Discovery of Niacin

Vitamin B3

MOA of Niacin

Niacin (also known as nicotinic acid or vitamin B3) has several mechanisms of action depending on its use.

1. Lipid-lowering effect

Niacin is used as an antihyperlipidemic agent primarily due to its effects on lipoprotein metabolism:

Inhibits hepatic diacylglycerol acyltransferase-2 (DGAT2): This reduces triglyceride synthesis in the liver.

Decreases VLDL and LDL levels: By reducing triglyceride synthesis, there’s less VLDL (very-low-density lipoprotein) produced, leading to lower LDL (low-density lipoprotein, or "bad cholesterol").

Increases HDL (high-density lipoprotein): Niacin inhibits hepatic uptake of apolipoprotein A-I, a major component of HDL, thus increasing HDL levels.

2. Inhibits lipolysis in adipose tissue

Niacin binds to the GPR109A receptor (a Gi-protein-coupled receptor) on adipocytes.

This leads to inhibition of hormone-sensitive lipase, decreasing free fatty acid (FFA) release into the bloodstream.

Lower FFA levels reduce liver triglyceride synthesis, contributing to decreased VLDL production.

3. Other effects

Vasodilation (flushing): Niacin causes prostaglandin-mediated vasodilation, especially via prostaglandin D2 (PGD2) and E2 (PGE2), leading to the common side effect of flushing.

Common Side Effects especially at high doses

• Flushing: Warmth, redness, itching or tingling of the face, neck, or chest

• Headache

• Dizziness

• Upset stomach

• Nausea

• Diarrhea

Serious Side Effects usually with high-dose

• Liver toxicity: Elevated liver enzymes, hepatitis, or liver damage

• Gout: Niacin can raise uric acid levels

• High blood sugar (hyperglycemia): Especially in diabetics

• Stomach ulcers: Can worsen or increase risk

• Muscle damage: Rare, but risk increases when combined with statins

symptoms

• Constipation or diarrhea.

• Vomitting.

• Skin rash.

• Depression.

• Bright red tongue.

• Headache.

• Fatigue.

• Memory loss.