Effects of NAD⁺-Boosting Interventions on Human Aging: A Systematic Review and Meta-analysis Protocol

This project is a systematic review and meta-analysis examining the effects of NAD⁺-boosting interventions on biological, dermatologic, metabolic, mitochondrial, and functional indicators of human aging. NAD⁺ levels decline with age, contributing to reduced mitochondrial function, impaired DNA repair, oxidative stress, inflammation, skin aging, and decreased metabolic and physiological resilience. Interventions such as nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), oral NAD⁺, and intravenous NAD⁺ infusions are widely used, but evidence remains inconsistent and scattered across studies with different designs, outcomes, and populations. The purpose of this review is to synthesize all available human clinical data to determine whether NAD⁺-boosting therapies produce measurable improvements in aging-related outcomes. Key endpoints include NAD⁺ levels, mitochondrial and oxidative stress biomarkers, inflammatory cytokines, epigenetic aging clocks, dermatologic aging measures (elasticity, wrinkles, collagen), metabolic markers (insulin sensitivity, glucose, lipids), functional outcomes (fatigue, cognition, physical performance), and safety. Eligible studies include randomized controlled trials and controlled intervention studies in adults. Major databases (PubMed, Embase, Scopus, Web of Science, CENTRAL) and clinical trial registries will be searched. Data extraction, risk of bias assessment, and synthesis will follow PRISMA guidelines. Meta-analyses will be performed when feasible, and subgroup analyses will evaluate differences by intervention type, route, dose, duration, and population. The expected outcome is a comprehensive, evidence-based evaluation of NAD⁺-boosting therapies to inform clinical practice in longevity, metabolic health, and aesthetic medicine, and to identify research gaps for future trials.