·Publication Number 36
AMERICAN LECTURE SERIES
A Monograph in
AMERICAN LECTURES IN ENDOCRINOLOGY
Edited by
WILLARD O. THOMPSON, M.D.
Editor, Journal of Clinical Endocrinology
Clinical Professor of Medicine
University of Illinois College of Medicine
Chicago, Illinois

·Obesity...
By
EDWARD H. RYNEARSON, MD, P.A.CP.
Dirision of Medicine, Mayo Clinic
Associate Professor of Medicine
Mayo Foundation
and
CLIFFORD F GASTINEAU, MD
Fellow in Aledicine, Mayo Foundation
Rochester, Minnesota
CHARLES C THOMAS. PUBLISHER
Springfield . Illinois - USA

·CHARLES C THOMAS PUBLISHER
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Published simultaneously in The British Commonwealth of
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Published simultaneously Canada by
THE RYERSON PRESS, TORONTO
This monograph is protected by copyright No
part of it may be reproduced in any manner
without wetten permission from the publisher.
Copyright, 1949, by CHARLES C THOMAS · PUBLISHER
First Edition

·FOREWORD Tuse of the practicing physician rather than for the investigator in this field Therefore, the bibliography includes only those articles which may be obtained and read relatively easily References to articles in foreign languages have been kept at a minimum. More detailed and comprehensive information can be obtained by referring to the splendid articles by Newburgh, Bruch, Evans, and Rony in particular. Much of the important German literature has been reviewed by Wilder. We are indebted to Alice Karslake Irmisch for the preparation of the chapter on diets. E.HR CFG

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·CONTENTS V 3 13 21 Foreword I INTRODUCTION. 11 PHYSIOLOGY OF OBESITY III ETIOLOGY The Hypothalamus Cecebcal Factocs Psychologic Factors, Endocrine Factors Petuitary Thyroid Adrenals Pancseas Gonads Pineal body Genetic Varieties Laurence-Afoon-B.cdl syndrome Morgagni-Stewart-Morel syndrome Common familial obesity Constitutional abnormality of adipose tissue Disorders in the Use of Energy Excessive gastro-intestinal absorption "Static" obesity Increased efficiency in doing nork Respiratory quotient and its vaganies Reduced specific dynamic action Negative phase of metabolism Theory of "Luxus Konsumption Ketosis. Energy changes Disorder of enzymatic activity Retention of Water IV COWTRAINDICATIONS TO REDUCTION V DETS FOR OBESITY (Alice Karlske Irmuseb) roon Nomogram... 22 25 26 30 31 33 33 34 35 37 37 37 38 39 42 46 48 48 48 49 31 52 32 53 54 > 33 38 61 81 > ·... 88 88 91 91 95 95 vili OBESITY VI OTHER THERAPY Psychotherapy Drugs. Thyroid, Other endocrine preparations Amphetamine Dinitrophenol Belladonna. Miscellaneous therapy Diuretics Heat Cabinet Treatments (Turkish Baths) and Salt Restriction ... Exercise and Massage Surgical Removal of Fat References ..... 101 .. 101 . 101 102 103 .. 103 .. 104 ... 106 ·Obesity...

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·Chapter 1 INTRODUCTION THE WORD obesity is derived from the Latin "obesus which means "eaten up" or "lean," gradually the term came to have the opposite meaning, that of being overweight 885 The term "adiposity may be used as a synonym and is perhaps a better choice since it is derived from the Latin "adeps" meaning "fat " 158) To define obesity is difficult and most of the definitions given have been quite arbitrary 82 Sevringhaus 839 defined obesity as an excess of fat over the normal expected for the height, age and sex of the patient Brucho defined obesity as a nutritional state in which the storage of fat exceeds the amount that is commonly associated with an expression of adequate alimentation Newburgh 28 defined the condition as a state in which the body contains an abnormally large amount of adipose tissue Epstein 123 held that obesity signifies an increase in body weight in excess of the limitation of skeletal and physiologic requirement, owing to the deposition of fat. Still another definition, given by Bauer,17 states that the term "obesity" should be limited to those persons who, it left to their own automatic regulation of diet and activity, exhibit a compulsory tendency toward a pronounced and abnormal accumulation of fat He would not apply the term "obesity" to the condition resulting from simple overcating, but rather to that inherent constitutional abnormality which leads to obesity. In fact, he expressed the opinion that stoutness could not arise from increased appetite due to faulty habits of cating. Such distinctions seem unnecessary, howcver, (3) ·4 OBESITY Life insurance statistics 263 show that the average weight, as given in the usual height-weight tables, after thirty years of age is too high and that for optimal life expectancy one should not weigh more than the average at thirty years. Wilder 407 concurred in this view. It is felt that longevity is probably the best single index to the ideal weight 264, 261 and if this premise is accepted, the tables of "ideal weight" are found to be considerably different from the ordinarily used tables of average weights The weight of the average person increases about twelve pounds (5 kg.) between the ages of twenty-five and fifty years, but this is true because many are gaining twenty or thirty pounds (9.1 to 13.6 kg.) or more and some are remaining constant in weight. It has been shown that maximal life expectancy is obtained if the average weight at ages twenty-five to thirty years is maintained the remaining years of one's life.263, 264 For this reason it is suggested that Tables I and II be used to determine the ideal weight of adult patients. These first two tables also have the advantage of allowing for variations in body build. Statistical studies by life insurance companies have also demon strated that it is of some advantage to be slightly over av. erage weight before the age of thirty years, to be of average weight from ages thirty to forty and to be definitely underweight after age forty.282 In allowing for variations in body build, some authors allow a 10 per cent range on either side of normal.339 A more exact method, which considers the variations in bodily proportion, is the determination of specific gravity.23 The lower the specific gravity, the greater the amount of adipose tissue in relation to other structures. Because this method requires weighing the patient under water, it will not likely become a common one. A close correlation has been found. between thoracic and abdominal measurements, and such measurements have been considered to be an adequate substitute for the elaborate procedure of underwater weighing.** It has been stated that obesity is the most frequent physi- ·INTRODUCTION 5 TABLE I IDEAL WEIGHTS FOR MEN OF AGES 25 AND OVER Weight in pounds according to frame (as ordinarily dressed) Height (with shoes on) Feet Inches Small Frame Medsom Frame Large Frame 5 2 116-125 124-133 131-142 5 3 119-128 127-136 133–144 5 4 122-132 130-140 137-149 S 5 126-136 134-144 141-153 S 6 129-139 137-147 145-157 5 7 133-143 141-151 149-162 5 8 136-147 145-156 153-166 S 9 140-151 149-160 157-170 5 10 144-155 153-164 161-175 S 11 148-159 157-168 165-180 6 0 152-161 161-173 169-185 6 1 157-169 166-178 17+-190 6 2 163-173 179-196 6 3 176-189 171-18+ 168-180 18+202 • From Metropolitan Life Insurance Company ** cal abnormality found in the general population." Ap proximately 28 per cent of the population are 10 per cent or more overweight (Table III). The gain in weight with ad. vincing age is greater in women than in men, and a greater proportion of women are overweight than men (Fig 1)."18 in childhood the inadence of obesity is about equal in the two sexcs.es The handicaps imposed by obesity have been enumerated by many authors but frequently the physician fails to em phasize sufficiently to the patient the scriousness of this discase. It is easy to shrug off "a few pounds of overweight" ·6 OBESITY TABLE II IDEAL WEIGHTS FOR WOMEN OF AGES 25 AND OVER Weight in pounds according to frame (as ordinarıly dressed) Height (with shoes on) Small Medium Large Feet Inches Frame Frame 4 11 10+111 110-118 117-127 Frame $ 0 105-113 112-120 119-120 5 1 107-115 114-122 121-131 5 2 110-118 117-125 124-135 5 3 113-121 120-128 127-138 5 4 116-125 124-132 131-142 5 5 119-128 127-135 133-145 5 6 123-132 130-140 138-150 5 7 126-136 13+144 142-154 5 8 129-139 137-147 145-158 9 133-143 141-151 149-162 5 5 10 136-147 145-155 152–166 5 148-158 11 139-150 155-169 * From Metropolitan Life Insurance Company *** as something of little consequence, but in so doing, the physician is ignoring what is perhaps his best chance to lengthen the life and diminish the future illnesses of his patient (Tables IV and V and Fig 2). Statisticians have recently pointed out the increase in deaths from the degenerative diseases, such as heart disease, diabetes and cancer; the implication has been that medicine is approaching a point of diminishing returns and that increasing efforts will reduce the death and illness rates only slightly. Actually a great improvement in the health of the nation is possible by means of the correction and prevention of obesity. In time of war, countries with diminished supplies of food have 405 ·INTRODUCTION 7 TABLE III PERCENTAGE INCIDENCE OF OVERWEIGHT AND UNDERWEIGHT ASIONG 10,000 EXAMINERS Actual Standardizedt Overweight 10% or more 25 8 309 257 303 Men Women Total 27 3 28 Men Women 10 2 15 8 10 2 15 3 11 9 12 8 Underweight 10% or more Tota! • From Editorul 14 + Standardized for age and sex according to the population of the United States in 1930 demonstrated a definite decrease in the inadence of degenes. ative discases.266 Statistical studies demonstrating the adverse influence of obesity on hypertension, 172, 227, 228, 346, 851, 382, 618 pulmonary emphysema,200, 350 diabetes, 132, 172, 196, 276, 283, 290 heart disease, 327, 256, B45 cancer, 303, 380 acute and chronic nephritis, 104 106, 227, 806 cirthosis, 104, 205, 366 appendicitis,104 accidents,los venous thrombosis and embolism,'s atherosclerosis "17 and toxemias of pregnancy," 1,258, 294 all suggest that by the treatment of obesity the physician may ameliorate considerably the effects of many diseases for which otherwise he has little really effective treatment. The increased dangers of surgical procedures in the presence of obesity,19, 82, 105, 112, 120 the greater severity of degenerative arthritis in the knees, hips and lumbar spine of the obesc, 88, 18, 91, 138, 274 increased incidence of gallbladder disease.". 105. 129 earlier appearance of varicose icins,1, 109 more frequent fractures, 62 increased fetal mortality and greater difficulty in obstetrical delivery 358 are further reasons for the correction of obesity. It is prob able that a longer duration of the obesity increases the chances of development of both hypertension and dia. betes.?T. 18, 19, 318 It has been suggested that since one ·8 OBESITY 60 SO Female 40 Per cent 30 Male 20 1 10-19 20-29 50-59 60 and over 30-39 40-49 Age groups Figure 1. Incidence of overweight (10 per cent or more) among 10,000 examinees for insurance by age and sex (From Editorial: A study of impairments found among 10,000 unselected examinees. Article II; Weight. Proc. Life Ext. Exam 1.89-93 (July-Aug ] 1939.) action of insulin is to convert carbohydrates to fat,108 a process of considerable magnitude in the development of obesity, the demand for insulin is correspondingly great and may exceed the capacity of the pancreas to produce it; thus, diabetes may result Smith and Willius 360, 415 in their study of the pathology of adiposity of the heart found that the degree of cardiac en largement in obesity is roughly proportional to the increase in surface area and that some of these otherwise normal, enlarged hearts may fail They consider "adiposity of the heart," which frequently accompanies obesity, as an increase in the amount of subepicardial fat and of the fat lying be- ·INTRODUCTION 9 TABLE IV DEATHS PER 100,000 -- ALL CAUSES - ALL AGES CODIBINED BY WEIGHT CLASSES * Death rates per 100,000 Percentage of tate in "normal" weight class 913 833 108 99 8# 100 Underweights 15% to 34% underweight 5% to 14 underweight Normal weights Overweights 5% to 14% overweight to 24% overweight Sy or more overweight From Editorial 150 23 1,027 1,215 1.472 122 144 174 TABLE V INFLUENCE OF OVERWEIGHT ON MORTALITY IN PERSONS AGED 45 TO 30 Years l'ounds overweight Increase in death rate over average, per cent 10 8 20 18 30 28 40 45 50 56 67 70 81 116 90 . From Nexburgh, LH fareen muscle bundles; fatty infiltration, on the other hand, 15. seen in pernicious anemia, carcinoma and similar con. ditions and consists of droplets of fat which appear within the cytoplasm of the cardiac muscle cells ·10 OBESITY Obesity causes a diminished vital capacity probabl through the mechanical restriction of respiratory movement by deposits of fat in the abdominal and thoracic walls. the duration of the obesity is great enough, emphysema de velops and the vital capacity is permanently impaired in spit of later adequate reduction in weight.209, 350 Evidence 12 been presented that a considerable degree of exertiona dyspnea can occur without a significant degree of impair ment of cardiac output, the dyspnea presurnably resulting from the decrease in vital capacity alone. 90% Obese person: have been found to be less able than the nonobese to toler: ate exertion at high temperatures and humidity.522 Electrocardiographic changes in obesity are frequently seen.254, 848 Diaphragmatic hernia is more frequently observed in the obese and it occasionally may be corrected by weight reduction alone.34 Further, surgeons have found that the case and success of a repair of a diaphragmatic hernia is greatly increased by the correction of obesity. In addition to the physical disorders mentioned, there are serious psychologic problems stemming from obesity. Marked obesity is essentially a repulsive disease; its victim tends to feel rejected, unable to join with others in many of the ordinary activities with complete acceptance. Because physical activity requires greater effort for the obese than for the nonobese, the victim is likely to retreat to a state of inactivity and thereby to perpetuate and accentuate the condition The frequent occurrence of neuroses in the obese has been emphasized by several investigators.63, 69, 70, 282, 910 It should be pointed out, however, that similar psychologic investigations of control groups of nonobese persons might have revealed a similar incidence and variety of neuroses. It is, of course, difficult to judge what proportion of psychologic difficulties is the result of, and how much is the cause of, the obesity. Esthetic reasons for the treatment of obesity are not the least important. The desire to be attractive is possibly the ·INTRODUCTION 11 INFLUENCE OF BODY WEIGHT ON MORTALITY Subsequent mortality among men, according to build classes, expressed as percentage of death rate of normal weight men ALL CAUSES OF DEATH 14** 122 162 11A 100% S- ISH 6-14% UNDERWEIGHT NORMAL WEIGHT 15-24 ONTIWINT 25% OVER MTX 161% DIABETES CARDIOVASCULAR RENAL DISEASES 100% 711 YOOX UNDERRIMI MARMAL OVANLIGT UNDERAKUNT MOIMAL OVERWERONT LA 707% LOBAR PNEUMONIA PULMONARY TUBERCULOSIS 100% ROO WELAT NOUMAL OVLIWIKI UNDEREA NORMAL DIWEKAT CANCER ACCIDENTS. 101% 100 100% OVLAWI L- WALIMAH OMAL OntwLION1 motiven drepta a tetrapolutaa lyf asurance Company of thon Central Lyt kanna Crapery Port, an an Figure 2 Influence of body weight on mortality from selected auses (From Dublin, L. 1.*) most frequent season that the overweight person goes to the physician for help in reduction, although in some cultures obesity has been considered a mark of beauty.

·12 OBESITY While there is no question but that obesity increases the incidence of a large number of pathologic processes, it cannot be assumed with such certainty that the reduction of the weight of an obese person to normal will give him health equivalent to that of the person who has never been obese. Some of the changes caused by obesity, such as emphysema,209,350 tend to become irreversible in time, but others may be corrected by reduction of weight, 298 It seems reasonable to assume that the shorter the duration and the less the degree of the obesity, the more easily will normal health expectancy be restored. It is, therefore, as important to prevent as to correct obesity.) In consideration of all these factors, it would seem desirable that more doctors dev something of the missionary spirit and zeal in correcting obesity.

·Chapter II PHYSIOLOGY OF OBESITY B EFORE the controversial questions of treatment and etiology are considered, it is best to have some understand ing of the physiologic mechanisms involved in obesity. Early in the investigations of obesity, several cases were reported in which there appeared to be a maintenance of obesity in spite of low caloric intakes.121, 268,879, 387 These findings seemed to confirm the popular idea that there are fat people who stay fat no matter how little they eat 11B, 371 However, in more recent and better controlled studies it has been shown that obese persons must eat more than the av. erage person in order to remain obesc. 81, 288, 282, 385, 870 This statement has been made previously in many forms and for emphasis it is here repeated:Eat comes only from food, and L ....-.11. those with a tendency toward leanness who can overeat with impunity and that there are those with a predisposition to obesity who will become fat although they eat no greater amount than does the lean person 156, 872 It is apparently felt by these investigators that some obese persons have an unusual mechanism, not possessed by other people, for conserving energy It is sufficient to say that such a mechanism has never been adequately demonstrated 284, 2MS and that the Scry multiplicity of suggested abnormalities of metabolism argues against such a possibility The wonderfully integrated ability of the body to main. tain itself in a constant state has been the subject of many discussions The French physiologist, Claude Bernard, was [13] ·14 OBESITY the first to make an extensive study in this field He coined the term "milieu interieur" and emphasized the remarkable stability of the composition of body fluids. Cannon To developed this concept further under the designation "homeostasis." Von Noorden 387 and Levy expressed the belief that the ingestion of only a small excess of food daily would soon result in obesity. This idea that a small continuing strain would ultimately cause a larger error in metabolism disagrees with the concepts of Bernard and Cannon as developed by Gamble.140 Gamble emphasized the ability of the bodily compensatory mechanisms to minimize and obscure the effects of any of the lesser strains on the various metabolic processes. Nevertheless, the ingestion of food appreciably in excess of requirements is a stress with which the body has only limited ability to cope, and a gain in weight of some degree will invariably follow. Therefore, the mechanism which determines appetite is a primary factor in the development of obesity. No one has been able to explain satisfactorily what determines satiation, but it probly depends on the interaction of a number of factors. The striking effect of hypothalamic damage in producing obesity through increased appetite *s suggests that an' important center for normal appetite regulation may reside there. The importance of psychic conflict in the development of obesity in persons exhibiting compulsive eating has frequently been observed, 84 thus demonstrating that the cerebral cortex may override the more automatic and primitive appetite control centers. It is the familiar plaint of the fat person that "I don't eat a thing and I still get fat" It has been well proved that they do eat excessively, 282, 870 and it is interesting to speculate why this belief should arise so frequently. A possible ex. planation is that the person with a predisposition to obesity has an appetite mechanism (whatever that may consist of) which requires a larger than normal amount of food before satiation is accomplished If he eats what would satisfy the ·PHYSIOLOGY OF OBESITY 15 normal person he remains hungry and feels that he has eaten very little; if he eats anything less than what is required for satiation he is likely to believe honestly that he has caten little, even though he has consumed large quantities of food A corresponding situation appears to exist for the person with a tendency toward leanness who insists that he eats a great deal and still fails to gain Hunger has been defined as an unpleasant sensation, physiologic in origin, best described as a hollow, empty feeling in the epigastrium, while appetite is considered to be a desire for the pleasurable sensations associated with food and drink and is of psychologic origin.16, 18 Both of these sensations lead to cating, however, and for our purposes they may be considered identical. The two terms will be used interchangeably. It was suggested by Cannon 78 that hunger was associated with gastric contractions, and it has been shown that insulininduced hypoglycemia will increase the concentration and amount of gastric acids by means of vagal stimulation 183 From this it would be easy to assume that lack of food leads to hypoglycemia; hypoglycemia causes incrcased gastric activity by means of vagal stimulation, and the increased gastric activity is in turn sesponsible for the sensation of hunger. It has been demonstrated, however, that denervation of the stomach does not prevent insulid-induced hunger in dogs 103 Thus, there must be other alternate mechanisms The efficacy of the odor and sight of food, and even of mere memories of good meals, in arousing appetite is familiar to everyone Other theories of hunger and appetite involve cerebral "hunger centers" and peripheral nerve impulses from chemosensitive tissues which detect changes in the composition of blood, such as the change in hypoglycemia.no It is more likely that hunger depends on the summation and integration of a large number of seasory impulses and that the complex mechanism by which it is aroused varies in ·16 OBESITY its function from person to person, and even from time to time in the same person. Maclagen 246 performed fundamental animal experimentation which showed the effects of fasting and of various drugs on appetite. The optimal duration of a fast for stimulating appetite was found to be eighteen hours. In addition to variations in food intake as a means of regulating weight, there are also other mechanisms which involve changes in the output of energy? 290, 823 More specifically, Newburgh has shown that the person fed a diet slightly greater than that which he required for maintaining his weight does not continue to gain indefinitely, but rather gains weight quickly at first, then more and more slowly as he approaches the increased weight at which the increased diet will maintain him. This mechanism for limiting the gain in weight seems related in some manner to the surface arca It has been well demonstrated that the number of calories required by the body at resting state is proportional to the surface area 280, 301, 369 Thus a 35 year old man, 5 feet and 7 inches (170 cm.) tall with a surface area of 1.79 square meters, will maintain a normal weight of 150 pounds (68 kg.) with an intake of 2,415 calories each 24 hours (Table VI) If he consumes 3,255 calories (34 per cent more) he will gradually gain in weight until he reaches 300 pounds (136 kg.) and a surface area of 24 square meters (34 per cent greater). The weight gain by such a man weighing 150 pounds and eating 3,255 calories will at first be 1.7 pounds (0.8 kg) per week The rate of gain will gradually become slower until gaining ceases at 300 pounds Similarly if this man weighed 300 pounds and were fed 2,415 calories daily he would lose 1.7 pounds a week at first, the rate of loss gradually slowing as his weight approached 150 pounds From these figures * it can be seen that a small daily excess of food does not lead to unlimited gains in weight as was • Calculations were made by means of the Boothby-Berkson nomogram and the factor for predicting loss of weight given by Wilder., ** ·PHYSIOLOGY OF OBESITY 17 once postulated by Von Noorden, a 397 but rather to definite calculable and limited increases This removes some of the mystery with which the appetite mechanism was surrounded when Von Noorden pictured it as a device of almost incredible accuracy. It also diminishes the necessity for postu. lating obscure aberrations in the metabolism of energy which would adjust the output of energy to fit the intake TABLE VI VARYING FOOD REQUIREMENTS FOR A THIRTY-FIVE YEAR OLD MAN AT DIFFERENT BODY WEIGHTS * Weight, pounds Surface area, square meters 100 1 50 Calories required per twenty-four hours At basat With moderate conditions activity 1,360 2,010 1,610 2,415 1,840 2,760 2,020 3,030 150 1 79 200 2 02 250 2 22 300 2 40 2.170 3.233 • These calculations assume basal metabolic rate of O and were ob tuned by use of the Boothby Berkson nomogram for thirty-five year old man 3 feet and 7 inches tall who had a standard weight of 150 pounds. (From Gastineau, CF and Rynearson, EH Obesity Ann Ini. Med, 27 883 897 (Dec ) 1947.) + Caloric requirements at moderate activity are assumed to be 50 per cent greater than those at basal conditions The relation of surface area to the rate of metabolism, which was first noted by Rubner, 109 is the basis for basal metabolic standards 260, 801, 369 The fact that basal metabolic rates are found to be normal in obesity has great importance., 61, 197, 191, 359, 260, 304, 373, 371, 379 It means that the person has a much greater rate of metabolism than he would have if he were of normal weight. He is eating more to maintain a metabolic fire of greater size His circu. latory and respiratory systems are carrying loads greater than obese ·18 OBESITY they were designed to carry. It is as though a passenger car motor were being used to propel a truck, Because standards are computed on the basis of surface area, this increased rate of metabolism is obscured by the normal basal metabolic rates found in obesity. The increased rate of metabolism in obesity has been compared to that seen in hyperthyroidism; indeed, there are certain clinical sunilarities in the tachycardia, cardiac failure, easy perspiration and other symptoms 369 It has been suggested that the excess adipose tissue in the obese is inert and that all of the exchanges of energy are taking place in the muscles and viscera.349, 369 Talbot, 379 however, expressed the belief that the adipose tissue in children contributes an appreciable fraction of the bodily heat production McCune and Bruch considered it virtually impossible to estimate "active mass” in obese children 241 Mirskı 306 characterized adipose tissue not as a passive source of stored fat but as an active organ with a specific carbohydrate metabolism, a concept supported by the experimental studies of Schoenheimer 332 Reduction of the caloric intake of an obese person may lower the basal metabolic rate, according to some authors, 58, 83, 88, 281, 869 but others have failed to find such a decrease. 127. 268, 275, 323 These contradictory reports may be explained by the fact that in the various studies different diets were utilized. Although all diets were inadequate in calories, some contained much larger amounts of protein than others. It is possible that a generous supply of protein may prevent this fall in the basal metabolic rate, although the basal metabolic rate is properly determined after an overnight fast when any effect of specific dynamic action should be absent. This question of the fall of the basal metabolic rate in the reduction of weight of obese persons is of some importance, but insufficient studies have been made to permit the formation of any definite conclusion. In spite of whatever lowering of the basal metabolic rate may occur, it seems fairly certain ·19 PHYSIOLOGY OF OBESITY that the rate of energy exchange never quite falls to that of the patient at normal weight Expressed in other terms, the basal metabolic rate computed on the basis of ideal weight will be perhaps a + 25 in an obese subject A lowered cal. onic intake may reduce somewhat this elevated basal metabolic rate before there is more than a moderate loss of weight, but the rate does not reach the zero level until the patient's weight reaches normal 369 The starvation of the normal or thin subject is an entirely different matter 232, 255, 923, 869 In such subjects the heat production diminishes markedly, work becomes difficult and there is much depression and emotional instability, 210 greatly in contrast with the increased feeling of well-being observed by obese patients who are undergoing successful reduction of weight 369 Some of the lowest basal metabolic rates are seen in anorexia nervosa, one of the clinical forms of starvation in contrast the obese patient during reduction has increased vigor, remains active and feels quite well The mechanisms which regulate metabolism thus tend to cause weight to remain within certain limits with certain variations of food intake, An increase in caloric intake causes weight to rise to a new level and then to be maintained, a decrease in diet causes the weight to descend to a new level where it will remain constant on a given supply of energy Another result of obesity is a diminution in the tolerance for carbohydrates 246 This phenomenon is observed more frequently in patients with long-standing obesity than in those with obesity of short duration 75, 100, 283, 305 but it is not an invariable companion of obesity." If the patient is Over forty years of age at the onset of glycosuri3 it is likely that reduction of weight will remose all evidence of disordered metabolism of carbohydrate Newburgh *** ex. pressed the belief that this variety of glycosuria and hyper. glycemia is distinct from true diabetes It would be difficult and of no great importance to prove that the hyperslycemia ·20 OBESITY is not the manifestation of a latent diabetes which is brought into the open by the obesity. There is little difference between the obesity of child. hood and that beginning in adult life. Obese children, judged by all criteria of development, are usually somewhat advanced 60, 66 except in social and emotional aspects. The basal metabolic rate is essentially normal although standards are very uncertain 61, 979 There are particular difficulties in estimating the progress and degree of obesity in children because of the constantly changing mass of skeletal and muscular tissue 87 but various devices, such as the grid devised by Wetzel, may aid in overcoming this difficulty.€7,602 Reduction of weight may possibly lead to an earlier puberty 06. 878 although obese children characteristically are advanced in this respect. Amenorrhea, sterility, and even dysmenorrhea have been ascribed to obesity.11, 127 Certainly, amenorrhea and sterility in the presence of obesity cannot be said to be good evidence for an endocrine etiology for obesity and are most likely secondary to obesity In summary, it can be said that the various phenomena observed in obesity are chiefly the result of it and not evi. dences of some quirk of metabolic processes which have caused the disease. Numerous errors of metabolism have been suggested as the cause of obesity and these will be discussed in the next section.

·Chapter III ETIOLOGY N TUMEROUS classifications of obesity have been made 16, 118, 523 and it is significant how little agreement there is among them The concept of endogenous and exogenous obesity was championed early in the century by Von Noorden 287 and it has remained popular since 111, 54 Engelbach 111 stated that endogenous obesity does not respond to dieting and exercise while the exogenous variety does Netv. burgh makes no distinction between exogenous and endogenous obesity, stating that obesity is always caused by the consumption of food in excess of requirements, a conception of obesity which many would label exogenous His wellcontrolled studies invariably have demonstrated that the obese person loses weight on a submaintenance diet in accord with metabolic calculations On the other hand, it has been argued that all or most obesity is endogenous since the factors which initiate the overeating, such as psychologic con. ficts or hypothalamic damage, originate within the person 173, 184, 208, 356 It would seem wisest to abandon the terms "endogenous" and "exogenous" obesity 329 Bernhardt 28 presented an involved classification Gold. zicher118, 119 maintained that there are many causes of obesity and that it should be regarded as a symptom common to many conditions rather than as an entity For this reason and Others he criticized Nettburgh and other workers who have advanced our knowledge of obesity tremendously by the de tailed study of individual patients Tlie etiology of obesity will be discussed under a number of headings in this paper but the outline should not be taken as a classification of obesity. Rather the outline should be ·22 OBESITY considered as a list of mechanisms which have been proposed, of which only a few have been accepted as of any importance THE HYPOTHALAMUS Injury to the hypothalamus has been shown to interfere with such important self-regulatory functions as temperature control, water balance, appetite, gastro-intestinal function and sleep 58, 144, 811 Damage to certain portions of the hypothalamus causes poikilothermia, that is, the animal loses the ability to control its temperature by means of sweating and vasomotor mechanisms and assumes the temperature of its surroundings Damage to the paraventricular hypothalamic nuclei will cause obesity to occur 171, 175, 176, 177, 403 as a result of voracious, cavenous appetite 45, 67, 203 which begins abruptly after the injury. Diminished production of heat and reduced activity may play some lesser role in the development of obesity from this cause Altered liabits of eating may also be a factor, 49, 50, 54 the rapid, single, large feedings of the animal with hypothalamic damage supposedly producing less of a specific dynamic action than the slower, smaller and more frequent feedings of the normal animals." Heinbecker, White and Rolf 171 have shown that bilateral destruction of the paired paraventricular nuclei is the crucial factor in the production of this variety of obesity. They have contrasted this experimental finding with the effects of the destruction of the supra-optic nuclei in causing diabetes in. sipidus. These experimental facts explain a few rare types of obesity and, in addition, suggest that the hypothalamus may be the center which is normally in control of a great number of mechanisms which regulate a variety of bodily functions, among them being those of appetite and other aspects of energy exchange 47, 61 Bernhardt 28 was one of the first to suggest that the hypothalamus may play an important role in the development of common obesity. In 1840, Mohr reported the case of a woman in whom ·ETIOLOGY 23 obesity developed rapidly before the patient died of a large pituitary tumor. In 1901 Frohlich described a patient who exhibited hypogenitalism, obesity, infantilism and a tumor at the base of the brain.20, 62 It was at first assumed that these changes resulted from the destruction of the pituitary body and Cushing 87 seemed to confirm this opinion Erdheim in 1904, however, maintained that damage to the base of the brain is primarily responsible for the adiposity which some times accompanies pituitary tumors. In 1912 Aschner 10 ob served that only those animals with injury to the hypothalamus became obese after hypophysectomy. As evidence has accumulated it has become more and more apparent that at Icast the obesity in Frohlich's original case must have been the result of damage to the hypothalamic region. The term "Fröhlich's syndrome" has been used frequently to describe the child or adolescent whose genitalia are partly obscured by masses of adipose tissue Such children may attain a more normal appearance spontaneously . 156 but many endocrinologists treat them with a variety of hormones 383 Bruch has warned of the real dangers of endocrine therapy in obese children She stated that the important factor of diet will be obscured by glandular therapy and that significant psychologic damage will be done to the child who is being treated for "gland trouble "os Some authors have described a syndrome similar that of Fröhlich which is not associated with tumor and is thought to respond to treatment with pituitary extracts or to dis. appear spontaneously. Mittelmann described this under the term "juvenile adiposogenital dystrophy" 267 but it is doubt. ful whether this is an entity In view of the frequent misuse of the term "Frohlich's syndrome” to include patients with out intracranial lesions and because of the doubtful nature of the condition known as adiposogenital dystrophy it would sccm wise to abandon both these terms The hypoplasia of the genitalia sometimes found asso ciated with hypothalamic injury and obesity was at first ·26 OBESITY has suggested that emotional experiences can actually cause derangements of hypothalamic function thereby possibly causing the obesity that accompanies neurosis. PSYCHOLOGIC FACTORS As the phylogenetic scale is ascended, the cerebral cortex exerts an ever greater modifying influence on the functions of the lower nervous centers. In the maturation of the individual, the cortex also assumes a greater control over such basic functions as eating, sleeping and procreation. There can be no argument but that our civilization has modified all such functions tremendously, and the aspect that each presents in various cultures is chiefly a mirror of that culture. Rousseau's "noble savage," that hypothetical person reared free of all such cultural pressures and taboos, does not exist Eating has acquired a considerable social significance in our own social order, not only in the nature and time of the meals but in the amount eaten. 180 While it is true that most infants and children have less modification of their hypothalamic impulses by the cerebral cortex than do adults, yet Bruch has shown in a series of fundamental articles that obesity of psychologic origin can begin early in childhood. The psychologic pattern of the mothers of these obese children is usually as distincitve as that of the children themselves. Such mothers usually go to extremes in protecting their children from even the minor conflicts of living but paradoxically entertain great ambitions for them. These children are prevented from striving with other children and are bathed and dressed by their mothers far beyond the usual age for such care. Often, the obese child, Bruch found, is the only or the youngest child in the family. Within the families containing obese children there is frequently great emphasis on food. Desserts and candies are used as rewards for good behavior; conversation centers around delicacies of the table, and the child gains the feeling that food is the end and purpose of life.178 The mothers of ·ETIOLOGY 27 obese children were found by Bruch to be emotionally starved themselves, disappointed in their husbands, worried over domestic strife and often disappointed in the sex of their children. As if in compensation, these mothers attempt to pour out to their children a love that they do not honestly feel. In such an attempt they give the most obvious things, namely, food and protection from the unpleasantness of work and contact with other children "who might play rough," but these mothers are still unable to give their children true affection Such circumstances occur in the lives of many lean persons, however. Such a situation acting on a child can lead to obesity in a number of ways. The protection from cough play and excrtion diminishes the amount of energy expended " The atmosphere of gourmandizing and the continued urging to cat will cause the ingestion of increased amounts of food Furthermore, the emotional starvation of the child who per. ceives the real emptiness of his mother's show of affection may lead to a compensatory increase in food consumption as though the child were trying to satisfy his emotional hunger by the cating of food While these factors have been repeatedly demonstrated by several observers, it may properly be asked whether simslar factors do not frequently occur without the development of obesity This view finds some confirmation in the investigations of the etiology of anorexia ner osa."10, 599 Here is a syndrome which is almost invariably a manifestation of an emotional conflict and which has many close similarities to obesity but which superficially is completely different. Both are disorders of the mechanism which regulates the quantity of food intake Frequently anorexia nervosa is preceded by obesity, or the two conditions may alternate."** Both are more frequent in women and both respond most dramatically when trcated by means of proper diet and psychotherapy This response to diet and psychologic treatment alone is im. pressive when contrasted with the numerous articles which ·28 OBESITY urge the use of endocrine substances and which give support to endocrinologic theories of causation. Johnson 191 reported the cases of a man who lost, and of his wife who gained, weight in response to the same emotional stress. One of the most nearly universal drives is the one to save face, to put on a good front for other people to see.? In keeping with this desire is the great dislike of obese per sons to admit that their disease is due to gluttony and their insistence that the doctor tell them that "it's your glands and we'll treat it with this gland extract "$91, 347 А program of endocrine therapy alone is greatly to the patient's immediate comfort, for it offers both preservation of self-respect and the illusory prospect of reduction by means of "gland extracts" while it permits continuance of the indulgence of appetite. But unless the consumption of food is curtailed, no therapeutic program will succeed. If the doctor once, even by implication, admits that "your trouble is glands" he may find it difficult to convince the subject of the importance of diet.291 To tell the obese person that "there's nothing wrong with you except that you eat too much" might arouse immediate antagonism, but frequently such an approach is necessary. It is striking how frequently the overweight person insists that he is a small eates," and when given a properly balanced reduction diet of 1,000 or 1,200 calories he may insist that that is more than he ordinarily eats. There are several reasons for this. First, the obese person frequently eats many concentrated carbohydrates and, mistaking bulk for caloric content, underestimates the energy value of his customary diet. Second, the obese person hates to admit his glut tony and convinces his conscious self that he is actually in the babit of consuming relatively small amounts of food. Third, it is possible that the appetite mechanism is distorted in the person "predisposed" to obesity so that more food is required for his satiation than for the normal person. If he ·ETIOLOGY 29 cats a more than average amount but still not enough to satisfy his increased demand, the obese person will feel that he is cating only a small amount.388 Similarly the thin person becomes easily satiated and, if he eats a normal diet, feels that he has eaten exceedingly heartily. Such psychologic and physiologic factors render the estimation of food intake by patients unreliable and misleading. It is the physician's task to limit the caloric intake, to aid the patient to adjust to his emotional problems and to teach hun new dietary habits so that he will not immediately relapse into overcating and obesity after completion of a successful reduction program A better criterion for the success of a weight reduction program is the state of the patrent's health two or five years after its initiation. The emotional factors which led to obesity initially should not cause the physician to overlook the conflicts which result from the obesity and which tend to perpetuate it. The obesity itself becomes a handicap which prevents the patient from joining in play and from obtaining exercise, which in turn results in diminished output of energy and further gain in weight. The obesity is sometimes unconsciously used by the patient as a means of protection against doing unpleasant things. Obesity may repel suitors and may protect the obese girl from the responsibilities and duties of marriage 829 It may play a part in the selection of an occupation, presenting the obese person from doing difficult work. The feeling of being "sct apart" from other people because of the physical disfigurement tends to cause a certain amount of emotional starvation which perpetuates the increased appetite Occasionally the problems thich precipitated the obesity may be solved by the changes in circumstance that time brings about, but usually some attempt to resolve the patient's difficulties must be made Not only must the physician osercome the factors shich initiated the gain in a cight but he must also solve those which haic arisen as a result of the obesity.

·28 OBESITY urge the use of endocrine substances and which give support to endocrinologic theories of causation. Johnson 191 reported the cases of a man who lost, and of his wife who gained, weight in response to the same emotional stress. One of the most nearly universal drives is the one to save face, to put on a good front for other people to sec.?" In keeping with this desire is the great dislike of obese persons to admit that their disease is due to gluttony and their insistence that the doctor tell them that "it's your glands and we'll treat it with this gland extract." 291, 017 A program of endocrine therapy alone is greatly to the patient's immediate comfort, for it offers both preservation of self-respect and the illusory prospect of reduction by means of "gland extracts" while it permits continuance of the indulgence of appetite. But unless the consumption of food is curtailed, no therapeutic program will succeed. If the doctor once, even by implication, admits that "your trouble is glands" he may find it difficult to convince the subject of the importance of diet.291 To tell the obese person that "there's nothing wrong with you except that you eat too much" might arouse immediate antagonism, but frequently such an approach is necessary. It is striking how frequently the overweight person insists that he is a "small eater," and when given a properly balanced redaction diet of 1,000 or 1,200 calories be may insist that that is more than he ordinarily eats. There are sev. eral reasons for this. First, the obese person frequently eats many canceаtrated carbohydrates and, mistaking bulk for caloric content, underestimates the energy value of his customary diet. Second, the obese person hates to admit his gluttony and convinces his conscious self that he is actually in the habit of consuming relatively small amounts of food Third, it is possible that the appetite mechanism is distorted in the person "predisposed” to obesity so that more food is required for his satiation than for the normal person. If he ·ETIOLOGY 29 cats a more than average amount but still not enough to satisfy his increased demand, the obese person will feel that he is eating only a small amount.299 Similarly the thin person becomes easily satiated and, if he cats a normal diet, feels that he has caten exceedingly heartily. Such psychologic and physiologic factors render the estimation of food intake by patients unreliable and misleading. It is the physician's task to limit the caloric intake, to ard the patient to adjust to his emotional problems and to teach him new dietary habits so that he will not immediately relapse into overeating and obesity after completion of a successful reduction program A better criterion for the success of a weight reduction program is the state of the patient's health two or five years after its initiation The emotional factors which led to obesity initially should not cause the physician to overlook the conflicts which result from the obesity and which tend to perpetuate it The obesity itself becomes a handicap which prevents the patient from joining in play and from obtaining cxercise, which in turn results in diminished output of energy and further gain in weight The obesity is sometimes unconsciously used by the patient as a means of protection against doing unpleasant things. Obesity may repel suitors and may protect the obese girl from the responsibilities and duties of marriage 820 It may play a part in the selection of an occupation, preventing the obese person from doing difficult work. The feeling of being "Set apart" from other people because of the physical disfigurement tends to cause a certain amount of emotional starvation which perpetuates the increased appetite Occasionally the problems which precipitated the obesity may be solved by the changes in circumstance that time brings about, but usually some attempt to resolve the patient's difficulties must be made Not only must the physician orercome the factors which initiated the gain in scight but he must also solve those which have arisen as a result of the obesity.

·30 OBESITY Emotional depression frequently leads to loss of weight but it also may cause a definite increase.316 In one wellstudied series of fifty patients, Schopbach and Matthews 933 found mild anxiety states with considerable "neuromuscular tension" and obsessive-compulsive tendencies most common. In this group, eating frequently served as a device to diminish tension. In all but five or six patients of the series, psychogenic factors seemed closely related to the onset and development of obesity. This correlation of insecurity and obesity is emphasized in Bruch's studies which showed that families whose financial condition was on the borderline of inadequacy tended to have obese children. Thus the fear of not having enough to eat leads to overeating. It is also true, however, that the cheaper foods, which are chiefly concentrated carbohydrate, are those with a low satiation value. Ingestion of alcohol possibly may stimulate appetite suffi. Ciently to lead to obesity; in addition, alcohol itself has a definite caloric value 240 It is also well known that the ingestion of alcohol is associated with many psychologic factors. A number of observers have suggested that "nervous shocks and strains" may cause obesity by modifying autonomic functions, but this proposal has never been con. firmed.180 A freudian concept of obesity as a manifestation of orality has been presented 43, 145 and Richardson 820 has suggested that the ingestion of food may be given the symbolic meaning of impregnation. Bram " has also noted that other fat people will frequently discourage the patient from following his diet. Hill 178 associated gastro-intestinal symptoms, including emaciation and obesity, in adult life with patterns of breast feeding. ENDOCRINE FACTORS One of the most regrettable practices in medicine is the attempt to diagnose numerous endocrinologic aberrations ·ETIOLOGY 31 by means of slight variations in distribution of body fat ini, $18, 119, 189, 190 These claborate classifications into types have little or no basis sa controlled experimeat and are usually misleading 156, 149 obesity: 197 303 Pituitary first advanced by Fröhlich, the concept of an obesity secondary to hypopitustacism has disappeared slowly 7 although, as stated before, there is little or no justifiction for its existence Traditionally the patient with socalled pituitary obesity has a large trusk and slendes wrists and ankles, * sf this condition is associated with dwarfism, at is known as the "Burauet" type of obesity." Although hypophyseal obesity is ascribed by many to disorders of the anterior lobe, Werner tos placed the blame on a lack of posccrtor lobe secretions and used pituitria as substitution therapy. Thus practice finds some slight support in experiments carried out by Keller and Noble who removed the posterior lobe of the pituitary of two dogs and produced The posterior lobe of the pituitary has been implicated by others because st is thought that an excess of the ants. diuretic hormone may cause obesity to occur as a result of setention of water a38 It should be pointed out that we know of no experimental studies in which obesity in animais has been produced by the injection of pituitrın, a simple proof If this theory of hyperfunction of the posterior lobe had any basis in fact. The destruction of the pituttary occasionally results in cmaciation which is known as Simmonds' cachexia, 113, 941, 150 but apparently panlıypopitustarism qusll usually have little effect on body weight." In fact, in Simmonds' original case the patient scighed 103 pounds (467 kg) after ten years of illness, a weight not necessarily significant of great cm.3- ciation. Heinbecker and co-norkers 135 reported that simple hypophysectomy in dogs tends to cause some gain in weight.

·32 OBESITY Kraus 214, 215 expressed the belief that there is an increase in basophils in the pituitary in constitutional obesity, and that in the four conditions of adiposis dolorosa, cerebral hyperglobulia, Morgagni-Stewart-Míocel syndrome and Laurence- Moon-Biedl syndrome there is a similar increase in the basophils of the hypophysis and hyperplastic changes in the adrenals Goldzieher 157 described histologic changes in the hypophysis in so-called "constitutional" obesity but these studies were not carried out with the cell-counting technic that Rasmussen 837 has shown to be necessary in the study of pituitary cells. Cushing's syndrome is the one variety of obesity which is associated with pituitary disordes, and even in this instance adrenal cortical hormones probably mediate the metabolic changes responsible for the characteristic distribution of adipose tissue. Raab 307,808 postulates a hypophyseal hormone called "lipoitrın" which acts on the tuber anereum to initiate neural reflexes by way of the splanchnic nerves; these reflexes, in turn, prevent the liver from taking up fat. The existence of such a mechanism has ceceived no confirmation Recently, Reiss 815 has associated obesity with the lactogenic hormone Because the peripheral stores of fat are reduced in lactating rats, it was thought that one effect of the lactogenic hormone might be the mobilization of fat. Reiss had observed also that the onset of obesity in some cases coincided with a failure of lactation. On this theo retical basis, lactogenic hormone of pituitary origin was administered to a number of obese patients and experimental animals. All lost weight, the loss being particularly rapid when thyroid was added to the program. This study opens a new avenue of research on the nature of obesity and requires confirmation. Lawrence 224 has postulated a "lipopexic hormone" of pituitary origin which causes fat to be deposited in depots ·ETIOLOGY 33 A hyperactivity of the anterior lobe which changes later to hypopituitarism has been suggested as a cause of ado lescent obesity. 141 Thyroid It is commonly but erroneously believed that myxedema and hypothyroidism without myxedema are usually associated with obesity.16, 119, 160 However, by both animal expers. ments and statistical analysis of findings on myxedematous patients246, 802 it has been well shown that hypothyroidism does not tend to cause obesity 860 Apparently the complex mechanism which regulates appetite also diminishes the in. take of energy in proportion to the lowered output of energy Of course this mechanism may fail in hypothyroidism bo cause of the patient's training, environment or neurosis just as it might fail in the euthyroid individual Then obesity would result. Adrenals Hyperfunction of the adrenal cortex results in either Cushing's syndrome or the adrenogenital syndrome * In the latter there is no characteristic obesity, but in Cushing's syn. drome there is accumulation of fat about the cheeks, the supraclavicular regions, the spines of the upper thoracic and lower cervical vertebrae, and the trunk. This distribution of fat is almost diagnostic of the condition and has been noted even when the semaining portions of the body are emacated 230, 244, 416 The glycosuria appears to result from ex. cessive adrenal cortical hormone and is not a result of the obesity., 21% This syndrome is frequently given as an example of true endocrine obesity, and there can be no argument but that the adrenocortical hormone in some way has cffected a characteristic distribution of fat It is a different matter to argue that there is an invariable increase in the total amount of adipose tissue, hon ever. 19 The patient with Cushing's disease will lose weight on a reduction diet exactly as will ·32 OBESITY Kraus 214, 315 expressed the belief that there is an increase in basophils in the pituitary in constitutional obesity, and that in the four conditions of adiposis dolorosa, cerebral hyper. globulia, Morgagni-Stewart-Morel syndrome and Laurence Moon-Biedl syndrome there is a similar increase in the basophils of the hypophysis and hyperplastic changes in the adrenals. Goldzieher 147 described histologic changes in the hypophysts in so-called "constitutional" obesity but these studies were not carried out with the cell-counting technic that Rasmussen 837 has shown to be necessary in the study of pituitary cells Cushing's syndrome is the one variety of obesity which is associated with pituitary disorder, and even in this instance adrenal cortical hormones probably mcdiate the metabolic changes responsible for the characteristic distribution of adipose tissue. Raab 807,808 postulates a hypophyseal hormone called "lipoitrin" which acts on the tuber cinereum to initiate neural reflexes by way of the splanchnic nerves; these seflexes, in turn, prevent the liver from taking up fat. The existence of such a mechanism has received no confirmation, Recently, Reiss 315 has associated obesity with the factogenic hormone. Because the peripheral stores of fat are reduced in lactating rats, it was thought that onc effect of the lactogenic hormone might be the mobilization of fat. Reiss had observed also that the onset of obesity in some cases coincided with a failure of lactation. On this theoretical basis, lactogenic hormone of pituitary origin was administered to a number of obese patients and experimental animals. All lost weight, the loss being particularly rapid when thyroid was added to the program. This study opens a new avenue of research on the nature of obesity and sequires confirmation, Lawrence 224 has postulated a "lipopexic hormone" of pituitary angin which causes fat to be deposited in depots.

·ETIOLOGY 33 A hyperactivity of the anterior lobe which changes later to hypopituitarism has been suggested as a cause of adolescent obesity 141 Thyroid It is commonly but erroneously believed that myxedema and hypothyroidism without myxedema are usually associated with obesity.88, 119, 180 However, by both anual experiments and statistical analysis of findings on myxedematous patients:<4, 102 it has been well shown that hypothyroidism does not tend to cause obesity.540 Apparently the complex mechanism which regulates appetite also dımınıshes the intake of energy in proportion to the lowered output of energy Of course this mechanism may fail in hypothyroidism because of the patient's training, environment of neurosis just as it might fall in the euthyroid individual Then obesity would result. Adrenals Hyperfunction of the adrenal cortex results in either Cushing's syndrome or the adrenogenital syndrome. In the latter there is no characteristic obesity, but in Cushing's syn. drome there is accumulation of fat about the cheeks, the supraclavicular regions, the spines of the upper thoracic and lower cervical vertebrae, and the trunk This distribution of fat is almost diagnostic of the condition and has been noted even when the remaining portions of the body are emacıated.230, 348, 116 The glycosuria appears to result from excessive adrenal cortical hormone and is not a result of the obesity.%, 231 This syndrome is frequently given as an example of true endocrine obesity, and there can be no argument but that the adrenocortical hormone in some way has effected a characteristic distribution of fat It is a different matter to argue that there is an invariable increase in the total amount of adipose tissue, however,185 The patient with Cushing's disease will lose weight on a reduction diet exactly as will ·OBESITY aus 214, 215 expressed the belief that there is an increase phils in the pituitary in constitutional obesity, and that four conditions of adiposis dolorosa, cerebral hypera, Morgagni-Stewart-Morel syndrome and Laurerice- Biedl syndrome there is a similar increase in the ils of the hypophysis and hyperplastic changes in the Is Idzieher 147 described histologic changes in the hypophso-called "constitutional" obesity but these studies pt carried out with the cell-counting technic that Ras- 337 has shown to be necessary in the study of pituitary hing's syndrome is the one variety of obesity which lated with pituitary disorder, and even in this instance cortical hormones probably mediate the metabolic ; responsible for the characteristic distribution of : tissue. b 807, 808 postulates a hypophyseal hormone called in" which acts on the tuber cinereum to initiate neural by way of the splanchnic nerves; these reflexes, in 'event the liver from taking up fat. The existence of mechanism has received no confirmation. antly, Reiss 315 has associated obesity with the lactoormone. Because the peripheral stores of fat are in lactating rats, it was thought that one effect of ogenic hormone might be the mobilization of fat ad observed also that the onset of obesity in some incided with a failure of lactation. On this theobasis, lactogenic hormone of pituitary origin was tered to a number of obese patients and experimental All lost weight, the loss being particularly rapid yroid was added to the program. This study opens renue of research on the nature of obesity and requires ition :ence 224 has postulated a "lipopexic hormone" of Origin which causes fat to be deposited in depots ·ETIOLOGY 35 The evidence for hypoglycemia as a consistent stimulus for appetite, then is not convincing A second objection to hypoglycemia as a frequent cause for the development and maintenance of the obese state is that hypoglycemia is rarely observed in the obese but hyperglycemia is observed frequently.283, 396 A third objection is that in the syndrome of functional hypoglycemia," obesity is not mentioned as a frequent symptom, although examples of such have been reported 181, 317 In this condition there is fatigue and neurasthenia associated with low blood sugar concentrations but with no true hyperinsulinism, that is, with no slet cell tumor. In spite of the fact that the patient discovers that frequent eating may relieve his symptoms, there is often no gain in weight. The neuroses that constitute the basic part of this syndrome would be an adequate explana. tron for any obesity that might occur The question of the obesity which is associated with islet cell tumors is another matter. In this condition, the hypoglycernia is so pronounced that the patient is forced to keep eating at frequent intervals to remain conscious Under such circumstances, a considerable gain in weight is usual.404 Gonads It would be difficult to argue that the sex hormones have no influence on the deposition of adipose tissue It is well known to everyone that women have a pattern of fat dis. tribution different from that of men. There is no adequate proof that there is a distinct relationship between the amount of adipose tissue and sex hormone dysfunction. The eunuch may be slender or he may be obese,121 but so may be the individuals who are normal with respect to gonadal function; there is no proof that obesity is more frequent among persons who suffer from hypogonadism 158, 159, 354 The in. constant association of obesity and gonadectomy in human beings is to be contrasted with the obesity that usually fol. lows gonadectomy in animals.168 Some authors, however, ·34 OBESITY any other subject,139 and examples of patients who had this disease but who displayed leanness have been observed.230, 248, 416 The appearance of obesity is heightened by the osteoporosis and flattening of the vertebral bodies which shortens the neck and trunk. Ingle stated the belief that the importance of adrenal cortical hormone in the production of this syndrome has not been adequately proved,185 but he considered Albright's hypothesis that cortical hormones may cause destruction of protein to form carbohydrates which are in turn converted to fat a good possibility. Pancreas One of the common symptoms of an insulin-induced hypoglycemia is hunger, 72, 279 which does not necessarily depend on the increased gastric motility and secretion 162, 183 For this reason it has been supposed that an excess supply of insulin might be responsible for ordinary obesity.24 Serious objections can be found to this view, however. First, it is doubtful that the appetite is stimulated by hypoglycemia unless the blood sugar is lowered to shock-producing levels 18, 138, 102, 249 Apparently much of the increased intake of food during the course of insulin therapy depends on the conscious knowledge of the subject that he will have to eat heartily to avoid unpleasant symptoms Less well-controlled studies have suggested that insulin is an excellent stimulus to the production of gain in weight,342, 843 but the powerful element of suggestion inherent in the procedure of parenteral medication appears to be an adequate explanation of its success.188 Studies of the effects of protamine zinc and regular insulins made at the Scripps Metabolic Clinic showed that regular insulin fails to increase appetite but that protamine zinc insulin is very effective in this respect.245, 249 The explanation offered for these contradictory findings is that rapidly developing hypoglycemia of short duration does not stunulate appetite, while long-continued and gradually increasing hypoglycemia is an effective stimulus for appetite.

·ETIOLOGY 35 The evidence for hypoglycemia as a consistent stimulus for appetite, then is not convincing A second objection to hypoglycemia as a frequent cause for the development and maintenance of the obese state 15 that hypoglycemia is rarely observed in the obese but hyperglycemia is observed frequently 233, 236 A third objection is that in the syndrome of functional hypoglycemia, * obesity is not mentioned as a frequent symptom, although examples of such have been reported.181, 117 In this condition there is fatigue and neurasthenia associated with low blood sugar concentrations but with no true hyperinsulinism, that is, with no slet cell tumor In spite of the fact that the patient discovers that frequent cating may relieve his symptoms, there is often no gain in weight The neuroses that constitute the basic part of this syndrome would be an adequate explanation for any obesity that might occur The question of the obesity which is associated with islet cell tumors is another matter in this condition, the hypoglycemia is so pronounced that the patient is forced to keep eating at frequent intervals to remain conscious Under such circumstances, a considerable gain in weight is usual 04 Gonads It would be difficult to argue that the sex hormones have no influence on the deposition of adipose tissue It is well known to everyone that women have a pattern of fat distribution different from that of men There is no adequate proof that there is a distinct relationship between the amount of adipose tissue and sex hormone dysfunction. The eunuch may be slender or he may be obese, 121 but so may be the individuals who are normal with respect to gonadal function; there is no proof that obesity is more frequent among persons who suffer from hypogonadism 158, 159, 354 The inconstant association of obesity and gonadectomy in human beings is to be contrasted with the obesity that usually follows gonadectomy in animals.158 Some authors, however, ·34 OBESITY any other subject, 139 and examples of patients who had this disease but who displayed leanness have been observed.230, 248, 418 The appearance of obesity is heightened by the osteoporosis and flattening of the vertebral bodies which shortens the neck and trunk, Ingle stated the belief that the importance of adrenal cortical hormone in the production of this syndrome has not been adequately proved,186 but he con. sidered Albright's hypothesis that cortical hormones may cause destruction of protein to form carbohydrates which are in turn converted to fat a good possibility, Pancreas One of the common symptoms of an insulin-induced hypoglycemia is hunger, 72, 279 which does not necessarily depend on the increased gastric motility and secretion 103, 193 For this reason it has been supposed that an excess supply of insula might be responsible for ordinary obesity." Serious objections can be found to this view, however. First, it is doubtful that the appetite is stimulated by hypoglycemia unless the blood sugar is lowered to shock-producing levels 16, 138, 162, 219 Apparently much of the increased intake of food during the course of insulin therapy depends on the conscious knowledge of the subject that he will have to eat heartıly to avoid unpleasant symptoms. Less well-controlled studies have suggested that insulin is an excellent stimulus to the production of gain in weight,842, 949 but the powerful element of suggestion inherent in the procedure of teral medication appears to be an adequate explanation of its success.138 Studies of the effects of protamine zinc and regulas insulins made at the Scripps Metabolic Clinic showed that regular insulin fails to increase appetite but that protamine zinc insulin is very effective in this respect.245, 249 The ex. planation offered for these contradictory findings is that lapidly developing hypoglycemia of short duration does not stimulate appetite, while long-continued and gradually increasing hypoglycemia is an effective stimulus for appetite. paren- ·ETIOLOGY 37 between masculine and feminine distribution of fat seerns to depend on genetic as well as on hormonal factors. Rabson 809 has discussed varrations in distribution of fat in obesity, and Reed and co-workers 814 have done animal experiments in this field Another possibility is that there are nerves which have some trophic influence on the deposition and maintenance of fat 117 This will be discussed later, Pineal body The pineal body has an histologic appearance in childhood which suggests that it might have an endocrine func. tion At puberty this structure undergoes degenerative changes, such as calafication, which make such function at that time unlikely This sequence of events has led to the theory that the pineal gland is one of internal secretion during childhood and that the cessation of its function leads to pubertal changes and accelerated growth º6 Some writers $4, 239 have interpreted the available evidence to mean that a hormone secreted by the pineal body itself, rather than the cessation of its formation, initiates puberty A syndrome called "pubertas praecox" or "macrogenitosomia," which results from pineal tumors, has been de. scribed.81 This syndrome consists of precocious sexual, physical and mental development Obesity was noted'ın fifteen of sixty-nine cases of pineal tumors in children reviewed by Bing, Globus and Simon. It is not certain, however, that the phenomena, such as obesity, associated with pineal tumors are not the result of hypothalamic changes due to pressure exerted by the nearby neoplasm #1 Therefore, we must conclude that obesity secondary to pineal disorders has not been proved to exist $27 GENETIC VARIETIES Laurence-Moon-Biedl syndrome This consists of (1) mental deficiency, (2) retinitis pigmentosa, (3) hypogenitalist, (4) obesity and (5) poly- ·36 OBESITY have expressed the belief that hypogonadism is an important cause of obesity.149, 887 It has been suggested that obesity may begin more frequently at periods of gonadal change, such as puberty, pregnancy and the menopause than at other times in life, 11, 121. 149, 164, 984 and this has been taken as evidence for an endocrine nature of obesity. The shifts in hormone production in each of these periods of gonadal change are completely different, in some periods an increase and in others a decrease in the production of the various hormones concerned with sex occurs Even more complicated and varied are the changes in the production of pituitary hormone, yet it is argued that these completely different stimuli will result in the same effect, obesity. It is obvious, however, that most varicties of hypogonadism, menopause, puberty and pregnancy are associated with psychic conflicts, and it would seem likely that the joys of eating might be resorted to in compensation for the denial of other pleasures Inspection of height-weight-age tables reveals no abrupt change in the increasing incidence of obesity which occurs with advancing age, such as might be expected if menopause were an important etiologic factor The manifestation of the presence of various hormones depends on the presence of responsive end-organs. The fact that a varying distribution of adipose tissue can occur as the result of hormonal influences is evidence that all fat cells do not respond in the same way to the same influences, that the adipose tissue of one part of the body is not entirely the same as that of the rest of the body. Hormones circulate freely in the blood, and presumably all tissues of the body are exposed to equal concentrations of them Therefore, if the fat-bearing tissues of one region of the body increase in amount in response to a change in concentration of a hormone while the adipose tissue in another part undergoes no change, there must be some difference in the adipose tissues of different regions. This difference may depend on the chromosomal influences that affect body build. Thus the difference ·ETIOLOGY 37 between masculine and feminine distribution of fat seems to depend on genetic as well as on hormonal factors Rabson 809 has discussed variations in distribution of fat in obesity, and Reed and co-workers 31t have done animal ex. periments in this field Another possibility is that there are nerves which have some trophic influence on the deposition and maintenance of fat 117 This will be discussed later 96 Pineal body The pineal body has an histologic appearance in child. hood which suggests that it might have an endocrine functron. At puberty this structure undergoes degenerative changes, such as calcification, which make such function at that time unlikely This sequence of events has led to the theory that the pineal gland is one of internal secretion dur. ing childhood and that the cessation of its function leads to pubertal changes and accelerated growth Some writers $4, 239 have interpreted the available evidence to mean that a hormone secreted by the pineal body itself, rather than the cessation of its formation, initiates puberty A syndrome called "pubertas praecox" or "macrogenitosomia," which results from pineal tumors, has been described 81 This syndrome consists of precocious sexual, physical and mental development. Obesity was noted'in fifteen of sixty-nine cases of pineal tumors in children reviewed by Bing, Globus and Simon It is not certain, however, that the phenomena, such as obesity, associated with pineal tu. mors are not the result of hypothalamic changes due to pressure exerted by the nearby neoplasm. 1 Therefore, we must conclude that obesity secondary to pineal disorders has not been proved to exist. 327 GENETIC VARIETIES Laurence-Moon-Biedl syndrome This consists of (1) mental deficiency, (2) retinitis PIS mentosa, (3) hypogenitalism, (4) obesity and (5) poly- ·38 OBESITY dactyly.223, ,223, 250, 296 It appears to be inherited in a recessive manner.363 This syndrome was first described by Laurence and Moon in 1866 and interest in it was reawakened by re. ports of several cases by Bardet in 1920 and by Biedl in 1922. Biedi suggested that the syndrome could be desccibed as dystrophia adiposogenitalis of cerebral origin. He considered that the pituitary played no part in the manifestation of the condition, but more recently a somewhat tenuous and complicated theory, which involves the concept that hypopituitarism is followed by hyperpituitarism, has been proposed by Jaso and Curbelo 189 These authors also postulate a hormone which regulates the consumption of fat. An important observation by these workers is that the obesity does not appear until after one month of age Jenkins and Poncher 100 consider that the syndrome is the result of at least three genetic characters, one causing genital dystrophy and dwarfism, a second causing retinitis pigmentosa and a thicd causing the skeletal anomalies such as syndactylism and polydactylısm. Perhaps the most reasonable view is that presented by Warkany 395 and his co-workers which is that the syndrome is the rare chance combination of relatively frequent heredofamilial anomalies. They found that in most of the reported cases the patient did not possess all of the five cardinal symptoms and that in many cases additional anomalies were demonstrated. In summary, it can be said that the Laurence-Moon-Biedl syndrome does not appear to be endocrine in origin, that it is an ill-defined and poorly understood entity and that no proof has been advanced that the obesity results from any factor other than a large appetite and decreased activity. What may cause the increased in take of food is not known. Morgagni-Stewart-Morel syndrome This is perhaps better called "hyperostosis frontalis interna." It is a second rare form of obesity which is associated with inherited anomalies. It is manifested almost invariably ·ETIOLOGY by internal hyperostosis of the frontal bone and hez ache; frequently by obesity, impotence, amenorrhea, benig hypertensive cardiovascular disease, hirsutism, psychosis psychoneurosis, fatigability and weakness; and sometime by disturbances in olfaction, Bell's palsy, diplopia ana amblyopia.161 Headache is so constant that this diagnosis should be considered in all patients complaining of cephalalgia.212 The condition tends to be inherited in a dominant manner. Almost all of the subjects are women Usually symptoms become disabling between the ages of forty and fifty years. Although seldom recognized, this syndrome is probably not rare in a group of 1,620 patients who had roentgenograms of the skull for one reason or the other, 41 per cent were found to have the deposition of dense cancellous bone on the inner table of the frontal bone which is considered characteristic of the syndrome 270, 271 This entity was first described by Morgagni in 1765, and the association with insanity or neurosis was recognized by Stewart367 in 1928 and by Morel in 1930. The latter was the first to make the diagnosis ante mortem Many causes have been suggested and, as might be expected, the pituitary has been incriminated 270, 273, 867 Moore2'reported recently a case in which there was considerable cortical atrophy. On the other hand, Schneeberg and co-workers have presented rather convincing evidence that hyperostosis frontalis interna is not associated with any distinct clinical syndrome 3316 In this condition, again there is no evidence of disturbance of fat metabolism or of endocrine dysfunction; the obesity seems to result from some derangement of the appetite. regulating mechanism Common familial obesity Obesity which occurs frequently in certain families but which not associated with other hereditary degenerative stigmas is often observed It is the frequent plaint of the fat person that "I can't help being fat; both my parents were r ·42 OBESITY Bauer 17, 954 has expressed the feeling that there is an inherited and abnormal avidity of the adipose tissue for fat which, by depriving other more vital body parts of nutrition, increases hunger and, therefore, the total intake of energy. While we cannot, at present, state definitely the importance of heredity in obesity, we can emphasize to the patient with fat parents that he will respond to treatment in exactly the same way as will a person who has normal parents Such a patient should be told that fat is just as dangerous to him as to anyone else and that the fact that his parents were fat cannot be used as an excuse for avoidance of the necessary corrective measures. Conscitutional abnormality of adipose tissue Lipophilia: This is a term introduced by von Bergman. He expressed the belief that the adipose tissues of the fat person have a greater avidity for fat than do the tissues of the normal person and that fat is lost from these deposits with difficulty, just as the fat in a lipoma is thought to be retained during starvation although other fatty tissues are consumed Wells, a99 however, in his reviews on adipose tissue could find little evidence that, during loss of weight, the loss of fat from a benign lipoma is not in proportion to the loss from other adipose tissue. He considered that a malignant lipoma would likely retain and add to its store of fat during loss of weight, however. Newburgh 385 expressed the belief that the obese utilize fat even more easily than do normal subjects. Two points of evidence for this view te: (1) the obese person, when losing weight, burns his fat but maintains nitrogen balance, while the starving person of normal weight loses both protein and fat; (2) respiratory quotients are lower in the obese than in the nonobese (see section on disorders of the use of energy). Newburgh has also been unable to find evidence for abnormalities of fat metabolism which might explain obesity. The adipose tissues of everyone seem to respond in the same way ·ETIOLOGY 43 to the stimulus of an excessive intake of energy by the laying down of predictable amounts of fat. The greater part of the synthesis of neutral fat, which forms the bulk of adipose tissue, takes place in the liver,27, 101 but there is evidence for some formation of fat in the peripheral tissues 385 Block 22 found no difference between obese and nonobese persons in the ease of release of fat from the adipose tissue. A later and more complicated theory of lipophilta than that advanced by von Bergman was devised by Lichtwitz 229 He assumed that there was a decreased permeability of satracellular interphase surfaces which protect lipord portions of the protoplasın Ecom the action of lipase The permeability of these surfaces was thought to be regulated by both nerves and hormones Evidence does not permit us to say that the metabolism of the adipose tissue of the obese is different from that of nomal persons, the doctrine of lipophils must be considered not proved. Progressive lipodystrophy: This is a clinical entity which was first described by Barraquce 183 It is characterized by almost complete loss of the subcutineous tissue of the upper half of the body and a relative or absolute obesity of the lower half The disease usually begins in childhood, occurs tivice as frequently in females as in males and is compatible otherwise with good health. The cause is unknown; some relation to facial hemiatrophy and scleroderma may exist. Simons,357 the first to use the name "lipodystrophy," expressed the belief that the nervous system, in some manner, controls the localized deposstion of fat. This concept is strengthened by the sharp demarcation between areas of total loss of subcutaneous tissue and areas of excessive or normal adipose tissue which is seen in all three conditions, tamely, Ispodystrophy, scleroderma and facial hemiatrophy. Beznik and Haschao reported that section of the splanchnic nerves slows the rate of deposition somewhat and the fate of mobilization of fat quite markedly, so that splanch- ·44 OBESITY nicotomy results in an accumulation of perirenal fat. Sionlar experiments have demonstrated the effect of the autonomic nervous system on the deposition of subcutaneous and peri. cardial fat 30 The importance of autonomic influences on the distribution and amount of fat in persons without neurologic lesions is impossible to state, since the anatomic interruption of nerve fibers is a distinctly abnormal condition and may cause a variety of changes not seen in common obesity. It has been postulated that the hypothalamus controls the de. position of fat at the periphery of the body by means of autonomic nerve fibers, 68 but that the experiments mentioned previously should be considered as offering no more than circumstantial evidence that regulation of the amount of fat in subcutaneous tissue is dependent on innervation is indi. cated by the early report of Strandberg. Strandberg grafted abdominal skin to the dorsum of the hands; when the subject later became obese, the grafted area accumulated a far greater thickness of fat than did the dorsum of the other hand 599 This suggests that considerable control of the deposition of fat exists independently of nerve supply, but it might be interpreted also as evidence that denervation itself might cause increased deposition of fat. As in the splanchnicotomy experiments, the studies in which the hypothalamus was injured and obesity followed are based on destructive lesions; thus, the results do not prove how important ase either peripheral nerves or the hypothalamus in the day-to-day regulation of the weight of the person who does not have a neurologic lesion. The hypothalamic injury experiment finds only occasional counterpast in naturally occurring obesity, and no good examples of localized obesity due to section of peripheral nerves have come to our attention. An endocrine theory which relates hyperthyroidism to lipodystrophy was advanced by Marañon and Soler. *** Zon occurs because of a localized failure to metabolize Tala, ·ETIOLOGY .. 4 spite of a generally increased oxidation. Lawrence 224 teported a case of lipodystrophy in a woman who had a basal metabolic rate of +150 but in whom, after thyroidectomy, myxedema developed while the basal metabolic rate was + 40 Parmelee 297 expressed the belief that infectious or toxic influences might modify diencephalic function and, thereby, might cause lipodystrophy Ziegler 420 discussed a number of hypothetical causes and added race, heredity, alteration of fat metabolism and congenital defect to the list of possible causes He emphasized the endocrine possibilities by finding that in five of his series of seven cases some tendency toward diabetes mellitus was exhibited Heteny: 174 found that oil injected subcutaneously into obese persons is absorbed slowly while that injected into normal persons is absorbed rapidly. He further observed that the wasted parts of a person with lipodystrophy absorb oil at a rate comparable to that in normal persons, while the obese portions of the body absorb oil slowly, as is the case in ordinary obesity. This phenomenon was interpreted as te fiecting an abnormal avidity of the obese person's subcu. taneous tissues for fat Another explanation, which does not resort to postulates of an anomalous metabolism of Tipids, is that the injected oil is exposed to a richer supply of blood vessels in the subcutaneous tissues of a normal person than in the tissues of the obese subject and that the wider absorbing surface facilitates a more rapid diffusion into the blood Zondek 21 has stated that limitation of diet will cause foss of weight of the obese portions of the body in lipodystrophy just as in ordinary obesity. Currier and Davsses reported a case of progressive lipodystrophy which appeared at the menopause, they also gave a good bibliography In summary, progressive lipodystrophy is a poorly understood entity The striking aspect of it is not the obesity of one site but rather the wasting of the subcutaneous tissue of another. Dercum's disease or adiposis dolorosa: This is a poorly ·OBESITY nicotomy results in an accumulation of pesirenal fat. Similar experiments have demonstrated the effect of the autonomic nervous system on the deposition of subcutaneous and pericardial fat.30 The importance of autonomic infuences on the distribution and amount of fat in persons without neurologic lesions is impossible to state, since the anatomic interruption of nerve fibers us a distinctly abnormal condition and may cause a variety of changes not seen in common obesity. I has been postulated that the hypothalamus controls the de position of fat at the periphery of the body by means of autonomic nerve fibers,83 but that the experiments mentioned previously should be considered as offering no more than circumstantial evidence that regulation of the amount of fat in subcutaneous tissue is dependent on innervation is india cated by the early report of Strandberg Strandberg grafted abdominal skin to the dorsum of the hands; when the subject later became obese, the grafted area accumulated a far greater thickness of fat than did the dorsum of the other hand.849 This suggests that considerable control of the de. position of fat exists independentiş of nerve supply, but it might be interpreted also as evidence that denervation itselt might cause increased deposition of fat. As in the splanchnicotomy experiments, the studies in which the hypothalamus was injured and obesity followed are based on destructive lesions; thus, the results do not prove how important are either peripheral serves or the hypothalamus in the day-to-day regulatioa of the weight of the person who does not have a neurologic lesion The hypothalamic injury experiment finds only occasional counterpart in naturally occurring obesity, and no good examples of localized obesity due to section of peripheral nerves have come to our attention, An endocrine theory which selates hyperthyroidisaa to lipodystrophy was advanced by Marañon and Soler.349 Zon " ---tarifin af forlized tatlure to mera WILL Suiw, -- ·ETIOLOGY 45 respite of a generally increased oxidation. Lawrence 224 ported a case of lipodystrophy in a woman who had a basal metabolic cate of + 150 but in whom, after thyroidectomy, myxedema developed while the basal metabolic rate was +- 40 Parmelee 297 expressed the belief that infectious or toxic influences might modify diencephalic function and, thereby, might cause lipodystrophy. Ziegler 620 discussed a number of hypothetical causes and added race, heredity, alteration of fat metabolism and congenital defect to the Itst of possible causes He emphasized the endocrise possabilities by finding that in five of his series of seven cases some tendency toward diabetes mellitus was exhibited Heteny: 174 found that oil injected subcutaneously into obese persons is absorbed slowly while that injected into normal persons is absorbed rapidly. He further observed that the wasted parts of a person with lipodystrophy absorb oil at a rate comparable to that in normal persons, while the obese portions of the body absorb oil slowly, as is the case in ordinary obesity This phenomenon was interpreted as re- Secting an abnormal avidity of the obese person's subcutaneous tissues for fat Another explanation, which does not resort to postulates of an anomalous metabolism of lipids, is that the injected oil is exposed to a richer supply of blood vessels in the subcutaneous tissues of a normal person than in the tissues of the obese subject and that the wider absorbing surface facilitates a more rapid diffusion into the blood Zondek 421 has stated that limitation of diet will cause loss of weight of the obese portions of the body in lipodystrophy just as in ordinary obesity. Curries and Davis 88 seported a case of progressive lipodystrophy which appeared at the menopause, they also gave a good bibliography In summary, progressive lipodystrophy is a poorly understood entity. The striking aspect of it is not the obesity of one site but rather the wasting of the subcutaneous tissue of another. Dercum's disease or ediposis dolorosa: This is a pooriui ·46 OBESITY 87, 08 understood and rarely observed syndrome characterized by tender and painful nodules of fat. The patient is said usually to be an obese woman in the latter middle life who is partly disabled by weakness and by symptoms of psychoneurosis A variety of mechanisms have been suggested for the development of this obesity, most of them endocrinc. 182 There is, however, no good proof that any gland of internal secre tion is at fault. Indeed, it is possible that this disease does not constitute an entity but is the chance occurrence of PSF choneurosis with simple obesity. Lyon 238 considered that all gradations between simple obesity and Dercum's disease occur. In Dercurn's earlier papers, atrophy of the thyroid in one case and eosinophilic adenocarcinoma of the pituitary were reported. He described the fat as occurring in wellencapsulated masses and nodules, Waldorp, 888 on the other hand, expressed the belief that the condition is diencephalic in origin but based much of his opinion on the distribution of the fat, which he considered "hypophyseal." Winkel. man 408 found an adenomatous hyperplasia of one adrenal gland, an adenoma of the anterior part of the pituitary and hemorrhages in the subthalamic region. He advocated a theory that the cause of the condition is a pluriglandular disturbance. In summary, Dercum's disease has not been established as an eatity and nothing of certainty is known of any cause or pathologic physiology. DISORDERS IN THE USE OF ENERGY Some have stated that a person can live on 100 calories per day and remain obese.es In well-controlled studies, however, it has been shown that obese persons must cat more than the average person in order to remain obese, 2s, 284, 285, 287, 290 yet each of these pessons will usually deny that he is a hearty cater. 211, 268, 262, 547 Strang and his co-workers 874 measured the caloric in- ·ETIOLOGY 47 at obese patients who ate as they said they ate he average intake was 2,570 calories per day this generous dret, the loss of weight was 0.5 : kg.) per day. Obese patients usually insist that y little but when really adequate control has been r dietary intake, such as is done with the patient loc ward, loss and gain in weight have proceeded calculation ound that relatives could frequently list the 21ch obese children ate and which caused their intake to exceed normal or, when his confidence the obese child himself might admit the true diet. Bruch observed that most mothers of ren were very reluctant to admit that they ate the average amount Lauter 221 noted that obese en those whose obesity was classified as "enorigin, consumed very large quantities of food mund that fifty obese persons ate 2,900 to 3,500 ly and still complained of hunger spressed the belief that all obese persons will be • heavy eaters despite their denial $47 Evans, 282 ig a paper by Newburgh, reported finding the ve obese women to range up to 4,500 calories per ch said she was a "small eater." Some capable lieve, however, that the person with a predisobesity will become stout if he eats as generously on with a tendency toward leanness who, in con. yvereat with impunity.58, 158, 872 as stated that the food requirement is subject to ridual variation and terms this factor the "indiabolic habıt" "This, he indicated, explains why and some lose on the same diet 42 Presumably blic habet depends on variability of activity, effinotions, basal metabolism and other less obvious but not on the well-studied factor of surface e can be no argument but that some such indi- ·48 OBESITY vidual variation does occur; most of the disagreement concerns whether such differences are large enough to be of importance. It is the authors' opinion that these variations are not so large but that loss of weight can be predicted with fair accuracy if the observer is given the surface area, age, sex, occupation of the patient and the caloric value of the reduction diet. Excessive gastro-intestinal absorption A common but erroneous theory of obesity is that the fat person absorbs a greater proportion of the food that he eats than does the average person. This has been effectively disproved by investigations which showed that obese and normal persons absorb the same proportion of calories, nitrogen and fat from their diets.281, 410 "Static" obesity Inactivity, such as that imposed by illness, immobilization by casts and "just plain lazıness," has been blamed for obesity.166, 287, 288 This "static" obesity is, of course, presumed to arise from a diminution in the output of energy. If the mechanism which regulates appetite were functioning normally, however, the intake of energy should diminish proportionately and the weight should remain normal. Thus, in order to explain this variety of obesity we are forced to return to psychologic, hereditary and other factors which might affect the appetite mechanism. The events (accidents, injuries and so forth) causing the inactivity may cause psychologic conflicts which, in turn, result in a normal or increased intake of food while the output of energy is diminished. Increased efficiency in doing work This has been postulated as a cause of obesity. It cannot be denied that there are variations in the amount of useless activity indulged in by different people. Some persons are ·ETIOLOGY 49 slow and careful, doing their work with a minimum of waste motion, while others accomplish the same work with considerable unnecessary motion. However, it has been convincingly demonstrated that the obese person has actually a decreased mechanical efficiency and expends extra energy to do the same work,285, 391, 322 It is as though the extra weight of the masses of fat required just that much additional work for it to be moved about during exertion Respiratory quotient and its vagaries These have been intensely studied for clues to the cause of obesity The respiratory quotient is determined by dividing the intake of oxygen into the output of carbon dioxide If the subject is existing on carbohydrate alone, his respiratory quotient will be 10; if on protein alone, it will be 0 80; if on fat alone, it will approach 0 71. If carbohydrate is converted to fat, the quotient becomes greater than 1.0.801 However, a similar rise in the respiratory quotient to more than unity is produced by the formation of lactic or other acids the process of metabolism. For instance, lactic acid 15 formed from the fructose fraction of sucrose so that after the ingestion of table sugar, the lactic acid so formed will relcase carbon dioxide from the blood so that the respiratory quotient will rise to more than 10.75 Hagedora 105 found that the postabsorptive respiratory quotient was lower in the obese than in the normal person on a carbohydrate diet and suggested that there was a qualitative anomaly in metabolism in the obese and in the potentially obese, characterized by an increased transformation of carbohydrate into fat. He found this lowering of the respiratory quotient to be proportional to the degree of overweight. Bowen and his co-workers 89 also discovered that the fasting respiratory quotient was low in the obese, but he found quotients determined after a meal of fat to be the same in normal as in the obese subjects. He also found that the specific dynamic action after the ingestion ·SO OBESITY of fat was the same in the obese as it was in normal persons. Lyon found that the respiratory quotient is low in the obese patient who is undergoing reduction of weight 235 but noted several factors, such as the carbohydrate content of the diet, which affected determination of the respiratory quotient. His findings, which parallel those of Strang, indocate that fat is being consumed at a more rapid rate in obese than in normal subjects. Krantz and Means 213 found that the respiratory quotient rises less in obese than in normal persons after injection of epinephrine and concluded that in obese persons fat is consumed preferentially to carbohydrate after injection of epinephrine. Brooks and Bridge ** found that the respiratory quotient is elevated during the dynamic phase, that is, during that period in which weight is increasing, thus indicating the deposition of fat, but that the respiratory quotient returns nearly to normal during the static or stable phase. It should be pointed out that determinations of the respiratory quotient are subject to considerable error and that interpretations should be made with caution. Few workers in this field have considered the rather large moment-tomoment variation in the respiratory quotient *01 and the sig nificant effects of acid metabolic products 75 When these variations are controlled, Tepperman, Brobeck and Longs have stated, the finding of a respiratory quotient greater than unity means the formation of an oxygen-poor substance from one rich in oxygen Such a respiratory quotient was found by them in rats made obese by hypothalamic lesions, but it could not be said that this finding is significant of anything more than the abnormally ravenous manner in which these rats eat and their rapid deposition of fat. In summary, it can be said that respiratory quotients exhibited by the fasting obese person tend to be somewhat lower than those of persons of normal weight, but there is no evidence that this is related to the cause of obesity. The increased caloric requirement of the obese person may tend to ·ETIOLOGY 51 exhaust carbohydrate stores more quickly and thereby cause the combustion of fat and a low respiratory quotient. There is the additional possibility that carbohydrate stores may be reduced by fatty infiltration of the liver in obesity. Reduced specific dynamic action This has been suggested as a cause of obesity 143, 253, 373, 387, 882, 393 The specific dynamic action is the increase in metabolism which follows the oral or parenteral administration of foods If this phenomenon were diminished, the resultant economy in loss of energy would account for a tendency to become obese The measurement of this exchange of energy is difficult, and the manner in which the exchange is expressed may alter the interpretation. If the rate of exchange is expressed as per cent of increase in basal heat production, the specific dynamic action is duninished in the obese and is raised to more than formal in the thin. However, the absolute increase in output of heat has been shown to be the same for meals of the same size and composition in persons of all weights 870 This work by Strang and McClugage conclusively rules out a diminished specific dynamic action as an explanation of obesity and shows how previous workers may have misinterpreted their findings to support such a hypothesis It has been suggested that eating all of the day's food in one meal may diminish the specific dynamic action enough to effect an appreciable economy in loss of energy.378 Lauter 221 has said that the specific dynamic action is so variable that it is of little or no significance unless it can be proved to be absent. An excellent review of specific dynamic action which was prepared by Wilhelm; “14 should be studied by anyone interested in this field Goldzieher 149 stated he had demonstrated that deficiency of secretions of the anterior pituitary lobe abolishes or diminishes the specific dynamic action and thereby causes obesity in cases of hypopituitarism DuBois 108, 109 stated that an absence of specific ·52 OBESITY dynamic action would account for a saving of only 6 percent in energy and such a saving would be trivial compared to the saving which might result from variations in activity, In summary, it can be said that there is no good evidence that changes in the specific dynamic action are related to the cause of obesity. Negative phase of metabolism This was postulated by Bernhardt 28 and is closely allied to the problem of specific dynamic action. Bernhardt stated that he had demonstrated a "rebound" of metabolism in which the metabolic rate is less than the basal rate after the rise characteristic of the specific dynamic action. He endicated that the obese person would, like the normal, have a rise in the rate of metabolism after a meal (the specięc dynamic action). Unlike the normal, the obese person would then undergo a fall in metabolic activity to a rate which is less than the basal rate This negative phase was thought to follow exercise also This saving in energy would then account for the obesity Wildes 11 then proved rather conclusively that this phenomenon did not occur and that Bern. hardt's findings could be explained by his failure to measure basal rates accurately Others24, 193 also have failed to dem. onstrate this negative phase. Theory of "Luxus Konsumption" 152, 153 Grafe expressed the belief that there is a mechanism in the normal person which causes an increase in metabolism after the ingestion of excess food; this increase continues until the excess of food is consumed. In this manner, the weight of the normal person would remain constant in spite of excessive intake The constitutionally obese person, howeves, was thought to have no such mechanism of "Luxus Konsumption" and, therefore, had no means of disposing of excess food.152 Lusk 222 stated that it is the condition of and denot a large influx of food the previous ·ETIOLOGY 53 termines the basal metabolic rate Morgulis 272 associated the increase in basal metabolic rate from subnormal values, that occurs when an undernourished person is given an adequate diet, with the nitrogen retention Keys, 210 in his studies on conscientious objectors, found that the undernourished subjects had strikingly low basal me. tabolic rates These rates gradually returned toward normal as the subjects approached their normal weight However, when these men were allowed to eat as they desired, they consumed enormous quantities of food and in some the basal metabolic rates became elevated considerably above normal The interpretation of these elevated rates is not immediately apparent, however; they may result simply from the specific dynamic action of the protein consumed, or perhaps from some degree of cardiac fatlure that may occur with the gorging of an undernourished individual Because they are observed in undernourished subjects these rates cannot be taken as proof of the doctrine of "Luxus Konsumption Gulick 183 stated the belief that there are thin persons who are difficult to fatten apparently because of an extravagant caloric expenditure, but found no increase in the basal metabolic rate from overfeeding. Wiley and Newburgh 418 found no evidence that either the total or the basal metab. olism was increased by superalimentation in a thin person Johnston and Maroney,193 in a careful study on children, demonstrated an increase in the basal metabolic rate with overfeeding which was shown to be dependent upon the increased protein intake rather than upon the increased caloric intake Rony 523 concluded that "caloric overfeeding does not cause an increase in basal metabolism unless it includes protein overfeeding." Ketosis This has been suspected of being a clue to the nature of obesity A greater amount of ketosis observed during the fasting of obese individuals has been thought to be related ta the cause of obesity.148, 243 Wilder has expressed the be.

·54 OBESITY lief that the phenomenon of increased ketosis may be explained by the assumption that the fat in the obese is mobilszed abnormally easily or in greater quantity than in a normal person.408 Evans and Strang 126 found that all their patients who were undergoing reduction in weight had ketonuria. MacKay and Sherrill 243 found a higher degree of ketosis in the fasting obese than in normal persons but also noted some instances of overweight in persons who exhibited no ketosis during fasting These instances of overweight they considered to be caused by deficiency of the ketogenic hormone of the anterior lobe of the pituitary, with the consequence that the fat was "locked" into storage spaces ®42, 243 Folin and Denis 184 treated patients by alternating periods of starvation with periods of free choice of diet in the expectation of reduction of ketosis. They found no difference between the amount of ketogenesis in the obese and the amount in normal persons 134 On the other hand, other workers 119 have maintained that there is no ketosis during fasting in obesity DuBors has expressed the belief that fat people have an unusual resistance to the development of ketosis It has not been proved that ketogenesis in one person is quantitatively or qualitatively different from that in another if such variables as total calories, proportions of carbohydrate and fat, time of observation, exercise and degree of obesity are controlled. On the basis of such conflicting evidence as we have at hand, it is impossible to consider any of these variations in ketogenesis as proof of a metabolic error responsible for obesity Energy changes The energy changes involved in the constant tearing down and building up of tissues have been accused of hiding economies in loss of energy that might explain obesity.149 Goldzieher has expressed the belief that such energy changes are beyond our means of measuring and, therefore, that all studies of energy balance are fruitless in the study of obesity This objection is easily answered by the thermodynamic ap ·ETIOLOGY proach. The formation of a large molecule from sr parts requires the same amount of energy as is release the breakdown of that molecule into those same sm parts It is contrary to all thermodynamic concepts f chemical reaction to yield more energy when going in direction than the energy absorbed when proceeding in opposite There is no reason to expect the body to vior these extensively studied and extremely well-control thermodynamic concepts The only possible loophole here that the protoplasm of the body might have a higher contes of energy at one time than a few weeks later even thougthe protoplasm remained constant in mass This concept 15 highly unlikely, since it implies a fundamental change in the nature of the protoplasm from one period of observation to the next It would also account for the loss of but relatively small and definitely limited quantities of energy No one, to our knowledge, has detected such losses in any studies of caergy balance Disorder of enzymatic activity A disorder of the enzyme system which causes oxidation of carbohydrate has been postulated According to this concept, the carbohydrate which cannot be oxidized normally is thought to be converted to fat 146 No convincing evidence has been offered in support of this theory, however In Grerke's syndrome, obesity may develop. In this disorder there are hepatomegaly, hypoglycemia and increased stores of glycogen in many tissues of the body The syndrome is seen in the first year of life. It is thought to be caused by a failure of the enzyme system which normally allows glycogenolysis to proceed The mechanism for the production of the obesity is not apparent, however.323 RETENTION OF WATER Since water constitutes the greater part of the mass of the body,140 variations in the amount of water retained are considered by some to be a major cause of obesity in - ·56 OBESITY cases. 149, 826 Because of this conception, many physicians have used diuretics of various sorts to dispose of the presumed excess of water.158 Newburgh has demonstrated, by accurate measurements, the fluctuations in weight that may occur with variations in the store of water.285, 290 The lag in loss of weight that frequently is observed after initiation of dietary therapy is usually caused by a temporary accumulation of water and its associated electrolytes. This water is usually excreted within a week without necessity for use of diuretics, so that loss of weight continues according to calculation. It is well known that the loss of several pounds may occur in a normal person who is given acidifying diuretics.251 Although Hawirko and Sprague found that the diuresis which occurred in response to administration of mersalyl (salyrgan) was much greater in the very obese subject than in the normal person, 170 a good response to treatment with druretics cannot be taken as evidence that the obesity in a certain case is caused primarily by retention of water. It is obvious that impaired cardiac function occurring as a result of the obesity may lead to considerable increase in extracellular fluid. The retention of water and corresponding gain of weight that precedes cach menstrual period in many women appears to be caused by a rise in the level of estrogens at that time. Since estrogens like desoxycorticosterone acetate appear to cause retention of water, an "endocrine" form of obesity in which the increase in weight is due to retention of svater has been postulated The retention of water in myxedema is well relieved by administration of thyroid extract; 802 for this reason thyroid extract has been used with questionable success as a diuretic in obese persons with normal metabolism The influence of the posterior lobe of the hypophysis and of the adrenal cortex on water balance suggests to some investigators that obesity may arise as a result of the increased function of those glands 119 But in spite of all these at- ·ETIOLOGY 57 tempts to relate dysfunction of the thyroid, pituitary, adrenal cortex and ovary to obesity by way of their effect on water balance, no one has proved that more than ten to fifteen pounds (45 to 68 kg.) of excess fluid may be present without pitting edema. This attempt to link hormones with obesity by way of water balance fails because no one has demonstrated that obesity can result primarily from retention of water In all commonly seen examples of water retention, such as occurs in nephritis, cardiac failure and intoxication from desoxycorticosterone acetate, pitting edema gives early evidence of the excess water and no obesity occurs Goldzieher expressed the belief that the water accumu. lated in obesity is intracellular, 149 but gave no proof. It is conceivable that an increase in the content of intracellular water might cause no edema, while a similar increase in extracellular fluid might do so, but no one to our knowledge has given adequate proof that there exists such a syndrome of increased volume of intracellular fluid as a cause of obesity.

·Chapier IV CONTRAINDICATIONS TO REDUCTION С ONTRAINDICATIONS to reduction are extreracly rare and possibly may not exist, but situations which demand caution and a slowes sale of reduction are not infrequently met. Active of recently active tuberculosis is frequentiy cited as an absolute contraindication to reduction. This prob lem is not met frequently, since most such patients are not well nourished. There is convincing evidence that the malnutrition which accompanies war will increase the incidence of tuberculosis 318 but the thesis that properly supervised teduction of excess weight to normal will possibly activate a latent tuberculosis has not been proved. There is little data available concerning obesity in tuberculosis, but one opinion ss that tuberculosis develops in fetver obese persons than in those of normal weight; however, once the infection is pres. ent, its course in the obese is no differeat from that in the person of normal weight. 318 Overfeeding as therapy for tuberculosis has been advised against.237 The importance of a genecous supply of carbohydrate and protein in the treatment of Circhosis has been emphasized. 85, 193 The obese person subsisting on a 600 calorie diet is actually metabolizing a mixture which is composed principally of fat (derived chiefly from his own body) and which contains relatively small amounts of protein and carbo. hydrate (derived entirely from the diet). It is reasonable to assume, therefore, that rigorous dieting would have an adverse effect on the cirrhotic process and that if reduction of weight becomes usgent in such cases it should be accomplished slowly. Actually this problems arises only occasion- (38) ·CONTRAINDICATIONS. TO REDUCTION 59 . ally, since many patients with cirrhosis have lost weight as a result of their disease An active duodenal or gastric ulcer is a contraindication to any considerable restriction of diet In such cases the program should provide for only a slow loss of weight and for the inclusion of foods in the diet which are appropriate to therapy of ulcer. Antacids would play a major part in such a program. A diet low in pusines and adequate in protein is difficult to devise unless it contains 1,500 calories or more. For this reason, reduction should proceed slosiy in patients with gaut. Since chronic ulcerative colitis usually causes considerable cmaciation, it is usually wise to keep such patients somewhat Overweight, if possible Addison's disease is a reason for slow reduction since compensatory mechanisms of many sorts, including the process of gluconeogenesis, are impaired and a too rigorously Ismited diet msght precipitate hypoglycemia or even an addısontan crisis Obesity in Addison's disease, as in tuberculosis, is unusual, however. "The presence of an inoperable malignant tumor or lymphoblastoma in which cachexia is likely to develop should make one less concerned about lesser grades of obesity and better satisfied with the slower rates of loss which may be obtained by simple warnings that the intake of food be liouted somewhat when the patient is exceedingly obese Age is no has to reduction of weight. It has been stated that children and old people bear reduction of weight poorly,494 but we have been unable to find any basis for this belief. It is particularly necessary to supply growing chil. dren and pregnant women with all essential food ciements, but properly designed reduction diets accomplish this. Evans 135 has pointed out that obesity in children is frequently complicated by emotional difficulties, sometimes ·OBESITY termed "behavior problems;" too great a restriction of food may precipitate further disciplinary crises in such circumstances and as a consequence, Evans has expressed the belief that the pediatrician may have to evaluate the emotional situation carefully before subjecting a child to a rigorous dietary program In elderly persons whose life expectancy is not great and whose ability to learn a strict diet is limited, one may again have to be satisfied with simpler and less effective programs, but the benefits of reduction of weight in the elderly obese are great and the physician's efforts frequently will be well rewarded by a considerable improvement in the health of these persons. Coronary artery disease and hypertension are sometimes given as contraindications to reduction, but rather they should be considered as urgent reasons for the procedure There is no reason to expect cardiac catastrophes to follow reduction in persons with coronary artery disease. The danger that acidosis might result from starvation ketogenesis was mentioned in earlier studies,19, 132, 208 but such has not been demonstrated to be of significance in properly devised programs of reduction, Once reduction is well under way, it is necessary to de cide how far the procedure should be carried. Should we attempt to tailor the patient exactly to the weight given in standard height-weight tables? This is a decision which must be made by the physician in each individual case; he may justifiably halt the program fifteen to tiventy pounds (68 to 9.1 kg.) short of the goal if the ends have been achieved, or, in some instances, he may find it wise to reduce the weight below that given by the standard tables as ideal for the patient. The latter situation may arise in the treatment of cardiac decompensation or coronary artery disease in which undernutrition may reduce the work of the heart 33 to 49 per cent and thus may diminish or abolish symp toms which might otherwise be manifest. 255, 257 ·Chapler V DIETS FOR OBESITY . ALICE KARSLAKE IRMISCH THILE there is much disagreement about other thera- W peutic measures, nearly every worker m this field agrees that restriction of food is the most important factor in the reduction of weight There is now rather general agreement that the diet should contain an adequate supply of proteini, a minunum of fat, enough carbohydrate to prevent wasting of protein and an adequate supply of vitamins and minerals The first recorded diet for obesity in the literature is that of William Banting of London in 1863 William Harvey restricted the carbohydrate and fat intake of this patient which resulted in a loss of forty-six pounds (209 kg). In 1915, Folin and Denis 154 recommended five days of starvation, repeated at intervals, as a safe and harmless treatment of obesity Evans and his co-workers have published what is probably the most thorough discussion of diets for obesity, In 1929 they 120 reported the use of a 600 to 700 calorie diet on ninety-eight patients The average loss of weight was teventy-six pounds (11.8 kg.). They predicted the amount of loss by calculating the caloric requirement (present weight, in kilograms, multiplied by 30 calories per kilogram) and subtracting the caloric intake, the result of which gave the caloric deficit; this result was divided by 9 to obtain the value for grams of lost, this value was increased by 14 per cent to obtain the value for grams of fatty tissue lost per day In 1930 Strang, MicClugage and Evans 379 gave diets even lower in calories They used only lean protein foods, with (61) ·62 OBESITY either 100 gm. of milk or orange juice containing 50 cc. of yeast. This diet provided, on the average, 58 gm of protein and only 360 calories. The thirteen patients treated showed an average loss in weight of 0.6 pounds (0.3 kg.) per day for fifty-nine days. All were benefited clinically, with no evidence of acidosis This is the first mention of the addition of vitamin preparations to low calorie diets. In 1931 the same authors 871 added viosterol as well as yeast A 335 calorie diet 127 given to 187 obese patients resulted in an average loss of thirty pounds (136 kg.) in eight or nine weeks Although a loss of nitrogen averaging 2 gm per was encountered, the fact that the creatinine coefficient underwent little change was thought to indicate that fat, mainly, rather than protein, was lost.238 The patients found the almost exclusively protein diet impalatable after a few weeks, so that 20 gm. of carbohydrate were added in the form of fruits and vegetables. The diet was much more palatable and only 01 gm. of nitrogen was lost per day, which is negligible. Keeton and Dickson 201 followed the 240 230 230 220H Pounds 210 200 1904 201 2 3 < Weeks Figure 3. Example of case given in Table VII 7 ·DIETS FOR OBESITY 63 nitrogen balance of obese patients on low calorie diets (1,024 to 1,600 calories) with a protein content varying from 13.5 to 90 gm. Even on the low protein intake, the loss of nitrogen was small. It was found that nitrogen balance could be maintained, 10 the reduction of an obese person, so long as I gm. of protein per kilogram of ideal body weight was supplied daily, although early in the reducing program there tended to be a negative balance, perhaps because of the consumption of protein for its antiketogenic properties. 071 Brown, Herman and Onison 59 found that when obese women of college age subsisted on reduction diets of 1,000 to 1,200 calories, they remained in approximate nitrogen, calcium and phosphorus equilibrium. These authors were concerned that appreciable positive balances of these min. erals were not observed, thus implying that reduction drets might past the health of persons of college age It would seem, however, that this group would have attained the major portion of their growth, and easily measurable positive balances of nitrogen, calcium and phosphorus should not occur. The greater the initial weight, the less the rate of nitrogen loss on a deficient diet 332 Grafe 152 expressed the thought that the American low calorie diets were too rigorous for Europeans. He considered a 984 calorie dict to be minimal. As in many other instances, his diets do not include milk A 500 calorie diet similar to those used by Evans and co-workers was given to obese patients by Wilder *08 with success Wilder has developed a formula «for predicting the loss of weight on a given caloric leve! The derivation of his method, its practical application and examples of its use may be found in Tables VII through XI and Figs 3 through 9 A chart of the predicted loss in weight is advantageous both to the patient and to the doctor, It is a guide to indicate how much weight the patient may be expected to lose every week on a given caloric intake If the actual loss approximates the predicted one, the patient is encouraged if he does not lose as ex- ·64 OBESITY 230 226 220 210 Pounds 200 190 190 1605 1 2 3 7 8 4 5 Weeks Figure 4 Calculation of predicted weight loss for a fifty-three year old man, 67 25 inches in height, weighing 226 pounds basal calories for 195 pounds, 1,740; basal calories plus 50 per cent, 2,610; caloric intake, 620, caloric deficit, 1,990; predicted average weight loss per week, 40 pounds, or 36 pounds for the nine week period. The actual loss was 33 pounds in nine wecks, the final weight being 193 pounds. (The solid line represents the predicted weight loss, the broken line, the actual weight loss ) pected, the physician is more careful to inquire as to the patient's intake of food so as to determine whether or not there is any discrepancy or variation. Perhaps the weight is due to a retention of water which will disappear after another week or two on the same regimen. Patients who carefully adhere to a low calorie diet in detail inevitably lose weight Figures 4 to 9 inclusive demonstrate the response of a number of patients to dietary therapy. The solid lines indicate the weight loss that was predicted for the patient at the beginning of each nine week period of therapy. In practice, we give the patient a graph similar to these with the line of the predicted weight loss drawn in place The patient then charts his actual weight at intervals of two to seven day's ·DIETS FOR OBESITY - Near the end of the nine veek period the patient is give. a second graph which shows the predicted rate of weigh. loss for the next period. As many as four or five graphs for succeeding nine week periods may be computed for the very obese patient. There are two reasons for recalculating the predicted rate of weight loss periodically rather than for the entire course of reduction at the initiation of therapy First, the rate of weight loss is rapid in the earlier weeks and becomes gradually slower as the patient's surface area becomes less This phenomenon is demonstrated in Figures 7, 8 and 9, where the predicted rate of weight loss becomes less with each succeding period Second, the use of the actual rather than predicted weight at the beginning of each nine veek period prevents a cumulative deviation from the predicted line (Fig 7) An amazıngly close correlation of predicted and actual weight loss is shown in Figure 8. It seems reasonable that the patient who discovers that he is a few pounds "ahead of schedule" may exceed his diet slightly, and the patient who is not losing quite as rapidly as predicted will adhere to his diet with increased determination, thus tailoring his actual weight loss to fit the predicted one It is our belief that such graphs of predicted weight loss are a real factor in helping the patient adhere to his dietary program and should be included in reduction programs which utilize the 620 calorie diet Anderson developed a formula somewhat similar to that of Wilder's, and with it demonstrated a close relation between weight loss and caloric deficit He found diets high in fat to cause weight loss at rates equal to those produced by high carbohydrate diets of the caloric deficit were kept constant. Mulier and Topper 275 in 1934, reported on the treatment of obesity in a group of ts enty-five children, many of whom had a basal metabolic rate which was somewhat greater than ·.. 66 OBESITY TABLE VII METHOD OP PREDICTING WEIGHT Loss 1. Determine the basal energy requirement using the Boothby and Berkson Food Nomogram (Fig. 10). The ideal or normal weight is used for the calculation unless the patient is more than 50 pounds (22.7 kg ) overweight. When actual weight exceeds the standard weight by 50 noinde the enemy par 1.1.3 -L. hgure represents the total calorie requirement. 2 The difference between the calorie requirement and the calorie in take is termed the "calorie deficit." This figure multplied by the factor .002* will give the loss of weight per week in pounds 3. A graph can be constructed by plotting the curve of predicted weight loss from day to day (Fig. 3). Example: The calculation for a woman who is thirty-six years old, whose height : 63 inches (160 cm), whose weight : 233. pounds 1000 • The factor 002 is obtained as follows D (calone defat) divided by 9 3 gives the grams of fat lost per day The grams of fat lost per day multiplied by the factor 100 gives the grams of weight lost per day, where 86 fat tissue contains 14 per cent of water Grams of weight lost per day multe plied by 7 gives the grams of weight lost per week. The grams of weight lost per week multiplied by the factor22 gives the pounds lost per week. Thus, the pounds fost per week = D X 100 X 7 X 22 =DX 000193, 93 86 1000 or approximately D x .002. normal. The intake of calories was reduced and the form of protein eaten was chiefly that of meat, fish, cheese and eggs A limited amount of milk was allowed the younger children Fluids were restricted to 500 to 600 cc. and salt to 0 3 go daily. Restriction of fluids and salt is common in many dietary programs for obesity,"? but is ordinarily unnecessary and undesirable. Doubtless some patients fail to lose weight ·DIETS FOR OBESITY TABLE VIII HEIGHT-WEIGHT-AGE TABLE (Boys) 67 Height inches fytyrsys yrs yrs.fyrsyrsys yrs yrs yrs yrs yrs yrs yrs والدراما واما ܟܐܫܬ + NNN 7500 Qo 88988 OO 8 122 123 128 NN 134 134 133 138 139 143 147 152 132 139 143 143 14:45 150 151 153 155 153 1601 1621 120 163 an CO2 Age is taken to the last boribdimore the outdoor clothing, shoes and • When taking measurements, From Wilder, R. M A primer for disbetic patients. El. 7, Philadelphia, W 8 Saunders Corepany, 1941 ·68 OBESITY consistently because of water retention, but this is a temporary condition, and continuance on the low calorie diet will eventually produce the predicted loss of weight. 2441 275 265 Pounds 255 245 241 - 235, 1 2 3 6 8 S Weeks Figure 5. Calculation of predicted weight loss for a forty-one year old man, 675 inches in height, weighing 284 pounds: basa! calories for 254 pounds, 2,020; basal calories plus 50 per cento 3,030, caloric intake, 620, caloric deficit, 2,410; predicted average weight loss per week, 48 pounds, or 32 6 pounds for seven weeks The actual loss was 38 pounds in seven wecks, the final weight being 246 pounds (The solid line represents the predicted weight loss, the broken line, the actual weight loss ) In 1938 McCullagh 240 reported the use of an 800 calorie diet for patients with obesity. For the first time, the importance of adequate intake of minerals, as well as of protein and vitamins, was stressed He stated that it might be advisable to prescribe calcium gluconate tablets, as well as yeast and vitamins A and D, and to include in the diet not only lean meat, cottage cheese and one egs but also tovo glasses of milk. Most other reduction diets include only one glass of milk, or even less, although Kemper,208 in 1940, gave two teaspoonfuls of dibasic calcium phosphate to his ·DIETS FOR OBESITY 69 TABLE IX HEIGHT-WEICHITAGE TABLE (GIRLS) * Heights 6 7 8 9 10 | 11 | 12 13 14 15 | 16 17 18 inches yrs (yrs, yrs. fyrs. yrsts. yrs. . Ts. yrs yrs. Tsyr yrs. 38 33 33 39 34 34 40 36 36 36 42 43 39 39 39 41 42 42 42 42 46 47 48 49 45 45 45 45 47 47 47 | 48 | 48 49 50 50 5050 52 S2 52 St 54 55 55 56 53 50 56 52 651 68 71 73 74 75 77 781 78 79 811 83 82 82 84 88 92 86 86 88 93 96 101 87 90 90 92 95 100 103 104 94 95 95 97 105 to 108 109 !!! 1001 1011 105) 108) 113 116 104 105 106 109) 113 218 110 110 112 116 120 114 115 117 119 122) 123 118) 120 121 122 123 123) 126 124 124 125 129 130 128 130 131 133 133 135 131 133 135 136 138 138 135 137 138 140 142 70 136 138 1401 142 144 71 138 140 142) 144 145 Wbco taking measurergents, rerpose the outdoor clothing, shocs coal Age is taken to the last burthday + From Wilder, R. M Armet for dubetic patients El 7, Puladelphs, W. B, Saunders Company, 1941 ·70 TABLE X AVERAGE HEIGHT-WEIGHT-AGB TABLE (MEN) * | Graded average weight in Age Na جا کا ou NON aan A km2%%% 117 1 in 2 in 3 in 4 in. 5 in. 6 in 7 in. 9 in. 101 107 109 112 109 111 114 115 128 122 126 144 149 154 159 164 113 115 146 151 156 161 166 11 118 121 148 153 158 163 168 123 126 134 150 155 119 122 149 153 159 161 166 171 176 181 186 118 120 126 130 134 138 141 145 150 151 152 162 167 172 177 182 187 139 142 146 151 15158 163 168 173 178 183 125 128 132 149 142 147 148 159 121128 185 156 160 187 192 124 126 129 133 130 134 138 142 146 to 1152 157 162 167 173 179 189 194 138 142 186 391 196 139 143 197 198 199 OBESITY 188 IKI 1 184 189 1997 ·TABLE X-Continued 64 LI 5%打的如行什 14 ONNN 131 133 139 12 161 169 177 178 184 ?? 154 162 167 173 85 192 132 134 11 14811151 137 173 85 192 140 44 118 168 174 145 1191153 168 163 168 174 180 186 193 133 135 138 141 1491 158 164 169 175 187 1801121 13 1 164 169 175 181 8/ 21.7 1998 50 46 79 165 176 188 133 135 137 140 143 15 160 165 170 176 182 188 105140143 17 1 161 166 171 177 183 189 190 16 134 136 138 141 14 148 139 110 181 166 171 177 183 197 134136 138 141 141 118 51 1156 161 166171 177 183 134 136 1380 1.** 10 15 156 161 166 171 177 19 134 136 138 141 144 70 166 | 171 1371 138 141414 119 153 157 167 167 172 137 1111111 110 111 115 1162167 172 123 Ut 149 133 ) 157 162 167 172 17 135 112 40153 158 163 168 78 184 10 112 168 173 55 and up! 135 13 49 153 158 178 | 184 139 1 142 145 • When taking measurements, remove the outdoor clothing, shoes and coat Age is taken to the . + From Wilder, RMA primer for diabetic patients EA 7, Philadelphia, WB Saunders Cor. DIETS FOR OBESITY 061 06 06 24 97 so ch od 24 >! 71 ·72 TABLE XI AVERAGE HEIGHT-WCIGHT~AGE TABLE (WOMEN) *7 Graded average weight ខ្ញុំ s t. =u. ។ N s 10 | 107 ៖ ត K ou S 5 109 | 112 | 115 118 14 ។ 001 n 10 II ១២ **** WN ។ ==== 911 Piizii 011 801 1j } 120 6 a រ 16 117 > 36. 37. 118 9 43 } 47 ពីរ OBESITY ia7 49 9 S 1 138 138 } 142 15 OZI 13 | 13s W! oc ST 8. 143 } 147 891 isi 151 ។ === #s 49 49 === v AA I AM A. 4- W === ·- Joan NO TABLE XI - Continued 118 19 20 124 10 124 122 14 124 121 17 135 139 143 129 132 17 130 133 133 142 في ليا طه -- : 3 151 155 15 221 148 149 150 160 152 153 153 157 158 124 126 167 119 ist 40 140 48 10 155 159 162 162 10 57 139 145 142 146 149 153 25 34 451 SSD 40 * 97 147 27 13 27 27 158 159 163 1120 10% 19 133 152 156 52 135 135 SZ 19 131 31 31 DIETS FOR OBESITY ce ce 148 152 11 12 135 35 91 44 33 13 162 152 S2 53 74 28 100 156 167 4 40 162 163 163 os 70 71 10 29 131 41 148 152 129 57 129 148 129 14 48 129 67 29 131 33 135 • When taking measurements, remove the outdoor clothing, shoes and coat Age is taken to the last birthday. + From Wilder, R M A primer for diabetic patients Ed , Philadelphia, W. B Saunders Company, 1941 73 ·TABLE XII LOW CALORIE DIETS 600 caloric 1,000 Special calorie 1,200 calorie Recommended 1,500 allowances, calorie normal range Women Men gm. 300 400 400 Vegetable 3% Vegetable 20% Fruit 5% gm 100 gm. 200 Fruit 10% Rm. 100 300 300 200 Fruit 25% Sm. 100 Bread &m. 10 60 40 60 Cream 20% Rm. 30 30 30 480 960 480 1 1 1 150 150 Milk, skimmed 8m. 400 Milk, whole fm Eggs, each em. Meat, very lean gm. 150 Meat, lean &m. Butter sm. Approximate composition: Carbohydrate gm. 53 Protein 8m 60 150 15 15 100 115 135 70 85 75 60 70 Fat sm 15 40 45 75 Calories 620 1,030 1,180 1,510 12,500 3,000 עCaJc 660 mg. 870 1,420 880 800 800 Iron mg 0 9 11 12 12 Vitamin A I.U. 2,400 6,200 6,000 7,300 5,000 5,000 16 12) is mg 1.3 16 Thiaminc Riboflavin Niacin 20 mg. 1.7 26 16! 18 13 mg. 10 12 13 Ascorbic acid 118 120 160 160 170 70 * Recommended dietary allow'antes, National Research Council, Reprint and Circular Series, No. 122, August, 1945.** ·DIETS FOR OBESITY probably has little effect on the satiety value If the patient becomes constipated, bulk may be added by medication. Bran is no longer in common use because of its tendency to irritate the large bowel Mineral oil, whether used as a laxative or as an ingredient in cooking, is also in disfavor because of the increased excretion of the fat-soluble vitamins following its use. Once the patient attains the desired weight, attention to the diet must not be abandoned, since unrestricted feeding will often cause the weight to return to its original figure. 111 Therefore, a moderately restricted diet, usually measured rather than weighed, of 1,500 to 1,800 calories should be prescribed Patients will usually cat a little more than this, thereby actually consuming about 20 to 40 per cent more than their basal requirement Such a diet should maintain their weight constant at a desirable level, but if not, the periodic return to a more rigorous diet may be necessary. Fellows 131 showed that five years after a successful loss of weight, 79 per cent of a group of patients had regained all or part of their lost weight Rony has emphasized that the once obese person must be constantly on guard to prevent gain of weight, since the body weight-regulating mechanism scarcely ever seems to regain an entirely normal func. tion Sample low calorie diets are included in Tables XII, XIII and XIV. Other caloric levels than these also may be used Diets of 600 or 800 calories are always weighed in grams whether served at home or in the hospital Other low calorie diets may be weighed or measured as the circumstances indicate. Every patient should be instructed in his diet individually, in a series of lessons, including a lesson on the adequate diet, one on the supplements nécessary in a low calorie diet, one on the menu plan for his individual diet and one or two lessons in menu planning by use of various substitutions, including not only menus of equal caloric value but also those of equal carbohydrate, protein ·TABLE XII LOW CALORIE DIETS 600 calorie Recommended 1,000 Special ) 1.500 allowancea, Calorie 1,200 calorie normal range caloric Women Men gm. 300 400 400 400 gm 100 Vegetable 3% Vegetable 20% Fruit 5% Fruit 10% Fruit 25% gm 200 gm. 100 300 300 200 gm. 100 Bread gmi. 10 60 40 60 Cream 20% gm. 30 30 30 400 480 960 480 Milk, skimmed gmn Allk, whole gm Eggs, cach gin, Meat, very lean gm Meat, lean gin. 1 1 1 1 150 150 150 150 15 15 25 Butter gm. Approximate composition. Carbohydrate gm. 55 100 115 135 Protein 70 gm 60 70 85 75 60 800 Fat gin. 15 40 45 75 Calories 620 1,030 1,180 1,510 2,500 3,000 Calcrum mg 660 870 1,420 880 800 Iron 0 mg 9 11 11 12 12 Vitamin A IU. 2,400 6,200 6,000 7,300 15,000 15,000 Thuamine mg. 11 15 1 Riboflavin mg 14 1.7 26 18 16 20 Niacin 10 mg 15 12 11 13 12 Ascorbic acid mg 75 120 160 160 170 70 • Recommended dietary allowances, National Research Council, Reprint and Circular Series, No. 122, August, 1945.*** 3 ·DIETS FOR OBESITY 77 probably has little effect on the satiety value. If the patient becomes constipated, bulk may be added by medication Bran is no longer in common use because of its tendency to ifritate the large bowel. Mineral oil, whether used as a laxative or as an ingredient in cooking, is also in disfavor because of the increased excretion of the fat-soluble vitamins following its use Once the patient attains the desired weight, attention to the dret must not be abandoned, since unrestricted feeding will often cause the weight to return to its original figure 111 Therefore, a moderately restricted diet, usually measured rather than weighed, of 1,500 to 1,800 calories should be prescribed. Patients will usually eat a little more than this, thereby actually consuming about 20 to 40 per cent more than theic basal requirement Such a diet should maintain their weight constant at a desirable level, but if not, the periodic return to a more cigorous diet may be necessary Fellows 131 showed that five years after a successful loss of weight, 79 per cent of a group of patients had regained all or part of their lost weight. Rony has emphasized that the once obese person must be constantly on guard to prevent gain of weight, since the body weight-regulating mechanism scarcely ever seems to regain an entirely normal function. Sample low calorie diets are included in Tables XII, XIII and XIÙ Other caloric levels than these also may be used Diets of 600 or 800 calories are always weighed in grams whether served at home or in the hospital Other low calorie drets may be weighed or measured as the arcum. stances indicate. Every patient should be instructed in his diet individually, in a series of lessons, including a lesson on the adequate diet, one on the supplements nécessary in a low calorie diet, one on the menu plan for his individual diet and one or two lessons in menu planning by use of various substitutions, including not only menus of equal caloric value but also those of equal carbohydrate, protein ·78 OBESITY and fat value (Tables XV, XVI, XVII and XVIII). Noncaloric fluids, such as broth, tea and coffee, are actually unlimited. "Per cent" refers to per cent of carbohydrate, except in the case of cream, in which case the per cent of fat is indicated, Four diets are given herein, with the approximate composition of a typical menu, and one menu is given for each diet (Tables XIII and XIV). Many more could be devised easily by use of the food tables. The special 1,200 calorie diet is included for use with patients who require a quart of TABLE XIII SAMPLE MENU FOR LOW CALORIE DIETS 600 calorie 1,000 calorie Food Weight, gm. Food Weights gm. Grapefruit Egg, soft cooked Whole wheat toast 100 one 10 100 one 20 Grapefruit Ege, soft cooked Whole wheat toast Batter 20% cream Coffee 30 1 cup Coffee 1 cup Breakfast 10% fruit Egg Bread, toasted Butter 20% cream Beverage Dinner Soup Lean meat Vegetable vegetable 5% fruit 10% fruit Skimmed milk Bread Butter Broth Lean roast beef New cabbage Tomato salad Water packed peaches Skimmed milk 1 cup 75 75 75 100 Broth Lean roast beef New cabbage Tomato salad 1 cup 75 100 100 200 Orange slices Skimmed milk Whole wheat bread Butter 100 240 20 5 75 100 50 Supret Lean meat Lean sliced ham 30% vegetable Green beans 3% vegetable Celery sticks Water packed pears Skimmed milk Skimmed milk Bicad Butter Beverage Ter with lemon 10% fruit 50 200 Lean sliced ham 75 Green beans 100 Celery and carrot sticks Water packed pears 100 Skirmed milk 240 Whole wheat bread 20 Batter Tes with lemon 1 cup 1 cup ·DIETS FOR OBESITY 79 TABLE XIV SAMPLE MENU FOR LOW CALORJE DIETS 1,500 calorie Weight, Food Grapefruit Egg, soft cooked Whole wheat toast Butter Cream Coffee 100 onc 20 5 30 Cream 1 cup Special 1,200 caloric Weight, Food gm. Breakfast 10% fruit Grapefruit 100 Egg Egg, soft tooked one Bread, toasted) Whole wheat toast 20 Butter Butter S 20% cream 30 Beverage Coffee 1 cup Dinner Soup Broth 1 сор Lean meat Lean roast beef 75 Meat 20% vegetable New cabbage 100 Tomato salad 100 Orange slices 100 Skimmed milk Skimmed milk 240 Whole milk Bread Butter Butter 5 Broth I cup 109 vegetable vegetable Roast beef Mashed potato New cabbage Tomato salad Orange slices Whole milk Whole wheat bread Butter 75 100 100 100 100 16% fruit 240 20 10 75 73 100 Supper Lean meat Lean cold bam Meat 3% vegetable Green beans 3% vegetable Celery and carrot sticks 10% fruit Water packed pears 25 fruit Skimmed milk) Skimmed milk Whole milk Bread Whole wheat bread Butter Butter Beverage Tea with lemon Cold sliced ham Green beans Celery and carrot sticks 100 50 23 100 Canned pears 100 240 20 5 Whole milk Whole wheat bread Butter Tea with lemon 240 20 10 1 cup 1 cup 3pm Skimmed milk Skimmed milk 240 8 pm Skimmed milk Skummed mulk 240 milk a day, It is suggested for children or pregnant requiring reduction of weight and could be used with fications in cases of obese patients with gastric or ulcer. 1 ·80 OBESITY 201 1106 spurned 190 100H 171 110 IMA fo 1 5 T . 15 16 17 18 9 10 13 12 13 14 Weeks Figure 7: Calculation of predicted weight loss for a thirty two year old woman, 63.5 inches in height, weighing 227.5 pounds: basal calories for 195 pounds, 1,640; basal calories plus so per cent, 2,460; caloric intake, 620; caloric deficit, 1,8t0; predicted average weight loss, 3.7 pounds per week for the first nine weeks, or 33 pounds After nine weeks the patient weighed 200 pounds, the actual loss being 27.5 pounds. Calculation of the predicted weight loss for the next nine weeks was as follows: basal calories for 170 pounds, 1,540; basal cal. ories plus 50 per cent, 2,310; caloric intake, 620; caloric deficit, 1,690, predicted average weight loss per week, 3 4 pounds, or 31 pounds in the second nine weeks The actual loss in this second nine week period was 26 pounds Six months later this patient weighed 143 pounds (The solid line represents the predicted weight loss; the broken line, the actual weight loss.) One multiple-vitamin capsule each day is routinely given to all patients on these diets Salt and water are not restricted. In hospitals using separated skimmed milk, the fat content of the 600 and 1,000 calorie diets will be even lower than indicated by about 4 gm. or 36 calories. Vegetables used may be either fresh, canned or frozen, but are limited either to those containing approximately 3 per cent of carbo hydrate or to half the number of grams of those containing per cent of carbohydrate, except in the 1,500 calorie diet, which allows 100 gm of a 20 per cent vegetable or a cooked ·1 ruler to the FOOD NOMOGRAM Direction. The standards for age are arranged on the basis of the common method of expressar.g 18as of the last caloric allowance, proceed as follows (1) Locate the weight on Scale 1 by means of a pin stuck through the craser of a lead pencil (2) Place the edge of the rulet against the pun and swing the other end of rulet to the patients height on Scale 11 (3) Trans fer pin to the point where the ruler Crosses Scale II which gives the surface area in sq meters (this value need not be read) (4) Holding the hand end of the patient standard for an and sex given on Scale IV (3) Trans for the pin to where the ruíct now crosses Scale v which gives the basit heat production of the patient for 24 hours and represents the calones fol requires by the fastang The calories necessary for activity bear minded for the resting condition The 2 percentage relationship to those de so-called white collar worker When 17 work will need about 50 per cent more than hos basal calories when ac tivity is restricted, as in the hospital. the extra caloties necessary will range from 10 to 30 per cent the baul Caloris Therefore (6) estimate the par cent of Calories above the basal and lo rate this point on Scale VI ruler connect this point with the point locatel previously on Scale Y. and Where the rulet DoW COSSCs Scale vil tead the amount of food calories to be frowne by the dict For your contenience, this may be remoued by tearing on perforated line Naye Foundation Standards_for_20han and sex Weight - 160 340 - 150 320 300 140 280 -130 260 -120 240 110 105 220-100 95 200 90 190 85 180 80 170 75 160 70 150 75 140 130 120 scale, swing me on the surface arcu Pounds 110 Kilograms 100 90 80- 35 70 30 60 of 25 the 50 20 40- . W M tray and Entson Outuber 1333 15 B. Saunders Company )

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·82 OBESITY 190 186.75 180 Pounds 170 160) 150.5 15715 19 ZD 21 15 26 27 2 23 Weeks Figure 8a and sb Calculation of predicted weight loss for a thirty-nine year old woman, 62 25 inches in height, weighing 2525 pounds basal calories for 222.5 pounds, 1700; basal plus 50 per cent, 2,550, caloric intake, 620; caloric deficit, 1,930; predicted average weight loss, 39 pounds per week or 35 pounds in the first nine weeks After nine wecks she weighed 218 pounds, an actual loss of 345 pounds Calculation of weight loss for the next nine weeks was as follows basal calories for 188 pounds, 1,580, basal plus 50 per cent, 2,370, caloric intake, 620, caloric deficit, 1,750; predicted average weight loss, 35 pounds per week or 31.5 pounds in the second nine weeks At the end of this period she weighed 1865, an actual loss of 31 3 pounds Calculation of weight loss for the third pine weck period was as follows, basal calories for 155 pounds, 1,480, basal plus 50 per cent, 2,220; caloric intake, 620, caloric deficit, 1,600; predicted average weight loss per week, 3 2 pounds, or a loss of 29 pounds on the third eine week period At the end of this period she weighed 159.5 pounds, an actual loss of 27 pounds. Two months later she weighed 148 pounds, a total loss of 104 3 pounds. (The solid line represents the predicted weight loss, the broken line, the actual weight loss ) Spices are allowed but condiments containing sugar or fat, such as relishes, chili sauce, catsup, pickles and olives must not be used. Saccharin may be used as a sweetener in bev- ·DIETS FOR OBESITY TABLE XV SUBSTITUTIONS Gm 50 335 165 200 Substitutions for 100 gm. of 3 per cent vegetable 1. 6 per cent vegetable 2. Sper cent fruit 3 10 per cent fruit 4. 15 per cent fruit or vegetable 5. 20 per cent fruit or vegetable Substitutions for 100 gm. of 10 per cent fruit 1. 3 per cent vegetable 2. 6 per cent vegetable 3.5 per cent fruit 15 per cent fruit or vegetable $. 20 per cent fruit or vegetable 6. Dry cerea! 7. Soda crackers 8. Bread Substitutions for 20 gm. of bread ! 3 per cent vegetable 2. 6 per cent yegetable 3. S per cent fruit 10 per cent fruit 5. 15 per cent fruit or vegetable 6 20 per cent frut or vegetable 7. Dry cercal 8. Soda crackers 9. Flour Substitutions for 240 gm of whole milk 1. 10 per cent fruit Egg 2. Bread Meat, cocked Butter Substitutions for 240 gm. of skimmed milk 1. $10 per cent frust Meat, very lean 2 Bread Meat, very keen 3 Buttermilk 3JS 120 ៩ដដមមី {ខវេទី J20 etages and fruits if desired. Clear tea, black coffee and fatfree broth or bouillon may be taken between meals to appcase the appetite. 240 ·84 OBESITY TABLE XVI FOOD VALUES Y 11.4.11.- kiven in 1 ADIC A FRUITS CLASSIFIED BY CARBOHYDRATE CONTENT 3 per cent 20 per cent 15 per cent Artichokes Green peas Parsnips 6 per cent Beets Carrots Kohlrabi Okra Onions Pumpkin Rutabagas Hubbard or winter squash Turnips Corn Hominy, cooked Lima beans, canned Macaroni, cocked Noodles, cooked Rice, cooked Shelled beans, cooked Spaghetti, cooked Potato Asparagus Beetgreens Broccoli Brussels sprouts Cabbage Cauliflower Celery Cucumbers Dandelion greens Eggplant Endive Green peppers Lettuce Mushrooms Radishes Sauerkraut Spinach String beans Summer squash Swiss chard Tomato Water cress Sample menus for one day for diets of various caloric levels are given in Tables XIII and XIV. Also groupings of vegetables and fruits, food composition tables and sub stitutions which are helpful to the average patient, may be found in Tables XV, XVI, XVII and XVIII.

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·86 OBESITY deficit, 2,095, predicted average weight loss, 4.2 pounds per week, or 38 pounds in the second nine week period. At the end of this period she weighed 253.5 pounds, an actual loss of 29 5 pounds Calculation of the predicted weight loss for the third nine weck period was as follows: basal calories for 223 pounds, 1,760, basal calories plas 50 per cent, 2,640, caloric intake, 620; caloric deficit, 2,020, predicted average weight loss, 4 pounds per weck, or 36 pounds in the third nine week period. At the end of this period she weighed 224 pounds, an actual loss of 295 pounds Calculation of the predicted weight loss for the fourth eine weck period was as follows: basal calories for 190 pounds, 1,620; basal calories plus 50 per cent, 2,430; caloric intake, 620; caloric deficit, 1,810, predicted average weight loss, 3.6 pounds per week, or 32 pounds in the fourth nine week period At the end of this period she weighed 195.5 pounds, an actual loss of 28.5 pounds ELE een weeks later she weighed 161 pou a total loss of 162 pounds in fifty-four weeks. TABLE XVII FRUITS CLASSIFIED BY CARSOHYDRATE CONTENT 1. Fresh or juice packed S per cent 20 per cent Rhubarb Bananas Grapes Plums 10 per cent 15 per cent Blackberries Apples Cantaloupe Apricots Cranberries Blueberries Gooseberries Chernes Grapefruit Currants Honeydew melon Huckleberries Lemons Pears Limes Raspberries Oranges Peaches Pineapple Strawberries Watermelon 2. Water packed Kadota figs Apricots Blackberries Cherries, red Cherries, white Loganberries Peaches Raspberries Strawberries Applesauce Cherries, black Fruit for salad Pears Pineapple Plums Whits grapes ·Cakfast cereals, dry, ST "termilk car cooked, very fat DIETS FOR OBESITY TABLE XVIII AVERAGE COMPOSITION OF COBIBON FOODS 87 Per 100 gm. of food Carbohydrate, gm. Protein, gm Fat, gm Green corn Vegetables and fruits 3 per cent vegetables 6 per cent vegetables 1 per cent vegetables 20 per cent vegetables Potato Shelied beans 5 per cent fruits 10 per cent fruits per cent fruits 20 per cent fruits cereals, cooked White bread Whole wheat bread Wheat flour Soda crackers Dary produces 20 76 bread 13 3 light or coffee heavy or whipping cheddar type Cottage cheese, dry Cottage cheese, creamed Eggs, each Meats and fish Meat, cooked, very lean Meat, cooked miscellaneous Oyuters Cooked bacon Liver FAN ៨៩១៩៨៥ ** -w8 SO Butter or oleomargande Lard or bacon fat Olive oil and other ouls Mayonnaise Peanut butter • Fat begligible 10 commercially separated milk 81 100 100 78 43 ·Chapter VI OTHER THERAPY PSYCHOTHERAPY HE MOTIVES which take the obese to the doctor are many THE and the success of the treatment in the individual case depends in some measure on that motive. 109 Almost univer. sally, patients in charity clinics have done poorly 70 unless they have shown some unusual desire to lose weight. If the patient comes only at the urging of someone else, it is unlikely that his determination will be sufficient to carry him through an adequate program of reduction It is the doctor's task to supply this determination by whatever means he can find Even more difficult is the problem of convincing the obese patient who visits his doctor for some other complaint of the necessity for reduction of weight. Better prospects face those patients who come voluntarily impressed, by some dramatic incidents of cardiac decompensation or the onset fact that obesity may cause harm Under the term “psychotherapy" pression which the personality and make on the patient. Under this all of those nebulous psychologic doctor-patient relationship. The P ner inspires confidence and a most likely to be successful. Ross 325 has shown quite wel completely convinced of the will, by his manner, transmit .. If there is a large psychologic remarkable improvement follo [ 88 ·OTHER THERAPY ther impressed the worth of his therapy. A similar ph nomenon may occur in the treatment of obesity. The docto who believes he has found an endocrine or other preparation that will cure obesity will have the patient return to his office at frequent intervals for injections. The patient, impressed by the doctor's enthusiasm for his drug, becomes hopeful for success and anxious to aid in every way possible Under such circumstances it is not surprising that the dietary instructions are followed more closely so that a good result is obtained. Thus the physician is further convinced of the efficacy of his drug. It is only when the doubting physician uses the drug that it fails. On the other hand, it may be difficult to maintain the faltering patient's morale without such a device. The patient may see little to be gained from periodic visits to the doctor's office if he receives no special treatment at these visits For this reason, the interval between visits may lengthen, the pa. tient's will to lose weight weakens and violations of the diet occur. McCullagh 240 has emphasized the importance of regular visits. The maintenance of the patient's determination to follow the diet and to lose weight is an important factor, and the success of the treatment may be determined by how well the physician ss able to do this. Since cach patient is different, the physician unconsciously adopts varying technics and approaches to such problems. Richardson 818, 870 pressed the belief that the success of a program of weight reduction depends largely on the patient's understanding of the psychologic factors involved and on the doctor's utilization of those factors Ordinarıly the patient is not sufficiently impressed with the seriousness of his condition, so that it frequently becomes necessary for the physician to alarm the patient deliberately The patient can be told that "between the ages of 45 and ss, 25 pounds of excess weight means a 250 increase in the chances of your dying within the next year; 50 pounds excess means a 50% greater chance of death; more weight ex ·90 OBESITY increases the hazard in proportion."284 Figure 1 illustrates this point, one can point to these mortality figures and accurately say to the patient, "You are digging your own grave with your teeth." The patient should be told that his heart is working overtime to pump blood through the masses of fat, that his knecs, hips and back are likely to become injured and parful because of long-continued obesity. The physician frequently will be able to tell the patient that "your heart is fine but the strain imposed on the heart by all this fat is just like the strain placed on an automobile motor by driving about with the brakes on. Although it may be a good motor, it's bound to wear out sooner if the brakes are kept on all the time." For the person who still seems complacent, it may be necessary to compare them and their urge to eat with the alcoholic and his compulsion to drink. They can be told truthfully that the circumstances leading to gluttony and to alcoholism are much the same and that the results are about equally harmful. The patient should be reassured that the reduction program will not harm him and that a familial tendency to or a long term duration of obesity is no bar to therapy. He should be told to disregard relatives and well-meaning friends who unconsciously associate loss of weight with ill health and tell him daily that "this diet makes you look terrible." Superficial psychotherapy in the form of encouragement and reassurance may be sufficient in the majority of cases, but not infrequently greater benefit may result from more extensive investigation and treatment. Discussion of the patient's conflicts and problems and simple explanation of their origin, after the patient has spent several hours un. burdening himself of them, can be given by the interested internist. It is only seldom that the internist will be forced to turn to the psychiatrist for help. Sometimes conflicts and ·OTHER THERAPY 91 $33 neuroses will be resolved by loss of weight so that systematic psychotherapy is not required. Schopbach and Matthews, is one series of cases, found that the patients were unable to sessin comfortable on theit diets without psychiatric help. There may be fears which the patient hesitates to express He may have some fear that he will become the victim of tuberculosis or some other wasting disease if he should be come thin.98 The pleasure of eating may have been a sub suture for other pleasures of life whsch were densed the patient by circumstances or perhaps by his inability to experence pleasure. Many people, through early training, have become inhibited to such an extent that these acceptable pleasures are few, and eating is one of those whuch remains respectable. Still other people have a great deal of nervous tension and find that during periods of stress there is a compulsion to est Such compulsive eating & us exernplified a the person who says "but I get so nervous I just have to eat something to qutet my nerves" Some people smoke, some drink, while others eat and get fat. Even more important than the accomplishment of the initial loss of weight is the maintenance of the weight at a normal level. Unless some progress has been made in the solution of the patient's psychologic difficulties and unless some insight has been gained, it is unlikely that the normal weight, when reached, will be maintained in the person who became fat because of a neurosis 291 The establishment of new habits of eating, however, which is often accomplished by the reduction program, is sometimes all that is required for maintenance of normal weight. DRUGS Thyroid This has been used since 1894 in the treatment of obesity."1* It obtained early fasor because obesity was, at that time, thought to stem frequently from hypothyroidism; therefore, it was felt that thyrond would act as a specific ·92 OBESITY remedy. However, as time proved that hypothyroidism was only occasionally associated with obesity, thyroid began to be used for its calorigenic action rather than as specific replace ment therapy. Bram has administered thyroid in amounts sufficient to cause basal metabolic rates of + 15 and + 20 with a pulse of 90 in a variety of conditions, including obesity. Winkler 417 expressed the belief that ordinary doses of thyroid administered to the individual with a normal thyroid are inactivated. Selye 836 pointed out that a gland is put at rest by the administration of the hormone specific for that gland, and Cramer 83 and Farquharson and Squires 128 advised that increasing doses of thyroid are required to maintain the basal metabolic rate. Soskin and Levine 364 stated that the administration of thyroid inhibits the formation of thyrotropic hormone by the pituitary. Although it has been adequately demonstrated that basal metabolic rates which are computed on the basis of surface area are essentially normal in obesity, studies related to the effect of low calorie diets on the basal metabolic rate in the obese are few. It is felt by some that the basal metabolic rate drops to less than normal during the process of reduction 25, 58, 88, 234, 261, 968 and that thyroid should be given in order to maintain metabolism at a normal rate.88, 110, 155, 233 Others have calculated that the energy output of the obese person is dangerously high, when computed on the basis of ideal weight, 110.. 125, 127 and have failed to find more than occasional falls in the basal metabolic rate as the result of restriction of diet. 191, 257, 268, 275 Walder 609 has stated that an adequate dietary supply of protein prevents this fall in basal metabolic rate The heart, lungs, muscles and liver of the obese are under increased strain because of the obesity. As was menttioned in the section on physiology, since the obese person has a dangerously high rate of metabolism although when computed on the basis of surface area it seems normaal, it is easy to see how thyroid might easily cause undesirable and ·OTHER THERAPY 93 excessive strains on the circulatory system of an obese person if the basal metabolic rate were even moderately clevated by administration of this substance In addition, the harmful effects of thyroid on the heart are not limited to the extra work occasioned by the elevation of the basal metabolic rate, but they also depend on a direct toxic action.915 These facts, however, should not prevent the use of thyroid in the treatment of obesity sn the person with hypothyroidism, provided periodic determinations of the basal metabolic rate are made as a guide to therapy It is felt by some that thyroid may be effective in doses too small to yield any calorigenic action.107 This is supposed to depend partly on a diuretic action of thyroid, 107, 107 but otherwise the mechanism is obscure. It is known that thy. roidectomy tends to cancel the diuresis of diabetes insipidus,"s but whether thyroid has a direct diuretic effect in the person with normal pituitary function has not been so well demonstrated, although the latter has been implied 220 Administration of thyroid was found by Plummer 803 to cause the loss of an average of thirteen pounds (59 kg ) of fluid from the tissues of the myxedematous patient, but convincing proof of such an action in the euthyroid individual is lacking Means *1 and Sevringhaus, 338, 339 on the other hand, agreed that thyroid is effective only by causing hyperthyroid. ism and that it should not be used in obesity except in very special situations Barborka 12, 13 and Bulger * cautioned against the indiscriminate use of thyroid Lyon and Dunlop suggested that thyroid may produce loss of weight partly by destruction of protein, that is, by causing a negative nitrogen balance, and by diuresis It is known that a considerably larger amount of water is asso cated in ith protein in the body than with fat, and if there is loss of isocaloric quantities of tissue protein and fat, there is a much greater (approximately nincfold) loss of sy eight be. cause of the destruction of protein 299 Mason noted con- ·94 OBESITY siderable losses of nitrogen when obese patients were given thyroid and diets containing 24 gm. of protein.242 Studies by Boothby and co-workers 88 demonstrated that a negative nitrogen balance follows administration of thyroxin Others 48, 61 simply found that thyroid is ineffective in causing reduction of weight. Fellows 131 found thyroid effective in a few patients with persistently low basal metabolic rate and obesity, but only as an adjuvant to diet. Bram has reported five cases of exophthalmic goiter following therapy with thyroid, 40 and exophthalmos alone fol. lowing such therapy has been described.23 Thyroid with minute amounts of bromide in chemical combination has been considered by some investigators to have fewer "toxic effects" for the same metabolic action 180 than does thyroid alone. It is questionable, however, whether any preparation of thyroid can be said to have fewer "toxic effects," sinc these symptoms seem to arise from the thyroxin molecu itself and are bound up closely with the desirable therapeut effects. It is probably wise in many cases to determine the bas metabolic rate prior to starting any reduction therapy in obese, if only to be able to tell the patient, with convicti that "your thyroid gland is functioning normally and important thing is diet and not the use of thyroid." results of determinations of basal metabolic rates in o children may be unreliable. In summary, the obese person is unusually susceptib harm from administration of thyroid because of his alelevated rate of metabolism Thyroid given in small do probably inactivated and is, therefore, likely to be ineffe Thyroid administered in larger doses may cause a res of weight through destruction of tissue proteins and vation of the basal metabolic rate, but its harmful effthe circulatory system make it a dangerous agent. I thyroidism is associated with the obesity, enough ir ment in subjective symptoms and mood may resul ·OTHER THERAPY 95 therapy with thyroid, so that proper dict, the mainstay of reduction therapy, may be adhered to with greater case. Other endocrine preparations Other endocrine preparations have been used to cause reduction of weight, 121, 149 and some authors have expressed the belief that there are cases in which reduction by diet alone is impossible and that endocrine therapy is essential Extracts of the anterior lobe of the pituitary gland have been tried; 80, 45, 141, 308 it is significant that the same extracts have been recommended for both the cachexia and the obesity that are supposed to follow pituitary disease 55, 74 Estrogens have been used 149, 151 but there is no adequate proof that a deficiency of them causes obesity In addition, estrogens tend to cause retention of water and hence, a temporary gain in weight. Therefore, their use cannot be advised for the treatment of obesity itself. Testosterone causes an increase in the amount of muscular tissue and a change in the pattern of distribution of fat in the male with hypogonadism, but such cases of hypogonadism are not frequent. It is unlikely that any benefit will follow the use of testosterone in obesity, although such use has been suggesetd *** Werner 600 has used obstetric pituitrin in conjunction with thyroid. A possible basis for this view might be found in experiments which s cre thought to demonstrate the accur- Tence of both obesity and diabetes insipidus after injury to the posterior lobe 203, 204 of the pituitary gland, but no adequate proof of the effectiveness of pituitrın has been advanced. Ovarian extracts 208 and chorionic gonadotropins, 15. I have been used but without convincing results. Amphetamine Various sympathomimetic amines have been used both as metabolic stimulants and as appetite depressors. The most ·96 OBESITY extensively used among these drugs is amphetamine sulfate (benzedrine sulfate).170, 217, 298, 299 One of the earliest studies on the use of benzedrine in obesity was performed by Lesses and Myerson 226 in 1938. They expressed the belief that the normal appetite mechanism will adjust the intake of energy to meet the requirements of expenditure of energy and, thereby, will cause maintenance of constant weight They pointed out that social and economic environments make food available with little exertion to many and that a symptom complex which they have named "anhedonia" is frequently seen 277 In this condition there is a diminution in the pleasure ordinarily derived from life's activities. When enjoyment from other activities is impaired, then the person turns to eating only to find that more and more food is required to give satisfaction. They expressed the belief that most of the food eaten by the person with anhedonia is characteristically consumed during the second half of the day Such patients, Lesses and Myerson considered, can be best treated with benzedrine, which is thought to have a direct depressing action on appetite and to cause increased activity They did not restrict use of this drug to the variety of obesity seen in anhedonia, and they obtained good results in all persons receiving it. Placebos failed to help control patients They found no tolerance toward this drug developed as far as the appetite was concerned. Others have observed such a tolerance, however.48, 878 Earlier, Myerson, Loman and Dameshek 278 studied ben. zedcine and cautioned against the use of this drug in the presence of hypertension, particularly if it is to be used in conjunction with atropine, since the synergistic action of the two drugs makes pressor response maximal. Results of laboratory studies suggest, however, that a tolerance to the pressor effects of many sympathomimetic drugs, including benzedrine, is rapidly acquired.203 Rosenthal and Solomon 924 expressed the belief that they obtained loss of weight from use of benzedrine without re- ·OTHER THERAPY 9 striction of diet, although they stated that the drug may be of greatest aid by helping the patient to stay on a diet as a result of improvement of mood No increase in basal met abolic rate $71 was found, although there appeared to be an increase in the output of energy as a result of increased activity These authors also expressed the belief that benzedine acts as a diuretic Ersner 125 found no clevation of the basal metabolic rate and observed that the blood pressure fell in association with benzedrine-induced loss of weight. Beyer, 29 in carefully controlled experimental work, found a 13 per cent increase in the basal metabolic rate, which lasted nine to twenty-four hours, and a considerable increase in blood pressure after 30 mg doses of benzedrine had been adminis. tered orally. Emerson 119, 120 has carried out determinations of basal metabolic rate during a three hour period which followed the ingestion of 20 mg doses of amphetamine by human subjects He found that the racemic form caused a maximal rise of 157 per cent, the levorotatory isomer, a cise of 5.5 per cent, and the dextrorotatory isomer, a rise of 11.5 per cent in the basal metabolic rate Thus it seems likely that ingestion of amphetamine will cause some elevation in the basal metabolic rate, according to the results of determinations made within several hours, but if there has been no medication for tveive to eighteen hours, little or no effect will be observed.219 Kunstadter and Necheles 218 found, after administration of benzedrine, diminished gastric motility which they con. sidered to be the mechanism of appetite depression A convincing study on both dogs and human subjects was carried out by Harris and Ivy 168, 169 They found that a definite loss of weight took place during therapy with face: mic or dextrorotatory amphetamine which was the result of soluntary reduction in intake of food No diuresis or increase in basal metabolic rate was noted, but the occurrence of a slightly greater than expected loss of scight suggested xhat there might be some increase in total metabolism the ·98 OBESITY first few days after administration of the drug had been started. Anorexia was proved, by experiments on dogs on which vagotomy and splanchnolumbar sympathectomy had been performed, to be central in origin and to be indepen dent of any effects of amphetamine on gastric motility of secretion. Appetite returned to normal quickly aftes ada ministration of the drug had been stopped. Sufficiently large doses of amphetamine prevented dogs from eating for as long as twenty-one days. The average dose employed in human subjects by these experiments was 5 mg. of dextrorota. tory amphetamine of 10 mg. of the racemic form three times daily. Maclagen,246 in well-controlled animal experiments, could demonstrate no effect of ephedrine or benzedrine on appetite, although pitressin and atropine in large doses had some diminishing effect. Cutting 88 found little help from use of amphetamine, propadrine or belladonna in programs of weight reduction Bruch" found that the results of benzedrine therapy were equivocal and stated that perhaps some of the apparent bene fit may result from the increased enthusiasm of the patient for the entire program if he is receiving a drug which he thinks is specific She noted that often an obese patient will ask for the renewal of some prescription given for some incidental reason because he feels that it has helped him to follow his diet Kalb 198, 199 has found that administration of neither amphetamine nor thyroid increases the rate of loss of weight that is obtained by use of a submaintenance diet alone. More recently, studies have differentiated the effects of the two optical isomers of benzedrine. Prinzmetal and Alles 5, 105 found that although the dextrorotatory, levorota. tory and racemic forms had equal pressor effects, the dex. trorotatory isomer had three to four times the stimulating effects on the central nervous system that the levorotatory form possessed. Other studies have confirmed this greater ·OTHER THERAPY 99 central activity of the dextrorotatory form in connection with variety of sympathomimetic amines Schulte and co-workers89s found that the major portion of the stimulating activity of racemic amphetamine on the central nervous system resides in the dextrorotatory isomer, and of a number of sympathomunetic amines, dextrorotatory amphetamine was by far the most potent. The opinion has been expressed that the "undesirable excitatory effects" of benzedrine reside chiefly in the levoro tatory form,while the desirable appetite-depressing effects, which also presumably result from stmulation of the central nervous system, are a property of the dextrorotatory form. This group of clinical investigators found dextrorotatory amphetamine, racemic amphetamine, propadrine, and les orotatory amphetamine to be decreasingly effective in the order listed. They also used thyroid, ammonium chlo ride, mercurial diuretics and decholin in varying succession as a means of preventing the patient from becoming discouraged 80 Dextrorotatory desoxyephedrine has also been used 147 but this substance is considered more likely to produce un desirable effects, such as emotional irritability, than does amphetamine.'s Albrecht? found that the increase in blood pressure which follows benzedrine therapy persists only a few days but expressed the belief that the drug should be used carefully or not at all in coronary artery disease, excitability, insomnia or hypersensitivity to epinephrine-like compounds Swanson and others 875 shoned that the les oro tatory isomers of a number of sympathomimetic amines al. ways had a greater pressor activity than the dextrorotatory forms Hirsh 179 considered propadrine to be the best of this group of drugs with which to control appetite Freed 137 has found that no increase in blood pressure esults from administration of benzedrine and expressed the clief that its use is unnecessary after about two months, ·100 OBESITY since by that time the appetite seems permanently depressed. The Council on Pharmacy and Chemistry of the Amer. ican Medical Association 558, 358 in 1943 condemned the use of benzedrine in the treatment of obesity because "whateves effectiveness the drug might possess might possibly be due to undesirable properties." More recently, however, the Council has accepted the use of amphetamine, with this statement: "In the light of recently developed evidence the Council now believes that amphetamine sulfate may be used in the management of obesity provided the dosage is held by the physician within such limits as may be necessary to produce the desired effect of reduction of appetite in the individual. This, of course, does not contemplate the indiscriminate use of the drug, either by prescription or over the counter sale."? The Council has particularly censured the use of benzedrine in complex mixtures of laxatives, atropine and sedatives.6, 358, 889 A system of treatment in which vasicolored pills composed of such mixtures are used has been called, popularly, the "technicolor method" of weight reduction. Addiction 353 and psychotic symptoms 202 associated with benzedrine therapy have been reported but seem to be sare. Suicide 14% caused by the ingestion of benzedrine has been reported In summary, the final estimation of the usefulness and dangers of amphetamine and allied drugs is yet to be made. The bulk of evidence suggests, however, that these drugs do produce a true anorexia and that, under ordinary circumstances and in moderate doses, they apparently cause little adverse effect on the cardiovascular system. The indiscriminate use of drugs of this group is to be deplored; particularly undesirable is the use of them in complex mixtures of other drugs A rise in blood pressure, psychologic deper dence on the drug, undue stimulation and sleeplessness, and nervousness are indications for stopping use of the drug. Although statements are frequently made that the blood ·OTHER THERAPY 101 pressure and the basal metabolic rate are not affected by amphetamine, it seems likely that adequate measurements made in the few hours after administration of the drus will detect appreciable and sometimes dangerous elevations in both. It must be remembered that careful instructions in diet are important whether or not amphetamine is used, in order that the diet which is limited in calories will not be dchcient in essential food elements. Dinitrophenol This is another drug which presents the advantages of a convenient pill and which promises the patient effortless reduction of weight. However, the frequent occurrence of skin rashes, neuritis, agranulocytosis and cataracts makes it an undesirable drug, so that now it is never used. 2as, 835, 877 This drug acts causing increase in the basal metabolic rate and, thereby, consumption of the excess tissue when diet is not restricted, dinitrophenol is of little benefit 24,953 Belladonna This drug has been used with some apparent success to diminish the appetite.197, 240, 299 The mechanism suggested is that castro-intestinal motility is diminished. No concu. J've studies have been carried out with this drus, honeses, and it seems to have no specific effect on the appetite unless it is used in large amounts *** Miscellaneous therapy Miscellancous therapy, none of which has been widely used, is mentioned only for the sale of completeness Sca. word, iodine and barium compounds have been the 13 Digitalis *1,41" and bulk.producing laxatives *97 have been proposed as devices to lessen appetite. Nonspecific protein therapy *st and ultraviolet irradiation 208 have been urged On the border of quackery is the use of soaps, bath salts and mechanical machines for reduction of weight and Emetics ·102 OBESITY and high colonic irrigations are ineffective and unwise.cos The use of candy in small amounts preceding each meal has been suggested as a means of "killing the appetite," but the effectiveness of this practice is to be questioned.", 150 It has been suggested that glucose eaten between meals is "consumed as fuel" and is not deposited as fat,158 but this opinion is also to be doubted. Diuretics Use of diuretics may give the physician and the patient a false sense of achievement by causing the excretion of a few pounds of water. Mason and Hellbaum 251 demonstrated that the ingestion of 36 gm, of sodium bicarbonate in three days by medical students caused an average gain of 2.28 pounds (1.03 kg.) while ingestion of 18 gm. of ammonium chloride in a period of similar length caused an avecage loss of 1.97 pounds (0.89 kg.). Occasionally the physician may find it necessary to encourage the faint-hearted patieat by means of diuretics which cause the rapid excretion of a few pounds of water, but this should be considered only as a means of psychotherapy and not as a specific device for the correction of obesity. "The success of a program for reduction of weight should not be judged by the day-to-day loss of weight, since variations in the amount of water ingested may amount to three or four pounds (1.4 to 1.8 kg.) daily so that such variations are of little significance in the final result of therapy. Diuretics have the fault common to all medications in that they also divert the patient's attention from the prin. cipal therapeutic device of diet, so that he is thereby tempted to eat as his appetite demands and rely on the needle or pill to cause reduction. Many capable voskers have used diuretics, however, 158, 170,299 Pelner 299 expressed the belief that there is sig. nificant retention of water in every obese patient and that most patients will require diuretics.

·OTHER THERAPY 103 Urea has been suggested as a druretic.15$ If diuretics are to be used it is suggested that the less harmful ones, such as ammonium chloride and urea, be employed. HEAT CABINET TREATMENTS (TURKISH BATHS) AND SALT RESTRICTION Treatment in heat cabinets causes the loss of water and electrolytes as a result of increased perspiration, so that any loss of weight obtained by this means is temporary and lum. ated in amount.386 The restriction of salt in the diet 275, 299 ads in the loss of weight in the same manner as does the administration of diuretics and Turkish baths, Sodium is the "backbone of the extracellulat fluid;" an excess of sodium encourages retention of water, but a scanty supply encourages the excre. tion of water. The restriction of water which is sometimes advised 152 serves no useful purpose.887 The starving person usually tends to consume an excess of water, perhaps in an attempt to assuage his hunger.310 This is rapidly excreted so that, unless the intake of salt is increased or unless "starvation edema" occurs, there is no gain in weight "Starvation edema" is not known to occur in the obese person but it is often observed when the weight has diminished to a value well below normal as a result of starvation, Zondek 23 expressed the belief that obesity due to retention of water and salt is a frequent occurrence in the Middle East and that it does not respond to endocrine, diet. aty or psychologic therapy He regards restriction of water and salt and the use of mercurial diuretics as the crucial therapeutic measures in these cases. We have observed no such patients in the United States. EXERCISE AND MASSAGE These offer tho popular but relatively ineffective methods of weight reduction. 's Nesburgh 39s estimated that the ·102 OBESITY and high colonic irrigations are ineffective and unwise.c09 The use of candy in small amounts preceding each meal has been suggested as a means of "killing the appetite," but the effectiveness of this practice is to be questioned.“4, 150 It has been suggested that glucose eaten between meals is "consumed as fuel" and is not deposited as fat,use but this opinion is also to be doubted. Diuretics Use of diuretics may give the physician and the patient a false sense of achievement by causing the excretion of a few pounds of water. Mason and Hellbaum 251 demonstrated that the ingestion of 36 gm, of sodium bicarbonate in three days by medical students caused an average gain of 2 28 pounds (1.03 kg.) while ingestion of 18 gm. of ammonium chloride in a period of sumilar length caused an average loss of 1.97 pounds (0.89 kg.). Occasionally the physician may find it necessary to encourage the faint-hearted patient by means of diuretics which cause the rapid excretion of a few pounds of water, but this should be considered only as a means of psychotherapy and not as a specific device for the correction of obesity. "The success of a program for reduction of weight should not be judged by the day-to-day loss of weight, since variations in the amount of water ingested manma daily so th final result willspy. Diuretics have the fault common to all medications in that they also divert the patient's attention from the prin: cipal therapeutic device of diet, so that he is thereby tempted to eat as his appetite demands and rely on the needle or pill to cause seduction. Many capable workers have used diuretics, however.158. 170,209 Pelnes 209 expressed the belief that there is sig nificant retention of water in every obese patient and that most patients will require diuretics.

·OTHER THERAPY 10 Urea has been suggested as a diuretic 158 If drarctics ar to be used it is suggested that the less harmful ones, such as ammonium chloride and urea, be employed. HEAT CABINET TREATMENTS (TURKISH BATHS) AND SALT RESTRICTION Treatment in heat cabinets causes the loss of water and electrolytes as a result of increased perspiration, so that any loss of weight obtained by this means is temporary and limited in amount.888 The restriction of salt in the diet 275, 289 aids in the loss of weight in the same manner as does the administration of diuretics and Turkish baths. Sodium is the "backbone" of the extracellular fluid, 140 an excess of sodium encourages retention of water, but a scanty supply encourages the excretion of water. The restriction of water which is sometimes advised 151 serves no useful purpose.887 The starving person usually tends to consume an excess of water, perhaps in an attempt to assuage has hunger.210 This is rapidly excreted so that, unless the intake of salt is increased or unless "starvation edema" occurs, there is no gain in weight "Starvation edema" is not known to occur in the obese person but it is often observed when the weight has diminished to a value well below normal as a result of starvation. Zondek 432 expressed the belief that obesity due to retention of water and salt is a frequent occurrence in the Middle East and that it does not respond to endocrine, dietary or psychologic therapy He regards restriction of water and salt and the use of mercurial diuretics as the crucial therapeutic measures in these cases We have observed no such patients in the United States EXERCISE AND MASSAGE These offer tivo popular but relatively ineffective methods of weight reduction.is Newburgh 285 estimated that the ·104 OBESITY energy consumed in walking a mile equals 100 calories and that one must walk thirty-six miles (57.9 km) to lose one pound (0.5 kg.) of adipose tissue. Because exercise tends to increase appetite, it is very questionable whether vigorous exercise is of seal aid in a program of seduction, 10% although hard physical labor may cause consumption of as much as 2,000 calories or more a day in excess of basal requirements One should remember that the cardiovascular and respiratory organs in an obese person are already laboring under the strain of increased metabolism and that vigorous exercise will impose on them an even greater demand. A moderate amount of light exercise is to be encouraged dur. ing a peri of reduction but such exercise should not be expected to increase significantly the rate at which weight is lost. Douthwaite 10% described exercises for strengthening the abdominal muscles and aiding posture which can be carried out by the patient while he is performing everyday tasks. Onc of the common misconceptions concerning the treatment af obesity is that certain exercises or localized massage will remove fat selectively from specified sites.323 Muscles can, of course, be developed selectively, and perhaps by this means some change in contour can be achieved. It has been faicly well demonstrated that vigorous massage will neither diminish the size of one limb compared to the corresponding member 200nor mobilize enough fat to increase appreciably the concentration of blood lipoids. 548 Some evidence that massage will diminish the fat in the "fat organs" of sats was advanced by Tuerkisher and Wertheimer, however. Cold baths have been suggested as a means of increasing the output of energy, but the increase accomplished by this means is probably smal}.594 SURGICAL REMOVAL OF FAT Procedures in which large masses of fat are surgically removed have been used but infrequently. Healing is often

·OTHER THERAPY
delayed, sometimes it is never completed and there is always
the danger of fat embolism. Plastic correction of large
folds of skin which are left after extensive loss of weight
may occasionally be necessary 195, 844
105

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