# Nicotinamide for skin cancer and glaucoma

Rating: Promising — Some human trials, or consistent animal work with a clear mechanism
Type: Compound
Updated: 2026-10-18
Canonical: https://heretic.bio/articles/nicotinamide-skin-cancer-and-glaucoma.html

> Nicotinamide, an inexpensive form of vitamin B3, reduced new non-melanoma skin cancers by 23% over a year in the Australian ONTRAC phase 3 trial of high-risk patients, and a large US veterans cohort supports the finding. But a trial in organ transplant recipients was null, and ONTRAC has not been replicated, so the rating is Promising. In glaucoma, small randomized trials show improved retinal function, and larger trials are under way.

Nicotinamide is the amide form of vitamin B3 and a direct precursor of NAD+. Unlike niacin (nicotinic acid), it does not cause flushing. It is one of the cheapest supplements on the shelf, and it has two medical uses most people have never heard of: preventing new skin cancers in people who have already had them, and possibly protecting the optic nerve in glaucoma. The skin-cancer evidence comes from a phase 3 randomized trial; the glaucoma evidence is earlier. For nicotinamide's place among NAD+ precursors such as NR and NMN, see [NAD+ and sirtuin activators](nad-and-sirtuin-activators.html).

## Skin cancer: ONTRAC and what followed

UV radiation damages skin DNA and suppresses the skin's local immune response by draining cellular energy. Nicotinamide replenishes that energy, which in lab studies speeds DNA repair and blunts UV immunosuppression. Two phase 2 trials first showed fewer actinic keratoses (precancerous lesions) on oral nicotinamide (PMID [22297641](https://pubmed.ncbi.nlm.nih.gov/22297641/)).

Study| Population| Result  
---|---|---  
ONTRAC, _NEJM_ 2015 (phase 3 RCT)| 386 Australians with at least two non-melanoma skin cancers in the past 5 years, 12 months| 23% fewer new non-melanoma skin cancers (95% CI 4 to 38); squamous-cell carcinomas 30% lower, basal-cell 20% lower (not significant); actinic keratoses 11-20% lower. Benefit disappeared within 6 months of stopping (PMID [26488693](https://pubmed.ncbi.nlm.nih.gov/26488693/))  
ONTRANS, _NEJM_ 2023 (phase 3 RCT)| 158 organ-transplant recipients on immunosuppressants, stopped early for poor recruitment| **No effect** : 207 vs 210 new keratinocyte cancers (rate ratio 1.0, 95% CI 0.8 to 1.3) (PMID [36856616](https://pubmed.ncbi.nlm.nih.gov/36856616/))  
US Veterans Affairs cohort, _JAMA Dermatology_ 2025| 12,287 nicotinamide users matched to 21,479 non-users| 14% lower skin-cancer risk overall, rising to 54% when started after a first skin cancer and fading when started later; no overall benefit in transplant recipients (PMID [40960808](https://pubmed.ncbi.nlm.nih.gov/40960808/))  
  
The picture: one positive phase 3 trial in immunocompetent high-risk patients, a null phase 3 trial in transplant recipients (small and underpowered after early stopping), and a large real-world cohort that agrees with ONTRAC and suggests starting early matters. Nicotinamide has not been shown to prevent melanoma, and the benefit appears to last only while it is taken.

## Glaucoma: an energy-failure hypothesis

Retinal ganglion cells, the neurons lost in glaucoma, are energy-hungry, and NAD+ falls with age and eye pressure. In mouse models nicotinamide strongly protects these cells, and blood nicotinamide is low in glaucoma patients.

  * **Crossover RCT (Hui et al., 2020):** 57 treated glaucoma patients received nicotinamide or placebo for 12 weeks each. A marker of inner-retinal function (PhNR amplitude) improved 14.8% on nicotinamide versus 5.2% on placebo, and more patients improved by at least 1 dB on visual-field testing (PMID [32721104](https://pubmed.ncbi.nlm.nih.gov/32721104/)).
  * **Ocular hypertension cohort (JAMA Ophthalmology 2026):** among 2,920 propensity-matched patients with high eye pressure, those taking nicotinamide were diagnosed with glaucoma less often over 3.7 years (3.5% vs 9.0%; HR 0.34, 95% CI 0.25 to 0.47) and needed pressure-lowering drops and laser less often (PMID [42424069](https://pubmed.ncbi.nlm.nih.gov/42424069/)). This is observational: people who take a supplement differ from those who don't.
  * **Systematic review (Nutrients 2026):** eight small human studies; short-term electrophysiological gains, inconsistent visual-field results, and "insufficient" evidence to support routine high-dose use. Long-term randomized trials are running (PMID [42739057](https://pubmed.ncbi.nlm.nih.gov/42739057/)).



## Safety

At the doses used in the skin-cancer trials, adverse events matched placebo in both ONTRAC and ONTRANS. The glaucoma studies used several times the skin-cancer dose, and the long-term safety of gram-level daily intake over years has not been established by trials. Nicotinamide is not the same as niacin, which flushes and has its own risks at high doses.

## Where it sits on the Heretic scale

**Promising** overall. For skin-cancer prevention in people with prior non-melanoma skin cancers, the evidence is close to Proven: a positive phase 3 trial, supportive phase 2 data and a large cohort. It stops short because the only other phase 3 trial (in transplant recipients) was null and ONTRAC has not been replicated in a second immunocompetent population. For glaucoma it is Early: one small crossover trial and an observational cohort. Related: [Sun exposure and health](sun-exposure-and-health.html), where nicotinamide is one of the few tested ways to reduce UV-driven skin cancer risk in people who are already at risk.

## Sources

1. Surjana D, et al. (2012). "Oral nicotinamide reduces actinic keratoses in phase II double-blinded randomized controlled trials." J Invest Dermatol . PMID 22297641 . DOI 10.1038/jid.2011.459 (PubMed 22297641, DOI 10.1038/jid.2011.459)
2. Chen AC, et al. (2015). "A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention." N Engl J Med 373(17):1618-26. PMID 26488693 . DOI 10.1056/NEJMoa1506197 (PubMed 26488693, DOI 10.1056/NEJMoa1506197)
3. Allen NC, et al. (2023). "Nicotinamide for Skin-Cancer Chemoprevention in Transplant Recipients." N Engl J Med . PMID 36856616 . DOI 10.1056/NEJMoa2203086 (PubMed 36856616, DOI 10.1056/NEJMoa2203086)
4. Breglio KF, et al. (2025). "Nicotinamide for Skin Cancer Chemoprevention." JAMA Dermatol 161(11):1140-1147. PMID 40960808 . DOI 10.1001/jamadermatol.2025.3238 (PubMed 40960808, DOI 10.1001/jamadermatol.2025.3238)
5. Hui F, et al. (2020). "Improvement in inner retinal function in glaucoma with nicotinamide (vitamin B3) supplementation: A crossover randomized clinical trial." Clin Exp Ophthalmol 48(7):903-914. PMID 32721104 . DOI 10.1111/ceo.13818 (PubMed 32721104, DOI 10.1111/ceo.13818)
6. Muayad J, et al. (2026). "Nicotinamide Supplementation and Primary Open-Angle Glaucoma in Patients With Ocular Hypertension." JAMA Ophthalmol 144(8):724-730. PMID 42424069 . DOI 10.1001/jamaophthalmol.2026.2472 (PubMed 42424069, DOI 10.1001/jamaophthalmol.2026.2472)
7. Giudiceandrea A, et al. (2026). "Nicotinamide Supplementation in Glaucoma: A Systematic Review of Human Studies." Nutrients 18(17):2885. PMID 42739057 . DOI 10.3390/nu18172885 (PubMed 42739057, DOI 10.3390/nu18172885)