Effects of HMB Supplementation

Nissen et al conducted one of the first studies addressing the effects of oral supplementation with different doses of HMB. Individuals were supplemented with 0, 0.5, and 3.0 g/day of HMB in conjunction with a resistance training program for 3 weeks. In the first 2 weeks urinary excretion of 3-methyl-histidine was decreased, indicating an attenuation of muscle proteolysis, and at the end of the protocol the muscle damage indicators—CK and lactate dehydrogenase (LDH) activities—were lower in the supplemented group. A significant increase in fat-free mass and strength was reported when 3.0 g/day of HMB was supplemented in association with resistance training for 7 weeks. However, controversial results have been reported in studies with humans assessing the effects of oral supplementation of HMB in tandem with resistance training . In previously untrained individuals, HMB supplementation (3.0 g HMB per day) during a resistance training program did not change the body composition, muscular strength levels, and biochemical markers of protein turnover and muscle damage, increased muscle mass or potentiated the strength gain and fat-free mass gain in elderly subjects. In addition, in athletes highly conditioned to resistance training, HMB was unable to promote gains in strength and fat-free mass in water polo, rowing, or football athletes and did not elicit attenuation of muscle damage markers (Creatine Kinase [CPK] and LDH) and gains in speed.

In untrained individuals oral supplementation of HMB in association with resistance training may elicit gains in strength and muscle mass because these effects appear to be more prominent among those who are in the initial phase of training. Untrained individuals submitted to a resistance training program exhibit lower levels of muscle damage markers when supplemented with 3.0 g/day of HMB. If HMB reduces the muscle protein catabolism associated with exercise, resistance-trained athletes may not respond to HMB supplementation in the same manner as untrained individuals, due to training-induced suppression of protein breakdown. To confirm the anticatabolic properties of HMB, further research using more precise techniques is required because most studies addressing this issue have used the urinary excretion of 3-methyl-histidine as an indicator of muscle catabolism, and this technique has been criticized.

It has been demonstrated that ingestion of 3.0 g/day of HMB increases its plasma levels and promotes gains in fat-free mass and peak isometric torque during a resistance training program. Greater amounts of HMB (6.0 g/day) did not elicit the same effect. Furthermore, 8 weeks of HMB supplementation (up to 76 mg/kg/day) appears to be safe and does not alter or adversely affect hematological parameters and hepatic and renal function in young male adults.

Mechanisms of Action

Based on studies evaluating the mechanisms of action of HMB, it is postulated that such supplementation could involve the following mechanisms:

(1) increased sarcolemmal integrity

(2) increased metabolic efficiency

(3) upregulation of IGF-1 expression in liver and skeletal muscle

(4) stimulation of protein synthesis by increasing the mTOR signaling pathway, and

(5) suppression of proteolysis by the inhibition of the ubiquitin-proteasome system.

The protective effect of HMB against contractile activity–induced damage may be associated to increased stability of muscle plasma membrane. HMB is converted to b-methylglutaryl-CoA (HMG-CoA) for cholesterol synthesis, and inhibition of HMG-CoA reductase affect the electrical properties of cell membrane in skeletal muscle. In addition, HMB supplementation may also promote an increase in acetyl-CoA content through the conversion of HMG-CoA into acetoacetyl-CoA by HMG-CoA synthase in mitochondria, increasing metabolic efficiency. HMB supplementation has also been reported to stimulate lipolysis in adipose tissue and increase fatty acid oxidation capacity of skeletal muscles. One other mechanism underlying the effects of HMB supplementation is the increased expression of IGF-1 expression in liver and skeletal muscles. Kornasio et al. demonstrated in vitro that HMB could stimulate IGF-1 expression, as well myogenic regulatory factors and thymidine incorporation (an indicator of DNA synthesis). Later Gerlinger-Romero et al. demonstrated that supplementation with HMB promoted an increased GH and IGF-1 expression in pituitary and liver, respectively. In vivo and in vitro animal data also pointed to a possible role of HMB in stimulation of mTOR signaling pathway and inhibition of ubiquitin-proteasome system, a proteolytic system involved in skeletal muscle atrophy. More studies are needed to determine whether the actions of HMB on protein synthesis and degradation signaling pathways are direct or mediated by an increased expression of IGF-1, as well to determine the molecular basis of HMB supplementation in humans.

Conclusions

In the recent years, the growing interest in HMB supplementation has arisen from previous demonstrations of its effects on fat-free mass and strength gains in combination with resistance exercise, its anticatabolic properties, and speculations related to the mechanisms of action involved. Most studies have used 3 g/day of HMB, grounded in evidence that this dose produces better results than 1.5 g/day and is equivalent to 6 g/day. If in untrained individuals HMB supplementation appears to act as an effective ergogenic, in well-trained individuals and athletes the positive effects of HMB are less clear. The physiological mechanisms involved increased sarcolemmal integrity and metabolic efficiency, stimulation of GH–IGF-1 axis, stimulation of protein synthesis, and suppression of proteolysis. Although some of these mechanisms were demonstrated in animal and in vitro studies, human studies are needed and could provide new insights into the mechanisms underlying the effects of supplementation.