Narrative review of intravenous NAD<sup>+</sup> and NAD<sup>+</sup> precursors in wellness and translational medicine.

<h4>Background</h4>Nicotinamide adenine dinucleotide (NAD⁺) is a major coenzyme critically involved in cellular metabolism, mitochondrial function, DNA repair, and stress-response signaling. Age-associated decline in NAD⁺ levels has generated interest in NAD⁺-augmenting strategies; however, recent large-scale human data indicate that whole-blood NAD⁺ concentrations do not decline with healthy aging <i>per se</i>. Despite increasing commercial use of IV NAD⁺ therapy in wellness settings, the clinical evidence supporting its efficacy and long-term safety remains limited.<h4>Methods</h4>Literature published between January 2018 and March 2026 was identified <i>via</i> PubMed and Google Scholar searches. Search terms were applied symmetrically across all target compounds and administration routes. Studies were included if they reported human clinical data on IV NAD⁺ or IV NAD⁺ precursor administration, or if they provided directly relevant mechanistic or safety evidence. Mechanistic and foundational studies published before 2018 were selectively incorporated <i>via</i> citation tracking of key included articles.<h4>Results</h4>Available human evidence is sparse and consists primarily of small uncontrolled studies, observational investigations, and isolated case reports. Short-term IV NAD⁺ or NMN administration has been associated with transient increases in circulating NAD⁺ levels and changes in selected biomarkers related to oxidative stress, inflammation, and cellular metabolism. Limited exploratory reports have also described self-reported improvements in sleep-related outcomes and neurologic symptoms. However, the clinical significance of these findings remains uncertain due to small sample sizes, lack of placebo controls, heterogeneous methodologies, and short follow-up durations. Reported adverse effects include nausea, cramping, flushing, and chest discomfort, while long-term safety data are lacking.<h4>Conclusion</h4>Current evidence regarding IV NAD⁺ therapy remains preliminary and insufficient to support routine clinical or wellness use. Although mechanistic and translational studies provide biological rationale for NAD⁺ augmentation, robust conclusions regarding efficacy, durability of benefit, optimal dosing, and long-term safety cannot currently be established. Larger randomized controlled trials with standardized protocols and clinically meaningful endpoints are required before IV NAD⁺ therapy can be considered evidence-based clinical practice.