Nicotinamide Riboside Supplementation Protects Against Heat-Induced Skeletal Muscle Injury in Female Mice

Micronutrients are essential for optimal muscle metabolic function. We previously showed that heat-induced skeletal muscle injury is associated with depletion of nicotinamide adenine dinucleotide (NAD⁺) and magnesium (Mg²⁺), and boosting NAD⁺ abundance with the precursor nicotinamide riboside (NR) improves skeletal muscle integrity against heat stress in male mice. In this study, we hypothesized that NR supplementation would prevent heat-induced skeletal muscle injury in female mice. Female 6-week-old C57BL/6J mice were orally administered vehicle or NR (185 mg/kg body weight) daily for 10 days. Subsequently, they underwent a single sham or heat exposure experiment. No significant differences in muscle NAD⁺ content were observed between vehicle and NR groups or between sham and heat groups. Heat groups showed significantly lower muscle Mg²⁺ levels compared to sham groups. In vehicle groups, heat exposure caused significant inflammation, oxidative stress, mitochondrial impairment, and apoptosis in skeletal muscle compared to the sham condition. NR treatment significantly reduced these alterations. While neither heat exposure nor NR affected muscle NAD⁺ homeostasis, the protective effects of NR on skeletal muscle against heat stress were similar to those observed in male mice. Together, our results demonstrate the preventive effect of NR on muscle heat injury in female mice. This effect is associated with anti-inflammatory and antioxidative activities, mitochondrial protection, and anti-apoptosis without NAD⁺ homeostatic alterations.