From the Guidelines
Niacin (nicotinic acid) lowers LDL cholesterol primarily by inhibiting hepatic VLDL production, which subsequently reduces LDL levels in the bloodstream. The mechanism involves niacin binding to the GPR109A receptor in adipose tissue, which inhibits hormone-sensitive lipase and decreases the release of free fatty acids into circulation. With fewer fatty acids reaching the liver, there is reduced substrate availability for triglyceride and VLDL synthesis. Additionally, niacin inhibits the enzyme diacylglycerol acyltransferase-2 (DGAT-2), which is critical for triglyceride synthesis in the liver. Niacin also increases apolipoprotein B degradation, further reducing VLDL production. Beyond its effects on VLDL, niacin inhibits hepatic removal of HDL apolipoprotein A-I, leading to increased HDL levels, which indirectly helps lower LDL. Some key points to consider when using niacin for LDL reduction include:
- Therapeutic doses for lipid management typically range from 1-3 grams daily, with extended-release formulations often preferred to minimize flushing side effects.
- Patients should start with low doses (100-250 mg) and gradually increase to minimize adverse effects like flushing, which can be reduced by taking aspirin 30 minutes before niacin and avoiding hot beverages during administration, as noted in various studies 1. The use of niacin in combination with other lipid-lowering agents, such as statins, can produce a marked reduction of LDL-C and a striking rise in HDL-C, as seen in several clinical trials 1. However, it is essential to consider the potential side effects and intolerance in a sizable minority of patients when prescribing nicotinic acid therapy.
From the FDA Drug Label
The mechanism by which nicotinic acid exerts these effects is not entirely understood, but may involve several actions, including a decrease in esterification of hepatic triglycerides Nicotinic acid treatment also decreases the serum levels of apolipoprotein B-100 (apo B), the major protein component of the very low-density lipoprotein (VLDL) and LDL fractions
The mechanism of niacin in lowering LDL cholesterol is not entirely understood. However, it may involve:
- A decrease in esterification of hepatic triglycerides
- A decrease in the serum levels of apolipoprotein B-100 (apo B), the major protein component of VLDL and LDL fractions 2
From the Research
Mechanism of Niacin in Lowering LDL Cholesterol
The mechanism of niacin in lowering Low-Density Lipoprotein (LDL) cholesterol is complex and involves several pathways. Some of the key mechanisms include:
- Decreasing fatty acid mobilization from adipose tissue triglyceride stores 3
- Inhibiting hepatocyte diacylglycerol acyltransferase and triglyceride synthesis, leading to increased intracellular apo B degradation and subsequent decreased secretion of VLDL and LDL particles 3
- Reducing the synthesis of triglycerides and very-low-density-lipoprotein (VLDL) and LDL cholesterol 4
Effects of Niacin on Lipid Parameters
Niacin has been shown to have a broad range of effects on serum lipids and lipoproteins, including:
- Lowering total cholesterol, low-density-lipoprotein (LDL) cholesterol, and triglycerides 5, 4
- Raising high-density-lipoprotein (HDL) cholesterol levels 5, 4
- Lowering Lp(a) lipoprotein 4
- Reducing triglycerides and VLDL cholesterol synthesis 4
Clinical Implications
The use of niacin in the treatment of dyslipidemia has been associated with improved serum lipid levels and reduced coronary artery disease, especially when combined with statins 4. However, the clinical use of niacin is limited by its side effects, such as flushing and hepatotoxicity 5, 6, 7. Therefore, niacin is typically recommended for patients with marked dyslipidemia who are closely monitored for side effects and potential toxicity 5.