Niacin

Category: vitamin

Aliases: Vitamin B3, Nicotinic acid, Pyridine-3-carboxylic acid

Pharmacological Mechanism

Precursor to NAD⁺ and NADP⁺ (via the de-novo Preiss-Handler pathway or NAMPT-mediated salvage from nicotinamide riboside/NMN). At pharmacologic doses (≥500 mg), activates the HCA2 (GPR109A) receptor on adipocytes → lowers lipolysis and FFA flux → reduces VLDL/LDL and raises HDL. The same receptor triggers the characteristic cutaneous flush via prostaglandin D2 release.

Half-Life (t½)

PO: 0.9h

Dosing Guidelines

• PO: Typical 14.7 mg (Range: 14–16 mg)

Target Organ Systems

• cardiovascular
• integumentary

Interactions

• NMN (synergistic): All three (niacin, nicotinamide, NR/NMN) feed into NAD⁺; niacin is the cheapest and only one that raises HDL / lowers Lp(a), but causes flush.

Pathways It Modulates

• Cholesterol absorption + reverse transport (activator) — HM74A receptor → modest HDL raise + Lp(a) lowering; flushing limits dosing
• Kynurenine pathway (inhibitor) — feedback suppression of de novo KP→NAD⁺ flux
• NAD+ / sirtuin / longevity axis (substrate) — NAD+ (Preiss-Handler precursor)
• NAFLD / MASH (inhibitor) — dyslipidemia in MASH (limited primary effect on liver)
• Niacin / NAD+ biosynthesis (substrate) — Preiss-Handler entry; high-dose Rx for dyslipidemia (HDL raise)
• Niacin GPR109A cutaneous flush (activator) — GPR109A (HCA2 / HM74A)
• PPAR α / γ / δ nuclear receptor signaling (activator) — PPARα target gene expression (indirect)

Chemical Identifiers

• PubChem CID: 938
• Formula: C6H5NO2
• Molecular weight: 123.11 g/mol
• InChIKey: PVNIIMVLHYAWGP-UHFFFAOYSA-N
• SMILES: C1=CC(=CN=C1)C(=O)O

References

• PMID 12901025