Creatine vs. HMB: Muscle Preservation and Growth Pathways

Beta-hydroxy beta-methylbutyrate (HMB) experienced a surge of interest in the mid-2010s following a series of studies reporting remarkably large effects on lean mass and strength. Those claims generated both enthusiasm and significant scientific controversy. Creatine, meanwhile, has remained the benchmark for ergogenic supplementation for over three decades. Comparing these two supplements reveals important lessons about evidence quality, replication, and what separates supplements with robust evidence from those with impressive but isolated findings.

How Creatine Works

Creatine monohydrate increases intramuscular phosphocreatine stores, enhancing the ATP regeneration capacity during short-duration, high-intensity exercise. The mechanism is well-characterized: more phosphocreatine means more rapid ATP resynthesis via the creatine kinase reaction, enabling greater total work during resistance training. Secondary effects include cell volumization (intracellular water retention), which may act as an anabolic signal, and emerging evidence for effects on satellite cell activation and myogenic regulatory factor expression.

Supplementation protocol is 3 to 5 g daily (with or without a loading phase of 20 g/day for 5 to 7 days). Effects require chronic supplementation to saturate intramuscular stores.

How HMB Works

HMB is a metabolite of the amino acid leucine, produced endogenously in small quantities (the body produces approximately 0.2 to 0.4 g per day from normal leucine metabolism). Only about 5% of dietary leucine is converted to HMB, making supplementation the only way to achieve the doses used in research (typically 3 g/day).

The proposed mechanisms of HMB are primarily anti-catabolic rather than directly ergogenic. HMB is believed to inhibit the ubiquitin-proteasome proteolytic pathway, which is a major driver of skeletal muscle protein degradation. By reducing protein breakdown, HMB theoretically shifts the protein balance toward net accretion. Additional proposed mechanisms include upregulation of the mTOR/p70S6k pathway (stimulating protein synthesis), stabilization of sarcolemma integrity via cholesterol synthesis, and modulation of the apoptotic signaling cascade in muscle cells.

HMB exists in two supplemental forms: HMB-Ca (calcium salt, the original form) and HMB-FA (free acid form), which has more rapid absorption kinetics.

Evidence for Creatine

The creatine evidence base needs little elaboration. Over 500 peer-reviewed studies, multiple meta-analyses, and consensus position statements from the ISSN, ACSM, and EFSA all confirm that creatine monohydrate is the most effective ergogenic nutritional supplement available. Meta-analyses consistently show approximately 5 to 10% strength improvements, 1 to 2 kg additional lean mass during training, and enhanced work capacity during repeated high-intensity exercise. The safety profile across decades of study is excellent.

Evidence for HMB: A Complicated Picture

HMB research can be divided into two eras that paint different pictures.

Early Research (Pre-2013)

Early studies, many conducted by Steven Nissen's research group (Nissen held the HMB patent), showed modest but statistically significant benefits. Meta-analyses from this period, including Nissen and Sharp (2003), found that HMB supplementation increased lean mass by approximately 0.28 kg and strength by about 1.4% over training periods of 3 to 8 weeks. These effects were smaller than those seen with creatine but consistent across several trials.

Jowko et al. (2001) conducted a notable study examining creatine, HMB, and the combination in untrained males during 3 weeks of resistance training. The combination group showed the greatest improvements in lean body mass and strength, with effects that appeared additive. This study was well-designed and frequently cited as evidence for the creatine-HMB stack.

The Wilson et al. (2014) Controversy

A pivotal study by Wilson et al. (2014) reported that 12 weeks of HMB-FA supplementation combined with resistance training in trained males resulted in 7.4 kg lean mass gain and a 25% increase in squat strength compared to placebo. These effect sizes were unprecedented for any legal supplement, exceeding what most anabolic agents produce. The study was published in the European Journal of Applied Physiology and immediately drew criticism.

Multiple researchers published correspondence and commentary questioning the plausibility of these findings. Phillips et al. (2017) argued that the reported effect sizes were physiologically implausible and noted several methodological concerns. The debate highlighted a broader issue in HMB research: many positive studies have come from groups with potential conflicts of interest, and independent replications have generally failed to show effects of the same magnitude.

Independent Research

When HMB has been studied by independent research groups in well-trained individuals with adequate protein intake, the results have been far more modest. Rowlands and Thomson (2009) conducted a meta-analysis finding that HMB augmented strength gains in previously untrained individuals but not in trained populations. Sanchez-Martinez et al. (2018) found similar patterns, with HMB showing its largest effects in untrained subjects, older adults, and clinical populations experiencing muscle wasting.

Side-by-Side Comparison

When to Use Each

Creatine: The Universal Choice

Creatine remains the top-tier ergogenic supplement for anyone engaged in resistance training, regardless of training status. Its effects are consistently demonstrated in trained and untrained populations, men and women, young and old. It is cheap, safe, and effective.

HMB: A Narrow Window of Utility

The current evidence most consistently supports HMB supplementation for populations at high risk of muscle loss: elderly individuals at risk of sarcopenia, patients in catabolic clinical states (bed rest, cachexia), and possibly individuals in severe caloric restriction who want to preserve lean mass. For trained individuals with adequate protein intake, HMB is unlikely to provide meaningful additional benefit.

Stacking

The Jowko et al. (2001) data suggested additive effects of creatine and HMB in untrained subjects. For the specific populations where HMB shows benefit (novice trainees, older adults, clinical populations), combining it with creatine is rational and supported by limited evidence. For experienced trainees, the HMB component of this stack is unlikely to justify its cost.

Verdict

The comparison between creatine and HMB is instructive about how to evaluate supplement evidence. Creatine's effects have been replicated hundreds of times by independent research groups worldwide, resulting in universal expert consensus. HMB's most impressive findings have come primarily from groups with financial ties to the supplement, and independent replications in trained populations have largely failed to confirm those large effect sizes.

For the general exercising population, creatine is the clear choice. HMB may have a legitimate role in clinical and anti-sarcopenia contexts, but for the typical gym-goer spending their own money, the $25 to $45 per month for HMB would be better spent on food, creatine, or protein. The evidence hierarchy here is not close.