Blackmores Institute

With the increasing global incidence of skin cancer in the last 10 years, reviewers of the Phase II and Phase III studies examining the role of nicotinamide (NAM) in primary chemoprevention of melanoma and non-melanoma skin cancer (NMSC), highlight the potential benefits of NAM intervention in addressing this public health issue. “Ultraviolet exposure causes, on human skin, different processes capable of triggering cutaneous carcinogenesis, including inflammation. UV exposure is an exogenous insult able to damage cellular DNA in the form of strand breaks, crosslinks, and modified bases. Cells are provided with different repair systems that require high levels of energy in the form of ATP. Because NAM is the precursor of NAD+ (a co-enzyme essential for ATP production), it was demonstrated that its UV protective effects on the skin are linked to the role of NAM in cellular energy pathways,” the authors explained. According to the authors, NAM interferes with skin carcinogenesis regulating immunosuppressor genes such as p53 and sirtuins. The protein p53 is able to induce cell cycle arrest and apoptosis when DNA damage is registered, and it can be activated by NAD+. Conducted over four months, both Phase II double-blinded controlled trials on actinic keratoses – one of the most common skin disorders – showed a significant relative reduction of actinic keratoses in both groups, specifically, 35 percent for nicotinamide twice daily and 29 percent in once daily. “During the four-month trial, 11 placebo-patients developed a total of 20 NMSC (12 basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)) while only four (2 BCC and 2 SCC) in the nicotinamide group,” the authors said. In the Phase III trial, the double-blinded ONTRAC (Oral Nicotinamide To ReduceActinic Cancer) study, a total of 386 patients were randomised to receive NAM 500mg twice daily or placebo for 12 months. The primary endpoint of the study, the number of new NMSC, and the secondary endpoint, the number of actinic keratoses and the number of BCC and SCC were assessed every three months during the intervention period. “Reduction of actinic keratoses was 11% lower in the nicotinamide group than in placebo group at three months, 14% at six, 20% at nine, and 13% at 12 months. During the 12-month treatment, the mean number of NMSC was 1.8 in the nicotinamide group and 2.4 in the placebo group. During the active treatment period at each three-month visit, the NAM group had a low incidence of new NMSC – the relative difference was 25%, 27%, 18%, and 29%, respectively, at 3, 6, 9 and 12 months. “Considering BCC and SCC, it was seen that the mean number of BCC was 1.3 in NAM group and 1.9 in the placebo group, with a lower rate of 20% after adjustment for the centre and 5-year basal-cell carcinoma history. This reduction appeared to be more linked to the superficial BCC than to other types. As for SCC, the mean number was 0.5 and 0.7, respectively, in NAM and placebo groups with a lower rate of 30% after adjustment for the centre and 5-year squamous-cell carcinoma history,” the authors stated. While the review authors claim that chemoprevention in melanoma remains a controversial topic, other studies continue on the role of non-steroidal anti-inflammatory drugs, statins, retinoids, calcium, vitamin D, and selenium in melanoma prevention have been conducted. With only a few trials investigating the relationship between NAM and melanoma, the results of the Phase II and Phase III studies may provide the stimulus for further investigations. The recommended dose for oral nicotinamide is 500 mg twice daily. The effectiveness of 500 mg twice daily and 500 mg once daily were compared, and the Phase II trials showed the superiority of nicotinamide's effectiveness in reducing actinic keratoses counts in the group taking 500 mg twice daily compared with 500 mg once daily. “As demonstrated in the ONTRAC study, chemopreventive effects of nicotinamide were shortly lost after discontinuation and reduction in skin cancer incidence was not maintained in the 6-months follow-up period after discontinuation of nicotinamide. For this reason, nicotinamide is an effective component in the prevention of skin cancer only when taken chronically,” the authors concluded. Source:
 Giacalone S, et.al.: Oral nicotinamide: The role in skin cancer chemoprevention. Dermatologic Therapics. <a href="https://doi.org/10.1111/dth.14892" target="_blank">2021;34:e14892</a>

Results from Phase II and Phase III clinical studies suggest that nicotinamide (vitamin B3) reduces skin cancer compared to placebo, which may warrant further consideration in prevention strategies, a recently published review in Dermatologic Therapies reports.

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