Niacin was discovered as a nutrient during studies of pellagra. It is not strictly a vitamin since it can be synthesized in the body from the essential amino acid tryptophan. Two com pounds, nicotinic acid and nicotinamide, have the biological activity of niacin; its metabolic function is as the nicotinamide ring of the coenzymes NAD and NADP in oxidation/reduction reactions. Some 60 mg of tryptophan is equivalent to 1 mg of dietary niacin. The niacin content of foods is expressed as:
mg niacin equivalents = mg preformed niacin + 1/60 × mg tryptophan
Since most of the niacin in cereals is biologically unavailable, this is discounted.
NAD Is the Source of ADP-Ribose
In addition to its coenzyme role, NAD is the source of ADP ribose for the ADP-ribosylation of proteins and polyADP ribosylation of nucleoproteins involved in the DNA repair mechanism. Cyclic ADP-ribose and nicotinic acid adenine dinucleotide, formed from NAD, act to increase intracellular calcium in response to neurotransmitters and hormones.
Pellagra Is Caused by Deficiency of Tryptophan & Niacin
Pellagra is characterized by a photosensitive dermatitis. As the condition progresses, there is depressive psychosis and possibly diarrhea. Untreated pellagra is fatal. Although the nutritional etiology of pellagra is well established, and either tryptophan or niacin prevents or cures the disease, additional factors, including deficiency of riboflavin or vitamin B6 , both of which are required for synthesis of nicotinamide from tryptophan, may be important. In most outbreaks of pellagra, twice as many women as men are affected, probably the result of inhibition of tryptophan metabolism by estrogen metabolites.
Pellagra Can Occur as a Result of Disease Despite an Adequate Intake of Tryptophan & Niacin
A number of genetic diseases that result in defects of tryptophan metabolism are associated with the development of pellagra, despite an apparently adequate intake of both tryptophan and niacin. Hartnup disease is a rare genetic condition in which there is a defect of the membrane trans port mechanism for tryptophan, resulting in large losses as a result of intestinal malabsorption and failure of renal reabsorption. In carcinoid syndrome, there is metastasis of a primary liver tumor of enterochromaffin cells, which synthesize 5-hydroxytryptamine. Overproduction of 5-hydroxytrypta mine may account for as much as 60% of the body’s tryptophan metabolism, causing pellagra because of the diversion away from NAD synthesis.
Niacin Is Toxic in Excess
Nicotinic acid has been used to treat hyperlipidemia when of the order of 1 to 6 g/d are required, causing dilation of blood vessels and flushing, along with skin irritation. Intakes of both nicotinic acid and nicotinamide in excess of 500 mg/d cause liver damage.
