AN EXPERIMENTAL INVESTIGATION OF THE _‘E.FFEC'I‘S OF VITAMIN E12 ON THE GROWTH AND PHYSICAL PERFORMANCE OF UNDERNOURISHED Boys; T "IS'PQR THE DEGREEOFM. AI . , MICHIGAN STATE UNIVERSITY . ~ JGHNEDWARD WALKER ' ‘ . 1955 .- This is to certify that the thesis entitled “W Investigation“ theEffeotaofVitamB-lzontho Grantham Physical Performance of WW presented by Johnwwalbr has been accepted towards fulfillment of the requirements for lh‘l"°3"£§';de ree mm chlxcetion and Recreation 3 %:r professor 5% Date W 124 1955 AN EXPERIMENTAL INVESTIGATION OF THE EFFECTS OF VITAMIN 8-12 ON THE GROWTH AND PHYSICAL PERFORMANCE OF UNDERNOURISHED BOYS By John Edward Walker A THESIS Submitted to the School of Education of Michigan State University of Agriculture and Applied Science in partial fulfillment of the {- requirements for the degree of{ \ MASTER OF ARTS Department of Health, Physical Education, and Recreation for Men 1955 AC K NOWL EDGM li Ni S The writer wishes to eXpress appreciation to his ad— visor, Dr. Henry J. Montoye, for his guidance and inspiration throughout this experiment. Appreciation is also extended to Paul Spata and Leo Barren of Boys Vocational School, whose help in the testings and diligent supervision of the daily capsule feedings made this experiment possible. The cooper— ation of the cottage parents who administered the capsules on the weekends was appreciated. Thanks are extended to Sharp and Dohme for their generous supply of Vitamin B—12 and placebo capsules. Finally, the writer wishes to eXpress his gratitude to his wife, Sue, for her help and suggestions throughout the writing of this thesis. J.E.W. AN t3dMfi£QMFNTUHI INVESTI(UYFION (H9'FHE LIT” CTS (H9 VITAMIAJIS—lfl ON THE GROWTH AND l’ll\'SICAL l’ERFOlC‘iAB-ICE OF UNDI‘RNOURISHED BOYS by John Edward Walker AN ABSTRACT OF A THESIS Submitted to the School of Education of Michigan State 'University of Agriculture and Applied Science in partial fulfillment of the requirements ' for the degree of MASTER OF ARTS Department of Health, Physical Education, and Recreation for Men 1955 J oh n ltld ward Na .1. k e I‘ 1 Statement 21 the Problem: This experim-nt wls designed to determine the effects, if any, of a daily fifty microgram oral supplement of Vitamin B-12 on the growth and physical performance of undernourished boys. Need for the Study: The need for this study stems from the reelization that the fullest development of an individual can not be ob~ tained when he is not "up to par" physically or nutritionally. It is felt that by improving the nourishment of a selected group of undernourished boys that their growth and physical performance onld likewise improve. A comprehensive review of the literature revealed few studies in this area of nutrition. Method: and Procedure: Twenty—five undern urished boys between the ages of twelve and seventeen were select d as subjects in this exper- iment. (H ‘tiese twenty-Tixwrlaoys, twelve ftnmaxt the experi- mental group and received the Vitamin H—12 capsule, while the remairdmu. lhlPlCKflllNLVS made Ln) the Contxntl group and r‘I‘Ct'lVL‘d the placebo (blank) capsule. The Wetzel Grid was empl yed to select subjects and to determine their degree of growth failure. Onc‘ the subjects were selected, they were randomly divided into the two experimental groups according ta) tlieiI‘ rtespec2tiv<) dewgrecw; :I‘ ginnvth tkiiltua*. iix;u:t iIeigdit and weight measurements, plus a batt-ry «f physical perform- ance tests were administered to each subject at the beginning and end of the three month eXperimental period. The Student "t", or small samplx technique, was used in analyzing and comparing the results of the two groups. Conclusions: 1. No significant differences were found in the initial measurements of growth and physical performance in the two groups. 2. In comparing the improvements of the two groups, there were no significant improvements in any of the cate- gories of growth and physical performance in favor of either group at the termination of the three month experimental period. 3. When the Vitamin B-12 and placebo groups were combined, an appreciable improvement in height was noted during the experiment. 4. The other "t" values for growth and physical performance with the two groups combined, although not sta- tistically significant, indicate general improvement in growth and physical performance during the period of the experiment. Henr&w{:;M0ntoye MaJIH‘I Ivistn‘ .\\.u.- r7......a..__ .....‘-__.. c TABLE OF CONTENTS C HAPT ER 1, INTRODUCTION . . . . . . . . . . . . . . . . . Need for the Study. . . . . . . . . . . . . Statement of the Problem. . . . . . . . . . Limitations of the Study. . . . . . . . . . Definition of Terms Used. . . . . . . . . . Growth Failure . . . . . . . . . . . . . Placebo . . 5 . . . . . . . . . . . . . 11.. REVIEW OF THE LITERATURE. . . . . . . . . . . Vitamin 8-12 . . . . . . . . . . . . . . Chemical and physical properties . . . . Source and requirements. . . . . . . . . Importance of Vitamin 8-12 in metabolism.. Absorption and retention of Vitamin 8—12. Vitamin 8-12 in pernicious anemia and other dis ases. . . . . . . . . . . . . Vitamin B-12 and Growth . . . . . . . . . . Vitamin B-12 and growth in animals. . . . Vitamin B—12 and growth in humans . . . . Vitamin ”-12 and Physical Performance . . . III. METHODOLOG’ . . . . . . . . . . . . . . .. . . Experimental Design. . . . . . . . . . Explanation of Wetzel Grid . . . . . . . Calibration of the Scales. . . . . . . . . Explanations of the Tests . . . . . . . . PAGE CI] 11 11 ll 12 13 14 15 16 18 CHAPTER IV. The Harvard Step Test Chin and dip tests Vertical Jump. . . . . Grip strength. . . . . Push and Pull strength Back and leg strength Half-Mile Run . . . . . Organization and Analysis RESULTS . . . . . . . . . Discussion of Results . SUMMARY, CONCLUSIONS AND RECOMMENDATIONS Summary . . . . . . . . Conclusions . . . . . . Recommendations . . . . BIBLIOGRAPHY. . . . . . . APPENDIX. . . . . . . . . PAGE 59 62 63 64 64 65 66 67 68 76 8O 8O 82 84 LIST OF TABLES TABLE PAGE I. Actual Weight of Barbells as Measured by the Calibrated Nutrition Scales of Michigan State University . . . . . . . . . . . . . . . . . . 58 II. Daily Weight Corrections as Determined by the Differences between the Actual Weight and Recorded Weight of Barbells. . . . . . . . . . 60 III. Comparison of Vitamin B-12 and Placebo Groups in Mean Initial Measurements of Growth and Physical Performance . . . . . . . . . . . . . 69 IV. Comparison of Vitamin B-12 and Placebo Groups in Weekly Mean Changes in Growth During Ex- periment Period. . . . . . . . . . . . . . . . 70 V. Comparison of Vitamin B-12 and Placebo Groups in Weekly Mean Changes in Physical Performance During Experimental Period . . . . ... . . . . 72 VI. Significance of Weekly Mean Changes in Growth and Physical Performance During the Experi- mental Period with Vitamin B—12 and Placebo Groups Combined . . . . . . . . . . . . . . . 74 VII. Significance of Weekly Mean Changes in Growth and Physical Performance During the Experi- mental Period with VitaminB-l2 and Placebo. . Groups Not Combined.. . . . . . . . . . . . . 75 VIII. Raw Score Data . . . . . . . . . . . . . . . . 95 IX. Raw Score Data . . . . . . . . . . . . u‘. . . 97 LIST OF FIGURES FIGURES PAGE 1. wetzel Grid 0 O O O O C O O O O O I O O . O C O 52 CHAPTER I INTRODUCTION Physical education is now recognized as an integral part of the educational program. Its aims are inextricably related to the general aims of education in that they are concerned with the total development of each individual mentally, physically, socially, and emotionally. The pos- ibilities of the physical education program are aptly ex- pressed by Voltmer when he states, "Physical education, when well taught, can contribute more to the goals of general ed- ucation than any other school subject."1 One of the most important aims of physical education is to give to each individual a workable knowledge of many sports skills. Thus, by the time a person leaves high school, he will have a repertoire of sport skills from which to choose to make his leisure hours as an adult worthwhile and enjoyable. Due to the increased amount of leisure time brought about by great technological advances, this phase of physical education has taken on new significance. In sup— port of this, one can justly predict that the amount of leisure time will continue to increase with the advent of 1Edward F. Voltmer and Arthur A. Esslinger, The Organization and Administration of Physical Education (Second edition; New York: Appletbn-Century-Crofts, Incor- porated, 1949) p. 14. the atomic age. A person usually thinks of the fundamentals of edu— cation as consisting of reading, writing, the ability to use numbers, and the elements of oral expression. These are the intellectual tools supplied by an education, but what about the physical tools? LaPorte, in the following paragraph, aptly expresses the status of our physical tools when he says: The physical tools to a large extent have been over- looked or disregarded. As a result, there can be found at all school levels a vast army of children below par physically, unable to protect themselves, unable to express themselves freely and efficiently, and woe- fully weak in adapting themselves readily to their phys- ical environment. . Voltmer and Esslinger fully realize this need for the physical tools and describe them as "fundamental processes" or defined, "those physical skills common to America in gen— eral and to one's own locality inparticular."3 The impor- tance of the child acquiring these fundamental processes is further crystallized in that: The child needs them now for happy living, but also because future physical endeavors and many life occupa- tions are based on them. . . . Children live on a dif- ferent level from that of adults. In play situations 2W.R. LaPorte, "Physical Education Contributes to the Seven Cardinal Principles of Education," Journal g: Health and Physical Education, 4:10, March, 1933. 3Voltmer and Esslinger, op. cit., p. 22. 3 the good performer is the hero and the poor performer is pushed into the background. Much of the child's life is play life and a large share of it deals with physical skills, where only a small part of adult life is play and a good performance is not stressed so much. . . . The child does not have those numerous other phases of endeavor to which he can turn for suc- cess if he fails miserably in his physical skills. He must master the fundamental processes or suffer the consequences of loss of standing among his fellows in one of the major fields of youthful endeavor. That is one of life's most severe punishments, aad it can be avoided by improving physical abilities. Although the preceding paragraph gives several reasons why the child's physical abilities should be devel- oped, it does not mention the psychological repercussions upon the child when poor ability in performance is exhibited. When lack of ability is displayed, feelings of inferiority and insecurity are often manifested. Physical education then becomes an annoying eXperience and methods are devised to obtain release from physical education classes. Some common excuses might be the feigning of illness or the ex- pression of a desire to indulge in some other activity of more interest, which in reality, is merely a less annoying activity. When such situations are permitted to exist, the very boys who need physical education the most are excused or delegated nonskill pastimes of negigible value. Health, which tops the list of the Seven Cardinal Principles of Education, rightfully merits such a position. 4Voltmer and Esslinger, 32. cit., p. 22. Such is expressed by the Commission on the Reorganization of Secondary Education when its members so wisely said, "To discharge the duties of life and to benefit from leisure, one must have good health. The health of the individual is essential also to the vitality of the race and the defense of the nation."5 Although this first applied more specifi- cally to health education, it is also very applicable to physical education. LaPorte aptly applies this statement to physical education in his statement that, "While all depart- ments and subjects in the school should contribute positively to this objective, physical education must accept it as a major responsibility."6 His definition of health is ex- pressed as: The state of being in which the individual (or group) within the limits of its native capacity is able to function most effectively and satisfyingly for self and others—-phy51cally, mentally, and 5001ally. Health is indeed a goal of first importance in ed- ucation, as is further illustrated by the Educational Pol- icies Commission when they formulated the Purposes of Ed- 5Commission on the Reorganization of Secondary Ed- ucation, United States Bureau 9: Education Bulletin, "Card- inal Principles of Secondary Education”, No. 35, (Washing- ton: United States Printing Office, 1928) p. 4. 6LaPorte, loc. cit. 71bid. p. 11. ucation in American Democracy. A part of this statement reads, "Health is a factor which conditions our success in all our undertakings, personal and social."8 Need for the Study The preceding paragraphs suggest the need for this study. Can we truly accomplish these worthy objectives and goals of physical education, and visualize at the same time the fullest development of each individual when some of them are obviously not "up to par" physically or nutritionally? The author cannot conceive the fullest physical and mental growth of each individual when malnutrition is evidenced, as in many physical education classes. Futhermore, many activities require strength, endurance, and quickness, which are not generally a part of the malnourished person's phys- ical makeup. Nutritionists are in agreement with the above contention and recognize that "where real deficiencies exist, there is little question that physical performance is hin- dered."9 In light of this, it is the investigators con- tention that all too often physical educators fail to 8Educational Policies Commission; Purgoses gglgg- ucation ig American Democracy, (Washington . .: National Education Association, 1938), p. 60. 9Ancel Keys, "Physical Performance in Relationship to Diet," Federation Proceedings, 2:164, June, 1943. 6 ascertain the underlying cause for poor physical performance. Instead, they frequently associate one's physical ineptness to lack of native ability, or to the fact that he just happens to be thinner or smaller than his healthier associates. Un- fortunately, this cursory observation is all too often the last step involved. Thus, the physical educator continues to teach a skill in the same routine manner, regardless of whether or not the individual is capable physically to ac- quire the skill readily, or at all. It is felt that the responsibility in part, rests with the physical education program, for it is this phase of the educational system which is primarily concerned with the deve10pment of one's physical tools. When certain in- dividuals leave high school without a basic knowledge of sports skills, they are handicapped in their own adult pur- suits of recreation and wise use of leisure time. Probably these same individuals would have deve10ped an interest and some skill in sports if they had experienced some success in the lower grades. Could the fact that some of them possibly exhibited growth failure have something to de with their lack of success? This experiment will be directed towards answering this question. The importance of health as one of the paramount goals of education has been mentioned in the introductory 7 paragraphs. It is also well recognized that the problem of malnutrition represents one of the crucial health problems of our country and nations abroad. This further suggests the need for this study, since it is concerned with improving one's health through better nutrition, specifically the ad- dition of Vitamin B—12 supplements to the diet of young, malnourished boys. That health is inextricably related to prOper nu- trition is quite generally accepted. Deihl, one of the fore- most authorities on health expresses his views on its impor— tance in the following words. Health and well being are dependent upon proper diet and wise choice of foods. Fatigue and lowered resis- tance to infection may be due to lack of certain es- sential nutrition requirements. Adequate nutrition is the first prerequisite to Vigorous health. It is also generally recognized that poor nutrition is related to mental, emotional and physical stress.11’12 Without proper nutrition, the delicate organic system‘of bal- ances and counterbalances will go askew. In addition, it is well recognized that undernourishment and malnutrition 10Harold S. Deihl, Textbook 9f Healthful Living, (Fourth edition; New York: McGraw—Hill Book Company, Inc., 1950), p. 80.- 11Tom D. Spies, Rehabilitation Through Better Nutri- tion, (Philadelphia: W.B. Saunders Company, 1947) pp.l-2TS 12H.H. Mitchell, "Nutrition and Stress", Borden's Review pf Nutritional Research, 13:97-107, November, 1952. 8 influence human emotions and behavior.13 In light of this, the nutrition of all people takes on added importance, for there is not a question that correction of nutritional dis- turbances is beneficial to behavior and to the physical per— formance of human beings.14 Probably the most important reason for this study lies in the fact that the boys themselves, who are under- nourished, are deeply sensitive to their physiques as well as their inability to perform. Bridgeman and Steitzl5 speak of this adolescent period as one in which there is a keen interest in the physical well-being of the body and that boys' inter- ests evolve around strength. Also, adolescents always want to know whether or not they are "normal" and how to correct abnormalities. This is further substantiated by the personal comments of two adolescents in the present experiment when they remarked, "I sure do hope these pills will help me grow," and "I've been this big for the last four years, 13"Vitamin Supplementation and Physical Performance,m Nutrition Reviews, 13:102—4, April, 1955. 14Ibid. 15Donald F° Bridgeman and Edward F. Steitz, "The Needs and Problems of Adolescents in the Area of Physical Develop- ment, " The High School Journal, 35: 39, October, 1951. and I sure do wish I could put on swme weight."16 It is with such statements as these in mind and with the realiza— tion that proper diet is related to one's health and physical performance that this study has been conducted. Statement of the Problem The problem is to determine the effects of Vitamin B-12 supplements to the diet on growth and physical perform- ance of boys exhibiting growth failure. More specifically, the aspects of physical performance to be studied will con- sist of measurements of strength, endurance, power and car- diovascular fitness. Limitations of the Study In any experimental study there is always the human element to consider. Even though the testing was carried out diligently and carefully in as scientific a manner as possible, "Human fallibility can never be completely elim- inated from any human effort."17 The number of subjects and 1()Comments made by two subjects in the experiment. 17Steering Committee of the Research Section and the Research Council of the Research Section of the American Association for Health, Physical Education, and Recreation, Research Methods Applied 13 Health, Physical Education and Recreation, (Revised edition; Washington: American Assoc- iation for Health, Physical Education and Recreation, 1952) p. 302. 10 the length of the experimental period represent other possible limitations. However, it was felt that accurate work done with a few subjects over a short period of time would result in some tentative conclusions. Previous growth records were not obtainable for the subjects. Hence, they were selected as subjects only on the basis of their present growth status as determined by their respective height and weight measurements, with age also being another consideration in the selection of stunted boys. There were no available data on their living and eating habits before they came to the institution. It was difficult, therefore, to judge whether their present growth failure was related to an inadequate consumption of the essential food elements or due to a special need for more of one particular kind of vitamin. Due to the small number of under nourished boys, borderline cases of undernourishment were used as sub- jects. A limitation of this study becomes apparent, for a good nutrition program, such as the one in operation at this institution, would correct the former types of malnutrition possibly without additional supplements of Vitamin B-12. It would be virtually impossible to find conditions wherein both the manner of living and nutrition were both known and controlled. Nevertheless, it is felt that the favorable conditions present justify this experiment. 11 Definition of Terms Used Growth Failure. The term growth failure will be used interchangeably with malnutrition and undernourishment through- out this thesis. Specifically, it applies to those boys whose growth status plots on the Wetzel Grid growth index chart18 in physique channels B2, B3, or B4. It also includes four small boys, who showed retarded growth by their respective developmental plottings on or near the 98 per cent auxodrome. Placebo. A placebo is a blank capsule, which looks exactly like a real Vitamin B-12 capsule. The placebo or control group represents the subjects who received the blank capsule. 18C.F. Wetzel Grid in Chapter III, Methodology. CHAPTER 11 REVIEW OF THE LITERATURE The effect of food on one's physical performance is not a new interest. Napoleon, realizing that his men were ill on the front lines as a result of food spoilage, stim- ulated action to improve the preservation of food, which ultimately resulted in the evolution of the canning industry. Although the canning of food and the use of food to promote physical fitness are not new, the use of vitamin supplements as aids in promoting physical performance is a relatively recent idea. World War II gave impetus to this interest, especially in the armed services and industrial fields where a high premium was placed on the physical performance of the soldier and industrial worker. Even though the early efforts to improve physical performance rest on tenuous ground,1 interest should not wane, for, with the discovery of each new vitamin, new fields of research are opened in its application to nutrition and physical performance. Also the fact that there is ample clinical experience and convincing experimental evidence available which show that a deficiency of vitamins, particularly 1"Vitamin Supplementation and Physical Performance", Nutrition Reviews, 13:103, April, 1955. 13 those of the B-complex, results in a marked deterioration in the ability to do work,2 further suggests a need for con- tinued research in this area of nutrition. Vitamin B-12 In recent years great advancements have contributed much to our knowledge of the nutritional needs of the body. Of particular importance in this respect was the discovery and identification of Vitamin B-12 in 1948.3 This discovery was ultimately stimulated by the work of Minot and Murphy, who, in 1926, observed that the blood count nearly doubled in all of forty-five patients treated for pernicious anemia with a diet rich in 1iver.4 At first it was thought that the folic acid in the liver was the solution, but it proved to be ineffective in relieving many of the symptoms of the disease.5 .Many studies were carried on to find this potent substance in liver extract, but it was not until 1948 that 2"Vitamin Supplements and Performance Capacity", Nutrition Reviews, 8:317, October, 1950. 3Lester E. Smith, "The Discovery and Identifications of Vitamin B-12," British_Journal.gf Nutrition, 6:295-299, January, 1952. - 4George R. Minot and William P. Murphy, "Treatment of Pernicious Anemia by a Special Diet", Journal 2: the American Medical Association, 87:476, August, 1926. 5Lenna F. C00per, et 1., Nutrition in Health gnd Disease, (Philadelphia: J.fiT‘Lippincott Comnafiy, 1953), p. 103. 14 Vitamin B —12 was isolated in the form of a red crystalline substance. From the start it was abundantly clear to re- searchers that this substance was definitely a member of the B—complex group of vitamins and resulted in labeling it "Vitamin B-12."5 Chemical and Physical Properties. The chemical struc- ture of Vitamin B-12 has only been partially determined.7 There is agreement, however, that this complex molecule con- sists of a nitrogenous compound containing one atom each of phosphorous and cobalt, plus minute quantities of carbon, hydrogen, and oxygen.8’9!10 Vitamin B—12 occurs in deep red crystals containing a variable amount of water of crystal- lization. It is moderately soluble in water (1.2 per cent) and in alcohol, but not in most other organic solvents. It is also very stable, even in a dry state of one hundred degrees 68mith,'gp. cit., p. 295. 7Smith, 10c. cit. 8Cooper t al., 10c. cit. 9 Smith, 22, c1t., p._297. 10Edward L. Rickes, 31 al., "Crystalline Vitamin B—12," Science, pp. 107-396, April, 1948. 15 Centigrade.11 From the foregoing statement, one might con— clude that Vitamin B—12 is capable of standing for long periods of time without decomposition concentrates. Source and Requirements. Natural Vitamin B-12 is not found in vegetable tissues because plants lack the abil— ity to synthesize this vitamin.12 The orginal source of Vitamin B—12 in nature appears in fungi, and perhaps certain 13,14 other micro-organisms. It is well known that Vitamin B-12 is widely distributed in foods of animal origin; the two richest sources being liver and kidney, with small quan- tities contained in meats, egg yolk, cheese and casein.15’16 11Smith, loc. cit. 12Ibid., p. 293. 13Ibid. 14James S. McLester and William J. Darby, Nutrition and Diet.in Health and Disease, (Philadelphia: W.B. Saunders, 1952), DP. 78—80. 15Smith, 2‘, cit., p. 299. 16"Vitamin B—12 Distribution in Nature," Nutrition Reviews, 13:113-4, April, 1955. 16 A common commercial source is the fermentation of liquor of 17’18 Since the source material, Streptomyces griseus. whether it be liver or fermentation liquor, contains about one part per million of Vitamin B—l2. The factors involved in purification entail a long sequence of steps including at least one chromatographic separation. The methods of .purification will not be elaborated on further except to mention that at the present time there are several assay methods for Vitamin B—12.19 The efficiency of absorption of Vitamin B-12 in normal individuals has not yet been clearly defined, but it is apparent that the normal human being requires a dietary supply of this factor; the level of which is of microgram 20:21 A deficiency of this vitamin in healthy proportions. men and women is rare, but their bodies do not seem immune to absorbing additional quantities of it when given intra— muscularly.22’23 17 , . McLester and Darby, 92. Cit., p. 79. 18Smith, 0 . cit., p. 296. 191bid., p. 298. 20Ibid. 21 McLester and Darby, pp, cit., p. 80. 22Calvin Lang, et. 21,, "Retention of Crystalline Vitamin B-12 by HealthyEMale Individuals following Intra— muscular Injection," Journal gf__NutritionJ 46:221, February, 1952 23Bacon F. Chow, "The Role of Vitamin B—12 in Metab— olism," Southern Medical Journal, 45:604—11, July, 1952. l7 Importance 2f Vitamin B-12 in Metabolism. Vitamin B-12 carries out many very important functions of the body. The fact that Vitamin B-12 contains nitrogenous compounds, that are alone found in proteins which are necessary for the building of new tissues and repairing of worn out tissues, enhances the carrying out of these important bodily functions. These are carried out in the process of digestion when the proteins are broken down into different amino acids, which are the building blocks of body tissue. Even though amino acids are a constant necessity, they are not stored by the body.24 It is, therefore, very important that the diet supply be furnished with adequate amounts of protein and Vitamin B—12. Another pertinent function of Vitamin B-12 is the decisive role it plays in the bio-synthesis of methionine, 25,26 a very essential amino acid. The use of Vitamin B—12 as a therapeutic measure with wounds has manifested good 24Haroid s. Diehl, Textbook of Healthful Living, (New York: McGraw-Hill Book Company, Inc. , 1950), pp. 90— 91. 25L. w. Charkey, et. a1. ., "Vitamin B 12 in Amino Acid Metabolism", Proceedingg of the Society* of Experimental Bio— logical Medicine, 73: 21— 4, —January, 1950. , cob Dubnoff, "Vitamin B-12 in Methionine For— mation", Fegeration Proceedingg, 10e178, 1951. 18 results by decreasing the wound healing time.27 Also, an absence of Vitamin B-12 in animals on a high glycine diet resulted in an earlier death.28 This indicates that Vitamin B-12 is necessary in the metabolism of glycine, another im— portant amino acid. Absorption and Retentiop_p§_Vitamin 8:12, Most vita- mins are readily absorbed from the intestine in man.' However, Vitamin Bv12 absorption is a much more difficult process re- quiring a special component or gastric juice in order to fulfill the body's requirements.29 When absorption diffi- culties are present in patients, they become of great concern to the physician. Consequently, many studies have been made to determine the absorption and retention of Vitamin B-12 in people with and without pernicious anemia. Wolf and associates made an interesting study of the intestinal absorption of Vitamin B—12 in man. The subjects were twenty, healthy young men. They were given varying amounts of Vitamin B-12 orally. It was concluded that the 27Charles W. Findlay Jr. "Effect of Vitamin B- 12 on Wound Healing," Proceedings of the Society of Experimental Biological Medicine, 82: 492—3, March, 1953. 28O.H. Menge and G.F. Combs, "Action of Vitamin B-12 in Counteracting Glycine Toxicity in the Chick", Proceedingo of the Socio_y_ of Experimental Biological MedicineL 75: 142, October, 1950. 29W.B. Castle, "Development of Knowledge Concerning the Gastric Intrinsic Factor and Its Relationship with Per- nicious Anemia,"_Ngw England Journal_pf Medicine, 249:603,12, October, 1953. 19 absorption and retention of Vitamin B-12 was directly related to the frequency and amount of daily doses. That is, with increased doses of 150 micrograms of Vitamin B-12 taken daily during four to eight days, absorption in the blood was in— creased in six patients, who were not affected by smaller single doses.30 These findings were confirmed by similar experiments carried on for basically the same purpose.31’32 Absorption and retention studies of Vitamin B-12 in humans of different age levels have also concluded that significantly greater amounts of Vitamin B-12 are secreted in the urine of young receiving all levels of dosage as coma pared to older men receiving like amounts.33’34 8OR. Wolff et al., "Intestinal Absorption of Vitamin B- 12 in Man," Nutrition Abstracts and Reviews, 23: 415, April, 1953. 31Lang, 2:, al,, Journal of Nutrition,_op. cit., p. 221. * 32Lockard Conley, et. al., "Observations on the Absorp— tion, Utilization and Excretion of Vitamin B- 12", Journal of Laboratory and Clinical Medicing, 38: 84- 94, July, 1951. 33Donald M. Watkin, et. al., "Agewise Differences in the Urinary Excretion of Vitamin—B— 12 Following Intramuscular Administration", Journal of Nutrition, 50: 341- 9, July, 1953. 34Calvin A. Lang and Bacon F. Chow, "Retention of Vitamin B-12 After Administration to Subjects of Different Ages", Federation Broceedings, 11:88, March, 1953. 20 Some observations of the metabolism of nineteen Jamaican children receiving Vitamin B-12 over a period of nine months showed a significantly higher plasma concentra- tion in the B-12 group as compared to the control group. Also, when comparing children of a normal growth pattern in the experimental group with children of retarded growth in the same group, no marked differences were observed between them in their urinary excretion of Vitamin B-12 or in the rate of its removal from the plasma.35 Thus, it might be said that growth patterns do not determine absorption and retention of Vitamin B-l2. Vitamin B-12413_Eernicious Anemia dnd Other Diseasgs. The discovery of Vitamin B-12 is inextricably related to the early efforts of physicians to find a remedy to cure or com- bat pernicious anemia.36 Such a cure was indeed necessary, for, prior to 1927, this condition was "uniformly fatal as inOperable cancer, and with each new attack, the red blood count of patients with pernicious anemia would go lower; 355.T. Patrick, "Some Observation on the Metabolism of Vitamin B-12 by Jamaican Children", Journal of Nutrition, 36. Minot and Murphy, 10c. Cit. 21 culminating in death within two to five years."37 With the discovery and isolation of Vitamin B-12 in 1948,38 physicians now had at their diSposal a substance which they could effec-- tively use in the treatment of rernicious anemia, and no longer would they have to rely solely on a liver-rich diet. The potency of Vitamin B-12 in effectively combating per- nicious anemia is estimated to have a biological activity of 11,000 times that of standard liver extract.39’4O The next problem was to find out why certain people would get pernicious anemia and others wouldn't. Castle and associates were pioneers in determining the reason for this. They postulated that the develOpment of pernicious anemia is dependent upon an inadequate gastric digestion of proteins, thus permitting a virtual deficiency of Vitamin B-12 in the face of a diet adequate for the normal man. Furthermore, they concluded that, in contrast to the condition 37Anton J. Carlson and Victor Johnson, The Machinery 9£_the Body, (Chicago: University of Chicago Press, 1953) pp. 1()2"4o 385mith,_92. cit., p. 195. 39Cooper, et. al., 10c. cit. w 405.5. Kahn and R.J. Stave, "Nutrition in Medicine", Annual Review_g§ Medicine, 1:127-52, 1950. 22 within the stomach of the pernicious anemia patient, there is found within the normal stomach some substance capable of promptly and markedly relieving the anemia of these patients during digestion of beef muscle.41 Since Castle was instrumental in determining the why of pernicious anemia, he attached the term "intrinsic factor" to that condition which does not allow the patient with pernicious anemia to absorb the normal amounts of Vitamin B-12 found in the usual diet.42 Confirmation has been given to Castle‘s Conclusions in a later study made by Callender and Lagtha.43 In recent years several studies showing the positive effects of Vitamin B—12 supplements in the treatment of per— 44,45,46 nicious anemia have been carried on. Ungley found, '41 William B. Castle, 23, 21., "Observation of Etiologic Relationships of Achylia Gastrica to Pernicious Anemia," American Journa1_2£ the Medical Spiences, 178:763, November, 1929. 421bid. 43Sheila T. Callender and L.J. Lagtha, "Nature of Castle's Hemapoietic Factor," Blood, 6:1239, December, 1951. 44Randolph West, "Activity of Vitamin B—12 in Addisonian Pernicious Anemia", Science, 107:398, April, 1948. 45M.C. Israels and S. Shubert, "The Treatment of Per- nicious Anemia by Insufflation of Vitamin B—12", Lancet, 266:341-43, February, 1954. 46C.C. Ungley, "Vitamin 3—12 in Pernicious Anemia: Par- enteral Administration", British Medical Journal, 2:1370, December, 1949. 23 in the treatment of fifty—three patients with pernicious anemia intramuscularly, that small doses of 1.25 micrograms had little effect, but doses of 2.5 micrograms produced a definite small response. Larger doses produced still greater increases in the red blood cells in fifteen days.47 In a- nother study using normal individuals and patients with per- nicious anemia in relapse, oral administration of one thousand micrograms of Vitamin B—12 showed no significant alteration in the serum concentration. .When the dosage was increased to five thousand micrograms, the serum concentration in both groups was increased?8 From the foregoing studies, one could conclude that smaller amounts of Vitamin B-12 are needed in the treatment of pernicious anemia when given intramuscularly as compared to oral administration: The difference being that when Vitamin B-12 is administered intramuscularly, it passes directly into the blood, whereas when it is given orally it must be absorbed into the blood stream. The insufflation of Vitamin B—12 has also been used effectively as a means of treating patients with pernicious anemia.49 The method involved the blowing of one—hundred 471bid. 48W.R. Pitney and M.F. Beard, "Serum and Urine Con- centrations of Vitamin B—12 Following Oral Administration of the Vitamin", The American Journal of Clinical Nutrition, 2: 94-5, March,April, 1954. 49Israels and Shubert, 22.cit., p. 342. 24 micrograms of Vitamin B-12 into the nasal passage of anemic patients. It was first blown into the nose from one to three times daily, and later, twice weekly for maintenance. It was well tolerated locally, and the five patients used as sub- jects were successfully treated.50 In light of these good results another method for the successful treatment of per- nicious anemia has found its place in the medical field. Vitamin B-12 has also found good use in the treat- ment of many other diseases. Specifically, some of these 51 52,53 include diabetes mellitus, spinal cord involvements 54 In the latter disease, early and recently poliomyelitis. treatment with Vitamin B-12 as Rubiviton Bayer given to thirty— four patients prevented the onset of paralysis in twenty-six 50Ibid. 51Salvatore M. Sancetta, Perry R. Ayres, and Ray W. Scott, "The Use of Vitamin B—12 in the Management of Neu- rologic Manifestations of Diabetes Mellitus, with Notes on the Administration of Massive Doses," Annuals of Internal Medicine, 35:1028—48, November, 1951 52F. Romeo, "Central Nervous Syndrome in Pernicious Anemia and Vitamin B—12", Nutrition Abstracts and Reviews, 21:735, January, 1952. 53Byron E. Hall, et 31., "Vitamin B-12 and Coordi‘ nation Exercises for Combined Degeneration of.the Spinal Cord in Pernicious Anemia," Journal of the American Medical Association, 141:257-60, September, 1949. 54W. Daur, "Vitamin B-12 in the Treatment of Polio- mylelitis," Nutrition Abstracts and Reviews, 25:239, January, 1955. 25 of the treated patients.55 The author questions very much whether or not this can be contributed solely to the good effects of Vitamin B—l2. Vitamin B-12 and Growth Vitamin B—122nu1 Growth in_Animals. It is well known that Vitamin B-12 is associated with growth in many 56,57,58,59,60,6l,62 species of animals. The study of this 55Daur, loc. cit. 56Arthur J. Hartman, Leslie P. Dryden, and Charles A. Cary, "A Role Lf Vitamin B- 12 in the Normal Mammal," Archives Lf Biochemistry, 23: 165, August, 1949. 57W.F. Cuthbertson and Doreen M. Thornton, "The Effect of Parenteral Nutrition on the Growth Response of the Rat To Vitamin B-l2," British Journal 2: Nutrition, 5;xii, May, 1951. 58W. C. Sherman, et. L1. "The Use of Depleted Rats For Investigation of VitaminfiB- 12 and Unidentified Factorsfl‘ Journal 2g Nutrition, 55: 255—63, February, 1955. 59J. E. Burnside et. Ll., "The Influence of Crystal- line Aureomycin and Vitamin B- 12 on the Protein Utilization of Growing and Fattening Swine", Journa1.g£ Animal Science, 13:184-200, 1954. 60A. Ferriot, J. Quentin and J. Robert, "Vitamin B—12 and Antibiotics in the Nutrition of Animals", Nutrition Ag; stracts and Reviews, 24:500, January, 1955. 61A. Trautman and Hill, "Vitamin B-12, Animal Protein Factors in Experiments on Pigs", Nutrition Abstracts and Re- views, 22:399, October, 1952. 62Charles A. Lassiter et. L1., "Crystalline Vitamin B- 12 Requirement of the Young D—iry Calf", Journal Lf Dairy Science, 36: 592, 1953. 26 series made by Hartman and associates dealing with rats led to conclusions showing that Vitamin B—12 plays a fundamental role in affecting the capacity of normal mammals for utilizing protein.63 Also, the growth of rats given a "deficient diet" improved greatly with supplements of Vitamin Bt-12.64 Burnside and his collaborators studied the effects of Vitamin B-12 when taken alone had little effect on growth, but when taken in combination, it improved utilization in all groups of pigs.65 Positive effects of Vitamin B-12 on the growth of swine were noted by others, who concluded that the increased growth resulted not in additional fat, but in high quality pork and ham.66’67 A favorable effect of Vitamin B-12 on calves has 68,69 also been observed. Draper and his associates showed that calves kept on a diet lacking Vitamin B-12 ceased to 63 Hartman, et. Ll., _p. , p. 167. 64 Hartman, 31. L1 ,_2. C1 it. , pp. 166-67. 65 . Burn51de, gl_. Ll.,0 _E. _., p. 200. 66 Ferriot, Quentin and Robert, loc. cit. * 67Trautman and Hill, 100. cit. 68Harold H. Draper, J.T. Sime, and B.C. Johnson, "A Study of Vitamin B-12 Defieiency in the Calf", Journal 22 Animal Science, 11:332—40, June, 1953. 69Lassiter,__e_1. al., loc. cit. — *— 27 grow, demonstrated poor ap etite, and exhibited poor oo- 70 With the addition of Vitamin B-12 ordination of movement. orally, growth was renewed in some cases, whereas further addition of casein to the diet demonstrated all calves growing normally. This suggests that casein might supply something in addition to Vitamin B-12 essential for the normal develop- ment of the calf, The amount needed for maximum growth was set at forty micrograms.71 Effects of Vitamin B-12 on Growth in Humans. Over- nourishment and undernourishment have long been problems of first concern to both physicians and nutritionists. The effects of Vitamin B-12 on human growth have been studied quite extensively , especially in relation to malnourishment and growth failure. Some of the first studies have been those concerned with the effects of Vitamin B-12 on the growth of premature infants. Generally, the results of these studies have been rather discouraging in that they indicated that 7ODraper, Sime and Johnson, loc. cit. 1Lassiter, loc. cit. 28 Vitamin B—12 does not enhance the growth of premature in- 72,73,74,75,76, fants. In only one study did Vitamin B-12 seem to help the growth of premature children, and in that 77 Due case only the larger ones seemed to benefit at all. to the negative outcomes of these studies, it is the con- tention of one writer that routine administration of Vitamin B-12 to premature infants is not justified.78 In the diet of infants not premature, some interest; ing effects of Vitamin B—12 supplementation have been 72F.J. Menchaca and D.S. Decorts, "Vitamin B—12 in Treatment of Premature Infants", Nutrition Abstracts and Reviews, 22:531, October, 1951. 73Daniel F. Dowing, "Failure of Vitamin B-12 to Pro— mote Growth in Premature Infants," Science, 112:181, August, 1950. 74Robert F. Chinnock and Harvey W. Rosenberg, "Results of Administration of Vitamin B-12 to Newborn Infants", Journal of Pediatrics, 40:182-5, February, 1952. 75Henry Rascoff, Alla Dunewitz and Robert Norton, "The Weight Progress of Premature Infants Given Supplementary Feedings of Vitamin B-12, A Comparative Study", Journal of Pediatrics, 39:61-4, July, 1951. 76Laurence Finberg and Bacon F. Chow, "Lack of Effect of Supplementary Vitamin B—12 Administered to Premature In— fants", American Journal of Diseases of Children, 84:165-7, August, 1952. 77Menchaca and Decorts, loc. cit. 78Finberg and Chow, loc. cit. 29 noted.79,80,81,82 Salmi, in his study of the nutritional disturbances in infants, found "dramatical" improvement clin- ically in five hypotropic infants. Under Vitamin B-12 treat— ment the blood levels of protein, amino acids, iron and chol— esterol reached normal levels.83 In a group of malnourished infants, DeMezei observed beneficial effects of Vitamin B-12 84 supplements on eight patients. Confirmation was given to this in a later study by Wilde when he observed an increase in the growth rate of seven Aleut infants treated with Vita- min B-12.85 79L. Salmi, "The Effect of Vitamin 3-12 in Chronic Nutritional Disturbances in Infants", Clinical Pediatrics, 32:617, November, 1953. 80M.B. DeMezei, "The Effect of Vitamin B-12 in Mal- nourished Infants," Archives of Argentina Pediatrics, 37:31, 1952. 81Edwin Wilde, "The Growth of Aleut Infants," Canadian Medical Association Journal, 68:70—1, January, 1951. 2Bacon F. Chow, "Sequelae to the Administration of Vitamin B—12 in Humans," Journal of Nutrition, 43:323-43, February, 1951. 838almi, loc. Ci t. 84DeMezei, loc. cit. 85Wilde, 92- cit., p. 71. 30 Chow carried on an interesting eXperiment on the ef- fects of Vitamin B-12 supplements upon sick children residing in a special home for the chronically ill.86 Alternate ad— missions to this home received the Vitamin B-12 supplement or remained untreated. At the end of three months the weight gained by the treated was significantly the greater; however, there was a higher incidence of rheumatic and congential 87 This could be at- heart disease in the treated group. tributed to the fact that there was a greater number of such cases in the supplemented group at the start than in the un— supplemented group. If however, Vitamin B-12 actually en- hanced these diseases, further studies should take a cogni— zance of these defects and not permit the affected subjects to partake in the experiments. Vitamin B—12 supplementation has been found to be extremely useful in its application in promoting the growth 86Chow, Journal gleutrition, op, cit. pp. 341-2. 87 Ibid. 31 88,89,90,91,92,93 of undernourished school children. The initial experiment carried on in this field was by Wetzel 94 The eXperiment was carried in one of the and associates. large school systems in Cleveland, Ohio, where growth failure among some of the school children was plainly evident. The number of subjects in this first study was eleven, with three 88Norman C. Wetzel, et. al., "Growth Failure with School Children as Associatedfwith Vitamin B-12 Deficency-- ReSponse to Oral Therapy", Science, 110:651-3, December, 1949. 89c.c. O'Neil and A.J. Lombardo, "Vitamin B—12 in the Treatment of Malnutrition and Celiac Disease in Infants and Children", Journal of the Omaha Mid-West Clinical Society, 12:57, April, 1951. 90N.C. Scrimshaw and M.A. Guzman, "Effects of Dietary Supplements of Vitamin B-12 and Aureomycin on the Growth of Children of School Age," Nutrition Abstracts and Reviews, 24:429, April, 1954. 91Edwin Wilde, "The Treatment of Growth Failure in Aleut School Children", Journal of Pediatrics, 40:565-9, May, 1952. 92John w. Larcomb, Claude 5. Perry and Robert A. Peterman, "Dietary Supplementation of Vitamin B-12 in Pre- Puberty School-Age Children: Growth Studies," Journal 32 W. 93Norman C. Wetzel, El-.§lv: "Growth Failure in School Children. Further Studies of Vitamin B—12 Supplementation", American Journal of Clinical Nutrition, 1:17-31, September, October, 1952. ' Wetzel, 31. al., Science, loc. cit. 32 being selected because of slow progress in growth, and the other eight selected at random from a group of seventy-six children being treated for varying degrees of malnourishment. Clinical examinations prior to the administration of Vitamin B-12 supplements revealed no characteristic abnormalities in the hair, skin, mouth or nervous system. With the addition of ten micrograms of Vitamin B—12 daily, beneficial results were noted in five of the treated children. This was shown by a rapid and dramatic improvement in growth and physical vigor, along with increased alertness, better behavior and increased appetite. Probably the most accurate of these observations was the increased appetite, which was evidenced by increased demands for "second helpings", as contrasted to comparatively indolent food habits prior to the supple- mentation.95 Statistically the effect of Vitamin B-12 on the weight of the five benefited school children was significant at the p= O. 01 level of confidence at the end of the first three weeks and at the end of four weeks it was statistically significant at the p=0.00l level of confidence.96 Confirmation 95Wetzel, 31, al,, Science, op. cit. p. 653. 96Ibid. 33 has been given to Wetzel results in a similiar study by Wilde.97 He observed the effects of Vitmnin B-12 supple- ments on nine undernourished Aleut school children. After plotting each subject's previous growth progress, he noted, in seven of the nine schoolchildren an increased growth of 65.2 per cent over their previous growth rate.98 Vitamin B-12 growth experiments on undernourished school children have not been limited to one sector of the world. Scrimshaw and Guzman observed the effects of Vitamin B—12 supplements on the growth of undernourished school children residing in the urban and rural areas of El Salvador. Eighty children served as subjects. When comparing the treated children with the children in the same area having no supplement, an increase in height and weight was noted in the treated group. When the Vitamin B—12 supplements were withdrawn, the growth rates of the treated children were lowered.99 No positive effects of Vitamin B—12 supplements on the growth of school children have been reported in one 97Wilde, Journa1_gf Pediatrics, loc. cit. p. 568. 981bid. 99Scrimshaw and Guzman, loc. cit. 34 case.100 The study was carried on in the famous "open air schools" of England, which are health centers for under- nourished school children. The subjects consisted of 418 British school children. Each subject received ten micro- grams of Vitamin B-12 on five days of the week for ten weeks. There was no greater gain in weight or height in the children receiving the Vitamin B-12 supplement than those receiving no supplement.101 The study was continued because it was later learned that the Vitamin B-12 supplements of ten micro- grams were weakened to a potency of five micrograms by a sugar concentrate.102 In the second study the subjects were classified into those who were initially up to expected weight and those grossly underweight. In comparing the weight gained between the treated and the untreated in the grossly underweight group it was concluded that there was no difference, nor was there a difference in their heights or in their morbidity 103 rates. Although the work of Benjamin and Pirrie appears 100B.Benjamin and G.D. Pirrie, "Vitamin B-12 by the Mouth", The Medical Officer, 87:137-40, April, 1952. 101Ibid. p. 138 102Benjamin and Pirrie, loc. cit. 103Ibid. 35 to be in conflict with the work of others in this area of nutrition, Wetzel claims that their findings are not incom- 104 patible with his. Wetzel's reasons are not entirely clear, however it is felt in reviewing the two studies that the findings of Benjamin and Pirrie were based on the group as a whole,105whereas Wetzel based his good results only on the 106 Therefore, the bene— cases who had definitely benefited. fits of Vitamin B-12 supplementation would tend not to be so noticeable in the former study. The effect of Vitamin B—12 on the growth of normal 107’108 and adults109 has shown no effect on weight children gained. In light of this, Chow has established criteria for’ future growth studies. They state that a response depends on (1) a previous history of some kind of physiological stress resulting in retardation of growth from the subjects' 104Wetzel gt al., The Journal gf Clinical Nutrition, _gp. cit., p. 31.. 105 Benjamin and Pirrie,_gp. cit., p. 1380 106Wetzel 21.31., SCience, 22. cit., p. 653. 107Benjamin and Pirrie, op. cit., p. 1370 108Henry J. Montoye 33 al., ”Effects of Vitamin B—12 Supplementation on Physical Fitness and Growth of Young Boys," Journal of Applied Physiology, 7:589-92, May, 1955. 109Gilbert M. Bayne and William P. Boger, "Vitamin B-12 Supplementation in the Diet of Healthy Adults," The Journal of Clinical Nutrition, 1:424-29, September-October, 1953. 36 expected pattern, (2) ad libitum feeding, and (3) distri- 110 The conditions of the bution of calories in the dietary. present experiment meet these requirements in that under- nourished boys and those showing retarded growth were used as subjects, they were given ample opportunity to eat all they wanted, and an adequate diet was administered through the nutrition department of the state institution where the eXperiment was carried out. Vitamin B-12 and Physical Performance The armed services and industry are the two fields where the effects of vitamin supplements have been studied most extensively. As previously stated, the demands of World War II directly stimulated an interest in this approach of improving the physical performance of both the soldier and industrial worker. Concerning industry, a review in 1950 noted the work of Borsook and associates who studied the effects of vitamin supplements on over one-thousand workers at the Lockheed Aircraft Corporation at Burbank, California.111 110Chow, Southern Medical Journal, 223 Cit" P' 610' 111"Vitamin Supplementation and Performance Capacity", Nutrition Reviews, 8:313-14, October, 1950, citing Melbank Memorial Fund Quarterly, 20:329, (1942); 21:115 (1943); 23:113 (1945); 24:99,?51 (1946); 37 The subjects were divided at random into two groups; one receiving supplements given five days per week for nine to twelve months, while the other group was given a placebo. The need for appropriate controls is evidenced by the response to the direct question as to whether the subjects were re- ceiving any benefits from the pills. Over seventy per cent of the men representing both groups reported benefits such as fewer colds, better appetite, general improvement in their feelings of well—being, and less eye discomfort.112 Thus, the benefits of vitamin supplementation would appear null, since both groups claimed benefits. The principal claim for the beneficial effects of the vitamin supplements was based on indirect indices of indus— trial morale and work performance. During the first six months there were no significant differences in the absenteeism rates. However, in the second six months, the total absenteeism rate of the vitamin sub— jects was 3.90 days per 100 working days as compared to 4.79 days for the placebo subjects. The non—military term— ination of employment was somewhat higher in the placebo group than in the vitamin group, (13.4 and 8.4 per 100 1121bid., p. 314. 38 employees respectively), but it did not reach the five per cent level of significance. In addition to absenteeism rates and non-military terminations, the results of the Merit Review ratings were utilized in evaluating the effects of vitamin supplements. Each man was rated by his immediate supervisor on six char- acteristics; the rating scale for each characteristic being 1 to 8. The average overall Merit Review score at the end of the study was 6.22 for the placebo and 6.38 for the vita— min group. Although the difference was very small, it was considered to be highly significant statistically.113 The results of this study give no index of an increase in out- put as a result of the vitamins. Therefore, the effects of vitamin supplements on the physical performance of the industrial worker are still to be determined, even though some evidence tends to show possible beneficial effects. Since the amount of research directly relating to this prob— lem is very limited, the need for carefully controlled re- search in this area of vitamins and industrial performance is great. The fact that the efficiency of any military unit depends on the maximal performance of each soldier had led 113Ibid. p. 315. 39 to studies concerned with vitamins and performance.114’115 One of the first studies was carried out by Keys and Henschel in 1942. The twenty-six soldiers used as subjects were given large daily supplements of thiamine chloride, nicotinic acid, calcium pantothenate, riboflavin, pyridoxine and ascorbic acid, These were given in daily doses over a period of four to six weeks alternating with equal periods of placebo ad- ministration. The men were repeatedly subjected to standard— ized severe physical exercise on a motor driven treadmill, and circulatory, metabolic and blood chemical responses to the imposed stress were measured. The specific character- istics studied were: pulse rate, heart size, stroke output of heart, oxygen consumption, reSpiratory quotient, urinary nitrogen and ketone body excretion, and concentration in the blood of lactate acid, sugar, hemoglobin and ketone bodies. "In neither brief but extremely severe exercise nor in pro— longed hard physical work had vitamin supplementation a significant effect on the ability to carry on exhausting 114Ancil Keys and Austin F. Henschel, "Vitamin Supple— mentation of U.S. Army Rations in Relation to Fatigue and the Ability to do Muscular Work", Journal pf Nutrition, 23:259- 67, March, 1942. 115Robert Ryer, et. al-: "The Effect of Vitamin Supple- mentation on Soldiers Residing in a Cold Climate, Part I of Physical Performance and ReSponse to Cold Exposure", American Journal of Clinical Nutrition, 2:97-131, March-April,‘1954. 40 work or on recovery from exertion"116 It was concluded that no useful purpose would be served by enriching the diet of the present United States Army garrison with the vitamins studied.117 Even with these discouraging results, within recent years Ryer and associates have carried on a study specif— ically designed to determine whether the functional capacity of a soldier exposed to a cold environment might be improved by supplements of ascorbic acid and of B—complex vitamins.118 The subjects in this study consisted of eighty-six volunteer army personrel. The experiment was carried out for a period of ten weeks with the subjects randomly divided into two groups, the supplemented and the placebo. The forty-two men who served as subjects in the placebo group each received a brown capsule containing six mg. of ascorbic acid four times daily. The supplemented group consisted of forty-four men, who each received an orange colored capsule four times daily. Each capsule provided the following ingredients: thiamine (10 mg.), riboflavin (10 mg.), niacinamide (100 mg.), 116Keys and Henschel, pp, cit., p. 267. 117Ibid. 118Ryer, £1, 31., loc. cit., p. 97. —* 41 calcium pantothenate (80 mg.), pyridoxene (40 mg.), folacin acid (2.5 mg.), ascorbic acid (300 mg.), and Vitamin B-12 (4 mcg.). Measurements of physical performance were made at weekly intervals during periods of calorie adequacy of 3,500 calories the first six weeks and a calorie deficit of 2,250 calories daily during the last three weeks. Motivation was offered through recognizing individual excellence and by having competition between platoons. Lighter clothing was worn, and the barracks fires were blanketed to promote stressing conditions. The conclusions showed that there were no statistical differences between the two experimental groups in the scores attained on the Harvard Step Test, the army 1 physical fitness test, the performance with the hand dyna— mometer, a standardized forced march, or a contest march. Also a battery of six psychological tests failed to reveal any differences between the two study groups.119 Due to the negative results of studies related to the effect of vitamin supplements on physical performance, the following summarizing statement was made. Until convincing evidence is presented to the con- trary, it seems reasonable to assume that maximal phys— ical performance can be expected of industrial workers or of soldiers if they are provided adequate diets 119Ryer, 31.21., Ibid., pp. 130-131. 42 consisting of natural foodstuffs and the specific nu- trients inherently contained therein, providing account is taken of the total energy requirement of the in— dividual under prevailing iigcumstances of physical ex- ertion and of environment. Although such a statement might hold true with most known vitamins, it is felt that increased study should be carried on using different approaches to the problem and also utilizing some of the more recently discovered vitamins. To the experimentor's knowledge there have been only three studies directly related to the effects of Vitamin B—12 on physical performance; one being concerned with back, leg 121 and grip strength, and the other two with its effect on 122’123 The former study was a continuation of a endurance. previous study by Wetzel, but included, in addition to an index of growth, a measurement of physical performance. Physical performance was measured by a comparison of leg, grip, and back strengths taken at weekly intervals for 120Vitamin Supplementation and Physical Performance," Nutrition Reviews, 13:104, April, 1955. 121Wet2e1,_gt..al., American Journal pi Clinical Nutrition, loc. cit. 122Montoye, 31, al., Journal 2£_Applied Phy5101OEY: loc. cit. 123 Montoye, et. al., "The Effects of Vitamin B-12 on Work Capacity," AEbeitSphysiologie, 16:20-4, October, 1954. 43 durations of six and sixteen weeks. The 236 subjects were divided into four groups. One represented a control group of normal children. Two groups represented those with growth failure, who were given the Vitamin.B-l2 supplements. (One group was supplemented for six weeks and the other for sixteen). The final group represented the unsupplemented 'subjects exhibiting growth failure. Although there was an increase in general sense of well-being in the supplemented groups, there was no definite correlation between the growth response to Vitamin B-12 and the physical performance as measured by back, leg or grip strength.124 Since this is the only known study related directly to the effects of Vitamin B-12 supplementation on physical performance, and since it covers only a limited number of tests measuring physical performance, another study is war- ranted. Also it is felt that the main purpose of Wetzel's study was to further substantiate the results of his first study,125 that is, the stimulating effect of Vitamin B-l2‘ on growth. To further support this contention, the author, 124Wetzel, p1, pl., American Journal pg Clinical Nutrition, pp. cit., p. 28. 125Wetzel,.p1..§l., Science, pp. cit., pp. 651—3. 44 in reviewing the report on Wetzel's study, found that little was mentioned concerning the procedure of testing the sub— jects used. In light of this, the conclusions of the study raise a question in the author's mind, and indicate a need for this study. Montoye and his co-workers made an initial study of the effects of Vitamin B—12 supplementation on the endurance of young boys.126 The subjects were fiftyoone boys between the ages of twelve and seventeen, who resided in a state correctional institution. They were divided into three groups as follows: (1) the Vitamin B-12 group of sixteen boys, (2) the placebo group of sixteen boys, and (3) the control group of nineteen boys. Every day for seven weeks, each boy in the Vitamin B—12 group received one capsule containing fifty micrograms of B-l2. The placebo group received an identical blank capsule, while the control group received no supplementation. The Harvard Step Test was administered at the beginning and end of the experiment. Also, the Vitamin B-12 and placebo groups ran the half-mile three times per week. Although there was a shift in the channels on the Wetzel Grid made by both groups, (B—12 and placebo), toward more 126 loc. cit. Montoye p1_pl., Journal p3 Applied Physiology, 45 linear body builds, there was no significant difference in the changes made by placebo subjects as compared to those supplemented by Vitamin B-12 in either the Harvard Step Test scores, half mile running time, or in weight and height. However, in the few thin subjects, (B1 channel, Wetzel Grid), weight loss was less in the B-12 subjects than in those re- ceiving placebos.127 An interesting study of the effect of Vitamin B-12 on the work capacity of three normal young men has been completed.128 The subjects were tested daily except Sundays at nearly the same time early each morning. On reporting to the laboratory, each subject's grip strength was taken five times, and each rode a frictional bicycle ergometer at ten miles an hour for one minute. Four pounds of resistance was used, and the pulse recovery was counted from one to one and a half minutes after the completion of the exercise. After a rest of about fifteen minutes, each subject then rode "all out" at the same speed and resistance until he could no longer maintain the required speed. The performance effort of each subject was recorded in seconds. 127Ibid., p. 592. 128Montoye, £1, 21,, Arbeitsphysiologie,._p. cit. pp. 21‘30 46 Vitamin B—12 administration did not start until after four weeks of training. Then during the following four weeks Vitamin B-12 was administered alternately every other week with placebo capsules. A graphic plotting of the scores showed no effect of the Vitamin B—12 supplements on the work capacity of the three subjects as measured by grip strength, pulse rate recovery following a standard exercise, or maximum work on a bicycle ergometer.129 In retrospect, the results showing the positive effects 130,131,132 of Vitamin B—12 supplements, or other vitamins 133,134,135 on one's physical performance have been rather discouraging. The probable reasons for this lack of effect of additional vitamin supplements on one's physical performance are: (1) that the subjects used in these exper— iments have been normal, healthy individuals and that (2) these same healthy individuals were receiving adequate amounts 129Ibid. 130Wetzel,.p1..al., American Journal pg Clinical' Nutrition, pp. cit., pp. 17—31. 13l‘Montoye, pl, p1,,LApbeitsphysiologie, loc. cit. 132Montoye, pl, 21,, Journal pg Applied Physiology, loc. cit. 133Ryer, p1, pl., loc. cit. 134 . Keys and Henschel, pp. c1t., pp. 259-57. 135 "Vitamin Supplementation and Performance Capacity," thrition Reviews, 8:312-7, October, 1950. 47 of the experimental vitamins in their regular daily diet so that additional amounts were not necessary for the promotion of optimum performance. In light of this, and since there has been only one limited experiment136 concerning the effects of Vitamin B-12 on the physical performance of undernourished individuals it is felt by the investigator that future studies along this line should include eXperiments related to the effects of vitamin supplementation on the physical perform— ance of undernourished indiViduals, which is the purpose of this study. 136Wetzel, p1.lpl., American Journal p£_Clinical Nutrition, 100. cit. CHAPTER III METHODOLOGY One of the first and most pertinent considerations in a study involving growth failure of young boys is the de— termination of those individuals who fall in such a group. The author was indeed fortunate in this respect, for age, height, and weight records were kept on file in the athletic director's office of the Boys Vocational School, where the experiment was to be carried out. By checking these records, prospective subjects were easily determined by replotting their respective heights and weights on the Wetzel Grid and also by checking for growth failure in stunted boys by merely plotting their growth in accordance with their age and de- velopmental level. In the latter respect, the investigator was again fortunate, for in the existing institutional or— ganization, all small boys were grouped in the same cottage, thus facilitating the process of determining those boys who were extremely small for their age. Experimental Design Boys, between the ages of twelve and seventeen, re- siding in a State Correctional Institution were the twenty— seven subjects used in this experiment. Two of these cases were later dropped; one because of an emergency, which 49 permitted him to leave before a final testing could take place and the other because of insufficient time in the eXperiment. Two of the twenty-five remaining subjects were cardiac cases. They took part in all the tests except the Harvard Step Test and the half—mile run. Once the subjects were selected on the basis of growth failure, they were divided into five groups according to the degree of their growth failure as indicated by their respective plottings on the Wetzel Grid. The five groups were: (1) B2 borderline, (2) B (3) B2-B (4) B4, and 2’ 3’ (5) four stunted subjects. The latter four cases were de- termined by their growth plottings on or near the 98 per cent auxodrome, The subjects in each group were then randomly divided into the experimental and control groups. The two twins in the study were placed in opposite groups. Late arrivals who classified as subjects were admitted alternately into the B—12 or placebo groups. The first testing took place in the field house of the institution on the two successive days after the sub- jects had been determined. The order of the test adminis- tration on the first day was height, weight, Harvard Step Test (modified), chins, dips and the vertical jump. On the second day the order of testing was grip strength, push and pull strength, back and leg strength and lastly the half- mile run. On one occasion, the half-mile run was scheduled 50 on a third successive day. The subjects wore their street shoes and with no trousers for all tests except the half- mile run, when gym shorts and tennis shoes were worn. Records were kept of the weather and the conditions of the track with a conscious effort made to test under sim- ilar conditions. Since the first testing of the half-mile run was carried out in early April, the track was a bit soggy in places. The final testing to be used for statistical com— parisons was carried out in exactly the same manner. Dr. Henry J. Montoye, a specialist in tests and measurement, ad— ministered some of the more difficult tests, as he did in the initial testing. At no time did he or the other helpers know which boys were in the experimental or control groups. Also, during the times when the author tested the subjects, he did not know which boys belonged in which group. A bias was further curtailed by encouraging all subjects to give a maximum performance. At the completion of each subject's first testing, a fifty microgram capsule (Vitamin B-12 or placebo) was ad— ministered daily to each subject, according to the group in which he belonged. The distribution of capsules took place at the field house between eight and nine o'clock in the morning on Monday through Friday. The subjects were watched to see that they swallowed the capsules. On week—ends, the capsules were sent to each subject's respective cottage where 51 the cottage parents, who were informed of the purpose and :hnportance of the daily supplementations, supervised the distribution of the capsules. Explicit instructions con— cerning the administration of the capsules were written on each envelope containing the week—end supply. A simple check to determine whether the capsules were distributed was noted by inspecting the returned cottage envelOpes. During one phase of the study several days were missed 'because of an unforeseen difficulty in securing a new supply of capsules. This was compensated for by double doses on the following four days. The regimentation that characterized the daily program of the institution provided an excellent climate for this study. As a part of the regimentation, all boys were required to attend physical education classes daily. Regular meals and regular hours of sleep further provided an ideal climate for this experiment. Explanation of Wetzel Grid1 The main purpose of the Grid is well described in the words of Wetzel, its orginator, who states; 1See Figure I on the following page. 52‘ a UKDUC II-IIIIIIIIIIII“ .- IIIH~.W ... ...-.... IIII'I v. . 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I . . lg I ”II I -I\.\\IIIII._I\I\ x . W. II ofI . 0.. Io. JHH\ - N‘ a \o‘ _ - I . . .. x . . - Samara-Inna IT .\ .. . o: I 2 . II II. II-l..- I.- II T I... III" “ I lano‘ .' v. . _ I“: “I .. . I8. I II II. III-III Y m . . _ I I558!3§83I£3§£.3333§-1 Weight (pounds) 107.732 12 114.58 13 .192 >.1 Developmental 136.12 12 142.85 13 .890 >.1 Level) Percentile 77.50 12 79.83 13 .419 >.1 Harvard Step Test (pulse recovery 58.00 10 58.38 13 .140 >.1 rate) Chins 3.42 12 4.46 13 .958 >.1 Dips 2.88 12 1.96 13 -.986 >.1 Vertical Jump 34.92 12 34.00 13 —.306 >.1 (centimetersfi Sum of Best Right > 1 and Left Grip 153.25 12 175.77 13 1.301 ' Strength (pounds) Push Strength 78.83 12 77.38 13 —.234 >.1 (pounds) >.1 Pull Strength 56.75 12 63.54 13 .931 (pounds) Back Strength 220.42 12 244.85 13 1.051 >.1 (pounds) Leg Strength 449.33 12 480.00 13 .598 >.1 (pounds) - 9 r ’918 >.1 Half4Mlle-Run 196.56 187.54 13 . (seconds) 70 .mo3Hm> a»: one Mcfiwsano ca macaw osmomam mo mmzmco some kHMooz Scam powompwnzm mzmsz macaw NHIm caeoww> mo omcmso some maxoo3* . Aaaaao Ao.AImo.v oo.v H.A mmm. ma Hoao. NH coco poflxoowm caozowv eoeam Hoccmno H.A mo.H H.A Hoe. ma H©ON.I NH wmom.u mafiwcoopom Ho>oa H.A em.m H.A mom. ma mam. NH aaa. Hoesosaoao>oo Ho.AImo.v as.e H.A was. ma mam. NH oaa. Amoaaoav agape: H.A oa.a H.A eee.a- ma omo. NH oso. Anonocev e:Mao= m a Mom? pom Mom: pom . m ,m m ....Ef: came—~32 omcmso cam: came—~32 mwcmnu mam: WMOomzad ommoaaa mH-m sz mezomo QOHmmm A mo zomHmH mdm 292 one MGHHSQEoo :« macaw onoomam mo omcmno some 2 HI szoez Scam covomhwn3m mam3Hm macaw manm caewwfl> mo mmcmno some waxwoZ: H.A No.N H.A mmN. NH poo. a HON.- Anacooomv cam oHH=IQHom H.A mH.H H.A ooh. mH owe. NH mNs. Amocaoav seasonem HHaa H.A as.H H.A mos. mH owe. NH Nam. Amocaoav nemsosem amaa H.A wH.N H.A emH.HI mH wa.m NH mso.OH Hoocaoav newcopwm Meg H.A NH.H H.A maN.I mH mOH. NH mom. Hmccaoav camcosem zoom Homecomv whoa paw H.A ma.H H.A was.I mH map. NH N©N.H eanm «mom Lo saw newcosem aHso . . . . . . mpoaoaHecoov H A 05 H H A OHo H mH oss NH aNN %saa HaoHebo> Ho.AImov Nm.m H.A Nos. mH Leo. NH Nso. maHa H.A so.H H.A ssN.H- mH sNH. NH omH. mcHnu H.A m©.N H.A mH©.H mH mao.- OH .ams.- Hopes abo>ooob omHaav 2 Home mowm cam>L¢m a e z moo: boa z woo: boa amoomeao a a a see omcono one: omcmsu coo: muzszmommma omm0 HauHmwma QOHmmm Amm ZH mmcz<=o z mo ZomHm mam.05 Developmental Level .218 25 .440 >.1 Percentile -.206 25 —.555 >.1 Harvard Step Test (pulse recovery rate) -.253 23 —.462 >.1 Chins .165 25 1.349 >.1 Vertical Jump (centimeters) .348 25 1.080 >.1 Push Strength (pounds) .533 25 1.095 >.1 Pull Strength (pounds) .532 25 .680 >.1 Sum of Best Right and Left Grip Strength 1.019 25 .410 >.1 (pounds) Back Strength I (pounds) .299 25 .091 >.1 Leg Strength (pounds) 6.906 25 .530 >.1 Half-Mile-Run (seconds) —.O43 22 -.021 >.1 *A minus mean change per week in percentile, Harvard Step Test, and the half-mile-run indicate improvenent and account for the corresponding minus "t" values. 75 TABLE VII SIGNIFICANCE OF WEEKLY MEAN CHANGES IN GROWTH AND PHYSICAL PERFORMANCE DURING THE EXPERIMENTAL PERIOD WITH THE VITAMIN B-12 AND PLACEBO GROUPS NOT COMBINED* Growth Mean Change N "t" P and Performance Per Week t Category Weight (pounds) Vitamin B—12 .190 12 .955 >.1 Placebo .253 13 .605 >.1 Channel Shiftx Vitamin B-12 .005 10 .023 >.1 Placebo .010 11 .244 >.1 Dips Vitamin 8-12 .042 12 .436 >.1 Placebo .067 13 .338 >.1 wDue to a significant F value when comparing the Vitamin B-12 and Placebo groups as in Table IV, the above growth and performance measurements were not combined in determining the significance in improvement during the ex- perimental period. ‘ xStunted subjects were not included for significance in improvement in channel shift. 76 Discussion of the Results The hypothesis upon which this experiment was for— mulated was based on the theory that by increasing the growth of undernourished boys, a concommittant improvement in phys- ical performance would result. Vitamin B-12 is a growth promoting vitamin as well as a vitamin capable of raising the red cell count of individuals nutritionally deficient, as in pernicious anemia. Since the undernourished boys in this experiment represent another kind of malnutrition, it seems possible that the red cell count of the Vitamin B-12 supplement group could have been increased by the supplements. In light of this assumption a possible explanation can be projected for the considerably better performance of the Vitamin B-12 group as compared to the placebo group in pulse recovery rate. The reason for this is that red cells are vehiCles for carrying oxygen to the tissues of the body, which in return utilize the oxygen for the contraction of muscles. Hence, an increase in the red blood cells per heart beat would decrease the number of beats necessary to resupply the oxygen lost during exercise. In the discussion of the limitations of the study, it was mentioned that neither previous growth records or previous living or food habits were available concerning the subjects. Therefore, they were selected solely on the basis of their 77 present growth status. It was felt that the climate in which this experiment was to be carried out was ideal, in that the supervision of the capsule feeding was carried out daily, and also the environmental conditions for all subjects were bas- ically the same. The environmental conditions, which were stabilized as a result of the regimentation of this insti- tution for wayward boys, were regular sleeping hours, reg- ular. ..- “w-J‘A—T J. ular and adequate feeding, and regular physical education. It seems that this regimentation, although desirable in a study such as this, could have worked at a disadvantage. For instance, most of the boys who served as subjects prob- ably came from homes of a low economic status, where the daily meals were irregular and deficient in essential vita- mins. Since the boys who are brought to this institution often come from broken homes where parental guidance is slight, it seems logical to assume that their conditions of growth failure could be contributed, not only to poor meals, but to poor and irregular hours of sleep. The very regimen- tation of the institution would solve both of these problems related to malnutrition without any diet supplementation being introduced. In view of these considerations, the lack of effect of Vitamin B-12 in promoting growth is probably due to the fact that the subjects in both groups were receiving enough Vitamin B-12 in their daily feedings at the institu- tion so that additional amounts had little or no effect on 78 the group receiving such amounts. This is further evidenced by the minus "t" value in Table VI, page 74, for percentile, and a plus "t" value in Table VII, page 75, for channel shift. The percentile shift is towards the standard auxodrome (67 per cent), while the channel shift favors the stockier type boy. Since the channel and percentile indices of growth are a fairly straight line under normal conditions, a movement away from the usual straight line, as in the experiment, indicates favorable growth. This can be shown graphically in the explanation of the Wetzel Grid,4 where the growth progressions of three subjects used in this experiment are plotted. Two of these subjects, Case A and Case C, received the fifty microgram capsule of Vitamin B-12 daily, while Case B received the Placebo. It can be shown by their plottings at the beginnimg and end of the three month experimental period that the growth of both B and C was enhanced favorably during the period, which Case A did not appear to have benefitted. These three cases give a general picture of the lack of effect of Vitamin B-12, on the experimental group. Channel shift toward stock— ier build and percentile shift toward the standard 67 per cent 4See Figure I, page 52. :I I 1" 'H"I-Ihl ”wt! 79 auxodrome is also evidenced in cases B and C. Loss of weight by two subjects in each group was also evidenced. The reason for this is not known in three cases, but in one case the subject was sick a good part of the ex- perimental period. Similar conditions might have been true with the other subjects without the experimenter's knowledge. The loss of weight in the two subjects of both groups probably explains why the growth categories of weight, developmental level, percentile, and channel shift were not significant when the two groups were combined as the Table VI, page 74 or uncombined as in Table VII, page 75. The same observation is probably related to the lack of significant "t's" in the improvement in physical performance during the experiment.5 It should also be noted that even though the other measurements of growth and physical performance were not sta- tistically significant, the positive "t" values indicate that the boys were growing and increasing in physical performance during the thirteen week experimental period. The explanation of why more growth and physical performance measurements were not significant statistically probably is related to the small number of cases and the shortness of the experimental period. 5See Table VI, page 74, and Table VII, page 75. CHAPTER V SUMMARY, CONCLUSIONS AND RECOMMENDATIONS Summary Twentyeseven undernourished boys between the ages of twelve and seventeen were selected as subjects in this exper- iment. Their degree of undernourishment was determined by their respective plottings on the Wetzel Grid. The five different degrees of grOwth failure were (1) B2borderline, (2) B2, (3) BZ-B (4) B3, and (5) four boys who showed 3, stunted growth. The subjects in each of these groups were then randomly divided into two groups, the experimental or Vitamin B-12 group and the control or placebo group. After two subjects dropped out, there were twelve boys in the ex— perimental group and thirteen boys in the control group. The subjects were then given a fifty microgram capsule of Vitamin B-12 or a placebo daily for a period of two to three months, except for one subject who was only in the experiment for seven weeks. Prior to the beginning of the feedings and at the end of the experimental period, growth and physical per- formance measurements were administered in the following order on two successive days, On the first day, height, weight, pulse recovery rate, chins, dips, and the vertical jump measurements were determined. On the second day, the 81 order of testing was right and left grip strength, push and pull strength, back and leg strength, and the half—mile—run. The measurements were then tabulated for further use in com— puting and comparing the results. I J “:A ‘8': rv-‘.w-~.—._-m ”Cw 5.1 82 Conclusions The following conclusions can be drawn on the basis of a statistical analysis of the data: 1. There was no significant difference in the mean initial measurements in growth and physical performance be- ‘ . h— tar}. as!” t tween the Vitamin B-12 and placebo groups. 2. There were no significant differences in the mean weekly growth changes as determined by height, weight, develop- mental level, percentile, or channel shift between the Vitamin B-12 group and the placebo group during the eXperimental period. 3. A comparison of the weekly mean change in the physical performance scores between the Vitamin B—12 and placebo groups resulted in no statistically significant changes in any of the measurements of physical performance in favor of one group over the other. However, the "t" value1 in the Harvard Step Test of 1.613 in favor of the Vitamin B—12 group indicates a trend that Vitamin B-12 might enhance cardio- vascular fitness. The basis being that Vitamin B-12 is known to increase the red cell count of anemic patients, and, since the red cells are known to be carriers of oxygen, an increase 1For twenty—one degrees of freedom, a "t" value of 1.721 is significant at the .10 per cent level. 83 in their number per heart beat might decrease the work of the heart and quicken the pulse recovery rate. 4. Although the "t" values for general improvement in growth and physical performance were not statistically significant, they all indicated improvement in growth and physical performance during the experimental period. I ..r' 84 Recommendations Even though the results of this experiment are con- firmed in the work of Wetzel and associates,2 in that Vitamin B-12 does not increase grip, back or leg strength, it is not felt that these results should be considered conclusive. In E the former study, there was a significant improvement in 3 growth in the Vitamin B-12 group when compared to the placebo 3 group, whereas in this study there was not. Therefore, one 5 would not expect a better performance by the Vitamin B-12 group as evidenced. Since Wetzel and his associates used only three measures of physical performance, their study should be continued using a greater number of physical performance measurements as in this experiment, but in a climate which would show the positive effects of Vitamin B-12 on growth in supplemented groups. The regimented conditions of this experiment obviously did not enhance growth in the Vitamin B-12 group more than in the placebo group, but tended to favor growth in both groups. Therefore, it is further recommended that future studies of growth and performance be made under conditions continuing to be deficient as in the subject's 2Norman Carl Wetzel pt. al., "Growth Failure in School Children. Further Studies of Vitamin B-12 Supplementation," American Journal p: Clinical Nutrition, 1:17-31, September- October, 1952. 85 pattern of living at the time of growth failure. 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S. et. aL "Further Studies on the Absorption of Vitamin B- 12 following Oral and Parenteral Administra- tion," Journal of Nutrition, 45: 507-19, December, 1951. APPENDIX siui," ..o\~fl\ Lady‘, Vn‘xfi, sufiyq ... usdx‘ ....»wQ by L0 L3... A. thQ , wzkxu 3.5. 9:337 §J\\\\ ,. 1“ :\ .‘,MM,..HH\..\+\\\\;\I\\\\ ott {33a 1‘2. _ 9.3.. 3:313:41! _ ‘AQ L\.\‘ §‘\s / 5. 3Q ”.33. “mug $1.3 ‘84:; . r \‘I‘l T||\|\. LI|\\|\\\1«\.$lyLl\.\h‘\!|\Hufl.anHrl\§l\ ni‘ ‘ >0 OtuD.(r “9‘“Q0KQVR waim ZO;xxl‘Kxx. HQ nxbwkkh 2.9 1 Hbt\ x ‘UQW acids-(h 3 up}. FWWIM ZO_F