While the longevity world focuses on NMN and NR, nicotinamide — the simplest form of vitamin B3 — has a Phase 3 RCT showing 23% reduction in skin cancers. That evidence deserves more attention.
Nicotinamide (also called niacinamide) is the amide form of vitamin B3. It is not the same as niacin (which causes flushing), and it is not the same as NMN or NR (which are NAD+ precursors further upstream in the biosynthetic pathway). Nicotinamide is the simplest, cheapest, and most studied form of B3 for skin applications — and it has a body of evidence that the longevity supplement industry has largely overlooked.
The most important piece of evidence is the ONTRAC trial, published in the New England Journal of Medicine in 2015. This was a Phase 3, randomised, double-blind, placebo-controlled trial (n=386) in patients with a history of at least two non-melanoma skin cancers (NMSCs) in the previous five years — a high-risk population. Participants received either 500 mg oral nicotinamide twice daily or placebo for 12 months.
The results: a 23% reduction in new NMSCs, a 20% reduction in basal cell carcinomas, a 30% reduction in squamous cell carcinomas, and up to a 20% reduction in actinic keratoses (precancerous lesions). These are not marginal effects. A 23% reduction in skin cancer incidence from a cheap, well-tolerated vitamin is a clinically significant finding.
23% reduction in new non-melanoma skin cancers. 30% reduction in squamous cell carcinomas. 20% reduction in actinic keratoses. All from 500 mg nicotinamide twice daily for 12 months.
— Chen AC et al., NEJM, 2015 — ONTRAC trial
The mechanism: nicotinamide is a precursor to NAD+, which is required for PARP-1 (poly-ADP-ribose polymerase), a key enzyme in DNA repair. UV radiation depletes cellular NAD+ by activating PARP-1 in response to DNA damage. Nicotinamide replenishes NAD+ levels, maintaining the capacity for UV-induced DNA repair. It also reduces UV-induced immunosuppression — a mechanism by which UV exposure impairs the immune system's ability to recognise and eliminate early cancerous cells.
One important caveat: the benefits disappeared after participants stopped taking nicotinamide. This is not a one-time intervention; it requires continuous supplementation for sustained protection. This is consistent with the mechanism — nicotinamide maintains NAD+ levels, and those levels decline again when supplementation stops.
Topical nicotinamide (4%) has been tested against established dermatological treatments in two important comparisons. Against 1% clindamycin gel for moderate inflammatory acne (Khodaeiani et al., 2013, n=80): comparable efficacy, with greater benefit in oily skin types. Against 4% hydroquinone for melasma (Navarrete-Solís et al., 2011, n=27): comparable reduction in hyperpigmentation, with significantly fewer side effects (hydroquinone commonly causes irritation and paradoxical hyperpigmentation).
Topical nicotinamide also increases ceramide biosynthesis in the stratum corneum (Tanno et al., 2000), improving barrier function — an effect that overlaps with the oral ceramide evidence reviewed elsewhere in this journal.
This is a question worth addressing directly. NMN and NR are upstream NAD+ precursors — they are converted to nicotinamide mononucleotide and then to NAD+ through a longer biosynthetic pathway. Nicotinamide is downstream of both and enters the salvage pathway directly. For skin applications specifically — UV protection, DNA repair, barrier function — the evidence base for nicotinamide is substantially larger than for NMN or NR. The ONTRAC trial has no equivalent in the NMN or NR literature. For longevity applications beyond skin, the picture is more complex and the evidence for NMN and NR is more relevant.
Vitaei verdict
Nicotinamide has Tier I evidence for skin cancer prevention in high-risk populations (ONTRAC trial, NEJM 2015). Topical nicotinamide has Tier II evidence for acne and hyperpigmentation. The oral dose is 500 mg twice daily; the topical concentration is 4–5%. It is inexpensive, well-tolerated, and mechanistically coherent. For anyone with a history of skin cancers or significant UV exposure, this is one of the most evidence-supported supplements available.
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