Kate Street

Skin cancer remains a significant global health burden, with particularly high incidence in regions with elevated ultraviolet (UV) exposure.1 In Australia, at least two in three people will be diagnosed with some form of skin cancer during their lifetime.2 Non-melanoma skin cancers (NMSCs), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are the most common malignancies worldwide and contribute substantially to the healthcare burden.3Despite increased awareness of sun protection, incidence rates remain high, particularly among females and older individuals.4 This highlights the need for adjunctive preventive strategies beyond UV avoidance alone.One strategy with growing interest is supplementation with nicotinamide (vitamin B3), a compound known for its role in cellular energy metabolism and increasingly recognised for its potential in skin cancer chemoprevention.5 Since our 2024 article on this topic, the evidence base has continued to build, further supporting nicotinamide's role in this setting.<h3>Understanding skin cancer</h3>The skin is the body’s largest organ, functioning as a protective barrier against environmental stressors.6 The epidermis, its outermost layer, is primarily composed of keratinocytes, which are continuously renewed and particularly susceptible to UV-induced damage.6UV radiation is the predominant environmental driver of skin cancer, inducing DNA damage and disrupting normal cellular repair processes.7 Over time, this cumulative damage can lead to the development of keratinocyte cancers, including BCC and SCC.7<h3>The role of nicotinamide</h3>Nicotinamide is a precursor to nicotinamide adenine dinucleotide (NAD+), a critical cofactor in cellular energy production and DNA repair.8 Its relevance in skin cancer prevention lies in its ability to counteract key processes involved in UV-induced carcinogenesis.8UV radiation contributes to skin cancer development through multiple pathways, including direct DNA damage, suppression of cutaneous immune responses, and depletion of cellular energy required for DNA repair.5Nicotinamide has been shown to target these pathways through several mechanisms:<ul><li>Enhancing DNA repair: Replenishes NAD+ to support ATP-dependent repair of UV-induced DNA damage</li><li>Restoring cellular energy: Prevents UV-induced reductions in ATP, supporting overall cellular function</li><li>Reducing immunosuppression: Helps preserve T-cell responses, supporting the skin’s immune defence</li><li>Modulating inflammation: Regulates local inflammatory mediators such as IL-6, IL-10, and TNF-α</li><li>Supporting skin barrier integrity: Contributes to skin resilience and repair mechanisms (see Figure 1).5
</li></ul><img src="https://images.contentstack.io/v3/assets/blt948bd74310fc0ad0/blta2983e836de3ab1a/6a02a9bab5a04087132168cf/Citric_Acid_Cycle_Glycolytic_Pathway.png" alt="Citric Acid Cycle Glycolytic Pathway.png" width="100" class="embedded-asset" style="" />Figure 1. Nicotinamide and photoprotection.5In addition, nicotinamide has demonstrated benefits in reducing actinic keratoses, recognised precursors to SCC.5
<h3>Established clinical evidence</h3>The role of nicotinamide in NMSC prevention was highlighted in a landmark randomised controlled trial funded by the National Health and Medical Research Council (NHMRC) involving high-risk individuals with a history of multiple skin cancers.9In this study, oral nicotinamide (500 mg twice daily) reduced the incidence of NMSCs by 23% over 12 months compared with placebo, alongside significant reductions in actinic keratoses.9Importantly, these protective effects were not sustained after discontinuation, indicating that continuous supplementation is required to maintain benefit.9<h3>Emerging insights</h3>A large 2025 study published in JAMA Dermatology provides large-scale, real-world evidence supporting the role of nicotinamide in skin cancer chemoprevention.10In this large retrospective cohort study of 33,822 veterans, nicotinamide supplementation of 500 mg twice daily for &gt;30 days was associated with a significant reduction in the risk of multiple skin cancer types, including BCC and SCC (see Figure 2).10<img src="https://images.contentstack.io/v3/assets/blt948bd74310fc0ad0/blt0ec514083f2150a0/6a02a9bacb288b054e6abe13/Screenshot_20260428_at_40742_pm.png" alt="Screenshot 20260428 at 40742 pm.png" width="100" class="embedded-asset" style="" />Figure 2. Overall skin cancer-free survival among patients with or without exposure to nicotinamide.10
Key findings include:<ul><li>Significant overall risk reduction: ~14% reduction in new skin cancer incidence</li><li>Greater effect in SCC: ~22% reduction</li><li>Timing matters: Up to ~50% risk reduction when initiated earlier, particularly after a first skin cancer</li><li>Diminishing returns: Reduced benefit with increasing prior disease burden.10</li></ul>These findings suggest that both timing of initiation and baseline risk profile are important determinants of clinical benefit, reinforcing the role of nicotinamide as an early secondary prevention strategy.<h3>Clinical implications</h3>The evolving evidence base suggests that nicotinamide may offer a safe, accessible, and evidence-based adjunctive approach to reducing the incidence of NMSCs in high-risk individuals.10<ul><li>Nicotinamide should complement, not replace, sun protection measures.</li><li>Benefits appear limited to periods of active supplementation.9</li><li>The strongest evidence exists in individuals with a history of skin cancer or significant cumulative sun exposure.9</li></ul><h3>Conclusion</h3>As the global burden of NMSC continues to rise, there is a clear need for effective, scalable preventive strategies. Nicotinamide represents a promising option, supported by a growing and consistent body of clinical evidence. While ongoing research will continue to refine optimal dosing, duration, and patient selection, current evidence supports nicotinamide as a valuable adjunct within a comprehensive skin cancer prevention approach.
<h3>References</h3><ol><li>Feng F, Ma Y, Zhao Y, Wan Z, Zhang R, Yang S. Global assessment of surface ultraviolet radiation and malignant skin melanoma incidence from 1990 to 2021. Scientific Reports. 2025 Nov 10 [cited 2025 Nov 29];15(1). Available from: https://www.nature.com/articles/s41598-025-23066-z</li></ol>2. Cancer Council. Incidence and mortality | National Cancer Prevention Policy Skin Cancer Statistics and Issues. Cancer Council. 2023. Available from: https://www.cancer.org.au/about-us/policy-and-advocacy/prevention/uv-radiation/related-resources/skin-cancer-incidence-and-mortality3. Amdad Hossain Roky, Mohammed Murshedul Islam, Fuad M, Md. Saqline Mostaq, Md. Zihad Mahmud, Mohammad Nurul Amin, et al. Overview of skin cancer types and prevalence rates across continents. Cancer Pathogenesis and Therapy. 2024 Aug 1;3(2). DOI: 10.1016/j.cpt.2024.08.0024. Dugan MM, Shannon AB, DePalo DK, Tsai KY, Farma JM, Gonzalez RJ, et al. Current management of nonmelanoma skin cancers. Current Problems in Surgery. 2024 Nov 26;62:101565. Available from: https://www.sciencedirect.com/science/article/pii/S00113840240012665. Snaidr VA, Damian DL, Halliday GM. Nicotinamide for photoprotection and skin cancer chemoprevention: A review of efficacy and safety. Experimental Dermatology. 2019 Jan 30;28:15–22. DOI: 10.1111/exd.138196. Yousef H, Alhajj M, Sharma S. Anatomy, Skin (Integument), Epidermis. PubMed. Treasure Island (FL): StatPearls Publishing; 2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK4704647. Vechtomova Y, Telegina T, Buglak A, Kritsky M. UV Radiation in DNA Damage and Repair Involving DNA-Photolyases and Cryptochromes. Biomedicines. 2021 Oct 28;9(11):1564. DOI: 10.3390/biomedicines91115648. Camillo L, Zavattaro E, Savoia P. Nicotinamide: A Multifaceted Molecule in Skin Health and Beyond. Medicina. 2025 Feb 1;61(2):254–4. DOI: 10.3390/medicina610202549. Chen AC, Martin AJ, Choy B, Fernández-Peñas P, Dalziell RA, McKenzie CA, et al. A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention. New England Journal of Medicine. 2015 Oct 22;373(17):1618–26. DOI: 10.1056/NEJMoa150619710. Breglio KF, Knox KM, Hwang J, Weiss R, Maas K, Zhang S, et al. Nicotinamide for Skin Cancer Chemoprevention. JAMA Dermatology. 2025 Sep 17; Available from: https://jamanetwork.com/journals/jamadermatology/article-abstract/2838591

<h3>Key highlights</h3><ul><li>Nicotinamide supports DNA repair and restores cellular energy after UV exposure, helping maintain normal skin cell function.</li><li>Oral nicotinamide therapy has been shown to reduce the incidence of non-melanoma skin cancer.</li><li>Recent clinical trials demonstrate that nicotinamide is well-tolerated and safe for long-term use as a preventive strategy.</li><li>Integrating nicotinamide supplementation with standard sun protection offers a practical, evidence-based approach for individuals at high risk of skin cancer.</li></ul>

Key highlights

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