Nicotinamide (niacinamide)

What nicotinamide is

Alongside nicotinic acid, nicotinamide is the second form of niacin, that is, vitamin B3. It is found in meat, fish, grains and dairy products, and the body also makes niacin from the amino acid tryptophan. Unlike nicotinic acid, nicotinamide does not trigger a flush, the typical sensation of heat with reddening of the skin.

The distinction matters: nicotinamide riboside (NR) and NMN are different molecules, sold as NAD precursors carrying a sugar residue. The skin cancer trials in this text were carried out with plain nicotinamide; their results cannot be transferred to NR or NMN.

How it works

Nicotinamide is a precursor of NAD+, a coenzyme that every cell needs for energy production and DNA repair. UV radiation damages the DNA of skin cells and at the same time dampens the skin’s defenses. According to the study authors, nicotinamide improves the repair of UV-induced DNA damage and reduces the UV-induced suppression of the skin’s defenses.

This is a plausible pathway, shown mainly in the laboratory and on skin endpoints. Whether it results in less skin cancer is decided by the controlled trials, and their results differ depending on the patient group.

What the studies show

ONTRAC 2015: phase 3 in people with several non-melanoma skin cancers

Chen and colleagues randomly assigned 386 people with at least two non-melanoma skin cancers in the previous 5 years to 500 mg of nicotinamide twice daily or placebo for 12 months, with dermatological checks every 3 months. New non-melanoma skin cancers occurred 23 percent less often under nicotinamide (95% interval 4 to 38, p = 0.02). For squamous cell carcinomas, the difference was 30 percent, for basal cell carcinomas 20 percent, the latter without significance. In the 6 months after stopping, there was no longer any advantage.

ONTRANS 2023: no effect in organ transplant recipients

The same research group tested the same regimen in 158 people after an organ transplant, who have a particularly high risk of skin cancer because of immunosuppression. After 12 months, there were 207 new non-melanoma skin cancers under nicotinamide and 210 under placebo (rate ratio 1.0). There was also no difference in actinic keratoses and quality of life. The trial was stopped early because of slow recruitment.

US veterans 2025: a large cohort

Breglio and colleagues analyzed health data from 12,287 veterans taking nicotinamide and 21,479 comparable veterans not taking it, with an average age of 77 and 98 percent men. The risk of skin cancer was 14 percent lower overall and 54 percent lower when started after the first skin cancer; the later it was started, the smaller the advantage. In transplant recipients, there was no significant reduction overall. As a retrospective observational study, it can show associations but cannot prove cause.

Two meta-analyses, two conclusions

Mainville 2022 found, across 5 studies with 552 patients, a halving of skin cancer risk (rate ratio 0.50; 0.29 to 0.85) with moderate strength of evidence, plus more gastrointestinal complaints. Tosti 2023 pooled 4 studies, including the transplant trial, and found no established effect (rate ratio 0.82; 0.61 to 1.12). The difference lies mainly in whether immunosuppressed patients are included.

Glaucoma: early signals

In a double-blind crossover trial with 57 treated glaucoma patients, an electrophysiological measure of the inner retina improved by 14.8 percent under nicotinamide and by 5.2 percent under placebo (Hui 2020). Whether this slows vision loss is to be clarified by an ongoing phase 3 trial with nicotinamide and pyruvate over 21 months (Shukla 2026).

Type 1 diabetes: ENDIT 2004

In the European ENDIT trial, 552 relatives of people with type 1 diabetes who already had islet cell antibodies received high-dose nicotinamide or placebo for 5 years. 82 versus 77 developed diabetes (hazard ratio 1.07). The number of serious adverse effects did not differ, and the children’s growth was not impaired.

Where the data stop

• Skin cancer protection for everyone. ONTRAC studied people with a history of several non-melanoma skin cancers. For people without this history, there is no trial.
• In immunosuppression. In organ transplant recipients, the only phase 3 trial showed no effect, and the cohort only a partial signal.
• Lasting protection. The effect lasted only during intake; data on skin cancer over more than one year of intake come only from observational studies.
• Melanoma. The endpoint of the trials was non-melanoma skin cancer, not melanoma.
• Anti-aging and “NAD booster”. For aging goals, there are no endpoint studies on nicotinamide as a tablet.

Status, approval and legal

In the EU, nicotinamide may be added to food supplements as a source of niacin. The German Federal Institute for Risk Assessment (BfR) recommends a maximum of 160 mg per recommended daily intake for this. In 2002, the EU’s former Scientific Committee on Food derived a tolerable upper intake level of 900 mg per day for adults. The daily amount of 1,000 mg used in ONTRAC is above both values; the trials ran under regular dermatological monitoring.

For products with more than 16 mg of nicotinamide per daily dose, the BfR recommends a warning that pregnant women should not take them.

Safety

In ONTRAC there were no appreciable differences in adverse effects over 12 months, nor in ONTRANS, including in blood and urine values. ENDIT found no accumulation of serious adverse effects over 5 years. The 2022 meta-analysis saw more gastrointestinal complaints. A review on the safety of high doses describes reversible liver damage at very high amounts and advises regarding nicotinamide in adults from 3 g per day as a drug with toxic potential and not taking it unsupervised. In the BK-Score, safety stands at 7 out of 10; this axis measures how well safety has been studied, not how safe the substance is. This text is information and does not replace medical advice.

Sources

• Chen AC et al., N Engl J Med 2015 – ONTRAC, phase 3, 386 patients, nicotinamide and non-melanoma skin cancer
• Allen NC et al., N Engl J Med 2023 – ONTRANS, phase 3, 158 organ transplant recipients
• Breglio KF et al., JAMA Dermatol 2025 – cohort of 33,822 US veterans
• Mainville L et al., J Cutan Med Surg 2022 – meta-analysis, 29 randomized trials, skin cancer and adverse effects
• Tosti G et al., Nutrients 2023 – meta-analysis, 4 studies, nicotinamide and non-melanoma skin cancer
• Gale EA et al., Lancet 2004 – ENDIT, 552 relatives, nicotinamide for the prevention of type 1 diabetes
• Knip M et al., Diabetologia 2000 – review on the safety of high-dose nicotinamide
• Hui F et al., Clin Exp Ophthalmol 2020 – crossover trial, 57 glaucoma patients
• Shukla AG et al., Ophthalmol Glaucoma 2026 – design of the phase 3 trial of nicotinamide and pyruvate in glaucoma
• BfR – proposed maximum levels for niacin in foods including food supplements (2021)