| CREVELD AND HUIJING posphorylase in hepatic. e deficient glycogen-stor- J. Clin, tnvest. 40-1841, mylo-1,6-glucosidase ae nal leukocytes and in let patients with glycogen ase. Clin, Chim. Acta, em. Weekblad 59:598, Kendig, E. M., and Levencyte debranching ycogen. storage disease st, 42:656, 10963, dur, H., and Arman, J Incestdase activity in lou "patients with glycogen se. Clin. Chim. Acta 6: ersonal_ communication, Gornlath, M., Fischer, rE: Glycogen in exythe patients with glycogen ase. Pediatrics» 27:103, Hewose monophosphate, lactato inthe peripher yeogen storage disease, Chim, Acta 7:193, 196 shiore, J, and Renold, tose tolerance in glyco: disease, Pediatrics 19 nd Abraham, S.: Chemi- es for analysis of paly- in (G. P. Colowick and an, Eds.:) Methods in Vol. Il, New York, ss, 1987, p. 34 , end Zilversit, D. B, for the direct determi- um tighyeerides. J. Lab, '50:152, 1957. if Pediatrics, nds il Chemistry, nds. Metabolism Clinical and Experimental VOL. XIII, NO. 3 MARCH, 1964 Calories Do Count By Laurance W. Kivsei, Bannara GuNwino, Gronce D. Micuazts, Jaees Riciianpson, Stiptex E. Cox anp Cavin LEMON ‘There have been statements in the medi cal and the lay literature to the effect that weight loss occurs more rapidly with diets high in fat and protein as Zompared to equicaloric diets contain- large amounts of carbohydrate. In the present study, subjects hve been ntained for many wecks on constant intake. At intervals, the composi- fat intake varying from 12 to 83.per cent, protein from 14 to 36 per cent, and car. Dohydrate from 3 to 64 per cent of total calories. In any given subject, the rate ‘of weight loss was essentially constant throughout the entire study. It is there: fore obvious that the significant factor responsible for weight loss is reduction ‘of calories, irrespective of the composi- tion of the diet has been’ changed, the tion of the diet. HE ACCUMULATION OF EXCESS ADIPOSE TISSUE is a malady which affects many padple. That undue preoccupation with the pleasures of the table contributes to the disease has geen generally accepted in most quarters; or, to express the matter differently, majority opinion has held that the first law of thermodyamics applies to the human machine quite as pre- Alictably as it does to inanimate machines. Despite this body of “official opin- ion” one finds many obese irdividuals who are either convinced that their food intake completely fail ‘0 explain their adiposity, or who spend time and money in the search for'the magic potion or pill which will enable them to consume food in any quantity but still maintain or achieve a slim figure. In 1951, Pennington advanced the thesis that diets containing large amounts of fat and small amounts of carbohydrate would result in weight Toss, es- sentially regardless of the level of caloric intake In a later paper, he Viewed the literature bearing on this concept and presented a somewhat novel concept to account for the alleged differences in the metabolism of the 2 foodstuffs in obese individuals.? Keckwick and Pawan in 1956 reported studies which they interpreted as supporting the concept that diets containing proportionately more fat than carbohydrate were associated with greater weight loss.* They pursued From Institute for Metabolic Research, Highland-Alameda County Hospital, Oakland, California Recetced for publication Nov. 27, 1963 195 Meranoussat Vou, 13, No.3 (Manca), 1964196 INSEL ET AL. ccatonies po count renter neon of ace-25 noneuTy wane re an 280 Become Bons : ee : = ane © 200 we | Fig, 2.—The const ‘under conditions of co ‘Tho studies extended covered atleast 1 day Food was supplied en . was consumed at 2 how rid solids or elem Fig. L_—Drastic changes in the dietary mitre in this young obese male were Sant amounts of erential not astociated with changes in rate of weight loss, 30 long at calories remained "The types of fats se constant. The initial rapid rate of weight los inthis and other individuals i atribut- and carbohydrate able to uid mobilization, in addition to eval voce a Se the subject further in a later report! Unfortunately, all of their metabolic Tn some patients, blo ! periods were of such short duration that the results have litle in the way ‘Activity was essential | of interpretable meaning from the standpoint of long-term weight loss. In view of the existing confusion, and the unsupported claims made for the virtues of high fat diets in material directed toward the laity, it seemed pees worthwhile to carry out a study which would attempt to place this matter ee Die eMee ues were essentially non Meruons ward was 270 poun Five subjects have een studied, Four were gros obese. One was slighty overweight His calorie intake “The sgniennt linia features of each patient wl be described ily. tein intake varied frXINSELL ET AL. young obese male were 1g as calories remained er individuals is attribut- all of their metabolic nave little in the way -rm weight loss. ted claims made for d the laity, it seemed t to place this matter » was slightly overweight. ely. ‘CALORIES DO COUNT 197 tee | i. i 2 ° 2 no) ON. eon et oo E2004... “ . me ; . rca 60 Bae oa DAYS, Fig. 2—The constancy of rate of weight loss in each of the 4 obese individuals under conditions of constant caloce intake, regardless of dietary mixture, is apparent. ‘The studies extended over pericds of from 65 to 77 days. Individusl dietary periods ‘covered at Ieast 21 days and frequertly 4 or more weeks. ‘Food sras supplied entirely in the fonn of quantitatively constant formula diet which ‘vas consumed at 2 hour intervals throughout the day, Protein was derived from defatted Inild solids or ealeium caseinate. The formulas were very adequately fortified with con Slant mounts of essential vitamins end mninerals. “The types of fats used aro indicated in the Bgures, as are the amounts of protein, fat and carbohydrate. ‘fn addition to evaluation of weight changes, all subjects were followed with regard to levels of plasinaglycerides® cholesterol and phospholipid? In some patients, blood sugar ketones® and nitrogen balance were also determined “Activity was essentially constant at all times during the study Resuuts Patient HCOR, was a young adult male, aged 25, who had been grossly obese since childhood. His only complaint other than obesity, was moderate dyspnea on exertion. History, physical, laboratory and roentgen findings \were essentially noncontributory. His weight on admission to the metabolic ward was 270 pounds (ideal weight was approximately 180 pounds) ‘His caloric intake was constant throughout at the 1,200 calorie Tevel. Pro- tein intake varied from 25 ta 35 per cent of total calories, fat from 13 to 52198 INsE Table 1.—Dictary Intakes on the 4 Patiente Maintained on Weight Loss Regimens 20h eaieee 1a00earie Seed cien wes ae saan pans Pom sg eet. at Bet aise Beso Fon te F@le Be | FO) ae Fa ae CHO Ge CHO tem HONIG Hime © CHOMINS eG oyna "wee ortaors Por) pee ey | Ce ee Pays 8 Fa) ase Fora ive Pas aT cho ig GHOMie tam Choe! 2 CHOTE awe ereraps nyse wavs esas Pare Poni | ror | reg) Fe) Se = F@)—In Ge FS ss ws FEISS ST cmOa %m% -CHOMS 1% GHO—ee 30g CHOSE Fike final (fourth) period Gn tia patent wan Hetil with the frat perils with rsard to aitany (i) = eter fat (8) = Suttower ot pet cent, and carbohydrate from 15 to 62 per cent. His dietary, weight and plasma lipid data are shown in figure 1. The actual amounts of protein, fat and carbohydrate consumed by each patient during each dietary period are shown in table 1. The weight loss patterns in the 4 grossly obese indi- viduals throughout the entire study are summarized in figure 2. ‘As is frequently the case, during the first week of low calorie intake the weight loss was very rapid, due to mobilization and excretion of fluid. After a steady state had been achieved, the rate of weight loss thereafter was essentially constant, regardless of the type of diet. Plasma lipids (which were in a “normal range” throughout) after an initial fall, fluctuated only to a modest degree. He was essentially in nitrogen equilibrium throughout the study. Patient MNIX was a 42 year old Negro premenopausal noninsulin depen- dent diabetic female, Diabetes was discovered 12 years previously in the course of @ routine examination, Her diabetes had been under fair control with diet (which she followed poorly), tolbutamide and “DBL.” Except for 4 few microaneurysms in each eye, cardiovascular findings were essentially \within normal limits. Except for obesity (present many years) and diabetes, hier history, physical, laboratory and roentgen findings were essentially non- contributory. Weight on admission to the study was 227% pounds (ideal weight was approximately 150 pounds) The pertinent findings in this patient are shown in figures 2 and 3 and table 1. She was maintained on a 1,200 calorie regimen throughout. Her pro- tein intake varied from 14 to 34 per cent of total calories, fat from 13 to 83 per cent, and carbohydrate from 3 to 60 per cent. Weight loss during the study (except for the fist few days) was essentially constant at all times Plasma lipids followed much the same general pattern as in the previous patient, Blood suger, as one might expect, was lowest during the period of very low carbohyclrate, high unsaturated fat intake (at which time the Ketones were Fig. 3.—In this obese mixture. elevated). She was in except during the tim total calories, at which Patient GMIT was 3 seizures present for | normality. Ventriculog sive medication. Mild Obesity had been pre history, physical, labo: At the time the stud: ight was approxima Alter the first 2 wem Weight Lose Regimens fee sreana ee Banas ite wae Hoe t. His dietary, weight ual amounts of protein, ng each dietary period e-4 grossly obese indi 1 igure 2. low calorie intake the excretion of fluid. After sht loss thereafter was sma lipids (which were 1, fluctuated only to a ibrium throughout the yusal noninsulin depen- cars previously in the yeen under fair control and “DBI.” Except for lings were essentially ry years) and diabetes, s were essentially non- ; 227% pounds (ideal n figures 2 and 3 and n throughout. Her pro- ries, fat from 13 t0 83 Weight loss during the “constant at all times sm as in the previous uring the period of very n time the Ketones were ‘CALORIES DO COUNT: 199 . .—In this obese diabetic, weight loss is a function of ealories, not of dietary nixture. elevated). She was in approximate nitrogen equilibrium throughout the study except during the time her protein intake represented only 13 per cent of total calories, at which time she had a slightly negative nitrogen balance. Patient GMIT was a 60 year old white female with a history of epileptiform seizures present for I2 years. An electroencephalogram showed some ab- normality. Ventriculograms were normal. She was maintained on anticonvu sive medication. Mild noninsulin-dependent diabetes was diagnosed in 1962. Obesity had been present for many years. Except for the preceding findings, history, physical, laboratory and roentgen findings were within normal limits At the time the study was undertaken her weight was 199 pounds (ideal ‘weight was approximately 13¢ pounds). After the first 2 weeks of the study, her intake was maintained at a level200 KINSELL ET AL. ramin-caer 9) ace59 i pee aig = cores Fa + _ a3 Fig. 4 Changes in I ipids may be a function of diet, weight loss, or both. of 850 calories (fg. 2 and 4, table 1). Protein intake varied from 24 to 35 pper cent of calories, fat from 12 to 35 per cent, and carbohydrate from 30 to 64 per cent. Rate of weight loss was essentially constant throughout. She was in nitrogen equilibrium or slightly negative nitrogen balance during the study. Fasting blood sugar levels were essentially constant. Glycerides were moder- ately elevated at all times, Cholesterol was significantly lower during the periods of unsaturated fat intake. Patient RTEA was a 26 year old Negro female with a history of resection of a cystic chromophobe adenoma of the pituitary in 1959, followed by radiation, (Some optic nerve damage was present.) Obesity had been present for many years, Except for the findings noted, absent menses and subnormal ‘urinary gonadotropins, her history, physical, laboratory and roentgen findings were within normal limits. At the time the study was undertaken, her weight i £38 z58 oe Fig, 5.—In this subje during the high fat, his apparent that the “stair for this finding. was 211% pounds (ic ‘Throughout the st table 1). Protein inta from 12 to 37 per cent loss was greater durin during either of the significance in view 0 ‘All of her plasma li rated fats, This may, k loss rather than diet y Patient GTAY was for more than 20 yes maintained in satisfac fasting plasma was di for coronary and peri partial removal of a g her stay in the metab ‘The study in thisr to the other subjects. oth varied from 24 to 35 sbohydrate from 30 to it throughout. She was lance during the study. ycerides were moder- ntly lower during the \ a history of resection in 1959, followed by sity had been present menses and subnormal and roentgen findings indertaken, her weight ‘CALORIES DO COUNT 201 DIET PATIENT=RTEAgAGE-24 CALORIES PER OY OF PITUTARY TUMOR 4/s0/e@-7/8/68 rar Mosrecrecrare 200 ele” 238 he a baa BE Bd3 Bes gig! |v eda seo, some suggestion of increased rate of weight loss imake. However, if one refers to figure 2, itis apparent thatthe “Staircase pater” of weight loss may and probably does account fortis nding ® was 211% pounds (ideal weight was approximately 135 pounds) Throughout the study calorie intake was constant at 800 (fig. 2 and 5, table 1). Protein intake varied from 25 to 36 per cent of total calories, fat from 12 to 37 per cent, and ca-bohydrate from 27 to 63 per cent. Rate of weight loss was greater during the last 2 weeks on high fat, high protein intake than during either of the other 2 dietary periods. This probably does not have significance in view of the “stair case pattem” of weight loss (see fig. 2). ‘All of her plasma lipids were somewhat lower during the intake of unsatu- rated fats. This may, however, be attributable to factors associated with weight loss rather than diet per se. Patient GTAY was a 61 year old white female with a history of diabetes for more than 20 years. She had received insulin in the past but could be maintained in satfsfactory diabetic control with diet and tolbutamide, Milky fasting plasma was discovered in July 1962. Other findings included evidence for coronary and peripheral a:herosclerosis, and diabetic retinopathy. She had partial removal of a goiter 40 years ago, but was essentially euthyroid during her stay in the metabolic ward The study in this patient was actually directed toward evaluation of her— 202 MINSELL ET AL. moat 9 ates vymenet Fig. 6.—Eucalorie diets with vastly different qualitative-quantitative composition are not associated with diflerential weight patterns. The significance of the lipid patterns inthis patient require clarification hyperlipidemia, but she is included in this report since she was maintained on quantitatively constant, eucaloric regimens containing high fat and high carbohydrate, respectively, and also received both saturated and unsaturated fat (fig, 6). On a hypocaloric regimen, weight loss occurred in a predictable fashion. On a nearly eucalorie regimen, the weight pattern was essentially identical whether the diet contained (as calories) 74 per cent of carbohydrate and 85 per cent of fat or 12 per cent of carbohydrate and 71 per cent of fat. Saturation or unsaturation of fat also appeared to be essentially unrelated to the weight pattern, Her weight at the mid-point of the high carbohydrate intake was 135% pounds and almost 2 months later, at the end of the high fat regimen, was 134% pounds. Plasma lipids and blood sugar after a pre- ‘CALORIES DO COUNT cipitous fall during | modest degree during From the foregoing constancy of ealoric i tive modification of t carbohydrate, and am of weight loss. ‘This obesity and to obese tions which occur din that data from short-t sources can be totally All of the above st regimens. To provide isocaloric intake, a st and kinds of fat were appeared to bear no caloric intake remaine None of the forego protein diets may not prevent weight gain to believe that the s carbohydrate and low adherence. Unfortuns sive eating tend to go greater satiety value ¢ 1, Penni ton, A Wes weight reducing di Mod. J. 23:79, 1951. 2. —: Pynwic acid met ‘Am. J. Digest Dis. 3. Keckwick, A, and I (Calorie. intake in weight changes in 2:15, 1956, 4. =) and 2 Metabo obesity with so-ca fat, protein and ca colin 6:47, 1957 5, Michaels, G. Dir A 1 termination of gly ty acids. Metaboli 6. — Fukayama, G., ‘Wheeler, P.° Techn plasma cholesteroljantitative composition ignificance of the lipid he was maintained on ; high fat and high ated and unsaturated ured in a predictable atten was essentially -cent of carbohydrate nd 71 per cent of fat. sentially unrelated to ne high carbohydrate t the end of the high od sugar after a pre- CALORIES BO COUNT 208 cipitous fall during the initial period of weight loss, changed only to a ‘modest degree during the remainder of the study. Discussion From the foregoing, it appears obvious that under conditions of precise constancy of caloric intake, and essentially constant physical activity, qualita- tive modification of the diet with respect to amount or kind of fat, amount of carbohydrate, and amount of protein, makes little or no difference in the rate of weight loss. This statement applies to patients with simple exogenous obesity and to obese noninsulin-dependent diabetics. In view of the fluctua- tions which occur during the course of any weight loss regimen, it is obvious that data from short-term studies such as those previously reported from other sources can be totally misleading All of the above statements refer to studies carried out with hypocaloric regimens. To provide additional controlled data under conditions of nearly ‘socaloric intake, a study is included in which drastic modifcations in amount and kinds of fat were employed. As in the previous studies, weight changes appeared to bear no relationship to such changes in nutrients, so long as the calorie intake remained constant ‘None of the foregoing is intended to suggest that relatively high fat, high protein diets may not have certain desirable features in regimens designed to prevent weight gain or to produce actual weight loss. There is good reason to believe that the satiety value of such diets is superior to diets high in carbohydrate and low in fat, ard hence, may be associated with better dietary adherence. Unfortunately, many obese individuals with a pattern of compul- sive eating tend to go on “carbohydrate binges,” regardless of the theoretically greater satiety value of a high fat regimen. REFERENCES 1. Pennington, A. W.: The use of fat in a nation of todine valve, and of cho- weight reducing diet. Delaware State Testerol. Proc, Soc. Exp. Biol. Med. Med. J. 23:79, 1951, 2, —: Pyrovie acld metabolism in obesity ‘Am, J. Digest Dis. 22:33, 1985. 3. Keckwick, Ay and Pawan, G. L. S. Calorie intake in. relation to body weight changes in the obese. Lancet 25155, 1956, and —: Metabolic study’ in human ‘bosty with Iso-eloric diets high in fat, protein and carbohydrate. Metab coli 6:447, 1957. 5. Michaels, G. D.: A method for the de- termination of glycerides and froe fat- ty acids. Metabolism 11:833, 1902, 6.—, Fokiyama, ©, Chin, H. P., and Wheeler, P.: Technic for separation of plasma cholesterol esters for determi- 198:826, 1958, 7. Youngbutg, G. E, and Youngbursy M. Vii Phosphorus metabolism. T. System of blood phosphorus analysis. J. Lab. ‘Clin, Med, 16:158, 1950. 8, Technicon Auto Analyzer Methodology for Determination of ‘Total Glucose ‘Techmnicon Laboratory Method file rev 2-11-60. Technicon Instruments Corp oration, Chauncey, New York 9, Michael, G., Margen, S., Liebert, C., ‘and. Kinsell, L. Was Studies in fat metabolism, I. The colorimetric de termination of ketone bodies in bio- logical fvids. J. Clin. Invest. 90:1489, 1951204 Laurance W. Kinsell, M.D., The Institute for Metabolic Re- search, Highland-Alameda County Hospital, Oakland, Calif. Barbara Gunning, Ph.D., The Institute for Metabolic Research, Highland-Alameda County Hospital, Oakland, Calif. George D. Michaels, Ph.D., The Institute for Metabolic Re- search, Highland-Alameda Gounty Hospital, Oakland, Calif. James Richardson, M.D., The Institute for Metabolic Re- search, Highland-Alameda County Hospital, Oakland, Cali. Stephen E. Cox, M.D., The Institute for Metabolic Research, Highland-Alameda County Hospital, Oakland, Calif. Calvin Lemon, M.D., The Institute for Metabolic Research, Highland-Alameda County Hospital, Oakland, Calif A Method | Exeha By J. M. Kiwney, Many problems of curr physiologie interest cou ‘a method were availab ‘change together with t pired radioactivity fol istration of tracer am« foodstuffs. Equipment} to collect and. record patient's expired CO, OME OF THE M Hism relate to th ergy exchange, Many could be explored if of over-all gas excha following the adminis The knowledge of of energy expenditur for measurement of v exchange. According determine the compo by measuring the int cretion of nitrogen. ' an evidence of thyroi a brief measurement the need to measure importance of measu has Ted to similar ef tions of such method: acutely ill patients. 4 change in ambulatory developed and used ‘From the Department Hospital ond The Gener ‘This work was suppor ‘mand under Research C the National Inatitutes 0 Received for publat