Beta-hydroxy-beta-methylbutyrate (HMB) and Sarcopenia: From Biological Plausibility to Clinical Evidence

An appropriate consumption of proteins with the usual diet is important to muscle mass maintenance as it guarantees the right amount of essential amino acids and consequently stimulates protein synthesis. Usually, older subjects are at high risk for inadequate protein intake. As people age, insufficient intake of protein is correlated to reduced muscle reserves, increased skin fragility, lower immune function, poor healing, and longer time needed to recover from illness. Older individuals are less reactive to the stimulatory effect of amino acids on muscle protein synthesis, but recent evidence demonstrated that a higher amount of protein/amino acid intake might preserve this stimulation and result in enhancements in lean body mass, strength, and physical function. In this respect, the current WHO recommended dietary allowance (RDA) for protein (0.8 g/kg/day) might be inadequate for maintaining muscle mass and quality among frail old people. Therefore, it is discussed whether the RDA for protein intake is appropriate to prevent major adverse events and negative outcomes in older persons. Given the fact that protein–energy malnutrition is one of the major risk factor for the onset and development of sarcopenia, a non-optimal nutritional status may mediate the association between sarcopenia and negative outcomes in older and frail individuals. In this respect, it is important to highlight that protein and/or specific amino acids supplementation per se may be required to increase muscle mass and muscle function in malnourished older inpatients.

Beta-hydroxy-beta-methylbutyrate (HMB) is an active metabolite of leucine, a branched-chain essential amino acid completely derived from dietary sources. HMB is found in very small amounts of some foods, such as avocado, citrus fruit, cauliflower, and catfish. HMB is synthesized from leucine in a two-step process occurring in muscle and liver cells. Leucine has a specific role in regulating and controlling protein synthesis at muscle cell level, and HMB acts as a key active metabolite in such regulation. However, only nearly 5% of leucine is transformed to HMB, which results in the production of 0.2–0.4 grams of HMB per day in a subject weighing 70 kg. Traditionally, bodybuilders and athletes to increase performance and to build muscle mass, as it is available commercially as a nutritional supplement in the form of its calcium salt CaHMB monohydrate, used HMB supplementation. More recent research has also focused on the use of HMB supplementation to preserve or rebuild muscle mass in populations at risk of sarcopenia, particularly the older people. Several studies have demonstrated the benefits of HMB supplementation, alone or in combination with other amino acids and exercise protocol, for maintaining and rebuilding lean body mass, muscle strength and function in older adults.