Effects on beta-hydroxy-beta-methylbutyrate (HMB) on exercise levels of age, sex and training experience: A review

Division of Nutritional Sciences, University of Illinois, Urbana, Illinois, USA. .
Nutrition & Metabolism (Impact Factor: 3.26). 02/2008; 5(1):1. DOI: 10.1186/1743-7075-5-1
Source: PubMed

ABSTRACT The leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) has been extensively used as an ergogenic aid; particularly among bodybuilders and strength/power athletes, who use it to promote exercise performance and skeletal muscle hypertrophy. While numerous studies have supported the efficacy of HMB in exercise and clinical conditions, there have been a number of conflicting results. Therefore, the first purpose of this paper will be to provide an in depth and objective analysis of HMB research. Special care is taken to present critical details of each study in an attempt to both examine the effectiveness of HMB as well as explain possible reasons for conflicting results seen in the literature. Within this analysis, moderator variables such as age, training experience, various states of muscle catabolism, and optimal dosages of HMB are discussed. The validity of dependent measurements, clustering of data, and a conflict of interest bias will also be analyzed. A second purpose of this paper is to provide a comprehensive discussion on possible mechanisms, which HMB may operate through. Currently, the most readily discussed mechanism has been attributed to HMB as a precursor to the rate limiting enzyme to cholesterol synthesis HMG-coenzyme A reductase. However, an increase in research has been directed towards possible proteolytic pathways HMB may operate through. Evidence from cachectic cancer studies suggests that HMB may inhibit the ubiquitin-proteasome proteolytic pathway responsible for the specific degradation of intracellular proteins. HMB may also directly stimulate protein synthesis, through an mTOR dependent mechanism. Finally, special care has been taken to provide future research implications.

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    • "The leucine metabolite, β-hydroxy-β-methylbutyrate (HMB) has been shown to improve satellite cell proliferation (Moore et al., 2005), reduce protein catabolism during disease, reduce muscle loss during disuse, and promote skeletal muscle hypertrophy in response to loading exercise (Wilson et al., 2008; Holecek et al., 2009; Aversa et al., 2011). We have previously shown that HMB could improve muscle recovery in old rats with sarcopenia that had been subjected to unloading, in part via an increase in satellite cell proliferation and a reduction of nuclear apoptosis (Hao et al., 2011). "
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    ABSTRACT: The mechanisms contributing to sarcopenia include reduced satellite cell (myogenic stem cell) function that is impacted by the environment (niche) of these cells. Satellite cell function is affected by oxidative stress, which is elevated in aged muscles, and this along with changes in largely unknown systemic factors, likely contribute to the manner in which satellite cells respond to stressors such as exercise, disuse, or rehabilitation in sarcopenic muscles. Nutritional intervention provides one therapeutic strategy to improve the satellite cell niche and systemic factors, with the goal of improving satellite cell function in aging muscles. Although many elderly persons consume various nutraceuticals with the hope of improving health, most of these compounds have not been thoroughly tested, and the impacts that they might have on sarcopenia and satellite cell function are not clear. This review discusses data pertaining to the satellite cell responses and function in aging skeletal muscle, and the impact that three compounds: resveratrol, green tea catechins, and β-Hydroxy-β-methylbutyrate have on regulating satellite cell function and therefore contributing to reducing sarcopenia or improving muscle mass after disuse in aging. The data suggest that these nutraceutical compounds improve satellite cell function during rehabilitative loading in animal models of aging after disuse (i.e., muscle regeneration). While these compounds have not been rigorously tested in humans, the data from animal models of aging provide a strong basis for conducting additional focused work to determine if these or other nutraceuticals can offset the muscle losses, or improve regeneration in sarcopenic muscles of older humans via improving satellite cell function.
    Frontiers in Aging Neuroscience 09/2014; 6:246. DOI:10.3389/fnagi.2014.00246 · 4.00 Impact Factor
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    • "Interestingly, while myotubes treated with MSTN only showed a significant decrease in myotube diameter, this effect was reversed in all three treatment groups (MSTN + Leu, MSTN + HMB, and MSTN + Crea). There is ample evidence to suggest that leucine and HMB are able to increase muscle protein synthesis in vitro and in vivo[26,27,45,46]. Thus, it is difficult to reconcile why MSTN + Leu and MSTN + HMB treatments in the current study did not statistically increase muscle protein synthesis compared to DM/CTL myotubes. "
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    ABSTRACT: The purpose of this study was to examine if L-leucine (Leu), β-hydroxy-β-methylbutyrate (HMB), or creatine monohydrate (Crea) prevented potential atrophic effects of myostatin (MSTN) on differentiated C2C12 myotubes. After four days of differentiation, myotubes were treated with MSTN (10 ng/ml) for two additional days and four treatment groups were studied: 1) 3x per day 10 mM Leu, 2) 3x per day 10 mM HMB, 3) 3x per day 10 mM Crea, 4) DM only. Myotubes treated with DM without MSTN were analyzed as the control condition (DM/CTL). Following treatment, cells were analyzed for total protein, DNA content, RNA content, muscle protein synthesis (MPS, SUnSET method), and fiber diameter. Separate batch treatments were analyzed for mRNA expression patterns of myostatin-related genes (Akirin-1/Mighty, Notch-1, Ski, MyoD) as well as atrogenes (MuRF-1, and MAFbx/Atrogin-1). MSTN decreased fiber diameter approximately 30% compared to DM/CTL myotubes (p < 0.001). Leu, HMB and Crea prevented MSTN-induced atrophy. MSTN did not decrease MPS levels compared to DM/CTL myotubes, but MSTN treatment decreased the mRNA expression of Akirin-1/Mighty by 27% (p < 0.001) and MyoD by 26% (p < 0.01) compared to DM/CTL myotubes. shRNA experiments confirmed that Mighty mRNA knockdown reduced myotube size, linking MSTN treatment to atrophy independent of MPS. Remarkably, MSTN + Leu and MSTN + HMB myotubes had similar Akirin-1/Mighty and MyoD mRNA levels compared to DM/CTL myotubes. Furthermore, MSTN + Crea myotubes exhibited a 36% (p < 0.05) and 86% (p < 0.001) increase in Akirin-1/Mighty mRNA compared to DM/CTL and MSTN-only treated myotubes, respectively. Leu, HMB and Crea may reduce MSTN-induced muscle fiber atrophy by influencing Akirin-1/Mighty mRNA expression patterns. Future studies are needed to examine if Leu, HMB and Crea independently or synergistically affect Akirin-1/Mighty expression, and how Akirin-1/Mighty expression mechanistically relates to skeletal muscle hypertrophy in vivo.
    Journal of the International Society of Sports Nutrition 08/2014; 11(1):38. DOI:10.1186/1550-2783-11-38 · 1.91 Impact Factor
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    • "This event has also been described in insulin resistant mice and related to a reduction of PI3-kinase activity and pS AKT content, leading to increased activation of caspase-3 and ubiquitin-proteasome pathway , both contributing to imbalanced proteogenic/ proteolytic activity (Wang et al. 2006, Chaudhary et al. 2012). These reports corroborate our results, which showed a reduction on pS AKT content on SOL of HMB-supplemented rats (Fig. 2b), but seem not to be in agreement with reports showing that HMB increases muscle mass (Wilson et al. 2008). However, most of these reports refer to conditions of muscle wasting, like cancer and sepsis (Smith et al. 2005, Kuhls et al. 2007), in which proteolysis is increased, and the energetic metabolism is seriously impaired. "
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    ABSTRACT: AimInvestigate, in healthy sedentary rats, the potential mechanisms involved on the effects of beta hydroxy beta methylbutyrate (HMB) supplementation upon the glycemic homeostasis, by evaluating the insulin sensitivity in liver, skeletal muscle, and white adipose tissue.Methods Rats were supplemented with either beta hydroxy beta methylbutyrate (320 mg kg−1 BW) or saline by gavage for 4 weeks. After the experimental period, the animals were subjected to the glucose tolerance test (GTT) and plasma non-esterified fatty acids (NEFA) concentration measurements. The soleus skeletal muscle, liver and white adipose tissue were removed for molecular (western blotting and RT-PCR) and histological analysis.Results: The beta hydroxy beta methylbutyrate supplemented rats presented: 1) higher ratio between the area under the curve (AUC) of insulinemia and glycemia during glucose tolerance test; 2) impairment of insulin sensitivity on liver and soleus skeletal muscle after insulin overload; 3) reduction of glucose transporter 4 (GLUT 4) total and plasma membrane content on soleus; 4) increased hormone sensitive lipase (HSL) mRNA and protein expression on white adipose tissue and plasma non-esterified fatty acids (NEFA) levels and 5) reduction of fibre cross-sectional area of soleus muscle.Conclusion The data altogether indicate that beta hydroxy beta methylbutyrate supplementation impairs insulin sensitivity in healthy sedentary rats, which, in the long-term, could lead to an increased risk of developing type 2 diabetes.This article is protected by copyright. All rights reserved.
    Acta Physiologica 06/2014; 212(1). DOI:10.1111/apha.12336 · 4.38 Impact Factor
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