Nutritional treatment for acquired immunodeficiency virus-associated wasting using beta-hydroxy beta-methylbutyrate, glutamine, and arginine: a randomized, double-blind, placebo-controlled study

BACKGROUND: The current study was designed to examine whether a combination of three nutrients, consisting of beta-hydroxy-beta-methylbutyrate (HMB), a metabolite of leucine, L-glutamine (Gln) and L-arginine (Arg), each of which has been previously shown to slow muscle proteolysis, could synergistically alter the course of muscle wasting in patients with established acquired immunodeficiency syndrome (AIDS). METHODS: Sixty-eight human immunodeficiency virus (HIV)-infected patients with a documented weight loss of at least 5% in the previous 3 months were recruited from the HIV clinic at Nassau County Medical Center. The subjects were randomly assigned in a double-blind fashion to receive either placebo containing maltodextrin or the nutrient mixture (HMB/Arg/Gln) containing 3 g HMB, 14 g L-glutamine, and 14 g L-arginine given in two divided doses daily for 8 weeks. Body weights (BW) were recorded weekly and lean body mass (LBM) and fat mass (FM) were measured by air displacement plethysmography and by a single computerized tomography (CT) slice through the thigh at 0, 4, and 8 weeks. RESULTS: Forty-three subjects completed the 8-week protocol, (placebo, n = 21; HMB/Arg/Gln, n = 22). At 8 weeks, the subjects consuming the HMB/Arg/Gln mixture gained 3.0 +/- 0.5 kg of BW while those supplemented with the placebo gained 0.37 +/- 0.84 kg (p = .009). The BW gain in the HMB/Arg/Gln-treated subjects was predominantly LBM (2.55 +/- 0.75 kg) compared with the placebo-supplemented subjects who lost lean mass (-0.70 +/- 0.69 kg, p = .003). No significant change in FM gain was observed (0.43 +/- 0.83 kg for the group receiving HMB/Arg/Gln and 1.07 +/- 0.64 kg for the group receiving the placebo, p > .20). Similar percentage changes in muscle mass and fat mass were observed with CT scans. Immune status was also improved as evident by an increase in CD3 and CD8 cells and a decrease in the HIV viral load with HMB/Arg/Gln supplementation. CONCLUSIONS: The data indicate that the HMB/Arg/Gln mixture can markedly alter the course of lean tissue loss in patients with AIDS-associated wasting.     

L-ornithine alpha-ketoglutarate in HIV infection: effects on muscle, gastrointestinal, and immune functions

OBJECTIVES: There have been claims that l-ornithine alpha-ketoglutarate (OKG) exerts anticatabolic, anabolic, and immunomodulating properties. This study aimed at quantifying the effects of OKG on muscle force, body composition, and immune function in outpatients infected with the human immunodeficiency virus (HIV) and presenting weight loss. METHODS: Forty-six HIV(+) patients were included in a double-blind, prospective, randomized, controlled trial for 12 wk (10 g/d of OKG or isonitrogenous placebo and nutritional counseling). Podometry, handgrip strength, step test, triceps skinfold thickness, 50-kHz bioelectrical impedance, 3-d diet record, CD4 cell count, HIV-1 RNA concentration (viral load), and gastrointestinal symptoms were assessed at 0, 4, 8, and 12 wk. RESULTS: At baseline, patients (OKG, n = 22; placebo, n = 24) has similar CD4 counts (338 +/- 172 and 310 +/- 136 cells/mL), viral load (3.6 +/- 1.3 and 3.5 +/- 1.3 log(10) copies/mL), body mass index (20.0 +/- 2.4 and 20.6 +/- 3.0 kg/m(2)), weight loss (9.0 +/- 3.12 and 9.4 +/- 3.0 kg), and food intake (2509 +/- 962 and 2610 +/- 808 kcal/d). Twenty-nine patients completed the protocol. Both groups increased their body mass index (P = 0.02 versus baseline) and triceps skinfold thickness (P < 0.01 versus baseline). They showed a similar positive correlation between handgrip strength and fat-free mass. Frequency of gastrointestinal symptoms increased in the OKG group (86% versus 54% in the placebo group, P = 0.025). No other differences were observed between groups. CONCLUSIONS: All patients increased their body mass index and triceps skinfold thickness due to food supplementation and diet counseling. Oral OKG failed to improve nutritional, functional, or immunologic status in these weight-losing HIV(+) patients and had important gastrointestinal side effects.     

Conjugated linoleic acid supplementation for 1 y does not prevent weight or body fat regain

BACKGROUND: Conjugated linoleic acid (CLA) is marketed as a safe, simple, and effective dietary supplement to promote the loss of body fat and weight. However, most previous studies have been of short duration and inconclusive, and some recent studies have questioned the safety of long-term supplementation with CLA. OBJECTIVE: Our aim was to assess the effect of 1-y supplementation with CLA (3.4 g/d) on body weight and body fat regain in moderately obese people. DESIGN: One hundred twenty-two obese healthy subjects with a body mass index (in kg/m2) > 28 underwent an 8-wk dietary run-in with energy restriction (3300-4200 kJ/d). One hundred one subjects who lost >8% of their initial body weight were subsequently randomly assigned to a 1-y double-blind CLA (3.4 g/d; n = 51) or placebo (olive oil; n = 50) supplementation regime in combination with a modest hypocaloric diet of -1250 kJ/d. The effects of treatment on body composition and safety were assessed with the use of dual-energy X-ray absorptiometry and with blood samples and the incidence of adverse events, respectively. RESULTS: After 1 y, no significant difference in body weight or body fat regain was observed between the treatments. The CLA group (n = 40) regained a mean (+/-SD) 4.0 +/- 5.6 kg body weight and 2.1 +/- 5.0 kg fat mass compared with a regain of 4.0 +/- 5.0 kg body weight and 2.7 +/- 4.9 kg fat mass in the placebo group (n = 43). No significant differences in reported adverse effects or indexes of insulin resistance were observed, but a significant increase in the number of leukocytes was observed with CLA supplementation. CONCLUSION: A 3.4-g daily CLA supplementation for 1 y does not prevent weight or fat mass regain in a healthy obese population.     

盐酸西布曲明治疗单纯性肥胖的对照研究

目的评价盐酸西布曲明治疗单纯性肥胖患者的有效性和安全性.方法采用多中心、随机、双盲、安慰剂平行对照的研究方法.选择年龄18～65岁,体质指数(BMI)27～40的单纯性肥胖患者.口服盐酸西布曲明10mg/d或安慰剂1粒/d,24周.观察体重变化及临床和常规实验室检查结果以评价药物的疗效和安全性.结果有效病例233例,其中对照组113例,治疗组120例.从第4周起盐酸西布曲明组体重降低值即大于安慰剂组,至24周盐酸西布曲明组平均体重降低值为(6.8±3.1)kg,安慰剂组为(0.48±2.6)kg.治疗组不良反应的发生率高于安慰剂组,但症状轻微,易于耐受.结论盐酸西布曲明10mg/d,治疗单纯性肥胖是有效和安全的.     

Increased body weight and improved quality of life in AIDS patients following V-1 Immunitor administration

OBJECTIVES: Development of affordable and safe therapy to reverse the loss of body mass is of critical importance since AIDS-related wasting is associated with increased mortality. METHOD: We have demonstrated earlier that oral therapeutic HIV vaccine, V-1 Immunitor (V1), tested in a small group of AIDS patients in Thailand not only increases T-cell counts and decreases the viral load but also results in weight gain and prolonged survival. To further expand this observation, we retrospectively analyzed 650 HIV-positive patients who were followed for an average of 23 weeks. RESULTS: The treatment with V1 resulted in a sustained and statistically significant increase in body mass across the whole population (mean+/-s.e.; 1.5+/-0.4 kg; P=6.5E-015). Among them, 384 (59%) patients gained an average of 4.2+/-0.2 kg; 107 (17%) had unchanged weight; and 159 (24%) had lost 3.8+/-0.3 kg. Thus, the prevailing majority of patients (76%) were able to gain or maintain weight. Treatment was well tolerated; in a survey of health status in a comparable but separate group of 382 patients, about 85% reported subjective improvement after V1 treatment, 6% reported no difference, and 9% of the patients reported minor adverse reactions, which did not last more than 1 week. Subjective improvement coincides with the reduction or clearance of oral thrush or mucocutaneous candidiasis in 87.5% of the patients. CONCLUSIONS: In an open label setting, V1 increases body weight, subjective assessment of quality of life, and is safe and effective for HIV patients with weight loss. These data provide the impetus of using V-1 Immunitor as an affordable and easy-to-administer means of treating AIDS-associated wasting and opportunistic infections.     

Resting energy expenditure is increased in stable, malnourished HIV-infected patients

Resting energy expenditure (REE) was measured by reference to body composition in 50 malnourished patients with human immunodeficiency virus (HIV) infection and compared with that of 14 healthy subjects. Among HIV patients, 40 had acquired immune deficiency syndrome (AIDS) and 10 had AIDS-related complex (ARC). All were in stable condition and had a previous history of progressive wasting, ie, a mean body weight loss of 14.2 +/- 8.1 kg over 16.6 mo (range 2-49 ms). The mean REE was 14% higher than estimated basal energy expenditure (EBEE), according to the Harris and Benedict formula. Thirty-four patients (68%) were classified as hypermetabolic (REE greater than 110% EBEE). The best predictable variable for REE was fat-free mass (FFM), as determined by an anthropometric method (r = 0.72; P less than 0.001). The mean REE was 12% higher in HIV patients than in the control group FFM (156 +/- 19 vs 124 +/- 17 kJ.kg FFM-1.d-1). We concluded that in stable and malnourished HIV patients, the progressive wasting may be partly related to an increase in REE. The mechanism of this hypermetabolic state remains to be established.     

Effects of equal weight loss with orlistat and placebo on body fat and serum fatty acid composition and insulin resistance in obese women

BACKGROUND: Dietary fat has been reported to influence insulin sensitivity. OBJECTIVE: The objective of the study was to determine how identical weight loss (target: loss of 8% of body weight over 3-6 mo) in women taking orlistat or placebo combined with a hypocaloric diet influences body composition and insulin sensitivity. DESIGN: Forty-seven obese women [body mass index (in kg/m(2)): 32.1 +/- 0.4] were randomly assigned to receive either orlistat (120 mg 3 times daily; n = 23) or placebo (n = 24) with a hypocaloric diet. Whole-body insulin sensitivity (insulin clamp technique), serum fatty acids, and body composition (magnetic resonance imaging) were measured before and after weight loss. RESULTS: The groups did not differ significantly at baseline with respect to age, body weight, intraabdominal and subcutaneous fat volumes, or insulin sensitivity. Weight loss did not differ significantly between the orlistat (7.3 +/- 0.2 kg, or 8.3 +/- 0.1%) and placebo (7.4 +/- 0.2 kg, or 8.2 +/- 0.1%) groups. Insulin sensitivity improved significantly (P < 0.001) and similarly after weight loss in the orlistat (from 4.0 +/- 0.3 to 5.1 +/- 0.3 mg x kg fat-free mass(-1) x min(-1)) and placebo (from 4.4 +/- 0.4 to 5.4 +/- 0.4 mg x kg fat-free mass(-1) x min(-1)) groups. Intraabdominal fat and subcutaneous fat decreased significantly in both groups, but the ratio of the 2 decreased significantly only in the orlistat group. The proportion of dihomo-gamma-linolenic acid (20:3n-6) in serum phospholipids was inversely related to insulin sensitivity both before (r = -0.48, P < 0.001) and after (r = -0.46, P < 0.001) weight loss, but it did not change significantly in either group. CONCLUSIONS: Weight loss rather than inhibition of fat absorption enhances insulin sensitivity. A decrease in fat absorption by orlistat appears to favorably influence the ratio between intraabdominal and subcutaneous fat, which suggests that exogenous fat or its composition influences fat distribution.     

Nutritional supplementation of the leucine metabolite beta-hydroxy-beta-methylbutyrate (hmb) during resistance training

The effects of supplementation of the leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) were examined in a resistance training study. Thirty-nine men and 36 women between the ages of 20-40 y were randomized to either a placebo (P) supplemented or HMB supplemented (3.0 g HMB/d) group in two gender cohorts. All subjects trained three times per week for 4 wk. In the HMB group, plasma creatine phosphokinase levels tended to be suppressed compared to the placebo group following the 4 wk of resistance training (HMB:174. 4 +/- 26.8 to 173.5 +/- 17.0 U/L; P:155.0 +/- 20.8 to 195.2 +/- 23.5 U/L). There were no significant differences in strength gains based on prior training status or gender with HMB supplementation. The HMB group had a greater increase in upper body strength than the placebo group (HMB:7.5 +/- 0.6 kg; P:5.2 +/- 0.6 kg; P = 0.008). The HMB groups increased fat-free weight by 1.4 +/- 0.2 kg and decreased percent fat by 1.1% +/- 0.2% while the placebo groups increased fat-free weight by 0.9 +/- 0.2 kg and decreased percent fat by 0.5% +/- 0.2% (fat-free weight P = 0.08, percent fat P = 0.08, HMB compared to placebo). In summary, this is the first short-term study to investigate the roles of gender and training status on the effects of HMB supplementation on strength and body composition. This study showed, regardless of gender or training status, HMB may increase upper body strength and minimize muscle damage when combined with an exercise program.     

Effects of calcium pyruvate supplementation during training on body composition, exercise capacity, and metabolic responses to exercise

OBJECTIVE: We evaluated the effects of calcium pyruvate supplementation during training on body composition and metabolic responses to exercise. METHODS: Twenty-three untrained females were matched and assigned to ingest in a double blind and randomized manner either 5 g of calcium pyruvate (PYR) or a placebo (PL) twice daily for 30 d while participating in a supervised exercise program. Prior to and following supplementation, subjects had body composition determined via hydrodensiometry; performed a maximal cardiopulmonary exercise test; and performed a 45-min walk test at 70% of pre-training VO2 max in which fasting pre- and post exercise blood samples determined. RESULTS: No significant differences were observed between groups in energy intake or training volume. Univariate repeated measures ANOVA revealed that subjects in the PYR group gained less weight (PL 1.2 +/- 0.3, PYR 0.3 +/- 0.3 kg, P = 0.04), lost more fat (PL 1.1 +/- 0.5; PYR -0.4 +/- 0.5 kg, P = 0.03), and tended to lose a greater percentage of body fat (PL 1.0 +/- 0.7; PYR -0.65 +/- 0.6%, P = 0.07), with no differences observed in fat-free mass (PL 0.1 +/- 0.5; PYR 0.7 +/- 0.3 kg, P = 0.29). However, these changes were not significant when body composition data were analyzed by MANOVA (P = 0.16). There was some evidence that PYR may negate some of the beneficial effects of exercise on HDL values. No significant differences were observed between groups in maximal exercise responses or metabolic responses to submaximal walking. CONCLUSIONS: Results indicate that PYR supplementation during training does not significantly affect body composition or exercise performance and may negatively affect some blood lipid levels.     

Is DL-fenfluramine a potentially helpful drug therapy in overweight adolescent subjects?

We have studied the therapeutic effects of two different doses (30 mg and 60 mg, twice daily) of DL-fenfluramine (DL-F) in, respectively, prepuberal (11-13 years old) and adolescent subjects (14-17 years old). Sixty-eight obese subjects were recruited for this study (22 boys, 36 girls, aged 10-17 years old) with body mass index ranging from 24.5 to 44.0 kg/m2, absolute weight ranging from 37.0 to 119.5 kg and % over IBW ranging from 122% to 260%. Results were compared to a placebo treated group of obese adolescent patients (n = 17), 6 boys and 11 girls, aged 10-17 years old, BMI ranging from 26-44 kg/m2, absolute weight 53.1 to 96.5 kg, and with 129% to 253% over IBW. In the DL-F-treated subjects most patients (n = 41) had a continuous weight loss during 12 months but 27 individuals were unable to lose any additional weight after the initial 6 months of the trial. Taken together 65% of all patients lost weight during DL-F treatment (12 months) whereas only 17.4% of the placebo group lost a significant (> 10% BMI) amount of excess weight. Also the placebo group had a higher withdrawal rate (57%) as compared with the DL-F-treated group (24%). There was a significant (p < 0.05) decrease of the mean +/- SD of the BMI (at 6 and 12 months of therapy). No significant change of the BMI was observed for control group. Minor adverse side effects consisted of a brief period of drowsiness and dry mouth. Our findings indicated that the continuous administration of DL-Fenfluramine might help obese adolescent subjects adhere to a diet and to maintain the weight loss achieved without major or harmful adverse effects.     

Does dietary fiber affect food intake and body weight?

The effect of dietary fiber on energy intake or body weight has been the subject of numerous clinical studies. Critical examination of the studies shows that many have methodological problems that limit their usefulness. Problems include the absence of a placebo treatment, confounding with time, inadequate measurement of food intake, very low doses of fiber, inappropriately short treatment and observation periods, and multiple changes in the diet. The reviewed evidence indicates that supplementation with wheat bran has no effect on energy intake or body weight; however, other types of fiber may have an effect. Four studies showed that fiber supplementation resulted in a 0.2 to 0.4 kg/week greater weight loss in the treatment than in the control subjects. One study showed a decrease of 1,071 kcal/week in a subject's spontaneous intake. None of the studies reviewed followed subjects for longer than 3 months.     

Dietary herbal supplements with phenylephrine for weight loss

This study was designed to evaluate the efficacy and safety of a dietary herbal supplement containing citrus aurantium and phenylephrine in the treatment of obesity. Two pilot studies enrolled healthy subjects with body mass indexes 25-40 kg/m(2) to similar 8-week weight loss programs. Safety was assessed by physical examination and laboratory tests at screening and 8 weeks. The first pilot study randomized eight subjects to citrus aurantium (herbal phenylephrine) or placebo. Body composition by DEXA scan, waist circumference, and resting metabolic rate (RMR) were measured at baseline and 8 weeks. Food intake and appetite ratings were measured at baseline and week 2. The second pilot study randomized 20 subjects to two 2-hour RMR tests a week apart after phenylephrine (20 mg) or placebo followed by phenylephrine (20 mg) three times a day for 8 weeks. In the first pilot study, the citrus aurantium group gained 1.13 +/- 0.27 (mean +/- SEM) kg compared with 0.09 +/- 0.28 kg in the placebo group (P < .04). RMR at baseline rose more in the citrus aurantium group, 144.5 +/- 15.7 kcal/24 hours, than the placebo group, 23.8 +/- 28.3 kcal/24 hours (P < .002), but not at 8 weeks. DEXA, waist circumference, food intake, and hunger ratings were not different. In the second pilot study, the phenylephrine group lost 0.8 +/- 3.4 kg in 8 weeks (not significant), and RMR increased more in the phenylephrine group (111.5 +/- 32.6 vs. 37.4 +/- 22.7 kcal/24 hours, P = .02). There were no significant safety issues in either study. Although no toxicity was seen, these pilot studies suggest phenylephrine is not efficacious for weight loss.     

Fluoxetine's effect on weight loss in obese subjects

Forty-five obese subjects with a mean weight of 102.9 kg and a body mass index (in kg/m2) of 37.6 were randomly assigned to a fluoxetine-diet group (n = 23) or a placebo-diet group (n = 22) for 52 wk. At week 29, 14 subjects on fluoxetine who completed the study attained their maximum weight loss of 12.4 kg, an amount significantly greater than the maximum weight loss of 4.5 kg for the 16 on placebo who completed the study. The fluoxetine group's significantly greater mean weight loss continued through week 45. However, those on fluoxetine regained a mean of 4.2 kg from their lowest weight (P less than 0.001) whereas the placebo group did not. By the end of the study, each group weighed significantly less than they did at baseline (fluoxetine: -8.2 kg; placebo: -4.5 kg; P less than 0.05) although the difference between groups was no longer significant (P greater than 0.05). Several factors were considered as possible causes for the regain with fluoxetine.     

Prolonged leucine supplementation does not augment muscle mass or affect glycemic control in elderly type 2 diabetic men

The loss of muscle mass with aging has been, at least partly, attributed to a blunted muscle protein synthetic response to food intake. Leucine coingestion has been reported to stimulate postprandial insulin release and augment postprandial muscle protein accretion. We assessed the clinical benefits of 6 mo of leucine supplementation in elderly, type 2 diabetes patients. Sixty elderly males with type 2 diabetes (age, 71 ± 1 y; BMI, 27.3 ± 0.4 kg/m(2)) were administered 2.5 g L-leucine (n = 30) or a placebo (n = 30) with each main meal during 6 mo of nutritional intervention (7.5 g/d leucine or placebo). Body composition, muscle fiber characteristics, muscle strength, glucose homeostasis, and basal plasma amino acid and lipid concentrations were assessed prior to, during, and after intervention. Lean tissue mass did not change or differ between groups and at 0, 3, and 6 mo were 61.9 ± 1.1, 62.2 ± 1.1, and 62.0 ± 1.0 kg, respectively, in the leucine group and 62.2 ± 1.3, 62.2 ± 1.3, and 62.2 ± 1.3 kg in the placebo group. There also were no changes in body fat percentage, muscle strength, and muscle fiber type characteristics. Blood glycosylated hemoglobin did not change or differ between groups and was 7.1 ± 0.1% in the leucine group and 7.2 ± 0.2% in the placebo group. Consistent with this, oral glucose insulin sensitivity and plasma lipid concentrations did not change or differ between groups. We conclude that prolonged leucine supplementation (7.5 g/d) does not modulate body composition, muscle mass, strength, glycemic control, and/or lipidemia in elderly, type 2 diabetes patients who habitually consume adequate dietary protein.     

Body composition in 70-year-old adults responds to dietary beta-hydroxy-beta-methylbutyrate similarly to that of young adults.

Studies in young adults have demonstrated that beta-hydroxy-beta-methylbutyrate (HMB) can increase gains in strength and fat-free mass during a progressive resistance-training program. The purpose of this study was to determine whether HMB would similarly benefit 70-y-old adults undergoing a 5 d/wk exercise program. Thirty-one men (n = 15) and women (n = 16) (70 +/- 1 y) were randomly assigned in a double-blind study to receive either capsules containing a placebo or Ca-HMB (3 g/d) for the 8-wk study. Skin fold estimations of body composition as well as computerized tomography (CT) and dual X-ray absorptiometry (DXA) scans were measured before the study and immediately after the 8-wk training program. HMB supplementation tended to increase fat-free mass gain (HMB, 0.8 +/- 0.4 kg; placebo, -0.2 +/- 0.3 kg; treatment x time, P = 0.08). Furthermore, HMB supplementation increased the percentage of body fat loss (skin fold: HMB, -0.66 +/- 0.23%; placebo, -0.03 +/- 0.21%; P = 0.05) compared with the placebo group. CT scans also indicated a greater decrease in the percentage of body fat with HMB supplementation (P < 0.05). In conclusion, changes in body composition can be accomplished in 70-y-old adults participating in a strength training program, as previously demonstrated in young adults, when HMB is supplemented daily.     

A randomized comparative trial of testosterone and protein supplements for weight loss in HIV+ men

This report presents findings from a randomized trial that compared the efficacy of 1) 400 mg biweekly IM injections of testosterone plus daily “placebo” standard nutritional supplements (containing 8 g of protein per serving), 2) high protein (37 g per serving) supplements and placebo IM injections, and 3) both testosterone and high protein supplements, in the treatment of HIV-related weight loss. Sixty-five HIV+ men with ≤90% of normative body weight or body cell mass entered the study, of whom 54 (83%) completed the 12-week trial. In an intention to treat analysis, the response rates (defined as an increase of at least 5% in the ratio of body cell mass to height) for testosterone (55%), high protein supplements (62%), and both testosterone and protein supplements (73%) were statistically similar (p = NS). Amount of change in body weight, body cell mass, fat free mass and body fat from baseline to Week 12 (as measured by bioelectric impedance analysis), all of which were statistically significant within each group, did not differ across the three groups. Among all completers, the average gain in body weight and body cell mass after 12 weeks was 3.5 kgs and 2.0 kgs, respectively; 77% of the increase in body weight was fat free body mass, compared to 23% fat. These data support the efficacy of both testosterone and high protein supplements as independent treatments for HIV-related weight loss, but do not demonstrate a further advantage of combining the treatments.     

Six-month treatment of obesity with sibutramine 15 mg; a double-blind, placebo-controlled monocenter clinical trial in a Hispanic population

OBJECTIVE: To evaluate the safety and efficacy of sibutramine 15 mg by mouth once per day in obese patients over a period of 6 months. RESEARCH METHODS AND PROCEDURES: A monocenter, double-blind, placebo controlled, parallel, prospective clinical trial was carried out. Sixty-nine male and female obese patients (body mass index [BMI] > 30 kg/m2) aged 16 to 65 years entered the trial. RESULTS: 22 of 35 patients in the sibutramine group and 9 of 34 patients in the placebo group completed the trial. The high dropout rate in the sibutramine group was due to adverse events in 3 cases, lack of efficacy (as judged by patients) in 7, loss to follow-up in 2, and an orthopedic device being worn in 1; in the placebo group the dropouts were ascribed to lack of efficacy (as judged by patients) in 17 cases and to loss to follow-up in 8 cases. Using the method of last observation carried forward, the weight loss in the sibutramine group was 10.27 kg (95% confidence intervals [95% CI] 7.66; 13.07) and 1.26 kg (95% CI 0.3; 2.23) in the placebo group. The BMI loss was 4.17 kg/m2 (95% CI 3.11; 5.22) in the sibutramine group and 0.53 kg/m2 (95% CI 0.13; 0.92) in the placebo group. The waist circumference reduction was 12.51 cm (95% CI 9.25; 15.77) in the sibutramine group and 3.26 cm (95% CI 1.38; 5.14) in the control group (p<0.05 by paired Student's t test for all the intragroup comparisons). Twenty-three sibutramine patients had 34 adverse events, the most frequent adverse events in the sibutramine group were upper respiratory tract infections (n = 6) and constipation (n = 6); 16 placebo patients had 21 adverse events. Three sibutramine patients withdrew their informed consent when they had adverse events. DISCUSSION: The results show that sibutramine induces significant loss of body weight and waist circumference. Cardiovascular function was not significantly affected by sibutramine. Sibutramine was well tolerated by most of the patients.     

Effect of capsaicin on substrate oxidation and weight maintenance after modest body-weight loss in human subjects

The aim of the present study was to investigate whether capsaicin assists weight maintenance by limiting weight regain after weight loss of 5 to 10 %. In this randomized double-blind placebo-controlled study, ninety-one moderately overweight subjects were randomly assigned to an intensive group that underwent all the measurements, and an extensive group that underwent the same measurements except the metabolism measurements. After a 4-week very-low-energy diet (VLED) intervention, a 3-month weight-maintenance period followed. During weight maintenance, subjects were divided into a capsaicin (135 mg capsaicin/d) and a placebo group. Body mass was measured before and after the VLED and after 1, 2 and 3 months of weight maintenance. The mean body-mass loss during the VLED was 6.6 (SD 2.0) kg (7.8 (SD 1.8) % initial body mass), and was not different between the subsequent treatment and placebo group. During weight maintenance, mean % regain during treatment was not significantly different compared with placebo (33.3 (SD 35.7) v. 19.2 (SD 41.8) %, P=0.09). RQ was significantly less increased during weight maintenance in the treatment group compared with placebo (0.04 (SD 0.06) v. 0.07 (SD 0.05), P<0.05), indicating a relatively more sustained fat oxidation. Fat oxidation (g/h) after weight maintenance was higher in the capsaicin group compared with placebo (4.2 (SD 1.1) v. 3.5 (SD 0.9), P<0.05). These results indicate that capsaicin treatment caused sustained fat oxidation during weight maintenance compared with placebo. However, capsaicin treatment has no limiting effect on 3-month weight regain after modest weight loss.     

Supplemental vitamin A improves anemia and growth in anemic school children in Tanzania

We conducted a randomized controlled trial of the effects of dietary supplements on anemia, weight and height in 136 anemic school children from a low socioeconomic background in Bagamoyo District schools in Tanzania. The aim of the current study was to investigate the impact of dietary supplements on anemia and anthropometric indices of anemic school children. The supplements were vitamin A alone, iron and vitamin A, iron alone or placebo, administered in a double-blinded design for 3 mo. All supplements were provided with local corn meals. Hemoglobin concentration, body weight and height were measured at baseline and at follow-up after supplementation. Vitamin A supplementation increased the mean hemoglobin concentration by 13.5 g/L compared with 3.5 g/L for placebo [P < 0.0001, 95% confidence interval (CI) 6.19-13.57), the mean body weight by 0.6 kg compared with 0.2 kg for placebo (P < 0.0001, 95% CI 0.19-0.65) and the mean height by 0.4 cm compared with 0.1 cm for placebo (P = 0.0009, 95% CI 0.08-0.42). However, the group of children who received combined vitamin A and iron supplementation had the greatest improvements in all indicators compared with placebo (18.5 g/L, P < 0.0001, 95% CI 14.81-22.23; 0.7 kg, P < 0. 0001, 95% CI 0.43-0.88 and 0.4 cm, P < 0.0001, 95% CI 0.22-0.56 for hemoglobin, weight and height, respectively). It is likely that vitamin A supplementation may have a useful role in combating the problems of vitamin A deficiency and anemia, as well as in improving children's growth, in developing countries.     

Creatine and beta-hydroxy-beta-methylbutyrate (HMB) additively increase lean body mass and muscle strength during a weight-training program.

We investigated whether creatine (CR) and beta-hydroxy-beta-methylbutyrate (HMB) act by similar or different mechanisms to increase lean body mass (LBM) and strength in humans undergoing progressive resistance-exercise training. In this double-blind, 3-wk study, subjects (n = 40) were randomized to placebo (PL; n = 10), CR (20.0 g of CR/d for 7 d followed by 10.0 g of CR/d for 14 d; n = 11), HMB (3.0 g of HMB/d; n = 9), or CR-and-HMB (CR/HMB; n = 10) treatment groups. Over 3 wk, all subjects gained LBM, which was assessed by bioelectrical impedance analysis. The CR, HMB and CR/HMB groups gained 0.92, 0.39, and 1.54 kg of LBM, respectively, over the placebo group, with a significant effect with CR supplementation (main effect P = 0.05) and a trend with HMB supplementation (main effect P = 0.08). These effects were additive because there was no interaction between CR and HMB (CR x HMB main effect P = 0.73). Across all exercises, HMB, CR, and CR/HMB supplementation caused accumulative strength increases of 37.5, 39.1, and 51.9 kg, respectively, above the placebo group. The exercise-induced rise in serum creatine phosphokinase was markedly suppressed with HMB supplementation (main effect P = 0.01). However, CR supplementation antagonized the HMB effects on serum creatine phosphokinase (CR x HMB interactive effect P = 0.04). Urine urea nitrogen and plasma urea were not affected by CR supplementation, but both decreased with HMB supplementation (HMB effect P < 0.05), suggesting a nitrogen-sparing effect. In summary, CR and HMB can increase LBM and strength, and the effects are additive. Although not definitive, these results suggest that CR and HMB act by different mechanisms.