Effects of Beta-Hydroxy-Beta-Methylbutyrate Supplementation on Elderly Body Composition and Muscle Strength: A Review of Clinical Trials.

BACKGROUND: The aging process has great impact on body composition, such as the increase of adipose tissue in abdominal region, and the decrease of lean body mass, due to skeletal muscle loss. A reduction in muscle mass is associated to high risk of fractures and falls, loss of mobility, and increased number of hospitalizations. Beta-hydroxy-beta-methylbutyrate (HMB) is a biological substance derived from leucine metabolism, with anabolic and anticatabolic properties. Some HMB effects are tissue repair stimulation and protein anabolism. AIMS: We aimed to evaluate the effects of HMB supplementation on body composition and muscle strength in elderly, as well as to identify the efficient dosages to reach these effects. METHODS: This review included studies that evaluated muscle mass and muscle strength, associated or not with physical exercise and diet in elderly people. Only studies published from 2008 to 2019 were selected for analysis. RESULTS: Six articles were included in the review. The used doses varied from 1.5 to 3 g. In 5 studies, HMB supplementation was associated with calcium; only 1 study did not use the oral administration route. Two studies used 4 g of maltodextrin as a vehicle; 1 used HMB with a hypercaloric and hyperproteic supplement; 1 associated HMB with lysine and arginine; and 1 with arginine and glutamine. Supplementation of 3 g of HMB has shown to be most beneficial in improving strength and body composition in people over 65 years, especially in bed rest and untrained conditions. CONCLUSION: Our findings suggest that HMB has a positive effect on body composition and strength, especially in bedridden or sedentary elderly, due to its anticatabolic properties.

Fourier Transform Infrared Microspectroscopy Combined with Principal Component Analysis and Artificial Neural Networks for the Study of the Effect of ß-Hydroxy-ß-Methylbutyrate (HMB) Supplementation on Articular Cartilage.

The potential of Fourier Transform infrared microspectroscopy (FTIR microspectroscopy) and multivariate analyses were applied for the classification of the frequency ranges responsible for the distribution changes of the main components of articular cartilage (AC) that occur during dietary ß-hydroxy-ß-methyl butyrate (HMB) supplementation. The FTIR imaging analysis of histological AC sections originating from 35-day old male piglets showed the change in the collagen and proteoglycan contents of the HMB-supplemented group compared to the control. The relative amount of collagen content in the superficial zone increased by more than 23% and in the middle zone by about 17%, while no changes in the deep zone were observed compared to the control group. Considering proteoglycans content, a significant increase was registered in the middle and deep zones, respectively; 62% and 52% compared to the control. AFM nanoindentation measurements collected from animals administered with HMB displayed an increase in AC tissue stiffness by detecting a higher value of Young's modulus in all investigated AC zones. We demonstrated that principal component analysis and artificial neural networks could be trained with spectral information to distinguish AC histological sections and the group under study accurately. This work may support the use and effectiveness of FTIR imaging combined with multivariate analyses as a quantitative alternative to traditional collagenous tissue-related histology.

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.

Cognitive function is preserved in aged mice following long-term ß-hydroxy ß-methylbutyrate supplementation.

ß-hydroxy ß-methylbutyrate (HMB) is a nutritional supplement purported to enhance skeletal muscle mass and strength, as well as cognitive function in older adults. The purpose of this study was to determine the potential for long-term HMB supplementation to preserve muscle function and cognition in aged mice, as well as provide evidence of a link between vessel-associated pericyte function and outcomes. Four- (Adult/Ad) and 17 month-old (Aged/Ag) C57BL/6J mice consumed chow containing 600 mg/kg BW/day of either Ca-HMB (Ad, n=16; Ag, n=17) or Ca-Lactate (Ad, n=16; Ag, n=17) for 6 months. HMB did not prevent age-related reductions in muscle mass, strength and coordination (Age main effect, P<0.05). The rate of muscle protein synthesis decreased within the mitochondrial fraction (age main effect, P<0.05), and this decline was not prevented with HMB. Despite no change in muscle mass or function, an age-dependent reduction in active avoidance learning was attenuated with HMB (Age and HMB main effects, P<0.05). Age detrimentally impacted muscle-resident pericyte gene expression with no recovery observed with HMB, whereas no changes in brain-resident pericyte quantity or function were observed with age or HMB. The findings from this study suggest that prolonged HMB supplementation starting in adulthood may preserve cognition with age.

Nutritional interventions for treating foot ulcers in people with diabetes.

BACKGROUND: Foot ulcers in people with diabetes are non-healing, or poorly healing, partial, or full-thickness wounds below the ankle. These ulcers are common, expensive to manage and cause significant morbidity and mortality. The presence of a wound has an impact on nutritional status because of the metabolic cost of repairing tissue damage, in addition to the nutrient losses via wound fluid. Nutritional interventions may improve wound healing of foot ulcers in people with diabetes. OBJECTIVES: To evaluate the effects of nutritional interventions on the healing of foot ulcers in people with diabetes. SEARCH METHODS: In March 2020 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated the effect of nutritional interventions on the healing of foot ulcers in people with diabetes. DATA COLLECTION AND ANALYSIS: Two review authors, working independently, assessed included RCTs for their risk of bias and rated the certainty of evidence using GRADE methodology, using pre-determined inclusion and quality criteria. MAIN RESULTS: We identified nine RCTs (629 participants). Studies explored oral nutritional interventions as follows: a protein (20 g protein per 200 mL bottle), 1 kcal/mL ready-to-drink, nutritional supplement with added vitamins, minerals and trace elements; arginine, glutamine and ß-hydroxy-ß-methylbutyrate supplement; 220 mg zinc sulphate supplements; 250 mg magnesium oxide supplements; 1000 mg/day omega-3 fatty acid from flaxseed oil; 150,000 IU of vitamin D, versus 300,000 IU of vitamin D; 250 mg magnesium oxide plus 400 IU vitamin E and 50,000 IU vitamin D supplements. The comparator in eight studies was placebo, and in one study a different dose of vitamin D. Eight studies reported the primary outcome measure of ulcer healing; only two studies reported a measure of complete healing. Six further studies reported measures of change in ulcer dimension, these studies reported only individual parameters of ulcer dimensions (i.e. length, width and depth) and not change in ulcer volume. All of the evidence identified was very low certainty. We downgraded it for risks of bias, indirectness and imprecision. It is uncertain whether oral nutritional supplement with 20 g protein per 200 mL bottle, 1 kcal/mL, nutritional supplement with added vitamins, minerals and trace elements, increases the proportion of ulcers healed at six months more than placebo (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.42 to 1.53). It is also uncertain whether arginine, glutamine and ß-hydroxy-ß-methylbutyrate supplement increases the proportion of ulcers healed at 16 weeks compared with placebo (RR 1.09, 95% CI 0.85 to 1.40). It is uncertain whether the following interventions change parameters of ulcer dimensions over time when compared with placebo; 220 mg zinc sulphate supplement containing 50 mg elemental zinc, 250 mg magnesium oxide supplement, 1000 mg/day omega-3 fatty acid from flaxseed oil supplement, magnesium and vitamin E co-supplementation and vitamin D supplementation. It is also uncertain whether 150,000 IU of vitamin D, impacts ulcer dimensions when compared with 300,000 IU of vitamin D. Two studies explored some of the secondary outcomes of interest for this review. It is uncertain whether oral nutritional supplement with 20 g protein per 200 mL bottle, 1 kcal/mL, nutritional supplement with added vitamins, minerals and trace elements, reduces the number of deaths (RR 0.96, 95% CI 0.06 to 14.60) or amputations (RR 4.82, 95% CI 0.24 to 95.88) more than placebo. It is uncertain whether arginine, glutamine and ß-hydroxy-ß-methylbutyrate supplement increases health-related quality of life at 16 weeks more than placebo (MD -0.03, 95% CI -0.09 to 0.03). It is also uncertain whether arginine, glutamine and ß-hydroxy-ß-methylbutyrate supplement reduces the numbers of new ulcers (RR 1.04, 95% CI 0.71 to 1.51), or amputations (RR 0.66, 95% CI 0.16 to 2.69) more than placebo. None of the included studies reported the secondary outcomes cost of intervention, acceptability of the intervention (or satisfaction) with respect to patient comfort, length of patient hospital stay, surgical interventions, or osteomyelitis incidence. One study exploring the impact of arginine, glutamine and ß-hydroxy-ß-methylbutyrate supplement versus placebo did not report on any relevant outcomes. AUTHORS' CONCLUSIONS: Evidence for the impact of nutritional interventions on the healing of foot ulcers in people with diabetes compared with no nutritional supplementation, or compared with a different dose of nutritional supplementation, remains uncertain, with eight studies showing no clear benefit or harm. It is also uncertain whether there is a difference in rates of adverse events, amputation rate, development of new foot ulcers, or quality of life, between nutritional interventions and placebo. More research is needed to clarify the impact of nutritional interventions on the healing of foot ulcers in people with diabetes.

Beta-hydroxy-beta-methylbutyrate and sarcopenia: from biological plausibility to clinical evidence.

PURPOSE OF REVIEW: Given the role of leucine as a major regulator of muscle protein turnover, the consumption of protein sources enhanced with this essential amino acid, or its metabolite beta-hydroxy-beta-methylbutyrate (HMB), is assumed to give the greatest benefit in terms of maintenance of muscle mass and function during aging. The aim of this review is to discuss recent literature about HMB metabolism, its pharmacokinetics compared with the metabolite leucine, effectiveness of HMB to improve outcomes in older adults, and novel approaches for HMB use. RECENT FINDINGS: Overall, this review article highlights the potential relationship between HMB dietary supplementation and parameters related to maintenance of muscle mass and strength in older people. However, there are limitations in the studies conducted so far, including low number of participants per study group, heterogeneity of study designs, methodologies, and outcomes. The combination of HMB with other amino acids or supplements limits the ability to determine the direct impact of HMB alone. SUMMARY: It is proposed that HMB may be utilized to protect or rebuild muscle mass in older people with reduced lean body mass.

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.

Two and Four Weeks of ß-Hydroxy-ß-Methylbutyrate (HMB) Supplementations Reduce Muscle Damage Following Eccentric Contractions.

OBJECTIVE: This study investigated the effect of ß-hydroxy-ß-methylbutyrate (HMB) supplementation for either 2 or 4 weeks on the muscle damage after elbow flexors after eccentric contractions (ECCs). METHODS: Twenty-eight untrained men were completed the double-blind, placebo-controlled, parallel design study. The subjects were randomly assigned to the ingestion of HMB supplement for 2 weeks (HMB 2-week, n = 10), for 4 weeks (HMB 4-week, n = 10), or a placebo group (PL, n = 8). Subjects of HMB 2-week and HMB 4-week consumed 3 g HMB per day, and they performed 6 sets of 10 ECCs at 100% maximal voluntary contraction (MVC) using a dumbbell. Changes in MVC torque, range of motion (ROM), upper arm circumference, muscle soreness, and muscle stiffness were assessed before, immediately after, and 1, 2, and 5 days after exercise. RESULTS: MVC torque and ROM were significantly higher in the HMB 2-week and HMB 4-week groups than in the PL group after ECCs (p < 0.05). The upper arm circumference was significantly smaller in the HMB 2- and 4-week groups than in the PL group after ECCs (p < 0.05). In addition, muscle stiffness at 150° was significantly lower in the HMB 2- and 4-week groups than in the PL group at immediately after ECCs (p < 0.05). However, there was no difference in all outcomes between HMB 2-week and HMB 4-week. CONCLUSION: We concluded that more than 2 weeks of HMB supplementation has a positive role for untrained subjects to prevent the muscle damage after ECCs.

A new in vitro muscle contraction model and its application for analysis of mTORC1 signaling in combination with contraction and beta-hydroxy-beta-methylbutyrate administration.

Several food constituents augment exercise-induced muscle strength improvement; however, the detailed mechanism underlying these combined effects is unknown because of the lack of a cultured cell model for evaluating the contraction-induced muscle protein synthesis level. Here, we aimed to establish a new in vitro muscle contraction model for analyzing the activation of mammalian target of rapamycin complex 1 (mTORC1) signaling. We adopted the tetanic electric stimulation of 50 V at 100 Hz for 10 min in L6.C11 myotubes. Akt, ERK1/2, and p70S6K phosphorylation increased significantly after electrical pulse stimulation (EPS), compared to untreated cells. Next, we used this model to analyze mTORC1 signaling in combination with exercise and beta-hydroxy-beta-methylbutyrate (HMB), an l-leucine metabolite. p70S6K phosphorylation increased significantly in the EPS+HMB group compared to that in the EPS-alone group. These findings show that our model could be used to analyze mTORC1 signaling and that HMB enhances muscle contraction-activated mTORC1 signaling.

Effects of ß-hydroxy-ß-methylbutyrate (HMB) supplementation in addition to multicomponent exercise in adults older than 70 years living in nursing homes, a cluster randomized placebo-controlled trial: the HEAL study protocol.

BACKGROUND: Evidence supports the fact that multicomponent exercise and HMB supplementation are, separately, effective in improving older adult's health and palliate functional metabolic diseases in older people. However, the true effect of HMB supplementation combined with a tailored exercise program in frail older adults is still unknown. Thus, the aim of the HEAL (HMB + Exercise = Adults Living longer) study is to assess the effects of the combination of a daily multicomponent exercise and resistance training (VIVIFRAIL program) intervention in addition to HMB supplementation on older adults' health. METHODS/DESIGN: A 24-week cluster randomized, double-blind, placebo-controlled study will be conducted on 104 adults ≥70 years. Nursing homes will be randomized to either of four groups: Ex-HMB (exercise intervention with HMB), Ex-Plac (exercise intervention with placebo), NoEx-HMB (no exercise intervention with HMB), and Controls (No exercise and no HMB). Intervention groups which include exercise will complete the individualized multicomponent (strength, balance and cardiovascular exercises) training program VIVIFRAIL. Intervention groups which include HMB supplementation will receive a 3 g/daily dose of free acid HMB in powder form. The primary outcome measure is the functional capacity. Secondary outcome measures are muscle strength and power, frailty and fall risk, body composition, biochemical analyses and cardiometabolic risk factor, disability and comorbidity, cognitive function and depression. DISCUSSION: The findings of the HEAL study will help professionals from public health systems to identify cost-effective and innovative actions to improve older people's health and quality of life, and endorse exercise practice in older adults and people living in nursing homes. TRIAL REGISTRATION: NCT03827499 ; Date of registration: 01/02/2019.

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.

Negligible Effects of ß-Hydroxy-ß-Methylbutyrate Free Acid and Calcium Salt on Strength and Hypertrophic Responses to Resistance Training: A Randomized, Placebo-Controlled Study.

This study evaluated the effects of ß-hydroxy-ß-methylbutyrate free acid (HMB-FA) and calcium salt (HMB-Ca) on strength, hypertrophy, and markers of muscle damage. In this randomized, double-blind, placebo-controlled study, 44 resistance-trained men (age: 26 ± 4 years; body mass: 84.9 ± 12.0 kg) consuming ≥1.7 g·kg-1·day-1 of protein received HMB-FA (3 g/day; n = 14), HMB-Ca (3 g/day; n = 15), or placebo (PL; cornstarch, 3 g/day; n = 15) for 12 weeks, while performing a periodized resistance training program. Before and after intervention, lean body mass (measured with dual X-ray absorptiometry), maximal dynamic strength (one-repetition maximum), knee extension maximal isometric strength (maximal voluntary isometric contraction [MVIC]), cross-sectional area (measured with ultrasound), and muscle soreness were assessed. MVIC was also measured 48 hr after the first and the last training sessions. All groups increased lean body mass (main time effect: p < .0001; HMB-FA: 1.8 ± 1.8 kg; HMB-Ca: 0.8 ± 1.4 kg; PL: 0.9 ± 1.4 kg), cross-sectional area (main time effect: p < .0001; HMB-FA: 6.6 ± 3.8%; HMB-Ca: 4.7 ± 4.4%; PL: 6.9 ± 3.8%), one-repetition maximum bench press (main time effect: p < .0001; HMB-FA: 14.8 ± 8.4 kg; HMB-Ca: 11.8 ± 7.4 kg; PL: 11.2 ± 6.6 kg), MVIC (main time effect: p < .0001; HMB-FA: 34.4 ± 39.3%; HMB-Ca: 32.3 ± 27.4%; PL: 17.7 ± 20.9%) after the intervention, but no differences between groups were shown. HMB-FA group showed greater leg press strength after the intervention than HMB-Ca and PL groups (Group × Time interaction: p < .05; HMB-FA: 47.7 ± 31.2 kg; HMB-Ca: 43.8 ± 31.7 kg; PL: 30.2 ± 20.9 kg). MVIC measured 48 hr after the first and the last sessions showed no attenuation of force decline with supplementation. Muscle soreness following the first and last sessions was not different between groups. The authors concluded that neither HMB-Ca nor HMB-FA improved hypertrophy or reduced muscle damage in resistance-trained men undergoing resistance training ingesting optimal amounts of protein. HMB-FA but not HMB-Ca resulted in a statistically significant yet minor improvement on leg press one-repetition maximum.

Maternal HMB treatment affects bone and hyaline cartilage development in their weaned piglets via the leptin/osteoprotegerin system.

It has been demonstrated in animal studies that prenatal administration of ß-hydroxy-ß-methylbutyrate (HMB, metabolite of leucine) influences general growth and mechanical endurance of long bones in newborn offspring in sex-dependent manner. The present experiment was conducted to evaluate the effect of HMB treatment of pregnant sows on bone development in offspring at weaning. From 70th day until the 90th day of gestation, sows received either a basal diet (n = 12) or the same diet supplemented with HMB (n = 12) at the dose of 0.2 g/kg of body weight/day. Femora obtained from six males and females in each group weaned at the age of 35 days were examined. Maternal HMB treatment significantly enhanced body weight and changed bone morphology increasing femur mechanical strength in both sexes. Maternal HMB supplementation also elevated bone micro- and macroelement concentrations and enhanced content of proteoglycans in articular cartilage. Based on the obtained results, it can be concluded that maternal HMB supplementation in the mid-gestation period significantly accelerated bone development in both sexes by upregulation of a multifactorial system including leptin and osteoprotegerin. However, the sex (irrespective of the HMB treatment) was the factor which influenced the collagen structure in cartilages and trabecular bone, as demonstrated both by the Picrosirius red staining and performed analysis of thermal stability of collagenous tissues. The structural differences in collagen between males and females were presumably related to a different collagen maturity. No studies conducted so far provided a detailed morphological analysis of bone, articular cartilage, growth plate and the activities of the somatotropic and pituitary-gonadal axes, as well as leptin/osteoprotegerin system in weaned offspring prenatally treated with HMB. This study showed also the relationship between the maternal HMB treatment and bone osteometric and mechanical traits, hormones, and growth and bone turnover markers such as leptin, osteoprotegerin and insulin-like growth factor-1.

Benefits of ß-hydroxy-ß-methylbutyrate supplementation in trained and untrained individuals.

ß-Hydroxy-ß-Methylbutyrate (HMB) is a metabolite of the branched-chain amino acid leucine and its ketoacid α-ketoisocaproate. HMB has been widely used as an ergogenic supplement to increase muscle strength, muscle hypertrophy and enhance recovery. The physiological mechanisms that underlie these benefits are related to HMB's ability to stimulate muscle protein synthesis and minimize muscle breakdown. Although evidence supporting the benefits of HMB supplementation is not conclusive, many of these studies have suffered from methodological flaws including different formulations, supplement duration and population studied. HMB in its free acid formulation is suggestive of having a greater potential for efficacy in both trained and untrained populations than its calcium-salt form. However, the evidence regarding HMB's role in limiting muscle degradation and increasing muscle protein synthesis has created an exciting interest in examining its efficacy among untrained individuals. Recent investigations examining intense training have demonstrated efficacy in maintaining muscle mass and attenuating the inflammatory response.

The Effects of Beta-Hydroxy-Beta-Methylbutyrate Supplementation on Recovery Following Exercise-Induced Muscle Damage: A Systematic Review and Meta-Analysis.

BACKGROUND: Growing evidence suggests beta-hydroxy-beta-methylbutyrate's (HMB) positive effects on recovery following exercise-induced muscle damage (EIMD). However, findings vary substantially across studies. OBJECTIVE: A meta-analysis of randomized controlled trials was conducted to assess the effects of HMB supplementation on recovery following EIMD by assessing indirect markers of muscle damage, namely creatine kinase (CK) and lactate dehydrogenase (LDH) serum levels among healthy participants. METHOD: A comprehensive search was performed on electronic databases (Medline, Scopus, Cochrane Library, and Google Scholar) up to October 2017 for trials evaluating the effects of HMB on recovery following EIMD. Mean ± standard deviation of follow-up CK and LDH concentrations were extracted to calculate the effect size for meta-analysis. RESULTS: A total of 324 participants for CK and 229 participants for LDH were found from the 10 and 8 studies, respectively. The results revealed a significant effect of HMB supplementation on CK (weighted mean difference [WMD] = -60.71 UL-1; 95% confidence interval [CI], -78.12 to -43.29; I2 = 4.1%; pheterogeneity = 0.40) and LDH reduction (WMD = -15.42 UL-1; 95% CI, -22.2 to -8.6; I2 = 0.0%; pheterogeneity = 0.53). In addition, a subgroup analysis based on study duration (< 6 weeks vs. ≥ 6 weeks) suggested that HMB effectiveness on EIMD was statistically significant in studies over 6 weeks (p < 0.001). CONCLUSIONS: The current evidence revealed a time-dependent effect of HMB in reducing LDH and CK serum levels among adults. HMB, therefore, may be seen as a priority muscle damage recovery agent in interventions.

Inducers of salmon innate immunity: An in vitro and in vivo approach.

Maintaining fish health is one of the most important aims in aquaculture. Prevention of fish diseases therefore is crucial and can be achieved by various different strategies, including most often a combination of different methods such as optimal feed and fish density, as well as strengthening the immune system. Understanding the fish innate immune system and developing methods to activate it, in an effort to prevent infections in the first place, has been a goal in recent years. In this study we choose different inducers of the innate immune system and examined their effects in vitro on the salmon cell line CHSE-214. We found that the butyrate derivatives 4-phenyl butyrate (PBA) and ß-hydroxy-ß-methyl butyrate (HMB) induce the expression of various innate immune genes differentially over 24-72 h. Similarly, lipids generated from fish oils were found to have an effect on the expression of the antimicrobial peptides cathelicidin and hepcidin, as well as iNOS and the viral receptor RIG-1. Interestingly we found that vitamin D3, similar as in mammals, was able to increase cathelicidin expression in fish cells. The observed induction of these different innate immune factors correlated with antibacterial activity against Aeromonas salmonicida and antiviral activity against IPNV and ISAV in vitro. To relate this data to the in vivo situation we examined cathelicidin expression in juvenile salmon and found that salmon families vary greatly in their basal cathelicidin levels. Examining cathelicidin levels in families known to be resistant to IPNV showed that these QTL-families had lower basal levels of cathelicidin in gills, than non QTL-families. Feeding fish with HMB caused a robust increase in cathelicidin expression in gills, but not skin and this was independent of the fish being resistant to IPNV. These findings support the use of fish cell lines as a tool to develop new inducers of the fish innate immune system, but also highlight the importance of the tissue studied in vivo. Understanding the response of the innate immune system in different tissues and what effect this might have on infections and downstream cellular pathways is an interesting research topic for the future.

ß-Hydroxy ß-Methylbutyrate (HMB) Supplementation Effects on Body Mass and Performance in Elite Male Rugby Union Players.

McIntosh, ND, Love, TD, Haszard, J, Osborne, H, and Black, KE. ß-hydroxy ß-methylbutyrate (HMB) supplementation effects on body mass and performance in elite male rugby union players. J Strength Cond Res 32(1): 19-26, 2018-Preseason is characterized by high training volumes with short recovery periods ß-hydroxy ß-methylbutyrate (HMB) has been postulated to assist with recovery. ß-hydroxy ß-methylbutyrate has been shown to improve strength and body composition among untrained groups; the benefits of HMB among trained populations are unclear because of the methodologies employed. This randomized control trail determined the effects of 11 weeks HMB supplementation on body mass and performance measures in 27 elite rugby players. ß-hydroxy ß-methylbutyrate group (n = 13), mean ± SD age 20.3 ± 1.2 years, body mass 99.6 ± 9.1 kg; placebo group (n = 14), age 21.9 ± 2.8 years body mass 99.4 ± 13.9 kg for placebo. During the supplementation period, body mass increased with HMB 0.57 ± 2.60 kg but decreased with placebo 1.39 ± 2.02 kg (p = 0.029). There were no significant differences in any of the 4 strength variables (p > 0.05). However, on the yo-yo intermittent recovery test (YoYo IR-1), the placebo group improved 4.0 ± 2.8 levels but HMB decreased 2.0 ± 3.0 levels (p = 0.003). The results of this study suggest that HMB could be beneficial for gaining or maintaining body mass during periods of increased training load. However, it appears that HMB may be detrimental to intermittent running ability in this group although further research is required before firm conclusions can be made. Only 6 participants on HMB managed to complete both YoYo IR-1 tests because of injury, a larger sample size is required to fully investigate this potentially negative effect. Further, the mechanisms behind this decrement in performance cannot be fully explained and requires further biochemical and psychological investigation.

In ovo feeding of nutrients and its impact on post-hatching water and feed deprivation up to 48 hr, energy status and jejunal morphology of chicks using response surface models.

A Box-Behnken design (BBD) in a response surface methodology (RSM) was used to investigate the response of broiler chicks to in ovo feeding (IOF) of beta-hydroxy beta-methylbutyrate (HMB), dextrin and the timing of the first water and feed deprivation. On day 18th of incubation, 1,500 eggs were randomly assigned to 15 experimental runs of BBD, each with 4 replicates, as 3 levels IOF of HMB (0%, 0.5% and 1%) and dextrin (0%, 20% and 40%), and 3 levels of the first water and feed deprivation (6, 27 and 48 hr). Day-old chicks from each replicate were then used to assess the effect of IOF and time first water and feed access on chick's responses. The IOF of dextrin leads to respectively 9.7%-15.5% lower hatchability for 20% and 40% inclusion (p < .05), whereas HMB inclusion appeared with no effect on hatchability (p > .05). Administration of dextrin or HMB into the amnion of embryos elevated length, width and surface area of villus, and increased glycogen content of liver and breast (p < .05). In all parameter models, the linear terms showed highest contribution (R2  = 0.81-0.97) to explain existing variation in chick's responses. The first water and feed deprivation had largest effect on BW2 and glycogen content of liver and breast. It is concluded that if possible, place chicks before 7 hr of hatch to preserve BW loss and have maximum response from IOF. If not possible, use IOF with 40% dextrin + 0.5% HMB to preserve gut integrity and energy status up to 48 hr. This should give advantage to chicks to recover fast after feeding, but that would have to be confirmed by trials growing birds to slaughter age.

In ovo feeding of beta-hydroxy beta-methylbutyrate and dextrin optimized growth performance of broiler for pre-placement holding time using the Box-Behnken response surface design.

To investigate the effect of in ovo feeding (IOF) of beta-hydroxy beta-methylbutyrate (HMB), dextrin and post-hatching water and feed deprivation time on growth performance of broilers, 1,500 eggs were assigned into 15 experimental runs of Box-Behnken design, including three levels IOF of HMB (0%, 0.5% and 1%), dextrin (0%, 20% and 40%) and three levels of the first water and feed deprivation (6, 27 and 48 hr). After hatching, day-old chicks (seven males and seven females) from each replicate were then selected and randomly assigned to 60 floor pens for a 42-day feeding trial. The experimental data were fitted to the quadratic response surface models, and the goodness of fit of the models was expressed by the R2 value. The interaction between IOF of dextrin and timing of first feed deprivation had the largest effect on body weight of chicks at day 7 (BW7) and corrected European production efficiency factor (EPEF). In ovo feeding of dextrin reduced negative effects of delayed access to feed and water after hatch up to 48 hr on BW7, body weight of chicks at day 42, EPEF and corrected EPEF. The results of the current study suggested that the EPEF corrected by hatchability could provide the better understanding of IOF experimental findings. The ridge optimization analysis revealed that the optimal levels of HMB and dextrin inclusion in eggs and timing of first feed deprivation for maximum corrected EPEF were 0.37, 15.94% and 7.22 hr, respectively. These results demonstrate that the Box-Behnken statistical design and response surface models are effective to describe the relationship between IOF of nutrients and pre-placement holding time and predict the performance of broilers to achieve the optimal target.

Enteral ß-hydroxy-ß-methylbutyrate supplementation increases protein synthesis in skeletal muscle of neonatal pigs.

Many low-birth weight infants are at risk for poor growth due to an inability to achieve adequate protein intake. Administration of the amino acid leucine stimulates protein synthesis in skeletal muscle of neonates. To determine the effects of enteral supplementation of the leucine metabolite ß-hydroxy-ß-methylbutyrate (HMB) on protein synthesis and the regulation of translation initiation and degradation pathways, overnight-fasted neonatal pigs were studied immediately (F) or fed one of five diets for 24 h: low-protein (LP), high-protein (HP), or LP diet supplemented with 4 (HMB4), 40 (HMB40), or 80 (HMB80) µmol HMB·kg body wt(-1)·day(-1) Cell replication was assessed from nuclear incorporation of BrdU in the longissimus dorsi (LD) muscle and jejunum crypt cells. Protein synthesis rates in LD, gastrocnemius, rhomboideus, and diaphragm muscles, lung, and brain were greater in HMB80 and HP and in brain were greater in HMB40 compared with LP and F groups. Formation of the eIF4E·eIF4G complex and S6K1 and 4E-BP1 phosphorylation in LD, gastrocnemius, and rhomboideus muscles were greater in HMB80 and HP than in LP and F groups. Phosphorylation of eIF2α and eEF2 and expression of SNAT2, LAT1, MuRF1, atrogin-1, and LC3-II were unchanged. Numbers of BrdU-positive myonuclei in the LD were greater in HMB80 and HP than in the LP and F groups; there were no differences in jejunum. The results suggest that enteral supplementation with HMB increases skeletal muscle protein anabolism in neonates by stimulation of protein synthesis and satellite cell proliferation.