HMB
Evidence Fact Sheet
β-Hydroxy β-Methylbutyrate
HMB (β-hydroxy β-methylbutyrate) is a leucine metabolite studied for muscle-mass preservation, strength and recovery. Meta-analyses show modest benefits in older/clinical populations but largely null effects in young trained athletes. Lawful dietary-supplement ingredient (US GRAS); EFSA found no authorized muscle-function claim.
Also known as: HMB · β-Hydroxy β-Methylbutyrate · Beta-hydroxy-beta-methylbutyrate · 3-Hydroxyisovaleric acid · Calcium HMB (HMB-Ca) · HMB free acid (HMB-FA) · β--β-
Overview
HMB (β-hydroxy β-methylbutyrate) is a downstream metabolite of the amino acid leucine. Mechanistic and preclinical models attribute its studied effects to stimulation of muscle protein synthesis via the mTOR/p70S6K pathway and attenuation of muscle protein breakdown through the ubiquitin-proteasome system. It is researched mainly for lean-mass preservation, muscle strength and exercise recovery, especially in older adults, disuse/immobilization and clinical muscle-wasting contexts. The typical research dose is around 3 g/day (often split 3 × 1 g), commonly as the calcium salt (HMB-Ca) or free acid (HMB-FA), over 8-24 week windows. Regulatory status: a lawful dietary-supplement ingredient under DSHEA with HMB-Ca self-affirmed GRAS in the US; in the EU it is lawful to market but EFSA established no authorized "muscle function" health claim; ANVISA permits it as a supplement constituent in Brazil. Educational information only; not intended to diagnose, treat, cure or prevent any disease.
Mechanism of Action
Leucine metabolite (~5% of dietary leucine is converted to HMB via the KIC intermediate); supplementation is used to reach research-level intakes (research-context) · Stimulation of muscle protein synthesis via the mTOR/p70S6K signaling pathway (research model) · Attenuation of muscle protein breakdown by downregulating the ubiquitin-proteasome system and caspase-3 apoptotic pathway (preclinical / mechanistic) · Support of skeletal-muscle mitochondrial biogenesis (Standley 2017 RCT mechanistic readout)
Body systems: Musculoskeletal · Mitochondrial & Cellular Energy · Cellular Renewal
Evidence-Based Benefits
Each benefit below is anchored to a specific PubMed-indexed study. Effect sizes, sample sizes, and p-values are reported as published; no values are inferred. Honest negatives and null results are kept alongside the positive findings, and disease-research populations are described as such — HMB is not characterized as a treatment for any disease.
Muscle strength (mixed/clinical populations)
Meta-analysis supported- SMD 0.31strength · 95% CI 0.12, 0.50
- P = 0.001strength · I2 = 0%
- 15 RCTs2137 patients
A systematic review and meta-analysis of HMB (alone or in HMB-containing supplements) pooled 15 RCTs in 2137 patients. It found strong evidence for improved muscle strength, while the effect on skeletal muscle mass was only borderline (SMD 0.25, 95% CI crossing zero, P = 0.05).
Reported effect: Strength SMD = 0.31 (95% CI: 0.12, 0.50; z = 3.25; P = 0.001; I2 = 0%); muscle mass SMD = 0.25 (95% CI: -0.00, 0.50; z = 1.93; P = 0.05; I2 = 58%)
“Fifteen randomized controlled trials were included, involving 2137 patients. Meta-analysis revealed some evidence to support the effect of HMB alone, or supplements containing HMB, on increasing skeletal muscle mass (SMD = 0.25; 95% CI: -0.00, 0.50; z = 1.93; P = 0.05; I2 = 58%) ... strong evidence to support improving muscle strength (SMD = 0.31; 95% CI: 0.12, 0.50; z = 3.25; P = 0.001; I2 = 0%)”
Source: PMID 30982854 · Bear 2019 · Am J Clin Nutr
Muscle mass in older adults
Meta-analysis supported- SMD 0.352 kgmuscle mass · 95% CI 0.11, 0.594
- P = 0.004muscle mass gain
- 7 RCTs287 older adults
A meta-analysis of 7 RCTs (147 HMB vs 140 control older adults) found greater muscle-mass gain with HMB versus control. By contrast, fat mass did not change significantly between groups, indicating the effect was specific to lean tissue rather than overall body composition.
Reported effect: Muscle mass SMD = 0.352 kg (95% CI: 0.11, 0.594; Z = 2.85; P = 0.004); fat mass SMD = -0.08 kg (95% CI: -0.32, 0.159; Z = 0.66; P = 0.511, non-significant)
“A total of seven randomized controlled trials were included, in which 147 older adults received HMB intervention and 140 were assigned to control groups. The meta-analysis showed greater muscle mass gain in the intervention groups compared with the control groups (standard mean difference=0.352kg; 95% confidence interval: 0.11, 0.594; Z value=2.85; P=0.004).”
Source: PMID 26169182 · Wu 2015 · Arch Gerontol Geriatr
Lean / fat-free mass in older adults
Meta-analysis supported- ES 0.37fat-free mass · 95% CI 0.16, 0.58
- P = 0.001fixed-effect model
- 9 studies448 participants
A meta-analysis of 9 studies (448 participants) found that oral HMB supplementation significantly increased fat-free mass in older people relative to control. This is consistent with HMB's studied role in lean-mass preservation in aging populations.
Reported effect: Fat-free mass effect size = 0.37 (95% CI 0.16, 0.58; Z = 3.47, P = 0.001; fixed-effect model)
“A total of 9 studies (448 participants) were eventually found eligible. The pooled results showed that HMB supplementation significantly increased fat-free mass in older people compared with the control group (effect size: 0.37; 95% Cl 0.16, 0.58; Z value = 3.47, P = 0.001; Fixed-effect model).”
Source: PMID 33034021 · Lin 2021 · Eur Geriatr Med
Resistance training in young adults (honest negative)
Null / no benefit Meta-analysis supported- 302 participantsbody composition analysis
- 248 participantsstrength analysis
A systematic review and meta-analysis in young adults (18-45 y) undergoing resistance exercise training found a small effect on total body mass but NO significant effects on fat-free mass, fat mass or strength. The authors concluded HMB does not translate into meaningfully greater lean-mass or strength gains in this population. The abstract reports participant counts but no pooled effect-size numbers for the null outcomes.
Effect size: this study reports the direction of the finding but does not state a specific numeric effect size, so none is given here rather than estimated.
“A total of 302 participants (18-45 y) were included in body mass and composition analysis, and 248 were included in the strength analysis. ... A significant effect was found on TBM. However, there were no significant effects for FFM, FM, or strength outcomes. ... HMB produces a small effect on TBM gain, but this effect does not translate into significantly greater increases in FFM, strength or decreases in FM during periods of RET.”
Source: PMID 32456217 · Jakubowski 2020 · Nutrients
Trained / competitive athletes (honest negative)
Null / no benefit Meta-analysis supported- ES 0.16fat-free mass · p>0.05
- ES 0.00bench press · p>0.05
- 6 studiesn=193 participants
A meta-analysis of 6 studies (n=193) in trained and competitive athletes found trivial, non-significant effects of HMB on every outcome measured — bench press, leg press, body mass, fat-free mass and fat mass — with no heterogeneity. The authors concluded HMB had no effect on strength or body composition in already-trained athletes.
Reported effect: All outcomes non-significant (p>0.05): bench press ES=0.00, leg press ES=0.09, body mass ES=-0.01, fat-free mass ES=0.16, fat mass ES=-0.20; I2=0.0%
“Six studies were selected for meta-analysis, as they fulfilled the inclusion criteria (n=193 participants). HMB supplementation interventions present a trivial non-significant ES in all variables studied (bench press ES=0.00, leg press ES=0.09, body mass ES=-0.01, fat-free mass ES=0.16, and fat mass ES=-0.20; all cases p>0.05, and null heterogeneity I2=0.0% p>0.05).”
Source: PMID 29249685 · Sanchez-Martinez 2018 · J Sci Med Sport
Muscle wasting in cancer patients (clinical context)
Emerging / indexed- 15 studies6 RCTs · cancer patients
- 4 of 4studies · muscle mass benefit
- 2 of 2studies · muscle function
A systematic review of HMB in cancer patients included 15 studies (6 RCTs). Among higher-quality studies, a beneficial effect on muscle mass was reported in 4 of 4 and on muscle function in 2 of 2. The authors note the evidence base remains limited and call for additional well-designed trials; no pooled effect size was reported.
Effect size: this study reports the direction of the finding but does not state a specific numeric effect size, so none is given here rather than estimated.
“Fifteen studies were included, in which six were randomized controlled trials in patients with various cancer types and treatments. ... evidence of a beneficial effect of HMB supplementation was found in four of four studies for muscle mass ... two of two for muscle function ... Although limited, current evidence suggests that HMB supplementation has a beneficial effect on muscle mass and function in patients with cancer.”
Source: PMID 35301826 · Prado 2022 · J Cachexia Sarcopenia Muscle
Dosage (research context · not a recommendation)
3 g/day, typically split into 3 × 1 g doses (the dose used in nearly all positive RCTs · educational reference); intervention windows of 8–24 weeks for muscle-mass outcomes and over the full immobilization period for disuse protection · 6 g/day studied short-term without added benefit · HMB-Ca is the predominant form in long-term trials, HMB-FA reaches a faster plasma peak (~30 min vs ~60 min)
Regulatory Status · 4 Markets
- US · FDA
- Lawful dietary-supplement ingredient under DSHEA · HMB-Ca self-affirmed GRAS (Metabolic Technologies / TSI Group) and treated as a pre-1994 Old Dietary Ingredient; HMB-FA (free acid) may require an NDI notification. Structure/function claims only (no FDA-authorized health claim); the FDA disclaimer is mandatory. ('FDA GRAS self-affirmed' — GRAS is a self-determination with no FDA objection, not an FDA approval/certification.)
- EU · EFSA
- Lawful to market as a food-supplement ingredient (HMB-Ca sold in the EU since the 2000s). NO authorized health claim: the EFSA NDA Panel (EFSA Journal 2011;9(6):2227) concluded that a cause-and-effect relationship was not established for the 'maintenance of normal muscle function' claim. EU material may state composition/source only — no efficacy wording.
- BR · ANVISA
- Authorized as a food-supplement constituent (Suplemento Alimentar) under RDC 243/2018; β-hidroxi-β-metilbutirato is listed in IN 28/2018 permitted-constituents annex (HMB-Ca as the principal form). Functional claims permitted only within the ANVISA framework; no disease-treatment claims.
Safety
3 g/day has been used long-term (12 months+) in adults without serious adverse events reported; occasional mild GI discomfort (nausea), usually linked to fasted dosing. Human RCTs report no adverse effect on liver/kidney function, blood counts, lipids or glucose, and no clinically significant drug interactions are documented. No adequate safety data in pregnancy or lactation, and trials were conducted in adults — not recommended for pregnant/breastfeeding women or individuals under 18. Educational information only; consult a healthcare professional. Not intended to diagnose, treat, cure or prevent any disease.
References
PubMed-indexed citations anchoring the benefit findings above. Effect sizes are reported as published.
- PMID 30982854 · Bear 2019 · Am J Clin Nutr — Muscle strength (mixed/clinical populations)
- PMID 26169182 · Wu 2015 · Arch Gerontol Geriatr — Muscle mass in older adults
- PMID 33034021 · Lin 2021 · Eur Geriatr Med — Lean / fat-free mass in older adults
- PMID 32456217 · Jakubowski 2020 · Nutrients — Resistance training in young adults (honest negative)
- PMID 29249685 · Sanchez-Martinez 2018 · J Sci Med Sport — Trained / competitive athletes (honest negative)
- PMID 35301826 · Prado 2022 · J Cachexia Sarcopenia Muscle — Muscle wasting in cancer patients (clinical context)
Frequently Asked Questions
1. What is HMB and where does it come from?
HMB (β-hydroxy β-methylbutyrate) is a metabolite of the essential amino acid leucine; only a small fraction of dietary leucine is converted to HMB, so supplements are used to reach research-level intakes. In mechanistic models it is studied for stimulating muscle protein synthesis (mTOR/p70S6K pathway) and reducing muscle protein breakdown.
2. Does HMB actually build muscle?
The evidence is population-dependent. Meta-analyses in older adults found significant gains in muscle mass (Wu 2015, SMD 0.352 kg) and fat-free mass (Lin 2021, ES 0.37), and a broad meta-analysis found strong evidence for improved strength (Bear 2019, SMD 0.31). However, in young resistance-trained adults (Jakubowski 2020) and trained athletes (Sanchez-Martinez 2018) the pooled effects on fat-free mass and strength were non-significant.
3. What dose was used in the research?
Most positive trials used around 3 g/day, often split into three 1 g doses, typically as calcium HMB (HMB-Ca) or the free-acid form (HMB-FA), over intervention windows of roughly 8-24 weeks. This is an educational reference to the doses studied, not a dosing recommendation.
Last evidence review: 2026-06-27