expert opinion

Nicotinamide (vitamin B3) may help prevent skin cancer: positive phase 3 trial

January 11, 2016

Dr Andrew C Chen, Royal Prince Alfred Hospital, University of Sydney, Australia

Results from the ONTRAC (Oral Nicotinamide to Reduce Actinic Cancer) phase 3 trial (1) indicate that a daily intervention dose of 500 mg nicotinamide (vitamin B3) for 12 months is protective against new cases of non-melanoma skin cancers (23% less in the intervention group compared with the placebo, P= 0.02). The study was made in Australia and there were 386 study participants, who had had at least two non-melanoma skin cancers in the previous five years. The median number of new skin cancers developed was 2.4 in the placebo group compared with 1.8 in the nicotinamide group.

Vitamin B3, also known as niacin or nicotinic acid, is a water-soluble vitamin, used by the human body as nicotinamide (also called “niacinamide”) to form the coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). Vitamin B3 can be synthesized in humans from the amino acid tryptophan, and this source can provide up to two thirds of the basic requirement. Good sources of vitamin B3 (niacin) include yeast, meat, poultry, red fish (e.g., tuna, salmon), cereals, legumes and seeds. Additionally, meat, milk and eggs are good sources of tryptophan. A sufficient intake of vitamin B3 (niacin) is important as it helps the body to convert food into glucose, produce important macromolecules (e.g., fatty acids and cholesterol) and repair DNA (2). Recommended daily intake levels are typically around 14 mg for men and 12 mg for women (expressed as niacin equivalents).

Oral consumption of a range of vitamins is believed to have protective properties on the skin against UV radiation, but full clinical trials are required to confirm and define the effect (3).

Non-melanoma skin cancer is the most common form of cancer in Caucasians. The cost of treating it in the USA alone has been estimated at USD 4.8 billion per annum (4). Exposure to UV radiation can lead to cumulative damage to basal views. This is typically characterized by rough, scaly patches of skin known as non-malignant actinic keratosis. These are common (typically 20%+) in adults over the age of 40 with white skin. The rate of conversion from keratosis to full non-melanoma skin cancer is a matter for debate, but it is certainly greatly accelerated if the damaged skin tissues continue to be exposed to the sun.

UV radiation damages the DNA in the skin causing immunosuppression, primarily by depleting ATP levels that could otherwise repair the damage. Nicotinamide (vitamin B3) is an essential co-factor for ATP production (1). Daily oral vitamin B3 supplementation of 500 mg and 1500 mg has been shown to be protective against UV radiation-induced immunosuppression (5).

Nicotinamide has a good safety profile and has been used at pharmacological doses of up to 3 g per day with minimal side effects. Dr. Chen has previously used doses of 1.5 g per day to treat autoimmune skin diseases (6).

The ONTRAC trial also demonstrated a reduction in the incidence of actinic keratosis in the treatment arm at similar reduction levels to those found for non-melanoma skin cancers. However, the benefit appears to be lost when the intervention is halted.

Whilst the results of the ONTRAC trial are highly encouraging, it must remembered that the incidence of skin cancers in Australia is amongst the highest in the world and the results may not be replicable to other populations. The size of the cohort was relatively small and the dose of vitamin B3 used was relatively high (when compared with typical intake recommendations). However, the ONTRAC team has concluded that it makes sense to use treatment with nicotinamide in high-risk skin cancer and pre-skin cancer patients in Australia.

Please note: Any dietary or drug treatment with high doses of micronutrients may override the body’s own control mechanisms; therefore, micronutrient therapies may be associated with potential side effects and toxicities. High-dosed micronutrients should not be used without medical supervision.

References

  1. Chen A C, Martin, A J, Choy B, Fernández-Peñas P, Dalziell, RA, McKenzie, CA & Damian, DL; " A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention"; New England Journal of Medicine 2015 , 373(17): 1618-1626.
  2. Nutri-Facts, "Vitamin B3";
  3. Nutri-Facts, "Sun protection - as important inside as outside"; August 2010; 
  4. Guy GP Jr, Machlin SR, Ekwueme DU& Yabroff KR: “Prevalence and costs of skin cancer treatment in the U.S., 2002-2006 and 2007-2011”; Am J Prev Med 2015; 48:183-7.
  5. Yiasemides E, Sivapirabu G, Halliday GM, Park J & Damian DL.; “Oral nicotinamide protects against ultraviolet radiation induced immunosuppression in humans”; Carcinogenesis 2009; 30: 101-5.
  6. Chen A & Damian D, “Nicotinamide and the skin”; Australasian Journal of Dermatology 2014, 55(3): 169-175.