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 in the mitochondria via the Krebs cycle. The theory is that by increasing NAD+, one can theoretically increase the energy available to the mitochondria which could help with hundreds of processes within the body.
Insert diagram from: https://www.nature.com/articles/s41392-020-00311-7/figures/1
Figure 1: Overview of the NAD+ metabolism and its physiological function. Nicotinamide = NAM. NAD+ is recycled via the salvage pathways from nicotinamide.
What is the evidence for nicotinamide?
The landmark study that got everyone interested in this vitamin was this study published in the New England Journal of Medicine in 2015.2 This randomised controlled trial enrolled 86 participants who had had at least two non-melanoma skin cancers in the previous 5 years to receive 500 mg of nicotinamide twice daily or placebo for 12 months. At 12 months, the rate of new non-melanoma skin cancers was lower by 23% in the nicotinamide group than in the placebo group.
What were the problems with this study?
There were statistical flaws in the study above as highlighted by this manuscript.3 In summary, there are:
- An underestimation of variance of non-melanoma skin cancer rates in the study population.
- An overestimation of effect size.
- The use of a composite (pooled outcome) endpoint.
- The use of a Bayesian model to predict the effect of the vitamin.
- A minimal post-outcome difference in non-melanoma skin cancer from the actual treatment effect.
More importantly, a follow-up study of oral nicotinamide did not lead to lower numbers of keratinocyte cancers or actinic keratoses in immunosuppressed solid-organ transplant recipients.4 These immunosuppressed people are at high risk of developing skin cancer, so we would have expected an even higher protective effect in this group. This clearly contradicts the 2015 study and raises the question of whether it provides any benefit at all.
What about topical nicotinamide?
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 the vitamin such as:
- Are studies on the oral form 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?
- How stable is the vitamin 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.
What can I do in view of the above?
At Skintel, we keep an open mind and will revise our view pending high-quality evidence of nicotinamide. Until then, regular skin checks with a dermatologist and using sunscreens are your best defence against skin cancer.
- Xie N, Zhang L, Gao W, Huang C, Huber PE, Zhou X, Li C, Shen G, Zou B. NAD(+) metabolism: pathophysiologic mechanisms and therapeutic potential. Signal Transduct Target Ther. 2020; 5: 227.DOI: 10.1038/s41392-020-00311-7.
- Chen AC, Martin AJ, Choy B, Fernandez-Penas P, Dalziell RA, McKenzie CA, et al. A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention. N Engl J Med. 2015; 373: 1618-26.DOI: 10.1056/NEJMoa1506197.
- Gilmore SJ. Nicotinamide and skin cancer chemoprevention: The jury is still out. Australas J Dermatol. 2018; 59: 6-9.DOI: 10.1111/ajd.12749.
- Allen NC, Martin AJ, Snaidr VA, Eggins R, Chong AH, Fernandez-Penas P, et al. Nicotinamide for Skin-Cancer Chemoprevention in Transplant Recipients. N Engl J Med. 2023; 388: 804-12.DOI: 10.1056/NEJMoa2203086.
- Boo YC. Mechanistic Basis and Clinical Evidence for the Applications of Nicotinamide (Niacinamide) to Control Skin Aging and Pigmentation. Antioxidants (Basel). 2021; 10.DOI: 10.3390/antiox10081315.
- Lane N. A unifying view of ageing and disease: the double-agent theory. J Theor Biol. 2003; 225: 531-40.DOI: 10.1016/s0022-5193(03)00304-7.