Guide
NAD+ benefits and side effects: what the evidence shows
What each NAD+ study measured, in whom and with what limits, and the side effects that trials have recorded for IV drips, injections and oral precursors.
By The NAD Team · Reviewed September 2026 · 10 min read
Most of the research behind NAD+ benefits was done in cells and mice, and the human trials are small (usually 40 people or fewer), short (weeks to a few months) and show more reliably that NAD+ levels rise than that anything about health changes. The side effects reported have mostly been short lived, though not always mild: one clinic study recorded moderate to severe nausea, cramping and chest pressure during NAD+ drips, injections under the skin have been followed by pain, redness or itching, and oral precursors have produced little that differs from placebo, while long-term safety and what extra NAD+ means for an existing tumour remain open questions.
None of the studies below used our kit, and nothing in this guide is a claim about what NAD+ or our kit will do for you.
What NAD+ is, and why it is studied
NAD+ (nicotinamide adenine dinucleotide) is a coenzyme present in every living cell. A 2021 review of NAD+ metabolism describes it as a cofactor in the redox reactions cells use to produce energy, and as a substrate that signalling enzymes, sirtuins and PARPs among them, break down as they work. Cells build it from dietary precursors, including the two forms of vitamin B3, nicotinic acid and nicotinamide. Our science page on what NAD+ does in a cell covers the biochemistry at more length.
Research interest follows from the finding that NAD+ levels fall with age. A 2012 study of 49 human skin samples, taken from newborns and from patients aged 15 to 77 who were having unrelated surgery, found a strong negative correlation between NAD+ and age in both male and female samples. It measured one tissue once per person, so it shows that older skin held less NAD+ and cannot show whether adding NAD+ back changes anything.
What have cell and animal studies found?
Much of the case made for NAD+ rests on mice. In a long-term study, male mice were given NMN, an NAD+ precursor, in their drinking water for 12 months, from 5 to 17 months of age, at 100 or 300mg per kg of body weight a day. Compared with untreated mice, they put on less weight as they aged, were more physically active and had higher insulin sensitivity. The authors saw no obvious toxicity, and survival did not differ between the groups over the year.
These were mice of a single strain, all male and fed standard chow, and results like these are the reason human trials were run. Most of those trials gave a precursor by mouth, nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN). The studies of NAD+ itself that we found were of drips and injections, and they are covered under side effects below. Our guide to NMN and NAD+ explains how the two differ.
What have human trials found?
A 2023 review of human precursor trials concluded that supplementation is safe and tolerable and can raise NAD+ and related metabolites in several tissues. It also noted that most trials so far have had 40 participants or fewer. Whether raising NAD+ changes how the body works is much less settled. A 2023 analysis of 25 published human studies of NR found few clinically relevant effects, and its authors wrote that the literature tends to exaggerate how important and reliable the reported effects are.
The table sets out six of the human trials.
| Trial | Who took part | What they took | What was found |
|---|---|---|---|
| Martens, 2018 | 30 men and women aged 55 to 79 randomised, 24 finished | NR 500mg twice a day for 6 weeks, crossover with placebo | NAD+ in white blood cells about 60% higher than on placebo. Blood pressure was an exploratory measure, and the authors called for further trials to test it |
| Conze, 2019 | 140 healthy overweight adults | NR at 100, 300 or 1,000mg a day for 8 weeks | Whole blood NAD+ rose with dose. Adverse events did not differ from placebo. Funded by ChromaDex |
| Elhassan, 2019 | 12 men, median age 75 | NR 1g a day for 21 days, crossover with placebo | Muscle NAD+ metabolites rose and circulating inflammatory cytokines fell. Mitochondrial function and grip strength did not change |
| Dollerup, 2018, as summarised in a 2023 review | 40 men with obesity and insulin resistance | NR 2,000mg a day for 12 weeks | No change in insulin sensitivity or body composition |
| Yoshino, 2021 | 25 postmenopausal women with prediabetes, 13 on NMN | NMN 250mg a day for 10 weeks | Muscle insulin sensitivity rose on NMN and did not change on placebo. Body composition, blood pressure, blood lipids, liver fat and muscle NAD+ did not change |
| Igarashi, 2022 | 42 men over 65 | NMN 250mg a day for 12 weeks | A supplier error swapped the products for 22 men at week 6, and 20 completed the 12 weeks. Walking speed and left grip strength rose on NMN; skeletal muscle mass did not differ |
In most of these trials NAD+ or its metabolites rose in blood or muscle, though muscle NAD+ did not change in Yoshino's. Changes in how the body worked were patchier. Muscle insulin sensitivity rose in the 13 women taking NMN in Yoshino's trial, while Dollerup's 40 men, taking NR at 2,000mg a day, showed no change in insulin sensitivity. Conze's trial was funded by ChromaDex, and Igarashi's by the firm that supplied its NMN.
Is there research on NAD+ benefits for women or men?
Very little of the research looks at the sexes separately. The 2023 review of precursor trials noted that most have studied only one sex, or small mixed groups without looking at sex-specific effects.
Of the trials above, one studied women only: Yoshino's postmenopausal women with prediabetes, whose results apply to that group and were not compared with men. Elhassan, Dollerup and Igarashi studied men only, as did the first IV infusion study described below. A 2022 safety trial of NMN gave 1,250mg a day for up to four weeks to 31 adults, 14 men and 17 women, to assess safety, and reported no adverse effects in either sex.
The 2012 skin study did report by sex. NAD+ fell with age in both male and female samples, while the activity of SIRT1, one of the sirtuin enzymes that depend on NAD+, fell with age in male samples and not in female ones. We found no trial testing whether men and women respond differently to NAD+ or its precursors, so searches for NAD+ benefits for women and NAD+ benefits for men lead back to the same small set of studies.
What side effects have been reported for NAD+?
They depend on how it is taken. Most capsules sold as NAD+ supplements contain a precursor rather than NAD+ itself. Clinics give NAD+ by IV drip, and our kit is a subcutaneous injection, given under the skin.
IV drips
Two small studies describe what happens during an NAD+ drip. In a 2019 pilot study, 8 men aged 30 to 55 received 750mg of NAD+ over six hours, about 2mg a minute, and 3 received saline. No adverse events were observed during the infusions. The study traced where the NAD+ went in blood and urine and did not test any benefit.
A 2026 retrospective study from a wellness clinic chain compared 500mg of NAD+ with 500mg of NR, each given by IV on four consecutive days. All six clients on NAD+ (four men and two women) reported moderate to severe abdominal cramping, diarrhoea, nausea, vomiting, a raised heart rate, throat pain, congestion and chest pressure during their infusions. The symptoms stopped as soon as each infusion finished. Clients set their own infusion rate, and the NAD+ infusions averaged 97 minutes against 37 for NR. The study had no placebo group and was funded by the clinic chain, with the NR donated by Niagen Biosciences.
The slow six-hour drip produced no recorded symptoms and the faster self-paced ones produced many, but the two studies differ in almost every other respect as well. The clinic study's authors note that slow, prolonged infusions have been proposed anecdotally as a way to manage these symptoms and that formal studies are lacking. They suggest the symptoms may come from inflammation set off when NAD+ outside cells reaches concentrations far above normal.
NAD+ injections under the skin
We found no peer-reviewed trial of NAD+ given as a subcutaneous injection. The closest is a 2026 preprint, not yet peer reviewed and funded by ChromaDex, describing two small trials. In the first, 45 adults were given an injection of placebo, NR or NAD+ (100mg for the active arms) on three consecutive days, into a vein, into a muscle or under the skin. Six of them had NAD+ under the skin. Pain and discomfort were the most frequent complaints across every product and route. The one adverse event in the NAD+ group, rated moderate, was judged unrelated to the injection.
The second trial injected NR only. Redness followed injections under the skin in 52.6% of participants and itching in 57.9%, and across both routes 45.9% reported pain lasting more than two minutes after the injection. With six people on subcutaneous NAD+, nobody can yet say how often these reactions occur with NAD+ itself. The reactions reported for injections under the skin, of either compound, were local pain, redness and itching.
Oral supplements: NR, NMN and vitamin B3
Trials of the oral precursors report few side effects that differ from placebo. In Conze's 140-person trial there were no reports of flushing, and adverse events did not differ between NR and placebo. In Martens's trial, people reported nausea, flushing, leg cramps and more bruising while on NR, and headache, skin rash, flushing, fainting and drowsiness while on placebo. The two who dropped out because of side effects were both taking placebo at the time. The 2023 review found no indications of serious adverse effects, with NR given at up to 2,000mg a day for up to 20 weeks and NMN for up to 24 weeks.
The older forms of vitamin B3 have their own guidance. The NHS says high doses of nicotinic acid supplements can cause skin flushes and, taken for a long time, liver damage. It puts the amounts unlikely to cause harm at 17mg or less of nicotinic acid, or 500mg or less of nicotinamide, a day from supplements.
Does NAD+ cause cancer?
We found no human study that has tested whether NAD+ or its precursors cause cancer or change how an existing cancer behaves. Most of the concern in the literature is about tumours that already exist, and it comes from cell and mouse work.
The 2021 review of NAD+ metabolism reports that NAMPT, the enzyme that sets the pace of the salvage pathway cells use to recycle NAD+, is upregulated in several solid human tumours, including colon, breast, prostate, thyroid and gastric cancers and glioma. It notes that cancer cells keep their NAD+ high mainly this way. Researchers therefore ask whether extra NAD+ from outside could help a tumour that is already there.
In a 2019 mouse study, NMN given daily for 13 days to mice engineered to develop pancreatic cancer raised inflammatory signals in the pancreas and shrank the proportion of normal tissue, which the authors read as an increase in precancerous and cancerous lesions. They concluded that NAD+ supplements should be given with precision, weighing possible benefits against possible tumour-promoting effects. A 2026 commentary describes mouse results that depend on the model. In pancreatic cancer models, NAD+ precursors including NMN made tumour cells more resistant to chemotherapy. In a mesothelioma model the tumour results went the other way, which the researchers linked to effects of NMN on immune cells. The commentary's authors call the potential for NAD+ to fuel cancer cell growth or survival a major concern.
The human trials in this guide were small, lasted weeks, and none of those we read measured cancer outcomes. If you have or have had cancer, speak to your oncologist before taking any NAD+ product.
What is still unknown
The longest trials in the 2023 review ran for 24 weeks, so trials say nothing yet about taking NAD+ or its precursors for years. The published data we found on NAD+ given under the skin amounts to six people in one preprint. The human trials that exist mostly show NAD+ measures rising, and whether that changes anything a person would notice or a doctor would measure is unsettled; the answer may differ between precursors, doses and routes. We also found no trial comparing how men and women respond.
Where our kit fits
Our kit is a pre-mixed 1000mg vial of NAD+ with a reusable metal auto-injector, single-use needles and wipes, for a subcutaneous injection at home. Every batch is tested by an independent laboratory to at least 99% purity by HPLC, and that batch's certificate is in the box. It is made in the UK and sold as a food supplement, legal for human intake. It is not a licensed medicine, none of the studies above tested it, and we do not claim it treats, cures or prevents anything.
Speak to a doctor first if you are pregnant, breastfeeding, taking prescribed medication or under medical supervision. The kit is not for anyone under 18. Our page on NAD+ injections at home explains how the kit is used, the guide to NAD+ injection dosage covers what is known about amounts, and the kit and delivery questions in our FAQ cover storage and delivery.
Questions
Read next
Sources
- Massudi et al. (2012). Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS One.
- Navas and Carnero (2021). NAD+ metabolism, stemness, the immune response, and cancer. Signal Transduction and Targeted Therapy.
- Mills et al. (2016). Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Cell Metabolism.
- Freeberg et al. (2023). Dietary supplementation with NAD+-boosting compounds in humans: current knowledge and future directions. The Journals of Gerontology: Series A.
- Damgaard and Treebak (2023). What is really known about the effects of nicotinamide riboside supplementation in humans. Science Advances.
- Martens et al. (2018). Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nature Communications.
- Conze, Brenner and Kruger (2019). 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. Scientific Reports.
- Elhassan et al. (2019). Nicotinamide riboside augments the aged human skeletal muscle NAD+ metabolome and induces transcriptomic and anti-inflammatory signatures. Cell Reports.
- Yoshino et al. (2021). Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science.
- Igarashi et al. (2022). Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men. npj Aging.
- Fukamizu et al. (2022). Safety evaluation of beta-nicotinamide mononucleotide oral administration in healthy adult men and women. Scientific Reports.
- Grant et al. (2019). A pilot study investigating changes in the human plasma and urine NAD+ metabolome during a 6 hour intravenous infusion of NAD+. Frontiers in Aging Neuroscience.
- Reyna et al. (2026). Intravenous infusion of nicotinamide adenine dinucleotide (NAD+) versus nicotinamide riboside (NR): a retrospective tolerability pilot study in a real-world setting. Frontiers in Aging.
- Nkrumah-Elie et al. (2026). Preliminary safety analysis of two pilot clinical trials involving injections of Niagen, nicotinamide riboside chloride. medRxiv (preprint, not peer reviewed).
- Nacarelli et al. (2019). NAD+ metabolism governs the proinflammatory senescence-associated secretome. Nature Cell Biology.
- Zuiker, Hemann and Long (2026). The NAD+ challenge: harnessing immune-mediated tumor control without fueling the enemy. Molecular Therapy Oncology.
- NHS. Vitamins and minerals: B vitamins and folic acid.
Food supplement. Not a substitute for a varied diet and a healthy lifestyle. Not intended to diagnose, treat, cure or prevent any disease.