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During a total fast in obese subjects, the daily rate of nitrogen excretion undergoes only a small further decline after 2 wk, the excretion rate being about 5 g N/day. At this time, ammonium and urea each constitute about one-half of this excretion. The purpose of this study was to consider two alternative hypotheses: first, that the near plateau in nitrogen excretion represents an irreducible minimum rate of net protein breakdown in order to supply essential organs with calories in the form of glucose; second, that protein breakdown could be further reduced by minimizing the requirement to provide nitrogen for ammonium excretion during the ketoacidosis of fasting. Because ammonium excretion is largely controlled by acid-base balance, 150 mmol of sodium bicarbonate plus 60 mmol of potassium chloride were administered daily to decrease ammonium excretion in eight obese subjects who were totally fasting for more than 14 days. Urine ammonium nitrogen fell with this treatment (from 3.8 +/- 0.4 to 2.0 +/- 0.4 g N/g creatinine). In addition, there was a smaller fall in the rate of urea excretion (from 2.5 +/- 0.2 to 2.1 +/- 0.3 g N/g creatinine) together with a fall in the blood urea nitrogen. Therefore, it appears that ammonium excretion contributes to the negative nitrogen balance of a prolonged total fast, as assessed over a 3-day period of observation, is responsible for about one-third of the net lean body mass loss.

To determine the effects of different hypocaloric diets on insulin secretion, 24-h urine C-peptide was measured in 11 obese subjects on a weight-maintaining baseline diet, and the results were compared with values obtained during 14-day periods of diets containing 400 kcal/day of only protein (n = 6) or glucose (n = 5), followed by 14 days of fasting and 14 days of refeeding on 800-1000 kcal/day. A significant positive correlation between total caloric intake and urine C-peptide excretion was found once the C-peptide excretion reached steady state after several days on each diet. Multiple regression analysis showed no contribution of body weight to urine C-peptide during the different diets. In contrast, a significant correlation was found between body weight and urine C-peptide in the fasting state. A marked and identical decrease of approximately 75% in urine C-peptide occurred over the first 5-7 days of the two 400-kcal diets, followed by a further decrease during fasting to 5% of baseline values. Refeeding was associated with a progressive increase. Plasma insulin and C-peptide followed the same trends as found for urine C-peptide, although the magnitude of change was much smaller. C-peptide clearance was not assessed because of the variation in plasma levels on eating meals. However, the same responses were found when C-peptide excretion was factored for creatinine excretion. Thus, the major determinant of urine C-peptide excretion appears to be food intake, and adaptations take 5-7 days to reach steady state.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this study was to determine the cause of an acute metabolic acidosis of the normal anion gap type which developed during a 3 day period when 64 mmol of KCl was administered daily to an obese but otherwise healthy subject fasted for 2 weeks (called the index case). She had typical ketoacidosis of fasting for the first 13 days of fasting; since the plasma [K] was 3.6 mmol/l, she was given 64 mmol of KCl daily for 3 days. On day 3 of KCl treatment, the plasma [HCO3] was 13 mmol/l with no change in the plasma anion gap or 3-hydroxybutyrate concentration; the plasma [K] had risen to 4.3 mmol/l. The cause of the acidosis was a reduction of urine ammonium excretion by 42 mmol/day without a parallel fall in the rate of 3-hydroxybutyrate excretion. Since renal ammonium production can be inhibited by K administration, 5 other obese subjects were studied in a similar fashion to gain insight into the problem. They had a similar reduction in the daily rate of ammonium excretion (41 mmol) after KCl; however, their daily 3-hydroxybutyrate excretions declined by a similar amount (47 mmol) and thus metabolic acidosis did not develop.

Two experiments were designed to investigate the neurobehavioral effects of phenylalanine (PHE; 0.84, 2.52, 5.04, and 10.08 g) and aspartame (APM; 5.04 and 10.08 g) on energy and macronutrient selection and on subjective feelings of hunger, mood and arousal in normal weight adult males. Neither phenylalanine nor aspartame altered mean energy intakes or macronutrient selection at a lunch begun 60 to 105 min after the amino acids were consumed. During this time, increased (p less than 0.05) visual analog scale (VAS) scores for emptiness, rumbling, weakness, degree of hunger and urge to eat were found in both experiments, but no treatment effects or interactions were seen for any variable in either experiment. Plasma PHE levels and ratios to other large neutral amino acids (NAA) rose significantly (p less than 0.05) after all treatments except 0.84 g PHE; plasma tyrosine (TYR) levels increased (p less than 0.05) only when greater than or equal to 2.52 g PHE was given. TYR/NAA ratios were higher (p less than 0.05) after 2.52 and 5.04 g PHE, and 10.08 g APM. No relationships were found between food intake and plasma amino acid levels. We conclude that, in normal weight men, PHE and APM, in doses up to 10 g, do not affect short-term energy and macronutrient intakes, or subjective feelings of hunger, mood and arousal.

Two experiments were conducted, each with 20 healthy 9-10-year-old children. After an overnight fast, subjects were given a standardized breakfast at 0830 hrs, the treatments at 1030 hrs, and a lunch containing an excess of foods at 1200 hrs. Visual analog scales of hunger, fullness, and desire to eat were administered 5 min before and 20 and 85 min after treatment. Lunch-time food intake was measured. In experiment 1, either aspartame (34 mg/kg), or the equivalent sweetness of sodium cyclamate, was given in an ice slurry (300 ml) of unsweetened strawberry Kool-Aid with carbohydrate (1.75 g/kg polycose). In experiment 2, drinks (300 ml) contained either sucrose (1.75 g/kg) or aspartame (9.7 mg/kg). In both experiments, significant meal- and time-dependent effects were observed for subjective feelings of hunger, fullness and desire to eat. Treatments, however, did not affect either subjective feelings of appetite or lunch-time food intake. Thus, aspartame consumed without or with carbohydrate, did not affect either hunger or food intake of children when compared with the sweeteners sodium cyclamate and sucrose, respectively.

This paper presents an overview of selected current concepts of the pathogenesis and treatment of obesity. It has been estimated using the 1981 Canada Fitness Survey data that 14.1% of Canadian adult men and 20.6% of women are greater than 20% above reference table weight. Recent advances in adipocyte metabolism and control have shown that hyperplastic obesity can occur at any age and that there are differences in the replicative rate of adipocyte precursor cells from the massively obese. Furthermore, a number of the complications of obesity, including hypertension, have been related to regional body fat distribution, independent of total body fat. It is suggested that some of the controversy on the relationship between body weight/weight loss and hypertension may be due to failure to account for this. There is now suggestive evidence that abnormalities in diet-induced thermogenesis and (or) brown adipose tissue may result in human obesity. The roles of the major treatment modalities (diet, behaviour therapy, and exercise) are reviewed as are the potential hazards of the weight loss process.

Muscle wasting may occur in patients with chronic renal failure (CRF). To determine whether this is due to a decrease in the synthesis or an increase in the breakdown of muscle protein, we evaluated postabsorptive whole-body protein breakdown, oxidation, and synthesis rates at steady state during a primed, continuous infusion of 13C-leucine. This was done in seven subjects on chronic maintenance hemodialysis (MHD) and in seven normal control subjects. The protein breakdown rate in MHD was not different from that in controls (103 +/- 19 and 106 +/- 19 mumol leucine.kg-1.h-1, respectively). In MHD, however, the protein oxidation rate was 43% greater than that in controls (20 +/- 6 and 14 +/- 4 mumol leucine.kg-1.h-1, p less than 0.05), whereas net protein synthesis was less (p less than 0.05). Reduced net synthesis and increased oxidation rates of protein in the postabsorptive state may therefore contribute to the muscle-wasting syndrome in patients with CRF.

This article reviews data relevant to the hypothesis that aspartame may have a unique effect on meal-time food intake regulation due to its amino acid composition and in addition to its effects as a high intensity sweetener. It is concluded that future studies involving aspartame should be directed towards developing a fundamental understanding of the effects of high intensity sweeteners on food intake, and not give undue attention to putative actions based on its amino acid constituents.