Skintel: Nicotinamide & Skin Cancer: Does It Help?

Quicktake

In spite of the hype, there is no good evidence that nicotinamide helps reduce the risk of skin cancer. Read on to understand the controversy and conflicting academic papers.

What is nicotinamide?

Nicotinamide is an amide form of vitamin B3 and the precursor of nicotinamide adenine dinucleotide (NAD+). NAD+ is a molecule that plays a key role via the Krebs cycle in the mitochondria of cells. The theory is that by increasing NAD+, one can increase the energy available to the mitochondria which could help with hundreds of processes within the body.¹

Does nicotinamide reduce skin cancer risk?

The landmark study that got many dermatologists interested in this vitamin was a study published in the New England Journal of Medicine in 2015.²

This randomised controlled trial enrolled 86 participants who previously had at least two non-melanoma skin cancers in the previous 5 years. Participants were given either:

nicotinamide 500 mg twice daily, or
placebo

The study was continued for 12 months. At 12 months, the rate of new non-melanoma skin cancers was lower by 23% in the nicotinamide group compared with the placebo group.

Flaws with the nicotinamide study

There were significant statistical flaws in the 2015 study. This was highlighted by a paper published in 2018.³ In summary, this paper highlighted that the original study:

Underestimated variance of non-melanoma skin cancer rates in the study population.
Overestimated the size of the effect of nicotinamide.
Used of a composite (pooled outcome) endpoint, compromising the outcomes.
Used a Bayesian model to predict the effect of nicotinamide.
Demonstrated a minimal difference in non-melanoma skin cancer from the actual treatment effect.

Lack of Reproducibility

More importantly, a further study assessing the efficacy of nicotinamide was published in 2023.⁴ This study looked at whether nicotinamide would reduce the risk of skin cancer in those with organ transplants. Organ recipients suffer with much higher rates of skin cancers, due to requiring immunosuppression to prevent transplant rejection.

This 2023 study did not reduce the rate of skin cancer or pre-cancerous lesions (actinic keratoses). If nicotinamide did help prevent skin cancer, then we would have expected an even higher protective effect in this high-risk group. This clearly contradicts the 2015 study and raises the question of whether it provides any benefit at all.

Does topical nicotinamide reduce skin cancer?

There is no evidence for nicotinamide’s use as a sunscreen ingredient to reduce the risk of sunburn.

However, there are small trials demonstrating some benefit to the topical use of nicotinamide for anti-ageing.⁵

Summary

It is tempting to think that something as simple as a vitamin can reduce the incidence of skin cancer. At present, there are many unanswered questions about nicotinamide such as:

Are studies regarding oral nicotinamide reproducible? Apart from the 2015 study, are there any other studies confirming it works?
Do we have biochemical evidence that it actually increases NAD+ levels? Understanding the metabolism of NAD+ is not the same as confirming that levels increase following supplementation with nicotinamide. Do we have a valid biomarker or test?
How stable is nicotinamide in the human body? How does it compare with nicotinamide riboside and nicotinamide mononucleotide?
What is the detailed mechanism of nicotinamide’s role in skin cancer prevention apart from increasing cellular energy?

The team at Skintel rely on high-quality evidence before recommending any treatment to our patients. Taking a vitamin to reduce the risk of skin cancer is like taking anti-oxidants to help with inflammation and ageing.⁶ Clinical trials of anti-oxidant use have not shown significant benefits and in fact, some anti-oxidants have been shown to reduce lifespan. The truth is far more complicated.

We are unable to recommend the use of nicotinamide to prevent skin cancer, due to the lack of evidence.

What can I do in view of the above?

At Skintel, we keep an open mind and will revise our position, provided we are presented with high-quality evidence supporting the use of nicotinamide. Until then, regular skin checks with a dermatologist and using sunscreens are your best defence against skin cancer.

References

1
Xie N, Zhang L, Gao W, et al. NAD⁺ metabolism: pathophysiologic mechanisms and therapeutic potential. Signal Transduct Target Ther. 2020;5(1):227. Published 2020 Oct 7. doi:10.1038/s41392-020-00311-7
2
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):1618-1626. doi:10.1056/NEJMoa1506197
3
Gilmore SJ. Nicotinamide and skin cancer chemoprevention: The jury is still out. Australas J Dermatol. 2018;59(1):6-9. doi:10.1111/ajd.12749
4
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. doi:10.1056/NEJMoa2203086
5
Boo YC. Mechanistic Basis and Clinical Evidence for the Applications of Nicotinamide (Niacinamide) to Control Skin Aging and Pigmentation. Antioxidants (Basel). 2021;10(8):1315. Published 2021 Aug 21. doi:10.3390/antiox10081315
6
Lane N. A unifying view of ageing and disease: the double-agent theory. J Theor Biol. 2003;225(4):531-540. doi:10.1016/s0022-5193(03)00304-7