sar disease: the Framingham study. In S1, London: Churchill Livingstone. rt Siease. A study ofrskfactors in 400 viet and coronary heart disease: dictary International Journal of Obesity (1981) 5, 31-236. Metabolic effects of substituting carbohydrate for proteinina low-calorie diet: a prolonged study in obese patients Mei-Uih YANG, Jose L. BARBOSA-SALDIVAR, F. Xavier PLSUNYER and Theodore B. VAN ITALLIE Obesity Research Center, Medical Service, St. Luke’s-Roosevelt Hospital and Department of Medicineand Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, N.Y., USA. Summary Obese individuals maintained for 64 days on either of two low-calorie dicts (600-800 kcal/day), consisting of protein alone or protein plus carbohydrate, varied widely in the extent of their cumulative nitrogen deficits. Rates of weight loss showed little correlation with rates of nitrogen loss after the first 28 days of the study. The low-calorie diet consisting entirely of protein increased blood g-hydroxybutyrate concentrations far more than did a diet consisting of equal parts of protein and carbohydrate. The diet which consisted lmost entirely of protein did not spare body protein better or induce a greater fate of weight loss than did the mixture of protein and carbohydrate. introduction For the last ten years, severe obesity has often been treated by means of very- lowscalorie (VLC) diets, a procedure sometimes referred to as “supplemented fisting,” A frequently used regimen is a very-low-calorie diet consisting fatirely or almost entirely of protein. Some workers have claimed that this ict is particularly effective in promoting fat loss while sparing body otein'~ % *. However, the metabolic effects of such hypocalorie protein iets used for prolonged periods deserve further scrutiny; in addition, more idies need to besslone in which VLC protein diets are compared with other its of similar caloric value but of different composition. We describe here tain metabolic responses obscrved in obese patients consuming low-calorie iets consisting of cither protein alone or a mixture of protein and carbo- ydrate. thods x obese but otherwise healthy males were studied on a metabolic ward for days. Their ages ranged from 19 to 33 years. Table 1 gives the heights and 231Table 1, Six male subjects (ages 19-33 yr}. *Percent of average desirable weight” Diet Admission Rolati ‘weight weight (kg) (3) Protein DP. 173 152 219 uw. 7 148, 196 Te. 173 135 199 ProteincHO De. 73 149 24 cs. 187 178 27 t SM. 180 143 188 weights of these subjects. Body weights on admission ranged from 135 to 178 kg, representing 188 to 219 percent of the average desirable weight standards recommended by the Metropolitan Life Insurance Company’. Subject D.P. was studied on two occasions, one year apart. On the first day of admission, all subjects consumed a regular hospital diet and baseline data were collected. On the second hospital day, the subjects were placed on one of two dietary regimens, providing (per kg average desirable weight) either 1.5 g of protein or 0.75 g of protein plus 0.75 g of carbohydrate, per day. The diets were consumed for the next 64 days. They were provided as liquid homogenates prepared in a research kitchen adjacent to the metabolic ward. The diets were served to the subjects in four equal portions at 0900, 1300, 1700 and 2100. The composition of each diet for a person weighing 73.6 kg is shown in Table 2. A small amount of safflower oil was added to ‘Table 2. Comparison of experimental diets. (designed Yor @ person with an average desirable weight of 736 kg). P Containing 94.5 g of carbohydrate/100 g and 3.8 keal/g; "Containing 87.0 9 of protein/100g and 5.2 kcal/a. including additional calories from flavouring. Protein Protein | carbohydrate @ @ Carbohydrate (Polycose™) © ° 584 Protein (SUPRO 630%) ¢ 1315 58 t Sefflower oil 26 26 \ led water 1175.6 11815 Total weight 1300.7 1308.3 Tota klocaloriesé 6 26 cach preparation to provide essential fatty acids. Vitamins and minerals, sufficient to provide 100 percent of the recommended dietary allowances* were mixed into the formulas. However, calcium, magnesium and potassium were given as separate supplements. Each day, the subjects received 60 mEq of 232 potassium (as potassium chlori¢ and $00 mg of magnesium (as Body weight was determined collected in 24-h lots. Feces we later analyzed for nitrogen (N) method®. Fasting venous blood study and every eight days ther Results The weight loss for each of the feeding is plotted cumulatively subjects ranged from 19.0 to 2 sd.) for the group fed the pro consuming the protein-carbohy ‘means is not statistically signif GMLATNE HERAT LOSS (Ay) |. Cumulative weight losses of jects on low-calorie diets (indivi {alues are plotted st fourday inter the first four days of the exp. protein group and 0.96 kg pe days, which comprised 25 per (35-40) of the ultimate weigh the rate of weight loss was sk per day. Nitrogen (N) balance is cal put, which includes urinary a not corrected for non-collecti healthy adults’, Cumulative | in Fig. 2. All subjects were in thereafter, N balances diverge in these six subjects representof average desirable weight? Relative Weight* (%) 2 219 8 196 5 199 o 214 8 217 3 188 mmission ranged from 135 to 178 erage desirable weight standards snce Company’. Subject D.P. was onsumed a regular hospital diet ad hospital day, the subjects roviding (per kg average desirable otein plus 0.75 g of carbohydrate t 64 days, They were provided ‘tchen adjacent to the metabolic four equ portions at 0900, h dict for a person weighing of safflower cil was added 1 for a person with an average bohydrate/100 g and 3.8 keal/g; ncluding additional calories from Protein. carbohydrate @ 58.4 5.8 26 1181.5 1308.3, 626 s. Vitamins and minerals nended dietary allowances* , magnesium and potassium he subjects received 60 mEq of potassium (as potassium chloride), 800 mg of calcium (as calcium carbonate) znd 300 mg of magnesium {as magnesium hydroxide). Body weight was determined at the same time each morning. Urine was collected in 24h lots. Feces were pooled in four-day lots. Urine and feces were later analyzed for nitrogen (N) content by an adaptation of the Kjeldahl ethod®. Fasting venous blood samples were taken at the beginning of the { study and every eight days thereafter to obtain blood chemistry data. ) Results The weight loss for each of the six subjects during the 64 days of formula feeding is plotted cumulatively in Fig. 1. The total weight loss for the six rubjects ranged from 19.0 to 24.7 kg with a mean of 21.17 + 2.67 kg (mean + $4) for the group fed the protein diet and 23.46 + 1.07 kg for the group consuming the protein-carbohydrate diet. The difference between these two | neans is not statistically significant. The most rapid weight loss occurred during 3 ' i i i Fig. 1. Cumulative weight losses of six subjects on low-calorie diets (individual ‘alues are plotted at four-day intervals) the first four days of the experiment, With a mean of 0.90 kg per day for the protein group and 0.96 kg per day for the protein-carbohydrate group. After 16 days, which comprised 25 percent of the study period, more than 35 percent (85-40) of the ultimate weight loss over 64 days had been achieved. Thereafter, the rate of weight loss was slower and steadier, ranging from 0.22 to 0.36 kg per day. Nitrogen (N) balance is calculated as the difference between intake and out- put, which includes urinary and fecal N. The N balance data in this study were hot corrected for non-collectible losses, judged to be about 0.5 g per day in healthy adults. Cumulative N balances for each of the six subjects are shown in Fig, 2. All subjects were in negative N balance until the 28th to 36th day; thereafter, N balances diverged widely. The wide variation in N loss observed in these six subjects represents a three-fold difference. It ranged from 77.6 233to 234.1 g of N lost over 64 days and corresponds to a deficit of 485 to 1468 g of protein, or a loss of 2.4 to 7.3 kg of lean body mass. Because of the wide variation and the small number of subjects studied, the difference in mean N loss (g/64 days) between the two groups was not statistically significant (146.8 + 33.9 for the protein group and 138.1 + 84.1 for the protein-carbohydrate group). However, itis interesting to note ‘that more than 70 percent of the N loss over the 64-day period was accomplished during the first half of the experiment, and that the widest variation was observed among subjects consuming the same type of diet. The pattern of N balance observed in these six subjects may be classified tentatively into three categories. One could be called a ‘maladaptive’ type in which a negative N balance is maintained throughout the entire study. As shown in Fig. 3A, one of the subjects who consumed the protein-carbohydlrate diet remained in negative N balance throughout the entire 64-day study period, The only discemible adjustment to the severe calorie deprivation in this individual was a small reduction in the rate of N loss as the experiment progressed. Another category of responses is shown in Figure 3B. This could be ealled an ‘unstable’ type and it was exemplified in two subjects consuming the all: protein formula. Following the initial rapid loss of N, equilibrium was achieved during 32nd to 36th day of the experiment. If the study had been terminated at this point, it might have been concluded that a ‘permanent’ N equilibrium had indeed been attained. But as the experiment continued, negative N balances were observed again and both subjects remained in some degree of N deficit for the remainder of the study. ‘The ‘adaptive’ type (Fig. 3C) is exemplified by three subjects, two from the protein-carbohydrate group and one from the protein group. After exhibiting an N deficit for 28 to 40 days, these subjects came into or very near to N equilibrium and remained there until the end of the study. Overall, five of six subjects showed varying degrees of adjustment to the severe caloric restriction by reducing N deficits after 28 or more days on the low-calorie diet. Blood f-hydroxybutyrate was measured in four subjects. Fig. 4 shows that the concentration of this substrate in the blood increased strikingly during the experiment. The elevation was much greater in subjects consuming the protcin formula than in those fed the protein-carbohydrate diet. The highest values were those achieved by two subjects in the protein group and represent 14 and 21-fold increases over baseline concentrations. The highest levels achieved by subjects on the protein-carbohydrate diet were eight and ten times baseline values. The effect of low-calorie diets on serum uric acid concentrations was not dependent on the composition of the diet in our series. All six subjects exhibited a transient elevation in serum uric acid levels by the eighth day of the study. After day 24, all but one returned to within the normal range (Fig. 5). 234 8 BE Uy ey Se pao g~ : : be ae 2 al err tenia . . E = Fig, 3. Nitrogen balances of three rep sisting of protein alone oF of an isocal diferent response patterns: (A) con type): (B) return toa slight nitrogen (Unstable type); (C) achievement and deficit adaptive type)ids to a deficit of 485 to ee ean body mass. Because of jects studied, the the two groups was not otcin group and 138.1 + 84.1 itis interesting to note c 64-day period was ment, and that the widest ng the same type of diet. six subjects may be classified called a ‘maladaptive’ type in ighout the entire study. As sumed the protein-carbohydrate ( the entire 64-day study period. alorie deprivation in this N loss as the experiment { raat t | : m | * hae “2 “2 NITROGEN BALANCE (9/807) cree e Dua ew PROTEIN (TC) igure 8B. This could be called o subjects consuming the all: sof N, equilibrium was achieved the study had been terminated t a ‘permanent’ N equilibrium it continued, negative N remained in some degree of N NITROGEN BALANCE (9/¢0y) by three subjects, two from the rotein group. After exhibiting ame into or very near to N the study. egrees of adjustment to the after 28 or more days on the ur subjects. Fig. 4 shows that increased strikingly during the subjects consuming the protein rate diet. The highest values ein group and represent 14 and the highest levels achieved by right and ten times baseline NITROGEN BALANCE (9/tay ) pays concentrations was not series. All six subjects levels by the eighth day of the i the normal range (Fig. 5). representative subjects consuming slow-alri det con- Farce ence fr nanscalote miure of poten and carboharate Note th te Sie eopome pater: ending ei tougtout the Gay study (maiadove ype return to a slight nitrogen deficit after transient achievement quitiberi P He Oe achiowemert and matntenance of nivogen equilibrium after 28 days of tt adaptive typed 235Fig, uRIC act Fig, 6. Serum levels of uric acid in six subjects on low-calorie diets References 1 236 ‘mg/d.) Intemational Journal of Obesity (198: Nonphysician sup very-low-calorie d cases 4. Blood levels of -hydroxybutyrate in four subjects on low. calorie diets R.L. ATKINSON and D.L. KAI Department of Internal Medicin Charlottesville, Virginia 22908, | PROTEIN-CHO Summary Nonphysician nutritional therap behavioral modification, nutritic weeks on a very-low-calorie diet to 85.8 kg after 12 weeks on VL was 17.2 kg. Blood pressure dec VLCD. In 91 hypertensive pati after 12 weeks of VLCD. No ser wo patients developed mild cas when premature ventricular con reveals that physician care is aln physician nutritional therapists. should be performed by nutritic ‘a comprchensive program of bel Days. Bistrian, BR, Blackburn, G.L., Flat, J.P, Ske, 3, Serknshaw, N.S, & Sherman, M. (1976): Nitrogen metabolism and insulin requiements in oboxe diabetic adults on a protein-sprine modified fast. Diabetes 25, 494-504, Bistran, BLR., Wintere,J..& Blackburn, G.1. (1977): Effect of a proteinspating dist and bret fast on nitrogen metabolism in mildly obese subjects J. Lab, Clin. Mes. 89, 1030-1035. Blckburn, G.L, Flatt, 1P., Clowes, GHA, O'Donnel, T.B. & Hansle, TB. (1973): Protein: sparing therapy during periods of starvation with sepsis or trauma. Ann, Surg, 17, $88-594 Calloway, D-H., Odell, A.GE. & Margen, S. (1971): Sweat and miscellaneous nitrogen loses in human balance studios. J. Nur. 101, 775-786. Ferrari, A. (1960): Nitrogen determination by a contiquous digestion and analysis system. Ann. ¥. Acad. Set 87, 192-800 Flat, LP. & Blackburn, G.L, (1974): The metabolic fusl regulatory system: implications for protein-sparing therapies during calorie deprivation and disease: Am. Clin Nutr. 27, 175187, Metropolitan Life Insurance Co. (1959): Stetitia! Bulletin 40, 1-4 National Research Council Food and Nutrition Board (1979): Recommended dictay allowances [National Academy of Sciences, Washington, DC. Introduction The treatment of obesity is a ti unsuccessful”. The introductioy the success rate of obesity treat (VLCD)? in a comprehensive pr However, the early enthusiasm serious complications such as ci published series, close supervis mentation scem to prevent such amounts of physician time mak that nonphysicians were as suce behavioral modification technic sive program of obesity treatme timphasison the results of VLC patient basis at the University ¢