Hydroxyplex
Also known as: HMB, Hydroxyplex, Beta-hydroxy-beta-methylbutyrate
Overview
Beta-hydroxy-beta-methylbutyrate (HMB) is a naturally occurring metabolite of the essential amino acid leucine, found in small quantities in foods such as grapefruit, alfalfa, and catfish. It is widely utilized as a dietary supplement, primarily to support muscle mass and function. HMB is recognized for its anti-catabolic properties, helping to prevent muscle protein breakdown, and its anabolic potential, stimulating muscle protein synthesis. It is commonly used in clinical settings to combat muscle loss in conditions like sarcopenia and in critically ill patients, as well as by athletes seeking to enhance muscle strength and recovery. Research on HMB is extensive, with numerous randomized controlled trials and meta-analyses supporting its modest benefits on muscle strength and mass, though effect sizes are generally small.
Benefits
HMB demonstrates a small but statistically significant effect on increasing skeletal muscle mass, with a Standardized Mean Difference (SMD) of approximately 0.25 (p=0.05), as indicated by meta-analyses. More consistent evidence supports its ability to improve muscle strength, showing an SMD of about 0.31 (p=0.001). These benefits are particularly noted in specific populations: critically ill patients may experience improved nutritional status and nitrogen balance, although evidence for mortality or broader clinical outcomes remains limited. Patients with sarcopenia show improvements in muscle strength, though physical performance gains are less clear. The clinical relevance of these effects may vary depending on an individual's baseline muscle status. Benefits typically manifest over several weeks to months of consistent supplementation.
How it works
HMB primarily modulates muscle protein turnover by influencing both anabolic and catabolic pathways. It stimulates protein synthesis through activation of pathways such as mTOR (mammalian target of rapamycin), which is crucial for muscle growth. Concurrently, HMB inhibits proteolysis, the breakdown of proteins, by interfering with mechanisms like the ubiquitin-proteasome pathway. This dual action helps to reduce muscle catabolism and promote anabolism, thereby preserving and potentially increasing muscle mass. HMB's primary interaction is with skeletal muscle tissue. It is well absorbed orally, allowing sufficient bioavailability to exert its systemic effects on muscle protein dynamics.
Side effects
HMB is generally considered safe with a very low incidence of adverse effects. No common side effects (occurring in >5% of users) have been consistently reported in clinical trials. Uncommon side effects (1-5% of users) may include mild gastrointestinal discomfort, though this is rare. There have been no reports of serious adverse events or rare side effects (<1% of users) directly linked to HMB supplementation. No significant drug interactions have been identified. While there are no established contraindications, caution is advised for individuals with metabolic disorders until more comprehensive data are available. In critically ill and elderly populations, HMB should be used under medical supervision.
Dosage
The minimum effective dose for HMB is approximately 1.5 grams per day, based on clinical trial data. Optimal dosage ranges from 1.5 to 3 grams per day, typically divided into multiple doses throughout the day. The maximum safe dose observed in trials is up to 3 grams per day. HMB can be taken with meals, and while timing relative to exercise may offer additional benefits, it is not considered critical for efficacy. HMB is available in both free acid and calcium salt forms, both of which have demonstrated effectiveness. No specific cofactors are required for absorption, but adequate protein intake in the diet may enhance its overall effects on muscle health.
FAQs
Is Hydroxyplex just HMB?
Hydroxyplex is a branded ingredient that contains HMB, and it may also include other compounds. The primary evidence for its effects is based on HMB itself.
How long does it take to see results from HMB?
Improvements in muscle strength may be noticeable within 4-8 weeks of consistent supplementation, while significant gains in muscle mass may require a longer duration of use.
Is HMB safe for long-term use?
Current research supports the safety of HMB for several months of continuous use. However, long-term data extending beyond 6 months are currently limited.
Does HMB work without exercise?
While HMB's effects are more pronounced when combined with resistance training, some benefits, particularly in preventing muscle loss, have been observed in clinical populations even without structured exercise.
Research Sources
- https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2025.1505797/full – This systematic review and meta-analysis by Ren et al. (2025) investigated HMB's effects in critically ill adults. It found that HMB may improve nutritional status and nitrogen balance, but provided limited evidence for its impact on mortality or muscle catabolism outcomes. The study noted heterogeneity among included studies and a lack of patient-centered outcomes.
- https://pubmed.ncbi.nlm.nih.gov/30982854/ – Bear et al. (2019) conducted a systematic review and meta-analysis of 15 RCTs involving 2137 patients with muscle loss conditions. They reported a small effect on muscle mass (SMD=0.25, p=0.05) and a stronger, more consistent effect on muscle strength (SMD=0.31, p=0.001). The study acknowledged moderate heterogeneity and a risk of bias in some included studies.
- https://pubmed.ncbi.nlm.nih.gov/39071082/ – Su et al. (2024) performed a systematic review and meta-analysis focusing on HMB in sarcopenia patients. The findings indicated that HMB improves muscle strength in this population, though evidence for improvements in physical performance was limited. The authors highlighted the need for more high-quality RCTs in this specific area.
