PracticalDermatology

Make no mistake: UV avoidance and proper use of SPF remain fundamentals of skin cancer prevention. However, recent scrutiny of sunscreen ingredients reminds us that SPF should not be the lone tool patients use to protect their skin from UV-induced damage.

Interest in the power of antioxidants to help prevent cancers has been growing for decades now, and there has clearly been interest in harnessing these compounds to help prevent or even reverse UV-induced skin damage. In the cosmetic arena, many cosmeceuticals formulated with topical antioxidants claim to visibly reduce the signs of photoaging, but it is unclear to what extent topically applied antioxidants may confer protective effects against skin cancer. To be clear, no OTC formulations make such claims, nor does it seem that any of the brands have undertaken study in this direction.

Likely, high concentrations of antioxidants would be preferred in order to reasonably influence skin cancer risk. A notable body of research has focused, therefore, on the potential benefit of orally-ingested antioxidants to prevent skin cancer, and recent studies add to the promise of oral antioxidant use. See the sidebar for a refresher on antioxidants and the skin. Below is a look at some of the latest research on two popular compounds: vitamin A and niacinamide.

Vitamin A and Skin Cancer

A recently published study assessed the potential protective effect of intake of vitamin A and carotenoids on SCC risk.¹ Data from the Nurses’ Health Study (1984-2012) and the Health Professionals Follow-up Study (1986-2012) were analyzed. A total of 3,978 pathology-confirmed squamous cell carcinoma (SCC) cases were identified in 75,170 women in the Nurses’ Health Study and 48,400 men in the Health Professionals Follow-up Study.

Researchers determined that higher total vitamin A intake was associated with a reduction in SCC risk. The hazard ratio for SCC dropped to 0.83 for the quintile with the greatest vitamin A consumption, relative to those with the lowest. Higher intakes of retinol and some carotenoids were also associated with a reduction in SCC risk. Researchers note that the results were generally consistent by sex and other SCC risk factors.

A meta-analysis found a similar protective effect of retinol intake (more so than for total vitamin A or beta-carotene) against melanoma. This review of eight case-control studies and two prospective studies including 3,328 melanoma cases and 233,295 control subjects found the odds ratios for melanoma for the highest versus the lowest intake of total vitamin A, retinol, and beta-carotene were 0.86, 0.80, and 0.87, respectively.²

Vitamin B and Skin Cancer

Similar to the recent vitamin A and SSC study described above, a prospective analysis evaluated the potential protective effect of niacinamide against skin cancer using data from 72,308 women in the Nurses’ Health Study (1984-2010) and 41,808 men in the Health Professionals Follow-up Study (1986-2010).³ Although there was an inverse association between total niacin intake and SCC risk, researchers found a “marginally positive association between total niacin intake and BCC risk.” There was also a marginally positive association of niacin intake with melanoma risk in men. However, this association was not seen in women.

A Phase 3, double-blind, randomized, controlled trial looked at the potential protective effect of consumption of 500mg of nicotinamide twice daily in individuals diagnosed with at least two nonmelanoma skin cancers in the previous five years. Participants were evaluated by dermatologists at three-month intervals for 18 months. At 12 months, the rate of new nonmelanoma skin cancers was 23 percent lower in the nicotinamide group than in the placebo group. Reductions in SCC and basal cell carcinoma (BCC) were similar. There were also fewer new actinic keratoses (AKs) in the nicotinamide group than in the placebo group. There were 11 percent fewer AKs at three months, 14 percent fewer AKs at six months, 20 percent fewer AKs at nine months, and 13 percent fewer AKs at 12 months.⁴

Implications

There are suggestions in the literature that intake of antioxidants may have beneficial effects in terms of reducing skin cancer risk. However, the data remain somewhat limited. Additionally, there is some data to suggest that the source of antioxidants may be relevant. Consider that one study showed that antioxidant supplementation may be associated with a slightly elevated risk for SCC and BCC.⁵ In fact, the study design showed a reduction in rates of non-melanoma skin cancers after subjects had discontinued antioxidant supplementation.

In light of the available evidence, advice to patients must be based on their specific risk factors. Supplementation with vitamin A or retinol and/or niacinamide (also known as nicotinamide) could be a reasonable option for interested patients.

Certainly all patients may be advised to pursue a balanced, nutritious diet high in antioxidant-rich foods. Dietary intake of antioxidants may confer a range of benefits, including potential protective effects against skin cancers. Coupled with UV avoidance and appropriate use of sunscreens, antioxidant consumption may help reduce an individual’s risk for developing skin cancer, especially SCC or BCC.

1. Kim J, Park MK, Li WQ, Qureshi AA, Cho E. Association of Vitamin A Intake With Cutaneous Squamous Cell Carcinoma Risk in the United States. JAMA Dermatol. 2019 Jul 31.

2. Zhang YP, Chu RX, Liu H. Vitamin A intake and risk of melanoma: a meta-analysis. PLoS One. 2014 Jul 21;9(7):e102527.

3. Park SM, Li T, Wu S, Li WQ, Weinstock M, Qureshi AA, Cho E. Niacin intake and risk of skin cancer in US women and men. Int J Cancer. 2017 May 1;140(9):2023-2031.

4. Chen AC, Martin AJ, Choy B, Fernández-Peñas P, Dalziell RA, McKenzie CA, Scolyer RA, Dhillon HM, Vardy JL, Kricker A, St George G, Chinniah N, Halliday GM, Damian DL. A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention. N Engl J Med. 2015 Oct 22;373(17):1618-26.

5. Ezzedine K, Latreille J, Kesse-Guyot E, Galan P, Hercberg S, Guinot C, Malvy D. Incidence of skin cancers during 5-year follow-up after stopping antioxidant vitamins and mineral supplementation. Eur J Cancer. 2010 Dec;46(18):3316-22.