Nicotinamide and Skin Cancer Prevention: What the Trials Found

Table of Contents

1. Nicotinamide and Niacin Are Different Molecules
2. How Nicotinamide Is Thought to Protect Sun-Damaged Skin
3. The First Small Trials Found Fewer Actinic Keratoses
4. ONTRAC: The 386-Person Trial
5. ONTRANS: No Benefit in Organ Transplant Recipients
6. The 2025 Study of Veterans' Health Records
7. What the Pooled Analyses Found
8. Melanoma: No Trial Has Shown a Benefit
9. Safety at the Doses Studied
10. What Is Still Not Known
11. Key Research Papers
12. Connections
13. Featured Videos

Nicotinamide and Niacin Are Different Molecules

"Vitamin B3" covers more than one molecule. The two oldest forms are nicotinic acid, usually sold as niacin, and nicotinamide, also called niacinamide. The body can turn both into nicotinamide adenine dinucleotide (NAD+), the helper molecule that cells use to make energy and to run many repair enzymes. The NAD+ precursor page maps those routes in detail.

The two forms behave differently as tablets:

• Niacin (nicotinic acid) causes flushing. In mice, the hot, red flush was traced to one receptor, GPR109A, and to the prostaglandins D2 and E2 released in the skin; mice lacking that receptor did not flush (Benyó 2005). Niacin at gram doses also changes blood fats, which is why it was once used as a cholesterol drug (see Cholesterol and Cardiovascular).
• Nicotinamide does not cause that flush. A 2023 review of the skin cancer trials states that, unlike niacin, oral nicotinamide has no blood-vessel-widening effect and is not linked to skin flushing (Tosti 2023, full text). A 2025 overview of 14 reviews found that oral nicotinamide was linked to fewer side effects than niacin (Young 2025).

Every skin cancer trial on this page used nicotinamide, almost always 500 mg twice a day (1,000 mg a day). No trial on this page tested niacin, so the results cannot be carried over to niacin tablets. The 1,000 mg a day used in the trials is many times more than the adult need for niacin, which is about 14 to 16 mg of niacin equivalents a day (see the main Vitamin B3 page), so these are supplement doses, not amounts reached by eating.

Food still matters for vitamin B3 in general. Nicotinamide comes from fish, meat, grains (whole grains such as brown rice keep more of the B vitamins than refined ones) and dairy, and the body also makes it from the amino acid tryptophan (Tosti 2023). That 2023 review found only one study of niacin in the everyday diet and skin cancer; it pointed to a possible link with less squamous cell carcinoma, but not with basal cell carcinoma or melanoma.

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How Nicotinamide Is Thought to Protect Sun-Damaged Skin

Ultraviolet (UV) light from the sun damages the DNA in skin cells and also weakens the skin's local immune defence, which normally helps clear damaged cells. Researchers in Sydney proposed three linked ways nicotinamide might help. Each rests on a different kind of evidence, labelled below.

1. Restoring cellular energy after UV damage

Evidence type: human skin cells grown in the laboratory. In human keratinocytes in culture, nicotinamide prevented the drop in the cell's energy molecule adenosine triphosphate (ATP) that follows UV exposure, and protected against UV blocking of glucose use (glycolysis). It had no effect on the formation of reactive oxygen species, the "oxidative stress" molecules, so the authors concluded that its protective effect works through energy pathways rather than as an antioxidant (Park 2010).

2. Faster DNA repair

Evidence type: cells in culture and pieces of donated human skin kept alive in the laboratory (ex vivo). Repairing UV damage costs energy. In keratinocytes, nicotinamide increased both the share of cells carrying out excision repair and the speed of repair in each cell. In both the cells and the donated skin, it lowered two types of UV damage, cyclobutane pyrimidine dimers and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxoG), and the fall appeared to come from faster repair (Surjana 2013). A similar effect was seen in human pigment cells (melanocytes) in culture (Thompson 2014; see the melanoma section).

3. Less UV suppression of the skin's immune response

Evidence type: small randomized studies in healthy human volunteers, plus earlier work in mice. The researchers measured immunity with the Mantoux skin test, the same small skin reaction used to test for tuberculosis exposure. Low doses of simulated sunlight weakened that reaction on the exposed skin.

• Applying 5% nicotinamide lotion to the skin prevented the weakening. In the same study, men's skin immunity was suppressed by UV doses three times lower than those needed in women (Damian 2008).
• Nicotinamide tablets of 500 mg or 1,500 mg a day, taken for one week in a randomized crossover study, significantly reduced the UV immune suppression and caused no immune change in skin that was not exposed (Yiasemides 2009). The same paper notes that nicotinamide had protected mice from UV immune suppression and from UV-caused skin cancer.

These are mechanism studies. They explain why trials were run; they do not by themselves show that nicotinamide prevents cancer in people. One review also notes that at high levels nicotinamide itself can inhibit poly(ADP-ribose) polymerases (PARPs), enzymes that protect the genome, which shows the biology is not one-directional (Hwang and Song 2020).

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The First Small Trials Found Fewer Actinic Keratoses

Actinic keratoses are rough, scaly patches on sun-damaged skin. A small share can turn into squamous cell carcinoma, so their number is used as an early signal in prevention trials.

In 2012 the Sydney group reported two small phase 2 double-blind randomized trials in people with heavily sun-damaged skin (Surjana 2012). The published record is a short research letter with no abstract; the figures below are taken from the table of a 2023 meta-analysis that extracted them from the full report (Tosti 2023, full text):

A later paper from the same group summarised these phase 2 studies as showing that oral nicotinamide significantly reduced actinic keratoses and "may reduce" new nonmelanoma skin cancers (Surjana 2013). With about 40 people in total, the trials were too small to settle the cancer question, and they led to the larger ONTRAC trial.

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ONTRAC: The 386-Person Trial

ONTRAC (Oral Nicotinamide to Reduce Actinic Cancer) was a phase 3, double-blind, placebo-controlled trial run from Sydney, Australia, and published in the New England Journal of Medicine in 2015 (Chen 2015).

• Who: 386 people who had had at least two nonmelanoma skin cancers in the previous 5 years.
• What: nicotinamide 500 mg twice a day or a placebo tablet, for 12 months.
• Follow-up: a dermatologist examined everyone every 3 months for 18 months, so the last 6 months showed what happened after the tablets stopped.
• Main measure: the number of new basal cell plus squamous cell carcinomas during the 12 months of treatment.

The results, both ways

Each result is shown as the percentage lower on nicotinamide, the matching figure per 100 cancers on placebo, and the range of uncertainty (95% confidence interval) the authors reported.

Actinic keratoses were counted at every visit. Compared with placebo, the count on nicotinamide was 11% lower at 3 months, 14% lower at 6 months, 20% lower at 9 months and 13% lower at 12 months. The largest gap was at 9 months, not at the end.

Two further findings matter as much as the headline:

• No lasting effect. In the 6 months after the tablets were stopped there was no evidence of benefit. Whatever nicotinamide does, it appeared to work only while it was being taken.
• Side effects. The trial found no noteworthy differences between the groups in the number or types of adverse events during the 12 months.

The basal cell result is often quoted as "20% fewer", but its uncertainty range runs from a small increase to a large decrease, so the trial did not show a clear effect on basal cell carcinoma by itself. A 2023 review notes that the trial's statistical methods drew criticism, although the critics still accepted a likely benefit for nonmelanoma skin cancer (Hunt 2023). All participants were at high risk; the trial says nothing about people who have never had skin cancer.

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ONTRANS: No Benefit in Organ Transplant Recipients

People who have had a kidney, liver, heart or lung transplant take drugs that suppress the immune system for life, and they get far more skin cancers, and die of them more often, than other people. Because nicotinamide was thought to work partly by protecting skin immunity, the same team tested it in this group.

ONTRANS was a phase 3 placebo-controlled trial, published in 2023 (Allen 2023):

• Who: 158 organ transplant recipients who had had at least two keratinocyte cancers in the past 5 years (79 on nicotinamide, 79 on placebo). The trial was stopped early because too few people joined.
• What: nicotinamide 500 mg twice a day or placebo for 12 months, the same dose as ONTRAC.
• Result: 207 new keratinocyte cancers in the nicotinamide group and 210 in the placebo group, a rate ratio of 1.0 (uncertainty range 0.8 to 1.3; P = 0.96). There was no significant difference in squamous cell carcinoma, basal cell carcinoma or actinic keratosis counts, or in quality of life.
• Safety: adverse events and changes in blood and urine tests were similar in the two groups.

Smaller and weaker studies in transplant recipients point the other way, and are listed here with their limits:

• An Italian study of 38 transplant recipients with actinic keratoses (19 given nicotinamide 500 mg once a day, 19 given nothing, no placebo) reported that the keratoses shrank in 18 of 19 treated patients over 6 months, while 91% of the untreated group had growing or new lesions (Drago 2017).
• A 2025 single-hospital records review of 47 transplant recipients compared each person's skin cancers in the year before and the year after starting nicotinamide 500 mg twice daily: 224 cancers before and 121 after (Hwang 2025). There was no comparison group, so a natural change over time cannot be ruled out.

The only full-size randomized trial in transplant recipients, ONTRANS, found no benefit.

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The 2025 Study of Veterans' Health Records

The largest study so far is not a trial. Researchers searched the US Department of Veterans Affairs health records from 1999 to 2024 (Breglio 2025):

• Who: 12,287 patients who filled prescriptions for nicotinamide 500 mg twice a day for more than 30 days, matched with 21,479 similar patients who did not (33,822 in all). The average age was about 77, only 2% were women and about 95% were White.
• How: each group was matched on number and timing of earlier skin cancers, age, sex, race, other skin cancer treatments, chronic lymphocytic leukemia and transplant history, and the time to the next skin cancer was compared.
• Overall: skin cancer risk was 14% lower in the nicotinamide group.
• Timing: when nicotinamide was started after a first skin cancer, the risk was 54% lower. The benefit shrank when it was started after later skin cancers.
• Cancer types: lower risk was seen for basal cell carcinoma and for squamous cell carcinoma, with the largest drop for squamous cell carcinoma.
• Transplant recipients (1,334 people, 3.9% of the matched group): no overall significant reduction, although early use was linked with less squamous cell carcinoma.

This is an observational study: people were not randomly assigned to take nicotinamide, so other differences between those who did and did not take it could explain part of the result. A 2026 critical appraisal listed specific concerns, including unmeasured confounders, immortal time bias (a statistical error that can make a treatment look better than it is), misclassification of who really took the tablets, flexible modelling and limited relevance to other populations, and concluded that the evidence does not yet confirm a preventive effect (Tan and Williams 2026). The same appraisal gives the study's squamous cell figure as a 22% reduction.

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What the Pooled Analyses Found

Several reviews have pooled these studies. Their conclusions differ, mostly because of which studies they included and whether transplant recipients were counted together with everyone else.

A rate ratio of 1.0 means no difference; below 1.0 means fewer cancers on nicotinamide. When the uncertainty range crosses 1.0, the result is not statistically clear. Mainville and colleagues graded their own advice in favour of nicotinamide as a weak recommendation based on moderate-quality evidence. The 2023 and 2026 reviews, which include ONTRANS, are more cautious.

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Melanoma: No Trial Has Shown a Benefit

Melanoma is the skin cancer that causes most skin cancer deaths. No completed randomized trial has tested nicotinamide for melanoma prevention, and none of the trials above showed a melanoma benefit. What exists is laboratory work and one look at tumours from ONTRAC:

• Cells in culture: in human melanocytes, nicotinamide sped up repair of UV damage to DNA (Thompson 2014).
• Cells in culture: at 50 micromolar nicotinamide did not change the growth, survival or invasiveness of four melanoma cell lines or two melanocyte lines; only far higher levels that cannot be reached in the body reduced cell survival and growth (Malesu 2020).
• Tumour tissue: melanomas that appeared in ONTRAC participants taking nicotinamide had more immune cells (CD4+ and CD8+ lymphocytes) in and around them than melanomas in the placebo group (Malesu 2020). This is a laboratory observation on a small number of tumours, not a count of melanomas prevented.
• Diet: the single study of dietary niacin found no link with melanoma (Tosti 2023).

The researchers concluded that these results justify melanoma prevention trials. A 2026 review of skin cancer prevention agents states that more research is needed to establish efficacy in melanoma (Ortiz-Brugués 2026). Until such trials report, a melanoma benefit is a hypothesis.

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Safety at the Doses Studied

The sources describe nicotinamide at 1,000 mg a day as well tolerated, with these specific findings:

• In the trials: ONTRAC found no noteworthy differences in adverse events between nicotinamide and placebo over 12 months (Chen 2015). ONTRANS found similar adverse events and similar blood and urine test changes in transplant recipients (Allen 2023).
• Digestive upset: the 2022 meta-analysis found a higher risk of digestive side effects with nicotinamide (Mainville 2022).
• Liver: a 2000 safety review found reversible liver toxicity reported at very high doses in animals and humans, and infrequent minor liver enzyme changes at the doses used in diabetes prevention research. It described nicotinamide as a drug with toxic potential at adult doses above 3 grams a day (Knip 2000). The same review reported minor insulin resistance in some studies and no evidence that nicotinamide causes cancer in people.
• Overview of reviews: across 14 reviews, side effects of niacin and nicotinamide included stomach and gut upset, liver dysfunction, flushing, rash and tiredness; they were dose-dependent and mostly eased when the dose was lowered or stopped. Nicotinamide caused fewer side effects than niacin, and the authors wrote that routine monitoring may not be needed below 1,500 mg a day (Young 2025). The same overview notes that side effects are more common at higher doses and that tolerability depends on other illnesses, such as reduced kidney function.
• Heart events: some breakdown products of niacin have been linked to heart risk (see the Benefits hub). A 2025 records study of 13,108 adults, 5,291 of whom took nicotinamide, found no increased risk of major heart and blood vessel events after nicotinamide exposure (Wheless 2025).
• Long-term high doses: a 2020 review found current usage levels safe but raised a possible risk of changes to gene regulation (epigenetic changes) with chronic use of high doses, which has not been studied directly in people (Hwang and Song 2020).

Niacin (nicotinic acid) has a different safety profile, including flushing and, with gram doses of slow-release forms, liver injury; the Vitamin B3 page covers it.

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What Is Still Not Known

• How much rests on one trial. The randomized evidence of fewer skin cancers in people with a normal immune system comes from ONTRAC alone; a 2026 systematic review calls that conclusion provisional (Guerra Jiménez 2026).
• Longer use. Every randomized trial lasted 12 months or less. Whether the effect holds, grows or fades over years of use has not been tested in a trial.
• Effect after stopping. ONTRAC found no benefit once the tablets stopped, so any effect seems to depend on continued use.
• Transplant recipients. The one full-size trial found no benefit; smaller uncontrolled studies and the early-use signal in the veterans data are hypotheses that a new trial would need to test.
• Timing. The larger reduction seen when nicotinamide was started after a first skin cancer comes from observational records and has not been tested in a trial.
• Who was studied. The trials enrolled people at high risk in Australia, and the veterans study was almost all older White men. People who have never had skin cancer, people with darker skin, and children were not studied.
• Melanoma. No trial has measured melanoma prevention.
• Basal cell carcinoma. ONTRAC's basal cell result was not statistically clear, and the pooled reviews disagree.

The trial reports compare nicotinamide with placebo, not with sun protection; the 2026 review of preventive agents in people with a normal immune system found that daily sunscreen lowered squamous cell carcinoma (rate ratio 0.61) and actinic keratoses in its own trials (Susanto 2026).

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Key Research Papers

1. Chen AC, Martin AJ, Choy B, et al. A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention. N Engl J Med. 2015;373(17):1618-26. PubMed PMID: 26488693
2. Allen NC, Martin AJ, Snaidr VA, et al. Nicotinamide for Skin-Cancer Chemoprevention in Transplant Recipients. N Engl J Med. 2023;388(9):804-812. PubMed PMID: 36856616
3. Breglio KF, Knox KM, Hwang J, et al. Nicotinamide for Skin Cancer Chemoprevention. JAMA Dermatol. 2025;161(11):1140-1147. PubMed PMID: 40960808
4. Surjana D, Halliday GM, Martin AJ, Moloney FJ, Damian DL. Oral nicotinamide reduces actinic keratoses in phase II double-blinded randomized controlled trials. J Invest Dermatol. 2012;132(5):1497-500. PubMed PMID: 22297641
5. Mainville L, Smilga AS, Fortin PR. Effect of Nicotinamide in Skin Cancer and Actinic Keratoses Chemoprophylaxis, and Adverse Effects Related to Nicotinamide: A Systematic Review and Meta-Analysis. J Cutan Med Surg. 2022;26(3):297-308. PubMed PMID: 35134311
6. Tosti G, Pepe F, Gnagnarella P, et al. The Role of Nicotinamide as Chemo-Preventive Agent in NMSCs: A Systematic Review and Meta-Analysis. Nutrients. 2023;16(1):100. PubMed PMID: 38201930
7. Guerra Jiménez AL, Ortegón Garciaherreros JC, Suárez Escobar LP, Vargas Monroy LV, Madariaga Estupiñán MC. Oral Nicotinamide for the Secondary Prevention of Cutaneous Squamous Cell Carcinoma and Other Keratinocyte Carcinomas: A Systematic Review. J Skin Cancer. 2026;2026:8756577. PubMed PMID: 42835758
8. Susanto A, Morgan E, Lindsay D, Collins LG. Chemoprevention of keratinocyte carcinomas and actinic keratoses in adults who were immunocompetent: a systematic review. Clin Exp Dermatol. 2026;51(7):1202-1212. PubMed PMID: 41671392
9. Tan E, Williams HC. Nicotinamide for Skin Cancer Chemoprevention: The Jury Was Out and Still is. Am J Clin Dermatol. 2026;27(2):209-215. PubMed PMID: 41505062
10. Hunt SV, Jamison A, Malhotra R. Oral nicotinamide for non-melanoma skin cancers: A review. Eye (Lond). 2023;37(5):823-829. PubMed PMID: 35347291
11. Yiasemides E, Sivapirabu G, Halliday GM, Park J, Damian DL. Oral nicotinamide protects against ultraviolet radiation-induced immunosuppression in humans. Carcinogenesis. 2009;30(1):101-5. PubMed PMID: 19028705
12. Damian DL, Patterson CR, Stapelberg M, Park J, Barnetson RS, Halliday GM. UV radiation-induced immunosuppression is greater in men and prevented by topical nicotinamide. J Invest Dermatol. 2008;128(2):447-54. PubMed PMID: 17882270
13. Park J, Halliday GM, Surjana D, Damian DL. Nicotinamide prevents ultraviolet radiation-induced cellular energy loss. Photochem Photobiol. 2010;86(4):942-8. PubMed PMID: 20492562
14. Surjana D, Halliday GM, Damian DL. Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in human keratinocytes and ex vivo skin. Carcinogenesis. 2013;34(5):1144-9. PubMed PMID: 23349012
15. Thompson BC, Surjana D, Halliday GM, Damian DL. Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in primary melanocytes. Exp Dermatol. 2014;23(7):509-11. PubMed PMID: 24798949
16. Malesu R, Martin AJ, Lyons JG, et al. Nicotinamide for skin cancer chemoprevention: effects of nicotinamide on melanoma in vitro and in vivo. Photochem Photobiol Sci. 2020;19(2):171-179. PubMed PMID: 31942903
17. Drago F, Ciccarese G, Cogorno L, Calvi C, Marsano LA, Parodi A. Prevention of non-melanoma skin cancers with nicotinamide in transplant recipients: a case-control study. Eur J Dermatol. 2017;27(4):382-385. PubMed PMID: 28468736
18. Hwang JC, Savage KT, Pugliano-Mauro M. Nicotinamide for secondary keratinocyte carcinoma prevention in solid organ transplant recipients. Arch Dermatol Res. 2025;317(1):807. PubMed PMID: 40498148
19. Wheless L, Guennoun R, Michalski-McNeely B, et al. Risk of Major Adverse Cardiovascular Events Following Nicotinamide Exposure. JAMA Dermatol. 2025;161(5):515-22. PubMed PMID: 40009360
20. Knip M, Douek IF, Moore WP, et al. Safety of high-dose nicotinamide: a review. Diabetologia. 2000;43(11):1337-45. PubMed PMID: 11126400
21. Young SL, Gazzard G. The adverse effects of oral niacin/nicotinamide - an overview of reviews. Eye (Lond). 2025;39(16):2852-2859. PubMed PMID: 40999226
22. Hwang ES, Song SB. Possible Adverse Effects of High-Dose Nicotinamide: Mechanisms and Safety Assessment. Biomolecules. 2020;10(5):687. PubMed PMID: 32365524
23. Benyó Z, Gille A, Kero J, et al. GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing. J Clin Invest. 2005;115(12):3634-40. PubMed PMID: 16322797
24. Ortiz-Brugués A, Orte Cano C, Corbella L, et al. Chemoprevention in Skin Cancer: What Advice? Cancers (Basel). 2026;18(3):436. PubMed PMID: 41681908

PubMed Topic Searches

1. PubMed: nicotinamide and skin cancer chemoprevention
2. PubMed: nicotinamide and actinic keratosis trials
3. PubMed: nicotinamide in transplant recipients
4. PubMed: nicotinamide and melanoma
5. PubMed: nicotinamide, UV DNA repair and immune suppression

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Connections

• Vitamin B3 (Niacin) — Benefits Deep Dive — the hub for this article
• Vitamin B3 — the main vitamin page, forms and intake
• Niacin for Pellagra and Skin Health — deficiency and the skin
• Vitamin B3 as a NAD+ Precursor — how the forms become NAD+
• Basal Cell Carcinoma — the most common skin cancer
• Squamous Cell Carcinoma — where the trial signal was strongest
• Actinic Keratosis — the precancerous patches the trials counted
• Skin Cancer — the overview page
• Melanoma — where no benefit has been shown

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