Nicotinamide

• How It Works

  In high-risk individuals, nicotinamide supplementation had protective effects against certain types of skin lesions and nonmelanoma skin cancers.

  Nicotinamide is a water-soluble form of vitamin B3 or niacin. It is made in the body by eating niacin-rich foods such as fish, poultry, nuts, legumes, eggs, and cereal grains. Nicotinamide supplements are used to treat skin conditions and niacin deficiencies.

  Recent studies suggest nicotinamide may protect against some forms of skin lesions in patients with sun-damaged skin. Additional studies are needed to confirm safety and effectiveness across different types of skin cancer and in different people. In addition, the protective effects of nicotinamide against UV exposure does not mean that it protects against sunburn.

• Purported Uses

  To prevent skin cancer
  A large study found that taking nicotinamide can reduce the risk of getting certain types of skin cancers. Additional long-term studies are needed.

  To treat acne and other skin conditions
  Nicotinamide is used as a medicine for treating skin conditions such as acne and rosacea.

• Do Not Take If
  • You are taking anticonvulsants such as carbamazepine: Nicotinamide may increase the blood levels and risk of side effects of this drug.
• Side Effects

  Nicotinamide appears to be largely well tolerated, but high oral doses may cause nausea, vomiting, headache, fatigue, dizziness, or liver toxicity.

• Special Point
  • Although nicotinamide appears to protect against ultraviolet (UV) light exposure, it is not a substitute for sunscreen and does not protect against sunburn.
  • Even though niacin can become nicotinamide in the body, their effects and side effects when used as supplements are different and not interchangeable.
• Scientific Name

  Pyridine-3-carboxamide

• Clinical Summary

  Nicotinamide, also known as niacinamide, is a water-soluble amide form of niacin or vitamin B3. It is found in foods such as fish, poultry, eggs, and cereal grains. It is also marketed as a dietary supplement, and as a non-flushing form of niacin.

  Nicotinamide has established medical uses to treat conditions stemming from niacin deficiency such as pellagra. Oral and topical formulations are used to treat a variety of inflammatory skin conditions including acne vulgaris and rosacea ^(1) (2).

  An animal study suggests nicotinamide supplementation can help prevent glaucoma by preserving mitochondrial function ⁽³⁾. Other preclinical models demonstrate photoimmunoprotective and chemopreventive effects against UV radiation ⁽⁴⁾. Nicotinamide enhances repair of UV radiation-induced DNA damage in human melanocytes ⁽⁵⁾ and keratinocytes ⁽⁶⁾ and similar effects have been demostrated in human studies ^{(4) (7) (8)}. Other clinical trials show oral nicotinamide reduces UV-induced ⁽⁹⁾ and photodynamic therapy (PDT)-induced ⁽¹⁰⁾ immunosuppression.

  In patients with sun-damaged skin, oral nicotinamide helped prevent the occurrence of nonaggressive skin cancers ⁽¹¹⁾. In a small trial among renal transplant patients however, such similar effects were not significant ⁽¹²⁾. Other studies found reduction in actinic keratoses, a predictor of melanoma risk ⁽¹³⁾. Additional studies are warrented ⁽¹⁴⁾.

  Nicotinamide appears to be largely well tolerated in clinical studies ^{(11) (12) (13)}. Even though niacin is converted into nicotinamide in the body ⁽¹⁾, these two supplements should not be viewed as interchangeable as they have different side effect profiles ^(11) (15).

• Food Sources

  Fish, poultry, eggs, nuts, legumes, beef, cereal grains, fortified foods; smaller amounts are also found in green vegetables.

• Purported Uses
  • Acne and other dermatological conditions
  • Skin cancer prevention
• Mechanism of Action

  Nicotinamide is chemically part of the coenzymes nicotinamide adenine dinucleotide NAD+ and NADH ⁽¹⁾. They are used in oxidation-reduction reactions in the body. Among these activities is the production of adenosine triphosphate (ATP) ⁽¹¹⁾, which fuels cellular metabolic activities.

  Photoimmunoprotective effects of oral or topical nicotinamide are linked to its support for DNA repair by preventing post-UV exposure declines in cellular energy or the repletion of energy to irradiated cells ^(4) (13). Its influence on several pathways contribute to this enhanced repair of UV-induced DNA damage ⁽¹⁶⁾. In UV-irradiated keratinocytes, nicotinamide reduced expression of IL-6, IL-10, MCP-1 and TNF-alpha mRNA, cytokine mediators whose activity may be involved in inflammation, cellular-tissue injury, cell death, and skin cancer ⁽¹⁷⁾. In human melanocytes, nicotinamide increased the global nucleotide excision repair rate and number of irradiated melanocytes undergoing DNA repair ⁽⁵⁾.

  Effects of topical nicotinamide on inflammatory skin conditions are attributed to its sebosuppressive and anti-inflammatory properties ⁽¹⁾.

  Although niacin and nicotinamide are considered similar in their role as vitamins, their pharmacologic indications, effects, and side effects are different. Niacin has high affinity to a G-protein-coupled receptor HM74A in human cells resulting in the releasing of prostaglandins that cause vasodilation or flushing of the skin. It also lowers cholesterol ^(11) (18) . However, nicotinamide does not have these effects.

• Adverse Reactions

  Nicotinamide appears to be largely well tolerated ^{(11) (12) (13)}. However nausea, vomiting, and other gastrointestinal symptoms, as well as headache, fatigue, dizziness ⁽⁹⁾ and liver toxicity ⁽¹⁹⁾ have been associated with high oral doses.

• Herb-Drug Interactions
  • Carbamazepine: Increased levels of this drug have been reported in patients who also received nicotinamide ⁽²⁰⁾.
• References

  1. Rolfe HM. A review of nicotinamide: treatment of skin diseases and potential side effects. J Cosmet Dermatol. Dec 2014;13(4):324-328.

  2. Niren NM. Pharmacologic doses of nicotinamide in the treatment of inflammatory skin conditions: a review. Cutis. Jan 2006;77(1 Suppl):11-16.

  3. Williams PA, Harder JM, Foxworth NE, et al. Vitamin B3 modulates mitochondrial vulnerability and prevents glaucoma in aged mice. Science. Feb 17 2017;355(6326):756-760.

  4. Damian DL. Photoprotective effects of nicotinamide. Photochem Photobiol Sci. Apr 2010;9(4):578-585.

  5. Thompson BC, Surjana D, Halliday GM, et al. Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in primary melanocytes. Exp Dermatol. Jul 2014;23(7):509-511.

  6. Thompson BC, Halliday GM, Damian DL. Nicotinamide enhances repair of arsenic and ultraviolet radiation-induced DNA damage in HaCaT keratinocytes and ex vivo human skin. PLoS One. 2015;10(2):e0117491.

  7. Sivapirabu G, Yiasemides E, Halliday GM, et al. Topical nicotinamide modulates cellular energy metabolism and provides broad-spectrum protection against ultraviolet radiation-induced immunosuppression in humans. Br J Dermatol. Dec 2009;161(6):1357-1364.

  8. Damian DL, Patterson CR, Stapelberg M, et al. UV radiation-induced immunosuppression is greater in men and prevented by topical nicotinamide. J Invest Dermatol. Feb 2008;128(2):447-454.

  9. Yiasemides E, Sivapirabu G, Halliday GM, et al. Oral nicotinamide protects against ultraviolet radiation-induced immunosuppression in humans. Carcinogenesis. Jan 2009;30(1):101-105.

  10. Thanos SM, Halliday GM, Damian DL. Nicotinamide reduces photodynamic therapy-induced immunosuppression in humans. Br J Dermatol. Sep 2012;167(3):631-636.

  11. Chen AC, Martin AJ, Choy B, et al. A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention. N Engl J Med. Oct 22 2015;373(17):1618-1626.

  12. Chen AC, Martin AJ, Dalziell RA, et al. A phase II randomized controlled trial of nicotinamide for skin cancer chemoprevention in renal transplant recipients. Br J Dermatol. Nov 2016;175(5):1073-1075.

  13. Surjana D, Halliday GM, Martin AJ, et al. Oral nicotinamide reduces actinic keratoses in phase II double-blinded randomized controlled trials. J Invest Dermatol. May 2012;132(5):1497-1500.

  14. Yelamos O, Halpern AC, Weinstock MA. Reply to ’A phase II randomized controlled trial of nicotinamide for skin cancer chemoprevention in renal transplant recipients’. Br J Dermatol. Feb 2017;176(2):551-552.

  15. Kademian M, Bechtel M, Zirwas M. Case reports: new onset flushing due to unauthorized substitution of niacin for nicotinamide. J Drugs Dermatol. Dec 2007;6(12):1220-1221.

  16. Surjana D, Halliday GM, Damian DL. Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in human keratinocytes and ex vivo skin. Carcinogenesis. May 2013;34(5):1144-1149.

  17. Monfrecola G, Gaudiello F, Cirillo T, et al. Nicotinamide downregulates gene expression of interleukin-6, interleukin-10, monocyte chemoattractant protein-1, and tumour necrosis factor-alpha gene expression in HaCaT keratinocytes after ultraviolet B irradiation. Clin Exp Dermatol. Mar 2013;38(2):185-188.

  18. Benyo Z, Gille A, Kero J, et al. GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing. J Clin Invest. Dec 2005;115(12):3634-3640.

  19. Winter SL, Boyer JL. Hepatic toxicity from large doses of vitamin B3 (nicotinamide). N Engl J Med. Nov 29 1973;289(22):1180-1182.

  20. Bourgeois BF, Dodson WE, Ferrendelli JA. Interactions between primidone, carbamazepine, and nicotinamide. Neurology. Oct 1982;32(10):1122-1126.