What this means
This is a plan for a study, so no results are available yet. It will test whether the supplements affect muscle, thinking, fitness and immune markers.
Plain-English summary written by an AI model from the abstract. The original is below.
- Who it was tested in
- 120 community-dwelling adults aged 65 and older, planned
- Kind of research
- A study
The science
- Original title
- Effects of β-hydroxy-β-methylbutyrate (HMB) and/or 2-hydroxybenzylamine (2-HOBA) on markers of healthspan in older adults (H2AGE trial): study protocol of a randomised controlled trial at the Canadian Translational Geroscience Network.
- Authors
- Hajj-Boutros G, Birtulescu S, Balram S et al.
- Journal
- BMJ open
- Published
- Oct 12, 2026
- Study type
- Study
- PMID
- 42864138 ↗
Abstract
Background
Ageing is associated with progressive declines in muscle mass, cognitive performance, cardiorespiratory fitness and immune function, which together compromise quality of life and increase healthcare burden. Nutritional interventions such as β-hydroxy β-methylbutyrate (HMB) and 2-hydroxybenzylamine (2-HOBA) have shown promise in mitigating muscle atrophy and neuroinflammation, respectively. HMB has demonstrated anabolic effects on skeletal muscle, while 2-HOBA has been shown to reduce oxidative stress and inflammation. Importantly, chronic low-grade inflammation and oxidative stress are recognised contributors to anabolic resistance in ageing muscle, suggesting that reducing inflammatory burden may potentiate the anabolic effects of HMB. To date, no study has evaluated their combined effect on healthspan-related outcomes in older adults. This trial aims to investigate the individual and synergistic effects of HMB and 2-HOBA supplementation on muscle mass and strength, cognitive function, cardiorespiratory fitness and immune biomarkers in healthy older adults.
What they did
This is a 12-week, randomised, double-blind, placebo-controlled, 2×2 factorial trial involving 120 community-dwelling adults aged ≥65 years. Participants (males and females; 1:1 ratio) will be randomised into four groups: HMB (1.5 g two times per day), 2-HOBA acetate (325 mg two times per day), HMB+2-HOBA or matching placebo. The primary outcome is change in total body skeletal muscle mass assessed by the D3-creatine dilution method. Secondary outcomes include muscle strength (Biodex dynamometry), VO2 peak (cycle ergometry), cognitive function (Cambridge Neuropsychological Test Automated Battery, digit span and the Rey Auditory Verbal Learning Test) and immune and inflammatory biomarkers assessed by multiparameter flow cytometry and Olink proteomic profiling. Statistical analyses will follow a 2×2 factorial framework using mixed-effects models with fixed effects for HMB, 2-HOBA, time and the HMB×2-HOBA interaction, allowing estimation of the main effects of each intervention and their combined effect. Ordinal or non-normally distributed functional outcomes will be analysed using generalised linear models as appropriate. Analyses will follow both intention-to-treat and per-protocol principles, with appropriate handling of missing data.
Other details
Ethics approval has been obtained from the Research Ethics Board at McGill University Health Centre (REB #2026-11610). Results will be published in peer-reviewed journals and made available to key aged care stakeholders, including providers, residents and government bodies. NCT07419633.
The authors' abstract, grouped under plain headings from its own section labels.
Hajj-Boutros G, Birtulescu S, Balram S et al. Effects of β-hydroxy-β-methylbutyrate (HMB) and/or 2-hydroxybenzylamine (2-HOBA) on markers of healthspan in older adults (H2AGE trial): study protocol of a randomised controlled trial at the Canadian Translational Geroscience Network. BMJ open. 2026. doi:10.1136/bmjopen-2026-119962. PMID: 42864138. https://pubmed.ncbi.nlm.nih.gov/42864138/