Vitamin B3

Overview

Niacin is a water-soluble B vitamin that can be synthesized in humans by converting tryptophan to niacin. Niacin functions metabolically as a component of two important co-enzymes: nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), known as the pyridine nucleotides. These niacin-containing co-enzymes play an essential role in over 200 chemical reactions in the body.

There are two forms of vitamin B3, each with different activities. Niacin, which is also known as nicotinic acid, lowers elevated blood lipids and may reduce mortality. (1) In addition to being used alone, it has also been used in combination with cholesterol-lowering drugs to increase the lipid-lowering effect of the drug. (2) Niacinamide, which is also known as nicotinamide has been used to treat newly diagnosed patients with Type 1 diabetes, (3) , (4) patients with Type 2 diabetes who cannot be controlled with sulfonylureas, (5) and people with arthritis. (6)

In the past, a high percentage of people discontinued niacin therapy for hyperlipidemia due to the unpleasant “flushing" side effect. Recently a new form of niacin called inositol hexaniacinate has become available. This reportedly provides the benefits or niacin without the vasodilatory side effects.

Dosage Info

Dosage Range

10-3,000mg daily is used commonly. (7) A few published studies report using dosages greater than 7,000mg daily. (8) Dosages above 2,000mg daily should only be administered under medical supervision.

Most Common Dosage

50mg daily.

Dosage Forms

Tablets, capsules, liquids, liposomal sprays, and effervescent tablets.

Adult RDI

20mg

Adult ODA

25-100mg

RDA

  • Infants < 6 months: 2mg (Adequate Intake, AI)
  • Infants 7-12 months: 4mg (AI)
  • Children 1-3 years: 6mg
  • Children 4-8 years: 8mg
  • Children 9-13 years: 12mg
  • Males >14 years: 16mg
  • Females >14 years: 14mg
  • Pregnancy: 18mg
  • Lactation: 17mg

Interactions and Depletions

Depletions

Active Forms

Niacin, also known as nicotinic acid; niacinamide, also known as nicotinamide; inositol hexaniacinate, also known as inositol hexanicotinate.

Absorption

Niacin is absorbed from the stomach, and both niacin and niacinamide are absorbed from the small intestine. Both niacin and niacinamide are converted to coenzymes in the liver, kidney, brain, and blood.

Toxicities & Precautions

General

There are no known toxicities associated with niacin when used appropriately.

Research indicates some sustained release forms of niacin can be hepatotoxic and should only be used under medical supervision. (9)

Side Effects

Large doses can cause transient side effects known as the "niacin flush," which produces tingling sensations, flushing of the skin, and head throbbing due to its vasodilating action. Although uncomfortable, the effects are not serious and usually disappear within 10 to 30 minutes. Starting with low doses and gradually titrating up may help reduce the incidence and severity of the adverse effects.

Functions in the Body

Metabolism

Carbohydrates, fatty acids, and amino acids.

Energy Production

Oxidation-reduction reactions in the Krebs cycle involving the production of energy from carbohydrates.

Enzyme Activity

Necessary for oxidative phosphorylation, as well as glutathione reductase and glutamate dehydrogenase enzymes.

Blood Cholesterol Levels

Reduces LDL (“bad" cholesterol) and triglycerides, and increases HDL (“good" cholesterol). (10)

Dyslipidemia

Lowers lipoprotein (a) (Lp(a)) and fibrinogen. (11)

Heart Attacks

May reduce the recurrence rate for heart attacks. One study showed reduction by nearly 30 percent at dosages of about 2 grams per day, and showed 11 percent reduced overall mortality rate. (12)

Glucose Tolerance Factor

A component to receptor complex.

Clinical Applications

Arthritis

Niacinamide has been used in both rheumatoid and osteoarthritis.

Diabetes, Type 2

niacinamide is effective in individuals uncontrollable with sulfonylureas

Glucose Tolerance

Niacin in combination with chromium improves glucose tolerance. (13)

Heart Attack Prevention

In individuals with a previous myocardial infarction, niacin provided an 11 percent reduction in subsequent heart attacks over 15 years. (14)

Schizophrenia

In a 9-year study, many schizophrenics improved with high-dose niacin treatment. (15)

Cataracts

Combining niacin and riboflavin resulted in a 44 percent reduction in cataracts. (16)

Intermittent Claudication

Inositol hexaniacinate increases circulation and walking distance while simultaneously reducing pain. (17)

Cholesterol, Triglyceride Lowering

Niacin, but not niacinamide effectively lowers elevated LDL cholesterol while simultaneously raising levels of the “good" HDL cholesterol (18) and elevated triglycerides – niacin effectively lowers elevated levels of triglycerides. (19) , (20) , (21)

Acne Vulgaris

4% niacinamide topical gel is superior to 1% clindamycin gel. (22)

Raynaud's Disease

Inositol hexaniacinate reduces peripheral vasospasms during cold weather. (23)

Diabetes, Type 1

Recent onset of Type 1 diabetes - niacinamide prevents further destruction of pancreatic beta cells. (24)

Symptoms and Causes of Deficiency

Severe deficiency is known as pellagra, which means rough skin. Symptoms of pellagra characterized by the “3 Ds”: dermatitis, dementia, and diarrhea. Pellagra occurs in areas where nutrition is meager and corn is the dietary staple. Tryptophan and niacin are poorly absorbed from corn. However, in Mexico, where corn is treated with lye before use, deficiency is less common because the alkali increases the absorption of tryptophan.

A niacin deficiency can result in cracked, pigmented, scaly dermatitis, especially on parts of the skin exposed to the sun. In the GI tract, inflammation of the mucous membranes can cause many digestive abnormalities including swollen tongue and diarrhea. A severe deficiency of niacin can affect the nervous system causing mental confusion and disorientation, which can lead to psychosis or delirium.

Dietary Sources

Both niacin and its precursor (tryptophan) are included when determining the niacin content of foods. Lean meats, poultry, fish, and peanuts are good sources of both niacin and tryptophan. Organ meats, brewer’s yeast, milk, legumes, peanuts, and peanut butter are the best sources of niacin. Niacin, like other B vitamins, is also synthesized by intestinal bacteria.

References

  1. View Abstract: Berge KG, et al. Coronary Drug Project: Experience with Niacin. Coronary Drug Project Research Group. Eur J Clin Pharmacol. 1991;40(1):S49-51.
  2. View Abstract: Gardner SF, et al. Combination of Low-dose Niacin and Pravastatin Improves the Lipid Profile in Diabetic Patients without Compromising Glycemic Control. Ann Pharmacother. Jun1997;31(6):677-82.
  3. View Abstract: Pozzilli P, et al. Meta-analysis of Nicotinamide Treatment in Patients with Recent-onset IDDM. The Nicotinamide Trialists. Diabetes Care. Dec1996;19(12):1357-63.
  4. View Abstract: 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. May2004;150(5):719-24.
  5. View Abstract: Polo V, et al. Nicotinamide Improves Insulin Secretion and Metabolic Control in Lean Type 2 Diabetic Patients with Secondary Failure to Sulphonylureas. Acta Diabetol. Apr1998;35(1):61-64.
  6. View Abstract: Jonas WB, et al. The Effect of Niacinamide on Osteoarthritis: A Pilot Study. Inflamm Res. Jul1996;45(7):330-34.
  7. View Abstract: Wolfe ML, Vartanian SF, Ross JL, et al. Safety and effectiveness of Niaspan when added sequentially to a statin for treatment of dyslipidemia. Am J Cardiol. Feb2001;87(4):476-9.
  8. View Abstract: Nessim SA, Chin HP, Alaupovic P, Blankenhorn DH. Combined therapy of niacin, colestipol, and fat-controlled diet in men with coronary bypass, effect on blood lipids and apolipoproteins. Arteriosclerosis. Nov1983;3(6):568-73.
  9. View Abstract: McKenney JM, et al. A Comparison of the Efficacy and Toxic Effects of Sustained- Vs Immediate-Release Niacin in Hypercholesterolemic Patients. JAMA. Mar1994;271(9):672- 77.
  10. View Abstract: Crouse JR, 3rd. New Developments in the Use of Niacin for Treatment of Hyperlipidemia: New Considerations in the Use of an Old Drug. Coron Artery Dis. Apr1996;7(4):321-26.
  11. View Abstract: Johansson JO, et al. Nicotinic Acid Treatment Shifts the Fibrinolytic Balance Favourably and Decreases Plasma Fibrinogen in Hypertriglyceridaemic Men. J Cardiovasc Risk. Jun1997;4(3):165-71.
  12. View Abstract: Urberg M, et al. Evidence for Synergism Between Chromium and Nicotinic Acid in the Control of Glucose Tolerance in Elderly Humans. Metabolism. Sep1987;36(9):896-99.
  13. View Abstract: Urberg M, et al. Evidence for Synergism Between Chromium and Nicotinic Acid in the Control of Glucose Tolerance in Elderly Humans. Metabolism. Sep1987;36(9):896-99.
  14. View Abstract: Canner PL, et al. Fifteen-year Mortality in Coronary Drug Project Patients: Long-term Benefit with niacin. J Am Coll Cardiol. Dec1986;8(6):1245-55.
  15. Osmond H, Hoffer A. Massive Niacin Treatment in Schizophrenia: Review of a Nine-year Study. Lancet. 1962;1:316-20.
  16. View Abstract: Sperduto RD, et al. The Linxian Cataract Studies. Two Nutrition Intervention Trials. Arch Ophthalmol. Sep1993;111(9):1246-53.
  17. O'Hara J, et al. The Therapeutic Efficacy of Inositol Nicotinate (Hexopal) in Intermittent Claudication: A Controlled Trial. Br J Clin Pract. Sep1988;42(9):377-83.
  18. View Abstract: Alderman JD, et al. Effect of a Modified, Well-tolerated Niacin Regimen on Serum Total Cholesterol, High Density Lipoprotein Cholesterol and the Cholesterol to High Density Lipoprotein Ratio. Am J Cardiol. Oct1989;64(12):725-29.
  19. View Abstract: Franceschini G, et al. Pharmacological Control of Hypertriglyceridemia. Cardiovasc Drugs Ther. Jun1993;7(3):297-302.
  20. View Abstract: Ryan MJ Jr, Gibson J, Simmons P, Stanek E. Effectiveness of aggressive management of dyslipidemia in a collaborative-care practice model. Am J Cardiol. Jun2003;91(12):1427-31.
  21. View Abstract: Goldberg AC. A meta-analysis of randomized controlled studies on the effects of extended-release niacin in women. Am J Cardiol. Jul2004;94(1):121-4.
  22. View Abstract: Shalita AR, et al. Topical Nicotinamide Compared with Clindamycin Gel in the Treatment of Inflammatory Acne Vulgaris. Int J Dermatol. Jun1995;34(6):434-37.
  23. View Abstract: Sunderland GT, et al. A Double-blind Randomised Placebo Controlled Trial of Hexopal in Primary Raynaud's Disease. Clin Rheumatol. Mar1988;7(1):46-49.
  24. View Abstract: Pozzilli P, et al. Meta-analysis of Nicotinamide Treatment in Patients with Recent-onset IDDM. The Nicotinamide Trialists. Diabetes Care. Dec1996;19(12):1357-63.