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.
