Nicotinamide

Purported Benefits, Side Effects & More

Nicotinamide

Purported Benefits, Side Effects & More
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Nicotinamide

Common Names

  • Vitamin B3
  • Niacinamide
  • Nicotinic acid amide
  • Nicotinic amide
  • Vitamin PP

For Patients & Caregivers

Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.


What is it?

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.

What are the potential uses and benefits?

To prevent skin cancer
A large study found that taking nicotinamide can reduce the risk of getting certain types of skin cancers. A few small studies suggest it may also reduce the occurrence of rough scaly patches. 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.

What are the side effects?

Largely well tolerated; high oral doses may cause

  • Nausea, vomiting
  • Headache
  • Fatigue, dizziness
  • Liver toxicity
  • Increased risk for low platelets
What else do I need to know?

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.
  • You have low platelets: A meta-analysis suggests that using nicotinamide may increase the risk for low platelets, so patients should consult with their healthcare provider.

Special Point:

  • If you have a history of cardiovascular disease, check with your cardiologist before starting nicotinamide.
  • 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.

For Healthcare Professionals

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) (24) (2), hyperpigmentation (25) and to prevent hair thinning (26).

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 demonstrated in human studies (4) (7) (8). It was also shown to improve inner retinal (27) and visual function (28) in patients treated for glaucoma. 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, similar effects were not significant (12). Other studies found a reduction in actinic keratoses, a predictor of melanoma risk (13) (21), and a meta-analysis reported association with significant reductions in basal cell and squamous cell carcinomas, but increased risk of digestive adverse events (29). Additional studies are warranted (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). In a recent prospective discovery cohort study (n = 1,162 total, n = 422 females), it suggested that a terminal metabolite from excess niacin supplementation was associated with increased incident of major adverse cardiovascular events (MACE) (31).  

Food Sources

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

Purported Uses and Benefits
  • 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), 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). Skin cancer chemoprevention is attributed in part to reductions in inflammatory macrophages (22). 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) .

Adverse Reactions

Nicotinamide appears to be largely well tolerated (11) (12) (13). However nausea, vomiting, and other gastrointestinal symptoms (29), as well as headache, fatigue, dizziness (9) and liver toxicity (19) have been associated with high oral doses.

Increased risk for thrombocytopenia has been noted in a meta-analysis of RCTs in hemodialysis patients with the use of nicotinamide  (23).

Increased risk of myopathy and rhabdomyolysis were reported in a review of patients on statins with nicotinamide use (30).

Increased incident of major adverse cardiovascular events (MACE) in excess niacin supplementation (31).  Providers will need to reassess risk and benefits in patient predisposed to cardiovascular conditions before prescribing niacin for low plasma HDL-cholesterol or high plasma triglyceride levels (32).

Herb-Drug Interactions
  • Carbamazepine: Increased levels of this drug have been reported in patients who also received nicotinamide (20).
Dosage (OneMSK Only)
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.
  21. Drago F, Ciccarese G, Cogorno L, et al. Prevention of non-melanoma skin cancers with nicotinamide in transplant recipients: a case-control study. Eur J Dermatol. Aug 1 2017;27(4):382-385.
  22. Minocha R, Martin AJ, Chen AC, et al. A Reduction in Inflammatory Macrophages May Contribute to Skin Cancer Chemoprevention by Nicotinamide. J Invest Dermatol. Feb 2019;139(2):467-469.
  23. Zhang Y, Ma T, Zhang P. Efficacy and safety of nicotinamide on phosphorus metabolism in hemodialysis patients: A systematic review and meta-analysis. Medicine (Baltimore). Oct 2018;97(41):e12731.
  24. Kozan A, Guner RY, Akyol M. A retrospective assessment and comparison of the effectiveness of benzoyl peroxide; the combination of topical niacinamide, gallic acid, and lauric acid; and the combination of benzoyl peroxide and erythromycin in acne vulgaris. Dermatol Ther. 2020 Jul;33(4):e13534.
  25. Kalasho BD, Minokadeh A, Zhang-Nunes S, et al. Evaluating the Safety and Efficacy of a Topical Formulation Containing Epidermal Growth Factor, Tranexamic Acid, Vitamin C, Arbutin, Niacinamide and Other Ingredients as Hydroquinone 4% Alternatives to Improve Hyperpigmentation: A Prospective, Randomized, Controlled Split Face Study. J Cosmet Sci. 2020 Sep/Oct;71(5):263-290.
  26. Davis MG, Piliang MP, Bergfeld WF, et al. Scalp application of antioxidants improves scalp condition and reduces hair shedding in a 24-week randomized, double-blind, placebo-controlled clinical trial. Int J Cosmet Sci. 2021 Nov;43 Suppl 1:S14-S25.
  27. Hui F, Tang J, Williams PA, et al. Improvement in inner retinal function in glaucoma with nicotinamide (vitamin B3) supplementation: A crossover randomized clinical trial. Clin Exp Ophthalmol. 2020 Sep;48(7):903-914.
  28. De Moraes CG, John SWM, Williams PA, Blumberg DM, Cioffi GA, Liebmann JM. Nicotinamide and Pyruvate for Neuroenhancement in Open-Angle Glaucoma: A Phase 2 Randomized Clinical Trial. JAMA Ophthalmol. 2022 Jan 1;140(1):11-18.
  29. Mainville L, Smilga AS, Fortin PR. Effect of Nicotinamide in Skin Cancer and Actinic Keratoses Chemoprophylaxis, and Adverse Effects Related to Nicotinamide: A Systematic Review and Meta-Analysis. J Cutan Med Surg. 2022 May-Jun;26(3):297-308.
  30. Hadeler EK, Maderal AD. Drug interactions of natural supplements in dermatology: a review. Int J Dermatol. 2021 Oct;60(10):1183-1189.
  31. Ferrell M, Wang Z, Anderson JT, et al. A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk. Nat Med. 2024 Feb;30(2):424-434. Epub 2024 Feb 19. Erratum in: Nat Med. 2024 Mar 6;: PMID: 38374343.
  32. Lim GB. Metabolic product of excess niacin is linked to increased risk of cardiovascular events. Nat Rev Cardiol. 2024 May;21(5):280.
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