Why niacinamide is one of my favorite nutrients

August 24, 2018

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 5, so a brief review of this valuable vitamin seems to be in order.

Nomenclature and biochemistry

Vitamin B3 occurs naturally in 2 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 niacin. 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. 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 3-4 weeks of treatment. Thereafter, progressive improvement occurred for 1-3 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 6 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).

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. 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 2 years or have had several remissions and relapses) recover within 2 years, and 65-75% of chronic schizophrenics are much improved or well within 10 years. Niacin or niacinamide (usually 1 g 3 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, but vitamin B3 was ineffective in a number of other clinical trials. 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. In my experience, niacinamide in doses ranging from 500 mg twice a day to 1,000 mg 3 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 effects 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 8 weeks was at least as effective as topical 1% clindamycin in patients with inflammatory acne. Similar results were seen in other double-blind trials comparing topical 4% niacinamide gel with 1% clindamycin gel and comparing 5% niacinamide gel with 2% clindamycin gel.

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. 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 1 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. 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 3 divided doses per day. According to one practitioner, 250 mg of niacinamide taken 6 times per day is more effective than 500 mg taken 3 times per day in the treatment of osteoarthritis.

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.

Reprinted with permission from the Townsend Letter.

Alan Gaby

Alan Gaby MD

Dr. Gaby received his undergraduate degree from Yale University, his M.S. in biochemistry from Emory University, and his M.D. from the University of Maryland. He was in private practice for 19 years, specializing in nutritional medicine.

He is past-president of the American Holistic Medical Association who has given expert testimony to the White House Commission on Complementary and Alternative Medicine on the cost-effectiveness of nutritional supplements. He is the author of Preventing and Reversing Osteoporosis (Prima, 1994), The Doctor’s Guide to Vitamin B6 (Rodale Press, 1984), the co-author of The Patient’s Book of Natural Healing (Prima, 1999). Dr. Gaby has written numerous scientific papers in the field of nutritional medicine. He has been the contributing medical editor for the Townsend Letter for Doctors since 1985, and was contributing editor for Alternative Medicine Review from 1996 to 2010.

Over the past 36 years, Dr. Gaby has developed a computerized database of more than 28,000 individually chosen medical journal articles related to the field of natural medicine. He was professor of nutrition and a member of the clinical faculty at Bastyr University in Kenmore, WA, from 1995 to 2002. He is Chief Science Editor for Aisle 7 (formerly Healthnotes, Inc.) and has appeared on the CBS Evening News and the Donahue Show. In 2010, Dr. Gaby completed a 30-year project: the textbook Nutritional Medicine. Over the past 6 years, he has worked on completing the updated second edition of Nutritional Medicine.