Riegler E
Med Klin 1976 Jun 11;71(24):1051-1056

A standardized high protein, low carbohydrate diet was tested in 128 overweight patients over a period of 12 months. Under this regimen a weight reduction of up to 38% of the original body weight was observed. Apart from the weight reduction there was a normalization of the blood pressure, blood lipids and blood glucose. The diet is easily adapted to out-patient care and is exceptionally well tolerated by the patients.

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Woody RC, Steele RW, Knapple WL, Pilkington NS Jr. Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock.
J Pediatr 1989 Sep;115(3):427-430

No abstract.

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Zwiauer K. Universitats-Kinderklinik Wien.
Infusionstherapie 1989 Aug;16(4):176-181

The importance of carbohydrates in weight reducing regimens on different metabolic aspects is shown by comparing the effects of two extreme dietary regimens: 'ketogenic' diet, consisting primarily of proteins and fat and the 'mixed' diet, containing mainly carbohydrates. The effects on hunger and satiety, weight loss and nitrogen balance are discussed as well as influences on electrolytes, body fluids and the sympathetic system. Hormonal changes of the two dietary regimens and the impact on mood and subjective acceptance are compared. Though no recommendation for a particular dietary regimen is given, the different implications on the parameters described are pointed out.

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Hinton W, Schwartz RH, Loach AB
Anaesthesia 1982 Jan;37(1):39-42

Ketogenic diets have a high fat and low carbohydrate and low protein content to induce ketosis which is monitored by daily urine testing. Lapses in diet are frequently associated with loss of anticonvulsant control. There has, as yet, been no report of children maintained on a ketogenic diet subject to anaesthesia and surgery: this paper records the changes in metabolic variables observed in three patients undergoing simple inhalation anaesthetics for minor surgery.

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Bialkowska M, Szostak WB, Chotkowska E, Szczyglowa H, Medrzejewski W
Mater Med Pol 1977 Jul;9(3):244-251

No abstract.

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Rabast U, Kustner H, Zang E, Ehl M, Kasper H
Med Klin 1978 Jan 13;73(2):55-59

No abstract.

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Gay G, Andre JL, Pierson M, Debry G
Nouv Presse Med 1977 Jun 11;6(24):2166

No abstract.

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Schurch PM, Feinendegen LE, Hollmann W
MMW Munch Med Wochenschr 1977 Mar 18;119(11):359-360

No abstract.

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Thenen SW, Mayer J
J Nutr 1977 Feb;107(2):320-329

Genetically obese Zucker rats, ob/ob mice and non-obese littermates were fed low carbohydrate (2%, 48%, and 50% of energy as carbohydrate, protein, and fat, respectively) and control (60%, 19%, and 21%, as carobhydrate, protein, and fat) diets. The oxidation of the energy components of these diets was measured by adding D-[U-14C]glucose, L-[U-14C]glutamic acid, and glyceryl tri-[1-14C]oleate to test meals given intragastrically and collecting respiratory CO2 for 4 hours. The animals responded to the low carbohydrate diet by oxidizing less glucose and more glutamic acid, but these amounts were proportional to dietary carbohydrate and protein composition, In contrast, the animals oxidized both higher amounts and percentages of glyceryl trioleate when fed the low carbohydrate diet. Obese Zucker rats oxidized less fat than non-obese rats when fed both diets, while obese mice oxidized fat to the same extent as non-obese mice. Feeding the low carbohydrate diet significantly increased body weight in the obese mice, but not in obese rats and non-obese mice and rats. The effect of obesity and the low carbohydrate diet on food intake, serum glucose and lipid values and CO2 production are also reported.

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Lutz W
Wien Med Wochenschr 1975 May 2;125(18-20):292-295

No abstract.

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Evans E, Stock AL, Yudkin J
Nutr Metab 1974;17(6):360-367

No abstract.

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Yudkin J
Postgrad Med 1972 May;51(5):151-154

No abstract.

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Ascherio A, Willett WC. Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.
Am J Clin Nutr 1997 Oct;66(4 Suppl):1006S-1010S

trans Fatty acids are formed during the process of partial hydrogenation in which liquid vegetable oils are converted to margarine and vegetable shortening. Concern has existed that this process may have adverse consequences because natural essential fatty acids are destroyed and the new artificial isomers are structurally similar to saturated fats, lack the essential metabolic activity of the parent compounds, and inhibit the enzymatic desaturation of linoleic and linolenic acid. In the past 5 y a series of metabolic studies has provided unequivocal evidence that trans fatty acids increase plasma concentrations of low-density-lipoprotein cholesterol and reduce concentrations of high-density-lipoprotein (HDL) cholesterol relative to the parent natural fat. In these same studies, trans fatty acids increased the plasma ratio of total to HDL cholesterol nearly twofold compared with saturated fats. On the basis of these metabolic effects and the known relation of blood lipid concentrations to risk of coronary artery disease, we estimate conservatively that 30,000 premature deaths/y in the United States are attributable to consumption of trans fatty acids. Epidemiologic studies, although not conclusive on their own, are consistent with adverse effects of this magnitude or even larger. Because there are no known nutritional benefits of trans fatty acids and clear adverse metabolic consequences exist, prudent public policy would dictate that their consumption be minimized and that information on the trans fatty acid content of foods be available to consumers.

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Pietinen P, Ascherio A, Korhonen P, Hartman AM, Willett WC, Albanes D, Virtamo J. Department of Nutrition, National Public Health Institute, Helsinki, Finland.
Am J Epidemiol 1997 May 15;145(10):876-887

The relation of intakes of specific fatty acids and the risk of coronary heart disease was examined in a cohort of 21,930 smoking men aged 50-69 years who were initially free of diagnosed cardiovascular disease. All men participated in the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study and completed a detailed and validated dietary questionnaire at baseline. After 6.1 years of follow-up from 1985-1988, the authors documented 1,399 major coronary events and 635 coronary deaths. After controlling for age, supplement group, several coronary risk factors, total energy, and fiber intake, the authors observed a significant positive association between the intake of trans-fatty acids and the risk of coronary death. For men in the top quintile of trans-fatty acid intake (median = 6.2 g/day), the multivariate relative risk of coronary death was 1.39 (95% confidence interval (CI) 1.09-1.78) (p for trend = 0.004) as compared with men in the lowest quintile of intake (median = 1.3 g/day). The intake of omega-3 fatty acids from fish was also directly related to the risk of coronary death in the multivariate model adjusting also for trans-saturated and cis-monounsaturated fatty acids (relative risk (RR) = 1.30, 95% CI 1.01-1.67) (p for trend = 0.06 for men in the highest quintile of intake compared with the lowest). There was no association between intakes of saturated or cis-monounsaturated fatty acids, linoleic or linolenic acid, or dietary cholesterol and the risk of coronary deaths. All the associations were similar but somewhat weaker for all major coronary events.

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Ascherio A, Rimm EB, Giovannucci EL, Spiegelman D, Stampfer M, Willett WC. Harvard School of Public Health, Boston, MA 02115, USA.
BMJ 1996 Jul 13;313(7049):84-90

OBJECTIVE--To examine the association between fat intake and the incidence of coronary heart disease in men of middle age and older. DESIGN--Cohort questionnaire study of men followed up for six years from 1986. SETTING--The health professionals follow up study in the United States. SUBJECTS--43 757 health professionals aged 40 to 75 years free of diagnosed cardiovascular disease or diabetes in 1986. MAIN OUTCOME MEASURE--Incidence of acute myocardial infarction or coronary death. RESULTS--During follow up 734 coronary events were documented, including 505 non-fatal myocardial infarctions and 229 deaths. After age and several coronary risk factors were controlled for significant positive associations were observed between intake of saturated fat and risk of coronary disease. For men in the top versus the lowest fifth of saturated fat intake (median = 14.8% v 5.7% of energy) the multivariate relative risk for myocardial infarction was 1.22 (95% confidence interval 0.96 to 1.56) and for fatal coronary heart disease was 2.21 (1.38 to 3.54). After adjustment for intake of fibre the risks were 0.96 (0.73 to 1.27) and 1.72 (1.01 to 2.90), respectively. Positive associations between intake of cholesterol and risk of coronary heart disease were similarly attenuated after adjustment for fibre intake. Intake of linolenic acid was inversely associated with risk of myocardial infarction; this association became significant only after adjustment for non-dietary risk factors and was strengthened after adjustment for total fat intake (relative risk 0.41 for a 1% increase in energy, P for trend < 0.01). CONCLUSIONS--These data do not support the strong association between intake of saturated fat and risk of coronary heart disease suggested by international comparisons. They are compatible, however, with the hypotheses that saturated fat and cholesterol intakes affect the risk of coronary heart disease as predicted by their effects on blood cholesterol concentration. They also support a specific preventive effect of linolenic acid intake.

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Ascherio A, Rimm EB, Stampfer MJ, Giovannucci EL, Willett WC. Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115.
N Engl J Med 1995 Apr 13;332(15):977-982

BACKGROUND. It has been hypothesized that a diet containing n-3 fatty acids from fish reduces the risk of coronary heart disease, but few large epidemiologic studies have examined this question. METHODS. In 1986, 44,895 male health professionals, 40 to 75 years of age, who were free of known cardiovascular disease completed detailed and validated dietary questionnaires as part of the Health Professionals Follow-up Study. During six years of follow-up, we documented 1543 coronary events in this group: 264 deaths from coronary disease, 547 nonfatal myocardial infarctions, and 732 coronary-artery bypass or angioplasty procedures. RESULTS. After controlling for age and several coronary risk factors, we observed no significant associations between dietary intake of n-3 fatty acids or fish intake and the risk of coronary disease. For men in the top fifth of the group in terms of intake of n-3 fatty acids (median, 0.58 g per day), the multivariate relative risk of coronary heart disease was 1.12 (95 percent confidence interval, 0.96 to 1.31), as compared with the men in the bottom fifth (median, 0.07 g per day). For men who consumed six or more servings of fish per week, as compared with those who consumed one serving per month or less, the multivariate relative risk of coronary disease was 1.14 (95 percent confidence interval, 0.86 to 1.51). The risk of death due to coronary disease among men who ate any amount of fish, as compared with those who ate no fish, was 0.74 (95 percent confidence interval, 0.44 to 1.23), but the risk did not decrease as fish consumption increased. CONCLUSIONS. Although the possibility of residual confounding by unmeasured factors cannot be entirely excluded, these data suggest that increasing fish intake from one to two servings per week to five to six servings per week does not substantially reduce the risk of coronary heart disease among men who are initially free of cardiovascular disease.

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Ascherio A, Willett WC. Department of Epidemiology, Harvard School of Public Health Boston, MA.
J Nutr 1995 Mar;125(3 Suppl):647S-655S

For several decades the debate on diet and coronary heart disease has been dominated by the classic diet-heart hypothesis, which predicts an adverse effect of dietary saturated fat and cholesterol and a beneficial effect of polyunsaturated fat intake. However, recent research suggests that the diet-heart relationship is much more complex than previously recognized. Antioxidants, and in particular vitamin E, are emerging as potentially useful protective factors, and there is increasing evidence that hyperhomocysteinemia is a risk factor that may be modified by dietary changes. However, substantial data support the notion that the trans fatty acids contained in partially hydrogenated vegetable oils adversely affect the risk of coronary heart disease. Other questions, such as the role of selenium and iron, the ideal amount in the diet of polyunsaturated fat of the n-6 or n-3 group (including fish oil) and how the benefits of a diet high in monounsaturated fat (such as the Mediterranean diet) compare with those of diet low in total fat (such as the traditional Asian diet) remain to be settled.

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Schutz Y, Ravussin E
Am J Clin Nutr 1980 Jun;33(6):1317-1319

No abstract.

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McDonald ME. Wayne State University, Detroit, MI, USA.
Pediatr Nurs 1997 Sep;23(5):461-464

Ketogenic diet therapy has been found to be an effective means of treating afebrile seizures that are refractory to antiepileptic medication alone. Controversies exist regarding its use. Potential harmful side effects include Staphylococcus aureus infections, retarded growth, hypoglycemia, hyperlipidemia, urolithiasis, and optic neuropathy. Pediatric nurses with knowledge about ketogenic diet therapy and current research regarding its use, will be better able to determine the appropriateness of this form of therapy for children with seizures that cannot be controlled by medication alone.

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Gay J, Porrata C, Hernandez M, Clua AM, Arguelles JM, Cabrera A, Silva LC. Institute of Nutrition and Food Hygiene, Havana, Cuba.
Bull Pan Am Health Organ 1995 Mar;29(1):25-36

An epidemic neuropathy that broke out in Cuba in late 1991 has exhibited clinical manifestations similar to those of other polyneuropathies of nutritional origin. To investigate its possible association with diet, a study was conducted on the Isle of Youth in 1993, at the start of an outbreak there. Thirty-four subjects with cases and 65 controls were interviewed regarding their diets, measured anthropometrically, and evaluated. As a whole, the subjects with cases demonstrated greater weight loss before the onset of disease, lower body mass indexes (BMI), lower percentages of body fat, and more deficient diets than the control subjects. Analysis of individual variables found associations between occurrence of the disease and the following: weight loss, low BMI, a broad range of specific dietary deficiencies, a sugar intake exceeding 15% of total caloric intake, alcohol consumption, and smoking. Also, protective associations were found between absence of the disease and regular consumption of certain foods at or above specified levels. Multivariate analysis indicated that while smoking and alcohol consumption reinforced the effects of the dietary deficiencies, they did not account for occurrence of the disease by themselves. Overall, the results indicate that diets which are deficient in caloric energy, protein, fat, and the micronutrients included in the study, and which reflect an imbalance resulting from a relative excess of sugar, with consequent effects on body weight, are strongly associated with, and causally related to, the occurrence of epidemic neuropathy in Cuba.

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Phinney SD, Bistrian BR, Evans WJ, Gervino E, Blackburn GL
Metabolism 1983 Aug;32(8):769-776

To study the effect of chronic ketosis on exercise performance in endurance-trained humans, five well-trained cyclists were fed a eucaloric balanced diet (EBD) for one week providing 35-50 kcal/kg/d, 1.75 g protein/kg/d and the remainder of kilocalories as two-thirds carbohydrate (CHO) and one-third fat. This was followed by four weeks of a eucaloric ketogenic diet (EKD), isocaloric and isonitrogenous with the EBD but providing less than 20 g CHO daily. Both diets were appropriately supplemented to meet the recommended daily allowances for vitamins and minerals. Pedal ergometer testing of maximal oxygen uptake (VO2max) was unchanged between the control week (EBD-1) and week 3 of the ketogenic diet (EKD-3). The mean ergometer endurance time for continuous exercise to exhaustion (ENDUR) at 62%-64% of VO2max was 147 minutes at EBD-1 and 151 minutes at EKD-4. The ENDUR steady-state RQ dropped from 0.83 to 0.72 (P less than 0.01) from EBD-1 to EKD-4. In agreement with this were a three-fold drop in glucose oxidation (from 15.1 to 5.1 mg/kg/min, P less than 0.05) and a four-fold reduction in muscle glycogen use (0.61 to 0.13 mmol/kg/min, P less than 0.01). Neither clinical nor biochemical evidence of hypoglycemia was observed during ENDUR at EKD-4. These results indicate that aerobic endurance exercise by well-trained cyclists was not compromised by four weeks of ketosis. This was accomplished by a dramatic physiologic adaptation that conserved limited carbohydrate stores (both glucose and muscle glycogen) and made fat the predominant muscle substrate at this submaximal power level.

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Sherwin RS
Acta Chir Scand Suppl 1981;507:30-40

To evaluate the effect ketone bodies on protein metabolism beta-hydroxybutyrate was infused into healthy nonobese and obese subjects and insulin dependent diabetics in the postabsorptive state and into obese subjects after 3 days and 3-10 wks of starvation. In association with blood ketone increments of 1-2 mM, plasma alanine fell by 25-35% in all treatment groups. Furthermore, the hypoalaninemic effect of beta-hydroxybutyrate was equally demonstrable in fasted subjects, in whom alanine was already reduced. In association with repeated 12 hr infusions of beta-hydroxybutyrate in subjects fasted 5-10 wks, urinary nitrogen fell by 30%, returning to baseline after cessation of the infusions and paralleling the changes in plasma alanine. When endogenous ketonemia was produced by isocaloric carbohydrate restriction (less than 25 gm/day), protein ingestion was associated with a 40-50% greater increase in plasma branched chain amino acids as well as a reduced rise in plasma insulin. The enhanced rise in branched chain amino acids was attributable to decreased net utilization since intravenous leucine also produced a 40% greater elevation in plasma leucine after carbohydrate restriction. When nitrogen balance was compared during hypocaloric (400 Kcal) feeding of a pure protein diet and a mixed diet containing 50% protein and 50% carbohydrate, no significant differences were observed. Isocaloric replacement with carbohydrate failed to accentuate nitrogen wasting, despite a marked lowering of blood and urinary ketones. Our findings support the possibility that ketone bodies contribute to the reduction in proteolysis and decrease in muscle alanine release which characterizes prolonged starvation. However, when endogenous hyperketonemia is induced by carbohydrate restriction, plasma insulin declines and the disposal of ingested protein is impaired. Furthermore, the addition of carbohydrate during hypocaloric feeding reduces hyperketonemia, but does not enhance negative nitrogen balance. These observations suggest that dietary carbohydrate and insulin also promote nitrogen retention and that ketogenic, high protein diets do not confer a unique protein sparing advantage.

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Burgess NS. Center for Exercise Science and Cardiovascular Research, Northeastern Illinois University, Chicago 60625.
J Am Diet Assoc 1991 Apr;91(4):430-434

Very-low-calorie diets (VLCDs) provide a rapid decrease in total body weight, but limited data are available regarding the extent of fat loss and whether body fat distribution is altered. The purpose of this study was to investigate body composition, body fat distribution, and resting metabolic rate in obese men and women and to compare bioelectrical impedance analysis (BIA) with hydrodensitometry before and after 12 weeks of treatment in a VLCD program. Body composition was assessed by hydrodensitometry and BIA. Circumference measures were used to determine waist:hip and waist:thigh ratios. Seventeen subjects lost a mean of 24.2 kg. A mean of 75.5% of the weight loss was adipose tissue as measured by hydrodensitometry. BIA underestimated body fat percentage compared with hydrodensitometry in this obese population. Waist:hip and waist:thigh ratios showed a small but significant decrease, implying a decreased risk for diabetes and cardiovascular disease after weight loss. Resting metabolic rate, as measured by oxygen consumption, dropped 23.8% during the 12 weeks of the VLCD. The findings indicate that a VLCD can provide a rapid weight loss of more than 75% fat and a concomitant decrease in waist:hip and waist:thigh ratios. The findings also indicate that BIA may not be a useful tool in assessing fat loss in obese subjects. Finally, it appears that the decrease in resting metabolic rate that occurs during treatment with VLCD does not correlate with changes in lean body mass.

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Kogon MM, Krauchi K, Van der Velde P, Van der Werf H, Keller U. Division of Endocrinology, University Hospital Basel, Switzerland.
Am J Clin Nutr 1994 Oct;60(4):488-493

Dietary carbohydrates and dexfenfluramine (dF) have been shown to influence serotoninergic neurotransmission. To assess their effect on spontaneous physical activity, mood, sleep quality, and resting metabolic rate (RMR), 32 obese females were studied while consuming diets providing 3970 kJ (950 kcal)/d. They were randomly allocated to either a diet relatively high in carbohydrates (carbohydrate:fat:protein, 49%:22%:29% of energy intake; group 1) or to a diet relatively high in fat (carbohydrate:fat:protein, 12%:59%:29%); subjects receiving the latter diet were treated additionally with either 30 mg dF (group 2) or placebo (group 3) daily in a double-blind fashion. Spontaneous physical activity decreased in the group treated with dF compared with the other two groups (P = 0.0002). Daily self-rated questionnaires indicated that mood and tiredness were negatively affected in two groups after the first week. Subjects treated with dF lost more weight than did those in the other two groups (P = 0.013). This occurred despite a decrease in physical activity and unchanged energy intake and resting energy expenditure.

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Herzberg GZ, Fivush BA, Kinsman SL, Gearhart JP. Department of Pediatrics, Johns Hopkins Children's Medical and Surgical Center, Baltimore, Maryland.
J Pediatr 1990 Nov;117(5):743-745

No abstract.

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Tsukamoto Y, Okubo M, Yoneda T, Marumo F, Nakamura H
Nephron 1982;31(3):236-241

An abnormal level of serum lipids may be one of the major risk factors for the development of atherosclerosis in patients with chronic renal failure (CRF). In the present study, the effect of polyunsaturated fatty acid-rich and low carbohydrate diet on serum lipids and HDL-cholesterol was studied in 6 nonnephrotic and nondialyzed patients with CRF on an isocaloric basis. Serum triglycerides decreased significantly from 2.08 +/- 0.93 mmol/l (183 +/- 82 mg/dl) to 1.49 +/- 0.83 mmol/l (131 +/- 73 mg/dl) by consumption of polyunsaturated diet (p less than 0.01). The 'HDL-cholesterol ratio' increased significantly and LCAT decreased on a polyunsaturated diet. In conclusion, the consumption of a polyunsaturated fatty acid-rich diet tends to normalise increased serum triglycerides and lowered 'HDL-cholesterol ratio' in patients with CRF and may be effective for prevention of atherosclerotic vascular sequellae.

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White MD, Bouchard G, Buemann B, Almeras N, Despres JP, Bouchard C, Tremblay A. Physical Activity Sciences Laboratory, Laval University, Ste-Foy, Quebec, Canada.
Int J Obes Relat Metab Disord 1997 Feb;21(2):135-140

OBJECTIVE: To examine the relationships between 24 h energy and macronutrient balances in a whole body metabolic chamber subsequent to periods when subjects maintained their normal food intake and physical activity levels. SUBJECTS: Thirteen males and 17 females were studied for two 24 h sessions while consuming an estimated isocaloric diet with a food quotient of 0.85. MEASUREMENTS: Energy expenditure and macronutrient oxidation rates were measured twice for 24 h in whole body indirect calorimeter. RESULTS: Positive and significant correlations were evident between energy and lipid balances (r = 0.38, P < 0.05 and r = 0.54, P < 0.01, respectively) and differences between the two sessions for energy and lipid balances were also significantly correlated (r = 0.40, P < 0.05). Accounting for carbohydrate or protein balances improved the strength of each of these associations. CONCLUSION: These results indicate that for subjects in a small but significant positive energy balance, with uncontrolled diet and activity preceding their metabolic chamber sessions, that 24 h energy balance is positively correlated with lipid balance. Accounting for associations between lipid, carbohydrate, protein and energy balances, improved the strength of the association between 24 h lipid and energy balances. The implications of these results are that in these conditions modifications to lipid balance are important for weight maintenance.

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Lieb, Clarence W., M.D.,
Journal of the American Medical Association (July 6, 1929) 20-22.

No abstract.

Comments: unfinished.

Allen LH, Oddoye EA, Margen S
Am J Clin Nutr 1979 Apr;32(4):741-749

Urine calcium excretion is known to be directly correlated with the level of dietary protein intake. In this experiment we examined the persistence of the hypercalciuria induced by the consumption of high protein diets, and the mechanism of the calciuric response. In a 95-day metabolic study, each of six adult male subjects received formula diets supplying 12 g nitrogen or 36 g nitrogen, and approximately 1400 mg calcium per day. Urine calcium increased rapidly and significantly from an average of 191 mg/day on the 12 g nitrogen diet to 277 mg/day on the 36 g nitrogen diet. There was no significant difference in the apparent absorption of calcium, so that overall calcium balance was -37 mg/day on the 12 g nitrogen diet, and significantly lower at -137 mg/day in subjects consuming the high protein diet. Levels of urinary hydroxyproline, serum insulin, and parathyroid hormone were not significantly increased by high intakes of protein. A decrease in the fractional reabsorption of calcium by the kidney seems to be the most likely cause of the protein-induced hypercalciuria. The consumption of high calcium diets is unlikely to prevent the negative calcium balance and probable bone loss induced by the consumption of high protein diets.

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Lithell H, Karlstrom B, Selinus I, Vessby B, Fellstrom B
Hum Nutr Clin Nutr 1985 Jul;39(4):289-295

Lipoprotein metabolism was investigated in 12 patients, healthy except for renal stone disease, who received a high-protein experimental diet for 2 weeks under metabolic ward conditions. The results were compared with those after 2 weeks on a control diet of ordinary composition. The patients were randomly allocated to begin with the control or experimental diet. The energy contributions from protein, carbohydrate and fat were 12, 48 and 41 per cent in the control diet and 29, 31 and 41 per cent in the experimental diet, respectively. Fasting concentrations of very-low-density lipoprotein (VLDL) triglycerides and cholesterol were lower with the high-protein than with the control diet (0.69 vs 1.4 mmol/l, P less than 0.0001, and 0.33 vs 0.47 mmol/l P less than 0.01, respectively). High-density lipoprotein cholesterol tended to be higher (0.05 less than P less than 0.10) with the high-protein diet. Lipoprotein-lipase (LPL) activity in skeletal muscle and the fractional catabolic rate constant of an intravenous fat tolerance test were higher with the high-protein than with the control diet (38 vs 21 mU/l, P less than 0.01, and 5.1 vs 3.6 mU/l, P less than 0.001, respectively). Neither fasting blood glucose, intravenous glucose tolerance nor insulin concentrations differed between the two dietary periods. These findings indicate that an 'ordinary' intake of refined carbohydrates has an inhibitory effect on the muscle LPL activity, thereby increasing the VLDL level and slightly decreasing the level of high-density lipoproteins, which may be of relevance for the atherosclerotic process.

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Kirchgessner M, Muller HL
Int J Vitam Nutr Res 1984;54(1):99-106

A respiration calorimetry experiment with 10 matures sows was conducted to study the effect of a ketogenic diet on heat production and energy utilization. The ketogenic diet contained no carbohydrates and 85% of its energy as fat. The control diet was a mixed diet with most of its energy as carbohydrates. Both diets provided the same daily protein intake, which was slightly below the calculated protein requirement. The level of energy intake was adjusted to a moderate positive energy balance. Both diets were allocated to the same animal for three weeks each according to a crossover design. Seven-day collection periods and 48-hours measurements of the gaseous exchange (carbon-nitrogen balance method) were conducted on individual sows per diet. The ketogenic diet substantially increased the energy losses in faeces, which resulted in a energy digestibility of 75% compared to 93% with the mixed diet. The methane production was also significantly depressed. In contrast, the urine energy excretion was not influenced by the extremely high fat diet. The nitrogen balance showed lower faecal nitrogen losses and a higher urine nitrogen excretion in the animals with the high fat diet. Because of this compensative response no difference in nitrogen retention was observed between the two dietary treatments. The ketogenic diet caused no detrimental effects on thermogenesis or energy utilization. The results of both criteria could be fully explained by the well accepted ideas of the efficiency of utilization of the energy from fat under balanced nutrition conditions. Overall the results demonstrate that a high fat diet has no regulatory effect on the usually diet-induced thermogenesis.

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Stanko RT, Tietze DL, Arch JE Clinical Nutrition Unit, Montefiore University Hospital, Pittsburgh, PA 15213.
Am J Clin Nutr 1992 Oct;56(4):636-640

To determine the effects on weight loss of feeding isonitrogenous diets in mildly restricted (4.2 MJ/d) and severely restricted (2.1 MJ/d) amounts, we measured body composition, weight loss-energy deficit ratio, and nitrogen metabolism in 14 obese women housed in a metabolic ward consuming hypoenergetic diets for 21 d. Subjects consumed either a 4.2-MJ/d diet (50 g protein, 175 g carbohydrate) or a 2.1-MJ/d diet (50 g protein, 75 g carbohydrate). Body composition and leucine oxidation and turnover were determined before and after weight loss. Energy deficit was calculated from resting metabolic rates. Subjects fed the 2.1-MJ/d diet showed a greater weight loss (6.1 +/- 0.5 vs 4.5 +/- 0.5 kg; mean +/- SE, P less than 0.05) and fat loss (3.9 +/- 0.3 vs 3.0 +/- 0.3 kg, P less than 0.05). Weight loss-energy deficit ratio was the same with both diets. Nitrogen balance and leucine oxidation and turnover were similar in both groups. We conclude that with feeding of isonitrogenous hypoenergetic diets, severe restriction of energy content (2.1 MJ/d, 75 g carbohydrate) will enhance weight and fat loss without increasing nitrogen loss compared with mild restriction of energy (4.2 MJ/d).

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Nirgiotis JG, Hennessey PJ, Black CT, Andrassy RJ Department of Surgery, University of Texas Medical School, Houston 77030.
J Pediatr Surg 1991 Aug;26(8):925-928

The specific effects of omega 3 and omega 6 polyunsaturated fatty acids on wound healing, nutrition status, or immune function are controversial. Therefore, we investigated the effects of fatty acid supplementation on wound healing and nitrogen retention in a surgically stressed rat model. Male Sprague-Dawley rats (weighing 250 g) were placed into three isocaloric, isonitrogenous feeding groups (controls [standard Vivonex]; 30% safflower oil [omega 6]; or 30% fish oil [omega 3]) for 8 days prior to receiving subcutaneous vascular graft wound cylinders in their dorsal midline. Nitrogen balance was monitored daily. Wounds healed for 10 days, animals were then euthanized, serum was drawn, and wound cylinders were harvested for analyses. The low-fat, high-carbohydrate control group had higher serum albumin levels at 10 days than either fatty acid-supplemented group (3.5 +/- 0.4 g/dL v 2.9 +/- 0.3 g/dL and 2.7 +/- 0.2 g/dL, omega 3 and omega 6, respectively; both P less than .05) and had better nitrogen balance (8.6 +/- 0.8 mg N/d v -2.6 +/- 0.9 mg N/d and 0.8 +/- 1.2 mg N/d, omega 3 and omega 6, respectively; both P less than .05). They also had better healed wounds at 10 days (450 +/- 290 micrograms 5-hydroxyproline [OHP]/cm of wound cylinder v 150 +/- 40 micrograms OHP/cm and 145 +/- 90 micrograms OHP/cm, omega 3 and omega 6, respectively). Surgically stressed rats had higher protein levels, better nitrogen balance, and improved wound healing when fed a diet high in carbohydrates and low in fat.

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Hennessey PJ, Nirgiotis JG, Andrassy RJ Department of Surgery, University of Texas Medical School, Houston.
J Pediatr Surg 1991 Apr;26(4):367-372

Recent reports have indicated a possible age-related component to the ability of various species to utilize either fat or carbohydrate as their preferential energy source. These studies have demonstrated that infant rats given a high-fat diet (50% fat, 35% carbohydrate, 15% protein) retain a significantly higher amount of nitrogen than do infant rats on a high-carbohydrate diet (82% carbohydrate, 3% fat, 15% protein). Conversely, adult rats maintain a higher positive nitrogen balance when given the high-carbohydrate diet. In light of these studies, and our interest in factors that contribute to wound healing in the surgical patient, we investigated the effects of low-, medium-, and high-fat enteral diets on wound healing and nitrogen balance in surgically stressed rats of various ages. Weanling (45 g) and young adult (175 g) male Sprague-Dawley rats (n = 16 per age group) were housed individually in metabolic cages. All animals had Impra vascular-graft wound cylinders placed subcutaneously in the dorsal midline and were placed in four dietary groups: high fat (50% kcal), medium fat (30% kcal), low fat (2.5% kcal), and chow (Purina Standard Laboratory Rodent Chow, 17% kcal as fat). All test diets were isonitrogenous (3.1 g nitrogen/1,000 kcal) and isocaloric for each age group. Animals in each age group were pair-fed (35 kcal/d, weanlings; 60 kcal/d, young adults) for 10 days and then euthanized. Wound cylinders were removed and analyzed for collagen content.

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Pasquali R, Casimirri F, Melchionda N Institute of Clinical Medicine 1, S. Orsola Hospital, University of Bologna, Italy.
Metabolism 1987 Dec;36(12):1141-1148

To assess long-term nitrogen sparing capacity of very low-calorie mixed diets, we administered two isoenergetic (2092KJ) liquid formula regimens of different composition for 8 weeks to two matched groups of massively obese patients (group 1: proteins 60 g, carbohydrate 54 g; group 2: proteins 41 g, carbohydrates 81 g). Weight loss was similar in both groups. Daily nitrogen balance (g) during the second month resulted more a negative in group 2 with respect to group 1. However, within the groups individual nitrogen sparing capacity varied markedly; only a few in group 1 and one in group 2 were able to attain nitrogen equilibrium throughout the study. Daily urine excretion of 3-methylhistidine fell significantly in group 1 but did not change in group 2. Unlike total proteins, albumins, and transferrin, serum levels of retinol-binding protein, thyroxin-binding globulin, and complement-C3 fell significantly in both groups but per cent variations of complement-C3 were more pronounced in the first group. Prealbumin levels fell persistently in group 1 and transiently in group 2. The results indicate that even with this type of diet an adequate amount of dietary protein represents the most important factor in minimizing whole body protein catabolism during long-term semistarvation in massively obese patients. Moreover, they confirm the possible role of dietary carbohydrates in the regulation of some visceral protein metabolism.

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Takase S, Morimoto A, Moriuchi S, Hosoya N
J Nutr Sci Vitaminol (Tokyo) 1981;27(3):219-229

This study was conducted to investigate the effects of various proportions of dietary carbohydrate and fat in diet on protein and carbohydrate metabolism. The growth rate, nitrogen balance, urinary and serum urea levels, and the activities of key ureogenic and gluconeogenic enzymes in the livers were examined in the weanling and growing rats. The rats were raised on a 20% casein diet containing various proportions of carbohydrate and fat, viz. 30% and 50%, 50% and 30%, 60% and 20% or 70% and 10% as calorie percent, respectively, for 10 days. For both weanling and growing rats, the growth rate was unaffected by the alteration in the proportions of carbohydrate and fat in the diets. However, in the rats fed on the 30% carbohydrate-50% fat diet, the urinary excretion of nitrogen and urea were reduced in both groups and these findings were reflected in the reduced serum urea level. Arginase activity decreased. In contrast, glucose-6-phosphatase activity was enhanced in the animals of the 30% carbohydrate-50% fat diet group as compared to the other groups. These results suggest that a low carbohydrate-high fat diet causes the reduction of urea formation and the enhancement of glucose formation at a fixed level of protein in the diets in weanling as well as in growing rats.

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Dunger A, Berg S, Kloting I, Schmidt S Institute of Diabetes Gerhardt Katsch Karlsburg, Germany.
Exp Clin Endocrinol Diabetes 1997;105 Suppl 2:48-50

The aim of this study was to compare the effect of long-term diabetes with that of a long-term high protein diet in vivo on the kidney function and in vitro on cellular parameters of isolated glomeruli of BB rats. Four groups of rats were investigated: Group 1 = normoglycaemic (N) rats > 250 days old; group 2 = age-matched diabetic (D) rats with a diabetes duration of more than 150 days; group 3 = BB rats which were fed a protein diet of 8% (low protein = LP) and group 4 = rats which received a high protein (HP) diet (32%) for more than 80 weeks. From 24-h-urine samples albumin, urea, creatinine and electrolyte excretion were estimated. At the end of the study the total kidney weight was determined and glomeruli were isolated for in vitro experiments. Hyperglycaemic and HP fed rats were characterised by a significantly increased excretion of albumin, urea and different electrolytes compared to normoglycaemic or LP fed animals. Creatinine excretion was neither affected by hyperglycaemia nor HP diet. HP and D caused a significant increase in total kidney weight when compared to the LP and N group, respectively (N: 1.79 +/- 0.08; D: 2.33 +/- 0.09; LP: 2.26 +/- 0.18; HP: 3.28 +/- 0.46 g; p < 0.05). The increased kidney weight of diabetic and HP rats correlated well with a significant enhanced DNA content of isolated glomeruli (N: 3.41 +/- 0.15; D: 4.45 +/- 0.19; LP: 4.18 +/- 0.35; HP: 6.40 +/- 0.62 micrograms/1000 glomeruli; p < 0.02). In addition, glomeruli obtained from either D or HP fed BB rats incorporated significantly more 3H-thymidine into their DNA indicating an elevated rate of DNA synthesis. The results demonstrate that HP diet caused markedly altered kidney function and induced cellular changes of glomeruli which are interpreted as enhanced proliferative processes. These alterations are comparable to those associated with diabetes mellitus. An unbalanced high protein diet represents a considerable risk factor for the development of functional and structural impairments of the kidney and should absolutely be avoided in patients suffering from diseases which are known to be associated with kidney alterations.

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Adams LG, Polzin DJ, Osborne CA, O'Brien TD Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul 55108.
Am J Vet Res 1993 Oct;54(10):1653-1662

To determine the effects of long-term dietary protein restriction in cats with chronic renal failure (CRF), 4 healthy adult cats and 7 cats with surgically induced CRF were fed a high-protein (HP, 51.7% protein) diet and 4 healthy adult cats and 7 cats with surgically induced CRF were fed a low-protein (LP, 27.6% protein) diet for 1 year. Cats with induced CRF that were fed the LP diet had reduced serum urea nitrogen concentrations, despite lower glomerular filtration rates, compared with cats with CRF fed the HP diet. Despite five-sixths reduction in renal mass, reduced glomerular filtration rate, and azotemia, 13 of the 14 cats with induced CRF retained the ability to concentrate urine and produced urine with a specific gravity > 1.035. Cats fed the HP diet consumed significantly more calories than did cats fed the LP diet, presumably because the HP diet was more palatable. As a result of the lower caloric intake in cats fed the LP diet, these cats were protein and calorie restricted, compared with cats fed the HP diet. Cats fed the HP diet weighed significantly more than did cats fed the LP diet. Mean hematocrit and mean serum albumin concentration were significantly lower in control cats and in cats with CRF fed the LP diet, compared with control cats and cats with CRF fed the HP diet. Hypokalemia developed in 4 of 7 cats with CRF fed the HP diet (containing 0.3% potassium); hypokalemia did not develop in control cats fed the same diet or in cats with CRF fed the LP diet containing 0.4% potassium. Excessive kaliuresis, hypomagnesemia, and metabolic acidosis did not appear to contribute to the hypokalemia. Subsequent supplementation of the HP diet with potassium gluconate prevented hypokalemia in cats with CRF.

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Kontessis P, Jones S, Dodds R, Trevisan R, Nosadini R, Fioretto P, Borsato M, Sacerdoti D, Viberti G. Unit for Metabolic Medicine, United Medical School, Guy's Hospital, London, United Kingdom.
Kidney Int 1990 Jul;38(1):136-144

Renal and hormonal responses were studied in a group of healthy individuals fed, in random order, for three weeks, a vegetable protein diet (N = 10), an animal protein diet (N = 10), or an animal protein diet supplemented with fiber (N = 7), all containing the same amount of total protein (chronic study). In seven additional subjects the acute renal, metabolic and hormonal response to ingestion of a meat or soya load of equivalent total protein content was investigated (acute study). In the chronic study GRF, RPF and fractional clearance of albumin and IgG were significantly higher on the animal than the vegetable protein diets (GFR: 121 +/- 4 vs. 111 +/- 4 ml/min/1.73 m2, P less than 0.001; RPF: 634 +/- 29 vs. 559 +/- 26 ml/min/1.73 m2, P less than 0.001; theta alb: 19.5 +/- 3.1 vs. 10.2 +/- 1.6 x 10(-7), P less than 0.01; theta IgG: 11.6 +/- 3.1 vs. 7.5 +/- 1.7 x 10(-7), P less than 0.05). Renal vascular resistance was lower on the animal than vegetable protein diet (82 +/- 5 vs. 97 +/- 5 mmHg/min/liter; P less than 0.001). Fiber supplementation to APD did not have any effect on the renal variables measured which were indistinguishable from APD. In the acute study, GFR and RPF both rose significantly by approximately 16% (P less than 0.005) and approximately 14% (P less than 0.05), respectively, after the meat load, while RVR fell by approximately 12% (P less than 0.05). There were no significant changes in these parameters following the soya load.

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Kok DJ, Iestra JA, Doorenbos CJ, Papapoulos SE. Department of Endocrinology, University Hospital, Leiden, The Netherlands.
J Clin Endocrinol Metab 1990 Oct;71(4):861-867

Dietary excesses in animal protein and/or salt have been implicated as risk factors in calcium oxalate urolithiasis. The underlying physicochemical mechanism is, however, not known. Eight healthy men were given four different diets varying in animal protein and in sodium content for 1 week each. On a high protein intake (2 g/kg.day) significant changes in urinary calcium, uric acid, and citrate excretion rates were found. Similar changes in calcium and citrate were induced by a high sodium intake (310 mmol/day). The changes were more pronounced when a high protein was combined with a high sodium diet. Urinary calcium increased from 3.79 +/- 0.31 to 6.42 +/- 0.61 mmol/24 h and urinary uric acid from 4.69 +/- 0.26 to 8.0 +/- 0.47, whereas urinary citrate decreased from 3.93 +/- 0.53 to 2.79 +/- 0.34 mmol/24 h. All three dietary regimens induced a significant decrease in the ability of urines to inhibit calcium oxalate monohydrate crystal agglomeration, which was most marked during the combined diet (from 345 +/- 39 to 205 +/- 28 min). The ability of urines to inhibit crystal agglomeration was related to their citrate content (r = 0.69, P less than 0.0001). These results show that high animal protein and/or sodium intake decrease the ability of urines to inhibit the agglomeration of calcium oxalate crystals and provide a possible physicochemical explanation for the adverse effects of dietary aberrations on renal stone formation.

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Jungers P, Daudon M, Hennequin C, Lacour B. Departement de Nephrologie, INSERM U 90, Hopital Necker, Paris.
Nephrologie 1993;14(6):287-290

In order to assess the influence of dietary protein and salt intake on urinary calcium excretion in calcium stone formers, we simultaneously determined 24 hour urinary excretion of Urea (UU) and sodium (UNa) together with that of calcium (UCa) in 184 patients (112 males) with idiopathic calcium nephrolithiasis studied on free diet. Mean (+/- SEM) values expressed as mmol/kg BW/day of both UU and UNa were higher in hypercalciuric (UCa > or = 0.1 mmol/kg/d, mean 0.15 +/- 0.01) male patients, respectively 6.63 +/- 0.25 and 2.71 +/- 0.13, than in normocalciuric males, respectively 5.33 +/- 0.22 (p < 0.001) and 2.36 +/- 0.15 (p = 0.06), while the latter did not differ from healthy controls. Similar findings were made in female stone formers. Linear regression analysis on the whole series showed a positive but weak correlation between UU and UCa (r = 0.47, p < 0.001) and between UNa and UC a (r = 0.33, p < 0.001), but the slope of the relation UCa/UU was increased only in hypercalciurics, whereas it did not differ between normocalciurics and controls. By multiple regression analysis, variations of UU and UNa altogether accounted only for 22% of variation in UCa. We conclude that in both sexes hypercalciuric stone formers have a higher protein and sodium intake than normocalciurics, and for a given urinary urea output, their mean urinary calcium excretion is higher, thus suggesting that hypercalciuric stone formers are electively sensitive to the hypercalciuric effect of high protein intake.

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Vazquez JA, Morse EL, Adibi SA
J Clin Invest 1985 Aug;76(2):737-743

To assess the effect of each dietary caloric source on the catabolism of branched-chain amino acids, we investigated the rate of leucine oxidation before and after obese volunteers consumed one of the following diets for one week: (a) starvation, (b) 300 or 500 cal of fat/d, (c) 300 or 500 cal of carbohydrate/d, (d) 300 or 500 cal of protein/d, (e) a mixture of carbohydrate (300 cal/d) and fat (200 cal/d), or (f) a mixture of carbohydrate (300 cal/d) and protein (200 cal/d). Starvation significantly increased the rate of leucine oxidation (1.4 +/- 0.11 vs. 1.8 +/- 0.16 mmol/h, P less than 0.01). The same occurred with the fat and protein diets. In sharp contrast, the 500-cal carbohydrate diet significantly decreased the rate of leucine oxidation (1.3 +/- 0.13 vs. 0.6 +/- 0.09 mmol/h, P less than 0.01). The same occurred when a portion of the carbohydrate diet was isocalorically replaced with either fat or protein. The cumulative nitrogen excretion during the fat diet and starvation was not significantly different. As compared with the fat diets, the carbohydrate diets on the average reduced the urinary nitrogen excretion by 12 g/wk. Nitrogen balance was positive during the consumption of the 500-cal protein diet, but negative during the consumption of carbohydrate-protein diet. The fat diets, like the protein diets and starvation, greatly increased plasma leucine (119 +/- 13 vs. 222 +/- 15 microM, P less than 0.01) and beta-hydroxybutyrate (0.12 +/- 0.02 vs. 4.08 +/- 0.43 mM, P less than 0.01) concentrations, and significantly decreased plasma glucose (96 +/- 4 vs. 66 +/- 3 mg/dl, P less than 0.01) and insulin (18 +/- 4 vs. 9 +/- 1 microU/ml, P less than 0.05) concentrations. These changes did not occur, or were greatly attenuated, when subjects consumed carbohydrate alone or in combination with fat or protein. We conclude that during brief caloric restriction, dietary lipid and protein, unlike carbohydrate, do not diminish the catabolism of branched-chain amino acids and the decrease in branched-chain amino acid oxidation is associated with protein sparing.

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Bistrian BR, Sherman M, Young V
J Clin Endocrinol Metab 1981 Oct;53(4):874-878

Estimated rates of total body protein synthesis breakdown, and amino nitrogen flux were determined in five obese females using [15N]glycine. The subjects were fed a baseline diet of 1.5 g protein/kg ideal BW and 1602 +/- 146 Cal total for at least 3 days, followed by 3 weeks where the sole caloric intake was a mixed diet of 0.8 g meat protein and 0.7 g carbohydrate/kg ideal BW and approximately 437 +/- 44 Cal. Amino nitrogen flux, total body protein synthesis, and breakdown values were 289 +/- 56, 198 +/- 37, and 202 +/- 47 g protein/day (187 +/- 24, 129 +/- 19, and 131 +/- 21 g protein/g creatinine) initially and fell significantly (P less than 0.01) to 192 +/- 30 (P less than 0.005), 138 +/- 27 (P less than 0.01), and 146 +/- 25 (P less than 0.01) g protein/day [125 +/- 13 (P less than 0.001), 90 +/- 14 (P less than 0.005), and 95 +/- 11 (P less than 0.005) g protein/g creatinine] by the final 60 h of the third week. Nitrogen balance remained significantly negative (P less than 0.01) during each week of the mixed diet and overall (--3.3 +/- 0.9 g N/day; P less than 0.01). Thus, total body protein synthesis and the net balance between synthesis and catabolism are not maintained with this diet.

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