Vitamin B3
Synonym: niacin

Characteristics: Vitamin B3 belongs to group B vitamins that are soluble in water. Niacin is the generic name for nicotinic acid, nicotinamide (niacinamide), or related derivatives such as nicotinamide riboside. Niacin is naturally present in many foods, is added to some food products, and is available as a dietary supplement. All tissues in the body convert absorbed niacin to its major metabolically active form, the coenzyme nicotinamide adenine dinucleotide (NAD). More than 400 enzymes require NAD to catalyze reactions in the body, more than any other vitamin-derived coenzyme. NAD is also converted to another active form, the coenzyme nicotinamide adenine dinucleotide phosphate (NADP). NAD and NADP are required in most metabolic redox processes in cells where the oxidation or reduction of substrates occurs. NAD is primarily involved in catabolic reactions that transfer the potential energy in carbohydrates, fats, and proteins to adenosine triphosphate (ATP), the cell's primary energy currency. NAD is also required for enzymes involved in critical cellular functions such as maintaining genome integrity, controlling gene expression, and cell communication. NADP, on the other hand, enables anabolic reactions such as cholesterol and fatty acid synthesis and plays an important role in maintaining cellular antioxidant function.

Absorption: Most dietary niacin is in the form of nicotinic acid and nicotinamide, only some foods contain small amounts of NAD and NADP. The body converts part of the amino acid tryptophan into NAD. When NAD and NADP are consumed in food, they are converted to nicotinamide in the intestine and then absorbed. Even at very high doses (3–4 g), niacin is almost completely absorbed and further metabolized to NAD. Some of the excess niacin is taken up by red blood cells and forms a circulating reserve.

Dietary supplements: Niacin is available in multivitamin-mineral products, in supplements containing other B-complex vitamins, and in supplements containing only niacin. Nicotinic acid and nicotinamide are the two most common forms of niacin in dietary supplements. If nicotinic acid is dosed in amounts exceeding nutritional needs, it can cause reddening of the skin. To minimize this unpleasant side effect, some formulations are made with sustained release. Nicotinamide does not cause skin redness due to its slightly different chemical structure. Niacin supplements are also available in the form of inositol hexanicotinate, which also does not cause flushing. Absorption of niacin from inositol hexnicotinate varies widely, but on average is 30% lower than from nicotinic acid or nicotinamide, which are almost completely absorbed.

Natural sources: Niacin is present in a wide variety of foods. Many animal foods, including poultry, beef, and fish, provide about 5–10 mg of niacin per serving, primarily in the highly bioavailable forms of NAD and NADP. Plant foods such as nuts, legumes, and grains provide about 2‒5 mg of niacin per serving, mainly as nicotinic acid. However, naturally occurring niacin in some cereal products is largely bound to polysaccharides and glycopeptides, making it only 30% bioavailable. Niacin, which is added to fortified foods, is in free form and is therefore highly bioavailable. Tryptophan is another dietary source of niacin because this amino acid—when present in amounts that exceed those needed for protein synthesis—can be converted to NAD, especially in the liver. The most commonly used estimate of efficiency for the conversion of tryptophan to NAD is 1:60 (ie, 1 mg of niacin [NAD] from 60 mg of tryptophan).
Effect: More than 100 times the recommended dose, taken for months or years, is an effective treatment for dyslipidemia.

Deficiency: A severe deficiency of niacin leads to pellagra, a disease characterized by a pigmented rash with a brown, burnt appearance. In addition, a bright red tongue and changes in the digestive tract that lead to vomiting, constipation or diarrhea can be observed. Neurological symptoms of pellagra can include depression, apathy, headache, auditory and visual hallucinations, fatigue, and memory loss that can progress to aggressive, paranoid, or suicidal behavior. As pellagra progresses, anorexia develops, and the affected individual eventually dies. People who are malnourished or suffer from anorexia, AIDS, inflammatory bowel disease or cirrhosis of the liver and alcoholics who often have insufficient intake of niacin and other nutrients are deficient. People who do not consume enough riboflavin (vitamin B2), pyridoxine (vitamin B6), or iron convert less tryptophan into niacin because the enzymes important for this conversion depend on these nutrients to function.

Recommended daily dose: adult: 35 mg for men, 35 mg for women (35 mg during pregnancy, 35 mg during breastfeeding).

Adverse effects: More than 30 mg of nicotinic acid causes reddening of the skin (niacin flush) on the face, arms, and chest due to vasodilation of small subcutaneous blood capillaries. Redness is accompanied by burning, tingling, and itching sensations. These symptoms are typically transient and may occur within 30 minutes of ingestion or within days or weeks of repeated dosing. They are considered an unpleasant rather than a toxic side effect. They can be alleviated by taking nicotinic acid supplements with food, increasing doses slowly, or waiting until the body develops a natural tolerance. When taking doses of 1,000‒3,000 mg/day, nicotinic acid can also cause more serious side effects. Many of these effects have occurred in patients taking high doses of nicotinic acid to treat hyperlipidemia. These adverse effects may include hypotension severe enough to increase the risk of falls; fatigue; impaired glucose tolerance and insulin resistance; gastrointestinal effects, such as nausea, heartburn, and abdominal pain; and eye effects such as blurred or impaired vision and macular edema (accumulation of fluid in the center of the retina). Nicotinamide does not cause skin redness and has fewer side effects than nicotinic acid, and these effects usually begin at much higher doses. Nausea, vomiting, and signs of liver toxicity may occur at 3,000 mg of nicotinamide per day.

Interactions: Isoniazid and pyrazinamide, drugs used to treat tuberculosis, are structural analogs of niacin that interrupt the production of niacin from tryptophan. In addition, isoniazid may interfere with the conversion of niacin to NAD. Large doses of nicotinic acid can raise blood glucose levels by causing or exacerbating insulin resistance and increasing glucose production in the liver.

Pregnancy: Niacin supplementation in doses greater than recommended and doses for the treatment of high cholesterol is not recommended during pregnancy.

Breastfeeding: Safe in recommended doses. Its supplementation is necessary only in cases of poor nutritional intake.

Toxicity: High doses (3000 mg) of nicotinic acid taken chronically can be hepatotoxic (more likely when extended-release forms of nicotinic acid are used). To minimize the risk of adverse effects of nicotinic acid supplementation, regular blood tests are recommended.