A Patented Dietary Supplement (Hydroxy-Methyl-Butyrate, Carnosine, Magnesium, Butyrate, Lactoferrin) Is a Promising Therapeutic Target for Age-Related Sarcopenia through the Regulation of Gut Permeability: A Randomized Controlled Trial.

Adequate diet, physical activity, and dietary supplementation with muscle-targeted food for special medical purposes (FSMP) or dietary supplement (DS) are currently considered fundamental pillars in sarcopenia treatment. The aim of this study is to evaluate the effectiveness of a DS (containing hydroxy-methyl-butyrate, carnosine, and magnesium, for its action on muscle function and protein synthesis and butyrate and lactoferrin for their contribution to the regulation of gut permeability and antioxidant/anti-inflammation activity) on muscle mass (assessed by dual X-ray absorptiometry (DXA)), muscle function (by handgrip test, chair test, short physical performance battery (SPPB) test, and walking speed test), inflammation (tumor necrosis factor-alpha (TNF-a), C-reactive protein (CRP), and visceral adipose tissue (VAT)) and gut axis (by zonulin). A total of 59 participants (age 79.7 ± 4.8 years, body mass index 20.99 ± 2.12 kg/m2) were enrolled and randomly assigned to intervention (n = 30) or placebo (n = 28). The skeletal muscle index (SMI) significantly improved in the supplemented group compared to the placebo one, +1.02 (CI 95%: -0.77; 1.26), p = 0.001; a significant reduction in VAT was observed in the intervention group, -70.91 g (-13.13; -4.70), p = 0.036. Regarding muscle function, all the tests significantly improved (p = 0.001) in the supplemented group compared to the placebo one. CRP, zonulin, and TNF-alpha significantly decreased (p = 0.001) in intervention, compared to placebo, -0.74 mg/dL (CI 95%: -1.30; -0.18), -0.30 ng/mL (CI 95%: -0.37; -0.23), -6.45 pg/mL (CI 95%: -8.71; -4.18), respectively. This DS improves muscle mass and function, and the gut muscle has emerged as a new intervention target for sarcopenia.

A Prospective, Observational Study of the Effect of a High-Calorie, High-Protein Oral Nutritional Supplement with HMB in an Old and Malnourished or at-Risk-of-Malnutrition Population with Hip Fractures: A FracNut Study.

BACKGROUND: Hip fractures are prevalent among older people, often leading to reduced mobility, muscle loss, and bone density decline. Malnutrition exacerbates the prognosis post surgery. This study aimed to evaluate the impact of a 12-week regimen of a high-calorie, high-protein oral supplement with ß-hydroxy-ß-methylbutyrate (HC-HP-HMB-ONS) on nutritional status, daily activities, and compliance in malnourished or at-risk older patients with hip fractures receiving standard care. SUBJECTS AND METHODS: A total of 270 subjects ≥75 years of age, residing at home or in nursing homes, malnourished or at risk of malnutrition, and post hip fracture surgery, received HC-HP-HMB-ONS for 12 weeks. Various scales and questionnaires assessed outcomes. RESULTS: During the 12 weeks of follow-up, 82.8% consumed ≥75% of HC-HP-HMB-ONS. By week 12, 62.4% gained or maintained weight (+0.3 kg), 29.2% achieved normal nutritional status (mean MNA score +2.8), and 46.8% improved nutritional status. Biochemical parameters improved significantly. Subjects reported good tolerability (mean score 8.5/10), with 87.1% of healthcare providers concurring. CONCLUSIONS: The administration of HC-HP-HMB-ONS markedly enhanced nutritional status and biochemical parameters in older hip-fracture patients, with high compliance and tolerability. Both patients and healthcare professionals expressed satisfaction with HC-HP-HMB-ONS.

Plasma beta-hydroxy-beta-methylbutyrate availability after enteral administration during critical illness after trauma: An exploratory study.

BACKGROUND: During critical illness skeletal muscle wasting occurs rapidly. Although beta-hydroxy-beta-methylbutyrate (HMB) is a potential treatment to attenuate this process, the plasma appearance and muscle concentration is uncertain. METHODS: This was an exploratory study nested within a blinded, parallel group, randomized clinical trial in which critically ill patients after trauma received enteral HMB (3 g daily) or placebo. Plasma samples were collected at 0, 60, and 180 min after study supplement administration on day 1. Needle biopsies of the vastus lateralis muscle were collected (baseline and day 7 of the HMB treatment intervention period). An external standard curve was used to calculate HMB concentrations in plasma and muscle. RESULTS: Data were available for 16 participants (male n = 12 (75%), median [interquartile range] age 50 [29-58] years) who received placebo and 18 participants (male n = 14 (78%), age 49 [34-55] years) who received HMB. Plasma HMB concentrations were similar at baseline but increased after HMB (T = 60 min: placebo 0.60 [0.44-1.31] µM; intervention 51.65 [22.76-64.72] µM). Paired muscle biopsies were collected from 11 participants (placebo n = 7, HMB n = 4). Muscle HMB concentrations were similar at baseline between groups (2.35 [2.17-2.95]; 2.07 [1.78-2.31] µM). For participants in the intervention group who had the repeat biopsy within 4 h of HMB administration, concentrations were greater (7.2 and 12.3 µM) than those who had the repeat biopsy >4 h after HMB (2.7 and 2.1 µM). CONCLUSION: In this exploratory study, enteral HMB administration increased plasma HMB availability. The small sample size limits interpretation of the muscle HMB findings.

Effect on an Oral Nutritional Supplement with ß-Hydroxy-ß-methylbutyrate and Vitamin D on Morphofunctional Aspects, Body Composition, and Phase Angle in Malnourished Patients.

This is a retrospective study of data from clinical practice to observe the effect of a high-calorie, high-protein oral nutritional supplement (ONS) with ß-hydroxy-ß-methylbutyrate (HMB) on nutritional status, body weight, and muscle-related parameters in 283 adult patients with or at risk of malnutrition under standard of care, 63% being cancer patients. They were recommended to increase physical activity and energy and protein intake from regular diet plus two servings per day of a specialized ONS enriched with HMB or standard ONS for up to 6 months. Dietary records, adherence and tolerance to ONS, nutritional status, body composition, handgrip strength, and blood analysis at the beginning and the end of the intervention were recorded. This program improved nutritional status from 100% malnourished or at risk of malnutrition at baseline to 80% well-nourished at final visit. It also increased body weight by 3.6-3.8 kg, fat-free mass by 0.9 to 1.3 kg, and handgrip strength by 4.7 to 6.2 kg. In a subgroup of patients (n = 43), phase angle (PhA), and body cell mass (BCM) increased only in the patients receiving the ONS enriched with HMB (0.95 (0.13) vs. -0.36 (0.4), and 2.98 (0.5) vs. -0.6 (1.5) kg, mean difference (SE) from baseline for PhA and BCM, respectively), suggesting the potential efficacy of this supplement on muscle health.

Malnutrition and Perioperative Nutritional Support in Retroperitoneal Sarcoma Patients: Results from a Prospective Study.

INTRODUCTION: Retroperitoneal soft tissue sarcomas (RPSs) are mesenchymal neoplasms. The prevalence of protein energetic malnutrition (PEM) and its impact in RPS patients who were candidates for surgery is unknown. MATERIALS AND METHODS: A prospective feasibility study enrolled 35 patients with primary RPS who were candidates for extended multivisceral resection. PEM was screened at enrollment. Preoperative high protein ß-hydroxy-ß-methyl butyrate oral nutritional support (ONS) was provided according to the degree of PEM. After surgery, nutritional support followed standard practice, targeting at least 1 g/kg/day protein and 20 kcal/kg/day caloric intake within the third postoperative day (POD). PEM was re-evaluated before surgery on POD 10, and at 4 and 12 months after surgery. Primary outcomes were the patient's compliance to preoperative ONS and the physician's compliance to postoperative nutritional targets. RESULTS: PEM was documented in 46% of patients at baseline; ONS met a 91% adherence (overall well tolerated). After ONS, PEM reduced to 38% (p = 0.45). The postoperative caloric target was reached on day 4.1 (standard error ± 2.7), with a protocol adherence rate of 52%. On POD 10, 91% of patients experienced PEM, the worsening of which was greater after resection of four or more organs (p = 0.06). At 4 and 12 months after surgery, almost all patients had fully recovered. A significant correlation between PEM at surgery and postoperative complications was found (p = 0.04). CONCLUSIONS: Relevant PEM prevalence in RPS is documented for the first time. PEM correlates with greater morbidity. In this setting, preoperative ONS was feasible and well-tolerated. Disease-related factors for PEM and the ideal perioperative caloric target in the context of extended multivisceral resection need to be further investigated. Nutritional support should be included in enhanced recovery after surgery programs for RPS. TRIAL REGISTRY: ClinicalTrials.gov identifier: NCT03877588.

Beta-hydroxy beta-methyl butyrate decreases muscle protein degradation via increased Akt/FoxO3a signaling and mitochondrial biogenesis in weanling piglets after lipopolysaccharide challenge.

The aim of this study was to investigate the effects of dietary ß-hydroxy-ß-methylbutyrate (HMB) on lipopolysaccharide (LPS)-induced muscle atrophy and to investigate the mechanisms involved. Sixty pigs (21 ± 2 days old, 5.86 ± 0.18 kg body weight) were used in a 2 × 3 factorial design and the main factors included diet (0, 0.60%, or 1.20% HMB) and immunological challenge (LPS or saline). After 15 d of treatment with LPS and/or HMB, growth performance, blood parameters, and muscle protein degradation rate were measured. The results showed that in LPS-injected pigs, 0.60% HMB supplementation increased the average daily gain and average daily feed intake and decreased the feed : gain ratio (P < 0.05), with a concurrent increase of lean percentage. Moreover, 0.60% HMB supplementation decreased the serum concentrations of blood urea nitrogen, IL-1ß, and TNF-α and the rate of protein degradation as well as cell apoptosis in selected muscles (P < 0.05). In addition, dietary HMB supplementation (0.60%) regulated the expression of genes involved in mitochondrial biogenesis and increased the phosphorylation of Akt and Forkhead Box O3a (FoxO3a) in selected muscles, accompanied by decreased protein expression of muscle RING finger 1 and muscle atrophy F-box. These results indicate that HMB may exert protective effects against LPS-induced muscle atrophy by normalizing the Akt/FoxO3a axis that regulates ubiquitin proteolysis and by improving mitochondrial biogenesis.

Eccentric resistance training and ß-hydroxy-ß-methylbutyrate free acid affects muscle PGC-1α expression and serum irisin, nesfatin-1 and resistin in rats.

The hypothalamus controls metabolism and feeding behaviour via several signals with other tissues. Exercise and supplements can change hypothalamic signalling pathways, so the present study investigated the influence of eccentric resistance training and ß-hydroxy-ß-methylbutyrate free acid supplementation on PGC-1α expression, serum irisin, nesfatin-1 and resistin concentrations. Thirty-two male rats (8 weeks old, 200±17 g body mass) were randomly allocated to control, ß-hydroxy-ß-methylbutyrate free acid supplementation (HMB), eccentric resistance training (ERT), and ß-hydroxy-ß-methylbutyrate free acid supplementation plus eccentric resistance training (HMB+ERT) groups. Training groups undertook eccentric resistance training (6 weeks, 3 times a week) and supplement groups consumed ß-hydroxy-ß-methylbutyrate free acid (HMB-FA) orally (76 mg kg-1 day-1). Twenty-four hours after the last training session, serum and triceps brachii muscle samples were collected and sent to the laboratory for analysis. Two-way ANOVA and Pearson correlation were employed (significance level: P<0.05). The results showed that eccentric resistance training increases skeletal muscle PGC-1α gene expression, as well as serum levels of irisin and nesfatin-1 (P=0.001). Eccentric resistance training decreased the serum concentration of resistin (P=0.001). HMB-FA supplementation increased skeletal muscle PGC-1α gene expression (P=0.002), as well as the serum concentration of irisin and nesfatin-1 (P=0.001), but decreased the serum concentration of resistin (P=0.001). Significant correlations were observed between PGC-1α gene expression and serum concentrations of irisin, nesfatin-1 and resistin. HMB-FA supplementation with eccentric resistance training may induce crosstalk between peptide release from other tissues and increases maximal muscle strength. The combination of the two interventions had a more substantial effect than each in isolation.

Leucine metabolites do not attenuate training-induced inflammation in young resistance trained men.

Leucine metabolites may reduce training-induced inflammation; however, there is scant evidence for this assertion. We conducted a double-blind randomized controlled pragmatic trial where 40 male participants were allocated into 4 groups: α-hydroxyisocaproic acid group ([α-HICA], n = 10, Fat-free mass [FFM] = 62.0 ± 7.1 kg), ß-hydroxy-ß-methylbutyrate free acid group ([HMB-FA], n = 11, FFM = 62.7 ± 10.5 kg), calcium ß-hydroxy-ß-methylbutyrate group ([HMB-Ca], n = 9, FFM = 65.6 ± 10.1 kg) or placebo group ([PLA]; n = 10, FFM = 64.2 ± 5.7 kg). An 8-week whole-body resistance training routine (3 training sessions per week) was employed to induce gains in skeletal-muscle thickness. Skeletal muscle thickness (MT), one repetition maximum (1RM), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP) and tumour necrosis factor alpha (TNF-α) were assessed at baseline and at the end of weeks 4 and 8. Time-dependent increases were detected from baseline to week 8 for MT (vastus lateralis: p = 0.009; rectus femoris: p = 0.018), 1RM (back squat: α-HICA, 18.5% ± 18.9%; HMB-FA, 23.2% ± 16%; HMB-Ca, 10.5% ± 13.8%; PLA, 19.7% ± 9% and bench press: α-HICA, 13.8% ± 19.1%; HMB-FA, 15.5% ± 9.3%; HMB-Ca, 10% ± 10.4%; PLA, 14.4 ± 11.3%, both p < 0.001), IL-6, hsCRP (both p < 0.001) and TNF-α (p = 0.045). No differences were found between groups at any time point. No leucine metabolite attenuated inflammation during training. Additionally, backwards elimination regressions showed that no circulating inflammatory marker consistently shared variance with the change in any outcome. Using leucine metabolites to modulate inflammation cannot be recommended from the results obtained herein. Furthermore, increases in inflammatory markers, from training, do not correlate with any outcome variable and are likely the result of training adaptations.

Efficacy of preoperative amino acid supplements on postoperative physical function and complications in open heart surgery patients: A study protocol for a randomized controlled trial.

BACKGROUND: Elderly patients undergoing cardiac surgery often show poor nutritional status, muscle wasting, and sarcopenia, which are reported to affect postoperative functional recovery and incidence of complications. Amino acids are essential in maintaining nutritional status, synthesizing muscle protein, and promoting beneficial energy balance of the heart muscle. ß-Hydroxy ß-methylbutyric acid (HMB) is a leucine metabolite known to increase muscle protein synthesis and inhibit protein catabolism; it has been used to more effectively support patients with muscle wasting due to wearing diseases. However, the efficacy of amino acid administration comprising HMB in patients undergoing open heart surgery remains unclear. This study aims to examine whether preoperative short-term aggressive amino acid administration helps support postoperative recovery of physical function and prevent complications. METHODS: This is a single-center prospective randomized controlled trial (UMIN000030490). Patients aged ≥65 years who will be hospitalized for medical examination before cardiac surgery will be recruited. The participants will be randomly assigned to the experimental or control group. The experimental group will be administered with an amino acid supplement with HMB 1200mg, l-glutamine 7000mg, and l-arginine 7000mg once or twice per day depending on the degree of renal dysfunction, for 14-28 days preoperatively. The control group will not receive any nutritional intervention. The main outcome will be a change in the 6-min walking test distance pre- and postoperatively as a sign of functional recovery. Secondary outcomes such as the incidence of complications; physical, nutritional, and psychological states; mortality; and length of hospital stay will also be evaluated. CONCLUSION: This clinical study will determine the effects of preoperative short-term oral amino acid supplementation with HMB, l-glutamine, and l-arginine on postoperative physical function in elderly patients undergoing cardiac surgery.

ß-Hydroxy-ß-methylbutyrate and its impact on skeletal muscle mass and physical function in clinical practice: a systematic review and meta-analysis.

BACKGROUND: Loss of skeletal muscle mass and muscle weakness are common in a variety of clinical conditions with both wasting and weakness associated with an impairment of physical function. ß-Hydroxy-ß-methylbutyrate (HMB) is a nutrition supplement that has been shown to favorably influence muscle protein turnover and thus potentially plays a role in ameliorating skeletal muscle wasting and weakness. OBJECTIVES: The aim of this study was to investigate the efficacy of HMB alone, or supplements containing HMB, on skeletal muscle mass and physical function in a variety of clinical conditions characterized by loss of skeletal muscle mass and weakness. METHODS: A systematic review and meta-analysis of randomized controlled trials reporting outcomes of muscle mass, strength, and physical function was performed. Two reviewers independently performed screening, data extraction, and risk-of-bias assessment. Outcome data were synthesized through meta-analysis with the use of a random-effects model and data presented as standardized mean differences (SMDs). RESULTS: Fifteen randomized controlled trials were included, involving 2137 patients. Meta-analysis revealed some evidence to support the effect of HMB alone, or supplements containing HMB, on increasing skeletal muscle mass (SMD = 0.25; 95% CI: -0.00, 0.50; z = 1.93; P = 0.05; I2 = 58%) and strong evidence to support improving muscle strength (SMD = 0.31; 95% CI: 0.12, 0.50; z = 3.25; P = 0.001; I2 = 0%). Effect sizes were small. No effect on bodyweight (SMD = 0.16; 95% CI: -0.08, 0.41; z = 1.34; P = 0.18; I2 = 67%) or any other outcome was found. No study was considered to have low risk of bias in all categories. CONCLUSION: HMB, and supplements containing HMB, increased muscle mass and strength in a variety of clinical conditions, although the effect size was small. Given the bias associated with many of the included studies, further high-quality studies should be undertaken to enable interpretation and translation into clinical practice. The trial was registered on PROSPERO as CRD42017058517.

Beta-Hydroxy-Beta-Methyl-Butyrate, L-glutamine, and L-arginine Supplementation Improves Radiation-Induce Acute Intestinal Toxicity.

We aimed to evaluate effects of ß-hydroxy-ß-methylbutyrate, L-glutamine, and L-arginine (HMB/GLN/ARG) on radiation-induced acute intestinal toxicity. Forty rats were divided into four groups: group (G) 1 was defined as control group, and G2 was radiation therapy (RT) control group. G3 and G4 were HMB/GLN/ARG control and RT plus HMB/GLN/ARG groups, respectively. HMB/GLN/ARG started from day of RT and continued until the animals were sacrificed 10 days after RT. The extent of surface epithelium smoothing, villous atrophy, lamina propria inflammation, cryptitis, crypt distortion, regenerative atypia, vascular dilatation and congestion, and fibrosis were quantified on histological sections of intestinal mucosa. Statistical analyses were performed using the analysis of variance (ANOVA) test. There were significant differences between study groups regarding extent of surface epithelium smoothing, villous atrophy, lamina propria inflammation, cryptitis and crypt distortion, regenerative atypia, vascular dilatation and congestion, and fibrosis (p values were 0.019 for fibrosis, <.001 for the others). Pair-wise comparisons revealed significant differences regarding surface epithelium smoothing, villous atrophy, lamina propria inflammation, cryptitis, vascular dilatation, and congestion between G2 and G4 (p values were <.001, .033, <.001, .007, and <.001, respectively). Fibrosis score was significantly different only between G1 and G2 (p = .015). Immunohistochemical TGF-ß score of G2 was significantly higher than G1 and G3 (p values were .006 and .017, respectively). There was no difference between TGF-ß staining scores of G2 and G4. Concomitant use of HMB/GLN/ARG appears to ameliorate radiation-induced acute intestinal toxicity; however, this finding should be clarified with further studies.

Equivalent Hypertrophy and Strength Gains in ß-Hydroxy-ß-Methylbutyrate- or Leucine-supplemented Men.

Ingestion of proteins with high leucine content during resistance training (RT) can augment hypertrophy. Some data suggest that a leucine metabolite, ß-hydroxy, ß-methylbutyrate (HMB), is substantially more anabolically efficacious than leucine. PURPOSE: We aimed to test whether supplementation with HMB versus leucine, added to whey protein, would result in differential muscle hypertrophy and strength gains in young men performing RT. METHODS: Twenty-six resistance-trained men (23 ± 2 yr) performed 12 wk of RT with three phases. Phase 1: 8 wk of periodized RT (three training sessions per week). Phase 2: 2 wk overreaching period (five sessions per week). Phase 3: 2 wk taper (three sessions per week). Participants were randomly assigned to twice daily ingestion of: whey protein (25 g) plus HMB (1.5 g) (whey+HMB; n = 13) or whey protein (25 g) plus leucine (1.5 g) (whey+leu; n = 13). Skeletal muscle biopsies were performed before and after RT. Measures of fat- and bone-free mass, vastus lateralis (VL) muscle thickness and muscle cross-sectional area (CSA) (both by ultrasound), muscle fiber CSA, and 1-repetition maximum (1-RM) strength tests were determined. RESULTS: We observed increases in fat- and bone-free mass, VL muscle thickness, muscle CSA and fiber type CSA and 1-RM strength with no differences between groups at any phase. We observed no differences between groups or time-group interactions in hormone concentrations at any phase of the RT program. CONCLUSIONS: ß-Hydroxy-ß-methylbutyrate added to whey did not result in greater increases in any measure of muscle mass, strength, or hormonal concentration compared to leucine added to whey. Our results show that HMB is no more effective in stimulating RT-induced hypertrophy and strength gains than leucine.

ß-Hydroxy-ß-methyl Butyrate/L-Arginine/L-Glutamine Supplementation for Preventing Hand-Foot Skin Reaction in Sorafenib for Advanced Hepatocellular Carcinoma.

BACKGROUND/AIM: Sorafenib is standard treatment for advanced hepatocellular carcinoma (HCC). Hand-foot skin reaction (HFSR) is a notorious side-effect of this therapy. This study evaluated prophylactic benefits of an oral nutritional supplement (ONS) on sorafenib-associated HFSR in advanced HCC. PATIENTS AND METHODS: This was a prospective, single-center, open-label trial arm using combined ONS and sorafenib in patients with unresectable HCC from August 2014 to February 2018. Control patients received sorafenib without ONS from 2011 to 2014. From September 2014, prophylactic ONS containing ß-hydroxy-ß-methylbutyrate (HMB), L-arginine, and L-glutamine was given. Sorafenib dosage was 400 mg/day for both groups. RESULTS: Each group comprised 22 men and three women. Age, sex, Child-Pugh score, and clinical stage excluding IV-B did not significantly differ between the groups. HFSR occurred after 2 weeks: 15/25 patients in the control group (60%; HFSR grade 1: 6, grade 2: 7, grade 3: 2) vs. 8/25 in the ONS group (32%; HFSR grade 1: 4, grade 2: 4, grade 3: 0; p=0.047, Pearson's Chi-square test). CONCLUSION: Prophylactic HMB, L-arginine and L-glutamine supplementation effectively prevented sorafenib-associated HFSR in patients with advanced HCC.

Effects of HMB supplementation on body composition of rats / Efectos de la suplementación con HMB sobre la composición corporal en ratas

The aim was to investigate the effects of HMB supplementation on the physical performance and anthropometric parameters of Wistar rats that underwent eight weeks of concurrent training. We used 22 male Wistar rats of approximately 60 days of age, And were divided into four groups: control (C), supplemented control (SC), exercise (E) and supplemented exercise (SE). The training consisted of 30 minutes of swimming with an overload corresponding to 70 % of the anaerobic threshold, a one-minute interval, and four sets of ten jumps in water with a one minute interval between sets and a load of 50 % of body weight. After the tests, the tLIM and tTESTE were obtained and used to evaluate the performance of the animals, and anthropometric indices evaluated. The weight increases during the treatment in the SC animals was significantly higher than the animals in groups C and E. The absolute weight of the muscles, kidney and epididymal fat showed higher values for the SC and SE groups in relation to the others.

Se investigaron los efectos de la suplementación con HMB en el rendimiento físico y los parámetros antropométricos de ratas Wistar sometidas a ocho semanas de entrenamiento concurrente. La muestra consistió en 22 ratas Wistar machos, aproximadamente de 60 días de edad, los que fueron divididos en cuatro grupos: control (C), control suplementado (CS), ejercicio (E) y ejercicio suplementado (ES). El entrenamiento consistió en 30 minutos de natación correspondiente a 70 % de la sobrecarga del umbral anaeróbico, un intervalo de un minuto y cuatro series de diez saltos en el agua con intervalo de un minuto entre series y una carga del 50 % del peso del cuerpo. El tLIM y tTESTE se utilizaron para evaluar el rendimiento de los animales, y los índices antropométricos. El aumento de peso durante el tratamiento CS fue significativamente más alto que las de los grupos C y E. El peso absoluto de los músculos, los riñones y la grasa del epidídimo mostraron valores más altos en los grupos CS y ES en relación con los demás.

Beta-hydroxy-beta-methylbutyrate supplementation and skeletal muscle in healthy and muscle-wasting conditions.

Beta-hydroxy-beta-methylbutyrate (HMB) is a metabolite of the essential amino acid leucine that has been reported to have anabolic effects on protein metabolism. The aims of this article were to summarize the results of studies of the effects of HMB on skeletal muscle and to examine the evidence for the rationale to use HMB as a nutritional supplement to exert beneficial effects on muscle mass and function in various conditions of health and disease. The data presented here indicate that the beneficial effects of HMB have been well characterized in strength-power and endurance exercise. HMB attenuates exercise-induced muscle damage and enhances muscle hypertrophy and strength, aerobic performance, resistance to fatigue, and regenerative capacity. HMB is particularly effective in untrained individuals who are exposed to strenuous exercise and in trained individuals who are exposed to periods of high physical stress. The low effectiveness of HMB in strength-trained athletes could be due to the suppression of the proteolysis that is induced by the adaptation to training, which may blunt the effects of HMB. Studies performed with older people have demonstrated that HMB can attenuate the development of sarcopenia in elderly subjects and that the optimal effects of HMB on muscle growth and strength occur when it is combined with exercise. Studies performed under in vitro conditions and in various animal models suggest that HMB may be effective in treatment of muscle wasting in various forms of cachexia. However, there are few clinical reports of the effects of HMB on muscle wasting in cachexia; in addition, most of these studies evaluated the therapeutic potential of combinations of various agents. Therefore, it has not been possible to determine whether HMB was effective or if there was a synergistic effect. Although most of the endogenous HMB is produced in the liver, there are no reports regarding the levels and the effects of HMB supplementation in subjects with liver disease. Several studies have suggested that anabolic effects of HMB supplementation on skeletal muscle do not occur in healthy, non-exercising subjects. It is concluded that (i) HMB may be applied to enhance increases in the mass and strength of skeletal muscles in subjects who exercise and in the elderly and (ii) studies examining the effects of HMB administered alone are needed to obtain conclusions regarding the specific effectiveness in attenuating muscle wasting in various muscle-wasting disorders.

ß-Hydroxy-ß-methylbutyrate attenuates cytokine response during sustained military training.

This study tested the hypothesis that of 23 days of ß-hydroxy-ß-methylbutyrate (HMB) supplementation can maintain muscle mass and attenuate the immune and inflammatory response in combat soldiers during highly intense military training. Soldiers were randomly assigned to either a HMB (n = 6) or placebo (PL; n = 7) group and provided with 3 g · day(-1) of either HMB or PL. During the final week of supplementation soldiers participated in extreme physical training, which included night navigation of 6-8 hours across difficult terrain carrying heavy loads combined with sleep deprivation (3.8 ± 3.0 h per night). Blood draws were performed prior to and following the supplementation period. Magnetic resonance imaging, which included diffusion tensor imaging sequence, was used for muscle fiber tracking analysis. Data was analyzed using a two-way mixed factorial analysis of variance. Magnitude-based inferences were used to provide inferences on the true effects that HMB may have had on the dependent variables compared to PL, calculated from 90% confidence intervals. Changes in tumor necrosis factor-α for HMB (-3.9 ± 8.2 pg · mL(-1)) were significantly lower (P = .043) compared to the change in PL (+4.0 ± 3.7 pg · mL(-1)). HMB ingestion was also very likely (92%-95% Likelihood) to lower granulocyte colony-stimulating factor and interleukin 10 compared to PL. In addition, HMB supplementation was likely (78%-87% likelihood) to reduce interferon-γ, interleukin 8, CX3CL1, and increase muscle volume for the adductor magnus (77% likelihood) compared to PL. In summary, the results of this study provides evidence that HMB supplementation may attenuate the inflammatory response to high intense military training, and maintain muscle quality.

Oral supplement enriched in HMB combined with pulmonary rehabilitation improves body composition and health related quality of life in patients with bronchiectasis (Prospective, Randomised Study).

BACKGROUND & AIMS: Pulmonary Rehabilitation (PR) is recommended for bronchiectasis but there is no data about its effect on body composition. The aim of this study is to assess the effect of Pulmonary Rehabilitation (PR) for 12 weeks in normally-nourished non-cystic-fibrosis bronchiectasis patients compared with the effect of PR plus a hyperproteic oral nutritional supplement enriched with beta-hydroxy-beta-methylbutyrate (HMB) on body composition, muscle strength, quality of life and serum biomarkers. METHODS: single center randomized controlled trial, parallel treatment design: Participants were randomly assigned to receive PR for 12 weeks or PR plus ONS (PRONS) (one can per day). Outcome assessments were performed at baseline, 12 weeks and 24 weeks: body composition (Dual-energy X-Ray Absorptiometry (DEXA), mid-arm muscle circumference (MAMC), phase angle by Bio-impedance), health related quality of life (Spanish QOL-B-V3.0, Physical Functioning Scale), handgrip strength, diet questionnaire, and plasma levels of prealbumin, myostatin and somatomedin-c. RESULTS: Thirty patients were randomized (15 per group) without differences in clinical and respiratory variables. In the PRONS group bone mineral density (BMD), mean and maximum handgrip dynamometry, MAMC, QOLB and prealbumin were significantly increased from baseline at 12 and 24 weeks and Fat free Mass (FFM) and FFM index, at 12 weeks. In the PR group only mean handgrip dynamometry and prealbumin were significantly increased at 12 and 24 weeks. In both groups plasma myostatin was reduced at 12 weeks (without significant differences). CONCLUSION: The addition of a hyperproteic ONS enriched with HMB to Pulmonary Rehabilitation could improve body composition, BMD, muscle strength and health related quality of life in bronchiectasis patients. Clinical Trials Number NCT02048397.

Effects of 6-month supplementation with ß-hydroxy-ß-methylbutyrate, glutamine and arginine on vascular endothelial function of older adults.

BACKGROUND/OBJECTIVES: Vascular endothelial function declines with advancing age, due in part to increased oxidative stress and inflammation, and this age-related vascular dysfunction has been identified as an independent risk factor for cardiovascular diseases. This double-blind, placebo-controlled trial investigated the effects of a dietary supplement containing ß-hydroxy-ß-methylbutyrate (HMB), glutamine and arginine on endothelial-dependent vasodilation of older adults. SUBJECTS/METHODS: A total of 31 community-dwelling men and women aged 65-87 years were randomly assigned to two groups. The treatment group received two doses of the supplement daily (totaling 3 g HMB, 14 g glutamine and 14 g arginine) for 6 months, whereas the control group received an isocaloric placebo. At baseline and week 24, vascular endothelial function was measured by flow-mediated dilation of the brachial artery, and fasting blood samples were obtained to measure high-sensitivity C-reactive protein (hsCRP) and tumor necrosis factor-α (TNF-α). RESULTS: Paired sample t-tests revealed a 27% increase in flow-mediated dilation among the treatment group (P=0.003), whereas no change was observed in the placebo group (P=0.651). Repeated-measures analysis of variance verified a significant time by group interaction (P=0.038). Although no significant changes were observed for hsCRP or TNF-α, a trend was observed for increasing hsCRP among the placebo group only (P=0.059). CONCLUSIONS: These results suggest that dietary supplementation of HMB, glutamine and arginine may favorably affect vascular endothelial function in older adults. Additional studies are needed to elucidate whether reduced inflammation or other mechanisms may underlie the benefits of supplementation.

A Diet Containing Beta-Hydroxy-Beta-Methylbutyrate, L-Glutamine and L-Arginine Ameliorates Chemoradiation-Induced Gastrointestinal Injury in Rats.

The aim of this study was to investigate the effects of a specific diet, containing beta-hydroxy-beta-methylbutyrate, L-glutamine and L-arginine (HMB/Glu/Arg), on chemoradiation-induced injuries of the rat gastrointestinal mucosa. Wistar albino rats were divided into 4 groups: control (n = 5); radiation (n = 14); 5-fluorouracil treatment (5-FU; n = 14); and radiation and 5-FU treatment (n = 14). Rats were fed either a standard diet or a specific diet (SpD) containing HMB/Glu/Arg supplementation for 7 days prior to radiation exposure and/or 5-FU treatment. The irradiated groups were exposed to an 1 Gy dose of 6 MV x rays delivered to the who-abdominal. The animals receiving 5-FU treatment were given a 100 mg/kg dose of the drug. In the radiation and 5-FU treatment group, the 5-FU was administered 30 min prior to irradiation. After irradiation and/or 5-FU treatment, feeding with either the standard rat diet or specific diet continued as before. All animals were sacrificed on day 4 after irradiation and 5-FU treatment. Data collected included microbiological, histological and immunohistochemical end points. We found that bacterial colony counts in the ceca and mesenteric lymph nodes of irradiated rats treated with 5-FU were significantly lower in the specific diet (SpD) group than in the standard diet group (P = 0.002-0.05). Morphometrically, gastric, duodenal and colonic mucosal injuries were less severe in the irradiated animals fed the specific diet, as well as the 5-FU-treated animals fed the specific diet, compared to the similarly treated standard diet groups. Apoptosis, measured by TUNEL, revealed significantly lower numbers of TUNEL positive cells in irradiated animals fed the specific diet, and irradiated animals treated with 5-FU and fed the specific diet compared to irradiated animals fed the standard diet, and irradiated animals treated with 5-FU and fed the standard diet. In the 5-Fu-treated and SpD group, the extent of apoptosis was significantly lower than that of the 5-Fu-treated and standard diet group in both the stomach and duodenum (P = 0.0001), but not in the colon. Apoptosis, measured by caspase 3 staining, was significantly less in all three organs of the SpD groups. In conclusion, these findings suggest that a diet supplemented with HMB/Glu/Arg may ameliorate the effect of radiation-induced gastrointestinal injury, coinciding with reduced bacterial growth.

Effects of amino acid derivatives on physical, mental, and physiological activities.

Nutritional ergogenic aids have been in use for a long time to enhance exercise and sports performance. Dietary components that exhibit ergogenic activity are numerous and their consumption is common and popular among athletes. They often come under scrutiny by legal authorities for their claimed benefits and safety concerns. Amino acid derivatives are propagated as being effective aids to enhance physical and mental performance in many ways, even though studies have pointed out that individuals who are deficient are more likely to benefit from dietary supplementation of amino acid derivatives than normal humans. In this review, some of the most common and widely used amino acids derivatives in sports and athletics namely creatine, tyrosine, carnitine, HMB, and taurine have been discussed for their effects on exercise performance, mental activity as well as body strength and composition. Creatine, carnitine, HMB, and taurine are reported to delay the onset of fatigue, improve exercise performance, and body strength. HMB helps in increasing fat-free mass and reduce exercise induced muscle injury. Taurine has been found to reduce oxidative stress during exercise and also act as an antihypertensive agent. Although, studies have not been able to find any favorable effect of tyrosine administration on exercise performance, it has been proved to be very effective in fighting stress, improving mood and cognitive performance particularly in sleep-deprived subjects. While available data from published studies and findings are equivocal about the efficacy of creatine, tyrosine, and HMB, more comprehensive researches on carnitine and taurine are necessary to provide evidence for the theoretical basis of their ergogenic role in nutritional modification and supplementation.