Why Niacinamide Is One of My Favorite Nutrients

By Alan R. Gaby, MD

When I first began studying nutritional therapies in the early 1970s, vitamin C was my favorite nutrient. As I learned more about individual nutrients, magnesium replaced vitamin C at the top of the list, and has remained there ever since. Students in my nutrition classes used to joke that, if they did not know the answer to a test question, they would have a good chance of getting it right by answering “magnesium.” Niacinamide has also been known for years to be beneficial for preventing or treating a number of common health conditions, including schizophrenia, osteoarthritis, anxiety, and various skin conditions. Recently, niacinamide was reported to be effective for preventing non-melanoma skin cancer and possibly (based on animal research) for preventing glaucoma. These new reports have propelled niacinamide into my top five, so a brief review of this valuable vitamin seems to be in order.

Nomenclature and Biochemistry

Vitamin B₃ occurs naturally in two forms: niacin (also called nicotinic acid) and niacinamide (also called nicotinamide). Vitamin B₃ is a precursor to nicotinamide adenine dinucleotide (NAD), which plays a role in the electron-transport chain and, consequently, in the synthesis of adenosine triphosphate (ATP), the body’s main storage form of energy. Vitamin B₃ is also a precursor to NAD phosphate (NADP), which functions as a coenzyme in oxidation-reduction reactions. In addition, vitamin B₃ is involved in brain function.

While most of the biochemical functions of vitamin B₃ can be performed either by niacin or niacinamide, only niacin influences serum lipid levels. In addition, niacin has a vasodilatory action, which does not appear to occur with niacinamide. When vitamin B₃ is being used for reasons other than improving lipid levels or promoting vasodilation, niacinamide is usually the preferred form, since it causes fewer adverse effects.

Key Clinical Uses

Osteoarthritis

Kaufman reported in the 1940s and 1950s that supplementation with niacinamide in doses of 900-4,000 mg per day produced good results in more than 600 patients with osteoarthritis.^1-4 Treatment with niacinamide usually resulted in an increase in joint mobility, as well as subjective improvements in joint discomfort, inflammation, and pain. Benefits were usually evident after three to four weeks of treatment. Thereafter, progressive improvement occurred for one to two years if niacinamide was continued.

The beneficial effect of niacinamide was confirmed in a double-blind trial published in 1996. In that study, supplementation with 500 mg of niacinamide six times per day for 12 weeks significantly decreased mean disease severity by 29% (p < 0.04 compared with placebo) and significantly increased joint range of motion (mean, 8.0 degrees vs. 3.5 degrees with placebo; p = 0.04).⁵

Actinic Keratoses and Non-Melanoma Skin Cancer

In double-blind studies of patients with actinic keratoses, with or without a history of non-melanoma skin cancer, oral administration of niacinamide (500-1,000 mg per day) for 4-12 months significantly decreased the number of actinic keratoses and significantly reduced the incidence of new non-melanoma skin cancers.^6,7 Niacinamide is believed to work by preventing ultraviolet irradiation-induced immunosuppression.

Schizophrenia

Abram Hoffer, one of the pioneers of the use of diet and nutritional supplements to treat schizophrenia, worked with more than 5,000 schizophrenic patients over a 50-year period. According to Hoffer, 90% of acute schizophrenics (i.e., those who have been sick less than two years or have had several remissions and relapses) recover within two years, and 65-75% of chronic schizophrenics are much improved or well within 10 years.^8-10 Niacin or niacinamide (usually 1 g three times per day) along with 3 g per day of vitamin C was a key component of the treatment in most cases.

Several double-blind trials confirmed the efficacy of vitamin B₃ in the treatment of schizophrenia,^11-13 but vitamin B₃ was ineffective in a number of other clinical trials.^14-17 None of the studies lasted long enough to examine Hoffer’s clinical observations regarding the efficacy of long-term treatment.

Anxiety

Anxiety is one of the manifestations of severe vitamin B₃ deficiency (pellagra). A number of practitioners have observed that supplementation with large doses of niacinamide can relieve anxiety in some patients. This anti-anxiety effect is presumably pharmacological, since patients who improved typically did not appear to be deficient in B vitamins, and “nutritional” doses of niacinamide (such as 20-100 mg per day) were of little or no benefit. Studies in mice and in vitro have found that niacinamide has benzodiazepine-like actions.^18,19 In my experience, niacinamide in doses ranging from 500 mg twice a day to 1,000 mg three times per day is beneficial for some patients with anxiety, including patients with anxiety related to alcohol abuse.

Acne (Topical Niacinamide)

Niacinamide has anti-inflammatory effects²⁰ and has been used both topically and orally to treat a variety of inflammatory skin disorders. In a double-blind trial, topical application of a gel containing 4% niacinamide twice a day for eight weeks was at least as effective as topical 1% clindamycin in patients with inflammatory acne.²¹ Similar results were seen in other double-blind trials comparing topical 4% niacinamide gel with 1% clindamycin gel²² and comparing 5% niacinamide gel with 2% clindamycin gel.²³

Glaucoma

Administration of large doses of niacinamide has been reported to prevent the development of glaucoma in mice that are genetically prone to developing glaucoma. Niacinamide did not decrease the elevated intraocular pressure but, rather, appeared to protect the optic nerve against the deleterious effects of elevated intraocular pressure.²⁴ Further research is needed to determine whether niacinamide can prevent glaucoma in humans.

Adverse effects

Hepatotoxicity has occurred on rare occasions with the use of large doses of niacinamide (such as 3 g per day or more). Hoffer stated, based on 30 years of experience with vitamin B₃ therapy (usually 3 g per day or more), that one of every 2,000 patients will develop hepatitis from large doses of this vitamin. In all of his patients who developed hepatotoxicity, liver function returned to normal after treatment was discontinued.²⁵ Nausea may be an early warning sign of niacinamide-induced hepatotoxicity. Treatment should be discontinued or the dosage reduced if nausea occurs. Patients taking large doses of niacinamide (such as 1,500 mg per day or more) should have periodic liver function tests (serum aminotransferase levels).

Niacinamide does not cause most of the other adverse effects that can occur with niacin, such as skin flushing, hyperuricemia, gastrointestinal distress, and reactivation of a pre-existing peptic ulcer. In addition, while long-term treatment with niacin has been reported to increase the incidence of diabetes in patients with cardiovascular disease risk factors, such an effect is not known to occur with niacinamide.

Dosage and Administration

The most frequently used therapeutic dosages of niacinamide are 500-3,000 mg per day. Because of its relatively short half-life, niacinamide should be taken in at least three divided doses per day. According to one practitioner, 250 mg of niacinamide taken six times per day is more effective than 500 mg taken three times per day in the treatment of osteoarthritis.⁴

References

1. Kaufman W. The Common Form of Joint Dysfunction: Its Incidence and Treatment. Brattleboro, VT, E. L. Hildreth Co., 1949.

2. Kaufman W. The use of vitamin therapy to reverse certain concomitants of aging. J Am Geriatr Soc. 1955;3:927-936.

3. Kaufman W. Niacinamide therapy for joint mobility. Therapeutic reversal of a common clinical manifestation of the “normal” aging process. Conn State Med J. 1953;17:584-589.

4. Kaufman W. Niacinamide: a most neglected vitamin. J Int Acad Prev Med. 1983(Winter):5-25.

5. Jonas WB, et al. The effect of niacinamide on osteoarthritis: a pilot study. Inflamm Res. 1996;45:330-334.

6. Surjana D, et al. Oral nicotinamide reduces actinic keratoses in phase II double-blinded randomized controlled trials. J Invest Dermatol. 2012;132:1497-1500.

7. Chen AC, et al. A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. N Engl J Med. 2015;373:1618-1626.

8. Wright JV. Interview with Abram Hoffer; Nutrition and Healing, September, 1994.

9. Hoffer A. Treating chronic schizophrenic patients. J Orthomolec Med. 2002;17:25-41.

10. Hoffer A. Chronic schizophrenic patients treated ten years or more. J Orthomolec Med. 1994;9:7-34.

11. Ananth JV, et al. Nicotinic acid in the prevention and treatment of methionine-induced exacerbation of psychopathology in schizophrenics. Can Psychiatr Assoc J. 1970;15:15-20.

12. Osmond H, Hoffer A. Massive niacin treatment in schizophrenia. Review of a nine-year study. Lancet. 1962;1:316-320.

13. Denson R. Nicotinamide in the treatment of schizophrenia. Dis Nerv Syst. 1962;23:167-172.

14. O’Reilly PO. Nicotinic acid therapy and the chronic schizophrenic. Dis Nerv Syst. 1955;16:67-72.

15. Ashby WR, et al. The effects of nicotinic acid, nicotinamide, and placebo on the chronic schizophrenic. J Ment Sci. 1960;106:1555-1559.

16. McGrath SD, et al. Nicotinamide treatment of schizophrenia. Schizophrenia Bull. 1972;5:74-76.

17. Vaughan K, McConaghy N. Megavitamin and dietary treatment in schizophrenia: a randomised, controlled trial. Aust N Z J Psychiatry. 1999;33:84-88.

18. Mohler H, et al. Nicotinamide is a brain constituent with benzodiazepine-like actions. Nature. 1979;278:563-565.

19. Woolley DW. Tranquilizing and antiserotonin activity of nicotinamide. Science. 1958;128:1277-1278.

20. Bernstein JE, Lorincz AL. The effects of topical nicotinamide, tetracycline, and dapsone on potassium iodide-induced inflammation. J Invest Dermatol. 1980;74:257-258.

21. Shalita AR, et al. Topical nicotinamide compared with clindamycin gel in the treatment of inflammatory acne vulgaris. Int J Dermatol. 1995;34:434-437.

22. Khodaeiani E, et al. Topical 4% nicotinamide vs. 1% clindamycin in moderate inflammatory acne vulgaris. Int J Dermatol. 2013;52:999-1004.

23. Shahmoradi Z, et al. Comparison of topical 5% nicotinamid gel versus 2% clindamycin gel in the treatment of the mild-moderate acne vulgaris: A double-blinded randomized clinical trial. J Res Med Sci. 2013;18:115-117.

24. Williams PA, et al. Vitamin B₃ modulates mitochondrial vulnerability and prevents glaucoma in aged mice. Science. 2017;355:756-760.

25. Hoffer A. On niacin hepatitis. J Orthomolec Psychiatry. 1983;12:90.