Effects of β‐hydroxy β‐methylbutyrate (HMB) supplementation on muscle mass, function, and other outcomes in patients with cancer: a systematic review

Abstract

Low muscle mass is prevalent among patients with cancer and a predictor of adverse clinical outcomes. To counteract muscle loss, β-hydroxy β-methylbutyrate (HMB) supplementation has been proposed as a potential therapy for older adults and various diseases states. This systematic review aimed to investigate the effects and safety of HMB supplementation in relation to muscle mass and function and other clinical outcomes in patients with cancer. A systematic search of MEDLINE, CINAHL, Embase, Cochrane Central Register of Controlled Trials, Scopus, ProQuest, and grey literature for reports published from inception to December 2021 was conducted. Included studies provided supplements containing any dose of HMB to adult patients with active cancer. A synthesis without meta-analysis was conducted using a vote-counting approach based solely on the direction of the effect (i.e. regardless of statistical significance). Risk of bias was assessed for each outcome domain, and evidence from higher-quality studies (i.e. those with either low or moderate risk of bias) was examined. Safety was evaluated using both lower-quality and higher-quality studies. Fifteen studies were included, in which six were randomized controlled trials in patients with various cancer types and treatments. Studies prescribed HMB combined with amino acids (73.3%), HMB in oral nutritional supplements (20.0%), or both supplement types (6.7%); Ca-HMB doses of 3.0 g/day were provided in 80.0% of the studies. Four studies had high risk of bias across all outcome domains. Considering the higher-quality studies, evidence of a beneficial effect of HMB supplementation was found in four of four studies for muscle mass, two of two for muscle function, three of three for hospitalization, and five of seven for survival. In contrast, no beneficial effects of HMB on quality of life or body weight was found in two of four and three of five studies, respectively. A limited number of higher-quality studies evaluating the impact of HMB on cancer therapy-related toxicity, inflammation, and tumour response were observed. No serious adverse effects directly related to the nutrition intervention were reported. Although limited, current evidence suggests that HMB supplementation has a beneficial effect on muscle mass and function in patients with cancer. Well-designed trials are needed to further explore the clinical benefit of HMB supplementation in this patient population.

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

“…A total of 231 studies were screened for eligibility, 92 were removed as duplicates, 104 articles were excluded based on title and abstract screening, and 20 were excluded upon full‐text assessment (see supporting information ). The 15 systematic reviews 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 that met our PICOS criteria ( Table 1 ) were included in our analysis (for details of studies, see supporting information ). AMSTAR scores for the included systematic reviews range from 1 to 9 ( Figure 2 , Table 2 ).…”

“…These papers were retrieved and reviewed in greater detail yielding 14 systematic reviews ( Figure 1 ) pertinent to the research question 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 25 , 26 and according to the PICOS statement ( Table 1 ). One additional study was added, 24 totalling 15 studies. Two authors screened all reviews (K. J. L. and A. C. D.), and a third author checked their results (S. M. P.).…”

“…Ten of the included reviews investigated the effect of HMB supplementation on functional outcome measures. [12][13][14][15]17,20,[23][24][25][26] Bear et al (QoE: level 3), 12 and Cruz-Jentoft et al (QoE: level 2) 17 supported the null hypothesis that HMB supplementation has no impact on functional outcomes in older adult and clinical populations. Specifically, Bear et al 12 found that 4/4 included RCT showed HMB supplementation to not affect functional outcome measures in chronic disease populations.…”

Advances in muscle health and nutrition: A toolkit for healthcare professionals

“…In patients with cancer, higher quality studies also support a beneficial effect of HMB supplementation on improving muscle mass and function, decreasing hospitalization, and improving survival in patients with cancer, in spite of the limited evidence [182].…”

High protein diet in digestive cancers

“…The interest in anabolic players has recently shifted toward a derivative of leucine, β-hydroxy-β-methylbutyrate (HMB). HMB is now included in the formula of different oral nutritional supplements, and has been shown to favour muscle anabolism [29]. Cornejo-Pareja et al [30 ▪ ] tested a HMB-enriched oral nutritional supplement, also containing vitamin D, in 283 adult patients with or at risk of malnutrition under standard of care, 63% being cancer patients.…”