t

only r e q u i r e d 30-40 days to
value

e x p e r i m e n t whe n i t
cod l i v e r

of the

control

oil

until

t h e end o f

su p p le m e n ta tio n lowered the

tocopherol

was 0 . 0 8 3 m g . / l O O m l .

blood plasma not only of
lambs.

g i v e n 1 0 0 mg.

In fa c t,

even the

of alpha tocopherol

30 d a y s a d r o p o f t o t a l

0.292

t o 0*072 mg/100 ml.

such a d r a s t ic

change,

dim inish

from 0 . 1 2 2 t o 0 . 0 9 2 mg./lOO

T his v a lu e however, changed very l i t t l e

level

in

and I I I

blood plasma to co p h e ro l

The

the

60 d a y s o f f e e d i n g .

the

d e f i c i e n t but a ls o

control

lam bs t h a t were

every o th e r

day e x p e r i e n c e d

tocopherol

Of

i n t h e blo o d plasma from

The d e p l e t e d a n i m a l s d i d n o t s u f f e r

the l e v e l

d ro p p e d o n l y 0 . 0 1 4 mg./lOO m l.

from 0 . 0 7 7 t o 0 . 0 6 3 mg./lOO ml.
The e f f e c t
total

of the alpha tocopherol

t h e r a p y on t h e l e v e l

t o c o p h e r o l s i n t h e b l o o d was n o t i c e a b l e

of tre a tm e n t.
or l a r g e r
It

At t h is

time

their

tocopherol

th a n th e v a lu e s found i n c o n tr o l

s h o u l d be p o i n t e d o u t t h a t

of

a f t e r 10-20 days
c o n t e n t was e q u a l

anim als.

the to co p h e ro l p i c t u r e

of

t h e b l o o d o f d e f i c i e n t l a m b s was n o t a l w a y s one o f a p r o g r e s s i v e
decrease.

I n many i n s t a n c e s ,

lam bs h a v i n g low v a l u e s

d a y s sh o wed a s u d d e n a n d e x t r a o r d i n a r y
pherols

in the

t h a n 10 d a y s ,
original

blood plasma.
a f t e r which the

low l e v e l s .

increase

fo r 20-30

of t o t a l

toco­

T h i s phenomenum d i d n o t l a s t m o r e
tocopherol

content

fell

to the

- 87 -

b)

Blood Hemoglobin:
The r e s u l t s

Tables VIII

of th e hemoglobin a n a l y s i s a re

and IX.

As i t

c a n be s e e n ,

the

m e n t a t i o n o f d i e t s A and B d i d no t a f f e c t
g lo b in values
sim ilar

of

the blood,

hemoglobin p i c t u r e

Likew ise,

the

since
to

the

that

tocopherol

anim als

showed a

c o n tro l lambs.

s u p p l e m e n t a t i o n o f cod l i v e r o i l

m odify the hemoglobin c o n te n t of e i t h e r

supple­

i n a n y way t h e hemo­

control

of th e

condensed in

control

did not

or d e f i c i e n t

lam bs.
However,

in five

lambs

fed vitam in E -d e fic ie n t
to

v e r y low v a l u e s ,

of blood.

c)

diets,

diet

tocopherol

D ifferential

for

50-60 day s,

therapy

c o n te n t of hemoglobin dropped

th e lambs

a n d t h e y c o u l d n o t be m o d i f i e d

( T a b l e I X , l a m b No.

50).

White Count:

o f pneumonia.

be a s s o c i a t e d
d)

44 39 a n d 50)

r a n g i n g from 6 . 5 t o 8 . 4 grams p e r 100 ml.

The c h a n g e s o f w h i t e
appearance

the

34,

These low l e v e l s were o b s e r v e d o n ly a f t e r

w e re on t h e
by t h e

(lamb Nos. 1 2 ,

with the

count only occurred along w ith th e
No c h a n g e o f w h i t e b l o o d c e l l s

deficiency

could

o f v i t a m i n E*

Blood P r e s s u r e :
A total

and d e f i c i e n t
distilled
certain

o f 24 b l o o d p r e s s u r e r e a d i n g s we r e t a k e n f r o m c o n t r o l
l a m b s on d i e t B ( d i e t

lard).

The r e s u l t s

correlation

was f o u n d ,

are

containing the m olecularly

s hown i n T a b l e X.

in d e f i c i e n t lambs,

Since a
between the

- 83 TABLE V I I I
HEMOGLOBIN CONTENT OF THE BLOOD OF LAMBS FED A COMMERCIAL
LARD DIET (DIET A) AND THE EFFECT OF 0(-TOCOPHEROL
THERAPY ON THE LEVEL OF HEMOGLOBIN IN THE BLOOD
(All v a lu e s

A plus
0( - t o c o ­
pherol

A plus
cod l i v e r
oil

A plus
0(-toco­
p h e r o l and
cod l i v e r
oil

Lamb
No *

0-10

6
8
11
12
14
17
18
19

11*4
13.3
13.3
12.9
12.5
11.8
12.9
11.1

10.1
13.3
11.8
13.7
11.6
12.7
11.6
12.5

10.1
11.1
10.8
11.4
11.6
11.4
10.8
12.1

A.V

12.4

12.1

11.1

10.6

7
10
13
15

12.7
12.5
12.7
11.8

10.8
10.8
11.4
12.3

11.1
10.8
12.5
12.3

12.0
12.2
cod l i v e r
c od l i v e r

Av

12.4

11.3

11.6

12.1

O
to
1
o

A

i n rag* p e r 100 ml* o f b l o o d )

(XI

D iet

expressed

Da ys on e x p e r i m e n t
40-50
30-40
50-60
10.8
10.4

11.6
12.1

--------

--------

60-70
12.5
10.4
6.5

cod l i v e r o i l
cod l i v e r o i l
cod l i v e r

oil

11.8

9.8

oil
oil

14
17
19

12.1
11.4
11.1

11.6
11.6
10.2

11.6
12.5
11.1

Av

11.5

11.1

11.7

13
15

12.3
10.9

12.1
11.8

12.9
12.7

Av

11.6

11.9

12.8

-

89 -

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- 91 -

TABLE X
THE INFLUENCE OF VITAMIN E DEFICIENCY ON THE
ARTERIAL BLOOD PRESSURE OF THE LAMBS
A*

Lambs Fed D i e t B p l u s 0 ( - T o e o p h e r o l

Lamb No. Age
____________ ( d a y s )

Heart Beats
B l o o d p r e s s u r e (mm o f Hg)_____
per minute
D iastolic
Systolic
Average
Controls

37
40
41

80
75
55
60
75

240
202
199
205
174

112
75
90
105
94

137
94
110
122
119

12 5
85
10 0
113
107

Av.

69

204

95

116

106

Recovered Animals
49

50
65
80

112
122
102

85
91
88

118
122
119

101
107
103

Av.

65

112

88

120

104

- 92 -

TABLE X ( c o n t i n u e d )
B. La mb s F e d D i e t B

Lamb No .

Age
(days)

H eart Beats
B l o o d p r e s s u r e (mm o f Hr )
per minute
Systoli c
Average
D iastoli c

N o t s h o w i n g s y m p t o ms o f d e f i c i e n c y
44
47

65
50
55
60

202
146
149
230

130
75
95
130

180
113
132
175

155
94
113
1 52

Av.

57

182

108

150

128

S ho w in g symptoms o f d e f i c i e n c y

47

75
85
60
75
90
50
70
55
70
55
70
70

242
224
180
219
153
132
137
140
162
127
160
171

1 15
87
75
84
78
72
75
65
69
87
31
77

1 25
122
90
100
100
100
1 16
90
94
120
63
112

120
106
82
92
89
86
95
77
81
103
47
94

Av.

69

171

76

103

89

34
38
43
44
45
46

- 93 blood p r e s s u r e s and th e

symptomatology of the

wa s

One ,

subdivided

and a n o t h e r ,

i n two.

for

those

for

those

showing the

disease,

no t showing the

the

group

symptoms

symptoms o f t h e v i t a m i n E

deficiency.
Due t o
tions

th e small

number o f r e c o r d i n g s and t h e

of blood p r e s s u r e s

a n a l y s i s was n o t c a r r i e d

in individual

diet

deficient

an im als, thes t a t i s t i c a l

out.

Taking th e blood p r e s s u r e s of the
lambs as a l e v e l

complex v a r i a ­

of referen ce,

it

control

can be s a i d

and r e c o v e r e d
t h a t l a m b s on a

of v i t a m i n E t e n d e d to have h i g h e r p r e s s u r e s

t h e y d i d n o t show a n y sympt om o f v i t a m i n E d e f i c i e n c y ,
l a m b s s h o w i n g symptoms o f t h e
had lo w e r b lood p r e s s u r e s
tions
the

phe nome num

are

deficient

lambs Nos.

44 a n d 4 7 ,

disease
e)

than co n tro l anim als.

of d e f i c i e n c y ,

and t h a t

d e f i c i e n c y of v i ta m in E g e n e r a l l y

of t h is

n o t s how s i g n s

g i v e n by t h e
taken

Good i l l u s t r a ­

blood p r e s s u r e s of
f i r s t when t h e y d i d

a n d a f t e r , when t h e

s y mpt oms o f t h e

were e v i d e n t .

The L e v e l

of P a n t o t h e n i c A cid i n the Blood:

The r e s u l t s

when

of the pantothenic

acid an aly sis

of blood

p lasm a of t h e e x p e r i m e n t a l lambs a r e summarized i n Table XI.

- 94 -

TABLE XL
THE EFFECT OF VITAMIN E DEFICIENCY ON THE
LEVEL OF PANTOTHENIC ACID IN THE BLOOD
Lamb No .

D iet

Symptom s

P.A.

gamma/ml•

37

Complete

none

0.44

40

it

ti

0.42

41

ii

ii

0.34

G-oose-s t e p p i ng

44

E - d e f ic i ent

45

ii

n

34

ti

it

38

it

ii

it

it

ii

0.46

46

n

ii

it

ii

ti

0.37

47

ti

it

it

it

it

0.46

49

it

ti

ti

it

ii

0.43-

50

ii

it

ti

M

it

0.36

0.38

it

0.56

V i t a m i n E de f i c i . e n c y

0.45

ii

T h e r e was n o t a c o n s i s t e n t

difference

in the

blood c o n te n t

o f p a n t o t h e n i c a c i d betw een lambs showing g o o s e - s t e p p i n g and
any of the o th e r

deficient

R esults
a)

or

control

lambs.

of the U rine S tu d ie s

E f f e c t o f V i t a m i n E on t h e U r i n a r y E x c r e t i o n o f C r e a t i n e
and C re a tin in e :
The r e s u l t s

C reatine:

In

of th ese

general

it

studies

are tab u lated

c a n be s t a t e d

that

in Table X II.

the level

of

creatine

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- 97 of U i-deficieat anim als
progressed*
creatine

i n c r e a s e d above

Some o f t h e l a m b s d i d n o t

e x c re tio n in the urine

of c r e a tin e

No* 4 0 ,

the

anim als

starting

creatine

values

t o show t h e
ranged

vitam in E -d eficien t

of

excretion

of c o n tro ls.

in c o n tro l anim als

o n l y i n one i n s t a n c e ,

lamb

In d e f i c i e n t

symptoms o f E d e f i c i e n c y ,

the

f r o m 177 t o 412 mg. p e r d a y .
therapy decreased

lambs.

creatine urinary excretion

the

creatinuria

A f t e r 10 d a y s o f t r e a t m e n t

Lamb No. 50 was a n e x c e p t i o n .

The c r e a t i n e

of d e c re a sin g with the alpha tocopherol
t o a new h e i g h t o f 3 0 6 m g . / d a y ,

f o l l o w i n g 10 d a y s d e c r e a s e d t o 42 a n d ,

to

that

T his animal remained

even though i t

a n y sympt om o f v i t a m i n E d e f i c i e n c y .

of
the

o f r e c o v e r e d l a m b s was e q u a l

in poor c o n d itio n a f t e r tre a tm e n t,

increased

increase

e x c r e t i o n was 185 mg. p e r d a y .

Alpha to c o p h e ro l

instead

show g r a d u a l

and d i d n o t m a i n t a i n h i g h l e v e l s

f r o m 1 8 t o 89 mg. p e r d a y ;

creatine

as t h e E d e f i c i e n c y

f o r a p r o l o n g e d time*

Common v a l u e s o f c r e a t i n e
ranged

normal

d i d n o t show
level,

treatm ent,

then d uring the

10 d a y s l a t e r ,

increased

a g a i n t o 1 8 2 mg. p e r d a y .
Cod l i v e r
creatinuria
lized

by t h e

o i l p r o v e d t o be e f f e c t i v e

of d e f i c i e n t lambs;

however,

in in cre a sin g the
its

fe e d in g of alp h a to co p h e ro l as

a c t i o n was n e u t r a ­
c a n be n o t i c e d

in

Table X II.
C reatinine:

The a n a l y s i s

v ita m in E does not a f f e c t

of c r e a t i n i n e

indicated

that

the u r in a r y e x c r e tio n of t h i s

the
compound.

- 98 The a m o u n t o f c r e a t i n i n e
animal

to anim al,

experim ental

but i t

ratio;

in order

to

creatine

and c r e a t i n i n e

diet.

remained about the

condense

It

is

(c re a tin e plus

The

creatinuria

varied

from

same d u r i n g a l l

and t h e

ratio

i n one e x p r e s s i o n t h e

the

calculated

relative

by d i v i d i n g t h e

preformed c re a tin in e )

creatine

has been c a l c u l a t e d
changes

of

p r o d u c e d by t h e a b s e n c e o f v i t a m i n E i n

Absence of v ita m in E in the d i e t
ratio

urine

period.

The c r e a t i n u r i a

the

e x c r e te d i n the

level

total

by p r e f o r m e d

in flu e n c e d the

creatinine
creatinine.

creatinuria

i n a s i m i l a r manner.

They i n c r e a s e d

a s t h e E d e f i c i e n c y b e c a m e mor e a c u t e .
In

c o n tro l anim als

the c re a tin u r ia r a t i o

to 1 .7 5 w ith an a v e ra g e of 1 .3 2 .
creatinuria ra tio
1.96.

varied

In d e f i c ie n t anim als the

from 1 . 0 0 t o 4 . 7 7 w i t h an a v e r a g e

I n e a c h d e f i c i e n t lamb t h e r a t i o

maximum a t t h e

r a n g e d from 1 . 0 5

tim e t h e lambs

of

was maximum o r c l o s e

to

s h o we d s i g n s o f v i t a m i n E d e f i ­

ciency.
b)

E f f e c t o f V i t a m i n E on t h e U r i n a r y E x c r e t i o n o f S o d i u m a n d
Potassium •
The a n a l y t i c a l

daily

results

are presented

in Table X I I I .

e x c r e t i o n o f sodium and p o t a s s i u m d i d n o t r e f l e c t

creasing

severity

d i e t A o r B,

of the v itam in E d e fic ie n c y

in

spite

of the f a c t th a t

c o n te n t of

sodium and p o t a s s i u m

the

oil.

the vitam in E a ffe c te d

in the

in­

i n lambs f e d e i t h e r

or e v e n d i e t A s u p p l e m e n te d w i t h cod l i v e r

Therefore,

The

skeletal

the

m uscles and t h e

-

99 -

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c h a n g e s were
and p o ta s s iu m

as w ill

be r e p o r t e d

next pages,

these

of the E le c tr o c a r d io g r a p h ic S tu d ie s

be s e e n i n t h e

follow ing pages,

deficiency

of v i t a ­

in the g reat m a jo rity of c a s e s ,

by

changes in the e le ctro ca rd io g ra m .

To f a c i l i t a t e
under

in the

in the u rin e .

m i n E l a m b s was m a n i f e s t e d ,
definite

-

n o t a p p a r e n t t h r o u g h t h e d e t e r m i n a t i o n o f sodium

R esults
As w i l l

101

the

exposition,

the

results

have been a rr a n g e d

the follow ing headings:
a)

b)

c)

The E l e c t r o c a r d i o g r a m

o f Lambs Fe d D i e t B S u p p l e m e n t e d

w ith Alpha Tocopherol

(controls).

The E l e c t r o c a r d i o g r a m

of V ita m in E D e f i c i e n t Lambs.

1)

La mb s S h o w i n g A c u t e C a r d i a c I n v o l v e m e n t .

2)

Lambs S h o w i n g C h r o n i c C a r d i a c I n v o l v e m e n t .

3)

La mb s n o t S h o w i n g Any Symptom o f C a r d i a c I n v o l v e m e n t .

The E l e c t r o c a r d i o g r a m

o f Lambs F e d D i e t A S u p p l e m e n t e d

w i t h Cod L i v e r O i l a n d A l p h a T o c o p h e r o l .
d)

The E l e c t r o c a r d i o g r a m
ceived In je c tio n s

a)

The E l e c t r o c a r d i o g r a m
Alpha T ocopherol:

o f Lambs F e d D i e t B, w h i c h R e ­

o f C o r t i s o n e and P r o s t i g m i n e .
o f Lambs F e d D i e t B S u p p l e m e n t e d w i t h

The H e a r t R a t e ;
The h e a r t r a t e
41) r a n g e d
ever,

in the three

control

lambs

f r o m 1 0 7 t o 250 b e a t s p e r m i n u t e

the average

rate

of in d iv id u a l

(Nos. 3 7 ,

(Table XIV).

anim als,

40 a n d
How­

taken ouring the

-

102

-

TABLE XIV
THE AVERAGE HEART RATES, PR AND QT INTERVALS
AND THE K CONSTANT (BAZETT' S) OF VITAMIN
E DEFICIENT AND CONTROL ALMBS
Types of
ECG-

Lamb
N o.

He a r t
Rate#

C ontrols

37
40
41

166
151
155

0.08
0.08
0.08

0.22
0.23
0.24

0.37
0.36
0.37

Av.

157

0.08

0.23

0.37

14
19
24
39
48

2 32
150
175
149
200

0.06
0.10
0.10
0.10
0.08

0.18
0.22
0.22
0.22
0.19

0.35
0.35
0.38
0.35
0.34

Av.

181

0.09

0.21

0.35

34
38
42
43
44
45
46
47
49

155
176
138
139
137
131
115
132 '
103

0.10
0.10
0.12
0.12
0.10
0.12
0.09
0.11
0.10

0.24
0.22
0.26
0.25
0.26
0.25
0.27
0.26
0.29

0.37
0.36
0.39
0.38
0.39
0.37
0.37
0.38
0.38

Av.

136

0.11

0.25

0.38

12
32
50

150
158
140

0.10
0.08

0.24
0.20
0.24

0.38
0.33
0.36

Av.

149

0.09

0.23

0.36

L a mb s s h o w i n g
Acute C ardiac
Involvement

L a mb s s h o w i n g
Chronic Card­
iac Involve­
ment

Lamb s n o t
Showing any
Sympt om o f
Cardiac
Involvement

# Average v a lu e s .

Intervals
PR#
QT#

--------

Bazett ' s
C o n s t a n t K#

- 103 course

of the

entire

had an average
the average

experim ent,

of 166,

for the

l a m b No.

was v e r y s i m i l a r .
40, 1 5 1 ,

l a m b No.

Lamb No.

37

41, 1 5 5 a n d

g r o u p was 1 5 7 b e a t s p e r m i n u t e .

I n e v e r y lamb t h e h e a r t r a t e
show a n y c o r r e l a t i o n w i t h t h e

was v e r y r e g u l a r a n d d i d n o t

i n c r e a s i n g age o f t h e young lam b.

The PR I n t e r v a l ;
The d u r a t i o n o f t h e PR i n t e r v a l
electrocardiogram

of the

wa s n o t a l w a y s p r e s e n t
leads

of the

in a l l

XXIV ( A p p e n d i x ) .

lambs

(Table XIV).

The P wave

i n e v e r y ECG# o f t h e l a m b s a n d i n a l l

same r e c o r d .

t h e PR i n t e r v a l

as th e o th e r

control

was 0 . 0 8 s e c o n d i n e a c h

Thus,

instances,

it

was i m p o s s i b l e t o m e a s u r e

a s c a n be n o t i c e d i n T a b l e

The m e a s u r e m e n t s o f t h e PR i n t e r v a l

intervals

the

w e r e made u s u a l l y i n l e a d I I

as well

because

it

was t h e m o s t f a v o r a b l e .
The v a r i a t i o n
the

s ame r e c o r d

rates
the

o f t h e PR i n t e r v a l s

never exceeded 0.01

among t h e t h r e e l e a d s

second.

Extremes in h e a r t

r a n g i n g f r o m 1 0 7 t o 250 b e a t s p e r m i n u t e d i d n o t i n f l u e n c e

d u r a t i o n o f t h e PR i n t e r v a l .

The QR$ I n t e r v a l :
The d u r a t i o n o f t h e QRS i n t e r v a l
plus alpha

tocopherol

The d i f f e r e n c e

d u r a t i o n o f QRS among t h e
second and v a r i a t i o n s

d u r a t i o n of t h i s

complex.

# E lectrocardiogram .

i n t h e lambs f e d d i e t B

was i n v a r i a b l y 0 . 0 6

( T a b l e XXIV, A p p e n d i x ) .

0.01

of

second in le a d I I

in the values f o r the

t h r e e l e a d s was r a r e l y
in h eart

rates

larger

than

did not a f f e c t the

- 104 -

Th e QT I n t e r v a l :
The d u r a t i o n
second in the
for

the

o f t h e QT i n t e r v a l

three

control

g r o u p was 0 . 2 3

of the

t wo p r e v i o u s

determ ine

the

lamb Nos.

second

m e a s u r e m e n t was s m a l l e r

37,

from 0*32 t o 0 . 2 4

40 a n d 4 1 .

(Table XIV).

(0.02 second)

intervals

end p o i n t

ranged

The a v e r a g e

The a c c u r a c y o f t h i s

than i n the measurement

because

it

o f t h e T wave,

was d i f f i c u l t

since

it

to ex ac tly

usually

joined

t h e TP s e g m e n t by mea ns o f a s m o o t h c u r v e .
T h e d u r a t i o n o f t h e QT i n t e r v a l
heart

rate.

For in s ta n c e ,

s e c o n d when t h e h e a r t r a t e
s e c o n d when t h e

rate

varied

i n l a m b No.

in v e rs e ly with the

41 t h e QT v a l u e

wa s 0 . 1 8

was 250 b e a t s p e r m i n u t e a n d 0 . 3 0

was 1 0 7 b e a t s p e r m i n u t e

( T a b l e XXIV,

A ppendix)•
The S y s t o l i c

Index:

I n 28 o u t o f 32 c o n t r o l
fell

i n the

calculations,

range of 0.35 to 0 .3 9 ,

K v a l u e s ra n g e d from 0 . 3 2 to 0 . 4 3
average K value

fo r the

B a ze tt's

whereas fo r

the

K values
32 r e c o r d s t h e

( T a b l e XXIV, A p p e n d i x ) .

w h o l e g r o u p was 0 . 3 7

The

( T a b l e XIV).

The P W a v e :
In general

the p o te n tia l

instances is o e le c tric .
potential

ranged

o f t h e P wave was l o w a n d i n some

When t h e P w a v e s we r e m e a s u r a b l e ,

from 0 .0 5 to 0 . 1 5 m i l l i v o l t .

The s h a p e o f t h e P w a v e s w e r e v a r i a b l e .
a n d p e a k e d w a v e s we r e
changed shape

their

found,

Sharp,

rounded,

a n d i n some i n s t a n c e s P w a v e s

from b e a t to b e a t o f t h e h e a r t .

Thus,

a n BCG o f

- 105 l a m b No .

37 showed e x t r a P waves w hi c h a p p e a r e d a t

increasing

intervals

In the
were a l s o

after

each h e a r t

same l a m b , No . 3 7 ,

successively

beat.

d i p h a s i c and i n v e r t e d

P waves

noticed.

The QRS C o m p l e x :
The v o l t a g e

o f t h e QRS c o m p l e x was v a r i a b l e

i n f l u e n c e d by a g e o f t h e l a m b s .
the

a n d was n o t

In the m a jo rity of the

QRS c o m p l e x was m o n o p h a s i c b u t i n a few c a s e s i t

diphasic

cases

b e c a me

i n o n e o f t h e l e a d s b u t n e v e r i n two l e a d s a t t h e

same

time •
When t h e QRS c o m p l e x was m o n o p h a s i c t h e p o t e n t i a l
in lead
to

-1.20

I,

from 4 0 .5 0 t o - 0 . 8 0 m i l l i v o l t ;

m illivolts;

and i n l e a d I I I ,

in lead I I ,

ranged,
from - 0 . 3 0

from 4 0.4 0 to - 1 . 4 0 m i l l i ­

volts .
When t h e QRS c o m p l e x was d i p h a s i c t h e
0.35

to 1.20

in lead I ,

a n d was 0 . 5 0 m i l l i v o l t
The a r i t h m e t i c a l
value

v o l t a g e r a n g e d from

from 0 . 2 5 t o 0 . 3 5 m i l l i v o l t i n

lead I I I ,

in lead I I .
total

of the

QRS p o t e n t i a l s

h a d a mini mum

o f 0 . 9 5 m i l l i v o l t a n d a maximum o f 4 . 3 5 m i l l i v o l t s .
S l u r r i n g o f t h e QRS c o m p l e x was n o t i c e d q u i t e

in l e a d I of the

co n tro l anim als,

but

frequently

n o t i n any o f t h e

other

leads.
The T W a v e :
The v o l t a g e

o f t h e T w a v e s was p o s i t i v e

However i n c e r t a i n

cases i t

most o f t h e

b e c a me i s o e l e c t r i c

tim e.

a n d i n t wo ECG-s,

- 106 taken w ithin

five

to

e i g h t days a f t e r

i n v e r t e d T waves we re

found i n l e a d

were o b s e r v e d i n any o f th e
The p o t e n t i a l
m illivolt
from - 0 . 1 5

of the

in lead I,

the

e x p e r i m e n t was

II.

No d i p h a s i c T w a v e s

records.

T waves v a r i e d from - 0 . 0 5

from 0 t o 0 .5 0 m i l l i v o l t

to 0.35 m il l iv o l t

to 0.45

in lead II

and

in lead I I I .

T h e s h a p e o f t h e T wave was n o t t h e
Some o f t h e more t y p i c a l

started,

same i n a l l

records.

ones are re p ro d u c e d in F ig u re 6.

T h e ST S e g m e n t :
In a very

few i n s t a n c e s

a p p e a re d low er or h i g h e r than

it

was n o t i c e d t h a t

the

t h e ST s e g m e n t s

base l i n e .

The E l e c t r i c a l A x i s :
The e l e c t r i c a l a x e s a s m e a s u r e d by W i l s o n ' s m e t h o d w e r e
quite

different

electrical

axis

f r o m l am b t o l a m b .

Thus,

i n l a m b No.

37 t h e

changed from - 9 0 ° to - 6 0 ° and t h e n a g a i n to

- 9 0 ° d u r i n g t h e 81 d a y s o f
41 t h e e l e c t r i c a l

axis

the experim ent.

I n lamb No s.

f l u c t u a t e d between -120 to -180°

40 a n d
(Table

XXIV, A p p e n d i x ) .
b)

The E l e c t r o c a r d i o g r a m
A l l th e lambs

m icropathological

o f V i t a m i n E D e f i c i e n t Lambs:

considered under t h i s

g r o u p s h o we d m a c r o a n d

changes of v ita m in E d e f i c ie n c y ,

uria

ratio,

low b l o o d t o c o p h e r o l

acid

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in the m uscles.

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high c r e a t i n ­

c o n te n t with m ineral

into

three

o n e wa s c o m p o s e d o f t h e l a m b s t h a t d i e d

categories.
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and amino

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- 108 by t h e p a r a l l e l i s m
mediate

changes

wa s c a l l e d
cardiac

in the

"acute

progressive

1)

electrocardiographic

type of d e f i c i e n c y

compared t o t h e

In th is

o f t h e EGG h a v e b e e n g a t h e r e d .

and c h e m ic a l

Finally,

t h e l a m b s w h i c h s howe d

changes c h a r a c t e r i s t i c

although l i t t l e

"chronic

of vitam in E

o r no c h a n g e was o b s e r v e d i n t h e ECG.

ECGs o f V i t a m i n E D e f i c i e n t Lambs S h o w i n g A c u t e C a r d i a c
Involvem ent:

Before

t h e e l e c t r o c a r d i o g r a p h was u s e d f o r

vitam in E deficiency
ready appeared.
v o l v e m e n t were
ing place

three

cases

T hereafter,
observed,

(Nos.

liver

oil

of acute

five

heart

the study of th e
failure

mor e c a s e s o f , a c u t e

w h i c h we r e

i n t h e ECGs p r i o r t o

lambs

fed

as

i m­

d a t a o f lambs showing

c a t e g o r y we r e p l a c e d a l l

pathological
deficiency,

involvement"

This

d e scrib e d in the next categ o ry .

alterations

third

s u d d e n d e a t h and t h e

electrocardiogram .

cardiac

involvement"

second categ o ry

in the

between th e lam bs'

the

detected
lam b's

by t h e

death.

had a l ­

heart

in­

changes t a k ­

Two o f t h e

1 4 a n d 1 9 ) h a d b e e n f e d d i e t A s u p p l e m e n t e d w i t h cod

and th e o t h e r

t h r e e lambs

(Nos.

24,

39 a n d 4 8 )

had been

d i e t B.
Up t o

t i m e o f t h e o c c u r r e n c e o f s u d d e n c h a n g e s i n t h e ECGs,

the e l e c t r i c a l

phenomena acc o m p a n y in g t h e h e a r t b e a t d i d n o t

a p p e a r t o be v e r y d i f f e r e n t
pherol

in th e ir

lambs of t h i s

diets.

from a n i m a l s r e c e i v i n g a l p h a t o c o ­

The m o s t o u t s t a n d i n g ECG c h a n g e i n t h e

g r o u p was a n i n c r e a s e

( T a b l e XXIV, A p p e n d i x ) .

These

rates

of the

heart

r a t e w ith age

have been summarized i n

- 109 Table

XIV w h e r e t h e a v e r a g e o f t h i s

of the

control

in the

same T a b l e ,

f o r t h e PR i n t e r v a l

besides

d u r a t i o n o f t h e QT i n t e r v a l

a slight

and B a z e t t ' s

fixed

interval

in the

c o n s t a n t K.

I n l am b N o s .

14,

24 a n d 4 8 ,

changes c o n s is te d of very la rg e

o f t h e T a n d QRS w a v e s ,

particularly

c o n s e q u e n tly assumed a very t y p i c a l
of

changes were

f i v e lambs and d i d n o t t a k e p l a c e a t any

before death.

sudden e l e c t r i c a l

c a n be

decrease in the

The a p p e a r a n c e o f a b r u p t e l e c t r o c a r d i o g r a p h i c
not id e n tic a l

whereas t h a t

was 1 5 7 b e a t s p e r m i n u t e .

A lengthening of the average
noticed

g r o u p was 1 8 1 ,

t h e R w a v e s , a s c a n be o b s e r v e d

o f t h e T wave v o l t a g e s

the

former.

voltage

increases

The T w a v e s

s h a r p form r e s e m b l i n g t h a t
in F ig u re 7.

The i n c r e m e n t s

h a v e b e e n s u m m a r i z e d i n T a b l e XV w h i c h

s h o w s t h a t t h e s e p o t e n t i a l s we r e much l a r g e r t h a n t h o s e
in the

the

found

c o n tro l lambs.
TABLE XV

THE T WAVE POTENTIALS IN ACUTE CARDIAC INVOLVEMENT
PRODUCED BY VITAMIN E DEFICIENCY IN THE LAMB
Lamb
Days
T potentials
Total T
No.
before
(m illivolts)
potentials
_________ d e a t h ________ L i __________ L»2___________ L3______ ( m i l l i v o l t s )
14

0.2

24

11
1

48

8
1

40.50
0
0
40.35
41.05

40.60

40.35

1.45

40.70
40.80

40.85
40.65

1.55
1.45

40.60
40.40

-0.15
-0.60

1.60
2.05

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It

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the

interesting

III

of lamb 48,

control

and e v id e n c e

were i n v e r t e d T waves

which d id not appear

changes in the

in the

cases

T h i s c a n be s e e n i n F i g u r e s
respectively.

deflections

in the records

d i r e c t i o n of the

showing a c u t e h e a r t

of

v a r i o u s waves

three

No. 1 4 b u t t h i s

i m m e d i a t e l y by l a r g e

Figure

in a p ro strate

imm ediately a f t e r

involvem ent.

The ECG s h o w e d e x t r e m e l y l a r g e

leads.

time

constituted

8 a n d 11 c o r r e s p o n d i n g t o l a m b No s *

which were f o l lo w e d

T waves i n a l l

taken

there

of d i s o r g a n i z a t i o n of the h e a rt b e a t,

finding

14 a n d 3 9 ,

that

lambs.

Tachycardia,

another

to note

-

that

QRS

inverted

8Bshows a n o t h e r ECG o f l a m b
position.

T h i s r e c o r d was

o f F i g u r e 6k was r e c o r d e d ,

whe n t h e

l a m b was m o r i b u n d .
I n l a m b No. 1 9 e l e c t r o c a r d i o g r a p h i c
differed

from any p r e v i o u s l y

of the

ST s e g m e n t

ations

in the p o te n tia l

contration,
2)

seen.

c h a n g e s were f o u n d w h ic h

T h e s e we r e m a r k e d d e p r e s s i o n

(-0.15 m illiv o lt)

in leads II

and I I I ,

vari­

and form o f t h e P waves w i t h e v e r y h e a r t

and d i p h a s i c T waves i n l e a d I I I

(Fig.

10).

ECGs o f V i t a m i n E D e f i c i e n t Lambs S h o w i n g C h r o n i c
Cardiac Involvement:

A n o t h e r t y p e o f ECG was f o u n d i n n i n e o f t h e v i t a m i n E d e f i c i e n t lambs
For p u r p o s e s

(Nos.

34,

38,

42,

of d i f f e r e n t i a t i o n

heart

disease

heart

failure.

since

it

it

did not f i t

43,

44,

45,

46,

47 a n d 4 9 ) *

was named ECG i n c h r o n i c
into

t h e p a t t e r n of a c u t e

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- 115 These

changes consisted, mainly in a decrease

and an in c r e a s e
it

i n d u r a t i o n of

wa s f o u n d t h a t ,

rate

in

contrast

to the

d ecreased with in c r e a s in g age.

was 1 3 6 b e a t s
control

per m inute.

g r o u p wa s 0 . 1 1
seen in the

consistently

second.

control

increased in a ll

s e c o n d and t h e a v e r a g e

(Fig.

was c h i e f l y

average

du e t o

f o r the whole

average value

d u r a t i o n of 0 .2 5 second,

the h e a r t r a t e ,

since

but

the K values

g ro u p and t h e c o n t r o l a n i m a l s were a l m o s t e q u a l .
ECGs o f V i t a m i n E D e f i c i e n t Lambs n o t S h o w i n g Any
Sympt oms o f C a r d i a c I n v o l v e m e n t :

and 50, as

c a n be p r o v e n by t h e
of blood u rin e

m icropathological

exam ination.

sive lesio n s

found in the h e a r t

were

4 and 1 4 ) ,

any time
In the

i n lamb Nos. 1 2 ,

data alre ad y p resen te d

chemical a n a ly s e s

at

t h e ECG-s.

than the averages

original

V i t a m i n E d e f i c i e n c y was a l s o p r o d u c e d

(Fig.

group

9).

i n c r e a s e d from i t s

second to a f i n a l

change

3)

the h e a rt

The a v e r a g e o f t h e

T h i s v a l u e was l a r g e r

group

The QT i n t e r v a l

of t h i s

group,

instances

T h i s was c o n s i d e r a b l y l o w e r t h a n t h e

The maximum v a l u e was 0 . 1 2

of 0 .2 3

first

In a ll

rate

group.

The PR i n t e r v a l s

this

t h e PR i n t e r v a l .

in heart

and m u s c l e s ,
In spite

32

on t h e

an d t h e macro and

of th e f a c t t h a t e x te n ­

o f e a c h one o f t h e s e a n i m a l s

no e l e c t r o c a r d i o g r a p h i c

c h a n g e s were n o t i c e d

(T ab le XIV).
case

o f l a m b No. 12 t h e l a s t

t a k e n 20 d a y s b e f o r e t h e
r e c o r d wa s s i m i l a r

to

d e a th of the

that

e l e c t r o c a r d i o g r a m was

anim al.

of c o n tro l lam bs.

At th is

time

the

- 116 In the
to

c a s e o f l a m b N o s . 32 a n d 50 t h e ECGs w e r e t a k e n up

t h e p o i n t wh e n t h e d e a t h o f t h e l a m b was e m i n e n t .

t h e EGG a p p e a r e d
c)

sim ilar

those

of c o n tr o l lambs.

The E l e c t r o c a r d i o g r a m o f Lambs F e d D i e t A S u p p l e m e n t e d w i t h
A l p h a T o c o p h e r o l a n d Cod L i v e r O i l :
Lamb N o s .

tocopherol

13 a n d 15 r e c e i v i n g

and cod l i v e r

The a v e r a g e

second.

different

The QT i n t e r v a l

age v a lu e
values,

of 0.33

was n o t

n o t be

showed r e m a r k a b l y l o w h e a r t

too,

i n c r e a s e d up t o

c a u s e d by t h e

r e v e r s e was o b s e r v e d i n l a m b No. 1 5 ,

deficient

d)

of the lamb.

o f T a n d QRS w e r e o b s e r v e d i n l a m b No.

or c o n tro l

so t h a t

of th e f e e d i n g r e g im e n .

some o f t h e T w a v e s o f l a m b No.

in lead II

the very high a v e r ­

a s was shown by t h e h i g h K

form which had ne v er been se en b e f o r e
either

The PR i n ­

decreased h eart r a te

c o n s i d e r e d a s an e f f e c t

theless,

(Table XVI).

rates.

from c o n t r o l lam bs and a v e r a g e d 0 . 1 1

second which,

Very h ig h v o l t a g e s
but the

oil

d i e t A supplemented w ith a lp h a

was 111 b e a t s p e r m i n u t e

t e r v a l s were a l s o

13,

to

Even t h e n ,

lambs.

it

can

Never­

13 h a d a v e r y p e c u l i a r

i n a n y o f t h e ECG o f

They h a v e b e e n r e p r o d u c e d

of F ig u re 2.

The E l e c t r o c a r d i o g r a m o f Lambs F e d D i e t B S u p p l e m e n t e d w i t h
A lp h a T o c o p h e r o l ( R e c o v e ry ), P r o s ti g m i n e and C o r t i s o n e :
The a d m i n i s t r a t i o n

cient

lam b Nos.

lambs

( T a b l e s XIV a n d X V I ) .

was t h e r e

42,

of a lp h a t o c o p h e r o l

to v ita m in E d e f i ­

29 a n d 50 d i d n o t m o d i f y t h e ECG o f

an i n c r e a s e

I n o n l y on e c a s e

in the voltage

( l a m b No.

the
42),

o f t h e ECG d e f l e c t i o n s .

- 1 17 -

TABLE XVI
THE AVERAGE HEART RATES, PR AND QT INTERVALS
AND THE K CONSTANT (BAZETT *S) OF LAMBS
FED THE VARIOUS EXPERIMENTAL DIETS
G-roup
Lambs f e d d i e t A
plus 0(-tocopherol
and cod l i v e r o i l
Lambs f e d d i e t B
plus 0(-tocopherol
(recove ry)

Lambs f e d d i e t B
receiving in jec­
t i o n s of p r o s t i g mi ne
La mb s f e d d i e t B
receiving in je c ­
tio n s of
c o r t i sone
# Average v alu es

Lamb
No.

Heart
rate#

13
15

128
95

0.10
0.12

0.30
0.35

0.44
0.42

Av.

111

0.11

0.33

0.43

42
49
50

139
73
143

0.12
0.10

0.25
0.30
0.24

0.39
0.38
0.37

Av.

118

0.11

0.26

0.38

34
38

161
1 86

0.11
0.08

0.21
0.22

0.34
0.39

Av.

174

0.09

0.21

0 • 36

45
46

107
125

0.11
0.10

0.25
0.25

0.33
0.37

Av.

116

0.10

0.25

0.35

Inte rv als
PR#
QT#

--------

B a z e t t *s
c o n s t a n t K#

- 118 L ikew ise,
influence

the prostigm ine

t h e ECG o f v i t a m i n E - d e f i c i e n t

O ccasionally,
of the

and c o r t i s o n e

injections

lambs

o t h e r EGG a l t e r a t i o n s

(Table XVI).

we r e n o t i c e d i n m o s t

anim als fea a vitam in E -d e fic ie n t d ie t.

beats,

arrythm ias

v o l u n t a r y muscle
or v e n t r i c u l a r

of d i f f e r e n t
effect),

types,

auricular

extrasystoles.

did not

tremors

T h e y we r e d r o p p e d
( p r o b a b l y due t o

fibrillations

Some o f t h e s e

are

and a u r i c u l a r
illustrated

in

Figure 11.
S t u d i e s o f th e M in e ra l Changes o f
and H e a r t M uscles due to V ita m in
The r e s u l t s
calcium ,

quantative analysis

magnesium and p h o sp h o ru s o f th e

muscles a re
values are
fresh

of the

g i v e n o n a n a s h b a s i s a s mg.
(muscle)

S tatistical

skeletal

the

small

and h e a r t

the

variable

a n a l y s e s of the d a t a have not been c a r r i e d
fo r not doing so.

degree of d e fic ie n c y

c a n be v e r i f i e d
and c r e a t i n e

The

p e r 1 0 0 mg. a n d on a

F irst,

n u mb e r o f a n i m a l s i n e a c h g r o u p a n d s e c o n d ,

Due t o

potassium ,

b a s i s a s mg. p e r 1 0 0 gm.

T h e r e w e r e t wo m a i n r e a s o n s

by t h e a n a l y s i s

because

of

b e c a u s e of

o b tain ed in the lambs,

of alpha tocopherol

out.

which

in the blood

in the u r i n e .
these reasons another

s e t up t o d i s t i n g u i s h

wh e n i t

of sodium,

s u m m a r i z e d i n T a b l e s X V I I , X V I I I , XIX a n d XX.

tissue

arbitrary

the S k e letal
E D eficiency

scale

system of d i f f e r e n t i a t i o n

the m agnitude of the

was

chemical changes.

was made i n w h i c h a c h a n g e was c a l l e d m o d e r a t e

d i d n o t become l a r g e r

than 5 or sm aller

than 1.5 tim es

An

- 119 the

value

observed

deemed l a r g e
control

the

when t h e s e

control

v alu es exceeded

study of th ese

has been o b ta in e d

tissue

chem ical

tables

in regard to

a s h and e a c h one o f t h e

fresh

anim als.

And a c h a n g e was

five

times t h a t

the

cited

the

follow ing inform ation

influence

o f v i t a m i n E on

elem ents.

b a s i s w e r e used to e v a lu a te

Data r e f e r r i n g to

the a l t e r a t i o n s

in the

com position of the m uscles.

Sulfated

ash:

The p e r c e n t

of s u lf a te d

ash of the muscles

o f e x p e r i m e n t a l l y E - d e f i c i e n t a n i m a l s was o n l y s l i g h t l y
creased.

The s k e l e t a l

ones t h a t

showed marked m i n e r a l i z a t i o n .

heart

of the

lambs.

From t h e

the

in

of the

m u s c l e s o f l a m b No. 12 w e r e t h e

lamb d i d not

In spite

show a n y i n c r e a s e

of the h e a r t but

not of

the

only

of t h i s ,

the

of su lfated ash.

T h e r e v e r s e h a p p e n e d i n t h e c a s e o f l a m b No. 4 3 ,
m ineralization

in­

w h i c h s h o we d

skeletal

muscles

(Table XVII).
Field
found t h a t
sulfated
tent

cases of
the

"s tif f - la m b M disease

skeletal

ash as the

of the h e a r t ,

were s t u d i e d and i t

muscles c o n tain ed th r e e

experimental
however,

control

t i m e s a s much

anim als.

was o n l y s l i g h t l y

was

The a s h c o n ­

higher

than the

controls.
Sodium:

The s o d i u m c o n t e n t

of th e l a m b s 1 t h i g h m u sc le s

i n c r e a s e d wh e n t h e v i t a m i n E d e f i c i e n c y was p r o d u c e d by f e e d i n g
a diet

containing

in the

field

cases

commercial or m o lecu lar d i s t i l l e d
(Table XVII).

lard,

or

-

120

-

TABLE XVII
INFLUENCE OF VITAMIN E ON THE PERCENT OF SULFATED
AjSH AND THE SODIUM AND POTASSIUM COMPOSITION
OF THE SKELETAL MUSCLES (THIGH)

Diet

A

Lamb % o f
No. s u l f a t e d
ash

Na______
ash
fresh
tissue
m g / 1 0 0 me mg/lOOem

4
6
8
12
18

1.26
1.20
1.35
3.11

12.06
10.77
9.43
5.49

-------------

Av.

K
ash
mg/lOOmg

fresh
tissue
mg/lOOem

15.08
15.61
17.76
4.09

-------------

151
128
126
1 70
172

-------------

189
186
239
127
225

1.73

9.44

149

13.13

193

5
7

1.49
1.27

6.71
4.59

100
66

20.14
18.35

300
233

Av.

1.38

5.65

83

19.25

266

14
17
19

1.23
1.34
1.14

9.96
8.99
14.60

122
120
166

16.06
20.28
15.97

197
271
182

Av.

1.24

11.18

136

17.44

216

A p l u s C(- 13
t o c o p h e r o l 15
and cod
Av.
liv e r oil

1.25
1.50

7.83
5.02

98
75

22.13
26.68

27 8
399

1.37

6.43

86

24.41

33 8

24
32
39
43
44
47

1.32
1.59
1.37
1.45
1.23
1.31

13.23
12.18
13.42
13.04
12.63
8.58

174
193
184
188
155
112

17.66
9.76
14.79
12.50
16.95
18.66

233
155
202
181
208
243

Av.

1.38

12.18

168

15.05

203

20
21
37
40
41

1.43
1.39
1.52
1.42
1.32

8.49
7.75

121
107

15.82
23.20

225
322

---------

- ————

4.96
6.37

70
84

23.88
23.11

338
305

Av.

1.41

6.89

95

21.50

2 97

A p l u s CXtocopherol

A plus
cod l i v e r
oil

B

B p l u s C(tocopherol
(controls)

-

TABLE XVII

Diet

B p l u s 0(tocopherol
(recovery)

B and
prostigmine
in,ie c t i o n
B and
c o r t i sone
i n j e c t i on
N atural
pasture
(stiff
lam bs)

121

-

(con tinued)

Na
Lamb % o f
ash
fresh
No* s u l f a t e d
t i s sue
ash
mg/lOOmg mg/ 100gm

K
ash
mg/lOOmg

fresh
tissue
mg/ 100gm

42
49
50

1.31
1.51
1.44

8.55
7.21
10.68

112
118
153

21.03
20.58
14.08

275
310
202

Av.

1.42

8.81

127

18.56

262

34
38

1.45
1.34

8.18
8.78

118
117

15.46
19.94

224
266

Av.

1.39

8.48

117

17.70

245

45
46

1.44
1.31

8.71
11.49

125
151

16.80
17.97

241
236

Av.

1.38

10.10

138

17.38

238

1.85
4.08
7.41

11.57
6.32
3.40

214
258
251

5.94
4.18
3.50

110
170
2 59

4 . 45

7.09

241

4.54

17 9

713
716
721
Av.

-

Cod l i v e r
increase

oil

122

s u p p l e m e n t a t i o n d i d not p ro du ce any f u r t h e r

in the l e v e l

of sodium i n t h e m u s c le s ,

r e c e i v i n g d i e t A and d i e t A p l u s
ly,

an equal
Of t h e

content of
several

deficiency,

wa s u n a b l e

therapies

to produce

cases,

the

sim ilar

anim als

find

in heart

and p r o s t i g m i n e were e f f e c t i v e
normal v a l u e s .

in

Cortisone

effects.
d i e t s A and B or i n t h e

sodium c o n t e n t o f the

h e a r t wa s n o t d i s t u r b e d

N evertheless,

i t was r e m a r k a b l e

muscle o f r e c o v e r e d anim al a h ig h sodium c o n t e n t

a v e r a g i n g 225#-, w h i d h i s
anim als

had, approxim ate­

fed p u r i f i e d

by t h e v i t a m i n E d e f i c i e n c y .
to

oil

used fo r tre a tm e n t of v ita m in £

sodium l e v e l s w i t h i n th e

In d e fic ie n t
field

cod l i v e r

s in c e lambs

sodium.

alpha tocopherol

re tu rn in g the

-

about double of th e found in c o n t r o l

(T a b le XIX).

Potassium :
sium c o n t e n t

of

Vitamin E d e fic ie n c y a ls o
skeletal

a f f e c te d the p o t a s ­

and h e a r t m u s c le s .

The c o n t e n t o f p o t a s s i u m

in the

th ig h muscles of c o n tro l

l a m b s i n d i e t A was 2 6 6 * a n d i n d i e t B 2 9 7 * ,
a n i m a l s on t h e d i e t s A o r B and t h e n a t u r a l
potassium

content,

a v e ra g in g 193,

whereas d e f i c i e n t
r a t i o n had a low

203 a n d 1 7 9 * r e s p e c t i v e l y

(Table XVII).
Lambs t r e a t e d
so n e o r cod l i v e r
between th e
cated th a t

with alpha to co p h ero l,
oil

had l e v e l s

prostigm ine,

of potassium in te r m e d ia te

c o n t r o l s and d e f i c i e n t a n im a ls .

This perhaps i n a i -

th e mentioned supplements p r o te c te d

* mg. p e r 1 0 0 gm. o f f r e s h

corti­

tissue

(muscle)

the

skeletal

-

123

-

TABLE X V I I I
INFLUENCE OF VITAMIN E ON THE PERCENT OF CALCIUM, MAGNESIUM
AND PHOSPHORUS COMPOSITION OF THE SKELETAL MUSCLES (THIGH)

Diet

Lamb
No*
_

A

A p l u s 0(tocopherol

A p l u s cod
liv er oil

A p l u s 0( tocopherol
and cod
liv e r oil
B

4
6
8
12
18

Ca ___________________Mg_________________ P
fresh
ash
fresh
ash
fresh
tissue
t i ssue
t i ssue
mg/100
mg / 1 0 0 m g / 1 0 0
rag/100
mg / 1 0 0
mg/ 100
m
mg
mg
gm
mg
gm
ash

__

3.46
1.48
0.60
19.26

2.05
2.16
1.29
0.73

-----------

43
18
8
599
194

--------

26
26
17
23
32

Av.

6.20

172

1.55

5
7

0.57
0.52

8
6

Av.

0.54

14
17
19

28.92
—_

363
— —

--------

255
208
29 5

25

18.19

280

1.67
2.33

25
30

18.99
20.44

283
260

7

2.00

27

19.72

271

0.64
1.78
0.77

8
24
9

1.87
1.99
1.70

23
27
19

23.04
17.91
17.94

283
240
20 5

A.v.

1.07

14

1.86

23

19.63

24 2

13
15

0.61
0.80

8
12

3.74
3.07

47
46

22.21
18.60

27 8
278

Av.

0.70

10

3.40

46

20.40

278

24
32
39
43
44
47

0.71
6.48
1.52
2.31
0.64
0.40

9
103
21
33
8
5

1.34
1.92
1.33
0.55
1.04
2.32

18
30
18
8
13
30

17.25
18.99

228
26 3

14.02
16.29
16.08

203
200
210

Av.

2.01

30

1.42

20

16.53

220

18.96
6.69

------

- 124 TABLE X V I I I

D iet

B p l u s 0(tocopherol
(controls)

B p l u s 0(tocopherol
(recovery)

B and p r o ­
stigm ine
injection
B and
c o r t i sone
i n j e c t i on
N atural
pasture
(stiff
lamb)

Lamb
No.

(continued)

Ca__________________Mg__________________p
f re sh
ash
fresh
ash
t i ssue
t i ssue
mg/100
mg / 100
mg/ 100
mg/100
mg / 1 0 0
mg
mg
gm
mg
__
gm
ash

20
21
37
40
41

0.44
0.71

6
10

--------

--

0.50
0.38

7
5

Av.

0.50

7

42
49
50

0.73
0.59
0.64

Av.

1.62
2.14

23
30

--------

——

2.85
3.02

f r e sh
t i ssue
mg/100
gm

40
40

17.73
17.13
17.41
20.80
21.42

253
238
265
295
283

2.40

33

18.89

266

10
9
9

1.13
1.69
1.23

15
25
20

17.53
17.44
21.42

230
263
308

0.65

9

1.35

20

18.80

267

34
38

0.47
0.79

7
10

0.57
2.13

8
28

16.91
25.73

245
344

Av.

0.63

9

1.35

18

21.32

294

45
46

0.64
1.54

9
20

0.93
0.85

13
11

17.04
18.65

245
245

Av.

1.09

15

0.89

12

17.84

245

33.23
47.00
16.20

616
871
1199

0.97
2.88
0.70

18
38
52

12.94
22.04
9.45

240
900
700

32.14

596

1.52

36

14.81

613

713
716
721
Av.

-

125

-

TABLE XIX
INFLUENCE OF VITAMIN E ON THE PERCENT OF SULFATED ASH AND
THE SODIUM AND POTASSIUM COMPOSITION OF THE HEART MUSCLE

Diet

A.

Lamb % o f
No. s u l f a t e d
ash

Na
ash
mg/lOOmg

K
fresh
tissue
mg/ 100gm

ash
mg/lOOmg

fresh
tissue
rag/lOOgm

4
6
12

1.22
1.20
1.27

12.30
10.47
10.12

149
125
128

10.39
15.54
17.02

126
186
215

Av .

1.23

10.96

134

14.31

175

A p l u s 0(tocopherol

7

1.29

18.49

238

A p l u s cod
liv er oil

14
19

1.34
1.14

6.13
10.09

81
118

14.19
10.18

189
116

Av.

1.24

8.11

99

12.18

152

13
15

1.31
1.36

8.47
7.92

110
107

15.89
15.19

207
206

AV.

1.33

8.20

108

15.54

206

B

24
32
39
43
Av.

1.41
1.29
1.49
2.16
1.58

6.92
12.72
8.24
11.26
9.79

95
163
123
242
155

15.54
9.89
17.25
6.59
12.32

21 9
127
257
142
186

B p l u s (Xtocopherol
(controls)

20
21

1.18
1.32

10.57
8.83

124
11 6

17.24
17.95

203
237

Av.

1.25
1.65

120
225

17.59

50

9.70
13.72

17.93

220
295

713
716

1.37
1.97

11.97
6.77

164
133

13.79
10.86

189
214

1.67

9.37

148

12.33

201

A p l u s 0(tocopherol
and cod
liv er oil

B p l u s 0(tocopherol
(recovery)
N atural
pasture
(stiff
lambs)

Av.

- 126 m u s c le s from c h a n g i n g t h e i r p o t a s s i u m
fe d an E - d e f i c i e n t
The l e v e l
t e d by t h e

diet.

of potassium of the h e art

152# r e s p e c t i v e l y .

Calcium:

but not in the

c o n te n t of the h e a r t

calcification

heart.

This

showing t h a t p r a c t i c a l l y
8,

took p lace

the lambs,

those

Cod l i v e r

of the
oil

as

control

skeletal

lamb

favored the

in the th ig h muscles

T a b l e XX shows

o f E - d e f i c i e n t l a m b s on
v a l u e s which a r e

(Av. 8 . 0 # ) .

c a l c i f i c a t i o n of the

h e a r t muscle

( a v e r a g e 5 0 # ) e v e n when a n i m a l s we r e f e d a l p h a

in the

c a s e o f l a m b N o s . 13 a n d 15

The m o l e c u l a r d i s t i l l e d
the

(T able XIX).

c o m m e r c i a l l a r d wa s

c o n tr o l lambs.

of calcium in the h e a rt

to a g re a t e x te n t
tocopherol

muscle

modified

w ith the e x c e p tio n of

d i e t A r a n g e d from 7 t o 1 0 # ( a v e r a g e 8 # ) ,
to

rations

showed an i n c r e a s e d c a l c i u m c o n t e n t o f t h e m u s c l e s

the le v e l

equal

lard

and h e a r t m u s c le s .

(Av.

18#).

d i e t produced c a l c i f i c a t i o n in
It

was e q u a l l y p r o n o u n c e d i n

b o t h t y p e s o f m u s c l e s a n d was a b o u t s e v e n t i m e s g r e a t e r
the

It

c a n be o b s e r v e d i n T a b l e X V I I I ,

all

f r o m 2 t o 25 t i m e s o v e r t h e
that

oil.

c o n t e n t o f t h e h e a r t m uscle t o 175 and

When d i e t A c o n t a i n i n g t h e

the lambs,

was o n l y a f f e c ­

cod l i v e r

N e ith e r d i e t B nor n a t u r a l

th e normal p o ta s siu m

l a m b No.

muscle

d i e t A alone or supplemented with

lowered the potassium

fed to

c o n t e n t when l a m b s w e r e

than in

controls.
Treatm ent w ith alpha tocopherol

th e h e a r t and s k e l e t a l
# mg. p e r 1 0 0 gm.

caused a f u l l

recovery of

m u s c l e s o f d e f i c i e n t lam b s from t h e

of f r e s h t i s s u e

(muscle)

cal-

- 127 TABLE XX
INFLUENCE OF VITAMIN E ON THE CALCIUM, MAGNESIUM AND
PHOSPHORUS COMPOSITION OF THE HEART MUSCLE
Ca
Diet

Lamb
No.

ash

fresh
t i ssue
mg / 1 0 0
_ gm
10
7
7

_. . .
Mg
ash
fresh
t i ssue
mg / 1 0 0
mg/100
mg
gm
26
2.10
1.73
20
22
1.70

4
6
12

mg/100
mg
0.81
0.63
0.52

Av.

0.65

8

1.84

A p l u s (Xtocopherol

7

0.63

8

A p l u s cod
liv er oil

14
19
Av.

5.39
2.93
4.16

13
15
Av.
24
32
39
43

A

A p l u s 0(tocopherol
and cod
liv er oil
B

B p l u s 0(tocopherol
(controls)
B p l u s 0( —
tocopherol
(recovery)
Natural
pasture
(stiff
lambs)

P
fresh
t i ssue
mg/100 mg/100
mg
gm
ash

27.88

353

23

27.88

35 3

3.40

44

20.20

260

66
33
50

1.36
1.88
1.62

18
21
20

22.32
23.67
21.63

29 8
239
268

2.33
0.46

30
6

2.26
1.74

30
23

26.83
23.67

351
321

1.39

2.00
0.88
0.67
4.92
0.84

26
12
9
25
18

25.25

2.34
0.58
2.29
3.00

18
33
7
34
65

23.33

336
329

16.13

348

Av.

2.05

35

20
21

0.50
0.47

6
6

1.83
2.13
1.07

16
25
14

19.73
22.29

338
263

Av.

0.48

6

1.60

20

22.29

263

50

0.61

9

1.73

25

21.26

350

713
716

4.47
6.68

61
132

1.85
0.60

25
12

16.49

325

5.57

97

1.23

19

16.49

325

Av.

- 128 c i f i c a t i o n p r o d u c e d by t h e a b s e n c e o f v i t a m i n £ .
also

appeared e ff e c tiv e

muscular
since
the

calcification.

fresh

two a n i m a l s t r e a t e d f o r

The a c t i o n o f c o r t i s o n e

i n one lamb t h e l e v e l

o t h e r one

cure of

was u n c e r t a i n

o f c a l c i u m was n o t a l t e r e d

s h o we d a n i n c r e a s e

whereas

o f 10 mg. p e r 1 0 0 g r a m s o f

tissue.
C alcification

extensive
skeletal
tissue
fresh

in the

Prostigm ine

in the

of the

field

skeletal

cases of

a n d h e a r t m u s c l e s was v e r y

"stiff-lam b H disease.

m u s c l e h a d 5 9 6 mg. o f c a l c i u m p e r 100 g r a m s o f f r e s h

and t h e h e a r t m uscle
tissue

97 mg. o f c a l c i u m p e r 1 0 0 g r a m s o f

( T a b l e s X V I I I a n d XX).

Magnesium:
w ith cod l i v e r

Lambs f e d d i e t A a l o n e ,
oil

and a n a t u r a l

d i e t A supplemented

feed r a t i o n

th a t produced

v i t a m i n E d e f i c i e n c y had s k e l e t a l m u s c l e s w i t h normal
o f magnesium,
content

The

which i s 27#.

of magnesium

prostigm ine

(18#),

content

B u t l a m b s f e d d i e t B showed l o w

( 2 0 # ) e v e n when t h e y w e r e s u p p l e m e n t e d w i t h

cortisone

(12.2#)

or a l p h a t o c o p h e r o l

(20#)

(Table X V III).
It

was s u r p r i s i n g

to fin d t h a t

s k e l e t a l m u sc le s of lambs

r e c e i v i n g d i e t A supplemented with alpha tocopherol
liver

oil

h a d 4 6 # , w h i c h was t w i c e

magnesium i n s k e l e t a l
plus

alpha to co p h e ro l,
Nothing d e f i n i t e

ges produced

in the

# mg. p e r 100 gm.

as l a r g e

a n d c od

as t h e l e v e l

of

m u s c l e s o f l a m b s on d i e t A a l o n e o r d i e t A
or d i e t A p l u s
c a n be

cod l i v e r

oil.

c o n c l u d e d a b o u t t h e magnesium c h a n ­

l a m b s * h e a r t by t h e E - d e f i c i e n t d i e t A,
of fresh t is s u e

(muscle)

- 129 because

the

high value

a n i m a l No. 7 d o e s
i um

(20#)

alpha

of th e

tocopherol
L a mb s

m entations
in the

c o n t r o l lambs Nos.

of magnes­

20 a n d 21 f e d d i e t B p l u s

( T a b l e XX).

showed l i t t l e

difference

or with the s e v e r a l

supple­

i n t h e i r magnesium c o n t e n t

E x p e rim e n ta lly produced v itam in E d e f ic ie n c y

t h e amount of p h o sp h o ru s

of E -d e fic ie n t

c re a se of phosphorus

In f ie ld

and h e a r t

( a b o u t 15$ a v e r a g e )

but c o n sis te n t

in­

However,

changes in th e phos­

s k e l e t a l m uscles did not occur a t a l l

in

i n v i t a m i n E.

cases of v itam in E d e fic ie n c y ,

marked changes i n the
m uscles.

skeletal

i n t h e h e a r t m u s c l e o f l a m b s made E d e f i ­

content of the

lambs d e f i c i e n t

in the

anim als very l i t t l e .

b y f e e d i n g d i e t s A o r B.

content

t h e r e w e r e more

of phosph orus of t h e

They c o n t a i n e d an a v e r a g e

changes o c c u rrin g in
cases)

control

not agree with the average le v e l

T h e r e was a s m a l l

phorus

of the

chemical a n a l y s i s .

affected

cient

(44#)

fed the b a sa l d i e t B alone

Phosphorus:

muscle

o f magnesium

skeletal

613# (T able X V I I I ) .

the h e a r t muscle of s t i f f

lambs

The

(field

a n d E - d e f i c i e n t e x p e r i m e n t a l a n i m a l s w e r e o f t h e same

m agnitude.
M ineral

ratios:

e a c h one o f t h e
greatest ratio

Mineral

ratios

elements analyzed

wer e

calculated

between

( T a b l e s XXI a n d X X I I ) .

The

c h a n g e o c c u r r i n g i n E - d e f i c i e n t l a m b s was i n t h e

Ca/Mg a n d t h e n i n t h e
# mg. p e r 1 0 0 gm.

ratio

o f Ca t o P .

of fre s h t i s s u e

But,

(muscle)

in th e case of

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- 132 lambs fed
ratio

cod l i v e r

oil,

the l a r g e s t a l t e r a t i o n

C a / N a , w h i c h was t h i r d

m e n ta lly E - d e f i c i e n t lambs.

in importance
The r a t i o

was i n t h e

in the other e x p e r i­

o f Ca t o K was a l s o

m odified.
In the
follow s:

hearts,

C a / Mg ,

In

the

Ca/K,

summar y t h e

characterized

o r d e r of r a t i o
Ca/P and Ca/Na.

chemical

in the

d i s t u r b a n c e was a s

changes of the muscles

f o l l o w i n g manner.

Thigh m u s c le s showed,

in general,

an i n c r e a s e

tent

o f c a l c i u m and sod iu m and a d e c r e a s e

diet

B,

the anim als a decrease

C o r t i s o n e was p r o t e c t i v e

to

calcium,

the

m ineral

con­
When

was f e d t o
Prostig-

sodium and p o t a s s i u m .

to potassium ,

p o t a s s i u m and magnesium.
normal

lard,

i n m a g n e s i u m was a l s o n o t i c e d .

m i n e wa s f o u n d p r o t e c t i v e

reversed to

in the

in potassium.

co n tain in g a m olecularly d i s t i l l e d

protected

c a n be

whereas

c od l i v e r

Alpha tocopherol

com position of the

oil

therapy

skeletal

m u s c le s w i t h magnesium as t h e o n ly e x c e p t i o n .
The c h a n g e s
we r e d i f f e r e n t ,
'When d i e t A,

i n the h e a r t muscle of E - d e f i c i e n t a n im a ls
a c c o rd in g to the type of d i e t

c o n t a i n i n g commercial l a r d ,

content of the

heart

m u s c l e was n o r m a l ,

wa s l o w a n d t h e p h o s p h o r u s l e v e l
tation

o f cod l i v e r

oil

largely

(A o r B) f e d .

was g i v e n t h e

calcium

but the potassium le v e l

s lig h tly high.
increased

the

The s u p p l e m e n ­

calcium content

of the h e a r t .
D i e t B,
increased

the

c o n ta in in g the m olecularly d i s t i l l e d
c a lc iu m and lo w e re d t h e p o t a s s i u m

lard,

greatly

content of the

- 133 heart.
sition
the

Lambs r e c o v e r e d from E d e f i c i e n c y had a m i n e r a l
sim ilar

to the

sodium c o n t e n t ,

control

animals with the

compo­

exception of

w h i c h was r a t h e r h i g h .

S t u d i e s o n t h e Ami no A c i d C h a n g e s i n t h e S k e l e t a l
and H e a r t M uscles due to V itam in E D e f i c i e n c y
The r e s u l t s
for

of the m icro b io lo g ical

t h e amino a c i d s p r o l i n e ,

are presented

i n Table XXIII.

have been c a l c u l a t e d
Again,
cal

in t h i s

analysis

leucine

and i s o l e u c i n e

The q u a n t i t i e s

o f a mi no a c i d s

i n mg. p e r 100 mg.
case,

because

the h e te ro g e n ie ty
grees

glycine,

the

it

is

small

n u mb e r o f s a m p l e s p e r

w i t h i n each group,

some l i g h t

occurring

in

on t h e

of muscle.

not p o s s ib le to apply s t a t i s t i ­

of vitam in E d e fic ie n c y .

do t h r o w

a n a l y s i s of the muscles

group and

due t o t h e d i f f e r e n t

In spite

of t h i s ,

de­

the f i g u r e s

n a tu re of the muscular changes

the absence of vitam in E in the d i e t .

1-Proline:
The c o m p a r i s o n b e t w e e n t h e p r o l i n e
h e a r t muscles of c o n t r o l s
o r B showed t h a t

relationship

Skeletal

m uscles of f i e l d

of

control

on t h e p r o l i n e

of proline,
lambs,

and E - d e f i c i e n t

anim als fed d i e t s A

v i t a m i n E d e f i c i e n c y d i d n o t have a d i r e c t

indirect

a low v a lu e

v a l u e s o f t h i g h and

c o n te n t of the m u scles.

c a s e s o f v i t a m i n E d e f i c i e n c y showed

0.59^ as

compared to t h e

0 . 8 0 ^ i n d i e t s A a n d B.

& mg. p e r 1 0 0 mg.

or

o f muscle

average values

-

134

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- 1 36 -

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- 137 -

Animals
content

treated

in the

w ith c o r t i s o n e had h i g h e r

t h i g h muscles th an c o n tr o l an im als;

compared to 0 .8 0 # .

Yet,

the h e a r t muscle of t h e

s h o w e d no c h a n g e i n p r o l i n e
(Av. 1.02#-) w h e r e a s t h o s e
1.02#,

(double) p r o l i n e

and 1 .3 3 #

content.

It

1.09# as

same a n i m a l s

was 0 . 9 9 a n d 1 . 0 5 #

of the c o n tro l

a n im a ls were 1 . 0 8 # ,

(Av. 1 . 1 4 # ) .

1-G lycine:
The g l y c i n e v a l u e s o f t h e s k e l e t a l

and h e a r t m uscles of

v i t a m i n E - d e f i c i e n t a n i m a l s fed e i t h e r d i e t s A o r B or o f t h e
field

c a s e s were not d i f f e r e n t

N otw ithstanding,
and

the

from t h o s e

of c o n tr o l lam bs.

combined a c t i o n of v i t a m i n E d e f i c i e n c y

cod l i v e r o i l lo w e re d th e g l y c i n e

m u s c l e s b u t t h e i r a c t i o n was l a r g e l y

c o n t e n t of t h e
counteracted

skeletal

by a l p h a

tocopherol

feeding.

The g l y c i n e v a l u e a v e r a g e d 1 . 0 6 # a n d 0 . 8 6 #

in control

a n i m a l s , 0 . 8 2 # i n lambs fed d i e t A supp lem en ted w i t h

cod

liver

o i l and 0 . 9 8 # i n lam bs f e d

d i e t A supplemented w ith

cod

liver

o i l and a l p h a t o c o p h e r o l .

However,

tent

o f h e a r t m u s c l e was t h e same i n d e f i c i e n t

the

glycine

con­

and c o n t r o l

anim als•
1-Leuci ne:
Th e l e u c i n e

c o n te n t of s k e l e t a l

and h e a r t m u sc le s o f E-

d e f i c i e n t a n i m a l s was f o u n d l o w e r t h a n c o n t r o l

lambs.

f e r e n c e wa s n o t v e r y d i s t i n c t when d i e t A was f e d ,
w e l l m a r k e d when t h e d i e t B was g i v e n .
the leu cin e

Thus,

The d i f ­

but i t

became

i n T a b le XXIII

v a l u e s o f lambs fed d i e t B a v eraged 1.07# i n s k e l e t a l

# mg. p e r 1 0 0 mg.

of muscle

- 138 -

m u s c l e s and 1 . 1 6 # i n h e a r t m u scle.
control

lambs

skeletal

for

and h e a r t m u sc le s.
oil

supplem entation a c c e n tu a te d the low ering

o f v i t a m i n E d e f i c i e n c y on t h e

skeletal

values of the

f o r d i e t B we r e 1 . 3 4 # a n d 1 . 7 5 # r e s p e c t i v e l y

Cod l i v e r
effect

The l e u c i n e

muscles

(Av.

p e r h a p s was p a r t l y

leucine

neutralized

le u c in e le v e l of the

content

0.95#).

But, i t s

action

by t h e f e e d i n g o f a l p h a t o c o ­

p h e r o l a s d e m o n s t r a t e d by t h e v a l u e 1 . 1 2 # o f t h e gr oup r e c e i v i n g
d ie t A plus

a l p h a t o c o p h e r o l and cod l i v e r

Prostigm ine
action

on t h e l e u c i n e

quantities
control

of leu cin e

and d e f i c i e n t

observed in the
I n the
the le u c in e
those

and c o r t i s o n e
level

se eme d t o

in the

oil.

exert a protective

skeletal

m uscles,

since

the

we r e i n t e r m e d i a t e

between th e v a lu e s of

anim als.

effects

Sim ilar

c o u l d n o t be

case of h e a r t muscle.

case

o f lambs d e f i c i e n t

v a lu e s of

skeletal

of c o n tr o l lambs,

on a n a t u r a l

feed r a t i o n ,

m u s c l e s were n o t d i f f e r e n t

but the h e a rt

contentof le u c in e

from
s e e me d

t o be l o w e r t h a n n o r m a l .
1-Isoleucine;
Lambs f e d d i e t A s howed a l o w e r i n g o f t h e i s o l e u c i n e
t e n t of the
0.77#

skeletal

m u s c l e s from 0 . 8 7 #

( d e f ic ie n t lam bs).

o f cod l i v e r

oil,

average of 0.59#.

This e f f e c t

(control

was e n h a n c e d by t h e

which low ered the i s o l e u c i n e
Alpha to c o p h e ro l,

# mg. p e r 1 0 0 mg. o f m u s c l e

anim als)

however,

content

con­
to
feeding

to an

a g a i n s e e me d t o

- 139 -

offer

protection

to the

detrim ental

effect

o f cod l i v e r

a s e v i d e n c e d by t h e a v e r a g e c o n t e n t o f i s o l e u c i n e
the

group fed

d ie t A p lus alpha tocopherol

The i s o l e u c i n e
d i e t A were l e s s
average

than in s k e le ta l

m uscles.

levels

vered 0.92#.
thus
in

c o n te n t of

skeletal

showed t h a t

isoleucine

Thus,

the

o f t h e c o n t r o l lamb s 1 . 0 3 # and t h o s e r e c o ­

In th e h e a r t muscle s i m i l a r

the average

control

muscles of anim als fed

c h a n g e s were n o t i c e d ;

c o n t e n t o f t h e l a m b s f e d d i e t B was 0 . 8 8 # ,

c o n t r o l s 1 . 1 1 # and 0 . 9 3 # i n t h e r e c o v e r y

res

The

p r o d u c e d by t h e d i e t B

w e r e mor e m a r k e d t h a n t h o s e p r o d u c e d by d i e t A .

d i e t B wa s 0 . 6 8 # ,

oil.

group fed d i e t A p lu s alp h a to c o p h e r o l.

The c h a n g e s i n i s o l e u c i n e

isoleucine

of

of lambs fed

c o n t e n t o f d e f i c i e n t m u s c l e s was 0 . 9 0 # i n t h e

group and 0 .9 1 # i n th e

average

(0.75#)

a n d c od l i v e r

changes o f th e h e a r t muscle

extensive

oil,

group.

v ita m in 2 d e f i c ie n c y lowered

of both s k e le ta l

r e c o v e r y from the

deficiency

and h e a r t

the

These f i g u ­

content of

m u s c l e s and t h a t

i s also r e f le c te d

the

in the c o n te n t

of i s o l e u c i n e .
The e f f e c t
isoleucine
the

case

could

of h e art

deficient

and c o r t i s o n e

n o t be fo u n d i n t h e
m uscle,

prostigmine

skeletal

c i e n t lambs
isoleucine
per

On t h e

o th e r hand,

cortisone

d i d n o t p r o d u c e any f u r t h e r
content.
1 0 0 mg.

of muscle.

on t h e

content of

muscles b u t,

injections

in v itam in E lowered the is o le u c in e

(Av. 0 . 6 0 # ) .

# mg.

of prostigm ine

in

in animals

content

injections

e v e n mor e
to E - d e f i ­

m o d i f i c a t i o n of th e

- 140 Field
different

cases

of E d e f ic ie n c y

from t h o s e

I n summary,
cine

the d e fic ie n cy

and i s o l e u c i n e

isoleucine

of c o n tro l

anim als

c o n t e n t were a l t e r e d

in e ith e r

d i e t A o r B.

of vitam in E decreased the le u ­

content of the

co n ten t of

The s e v e r i t y

d i d n o t show i s o l e u c i n e v a l u e s

the h e a r t .

skeletal
N either

muscles,

and t h e

the p r o lin e

or glycine

by t h e E d e f i c i e n c y .

o f t h e E d e f i c i e n c y was m o s t p r o n o u n e e d when

d i e t B was f e d .
Cod l i v e r
by t h e

oil

decrease

decrease

in the

in the

glycine

reversed

isoleucine

o f cod l i v e r

feeding.

the actio n

effect

on v i t a m i n E s hown

g l y c i n e a n d by t h e l a r g e r

oil

c o n te n t of s k e l e t a l

by a l p h a t o c o p h e r o l
partly

co n ten t of

l e u c i n e and i s o l e u c i n e

The l o w e r i n g e f f e c t
E on t h e

had an a n t a g o n i s t i c

content of the muscles.

in the absence of vitam in
m u s c l e s was c o u n t e r a c t e d

Alpha to c o p h e r o l,

o f cod l i v e r

oil

tion,

and

c o n te n t of t h e la m b 's muscle.

and i s o l e u c i n e

cortisone

skeletal

only

on t h e l e u c i n e

P r o s t i g m i n e and c o r t i s o n e had a p r o t e c t i v e
leucine

however,

level

caused the

m uscles.

of the

increase

effect

s k e l e t a l muscles.
of t h e p r o l i n e

on t h e
In addi­

level

of

DISCUSSION
Growth:
I n t h e p r e s e n t work t h e w e i g h t
indicated
findings

that

often

vitam in E d eficiency reta rd ed

do n o t c o n f i r m

who r e p o r t e d

that

the

growth#

clearly

These

t h e o b s e r v a t i o n o f W i l l m a n ejb al_.

best

d e v e l o p e d lam bs were a f f e c t e d

(1934)
more

by v i t a m i n E d e f i c i e n c y #
It

on t h e

was a l s o

found,

in regard to the

g row th of young lam b s,

wa s a v e r y i m p o r t a n t
chem ical d i f f e r e n c e
ber,

c u r v e s of th e lambs

before

factor*

that
This,

between the

and a f t e r

the type

a detrim ental

effect

lard*

in the d ie t

was due t o

the

A high peroxide

num­

of a e r e a t i o n a t a p p r o x i m a t e l y

9 8 ° C . , was t h e m o s t i m p o r t a n t d i f f e r e n c e
distilled

of l a r d

no d o u b t ,

two l a r d s *

four hours

and m o l e c u l a r

i n f lu e n c e of v ita m in E

between the

commercial

P e r o x i d e s seemed t o h a v e p r o d u c e d

on g r o w t h b e c a u s e

rancid f a t ,

a product

having a high c o n c e n tr a tio n of p e ro x id e s,

not on ly had been

s h o wn d e s t r u c t i v e

t o hav e an i n t r i n s i c

to v itam in E but,

t o x i c a c t i o n on t h e
However,

animal

Dam ( 1 9 4 9 )

containing thoroughly
exudative’ d ia th e s is
p r o d u c e d by d i e t s
He a l s o
before
produce

either

has r e p o r te d
cod l i v e r

that
oil

chickens fed d i e t s
did not c o n tr a c t

encephalom alacia, d iseases

containing highly unsaturated

found t h a t
t h e y were

( F i t z h u $ i e t _ al_. 1 9 4 4 ; Q u a c k e n b u s h 1 9 4 5 ) .

rancid

or

also,

if

the u n s a tu r a te d

consumed

disease.

(peroxide

fatty

constantly

fatty

acids#

a c i d s were o x i d i z e d

form ation),

they did not

- 142 In spite
secondary in
chicken,

of the

f a c t t h a t p e r o x i d e s were

the developing of vitam in E d e fic ie n cy in the

there

is

no d o u b t t h a t

t h e y were i m p o r t a n t i n t h e

p r o d u c tio n of v ita m in E d e f ic ie n c y of
fatty

c o u l d n o t have

d e fic ie n c y because

the

th e lamb.

a c i d s may a l s o p l a y a s i m i l a r r o l e ,

experim ent they

and,

considered

even more,

both la r d s

the

a cid value

m olecular d i s t i l l e d

lard

but in the p re s e n t

influenced
had v e r y
(free

the

severity

sim ilar

fatty

than in the

The u n s a t u r a t e d

of the

iodine v alues

acids)

was l o w e r i n

commercial l a r d .

A q u e s t i o n h a s been r a i s e d as to w h e th er or not the
of alpha

tocopherol

counteract

the

be d e f i n i t e l y
c a n be

stated,

given to

effects

c o n t r o l l a m b s was a b l e t o

of the p e ro x id e s.

a n s w e r e d on t h e b a s i s o f
however,

c o n t r o l lambs p r e v e n t e d
the appearance

the

that

amount

the alpha

This q u e stio n cannot

the p r e s e n t d a ta .
tocopherol

It

given to the

t h e s ympt oms o f v i t a m i n E d e f i c i e n c y ,

o f macro and m i c r o s c o p i c a l l e s i o n s

typical

vitam in E d e fic ie n c y ,

and k e p t a l l

ponents of the

u r i n e and m u sc le s w i t h i n t h e normal ra n g e

blood,

r e p o r t e d i n h e a l t h y young lam bs.
alpha

tocopherol

Y et,

in the

fed the d i e t

the milk fe e d in g ,

gastrointestinal

the d e le te rio u s

g r o w t h wa s e v i d e n t
mals

Probably the

tract

com­

success of the

s u p p l e m e n t a t i o n wa s d u e t o t h e f a c t

was g i v e n s o m e t i m e a f t e r
destruction

the an aly ze d chemical

of

that

which saved i t

it
from

(M atill 1938).

a c t i o n o f t h e p e r o x i d e s on t h e l a m b ' s

by c o m p a r i n g t h e
c o n ta in in g the

growth r a t e

commercial l a r d

of c o n tro l a n i ­
with c o n tr o ls

- 143 fed the d ie t
first

co n ta in in g the m olecular d i s t i l l e d

o n e s grew f a s t e r

than the

second.

be r e c o g n i z e d t h a t t h e l o w g r o w t h r a t e
m e n t was d u e t o t h r e e
growth d e p re s s iv e
lard

and the

reasons:

lard.

The

Consequently, i t
o f lambs i n t h i s

t h e a c t i o n o f v i t a m i n E,

e f f e c t of peroxides

must

experi­
the

in the m olecular d i s t i l l e d

f o u r t i m e s a day f e e d i n g r e g i m e n .

Symptoms:
The

fact

t h a t the

ment d e v e l o p e d
the e x is te n c e

v i t a m i n E - d e f i c i e n t lambs of t h i s

m uscular weakness r a t h e r
of an a n t i - s t i f f n e s s

factor

mi n E d e f i c i e n c y a s s e e n i n f i e l d c a s e s
On t h e b a s i s
nature

of our p r e s e n t knowledge,

of t h i s

the e ff e c t

of

anti-stiffness
steroid

than s t i f f n e s s

factor

experi­
suggested

associated with v i t a ­

of " s t i f f - l a m b "
several

h y p o t h e s e s on t h e

c a n be ma de .

and of c e r t a i n m in e r a l

disease.

Among t h e m ,

e le m e n ts were t h e

most a t t r a c t i v e .
Extensive

i n v e s t i g a t i o n h a s b e e n c a r r i e d o u t by v a n w a g t e n -

donk and Wulzen
by g u i n e a p i g s
ample amounts

(1950)

to

o f v i t a m i n E and a s c o r b i c a c i d .

those

diets,

The e f f e c t

c o mp o u n d was o f a s t e r o i d n a t u r e .
that

the

shown

containing

In sp ite

of t h e

steroid

a c i d d e f i c i e n c y and o t h e r s

of s e v e r a l

s u g a r c a n e a n d r a w c r e a m on d e f i c i e n t

bolism in d ic a te d

syndrome

some o f t h e l e s i o n s p r o d u c e d were

oocurring in ascorbic

to v itam in E d e p le ti o n .

the

stiffness

when t h e y w e r e f e d s k i m m i l k d i e t s

co m p o sitio n of the
sim ilar

in re g a rd to the

extracts

from

guinea pigs suggested t h a t
Studies

on t i s s u e

meta­

s u b s t a n c e s p l a y e d an i m p o r t a n t

- 144 role

in the

adenylic

energy metabolism through i t s

atiff

on t h e

system .

Excessive
in

influence

calcification

guinea pigs

o f t h e m u s c l e s was a l w a y s p r e s e n t

deficient

in stero id s.

T h is has been

explained

by v a n W a g t e n d o n k a n d W u l z e n ( 1 9 5 0 ) who c o n s i d e r e d i t

dependent

on t wo f a c t o r s ,

the

b lo o d and t h e

in the

tissues.

influenced

t h e low c o n c e n t r a t i o n o f a l b u m i n i n

increased

c o n c e n tra tio n of in organic phosphate

These w o rk ers f e l t

by t h e a n t i - s t i f f n e s s

c a l c i u m and p h o s p h o r u s

that

the l a t t e r

f a c t o r was

f a c t o r and the u n b a l a n c e o f

( l o w C a /P r a t i o )

i n the

diet.

Van W a g t e n d o n k a n d W u l z e n ( 1 9 5 0 ) p r o p o s e d t h e f o l l o w i n g
mechanism f o r t h e p r o c e s s of c a l c i f i c a t i o n :
the

anti-stiffness

factor,

l a r g e p ro p o rtio n s of the p r o te in

bound c a lc iu m were l i b e r a t e d which,
c o n c e n tra tio n of in o rg an ic
a colloidal
There
t& t h e
ease

a great

steroid

of sheep

quirem ent of

of m inerals

to the

between the f i n d in g s r e l a t e d

(s)

ration.
for

a p p e a lin g and s u g g e s ts f u r t h e r
work a l s o p o i n t s

the n u t r it io n

investigation.

need f o r

dis­

For t h i s r e a s o n t h e r e ­
of the lamb i s
Van W a g e n d o n k * s

res ea rch concerning the e f f e c t

i n t h e r a t i o n and b l o o d p r o t e i n

p ro cess of c a l c i f i c a t i o n

form ation of

i n g u i n e a p i g s and " s t i f f - l a m b "

fed a n a t u r a l
such f a c t o r

favored the

complex.

sim ilarity

deficiency

coupled with the h ig h er

phosphate,

calcium phosphate
is

due t o t h e l a c k o f

components on t h e

o c cu rrin g in vitam in E d e f i c ie n t lambs.

- 14 5 Marsh
the

(1932)

"stiff-lam b"

suggested th a t
disease,

but i t

the r a tio

was n o t u n t i l

and c o -w o rk e rs

s e t up e x p e r i m e n t a l

this

They fo u n d t h a t b a l a n c i n g

problem.

"stiff-lam b
nificantly

ration"

with dibasic

influence

conditions

could a f f e c t
1939 t h a t W illman

fo r the study of

the r a t i o

Ga/P o f t h e

sodium p h o sp h a te d id not s i g ­

t h e o c c u r r e n c e o f lamb s t i f f n e s s .

Their experiment
was c a r r i e d

C a /P

c a n n o t be c o n s i d e r e d

conclusive

since

o u t w i t h s u c h a s m a l l number o f a n i m a l s a n d i t wa s

difficult

to

rations.

In ad d itio n ,

control

by Hogan a n d Regan

the

in flu e n ce of o th e r fa c to rs

investigation carried

(1946)

in natural

o u t on o t h e r a n i m a l s

h a v e shown t h a t l o c a l i z e d

d e p o s its of

c a l c i u m p h o s p h a t e a p p e a r e d i n b one a n d m u s c l e s o f a n i m a l s
an excess

"stiff-lam b"

disease

strictly

stance

the use

investigate

the

of the fa c to rs

w o u l d be a n i n t e r e s t i n g

controllable

experimental

to

concerned
problem to

conditions.

in
study

For i n ­

of p u rifie d

d i e t s w o u l d be v e r y v a l u a b l e t o

influence

o f c a l c i u m a n d p h o s p h o r u s on t h e

development of v ita m in E d e f i c ie n c y .
ficant

fed

of phosphorus.

Th e i n d e p e n d e n t i n f l u e n c e

under

it

study under these

M a g n e s i u m w o u l d be s i g n i ­

c o n d itio n s because

it

i s knov^n t o

be a n i m p o r t a n t f a c t o r i n a b n o r m a l m u s c u l a r and bone c a l c i f i c a ­
t i o n as has

b e e n d e m o n s t r a t e d by O r e n t ,

T u f ts and G reen b erg
also

(1936)

w o u l d be o f i n t e r e s t

a n d Moor e e t a l .
because i t s

to b rin g alo n g muscular p a r a ly s is
1946).

K r u s e a n d McCol l um ( 1 9 3 4 ) ,
(1938).

Potassium

d e p l e t i o n ha s b e e n shown

( Ru e g a me r e_t al_. 1 9 4 6 ;

B erlin

- 146 One o f t h e m o s t i n t e r e s t i n g
r e g u la r appearance
lam bs,

since

all

of h eart

injuries

is

difficult

of the

to

so-called

m u s t be s t a t e d

It

the older

quite

w e r e mor e f a v o r a b l e

for

that

of other

ed i n

did not allow for

strict

of the r a t i o n .

in the p r e s e n t study c o n d itio n s

support to t h i s

injury;

the

explanation

since

t h e s y mpt oms o f v i t a m i n E d e f i c i e n c y

c h i c k e n d e p e n d e d on t h e

iodine

number o f t h e f a t

contain­

the d i e t .
This reaso n in g ,

cardiovascular
lated

it

fa c to rs present in the natural ra tio n .

wa s d e m o n s t r a t e d t h a t

in the

However,

c o u l d h a v e b e e n m o d i f i e d by t h e

The w o r k o f Dam ( 1 9 4 4 b ) g i v e s
it

disease.

d ifferen t m anifestations

th e p r o d u c t i o n of h e a r t

vitam in E deficiency e ffe c t
interaction

"stiff-lam b"

in o ther c o n s titu e n ts

possible

heart

work on t h i s p r o b l e m , u s i n g

feed in g re d ie n ts ,

of v a ria tio n s
is

of the

that

v ita m in E d e f i c i e n c y in the lamb.

that

wor k wa s t h e

in vitam in E -d e fic ie n t

finding in

explain a ll

m ixtures of n atu ral
control

of t h i s

p r e v i o u s r e p o r t s had i n d i c a t e d

d a ma g e was o n l y a n o c c a s i o n a l
It

findings

lo g ic a lly leads

to a c o n s id e r a tio n of

d i s e a s e s i n t h e h uma n,

some o f w h i c h may be r e ­

to v i t a m i n E.
Due t o t e c h n i c a l

humans,

it

schools

of th o u g h t to

in experiments

has been extrem ely d i f f i c u l t

min E on t h e
laborators

lim itation

cure

importance of v i t a ­

disease*

found v ita m in E a very u se fu l

o u t on

t o g e t t h e two d i f f e r e n t

concur concerning the

of card io v ascu lar

carried

tool

Shute and c o l —
in the treatm ent

- 147 of c e r ta in h e a rt

diseases^*;

w h e r e a s o t h e r w o r k e r s h a v e s hown

t h a t v i t a m i n E does n o t have a b e n e f i c i a l
cardiovascular diseases reported
Many a n i m a l

a c t i o n in the

same

by S h u t e ^ .

s p e c i e s have been found to r e q u i r e v i t a m i n E

f o r t h e p r e v e n t i o n o f a numbe r o f d i s o r d e r s r e l a t e d t o t h e
circulatory,
excretory
respect,

m uscular,

system.

Therefore,

it

is

nervous,

the ph y sio lo g ical

very u n lik e ly th a t ,

of t h i s

and o t h e r r e c e n t

i m p o r t a n c e o f v i t a m i n E,

the t h e s i s

and
in th is

one o f i t s

such c a se s,

the

i n v e s t i g a t i o n s of
one i s

th a t vitam in E d efic ie n cy ,

a ss o c ia te d with vitam in E deficiency,
and t h a t

digestive

t h e human c o u l d be a n e x c e p t i o n .

In the l i g h t

support

reproductive,

m anifestations

in c lin e d to

or a c o n d itio n

may o c c u r i n t h e huma n ;

could in v o lv e the h e a r t .

vitam in E deficien cy

In

no d o u b t m i g h t be a l l e ­

v i a t e d by t r e a t m e n t w i t h a n a c t i v e f o r m o f v i t a m i n E w h i c h t h e

1 V o g e l s a n g , A. B . , E. V. S h u t e a n d W. E . S h u t e ( 1 9 4 8 ) p r o ­
p o s e d t h a t v i t a m i n E may p l a y a h e l p f u l r o l e w h e r e v e r b e t t e r
c a p i l l a r y c i r c u l a t i o n or oxygen u t i l i z a t i o n can improve any
p ath o lo g ical condition lik e :
indolent u lc e rs, a r t e r io s c l e ­
r o t i c g a n g re n e , t h r o m b o p h l e b i t i s , p h l e b o t h r o m b i t i s , thromb o a n g itis o b l i t e r a n s , m azoplasia, c ereb ra l throm bosis,
n e u t o c i r c u l a t o r y a s t h e n i a , n e p h r i t i s , p u r p u r a , and h e a r t
disease.
I n t h i s l a s t d i s e a s e he r e p o r t e d impro ve me nt i n
80% o f t h e c a s e s .
^ D i s c u s s i o n o f E. V. S h u t e ' s p a p e r :
" N o t e s on t h e Use o f
A l p h a - T o c o p h e r o l i n t h e Ma n a g e m e n t o f A c u t e a n d S u b a c u t e
V a sc u la r O b s tr u c tio n as well as in B urns", p re s e n te d a t th e
1 9 4 9 I n t e r n a t i o n a l C o n v e n t i o n on v i t a m i n E . ( S h u t e 1 9 4 9 ) .

- 148 human o r g a n i s m
• Si nc e i t
c o u l d be t h e

could r e a d i ly m etab o lize1 .
seems d o u b t f u l

th a t vitam in E d e fic ie n cy alone

cause of th e h e a r t

diseases

in question,

it

t h a t v i t a m i n E t h e r a p y c a n n o t a l w a y s be a n e f f e c t i v e
Therefore,

until

o c a lly as the

cause of

Vogelsang e t a l .
b u t not a cure
At the
observe
cle

the

vitam in E deficien cy

(1947)

for heart

that

treatm ent.

c a n be i d e n t i f i e d

some h e a r t a i l m e n t s ,

follow s

unequiv­

we m u s t a g r e e w i t h

" v i t a m i n E i s a mode o f t r e a t m e n t

disease".

b e g i n n i n g o f t h e e x p e r i m e n t i t was i n t e r e s t i n g
c o n sta n t appearance of l e s io n s

of the h e a r t

in the r i g h t

in th e v ita m in E - d e f i c i e n t lambs.

ventri­

The same

findings

h a d b e e n m e n t i o n e d i n t h e r e p o r t o f W i l l m a n ejt al^

(1945).

However,

t h e phenomenum.

no e x p l a n a t i o n h a s b e e n p r e v i o u s l y g i v e n t o
One m i g h t p o s t u l a t e

macroscopic l e s io n s
difference

t h a t the presence of

only in the r i g h t v e n tr ic le

was d u e t o t h e

o f m u s c u l a r m a s s b e t w e e n t h e two v e n t r i c l e s .

haps a t h i n n e r

to

muscular wall

c o u l d be a f f e c t e d e a s i e r

Per­

than a

t h i c k one.
B u t t h e r e w e r e o t h e r d i f f e r e n c e s b e t w e e n t h e r i g h t a nd
left

v e n t r i c l e s w h i c h s h o u l d be c o n s i d e r e d s u c h a s t h e

ences in both mineral

differ­

c o m p o s i t i o n and v a s c u l a r i z a t i o n o f b o t h

ventricles.
1 ^ I p h a t o c o p h e r o l may n o t a l w a y s be t h e m o s t a c t i v e v i t a m i n iii
c o mp o u n d f o r t h e c u r e o f v i t a m i n E d e f i c i e n c y .
M ilh o ra t and
c o —w o r k e r s ( 1 9 4 9 ) f o u n d t h a t a l p h a t o c o p h e r o l o r i t s e s t e r s
were i n e f f e c t i v e i n p a t i e n t s w ith p r o g r e s s iv e m uscular dys­
t r o p h y ,whSf©Jas d l —a l p h a —t o c o p h e r y l h y d r o q u i n o n e r e d u c e d c r e a t i n —
u r i a in p a t i e n t s w ith s i m i l a r d i s e a s e and in r a b b i t s d e f i ­
c i e n t i n v i t a m i n E.

- 149 Myers
higher

(1942)

reported

concentration

adenine

that

the l e f t

of c r e a t i n e ,

than the r ig h t

ventricle

p h o s p h o r u s , p o t a s s i u m and

ventricle.

Moe a n d V i s s c h e r

found t h a t the

Thebesian veins are r e l a t i v e l y

factors

n u t r i t i o n of the l e f t

in the

very im portant

in the

v e i n s empty i n t o
to the
right

is

intraventricular
embolism,

Thus,

whereas t h e y were

right heart.

the

d e p e n d e n t on f a c t o r s

pressure like m itral

(1940)

insignificant

chamber and t h e r e f o r e

changes of h e a rt lo a d s .
ventricle

heart,

n u t r i t i o n of the

the h e a r t

contained

These

are

subjected

n u t r i t i o n of the

affecting

stenosis,

the r i g h t

pulmonary

pulmonary f i b r o s i s .

A u t o p s y o f more v i t a m i n E - d e f i c i e n t l a m b s s howed t h e
in d is c rim in a te appearance
heart.

Consequently,

Was a f a c t o r

it

study of

both sid e s

of the

the t o t a l

heart.

relative

However,

size

the

of i n j u r e d

of pneumonia to t h e l o c a l i z a t i o n

the r ig h t v e n tr ic le
In s p ite
vitam in E to

bances

was r e a s o n e d t h a t p e r h a p s p n e u m o n i a

simul­
areas in

o f th e h e a r t and i n th e l u n g s d id not d i s c l o s e

relationship

sib ility

in both sid e s of the

p r o d u c i n g mor e m a r k e d sympt oms o f v i t a m i n E d e f i ­

ciency in the r i g h t side
taneous

of le s io n s

since

in the

1947 a nd 1 949)

of i n j u r i e s

in

the r e l a ti o n s h i p

of

of th e h e a r t.

of these
the

any

negative

circulatory

findings

system s t i l l

s e e ms t o be a p o s ­

v ita m in E d e fic ie n c y produces v a s c u la r
chicken

(Pappenheimer 1939)

and in th e r a t

distur­

i n t h e dog ( Hol man

( T e l f o r d ej^ al_. 1 9 4 5 a n d Mason

- 150 1943)

and i n t h e g u i n e a p i g

S l a g s v o l d a n d L u n d —L a r s e n
capillary
was a l s o

(1934)

found i n

Moreover

observed the presence

b l e e d i n g a n d e d e ma a t a u t o p s y o f s t i f f

experim ent.
(1950)

(Farmer e t a l . 1 9 5 0 ).

lambs,

(1947), Vogelsang

concluded t h a t vitam in E brin g s about c l i n i c a l

proposed th a t
cap illaries,
fluence

which

some o f t h e v i t a m i n E - d e f i c i e n t l a m b s o f t h i s

F u r t h e r m o r e V o g e l s a n g et_ a l ^

ment o f p a t i e n t s

of

suffering

from c a r d i o v a s c u l a r

v i t a m i n E a c t e d by:
direct

improve­

diseases.

They

p r o l i f e r a t i n g or r e o p e n i n g

n o r m a l i z i n g e f f e c t on t h e m y o c a r d i u m ,

in­

on t h e p a c e m a k e r o f t h e h e a r t a n d by d i r e c t a c t i o n on

throm bi.
The d a t a on t h e a r t e r i a l
support to

the

blood p r e s s u r e gives a d d i t i o n a l

im portance of th e

circulatory

system i n t h e

d e v e l o p m e n t o f t h e v i t a m i n E d e f i c i e n c y . . Lambs s h o w i n g t h e
symptoms o f v i t a m i n E d e f i c i e n c y had low d i a s t o l i c
blood p re ssu re
This p re v io u s
of the

after

a short period

increase

sonable e x p la n atio n at
o c c u r r in g in the
related

to

the

the

findings

the

mome nt ,

the a p p earan ce

since

none o f t h e c h a n g e s

v i t a m i n E d e f i c i e n c y was s y n c h r o n o u s w i t h o r
changes.

The l o w b l o o d p r e s s u r e ,

d e f i c i e n c y was w e l l a d v a n c e d ,

of T e lfo rd et a l .

E -deficient ra ts ,

before

symptoms, do e s n o t b e a r any r e a ­

blood p ressu re

r e c o r d e d when t h e

of high blood p r e s s u r e .

of blood p re s s u re ,

vitam in E -d eficien cy

and s y s t o l i c

( 1 9 4 5 ) who, w o r k i n g w i t h v i t a m i n

found t h a t a f t e r

d u c t i o n o f 2 9 . 4% o f s y s t o l i c

coincided with

one y e a r t h e y showed a r e ­

blood p r e s s u r e as compared t o normal

- 151 -

rats

of s im ila r age.

of the lambs
cient

In th is

work t h e a v e r a g e b l o o d p r e s s u r e

d r o p p e d 16% i n o n l y 69 d a y s on a v i t a m i n E - d e f i -

diet.
A ccording to

the p re s e n t knowledge,

there

are

two p o s s i b l e

ways by w h i c h t h e

d e f i c i e n c y o f v i t a m i n 2 may a l t e r

the

pressure.

(1949)

in blood

pressure

Ruppel

was d u e t o t h e

the muscles
the

(1950).

changes ta k in g place

skeletal

c o u l d be d e r i v e d

for

inhibited
the

s tu d ie s t h a t alpha

restraint

of h y p e rte n sin .

be d u p l i c a t e d

in the

way o f e x p l a i n i n g
deficiency,

that

the

s u c h _in v i t r o

be e s s e n t i a l

to

Therefore,

it

a c t i o n of v ita m in E could

l i v i n g organism.

T h i s would p r o v i d e a n o t h e r

low ering of blood p ressu re

provided hypertension

The l a r g e r

t h e g r e a t e r was t h e

o f h y p e r t e n s i o n by h y p e r t i n s i n a s e .

c o u l d be p o s s i b l e

proven yet

and w h ite m u s c l e s .

t h e enzyme h y p e r t e n s i n a s e w h i c h

t h e amount o f a l p h a t o c o p h e r y l p h o s p h a t e ,
inhibition

in

f r o m t h e wo r k o f G r o x a t t o

T h e y s howed i n i n v i t r o

phosphate

was r e s p o n s i b l e

the decrease

w h i c h w o u l d become a s a f f e c t e d by

of vitam in E as the

A second e x p la n a tio n

tocopheryl

degenerative

of the v e s s e l s ,

deficiency

and Mois

believed th a t

blood

in vitam in E

c o u l d be d e f i n i t e l y

c ir c u la to ry hom eostasis,

shown t o

which has not been

(Braun-Menendez e t a l . 1946).

Pathology:
The m i c r o s c o p i c e x a m i n a t i o n o f t h e
cles
tally

revealed

that

the h is to p a th o lo g ic a l

s k e l e t a l a n d h e a r t mus­
alterations

experimen—

p r o d u c e d by t h e d e f i c i e n c y o f v i t a m i n £ we r e s i m i l a r

to

- 152 those

found in f i e l d

findings

c a s e s o f 11s t i f f - l a m b "

o f M e t z g e r a n d H a g a n ( 1 9 2 7 ) , W i l l m a n ejt al_.

S l a g s v o l d and L u n d - L a r s e n
the

identity

of the

the p a th o lo g ica l

of t h i s

This,

once m ore,

(1934) and
confirmed

disease.

s tu d y to

the b e t t e r

knowledge of

changes o o curring in vitam in E d e fic ie n c y

be s u m m a r i z e d a s :

c o n stan t appearance

from t h e

can

of h e art le s io n s pro­

e n d o c a r d i u m t o t h e e p i c a r d i u m w i t h o u t da ma g ­

ing the p u r k in je
degenerated

(1934).

"stiff-lam b"

The c o n t r i b u t i o n

gressing

d i s e a s e and t o th e

fibers

and th e ab sen c e of g i a n t

cells

in the

c ard ia c muscle.

Blood T ocopherol :
The g r e a t v a r i a t i o n
tocopherol

in the

of lambs p r o n o s t i c a t e d t h a t

of tocopherol

of to co p h ero ls.
experim ent.

T h i s was n o t p r o v e n t o be t r u e

to

disease

The t o t a l

only to

of tocopherol,

show v i t a m i n E i n s u f f i c i e n c y

nor in the l o c a l i z a t i o n
tocopherol

content

a l o n g e r time

the lower to co p h e ro l

in the p r e s e n t
between

n e it h e r in the
in the s e v e rity

of i n j u r i e s .

w h i c h a p p a r e n t l y was due n o t

c o n t e n t o f d i e t B, b u t a l s o

since

the tocopherol value

f e d d i e t B wa s a l s o l o w e r

content

of lambs fed d i e t B d e c r e a s e d

t h a n t h o s e f e d d i e t A,

h i g h amount o f p e r o x i d e s ,
anim als

lambs h a v i n g h i g h l e v e l s

T h e r e was n o t a c o n s i s t e n t d i f f e r e n c e

required

more r a p i d l y

of blood plasma

than th o se having a small

lam b s w i t h h i g h and low v a l u e s

of the

values

i n t h e b l o o d p l a s m a would r e q u i r e

t o b e c o me v i t a m i n E d e f i c i e n t

time

initial

the

of c o n t r o l

t h a n t h o s e f e d d i e t A.

- 153 The l o w t o c o p h e r o l

content of E -d e p lete d anim als did not

a l w a y s mea n a p p e a r a n c e o f e x t e r n a l
lambs

showing outw ard

had low v a l u e s

of

gram s p e r 100 m l.
The e f f e c t

signs

of v ita m in E d e f i c ie n c y

noticed

oil

on t h e v i t a m i n E - d e p l e t e d

in the tocopnerol

fed E -d e fic ie n t

Cod l i v e r

the tocopherol le v e l

decreased

plasm a which confirm ed th e r e s u l t s
and co -w o rk ers

invariably

of blood plasma.

blood plasma of anim als
oil

But

t o c o p h e r o l r a n g i n g from 0 . 0 4 7 t o 0 . 0 8 1 m i c r o ­

o f cod l i v e r

l a m b s was c l e a r l y

v i t a m i n 2 symptoms.

content of the

and E - c o n t a i n i n g d i e t s .
of the blood

o b t a i n e d i n cows by F e r r a n d o

(1949).

C r e a t i n e and C r e a t i n i n e E x c r e t i o n :
Th e w e l l known I n c r e a s e
a g a i n was r e p r o d u c e d
The c r e a t i n u r i a

of c r e a t i n e

in th is

ratio

e x c re tio n in the u rin e

e x p e r i m e n t on v i t a m i n E d e f i c i e n c y .

increased

as w e l l ,

but the

creatinine

e x c r e t i o n r e m a i n e d r e l a t i v e l y u n c hanged d u r i n g t h e whole e x p e r i ­
mental p e rio d .
F requently the
started
In sp ite

to

c r e a t i n u r i a was h i g h e r a t t h e

show e x t e r n a l

of the

fact that

m a n ife s ta tio n s of vitam in E d e fic ie n c y .
sim ilar

the blood plasma to c o p h e ro ls ,
coincide

time the lambs

o b s e r v a t i o n h a d b e e n made a b o u t

the high c re a tin e

e x c re tio n did not

w i t h t h e l ow b l o o d p l a s m a c o n t e n t o f t o c o p h e r o l s .

The c r e a t i n u r i a
lambs of t h i s
by W h i t i n g ,

ratios

calculated

e x p e r i m e n t were

Willman and L o o s l i

f o r t h e v i t a m i n E—d e p l e t e d

s ome wh at s i m i l a r t o
(1949)

those

found

i n sheep fe a n a t u r a l

feeds.

- 154 They c o n s i d e r e d a n u m e r i c a l
as

indicative

the

average

while those

creatinuria ratio

o f m o s t o f t h e a n i m a l s e x c e p t i n one a d v a n c e d
A p p a r e n t l y t h e damage p r o d u c e d

creatinuria

ratio

s i n c e Ma s o n

reported
sible

that

(1933) and B u t t u r i n i

(1949)

because

when c o n n e c t i v e

tissue

not

have a l r e a d y

w i t h v i t a m i n E t h e r a p y up t o a c e r t a i n p o i n t ,
is

rever­

but i t

substituted

for

f u n c t i o n i n g parenchyma.
N either

creatinuria
Since
is

This fin d in g i s

t h e d e g e n e r a t i o n p r o d u c e d by v i t a m i n E i s

becomes i r r e v e r s i b l e
the

irreversible

nor the e m a c i a t i o n o f t h e a n im a l

improved w ith th e v ita m in E t r e a t m e n t .
novel

In th is study

l a m b s was 1 . 9 6 .

v i t a m i n E i n s u f f i c i e n c y was l a r g e l y
the

than 1.3

t h e r a p y of E - d e f i c i e n t lambs re d u c e d

of v ita m in E d e f ic ie n c y .

neither

larger

o f c o n t r o l a n i m a l s was 1 . 3 2

of v itam in E - d e f i c i e n t

the c r e a tin u r ia

by t h e

ratio

of a c t iv e muscular dystrophy.

The a l p h a t o c o p h e r o l

case

creatinuria

cortisone
or

or p ro s tig m in e

creatinuria

ratio

c o r r e c t e d the

of v i t a m i n E - d e f i c i e n t lam b s.

o n l y t wo l a m b s p e r g r o u p w e r e t r e a t e d w i t h t h e

not p o s s ib le

however,

t o draw a d e f i n i t e

th a t M artin

ducing th e abnormal
deficient

rats

(1946)
creatine

abnormal

conclusion.

drugs,

I t m u s t be s a i d

found p ro stig m in e e f f e c t i v e
— creatinine ra tio

it

in r e ­

o f v i t a m i n E—

and r a b b i t s .

M in e ral Changes i n the M uscles:
M ineral
alm ost

changes observed in the p re s e n t experim ent are in

complete

agreement with the r e s u l t s

o b t a i n e d by i4 e n n a n d

- 155 G oettsch
It

(1937)

in vitam in E -d e fic ie n t

was d i f f i c u l t

depletion d ire c tly

to d i s c e r n whether or not the v ita m in E

affected

a n aly zed m in e ra ls because
in g between each o th er
Mc C o l l u m 1 9 3 4 ,

Tufts

rabbits.

t h e m e t a b o l i s m o f some o f t h e

t h e a n t a g o n i s m s and s y n e r g i s m s e x i s t ­

( M e l t z e r and Auer 1908;

Orent,

Kruse and

a n d G r e e n b e r g 1 9 3 6 ; E p p r i g h t and S m i t h 1 9 3 7 ;

Sm ith 1949 and G i l l i s 1 9 5 0 ) .
The m o s t p r o n o u n c e d m i n e r a l

disturbance of dystrophic

m u s c l e s wa s t h e l a r g e

Ca/Mg r a t i o ,

sim ultaneous

i n c a l c i u m and a d e c r e a s e i n magnesium.

increase

The i n v e s t i g a t i o n

o f S n y d e r a n d Tweedy ( 1 9 4 2 )

serum magnesium d im i n i s h e d
c h a n g e was s u f f i c i e n t
was a l s o

calcification.

a nd t h a t t h i s
Whether t h i s

o f m u s c u l a r c a l c i u m c o u l d n o t be b l a m e d a s t h e
of the

nevertheless,

m a g n e s i u m c o u l d be f a c t o r s
of th e lambs

little

muscles

(Lu, Emerson

e x c e s s o f m uscular calcium or

i n f l u e n c i n g th e muscular weakness

of th e

im portance of v ita m in E in phosphorus meta­

o r no e f f e c t on t h e p h o s p h o r u s c o n t e n t o f d y s t r o ­

muscles has been re p o rte d

B asically

skeletal

( E n g e l et_ al^. 1 9 4 9 a n d B i r d 1 9 4 9 ) .

In s p ite

phorus

serum p h o s p h a t a s e ,

to in cre ase

causing p a ra ly s is

and Evans 1 9 4 1 );

phic

s howed t h a t l o w

be s t u d i e d .

The i n c r e a s e

bolism ,

the

of a

t h e mechanism i n v o lv e d i n th e v i t a m i n E d e f i c i e n c y

remained to

agent

w h i c h was t h e r e s u l t

this

by w e i s s b e r g e r a n d H a r r i s

ag rees with the s l i g h t

difference

(1943).

in the phos­

c o n t e n t o f normal and d y s t r o p h i c m uscles found i n t h i s

- 156 study.

Yet o th e r workers

marked

(L u, Emerson and Evans 1941)

changes in the t o t a l

pyro and o rg a n ic

ester

acid soluble

be tw e e n t h e v i t a m i n E and p o t a s s i u m

h a s b e e n o b s e r v e d by C u t i l l o

(1944).

of a d d i t i o n a l

follow ing potassium d eficiency

m uscular p a r a l y s i s

necrosis
1942;

T h i s c a n be i n d i r e c t l y
investigations;

muscular weakness

( Ru e g a m e r e_t a l . 1 9 4 6 )

( Thomas ejb al_. 1 9 4 0 ;

thus,

the

s ympt oms r e m i n d e d u s o f t h o s e

o c c u rrin g in vitam in E d e fic ie n cy :
1948),

p h o s p h o r u s and i n t h e

of phosphorus.

A direct relationship

s u p p o r t e d by a s e r i e s

described

Schrader et a l.

K ornb erg and E n d i c o t t 1946;

F o l l i s 1948;

(G illis

and h e a r t

1937;

Follis et al.

and Smith e t a l .

1950).
A lso,

other

of p o tassium
choline.

sim ilarities

have been found between t h e a c t i o n

a n d v i t a m i n E on t h e i m p o r t a n t c o mpound, a c e t y l ­

In fa c t,

the lib e r a tio n

o f a c e t y l c h o l i n e from t h e

n e r v e e n d i n g s d e p e n d e d on t h e p o t a s s i u m i o n
1935;
the

Harvey and M c In to sh 1939;

a n d W e l s h a n d Hyde 1 9 4 4 )

and

d e f i c i e n c y of v ita m in E produced a decrease of the c h o lin e -

esterase

enzyme

Therefore,
tylcholine,
transm ission

(B loch 19 4 2 , Hess and B i o l l i e r 1 9 4 8 ) .
if

p o t a s s i u m and v i t a m i n E a r e r e l a t e d

and a c e t y l c h o l i n e
of e l e c t r i c a l

i s an e s s e n t i a l

impulses,

E s h o u ld p l a y an i m p o r t a n t r o l e
s e e m e d t o be t h e

sodium,

to a c e ­

c ompound f o r t h e

t h e n p o t a s s i u m and v i t a m i n

in the muscular a c t i v i t y .

Such

c a s e o f p o t a s s i u m b e c a u s e Fenn (1940) r e p o r t e d

t h a t muscular a c t i v i t y
for

(Brown a n d F e l d b e r g

a n d Towe r

leads
(1939)

to a l o s s

of p o tassiu m in exchange

found t h a t d e n e r v a tio n of muscles

- 157 produced a decrease
in the le v e ls
wise,

the

(1940)
develop

c o n t e n t o f p o t a s s i u m and an i n c r e a s e

of phosp h o ru s and calcium of the m u sc le s.

close

E was e v i d e n t

in the

Like­

c o n n e c t i o n b e tw e e n m u s c u l a r a c t i v i t y and v i t a m i n

th r o u g h th e e x p e rim e n ts of Pappenheimer and G o e tts c h

who f o u n d t h a t d e n e r v a t e d m u s c l e s o f y o u n g r a t s

did not

s i g n s o f v i t a m i n E d e f i c i e n c y when f e d d i e t s l a c k i n g

v i t a m i n E.
Fr om t h i s
tylcholine

inform ation

and p o ta ssiu m

vitam in E d eficien cy .
investigate
of the

the

to i n f e r

that ace­

Hence,

it

was t h e

was e x t r e m e l y i n t e r e s t i n g t o

of a c e t y l c h o l i n e

drug s e le c te d f o r

of a c e ty l c h o l i n e

availability

on t h e d e v e l o p m e n t

disease

in the

myotonia c o n g e n ita
The d e f i n i t e

of h a n d lin g .

Prostigm ine

Accordingly,

prostigmine

lambs sh o u ld i n c r e a s e

the

same m a n n e r t h a t p r o s t i g m i n e

injections

s e v e rity of
aggravated

(Goodman a n d G i l m a n 1 9 4 9 ) .
effect

of p r o s t i g m i n e

on v i t a m i n E d e f i c i e n c y

i n la m b s c o u l d n o t be d e t e r m i n e d b e c a u s e o f i n s u f f i c i e n t
mental a n im als.

because

f r o m d e s t r u c t i o n by c h o l i n e s t e r a s e

(Goodman a n d G i l m a n 1 9 4 9 ) .
to v ita m in E - d e f i c i e n t

the study of the

on t h e v i t a m i n E d e f i c i e n c y ,

and e a s i n e s s

preserv es a cety l choline

The r e s u l t s

on t wo l a m b s s e e m e d t o
theory,

in the

vitam in E d eficiency.

influence

the

was r e a s o n a b l e

s h o u ld have a p red o m in a n t r o l e

influence

Prostigm ine

of i t s

it

vitam in E d e fic ie n cy .

of th e p r e s e n t experim ent perform ed

indicate,

th a t prostigm ine

experi­

i n o p p o s i t i o n to

in je ctio n s attenuated

T h i s was e v i d e n t

the proposed

the e f f e c t s

of

through the h i s t o l o g i c a l

- 158 studies
Slices

and t h e m i n e r a l and amino a c i d a n a l y s e s
o f l a m b *s t i s s u e s

vanced as in the
the p ro stig m in e
sodium,

case

of lambs n o t h a v i n g any t r e a t m e n t ,

leucine

B e f o re any e f f o r t
it

s h o we d d e g e n e r a t i o n b u t n o t a s a d ­

therapy protected

potassium ,

of m u sc le s.

the

levels

and i s o l e u c i n e

c a n be made t o

would be a d v i s a b l e t o r e p e a t

the

and

of calciu m ,

of the m uscles.

explain these

results

experiment w ith a la r g e r

number o f l a m b s .
Increase

in

the

s o d i u m c o n t e n t o f t h e m u s c l e s was a n o t h e r

feature

of vitam in E d eficien cy .

sodium,

no p o t a s s i u m

d i s a g r e e s w ith the
the

increase

sodium i s

findings

of t h i s

augment o f

was n o t i c e d a t a n y t i m e ,

o f L e a f £t_ al_.

(1949).

which

Otherwise,

o f s o d i u m i n t h e m u s c l e s was f o r e s e e n b e c a u s e

known t o

the organism

diuresis

In sp ite

is

enter

the

tissues

t o r e p l a c e p o t a s s i u m when

d e p le te d of the l a t t e r

element

(O rent-K eiler

a n d McCol l um 1 9 4 1 ) .
Ami no A c i d s :
The w o r k o f S t e i n b e r g
to

c o llag en in rheum atic

change

(1949)

on t h e r e l a t i o n

of v ita m in E

fever indicated th at there

m i g h t be a

i n t h e a m i n o a c i d c o m p o s i t i o n o f t h e m u s c l e s c a u s e d by

the l a c k of v i ta m in E.
If

the

v i t a m i n E,
levels
the

c o l l a g e n s were a f f e c t e d
th en p ro b a b ly the muscles

during the d e f ic ie n c y of
should co n ta in d i f f e r e n t

o f t h o s e a m i n o a c i d s w h i c h ma r k t h e

collagen

and muscle p r o t e i n .

d i f f e r e n c e between

According to th e T ables of

- 159 B lock and B o l l i n g

(1951)

arginine,

leucine,

lysine,

those

differential

isoleucine,

amino a c i d s w e r e ;

glutam ic a c id ,

glycine

and p r o l i n e .
This

selection

t o be d i s t u r b e d
hypotheses
Roderuck

place

in

o f Ma s o n ( 1 9 4 4 )

pointed

p ro d uction or u t i l i z a t i o n

(1946)

tween a lp h a

and H e r s c h e l

Mason ( 1 9 4 4 )

the m etabolic

Herschel

on t h e a m i n o a c i d s m o s t l i k e l y

by v i t a m i n E d e f i c i e n c y was s u p p o r t e d by t h e

(1949).

a defective

criteria

(1946) and th e work o f
out the p o s s i b i l i t y

o f a r g i n i n e may t a k e

d y sfu n c tio n of d y stro p h ic muscles.

theoretically

c o n sid e re d the r e l a t i o n s h i p be­

t o c o p h e r o l a n d t h e m e t a b o l i s m o f t h e a mi n o a c i d s ,

and concluded t h a t

c y s t i n e and i s o l e u c i n e

especially

involved in v itam in E - d e f ic ie n t organisms.
found t h a t

that

the

glutam ine

Roderuck

c o n te n t of d y s tr o p h ic

s h o u l d be
(1949)

guinea pig*s

m u s c l e s was o n l y a b o u t o n e - t h i r d a s much o f t h e g l u t a m i n e
c o n te n t of the

m u s c l e s from c o n t r o l a n i m a l s .

I n t h e p r e s e n t work,

the leucine

and i s o l e u c i n e

levels

o f d y s t r o p h i c m u s c l e s we r e f o u n d t o be l o w e r t h a n t h o s e
muscles of c o n tr o l
hypothesis.

anim als,

which p a r t l y

confirmed H erschel»s

L e u c i n e h a s b e e n shown a s e s s e n t i a l

f o r m a t i o n o f p l a s m a p r o t e i n and h e m o g l o b i n
Isoleucine
of the

h o w e v e r s e e me d t o be l e s s

same b l o o d c o n s t i t u e n t s ,

isoleucine

were r e q u i r e d

p r o t e i n and hem o glob in
been p o s s i b l e

for

in the

for the

(Madden e t a l . 1 9 4 5 ) .

im p o rtan t in the

synthesis

s i n c e o n ly small amounts of

t h e r e g e n e r a t i o n o f human p l a s m a

(Albanese 1945).

Hence,

it

co u ld have

t h a t v i t a m i n E d e f i c i e n c y may h a v e a l t e r e d

the

- 160 normal

c o n t e n t o f b l o o d p lasm a p r o t e i n s and h e m o g l o b i n .

o f th e lambs

i n t h e p r e s e n t e x p e r i m e n t ha d l e v e l s

comparable to those
cases
half

of c o n tro l lambs.

Mo s t

of hemoglobin

But i n g e n e r a l ,

severe

o f v i t a m i n E d e f i c i e n c y had hem oglobin v a l u e s of a lm o s t
of control

in the m ajo rity

levels.

Therefore,

of the lambs,

it

m u s t be c o n c l u d e d t h a t ,

changes i n the l e u c i n e l e v e l s of

skeletal

m uscle o c c u rrin g in vitam in E d e fic ie n c y

verified

by t h e d e t e r m i n a t i o n o f b l o o d h e m o g l o b i n .

Regarding the p ro lin e
m uscles in t h i s
ciency.

It

work,

and g l y c i n e

c o u l d n o t be

c o n te n t of the d y s tr o p h ic

no c h a n g e was n o t i c e d i n v i t a m i n E d e f i ­

was r a t h e r

surprising that

the glycine

co n ten t of

t h e m u s c l e s wa s n o t m o d i f i e d by t h e l a c k o f v i t a m i n E i n t h e
diet,

because

specific

glycine

precursors

e t a l . 1941)

beneficial

(Bloch and Shoenheimer 1941, A lm q u is t

and c r e a t i n e

tr o p h ic muscles
Recent

h a s b e e n shown t o be o n e o f t h e c r e a t i n e

has been found to d i m i n i s h i n d y s­

(Houchin and M a t i l l 1 9 4 2 ).

r e s e a r c h w o r k on c o r t i s o n e
value of t h i s

drug f o r the

disease

and o t h e r d i s o r d e r s

cessful

has b een t h e use of c o r t i s o n e

m uscular fu n c tio n s l i k e ,
menopausal
1951)

tre a tm e n t of c o lla g e n

(Engleman 1 9 5 0 ) .

Sim ilarly

suc­

in several d iso rd ers of

Myotonia co n g e n ita

m u s c u la r myopathy

and p o s t o p e r a t i v e

has d e m o n s tr a te d th e

(McEachern 1 9 5 1 ) ,

(Shy e t al_. 1950 a n d k c E a c h e r n

stiffness

of t h e nand (B a x te r e t a l .

1950).
Vitamin E d e fic ie n c y
affecting

the

i n t h e l a mb i s

e sse n tia lly a disease

m u s c u la r and c o n n e c t i v e t i s s u e s o f s k e l e t a l

mus­

- 161 -

cles,

therefore

cortisone

The e x p e r i m e n t p r o v e d t h a t

t h e r a p y c o u l d be u s e f u l
cortisone

from t h e v i t a m i n E d e f i c i e n c y *

of the

cortisone

S till,

the

tr e a tm e n t the lam bs'

they looked the

During the

analyses revealed

on t h e l e v e l s

that

of potassium,

part

a p p e a r a n c e was b e t t e r e d ,

s howe d t h a t

some i m p r o v e m e n t a s a c o n s e q u e n c e o f t h e

action

initial

same a s v i t a m i n E - d e f i c i e n t

s l i c e s of muscular t i s s u e

The c h e m i c a l

cure.

t h e r a p y p r o d u c e d some

relief

though l a t e r

for i t s

lambs.

t h e r e had been

cortisone

therapy.

c o r t i s o n e had a p r o t e c t i v e
leucine

and i s o l e u c i n e o f

th e muscles*
The p r o l i n e

content of s k e le ta l

m u s c l e s was h i g h .

This

wa s i n a c e r t a i n d e g r e e u n e x p e c t e d b e c a u s e t h e p r e v i o u s wo r k
o f U m breit and Tonhazy
proline
rats

oxidation

wa s r e l a t e d
There is

enters

t o t h e amount o f c o r t i s o n e

a g rea t deal

in the

E deficiency

of the

(Hove a n d H a r r i s 1 9 4 7 a

Kemeneny . et al_. 1 9 4 9 ; L i n d a n a n d H i m s w o r t h

indirectly

s u p p o r t e d by t h e e f f e c t o f v i t a m i n

on t h e amino a c i d

Since the

supplied.

of evidence p roving t h a t v itam in E

metabolism of p r o te in s

which i s

of

i n kidney homogenates of a d re n a le c to m iz e d

a n d b ; Moore 1 9 4 8 ;
1950),

(1951) p o i n t e d o u t t h a t t h e r a t e

c o m p o s itio n of t h e muscles*

a c tio n of vitam in E is

systems of the organism,

review of l i t e r a t u r e ,

so w i d e l y s p r e a d i n m o s t

as has been p o i n te d out i n th e

t h e n p e r h a p s t h e most i m p o r t a n t e f f e c t

o f v i t a m i n E c a n be e x e r t e d on t h e m e t a b o l i s m o f p r o t e i n s ,
which s u b s e q u e n t ly could induce a l t e r a t i o n s
processes.

For

instance,

in o ther m etabolic

i f v i t a m i n E would i n f l u e n c e a b a s i c

- 162 m etabolic re a c tio n
could

induce

charge
are

common t o

certain proteins,

changes in determined

of o th er

likew ise,

it

enzymes and hormones i n

n u t r i e n t !s metabolism sin c e

they them selves

proteins.
On t h e o t h e r h a n d ,

there

vitam in E deficiency th a t

a r e many f a c t s p e r t a i n i n g t o

seem t o h a v e some c o n n e c t i o n w i t h

t h e mechanisms of th e m uscular c o n t r a c t i o n
1938).

Furthermore

and 1949)
tion.

the

intensive

s t u d i e s of Szent-G yorgi

on t h e m uscle c h e m i s t r y p o i n t toward th e

For example,

stiffness

c o u l d be p r o d u c e d by t h e

triphosphate

(ATP) s i n c e

it

c a u s e d by t h e l a c k o f ATP.

the m ineral

same d i r e c ­

d e crea se of adenosine

was f o u n d t h a t r i g o r m o r t i s was
The s t r i k i n g e f f e c t

p o t a s s i u m a n d m a g n e s i u m on t h e p h y s i c a l

and s o l u b i l i t y

(1947

o f muscles o c c u rrin g in v ita m in

E deficiency

sodium,

(Knowlton and H i n e s

o f m y o s in would s u g g e s t t h a t

content of vitam in E -d e fic ie n t

of th e ions
state,

charge

the d istu rb a n c e

d y stro p h ic muscles

would l e a d to

the m o d i f i c a t i o n of the myosin p r o p e r t i e s an d,

subsequently,

to

the a l t e r a t i o n

in

of th e m u s c l e ’s p h y s i c a l p r o ­

perties.
A c tin has a lso
(Szent-Gyorgi
are

able

to d e v elo p

in th e muscle
deficiency
other
nature

1949)

b e e n shown t o h a v e t h e a m a z i n g p r o p e r t y
of fo rm in g t h i n m o le c u la r t h r e a d s which
cross s t r i a t i o n s .

fibers

The l a c k o f s t r i a t i o n

o f d y s t r o p h i c m u s c l e s p r o d u c e d by t h e

of v ita m in E has been d e s c rib e d

investigations.
of a c tin

Does t h i s

i n t h i s a n d many

mean a d i s t u r b a n c e

c a u s e d by t h e v i t a m i n E d e f i c i e n c y ?

in the
C ertainly

- 163 -

it

w o u l d be m o s t i n t e r e s t i n g t o f i n d o u t w h e t h e r t h e s e

proteins,

actin

and m y osin,

o r ATP a r e

important

i n f l u e n c e d by v i t a m i n E .

E lectrocardiogram :
The s c a r c i t y

o f i n f o r m a t i o n on t h e s h e e p ' s

c a r d i o g r a m and a b sen c e
some o f t h e o r i g i n a l
this

reason

it

is

normal e l e c t r o -

o f a n y c o n c e r n i n g t h e l a m b ' s ECG w e r e

lim itations

in th is

probably unfortunate

investigation.

that

For

o n l y a few a n i m a l s

c o u l d be u s e d a s c o n t r o l s .
N otw ithstanding,
of c o n tro l

was r e m a r k a b l e

lam bs d i d n o t change

81 d a y s o f l i f e ,
M ullick e t a l .
reported

it

to fin d

still

fed a l i q u i d

(1948) working w ith o l d e r s h e e p ,
variations

t h e ECG

c o n s i d e r a b l y d u r i n g the

w h i l e t h e y wer e

definite

that

diet.

however,

i n s e r i a l ECGs on t h e i r

first

have

control

anim als.
The m o s t
deficient
terval,
cal

consistent

l a m b s was a n i n c r e a s e

whereas t h i s

in a ll

serial

E showed a g r a d u a l
m illiv o lt

c h a n g e i n s e r i a l ECGs o f v i t a m i n E

interval

records.

in the

i n t h e c o n t r o l l a m b s was i d e n t i ­

Those becoming d e f i c i e n t

increase u n til

was a t t a i n e d .

lambs r e p o r t e d

cattle
years

in vitam in

t h e maximum v a l u e o f 0 . 1 2

The i n c r e m e n t o f t h e PR i n t e r v a l

results

d u r a t i o n o f t h e PR i n ­

f o u n d i n t h e E—o e f i c i e n t

i n t h e p r e s e n t w o r k was i n a g r e e m e n t w i t h t h e

of G u l l i c k s o n and C a lv e r le y

( 1 9 4 6 ) who o b s e r v e d t h a t

f e d a v i t a m i n E - d e f i c i e n t r a t i o n f o r one a n d o n e - h a l f
s h o w e d a u g m e n t a t i o n o f t h e PR i n t e r v a l ,

i n some i n s t a n c e s

- 164 a s h i g h a s 0 . 0 8 and 0 . 1 2 m i l l i v o l t .
interval
less

The l e n g t h e n i n g o f t h e PR

i n v i t a m i n E - d e f i c i e n t lambs of t h i s

marked t h a n i n c a t t l e

consistent

in

e x p e r i m e n t was

(0.02 to 0 .0 4 m i l l i v o l t )

the m a jo r ity of the r e c o r d s ,

bu t

it

was

a nd a p p e a r e d a f t e r

o n l y 81 d a y s .
A remarkable
deficient
orders

feature

l a m b s was t h e

in the

deflections.

o f t h e ECGs o f some o f t h e v i t a m i n E—

sudden appearance o f pronounced d i s ­

character,

voltage

In c e rta in

cases,

and s e q u e n c e o f th e v a r i o u s
t h e r e were l a r g e

t h e T a n d QRS v o l t a g e s a l o n g w i t h t y p i c a l
other

instances,

lead III

the

by B r a g d o n a n d L e v i n e

t h e ST s e g m e n t s a n d i n v e r s i o n
the l a t t e r pa.rt of
The f i n d i n g s
s t u d y nor

the

in neither

anim al,

developed e le v a t i o n s

of

during

c h e m i c a l a n a l y s e s of t h e h e a r t muscle o f v i t a m i n

that

and " c h r o n i c "

even though h e a r t s

4) wh o s e ECG,

did not d i f f e r

but the m icroscopic

heart

w i t h c h a n g e s i n t h e ECG.

d e f i c i e n c y o f v i t a m i n E, y e t

(Fig.

( 1 9 4 9 ) who f o u n d t h a t

t h e ma c r o and m i c r o p a t h o l o g i c a l

n o t show a n y a b n o r m a l i t y w h a t s o e v e r .
12

changes

the o b se rv a tio n p e rio d .

ment c o u l d be c o r r e l a t e d

No.

Sim ilar

o f t h e T wa ves i n l e a d I I

E - d e f i c i e n t lambs showing " a c u t e "

in g to f in d

In

c h a n g e s we r e i n v e r s i o n o f t h e T w a v e s i n

t h e ECG o f v i t a m i n E - d e f i c i e n t r a b b i t s

by t h e

sharp T waves.

a n d d e p r e s s i o n o f t h e ST s e g m e n t s .

have been r e p o r t e d

increments in

I t was a m a z ­

appeared s e r i o u s l y

injured

t h e ECG o f t h e l a m b s d i d
S u c h was t h e c a s e o f l am b

t a k e n 20 d a y s b e f o r e

at all

involve­

th e d e a th of the

f r o m t h e ECG o f c o n t r o l l a m b s ,

o b s e r v a t i o n s h o we d e x t e n s i v e d e g e n e r a t i o n

- 165 of the

c a r d i a c muscle

(Fig.

duced i n only twenty days?

12).

C o u l d t h e s e l e s i o n s be p r o ­

Our o p i n i o n i s

that

it

is

not

l i k e l y , since

ECGs o f o t h e r l a m b s t a k e n a few d a y s b e f o r e t h e i r

sacrifice

not

did

show a n y a b n o r m a l i t y a l t h o u g h t h e m a c r o a n d

m icropathological

exam ination revealed

lesions

of the

cardiac

m uscle.
It

is possible

lesions
tion

that

these d iffe re n c e s.

r e n d e r e d more t e n a b l e

showing " a c u te "

pared to

that

14).

w all,

For example,

this

heart

involvement

(Fig.

c o u l d be o b s e r v e d

th a t the n e c ro tic a re a s of the

were e v e n l y d i s t r i b u t e d and c o v e r e d a l l

localized

1 3 ) w e r e com­

o f a n E - d e f i c i e n t l a mb n o t s h o w i n g a b n o r m a l ECG

It

while

supposition is

when t h e d i s t r i b u t i o n o f t h e h e a r t l e s i o n s

i n lambs

latter

of d i s t r i b u t i o n of the

t h r o u g h o u t t h e c a r d i a c muscle might a f f o r d an e x p l a n a ­

for

(Fig.

the p a tte rn

those

of the

"acute"

in a defined area

the v e n tric u la r

h e a r t i n v o l v e m e n t had l e s i o n s

(Fig.

13).

La mb s f e d d i e t A a n d s u p p l e m e n t e d w i t h a l p h a t o c o p h e r o l a n d
cod l i v e r

oil

resulted

a n d QT i n t e r v a l s .
of Barnes

et a l .

These f i n d i n g s

influenced

cardiac

lesions

tent

d i d n o t c o i n c i d e w i t h t h e work

by c o d l i v e r

oil

found as a r e s u l t of t h i s
was q u i t e a p p a r e n t ,

treatm ent.

through the

an a n t a g o n i s t i c

factor

of calves
were

In the

tocopherol

con­

se v ere n ess of vitam in E

i n l a m b s s u p p l e m e n t e d w i t h cod l i v e r

was d e f i n i t e l y

ji CG

feed in g but n e ith e r

of th e blood plasma and i n c r e a s e d

deficiency

i n t h e d u r a t i o n o f t h e PR

( 1 9 3 8 ) who n o t o n l y fouQQ t h a t t h e

was n o t

p r e s e n t work i t

i n an i n c r e a s e

oil,

to v ita m in E.

tnat

it

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METRIC I

- 169 It

h a s b e e n shown a b o v e t h a t

h e a r t muscle

the m ineral

composition of the

was m o d i f i e d by a d e f i c i e n c y o f v i t a m i n IS.

i n v e s t i g a t i o n has been c a r r i e d

o u t on t h e

the m inerals

on t h e ECG o f s e v e r a l

to look in to

some o f t h o s e

The l e v e l

influence

anim als,

it

Since

o f some o f

i s worthwhile

findings*

of potassium in the

organism has an o u t s t a n d i n g

i n f l u e n c e o n t h e ECG o f mammals a n d b i r d s .
ciency of potassium increased

I n t h e dog,

t h e PR i n t e r v a l

a defi­

(Spealman 1942)

b u t a n e x c e s s o f p o t a s s i u m p r o d u c e d s h a r p T wa ves o f h i g h a m p l i ­
tude

( N ic h o ls o n 1937;

A lfredson

(1940)

Thomson 1 9 3 9 ) .

o f t h e c a l v e s ' ECG.

was a f f e c t e d

by t h e d e f i c i e n c y

and

(Br own e t a l . 1 9 4 4 ;

Sturkie

1950).

depression

Besides,

1944;

system
cattle

Sykes and A l f r e d s o n 1940;

and

potassium d e fic ie n c y produced

voltage

l o w e rin g or i n v e r s i o n of

i n d u r a t i o n o f t h e QT i n t e r v a l s

H o l l e r 1 9 4 6 ; E n g e l et_ a l .

These o b s e r v a t i o n s

The c o n d u c t i v e

of p o t a s s i u m i n humans,

i n humans,

o f t h e ST s e g m e n t s ,

t h e T waves and i n c r e a s e
£t_al.

Sykes and

r e p o r t e d t h a t low p o t a s s i u m r a t i o n s p r o l o n g e d

t h e QRS i n t e r v a l s

chickens

In c a t t l e ,

(Brown

1949).

show g r e a t r e s e m b l a n c e b e t w e e n t h e j^CGs

i n p o t a s s i u m a n d i n v i t a m i n E d e f i c i e n c y w h i c h s h o u l d n o t be
overlooked because,
which p o i n t s
Field

of m uscles,

above,

there

is

some e v i d e n c e

t o an i n t e r a c t i o n between v i t a m i n E and p o t a s s i u m .

Cases of
Except

as d iscu ssed

for

" S t i f f - L a m b 11 D i s e a s e :
certain differences

i n t h e a mi n o a c i d

content

t h e e q u a l i t y o f v i t a m i n E d e f i c i e n c y and " s t i f f -

- 17 0 lamb"
cal

disease

h a s b e e n p r o v e n by v a r i o u s

studies*
The

mor e

sympt om o f b i l a t e r a l l i t y

noticeable

in s t i f f

that

the only

bilaterally
tory

activity,
sides

three possible

the l a t t e r

of th e body.

play a role

The h i s t o l o g i c a l
disease

diet

c o l o s t r u m and m ilk ,
rumen d e v e l o p m e n t ,

is also
it

e v e n l y d i s t r i b u t e d on b o t h
w o u l d seem t h a t v i t a m i n E m u s t

s y s t e m o r on t h e m u s c u l a r a c t i v i t y .
stu d ies revealed

that

field

cases of

of sev eral
of the

the

T h i s p r o b a b l y was due t o

factors,

dams ,

like

the absence of

low t o c o p h e r o l

physiological

content

of

c h a n g e s p r o d u c e d by t h e

and o t h e r f a c t o r s l i k e

m i n e r a l s and s p e c i f i c

t o v i t a m i n E t h a t may s e n s i t i z e

t h e l amb t o t h e

of the v ita m in E d e fic ie n c y .

W h i t i n g ejb al_.

(1949)

t h e d a ms h a d b e e n f e d
of the

circula­

we r e more s e v e r e l y a f f e c t e d t h a n t h e e x ­

effect

v ita m in E in the

attack

s h o u l d be m e n t i o n e d

s y s t e m i s by a f f e c t i n g t h e

v ita m in E - d e f i c i e n t lambs.

additional

antagonists

it

ways m u s c u l a r d y s t r o p h y c a n a p p e a r

Therefore,

in eith er

"stiff-la m b "

time

t h e n e r v o u s sy s te m or t h e mechanism o f t h e m u s c u la r

since

perim ental

At t h i s

i n the muscular

system,

o f t h e m u s c u l a r d y s t r o p h y was

l a m b s du e t o t h e more ma r k e d c a l c i f i ­

c a t i o n of t h e i r muscles*

the

chem ical and p a t h o l o g i ­

showed t h a t l a m b s became s t i f f

"stiff-lam b

ration"

when

which produced l o w e r i n g

b l o o d p l a s m a t o c o p h e r o l o f newborn lambs and o f t h e c o l o ­

s t r u m a n d m i l k o f t h e ewes*
The r u m e n d e v e l o p m e n t o f y o u n g a n i m a l s h a s b e e n shown t o
b rin g along

several

physiological

changes,

o u t s t a n d i n g among

- 171 -

w h i c h wa s t h a t y o u n g r u m i n a n t s h a d a h i g h e r g l u c o s e t o l e r a n c e
test
the
of

than a d u lt rum inants
glucose

the

or other

ruminal a c t i v i t y

lam b's

stiffness

But t h e r e
portance
gators
the

tolerance

is

w ill

t h e r u me n m u s t h a v e a c e r t a i n
since

th e appearance

o f ft s t i f f - l a m b "

lamb"

(1945)

heart
it

to

of them.

but
Never­

insufficiency
group,

s howed h e a r t i n j u r y ,

c a r d i a c damage was v a r i a b l e .
o f c e r t a i n l a m b s was d u e t o a

anatom ic p a t t e r n of th e

coronary v e s s e ls,

coronary a r t e r i o s c l e r o s i s
1940).

o f 11s t i f f - l a m b "

some l a m b s may be mor e

th e lambs c o n s i s t e n t l y

the h igh s u s c e p t i b i l i t y

(Schlesinger

of " s t i f f -

sin c e in the e x p e rim e n ta l

and s e v e r i t y of th e

been found i n

F ield cases

t h e h e a r t l e s i o n s p r o d u c e d by t h e

even though a l l

particular

in cases

i n j u r i e s we r e o b s e r v e d i n a l l

of vitam in E than o th e rs,

the extent

(1945) p o i n t e d

t h i s w o r k was c a r r i e d o u t ,

c o u l d be p o s s i b l e t h a t

susceptible

Perhaps

with

S l a g s v o l d and Lund-

a nd W i l l m a n e ^ al_.

was o n l y o c c a s i o n a l .

were exam ined w hile

extensive
theless,

Ch e n g

(1927),

the appearance of h e a rt le s io n s

disease

disease

disease

day of g r a z i n g .

(1934),

out th at

i m­

t h e r e p o r t o f many i n v e s t i ­

The o b s e r v a t i o n s o f M e t z g e r
Larsen

in the development of

h a v e t o be d e t e r m i n e d by f u r t h e r r e s e a r c h .

deficiency

correlated

Whether

fa c to rs re la te d to the beginning

are c r i t i c a l

no d o u b t t h a t

in the

first

( M c C a n c l e s s et_ al_. 1 9 5 0 ) .

as has

o f human h e a r t s

- 172 C oncluding Remarks:
The p r e s e n t
tim e t h a t
the

lamb.

i n v e s t i g a t i o n has dem onstrated f o r the

v ita m in E is re q u ire d fo r the adequate

"stiff-lam b"

H istological
been observed

sib ilities

n u tr itio n of

The v i t a m i n E d e f i c i e n c y was f o u n d s i m i l a r t o t h e

m a l a d y known a s

depletion.

disease.

and chem ical changes of v a r i o u s

deg rees have

i n d y s t r o p h i c m u s c l e s p r o d u c e d by v i t a m i n E

The c h e m i c a l a n a l y s e s showed many d i f f e r e n t p o s ­
of i n t e r r e l a t i o n

betw een v i t a m i n E and t h e m eta ­

b o l i s m o f amino a c i d s and m i n e r a l s .
Also,
deficient

first

it

was p r o v e n t h a t t h e

sudden d e a t h of lambs

i n v i t a m i n E was c a u s e d by h e a r t

failure.

SUMMARY AND CONCLUSIONS
V i t a m i n E d e f i c i e n c y has been s t u d i e d
l a m b s by f e e d i n g l i q u i d
the

nature

lard,

of the f a t

purified

components.

which d i f f e r e d

only in

D iet A c o n ta in e d commercial

and d i e t B a m olecular d i s t i l l e d

centration

lard

having a high con­

of peroxides.

F in d in g s of the p r e s e n t
as

diets

i n a g r o u p o f 51

investigation

c a n be s u m m a r i z e d

follow s:

Growth:
1)

V i t a m i n E d e f i c i e n c y was s h o wn t o i n f l u e n c e

th e growth

o f l a m b s e s p e c i a l l y when p e r o x i d e s we r e p r e s e n t i n
the

diet.

Symptoms:
1)

2)

The m a i n s ympt oms o f v i t a m i n E d e f i c i e n c y w e r e w e a k ­
ness of the

skeletal

accelerated

by t h e p r e s e n c e o f p e r o x i d e s

Oral

1)

diet.

s y m p t o ms o f v i t a m i n E d e f i c i e n c y .

Studies:

M icroscopic exam ination of f i e l d
lamb"
the

in the

f e e d i n g o f 1 0 0 mg. o f d l - a l p h a t o c o p h e r o l p r e ­

v e n t e d and c u r e d t h e
Pathological

m u s c l e s w h i c h a p p e a r e d t o be

d i s e a s e and v i t a m i n E

equality

of the

cases of " s t i f f -

deficient

two d i s o r d e r s .

l a m b s s howed

- 174 2)

The h e a r t was c o n s i s t e n t l y

found a f f e c t e d

by t h e

vitam in E deficien cy .
Blood S t u d i e s :
1)

V itam in E d e fic ie n c y lowered the alpha tocopherol
c o n te n t of the blood plasma.

2)

The

in itial

v alu es of alph a to co p h ero l

b lood plasma did not in flu e n c e

th e time r e q u i r e d to

become d e f i c i e n t ,

of the d is e a s e

the l o c a l i z a t i o n
3)

in the la m b 's

A ll

the s e v e r i t y
of the

or

heart lesions.

l a m b s s h o w i n g s y mp t o ms o f l a c k o f v i t a m i n E h a d

low b lo o d plasma to c o p h e r o l c o n t e n t .
4)

When d i e t B c o n t a i n i n g a h i g h a m o u n t o f p e r o x i d e s o r
d ie t A plus

cod l i v e r

alpha tocopherol

In general,

were f e d t o t h e l a m b s ,

the

c o n te n t of th e la m b 's blood plasma

was l o w e r e d f a s t e r
5)

oil

than in those fed d i e t A alo n e .

lambs d e f i c i e n t

i n v i t a m i n E had lower

blood p re s su re than c o n tro l anim als.
C reatine-C reatinine
1)

C r e a t i n e and c r e a t i n u r i a r a t i o s
creased

2)

Studies:
of t h e u r i n e were i n ­

i n lambs d e p r i v e d of v i t a m i n E.

Alpha tocopherol
creatinuria

ratio

th e ra p y reduced the
i n lambs t h a t

c r e a t i n e and

were n o t s e v e r e l y

a ff e c te d with vitam in E d e fic ie n cy .

- 17 5 M ineral S tu d ies:
1)

An i n c r e a s e

i n th e c o n c e n t r a t i o n of calciu m and sod­

ium and a d e c r e a s e i n t h e

c o n t e n t o f p o t a s s i u m was

found i n d y s tr o p h ic th ig h m uscles.
2)

H e a r t m u s c l e s o f E - d e f i c i e n t l a m b s ha d a low c o n t e n t
o f p o t a s s i u m and a s l i g h t l y

high content of phos­

phorus.
3)

The d i e t

B c o n ta in in g the

produced a s l i g h t

increase

h i g h amount o f p e r o x i d e s
of calcium in the h e a r t

m u s c l e s and d e c r e a s e o f magnesium i n t h e

t h i g h mus­

cles.
4)

An i n t e r a c t i o n

betw een v i t a m i n E and p o ta s s iu m

s e e ms

possible.
Ami n o A c i d S t u d i e s :
1)

The v i t a m i n E i n s u f f i c i e n c y p r o d u c e d d e c r e a s e
leucine

and i s o l e u c i n e

and a ls o
2)

content

of the is o le u c in e

The p r o l i n e

of s k e l e t a l m uscles

c o n te n t of h e a r t m u scles.

and g l y c i n e l e v e l s

o f lam b s were s i m i l a r

of th e

of d y stro p h ic muscles

to th o s e of c o n t r o l a n im a ls .

Drug t h e r a p y :
1)

In general,

it

c a n be s t a t e d

th a t vitam in E -d e fic ie n t

la m b s t r e a t e d w i t h p r o s t i g m i n e and c o r t i s o n e showed
a certain

improvement.

- 176 E lectrocardiographic

Studies;

Th e e l e c t r o c a r d i o g r a m s o f l a m b s d e p l e t e d
were

divided
1)

into

three

in vitam in E

categories:

ECG o f v i t a m i n E - d e f i c i e n t l m a b s s h o w i n g a c u t e

cardiac

involvem ent,

in­

w h i c h h a d i n c r e a s e d PR i n t e r v a l s ,

creased heart r a te ,
tachycardia,

a n d s u d d e n c h a n g e s i n t h e ECG o f

d i s o r g a n i z a t i o n of the h e a r t b e a t ,

T waves of h ig h v o lta g e

sharp

a n d d e p r e s s i o n o f t h e ST

intervals*
2)

ECG o f v i t a m i n E - d e f i c i e n t l a m b s s h o w i n g c h r o n i c
cardiac

involvement,

w h i c h h a d i n c r e a s e d PR i n t e r v a l s

and d e c r e a s e d h e a r t r a t e s .
3)

ECG o f v i t a m i n E - d e f i c i e n t l a m b s n o t s h o w i n g a n y
electrocardiographic

disorder,

degenerative

in the h e a r t m uscle.

lesions

even t h o u g h t h e y had

Concluding S ta te m en ts:
1)

Vitamin E is
nutrition

2)

an e s s e n t i a l

vitam in for

the adequate

o f t h e l amb*

Vitamin E d e fic ie n c y r e ta r d s

the growth of young

lam bs.
3)

Vitam in E d e fic ie n c y produces
h e a r t and s k e l e t a l

4)

d e g en e ra tio n of the

m uscles of th e lamb.

V ita m in E - d e f i c i e n t lambs e x c r e t e
creatine

in the u rin e .

l a r g e amount o f

- 177 5)

D ystrophic

s k e l e t a l m usc le s of v i t a m i n E - d e f i c i e n t

lam bs have an a b n o rm a lly h i g h c o n t e n t of

calcium

a n d sod iu m and low c o n t e n t o f p o t a s s i u m *
6)

V i t a m i n E d e f i c i e n c y and " s t i f f - l a m b "
cases)

produce

changes in the

7)

sim ilar h isto lo g ic al
content of calcium ,

of th e

skeletal

Injury

of the h e a rt

ciency is
increase

(field

d i s t u r b a n c e s and
sodium and p o t a s s i u m

muscles*

reflected,

m u s c l e p r o d u c e d by v i t a m i n E d e f i ­
in the m a jo r ity of c a se s,

o f t h e PR i n t e r v a l

gr am o f l a m b s .

disease

by

in the e le c tr o c a r d io ­

APPENDIX

- 178
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BIBLIOGRAPHY

A b d erh a ld en , R.
Der V ita m in E -G eh alt d er F rau en - und K uhm ilch.
(Tlie V itam in E -c o n te n t o f Human and Cow*s M ilk ),
B iochem , Z ., 318s 4 7 -5 3 , 1 9 4 7 .
A dam stone, F , B.
The E f f e c t s o f V itam in -E D e f ic ie n c y on th e Developm ent
o f th e C h ick , J , M orp h ol., 52s 4 7 -8 9 , 1 9 3 1 ,
Agduhr, E, and N, S ten stro m ,
The A ppearance o f th e E le c tr o c a r d io g r a m i n H eart
L e s io n s Produced by Cod L iv e r O il T reatm ent,
P a r t V I I . A cta P a e d r la t ic a , 8s 2 0 3 , 1 9 2 9 ,
A lb a n e se , A, A,
S t u d ie s on Human Blood P r o t e in s , I , The I s o le u c in e
D e f ic i e n c y o f H em oglobin. J . B i o l . Chem., 157$
6 1 3 -6 1 9 , 1 9 4 5 .
A lf r e d s o n , B. V. and J . F . S y k es.
E le c tr o c a r d io g r a p h S tu d ie s i n Normal D a iry C a t t l e .
J . o f A g r lc , R e s ., 65s 6 1 -8 7 , 1 9 4 2 .
A lm q u ist, H. J . , E. Mecchi and F . H. K r a tz er.
C r e a tin e F orm ation in t h e C h ick . J . B i o l . Chem.,
141S 3 6 5 -3 7 3 , 1 941.
Ames, S. R ., J . G. B a xter and J . Q. G r i f f i t h , J r .
P r e v e n tio n o f drQ(- to c o p h e r o l o f In c r e a se d C a p illa r y
F r a g i l i t y In R ats F o llo w in g I r r a d ia t i o n . I n t e r . Z.
V ita m in fo r sc h ; C. A ., 45s 5 7 7 8 , 1951.
A nd erson , H. D ., C. A. E lvehjem and J . E. Gonce, J r .
A Comparison o f N u t r i t iv e Valu e s o f Raw, P a s te u r iz e d
and E vap orated M ilks f o r th e Dog. J . N u t r it io n , 20s
4 3 3 -4 4 3 , 1 9 4 0 .
Anonymous •
I n s t r u c t io n Manual Flame Photom eter Model 52 A. The
P erk in -E lm er C o r p o r a tio n . G lenbrook, C o n n e c tic u t,
54 p p ., 1 9 4 9 .
A th a n a s s iu , G.
V ita m in -E -S to ffw e c h s e l zw isch en P la c e n ta und j?etu s.
(Exchange o f V itam in E betw een P la c e n ta and F o e t u s ) •
K lin * W och en sch r., 24-25$ 3 6 2 -3 6 4 , 1947; N u t r it io n
A b s tr a c ts and R eview s 17s 9 9 1 , 1 9 4 8 .

- 187 -

B a r n e s, L. L . , G. K. D avis and C. M. McCay.
I n t e r v a l s i n th e E le c t r o cardiogram s o f C a lv es Fed
Cod L iv e r O i l . C o r n e ll V e t . , 28: 1 6 -2 2 , 1 9 3 8 .
n a u e r , C .D ., and C. P . B erg.
Ih e *imino A cid s R equired f o r Growth In Mice and th e
A v a i l a b i l i t y o f t h e i r O p tic a l Iso m e r s. J . N u t r it io n ,
26$ 5 1 -6 3 , 1 9 4 3 .
B a x te r , H ., L. Joh n son , V. Mader and C. S c h i l l e r .
C o r tis o n e as an A djunct in th e Treatm ent o f P o s t ­
o p e r a t iv e S t i f f n e s s o f th e Hand. Canad. M. A. J . ,
63: 5 4 0 -5 4 2 , 1 9 5 0 .
B e r l i n , R.
M yo p leg ia K a lio p e n ic a . (M uscular P a r a ly s is due to
P o ta sslu m D e f i c i e n c y ) . Nord. M ed., 30: 1 0 9 9 -1 1 0 1 ,
1946; N u t r it io n A b s tr a c ts and R e v ie w s,16: 3 2 1 4 , 1 9 4 7 .
B i c k n e l l , F . and F . P r e s c o t t .
The V ita m in s i n M e d icin e. W illia m Heinemann M edical
B ook s, L td . London p p . 7 0 8 -7 8 4 , 1 9 4 8 .
B ir d , F . H.
Magnesium D e f ic ie n c y i n th e C hick. I . C l i n i c a l and
N e u r o p a th o lo g ic F in d in g s . J . N u t r it io n , 39: 1 3 -2 9 ,
1949.
B ir d , H. R. and T. G. C u lto n .
G e n e r a liz e d Edema in C hicks P rev en ted by d , 1 -a lp h a
t o c o p h e r o l. P r o c . S o c. Exp. B i o l . M ed., 44: 5 4 3 -5 4 7 ,
1940.
B lo c h , H.
E f f e c t o f V itam in S D e f ic ie n c y on C h o lin e - e s t e r a s e
A c tiv ity .
H e lv . Chim. A cta , 25: 7 9 3 -7 9 7 , 1 942.
B lo c h , K. and R. Sch oen heim er.
The B i o l o g i c a l P r e c u r so r s o f C r e a tin e .
1 3 8 : 1 6 7 -1 9 4 , 1 9 4 1 .

J . B i o l . Chem.,

B lo c k , R. J . and D. B o l lin g .
The Amino A cid C om p osition o f P r o te in s and F o o d s.
A n a ly t ic a l Methods and R e s u lt s . C h a rles C. Thomas.
S p r i n g f i e l d , 1 1 1 . , 576 p p ., 1 9 5 1 .
B o y e r , P . D ., M. R a b in o v itz and E. L ie b e .
C hem ical S tr u c tu r e t o V itam in E F u n c tio n .
Chem., 1 9 2 : 9 5 -1 0 3 , 1 9 5 1 .

J. B io l.

- 188 -

B ragdon, J . H. and H. D. L evine*
M y o c a r d itis i n V itam in E - d e f ic ie n t R a b b its.
J . P a t h ., 25: 2 6 5 -2 7 1 , 1 9 4 9 .

Am.

B r a t z l e r , J . W., J . K. L o o s l i , V. N. Krukovsky and
L. A. Maynard.
E f f e c t o f th e D ie ta r y L e v el o f T o co p h ero ls on t h e i r
M etab olism in S w in e. J . N u t r it io n , 42: 5 9 -6 9 , 1 9 5 0 .
Braun-M enendez, js. , J . C. F a s c i o lo , L. F. L e lo ir , J . M.
Munoz and A. C. T a q u ln i.
R enal H y p e r te n sio n . C h a rles C. Thomas. S p r in g f ie ld ,
1 1 1 . , 451 p p ., 1 9 4 6 .
B r ig g s , A. P.
Some A p p lic a tio n s o f th e C o lo r im e tr ic Phosphate Method.
J . B i o l . Chem., 59: 2 5 5 -2 6 4 , 1 9 2 4 .
B r in k h o u se , K. M. and E. D. Warner.
M uscular D ystrop hy in B i l i a r y F i s t u l a Dogs; P o s s ib le
R e la t io n s h ip to V itam in E D e f ic ie n c y . Am. J . P a t h .,
17 : 8 1 - 8 6 , 1 9 4 1 .
Brown, G. L. and W. F e ld b e r g .
E f f e c t o f P o ta ssiu m C h lo r id e on a Sym pathetic G a n g lio n .
J . P h y s i o l . , 84: 12P -14P , 1 935.
Brown, M. R ., J . H. Currens and J . F. Marchand.
M uscular P a r a ly s is and E le c tr o c a r d io g r a p h ic A b n o rm a litie s
R e s u lt in g from P o ta ssiu m Loss in Chronic N e p h r it is .
J . A. M. A ., 124: 5 4 5 -5 4 9 , 1 9 4 4 .
B u t t u r i n i , U.
H eart i n V itam in E D e f ic ie n c y ; E xp erim en tal S tu d y .
G io r n . C lin . M ed., 27: 4 0 0 -4 1 0 , 1946; Ann. Rev. o f
B io ch em ., 17: pp. 4 1 6 -4 1 7 , 1 9 4 9 .
B u t t u r in i, U.
C l i n i c a l and E xp erim en ta l S tu d ie s on V itam in E.
N. Y. Acad. S c i . , 52: 3 9 7 -4 0 5 , 1949.

Ann.

Cheng, C.
The D is e a s e o f New-born Lambs w ith S p e c ia l Emphasis
on B a c t e r lo - p a t h o lo g y . T h e s is o f Ph. D. in th e
S ch o o l o f Graduate S t u d ie s , M ichigan S ta t e C o lle g e ,
p p . 1 6 4 -1 7 9 , 1 9 4 5 .

- 189 -

G o r m i e r , M.
L es A c t i o n s A n t i v i t a m i n i q u e s d e s H u i l e s de F o ie
de P o is s o n .
(A n tiv ita m in A ction o f F is h L iv e r
O ils).
B u l l . S o c . Ghim. b i o l . , 3 0 :
9 2 1 -9 3 7 , 1948;
N u t r i t i o n A b s t r a c t s and R ev iew s, 19:
1979, 1949.
C rid d le ,
The
and
6:

J . E . a n d A. F . Morgan*
E f f e c t o f T o c o p h e r o l F e e d in g on t h e T o c o p h e r o l
P e ro x id e C o n ten t o f Turkey T is s u e s .
Fed. P ro c .,
247, 1947.

G r o x a t t o , H. a n d M, M0 i S .
I n f l u e n z a d e l F o s f a t o d i C( - T o c o f e r o l o S u l l 1
A ttiv ita d e ll1 Ip erten sin asi•
( E f f e c t o f C( t o c o p h e r o l P h o s p h a t e on t h e A c t i v i t y o f
H y p erten sin ase) .
A rch . S c i . B i o l . B o lo g n a , 34:
7 9 - 8 8 , 1 950; N u t r i t i o n A b s t r a c t s and R ev iew s, 20:
1656, 1950.
G u l i k , R.
V i t a m i n S t u d i e s I n t h e Lamb.
I . R ib o flav in
D e f ic ie n c y and R eq u irem en t.
I I . V itam in E
D e f ic ie n c y and E stim a te d R equirem ent.
T hesis o f
P h . D. i n t h e S c h o o l o f G r a d u a t e S t u d i e s , M i c h i g a n
S t a te C o lle g e , p p . 98-102, 1951.
O u t i l l o , F.
I n f l u e n c e o f V i t a m i n E o n Serum P o t a s s i u m a n d
Sodium .
B o ll. Soc. I t a l . B io l. S p e r ., 19:
20-21,
1944;
0 . A ., 41:
1018, 1947.
Dam, H. a n d J . G l a v i n d .
V ita m in E and C a p i l l a r y P e r m e a b i l i t y .
s c h a f t e n , 28:
207, 1940;
G. A . , 3 4 :

N aturw issen6333, 1940.

Dam, H.
S t u d i e s on V ita m in E D e f i c i e n c y i n C h ic k s .
J . N u t r i t i o n , 27:
193-211, 1944a.
Dam, H.
T o x i c i t y o f F r a c t i o n s o f Hog L i v e r F a t t y A c i d s t o
C h ic k s Fed a V itam in E D e f i c i e n t D i e t .
J. N u tritio n ,
28:
297-302, 1944b.
Dam, H . , I . K r u s e , I . P r a n g e a n d &• S ^ n d e r g a a r d .
I n f l u e n c e o f D i e ta r y A sco rb ic A cid, N o rd ih y d ro g u a ia r e t i c A c i d a n d C y s t i n e o n V i t a m i n E D e f i c i e n c y Symptoms
in C hicks.
B io ch im . e t . B io p h y s. A c ta , 2:
501-513,
1948a.

- 190 -

Dam, H.
The E f f e c t o f F ee d in g H ig h ly U n sa tu ra ted F a tt y A cids
i n t h e Absence o f V itam in E and P e r o x id a tio n o f Fat
n a /io iVO* Ac^a F h y s io l. S c a n d ., 16; S u p p l., 2 6 -2 6 ,
Dam, H.
R e la t io n s h ip o f V itam in E D e f ic ie n c y to T iss u e
P e r o x id e s *
Ann. N. Y. Acad. S c i . , 52; 1 9 5 -1 9 9 ,
1949.
D a v is , G ., L. A. Maynard, and C. M. McCay.
S tu d ie s o f th e F a c to r in God L iv e r O il Concerned
i n th e P r o d u c tio n o f M uscle D ystrophy i n C e r ta in
H e r b iv o r a . C o r n e ll U n iv . Agr* E x p t l. S ta . Memoir,
217; 1 - 2 8 , 1 9 3 8 .
E lv eh jem , C. A ., J . E. D onee, J r . and 0 . W. N e w e ll.
E f f e c t s o f V itam in E on R ep rod u ction i n Dogs
on M ilk D i e t s . J . P e d i a t ., 24; 4 3 6 -4 4 1 , 1 9 4 4 .
Em erson, 0 . A. and H. M. E vans.
The E f f e c t o f V itam in E D e f ic ie n c y upon Growth.
J . N u t r i t io n , 14; 1 6 9 -1 7 8 , 1 9 3 7 .
E n g e l, F . L . , S . P . M artin and H. T a y lo r .
On th e R e la t io n o f P o ta ssiu m to th e N e u r o lo g ic a l
M a n if e s t a t io n s o f H ypocalcem ic T eta n y . B u l l . Johns
H opkins H o s p ., 84; 2 8 5 -3 0 1 , 1 9 4 9 .
Englem an, E.
C o r tis o n e i n C o lla g e n D is e a s e and o th e r D is o r d e r s .
B u l l . U n iv . C a lif o r n ia , M. C en te r, 11; 1 2 -1 7 , 1950;
The C o r tis o n e I n v e s t i g a t o r , Merck & C o ., I n c , Rahway,
N. J . , 18; 2 5 0 , 1 9 5 1 .
E n so r , C. R.
E le c tr o c a r d io g r a m o f R ats on V itam in E D e f ic ie n c y .
Am. J . P h y s i o l . , 147; 4 7 7 -4 8 0 , 1 9 4 6 .
E p p r ig h t, E. S . , and A. H. Sm ith .
I n f lu e n c e o f th e In o r g a n ic S a l t s i n th e D ie t on th e
C o m p o sitio n o f th e Ash o f C e r ta in T is s u e s o f th e R at.
J . B i o l . Chem., 118; 6 7 9 -6 9 2 , 1 9 3 7 .
E scu d e ro , A ., M. L. H e rra iz and M. P o la k .
I n f lu e n c e o f V itam in E on th e S tr u c tu r e o f th e A d r en a ls.
P u b s. I n s t . N a c l. N u tr ic io n (Buenos A i r e s ) . Pubs. C ie n t.
CPa5, 4 8 - 5 7 , 1942; C. A ., 39; 1 4 4 5 , 1 9 4 5 .

- 191 -

E v a n s, H. M. and. K. S . Bishop*
J* M e ta b o lic K e s ., 3: 2 3 3 , 1923; Pappenheim er, A* M •
On C e r ta in A sp e c ts o f V itam in E D e f ic ie n c y , p . 3 ,
Farm er, F . A*, B. C. Mutch, J* M. B e l l , L. D. W oolsey
and E. W. Cramp t o n .
The V ita m in E R equirem ent o f Guinea P ig s . J .
N u t r i t i o n , 42s 3 0 9 -3 1 8 , 1 9 5 0 .
F enn, W. G. and M. G o e tts c h .
E l e c t r o l y t e s i n N u t r it io n a l M uscular D ystrophy in
R a b b it s . J . B i o l . Chem., 120: 4 1 - 5 0 , 1 9 3 7 .
F en n, W. 0 .
The R ole o f P o ta ssiu m i n P h y s io lo g ic a l P r o c e s s e s .
P h y s i o l . R ev s. 20: 3 7 7 -4 1 5 , 1 9 4 0 .
F erra n d o , R ., P . C henavier and M. C orm ier.
A c tio n de l fH u ile de F o ie de Morue sur l e Taux du
T o co p h ero l Sanguin de l a Vache l a i t i e r e e t l e Taux
B u ty reu x de Son L a i t .
( E f f e c t o f Cod L iv e r O il on
th e L e v e l o f T ocop h erol i n th e Blood o f th e D airy
Cow and th e B u tt e r f a t C ontent o f th e M ilk) • B u ll.
S o c . Chim. b i o l . , 31: 8 1 0 -8 1 6 , 1949; N u t r it io n
A b s tr a c ts and R ev iew s, 19: 4 7 2 3 , 1950#
F i l e r , L. J . , J r , R. E. Rumery, P. N. G. Yu and K. E.
Mason.
S tu d ie s on V itam in E D e f ic ie n c y i n th e Monkey.
Ann. N. Y. Acad. S c i . , 52: 2 8 4 -2 9 1 , 1949.
F is k e , C. H. and Y. Subbarow.
The C o lo r im e tr ic D eterm in a tio n o f P hosphorus.
B i o l . Chem., 66: 3 7 5 -4 0 0 , 1 9 2 5 .

J.

F itz h u g h , 0 . G ., A. A. N elso n and H. D. C a lv er y .
R ancid F at i n E x p erim en ta l D ie t s . P ro c. S o c . Exp.
B i o l . M ed., 56: 1 2 9 -1 3 1 , 1 9 4 4 .
F o l l i s , R . H . , J r . , E. O r e n t-K e ile s and E . V. McCollum.
The P r o d u c tio n o f C ardiac and Renal L e sio n s i n R ats
by a D ie t E x trem ely D e f ic i e n t i n P o ta ssiu m . Am. J .
P a t h ., 18: 2 9 -3 5 , 1 9 4 2 .
F o l l i s , R. H ., J r .
The P a th o lo g y o f N u t r it io n a l D is e a s e . C h a rles C.
Thomas, S p r i n g f i e l d , 1 1 1 ., pp. 3 2 -3 9 , 1 9 4 8 .

- 192 G atz,

A. J . a n d 0 . B. H o u c h i n .
S tu d ie s on th e H e a rt o f E - d e f i c i e n t R a b b it s .
R ecord, 99:
578, 1947.

G i l l i s , M. B.
P o ta s s iu m R equirem ent o f th e C hick.
36:
351-357, 1948.

J.

A nat.

N u tritio n ,

G i l l i s , M. B.
F u r t h e r S t u d i e s o n t h e R o l e o f P otassiu m i n G r o w t h
a n d B one F o r m a t i o n .
J. N u t r i t i o n , 42:
4 5 -5 7 , 1950.
G o l d h a b e r , P . , L . Z a c h a r i a s a n d V. E. X i n s e y .
V itam in E D e fic ien c y in C hicks.
I I . Plasm a X anthop h y l l l e v e l s a n d V i t a m i n E D e f i c i e n c y Sy m p to m s.
J. N u tritio n , 42:
453-462, 1950.
G o e t t s c h , M. a n d A. M. P a p p e n h e i m e r .
N u t r i t i o n a l M u s c u la r D y s tr o p h y I n t h e G u in ea P i g and
R ab b it.
J . Exp. M ed., 54:
145-165, 1931.
G o e t t s c h , M. a n d E. F . B ro w n .
M uscle C r e a t i n e i n N u t r i t i o n a l M u scu lar D y stro p h y
o f th e R ab b it.
J . B i o l . Chem., 9 7 :
549-561, 1932.
G o o d m a n , L. A. a n d A. G i l m a n .
The P a r m a c o l o g i c a l B a s i s o f T h e r a p e u t i c s . The
M a c M i l l a n C o . New Y o r k , p p . 3 4 2 , 3 8 3 - 3 8 6 , 1 9 4 9 .
G o t t l i e b , H . , F . Vtf. Q u a c k e n b u s h a n d H. S t e e n b o c k .
The B i o l o g i c a l D e t e r m i n a t i o n o f V i t a m i n S .
J.
N u t r i t i o n , 25:
433-440, 1943.
G u l l i c k s o n , T . W. a n d C. E. C a l v e r l e y .
C a r d i a c F a i l u r e i n C a t t l e on V ita m in E - f r e e R a t i o n s
as R e v e a le d by E le c tr o c a r d io g r a m s .
S c ien c e, 104:
312-313, 1946.
G u l l i c k s o n , T . W., L . S . P a l m e r , w. L. B o y d , J . W. N e l s o n ,
F . C. O l s o n , C. E. C a l v e r l e y a n d P . D. B o y e r .
V itam in E i n th e N u tr itio n o f C a tt l e .
1. E ffect of
F e e d i n g v i t a m i n E - p o o r R a t i o n s on R e p r o d u c t i o n , H e a l t h ,
M ilk P r o d u c t i o n and G row th. J . D a iry S c i . , 3 2 : 4 9 5 - 5 0 8 ,1 9 4 9 .
H a r r i s , P . L . , J . L . J e n s e n , M. J o f f e a n d K. S. M a s o n .
B i o l o g i c a l A c t i v i t y o f N a t u r a l and S y n t h e t i c
T oco p h ero l.
J* B i o l . C h e m . , 1 5 6 :
491-498, 1944.
H a r r i s , P . L . a n d W* K u j a w s k i .
A n n o t a t e d B i b l i o g r a p h y o f V i t a m i n E, 1 9 4 0 t o 1 9 5 0 .
T he R e s e a r c h L a b o r a t o r i e s o f D i r f i l i a t i o n P r o d u c t s
i n d . R o c h e s t e r , New Y o r k . ,
184 p p . , 1 9 5 0 .

- 193 -

H arvey, A. M. and F . C. M acintosh..
C alcium and S y n a p tic T ra n sm issio n i n a S ym p ath etic
G a n g lio n . J . P h y s i o l . , 97: 4 0 8 -4 1 6 , 1 9 3 9 .
H e in s e n , H. A.
V ita m in E and C arbohydrate M etab olism . I I . The
R e g u la to r y E f f e c t o f V itam in E on C arbohydrate
M eta b o lism i n P it u it a r y - d ie n c e p h a lic D y s fu n c tio n .
D e u t. Med. W och sch r., 7 6 : 7 3 -7 7 , 1951: C. A ., 45:
5778, 1951.
H ep d in g, L.
V ita m in E D e f ic ie n c y in C h ic k s. T r ia l o f V itam in E
Therapy i n C e r e b e lla r D is o r d e r s . B e r lin U. Munch.
T i e r a r z t l . W och schr., 8 8 -9 1 , 1947; H a r r is , P. L and
W. K u ja w sk i. A nnotated B ib lio g r a p h y o f V itam in E,
1940 t o 1 9 5 0 , p . 1 7 0 , 1 9 5 0 .
H e r s c h e l, A.
H y p o th e tis c h e b esc h o u v in g o v er h e t verband tu s s c h e n
de C( - to c o p h e r o l - en de c y s t in e - i s o l e u c i n e
s t o f f w i s s e l i n g . ( T h e o r e t ic a l C o n s id e r a tio n on th e
R e la t io n s h ip b etw een C( - to c o p h e r o l and th e M etabolism
o f C y s tin e and I s o l e u c i n e ) . T ij d s c h r . D ie r g e n e e sk ,
7 1 : 6 9 9 -7 0 7 , 1946; N u t r it io n A b s tr a c ts and R eview s,
16: 4 , 1947.
H e ss, W. and G. B i o l l i e r .
D ie A k t l v i t a t der L ip a se und d er C h o lin e s te r a s e b e i
F e t t f r e i e r D ia t und b e i E -A v ita m in o se. (The A c t i v i t y
o f L ip a se and C h o lin e s t e r a s e in C ases o f F at Free
D ie t s and o f A v ita m in o sis E. H e lv . Ghim. A cta , 31:
3 8 1 -3 8 6 , 1 9 4 8 .
Hickman, K.. C. D« and P. L. H a r r is .
T o co p h ero l I n t e r r e l a t i o n s h i p s .
4 6 9 -5 2 4 , 1 9 4 6 .
Hickman, K.
A ddress on V itam in E.
2 0 0 -2 0 1 , 1 9 4 9 .

Adv. in E n zym ol., 6:

,
Ann. N. Y. Acad* S c i . , 52:

Hogan, A. G. and VV. 0 . Regan.
D ie t and C alcium P hosphate D e p o s its in Guinea P ig s .
F e d e r a tio n P r o c ., 5: 1 3 8 , 1 9 4 6 .

-

194

-

H o l l e r , J* W.
P o ta ssiu m D e f ic ie n c y O ccurring During th e Treatm ent
oi Of D ia b e t ic A c id o s is .
J . A. M. A ., 131: 1 1 8 6 -1 1 8 9 ,
A

*

*

Holman, R. L.
P r e v e n tio n o f E xp erim en tal A r t e r i t i s i n Dogs by
V ita m in E. P r o c . S o c. Exp. B i o l . M ed., 66: 3 0 7 -3 0 9 ,
Holman, R. L.
S t u d ie s on th e P a th o g e n e s is o f A r t e r ia l D is e a s e ,
so u th e r n Med. J . , 42: 1 0 8 -1 1 4 , 1 9 4 9 .
H ou ch in , 0 . B. and H. A. M a t t i l l .
The Oxygen Consum ption, C r e a tin e and C h lo rid e C ontent
o f M u scles from V itam in E - d e f ic ie n t Animals as
I n flu e n c e d by F eed in g 0 (-to c o p h e r o l. J . B i o l . Chem.,
1 4 6 : 3 0 1 -3 0 7 , 1 9 4 2 .
H ou ch in , 0 . B. and P. W. Sm ith.
C ard iac I n s u f f i c i e n c y in th e V itam in E - d e f ic ie n t R a b b it.
Am. J . P h y s i o l . , 141: 2 4 2 -2 4 8 , 1 9 4 4 .
H ove, E . L. and 2 . Hove.
E f f e c t o f Tem perature on th e R e la t iv e A n tio x id a n t
A c t i v i t y o f a lp h a , b e ta and gamma T o co p h ero ls and
o f G o ss y p o l. J . B i o l . Chem., 156: 6 2 3 -6 3 2 , 1 9 4 4 .
H ove, E. L. and P . L. H a r r is .
C ovitam in S t u d ie s . V. The I n t e r r e l a t i o n o f Alphat o c o p h e r o l and E s s e n t i a l U n sa tu ra ted F at A cid s.
J . N u t r i t io n , 31: 6 9 9 -7 1 3 , 1 9 4 6 .
H ove, E. L. and P. L. H a r r is .
R e la t iv e A c t i v i t y o f th e T o co p h ero ls in Curing
M uscular D ystrop hy i n R a b b its . J . N u t r it io n ,
33: 9 5 -1 0 6 , 1 9 4 7 a .
H ove, E. L. and P . L. H arris*
I n t e r r e l a t i o n b etw een 0( - to c o p h e r o l and P r o te in
M eta b o lism . 2 . The I n c r e a se d U t i l i z a t i o n o f
C a se in Produced by G( - to c o p h e r o l, Y ea st D ig e s t ,
o r X a n th in e i n th e R at-grow th P r o t e in - q u a lit y
T e s t . J . N u t r it io n , 34: 571*579, 1947b.
H ove, E. L.
0( - to c o p h e r o l and C e r ta in N itro g en o u s Compounds
as F a c to r s I n f lu e n c in g th e M o r ta lity o f R ats
a f t e r CC14 P o is o n in g . F e d e r a tio n P r o c ., 7: 2 9 0 ,
1948.

-

Hove,

195

-

E . L . , D* H. C o p e l a n d a n d W. D. S a l m o n .
A F a t a l V itam in E D e f ic ie n c y D ise a se In R ats
C h a r a c t e r i zed by M a s s iv e Lung H em orrhage and L i v e r
N ecro sis.
J . N u t r i t i o n , 39;
397-411, 1949.

J u n g h e r r , E . a n d H. W e l c h .
A R e p o r t o n Lamb D i s e a s e s .
A sso c ., 72;
317-326, 1927.
K achm ar, J . F . ,
a n d R. M.
V itam in E
L ev els I n
and o t h e r
1950.

Jour.

Am. V e t . Med.

P . D. B o y e r , T . W. G u l l i c k s o n , E . L i e b e
P o rter.
in the N u tritio n of C a ttle .
I I . V itam in E
t h e B lo o d , V ita m in A and C a r o te n e U t i l i z a t i o n
C hem ical S t u d i e s .
J . N u tr itio n , 42;
391-403,

K a u n l t z , H. a n d R. E . J o h n s o n .
I n f l u e n c e o f a S i n g l e D o se o f A l p h a T o c o p h e r o l
A d m i n i s t e r e d t o V ita m in E D e f i c i e n t R a ts on t h e
F i f t e e n t h Day u p o n S u b s e q u e n t G r o w t h .
J. N u tritio n ,
32;
327-336, 1946.
K e m e n y , T . , P . V e g h e l y i a n d J . So s .
E - v it a m i n H a ta s a M inosegi F e h e r je h n ia n y e s e t e n .
( E f f e c t o f V itam in E i n Q u a l ita ti v e P r o te in
D eficien cy ).
K is e r l. O rv o stu d ., 1:
111-113, 1949;
N u t r i t i o n A b s t r a c t s and R eview s,
20;
3364, 1951.
K n o w l t o n , G. A . , a n d H. M. H i n e s .
E f f e c t o f V i t a m i n E D e f i c i e n t D i e t Upon S k e l e t a l
M uscle.
P r o c . S o c. Exp. B i o l . M ed., 3 8 :
665-669,
1938.
K o r n b e r g , A. a n d K. M. E n d i c o t t .
P o ta ssiu m D e fic ie n c y i n th e R at.
145:
291-298, 1946.
L eaf,

Lee,

Am. J .

P h y sio l.,

A . , W. T . C o u t e r a n d L . H. N e w b u r g h .
Some E f f e c t s o f V a r i a t i o n i n So d iu m I n t a k e
D i f f e r e n t Sodium S a l t s I n Normal S u b j e c t s .
C l i n . I n v e s t . , 28:
1082-1090, 1949.

and o f
J.

A. M. a n d L . H. S c r i v n e r .
S t i f f Lamb I n v e s t i g a t i o n s . P r e l i m i n a r y R e p o r t .
J o u r . Am. V e t . Med. A s s o c . , 8 6 :
644-655, 1935.

- 196 -

L i n d a n , 0 . a n d H. P . H i m s w o r t h .
T o c o p h e ro l and P r o t e i n d e f i c i e n c y i n R e l a t i o n t o th e
D evelopm ent o f D i e t e t i c M assive N e c r o s is o f th e L iv e r
i n R ats.
B r i t . J . Exp. P a t h o l . , 31:
651-663, 1950;
N u t r i t i o n A b s t r a c t s and R ev iew s, 20:
4940, 1951.
L i p s h u t z , M. D.
L e s V o i e s A t t e i n t e s Chez l e s J e u n e s R a t s M a n q u a n t
d e V i t a m i n e E.
Rev. N e u r o l . , 65:
221, 1936;
Ann.
N. Y. A c a d . S c i . , 5 2 :
135-141, 1949.
L u , G. D . , G. A. En?.erson a n d H. M. E v a n s .
P h o sp h o ru s M etabolism o f th e M u scu la tu re o f E - d e f i c i e n t
S u ck lin g R a ts.
Am. J . P h y s i o l . , 1 3 3 ;
P367-P368, 1941.
L u e c k e , R. W ., F . T h o r p , J r . , W. N. M c M i l l e n a n d H. W. D u n n e .
P a n t o t h e n i c A cid D e f i c i e n c y i n P ig s Fed D ie ts o f
N atural F e e d stu ffs.
J . An. S c i . , 8 :
464-469, 1949.
L u e c k e , R. W ., R. G u l i k , F . T h o r p , J r . , L . H. B l a k e s l e e
a n d R . H. N e l s o n .
R i b o f l a v i n D e f i c i e n c y i n t h e Lamb.
J . An. S c i . , 9 :
420-425, 1950.
L u t r e l l , G. N. a n d K. E. M a so n .
V i t a m i n E D e f i c i e n c y , D i e t a r y F a t and S p i n a l Cord
L esio n s In th e R at.
Ann. N. Y. A c a d . S c i . , 5 2 :
113-120, 1949.
M a c k e n z i e , C . G . , J . B. M a c k e n z i e a n d E. V. M c C ollu m .
U n c o m p lic a te d V ita m in E D e f i c i e n c y i n t h e R a b b it and
i t s R e l a t i o n t o t h e T o x i c i t y o f God L i v e r O i l .
J . N u t r i t i o n , 21:
225-234, 1941.
M a d d e n , S . 0 . , F . W. A n d e r s o n , J . C. D o n ov a n a nd G. H.
W hipple.
P l a s m a P r o t e i n P r o d u c t i o n I n f l u e n c e d b y Amino A c i d
M i x t u r e s a n d L a c k o f E s s e n t i a l Amino A c i d s .
A
D e f i c i e n c y S t a t e R e l a t e d t o Unknown F a c t o r s .
J.
Exp. M ed., 8 2 :
77-92, 1945.
M a l a m u d , N. M . , M. N e l s o n a n d H. M. E v a n s .
The E f f e c t o f G h r o n ic V i t a m i n E D e f i c i e n c y on t h e
N ervous System I n th e R a t.
Ann. N. Y. Acad* S c i . ,
52:
135-138, 1949.
M a r s h , H.
P r e v e n t i o n o f D i s e a s e s i n Young Lam bs.
Med. A s s o c . , 81#
187-194, 1932.

J.

Am. V e t .

- 197 -

M a r tin , A. J . P . and T. Moore.
Some E f f e c t s o f P ro lo n g ed V itam in E D e f ic ie n c y i n t h e
R a t. J . H y g ., 39s 6 4 3 -6 5 0 , 1 9 3 9 .
M a r tin , G. J .
A c tio n o f P r o stig m in e in th e N u t r it io n a l M uscular
D ystro p h y o f V itam in E D e f ic ie n c y . E x p t l. Med.
and S u r g ., 4s 3 2 6 -3 3 2 , 1 9 4 6 .
Mason, K. E.
T e s t i c u l a r D eg e n e ra tio n in A lb ino Rats Fed a P u r if ie d
Food R a tio n . J . Exp. Z o o l., 45; 1 5 9 -2 2 9 , 1 9 2 6 .
Mason, K. E.
D if f e r e n c e s i n T e s t i s In ju r y and R epair a f t e r V itam in
A - d e f ic ie n c y , V itam in-E D e f ic ie n c y and I n a n it io n .
Am. J . A n a t., 52; 1 5 3 -2 3 9 , 1 933.
Mason, K. E.
A H em orrhagic S t a t e i n th e V itam in E - d e f ic ie n t F etu s
o f th e R a t.
"E ssays In B io lo g y ”. U n iv . C a lif o r n ia
P r e s s , B e r k e le y , C a l i f . , p p . 4 0 1 -4 0 9 , 1943.
Mason, K. E.
P h y s i o l o g i c a l A ctio n o f V itam in E and i t s H om ologues.
V ita m in s and Hormones, 2; 1 0 7 -1 5 3 , 1 9 4 4 .
Mason, K* E. and A. F. Emmel.
V itam in E and M uscle Pigm ent in th e R at.
92 : 3 3 - 5 9 , 1 9 4 5 .

A nat. R ecord,

M ason, K. E. and I . R. T e lfo r d .
Some M a n if e s t a t io n s o f V itam in E D e f ic ie n c y in th e
Monkey. A rch. P a t h ., 43; 3 6 3 -3 7 3 , 1 9 4 7 .
M a t t i l l , H. A.
V ita m in E.

J . A. M. A ., 110:

1 8 3 1 -1 8 3 7 , 1 9 3 8 .

M cC andless, E* L. and J . A* Dye.
P h y s i o l o g i c a l Changes i n In te rm ed ia ry M etabolism
o f V a rio u s S p e c ie s o f Ruminants I n c id e n t to
F u n c tio n a l D evelopm ent o f Rumen. Am. J . P h y s i o l . ,
1 6 2 : 4 3 4 -4 4 6 , 1 9 5 0 .
M cEachern, D.
D is e a s e s and D is o r d e r s o f M uscle F u n c tio n .
Y. Acad. M ed., 27: 3 - 2 3 , 1 9 5 1 .

B u ll. N.

- 198 -

M e lt z e r , S . J . and J . Auer*
The A n t a g o n is t ic A c tio n o f C alcium upon th e
I n h i b i t o r y E f f e c t o f Magnesium. Am. J . P h y s i o l . ,
21s 4 0 0 -4 1 9 , 1 9 0 8 .
M e l v i l l e , R. S . and J . P. Hummel.
C r e a tin e and G lyeocyam ine M etabolism i n R a b b its in
V ita m in E D e f ic ie n c y . J . B i o l . Chem., I s 3 8 3 -3 8 9 ,
1951.
M e tz g e r , H. J . and W. A. Hagan.
The S o - c a lle d S t i f f Lambs.
1927.

C o r n e ll V e t ., 17s

3 5 -4 4 ,

M eu n ier, P . and P. C h en a v ler.
Un n o u v e l an tagon ism s de l a V itam ine Es l e S u c c in a te
de d i - o r t h o - c r e s y l e . (A new A n ta g o n ist o f V itam in Es
d i - o - c r e s y l S u c c in a t e ) . C. R. S o c. B i o l . , 143s
1 0 4 6 -1 0 4 8 , 1949; N u t r it io n A b s tr a c ts and R eview s,
20s 2 9 6 , 1 9 5 0 .
M ilh o r a t, A. T ., J . B. M ackenzie, S . U lic k , H. R osenkrantz
and W. E. B a r t e l s .
O b se r v a tio n s on a B i o l o g i c a l l y A c tiv e V itam in E
D e r iv a t iv e P r e se n t i n Hog G a s tr ic Mucin and i n Hog
Stomach L in in g . The B io lo g ic A c t i v i t y o f DL,AlphaT o co p h ery lh y d ro q u ln o n e. Ann. N. Y. Acad. S c i . , 52s
3 3 4 -3 4 0 , 1 9 4 9 .
Moe, G. K. and M. B. V is s c h e r .
The D is t r ib u t io n o f Coronary B lood F low . B lood ,
H eart and C ir c u la t io n . The S c ie n c e P r e s s , W ashington,
D .C ., p p . 1 0 0 -1 0 4 , 1 9 4 0 .
M oore, L. A ., E. T. Hallman and L. B. S h o ll.
C a r d io v a sc u la r and O ther L e sio n s in C a lv es Fed D ie t s
Low i n Magnesium. A rc h iv . o f P a t h o l., 26s 8 2 0 -8 3 8 ,
1938.
M oore, T.
Combined D e f ic ie n c y o f V itam in E and P r o te in in R a t s . .
B r i t . J . N u t r it io n , 2s i v - v , 1 9 4 8 .
Moore, T.
The S ig n i f ic a n c e o f P r o te in in V itam in E D e f ic ie n c y .
Ann. N. Y. Acad. S c i . , 52s 2 0 6 -2 1 6 , 1 9 4 9 .

- 199M o r g u l i s , S . a n d H. p . J a c o b i .
Q u a r t . B u l l . N o r t h w e s t . U n i v . Med.. S c h o o l , 2 0 :
92-9 8 , 1946;
Ann. R e v s , o f B i o c h e m , 1 6 :
p. 188,
M u l l i c k , D. N . , B. V* A l f r e d s o n a n d E. P . H e i n e k e .
I n f l u e n c e o f T h y r o i d S t a t u s on t h e E l e c t r o c a r d i o g r a m
and C e r t a i n Blood C o n s t i t u e n t s o f th e S heep.
Am. J .
P h y s i o l., 152:
100-105, 1948.
M y e r s , V. C.„
Some C h a n g e s i n
F ailu re.
B u ll.
K l e i n e r , I . S.
C o ., S t. B olus,

t h e M yocardium A ccom panying H e a r t
N. Y. A c ad . M e d . , 1 8 :
305, 1942;
Human B i o c h e m i s t r y , The C. V. Mobsby
p . 374, 1948.

N e l s o n , M. M . , G-. A. E m e r s o n a n d H. M. E v a n s .
G r o w t h - s t i m u l a t i n g A c t i v i t y o f Alpha T o c o p h e r o l.
P r o c . S o c . Exp. B i o l . M ed., 4 5 :
157-158, 1940.
N i c h o l s o n , W. M. a n d A. J . S c h e c t e r .
C a rd ia c A rrh y th m ia a f t e r B i l a t e r a l U r e te r a l L ig a tio n
i n t h e Dog.
B u l l . Jo h n s H opkins H o sp ., 60:
346-357,
1937.
O l c o t t , H. S . a n d H. A. M a t t i l l .
V ita m in E and G row th.
J. N u tritio n ,
1937.

14:

305-315,

O l c o t t , H. S .
The P a r a l y s i s i n t h e fo u n g o f V ita m in E D e f i c i e n t
Fem ale R a t s .
J . N u t r i t i o n , 15:
221-227, 1938.
O r e n t , E . R . , H. D. E r u s e a n d E. V. Mc Collum.
S t u d i e s o n Magnesium D e f i c i e n c y i n A n im als.
VI.
C h e m ica l Changes i n t h e Bone, w i t h A s s o c i a t e d B lood
C h a n g es R e s u l t i n g fr o m Magnesium D e p r i v a t i o n .
J.
B i o l . Chem ., 106:
573-593, 1934.
G r e n t - K e i l e s , E . a n d E. V. M c C ollu m .
P o t a s s i u m i n A nim al N u t r i t i o n .
J . B i o l . Chem., 140:
337-352, 1941.
P a m u c k c u , A. M.
O b s e r v a tio n s on th e P a th o lo g y o f N u t r i t i o n a l l y
In d u c e d M u scu la r D y stro p h y i n th e G uinea P ig .
T h esis
o f P h . D. i n t h e S c h o o l o f G r a d u a t e S t u d i e s , M i c h i g a n
S t a t e C o lle g e , pp. 68-84, 1948.

-

200

-

P ap p en h eim er, A. M. and M. G o e tts c h .
A C e r e b e lla r D iso r d e r In C h ic k s, A p p a ren tly o f
N u t r i t i o n a l O r ig in . J . Exp. M ed., 53:
1 1 -2 6 ,
1931.
*
P app en h eim er, A. M ., M. G o e ttsc h and E. Ju ngh err.
N u t r i t i o n a l E n cep h a lo m a la cia in C hicks and C e r ta in
R e la te d D iso r d e r s o f D om estic B ir d s . S to r r s A g r ic .
Exp. S t a . B u l l . 2 2 9 , 121 p p ., 1 9 3 9 .
P app en h eim er, A. M. and M. G o e tts c h .
E f f e c t o f Nerve S e c t io n upon Developm ent o f
N u t r i t io n a l M uscular D ystrophy i n Young R a ts.
P r o c . S o c . Sxp. B i o l . M ed., 43: 3 1 3 -3 1 6 , 1 9 4 0 .
P app en h eim er, A. M.
M uscular D ystrophy in Mice on V itam in E - d e f ic le n t
D ie t . Am. J . P a t h ., 18: 1 6 9 -1 8 1 , 1 9 4 2 .
P appenheim er, A. M.
M uscular D is o r d e r s A s s o c ia te d w ith D e f ic ie n c y o f
V ita m in E. P h y s io l. R evs. 23: 3 7 -5 0 , 1 9 4 3 .
P appenheim er, A. M.
On C e r ta in A sp ects o f V itam in E D e f ic ie n c y .
C h a r le s C. Thomas. S p r in g f ie ld , 1 1 1 ., 33 p p ., 1 9 4 8.
P a r d e e , H. B. B.
C l i n i c a l A sp ects o f th e E le c tr o c a r d io g r a m . P aul B.
Hoeber I n c . M ed ical Book Department o f Harper &
B r o th e r s , New York, 1 9 3 6 .
P a r r is h , D. B . , G. H* Wise and J . S . Hughes.
P r o p e r t ie s o f th e C olostrum o f th e D airy Cow.
I . T o co p h ero l L e v e ls i n th e C olostrum and in th e
E a r ly M ilk . J . D a iry S c i . , 30: 8 4 9 -8 6 0 , 1 9 4 7 .
P e t e r s , J . H.
The D e te r m in a tio n o f C r e a tin in e and C r e a tin e i n
B lood and U rin e w ith th e P h o t o e le c t r ic C o lo r im e te r .
J . B i o l . Chem., 146: 1 7 9 -1 8 6 , 1 9 4 2 .
P i e r a n g e l i , E . , J . C. R adice and M. L. H e r r a iz .
D e p o s it s o f F lu o r e s c e n t Pigm ent in th e A trop h ic
T e s t i s o f V itam in E - d e f i c i e n t R a ts. Ann. N. Y.
Acad. S c i . , 52: 1 2 9 —1 3 1 , 1 9 4 9 .

- 201 -

P r o s p e r i, P. and A, L o t t i n i .
V ita m in E a s a C oagulant F a c to r in H em ophilia
T herapy. Rend. Adunanze A ccad. M ed-Fig. F io r e n t in a
S p e r im e n ta le 100: 2 5 8 -2 6 2 , 1950; C. A ., 45: 2555,
Q uackenbush, F . w ., R. P. Cox and H. S teen b o ck .
T o c o p h er o l and th e S t a b i l i t y o f C a ro ten e. J . B i o l .
Chem., 1 4 5 : 1 6 9 -1 7 7 , 1 9 4 2 .
Q uackenbush, F . w.
T o x i c i t y o f Rancid F a ta .
1945.

O il & Soap, 22:

5 3 6 -3 3 8 ,

Q u a ife , M. L. and P. L* H a r r is .
C hem ical E s tim a tio n o f T o co p h ero ls in B lood Plasm a.
J . B i o l . Chem., 156: 4 9 9 -5 0 5 , 1 9 4 4 .
Q u a ife , M. L. and R. B ie h le r .
S im p lif ie d H yd rogen ation T echnique f o r th e D eterm in a tio n
o f B lood Plasm a T o c o p h er o l. J . B i o l . Chem., 159:
6 6 3 -6 6 5 , 1 9 4 5 .
R oderuck, C. E.
A n a ly s is o f C e r ta in Components o f S k e le t a l M uscle
D uring V itam in E D e f ic ie n c y . J . B i o l . Chem., 181:
1 1 -1 6 , 1949.
Ruegamer, W. R ., C. A. E lvehjem and E. B. H a rt.
P o t a s s iu m D e f ic ie n c y i n th e Dog. P ro c. S o c. Exp.
B i o l . M ed., 61: 2 3 4 -2 3 8 , 1 9 4 6 .
R u p p el, W.
O rganveranderungen b e i E -a v ita m in o tis c h e n R a tte n .
(C hanges in th e Organs o f R ats in V itam in E D e f ic i e n c y ) .
A rch. Exp. P a th o l. P harm akol., 206: 5 8 4 -6 0 1 , 1949;
N u t r i t io n A b s tr a c ts and R ev iew s, 19: 3335, 1 9 5 0 .
Sadhu, D. P.
Growth and D evelopm ent. LX II. The S p e c if ic Dynamic
A c tio n o f N u t r ie n ts w ith S p e c ia l R eferen ce to th e
E f f e c t s o f V ita m in s and Hormones. U n iv. Mo. A g r ic .
E x p t l. S t a . R es. B u i. 408: 1 -6 4 , 1 9 4 7 .
S a u b e r lic h , H. E* and C* A. Baumann.
The E f f e c t o f D ie ta r y P r o te in upon Amino Acid E x c r e tio n
by R ats and M ice. J . B i o l . Chem., 166: 4 1 7 -4 2 8 , 1 9 4 6 .

-

202

-

S c h le s i n g e r , M. J .
S i g n i f i c a n t V a r ia t io n s i n th e Anatomic P a tte r n of* th e
C oronary V e s s e l s . B lo o d , H eart and C ir c u la tio n * The
S c ie n c e P r e s s , W ashington, D. 0 . , p p . 6 1 -7 2 , 1 9 4 0 .
S c h r a d e r , G. A ., G. 0 . P r ic k e t and W. D. Salmon.
Sym ptom atology and P a th o lo g y o f P o ta ssiu m and
Magnesium D e f i c i e n c i e s i n th e R a t. J . N u t r it io n .
14: 8 5 -1 0 4 , 1937.
S c h w e ig e r t, B. S . , J . M. M c ln tir e , C* A. E lvehjem and F.
M. S tr o n g .
The D ir e c t D e te r m in a tio n o f V a lin e and L eucine i n
* r e s h Animal T i s s u e s . J . B i o l . Chem., 155: 1 8 3 -1 9 1 ,
1944.
S h o h l, A. T.
The E f f e c t o f Hydrogen Ion C o n c en tr a tio n upon th e
D e te r m in a tio n o f C alcium . J . B i o l . Chem., 50: 5 2 7 536, 1922.
S h o l l , L. B.
S t i f f Lamb D is e a s e i n M ich igan .
A s s o c ., 95: 1 0 8 -1 0 9 , 1 9 3 9 .

J o u r. Am. V e t. Med.

S h u te , E. V.
N o te s on th e Use o f A lp h a -to c o p h e r o l In th e Management
o f A cute and Subacute V a scu la r O b s tr u c tio n s , a s w e ll
as i n B u rn s. Ann. N. Y* Acad. S c i . , 52: 3 5 8 -3 6 7 ,
1949.
Shy, G. M ., S . B r e n d le r , R. R a b in o v itch and D. McEachern.
E f f e c t s o f C o r tiso n e i n C e r ta in Neurom uscular D is o r d e r s .
J . A.
M. A ., 144: 1 3 5 3 -1 3 5 8 , 1 9 5 0 .
S k e g g s, H.
R. and L. D. W right.
The Use o f -bac to b a c i l l u s A rabinosus i n th e M ic r o b io lo g i­
c a l D e te r m in a tio n o f P a n to th e n ic A cid . J . B i o l . Chem.,
15 6 : 2 1 - 2 6 , 1 9 4 4 .
S la g s v o ld , L. and L und-L arsen.
M y o sit h o s Lam, K alver og U n gfe.
(M y o s itis i n Lambs,
C a lv e s and H e i f e r s ) . Norsk. V et. T id s k r ., 46: 5295 5 2 , 1934; V e t. B u l l . , 5: 5 1 2 , 1 9 3 5 . ( A b s t r a c t ) .
S m ith , B. B.

M a g n e s iu m - p o t a s s iu m A ntagonism .

4 7 3 -4 7 5 , 1 9 4 9 .

,
Arch. B io ch em ., 20 .

-

203

-

Sm ith., S . a , , B. B la c k -S c h a ffe r and T. E. L a s a te r .
P o ta ssiu m d e f i c i e n c y Syndrome in th e Hat and th e d og.
A D e s c r ip t io n o f th e M uscle Changes i n th e P o ta ssiu m d e p le t e d Dog. A rch. P a t h ., 49s 1 8 5 -1 9 9 , 1950.
s n y d e r , F . H. and W. R. Tweedy.
The E f f e c t s o f a M a g n e siu m -d e fic ie n t D ie t on th e
Serum P h o sp h a ta se A c t i v i t y in th e A lb in o R at.
J . B i o l . Chem., 146s 6 3 9 -6 4 7 , 1 9 4 2 .
op ealm an, G. R.
The A c tio n o f io n s on th e Mammalian H ea rt.
P h y s i o l . , 136s 3 3 2 -3 3 9 , 1 9 4 2 .

Am J .

S t e in b e r g , C. L.
V ita m in E and C o lla g e n i n th e Rheumatic D is e a s e s .
Ann. N. Y. Acad. S c i . , 52: 3 8 0 -3 8 9 , 1 9 4 9 .
S t o k e s , J . L . , M. G unness, I . M. Dwyer and M. C. C a sw e ll.
M ic r o b io lo g ic a l Methods f o r th e D eterm in a tio n o f
Amino A c id s . I I . A Uniform A ssay f o r th e Ten
E s s e n t i a l Amino A c id s . J . B i o l . Chem., 160s 3 5 -4 9 ,
1945.
S t u r k ie , P. D.
The E le c tr o c a r d io g r a m o f th e C hicken.
R e s ., 10s 1 6 8 -1 7 5 , 1 9 4 9 .

Am. J . V e t.

S t u r k ie , P. D.
Abnormal E le c tr o c a r d io g r a m s o f C hickens Produced by
P o ta ssiu m D e f ic ie n c y and E f f e c t s o f C e r ta in Drugs
on th e A b n o r m a litie s . Am. J . P h y s i o l ., 162s 5 3 8 -5 4 4 ,
1950.
S y k e s, J . F . and B. V. A lfr e d s o n .
S tu d ie s on th e B ovin e E le c tr o c a r d io g r a m . I . E le c t r o ­
c a r d io g r a p h ic Changes in C alves on Low P otassiu m
R a tio n s* P ro c . S o c. Exp. B i o l . M ed., 43s 5 7 5 -5 7 9 ,
1940.
S z e n t-G y o r g y i, A.
C h em istry o f M uscular C o n tr a c tio n .
P r e s s , N. Y ., 150 p p ., 1 9 4 7 .

New York Academic

S z e n t-G y o r g y i, A.
A tta c k s on M u scle.

4 1 1 -4 1 3 , 1 9 4 9 .

S c ie n c e s

110s

- 204 -

T e l f o r d , I * R.
L oss o f N erve E ndings i n D e g en e rate d S k e l e t a l
M u s c l e s o f Young V i t a m i n E - d e f i c i e n t R a t s .
A nat.
R ecord, 81:
171 -1 8 1 , 1941.
T e l f o r d , I . R . , J . E. S w e g a r t a n d F . 0 . S c h o e n e .
B l o o d - p r e s s u r e s S t u d i e s o n N o r m a l a n d V i t a m i n Ed e f ic ie n t R ats.
Am. J . P h y s i o l . , 1 4 3 :
214-219,
1945.
T h o m a s , R. M . , E . M y lo n a n d M. C. W i n t e r n i t z .
M y o card ial L e sio n s R e s u ltin g from D ie ta r y
D eficien cy .
Y a le J . B i o l , and M ed., 12:
345-360,
1940.
T h o m s o n , W. A. R.
The E f f e c t o f P o t a s s i u m o n t h e H e a r t i n Man.
B r i t . H e art J . , 1:
269, 1939.
T horp, F . , J r .
P r e v e n t i n g Lamb L o s s e s .
M ich. A g r i c . E x p t l .
Q u a rt. B u l l . , 25:
136-137, 1942.
T o w e r, S. S.
The R e a c t i o n o f M u scle t o D e n e r v a t i o n .
R e v s., 19:
1-48, 1939.

S ta.

P h y sio l.

T u f t s , E . V. a n d D. G r e e n b e r g .
C a lc iu m I n v o l v e m e n t i n Magnesium D e f i c i e n c y .
P r o c . S o c . Exp. B i o l . M ed., 34:
292-294,
1936.
U m b r e i t , W. W. a n d N. E . T o n h a z y .
The M e t a b o l i c E f f e c t o f C o r t i s o n e .
I . The
O xidation o f P ro lin e .
J . B i o l . Chem., 191:
256, 1951.

249-

v a n W a g t e n d o n k , W. J . a n d R. #ulz©n*
P h y s i o l o g i c a l and C h em ical A s p e c ts o f t h e A n t i s t i f f n e s s
F a c t o r E s s e n t i a l f o r G uinea P ig s .
V ita m in and
Horm ones, 8 :
89-125, 1950.
V a w t e r , L . R. a n d
O b serv atio n s
R eference to
Med. A s s o c . ,

E. R e c o rd s .
on t h e S t i f f - l a m b P ro b le m w i t h S p e c i a l
W hite M u scle D i s e a s e .
J . Am. V e t .
94:
489-491, 1939.

- 205 -

V Iv a n co , F . , J . M. de P a la c i o s , E. O rti and A. B u y lla .
I n f l u e n c i a d e l G ontenldo en C o lin a y o t r o s Dadores
de M e tilo s de l a D ie ta so b re l a E v o lu cio n de l a
D i s t r o f i a M uscular E xp erim en ta l d e l ConeJo.
( E f f e c t o f th e C onten t o f C h o lin e and o th e r M ethyl
Donors i n th e D ie t on th e P ro d u ctio n o f E xp erim en tal
M uscular D ystrop h y i n th e R a b b it). Rev. C lin .
E sp a n o la , 31s 2 9 7 -3 0 2 , 1948; N u t r it io n A b str a c ts
and R ev iew s, 19s 3 7 2 , 1 9 4 9 .
V o g e ls a n g , A. B . , E. V. Shute and W. E. S h u te .
V ita m in E in H eart D is e a s e . IV. G eneral Remarks.
Med. R e c ., 160s 2 7 9 -2 8 4 , 1 9 4 7 .
V o g e ls a n g , A. B ., E. V. Shute and W. E. S h u te.
Some M ed ica l U ses o f V itam in E. Med. R e c ., 161s
8 3 -8 9 , 1948.
V o g e ls a n g , A.
E f f e c t o f Alpha T ocop h erol on Abnormal E le c t r o c a r d io ­
g r a p h ic F in d in g s . Med. R e c ., 163s 9 4 -9 8 , 1 9 5 0 .
V o g t-M ^ lle r , P.
V itam in E a l s W uchsfaktor.
(V itam in E as a Growth
F a c t o r ) • V itam in e u Hormone, 3s 8 - 2 0 , 1942;
N u t r it io n A b s tr a c ts and R eview s, 17s 4 3 8 3 , 1948.
Wachs, W.
K ennzeichnung d er B io lo g is c h e n A k t iv it a t s u n t e r c h ie d e
von N a tu rlich em und S y n th e tisch em 0( - to c o p h e r o l
d urch R e d o x e le k tr o m e tr isc h e M essungen.
(D eterm in a tio n
o f th e D if f e r e n c e s In B i o l o g i c a l A c t iv it y betw een
n a t u r a l and S y n t h e tic C( - to c o p h e r o l by a Redoxe le c t r o m e t r ic M ethod). Ernahrung V er p fleg u n g , Is
1 1 8 -1 1 9 , 1949; N u t r it io n A b str a c ts and Reviews 19s
1970, 1949.
Waisman, H. A. and K. B. M cC all.
A Study o f Thiam ine D e f ic ie n c y in th e Monkey (Macaca
(M u la ta ). A r c h iv . o f B io ch em ., 4s 2 6 5 -2 7 9 , 1 944.
Warner, R. G. and T. S. S u tto n .
The N u t r it io n o f th e Newborn D airy C a lf . I I I . The
R esp on se to a P h o to ly z e d M ilk D ie t . J . D airy S c i . ,
1 1 : 9 7 6 -9 8 5 , 1 9 4 8 .

- 206 -

W e i s s b e r g e r , L . H. a n d P . L* H a r r i s .
E f f e c t o f T o c o p h e r o ls on P h o so h o ru s M e ta b o lis m .
B i o l . Chem ., 1 5 1 :
543-551, 1943.

J.

W e l c h , H . , H. M a r s h a n d E . A. T u n n i c l i f f .
R e p o rt o f th e D epartm ent o f V e te r in a r y S c ie n c e .
M ontana A g r ic . K x p t l . S t a . R p t . , pp . 7 9 -8 0 , 1929.
W e l s h , J . H. a n d J . E. H y d e .
The E f f e c t s o f P o t a s s i u m o n t h e S y n t h e s i s o f
A c e ty lc h o lin e in B rain .
Am. -J. P h y s i o l . , 1 4 2 :
512-518, 1944.
W h itin g ,
The
th e

P . a n d J . K. L o o s l i .
I n f l u e n c e o f T o c o o h e r o ls on th e F a t C o n te n t o f
M ilk . J . D a i r y S c i . , 31:6 6 5 -6 6 6 ,
1948a.

W h i t i n g , F . a n d J . K* L o o s l i .
T h e P l a c e n t a l a n d Mammary T r a n s f e r o f T o c o p h e r o l s
( V i t a m i n E) I n S h e e p , G o a t s a n d S w i n e .
J. n u tritio n ,
36:
721-726, 1948b.
W i l l m a n , J . P . , S . A. A s d e l l a n d P . O l a f s o n .
An I n v e s t i g a t i o n o f t h e C a u s e o f t h e S t i f f - l a m b
D isease.
New Y o r k ( C o r n e l l ) U n i v . A g r i c . E x p t l .
B u ll. 603, pp. 1-2 0 , 1934.

S ta.

W i l l m a n , J . P . , F . B. M o r r i s o n a n d P. O l a f s o n .
R e l a t i o n o f F e e d i n g a n d M a n ag e m en t t o t h e C a u s e o f
th e "S tiff-lam b * 1 D isease.
New Y o r k ( C o r n e l l ) A g r i c .
E x p t l . S t a . Annual R p t . , p . 79, 1935.
W i l l m a n , J . P . , F . B. M o r r i s o n a n d P . 0 1 s f s o n .
R e l a t i o n o f F e e d i n g and M a n ag e m en t t o t h e C a u s e o f
th e " S tiff-la m b " D isease.
New Y o r k ( C o r n e l l ) A g r i c .
E x p tl. S ta.
Annual R p t . , p . 84, 1936.
W i l l m a n , J . P . , C. M. Me C a y , F . B. M o r r i s o n a n d P. O l a f s o n .
R e l a t i o n o f F e e d i n g a nd M anage m en t t o t h e C a u s e o f
th e S tiff-la m b D isease.
New Y o r k ( C o r n e l l ) A g r i c .
E x p tl. S ta .
Annual R p t . , p . 120, 1939.
W i l l m a n , J . P . , J . K. L o o s l i , S . A. A s d e l l , F . B. M o r r i s o n
and P. O l a f s o n .
_
P r e v e n t i o n and C ure o f M u scu lar S t i f f n e s s ( S t i f f —
Lamb" D i s e a s e ) I n L am b s.
J . An. £ > c i ., 4 :
128-132,
1945.

- 207 -

W illm an, J . P . , J . K. L o o s l i , S. A. A s d e ll, F. B. M orrison
and P. O la fs o n .
V ita m in E P r e v e n ts and Cures th e " S tiff-la m b D ise a se "
C o r n e ll V e t ., 36: 2 0 0 -2 0 4 , 1 9 4 6 .
W ilso n , F . N.
R ecen t P r o g r e s s i n E le c tr o c a r d io g r a p h y and th e
I n t e r p r e t a t i o n o f B o r d e r lin e E le c tr o c a r d io g r a m s.
A s s o c . L if e I n s . Med. D ir . Amer. P r o c ., 48: 9 6 -1 5 3 ,
1938.
W olf, A. and A. M. Pappenheim er•
The H is to p a th o lo g y o f N u t r it io n a l E n ceph alom alacla
o f C h ic k s. J . Exp. M ed., 54: 3 9 9 -4 0 6 , 1 9 3 1 .
W o o lle y , D. W.
Some B i o l o g i c a l E f f e c t s Produced by 0( - to c o p h e r o l
q u in o n e . J . B i o l . Chem., 159: 5 9 -6 6 , 1 9 4 5 .
Z a c h a r ia s , L ., P. G oldhaber and V. E. K in se y .
V ita m in E D e f ic ie n c y In c h ic k s . 1 . The E f f e c t s o f
D ie t a r y Supplem ents on Plasm a T ocoph erol L e v e ls
and V itam in E D e f ic ie n c y Symptoms. J . N u t r it io n ,
4 2 : 3 5 9 -3 7 3 , 1 9 5 0 .