Clinical Information

Vitamin B3 is the term used for a group of closely related water-soluble pyridine derivatives, primarily derived from tryptophan. Niacin (also known as nicotinic acid) is converted to nicotinamide, which can also be synthesized directly from tryptophan. Nicotinamide serves as the precursor of nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP), essential coenzymes for numerous dehydrogenases. Many of these enzymes play a role in energy release from carbohydrates and fats, but numerous other pathways are also NAD/NADP dependent, ranging from intra- and inter-cell signaling, to DNA repair, to fatty acid-, cholesterol- and steroid hormone synthesis, and many other vital biochemical functions.

Nicotinuric acid is a major inactive metabolite of niacin and nicotinamide.

Vitamin B3 deficiency most severely impacts tissues with high energy requirements or high turnover. Thus, the skin, the gastrointestinal tract, and the brain are primarily affected, but the function of numerous other organ systems, such as bone marrow and heart, might also be impaired. Severe vitamin B3 deficiency manifests as a distinct clinical syndrome, called pellagra, which is clinically characterized by the "3Ds": dermatitis, diarrhea, and dementia; if untreated, it will result in death.

The onset of deficiency symptoms is subacute or chronic.

The most common cause of vitamin B3 deficiency is inadequate dietary intake of niacin or tryptophan. At-risk populations are older adults, those with limited income, and those who are malnourished or suffer from malabsorption. Malnourished individuals with severe chronic alcoholism are at particularly high risk, as high alcohol intake impairs absorption of niacin and tryptophan as well as further downstream liver metabolism to bioactive of vitamin B3 compounds.

Liver disease in general is also a risk factor, as nicotinamide is derived in the liver from tryptophan. This process requires vitamins B6, B2, and iron, so deficiencies of any of these factors might also predispose the individual to vitamin B3 deficiency.

Issues that impact the availability of tryptophan for vitamin B3 synthesis can also lead to deficiency. Examples include:

-Hartnup disease, a hereditary disorder that reduces tryptophan absorption

-Carcinoid syndrome, a gastro-entero-pancreatic neuroendocrine tumor disorder that results in serotonin overproduction, with the majority of available tryptophan being channeled into serotonin synthesis

-Various drugs (eg, isoniazid, chloramphenicol, fluorouracil, mercaptopurine)

In most cases, vitamin B3 supplementation should result in a cure, even if the deficiency has progressed to the state of pellagra.

Vitamin B3 toxicity is much less common than deficiency. Its occurrence is essentially limited to individuals who consume vitamin B3 supplements in extremely excessive doses or to patients who are prescribed niacin for treatment of hypercholesterolemia, as the doses used in this setting are very high. Common symptoms are flushing, itching, dizziness, tachycardia, nausea and vomiting, diarrhea, and gout. Rarely liver damage or stroke has been observed. The onset of symptoms is acute or subacute.