Rita Tsay

D-Fenfluramine selectively suppresses carbohydrate snacking by obese subjects

Twenty obese inpatients who claimed to crave carbohydrate-rich foods were given d-fenfluramine (15 mg p.o., twice daily) or its placebo, double-blind, for two consecutive eight-day periods. Food choices were measured on treatment days 1, 7, and 8 by giving the subjects access to unlimited portions of six isocaloric meal foods (three high in carbohydrate and three high in protein) and of 10 isocaloric snack foods (five high in protein and five high in carbohydrate) available 24 hours a day in a computerized vending machine. d-fenfluramine reduced mealtime calorie intake by only 16% (from 1940 +/- 94 to 1630 +/- 92; p < .001), mealtime carbohydrate by 22%, and had no significant effect on mealtime protein consumption; in contrast, snack calorie intake was reduced by 41% (from 707 +/- 97 to 414 +/- 46; p < .001), and snack carbohydrate intake by the same proportion. The mean number of carbohydrate-rich snacks consumed per day decreased from 5.8 +/- 0.8 to 3.4 +/- 0.4 (p < .01), while that of protein-rich snacks failed to change signficantly (i.e., from 0.7 +/- 0.2 to 0.5 +/- 0.2).

Arginine, citrulline, and nitric oxide metabolism in end-stage renal disease patients

The kidneys are thought to be a major site of net de novo arginine synthesis, but the quantitative status of arginine metabolism and its substrate precursor relationship to nitric oxide (NO) synthesis in end stage renal disease (ESRD) patients have not been characterized. We have investigated kinetic aspects of whole body arginine metabolism in six patients with ESRD. They received two pre- and two post-hemodialysis intravenous tracer infusion studies with L-[guanidino-(15)N(2)]arginine and L-[(13)C]leucine during the first study, and L-[5-(13)C]arginine and L-[5-(13)C-ureido,5,5, (2)H(2)]citrulline during the second study. Arginine homeostasis in ESRD patients was found to be associated with a lower rate of arginine oxidation, and despite the decrease in renal function, the rate of de novo arginine synthesis appeared to be preserved. Plasma citrulline concentrations and flux were also elevated in these subjects compared with healthy adults. The rate of whole body NO synthesis was increased in the ESRD patients, but apparently not different pre- and post-hemodialysis therapy. The anatomic site(s) responsible for the maintenance of net de novo arginine synthesis and for the elevated NO synthesis and its pathophysiological importance in ESRD remain to be established.

Modifiable Dietary Habits and Their Relation to Metabolic Abnormalities in Men and Women with Human Immunodeficiency Virus Infection and Fat Redistribution

We assessed the relationship between dietary intake, body composition, and metabolic parameters in 85 consecutive human immunodeficiency virus (HIV)-infected patients with fat redistribution. Dietary history and values for fasting glucose, insulin, lipids, and oral glucose tolerance were obtained for 62 men and 23 women with HIV infection and fat redistribution (mean age +/- standard error of the mean [SEM], 43.5+/-0.9 years; mean body mass index [BMI] +/- SEM, 26.3+/-0.5 kg/m2). A multivariate regression analysis was used to predict insulin area under the curve (AUC) following the oral glucose tolerance test; this included age, sex, BMI, waist-to-hip ratio, kilocalories, duration of protease inhibitor (PI) use, fat redistribution pattern, alcohol intake, dietary fiber intake, and polyunsaturated-to-saturated (P:S) fat ratio. Only age (P=.004), PI use duration (P=.02), and P:S fat ratio (P=.003) were positively associated with insulin AUC. Dietary fiber intake was inversely associated with the insulin AUC (P=.001). In a similar analysis, alcohol consumption was a significant positive predictor of low-density lipoprotein cholesterol. Polyunsaturated fats, fiber, and alcohol are strongly associated with insulin resistance and hyperlipidemia in this population and may be important targets for dietary modification.

Fenfluramine suppresses snack intake among carbohydrate cravers but not among noncarbohydrate cravers

Two groups of obese individuals who consume excessive calories primarily as snack foods have been distinguished: carbohydrate cravers and noncarbohydrate cravers. Both groups consume about 800 calories from snacks (860 kcal vs 879 kcal) and about 2000 calories from meals (1906 kcal vs 2080 kcal) daily. The carbohydrate-cravers consume almost all of their snacks as carbohydrate-rich foods (7 ± 0.4 CHO snacks/day vs 0.9 ± 0.12 protein snacks/day) whereas the noncarbohydrate cravers consume approximately equal numbers of protein and carbohydrate snacks (4.5 ± 0.6 carbohydrate snacks/day vs 3.5 ± 0.5 protein snacks/day). D-fenfluramine significantly reduced the intakes of calories (range 24–44%) and carbohydrates (range 28–41%) from snacks among the carbohydrate cravers over a three month treatment period. The drug did not affect snack intake by the noncarbohydrate cravers until the third month of treatment when the consumption of both types of snacks decreased significantly. D-fenfluramine decreased mealtime carbohydrate intake among the carbohydrate cravers throughout the treatment period (range 16–23%); mealtime protein intake declined comparably (range 14–18%) during the first and third treatment months. The drug had no effect on mealtime carbohydrate nor protein intake by noncarbohydrate cravers.

Dexfenfluramine, fluoxetine, and weight loss among female carbohydrate cravers.

The consumption of excess calories as carbohydrates (CHO)-rich, protein-poor snacks characterizes the overeating of obese CHO cravers, premenstrual women, patients with Seasonal Affective Disorder, and former smokers. This specific appetite for CHOs may involve brain serotonin, as the synthesis and release of this neurotransmitter can increase following consumption of CHO-rich foods. To examine whether weight loss produced by serotoninergic drugs involves a selective reduction in CHO intake, obese females who consumed at least 30% of their daily calories from CHO-rich snacks were treated with dexfenfluramine ([DF] 15 mg b.i.d.); fluoxetine ([FL] 20 mg t.i.d.); or placebo (PL) for 12 weeks. Weekly weight loss for 25 of 29 PL completers was 0.22 kg ± 0.06 (mean ± SEM); for 21 of 28 DF completers, 0.56 ± 0.08 kg; and for 18 of 30 FL completers, 0.58 ± 0.09 kg (PL < DF = FL; p = .039). Seven FL subjects, 2 PL subjects, and 1 DF subject withdrew from the study due to side effects; other withdrawals were due to intercurrent illness or personal problems. Prior to treatment, subjects consumed over 40% of their daily CHO intake from snacks. Both of the drugs selectively decreased CHO snack intake (p < 0.05); DF, but not FL, also decreased meal CHO intake (p < .025). These results suggest that weight loss following treatment with serotoninergic drugs may relate to a selective decrease in CHO appetite.

Use of Food Quotients in Human Doubly Labeled Water Studies: Comparable Results Obtained with 4 Widely Used Food Intake Methods

Information on the macronutrient composition of the diet is needed in doubly labeled water studies to convert measured rates of carbon dioxide production into values for total energy expenditure. There is no general consensus, however, about the best method to determine food intake for this purpose. Four common methods of measuring food intake (7-day weighed food intake, 24-hour recall, and Fred Hutchinson Cancer Research Center/Block and Willett food frequency questionnaires) were tested for their ability to provide comparable food quotient and total energy expenditure data in doubly labeled water studies in 10 young and 10 older women. All methods gave mean values for total energy expenditure that were within 1% of each other. Individual values obtained using the 24-hour recall and food frequency questionnaires were within +/- 3% (standard deviation) of values determined using data from the 7-day weighed food record. These results suggest that it is not necessary to use time-consuming and expensive 7-day food records in doubly labeled water studies; instead, food intake data obtained more easily by 24-hour recall or food frequency questionnaire can provide comparable data.

Body Mass Index of Obese Women Determines the Response to a Carbohydrate-Rich Weight Loss Diet Plan

Abstract LEARNING OUTCOME: To understand the factors that might determine a weight loss regime that is appropriate for obese patients. Consumption of carbohydrate (cho)-rich, protein-poor foods is often associated with emotional distress that characterizes the overeating in many obese individuals. The subsequent insulin-mediated increase in blood and brain tryptophan (TP) levels and serotonin synthesis may improve mood and eating behavior. Healthy obese women with a mean Body Mass Index (BMI) of 32 ± 0.16 (Mean ± SD) or 37 ± 0.85 who overeat when stressed were treated for 7 weeks (BMI 32 group) or 5 weeks (BMI 37 group) with a 1400 calorie protein-rich or cho-rich liquid meal and snack replacement Plasma TP/Large Neutral Amino Acids (LNAA) ratios which reflect brain TP uptake were measured following consumption of the diets. The TP/LNAA ratio increased significantly after intake of the cho-rich (0.094 pre vs 0.111 post drink; p

The effect of a cars oh yd rate-rich diet on weight loss among obese females who overeat when stressed

Abstract Thirty-nine obese females weighing between 40–60 pounds above medically desirable weight, who describe themselves as consuming excessive amounts of carbohydrate (CHO)-rich foods when stressed, were randomly assigned to a CHO-rich or protein-rich diet for 7 weeks. Both diets provided 1350 calories and consisted of specially formulated liquid breakfast, lunch and snack, as well as a dinner of traditional foods. An increase in the ratio of tp to that of the large neutral amino acids which compete with tp for uptake into the brain was observed after consumption of the CHO-rich but not the protein-rich diet The number of subjects who lost weight differed significantly between the two groups. All 20 subjects on the CHO-rich diet lost 2 or more pounds whereas only 12 of the 19 subjects on the protein-rich diet lost weight (p A significant improvement in self-reported vigor and decrease in CHO craving was seen among subjects on the CHO-rich diet No change was observed among those on the protein-rich diet (p Tryptophan uptake in the brain is associated with increased synthesis and release of brain serotonin. Since serotonin is involved in regulating both CHO appetite and mood, dietary interventions that presumably increase brain serotonin may be useful in controlling stress-related overeating.

d-Fenfluramine selectively suppresses carbohydrate snacking by obese subjects

Twenty obese inpatients who claimed to crave carbohydrate-rich foods were given d-fenfluramine (15 mg p.o., twice daily) or its placebo, double-blind, for two consecutive eight-day periods. Food choices were measured on treatment days 1, 7, and 8 by giving the subjects access to unlimited portions of six isocaloric meal foods (three high in carbohydrate and three high in protein) and of 10 isocaloric snack foods (five high in protein and five high in carbohydrate) available 24 hours a day in a computerized vending machine. d-fenfluramine reduced mealtime calorie intake by only 16% (from 1940 +/- 94 to 1630 +/- 92; p < .001), mealtime carbohydrate by 22%, and had no significant effect on mealtime protein consumption; in contrast, snack calorie intake was reduced by 41% (from 707 +/- 97 to 414 +/- 46; p < .001), and snack carbohydrate intake by the same proportion. The mean number of carbohydrate-rich snacks consumed per day decreased from 5.8 +/- 0.8 to 3.4 +/- 0.4 (p < .01), while that of protein-rich snacks failed to change signficantly (i.e., from 0.7 +/- 0.2 to 0.5 +/- 0.2).