Nicotinamide
Nicotinamide, the amide form of vitamin B3
Written by Aaron CuhaReviewed Sep 2026
Also known as: Niacinamide, Nicotinic acid amide, Vitamin B3 (amide form), NAM
In the ONTRAC phase 3 trial, 500 mg twice daily cut the rate of new non-melanoma skin cancers by 23 percent over 12 months in 386 high-risk patients, with no benefit once the tablets stopped. The identical trial in 158 organ transplant recipients found nothing, and no trial has ever tested nicotinamide against an ageing outcome.
Overview
Nicotinamide is the cheapest thing in this entire category and it is the only NAD-pathway compound with a positive phase 3 result on a clinical endpoint a patient would notice. That result is about skin cancer, not ageing, and the distinction matters more than anything else on this page.
Every time a cell spends an NAD molecule, a sirtuin, a PARP enzyme or CD38 cleaves it and releases nicotinamide. So nicotinamide is not just a precursor fed in from outside. It is the waste product of NAD consumption, continually recycled back into NAD by the salvage enzyme NAMPT. That closed loop is the reason nicotinamide behaves differently from the riboside and mononucleotide forms sold at a hundred times the price.
The most direct human comparison available found exactly that. In a randomised open-label trial of 65 healthy adults over 14 days, nicotinamide riboside and NMN comparably raised circulating NAD, and plain nicotinamide did not do so chronically, although it did acutely and transiently shift the whole blood NAD metabolome. If you want blood NAD to go up and stay up, nicotinamide is not the molecule that does it.
What nicotinamide does do is supply substrate for PARP-mediated DNA repair in skin that has been damaged by ultraviolet light, and reduce the local immune suppression that UV causes. That is the mechanism behind ONTRAC, and it is a mechanism that runs out when you stop taking it.
The compound also carries a genuine theoretical problem for anyone taking it as a longevity supplement. Nicotinamide is a direct non-competitive inhibitor of sirtuins, the enzyme family the whole NAD story is built on. That has been shown in purified enzyme work at physiological concentrations, and in yeast, high nicotinamide shortened replicative lifespan to that of a sirtuin-null mutant. Nobody has shown this happens in a human taking a supplement. Nobody has shown it does not.
Mechanism of action
Nicotinamide enters NAD synthesis through the salvage pathway. NAMPT, nicotinamide phosphoribosyltransferase, converts it to NMN, and NMNAT enzymes convert NMN to NAD. NAMPT is the rate-limiting step, which is the structural reason more nicotinamide does not translate linearly into more NAD: the bottleneck is enzymatic, not substrate supply. Separately, nicotinamide is the product released when sirtuins, PARPs and CD38 consume NAD, and it inhibits sirtuin deacetylation by binding a conserved pocket adjacent to NAD and switching the enzyme toward base-exchange chemistry rather than deacetylation. In skin, the proposed cancer-prevention mechanism is different again and does not depend on systemic NAD at all: nicotinamide supports PARP-dependent repair of UV-induced DNA damage and reduces UV-induced cutaneous immunosuppression.
Human evidence
Unusually good for a vitamin, and almost all of it is about something other than ageing. Two phase 3 skin-cancer trials, one 5-year diabetes-prevention trial and one 12-month kidney trial, totalling well over a thousand randomised participants.
- ONTRAC, n=386, 12 months: 23 percent lower rate of new non-melanoma skin cancers (95 percent CI 4 to 38, P=0.02), and no benefit after discontinuation.
- ONTRANS, n=158 transplant recipients, 12 months: rate ratio 1.0 (95 percent CI 0.8 to 1.3, P=0.96). Stopped early for poor recruitment, so it was also underpowered against the effect size it was designed to detect.
- ENDIT, n=552, 5 years at 1.2 g per square metre: no effect on progression to type 1 diabetes, hazard ratio 1.07.
- COMBINE, n=205, 12 months at 750 mg twice daily: no effect on serum phosphate or FGF23 in chronic kidney disease.
- Head-to-head comparison of three NAD boosters, n=65 healthy adults over 14 days: plain nicotinamide did not chronically raise circulating NAD, while nicotinamide riboside and NMN did.
- No human trial has measured lifespan, healthspan, cognition, muscle function or any geroscience endpoint with nicotinamide.
What this does not tell you: The one positive result is population-specific and mechanism-specific. ONTRAC enrolled people with a history of at least two non-melanoma skin cancers in five years, which is a heavily sun-damaged group, and the effect disappeared within the six-month post-intervention window. It says nothing about a person with ordinary skin, about melanoma, or about ageing. ONTRANS was stopped early for recruitment rather than futility, so it is a failed replication in a different population rather than a clean refutation. Nothing in this record supports taking nicotinamide to raise blood NAD, because the direct comparison says it does not chronically do that.
Reading the research record
Three claim types get collapsed into one in almost all consumer writing about this pathway, and keeping them apart is most of the work. A biomarker claim is that a compound raises blood NAD. That is easy to demonstrate and for several of these compounds it is simply true. A surrogate claim is that it moves something sitting between a biomarker and a symptom, such as arterial stiffness or an acylcarnitine profile. A clinical claim is that a person walks further, remembers more, gets fewer cancers or lives longer. A compound can be firmly established at the first level and have nothing at all at the third, and that is the actual position of most of the NAD pathway. There is no published human trial of any NAD precursor with a hard clinical endpoint that reported a benefit, with one exception on this list, and that exception is nicotinamide in skin cancer, which works through DNA repair in sun-damaged skin rather than through anything to do with ageing.
The sirtuin question is the awkward one for anyone selling nicotinamide as a longevity supplement. The entire NAD story rests on sirtuins needing NAD to work. Nicotinamide is the molecule those enzymes release when they do work, and it feeds back to inhibit them. That inhibition is real and well characterised in purified enzymes at concentrations the papers call physiological, and in yeast the effect on lifespan was large and in the wrong direction. What is missing is any measurement of sirtuin activity in a human taking nicotinamide at supplement doses. The honest statement is that the feedback exists, that its relevance at human oral doses is unknown, and that the compound is being sold on a mechanism that its own chemistry partly opposes.
There is also a salvage-pathway bottleneck. NAMPT, not substrate supply, is the rate-limiting step converting nicotinamide to NMN and then to NAD. Flooding the system with the substrate of a saturable enzyme is not the same as raising the product, which is the most plausible explanation for why nicotinamide did not chronically raise circulating NAD in the head-to-head trial while the two forms that bypass NAMPT did.
The evidence, charted
Fig. 1 · evidence composition
4of 5 citations (80%) are in people
Counted from the citation list on this page. The Human count is the same number shown in the badge at the top. Both understate any literature larger than the sources we cite.
Fig. 2 · evidence over time
Evidence spans 5 distinct years, 2002 to 2023, counted from the citation list on this page.
Fig. 3 · legal status at a glance
US
Not approved
UK
Not approved
AU
Not approved
CA
Not approved
Not approved in any of the four jurisdictions shown. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Key studies & citations
- Human2015
A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention
ONTRAC. 386 people who had had at least two non-melanoma skin cancers in the previous 5 years were randomised 1:1 to nicotinamide 500 mg twice daily or placebo for 12 months. The rate of new non-melanoma skin cancers at 12 months was 23 percent lower with nicotinamide (95 percent CI 4 to 38, P=0.02). Basal-cell carcinomas were 20 percent lower (95 percent CI -6 to 39, P=0.12) and squamous-cell carcinomas 30 percent lower (95 percent CI 0 to 51, P=0.05), so only the combined endpoint was clearly significant. Actinic keratoses were 13 percent lower at 12 months. Adverse events did not differ from placebo. The paper states there was no evidence of benefit after nicotinamide was discontinued. Funded by the National Health and Medical Research Council.
New England Journal of Medicine - Human2023
Nicotinamide for Skin-Cancer Chemoprevention in Transplant Recipients
ONTRANS, the replication attempt by the same group in a higher-risk population. 158 organ-transplant recipients with at least two keratinocyte cancers in the previous 5 years, randomised 1:1 to the same 500 mg twice daily for 12 months. The trial was stopped early for poor recruitment. There were 207 new keratinocyte cancers on nicotinamide and 210 on placebo, rate ratio 1.0 (95 percent CI 0.8 to 1.3, P=0.96). No difference in squamous-cell or basal-cell counts, actinic keratoses or quality of life.
New England Journal of Medicine - Human2004
European Nicotinamide Diabetes Intervention Trial (ENDIT): a randomised controlled trial of intervention before the onset of type 1 diabetes
The largest long-duration nicotinamide trial ever run, and it was negative. 552 first-degree relatives with confirmed islet-cell antibodies received modified-release nicotinamide at 1.2 g per square metre or placebo for 5 years. 159 developed diabetes, 82 on nicotinamide and 77 on placebo, unadjusted hazard ratio 1.07 (95 percent CI 0.78 to 1.45, P=0.69). Serious adverse events did not differ. This is the trial that establishes what multi-year high-dose nicotinamide safety looks like, and that a strong animal rationale does not survive a properly powered human test.
The Lancet - In vitro2002
Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1
Purified enzyme and yeast work. Physiological concentrations of nicotinamide non-competitively inhibited both yeast Sir2 and human SIRT1 in vitro, with an IC50 below 50 micromolar, which the authors describe as equal to or better than the best synthetic inhibitors of the class. In yeast, nicotinamide abolished silencing, increased rDNA recombination and shortened replicative lifespan to that of a sir2 mutant. This is yeast and test-tube data. It has never been shown to occur in a person taking a supplement, and it has never been shown not to.
Journal of Biological Chemistry - Human2019
Effects of Nicotinamide and Lanthanum Carbonate on Serum Phosphate and Fibroblast Growth Factor-23 in CKD: The COMBINE Trial
205 people with stage 3b or 4 chronic kidney disease randomised to nicotinamide 750 mg twice daily, lanthanum carbonate, both, or double placebo for 12 months. Neither drug significantly lowered serum phosphate or intact FGF23, the dual primary endpoints. Adverse event rates were similar across arms but gastrointestinal symptoms limited adherence. Another well-run, independently funded, multi-year nicotinamide trial that missed its primary endpoint.
Journal of the American Society of Nephrology
Frequently asked questions
Is nicotinamide the same as niacin?
They are both vitamin B3 and they are not interchangeable. Nicotinamide is the amide and does not cause flushing. Nicotinic acid is the acid, causes flushing through a receptor called GPR109A, and has lipid effects that nicotinamide does not have. The large negative cardiovascular trials were run with nicotinic acid, not with nicotinamide.
Does nicotinamide raise NAD?
Not chronically, on the best direct comparison available. In a randomised trial of 65 healthy adults over 14 days, nicotinamide riboside and NMN comparably raised circulating NAD and nicotinamide did not, although it did acutely and transiently shift the blood NAD metabolome. The likely reason is that the salvage enzyme NAMPT is the rate-limiting step and adding more of its substrate does not move a saturated enzyme.
Should I take nicotinamide to prevent skin cancer?
That is a conversation for a dermatologist, and the honest summary is this. In people who have already had at least two non-melanoma skin cancers in five years, 500 mg twice daily cut the rate of new ones by 23 percent over 12 months in a 386-person phase 3 trial. The benefit stopped when the tablets stopped. The same protocol in 158 organ-transplant recipients found no effect at all. There is no evidence for it in people without that history.
Does nicotinamide block sirtuins?
In purified enzyme assays, yes, at concentrations the authors describe as physiological, and in yeast it shortened replicative lifespan to that of a sirtuin-null mutant. Whether that happens in a person taking an oral supplement has never been measured. It is a real open question rather than a settled objection, and a supplement sold on sirtuin activation should have to answer it.
Is high-dose nicotinamide safe?
The multi-year safety record is better than almost anything else in this category. ENDIT gave 552 people 1.2 g per square metre for five years with no difference in serious adverse events, and ONTRAC gave 500 mg twice daily for a year with no difference in adverse events from placebo. Liver toxicity has been described at gram-level doses of the acid form, nicotinic acid, rather than the amide. None of that safety record speaks to anyone with an active cancer, because those trials excluded them.
Will it help me live longer?
There is no evidence either way, because no trial has ever asked. Every human trial of nicotinamide has measured skin cancers, diabetes onset, or kidney chemistry. Lifespan, healthspan and cognition have never been endpoints.