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.
Dietary sources of niacin include liver, red meat, fish, poultry, legumes, and whole-grain or enriched cereals and breads. Because dietary tryptophan can be metabolized to niacin, foods rich in tryptophan (eg, dairy products) can compensate for inadequate dietary niacin.
(See also Overview of Vitamins Overview of Vitamins Vitamins may be Fat soluble (vitamins A, D, E, and K) Water soluble (B vitamins and vitamin C) The B vitamins include biotin, folate, niacin, pantothenic acid, riboflavin (B2), thiamin (B1)... read more .)
Etiology of Deficiency
Primary niacin 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 gastrointestinal 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 niacin deficiency may be due to diarrhea, cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic fibrosis that has resulted in widespread distortion of normal hepatic architecture. Cirrhosis is characterized by regenerative nodules surrounded by dense... read more , or alcohol use disorder Alcohol Use Disorder and Rehabilitation Alcohol use disorder involves a pattern of alcohol use that typically includes craving and manifestations of tolerance and/or withdrawal along with adverse psychosocial consequences. Alcoholism... read more . Pellagra also may occur in carcinoid syndrome Carcinoid Syndrome Carcinoid syndrome develops in some people with carcinoid tumors and is characterized by cutaneous flushing, abdominal cramps, and diarrhea. Right-sided valvular heart disease may develop after... read more (tryptophan is diverted to form 5-hydroxytryptophan and serotonin) and in Hartnup disease Hartnup Disease Hartnup disease is a rare autosomal recessive disease involving malabsorption and increased renal excretion of tryptophan and other amino acids. Also, conversion of tryptophan to niacinamide... read more (absorption of tryptophan by the intestine and kidneys is defective).
Symptoms and Signs of Deficiency
Pellagra is characterized by skin, mucous membrane, central nervous system, and gastrointestinal 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 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.
Gastrointestinal 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.
Central nervous system 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.
Any relationship between niacin status and hypertension is uncertain.
Diagnosis of Deficiency
Diagnosis of niacin deficiency 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 central nervous system changes from those in thiamin deficiency Thiamin Deficiency Thiamin deficiency (causing beriberi) is most common among people subsisting on white rice or highly refined carbohydrates in countries with high rates of food insecurity and among people with... read more 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 mcmol/day) suggests a niacin deficiency.
Treatment of Deficiency
Nicotinamide and other nutrients
Because multiple deficiencies are common, a balanced diet, including other B vitamins (particularly riboflavin and pyridoxine), is needed.
Nicotinamide is usually used to treat niacin 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 of 250 to 500 mg orally daily.
Niacin deficiency can cause pellagra, mainly in countries with high rates of food insecurity.
Pellagra causes a photosensitivity rash, mucositis, gastrointestinal disturbances, and neuropsychiatric dysfunction.
Diagnose clinically if possible.
Use nicotinamide to treat the deficiency; a favorable response can confirm the diagnosis.