Supplementation with a combination of beta-hydroxy-beta-methylbutyrate (HMB), arginine, and glutamine is safe and could improve hematological parameters.

BACKGROUND: Combining the amino acids arginine and glutamine with the leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) has been shown to reverse lean tissue loss in cancer and acquired immunodeficiency syndrome (AIDS) patients. Although each of these nutrients has been shown to be safe, the safety of this mixture has not been reported. Three double-blind studies examined the safety of the combination of HMB, arginine and glutamine on blood chemistries, hematology, emotional profile, and adverse events. METHODS: Study 1 was conducted in healthy adult males (n = 34), study 2 was in HIV patients with AIDS-associated weight loss (n = 43), and study 3 was in cancer patients with wasting (n = 32). Volunteers were assigned to either a placebo or a mixture of 3 g HMB, 14 g arginine, and 14 g glutamine per day. RESULTS: Across the 3 studies, HMB, arginine, and glutamine supplementation was not associated with any adverse indicators of health. The only significant changes noted were positive indicators of health status. HMB, arginine, and glutamine supplementation was associated with an improvement in emotional profile (p = .05), a decreased feeling of weakness (p = .03), and increased red blood cells, hemoglobin, hematocrit, lymphocytes, and eosinophils (p < .05) when compared with placebo-supplemented subjects. Blood creatinine levels were not changed. However, blood urea nitrogen increased (p = .01) with HMB, arginine, and glutamine supplementation, which was possibly caused by the additional nitrogen consumed or to the fact that ureagenesis is influenced by arginine and glutamine supplementation. CONCLUSION: These results show that HMB, arginine, and glutamine can be safely used to treat muscle wasting associated with AIDS and cancer.

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.

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.

beta-hydroxy-beta-methylbutyrate (HMB) supplementation in humans is safe and may decrease cardiovascular risk factors.

The leucine metabolite, beta-hydroxy-beta-methylbutyrate (HMB) enhances the effects of exercise on muscle size and strength. Although several reports in animals and humans indicate that HMB is safe, quantitative safety data in humans have not been reported definitively. The objective of this work was to summarize safety data collected in nine studies in which humans were fed 3 g HMB/d. The studies were from 3 to 8 wk in duration, included both males and females, young and old, exercising or nonexercising. Organ and tissue function was assessed by blood chemistry and hematology; subtle effects on emotional perception were measured with an emotional profile test (Circumplex), and tolerance of HMB was assessed with a battery of 32 health-related questions. HMB did not adversely affect any surrogate marker of tissue health and function. The Circumplex emotion profile indicated that HMB significantly decreased (improved) one indicator of negative mood (Unactivated Unpleasant Affect category, P < 0.05). No untoward effects of HMB were indicated. Compared with the placebo, HMB supplementation resulted in a net decrease in total cholesterol (5.8%, P < 0.03), a decrease in LDL cholesterol (7.3%, P < 0.01) and a decrease in systolic blood pressure (4.4 mm Hg, P < 0.05). These effects of HMB on surrogate markers of cardiovascular health could result in a decrease in the risk of heart attack and stroke. In conclusion, the objective data collected across nine experiments indicate that HMB can be taken safely as an ergogenic aid for exercise and that objective measures of health and perception of well-being are generally enhanced.

The effect of a high dose of 3-hydroxy-3-methylbutyrate on protein metabolism in growing lambs.

The effect of a high dose of 3-hydroxy-3-methylbutyrate (HMB, a leucine catabolite) on protein metabolism was investigated in growing male lambs fed on hay and concentrate. Concentrate was supplemented with either Ca(HMB)2 (4 g/kg) or Ca(CO3)2 in experimental (HMB) and control groups respectively. Both groups consisted of six 2-month old lambs. Three complementary methods to study protein metabolism were carried out consecutively 2.5 months after beginning the dietary treatment: whole body phenylalanine fluxes, postprandial plasma free amino acid time course and fractional rates of protein synthesis in skeletal muscles. Feeding a high dose of HMB led to a significant increase in some plasma free amino acids compared with controls. Total, oxidative and non-oxidative phenylalanine fluxes were not modified by dietary HMB supplementation. Similarly, an acute infusion of HMB, in the control group, did not change these fluxes. In skeletal muscles, fractional rates of protein synthesis were not affected by long-term dietary supplementation with HMB. Taken together our results showed that administration of a high dose of HMB to lambs was able to modify plasma free amino acid pattern without any effect on whole-body protein turnover and skeletal muscle protein synthesis.

Effects of excess dietary leucine and leucine catabolites on growth and immune responses in weanling pigs.

Two experiments with weanling pigs were conducted to study the effects on growth and immune responses of excess dietary L-leucine (LEU) and dietary supplementation with the LEU catabolites, alpha-ketoisocaproic acid (KIC) and beta-hydroxymethyl butyrate (HMB). In Exp. 1, 80 pigs were randomly allocated according to initial BW and ancestry to five replications of four dietary treatments (four pigs/pen). The control diet contained wheat, oat groats, menhaden fish meal, and dried whey and provided 1.12% LEU. Treatment diets were the control plus 1.12% LEU, 1.12% KIC, or .4% HMB. The experiment lasted 6 wk. In Exp. 2, 36 pigs were randomly allocated to nine replications of four dietary treatments in a 2 x 2 factorial arrangement. Treatments consisted of two concentrations of dietary LEU and a daily i.m. injection of dexamethasone (DEX) or saline. Pigs were fed a control corn-soybean meal and dried whey diet (1.56% LEU) or the control diet plus 1.56% of crystalline LEU. Pigs were individually penned and the experiment lasted 4 wk. Growth performance, plasma free amino acids, plasma urea nitrogen, and humoral and cellular immune responses were measured. Results indicated that LEU concentrations in practical diets and supplementation with KIC and HMB (Exp. 1) did not detrimentally affect growth and immune response. The high LEU concentration and DEX injection used in Exp. 2, however, were detrimental to both growth and immune response.

Colostral milk fat percentage and pig performance are enhanced by feeding the leucine metabolite beta-hydroxy-beta-methyl butyrate to sows.

Three trials were conducted to test whether feeding the leucine metabolite beta-hydroxy-beta-methyl butyrate (HMB) would increase fat content of sows' milk and pig weight gain. All sows received a basal diet and were assigned at random to receive either 2 g of CaCO3/d (control) or 2 g of Ca(HMB)2/d (HMB), which was top-dressed to the basal diet. Treatment began 3 to 4 d before farrowing. In Trials 1, 2, and 3 there were 4, 19, and 11 pairs of sows, respectively. In a combined analysis that included all three trials, milk fat at d 1 was increased by 41% (P = .01) and pig weight at d 21 was increased by 7% (P = .01) for sows fed diets containing HMB compared with sows fed control diets. Sows fed HMB lost more backfat (P = .03); however, sows receiving HMB had more (P < .05) backfat depth at farrowing than control sows. At weaning there was no difference in backfat depth between the treatment groups. Sows fed HMB tended to consume less feed (P = .07) than control sows. In Trials 2 and 3, data were collected on the subsequent reproductive cycles of the sows. A combined analysis of the data revealed no differences in sow performance when sows previously fed the diet containing HMB were compared with sows previously fed the control diet. In conclusion, beta-hydroxy-beta-methyl butyrate, when fed to sows at 2 g/d, resulted in an increase in fat percentage of sow's milk and pig performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of beta-hydroxy-beta-methyl butyrate on performance and carcass quality of feedlot steers.

Beta-hydroxy-beta-methyl butyrate (HMB), a compound formed during catabolism of leucine, was fed to 256 crossbred steers as 0 or .03% of diet dry matter. Effects on performance, carcass characteristics, and tissue composition were measured. Groups of 32 steers per diet were slaughtered after 105, 119, 133, and 147 d on feed. The HMB was fed to each group only during the final 82 d they were fed. Averaged across slaughter date, animal performance was not altered by HMB; however, an interaction between HMB and time on feed was detected. Feeding HMB increased (P < .01) daily gain of steers slaughtered at 105 d but decreased (P < .01) daily gain of steers slaughtered at 147 d. Steers fed HMB had numerically higher marbling scores that resulted in a trend toward higher carcass quality grades. Steers receiving HMB tended to have less (P < .08) s.c. fat and fewer steers with yield grades of 4 or greater (1.6 vs 4.7%). Supplementation of HMB to feedlot steers tended to increase (P < .07) the ratio of intramuscular fat to subcutaneous fat. Steers fed HMB had higher (P < .001) blood plasma concentrations of HMB (3.06 vs 1.70 mg/L) and lower (P < .03) blood plasma concentrations of cholesterol (108.4 vs 118.7 mg/dL). Feeding HMB tended to increase (P < .10) lipid content of the longissimus muscles of those steers slaughtered at 105 d.

The effect of beta-hydroxy-beta-methylbutyrate on growth, mortality, and carcass qualities of broiler chickens.

Experiments were conducted to determine whether the leucine catabolite beta-hydroxy-beta-methylbutyrate (HMB) could influence protein metabolism in broilers. In Experiment 1, HMB was fed at either .01 or .05% of the diet. beta-Hydroxy-beta-methylbutyrate did not improve feed conversion or BW gain; however, broilers fed HMB at .01% in a diet formulated to meet NRC (1984) recommendations had no mortality (P < .03) from 0 to 21 d of age. In Experiment 2, HMB fed at .003, .01, .03, and .09% of the diet had no significant affect on growth or carcass yield of the broilers when compared with control-fed broilers. In Experiment 3, HMB fed at .001, .003, and .01% of the diet had no effect on broiler growth. In Experiment 4, HMB was fed at .01% of the diet in combination with an antibiotic and coccidiostat (GP). Use of GP increased (P < .01) BW, feed conversion, and carcass yield when compared with the control broilers. In Experiment 5, HMB was fed at .1% of the diet, and effects of sex and GP were examined. beta-Hydroxy-beta-methylbutyrate decreased (P < .01) mortality by 72% in the male broilers. In a combined analysis, HMB fed at .01% of the diet (Experiments 1, 2, and 3) increased breast yield (P < .05) and reduced mortality by 56% (P < .04) from 0 to 21 d of age. In a combined analysis, HMB fed at .003% of the diet (Experiments 2 and 3) increased 42-d BW (P < .02) and hot (P < .04) and chilled (P < .05) carcass yields. In conclusion, across all HMB dosages mortality of male broilers was decreased from 6.37 to 4.39% (-31%, P < .04) by feeding HMB, with the pattern of death suggesting that HMB decreased the incidence of sudden death syndrome in these broilers.

Formulation of a drug delivery system based on a mixture of monoglycerides and triglycerides for use in the treatment of periodontal disease.

This paper describes the development of a stable, controlled-release formulation of metronidazole for use in the treatment of periodontal disease. It is formulated as a suspension, which undergoes transformation to a release-controlling, semi-solid on contact with gingival fluid. The system is based on the ability of mixtures of monoglycerides and triglycerides to form liquid crystals, i.e., reversed hexagonals, in contact with water. The reversed hexagonal form was found to have the most favourable sustained release properties, compared with those from the cubic form. The source of metronidazole is the prodrug, metronidazole benzoate, which further helps to slow down the release rate. Product characteristics are assessed by differential scanning calorimetry and viscometry. The release data derive from the results of in vitro dissolution tests. X-ray diffraction, phase diagrams, and polarized light microscopy were used to elucidate the structure of the liquid crystalline phases.

Milk production and composition in cows and goats fed alpha-ketoisocaproate.

To examine whether alpha-ketoisocaproate supplementation affects milk production, 10 goats were fed either 0 or 1.1% calcium-alpha-ketoisocaproate for 2 wk and 12 cows were fed either 0 or .75% Na alpha-ketoisocaproate for 3 wk. Supplementation with alpha-ketoisocaproate increased milk fat content, milk fat yield, and 4% FCM yield in cows by an average of 5, 10, and 8%, respectively, for the treatment period. In cows, response of milk fat yield to alpha-ketoisocaproate was 120 g during wk 1 of treatment but diminished to 55 g by wk 3. Milk yield and milk protein yield tended to be greater in cows fed alpha-ketoisocaproate, but milk production efficiency and body weight were not altered by treatment in either species. Supplementation with alpha-ketoisocaproate had no significant effect on fatty acid composition of milk but tended to increase the percentage of C10 and C12 fatty acids. In goats, supplementation with alpha-ketoisocaproate had no significant effect on milk production or composition, but trends toward increased milk fat and protein content were observed. Results indicate that alpha-ketoisocaproate acutely stimulates milk fat production in lactating cows and that this effect seems to diminish with time.

Ant-egg cataract. A study of a family with dominantly inherited congenital (ant-egg) cataract, including a histological examination of the formed elements.

A family with "ant-egg" cataract in three generations is described. The cataract is congenital, probably of autosomal dominant inheritance. Light microscopy of the ant-eggs showed that they are made up of a peripheral zone of lens material and a large almost homogenous centre. Element analysis by X-ray spectrophotometry showed a high content of calcium and phosphorus in the centre. The cataract has been easy to operate on and the postoperative visual results have been good.