Dry January, Veganuary…, it’s been a bit of a quiet month for us with many an evening tucked up on the sofa watching a brief something on Netflix. On the recommendation of certain work colleagues (and even the eldest of my children – blush!), we were directed towards a short Netflix series called The Witcher.
I must admit, I was a little put off in the beginning what with all the white hair and yellow eyes and monsters. Also, having no magical powers myself, I had trouble following all the magic stuff that was going on. But then having realised Henry Cavill was involved and after a little necessary explanation from the aforementioned child about mutations and potions providing immunity to diseases and superhuman healing, I must admit, we were a little hooked.
So even though that was all fiction and fantasy, it was interesting therefore to have discussed (albeit briefly) at the recent Royal Society of Medicine symposium on skin immunity and autoimmunity the use of topical and oral agents that might actually prevent the development of skin cancers.
What are these?
The agent discussed was nicotinamide.
What is nicotinamide?
Nicotinamide (NAM) is a form of vitamin B3 and a precursor of a co-enzyme (NAD+) required for energy production and other metabolic processes. NAD+ is crucial in cells that have high cellular energy. Tissues with high cellular turnover, such as the skin have a higher need for NAD+ in order to withstand DNA damage.
In animal studies, low levels of NAD+ increases the sensitivity of skin to UV radiation, impairs the response of the skin to DNA damage, increases genomic instability and increases cancer incidence.
[Damian, D.L. Nicotinamide for skin cancer chemoprevention. Australas. J. Dermatol. 2017, 58, 174–180]
[Surjana, D., Halliday, G.M., Damian, D.L. Role of nicotinamide in DNA damage, mutagenesis, and DNA repair. J. Nucleic Acids 2010, 2010, 1–13]
So can taking nicotinamide prevent DNA damage to the skin?
Nicotinamide or NAM both topically and orally has been shown to prevent the immuosuppressive effects of UV radiation in mice.
[Gensler, H.L. Prevention of photoimmunosuppression and photocarcinogenesis by topical nicotinamide. Nutr. Cancer 1997, 29, 157–162]
[Gensler, H.L., Williams, T., Huang, A.C et al. Oral niacin prevents photocarcinogenesis and photoimmunosuppression in mice. Nutr. Cancer 1999, 34, 36–41]
What about in humans?
Topical NAM significantly protected against UVB and UVA related skin immunosuppression in humans.
[Sivapirabu, G., Yiasemides, E., Halliday, G.M et al. Topical nicotinamide modulates cellular energy metabolism and provides broad-spectrum protection against ultraviolet radiation-induced immunosuppression in humans. Br. J. Dermatol. 2009, 161, 1357–1364.]
This was also found with oral NAM in humans.
[Yiasemides, E., Sivapirabu, G., Halliday, G.M et al. Oral nicotinamide protects against ultraviolet radiation-induced immunosuppression in humans. Carcinogenesis 2009, 30, 101–105.]
And can NAM also prevent skin ageing then?
There have been several studies showing that topical NAM can reduce the signs of ageing.
[Bissett, D.L., Oblong, J.E., Berge, C.A. Niacinamide: A B vitamin that improves aging facial skin appearance. Dermatol. Surg. 2005, 31, 860–865.]
[Kawada, A., Konishi, N., Oiso, N et al. Evaluation of anti-wrinkle effects of a novel cosmetic containing niacinamide. J. Dermatol. 2008, 35, 637–642.]
[Kimball, A.B., Kaczvinsky, J.R., Li, J et al. Reduction in the appearance of facial hyperpigmentation after use of moisturizers with a combination of topical niacinamide and N-acetyl glucosamine: Results of a randomized, double-blind, vehicle-controlled trial. Br. J. Dermatol. 2010, 162, 435–441.]
What about preventing skin cancers?
Two trials in Australians with sun-damaged skin and an average of 30 actinic keratoses (sun induced crusty spots) who were given oral NAM showed significant reductions in numbers of actinic keratoses within 4 months.
[Surjana, D., Halliday, G.M., Martin, A.J. et al. Oral nicotinamide reduces actinic keratoses in phase II double-blinded randomized controlled trials. J. Investig. Dermatol. 2012, 132, 1497–1500.]
Another trial looked at the use of oral NAM in 386 Australians who had had at least two non-melanoma skin cancers in the previous 5 years. This study showed a 23% relative rate reduction in new non-melanoma skin cancers in those patients who had received oral NAM for at least 12 months.
[Chen, A.C., Martin, A.J., Choy, B et al. A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention. N. Engl. J. Med. 2015, 373, 1618–1626.]
And is it safe to take?
There have been reported nausea and diarrhoea and an elevation in liver function blood tests in patients taking NAM, together with a drop in the platelet count in the blood. Some of these reported side effects are only at high doses and some resolved once NAM was stopped.
[Damian, D.L. Nicotinamide for skin cancer chemoprevention. Australas. J. Dermatol. 2017, 58, 174–180.]
[Lenglet, A., Liabeuf, S., El Esper, N et al. Efficacy and safety of nicotinamide in haemodialysis patients: The NICOREN study. Nephrol. Dial. Transplant. 2017, 32, 870–879.]
Overall, it seems that NAM has an established side effect profile and has been used for some time for a wide range of clinical indications.
[Fania L, Mazzanti C, Campione E. et al. Role of nicotinamide in genomic stability and skin cancer chemoprevention. Int. J .Mol. Sci. 2019, 20, E5946.]
Is nicotinamide available currently?
It is available currently in the UK on prescription as a gel in the treatment of acne vulgaris only. However, it is available orally via various internet sources.
So the future is?
It seems that the attention has now switched to looking at whether NAM can affect melanoma development. There has been a study published last month looking at the use of oral NAM on human melanoma cell lines. The results were somewhat promising with enhanced tumour-infiltrating lymphocytes (types of white cells) arising in melanomas arising on NAM compared to those arising on placebo.
[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, doi: 10.1039/c9pp00388f.]
Again, we will have to watch this space!
Dr Sandy Flann, Consultant Dermatologist.