Niacin or vitamin B3 are generic terms for nicotinic acid and nicotinamide (niacinamide). Niacin was initially referred to as the anti-black tongue factor due to niacin's effect on dogs.[1] In humans, niacin was discovered through the niacin deficiency condition pellagra. In the 1700s, pellagra first appeared in Italy and, the name translates to "pella," skin, and "agra," rough or rough skin.[2] In the early 1900s, pellagra was prevalent in the Southern Unites States due to the low availability of corn, at the time the main dietary source of niacin.[3] In 1937, Elvehjem and his colleagues isolated the vitamin and demonstrated that pure nicotinic acid and nicotinic acid amide would reverse the black tongue and pellagra.[4] Today, niacin deficiencies are uncommon in industrialized nations primarily due to sufficient dietary intake; however, specific populations remain at risk of this mostly eradicated condition.

Niacin deficiency can occur from a lack of consuming dietary sources containing niacin.[5] In dietary sources, niacin is present in fish and meats, fortified foods such as cereal and bread, and in legumes. To a lesser extent, niacin is in coffee, tea, and nuts. During meat processing, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) can become hydrolyzed to free nicotinamide. In some foods, such as corn, niacin can be covalently bound to carbohydrates or small peptides, decreasing the bioavailability for absorption in the small intestines. Therefore, some of the earliest signs of pellagra occurred in populations consuming a high corn-based diet. In addition to dietary sources, the liver can synthesize niacin from tryptophan; thus, a diet containing both niacin and tryptophan is necessary to maintain adequate niacin levels.[6] 

Excessive and chronic alcohol intake can induce pellagra due to reducing the absorption of niacin. Alcohol use disorder is associated with increased malnutrition and can impair the conversion of tryptophan to niacin.[7] Niacin is primarily absorbed in the small intestine; therefore, malabsorptive disorders such as chronic diarrhea, inflammatory bowel disease, and malignancy can impair niacin absorption. Further, Hartnup disease results in impaired tryptophan absorption.[8] Also, some medications, such as isoniazid, may cause an increase in the risk of niacin deficiency. Isoniazid binds with vitamin B6 and reduces PLP-dependent kynureninase activity, which is a required substance for niacin synthesis.[9][10] 

Niacin deficiency results in the condition, pellagra, which, although uncommon in industrialized nations, may be seen in individuals living in poverty or those with extremely low niacin and protein-deficient diets.[11] Malnutrition in individuals that are homeless or have other comorbid conditions such as anorexia nervosa should be assumed to have a potential deficiency. Further individuals with malabsorption, alcohol use disorder, or taking specific medication are at risk of deficiency.[2] 

Corn was the staple food in China, India, Africa, and Latin America, yet pellagra was common in African nations.[12] For instance, in 1990, pellagra was prevalent in 6.3% of Mozambican refugees in Malawi.[13] Over nine months, 691 Malawians living in Kasese have developed pellagra, which primarily was due to eating a niacin-deficient diet.[14] In Angola, about one-third of 723 women and 6% of 690 infants and children (6 months to 5 years) had pellagra.[15] On the other hand, 0.7% of 142 Tanzanian patients (aged 55 to 99 years) with skin diseases were diagnosed with pellagra.[16] 

In the United States, pellagra is very rare due to the enrichment of processed flour with B vitamins. In the past, native people in North, Central, and South America consumed maize treated with lime or wood ashes, which increased the bioavailability of niacin in maize.[12] In India, niacin was deficient among 13% of 34 adolescent girls 10 to 13 years but not in boys.[17] In Thailand, the consumption of a traditional meal provides about 13% of the recommended intake of niacin. Traditional meals consisted of: canned fish and stir-fried roselle, or ivy gourd omelets and mung bean noodle soup; or canned fish curry with chili paste and pumpkin.[18] In Switzerland, compared with vegetarian (n = 53) and vegan (n = 53) adults, omnivores (n = 100) had the lows intake of niacin (P < 0.05). Yet plasma vitamin levels showed that vegetarians were the only deficient group (mu = 398 nmol/l).[19]

Within the United States and industrialized nations, with enrichment of foods and an overall decrease in nutritional deficiency-related diseases, pellagra is rarely seen.[20] Outside of the United States, pellagra still occurs in African nations, India, and parts of China. Further, there were recent reports of pellagra in refugees.[21]

Niacin is important for the metabolism of macronutrients (carbohydrate, protein, and fat), due to being part of the NAD and NADP coenzymes.[22][23] Niacin deficiency results in decreased NAD and NADP coenzymes, which occur in malnutrition or resource-limited countries. Additionally, other mechanisms contribute to niacin deficiency. Altered metabolism of tryptophan presents in carcinoid syndrome, impaired absorption of tryptophan is seen in the autosomal recessive condition Hartnup disease, and prolonged use of certain medications may decrease the production of tryptophan (isoniazid) or inhibit the conversion of tryptophan to niacin (azathioprine, 6-mercaptopurine, or 5-fluorouracil).[24][25][26]

Dermatitis in pellagra characteristically demonstrates erythematous bullous changes secondary to mild acute inflammation, which leads to degeneration of the stratum corneum, followed by increased cellularity and fibroblasts, capillary dilation, and increased proliferation and thickening of the epidermis. Inflammatory cells include lymphoid cells and few plasma cells. Hyperpigmentation also occurs.[27] In the gastrointestinal tract, inflammation can spread, causing chronic gastritis. Inflammation also leads to diarrhea. There are also reports of neuronal chromatolysis in motor neurons and edema in glial and ependymal cells.