Beta-hydroxy-beta-methylbutyrate supplementation in health and disease: a systematic review of randomized trials

Abstract

Beta-hydroxy-beta-methylbutyrate (HMB), a metabolite of the branched-chain amino acid leucine, is extensively used by athletes and bodybuilders in order to increase strength, muscle mass and exercise performance. We performed a systematic review of the clinical literature on the effectiveness of HMB supplementation in healthy and pathological conditions (i.e. training programs, aging, acute and chronic diseases, and after bariatric surgery). We reviewed all clinical trials indexed in Medline that tested HMB supplementation as well as all the experimental data regarding HMB intracellular mechanisms of action. Search terms included: randomized controlled trials, controlled clinical trials, single- and double-blind method, HMB, proteolytic pathways, muscle atrophy, cachexia, and training. We found out 13 studies testing HMB in healthy young trained subjects, 11 in healthy young untrained subjects, 9 in patients affected by chronic diseases (i.e. cancer, HIV, chronic obstructive pulmonary disease), and 6 in elderly subjects. The indexed studies support that HMB is effective in preventing exercise-related muscle damage in healthy trained and untrained individuals as well as muscle loss during chronic diseases. Most of the selected studies showed the effectiveness of HMB in preventing exercise-related muscle damage in healthy trained and untrained individuals as well as muscle loss during chronic diseases. The usual dose of 3 g/day may be routinely recommended to maintain or improve muscle mass and function in health and disease. The safety profile of HMB is unequivocal. Further, well-designed clinical studies are needed to confirm effectiveness and mode of action of HMB, particularly in pathological conditions.

Nutritional Supplements in Support of Resistance Exercise to Counter Age-Related Sarcopenia

“…This effect is associated with the ability of Leu to activate mTORC1, which subsequently targets downstream signaling protein kinases such as 4E binding protein 1 (4EBP1) and p70S6K1, both of which facilitate translation initiation and stimulation of MPS (81). The discovery that Leu positively influences skeletal muscle metabolism makes it perhaps unsurprising that other molecules related to Leu, such as b-hydroxyb-methylbutyrate (b-HMB), a Leu metabolite, would also possess anabolic properties capable of influencing skeletal muscle protein turnover (82). Currently, b-HMB is a patentprotected compound with a number of applications but most relevant to this review are US patents: 5,348,979 (83), b-HMB is described as useful for promoting nitrogen retention in humans; and 6,031,000 (84), which, among other claims, is a compound stated as being used, ".to treat disease-associated wasting of an animal.." In addition, other patents list b-HMB (in combination with vitamin D) as being useful in the promotion of muscular function and strength (85).…”

“…Currently, b-HMB is a patentprotected compound with a number of applications but most relevant to this review are US patents: 5,348,979 (83), b-HMB is described as useful for promoting nitrogen retention in humans; and 6,031,000 (84), which, among other claims, is a compound stated as being used, ".to treat disease-associated wasting of an animal.." In addition, other patents list b-HMB (in combination with vitamin D) as being useful in the promotion of muscular function and strength (85). In a recent systematic review of trials involving b-HMB in health and disease, Molfino et al (82) concluded that a meta-analysis of the effects of b-HMB supplementation in the elderly was not possible mostly because of the heterogeneity of trials and the lack of pure b-HMB being compared with a placebo; nevertheless, a recent review states that, "Essential amino acid (EAA) supplements, including. b-hydroxy b-methylbutyric acid (HMB) supplements, show some effects in improving muscle mass and function parameters (86)"; thus, the trials relevant to aging are reviewed here.…”

Effect of beta-hydroxy-beta-methylbutyrate supplementation on muscle loss in older adults: A systematic review and meta-analysis

“…Multiple studies have explored mechanisms that link HMB to muscle loss; it has been suggested that HMB can enhance protein synthesis via upregulation of anabolic signaling pathways and attenuate proteolysis via downregulation of catabolic signaling pathways (Hasselgren, 2014). Likewise, population surveys and clinical studies suggest that HMB treatment decreased muscle proteolysis (Baier et al, 2009) and muscle damage and increased fat-free mass gain both in young and older adults (Molfino, Gioia, Rossi Fanelli, & Muscaritoli, 2013). Indeed, HMB has been extensively used as an ergogenic aid, especially among bodybuilders and power athletes, who use it to promote exercise performance and skeletal muscle hypertrophy (Wilson et al, 2013a).…”

The ergogenic supplement β-hydroxy-β-methylbutyrate (HMB) attenuates insulin resistance through suppressing GLUT-2 in rat liver

“…Many of these supplements have hazardous effects on health if taken without any considerations of the athlete's medical condition or without consulting a physician. One of the most widely used supplements is β-hydroxy-β-methylbutyrate (HMB) (Molfino et al 2013).…”