By Dr. Hasina Akhtar

INTRODUCTION OF VITAMIN B3 or NIACIN

Vitamin B3 also known as niacin or nicotinic acid (pyridine-3-carboxylic acid) is a water soluble B vitamin. Its derivative nicotinamide is the precursor of two vital coenzymes produced in human body, Nicotinamide Adenine Dinucleotide Phosphate (NADP) and Nicotinamide Adenine Dinucleotide (NAD). NAD is involved in the breakdown of carbohydrate, fat and protein whereas NADP is needed in fat as well as cholesterol biosynthesis [1]. None of the coenzymes are related to the nicotine found in tobacco, although their names are similar.

DISCOVERY [2, 3]

Vitamin B3 was first described by Hugo Weidel in 1873. In 1937, Conrad Elvehjem extracted it from the liver. Dr. Tom Spies found nicotinic acid (or vitamin B3) as pellagra-curative. It was thus named as Pellagra preventative factor. When the biological significance of nicotinic acid was realized, it was named as niacin to avoid the perception that niacin-rich food contains nicotine. The name ‘niacin’ was derived from nicotinic acid +vitamin.

STRUCTURE (4)

The basic structure of Vitamin B3 contains a pyridine ring, with a carboxyl group (-COOH) at the 3-position. Its derivative nicotinamide is produced when the carboxyl group is

replaced by carboxamide (-CONH2) group. The structure of vitamin B3 (niacin and nicotinamide) are given below:

Niacin

Nicotinamide

DIETARY SOURCES [5, 6]

Major dietary sources of vitamin B3 are beef liver, fish (Tuna, Swordfish, Salmon), beets, sunflower seeds, peanuts, brewer’s yeast, mushrooms, avocado, carrots, broccoli, tomatoes. In addition, foods containing Tryptophan such as poultry, red meat, eggs, and dairy products are good source of this vitamin as this amino acid can be converted into niacin in human body. Fortified breakfast cereals and breads may also contain this vitamin.

RECOMMENDED DIETARY ALLOWANCES [RDAs (mg/day) FOR VITAMIN B3 (5)]

Adults > 50 years of age should take supplement as dietary intake of niacin tends to decrease at this age.

WHO ARE AT RISK FOR VITAMIN B3 DEFICIENCY

Vitamin B3 deficiency is observed

• Among homeless population, in individuals suffering from anorexia or obesity, and in areas where people eat corn (maize as a staple food) due to low bioavailability of niacin from this grain. (7–10).

• Among individuals suffering from chronic alcoholism (11).

• In patients with Hartnup’s disease, a hereditary nutritional disorder where body cannot break down and absorb dietary tryptophan due to a deficit in the intestines and kidneys. The resulting condition is similar to pellagra (12).

• Cancer patients, in patients on anti-tuberculosis drugs (13, 14).

FUNCTIONS (15–18)

• Living organisms derive most of their energy from oxidation–reduction (redox) reactions and >400 enzymes require the niacin coenzymes, NAD and NADP for redox reactions (2).

• NAD is involved in the catabolism of proteins, lipids, and carbohydrates.

• NADP is involved in the synthesis of cholesterol and fatty acids.

• It is also involved in DNA repair, cell signaling as well as the production of steroid hormones in the adrenal gland.

Thus organs that require higher energy such as brain or organs that have higher turnover rate (gut, skin) are most susceptible to this vitamin deficiency.

DEFICIENCY OF VITAMIN B3 [17]

• Severe dietary deficiency of this vitamin causes pellagra, a disease characterized by diarrhea, dermatitis, and dementia. Other common symptoms of pellagra include hyperpigmentation, thickening of the skin, inflammation of the mouth and tongue, digestive disturbances and eventually death, if left untreated.

• Niacin deficiency may also results in psychiatric symptoms including irritability, poor concentration, anxiety, fatigue, restlessness, apathy, and depression.

TOXICITY (19–20)

Vitamin B3 is a water-soluble vitamin and is excreted in the urine. No known risk of dietary toxicity from naturally occurring niacin in foods has been reported. However, use of higher amounts of niacin supplements to treat certain medical conditions, can be risky. Doses >50 mg niacin can cause side effects such as “niacin flush,” which is a burning, tingling sensation in the face and chest accompanied by red skin. Therefore, children and pregnant women or lactating mother should not take niacin supplements in excess of the daily requirements (RDA) unless it’s recommended by their doctor. Moreover, niacin at extremely high doses can cause niacin maculopathy, a thickening of the macula as well as ratina leading to blurred vision and blindness. Hyperuricemia, abnormally high uric acid level in blood, is another side effect of taking high-dose niacin that may exacerbate gout.

VITAMIN B3 AND HEALTH [21–25]

Vitamin B3 (niacin) helps convert foods (carbohydrates, proteins) into fuel (glucose), to be used up by the body to produce energy. Moreover, it also helps the body make various sex and stress-related hormones in the adrenal glands and other parts of the body. Besides, it has beneficial roles for our heart’s health as well as skin:

Cardiovascular disease

Niacin alone appears to reduce the risk of cardiovascular disease. In 2001, the National Cholesterol Education Program (NCEP) recommended niacin alone for cardiovascular and atherogenic dyslipidemia, an abnormal level of lipids (cholesterol and fats) in the blood, in mild or normal LDL levels or in combination for higher HDL levels. By lowering VLDL levels, niacin increases the level of HDL, the good cholesterol in blood, and therefore it is sometimes prescribed for people with low HDL, who are also at high risk of a developing a heart attack. However, high doses of niacin may have side effects including flushing of the skin, headache, dizziness, blurred vision, stomach upset as well as an increased risk of liver damage. Niacin should not be taken in higher doses without consulting the doctor.

Vitamin B3 and skin

The Food and Drug Administration (FDA) has approved vitamin B3 for the treatment of pellagra. Due to its antioxidant, anti-wrinkle, and whitening effects, many cosmetic products such as skin cream, lip bum etc contain vitamin B3.

DRUG INTERACTIONS (13, 26–28)

REFERENCES

1. Wan P, Moat S, Anstey A. Pellagra: a review with emphasis on photosensitivity.  Br J Dermatol. 2011. 164(6):1188-200.

2. Weidel, H (1873). Zur Kenntniss des Nicotins. Justus Liebigs Annalen der Chemie und Pharmacie 165 (2): 330–349.

3. Pellagra And Its Prevention and Control in Major Emergencies” (PDF).World Health Organization. World Health Organization. Retrieved 17 April 2015.

4. Brody T. Nutritional Biochemistry. 2nd ed. San Diego: Academic Press; 1999.

5. Food and Nutrition Board, Institute of Medicine. Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. Washington, DC: National Academy Press; 1998; 58-86.

6. Jacob R, Swenseid M. Niacin. In: Ziegler E, Filer L, eds. Present Knowledge in Nutrition. 7th ed. Washington D.C.: ILSI Press; 1996:185-190.

7. Dawson B, Favaloro EJ, Taylor J, Aggarwal A. Unrecognized pellagra masquerading as odynophagia. Intern Med J. 2006; 36(7):472-474.

8. Jagielska G et al. Pellagra: a rare complication of anorexia nervosa. Eur Child Adolesc Psychiatry. 2007; 16(7):417-420.

9. Kertesz SG. Pellagra in 2 homeless men. Mayo Clin Proc. 2001; 76(3):315-318.

10. Prakash R et al. Rapid resolution of delusional parasitosis in pellagra with niacin augmentation therapy. Gen Hosp Psychiatry. 2008; 30(6):581-584.

11. Oldham MA, Ivkovic A. Pellagrous encephalopathy presenting as alcohol withdrawal delirium: a case series and literature review. Addict Sci Clin Pract. 2012; 7(1):12.

12. Cervantes-Laurean D, McElvaney NG, Moss J. Niacin. In: Shils M, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease. 9th ed. Baltimore: Williams & Wilkins; 1999:401-411.

13. Bilgili SG et al. Isoniazid-induced pellagra. Cutan Ocul Toxicol. 2011; 30(4):317-319.

14. Dreizen S et al. Nutritional deficiencies in patients receiving cancer chemotherapy. Postgrad Med. 1990; 87(1):163-167, 170.

15. Penberthy WT, Kirkland JB. Niacin. In: Erdman JW, MacDonald I, Zeisel SH, eds. Present Knowledge in Nutrition. 10th ed. Ames: International Life Sciences Institute; 2012:293-306.

16. Pitsavas S, Andreou C, Bascialla F, Bozikas VP, Karavatos A (2004). “Pellagra encephalopathy following B-complex vitamin treatment without niacin”. Int J Psychiatry Med 34 (1): 91–5.

17. Prakash R, Gandotra S, Singh LK, Das B, Lakra A (2008). “Rapid resolution of delusional parasitosis in pellagra with niacin augmentation therapy”. General Hospital Psychiatry 30 (6): 581–4.

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18. Wan P, Moat S, Anstey A (2011). “Pellagra: A review with emphasis on photosensitivity”. The British journal of dermatology 164 (6): 1188–200.

19. Gass JD. Nicotinic acid maculopathy. Retina (Philadelphia, Pa.) 2003. 23 (6 Suppl): 500–10.

20. Capuzzi DM et al. Niacin dosing: relationship to benefits and adverse effects. Curr Atheroscler 2000. Rep 2 (1): 64–71.

21. Bruckert E, Labreuche J, Amarenco P (2010). Meta-analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosis. Atherosclerosis 210 (2): 353–61.

22. Duggal JK, Singh M, Attri N, Singh PP, Ahmed N, Pahwa S, Molnar J, Singh S, Khosla S, Arora R (2010). Effect of niacin therapy on cardiovascular outcomes in patients with coronary artery disease. Journal of cardiovascular pharmacology and therapeutics 15 (2): 158–66.

23. NCEP (2002). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 106 (25): 3143–3421.

24. McGovern ME (2005). Taking aim at HDL-C. Raising levels to reduce cardiovascular risk. Postgrad Med 117 (4): 29–30, 33–5, 39 passim.

25. Sinthupoom, Nujarin; Prachayasittikul, Veda; Prachayasittikul, Supaluk; Ruchirawat, Somsak; Prachayasittikul, Virapong. Nicotinic acid and derivatives as multifunctional pharmacophores for medical applications. Eur Food Res Technol 240 (1): 1-17.

26. Hendler SS, Rorvik DR, eds. PDR for Nutritional Supplements. Montvale: Medical Economics Company, Inc; 2001.

27. Kar S, Chockalingam A. Statin-associated rhabdomyolysis with acute renal failure complicated by intradialytic NSTEMI: a review of lipid management considerations. Am J Ther. 2013; 20(1):57-60.

28. Cziraky MJ et al. Risk of hospitalized rhabdomyolysis associated with lipid-lowering drugs in a real-world clinical setting. J Clin Lipidol. 2013; 7(2):102-108.