The Effect of Nicotinamide Mononucleotide and Riboside on Skeletal Muscle Mass and Function: A Systematic Review and Meta‐Analysis

Introduction Sarcopenia is associated with the loss of skeletal muscle function and mass. Nicotinamide precursors, such as nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), have received attention for their potential to improve NAD + levels and mitigate age‐related sarcopenia in preliminary models, though evidence on their effects in older adults remains inconclusive. Methods We searched PubMed, Cochrane Library, Web of Science, and Scopus to identify randomized controlled trials (RCTs), comparing NR or NMN vs. placebo. A random‐effects meta‐analysis was employed to determine their impact on measures of sarcopenia such as skeletal muscle index (SMI), handgrip strength (HGS) and gait speed. A narrative synthesis was used for 5‐time chair stand test (5CST), short physical performance battery (SPPB), timed‐up‐and‐go (TUG), 6‐min walking distance (6MWD), leg and chest press 80% 1RM (repetition maximum) and thigh muscle mass. Results Included participants had a mean age range from 60.9 to 83 years. NMN supplementation showed no significant effects on SMI ( n = 3; mean difference (MD): −0.42, 95% confidence interval (CI): −0.99 – 0.14, I 2 = 63%, p = 0.14), HGS (One study estimating left grip; n = 5; MD: 0.61, 95%CI: −0.89 – 2.10, I 2 = 0%, p = 0.42; One study estimating right grip; n = 5; MD: 0.45, 95%CI: −1.06 – 1.96, I 2 = 0%, p = 0.56), gait speed ( n = 4; MD: ‐0.01, 95%CI: −0.08 – 0.06, I 2 = 0%, p = 0.79), or 5CST ( n = 2; MD: ‐0.21, 95%CI: −0.70 – 0.29, I 2 = 11%, p = 0.41). Additionally, our narrative synthesis showed that NMN did not improve knee extension strength, SPPB, or thigh muscle mass. NR supplementation was associated with a longer 6MWD among individuals with peripheral artery disease. However, lower scores in the SPPB and slower 5CST were observed in those with mild cognitive impairment. Conclusions Current evidence does not support NMN and NR supplementation for preserving muscle mass and function in adults with mean age of over 60 years. Future research should explore supplementation dosage, NAD + baseline deficiency, and combined interventions.