Butyrate improves handgrip strength and physical performance by reducing intestinal leak in post-menopausal women, a randomized controlled trial.

Abstract

Purpose: Menopause is associated with muscle detriment and physical compromise. However, relevant mechanisms and effective interventions remain elusive. We investigated the therapeutic effects of exogenous butyrate administration on skeletal muscle and physical capacity with relevance to intestinal leak as a potential mechanism in post-menopausal women.

Methods: We recruited post-menopausal women as placebo (age = 55.4 ± 3.3 years, n = 76) and butyrate (age = 54 ± 2.8 years, n = 70) groups, along with pre-menopausal women (age = 42.3 ± 3 years, n = 75) as controls. The butyrate group received sodium butyrate (570 mg capsules) daily for 12 weeks. We measured plasma biomarkers of intestinal leak (zonulin) and sepsis (lipopolysaccharide-binding protein, LBP) along with handgrip strength (HGS), gait speed, and physical performance (short physical performance battery, SPPB).

Results: Post-menopausal women had higher zonulin and LBP and lower HGS, gait speed, and SPPB scores than pre-menopausal women (all p < 0.05). Butyrate reduced plasma zonulin and LBP levels and improved HGS and SPPB scores in post-menopausal women (all p < 0.05). We found significant correlations of reduction in plasma zonulin and LBP with improvement in HGS and SPPB in the butyrate group (all p < 0.05). Butyrate also modestly improved respiratory muscle strength and reduced systemic inflammation and oxidative stress in post-menopausal women (all p < 0.05).

Conclusion: Collectively, our findings demonstrate the muscle-protective effects of butyrate through intestinal mucosal repair. Future research is warranted to elucidate the underlying mechanisms of butyrate in post-menopausal women.