Background/Objectives: Nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD+), is used as a dietary supplement, but its safety and metabolic effects in adults remain unclear. This review assessed the short-term safety and tolerability of oral NMN or NMN-related supplementation and examined metabolic and vascular outcomes. Methods: PubMed, Embase, Scopus, Web of Science, CNKI, and Wanfang were searched from inception to 13 May 2026. Eligible studies were parallel randomized controlled trials comparing oral NMN or NMN-related preparations with placebo, blank control, lifestyle control, or the same background intervention without NMN. Safety outcomes included adverse events, serious adverse events, withdrawals due to adverse events, system-specific adverse events, alanine aminotransferase, and aspartate aminotransferase. Random-effects models were used, with GRADE for evidence certainty. Results: Fifteen trials were included, with 10 contributing to safety analyses. NMN doses ranged from 250-2000 mg/day, and durations ranged from 14 days to 24 weeks. NMN did not increase overall, serious, withdrawal-related, or system-specific adverse events, nor did it significantly elevate ALT or AST. No significant effects were observed on body weight, BMI, fasting glucose, HbA1c, lipid profiles, or systolic blood pressure. Diastolic blood pressure decreased slightly, while HOMA-IR showed a non-significant downward trend. Conclusions: Short-term oral NMN or NMN-related supplementation showed favorable tolerability, with no clear increase in adverse events or hepatic biochemical abnormalities. Broad metabolic benefits were not evident, but changes in diastolic blood pressure and HOMA-IR suggest preliminary vascular-metabolic signals, especially in older adults or people with early metabolic risk. Larger and longer trials should confirm efficacy and long-term safety. This review was registered in PROSPERO (CRD420261382497).
