ReviewEfficacy of β-hydroxy-β-methylbutyrate supplementation in elderly and clinical populations
Introduction
Muscle loss is common throughout the aging process and may begin as young as 30 y of age [1]. Approximately 30% of muscle mass is lost between the fifth and eighth decades of life and rates of muscle loss can reach up to 15% per decade by 70 y of age [2], [3]. Moreover, low levels of muscle mass in the elderly have been correlated with decreased physical function [4], decreased quality of life [5], and increased mortality [6]. A similar relation exists in many clinical populations such as patients with cancer or acquired immune deficiency syndrome (AIDS), where muscle wasting is common. Indeed, low levels of lean mass in clinical populations have been correlated with decreased physical function, decreased quality of life, poorer response to treatment, and increased mortality [7], [8], [9], [10]. Therefore, interventions to maintain or potentially increase lean mass in elderly and clinical populations are needed. Recently, β-hydroxy-β-methylbutyrate (HMB) has been researched for its muscle-sparing properties in these populations. The present review summarizes the evidence for use of HMB in human elderly and clinical populations.
Section snippets
Methods
Searches were performed using the PubMed database with terms such as HMB, beta-hydroxy-beta-methylbutyrate, HMB muscle, HMB supplementation, and HMB exercise. Results were thoroughly reviewed for primary research studies on HMB supplementation in clinical and elderly populations, HMB supplementation in animal models of disease, HMB safety and dosage studies, and studies on the potential mechanism of action of HMB. In addition, review articles on HMB supplementation were obtained and the
Metabolism and dosage
HMB is a metabolite of the ketogenic amino acid leucine. A small amount (∼0.3–0.4 g/d) of HMB is produced endogenously through leucine metabolism. The first step in leucine oxidation is transamination to ketoisocaproate. The majority (approximately 95%) of ketoisocaproate is metabolized to isovaleryl coenzyme A by the mitochondrial enzyme branched-chain α-keto-acid dehydrogenase and ultimately enters the citric acid cycle. However, a small amount of ketoisocaproate (approximately 5%) is
Safety of HMB
With consumption of any dietary supplement, safety is a concern. Accordingly, the safety of HMB supplementation has been widely studied [17], [18], [19], [20]. Early studies in animals found that the consumption of HMB in dosages as high as 100 g/d in pigs weighing 20 kg (approximately 100 times the HMB dose used in most human studies) for 4 d had no effect on changes in blood cell numbers, organ weights, or histologic lesions [17]. Likewise in humans, the consumption of dosages as high as 6
Efficacy of HMB in healthy populations and athletes
Previous studies investigating HMB supplementation in athletes and healthy populations have shown mixed results. A meta-analysis of nine studies found that HMB resulted in significant gains in muscle size and strength [24]. However, a more recent meta-analysis of 11 studies by Rowlands et al. [25] concluded that 3 to 9 wk of HMB supplementation at a dosage of around 3 g/d resulted in only small to trivial increases in muscle strength and only trivial increases in muscle size, regardless of
Efficacy of HMB in the elderly
The effects of HMB supplementation in elderly populations have been examined in several studies (Table 1) [23], [26], [27], [28], [29]. Hsieh et al. [26] investigated the effects of HMB in elderly subjects receiving tube feeding. The subjects were assigned to usual care (n = 40) or HMB 2 g/d (n = 39) for 28 d. All tube-feeding protocols remained the same throughout the study. After 28 d, HMB supplementation increased weight, body mass index, and waist, hip, and calf circumferences. In addition,
Efficacy of HMB in clinical populations
Patients with a chronic disease such as cancer and AIDS develop significant muscle loss, which leads to decreased physical function, quality of life, and survival [10]. Numerous nutritional interventions have been investigated in an attempt to counteract muscle wasting in these populations; however, many of these interventions have been unsuccessful in attenuating muscle loss (reviewed in Klein et al. [32]). Recently, HMB has been investigated for its anticatabolic effects in clinical
Efficacy of HMB in animal models of disease
The previously discussed studies are the only published investigations on the efficacy of HMB supplementation in human clinical populations. However, HMB supplementation has also been investigated in animal models of muscular unloading, sepsis, and muscular dystrophy. Hao et al. [43] investigated the effects of HMB using an animal model of unloading and reloading. They found that rats supplemented with HMB had significantly greater force production and increased plantaris and soleus
HMB mechanism of action
Muscle tissue mass represents the net balance between muscle protein synthesis and degradation. The continuous process of building and replacing muscle protein allows muscle to repair and adapt to environmental conditions. Net protein balance is positive during growth when protein synthesis exceeds degradation, whereas the net balance is negative during weight loss, aging, and in clinical populations when degradation exceeds synthesis. Accordingly, numerous studies have investigated the effects
Conclusions
Muscle loss is common during aging and in chronic diseases, leading to decreased physical function, a decreased quality of life, and increased mortality. Recently, HMB has been shown to attenuate muscle loss in the elderly and in clinical populations such as patients with AIDS and those with cancer; however, a limited number of studies have investigated this question, with relatively small samples. In addition, the effects of HMB in clinical populations appear to differ depending on the
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