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

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.

Superior bioavailability of the calcium salt form of β-hydroxy-β-methylbutyrate compared with the free acid form

“…HMB has been shown to have anabolic and anti-catabolic effects in human skeletal muscle (Wilkinson et al 2013 , 2018 ). However, controversy still exists as to whether these properties can be translated into benefits for athletic populations, although emerging evidence suggest benefits for clinical populations under muscle wasting conditions (Tritto et al 2019 ; Jakubowski et al 2020 ; Phillips et al 2022 ; Wu et al 2015 ; Bear et al 2019 ). It has been argued that the effectiveness of HMB is linked to its pharmacokinetics properties, with current knowledge indicating that HMB-FA is the preferred form due to its superior bioavailability (Wilkinson et al 2013 ; Wilson et al 2013a , b , 2014 ).…”

“…Human studies showed that HMB can counteract age-related muscle loss (Oktaviana et al 2019 ) and muscle wasting in conditions such as bed rest (Deutz et al 2013 ) and cancer (Clark et al 2000 ). The potentially beneficial effects of HMB supplementation on muscle strength and muscle mass in conditions of exacerbated muscle loss has been supported by meta-analyses (Wu et al 2015 ; Bear et al 2019 ), although controversy still exists as to whether HMB can effectively support muscle growth in healthy individuals undergoing resistance training, with current evidence not supporting its use for enhancing training adaptations in young, healthy, trained individuals (Tritto et al 2019 ; Jakubowski et al 2020 ; Phillips et al 2022 ).…”

The influence of resistance exercise training prescription variables on skeletal muscle mass, strength, and physical function in healthy adults: An umbrella review

“…The methodological quality of all included reviews was determined in duplicate using A Measurement Tool to Assess Systematic Reviews (AMSTAR), 9 as previously described, 10 , 11 to yield a score ranging from 1 to 11. Three authors (BSC, CVL, and JCM) systematically synthesized the evidence from each review to produce a standardized effectiveness statement (sufficient evidence, some evidence, insufficient evidence, insufficient evidence to determine; see Supplementary Table 2 ) for each outcome.…”

Nobiletin Improves D-Galactose-Induced Aging Mice Skeletal Muscle Atrophy by Regulating Protein Homeostasis

“…Given the inconsistent results of previous studies on the benefits of protein supplementation on skeletal muscle mass and function in the elderly, it is still unclear if it is necessary or should be increased [9]. Notably, contradictory results have been reported in recent study on the effect of HMB on improving skeletal muscle mass and function in older individuals [10]. Although vitamin D supplementation has been shown to increase muscle mass in older individuals, the exact dosage, frequency, and length of treatment are unknown [9].…”