NAD+

NAD+ is a coenzyme that every cell needs. It carries electrons in the reactions that release energy from food. It is also used up by enzymes that act on DNA repair, gene regulation and immune function: the sirtuins, the PARPs and CD38 [1].

Does NAD+ fall with age? Rodent studies and a 2021 review say tissue NAD+ declines with age, and link that decline to many age-related diseases [1]. In mice, CD38-rich inflammatory immune cells, activated by senescent cells, drain NAD+ from fat and liver [4]. The human evidence is weaker. A 2025 review found the age-related fall has been seen consistently in only a few human studies [5]. In 2026, a validated mass-spectrometry method measured whole-blood NAD+ across seven human cohorts. Levels did not change with age or lifestyle, but did rise with NR supplements [6].

Intravenous NAD+. Clinics offer NAD+ drips, but a 2026 systematic review found no outcome trials of intravenous or intramuscular NAD+ for anti-ageing or wellness. Only a pharmacokinetic pilot could be found [2]. In that pilot, 8 healthy men received 750 mg over 6 hours. Plasma NAD+ did not rise at all for the first 2 hours: the infused NAD+ was removed as fast as it went in [3]. In a retrospective review from a wellness-clinic chain, 6 clients received 500 mg a day for 4 days. All of them had moderate to severe side effects during the drip [7].

Oral precursors. Most human trials use nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN), which cells turn into NAD+:

• NR 500 mg twice daily for 6 weeks was well tolerated and raised NAD+ in blood immune cells by about 60% in healthy middle-aged and older adults [8].
• NR 1 g a day for 21 days raised NAD+ metabolites in the muscle of 12 older men and lowered inflammatory cytokines, but did not change mitochondrial function [9].
• NMN 250 mg a day for 10 weeks improved muscle insulin sensitivity in 25 postmenopausal women with prediabetes [10].
• NR 1 g a day for 30 days raised brain NAD+ in 30 people with newly diagnosed Parkinson's disease, by varying amounts [11].
• In 90 people with peripheral artery disease, 6 months of NR improved the 6-minute walk compared with placebo [12].
• In 40 people with COPD, NR 2 g a day for 6 weeks roughly halved sputum IL-8, an inflammatory marker, and more than doubled whole-blood NAD+ [13].

There are negative results too. A 2025 meta-analysis found NR and NMN did not improve muscle mass, grip strength or walking speed in adults over 60 [14]. The 2026 systematic review concluded that the precursors clearly engage their target, but that effects on function, metabolism and blood vessels are inconsistent and often absent [2].

NAD+ switches between its oxidised form (NAD+) and its reduced form (NADH) as it carries electrons through metabolism. Separately, sirtuins, PARPs and CD38 break it down to do their jobs, so the cell has to keep remaking it [1]. The rationale for supplements is that raising NAD+ keeps these enzymes supplied, especially when consumption rises, for example when CD38-rich immune cells accumulate with ageing [4].

Infused NAD+ does not simply stay in the blood as NAD+. The metabolites seen during an infusion point to breakdown by NAD+ glycohydrolase and pyrophosphatase enzymes [3]. In a 2026 comparison, NR and NMN (1 g a day) raised blood NAD+ by similar amounts after 14 days, but nicotinamide did not. Lab work suggested gut bacteria convert NR and NMN into nicotinic acid, which then feeds NAD+ synthesis [15].

NAD+ itself is sold for injection, as intravenous drips or smaller subcutaneous shots. Oral products usually contain NR or NMN, the forms tested in most trials [2]. Its reduced form, NADH, has also been tested by mouth, mainly in chronic fatigue syndrome. A systematic review of trials of NADH and precursors found them well tolerated [16].

Intravenous NAD+ is poorly tolerated at the rates clinics use. In the clinic review, all 6 people given 500 mg had abdominal cramping, diarrhoea, nausea, vomiting, a faster heart rate and chest pressure. These stopped when the infusion ended. The same dose of NR by drip caused only mild tingling and cramping. Liver, kidney and thyroid markers did not change, but HDL cholesterol fell after NAD+ [7]. That study was small and retrospective, and its authors worked for the clinic chain [7].

The oral precursors were well tolerated for weeks to months in trials [2][8].

No drug interactions have been documented for NAD+ itself.