How does it work?
NAD+ exists in two forms that cells switch between (NAD+ and NADH), and this switching drives energy production in the mitochondria. In addition, NAD+ is "consumed" by enzymes such as sirtuins and PARPs, which help regulate genes and repair damaged DNA. The body makes NAD+ from, among other things, precursors (building blocks) such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). Because the NAD+ molecule itself is large and poorly absorbed through the gut, the vast majority of human studies have used these precursors to raise NAD+ levels indirectly, rather than giving NAD+ directly.
Technical mechanism
Universal redox cofactor in cellular energy metabolism. Activates sirtuins and PARP enzymes involved in DNA repair and epigenetic regulation.
What is being researched?
- How cells convert nutrients into energy (energy metabolism)
- The activity of sirtuins and enzymes that repair DNA
- Changes in NAD+ levels with increasing age
- Whether the precursors NR and NMN can raise NAD+ levels in blood and muscle
- Physical capacity, metabolic markers and safety when using precursors
About the evidence: Much of what is described as "NAD+ research" in humans has actually been carried out with precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), not with NAD+ directly. These precursor studies fairly consistently show that NAD+ levels in the blood rise, but the effects on performance, health and ageing remain unclear and partly mixed. Direct NAD+ (for example given intravenously) has very limited controlled documentation in humans. Much of the basic research is also preclinical (cells and animals). The content here is intended for research and education only, and is not health advice.
Research profile
Studies and sources
The links go to independent research databases (PubMed, PubMed Central, ClinicalTrials.gov). The studies are in English and open in a new tab.
NAD+ biology: energy, sirtuins and ageing
Fundamental review articles describe how NAD+ drives energy metabolism and supplies sirtuins and DNA repair enzymes, and how NAD+ levels appear to fall with age. Much of this is based on cell and animal experiments.
- NAD+ metabolism and its roles in cellular processes during ageing ReviewPubMed· 2020
This review article describes how the molecule NAD+ is central to cells' energy turnover, DNA repair and other important functions. The authors explain that the level of NAD+ in the body gradually falls with age in both animals and humans, and that this is linked to several age-related diseases. They point out that restoring NAD+ levels in experiments has been able to slow certain conditions, but stress that much is still uncertain, including whether it is safe and useful in humans.
- Sirtuins, Metabolism, and DNA repair ReviewPubMed· 2014
This review article describes how cells coordinate the availability of nutrients with their own activity, and how repair of damaged DNA is important for avoiding instability in the genetic material. The authors explain that a family of proteins called sirtuins appears to control both energy turnover and DNA repair. The article summarises recent research on how these two processes may be connected. This is a review of existing knowledge, not a new study.
The precursor nicotinamide riboside (NR) in humans
Several placebo-controlled studies have investigated whether oral NR safely raises NAD+ levels in blood and muscle, and what effects, if any, it produces. Levels rise reliably, but the clinical effects are mixed.
- Nicotinamide riboside is uniquely and orally bioavailable in mice and humans Clinical (human)PubMed· 2016
In this study, the researchers investigated how supplementation with nicotinamide riboside (NR) affects NAD+ in the blood in humans. They found that a single dose could clearly raise the NAD+ level, and that higher doses (100, 300 and 1,000 mg) produced a greater increase. The researchers also discovered a substance (NAAD) that proved to be a sensitive marker that NAD+ really was being replenished. This was the first clinical investigation of how NR is metabolised in humans.
- Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures Clinical (human)PubMed· 2019
In this study, twelve older men received supplementation with nicotinamide riboside (NR), 1 gram daily for 21 days, compared with a dummy treatment (placebo). The researchers found that NR increased NAD+-related substances in skeletal muscle, but without changing the muscles' energy production. NR also appears to have an anti-inflammatory effect, in that the level of inflammatory substances in the blood fell. The study was small and short.
- Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults Clinical (human)PubMed· 2019
In this study, overweight but otherwise healthy adults received supplementation with nicotinamide riboside (NR) for eight weeks. Doses of 100, 300 and 1,000 mg raised NAD+ in the blood in a dose-dependent manner (by 22, 51 and 142 per cent respectively), and the increase was maintained throughout the study. There was no difference in side effects between NR and placebo, and no flushing. NR also did not raise "bad" cholesterol. The researchers consider that the data support NR being safe at these doses.
- Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study Clinical (human)PubMed· 2017
In this study, 120 healthy adults aged between 60 and 80 received either placebo, a recommended dose or a double dose of a dietary supplement (NRPT) combining nicotinamide riboside and pterostilbene. The researchers found that the supplement raised NAD+ in the blood in a dose-dependent manner, with an increase of around 40 per cent at the standard dose and around 90 per cent at the double dose, and the increase was maintained for eight weeks. No serious side effects were reported.
- Effects of nicotinamide riboside on NAD+ levels, cognition, and symptom recovery in long-COVID: a randomized controlled trial Clinical (human)PubMed· 2025
In this study, 58 people with long-term COVID symptoms received either nicotinamide riboside (NR) or placebo for up to 20 weeks. NR raised NAD+ in the blood 2.6 to 3.1 times. Even so, the researchers found no clear difference between the groups in thinking ability, fatigue, sleep, anxiety or low mood. Many participants in the NR group dropped out along the way. NR raised the level of NAD+, but did not clearly improve symptoms compared with placebo.
The precursor nicotinamide mononucleotide (NMN) in humans
Randomised studies have explored the safety and possible effects of NMN on NAD+ levels, physical capacity and metabolic markers in healthy adults. NMN appears well tolerated in these studies, but long-term data are still lacking.
- The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial Clinical (human)PubMed· 2023
In this study, 80 healthy middle-aged adults received placebo or nicotinamide mononucleotide (NMN) at doses of 300, 600 or 900 mg daily for 60 days. NMN raised NAD+ in the blood in all dose groups. Those who received NMN walked further in a six-minute walk test, and a calculated "biological age" remained stable instead of increasing as it did in the placebo group. NMN was well tolerated with no safety problems. The effect was greatest at 600 and 900 mg.
- Safety evaluation of β-nicotinamide mononucleotide oral administration in healthy adult men and women Clinical (human)PubMed· 2022
In this study, the researchers investigated the safety of nicotinamide mononucleotide (NMN). 31 healthy adults aged between 20 and 65 took 1,250 mg of NMN once daily for up to four weeks. Blood tests, urine tests and body measurements showed no changes beyond normal variation, and no serious side effects were observed. The researchers concluded that this dose of NMN was safe and well tolerated over the short period the study lasted.
- Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study Clinical (human)PubMed· 2021
In this study, 48 recreational runners did six weeks of training combined with either placebo or nicotinamide mononucleotide (NMN) at doses of 300, 600 or 1,200 mg daily. The researchers measured fitness with an exercise test. Those who received the medium and high doses of NMN increased their oxygen uptake and performance more than the placebo group. Maximal fitness (VO2max) did not change. The researchers consider that NMN improved the body's use of oxygen in the muscles during exercise.
- Nicotinamide Mononucleotide Is Safely Metabolized and Significantly Reduces Blood Triglyceride Levels in Healthy Individuals Clinical (human)PubMed· 2022
In this study, the researchers investigated administration of nicotinamide mononucleotide (NMN) directly into a vein in ten healthy volunteers. The treatment did not affect heart rhythm, pulse, blood pressure or markers for the liver, heart, pancreas and kidneys. NMN raised NAD+ in the blood without damaging blood cells, and also lowered the level of fat (triglycerides) in the blood. The researchers consider that this suggests intravenous NMN is safe, but the study was small.
- The Safety and Antiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: an Update ReviewPubMed· 2023
This review article summarises knowledge about nicotinamide mononucleotide (NMN), a precursor of NAD+. The authors describe how NAD+ is thought to fall with age, and how experiments in cells and animals suggest that NMN can raise NAD+ and dampen age-related conditions. They stress that most of the research has been done in cells and animals, so safety and efficacy in humans are still uncertain. Several clinical studies in humans are ongoing.
Direct NAD+ (intravenous): limited data
There is little controlled research on NAD+ given directly to humans. A small pilot study has mapped what happens to NAD+ and its breakdown products in blood and urine during a six-hour intravenous infusion.
- A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD+ Clinical (human)PubMed· 2019
In this study, the researchers followed what happened when NAD+ was given directly into a vein over six hours in humans. NAD+ and several breakdown products did not change in the blood until after two hours. The researchers found that NAD+ was at first rapidly and completely cleared from the blood, and that the breakdown pattern pointed to specific enzymes at work. After six hours, more NAD+ and one breakdown product were excreted in the urine. This was a small pilot study.