NIACIN

Niacin (nicotinic acid or nicotinamide) is essential in the form of the coenzymes NAD and NADP in which the nicotinamide moiety acts as electron acceptor or hydrogen donor in many biological redox reactions. NAD functions as an electron carrier for intracellular respiration as well as a codehydrogenase with enzymes involved in the oxidation of fuel molecules. NADP functions as a hydrogen donor in reductive biosyntheses such as in fatty acid and steroid syntheses and, like NAD, as a co-dehydrogenase. NAD, in its only non-redox role, is the substrate for three classes of enzymes that transfer ADP-ribose units to proteins involved in DNA processing, cell differentiation, and cellular calcium mobilization.

Nicotinic acid and nicotinamide are rapidly absorbed from the stomach or the intestine. Nicotinamide, the major form in the bloodstream, arises from enzymatic hydrolysis of NAD(P) in the intestinal mucosa and liver, and is transported to tissues that synthesize their own NAD as needed. Niacin and NAD are biosynthesized from dietary tryptophan via the kynurenine pathway and quinolinic acid. Excess niacin is excreted in the urine primarily as Nl-methylnicotinamide and Nl-methyl-2-pyridone-5-carboxamide.

Deficiencies: Pellagra, the classic niacin deficiency disease, is characterized by bilateral dermatitis, diarrhea, and dementia. Often associated with a largely cereal diet such as maize or sorghum, the disease is now rarely seen in industrialized countries but still appears in India, China, and Africa. Pellagra often is associated with other micronutrient deficiencies and may develop also in cases of disturbed tryptophan metabolism (carcinoid syndrome, Hartnup's).

Diet recommendations: The RDA is expressed in mg niacin equivalents (NE) in which 1 mg NE = 1 mg niacin or 60 mg tryptophan. For individuals above 13 years of age, the 1998 RDA is 16 mg/d for males and 14 mg/d for females, with an additional allowance of 4 mg/d during pregnancy and 3 mg/d during lactation. The RDAs range from 6-12 mg/d for children 1-13 years and 2-3 mg/d for infants to one year.

Food sources: Niacin is widely distributed in plant and animal foods, mainly as the pyridine nucleotides NAD and NADP. Good sources are yeast, meats including liver, cereals, legumes, seeds, milk, green leafy vegetables, and fish.

Clinical uses: Nicotinic acid (but not nicotinamide) given as a drug in doses of 1.5-3 g/d improves the blood cholesterol profile. Nicotinamide acts as a tumor-specific radiosensitizer, possibly due to its effect on vasorelaxation and increased tumor oxygenation.

Toxicity: Large doses of nicotinic acid given to lower cholesterol may produce flushing of the skin, hyperuricemia, and hepatic abnormalities. These effects are reversed if the drug is reduced in amount or discontinued. The 1998 Tolerable Upper Intake Level (UL) of niacin, based on flushing produced by nicotinic acid, is 35 mg/d for adults.

Recent research: Nicotinamide may counteract hepatotoxic effects of alcohol by ameliorating the redox state. Nicotinamide is under investigation for helping prevent and control diabetes.

For further information:

Jacob, R. A. & Swendseid, M. E. (1996) Niacin, In: Present Knowledge in Nutrition (Ziegler, E. E. & Filer, L. J., eds.), 7th ed., pp. 184-190, International Life Sciences Institute Press, Washington, DC.

Prepared By:

Robert A. Jacob, Ph.D.
USDA/ARS Western Human Nutrition Research Center
c/o Department of Pomology, UC Davis
One Shields Avenue
Davis, CA 95616-8683
Phone: 530-752-4726
FAX: 530-752-8502
rjacob@whnrc.usda.gov

Robert M. Russell, M.D.
Professor of Medicine and Nutrition
Human Nutrition Research Center
on Aging at Tufts University
711 Washington Street
Boston, MA 02111-1525
Phone: 617-556-3330
FAX: 617-556-3295
Email: russell@hnrc.tufts.edu