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. 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. 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. 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. 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. 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.
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. 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. 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.
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. 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.
Corn was the staple food in China, India, Africa, and Latin America, yet pellagra was common in African nations. For instance, in 1990, pellagra was prevalent in 6.3% of Mozambican refugees in Malawi. Over nine months, 691 Malawians living in Kasese have developed pellagra, which primarily was due to eating a niacin-deficient diet. In Angola, about one-third of 723 women and 6% of 690 infants and children (6 months to 5 years) had pellagra. On the other hand, 0.7% of 142 Tanzanian patients (aged 55 to 99 years) with skin diseases were diagnosed with pellagra.
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. In India, niacin was deficient among 13% of 34 adolescent girls 10 to 13 years but not in boys. 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. 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).
Within the United States and industrialized nations, with enrichment of foods and an overall decrease in nutritional deficiency-related diseases, pellagra is rarely seen. 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.
Niacin is important for the metabolism of macronutrients (carbohydrate, protein, and fat), due to being part of the NAD and NADP coenzymes. 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).
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. 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.
Pellagra is a condition caused by low levels of niacin or its precursor tryptophan. Niacin deficiency results in the condition of pellagra, which includes the triad or "three D's," dermatitis, dementia, diarrhea, and can result in death. Similar to a sunburn, brown discoloration, and skin lesions on the skin typically exposed to the sun such as hands, elbows, knees, and feet are present. Initially, neurological changes such as anxiety, poor concentration, fatigue, and depression can manifest, but as pellagra advances, dementia, and delirium may occur. Also, gastrointestinal complications, glossitis, cheilosis, stomatitis, nausea, vomiting, and diarrhea or constipation may be present.
Physical signs and symptoms include skin and mouth lesions, diarrhea, and delirium. Laboratory testing should be completed to confirm the results and can incorporate examining levels of tryptophan, NAD, NADP, and niacin. Urinary excretion of N1-methylnicotinamide (NMN) of less than <5.8 micromols (0.8 mg/d) may suggest niacin deficiency. Erythrocyte nicotinamide adenine dinucleotide (NAD) concentrations are also a sensitive indicator of niacin deficiency.
Typically a niacin deficiency may indicate multiple nutritional deficiencies; therefore, a balanced diet is a strong recommendation. Nicotinamide doses of 250 to 500 mg/day orally should be given. Despite nicotinic acid being the more common form of niacin, nicotinamide is used for niacin deficiencies as it does not cause symptoms such as tingling sensation, itching, or flushing. Patients with pellagra should avoid sun exposure and alcohol intake. The recommended dietary allowance (RDA) for niacin is expressed as niacin equivalents (NE). The RDA for children ages 1 to 3 and 4 to 8 years of age is 6 and 8 mg/day of NE. For both boys and girls ages 9 to 13, the RDA is 12 mg/day of NE. For individuals 14 years or older, the RDA is 16, and it is 14 mg/day of NE for males and females, respectively. RDA during lactation is 17 mg/day of NE.
Pellagra is a condition that requires differentiation from generalized dermatitides, such as skin lesions due to sun exposure. Also, pellagra should be distinguished from malnourishment, such as with anorexia nervosa and kwashiorkor or the severe protein malnutrition typically characterized by an enlarged liver and edema seen during a famine. Further, niacin deficiency can be overlooked with alcohol-induced pellagra and during alcohol-withdrawal delirium.
Although there is no evidence of toxic levels for consuming niacin through foods, niacin consumption of heavily fortified foods, pharmacological, or supplemental levels can result in adverse events. High levels of niacin (3000 mg/day) may cause flushing, jaundice, impaired vision, abdominal discomfort, and a sustained high level can cause hepatotoxicity. The tolerable upper intake level of 35 mg/day of niacin in adults 19 years of age or older may cause adverse effects.
If left untreated, pellagra will progress and eventually lead to death. Death can result as a complication of continued severe malnutrition due to a lack of dietary intake or continual diarrhea, infections, or neurological factors. Death may occur within 4 to 5 years of continued non-treatment.
Complications of niacin deficiency include the condition of pellagra( associated symptoms include mental confusion, glossitis, alopecia, dermatitis, sensitivity to sunlight, enlarged heart, peripheral neuritis, and dementia).
Pellagra is preventable with an adequate diet rich in protein; therefore, nutritional education and access to foods are crucial to prevention. In individuals with malabsorptive conditions or those taking medications that reduce the availability of niacin, supplementation may be desirable. In regions with a high risk of famine or a diet high in corn and low in protein (commonly seen in tribal populations), access and fortification of food are essential.
Pellagra is a condition of niacin deficiency, which is rare in industrialized nations. In individuals with malabsorption, lack of access to food, the use of certain medications, or alcoholism that may impair the absorption or synthesis of niacin, may lead to a presentation of pellagra. After diagnosis and treatment, the prognosis of patients is excellent. Together health care professionals should use nutritional education to inform the patients and continue to monitor the patient throughout recovery. An interprofessional team, including clinicians, nursing, pharmacists, and nutritionists/dieticians, can best guide patient treatment to an optimal recovery.
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