Combined effects of a low-dose multi-target supplement (CaHMB, CBP, and HA) on delaying musculoskeletal aging

Abstract

Age-related musculoskeletal diseases underscore the importance of comprehensive dietary interventions. The individual benefits of calcium β-hydroxy-β-methylbutyrate (CaHMB), colostrum basic protein (CBP), and hyaluronic acid (HA) on the musculoskeletal system have been well documented; however, their combined effects remain unclear. This study aims to investigate the effects of combined supplementation with CaHMB, CBP, and HA on age-related musculoskeletal degeneration and to explore the underlying mechanisms, with a particular focus on the muscle–bone axis. Twelve-month-old male C57BL/6J mice received a 6-month dietary intervention. The combination (COM) group was supplemented with CaHMB, CBP, and HA at substantially reduced doses (37.5%, 20%, and 14%, respectively). The COM group showed higher lean mass (18%) and a greater muscle cross-sectional area (35%) compared to the OLD group, with significantly enhanced grip strength by 41% and exercise performances. The COM group presented less decline in whole-body bone mineral density (5%) than the OLD group. The bone microstructure was improved by increasing the bone volume fraction and trabecular thickness/number, while a decrease in trabecular separation was observed in the COM group. Musculoskeletal improvements either matched or surpassed the benefits of individual components. Mechanistically, interventions modulated the key mediators of the muscle–bone axis, significantly upregulating beneficial myokines (irisin and IGF-1) and osteokine osteocalcin, while downregulating negative regulators (myostatin and sclerostin). These changes were correlated with the observed phenotypic enhancements. The low-dose combination of CaHMB, CBP, and HA provides comprehensive benefits against age-related muscle and bone loss, likely by modulating the muscle–bone axis, and outperforms individual components. Our findings support its potential as a multi-targeted nutritional strategy for the aging population.