Position Statement: The International Society of Sports Nutrition (ISSN) bases the following position stand on a critical analysis of the literature on the use of beta-hydroxy-beta-methylbutyrate (HMB) as a nutritional supplement. The ISSN has concluded the following. 1. HMB can be used to enhance recovery by attenuating exercise induced skeletal muscle damage in trained and untrained populations. 2. If consuming HMB, an athlete will benefit from consuming the supplement in close proximity to their workout. 3. HMB appears to be most effective when consumed for 2 weeks prior to an exercise bout. 4. Thirty-eight mg·kg·BM-1 daily of HMB has been demonstrated to enhance skeletal muscle hypertrophy, strength, and power in untrained and trained populations when the appropriate exercise prescription is utilized. 5. Currently, two forms of HMB have been used: Calcium HMB (HMB-Ca) and a free acid form of HMB (HMB-FA). HMB-FA may increase plasma absorption and retention of HMB to a greater extent than HMB-CA. However, research with HMB-FA is in its infancy, and there is not enough research to support whether one form is superior. 6. HMB has been demonstrated to increase LBM and functionality in elderly, sedentary populations. 7. HMB ingestion in conjunction with a structured exercise program may result in greater declines in fat mass (FM). 8. HMB’s mechanisms of action include an inhibition and increase of proteolysis and protein synthesis, respectively. 9. Chronic consumption of HMB is safe in both young and old populations.

Betaine is a methyl derivative of glycine first isolated from sugar beets. Betaine consumed from food sources and through dietary supplements presents similar bioavailability and is metabolized to di-methylglycine and sarcosine in the liver. The ergogenic and clinical effects of betaine have been investigated with doses ranging from 500 to 9,000 mg/day. Some studies using animal models and human subjects suggest that betaine supplementation could promote adiposity reductions and/or lean mass gains. Moreover, previous investigations report positive effects of betaine on sports performance in both endurance- and resistance-type exercise, despite some conflicting results. The mechanisms underlying these effects are poorly understood, but could involve the stimulation of lipolysis and inhibition of lipogenesis via gene expression and subsequent activity of lipolytic-/lipogenic-related proteins, stimulation of autocrine/endocrine IGF-1 release and insulin receptor signaling pathways, stimulation of growth hormone secretion, increased creatine synthesis, increases in protein synthesis via intracellular hyper-hydration, as well as exerting psychological effects such as attenuating sensations of fatigue. However, the exact mechanisms behind betaine action and the long-term effects of supplementation on humans remain to be elucidated. This review aims to describe evidence for the use of betaine as an ergogenic and esthetic aid, and discuss the potential mechanisms underlying these effects.

Amino acids such as leucine and its metabolite α-ketoisocaproate (KIC), are returning to be the focus of studies, mainly because of their anti-catabolic properties, through inhibition of muscle proteolysis and enhancement of protein synthesis. It is clear that these effects may counteract catabolic conditions, as well as enhance skeletal muscle mass and strength in athletes. Moreover, beta-hydroxy-beta-methylbutyrate (HMB) has been shown to produce an important effect in reducing muscle damage induced by mechanical stimuli of skeletal muscle. This review aims to describe the general scientific evidence of KIC and HMB supplementation clinical relevance, as well as their effects (e.g., increases in skeletal muscle mass and/or strength), associated with resistance training or other sports. Moreover, the possible mechanisms of cell signaling regulation leading to increases and/or sparing (during catabolic conditions) of skeletal muscle mass are discussed in detail based on the recent literature.

β-Hydroxy-β-methylbutyrate (HMβ) supplementation is used to treat cancer, sepsis and exercise-induced muscle damage. However, its effects on animal and human health and the consequences of this treatment in other tissues (e.g., fat and liver) have not been examined. The purpose of this study was to evaluate the effects of HMβ supplementation on skeletal muscle hypertrophy and the expression of proteins involved in insulin signalling. Rats were treated with HMβ (320 mg/kg body weight) or saline for one month. The skeletal muscle hypertrophy and insulin signalling were evaluated by western blotting, and hormonal concentrations were evaluated using ELISAs. HMβ supplementation induced muscle hypertrophy in the extensor digitorum longus (EDL) and soleus muscles and increased serum insulin levels, the expression of the mammalian target of rapamycin (mTOR) and phosphorylation of p70S6K in the EDL muscle. Expression of the insulin receptor was increased only in liver. Thus, our results suggest that HMβ supplementation can be used to increase muscle mass without adverse health effects.

The paraneoplastic syndrome of cachexia is considered a degenerative chronic inflammatory disease, being deeply related to the increase of pro-inflammatory factors, especially tumour necrosis factor alpha (TNF-a). It is known that the adipose tissue is affected by cachexia and contributing with the secretion of pro-inflammatory factors which reach the adjacent tissues and the circulation. The effect of proinflammatory factors is balanced by the effect of anti-inflammatory factors, such as interleukin 10 (IL-10). The IL-10/TNF-a ratio has been recently postulated as a marker for the assessment of the degree of inflammation, which correlates with disease-associated morbidity and mortality. In order to counteract inflammation in chronic disease, our group has currently adopted chronic endurance exercise in models of cancer cachexia and chronic heart failure. Since it is clear that white adipose tissue is strongly implicated in the secretion of both pro-and antiinflammatory factors in disease, we chose to address its contribution to cachexia-related inflammation and the effect of endurance training on the capacity of cytokine expression and secretion by this tissue. Our results show an enhancement of IL-10 adipose tissue content, and increased IL-10/TNF-a ratio induced by endurance training. The mechanisms are discussed.