Niacin (nicotinic acid, nicotinamide) derivatives include nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which are coenzymes in oxidation-reduction reactions. They are vital in cell metabolism. Because dietary tryptophan can be metabolized to niacin, foods rich in tryptophan (eg, dairy products) can compensate for inadequate dietary niacin.

Niacin Deficiency

Dietary niacin deficiency (causing pellagra) is uncommon in developed countries. Clinical manifestations include the “three Ds”: localized pigmented rash (dermatitis); gastroenteritis (diarrhea); and widespread neurologic deficits, including cognitive decline (dementia). Diagnosis is usually clinical, and dietary supplementation (oral or, if needed, IM) is usually successful.

Etiology

Primary deficiency results from extremely inadequate intake of both niacin and tryptophan, which usually occurs in areas where maize (Indian corn) constitutes a substantial part of the diet. Bound niacin, found in maize, is not assimilated in the GI tract unless it has been previously treated with alkali, as when tortillas are prepared. Corn protein is also deficient in tryptophan. The high incidence of pellagra in India among people who eat millet with a high leucine content has led to the hypothesis that amino acid imbalance may contribute to deficiency. Deficiencies of protein and many B vitamins commonly accompany primary niacin deficiency.

Secondary deficiency may be due to diarrhea, cirrhosis, or alcoholism. Pellagra also may occur in carcinoid syndrome (tryptophan is diverted to form 5-hydroxytryptophan and serotonin) and in Hartnup disease (absorption of tryptophan by the intestine and kidneys is defective).

Symptoms and Signs

Pellagra is characterized by skin, mucous membrane, CNS, and GI symptoms. Advanced pellagra can cause a symmetric photosensitive rash, stomatitis, glossitis, diarrhea, and mental aberrations. Symptoms may appear alone or in combination.

Skin symptoms include several types of lesions, which are usually bilaterally symmetric. The distribution of lesions—at pressure points or sun-exposed skin—is more pathognomonic than the form of the lesions. Lesions can develop in a glovelike distribution on the hands (pellagrous glove) or in a boot-shaped distribution on the feet and legs (pellagrous boot). Sunlight causes Casal's necklace and butterfly-shaped lesions on the face.

Mucous membrane symptoms affect primarily the mouth but may also affect the vagina and urethra. Glossitis and stomatitis characterize acute deficiency. As the deficiency progresses, the tongue and oral mucous membranes become reddened, followed by pain in the mouth, increased salivation, and edema of the tongue. Ulcerations may appear, especially under the tongue, on the mucosa of the lower lip, and opposite the molar teeth.

GI symptoms early in the deficiency include burning in the pharynx and esophagus and abdominal discomfort and distention. Constipation is common. Later, nausea, vomiting, and diarrhea may occur. Diarrhea is often bloody because of bowel hyperemia and ulceration.

CNS symptoms include psychosis, encephalopathy (characterized by impaired consciousness), and cognitive decline (dementia). Psychosis is characterized by memory impairment, disorientation, confusion, and confabulation; the predominant symptom may be excitement, depression, mania, delirium, or paranoia.

Diagnosis and Treatment

Diagnosis is clinical and may be straightforward when skin and mouth lesions, diarrhea, delirium, and dementia occur simultaneously. More often, the presentation is not so specific. Differentiating the CNS changes from those in thiamin deficiency is difficult. A history of a diet lacking niacin and tryptophan may help establish the diagnosis. A favorable response to treatment with niacin can usually confirm it. If available, laboratory testing can help confirm the diagnosis, particularly when the diagnosis is otherwise unclear. Urinary excretion of N¹-methylnicotinamide (NMN) is decreased; < 0.8 mg/day (< 5.8 µmol/day) suggests a niacin deficiency.

Because multiple deficiencies are common, a balanced diet, including other B vitamins (particularly riboflavin and pyridoxine), is needed. Nicotinamide is usually used to treat deficiency, because nicotinamide, unlike nicotinic acid (the most common form of niacin), does not cause flushing, itching, burning, or tingling sensations. Nicotinamide is given in doses ranging from 40 to 250 mg/day po in divided doses 3 to 4 times a day.

Niacin Toxicity

Niacin (nicotinic acid) in large amounts is sometimes used to lower LDL cholesterol and triglyceride levels and to increase HDL cholesterol levels. Symptoms may include flushing and, rarely, hepatotoxicity.