Photoprotective effects of nicotinamide

In Australia, the lifetime risk of developing non-melanoma skin cancer such as basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) is almost 70% for men and 60% for women. Actinic keratoses (AKs) are premalignant lesions which can progress to SCC. AKs affect more than 60% of Australians over the age of 40 and not only pose a risk ofmalignant transformation but can also impede the diagnosis of early BCCs and SCCs in AK-obscured skin as well as causing discomfort and cosmetic disfigurement.

Although a large proportion ofmelanoma and BCCrisk reflects sun exposure in early life, there is now growing evidence that sunburns in adult life are also a large determinant of melanoma risk, whilst risk of SCC is associated with chronic and recent sun exposure. Daily use of a sunscreen with sun protection factor (SPF) 16 can reduce numbers of SCCs by up to 40%within 2 years, and can reduce numbers of AKs by 30–40%within a fewmonths. Withmore prolonged followup of 8 years, a trend towards reduced BCC risk with sunscreen use has also been found, although there is as yet no conclusive evidence that sunscreens prevent melanoma.

As well as sun exposure, other risk factors for skin cancer development are also reversible in adult life. Smoking doubles the risk of both AKs and cutaneous SCCs and very recent research now suggests that smoking may be an independent risk factor for melanoma, presumably in part because of its immune suppressive effects on the skin. Dietary modification also has potential to substantially modify skin cancer risk. Diets higher in leafy greens and lower in meat and saturated fats have been shown to correlate with substantially reduced SCC risk in humans, whilst halving dietary fat intake can reduce SCC risk by almost 40%. More recently, emerging evidence links obesity with increased photocarcinogenesis. In SKH-1 hairless mice, increased body weight inmice fed powderised versus pellet forms of the same feed mix resulted in accelerated tumour development after UVB irradiation. A large cohort study has also found a correlation between obesity and melanoma risk, with the highest body mass index category showing an odds ratio for melanoma of 2.5. Hence general measures which offer cardiovascular as well as dermatologic benefit, such as weight loss, a low fat diet and cessation of smoking, should be emphasised to patients along with sunscreen use as key components of both primary and secondary skin cancer prevention.

Immunosuppression is a potent promoter of skin carcinogenesis, as seen most floridly in transplant recipients. It is thought that protection of skin immunity from solar UV is central to the rapid regression of AKs observed both after starting sunscreen use and also spontaneously, especially during the winter months. Hence measures designed to protect the skin from UV-immunosuppression have the potential to further reduce AK and SCC risk within relatively short periods of time. Immunosuppression also increases the risk of both BCC and melanoma, and it may be that immune protective strategies could further reduce the risk of these tumours, albeit over longer timeframes. Sunscreens, especially those offering broad-spectrum protection against both UVA and UVB, can reduce UV immunosuppression in humans, but in practice these topical products tend to be applied much more sparingly than recommended. On average, sunscreen users tend to apply less than one third of the 2 mg per cm2 used in SPF testing. Even in patients with an extremely high risk of skin cancer, compliancewith sunscreen is surprisingly poor, and it may be that a once or twice-daily oral photoprotective agent is associated with better

levels of compliance in patients reluctant to take the time required to adequately apply sunscreen.

 

Vitamin D deficiency is increasingly recognised as a frequent side effect of rigorous sun protection, even in areas with high year-round solar irradiance. Hence some advisory groups have now recommended that brief, non-sunburning exposures to sunlight comprising a few minutes, several times per week, are required to maintain adequate vitamin D, although the required level of exposure remains controversial. As the correlation between vitamin D deficiency and risk of not only osteoporosis but also cardiovascular, autoimmune and malignant disease is better recognised, the lower limit of “normal” vitamin D levels is likely to continue to increase. This requires a difficult balance between UV exposure, with its attendant immune suppressive and mutagenic effects even at extremely low exposure levels27 and maintaining population health via adequate vitamin D levels. Agents which might reduce skin cancer risk without impairing vitamin D production are thus increasingly attractive.

Nicotinamide, the amide form of vitamin B3, has a range of photoprotective and anticarcinogenic effects in mice and in humans. Nicotinamide is inexpensive, patent-free and well- tolerated, and is already widely commercially available in pharmacies and health food stores as a vitamin supplement. It may thus be a valuable adjunctive measure for preventing premalignant and malignant skin lesions, particularly in high-risk groups who would be able to readily access this intervention after advice from their treating physician.

 

Reference:

Diona L. Damian*. Photochem. Photobiol. Sci., 2010, 9, 578–585

 

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