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.     

Dietary treatment of rheumatoid cachexia with beta-hydroxy-beta-methylbutyrate, glutamine and arginine: a randomised controlled trial

BACKGROUND & AIMS: Rheumatoid arthritis (RA) is complicated by cytokine-driven alterations in protein and energy metabolism and consequent muscle wasting (cachexia). The aim of this randomised controlled trial was to investigate the efficacy of a mixture of beta-hydroxy-beta-methylbutyrate, glutamine and arginine (HMB/GLN/ARG) as nutritional treatment for rheumatoid cachexia. METHODS: Forty RA patients supplemented their diet with either HMB/GLN/ARG or a nitrogen (7.19 g/day) and calorie (180 kcal/day) balanced mixture of alanine, glutamic acid, glycine, and serine (placebo) for 12 weeks. Body composition and other outcomes were assessed at baseline and follow-up, and analysed by mixed ANOVA. RESULTS: Dietary supplementation with HMB/GLN/ARG was not superior to placebo in the treatment of rheumatoid cachexia (groupxtime interactions P>0.05 for all outcomes). Both amino acid mixtures significantly increased (main effect of time) fat-free mass (727+/-1186 g, P<0.01), total body protein (719+/-1703 g, P=0.02), arms (112+/-183 g, P<0.01) and legs (283+/-534 g, P<0.01) lean mass, and some measures of physical function. No significant adverse event occurred during the study, but patients in the HMB/GLN/ARG group reported fewer gastrointestinal complaints compared to placebo. CONCLUSIONS: Dietary supplementation with HMB/GLN/ARG is better tolerated but not more effective in reversing cachexia in RA patients compared to the mixture of other non-essential amino acids used as placebo. Further controlled studies are necessary to confirm the beneficial anabolic and functional effects of increased nitrogen intake in this population.     

Anti-inflammatory and anticatabolic effects of short-term beta-hydroxy-beta-methylbutyrate supplementation on chronic obstructive pulmonary disease patients in intensive care unit

Elevated inflammatory markers and muscle wasting were common in chronic obstructive pulmonary disease (COPD) patients. The purpose of this study was to investigate the effect of 7-day beta-hydroxy-beta-methylbutyrate (HMB) supplementation on inflammation, protein metabolism, and pulmonary function in COPD patients in an intensive care unit. Thirty-four COPD patients who required mechanical ventilators were randomly assigned to HMB (n=18) or control (n=16) groups. The HMB group received HMB 3 g/d for 7 days. White blood cell count, C-reactive protein, and creatinine were significantly lower, while cholesterol and total protein were significantly higher after HMB supplementation. The body weight remained unchanged in both groups. Ten subjects (55.6%) in the HMB group and 4 subjects (25.0%) in the control group had improved pulmonary function, indicated by their ventilator modes. This short-term study suggests that HMB supplementation may have anti-inflammatory and anticatabolic effect and improve pulmonary function in COPD patients in an intensive care unit setting.     

The effects of beta-hydroxy-beta-methylbutyrate (HMB) and HMB/creatine supplementation on indices of health in highly trained athletes

This study aimed to investigate the effects of 6 wk oral supplementation of beta-hydroxy-beta-methylbutyrate (HMB) and HMB combined with creatine monohydrate (HMBCr) on indices of health in highly trained athletes. Elite, male rugby league players (n=28) were allocated to 1 of 3 groups: a control group (n=6), a HMB group (3 g/d; n=11), or a HMBCr group (3 g/day HMB, 3 g/d Cr; n=11). Testing prior to, and immediately following, supplementation included a full blood count, plasma testosterone and cortisol, blood electrolytes, lipids, urea and glucose, sperm count and motility, and assessment of psychological state. A 3 x 2 factorial ANOVA revealed no effect of HMB or HMBCr on any of the measured parameters except minor changes in blood bicarbonate and blood monocyte and lymphocyte counts. Blood bicarbonate was significantly decreased in the HMB post-supplementation sample compared to the control and HMBCr groups. Blood monocyte and lymphocyte counts showed no within-group changes for HMB or HMBCr supplementation but were significantly different from the control. However, the majority of these readings remained within normal range. HMB and HMBCr were concluded to have no adverse effects on the parameters evaluated in this study when taken orally by highly trained male athletes over a 6-wk period.     

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.     

Glutamine supplementation in cancer patients

OBJECTIVES: Three series of studies investigated whether 1) glutamine deficiency occurs in tumor-bearing rats, 2) glutamine supplementation improves protein metabolism during chemotherapy in tumor-bearing rats, and 3) oral glutamine supplement improves systemic immune and gut-barrier function in patients with esophageal cancer receiving radiochemotherapy. METHODS: In the animal studies, AH109A hepatoma cells or Yoshida sarcoma cells were inoculated into male Donryu rats to induce tumors. Glutamine production was measured by U-14C-glutamine infusion and the conversion of arginine to glutamine was measured by infusion of U-14C-arginine. The effect of glutamine on protein metabolism was investigated by 1-14C-leucine infusion. In the clinical study, 13 patients with esophageal cancer were randomized into two groups, control and glutamine supplemented (30 g/d), for 4 wk. RESULTS: Glutamine levels in plasma and skeletal muscle were decreased in tumor-bearing rats, although glutamine production and the conversion of arginine to glutamine were increased. Glutamine-supplemented total parenteral nutrition reduced whole-body protein breakdown rate during chemotherapy in tumor-bearing rats. Oral supplementation of glutamine to the patients with esophageal cancer enhanced lymphocyte mitogenic function and reduced permeability of the gut during radiochemotherapy. CONCLUSIONS: Glutamine depletion in host tissues occurs in tumor-bearing rats. Glutamine supplementation can attenuate loss of protein in the muscle in tumor-bearing animals and protect immune and gut-barrier function during radiochemotherapy in patients with advanced cancer.     

Arginine supplementation is well tolerated but does not enhance mitogen-induced lymphocyte proliferation in elderly nursing home residents with pressure ulcers

BACKGROUND: Immune function declines with age, increasing risk for infection and delaying wound healing. Arginine enhances immune function and healing of standardized wounds in healthy elderly persons. The purpose of this study was to determine what level of arginine supplementation was orally and metabolically tolerated and effective in enhancing immune function in elderly persons with pressure ulcers. METHODS: Residents with one or more pressure ulcers were recruited from two local nursing homes. Subjects were randomized to receive 0 g (n = 10; age, 82 +/- 3 years), 8.5 g (n = 11; 81 +/- 3 years), or 17 g (n = 11; 87 +/- 2 years) of supplemental arginine each day for 4 weeks. Oral tolerance, ie, absence of nausea, vomiting, abdominal distention, or diarrhea, was assessed daily. Metabolic tolerance was assessed weekly by evaluating serum electrolytes. Lymphocyte proliferation to phytohemagglutinin and interleukin 2 production were measured at baseline and after 4 weeks of supplementation as indicators of immune function. RESULTS: Supplemental arginine significantly increased plasma arginine levels and was orally and metabolically tolerated with no complaints of abdominal distress or no clinically relevant changes in electrolyte levels among groups. Lymphocyte proliferation and interleukin 2 production were significantly different between nursing homes. When data from nursing homes were considered individually, arginine supplementation did not enhance the proliferative response. In subjects from nursing home 2 only, there was a 38% and 75% decrease (p < .05) in lymphocyte proliferation with 8.5 and 17 g of supplemental arginine, respectively. Interleukin 2 production was no different among supplementation groups. CONCLUSIONS: Pharmacologic doses of arginine were well tolerated but did not enhance lymphocyte proliferation or interleukin 2 production in nursing home residents with pressure ulcers. CLINICAL RELEVANCY: Enteral formulas supplemented with pharmacologic levels of arginine are frequently administered to elderly persons. This study demonstrates that the very old can tolerate these nitrogen loads if baseline renal function is normal and fluid intake is encouraged. Further research needs to be completed investigating the effect of arginine supplementation on immune function in this population before recommending arginine use.     

Effect of a Food for Special Medical Purposes for Muscle Recovery,Consisting of Arginine,Glutamine and Beta-Hydroxy-Beta-Methylbutyrate on Body Composition and Skin Health in Overweight and Obese Class I Sedentary Postmenopausal Women

The consumption of dietary amino acids has been evaluated for therapeutic and safety intervention in obesity. In particular, three molecules have been shown to be effective: arginine, glutamine and leucine (and its metabolite beta-hydroxy-beta-methylbutyrate, HMB). This randomized, double-blinded pilot study in obese postmenopausal patients aimed to evaluate the efficacy of the administration of a specific food for special medical purposes (FSMP) consisting of arginine, glutamine and HMB on body composition, in particular, visceral adipose tissue (VAT), assessed by dual-energy X-ray absorptiometry (DXA), as the primary endpoint. The secondary endpoint was to evaluate the effects on skin health through a validated self-reported questionnaire. A significant improvement on VAT of Δ = −153.600, p = 0.01 was recorded in the intervention group. Skin health showed a significant improvement in the treatment group for the following: bright Δ = 1.400 (0.758; 2.042), elasticity Δ = 0.900 (0.239; 1.561), wrinkles Δ = 0.800 (0.276; 1.324), and on total score, Δ = 3.000 (1.871; 4.129). In the intervention group, the improvement in VAT was associated with an improvement in the bright score (r = −0.58; p = 0.01). In conclusion, this study demonstrated that the intake for 4-weeks of arginine, glutamine and HMB effects a significant reduction in VAT and improves skin condition, while fat free mass (FFM) is maintained, thus achieving “high-quality” weight loss.     

Optimizing the dose of glutamine dipeptides and antioxidants in critically ill patients: a phase I dose-finding study

BACKGROUND: Supplementation with glutamine and antioxidants may be associated with an improvement in clinical outcomes, but the optimal dose of these substrates is unknown. The purpose of this study was to determine the safety of high doses of glutamine combined with antioxidants in critically ill patients. METHODS: We conducted a single-center, open-label, dose-escalating clinical trial. Mechanically ventilated adult patients with clinical evidence of hypoperfusion were sequentially enrolled to 1 of 5 groups. Group 1 (n = 30): no supplementation; group 2 (n = 7): 0.35 g/kg/d of glutamine IV; group 3 (n = 7): same as group 2 plus 15 g/d of glutamine and 150 microg of selenium enterally; group 4 (n = 7): same as group 2 plus 30 g/d of glutamine and 300 microg of selenium enterally; and group 5 (n = 7): same as group 4 plus an additional 500 microg of selenium IV. After enrollment, nutrients were started as soon as possible. All patients were fed enterally according to clinical practice guidelines. RESULTS: The primary outcomes for this study were change in sequential organ function assessment (SOFA) score and safety parameters. Secondary outcomes included whole blood glutathione (GSH), thiobarbituric acid reactive substances (TBARS), and blood cells' mitochondrial DNA/nuclear DNA ratio (RATIO). There were no adverse events attributable to the study nutrients, and the maximum and Delta SOFA did not differ across groups. In group 2, a significant decrease in GSH levels was observed (p = .03). With subsequent groups, the slopes straighten out and the p values are no longer significant, suggesting a greater preservation of GSH levels with escalating doses. In group 2, the slope of the line representing TBARS was horizontal. With subsequent groups, the slopes decrease, and by group 5, this decrease reaches statistical significance (p = .03), suggesting a greater reduction in oxidative stress with the higher doses in group 5. The difference in slopes across all groups describing the mitochondrial RATIO is statistically significant (p = .001), again suggesting that, with higher doses, there is increased mitochondrial function. CONCLUSIONS: The doses of glutamine and antioxidants tested in this study seem to be safe and may have positive effects on some mechanistic endpoints. A larger trial will be necessary to confirm their therapeutic effects.     

Effect of alanyl-glutamine supplementation on plasma and tissue glutamine concentrations in rats submitted to exhaustive exercise

OBJECTIVE: We investigated the effect of supplementation with L-glutamine and L-alanyl-L-glutamine (DIP) on the plasma and tissue glutamine concentrations of exercise-trained rats immediately and 3 hours after a single exercise session until exhaustion. METHODS: Thirty-six male rats were divided into six groups, and then subdivided into groups submitted only to the exhaustion test: control (CON-EXA, n = 6), glutamine (GLN-EXA, n = 6) and DIP-EXA (n = 6), or to the exhaustion test followed by a recovery period lasting 3 hours: control (CON-REC, n = 6), glutamine (GLN-REC, n = 6) and DIP-REC (n = 6). The training protocol consisted of bouts of swimming exercise (60 min x day(-1)) for 6 weeks. During the last 21 days, before sacrifice, the glutamine and DIP groups received a daily dose of 1 g x kg(-1) of glutamine and 1.5 g x kg(-1) of DIP, respectively. The GLN-REC and DIP-REC groups were also supplemented immediately after the exhaustion test. Concentrations of glutamine, glutamate, glucose and ammonia in plasma and of glutamine, protein and glycogen in liver and muscle were evaluated. RESULTS: The time to exhaustion did not differ between groups. A higher concentration of glutamine in the gastrocnemius and soleus muscles was observed for the DIP-EXA group compared to the CON-EXA and GLN-EXA groups (P < 0.05). The DIP-REC group presented a higher plasma and liver glutamine concentration than the CON-REC group (P < 0.05). Muscle glutamine and protein concentration was higher in both the GLN-REC and DIP-REC groups compared to the CON-REC group (P < 0.05). CONCLUSIONS: Chronic supplementation with DIP promoted a higher muscle glutamine concentration than chronic supplementation with glutamine immediately after exercise. However, no significant difference in plasma or tissue glutamine concentrations was observed between acute supplementation with glutamine and DIP during the post-exhaustive exercise recovery period.     

β-Hydroxy-β-methylbutyrate supplementation reduces tumor growth and tumor cell proliferation ex vivo and prevents cachexia in Walker 256 tumor-bearing rats by modifying nuclear factor-κB expression

Cancer cachexia syndrome contributes to wasting and weight loss leading to inefficacy of anticancer therapy. In this study, the anticatabolic agent β-hydroxy-β-methylbutyrate (HMB) was supplemented to adult Walker 256 tumor-bearing rats during 8 weeks aiming to determine if tumor burden could be reduced. Male Wistar rats were randomly assigned to nontumor and tumor-bearing groups and fed regular chow or regular chow plus HMB supplemented (76 mg/kg body weight). β-Hydroxy-β-methylbutyrate supplementation induced a lower tumor weight and tumor cell proliferation ex vivo, totally prevented glycemia reduction, as well as blunted the increase in the serum lactate concentrations and also preserved glycogen stores in tumor-bearing rats. Reduction in tumor cell proliferation ex vivo was accompanied by increased nuclear factor-κB inhibitor-α content by more than 100%. In contrast, nuclear factor-κB p65 subunit content was suppressed by 17% with HMB supplementation. In conclusion, HMB supplementation, at a similar dose used in humans to increase muscle mass, caused antitumor and anticachectic effects, with tumor-cell nuclear factor-κB pathway participation, which might be a potential nutritional strategy in cancer therapy.     

Metabolic response of muscle to alanine,glutamine, and valine supplementation during severe illness

BACKGROUND: Alanine and glutamine are released from muscle in response to critical illness. Subsequent depletion of glutamine from muscle is proposed as a principal factor in the limitation of muscle protein synthesis in severely ill patients. The objective of this study was to assess the peripheral metabolic response to enteral supplementation of alanine, glutamine, and valine in critically ill patients. METHODS: Isotopic tracers of alanine, glutamine, and phenylalanine were given IV to 6 critically ill patients and 6 healthy volunteers. Blood sampling from the femoral artery and vein along with muscle biopsies provided assessment of leg (ie, muscle) kinetics. Measurements were obtained during enteral nutrition alone and then with combined alanine (11.25 g), glutamine (7.5 g) and valine (11.25 g) supplementation for 3 hours. RESULTS: Compared with healthy volunteers, critically ill patients had significantly reduced concentrations of alanine and glutamine in arterial plasma (p < .05), which increased significantly with amino acid supplementation. Muscle glutamine concentrations were significantly less in the patients and were not significantly affected by supplementation. Alanine and glutamine transport into and out of muscle and the rates of alanine and glutamine incorporation into and production from muscle were not affected by supplementation. Phenylalanine kinetics, as a marker of muscle protein metabolism, were not significantly altered by alanine, glutamine, and valine intake. CONCLUSIONS: These results demonstrate that alanine, glutamine, and valine administration fails to significantly affect muscle glutamine availability or muscle protein metabolism. These findings suggest that accelerated muscle catabolism in critically ill patients is not in response to any deficiency in alanine or glutamine availability.     

A pilot study of the safety and efficacy of supplemental arginine to enhance immune function in persons with HIV/AIDS

OBJECTIVE: We collected preliminary data on the safety and efficacy of supplemental arginine to improve natural killer cell cytotoxicity in a sample of persons with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). METHODS: In a randomized, double-blind, placebo-controlled pilot study in an academic medical center-based infectious disease clinic, 11 clinically stable, HIV-infected adults had been treated with highly active, antiretroviral therapy and had HIV plasma RNA levels of less than 10 000 copies/mL. Participants were randomly assigned to receive 19.6 g of arginine/d (n = 6) or placebo (n = 5) for 14 d. Plasma HIV RNA levels, neuropsychologic functioning, and self-reported adverse events were analyzed for safety of treatment. Efficacy was measured by natural killer cell cytotoxicity. RESULTS: None of the participants experienced any adverse clinical, virologic, or neuropsychologic events that necessitated withdrawal from the study. The arginine-supplemented group showed a mean natural killer cell cytotoxicity increase of 18.9 lytic units, whereas the placebo group showed an increase of 0.3 lytic units. This difference was not statistically significant (P = 0.79). CONCLUSIONS: Short-term arginine supplementation is safe for persons with HIV/AIDS. Additional studies with larger samples and longer periods are warranted to determine the effects of arginine supplementation on other indices of immune function and on clinical outcomes such as intercurrent illnesses.     

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.     

Plasma Arginine Levels and Blood Glucose Control in Very Preterm Infants Receiving 2 Different Parenteral Nutrition Regimens

Background: Improving parenteral nutrition (PN) amino acid (AA) intake in very preterm infants is associated with less hyperglycemia. AAs stimulate newborn insulin secretion with arginine, demonstrating a specific effect. We hypothesized that low arginine levels would be associated with increased insulin‐treated hyperglycemia and higher mean daily blood glucose levels in very preterm infants. Methods: We performed a secondary analysis on previous study data comparing high‐protein/calorie PN (HPC‐PN) and control groups in infants <29 weeks’ gestation. Infants were substratified (within original groups) according to high (highARG) and low (lowARG) plasma arginine levels on days 8–10 using a reference population‐derived threshold for high/low arginine (57 µmol/L). Daily protein, arginine, carbohydrate intake, mean daily blood glucose, and insulin treatment data from the first 15 days of life were collected. Results: Control group infants (n = 60) were stratified into lowARG (n = 41) and highARG (n = 19) groups. There were no differences in basic demographic data or carbohydrate intake. LowARG infants had higher mean daily blood glucose levels (P < .05) and a trend to more insulin treatment on days 6–10. HPC‐PN group infants (n = 55) were stratified into lowARG (n = 33) and highARG (n = 22) groups. LowARG infants had lower gestation and birth weight and were sicker than highARG infants. There were no differences in carbohydrate intake. LowARG infants had higher mean daily blood glucose levels (P < .01) and more insulin treatment (P < .01) on days 1–5 and 6–10. Insulin‐treated hyperglycemia was also associated with low plasma glutamine levels. Conclusion: Low plasma arginine levels (≤57 µmol/L) in very preterm infants are associated with poorer blood glucose control.     

Adaptations of Arginine's Intestinal-Renal Axis in Cachectic Tumor-Bearing Rats

Malignancies induce disposal of arginine, an important substrate for the immune system. To sustain immune function, the tumor-bearing host accelerates arginine's intestinal-renal axis by glutamine mobilization from skeletal muscle and this may promote cachexia. Glutamine supplementation stimulates argi-nine production in healthy subjects. Arginine's intestinal-renal axis and the effect of glutamine supplementation in cancer cach-exia have not been investigated. This study evaluated the long-term adaptations of the interorgan pathway for arginine production following the onset of cachexia and the metabolic effect of glutamine supplementation in the cachectic state. Fischer-344 rats were randomly divided into a tumor-bearing group (n = 12), control group (n = 7) and tumor-bearing group receiving a glutamine-enriched diet (n = 9). Amino acid fluxes and net fractional extractions across intestine, kidneys, and liver were studied. Compared to controls, the portal-drained viscera of tumor-bearing rats took up significantly more glutamine and released significantly less citrulline. Renal metabolism was unchanged in the cachectic tumor-bearing rats compared with controls. Glutamine supplementation had no effects on intestinal and renal adaptations. In conclusion, in the cachectic state, an increase in intestinal glutamine uptake is not accompanied by an increase in renal arginine production. The adaptations found in the cachectic, tumor-bearing rat do not depend on glutamine availability.     

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.     

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.     

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.