Niacin encompasses nicotinic acid and nicotinamide. Nicotinamide is an essential part of the two pyridine nucleotides, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which play a key role as hydrogen acceptors and donors for many enzymes. Niacin can be synthesized in the body in limited amounts from the amino acid tryptophan. This vitamin can be synthesized in the body from tryptophan; however, the conversion ratio is 60:1, requiring large amounts of tryptophan to meet niacin needs. Niacin or nicotinic acid (B3) is essential for the metabolism of carbohydrates, fat, and protein. It is also essential for the normal functioning of the skin, intestinal and nervous systems. This vitamin differs from the other vitamins of the B-complex group in that essential amino acid, tryptophan serves as its precursor. Another characteristic of niacin is that it is not excreted in urine as such, but is metabolized to at least 2 major methylated derivatives N-methyl-nicotinamide and N-methyl pyridones.
Foods rich in niacin and/or tryptophan are liver, kidney meat, poultry, fish, legumes, and groundnut. Milk is a poor source of niacin but its proteins are rich in tryptophan which is converted in the body into niacin (about 60 mg of tryptophan is required to result in 1 mg of niacin). In many cereals, especially maize, niacin occurs in "bound" form unavailable to the consumer. Deficiency occurs in areas where maize is the staple food as the niacin in maize is present in bound form and not easily absorbed. The vitamin is resistant to heating. Human milk contains 30 mg/100 Cal of niacin compared with 0.12 mg/100 Cal in cow milk.
Requirements are expressed in terms of niacin equivalents (NE). One NE equals 1 mg of niacin or 60 mg of tryptophan. Recommended dietary allowance for niacin is related to dietary energy intake; the recommended intake is 6.4 to 8 NE/ 1000 Cal, and human milk provides about 8 NE/1000 cal.
Niacin deficiency results in pellagra. The disease is characterized by - diarrhea, dermatitis, and dementia. In addition glossitis and stomatitis usually occur. Pellagra was formerly endemic among poor people who subsisted chiefly on maize, which contains niacytin, a form of niacin that the body is unable to utilize. Pellagra can develop in only 8 weeks in individuals eating diets that are very deficient in niacin and tryptophan. It remains a problem in parts of Africa and is occasionally seen in alcoholics and in patients with chronic small intestinal disease in developed countries. Pellagra can occur in Hartnup’s disease, a genetic disorder characterized by impaired absorption of several amino acids, including tryptophan.
It is also seen occasionally in carcinoid syndrome when tryptophan is consumed in the excessive production of 5-hydroxytryptamine (5-HT, serotonin). Pellagra has been called the disease of the three Ds:
• Dermatitis. Characteristically, there is erythema resembling severe sunburn, appearing symmetrically over the parts of the body exposed to sunlight, particularly the limbs and especially on the neck but not the face. The skin lesions may progress to vesiculation, cracking, exudation, and secondary infection.
• Diarrhea. This is often associated with anorexia, nausea, glossitis, and dysphagia, reflecting the presence of a non-infective inflammation that extends throughout the gastrointestinal tract.
• Dementia. In severe deficiency, delirium occurs acutely and dementia develops in chronic cases.
Once a formidable and widespread deficiency disease among malnourished population subsisting mainly on maize diets, pellagra has declined in all parts of the world. It is still prevalent in some parts of Western Asia and Southern Africa where people subsist on maize and little else. While pellagra is historically a disease of the maize-eating population, it was reported in India in the Telangana area of Andhra Pradesh in some segments of the population eat another cereal, these people consume very little milk or other foods of animal origin. Excess leucine appears to interfere in the conversion of tryptophan to niacin.
The diagnosis is suspected on a history of inadequate diet, isoniazid treatment, or chronic alcohol ingestion when typical manifestations are present. Determination of urinary excretion of N1- methylnicotinamide is most helpful; normal 24 hours excretion is between 4 and 6 mg, and values below 3 mg indicate deficiency. In pellagra, these values are usually between 0.5 and 0.8 mg/ day.
The daily dose for treatment is about 10 times the recommended dietary intake (50-300 mg/ day). Parenteral therapy is considered when gastrointestinal absorption is deficient. Prevention of pellagra is achieved by an adequate protein diet containing tryptophan and niacin-rich foods. Treatment is with nicotinamide, given in a dose of 100 mg 3 times daily orally or parentally. The response is usually rapid. Within 24 hours the erythema diminishes, diarrhea ceases and a striking improvement occurs in the patient’s mental state.
Excessive intakes of niacin may lead to reversible hepatotoxicity. Nicotinic acid is a lipid-lowering agent but at doses above 200 mg a day gives rise to vasodilator symptoms (‘flushing 'and/or hypotension).
Pellagra is a preventable disease. A good mixed diet containing milk and/or meat is universally regarded as an essential part of prevention and treatment. Avoidance of total dependence on maize or sorghum is an important preventive measure. Pellagra is a disease of poverty. Given modern knowledge and opportunities for economic, agricultural and social development, there is every reason to hope that this disease could be eliminated.