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.     

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.     

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.     

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.     

Evidence that glutamine modulates respiratory burst in stressed rat polymorphonuclear cells through its metabolism into arginine

Glutamine (GLN) and arginine (ARG) are recognized for their ability to modulate immune cell function. However, the metabolic pathways involved in their action remain unclear. It was recently shown that GLN- or ARG-enriched diets increased radical oxygen species (ROS) production by neutrophils from stressed rats. Since these two amino acids have a tied metabolism, we hypothesized that conversion between GLN and ARG (and its active metabolites NO* and polyamines) might be involved. To test this hypothesis male Sprague-Dawley rats (n 117) were randomized into thirteen groups: rats in eleven groups were rendered catabolic by dexamethasone injection (1.5 mg/kg per d for 5 d) and 6.8 mmol either GLN, ARG or non-essential amino acids (NEAA; glycine, alanine and histidine)/kg per d were given by the enteral route; one group was pair-fed to the treated groups. The regimens of all the groups were rendered isonitrogenous by the addition of NEAA. The last group was not treated and was fed ad libitum. For each supplementation three subgroups were formed, each of which received a specific inhibitor: methionine sulfoximine (inhibitor of GLN synthase; 100 mg/kg per d), S-methylthiourea (inhibitor of inducible NO* synthase (iNOS); 50 mg/kg per d) and difluoromethylornithine (inhibitor of ornithine decarboxylase (ODC); 50 mg/kg per d). Oxidative metabolism, intracellular H2O2, and extracellular O2*- production were measured in unstimulated and phorbol myristate acetate-stimulated polymorphonuclear neutrophils. GLN- and ARG-enriched diets increased respiratory burst by neutrophils (oxidative metabolism of 152 (sem 24) and 138 (sem 45) v. 57 (sem 18) mV for GLN-, ARG- and NEAA-enriched diets respectively, P<0.05). In vivo inhibition of iNOS or ODC decreased ROS production induced by GLN and ARG. In vivo inhibition of GLN synthase did not modify the effect of ARG on ROS production. In conclusion, GLN and ARG modulate ROS production in neutrophils from stressed rats by the same pathway involving polyamine and NO* synthesis.     

Conjugated linoleic acid supplementation alters the 6-mo change in fat oxidation during sleep

BACKGROUND: Conjugated linoleic acid (CLA) is a family of positional and geometric isomers with 2 conjugated double bonds formed from linoleic acid and linolenic acid. CLA has a wide range of biological effects, including body fat reduction. OBJECTIVE: The aim of our study was to determine CLA's effects on energy expenditure, macronutrient utilization, and dietary fat oxidation in overweight adults after 6 mo of supplementation. DESIGN: We recruited 23 subjects from our main CLA efficacy study who were receiving either 4 g/d of 78% active CLA isomers (3.2 g/d: 39.2% cis-9,trans-11 and 38.5% trans-10,cis-12) or 4 g/d of safflower oil. Energy expenditure and substrate utilization were measured before and after 6 mo of CLA supplementation by using whole-room indirect calorimetry. Dietary fat oxidation was measured by using stable isotope-labeled oleate and palmitate. RESULTS: Our substudy detected a difference in the change in fat utilization between the CLA (4 +/- 8 g) and placebo (-7 +/- 11 g) groups during sleep after 6 mo of supplementation. In addition, the percentage of energy from protein was reduced during sleep in the CLA group (CLA: -3.3 +/- 2.6%; placebo: 0.3 +/- 5.7%). We also detected a difference in the change in energy expenditure during sleep (CLA: 0 +/- 38 kcal; placebo: -43 +/- 90 kcal). We did not detect a change in labeled dietary fat oxidation after 6 mo of CLA supplementation given with a breakfast meal. CONCLUSION: Mixed isomer CLA supplementation, but not placebo, positively altered fat oxidation and energy expenditure during sleep.     

The effect of exercise on water balance in premenopausal physically active women

OBJECTIVE: This controlled feeding study examined the effects of exercise on daily water intake (particularly ad libitum water intake), water output, whole-body water balance, and hydration status in physically active, premenopausal women. DESIGN: The randomized crossover design consisted of three 8-day trials: placebo and no exercise, placebo and exercise (1-hour cycling bout per day at 65%-70% of heart rate reserve), and 800 mg calcium supplementation and exercise. During each trial, controlled quantities of the same foods and beverages were provided and ad libitum water intake was quantified. Water input included measured water from foods and beverages, measured ad libitum intake, and estimated metabolic production. Water output included measured losses in urine and stool, and estimated insensible losses from respiration and non-sweating perspiration (insensible diffusion through the skin). SUBJECTS: Participants were 26 women, age 25+/-5 years, body mass index 22+/-2, and VO(2peak) 43+/-6 mLxkg(-1)xmin(-1) (mean+/-standard deviation). RESULTS: Ad libitum water intake was 363 g/day more (P<0.05) for the placebo and exercise (1,940+/-654 g/day) and calcium supplementation and exercise (1,935+/-668 g/day) trials, compared with placebo and no exercise trial (1,575+/-667 g/day), and total water input was correspondingly higher in placebo and exercise and calcium supplementation and exercise trials compared with the placebo and no exercise trial. Urine, stool, and total water outputs were not different among trials. Apparent net water balance (representative of sweat water output) was 367 g/day more (P<0.05) in placebo and exercise (679+/-427 g/day) and calcium supplementation and exercise (641+/-519 g/day) trials compared with placebo and no exercise trial (293+/-419 g/day). Hydration status was clinically normal during all three trials. Calcium supplementation did not influence water balance. CONCLUSION: These results support that young, physically active women can completely compensate for exercise-induced sweat losses by increasing ad libitum water intake, and not decreasing non-sweat water outputs or impairing hydration status.     

Iron supplementation maintains ventilatory threshold and improves energetic efficiency in iron-deficient nonanemic athletes

OBJECTIVE: To determine the effect of iron supplementation on iron status and endurance capacity. DESIGN: Randomized, double-blind iron supplementation. SETTING: University of Missouri-Columbia and surrounding community. SUBJECTS: Twenty iron-deficient (serum ferritin, sFer<16 microg/l; serum transferrin receptor, sTfR>8.0 mg/l; or sTfR/log sFer index >4.5), nonanemic (hemoglobin, Hb>120 g/l, women; >130 g/l, men) men and women (18-41 years) were recruited via fliers and newspaper advertisements; 20 of 31 eligible subjects participated. INTERVENTIONS: A 30 mg measure of elemental iron as ferrous sulfate or placebo daily for 6 weeks. RESULTS: Dietary iron intake and physical activity did not differ between groups before or after supplementation. Iron supplementation significantly increased sFer compared to placebo (P=0.01), but did not affect Hb or hematocrit. Iron supplementation prevented the decline in ventilatory threshold (VT) observed in the placebo group from pre- to post-supplementation (P=0.01); this effect was greater in individuals with lower sFer before intervention (P<0.05). Changes in sFer from pre- to post-treatment were positively correlated with changes in VT (P=0.03), independent of supplementation. The iron group significantly increased gross energetic efficiency during the submaximal test (P=0.04). Changes in sFer were negatively correlated with changes in average respiratory exchange ratio during the submaximal test (P<0.05). CONCLUSIONS: Iron supplementation significantly improves iron status and endurance capacity in iron-deficient, nonanemic trained male and female subjects.     

Arginine-enriched diet limits plasma and muscle glutamine depletion in head-injured rats

OBJECTIVE: Injury is associated with a depletion in glutamine (GLN) pools, which may contribute to impairment of immune and nutritional statuses. Total parenteral nutrition enriched with arginine (ARG) is able to generate GLN in surgical patients. We hypothesized that this same concept may be applicable to enteral administration and could be extended to muscle GLN reserves. This study investigated the ability of an enteral formula enriched with ARG to restore the GLN pools in an experimental model of head injury. METHODS: Twenty-five male Sprague-Dawley rats were randomized into 4 groups: ad libitum access to food, head injury plus free access to nutrition, head injury plus standard enteral nutrition (Sondalis), and an immune-enhancing diet (IED). The two enteral diets were adjusted to be isocaloric (290 kcal.kg(-1).d(-1)) and isonitrogenous (3.29 g.kg(-1).d(-1)) and were delivered for 4 d (24 h/24 h). After sacrifice, plasma and muscle amino acids were determined. RESULTS: Head injury was associated with a large depletion of muscle and plasma GLN pools that were restored by IED administration but not by the standard diet. Moreover, the IED but not the standard diet improved or normalized ornithine and glutamate pools, suggesting that the modification of GLN pools is related to ARG administration. CONCLUSION: In our model of head injury, our IED, a diet without free GLN, is efficient in restoring the plasma and muscle pools of GLN, probably due to its high ARG content.     

Vitamin D status affects strength gains in older adults supplemented with a combination of β-hydroxy-β-methylbutyrate, arginine, and lysine: a cohort study

Background: Older adults supplemented for 1 year with β‐hydroxy‐β‐methylbutyrate, arginine, and lysine (HMB/ARG/LYS) were previously shown to have significant gains in fat‐free mass (FFM) but not muscular strength. Objective: Recently, increasing levels of serum vitamin D have been associated with an increase in muscle function, particularly in the elderly. To determine if vitamin D status may have limited strength gain in participants supplemented with HMB/ARG/LYS, the authors performed post hoc analysis of strength based on the participants' vitamin D status. Methods: Elderly (age 76.0 ± 1.6 years) adults were recruited for a double‐blinded, controlled study and were randomly assigned to either an isonitrogenous control (n = 37) or HMB/ARG/LYS (n = 40) for the yearlong study. Participants were further segregated based on their vitamin D status of either <30 or ≥30 ng 25OH‐vitD₃/mL serum, and an analysis was performed on the 4 cohorts. Results: Regardless of vitamin D status, HMB/ARG/LYS resulted in significantly increased FFM (P < .02), but only in those with vitamin D status ≥30 ng 25OH‐vitD₃/mL was there a significant increase in strength with HMB/ARG/LYS (P < .01). Control‐supplemented participants, regardless of vitamin D status, and the HMB/ARG/LYS‐supplemented participants with vitamin D status <30 ng 25OH‐vitD₃ failed to show improvements in strength. Conclusions: The nutrient cocktail of HMB/ARG/LYS alone was effective in increasing muscle mass regardless of vitamin D status, but accompanying strength increases were observed only when participants also had adequate vitamin D status indicating a synergistic effect between the HMB/ARG/LYS and vitamin D.     

Evaluation of the effects of a preoperative 2-hour fast with maltodextrine and glutamine on insulin resistance, acute-phase response, nitrogen balance, and serum glutathione after laparoscopic cholecystectomy: a controlled randomized trial

Background: Prolonged preoperative fasting increases insulin resistance (IR). The authors investigated whether an abbreviated preoperative fast with glutamine (GLN) plus a carbohydrate (CHO)–based beverage would improve the organic response after surgery. Methods: Forty‐eight female patients (19‐62 years) were randomized to either standard fasting (control group) or to fasting with 1 of 3 different beverages before video‐cholecystectomy. Beverages were consumed 8 hours (400 mL; placebo group: water; GLN group: water with 50 g maltodextrine plus 40 g GLN; and CHO group: water with 50 g maltodextrine) and 2 hours (200 mL; placebo: water; GLN: water with 25 g maltodextrine plus 10 g GLN; and CHO: water with 25 g maltodextrine) before anesthesia. Blood samples were collected pre‐ and postoperatively. Results: The mean (SEM) postoperative homeostasis model assessment–insulin resistance was greater (P < .05) in control patients (4.3 [1.3]) than in the other groups (placebo, 1.6 [0.3]; CHO, 2.3 [0.4]; and GLN, 1.5 [0.1]). Glutathione was significantly higher (P < .01) in the GLN group than in both CHO and control groups. Interleukin‐6 increased in all groups except the GLN group. The C‐reactive protein/albumin ratio was higher (P < .05) in controls than in CHO and GLN groups. The nitrogen balance was less negative in GLN (–2.5 [0.8] gN) than in both placebo (–9.0 [2] gN; P = .001) and control (–6.6 [0.4] gN; P = .04) groups. Conclusions: Preoperative intake of a GLN‐enriched CHO beverage appears to improve IR and antioxidant defenses and decreases the inflammatory response after video‐cholecystectomy.     

Effects of beta-hydroxy-beta-methylbutyrate on aerobic-performance components and body composition in college students

The aim of this study was to determine the effects of oral beta-hydroxy-beta-methylbutyrate (HMB) supplementation (3 g/d) on selected components of aerobic performance and body composition of active college students. Subjects were randomly assigned to either an HMB (n=8) or a placebo (PLA) group (n=8) for a 5-wk supplementation period during which they underwent interval training 3 times a week on a treadmill. Aerobic-performance components were measured using a respiratory-gas analyzer. Body composition was determined using dual-energy X-ray absorptiometry. After the intervention, there were significant differences (P<0.05) between the 2 groups in gains in maximal oxygen consumption (+8.4% for PLA and +13.4% for HMB). Regarding body composition, there were no significant differences. The authors concluded that HMB supplementation positively affects selected components of aerobic performance in active college students.     

Oral glutamine and the healing of colonic anastomoses in rats

BACKGROUND: Recent evidence has suggested that glutamine is one of the primary energy sources of the colon. The aim of this study was to evaluate the effects of oral glutamine supplementation on the healing of colonic anastomoses in rats. METHODS: Forty-eight adult male Wistar rats, weighing 174.41 +/- 37.39 g, were housed in individual cages. All rats had free access to water and standard rat chow. The rats were randomized to receive daily, for 7 days before the operation and during the postoperative period, 10% L-glutamine (GLN group) or 10% glycine (GLY group) in isonitrogenous and isovolumetric solutions (1.5 g/kg per day), through an orogastric tube. On the eighth day, rats were anesthetized and subjected to 2 colonic transections, one 6 cm distal from the ileocecal valve and another 5 cm distal from the first transection. Bowel continuity was restored by 2 end-to-end, single layer, everted, anastomoses with 8 interrupted sutures (6-0 nylon). After the operation, the rats were kept in individual cages and had free access to water and rat chow. One-half of the rats in each group were killed either on postoperative day 3 or 8, and the 2 colonic anastomoses of each animal were resected and stored in 0.9% saline and 10% formalin for tensile strength and histologic (hematoxylineosin and collagen densitometry) studies, respectively. Student's t-test and Kruskal Wallis tests were used for statistical analysis. RESULTS: Total rupture strength was significantly higher in the GLN group (GLN: 0.068 +/- 0.045 kgf versus GLY: 0.042 +/- 0.027 kgf, p = .04). The mean monocytes infiltrate was significantly smaller in the GLN group (p = .04). The collagen densitometry analysis demonstrated greater percent area of type I (mature) in the GLN group compared with GLY (58.65 +/- 11.70% versus 41.79 +/- 10.54%, p = .0000), respectively. Subgroup analyses according to the day of rat death were still significant: GLN 3: 54.22 +/- 10.02% versus GLY 3: 41.92 +/- 13.31% (p = .04) and GLN 8: 62.63 +/- 12.13% versus GLY 8: 41.67 +/- 7.69% (p = .0004). Type III collagen (immature) percent area was significantly smaller in the GLN group's colonic anastomoses (GLN: p = .0000; GLN 3: p = .04 and GLN 8: p = .0003, respectively). CONCLUSIONS: Perioperative oral glutamine supplementation increases total rupture strength and improves the percent area of mature collagen at the anastomoses sites on postoperative days 3 and 8.     

Oral arginine improves blood pressure in renal transplant and hemodialysis patients.

BACKGROUND: Hypertension in kidney transplant (KT) patients may result from attenuated whole-body nitric oxide (NO) content and abnormal NO-mediated vasodilation. Increasing NO bioavailability with L-arginine (ARG) could theoretically restore the NO-mediated vasodilatory response and lower blood pressure. METHODS: In a prospective pilot study, 6 normotensive volunteers and 10 KT patients received oral supplements of ARG (9.0 g/d) for 9 days, then 18.0 g/d for 9 more days. Six hemodialysis (HD) and 4 peritoneal dialysis patients received the same dose for 14 days. Five KT patients received 30 mL/d of canola oil (CanO) in addition to ARG. Systolic (SBP) and diastolic (DBP) blood pressure, creatinine clearance (CCr), and serum creatinine (Cr) were measured at baseline, day 9, and day 18. In a subsequent study, 20 hypertensive KT patients with stable but abnormal renal function were randomized in a crossover study to start ARG-only or ARG+CanO supplements for two 2-month periods with an intervening month of no supplementation. SBP, DBP, CCr, and Cr were measured monthly for 7 months. RESULTS: In the pilot study, ARG reduced the SBP in HD patients from 171.5 +/- 7.5 mmHg (baseline) to 142.8 +/- 8.3 mmHg (p = .028). In the crossover study, SBP was reduced from baseline (155.9 +/- 5.0 mmHg), after the first 2 months (143.2 +/- 3.2 mmHg; p = .03) and subsequent 2 months (143.3 +/- 2.5 mmHg; p = .014) of supplementation. DBP was also reduced after supplementation in both studies. CanO had no effect on blood pressure. Renal function did not change. CONCLUSIONS: Oral preparations of ARG (+/-CanO) were well tolerated for up to 60 consecutive days and had favorable effects on SBP and DBP in hypertensive KT and HD patients.     

Maintenance of skeletal muscle intracellular glutamine during standard surgical trauma

Skeletal muscle glutamine (GLN) concentration falls following injury and infection. In an attempt to prevent this decline and to characterize its influence on the efflux of amino acid (AA) from skeletal muscle, we administered varying quantities of AA (0,2, and 4 g/kg X day) as saline or AA solutions with or without GLN enrichment to 22 postoperative dogs. Plasma and muscle AA were determined before and 24 hr after standard laparotomy. Hindquarter AA efflux was measured at 6 and 24 hr. Skeletal muscle nitrogen declined in saline controls (69.8 +/- 8.5 vs 52.8 +/- 8.4 mmol/liter; p less than 0.01), largely due to the fall in intracellular GLN (21.48 +/- 3.21 vs 15.86 +/- 3.80; p less than 0.05). Similar alterations were seen in the animals receiving 2 g/kg. However, both intracellular nitrogen and GLN were maintained in animals receiving 4 g/kg, whether the AA solutions contained GLN or not (skeletal muscle nitrogen before 64.3 +/- 8.6 mmol/l vs 65.4 +/- 7.0 after, GLN 19.2 +/- 3.4 vs 19.9 +/- 3.0). Hindquarter AA efflux was reduced in those animals at 6 hr compared with saline-treated animals (-6.52 +/- 1.8 and -7.70 +/- 5.90 vs -19.05 +/- 4.06 mumol/kg X min; p less than 0.05). Intracellular GLN can be maintained during operative stress with adequate nitrogen infusion. Replacing 50% of the balanced AA solution with GLN resulted in equally effective maintenance of intracellular GLN levels and a comparable reduction in skeletal muscle AA efflux. Preservation of normal intracellular GLN levels with adequate AA nutrition may be essential for the conservation of muscle protein.     

Effect of beta-hydroxy-beta-methylbutyrate, arginine, and lysine supplementation on strength, functionality, body composition, and protein metabolism in elderly women

OBJECTIVE: With advancing age, there is a gradual loss of muscle mass, strength, and functionality. The current studies were conducted to determine whether a mixture of specific nutrients, arginine and lysine, which support protein synthesis, and beta-hydroxy-beta-methylbutyrate (HMB), which can slow protein breakdown, could blunt the gradual loss of muscle that occurs in the elderly, thus improving strength and functionality. METHODS: In double-blind studies conducted at two separate sites, women (mean 76.7 y) were randomized to a placebo group (n = 23) or an experimental treatment group (2 g beta-hydroxy-beta-methylbutyrate, 5 g arginine, and 1.5 g lysine daily; n = 27). RESULTS: After 12 wk, there was a 17% improvement in the "get-up-and-go" functionality test in the experimental group (-2.3 +/- 0.5 s) but no change in the placebo group (0.0 +/- 0.5 s; P = 0.002). The improvement in functionality also was reflected by increased limb circumference, leg strength, and handgrip strength (all P < 0.05) and positive trends in fat-free mass (P = 0.08). Whole-body protein synthesis, estimated with the (15)N-glycine tracer technique over a 24-h free-living period, increased approximately 20% in the experimental treatment group as opposed to the placebo group (P = 0.03). CONCLUSION: These studies indicated that daily supplementation of beta-hydroxy-beta-methylbutyrate, arginine, and lysine for 12 wk positively alters measurements of functionality, strength, fat-free mass, and protein synthesis, suggesting that the strategy of targeted nutrition has the ability to affect muscle health in elderly women.     

Beta-hydroxy-beta-methylbutyrate (HMB) supplementation does not affect changes in strength or body composition during resistance training in trained men

This investigation evaluated the effects of oral beta-hydroxy-beta-methylbutyrate (HMB) supplementation on training responses in resistance-trained male athletes who were randomly administered HMB in standard encapsulation (SH), HMB in time release capsule (TRH), or placebo (P) in a double-blind fashion. Subjects ingested 3 g x day(-1) of HMB or placebo for 6 weeks. Tests were conducted pre-supplementation and following 3 and 6 weeks of supplementation. The testing battery assessed body mass, body composition (using dual energy x-ray absorptiometry), and 3-repetition maximum isoinertial strength, plus biochemical parameters, including markers of muscle damage and muscle protein turnover. While the training and dietary intervention of the investigation resulted in significant strength gains (p < .001) and an increase in total lean mass (p = .01), HMB administration had no influence on these variables. Likewise, biochemical markers of muscle protein turnover and muscle damage were also unaffected by HMB supplementation. The data indicate that 6 weeks of HMB supplementation in either SH or TRH form does not influence changes in strength and body composition in response to resistance training in strength-trained athletes.     

Acute L-Arginine supplementation does not increase nitric oxide production in healthy subjects

ABSTRACT: Dietary supplements containing L-arginine have been marketed with the purpose of increasing vasodilatation, and thus, blood and oxygen supply to the exercising muscle. The present study evaluated the acute effect of L-arginine supplementation on indicators of NO production, nitrite (NO2 -) + nitrate (NO3 -) (NOx), in healthy subjects. Plasma concentrations of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) have also been addressed. Seventeen healthy males participated in a randomized, double-blind, placebo-controlled study. Blood samples were drawn from a left antecubital vein at baseline (T0). Afterwards, subjects were randomly submittedto 6 g of oral L-arginine supplementation (as L-arginine hydrochloride) or placebo (as corn starch); afterwards, the subjects remained at rest in supine position and blood samples were drawn again at 30 (T1), 60 (T2), 90 (T3) and 120 minutes (T4) after supplementation. To analyze NO production, NO3 - was converted to NO2 - by nitrate reductase, followed by the derivatization of NO2 - with 2,3- diaminonaphthalene. NOx, ADMA and SDMA were analyzed using a high-performance liquid chromatography system and monitored with a fluorescence detector. Two-way ANOVA with repeated measures showed no significant changes in NOx concentrations on the L-arginine group as compared to placebo group at any of the fivetime points (T0: 17.6 +/- 3.9 vs 14.6 +/- 2.3 mumol/L; T1: 15.8 +/- 2.4 vs 14.3 +/- 1.7 mumol/L; T2: 16.8 +/- 4.9 vs 13.7 +/- 2.7 mumol/L; T3: 16.7 +/- 3.9 vs 14.6 +/- 2.1 mumol/L; T4: 15.1 +/- 2.8 vs 13.5 +/- 3.5 mumol/L). Furthermore, plasma levels of ADMA and SDMA were not statistically significant between the L-arginine and placebo groups at T0 (0.43 +/- 0.19 vs 0.39 +/- 0.15 mumol/L and 1.83 +/- 1.13 vs 1.70 +/- 0.62 mumol/L), respectively. In conclusion, acute L-arginine supplementation does not increase plasma concentration of NOx in healthy individuals with normal plasma concentrations of ADMA.     

Elevated plasma homocysteine and low vitamin B-6 status in nonsupplementing older women with rheumatoid arthritis

OBJECTIVE: The purpose of this study was to determine if nonsupplementing older women (aged >or=55 years) with rheumatoid arthritis had higher plasma homocysteine and lower B-vitamin status compared to healthy controls. Elevated plasma homocysteine, a risk factor for cardiovascular disease, may help explain why individuals with rheumatoid arthritis have an increased risk of cardiovascular disease. METHODS: Older, free-living women were classified as rheumatoid arthritis (n=18) or healthy control (n=33). Participants were not using B-vitamin supplements. Fasting blood samples were measured for pyridoxal 5'phosphate (PLP) (the metabolically active coenzyme form of vitamin B-6), folate, red blood cell folate, vitamin B-12, transcobalamin II, homocysteine, C-reactive protein, and lipid concentrations. Participants completed 7-day weighed food records, the Stanford Health Assessment Questionnaire (HAQ), and a visual analog pain scale. RESULTS: PLP concentrations were lower in the rheumatoid arthritis vs healthy control participants (4.93+/-3.85 vs 11.35+/-7.11 ng/mL [20+/-16 vs 46+/-29 nmol/L]; P<0.01) whereas plasma homocysteine was higher in the rheumatoid arthritis group (1.63+/-0.74 vs 1.15+/-0.38 mg/L [12.1+/-5.5 vs 8.5+/-2.8 micromol/L]; P=0.02). Red blood cell folate concentrations were lower in the rheumatoid arthritis vs healthy control participants [414+/-141 vs 525+/-172 ng/mL [938+/-320 vs 1,190+/-390 nmol/L]; P=0.02). No significant differences were found for plasma folate, vitamin B-12, and transcobalamin II. An inverse correlation was found between PLP concentrations and the HAQ disability index (r=-0.37; P<0.01). A positive correlation was found between homocysteine concentrations and the HAQ disability index (r=0.36; P=0.01). Total cholesterol and low-density lipoprotein cholesterol levels were lower in the rheumatoid arthritis group (cholesterol 191+/-43 vs 218+/-33 mg/dL [4.95+/-1.11 vs 5.65+/-0.85 mmol/L]; P=0.02; low-density lipoprotein cholesterol 110+/-36 vs 137+/-29 mg/dL [2.85+/-0.93 vs 3.55+/-0.75 mmol/L]; P<0.01). No significant differences were seen between groups for protein (g/day), fat (g/day), cholesterol (mg/day), folate (microg/day), vitamin B-12 (microg/day), and vitamin B-6 (mg/day) dietary intakes. CONCLUSIONS: Poor vitamin B-6 status and elevated plasma homocysteine concentrations were seen in older women with rheumatoid arthritis compared to healthy controls and may contribute to their increased risk of cardiovascular disease.