Vitamin B deficiency and sarcopenia: an integrated narrative review of metabolic, inflammatory, endoplasmic reticulum stress, and myokine signaling pathways.

Abstract

Sarcopenia is an age-related skeletal muscle disorder characterized by progressive decline in muscle mass, strength, and physical performance, leading to frailty, disability, falls, and increased mortality. Although its pathogenesis is multifactorial, growing evidence indicates that vitamin B complex deficiency contributes to muscle deterioration through interconnected metabolic and signaling pathways. This narrative review summarizes current evidence regarding the roles of B vitamins in skeletal muscle biology and their potential contribution to sarcopenia. Vitamin B deficiency impairs mitochondrial energy metabolism by reducing cofactor availability and adenosine triphosphate production, thereby increasing oxidative stress and chronic inflammation. These disturbances may trigger endoplasmic reticulum stress and the integrated stress response, leading to activating transcription factor 4 (ATF4)-dependent induction of growth differentiation factor 15 (GDF15) and fibroblast growth factor 21 (FGF21) expression. Collectively, these changes disrupt protein homeostasis, suppress anabolic signaling, impair neuromuscular function, and alter myokine secretion by reducing anabolic mediators while increasing catabolic and inflammatory myokines, thereby accelerating muscle loss and functional decline. Current evidence is the strongest for vitamins B6, B9, and B12, whereas mechanistic and clinical data for B2, B3, B5, and B7 remain limited. Overall, vitamin B deficiency can be viewed as a modifiable biological contributor to sarcopenia. Well-designed prospective studies and randomized clinical trials are required to clarify causality, validate biomarkers, and determine whether targeted vitamin B supplementation can enhance exercise- and nutrition-based strategies for preserving muscle health in older adults.