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Review
. 2025 Dec;22(1):2434734.
doi: 10.1080/15502783.2024.2434734. Epub 2024 Dec 19.

International society of sports nutrition position stand: β-hydroxy-β-methylbutyrate (HMB)

John A Rathmacher  1   2 , Lisa M Pitchford  1   3 , Jeffrey R Stout  4 , Jeremy R Townsend  5   6 , Ralf Jäger  7 , Richard B Kreider  8 , Bill I Campbell  9 , Chad M Kerksick  10 , Patrick S Harty  10 , Darren G Candow  11 , Brandon M Roberts  12 , Shawn M Arent  13 , Douglas S Kalman  14 , Jose Antonio  15
Affiliations
Review

International society of sports nutrition position stand: β-hydroxy-β-methylbutyrate (HMB)

John A Rathmacher et al. J Int Soc Sports Nutr. 2025 Dec.

Abstract

Position Statement: The International Society of Sports Nutrition (ISSN) bases the following position stand on an analysis of the literature regarding the effects of β-Hydroxy-β-Methylbutyrate (HMB). The following 12 points have been approved by the Research Committee of the Society: 1. HMB is a metabolite of the amino acid leucine that is naturally produced in both humans and other animals. Two forms of HMB have been studied: Calcium HMB (HMB-Ca) and a free acid form of HMB (HMB-FA). HMB-FA appears to lead to increased appearance of HMB in the bloodstream when compared to HMB-Ca, though recent results are mixed. 2. The available safety/toxicity data suggest that chronic HMB-Ca and HMB-FA consumption are safe for oral HMB supplementation in humans up to at least one year. 3. There are no negative effects of HMB-Ca and HMB-FA on glucose tolerance and insulin sensitivity in humans. There may be improvements in glucose metabolism in younger adults. 4. The primary mode of action of HMB appears to be through its dual mechanism to enhance muscle protein synthesis and suppress muscle protein breakdown. HMB's activation of mTORC1 is independent of the leucine-sensing pathway (Sestrin2-GATOR2 complex). 5. HMB may help reduce muscle damage and promote muscle recovery, which can promote muscle growth/repair. HMB may also have anti-inflammatory effects, which could contribute to reducing muscle damage and soreness. 6. HMB consumption in close proximity to an exercise bout may be beneficial to increase muscle protein synthesis and attenuate the inflammatory response. HMB can provide a beneficial physiological effect when consumed both acutely and chronically in humans. 7. Daily HMB supplementation (38 mg/kg body weight) in combination with exercise training may improve body composition through increasing lean mass and/or decreasing fat mass with benefits in participants across age, sex, and training status. The most pronounced of these improvements in body composition with HMB have been observed in studies with robust resistance training programs and dietary control. 8. HMB may improve strength and power in untrained individuals, but its performance benefits in trained athletes are mixed and increase with an increase in study duration (>6 weeks). HMB's beneficial effects on athletic performance are thought to be driven by improved recovery. 9. HMB supplementation appears to potentially have a positive impact on aerobic performance, especially in trained athletes. The mechanisms of the effects are unknown. 10. HMB supplementation may be important in a non-exercising sedentary and aging population to improve muscle strength, functionality, and muscle quality. The effects of HMB supplementation with exercise are varied, but the combination may have a beneficial effect on the treatment of age-associated sarcopenia under select conditions. 11. HMB may be effective in countering muscle disuse atrophy during periods of inactivity due to illness or injury. The modulation of mitochondrial dynamics and lipid metabolism by HMB may be a potential mechanism for preventing disuse atrophy and aiding rehabilitation beyond HMB's effects on rates of muscle protein synthesis and degradation. 12. The efficacy of HMB in combination with certain nutrients may be enhanced under select conditions.

Keywords: leucine; sport nutrition; supplementation; β-Hydroxy-β-Methylbutyrate.

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Conflict of interest statement

JAR is currently employed by MTI Biotech Inc., Ames IA and continues his research with HMB studies. JAR was a principal investigator for clinical and animal studies with HMB while previously employed at Metabolic Technologies, Inc., which until recently had marketed HMB-Ca and HMB-FA. JAR is listed as an inventor on a number of active HMB-related patents. JAR has received federal grants to conduct research on HMB-Ca.

LMP is a former full-time employee of and current consultant for MTI Biotech Inc., Ames IA. LMP was involved in the conduct and reporting of results for clinical and animal studies with HMB while previously employed at Metabolic Technologies, Inc., which until recently had marketed HMB-Ca and HMB-FA. LMP is listed as an inventor on active HMB-related patents.

JRT has no conflict of interest related to this manuscript in terms of financial or business interests. JRT has received grants and contracts to conduct research on dietary supplements, has served as a paid consultant for industry, and has received honoraria for speaking at conferences. JRT is listed as an inventor of previously filed HMB-related patents.

JRS has no conflict of interest related to this manuscript in terms of financial or business interests. He has received grants and contracts to conduct research on dietary supplements, including HMB, over the past 25 years. He has also served as a paid consultant for the industry and received honoraria for speaking at conferences and writing lay articles about sports nutrition ingredients and topics. In addition, JRS has received financial support from the National Institute on Aging (R03AG06799) and the National Institute on Minority Health and Health Disparities (R01MD018025).

RJ has received grants and contracts to conduct research on dietary supplements; has served as a paid consultant for industry; has received honoraria for speaking at conferences and has served as an expert witness on behalf of the plaintiff and defense in cases involving dietary supplements. RJ is listed as an inventor of HMB-related patents.

CMK has received grants and contracts to conduct research on dietary supplements; has served as a paid consultant for industry and has received honoraria for speaking at conferences involving dietary supplements. CMK currently serves as the President of the International Society of Sports Nutrition (ISSN).

PSH has received grants and in-kind support to conduct research on dietary supplements and has received honoraria for speaking at conferences involving dietary supplements.

DGC has conducted industry-sponsored research involving creatine supplementation and received creatine donations for scientific studies and travel support for presentations involving creatine supplementation at scientific conferences. In addition, DGC. serves on the Scientific Advisory Board for Alzchem and Create (companies that manufacture creatine products) and as an expert witness/consultant in legal cases involving creatine supplementation.

BMR has no poteintial conflicts of interest related to this manuscript.

SMA has received federal and industry grants to conduct research on dietary supplements, has served as a paid consultant for industry, and has received honoraria for speaking at conferences involving dietary supplements.

DSK has received research grants and honorarium from companies in the dietary supplement and foods industry. This includes companies that may retail HMB.

JA is the CEO of the International Society of Sports Nutrition (ISSN), which is a 501c3 academic non-profit. The ISSN has received on occasion grant support from companies that sell, market, or manufacture HMB.

The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of the Army or the Department of Defense. Any citations of commercial organizations and trade names in this report do not constitute an official Department of the Army endorsement of approval of the products or services of these organizations

Figures

Figure 1.
Figure 1.
HMB (β-hydroxy-β-methylbutyrate) is the active metabolite of leucine, a branched chain amino acid. HMB is naturally occurring in humans and animals.
See this image and copyright information in PMC

References

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