HMB

Beta-hydroxy beta-methylbutyrate is produced in the body from leucine, though only a small fraction of leucine, roughly five per cent, takes this route. Getting a supplemental dose from food alone would require an implausible amount of protein.

Two forms exist. Calcium HMB is the original and cheaper form. HMB free acid is absorbed faster and reaches higher peak plasma levels, and is marketed on that basis, though whether the difference translates into better outcomes is not clearly established.

HMB is unusual in the muscle category for being positioned around preservation rather than growth. Its clearest applications are situations where muscle is at risk of being lost: periods of inactivity, immobilisation, ageing, or aggressive dieting.

The primary proposed action is inhibition of muscle protein breakdown, principally through downregulation of the ubiquitin-proteasome pathway, the main route by which muscle protein is degraded.

HMB also appears to stimulate protein synthesis via mTOR, though less potently than leucine itself, and has been reported to support cell membrane integrity through effects on cholesterol synthesis in muscle cells.

This anti-catabolic emphasis is the key to interpreting the evidence. Where muscle breakdown is elevated, as in untrained people beginning training, older adults, or people in a large energy deficit, there is something for HMB to reduce. In a trained lifter eating adequately, breakdown is not the limiting factor, and this is why results differ so sharply by population.

Early research in untrained individuals starting resistance training reported meaningful gains in lean mass and strength, and these findings drove HMB's initial reputation.

Subsequent work in trained athletes has been far less impressive, with most well-controlled trials finding little or no benefit. A small number of trials reporting very large effects in trained subjects have attracted substantial methodological criticism, and the results have not been independently replicated.

Where HMB looks more genuinely useful is in older adults and in periods of enforced inactivity. Trials in bed rest and in older populations have reported preservation of lean mass, and this is the application best supported by the literature.

HMB has a good safety record across a substantial number of trials, including in older and clinical populations. Adverse effects reported are minimal and generally comparable to placebo.

Studies examining blood chemistry, liver and kidney markers over extended supplementation have not found significant abnormalities. Occasional digestive discomfort is the main complaint.

Long-term data beyond the durations used in trials is limited, as is the case for most supplements, and safety in pregnancy has not been established.