B Vitamins to Reduce Skin Cancer

Introduction

The most common malignancy in the United States is nonmelanoma skin cancer with an estimated 5.4 million new cases in 2012.¹ And the incidence is rising. In 2006 there were an estimated 4 million cases.¹ Topical sunscreens are effective prevention for nonmelanoma skin cancer when they are used as directed but compliance with these is poor, even in patients who have already been diagnosed with melanoma.² Long used for various dermatologic conditions, niacinamide is now being looked at for its effects on adenosine triphosphate (ATP) production and skin immunity.³ This article will review niacinamide and its role in the prevention of nonmelanoma skin cancers.

Mechanism

The leading cause of skin cancer is UV light from the sun.^2,4 UV light inhibits the production of ATP, a key component in cellular energy, creating an “energy crisis.”³ This decrease in cellular energy reduces the skin’s immunity and the ability to repair DNA, which can both lead to skin cancer.^3,5

Niacinamide, also known as nicotinamide, is the amide form of vitamin B3. It enhances ATP production, boosting cellular energy which protects against skin immunosuppression and leads to DNA repair.^3,5,6

A randomized, double-blind, crossover trial compared the immunosuppressive effects of UV radiation on 64 patients receiving oral nicotinamide 500 mg or 1500 mg daily versus placebo.⁷ The Mantoux model of skin immunity was used and results showed significant reduction in UV immunosuppression in the nicotinamide treated group.⁷

Efficacy

The recent Oral Nicotinamide to Reduce Actinic Cancer (ONTRAC) study was a phase three, randomized, double-blind, placebo-controlled study that compared nicotinamide 500 mg orally twice daily to placebo in 386 Australian patients for 12 months.⁶ Participants were immune competent and had at least two confirmed nonmelanoma skin cancers in the five years prior to enrollment in the study. The primary endpoint was number of new nonmelanoma skin cancers in 12 months with secondary endpoints of the number of basal cell carcinomas, squamous cell carcinomas, and actinic keratoses. The mean age of patients was 66 years, the mean number of previous skin cancers was eight, and 63% of those enrolled were men. The number of new nonmelanoma skin cancers was significantly lower in the nicotinamide group at an average of 1.77 compared to 2.42 in the placebo group (RRR 0.23 [95% CI; 0.04-0.38; p=0.02]). The ONTRAC study is not yet published.

Actinic keratoses are premalignant lesions that can progress to nonmelanoma skin cancer.² Researchers are also evaluating niacinamide for use in patients with actinic keratoses. Preliminary evidence suggests that use of oral niacinamide (500 mg once or twice daily) may help to reduce actinic keratoses lesions in these patients.⁸

Safety

There was no difference in adverse drug events reported with nicotinamide 500 mg twice daily compared to placebo in the ONTRAC study mentioned above.⁶

A full literature review in 2000 concluded that niacinamide was very well tolerated at doses up to 3 g per day.⁹ Adverse effects reported with oral doses of greater than 6 g per day include nausea, vomiting, headache, fatigue, and dizziness.⁷

There have been no well-established drug interactions reported with usual doses of niacinamide.

Patient Counseling

Niacinamide (nicotinamide) is not an alternative to established measures to protect the skin from the sun or to having regular check-ups with a dermatologist. Sun exposure should be limited and patients should be encouraged to cover up with clothing, hats, and sunglasses.

Patients should be instructed on the proper use of sunscreens which are not usually used correctly. Most people use one-quarter to one-half of the needed amount of sunscreen which can effectively reduce a product with an SPF 30 down to 10.¹⁰ Instruct patients to use about an ounce to one and a half ounces of sunscreen to cover an average adult body.¹⁰ That’s about 45 mL or enough to fit in the palm of your hand.¹⁰ Apply thoroughly to all exposed skin 30 minutes prior to sun exposure and reapply after swimming, sweating, and being in the sun for two hours.¹⁰ To help your patients use their sunscreens correctly, see our PL Patient Education Handout, Staying Safe in the Sun.

Other measures that can reduce the incidence of skin cancer include smoking cessation, weight loss, and a low fat diet.²

Other Supplements

There are several products on the market that claim to be oral “sunscreens” and are promoted as an addition to the use of topical sunscreens. Heliocare contains Polypodium leucotomos extract, a natural ingredient that may have antioxidant properties.¹¹ The SunPill contains vitamins A, C, D, and E, calcium, zinc, selenium, and an herbal combination of ashwaganda, beet root, pomegranate, PABA, green tea extract, and aloe.¹¹ The efficacy and safety of these products is questionable and their use is not generally recommended. Commentary

Niacinamide 500 mg orally twice daily costs less than $10 per month, is widely accessible to patients over the counter, and is well tolerated.

Vitamin B complex products generally do contain niacinamide but usually have only 20 to 100 mg per tablet, so these products should not be used for this indication as they will not provide the dose studied for skin cancer prevention.

Be careful not to confuse niacinamide with another common form of vitamin B3, niacin (nicotinic acid) which is used for treatment of hyperlidipemia.^3,5 You may see vasodilatory adverse effects with niacin, which include pruritus, cutaneous flushing, headaches, and hypotension that are not seen with niacinamide.^3,5

Conclusion

The use of niacinamide (nicotinamide) 500 mg orally twice daily, as an addition to other sun protective measures, looks promising for the prevention of recurrent nonmelanoma skin cancer.⁶ Large, multicenter, international studies looking at the efficacy of niacinamide for the prevention of skin cancer are still needed to establish this as standard practice. Also keep in mind, there is no proof that niacinamide is effective in patients who do not have a history of skin cancer. Continue to recommend established sun protection measures (e.g., use of sunscreen, protective clothing, etc) to your patients.

 

References

1. Rogers HW, Weinstock MA, Feldman SR, Coldiron BM. Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the US population, 2012. JAMA Dermatol 2015 doi:10.1001/jamadermatol.2015.1187.
2. Damian DL. Photoprotective effects of nicotinamide. Photochem Photobiol Sci 2010;9:578-85.
3. Chen AC, Damian DL, Halliday GM. Oral and systemic photoprotection. Photodermatol Photoimmunol Photomed 2014;30:102-11.
4. Surjana D, Halliday GM, Damina DL. Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in human keratinocytes and ex vivo skin. Carcinogenesis 2013;34:1144-9.
5. Chen AC, Damian DL. Nicotinamide and the skin. Australas J Dermatol 2014;55:169-75.
6. Martin AJ, Chen A, Choy B, et al. Oral nicotinamide to reduce actinic cancer: a phase 3 double-blind randomized controlled trial [Abstract 9000]. J Clin Oncol 2015;33.
7. Yiasemides E, Sivapirabu G, Halliday GM, et al. Oral nicotinamide protects against ultraviolet radiation-induced immunosuppression in humans. Carcinogenesis 2009;30:101-5.
8. Surjana D, Halliday GM, Marin AJ, et al. Oral nicotinamide reduces actinic keratoses in phase II double-blinded randomized controlled trials. (Letter). J Invest Dermatol 2012;132:1497-500.
9. Knip M, Douek IF, Moore WP, et al. Safety of high-dose nicotinamide: a review. Diabetologia 2000;43:1337-45.
10. Canadian Dermatology Association. The truth about sunscreen. 2015. http://myskinmagazine.therac.ca/magazine/the-truth-about-sunscreen (accessed June 11, 2015).
11. Jellin JM, Gregory PJ, et al. Natural Medicines Comprehensive Database. http://www.naturaldatabase.com. (Accessed June 11, 2015).