Combined creatine and β-hydroxy-β-methylbutyrate supplementation with integral conditioning exercise enhances functional performance and metabolic health in physically active older adults: A randomized controlled crossover trial
Rafael Ramos-Hernández, Natalia Busto, et al. • Aging Clinical and Experimental Research • 2026
Six weeks of combined creatine monohydrate and β-hydroxy-β-methylbutyrate supplementation integrated with supervised multicomponent training enhanced mobility, metabolic efficiency, and selected physiological outcomes in physically active older adults.
Key Findings
Results
CRE + HMB supplementation significantly improved all four functional performance measures compared to placebo.
Functional tests assessed included 4-m gait speed, 5-repetition sit-to-stand (STS), Timed Up and Go (TUG), and 400-m walk
All improvements reached statistical significance at p < 0.05
Effect sizes were large, with partial eta-squared values (η²p) ranging from 0.15 to 0.29
Sample included 30 physically active adults aged ≥ 60 years (20 men, 10 women)
Intervention duration was 6 weeks with 4 exercise sessions per week
Results
CRE + HMB supplementation increased basal metabolic rate and metabolic rate index, with favorable trends in visceral adiposity.
Basal metabolic rate and metabolic rate index both increased significantly with CRE + HMB supplementation
Visceral adiposity showed favorable trends, though the paper notes these as trends rather than reaching full statistical significance
These metabolic outcomes were assessed pre- and post-intervention in both conditions
The crossover design allowed within-subject comparison of CRE + HMB versus placebo effects
Results
Sex-specific differences were observed in physiological responses to CRE + HMB supplementation.
Women exhibited reductions in diastolic blood pressure with CRE + HMB supplementation
Women also showed higher expiratory strength compared to the placebo condition
Men showed a transient rise in endothelial protein C receptor (EPCR) during the CRE + HMB condition
The clinical significance of the transient EPCR rise in men was not characterized as adverse
Results
The crossover trial design showed no period, sequence, or carryover effects between the two intervention phases.
The study used a randomized, double-blind, placebo-controlled crossover design
Two 6-week intervention phases (CRE + HMB or placebo) were separated by a 3-week washout period
Absence of period, sequence, and carryover effects supports the validity and internal consistency of the crossover methodology
30 participants completed both intervention phases
Methods
The multicomponent exercise program combined strength, endurance, and coordination training delivered at 4 sessions per week over 6 weeks.
Exercise was described as an 'integral conditioning exercise' or 'supervised multicomponent exercise program'
Training included strength, endurance, and coordination components
Sessions were delivered 4 times per week for 6 weeks
The exercise program was the same in both the CRE + HMB and placebo phases of the crossover
Participants were physically active older adults aged ≥ 60 years at baseline
Conclusions
The authors characterized the CRE + HMB combined supplementation strategy as safe and feasible in physically active older adults.
No serious adverse events were reported that would contraindicate the approach
The authors described the strategy as 'safe, feasible, and practical'
The approach was evaluated specifically in physically active adults aged ≥ 60 years, a population for whom evidence was described as scarce
The goal framed was sustaining 'functional independence and metabolic health with aging'
What This Means
This research suggests that combining two dietary supplements — creatine monohydrate and β-hydroxy-β-methylbutyrate (HMB) — with a structured exercise program can improve physical function and metabolic health in older adults who are already physically active. In a study of 30 adults aged 60 and older, participants who took the supplement combination for six weeks showed improvements in walking speed, ability to rise from a chair, balance and mobility (Timed Up and Go test), and endurance walking compared to when they took a placebo. The effect sizes were described as large, meaning the differences were not just statistically significant but also practically meaningful.
The study also found that the supplement combination increased resting metabolic rate and showed favorable trends in visceral (belly) fat. Some differences emerged between men and women: women experienced reductions in diastolic blood pressure and showed greater expiratory (breathing out) strength, while men had a temporary increase in a blood protein called EPCR. The crossover design — where every participant experienced both the supplement and placebo conditions — strengthened the reliability of the findings, and no problematic carry-over effects were detected between the two phases.
This research matters because maintaining physical function and independence is a major concern as people age, and many older adults struggle with declining muscle strength and mobility even when they are relatively active. This study suggests that adding creatine and HMB to a structured multicomponent exercise program may provide additional benefits beyond exercise alone, offering a potentially practical and safe strategy for supporting healthy aging. The authors note that evidence for this combination specifically in active older adults was previously scarce, making this study a meaningful contribution to the field.
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Rafael Ramos-Hernández, Natalia Busto, Álvaro Miguel-Ortega, María Martínez-Ferrán, Mirian Santamaría-Peláez, Miriam Saiz-Rodríguez, et al.. (2026). Combined creatine and β-hydroxy-β-methylbutyrate supplementation with integral conditioning exercise enhances functional performance and metabolic health in physically active older adults: A randomized controlled crossover trial. Aging Clinical and Experimental Research. https://doi.org/10.1007/s40520-025-03312-0