Vitamin B3 (Niacin/Niacinamide)
Niacin, also known as nicotinic acid, is a B-vitamin involved in the body’s energy generation process as part of the molecule nicotinamide adenine dinucleotide (NAD). Niacin has been used for treatment of hypercholesterolemia for decades. It was considered a possible therapy for MS as early as 19541, and is currently of interest in conventional medicine as a candidate for use in MS2.
In animal models of MS, both niacin and its metabolized form niacinamide have be observed to be beneficial, as they are both precursors to metabolically active NAD.
Niacinamide at a dose of 500 mg/kg was shown to be anti-inflammatory and highly protective against microglial neurotoxicity induced by a bacterial toxin. It was also shown to significantly prevent the degeneration of demyelinated nerve fibers and improve behavioral deficits characterizing EAE3.
Niacin at a lower dose of 100 mg/kg was observed to significantly increase neurological functional recovery compared to control treatment, likely via reducing inflammatory infiltrates and demyelination areas, and stimulating regeneration of key brain cells4. In a similar study, niacin at the same dose was also found to promote myelin debris clearance in lesions, accompanied by enhancement of healthy brain cell numbers and improved remyelination5.
Niacin at very high doses has been associated with side effects, from the uncomfortable to the dangerous. The following are the best known: severe skin flushing combined with dizziness, rapid heartbeat, Itching, nausea and vomiting, abdominal pain, diarrhea, gout, liver damage, and diabetes. Note that serious side effects are more likely with amounts exceeding 3,000 mg per day6. Niacinamide is also associated with some of the above, but to a lesser degree7.
Nicotinamide riboside and nicotinamide mononucleotide are further metabolized forms of niacinamide that are used to make NAD, and may be more available to the body. They both can be found as supplements, and are not associated with the negative side effects attributed to niacin and niacinamide. In an animal study, nicotinamide riboside 400 mg/kg given before exposure to a neuroinflammatory toxin was shown to increase the NAD level and significantly suppress cytokines, chemokines, a neuroinflammation trigger known as glial activation, and subsequent neurodegeneration.
The recommended daily intake of niacin is 16 mg/day of for men and 14 mg/day for women. The safe upper intake limit is considered to be 35 mg/day niacin, and 900 mg/day niacinamide. Inadequate maternal niacin intake in pregnancy has been linked to birth defects9, and an animal study demonstrated improvements in healthy live births with 90 mg/kg/day niacin supplementation, given as 15 mg/L drinking water10. Because human research has not been conducted in pregnant humans with the high doses recommended as complementary therapy in MS, caution should be taken and niacinamide preferred over niacin.
In a study with lactating women taking niacin 2-60 mg/day, the average milk concentration ranged from 1.17 to 2.75 mcg/mL, directly proportional to maternal dietary intake11 and consistent with the daily recommendations for infants12. It is generally recommended for lactating/nursing women to consume an additional 3 mg/day of niacin to ensure adequacy in her breastmilk13.
Food sources of niacin include red meat, poultry, fish, brown rice, fortified cereals and breads, nuts, seeds, legumes, and bananas14.
References
1.Kuberski Z, Kuklinska Z. [Nicotinic acid therapy of multiple sclerosis]. Neurol Neurochir Psychiatr Pol. Mar-Apr 1954;4(2):145-52. Leczenie stwardnienia wieloogniskowego kwasem nikotynowym.
2.Cunniffe N, Vuong KA, Ainslie D, et al. Systematic approach to selecting licensed drugs for repurposing in the treatment of progressive multiple sclerosis. J Neurol Neurosurg Psychiatry. Mar 2021;92(3):295-302. doi:10.1136/jnnp-2020-324286
3.Kaneko S, Wang J, Kaneko M, et al. Protecting axonal degeneration by increasing nicotinamide adenine dinucleotide levels in experimental autoimmune encephalomyelitis models. J Neurosci. Sep 20 2006;26(38):9794-804. doi:10.1523/JNEUROSCI.2116-06.2006
4.Zhang J, Chen J, Li Y, et al. Niaspan treatment improves neurological functional recovery in experimental autoimmune encephalomyelitis mice. Neurobiol Dis. Nov 2008;32(2):273-80. doi:10.1016/j.nbd.2008.07.011
5.Rawji KS, Young AMH, Ghosh T, et al. Niacin-mediated rejuvenation of macrophage/microglia enhances remyelination of the aging central nervous system. Acta Neuropathol. May 2020;139(5):893-909. doi:10.1007/s00401-020-02129-7
6.MedlinePlus. Niacin. Herbs and Supplements Accessed 27 Jan 2022. https://ods.od.nih.gov/factsheets/Niacin-Consumer/
7.MedlinePlus. Niacinamide. Herbs and Supplements Accessed 27 Jan 2022. https://medlineplus.gov/druginfo/natural/1534.html
8.Roboon J, Hattori T, Ishii H, et al. Inhibition of CD38 and supplementation of nicotinamide riboside ameliorate lipopolysaccharide-induced microglial and astrocytic neuroinflammation by increasing NAD(). J Neurochem. Jul 2021;158(2):311-327. doi:10.1111/jnc.15367
9.Palawaththa S, Islam RM, Illic D, et al. Effect of maternal dietary niacin intake on congenital anomalies: a systematic review and meta-analysis. Eur J Nutr. Apr 2022;61(3):1133-1142. doi:10.1007/s00394-021-02731-9
10.Shi H, Enriquez A, Rapadas M, et al. NAD Deficiency, Congenital Malformations, and Niacin Supplementation. N Engl J Med. Aug 10 2017;377(6):544-552. doi:10.1056/NEJMoa1616361
11.Briggs GG, Freeman, R.K., Tower, C.V., et al. Niacin. Brigg’s Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 12th Edition. Lippincott Williams and Wilkins; 2021.
12.Niacin. National Institutes of Health. Accessed August 23, 2024, https://ods.od.nih.gov/factsheets/Niacin-HealthProfessional/
13.Gluckman PH, M., Seng, C.Y., Bardsley, A. Vitamin B3 (niacin) in pregnancy and breastfeeding. Nutrition and Lifestyle for Pregnancy and Breastfeeding. Oxford University Press; 2014:67-70:chap 9.
14.Health HCSoP. Niacin – Vitamin B3. The Nutrition Source Accessed 18 Feb 2022. https://www.hsph.harvard.edu/nutritionsource/niacin-vitamin-b3/