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THE AMERICAN JOURNAL or CLINICAL NUTRITIONVol.21, No. 11, November, 1968, pp. 1291-1301

Printed in U.S.A.

Fat, Carbohydrate, Salt, and Weight Loss

Further Studies12

WALTER M. BORTZ, M.D.,3 PAULA HOWAT, B.S., M.P.H.,4 ANDWILLIAM L. HOLMES, PH.D.5

T HE INCONSISTENT RATE of weigimt loss is asource of confusion to dieters. Weight

plateaus are frequently observed and arediscouragiimg. Obviously a number of fac-tors could be responsible. A variance intime number of daily calories is the mostfrequent explanation. However, timere areotimer 1)055i1)ilities. Hormonal anti physicalactivity l)atterns (1) are influential; Smithalmd Drenick (2) imave simown time effect ofcimanging time level of dietary salt; and anumber of workers (3-6) Imave been in-trigued with time idea that varying time con-stituencv of tlailv calories may be respon-sil)ie. \\Te have recently reported a tietailedstudy (7) 1)erformed on the MetabolicWard iim mvlmiclm dietary fat and carbohy-drate weie interchanged isocalorically andexclusively in time presence or absence of agiven amount of added salt. In that studyall diets contained 40 g protein/day. Weconsidered it possible that some of theobserved tlifferences between time fat andcarbohydrate periods were due directly togluconeogenic nmeclmanisms activated by thenoncarboimydrate, low protein, lmigh fatdiet or were coupled in some way to timesemecimanisms. It also seemed possible timatproviding lmiglmer levels of dietary protein

From time Division of Research, Lankenau Hos-pital, Philadelphia, Pennsylvania.

Supported b- National Institutes of HealthGrant AM-08887.

Research .-ssociate, Division of Research, andAssistant, Department of Medicine. Formerly Re-search Assistant, Division of Research. Director,I)ivision of Researcim.

nmay offset such effects. In addition we be-came interested, as imave others (8), in timecapacity of time body to conserve its nitro-gen content wimen confronted with a severecalorie restriction. Timerefore, we felt it wasof interest to extenti our earlier study tosimilar observations of (liets isitim Imigimerprotein content.

EXPERt MENTAL

The general protocol of the study was nearlyidentical to time previous one (7). Time nine sub-jects (five mets, four women) were 19-34 yearsold; all but two weigimed more timan 300 lb. atthe start of the project; all were free from conm-plicating disease. Aside from two 3-hr passes/week, the subjects were confined to the Meta-bolic Ward. They were not permitted any physi-cal activity other than time usual sedentary wardactivities.

The initial diet was one designed to maintainweight. All feedings were given iim a liquid for-mula diet (9) providing 80 g or 120 g protein/day. The remaining calories were fat (to 35%of time total calories) and carbohydrate. Follow-ing this stabilization formula timat was usually

fed for a period of 2-3 weeks, calories were re-duced to 800 kcal for the rest of time study. Insix subjects, in the first hypocaloric period, fatand carbohydrate were reduced in proportion totheir percentage in the high calorie diet. Thisperiod was contilmued until weigimt loss becamerelatively constant. Following time control pe-riods, time subjects were placed on 24-day dietscontaining 40 to 60% protein; time remainingcalories were made up of fat or carbolmydrate totime total exclusion of time other. 1mm seven of time

studies 4 g NaCl and 3 g KC1 were used; in time

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6TECalories 4400 *

CHO 663Diel FAT 169

PRO 80

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395

385

375

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Subj N SCalories

CHODiet FAT

PRO

340

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310

300

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6 Supplied as Casec by Mead Johnson Labora-tories, Evansville, Indiana

Coories 3300

CHO 469Diet FAT 32gin PRO 80

304

294

284

274

264

254

244

FIGS. 1-4. Daily weight loss on 800-kcal diets without added NaCI or KC1.

otimer studies no sodium or potassium was added,and chenmical analysis of these diets showed ap-proximriately 100 mg sodium and 180 mg potas-

siunm per total daily feedimmg. The basic ingre-dients of the diet were purified powderedcasein,6 sucrose, cornstarclm, corn oil, and butter.Artificial flavorings were added to improvetaste. The diets were analyzed chemically forprotein content. The subjects were weigheddaily before the first feeding.

Every 6 days venous blood was collected andanalyzed for free fatty acids (10), triglycerides

(1 1), and cholesterol (12). Correspolmding urinecollections were made and measured for urinary

nitrogen (13), sodium (14), and potassium (15).In five experiments, levels of urea mmitrogen (16)and ammonia mmitrogen (17) were also deter-milled. Urinary creatinine was nmeasured as a

check on completeness of collection (18). Pe-riodic measurements of oxygen consumption andcarbon dioxide production were made and res-piratory quotients determined (19).

RESULTS

Figures 1-4 slmow weigimt response to al-terations in dietary carbolmydrate anti fat


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Fat, Carbohydrate, Salt, and Weight Loss 1293

in time absence of added sodium. In con-firmation of the results of our previouspaper, after initial rapid weight loss, therate of weight loss was essentially linearwitim time and independent of the sourceof calories.

Figures 5-1 1 show weight response to thepresence of added sodium and potassium.Whereas time results are grossly similar tothose above, in six of the seven subjectsstudied timere was a period of weight stabi-lization following introduction of time car-boimydrate formula and a period of rapidweigimt loss upon reinstitution of time fatdiet.

Subject CC imad been a subject in ourearlier study, anti time results in the presentstudy (Figs. 4-6) are comparable to those,except that time fluctuations in weight areof a lesser degree.

In Figures 12-18 the sodium, nitrogen,and potassium balances in the subjects re-ceiving mineral supplements are shown.Time first parts of time high fat diet periodsare characterized generally by sodium loss,as iim time initial mixed-diet period. Con-versely, the early carbohydrate periodssimow sodium retention. It should be em-pimasized, imowever, as previously observed,that these changes are self-limited, as othersodi tim-sensitive homeostatic mechanismsovercome the nutritional effect. One canimagine a crude sine-wave curve, extendingthrough all time sodium data, which be-comes offset by dietary changes. Changesin urinary potassium appear to bear arougim correlation with urinary sodium.Body weigimt cimanges seem to be related totime urinary sodium fluctuations.

Figures 19-22 represent the nitrogen bal-ances in those subjects to whose diet nominerals were added. All subjects demon-strateti an amazing capacity to stay nearnitrogen equilibrium despite marked calo-rie restriction. This was particularly evi-dent during time high carbohydrate dietperiods.

More definitive analyses of urinary ni-

trogen content were made in five subjects(Table i). In all, total urinary nitrogenexcretion was highest during time initialhypocaloric period. There was higimer ni-trogen excretion during time fat periodsthan during the carbohydrate periods (seebar graphs, Figs. 12-22), particularly in the80-g protein formula diet studies.

Serum lipid values show higher free fattyacids and lower triglycerides on the highfat diet, althougim the latter difference isnot statistically significant (Table mm). Onboth formulas the serum clmoiesterol wasextremely low.

The average respiratory quotient of allsubjects on time stabilization diet was 0.85;on time carbohydrate diet, 035; and on thefat diet, 0.73.

DISCUSSION

The roles of dietary carbohydrate andfat in a host of metabolic events are theobject of intense study. It imas been shownthat modifications of diet are of criticalimportance to serum lipids (20), body wa-ter and electrolyte balance (21), hormonallevels (22), and body composition andweiglmt (23).

Recently we reported the results ofstudies (7) in a group of obese subjects inwhich fat and carbohydrate were switchedisocaioricaliy witimin an 800-kcal formuladiet. The data of the present study con-firm those of our earlier report and bringfat-carbohydrate interclmange experimentsto a total of 22. The higher protein contentof tlmis study did not affect the prior con-cltmsion that any difference in time rate ofweight loss between fat and carbohydrate-containing diets was due to the sodium-and fluid-retaining capacity of dietary car-bohydrate. Katz et al. (24) have reportedthat protein was as effective as carbohy-drate in the reversal of salt loss due tofasting. Our stutiies, however, indicate thatregardless of time level of protein intakedietary carbohydrate appears to mediatesodium retention. This confirms an earlier


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Fat, Carboimydrate, Salt, and Weight Loss 1297


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FIGS. 19-22. Effect of dietary fat and carbohydrate interchange on urinary nitrogen. The x-axis representsthe equilibriunm between nitrogen intake and urinary excretion.

1298


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The data represent the averages of the bloodsamples obtained every 6 days during the dietaryperiods and their standard errors.

a Numbers in parentheses are the number of 24-day dietary periods represented by each value.

TotalUrinaryN, g/24

hr

11.117.214.012.6

Urea N,g/24 hr

8.8812.93

9.668.20

Am-monia

N, g/24hr

0.821 .061 .650.96

1.151.191 .251 .34

Coeati-nine N,g/24 hr

0.710.740.710.58

0.590.690.510.54

a Data represent the averages of all urinary

nitrogen values obtained in 1 to 6-day collectionsduring the appropriate deitary periods.

Un-account-ed for N,g/24 hr

0.692.471 .982.86

2.212.782.392.01

16.1112.1619. 7215 .06

l9.0714.92l8.53l4.64


The data represent averages of values of urinecollections for the respective dietary periods.

report of Bloom (21) that indicated timespecificity of carbohydrate in this regard.In sum: essentially, over a long period ofweight loss, a calorie is a calorie.

Table iii illustrates urimmary nitrogen ex-cretion figures derived from the presentstudy and our earlier one. To relate theseexcretion values to protein intake, one usesthe figure 635 g protein/ 1 g nitrogen antiderives the figures 6.3, 12.6, and 18.9 as timegram per day nitrogen intake for the 40-,80-, and 120-g protein studies, respectively.It is apparent, then, timat during all carbo-hytirate periods, nitrogen balance ap-proaches equilibrium. During the fat-dietperiods there was a slightly more negativenitrogen balance on the lower protein in-take than on the higher, but the differenceis not striking. Tlmis has previously beendemonstrated by Keys et al. (25) in theirclassic experiments on senmistarvation.

TABLE I

Urinary nitrogen excretion in the different______________dietary periods

Subjects NW andVB (80-gprotein in-take)

DietStabilizationMixedFatCarbohy-

drateSubjects CC, GS,

and PP(120-g pro-tein intake)

DietStabilizationMixedFatCarbohy-

drate

TABLE II

Effect of dietary fat-carbohydrate inter-change on serum lipid levels

Diet N5FFA,onEq/liter

Trigly-cerides,

mg/100 aol

Cho-lesterol,

mg/100 ml

Fat

Carbohydrate

(12)

(14)

0.92 0.090.68 0.06

99.4 11.8118.4 18.4

136.4 7.4

141.0 8.2

TABLE III

Total urinary nitrogen excretion as relatedto protein intake and fat-carboimydrate

interchange

N Intake,g/24 hr

Urinary N,g/24

40-g protein diet studiesFat periods 6.3 8.5Carbohydrate periods 6.3 6.2

80-g protein diet studiesFat periods 12 . 5 13.9Carbohydrate periods 12 .6 11 .3

l20-g protein diet studiesFat periods 18.9 19.1Carbohydrate periods 18.9 18.5

Acknowledging an additional fecal in-trogen loss of 1-2 g/day, it is apparent thattiespite the marked calorie restriction oursubjects were in only slight negative nitro-gen balance. Time significance of this ob-

servation, on the fat diet particularly re-lates to time obligate glucose requirementof brain which is said to be about 200g/day for humans (26). Body carbohydratestores are extremely limited anti obviouslycannot sustain any prolonged glucose need.During our fat-diet periods, time subjectsreceived no dietary carbohydrate at all; yet


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their nitrogen excretion exceeded intakeby only a small amount. Under these die-tary conditions, therefore, one must con-dude either that brain and other glucose-dependent organs do not require as muchglucose as proposed, or that glucose is be-ing formed by processes as yet uneluci-dated. Cahill et al. (27) have shown thatpotential gluconeogenic substrates othertiman protein (i.e., glycerol, pyruvate), gen-erated during calorie privation, cannotprovide sufficient substrate carbon for thesupposed glucose requirement. Wrenshallet al. (28) have reported that glucose pro-duction as calculated from the urinary ni-trogen content gives erroneously low fig-ures for this process when compared toglucose production as estimated from theglucose-14C turnover data. Tlmey suggest

time possibility of glucose formation fromanother major source, which by implica-tion is body fat. Alternatively, Owen et al.(29) have documented the oxidation ofketone bodies by human brain during star-vation. A study in vitro in our laboratoryon brains of starved rats, however, did notdemonstrate preferential use of ketonebodies over glucose by time brain, even af-ter a period of ketosis (30).

Whatever the reconciliation of time mi-nor urinary nitrogen loss and the supposedglucose need, the body demonstrates itswisdom in conserving its nitrogen sub-stances from use as an energy substrate.

The bulk of the total urinary nitrogenunder our feeding conditions is urea nitro-gen. Change in one is directly reflectedby a change in the other. A smaller per-centage of time urinary nitrogen is presentas ammonia nitrogen. Under conditions oftotal starvation Owen et al. (31) haveshown that ammonia is the major nitroge-nous excretory product. Ammonia repre-sents a byproduct of transamination reac-tions that yield three- and four-carbonskeletons for glucose formation. It also rep-resents a potential cation cover for the in-creased organic acid excretion observed dur-ing starvation or during our dietary fat

periods. In our two studies on subjects onthe 80-g protein diet, urinary ammonia wasdistinctly Imigher during the fat-formulaperiods. This was not observed in the stud-ies on subjects on the higher protein in-take. Ketosis (as judged by quantitativeurinary ketones in several random urinespecimens) was less marked in subjects onthe higher protein diets. Whether thesetwo observations bear a cause and effectrelationsimip is unknown. The increasedsodium excretion noted during the earlypart of the fat-tiiet period has also beenimplicated (32) as a cation cover for ele-vated organic acids.

SUMMARY

Eleven studies were perfornmed on nineobese subjects. Fat and carboimydrate wereinterchanged in an 800-kcal constant-pro-tein diet. No difference in rate of weightloss was noted apart from that attributableto alterations in sodium- and fluid-balancedynamics. Nitrogen excretion was remark-ably low on all regimens. These resultsconfirmed those from our previous studiesinvolving a lower protein intake.

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energy balance of obese high school girls. Am.I. Gun. Nutr. 4: 37, 1956.

2. SMITH, R., AND E. J. DsiNIcK. Changes in bodywater and sodium during prolonged starvation

for extreme obesity. Clin. Sci. 31: 437, 1966.3. ANDERSON, A. B. Loss of weight in obese patients

on submaintenance diets and the effect of varia-

tion in the ratio of carbohydrate to fat in thediet. Quart. J. Med. 13: 27, 1944.

4. KEKWICK, A., AND G. L. S. PAWAN. Metabolicstudy in human obesity with isocaloric diets highin fat, protein or carbohydrate. Metab. Clin.Exptl. 6: 447, 1957.

5. PENNINGTON, A. W. A reorientation on obesity.New Engi. J. Med. 248: 959, 1953.

6. LYON, D. M., AND D. M. DUNLOP. The treatmentof obesity. A comparison of the effects of dietand of thyroid extract. Quart. 1. Med. 1: 33,1932.

7. BORTZ, \V. M., A. WROLDSEN, P. MORRIs AND B.ISSEKUTZ, JR. Fat, carbohydrate, salt, and weightloss. Am. J. Clin. Nutr. 20: 1104, 1967.


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8. STRANG, J. M., H. B. MCCLUGAGE AND F. A. EVANS.Nitrogen balance during dietary correction ofobesity. A,n. J. Med. Sci. 181: 336, 1931.

9. BORTZ, W. M., A. WROLDSEN, B. I5SEKUTZ, JR. ANDK. RODAHL. Weight loss and frequency of feed-ing. New Engi. J. Med. 274: 376, 1960.

10. DOLE, V. P., AND H. MEINERTZ. Microdetermina-tion of long chain fatty acids in plasma and tis-sues. J. Biol. Chem. 235: 2595, 1960.

1 1. VAN HANDEL, E., AND \V. ZILVERSMLT. Micro-metimod for the direct determination of serumtriglycerides. J. Lab. Clin. Med. 50: 152, 1957.

12. ABELL, L. L., B. B. LEVY, B. B. BRODIE AND F. E.KENDELL. Simplified method for estimation oftotal cholesterol in serum and demonstration ofits specificity. J. Biol. C/tern. 195: 357, 1952.

13. NIEDERL, J. B., AND V. NIEDERL. Micromethods ofQuantitative Organic Analysis (2nd ed.). NewYork: \\Tiles- 1942, 347 pp.

14. Adapted from BERRY, J. W., D. G. CHAPPEL ANDR. B. BARNES. Improved method of flame pho-tometry. hid. Eng. Chen. 18: 19, 1946.

15. MACINTYRE, I. Flame photometry. In: Advancesin Clinical Chemistry, edited by H. Sobotka andC. P. Stewart. New York: Academic, vol. 4, 1961.

16. AutoAnalyzer Method File N-lc. Modification ofmethod of W. H. Marsh, B. Fingerhut and H.Miller. Ardsley, New York: Technicon Corp.

17. HAFF, A. Modification of the method of A. Kap-lan. In: Standard Methods of Clinical Chem-istry. New York: Academic, 1965, vol. 5, p. 245.

18. Medical and Public Health Methods: Successorto Fifth Edition of Laboratory Methods of theUnited States Army (6th ed), edited by J. S.Simmons and C. J. Gentzkow. Philadelphia: Lea& Febiger, 1955, p. 844.

19. Procedure for calculating RQ. Deift, Holland:Kipp Analyzer.

20. MCGANDY, R. B., D. M. HEG5TED AND F. J. STARE.Dietary fats, carbohydrates and atherosclerotic

vascular disease. New Engi. J. Med. 277: 186,1967.

21. BLoosi, \V. L. Inhibition of salt excretion bycarbohydrate. Arch. Internal Med. 109: 26, 1962.

22. KREISBERG, R. A., B. R. BOSHELL, J. DI PLACIDOAND R. F. R0DDAM. Insulin secretion in obesity.New Engl. I. Med. 276: 314, 1967.

23. GRANDS, F. Energy balance and body compositionchanges. Ann. Internal Med. 68: 467, 1968.

24. KATZ, A. I., D. R. HOLLINGSWORTH AND I. H. Ep-STEIN. Renal sodium excretion during fastingand refeeding. Clin. Res. 15: 361, 1967.

25. KEYS, A., J. BR0ZEK, A. HEN5CHEL, 0. MICKELSENANI) H. L. TAYLOR. The Biology of Hutnan Star-vation. Minneapolis: University of MinnesotaPress, 1950, vol. 1, p. 381.

26. KETY, S. In: Metabolism of the Nervous System,2nd Intern. Neurochem. Symp., edited by D.Richter. New York: Pergamon Press, 1957, p.221.

27. CAHILL, G. F., M. G. HERRERA, A. R. MORGAN,J. S. SOELDNER, J. STEINKE, P. L. LEVY, G. A.RIOICHARD AND D. M. KIPNIs. Hormone-fuel in-terrelationships during fasting. I. Clin. Invest.45: 1751, 1966.

28. WRENSHALL, G. A., J. S. COWAN, G. HETENYI,A. M. RAPPAPORT, A. KUK5I5, E. M. PAUL ANDM. VRANIC. Tracer determined glucose produc-

Lion versus nitrogen excretion in fasting normal

and depancreatized dogs. Diabetes 16: 507, 1967.29. OWEN, 0. E., A. P. MORGAN, H. G. KEMP, J. M.

SULLIVAN, M. G. HERRERA AND G. F. CAHILL, JR.Brain metabolism during fasting. J. Clipz. Invest.46: 1589, 1967.

30. OlENsHAw, H., AND W. BORTZ. Oxidation of glu-cose, acetoacetate, and palmitate in brain mince

of normal and ketotic rats. Diabetes 17: 90,1968.

31. OWEN, 0. E., J. WAHREN, P. FELIG AND G. CAHILL.Changing patterns of gluconeogenesis duringprolonged starvation. Clin. Res. 16: 348, 1968.

32. ACKERMAN, J. P. Aldosterone secretion and na-tritlresis of total fast in obese subjects. Clin Res.12: 261, 1964.


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