Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Oct;13(5):2265-2275.
doi: 10.1002/jcsm.13030. Epub 2022 Jul 12.

An umbrella review of systematic reviews of β-hydroxy-β-methyl butyrate supplementation in ageing and clinical practice

Affiliations

An umbrella review of systematic reviews of β-hydroxy-β-methyl butyrate supplementation in ageing and clinical practice

Stuart M Phillips et al. J Cachexia Sarcopenia Muscle. 2022 Oct.

Abstract

The compound β-hydroxy-β-methyl butyrate (HMB) is proposed to increase or mitigate the loss of skeletal muscle and improve muscle function. We undertook a review of systematic reviews of HMB supplementation to promote gains or mitigate muscle loss in ageing and clinical populations. Following PRISMA guidelines, we searched for systematic reviews reporting the effect of HMB in our target populations. Dual-energy X-ray absorptiometry (DXA) measured lean soft-tissue mass (LSTM) was accepted as a proxy for muscle. We identified 15 systematic reviews that met our inclusion criteria, which were independently evaluated. The methodological quality of the reviews was assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR), and standardized effectiveness statements were generated. Five of 15 studies found some evidence that HMB augmented LSTM; the remaining 10 studies reported some evidence favouring no difference (6/10 studies) or insufficient evidence to determine an effect (4/10 studies). Of the 12 studies that evaluated strength, 4/12 found some evidence, 5/12 found some evidence of no effect with one article finding some evidence in favour of patients in peri-hospitalized and no evidence for those that are community-dwelling, 4/12 had insufficient evidence to determine an effect, and 1/12 had insufficient evidence. No]study reported a positive effect of HMB on physical function; however, 2/10 studies found some evidence favouring no effect, and 7/10 studies reported insufficient evidence to determine an effect. The effectiveness of HMB supplementation in augmenting LSTM was heterogeneous, with most reviews finding no effect or inconclusive evidence to determine an effect. Most reviews concluded that HMB supplementation did not affect strength outcome measures or studies were inconclusive. The current evidence is insufficient to assess the impact of HMB supplementation on functional outcome measures. Our analysis shows minor, inconsistent support for HMB as part of an oral nutritional supplement or as a stand-alone supplement (or combined with other amino acids) to increase or promote retention of LSTM, improve strength, and no evidence that it improves physical function in older persons or clinical populations.

Keywords: Function; Muscle mass; Sarcopenia; Strength; Supplement.

PubMed Disclaimer

Conflict of interest statement

Dr. Phillips reports currently (or in the prior five years) held grants from the US National Dairy Council and a contract with Roquette during the conduct of the study; personal fees from US National Dairy Council, non‐financial support from Enhanced Recovery, outside the submitted work. In addition, Dr. Phillips has a patent Canadian 3052324 issued to Exerkine, and a patent US20200230197 pending to Exerkine but reports no financial gains. All other authors report no conflicts of interest.

Figures

Figure 1
Figure 1
PRISMA flowchart of papers identified, screened, removed, and included in the review. WoS, Web of Science.
Figure 2
Figure 2
A Measurement Tool to Assess Systematic Reviews (AMSTAR) scores. ‘‐’ indicates no; ‘?’ indicates cannot answer/not applicable; and ‘+’ indicates yes for included reviews.
Figure 3
Figure 3
Comparative stimulation of muscle protein synthesis from resting (fasted) to 150 min post‐ingestion of leucine (3.42 g; Leu), HMB as a free acid (2.42 g; HMB‐FA), and HMB as a calcium salt (3.42 g; Ca‐HMB, equivalent to 2.72 g HMB‐FA). Data are from previous studies., Values are means only.

Similar articles

Cited by

References

    1. Choudry HA, Pan M, Karinch AM, Souba WW. Branched‐chain amino acid‐enriched nutritional support in surgical and cancer patients. J Nutr 2006;136:314–8s. - PubMed
    1. Anthony JC, Yoshizawa F, Anthony TG, Vary TC, Jefferson LS, Kimball SR. Leucine stimulates translation initiation in skeletal muscle of postabsorptive rats via a rapamycin‐sensitive pathway. Journal of Nutrition 2000;130:2413–2419. - PubMed
    1. Norton LE, Layman DK, Bunpo P, Anthony TG, Brana DV, Garlick PJ. The leucine content of a complete meal directs peak activation but not duration of skeletal muscle protein synthesis and mammalian target of rapamycin signaling in rats. Journal of Nutrition. 2009;139:1103–1109. - PubMed
    1. Combaret L, Dardevet D, Rieu I, Pouch MN, Bechet D, Taillandier D, et al. A leucine‐supplemented diet restores the defective postprandial inhibition of proteasome‐dependent proteolysis in aged rat skeletal muscle. J Physiol 2005;569:489–499. - PMC - PubMed
    1. Baier S, Johannsen D, Abumrad N, Rathmacher JA, Nissen S, Flakoll P. Year‐long changes in protein metabolism in elderly men and women supplemented with a nutrition cocktail of beta‐hydroxy‐beta‐methylbutyrate (HMB), L‐arginine, and L‐lysine. JPEN J Parenter Enteral Nutr 2009;33:71–82. - PubMed

Publication types