Nicotinic acid

Nicotinic acid, also called niacin, is an organic compound that serves as one of the active forms of vitamin B3, a nutrient essential for humans. Both plants and animals can synthesize it from the amino acid tryptophan. It also functions as a prescription drug. When taken at doses far above the daily vitamin requirement, it reduces blood triglycerides and low-density lipoprotein cholesterol (LDL-C) while raising high-density lipoprotein cholesterol (HDL-C, often called "good" cholesterol). The medication comes in immediate-release and sustained-release forms. Treatment typically starts at 500 mg per day, with gradual increases until a therapeutic effect is reached; immediate-release doses may go up to 3,000 mg daily, and sustained-release up to 2,000 mg daily. Despite these favorable changes in blood lipids, nicotinic acid has not been shown to lower the risk of cardiovascular disease in patients already on a statin. A 2010 review found it effective as a standalone therapy, but a later 2017 review—which included twice as many trials—concluded that while prescription nicotinic acid alters lipid levels, it does not reduce all-cause mortality, cardiovascular mortality, heart attacks, or fatal or non-fatal strokes. It has also been linked to liver toxicity and an increased risk of developing type 2 diabetes. Prescriptions for nicotinic acid in the United States peaked at 9.4 million in 2009, falling to 800,000 by 2020. In 2023, it ranked as the 288th most prescribed medication in the US, with over 500,000 prescriptions.

Chemically, nicotinic acid has the formula C₆H₅NO₂ and belongs to the pyridinecarboxylic acids. As a precursor to nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), it plays a role in DNA repair. Nicotinic acid has also been detected in carbonaceous chondrite meteorites and in samples returned from the asteroids 162173 Ryugu and 101955 Bennu.

The term "niacin" was originally coined from "nicotinic acid vitamin" to distinguish the nutrient from the drug nicotine found in tobacco. Initially, it referred only to the nutritional form of vitamin B3. In American English, however, "niacin" has come to also mean nicotinic acid when used in high-dose prescription form. In other varieties of English, the medication is called only "nicotinic acid." The term "nicotinic acid" unambiguously refers to both the substance and the prescription medicine used to treat high cholesterol and triglycerides. When used as a drug, daily doses range from 500 to 3,000 mg. High-dose nicotinamide does not produce this medicinal effect.

Vitamin B3 includes several vitamers that can substitute for one another, such as nicotinic acid and nicotinamide. Both are precursors to the coenzymes NAD and NADP. These coenzymes are essential for many dehydrogenases involved in hydrogen transfer. NAD is important for breaking down fats, carbohydrates, proteins, and alcohol, as well as for cell signaling and DNA repair; NADP is mainly involved in anabolic processes like fatty acid and cholesterol synthesis. Health authorities in several countries recommend that healthy adults consume 14–18 mg of vitamin B3 per day. Both nicotinic acid and nicotinamide are used to prevent and treat pellagra, the disease caused by vitamin B3 deficiency.

In the United States, nicotinic acid is sold as an over-the-counter dietary supplement, with servings ranging from 100 to 1,000 mg. These products often carry a Structure/Function health claim approved by the FDA, such as "Supports a healthy blood lipid profile." The American Heart Association strongly advises against substituting dietary supplement nicotinic acid for the prescription version due to potentially serious side effects, and because the manufacture of supplements is less tightly regulated by the FDA. Taking more than 30 mg of nicotinic acid as a supplement can cause skin flushing—a reddening of the face, arms, and chest due to dilation of small blood vessels under the skin, along with sensations of heat, tingling, and itching. These effects are temporary, lasting minutes to hours, and are considered unpleasant rather than toxic.

As a lipid-modifying medication, prescription nicotinic acid—often labeled as niacin in the US—is available in immediate-release and slow-release forms. It is used to treat primary hyperlipidemia and hypertriglyceridemia, either alone or combined with other lipid-lowering drugs. Dosing starts at 500 mg per day and is often gradually increased to up to 3,000 mg daily for immediate release or 2,000 mg daily for slow release to achieve the desired lipid changes. Systematic reviews have found no effect of prescription nicotinic acid on all-cause mortality, cardiovascular mortality, heart attacks, or fatal or non-fatal strokes, despite raising HDL cholesterol in patients already on statins. Reported side effects include an increased risk of new-onset type 2 diabetes.