Niacin, also known as vitamin B3, is a water-soluble vitamin. It refers to nicotinic acid (pyridine-3-carboxylic acid), nicotinamide (niacinamide or pyridine-3-carboxamide), and related compounds like nicotinamide riboside. In the body, nicotinamide is used to create coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). These coenzymes play key roles in oxidation-reduction reactions by transferring electrons and hydrogen ions, and around 200 enzymes, mainly dehydrogenases, require NAD and NADP for proper function. NADH (nicotinamide adenine dinucleotide + hydrogen) is essential for ATP production, while NADPH (reduced nicotinamide adenine dinucleotide phosphate) is involved in biosynthetic pathways, such as fatty acid and cholesterol synthesis, as well as in maintaining cellular antioxidant defenses.
Clinical Pharmacology:
Niacinamide is efficiently absorbed from intramuscular injection sites or through the bloodstream after intravenous infusion. Once in the body, it is metabolized to form coenzymes, with excess amounts stored in red blood cells or methylated by the liver and excreted in the urine. The half-life of niacinamide is about 25-50 minutes, with 60-80% excreted through urine.
Indications and Usage:
Pellagra, a disease caused by a niacin or tryptophan deficiency, is often seen in regions where corn is a staple food. Symptoms include skin rash, diarrhea, mental confusion, and inflammation of mucous membranes. Niacinamide may also help correct abnormal tryptophan metabolism in Hodgkin’s disease. Niacin has been effective in treating schizophrenia, depression, dementia, and possibly migraines. Although niacin can affect lipid levels, its side effects limit its use. Niacinamide, however, does not impact serum lipids. Niacin is primarily used to lower triglycerides by reducing free fatty acid mobilization and very low-density lipoprotein (VLDL) production in the liver. It also raises HDL-C and lowers lipoprotein (a).
Contraindications:
- Active liver disease or unexplained elevations in liver enzymes
- Active peptic ulcer disease (for oral dosing)
- Arterial bleeding
- Hypersensitivity to niacin or its components
- No contraindications at doses of 35 mg or less daily for adults
- Safe during pregnancy or lactation at doses of 18-20 mg daily
Precautions:
High doses of leucine can increase niacin requirements. Use caution when administering niacin alongside antihypertensive drugs, as it can cause severe postural hypotension. High-dose niacin can raise blood glucose levels, so blood sugar should be monitored in patients taking anti-diabetes medications. Caution is also advised for patients consuming large amounts of alcohol due to an increased risk of liver dysfunction. During pregnancy, the recommended dietary allowance of niacin increases, but it is unclear if lipid-lowering doses of niacin are harmful to the fetus. If pregnancy occurs while taking niacin for hypercholesterolemia, it should be discontinued.
Adverse Reactions:
The most common side effect of niacin is flushing, which typically occurs within 20 minutes of ingestion and lasts up to 60 minutes. Adverse reactions at therapeutic doses (100-250 mg daily) are rare, but niacin can cause abnormal liver tests and potentially significant liver toxicity. It should be discontinued if liver enzyme levels exceed three times the normal limit. Niacin can also raise uric acid levels and should be used cautiously in patients with gout. In higher doses (1,000-3,000 mg/day), niacin can cause more serious side effects, including hypotension, fatigue, impaired glucose tolerance, gastrointestinal issues, and ocular effects.
Overdosage:
Symptoms of niacin overdose include severe skin flushing, dizziness, rapid heart rate, itching, abdominal pain, nausea, vomiting, diarrhea, and liver toxicity.