Mainville L, Smilga A-S, Fortin PR. Effect of Nicotinamide in Skin Cancer and Actinic Keratoses Chemoprophylaxis, and Adverse Effects Related to Nicotinamide: A Systematic Review and Meta-Analysis. Journal of Cutaneous Medicine and Surgery. 2022:120347542210782. doi:10.1177/12034754221078201.
Oral nicotinamide was associated with ~50% lower rate of developing new (non-melanoma) skin cancers based on 5 trials of 52 patients total and gastrointestinal adverse effects that improved on nicotinamide cessation.
Clinical Pearls
This was a systematic review and meta-analysis of 29 clinical trials comprising 3039 patients
Oral nicotinamide was associated with ~50% lower rate of developing new (non-melanoma) skin cancers based on 5 trials of 552 patients total and gastrointestinal adverse effects that improved on nicotinamide cessation
Overall authors provided a weak-recommendation based on moderate quality evidence for the use of nicotinamide for healthy patients and organ transplant recipients with a history of cutaneous squamous cell carcinoma, basal cell carcinoma.
Discussion:
Ultraviolet light is a well-documented modifiable risk factor for both melanoma and non-melanoma skin cancer (NMSC). Prior studies, including a randomized, placebo-controlled trial (RCT) in Australia of 386 participants found evidence that 500 mg nicotinamide taken orally twice daily may benefit patients with field cancerization (i.e., diffuse actinic damage, with actinic keratoses, and in situ cutaneous squamous cell carcinomas (cSCCis)) or >1 prior cSCC. This meta-analysis sought to assess the literature to determine the effect nicotinamide may have as a chemoprophylactic agent for skin cancer.
In this systematic review and meta-analysis, the authors included 29 RCTs between 1979-2020 studying nicotinamide as a primary, secondary, or tertiary skin cancer preventative agent (i.e., primary outcome: number of new skin cancers) in a total of 3039 patients (age range 10-75), with secondary outcomes of number of new basal cell carcinomas (BCC), new cSCC, average number of actinic keratoses (AKs), or occurrence of melanoma. Biochemical and gastrointestinal adverse effects (AEs) were also monitored.
In 5 studies that assessed patients with prior BCCs and cSCCs or AKs, the authors found a significant reduction in skin cancer rate (rate ratio 0.5, 95% confidence interval 0.29-0.85, I2=64%). They also found an increasing efficacy of oral nicotinamide correlated with decreasing risk of bias. Nicotinamide was also associated with significant reduction in BCC (rate ratio 0.46, 95%CI 0.22-0.95, I2=53%; n=552, 5 trials), but no significant impact on AKs (however strength of evidence was very low quality) nor melanoma (RR 0.89, 95%CI 0.29-2.79, I2=0%; n=416, 2 trials), or from topical preparations of nicotinamide. Nicotinamide was also associated with gastrointestinal AEs (RR 1.78, 95%CI 1.30-2.45, I2=0%; n=1859, 21 trials), with 2 trials noting “severe diarrhea” that resolved with decreased dosing (to 500 mg/day) or cessation.
Overall, this meta-analysis provides insight that oral nicotinamide may provide benefit to patients prone to developing non-melanoma skin cancer. Of note, the studies included in this analysis had a treatment duration range of 1 month to 1 year. Further prospective studies are as well as how alternative dosing or preparations necessary to determine the long-term safety of oral nicotinamide and to minimize AEs while preserving efficacy.
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