NAD+

Nicotinamide adenine dinucleotide (NAD+) is a coenzyme found in every living cell, where it plays a central role in cellular energy metabolism — shuttling electrons between molecules in the electron transport chain, serving as a substrate for sirtuins (NAD+-dependent deacetylases involved in gene regulation, DNA repair, and stress response), and functioning as a co-substrate for poly(ADP-ribose) polymerases (PARPs) involved in DNA repair. NAD+ levels decline substantially with age, and this decline has been associated with impaired mitochondrial function, reduced DNA repair capacity, and other hallmarks of cellular aging in animal models — providing the scientific rationale for NAD+-boosting interventions.¹

NAD+ itself is not effectively absorbed when taken orally because it does not readily cross cell membranes. Practical supplementation strategies instead use biosynthetic precursors that are absorbed and converted to NAD+ inside cells. The two most widely used oral precursors are:

• Nicotinamide riboside (NR): A form of vitamin B3 that is taken up by cells and converted to nicotinamide mononucleotide (NMN) by NR kinases, then to NAD+. NR (sold as NIAGEN and other brands) has GRAS status and New Dietary Ingredient notification status with the FDA. Multiple human pharmacokinetic studies have demonstrated that oral NR dose-dependently and significantly increases whole blood NAD+ levels.²
• Nicotinamide mononucleotide (NMN): A direct precursor to NAD+ that is one step closer in the biosynthetic pathway than NR. NMN is absorbed from the gut — partly by direct cellular transport via the Slc12a8 transporter and partly after conversion to NR — and raises NAD+ levels in human subjects in clinical trials. NMN's regulatory status as a dietary supplement has been contested: in 2022 the FDA notified the industry that NMN was excluded from the dietary supplement definition because it had been investigated as a new drug prior to being marketed as a supplement, though subsequent FDA guidance has been ambiguous and NMN products remain widely commercially available as of 2025.

IV NAD+: Intravenous NAD+ infusions are offered by some wellness clinics as a direct delivery method that bypasses the absorption limitations of oral dosing. IV NAD+ is not FDA-approved for any indication and is administered in clinical settings as an off-label use, sometimes in the context of addiction recovery or anti-aging protocols.

NAD+ precursors are used primarily for longevity and anti-aging support, energy and mitochondrial function, cognitive health, and recovery. The mechanistic case rests on robust animal model data showing that NAD+ repletion reverses or attenuates multiple age-related physiological declines in rodents.

Human clinical trial data is more limited. Studies of NR and NMN in humans have consistently demonstrated that oral supplementation raises NAD+ levels in blood, but translating elevated NAD+ into measurable clinical benefits has proved more difficult. Randomized controlled trials in humans have shown mixed results for outcomes including muscle function, metabolic markers, cognitive performance, and cardiovascular parameters. As of 2025, no large Phase III trial has established clinical efficacy for any aging or longevity indication in humans.¹²

NR: Clinical studies have used doses from 100 mg to 1,000 mg per day. The 8-week dose-ranging study by Trammell et al. found that 100 mg, 300 mg, and 1,000 mg doses produced dose-dependent increases in whole blood NAD+ of approximately 22%, 51%, and 142% respectively, without significant adverse events.² Common supplement doses are 250–500 mg per day.

NMN: Clinical studies have used doses from 100 mg to 1,200 mg per day. No consensus optimal dose is established.

Both precursors are typically taken orally once daily, often in the morning.

Oral (NR and NMN supplements). Intravenous infusion (clinic-administered IV NAD+, off-label).

Store at room temperature away from heat, moisture, and direct light. NMN in particular may degrade at elevated temperatures; refrigeration can prolong stability in some formulations.

NR and NMN are generally well-tolerated in clinical studies at doses up to 1,000–1,200 mg/day. Common mild side effects include nausea, fatigue, and flushing at higher doses. Unlike nicotinic acid (niacin), NR does not cause the characteristic flushing associated with niacin flush at typical supplement doses.²

• NMN regulatory ambiguity: The FDA's 2022 position on NMN's supplement status created commercial uncertainty. Individuals purchasing NMN should be aware that this regulatory status remains unsettled and may affect product availability.
• Precursor vs. outcome gap: Oral precursors reliably raise NAD+ levels, but elevated NAD+ has not yet been definitively linked to the clinical outcomes seen in animal models in human RCTs.
• IV NAD+: Intravenous administration is associated with a characteristic transient flushing, tightness, and nausea during infusion; these effects are related to the infusion rate and typically resolve quickly. The lack of FDA approval and standardized protocols means quality, dosing, and safety oversight varies between clinics.
• Drug interactions: NAD+ precursors may interact with medications that affect NAD+ metabolism, including chemotherapy agents that target NAD+ pathways.