GPR109A (Niacin Receptor)

GPR109A (also called HM74A or NIACR1) is a G-protein coupled receptor activated by nicotinic acid (niacin) and beta-hydroxybutyrate (a ketone body). Activation of GPR109A on skin Langerhans cells triggers prostaglandin release, causing the characteristic niacin flush (vasodilation, warmth, redness, tingling).

Niacinamide (nicotinamide) does not activate GPR109A, so it doesn't cause flushing but also lacks some of niacin's benefits. Extended-release niacin and taking niacin with food can reduce flushing. Aspirin blocks prostaglandin synthesis and can reduce flush.

Metabolic Connections

GPR109A (Niacin Receptor) connects to 7 other pathways.

B Vitamins

B3

GPR109A is activated by nicotinic acid (niacin form of B3)

Niacin - precursor to NAD+ and NADP+. Essential for energy metabolism, DNA repair, and cell signaling.

Cell Membrane

Cholesterol

GPR109A activation contributes to niacin's cholesterol-lowering effects

Essential sterol in cell membranes. Precursor to all steroid hormones, vitamin D, and bile acids.

Nutrient Groups

Fatty Acids

GPR109A activation inhibits lipolysis, reducing free fatty acid release

Lipid building blocks; energy source via beta-oxidation; components of membranes; include saturated, mono, and polyunsaturated types.

Metabolites

Ketones

Beta-hydroxybutyrate activates GPR109A during ketosis

Alternative brain fuel produced from fat during fasting or low-carb eating. Include beta-hydroxybutyrate, acetoacetate, and acetone.

Side Effects

Niacin Flush

Niacin activates GPR109A, triggering the flush mechanism

Harmless skin flushing from niacin; caused by prostaglandin release via GPR109A; indicates niacin activity.

Signaling Molecules

Prostaglandins

GPR109A activation triggers prostaglandin release, causing niacin flush

Lipid signaling molecules from arachidonic acid; mediate inflammation, pain, fever; target of NSAIDs.

Prostaglandins

GPR109A activation triggers prostaglandin release causing niacin flush

Lipid signaling molecules from arachidonic acid; mediate inflammation, pain, fever; target of NSAIDs.