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TASTE ALTERATIONS IN PATIENTS

WITH RENAL DISEASE
presented by

JEAN CATHLEEN BURGE

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© 1979

JEAN CATHLEEN BURGE

ALLRIGHTS RESERWED

TASTE ALTERATIONS IN PATIENTS
WITH RENAL DISEASE

by

Jean Cathleen Burge

A DISSERTATION
Submitted to
Michigan State University

in partial fulfillment of the requirements
for the degree of

DOCTOR OF PHILOSOPHY

Department of Food Science and Human Nutrition

1979

ABSTRACT
TASTE ALTERATIONS IN PATIENTS
WITH RENAL DISEASE
by

Jean Cathleen Burge

Low protein, high calorie, low electrolyte dietary
programs have been used to delay the need for dialysis
in patients with uremia. These programs depend upon a
patient's ability to adhere to these restrictive diets.
Anorexia is a common interfering factor with the success
of these programs. Anorexia continues to be a problem
among many patients undergoing hemodialysis. Taste
abnormalities, a component of anorexia, may interfere with
food acceptance among these patients. Since it is known
that many disease states affect taste, this investagation
was designed to assess the extent to which taste was af-
fected in ESRD patients undergoing routine hemodialysis
and to assess when in the progression of chronic renal
failure (CRF) deterioration of taste occurs.

Recognition taste thresholds for four primary tastes,
sour, sweet, salty and bitter were determined in 18 pa-
tients (age range 17 to 65 years) with end-stage renal

disease undergoing maintenance hemodialysis and were

Jean Cathleen Burge

compared to 10 controls, matched for age and sex. In
experimental subjects, mean taste thresholds before and
after dialysis for tartaric acid were 0.004N and 0.002N,
respectively, compared to 0.0002N for controls. For
sucrose, before and after dialysis, mean thresholds

were 0.039M and 0.023M, respectively, and 0.014M for
controls. When we used the same modalities, that is,
sweet or sour, all possible comparisons were signifi-
cant except the one for sweet between patients after dialy-
sis and controls. Mean recognition taste thresholds for
salty and bitter were not significantly impaired in
dialysis patients when compared to controls. Mean serum
zinc concentrations were 77 ug/dl, both before and after
dialysis. Since these are low-normal values, zinc could
be a factor in loss of taste among these patients, but
it can not explain the improvement seen in taste acuity
associated with dialysis for 6 to 8 hours.

In the second phase of the study, 27 CRF patients
were selected and divided according to their degree of
renal insufficiency by creatinine clearance (CC) levels.
Mild CRP (CC of 41-75 ml/min), moderate (CC of 15-40 ml/
min) and severe (CC of <15 ml/min). Recognition taste
thresholds were done for sucrose and tartaric acid using
a staircase method and choice between distilled water and
stimulus.

In severe CRF patients, mean recognition taste thres-

holds were significantly higher (P<0.001) than those with

Jean Cathleen Burge

mild CRF or those with moderate CRF (P<0.05). The mean
threshold of tartaric acid was not significantly different
with mild CRF and moderate CRF patients were compared
even though the means almost doubled in value. Mean
recognition thresholds for sucrose are not different
among any of the patient groups tested; the trend, how-
ever, was tc increase threshold concentrations as renal
function decreased (mean 0.016, 0.017, and 0.028M for mild,
moderate and severe CRP patients, respectively). Serum zinc
levels of CRP patients declined as renal function declined,
92;8, 82.8, and 75.0 ug/dl. The difference between mild
and severe CRP patients was snigificant (P<0.01). Salivary
zinc levels rose as renal function declined (mild, <30 ppb;
moderate, 66.5 ppb; and severe 141 ppb) however, these dif-
ferences were not significant. Urinary zinc excretiOn,
when expressed in terms of creatinine in the urine, was
not different in any of the three groups. Also, dietary
zinc intakes did not differ in any of the groups studied.
Loss of taste may be associated with the accumulation
(H3 basic protein metabolites in the saliva which neutralize
the ions which provide the sour stimulus. Loss of taste
increases in severity as renal function declines and con-
tinues in patients on dialysis. Dialysis improves the
patient's taste response and also decreases the concentration

of these protein metabolites in the saliva.

The

Dr.

Dr.

Dr.

Dr.

ACKNOWLEDGEMENTS
author would like to express her sincere thanks to:

Rachel Schemmel
for her guidance, understanding and encouragement

throughout this study

James A. Greene, III

for his encouragement, advice and understanding

Hi Sung Park
for his unfailing belief in nutrition and in the

author

Leveille, Dr. Dawson and Dr. Burnell Selleck
for their aid and advice, and for their encouragement

to "Do it"

Family, friends and fellow graduate students who provided

support

her husband Charles

for his understanding, patience, encouragement and

love

ii

TABLE OF CONTENTS

Page
LIST OF TABLES ..................................... v
LIST OF FIGURES .................................... vi
INTRODUCTION ....................................... 1
REVIEW OF LITERATURE ............................... 4
Taste: A Chemical Sense............. ......... 4
Measurements of Taste Acuity .................. 5
The Effect of Area, Exposure, Duration
and Temperature ............................ 6
Recognition Taste Thresholds .................. 7
Taste Thresholds in Disease States ............ 9
Zinc and Taste: Zinc Absorption .............. 16
Excretion ..................................... '18
Zinc in Disease and Stress .................... 19
Zinc and Taste ................................ 22
METHODS ............................................ 24
Hemodialysis Study ............................ 24
Subjects ................................. 24
Measurement of recognition thresholds
for primary tastes .................... 24
Blood analysis ........................... 27
Chronic Renal Failure Study ................... 27
Subjects ................................. 27
Measurement of recognition thresholds
for sour and sweet ............. ....... 28
Biological fluid analysis ................ 31
RESULTS ............................................ 33
Hemodialysis Study ............................ 33
Mean recognition thresholds .............. 33
Chronic Renal Failure Study ..... . ............. 40
Mean recognition thresholds .............. 40
Zinc levels .............................. 41
Dietary zinc levels ...................... 48

iii

DISCUSSION ......................................... 51
CONCLUSION AND SUGGESTIONS FOR FURTHER STUDIES ..... 56
BIBLIOGRAPHY ....................................... 60

iv

LIST OF TABLES

Table Page

1 Concentration of solutions used for re-

cognition taste testing for subjects on

hemodialysis and control subjects ....... 25
2 Concentration of solutions used for re-

cognition taste testing for chronic

renal failure subjects ........ . ......... 29
3 Individual blood and serum values and

recognition taste thresholds ............ 35
4 Zinc in serum of end-stage renal dis-

ease (BSRD) subjects... ................. 39
5 Recognition thresholds for sour and

sweet of patients with mild chronic

renal failure (CC 41-75 m1/min) ......... 43
6 Recognition thresholds for sour and

sweet of patients with moderate
chronic renal failure (CC 15-40 ml/
min) .......... . ......................... 44

7 Recognition thresholds for sour and
sweet of patients with severe chronic
renal failure (CC less than 15 ml/

min) .............................. . ..... 45
8 Zinc in serum, saliva, urine of pa-

tients with chronic renal disease ....... 47
9 Protein and zinc content of food

diaries ................................. 49

Figures

1

LIST OF FIGURES
Page

Recognition taste threshold data
sheet (sweet) .......................... 30

Mean taste recognition thresholds

for sour, sweet, salty, and bitter

for end-stage renal disease patients
before and after hemodialysis and

control subjects ....................... 34

Mean taste recognition thresholds

for sour for patients with mild,

moderate, and severe renal fail-

sure and control subjects .............. 42

Mean taste recognition thresholds

for sweet for patients with mild,
moderate, and severe renal fail-

ure and control subjects ............... 46

vi

INTRODUCTION

In 1975, Congress classified chronic renal disease
as a disabling condition and allowed social security
payments for maintenance hemodialysis and kidney trans-
plantation (Anonymous, 1975). It is estimated that ap-
proximately 8 million people in the United States are
affected by kidney disease, and that 67-84 patients per
million population will begin hemodialysis annually.
Approximately 83 percent of all patients with end-stage
renal disease chose chronic maintenance hemodialysis
(Pearson, 1975). The success of chronic maintenance hemo-
dialysis depends on a number of factors.

Nutritional care, including consumption of sufficient
protein and calories and restriction of sodium, potassium
and phosphorus, is important in providing and maintaining
optimal health of the patient undergoing routine hemo-
dialysis.

Anorexia coupled with increased caloric needs pre-
sent problems in nutritional management. Altered taste
perception is a distressing problem which may affect an
individual's food and fluid intake (Carson, 1977). Meat,
sweet desserts and supplements such as high calorie liquid

glucose solutions, which are important sources of calories,

are frequently refused by patients with chronic renal
disease. Bartoshuk (1978) States that meat is a food
frequently avoided by dysguesics. Cachectic cancer pa-
tients have been shown to have an enhanced taste acuity
for bitter (DeWys and Walters, 1975) which correlated with
an aversion to meat. A number of amino acids, peptides,
and purines in pure form have a bitter taste (Jones, 1969).
Morrison (1978) also showed a correlation between increased
taste acuity in respect to urea and aversion to meats and
suggested that since meat was composed of high concentrations
of amino acids and polypeptides, that this might be an ex-
planation for the aversion reaction of these patients to meat.
Patients with renal disease are especially susceptible
to malnutrition. Recently, Butterworth and Blackburn
(1975) reported that malnutrition was a prevalent health
problem among hospitalized patients. Appetite and those
factors which affect food intake become important in the
attempt to prevent malnutrition in the hospitalized
patient population. Identification of ways in which taste
is altered should lead to corrective measures or at least
better understanding by professional personnel of the
problems imposed upon the renal patient, especially in
relationship to acceptance of special diets. Further-
more, it should help the food industry in the development

of more acceptable food products for patients with renal

disease.

The present study was undertaken to evaluate taste
alterations associated with renal disease, when in the
progression of renal disease these changes occur and to
determine whether or not there is a correlation between
recognition taste thresholds and certain biochemical
parameters such as, creatinine clearances, serum and
salivary zinc levels and urinary zinc excretion over a

24 hour period.

REVIEW OF LITERATURE

Taste: A chemical sense

 

The human taste response requires the incorporation
of minute amounts of a sapid substance into the neuro-
epithelial cells of the taste buds (Alpern et al., 1967).
Four distinct tastes;sweet, sour, salty and bitter are
perceived by humans. The perception of sweet and salty
occurs most acutely at the tip of the tongue, sour at
the sides and bitter at the back of the tongue.

Taste buds are for the most part located on papil-
lae, which are small elevations visible on the surface
of the tongue. There are a number of receptor cells
containing finger-like extensions known as microvilli
located in each taste bud. Chemical materials in solu-
tion reach the microvilli by way of tiny pores in the
papillae and produce a neural response in the sensitive
taste receptors. '

Pfaffman (1978) suggests that chemicals do not
penetrate the taste cell membrane, but quickly absorb
to the surface, to cause depolarization by some as yet
unknown process. This is rapidly transmitted to the
nerve fiber. Presumably, there are different molecular

sites on the receptor cell membranes sensitive to different

5

chemical configurations for different basic tastes.

The sourness of a stimulus results from the presence
of a weak acid in solution. H+ ions in solution appear
to be necessary for the normal taste experience of sour
(Christman, 1971). The sourness of a solution may in-
crease with falling pH; however, acid concentration alone
does not correlate with sourness. A weak solution of
acetic acid tastes just as sour as hydrochloric acid,
even though HCl may have four or five times the acid
concentration of acetic acid. The higher degree of
dissociation of an acid, the more sour the taste will
be, especially in weak acids (Gorman, 1964).

The cation chloride plays an important role in the
experience of salty and an increase in the degree of
dissociation may increase the sensation of saltiness
elicited from a sodium chloride solution (Gorman, 1964).
Sweet and bitter taste responses appear to be much more
complex and may be mediated by enzymatic reactions
(Christman, 1971). In general, compounds of sugars

produce sweet, while most alkaloids produce bitter sensations.

Measurements of taste acuity

 

Hollingsworth and Paffenberger (1917) state that
sensations of taste perceived from weak solutions depends
upon many other factors besides concentration of the

solution. These factors include:

l. The amount of solution applied

2. The extent of surface excited

3. The duration of the application

4 The temperature of the solution

5. The state of rest or movement of the sense organ

6. The nature of the preceeding stimuli.

The effect of area, exposure duration and temperature

Mueller (1965) reports that there is an inverse re-
lation between the size of the stimulated area and the
threshold concentration. Lower concentrations of stimulus
are required to elicit a taste response when large numbers
of taste buds are exposed to the solution. The area of
the tongue stimulated must be held relatively constant.
Bartoshuk (1978) states that variation in the condition
of the tongue as in some disease or deficiency states
might effect the spread of small amounts of stimulus and
produce differences in patient and control populations
that are actually artifacts of the method, and not true
taste differences.

Temperature influences on taste sensitivity differ
with each of the four basic tastes. Shimizie et a1. (1959)
reports that the greatest taste sensitivity for sucrose
and sodium chloride occurred at 30-350 C.; however, this
temperature did not elicit the greatest taste sensitivity

for acid and quinine. Pfaffman (1951) reports that the

sensitivity for some sweet substances, for example dulcin,
may rise with an increase in temperature up to 379 C. and
then decrease above 370 C. Others like glycol produce

no change in sweet taste thresholds with alterations in
temperature, and still others may show intermediate ef-
fects. He further suggests that stimulation of the taste
receptors can not be a simple chemical reaction between
stimulus and taste cell. If this were so, one would
expect the reaction to be enhanced as temperature in-

creases .

Recognition taste thresholds

O'Mahony et a1. (1976) defines recognition.threshold
as that concentration of a solution which elicits the
characteristic taste of the stimulus, while at lower
concentrations the detection threshold is that concentra-
tion at which the stimulus can be distinguished from
distilled water. Determination of thresholds have been
done using several different methods, which for reasons
cited in the previous section may result in different
threshold values.

The three drop method first described by Henkin et
a1. (1971) requires the subject to distinguish a difference
between two drops of distilled water and a single dr0p
of stimulus. These drops are placed on the protruding

tongue in a random sequence. Due to the limited area

exposed to the stimulus, this method may result in a
higher taste threshold than the sipping method. The
data derived may be difficult to reproduce both within
the subjects or between subjects (Bartoshuk, 1978) due
to changes in the geography of the tongue which may re-
sult from disease or deficiency states.

A second method; the sipping or swishing method
requires a subject to swish a specified amount of stimulus
in the mouth, usually 10 cc or more, and swallow or ex-
pectorate the sample. The subject may be asked to dis-
tinguish the test stimulus from distilled water, and/or
identify the stimulus. Cornsweet (1962) describes a
method where the concentration of the stimulus changes
depending upon the subjects response to the previous
stimulus. If the subject indicates the presence of the
correct stimulus, then the concentration of the test
stimulus is decreased; if the subject can no longer iden-
tify the stimulus, the concentration is increased. This
up and down or staircase method continues until 6 to 8
runs or reversals are completed. The first two runs are
discarded and the next 4 to 6 runs are averaged in order
to determine threshold. Either detection or recognition
thresholds can be determined using this method. The pro-
blem of insufficient numbers of taste buds being stimulated

is eliminated by this method.

Taste thresholds in disease states

 

As early as 1917, investigators noticed changes in
taste thresholds associated.with disease states. Hol-
lingsworth and Paffenburger (1917) reported that ele-
vated blood glucose decreases sensitivity to sweetness.
Fabbi in 1954, reported an impairment of taste for a
variety of substances including sugar in aged diabetic
subjects. Schaupp in 1969, also reported that diabetic
subjects had decreased sensitivity to sweet, which appeared
to be related to the blood sugar level. Plausible ex-
planations for this include: 1) Diabetic neuropathy,
which may be related to a generalized taste deficit-inv
this population, or; 2) adaptation of the tongue to
high sugar levels which may interfere with sweet per-
ception alone. Schellings et al. in 1965, reported that
in 63 diabetic patients tested, there was no change in
salt thresholds while there was an increase in the thres-
hold for dextrose. In addition, these investigators
could not find a correlation between these taste dif-
ferences and the blood sugar levels of their subjects.
Both treated and untreated subjects revealed abnormal
sweet taste thresholds. Schellings and co-workers
postulated that this change could be due to; 1) genetic
differences in the diabetic population, or 2) due to a

chronic elevation of blood sugar.

10

Obesity does not appear to result from or cause
changes in sweet thresholds. Grinker in 1978, reported
no difference in taste thresholds for sweet between sub-
jects 55 to 211% overweight and normal weight control
subjects. The degree of obesity, however, was positively
correlated with the degree of sucrose aversion. Under-
wood in 1977, also reported a lower sweet preference
function for obese subjects than for normal weight subjects.

Enhanced sensitivity to taste in cystic fibrotic
patients and patients with adrenal cortical insufficiency
was reported by Henkin in 1962. Henkin and co-workers, (1962)
reported that patients with cystic fibrosis had taste
sensitivity of 100 times greater than controls. Patients
with adrenal insufficiency showed similar hypersensitivity
which was corrected by carbohydrate-active steroids
(Henkin, 1963). Wotman et al. in 1964, Desor and Maller
in 1975, and Hertz et al. in 1974, could not reproduce
these findings in patients with cystic fibrosis. Wotman,
Desor and Hertz used a sipping method coupled with a
forced choice descrimination method. In addition, each
group asked their subjects to rinse with distilled water
between each sample. They found no differences in salt
taste thresholds between control and cystic fibrotic chil-
dren.

The controversy as to whether a generalized abnor-

mal sensitivity of the chemoreceptive system exists in

11

cystic fibrotic children may be due to differences in

the methods used to assess sensitivity or to differences
in the clinical p0pu1ations tested. Henkin used a three
drop forced choice method which requires the subject to
identify which stimulus is different from water. Whether
the stimulus is stronger or weaker in taste than the
other two distilled water samples is not asked. Adap-
tation of the tongue to a stimulus may occur in cystic
fibrotic patients, resulting from higher levels of sodium
via their own saliva, than normal subjects Erawley et al.,
1951). This adaptation phenomenon may have interfered
with the detection of salt in the study. A low concen-
tration of sodium chloride or sucrose could give rise to
a just-detectable decrement in bitterness or sourness

of water and thus allow for discrimination from the test
stimulus. Henkin's subjects were not asked to rinse

with distilled water between each sample as was the case
in the other three reports.

Changes in salt taste thresholds associated with
hypertension is a second area which is controversial.
Fallis et al. in 1962, reported that hypertensive
subjects showed a decreased ability to recognize sodium
chloride as compared with non-hypertensive controls.
Detection thresholds for sodium chloride and sucrose
between hypertensive and control subjects were not dif-

ferent . Wotman et al. confirmed these findings among

12

a similar group of subjects in 1967. Bisht et a1. (1971)
further reported that offspring of hypertensive adults
had higher salt taste thresholds (decreased ability to
recognize salt) than did children of normotensive adults.
Henkin (1974) could not confirm these reports, however,
and suggested that there was no difference in taste
thresholds. Henkin did report that uncontrolled hyper-
tensive subjects showed a preference for saline solutions
over distilled water. SChrechter et al. in 1974, found
that hypertensive individuals consumed more than four
times as much salt as did normotensive controls, when
given the choice between water and saline. These in-
vestigators further suggested that controlling blood
pressure with antihypertensive medications decreased the
desire for salt. Lauer et al. in 1976, did not find

any differences in salt thresholds or preference in
children with a wide range of blood pressures.

Stinbaugh et al. in 1975, reported that salt taste
thresholds were not associated with changes in extra-
cellular volume or external sodium balance alterations.
Conteras in 1978, also reported that salt thresholds
were not altered by sodium deficiency in rats.

Anorexia has been associated with cancer for some
time (DeWys, 1974). MacCarty-Leventhal (1959) described

a personal account of her battle with post radiation

13

mouth blindness following treatment for cancer of the
pharynx. She described fruit as cinders, and juice as
an acid liquid flavored with bicarbonate of soda or
copper, and found food palatable only if it was hot and
steaming so as to stimulate the sense of smell. DeWys
and Walters in 1975, reported altered taste thresholds
among 50 cancer patients with reduced appetite. Detection
thresholds for sodium chloride and HCl were essentially
similar in the control group and cancer patients. The
detection threshold for sucrose was increased in the
tumor group as compared to the controls and there was a
trend of lower urea thresholds in the tumor group. ‘The
specific tumors were not identified in this study. Simi-
lar patterns were observed for the recognition thresholds,
sodium chloride and HCl were not significantly different
whereas sucrose recognition thresholds were elevated and
urea recognition thresholds were decreased. DeWys (1974)
further reported that decreased taste activity for sucrose
in cancer patients could be positively correlated with
the presence of decreased taste sensation in response to
food and depressed appetite. Enhanced urea taste ac-
tivity positively correlated with the presence of a meat
aversion in this same group of cancer patients.

Carson and Gormican in 1977, studied 48 cancer

patients with breast and colonic cancer before and after

14

treatment with 5-f1uorouracil, a cancer chemotherapeutic
agent. The ability to recognize salty solutions was
impaired among both cancer groups prior to treatment when
compared to controls. The salt recognition was signifi-
cantly impaired among patients with active cancer when
compared to resected tumor patients, in addition, colonic
cancer patients tended to have greater salt taste impair-
ment than did the breast cancer patients. Sweet recogni-
tion was also slightly impaired in the cancer patients
when compared to controls, however, unlike DeWys, urea
recognition was not different. Treatment with 5-fluoro-
uracil resulted in slight but non-significant changes in
all taste recognition thresholds.

Williams and Cohen in 1978, observed that in patients
with lung cancer, recognition of sour was significantly
impaired, sweet recognition was also impaired, although
not significantly. Ten percent of the patients were
also hypersensitive to bitter, however, the lung tumor
group as a whole were not significantly different from
the controls with respect to urea thresholds. Salt
taste recognition thresholds were not different in the
cancer patients when compared to the controls.

Differences in taste threshold results reported.by various
investigators studying cancer may be due to differences

in patient populations and/or the type of cancers studied.

15

Differences in treatment modes may also affect the taste
threshold results. Bonanni and Perazzi (1965) reported
that bitter and sour acuity were most often affected in
patients who received or0pharyngeal radiation treatments.
The other factor which may have affected the results is
the degree of involvement of the tumor. Carson and
Gormican (1977) were the only investigators who identi-
fied the degree of involvement of tumor in their pop-
ulation.

Several other disease states also affect taste.
Cohen et al. in 1973, reported hypogeusia with elevated
detection and recognition thresholds for each tastei
quality among thermal burn patients. Decreased ability
to detect sucrose was reported by Wrobel (1978) in caries
active naval recruits when compared to caries-free con-
trols. Hypothyroidism has also been reported to decrease
taste sensitivity (McConnel et al., 1975).

Although very little work has been done on taste
acuity among patients with end-stage renal disease,
anorexia and meat aversion is a common problem in these
patients. In our dialysis unit we have frequently ob-
served aversions for sweet products as well. Atkin-Thor
et a1. (1978) recently reported hypogeusia among renal
patients which improved when zinc supplementation was
begun. These investigators did not identify which tastes

were altered, nor did they look at the effect of hemodi-

16

alysis treatment upon the altered taste.

Zinc and taste

 

Zinc Absorption

 

Approximately 20 to 30 percent of dietary zinc is
absorbed from the duodenum, illeum and jejunum with
very little being absorbed from the colon or stomach
(Underwood, 1977). Control of body zinc levels is regu-
lated by variations in zinc absorption. Zinc uptake
by the intestinal wall of the zinc-deficient rat was four
times that of the pair-fed and twice that of the ad-
libitum fed control (Schwarz et al., 1974). Evans and
co-workers (1975) have described a low molecular weight
zinc-binding factor in the intestinal lumen of the rat.
The uptake of zinc-65 by epithelial cells from everted
intestinal rat segments was enhanced by the presence
of this zinc-binding ligand from pancreatic secretions.
Evans et a1. (1975) has postulated a series of events
associated with zinc absorption. These include: 1) The
pancreas secretes a zinc-binding ligand into the intes—
tinal lumen; 2) in the intestinal lumen, zinc binds to lig-
and; 3) the complexed zinc plus zinc ligand, is transported
through the intestinal microvillus and into the epithelial
cell; 4) in the epithelial cell, zinc is transported to
binding sites on the basolateral plasma membrane, or;

5) metal-free albumin interacts with the plasma membrane

 

 

17

and removes zinc from the receptor site. The quantity
of zinc entering the body is determined by the quantity
of metal-free albumin available. Prasad (1977) suggests
that although most zinc is bound to albumin in plasma,
other proteins such as alpha-Z-macroglobulin, transferrin
and ceruloplasmin also bind zinc.

Zinc absorption depends upon a number of factors.
Zinc is more available for absorption from animal pro-
tein than from cereal grains and fruits. Other factors
that appear to have some effect upon absorption are body
size, level of zinc in the diet and the presence of
potentially interfering substances in the diet, such as;
phytate, fiber, chelating agents, calcium and vitamin D.

Calcium interfers with zinc absorption and may po-
tentiate a zinc deficiency (Underwood, JB'TD. On the
other hand, low calcium intakes may result in elevating
plasma zinc. Bone resorption that may occur in calcium
depleted states results in the release of zinc from bone
(Tao, 1975). Vitamin D has been reported to increase
zinc absorption, but this appears to be an indirect ef-
fect of the vitamin resulting from a homeostatic
response to increased zinc requirements which accompanies
stimulated skeletal calcification and growth.

The average American diet contains from Hlto 15 mg

zinc per day (0515, 1972). Vegetarian diets, when com-

18

pared to animal protein diets, contain less zinc (ap-
proximately 12 mg zinc per day). The increased intake of
cereal grains and therefore phytates by vegetarians, may
further decrease the availability of zinc in these diets.
In diets containing 40 grams of protein or less per day,
the zinc content may be as low as 4 to 7 mg zinc per day.
0515 et al. (1972) reported a value of 4.75 mg zinc in a
37 gram protein diet. Diets which derive most of their
protein from fish and poultry, such as a low cholesterol
diet may also be low in zinc, as these particular protein
sources are not high in zinc, approximately .7 mg/lOO

grams (Brown, 1976).

Excretion

 

Zinc is excreted primarily via the feces, which ac-
counts for approximately 1 to 2 mg per day. Urinary
zinc losses account for approximately 0.5 mg per day and
losses in perspiration account for an additional 0.5 mg
or more per day. With a 20 to 30 percent absorption
rate and an average loss of 2 to 4 mg zinc per day, the
recommended zinc intake is 15 mg per day. The inges-
tion of 15 mg. zinc would result in the absorption of
approximately 3 to 4.5 mg per day and zinc homeostasis
in an adult. In a child, when bone growth is rapid, zinc

requirements are increased.

19

Zinc in disease and stress

Profound changes occur in tissue and plasma levels
of zinc in response to various diseases. Halsted and
Smith (1970) reviewed several diseases which affect zinc
levels in humans. They reported significant depression
in serum zinc in patients with leg ulcers, liver disease,
active pulmonary tuberculosis, acute and chronic pulmonary
infection, uremia, pregnancy, oral contraceptive users,
and children with cystic fibrosis. These investigators
also reported that plasma zinc levels fell to 75 percent
of control levels within 24 to 48 hours post myocardial
infarction. These levels gradually rose to normal levels
by two weeks after recovery. Lindeman et al. (1972) de-
scribed the influence of acute tissue injury on plasma
and urinary zinc concentrations in post surgical, post
myocardial infarction and acute suppurative infection
patients. The plasma zinc levels in surgical patients
fell from 77:4.7 ug/dl to a low of 5312.0 ug/dl, 24 hours
post-operatively. Mean plasma zinc concentrations fell
to 58:3.8 ug/dl on the second post infarction day; while
mean levels of zinc in plasma fell to 68:8.1 ug/dl in
infection patients. Although urinary zinc losses sig-
nificantly increased after surgery, patients with suppura-
tive infection and myocardial infarction did not exper-

ience any significant increase in urinary loss of zinc.

20

Lindeman concluded that an acute fall in plasma zinc
occurs post tissue injury regardless of origin and that
an effective homeostatic mechanism operates to return
plasma zinc levels to normal. Wacker et a1. (1956) also
noted a significant fall in plasma zinc in patients after
acute myocardial infarction. Concomitant with this de-
creased plasma zinc was an increase in malic and lactic
dehydrogenase activity. Lactic dehydrogenase and malic
dehydrogenase are both zinc metalloenzymes (Riordan, 1976)
and Wacker suggested that a redistribution of zinc occurs
post myocardial infarction to account for falls in plasma
zinc levels.

Tissue injury, infections and bacterial endotoxins
result in the release of leukocyte endogenous mediator
(L.E.M.). L.E.M. is a heat liable trace protein possibly
identical with endogenous pyrogen. Liberation of L.E.M.
following tissue injury results in a series of events
which include; 1) a net flow of amino acids into the liver,
2) uptake of iron by the reticuloendothelial system, and
3) a net flux of plasma zinc to the liver. This uptake
of zinc by the liver is followed by a hepatic synthesis
of acute phase reaCtants over the next few hours. These
acute phase reactants include fibrinogen, al-acid glyco-
protein, az-acute phase globulins and haptoglobin (Burch
and Sullivan, 1976). Beisel (1976) postulated that leuko-

cytic endogenous mediator was responsible for the

21

redistribution of zinc and iron from serum into the liver
following acute tissue injury.

Tucker (1976) reported a case of severe zinc de-
ficiency which occurred in a patient receiving total
parenteral nutrition support. This deficiency was mani-
fested by suppressed serum and hair zinc levels, along
with cutaneous lesions typical of acrodermatitis entero-
pathica and alopecia. Both of these symptoms were cor-
rected after zinc supplementation. Prasad (1976) re-
ported decreased levels of zinc in hair, red blood cells
and plasma of adult patients with sickle cell disease.
The zinc excretion in the urine of the patients with
sickle cell disease was increased. Retarded growth and
hypogonadism was an apparent side effect of sickle cell
disease seen in many of these patients.

The information concerning zinc metabolism among
hemodialysis patients is controversial. Mahler et al.
(1971) and Mansouri et al. (1970) reported decreased con-
centrations of serum zinc among end-stage renal disease
patients on hemodialysis, whereas Bloomfield et al. (1969)
and Rose et al. (1972) reported normal or slightly ele-
vated concentrations of serum zinc in their patients.
Mahajan et a1. (1978) reported that although patients
with chronic renal failure had mean plasma zinc levels

significantly lower than controls; the mean erythrocyte

22

zinc level was significantly higher in all patients with
chronic renal failure than in the controls. These in-
vestigators postulated that the low plasma and high ery-
throcyte zinc concentrations in chronic renal failure
could be secondary to an abnormal shift of plasma zinc
into erythrocytes or the result of an ineffective ery-
thropoiesis associated with decreased rate of cell di-

vision and maturation.

Zinc and taste

 

A physiological role of zinc in taste acuity was
first reported by Henkin in 1971. Cohen et al.(1973)
and Henkin (1971) reported improvement of taste acuity
associated with thermal burns and patients with idio-
pathic hypogeusia by zinc supplementation. Hambridge et
al. (1976) reported that poor growth and appetite together
with hypogeusia in young children in Denver was associated
with subnormal zinc in hair. Supplementation with zinc
improved growth, normalized taste acuity and increased
hair zinc concentrations.

Henkin et al. (1971) has suggested that zinc acts
as a cofactor involved in the gustatory protein called
gustin. This protein has been postulated to be a carrier
for the chemical responsible for a particular taste to
the taste receptor. Henkin et al. (1975) measured paro-

tid saliva zinc concentrations in normal and control

23

subjects who complained of hypogeusia. Henkin reported
depressed parotid saliva zinc levels in the hypogeusia
subjects. These investigators consequently believed
that even though serum and other tissue levels of zinc
are normal, salivary zinc levels may play an important

role in taste acuity.

METHODS

HEMODIALYSIS STUDY

Subjects
Eighteen ambulatory end-stage renal disease (ESRD)

patients, who were routinely hemodialyzed for 6 hours
three times per week at the Michigan Nephrology Center,
were selected as experimental subjects. There were 9
males and 9 females between the ages of 17 and 65 years
(mean age 46.5 years). All 10 control subjects, 3 males
and 7 females between the ages of 21 and 65 years (mean
age 45.8 years), were hospital personnel or patient's

spouses.

Measurement of recognition thresholds for primary tastes
The solutions used for evaluation of each recognition
threshold were USP purity quinine sulfate (bitter),
tartaric acid (sour), sodium chloride (salty), and
sucrose (sweet). All solutions were made fresh daily
with sterile distilled water used as solvent. Table 1.
lists the concentrations of the solutions for each taste
modality.
All subjects were asked to fast and not smoke for at
least 2 hours prior to tasting. Recognition thresholds

for representative solutions of the four primary tastes

 

25

OHo.o

 

 

moo.o
woo.o
ooa.o noo.c
o-oaxov omo.o ooo.o oa.o
o-oHXmm owo.o moo.o mo.o
0-0onm ono.o voo.o mo.o
c-0meN ooo.o moo.o Ro.o
o-oaXo~ omo.o Noo.o oo.o
o-o~XmH oeo.c Hoo.o mo.c
0-0HxOH omc.o wooo.o vo.o
o-oaXm c~o.c eooo.o mo.o
e-oflxe OHc.o Nooo.o No.o
o-oaxN moo.o Hooo.o Ho.o
o-cHxH o o o
2 . z z 2
mummazm mafiafiso ooflnofino Eswuom evMo< ufiaeuhme momoaosm
.muoonnnm Hoaucoo can mflmxamfieoso; :o
muoomnzm uom mcflpmou opmmp :oflpflemooou wow wow: maofiasflom mo sewumuucoocou .H oflnee

26

were determined in each subject. This was done between

0 and 30 minutes before dialysis and repeated between

0 and 30 minutes after dialysis. For tasting, each sub-
ject swished 10 cc of solution around in the mouth and then
expectorated. The subject described the taste of each
solution in the series as being either sweet, sour, salty,
bitter or having no taste, and indicated the intensity

of taste on a scale of one to ten (from slight to extreme).
Each subject then waited one minute before continuing

to the next sample. After the subject correctly identified
two conseCUTIVe‘ samples, the sample with the lower con-
centration of solute was defined as the recognition thres-
hold. All subjecxs were tested for the same taste modality
on at least two occasions.

During the second testing period, solutions with
concentrations between the first recognizable concen-
tration and the last negative response stimulus were
prepared and used for testing. As an example, if subject
A recognized a .05M solution of sucrose as sweet, .04,
.041, .042, etc. solutions were used for the second
testing. Again, after the subject correctly identified
two consecutive samples, the sample with the lower con-
centration of solute was defined as the recognition
threshold. The patient was offered different taste

stimulus before and after dialysis treatments the same

27

day, in order to eliminate guessing or criteria changes

due to knowledge of taste stimulus.

Blood analyses

 

A 10 ml sample of blood was taken from the venous
shunt of each experimental subject 0 to 30 minutes prior
to dialysis and 0 to 30 minutes after dialysis, and by
venipuncture from each control and was placed into hepar-
inized tubes. Hematocrits were done, and the remainder
of the blood was prepared for use as serum samples.

The latter were frozen and subsequently analyzed for creat-
inine by the Folin and Wu technique (1919) and serum

urea nitrogen (SUN) by the technique of Marsch, Fingerhut
and Miller (1965). Serum zinc concentration was deter-
mined with an atomic absorption method (Burch et al.,

1975) on 15 ESRD patients both before and after dialysis.

CHRONIC RENAL FAILURE STUDY

Subjects

Twenty-seven ambulatory chronic renal failure pa-
tients were selected as experimental subjects. The
subjects were separated into three groups of subjects
according to their creatinine clearances: Group 1, n=9,
creatinine clearance of 41-75 ml/min; Group II, n=8,
creatinine clearance of 15-40 ml/min; Group III, n=10,

creatinine clearance of less than 15 ml/min. There

28

were twenty males and seven females between the ages of
17 and 74 years (mean age 49.7 years). There were 3
females in Group I and two females in the remaining

two groups.

Measurements of recognition thresholds for sour and sweet

 

The solutions used for evaluation of each recogni-
tion threshold were USP purity tartaric acid (sour) and
sucrose (sweet). All solutions were made fresh daily
with sterile distilled water as solvent. Table 2. lists
the concentrations of the solutions for each taste mo-
dality.

All subjects were asked to fast and not smoke for
at least four hours prior to tasting. Recognition thres-
holds for tartaric acid and sucrose were determined in
each subject. For tasting, each subject swished 10 cc
of solution around in the mouth and then swallowed the
solution. The subject was asked to discriminate between
the test solution and distilled water. Each subject
rinsed with distilled water between each set of samples
and waited approximately one minute before proceeding to
the next sample set. The staircase method of Cornsweet
(1962) was used to determine threshold. Figure 1. shows
a representative test. The first two trials of each test
were discarded and the average of the next four trials

was used as the value of the recognition taste threshold.

29

Table 2. Concentrations of solutions used for recog-
nition taste testing for chronic renal fail-
ure subjects.

 

Sucrose Tartaric Acid
M N

0 0

0.0025 0.0004
0.005 0.0008
0.010 0.0016
0.015 0.0024
0.020 0.0032
0.030 0.0048
0.040 0.0064

0.050 0.0080

30

.eoumz uoflafiumfiw anm unouommfiw no: u z .m

 

 

+ + + + +
woozm
poozm poozm -
“oozm woozm z Hoozm xuamm
z z z z -
z
z
z
mz
m e m N H
mamflne

mafiamsmm mo :ofiuookfin

ovo.o

omo.c

omo.o

mao.o

oao.o

moo.o

mmoo.o

o

cemgmupcoocou :owusaom

.mpoozmv pooem spew eflogmoueu epmmu :ofiufiamooom .H oasmfim

31

Biological fluid analysis

 

A 15 ml sample of blood was taken by venipuncture
from each experimental subject and transferred into
plastic vials. Blood was prepared for use as serum and
red blood cell samples immediately following collection.
Both samples were frozen and subsequently analyzed for
zinc using an atomic absorption method (Burch et al.
1975). The serum samples were also analyzed for creatinine
by the Folin and Wu technique (1919).

A 24 hour urine sample was collected on the day
prior to testing and analyzed for zinc using an atomic
absorption method (Burch et al., 1975), and creatinine
by the Folin and Wu technique (1919).

For saliva collection each subject, after a 12 hour
fast and prior to tasting the test solutions, tilted their
head forward and allowed saliva to collect in the front
of the mouth. The subject then expectorated this ac-
cumulated saliva into a plastic cup until 10 cc of total
saliva was collected. This was unstimulated saliva.

All collections were completed between 8:00 A.M. and
10:00 A.M., the collection was completed within 15 to 30
minutes. The saliva was immediately frozen and subse-

quently analyzed by a testing laboratory.3

8Trace Elements Inc., 460 S. Northwest Hwy., Park
Ridge, Illinois, 60068.

 

32

Each subject kept a food diary which included the
amounts of all food consumed for two days prior to testing.
Zinc content was calculated using provisional zinc tables
(Murphy et al., 1975, and Freeland et al., 1976). Pro-
tein was calculated using Agricultural Department Hand-
book No. 456. Analysis of Variance, Duncans multiple
range test (1957) and least significant difference tests
(Sokal and Rohlf, 1969) were used to determine if sig-

nificant differences existed between each group.

RESULTS

Hemodialysis Study
Mean recognition thresholds

Mean recognition taste thresholds of tartaric acid
(sour) for ESRD subjects before dialysis were signifi-
cantly higher (P < 0.001) than those of control subjects
(0.004N vs. 0.002N) as shown in Figure 2. and Table 3.
Following hemodialysis, mean recognition taste thresholds
improved (P < 0.01) twofold to a value of 0.002N, but this
was still significantly higher than that of controls.
(P < 0.01). Mean recognition taste thresholds for sucrose
(sweet) of ESRD subjects before dialysis were also signi-
ficantly higher than that of controls (P < 0.01) (0.03M
vs 0.014M). Hemodialysis brought about significant im-
provement (P < 0.05) in the mean recognition taste thres-
holds for sweet, but at no time did it reach the levels
of the control subjects even though differences between
post- dialytic patients and controls were never significant
(P > 0.05).

Although the mean recognition taste thresholds of
0.043M sodium chloride before dialysis and 0.034M sodium
chloride after dialysis were not significantly higher

than the control value of 0.026M sodium chloride, the

34

 

 

0.005 -
'3 SOUR
4 ’8
0 (D
'g 0904‘ ‘ Predialysis g
t C3 Post Dialysis 0:;
lc-J I Control 5
0
S22 0.003 i:
F- '4
4 E
a: 2
l- A w
3 0.002 // 0
0 5
5 o
0 e
3' a
2 2
8
z

 

30 x l0'6

20x10"6

 

|0x|0'6

MOLAR CONCENTRATION (Sodium Chloride)

 

MOLAR CONCENTRATION (Quinine Sulfate)

 

 

40xl0’6-

 

 

 

BITTER

Figure 2. Mean taste recognition thresholds for sour,
sweet, salty, and bitter for end-stage renal disease pa-
tients before and after hemodialysis and control subjects.

35

mflmxfimfivoaosumom no mflmzamwwoaocohd .m

 

 

 

 

o.m~ m.v~ e.m m.cH o.ue c.0m A
m.n~ m.w~ o.m w.NH o.wv o.wm o
o.m~ o.m~ 0.0 o.HH m.ee o.~oH m
o.mH o.mH m.m m.NH m.em o.eoa e
o.m~ o.m~ m.m c.5H o.oe o.eoa m
m.c~ o.e~ ~.m N.oH o.~e o.coa N
o.h~ m.m~ n.m e.mH o.om o.~HH H
pmom one umom ohm umom moan woonnzm
”Momma oouamwhaofi 055 umouo coamuowmufi:

«on: Enuom

 

mwaonmoazp oummu :owuwamoooh can monam> assom use voofls Hmsww>wucH .m oases

36

.mflmzaewvoaonumom no mfimxfimfiuosocopm .m

 

 

 

 

 

o.vm c.0m -- m.n -- o.we ea
0.00 o.~m o.e o.m o.o~ o.Hm ma
0.50 0.5m -- 0.NH -- 0.00 NH
o.u~ 0.5N 5.0 o.eH o.mm c.0n HH
o.e~ m.m~ 0.0 m.mH 0.0m o.~m 0H
o.o~ 0.5H 0.¢ w.HH m.m~ o.vm a
0.0m o.~m 0.0 m.HH 0.50 0.0m a
“mom ohm “mom ohm pmom «one pomnnnm

wooan oHonz H0\we H0\ma

.wuflhooumEo: ocflcfiueouo :omonuflc

. asuom mo»: ezpom
.m.p:oo0m0HonmoH:u opmeu :ofluwamooon 0cm mosfim> Enuom 0am wooHn Hm30w>fiweH .m magma

37

.mcoprHOm 020 90005 no 020 HwEHOZ .0

 

 

 

 

 

 

0N0.0 000.0 000.0 000.0 0000.0 0000.0 5
000.0 000.0 000.0 000.0 0000.0 0000.0 0
00.0 000.0A 000.0 050.0 0000.0 00H0.0 0
500.0 000.0 000.0 000.0 0000.0 0500.0 0
000.0 000.0 000.0 000.0 0000.0 5000.0 0
000.0 000.0 50.0 50.0 0000.0 0000.0 N
000.0 000.0 50.0 50.0 0000.0 0000.0 0
um00 ohm “mom ohm umom 0&0 womnnsm
z .5uamm z .uoozm 02 .nsom
0Hogmounu oummu :ofluwnmooom
.m.u:oov m0Honmounu mummu :owuwcmooon 0:0 mosflm> asuom 000 00000 Hms0w>fi0zm .0 manna

38

.000000000 020 00000 00 020 000002 .0

 

 

 

 

 

 

000.0 000.0 000.0 000.0 5000.0 0000.0 00
000.0 000.0 000.0 000.0 0000.0 0000.0 00
000.0 500.0 000.0 000.0 000.0 000.0 00
000.0 00.0A 000.0 050.0 0000.0 0000.0 00
000.0 000.0 000.0 000.0 0000.0 0000.0 00
000.0 000.0 000.0 .000.0 000.0 000.0 0
000.0 00.0A 000.0 000.0 0000.0 0000.0 0
0000 000 0000 000 0000 000 0000000
2 .50000 2 .00030 02 .0000
000000000 00000 00000000000
.0.00000 0000000000 00000 00000000000 000 00000> 00000 000 00000 00000>0000 .0 00000

39

 

 

000-00 00 05 00 000000000000
000-00 00 00 00 00000000000
00000 00 000: 2 00000000 00 000000

 

00\0: .0000 00000

 

.00000000 000000 0000000 00000

00000-000 mo

590m

EH

0000

.0 0000b

40

mean value for pre and post dialysis subjects was cal-
culated using a recognition taste threshold of 0.100M
for four subjects who were unable to detect sodium (salty)
below this range. Although ideally these subjects should
have been further tested to identify their true recogni-
tion taste threshold, that was not possible, since for
various reasons they were no longer available to the
unit. If, indeed, their true recognition taste thresholds
could have been determined, this group would surely have
approached significance. As serum urea nitrogen. increased
in value, there was a tendency for patients to be less
able to detect saltiness.

Serum zinc concentrations for 15 experimental sub-
jects ranged from 50 to 114 ug/dl before dialysis and
39 to 111 ug/dl after dialysis (Table 4.). The remaining
three subjects were not available for zinc analysis.
Zinc serum values were in the low range for normal (75

to 160 ug/dl) for the method (Burch et al., 1973) used.

Chronic Renal Failure Study
Mean recognition thresholds

Mean recognition thresholds of tartaric acid (sour)
for patients with severe renal failure, creatinine clear-
ance less than 15 ml/min, were significantly higher

(P‘<0.05) than those of patients with moderate ;

41

renal failure, creatinine clearance 15 to 40 ml/min.

These mean recognition thresholds for tartaric acid (sour)
for patients with severe renal failure were also sig-
nificantly higher (P<<0.001) than those patients with
mild renal failure, creatinine clearance 75 to 41 ml/min.
That is, patients with severe renal failure had signifi-
cantly decreased ability to recognize sour when compared
to moderate and mild renal failure patients. The mean
recognition thresholds of tartaric acid were not signi-
ficantly different when mild chronic renal failure patients
were compared to moderate chronic renal failure patients,
even though the means doubled in value (.0007N, .0014N,
and .0026N) Figure 3. Individual data.areshown in Tables
5, 6, and 7.

Mean recognition thresholds for sucrose were not
different in any of the groups tested, although, the trend
was to increase threshold concentrations as renal func-
tion decreased (mean 0.016, 0.017, and 0.028) for mild,
moderate and severe renal failure patients respectively,
Figure 4. That is as renal function decreased, taste
acuity in respect to sucrose also decreased.

Zinc levels

 

Serum zinc levels of patients with chronic renal
disease declined as renal function declined (92.8 ug/dl,

82.8 ug/dl and 7S ug/dl) (Table 8.) for patients with

0.004

0.003

0.002

0.00 l

NORMAL CONCENTRATION (Tartaric Acid)

 

42

 

- CONTROL
GROUP I

C] GROUP ll
GROUP Ill

 

 

 

 

Figure 3. Mean taste recognition thresholds for sour
for patients with mild, moderate, and severe renal fail-

ure and control subjects.

 

 

43

 

 

aflo.o Naoo.o m.Hv .m
ouo.o Haoc.c w.¢v .m
mHo.o mooo.o o.m¢ .n
mmo.o mooo.o H.wv .o
HHo.o mooo.o m.mv .m
mHo.o oaoo.o ~.mm .e
mao.o omoo.o o.Ho .m
mmo.o oaoo.o N.¢o .N
oao.o mooo.o m.~n .H
z z
poozm 930m :HE\HE
museumoao
ocfinwumouu goonnam

 

mwfionmouas downwawouom

 

.finfls\fis mh-He uuv ousflflmm Hanan

ofiaouco vfifie no“: uzowumm mo woozm wan poem How muaonmoRSH nofiuwamouom .m macaw

44

 

 

mHo.o mHoo.c H.0H .m
oNo.o ouoo.o m.ma .5
«Ho.o afloo.o o.HN .o
mHo.o Nmoo.o m.- .m
mHo.o NHoo.o e.m~ .e
mHo.o mooo.o v.n~ .m
oqo.o mooo.o m.m~ .N
ooo.o mooo.o H.mm .H
z z
poozm Room :wE\HE
oucmpmoau
ocfizwpmouu muoonnom

 

mwfionmopne :ofiufiamooom

 

oumnouoe zuwz mucowumm mo poozm wan poem new mwaogmounu :ofiuficmooom

.ficwe\ae o¢-mfl uuv mending Hanan uflaopgu

.o oHan

45

 

. w~o.o mmoo.o m.m .oH
mHo.o cHoo.o o.m .m
omo.o vmco.o o.ou .w
mmo.o omoo.o o.o~ .5
moc.o o~oo.o m.oH .o
omo.o caoo.o m.HH .m
mHo.o vooo.o ¢.HH .q
omo.o oaoo.o H.NH .m
omo.o oHoc.o m.~H .N
omo.o «Noo.o o.mH .H

z z
poozm “sow :HE\HE
oocwnmoau
ocficfiumoho poomnsm

 

mwfioamopne :OMuficmooom

 

ofiQOpno ono>om aufiz mucofipmm mo poozm can usom how mufiosmouzu :owuficmooom

.Acfis\fla ma can» mmofi cow ouzflfimm Hence

.5 oHan

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

EICONTROL
.3 0,04 I®IGROUP l
1;? IEIGROUPH
55 . -GROUP m
" 0.03
2:
9.
'_.
E
+- 0.02 e
z \
a \\
'6’
0 0.0! \
CE
<
a \
5 \\ _.

 

 

 

Figure 4. Mean taste recognition thresholds for sweet
for patients with mild, moderate, and severe renal fail-
ure and control subjects.

47

.oo.o H can omv n muoonn3m Houucou m we can: .6

Acma\fis mHv uuv .u A=He\fle o4-mH uuv .a mafis\fla ma-H¢ uuv .m

 

 

mm.onmq.o H.H 4.44Mfim.hn¢ m.ooNHH¢H H.4HHH.mB OH .uHHH macho
mH.OHom.o o.H m.¢mNHH.~om «.mmfiou q.mwm.~m w .nHH macho
4N.OHN©.Q o.H o.NNeHm.¢ooH o.oaomv o.oHHm.Nm m .mH macho
.umonu .EM\u:mN m: owmmEm pm pmmmm: am mam pm Hmmm: muuomnsm
onwhs .umouu mawua .wm>wamm eahom 2 mo mzpmum

 

.ommomfiw Hench owcogno spa: mucowumm mo mafia: .m>wamm .Espom :fl ucfim .m oases

48

mild, moderate and severe renal failure. The patients
with mild renal impairment had significantly higher (P<
0.01) serum zinc levels than did the patients with severe
renal impairment. Urinary zinc, when expressed as ug/240
also decreased significantly with severe renal impair-
ment when compared to mild renal impairment (P S0.05),
however, if expressed as ug/gm creatinine, there was no
significant difference among the three groups. However,
the difference between Group I, mild renal failure, and
Group III, severe renal failure, did approach significance
(P<<.057). Salivary zinc levels rose as renal function
declined: Mild $30 ppb; moderate 66.5 ppb; and severe
141 ppb zinc. (Table 8.) However, these differences
were not significant.

Mean dietary zinc intake did not differ between
the three groups of patients (10.0 mg, 13.5 mg and 14 mg
/24 hours) with mild, moderate and severe chronic renal
failure respectively. Dietary zinc intake generally
fell as protein intake decreased (Table 9.), however,
depending upon the sources of protein, this was not al-
ways true. Patient PN consumed wine and nuts which are
high in zinc, whereas patient AV consumed primarily eggs,
milk products and hotdogs which are not high in zinc.
Many of the patients in Group III, severe renal impair-

ment, had not yet decreased their intake of protein and

49

ocHN .zumww woom zap N we ommuo>m .muso: em you mamumHHHHE

:Hououm .zumHv doom zap N we ommuo>m .mgno: em you mamum .n

.:H5\Ha mH saga mmoH oucmpmoHu ocwzwumopu HHH macho H:HE\HE ov-mH
moamhmoHo oanHumouo HH macho maHe\He mn-He oucmHmoHo ocflnHumouo H @3090 .m

 

 

 

wmopm cu m HH :>

moon .xhoa me a HHH zo

anon we a HHH 2m

mcmon onHw .omoocu om m H mm

moon co m H 20

xHHE .umoz ma HH H He

MHHE .ummz omH HH . H ><

woom om NH HH mu

omoonu mo mH H on

ummmxmopm .pmcH .xuom cm «H HH 4:

omooso .Hoom ow 0H HH mu

amen: oHonz .Hoom om NH HHH mm

mun: .coonno .ocHz Nu wH HHH 2m
osHN Ho oohsom sown: .omwmmmmm .noch .mmsopw use ucoHumm

.moHpme woom Ho ucoucoo uamN wan :Hououm .m oHan

50

averaged an intake of 64.4 gms protein per day (range

42-80 gm protein per day). Patients in Groups I and II
were not on any dietary restrictions at the time of the
study and averaged 78.0 gm protein per day (range 50-120
gm protein per day) for Group I and 60.0 gm protein per

day (range 40-80 gm protein per day) for Group II.

DISCUSSION

End-stage renal disease patients (ESRD) undergoing
hemodialysis had impaired ability to recognize primary
tastes. Recognition of sour and sweet taste was more
seriously impaired than salty and bitter. Improvement
of all four primary taste recognition thresholds occurred
following hemodialysis. The impairment in the ability
to recognize sour appears to precede end-stage renal
disease. Patients with moderate renal impairment also
begin to require greater concentrations of solutions
of tartaric acid in order to recognize sour. The sweet
taste, however, begins to deteriorate later in the pro-
gression of renal disease and does not become signifi-
cantly impaired until end-stage renal disease occurs.
Salty and bitter recognition thresholds do not appear
to change in response to renal disease, although for
some patients, salt recognition thresholds may be im-
paired.

Zinc has been implicated in many conditions associ-
ated with hypogeusia including end-stage renal disease
(Atkin-Thor et al., 1978). Henkin et al. (1972) have
postulated that zinc acts as a cofactor in a gustatory

protein called gustin. This protein has been proposed

52

as the carrier of the chemical responsible for a particular
taste to the taste receptor. Gershoff (1977) postulated
that the zinc molecule may interact with the membrane of
the taste pore in order that chemicals may more easily
penetrate the taste pore and reach the taste bud. The
information concerning zinc metabolism among hemodialyzed
patients is controversial. Mahler et al. (1970), and
Mansouri et a1. (1970) reported decreased concentrations
of serum zinc among end-stage renal disease patients,
whereas Bloomfield et al in 1969, and Rose et al. in 1972,
reported normal or slightly elevated concentrations of
serum zinc in their patients. Atkin-Thor and co-workers
(1978) reported that 95% of their dialysis patients tested
had some degree of hypogeusia, although specific taste
abnormalities were not identified. Six weeks after sup—
plementation with 440 mg zinc sulfate, three times per
week, taste acuity and appetite improved in 90% of the
experimental subjects. Improvement in taste acuity was
seen, even though in 5 patients there was a decrease in
hair zinc concentration following supplementation. Two
patients with increased hair zinc concentrations exper-
ienced no improvement in taste acuity. Fifteen percent

of patients on zinc supplementation experienced side
effects which resembled hypoglycemia. Petrie and Row

(1977) reported 11 cases of zinc toxicity in patients who

53

were dialyzed using a galvanized piping system for water
delivery to the dialyzer. Severe anemias developed in
all patients, with hemoglobin as low as 3.2 g/dl. There
was no evidence of blood loss, however, red cell life
spans averaged three days. The amount of zinc present
in the dialysate solution was 6.54 ug/dl. Nausea and
vomiting was also noted among these patients.

Serum zinc values for ESRD patients in the present
study did not change after dialysis, and were low-normal
both before and after dialysis. Although several pa-
tients in this study had low-normal serum zinc concen-
trations, there was improvement in taste acuity after
dialysis. Since no changes in serum zinc concentrations
occurred, this would tend to disqualify zinc deficiency
as an explanation for the observed hypogeusia. Other mea-
surements for zinc deficiency also failed to provide
evidence for a causal relationship between zinc de-
ficiency and hypogeusia in the chronic renal disease
patient p0pu1ation. Salivary levels of zinc rose as
kidneyfunction decreased, rather than fell as others
have reported for patients with hypogeusia (Henkin, 1975).

If zinc deficiency were the explanation for hypogeu-
sia among these patients, one would expect to see impair-
ment of all four tastes. Instead, we observed impair-

ment of sour and sweet in the hemodialysis patients, and

54

sour alone in patients with moderate to severe renal
impairment.

Considering the clinical complications which have
been identified with zinc supplementation programs, further
research identifying a close relationship with zinc de-
ficiency in the ESRD patient and taste impairment should
be completed before widespread zinc supplementation pro-
grams are advanced.

The presence of H+ ions in solution appear to be
necessary for the normal experience of sour, and the sour-
ness of a solution can be decreased by neutralization with
an anion. Simenhoff and co-workers (1977) have shown
that the level of dimethyl and trimethyl amines are in-
creased in patients with end-stage renal disease. A
significant decrease in these amines also occurs after
a hemodialysis treatment. Dimethyl and trimethyl amines
are strong basic compounds which may result in neutrali-
zing an acid solution placed in the mouth. Consequently,
higher concentrations of the acid would be required to eli-
cit a sour response. This phenomenon may be a reasonable
explanation for sour taste recognition impairment among
ESRD and chronic renal disease patients, and further
identify a plausible reason why these thresholds improve
with a single dialysis treatment.

The taste threshold test is a relatively inexpensive

55

and simple test which may be useful in assessing the
adequacy of hemodialysis programs. Sour and sweet taste
threshold measurements appear to be the most sensitive
in delineating potential gustatory differences in these
patients. These modalities are significantly impaired
before dialysis and improve significantly with a single
dialysis treatment.

End-stage renal disease patients who are maintained
on routine hemodialysis have an increased need for calories.
Many of these calories must come from low-electrolyte,
low-protein sources. Many patients find it difficult
to ingest sufficient amounts of these products, and con-
sequently, they lose body weight. One factor which af-
fects palatability of food is the ability to taste food.
Identification of mechanisms for taste alterations should
lead to correction, or at least a better understanding
by professional personnel of the problems imposed upon
these patients in acceptance of special diets. In ad-
dition, it could help the food industry to prepare pal-
atable and acceptable foods for renal failure patients.
Some food companies are already employing taste panels
composed of patients with end-stage renal disease to
identify acceptable products for this patient popula-

tion.

CONCLUSIONS AND SUGGESTIONS FOR FURTHER STUDIES

Recognition taste thresholds for tartaric acid (sour)
and sucrose (sweet) are significantly impaired in
end-stage renal disease patients, as compared to
controls, prior to a hemodialysis treatment. Qui-
nine sulfate (bitter) and sodium chloride (salty)
recognition thresholds are not significantly al-

tered in patients with end-stage renal disease.

Recognition taste thresholds for the first two taste
modalities (sour, sweet) improve significantly after

a single hemodialysis treatment.

Taste acuity in respect to tartaric acid (sour) de-
clines as renal function declines in patients with

chronic renal disease, and becomes significantly im-
paired when creatinine clearance falls below 15 ml/

min.

Serum zinc levels fall as creatinine clearance de-
clines, however, serum zinc levels do not significant-

ly change with a single hemodialysis treatment.

Salivary zinc levels rise as creatinine clearances

decline, however, these trends are not significant.

S7

6. Dietary zinc levels tend to fall as protein intake
falls. There was no correlation with average zinc
intake and taste acuity. Specific food differences
greatly affect zinc intake and are independent of

protein intake.

Taste acuity impairment was most apparent in respect
to sour. Changes in salivary concentrations of trimethyl
and dimethyl amines may be a plausible explanation for this
alteration. Determining levels of these amines in the
ESRD patient, and correlating these findings with the
degree of taste threshold impairment would be a stronger
defense of this theory. In addition, a study of the pH
changes which occur in saliva in response to additions
of graded amounts of these chemicals would identify whether
these pH changes would be sufficient to neutralize the
H+ ions present in the sour solutions.

We noted increases in salivary zinc as renal func-
tion decreased. The possibility of salivary concentra-
tion, due to decreased salivary flow was not ruled out
as an explanation of this zinc accumulation. Identifying
whether there are changes in salivary flow rate with pro-
gressive decline in renal function may not only identify
a mechanism for the increased zinc levels in saliva, but
may also identify a mechanism for meat aversion or de-

creased appetite in this patient population.

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