Effects of Exercise Training Combined With β-Hydroxy-β-Methylbutyrate Supplementation on Physical Function in Older Adults With Frailty

Objective To evaluate the additional effects of β-hydroxy-β-methylbutyrate (HMB) supplementation combined with multicomponent exercise training on physical function, muscle mass, and nutritional status in older adults with frailty.

Methods  A randomized, double-blind, placebo-controlled trial was conducted. A total of 136 older adults with frailty admitted to West China Hospital, Sichuan University between March 2023 and March 2025 were enrolled and randomly assigned at a ratio of 1∶1 to an intervention group (n = 68) and a control group (n = 68). Participants in the intervention group received oral calcium HMB supplementation at 3 g/d in addition to exercise training, while those in the control group received maltodextrin placebo on top of the same exercise program. The intervention lasted 12 weeks. Assessments were performed at baseline and after 4 and 12 weeks. The primary outcome measure was the Short Physical Performance Battery (SPPB) score. Secondary outcome measures included the 6-minute walk test (6 MWT), handgrip strength, modified Barthel index (MBI), timed up-and-go test (TUGT), appendicular skeletal muscle index (ASMI), and serum albumin level.

Results Generalized estimating equation analysis showed that SPPB total score had significant time effect (Wald χ² = 235.867, P < 0.001), group effect (Wald χ² = 8.148, P = 0.004), and interaction effect (Wald χ² = 13.846, P < 0.001), indicating greater overall improvement in physical function in the intervention group than that in the control group. After 4 weeks, the intervention group showed significantly better total SPPB score, balance score, 6MWT performance, MBI score, and serum albumin level than the control group did (all P < 0.05). These between-group differences further increased after 12 weeks, with the intervention group continuing to outperform the control group (all P < 0.05). Additionally, at week 12, the intervention group showed significantly better results than the control group did in gait score and ASMI (P < 0.05). Although TUGT was lower in the intervention group than that in the control group at week 12 in the single-timepoint comparison (P < 0.05), the generalized estimating equation analysis showed no significant group effect (P > 0.05). No significant differences were found between the two groups in chair stand test score or handgrip strength at any time point (P > 0.05).

Conclusion Among older adults with frailty, HMB supplementation (3 g/day for 12 weeks) in addition to conventional multicomponent exercise training further improves physical function, muscle mass, and nutritional status. The findings provide new evidence-based support for nonpharmacological intervention for frailty in older adults.