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Nutritional Supplement

Vitamin B3

Possible Deficiencies

Pellagra, the disease caused by a vitamin B3 deficiency, is rare in Western societies. Symptoms include loss of appetite, skin rash, diarrhea, mental changes, beefy tongue, and digestive and emotional disturbance.

Side Effects

Niacinamide is almost always safe to take in amounts of 1,000 mg per day or less, though rare liver problems have occurred at amounts in excess of 1,000 mg per day. Niacin, in amounts as low as 50–100 mg, may cause flushing, headache, and stomachache in some people. Doctors sometimes prescribe very high amounts of niacin (as much as 3,000 mg per day or more) for certain health problems. These large amounts can cause liver damage, diabetes, gastritis, damage to eyes, and elevated blood levels of uric acid (which can cause gout).72 Symptoms caused by niacin supplements, such as flushing, have been reduced with sustained-release (also called ‘time-release’) niacin products. However, sustained-release forms of niacin have caused significant liver toxicity in some cases and, rarely, liver failure.73,74,75,76,77 One partial time-release (intermediate-release) niacin product has demonstrated clinical efficacy without flushing, and also with much less of the liver function abnormalities typically associated with sustained-release niacin formulations.78 However, this form of niacin is available by prescription only.

In a controlled clinical trial, 1,000 mg or more per day of niacin raised blood levels of homocysteine, a substance associated with increased risk of heart disease.79 Since other actions of niacin lower heart disease risk,80,81 the importance of this finding is unclear. Nonetheless, for all of the reasons discussed above, large amounts of niacin should never be taken without consulting a doctor.

The inositol hexaniacinate form of niacin has not been linked with the side effects associated with niacin supplementation. In a group of people being treated alternatively with niacin and inositol hexaniacinate for skin problems, niacin supplementation (50–100 mg per day) was associated with numerous side effects, including skin flushing, nausea, vomiting and agitation.82 In contrast, people taking inositol hexaniacinate experienced no complaints whatsoever, even at amounts two to five times higher than the previously used amounts of niacin. However, the amount of research studying the safety of inositol hexaniacinate remains quite limited. Therefore, people taking this supplement in large amounts (2,000 mg or more per day) should be under the care of a doctor.

References

1. Brown WV. Niacin for lipid disorders. Postgrad Med 1995;98:185-93 [review].

2. Guyton JR, Blazing MA, Hagar J, et al. Extended-release niacin vs gemfibrozil for the treatment of low levels of high-density lipoprotein cholesterol. Niaspan-Gemfibrozil Study Group. Arch Intern Med 2000;160:1177-84.

3. McKenney JM, Proctor JD, Harris S, Chinchili VM. A comparison of the efficacy and toxic effects of sustained—vs immediate-release niacin in hypercholesterolemic patients. JAMA 1994;271:672-7.

4. Knopp RH, Ginsberg J, Albers JJ, et al. Contrasting effects of unmodified and time-release forms of niacin on lipoproteins in hyperlipidemic subjects: clues to mechanism of action of niacin. Metabolism 1985;34:642-50.

5. Gray DR, Morgan T, Chretien SD, Kashyap ML. Efficacy and safety of controlled-release niacin in dyslipoproteinemic veterans. Ann Intern Med 1994;121:252-8.

6. Rader JI, Calvert RJ, Hathcock JN. Hepatic toxicity of unmodified and time-release preparations of niacin. Am J Med 1992;92:77-81 [Review].

7. Knopp RH. Niacin and hepatic failure. Ann Intern Med 1989;111:769 [letter].

8. Goldberg A, Alagona P Jr, Capuzzi DM, et al. Multiple-dose efficacy and safety of an extended-release form of niacin in the management of hyperlipidemia. Am J Cardiol 2000;85:1100-5.

9. Brown WV. Niacin for lipid disorders. Postgrad Med 1995;98:183-93 [review].

10. Head KA. Inositol hexaniacinate: a safer alternative to niacin. Alt Med Rev 1996;1:176-84 [review].

11. Murray M. Lipid-lowering drugs vs. Inositol hexaniacinate. Am J Natural Med 1995;2:9-12 [review].

12. Taylor AJ, Villines TC, Stanek EJ, et al. Extended-release niacin or ezetimibe and carotid intima-media thickness. N Engl J Med 2009 [E-pub ahead of print].

13. Mishima Y, Kamiya K, Sakaguchi S, et al. A multiclinic double-blind trial of pyridinolcarbamate and inositol niacinate in ischemic ulcer due to chronic arterial occlusion. Angiology 1977;28:84-94.

14. Aylward M. Hexopal in Raynaud's disease. J Int Med Res 1979;7:484-91.

15. Holti G. An experimentally controlled evaluation of the effect of inositol nicotinate upon the digital blood flow in patients with Raynaud's phenomenon. J Int Med Res 1979;7:473-83.

16. Ring EF, Bacon PA. Quantitative thermographic assessment of inositol nicotinate therapy in Raynaud's phenomenon. J Int Med Res 1977;5:217-22.

17. Kaufman W. The use of vitamin therapy for joint mobility. Therapeutic reversal of a common clinical manifestation of the ‘normal' aging process. Conn State Med J 1953;17(7):584-9.

18. Kaufman W. The use of vitamin therapy to reverse certain concomitants of aging. J Am Geriatr Soc 1955;3:927-36.

19. Hoffer A. Treatment of arthritis by nicotinic acid and nicotinamide. Can Med Assoc J 1959;81:235-8.

20. Jonas WB, Rapoza CP, Blair WF. The effect of niacinamide on osteoarthritis: a pilot study. Inflamm Res 1996;45:330-4.

21. Hudgins AP. Am Practice Digest Treat 1952;3:892-3.

22. Hudgins AP. Vitamins P, C and niacin for dysmenorrhea therapy. West J Surg 1954;Dec:610-1.

23. Hudgins AP. Am Practice Digest Treat 1952;3:892-3.

24. Hudgins AP. Vitamins P, C and niacin for dysmenorrhea therapy. West J Surg 1954;Dec:610-1.

25. Hudgins AP. Am Practice Digest Treat 1952;3:892-3.

26. Hudgins AP. Vitamins P, C and niacin for dysmenorrhea therapy. West J Surg 1954;Dec:610-1.

27. Hudgins AP. Am Practice Digest Treat 1952;3:892-3.

28. Hudgins AP. Vitamins P, C and niacin for dysmenorrhea therapy. West J Surg 1954;Dec:610-1.

29. Nagalski A, Bryla J. [Niacin in therapy]. Postepy Hig Med Dosw (Online) 2007;61:288-302.

30. Subramanian S, Chait A. Hypertriglyceridemia secondary to obesity and diabetes. Biochim Biophys Acta 2012;1821:819–25.

31. Fukaya M, Tamura Y, Chiba Y, et al. Protective effects of a nicotinamide derivative, isonicotinamide, against streptozotocin-induced beta-cell damage and diabetes in mice. Biochem Biophys Res Commun 2013;442:92–8.

32. Elliott R, Pilcher C, Stewart A, et al. The use of nicotinamide in the prevention of type 1 diabetes. Ann N Y Acad Sci 1993;696:333–41.

33. Skyler J. Primary and secondary prevention of Type 1 diabetes. Diabet Med 2013;30:161–9.

34. Crino A, Schiaffini R, Ciampalini P, et al. A two-year observational study of nicotinamide and intensive insulin therapy in patients with recent onset type 1 diabetes mellitus. J Pediatr Endocrinol Metab 2005;18:749–54.

35. Visalli N, Cavallo MG, Signore A, et al. A multi-centre randomized trial of two different doses of nicotinamide in patients with recent-onset type 1 diabetes (The IMDIAB VI). Diabetes Metab Res Rev 1999;15:181–5.

36. Crino A, Schiaffini R, Manfrini S, et al. A randomized trial of nicotinamide and vitamin E in children with recent onset type 1 diabetes (IMDIAB IX). Eur J Endocrinol 2004;150:719–24.

37. Linder K, Willmann C, Kantartzis K, et al. Dietary Niacin Intake Predicts the Decrease of Liver Fat Content During a Lifestyle Intervention. Sci Rep 2019;9:1303.

38. Collins P, Sattar N. Glycaemic Effects of Non-statin Lipid-Lowering Therapies. Curr Cardiol Rep 2016;18:133.

39. Fangmann D, Theismann E, Turk K, et al. Targeted Microbiome Intervention by Microencapsulated Delayed-Release Niacin Beneficially Affects Insulin Sensitivity in Humans. Diabetes Care 2018;41:398–405.

40. Anderson RA et al. Chromium supplementation of humans with hypoglycemia. Fed Proc 1984;43:471.

41. Stebbing JB et al. Reactive hypoglycemia and magnesium. Magnesium Bull 1982;2:131-4.

42. Shansky A. Vitamin B3 in the alleviation of hypoglycemia. Drug Cosm Ind 1981;129(4):68-69,104-5.

43. Gaby AR, Wright JV. Nutritional regulation of blood glucose. J Advancement Med 1991;4:57-71.

44. Hawkins DR, Bortin AW, Runyon RP. Orthomolecular psychiatry: niacin and megavitamin therapy. Psychosomatics 1970;11:517-21 [review].

45. Autry JH. Workshop on orthomolecular treatment of schizophrenia: a report. Schizophr Bull 1975:94-103.

46. Petrie WM, Ban TA. Vitamins in psychiatry. Do they have a role? Drugs 1985;30:58-65 [review].

47. Hoffer A. Megavitamin B-3 therapy for schizophrenia. Can Psychiatr Assoc J 1971;16:499-504.

48. Wittenborn JR, Weber ES, Brown M. Niacin in the long-term treatment of schizophrenia. Arch Gen Psychiatry 1973;28:308-15.

49. Newbold HL, Mosher LR. Niacin and the schizophrenic patient. Am J Psychiatry 1970;127:535-6.

50. Petrie WM, Ban TA, Ananth JV. The use of nicotinic acid and pyridoxine in the treatment of schizophrenia. Int Pharmacopsychiatry 1981;16:245-50.

51. Ananth JV, Ban TA, Lehmann HE. Potentiation of therapeutic effects of nicotinic acid by pyridoxine in chronic schizophrenics. Can Psychiatr Assoc J 1973;18:377-83.

52. Vaughan K, McConaghy N. Megavitamin and dietary treatment in schizophrenia: a randomised, controlled trial. Aust N Z J Psychiatry 1999;33:84-8.

53. Sandyk R, Pardeshi R. Pyridoxine improves drug-induced parkinsonism and psychosis in a schizophrenic patient. Int J Neurosci 1990;52:225-32.

54. Yamauchi M. Effects of L-dopa and vitamin B6 on electroencephalograms of schizophrenic patients: a preliminary report. Folia Psychiatr Neurol Jpn 1976;30:121-51.

55. Bucci L. Pyridoxine and schizophrenia. Br J Psychiatry 1973;122:240 [letter].

56. Mohler H, Polc P, Cumin R, et al. Niacinamide is a brain constituent with benzodiazepine-like actions. Nature 1979;278:563-5.

57. Vescovi PP, et al. Nicotinic acid effectiveness in the treatment of benzodiazepine withdrawal. Curr Ther Res 1987;41:1017.

58. Mohler H, Polc P, Cumin R, et al. Niacinamide is a brain constituent with benzodiazepine-like actions. Nature 1979;278:563-5.

59. Vescovi PP, et al. Nicotinic acid effectiveness in the treatment of benzodiazepine withdrawal. Curr Ther Res 1987;41:1017.

60. Shakir KMM, Kroll S, Aprill BS, et al. Nicotinic acid decreases serum thyroid hormone levels while maintaining a euthyroid state. Mayo Clin Proc 1995;70:556-8.

61. O'Brien T, Silverberg JD, Nguyen TT. Nicotinic acid-induced toxicity associated with cytopenia and decreased levels of thyroxine-binding globulin. Mayo Clin Proc 1992;67:465-8.

62. Jacques PF, Chylack LT Jr. Epidemiologic evidence of a role for the antioxidant vitamins and carotenoids in cataract prevention. Am J Clin Nutr 1991;53:352S-5S.

63. Knekt P, Heliovaara M, Rissanen A, et al. Serum antioxidant vitamins and risk of cataract. BMJ 1992;305:1392-4.

64. Bhat KS. Nutritional status of thiamine, riboflavin and pyridoxine in cataract patients. Nutr Rep Internat 1987;36:685-92.

65. Prchal JT, Conrad ME, Skalka HW. Association of presenile cataracts with heterozygosity for galactosaemic states and with riboflavin deficiency. Lancet 1978; 1:12-3.

66. Sperduto RD, Hu TS, Milton RC, et al. The Linxian cataract studies. Arch Ophthalmol 1993;111:1246-53.

67. Murray MF. Niacin as a potential AIDS preventive factor. Med Hypotheses 1999;53:375-9.

68. Murray MF, Srinivasan A. Nicotinamide inhibits HIV-1 in both acute and chronic in vitro infection. Biochem Biophys Res Commun 1995;210:954-9.

69. Tang AM, Graham NMH, Saah AJ. Effects of micronutrient intake on survival in human immunodeficiency type 1 infection. Am J Epidemiol 1996;143:1244-56.

70. Neumann R, Rappold E, Pohl-Markl H. Treatment of polymorphous light eruption with nicotinamide: a pilot study. Br J Dermatol 1986;115:77-80.

71. Gaby, AR. Nutritional Medicine. Concord, NH: Fritz Perlberg Publishing, 2011.

72. Goldie C, Taylor AJ, Nguyen P, et al. Niacin therapy and the risk of new-onset diabetes: a meta-analysis of randomised controlled trials. Heart 2016;102:198–203.

73. McKenney JM, Proctor JD, Harris S, Chinchili VM. A comparison of the efficacy and toxic effects of sustained—vs immediate-release niacin in hypercholesterolemic patients. JAMA 1994;271:672-7.

74. Knopp RH, Ginsberg J, Albers JJ, et al. Contrasting effects of unmodified and time-release forms of niacin on lipoproteins in hyperlipidemic subjects: clues to mechanism of action of niacin. Metabolism 1985;34:642-50.

75. Gray DR, Morgan T, Chretien SD, Kashyap ML. Efficacy and safety of controlled-release niacin in dyslipoproteinemic veterans. Ann Intern Med 1994;121:252-8.

76. Rader JI, Calvert RJ, Hathcock JN. Hepatic toxicity of unmodified and time-release preparations of niacin. Am J Med 1992;92:77-81 [Review].

77. Knopp RH. Niacin and hepatic failure. Ann Intern Med 1989;111:769 [letter].

78. Goldberg A, Alagona P Jr, Capuzzi DM, et al. Multiple-dose efficacy and safety of an extended-release form of niacin in the management of hyperlipidemia. Am J Cardiol 2000;85:1100-5.

79. Garg R, Malinow M, Pettinger M, Upson B, Hunninghake D. Niacin treatment increases plasma homocyst(e)ine levels. Am Heart J 1999;138:1082-7.

80. Brown WV. Niacin for lipid disorders. Postgrad Med 1995;98:185-93 [review].

81. Guyton JR. Effect of niacin on atherosclerotic cardiovascular disease. Am J Cardiol 1998;82(12A):18U-23U [review].

82. Welsh AL, Ede M. Inositol hexanicotinate for improved nicotinic acid therapy. Int Record Med 1961;174:9-15.

Copyright © 2020 TraceGains, Inc. All rights reserved.

Learn more about TraceGains, the company.

The information presented by TraceGains is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires December 2020.

Copyright © 2020 TraceGains, Inc. All rights reserved.

The information presented by TraceGains is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. Self-treatment is not recommended for life-threatening conditions that require medical treatment under a doctor's care. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires December 2020.