Apigenin
Apigenin
Apigenin is a naturally occurring flavonoid found in chamomile, parsley, celery, and other plants, used primarily for its anxiolytic, anti-inflammatory, and potential longevity-promoting properties. It is notable for its ability to inhibit CD38, an enzyme that degrades NAD+, making it popular as an adjunct to NAD+ precursor supplementation. Research also supports its use for mild anxiety reduction and sleep quality improvement.
Mechanism of Action
Apigenin acts as a partial agonist at GABA-A receptors (particularly at benzodiazepine-binding sites), producing mild anxiolytic and sedative effects without significant dependence risk. It inhibits CD38, a major NAD+-consuming enzyme, thereby supporting cellular NAD+ levels and downstream sirtuin and PARP activity. Additionally, apigenin inhibits pro-inflammatory enzymes including COX-2 and suppresses NF-κB signaling, contributing to its anti-inflammatory and potential anti-cancer properties.
Evidence by Health Goal(16 goals)
Dosing Protocols
30-60 minutes before bed, or with evening meal
50mg is the common starting dose for sleep and anxiety support; 100-200mg is used for NAD+ optimization in combination with NMN or NR. Higher doses (>200mg) have not demonstrated additional benefit and may increase sedation during daytime use.
Safety & Side Effects
Apigenin has a generally favorable safety profile at typical supplemental doses (50-200mg/day), with decades of dietary human exposure through plant-based foods providing reassurance. However, its anti-estrogenic effects via aromatase inhibition warrant caution in women who are pregnant, breastfeeding, or managing hormone-sensitive conditions, and it should be used carefully alongside sedative medications due to additive CNS depression.
Possible Side Effects
- !Daytime drowsiness or sedation, particularly at doses above 100mg
- !Mild gastrointestinal discomfort or nausea at higher doses
- !Potential hormonal effects - apigenin inhibits aromatase and may modestly reduce estrogen levels with prolonged use
- !Thyroid function interference at very high doses in preclinical models
- !Photosensitivity with excessive intake in sensitive individuals
- !Mild headache reported by some users during initial use
Interactions
- -May potentiate benzodiazepines, sedatives, and sleep aids (e.g., zolpidem, clonazepam) through additive GABA-A receptor activity
- -Inhibits CYP1A2, CYP2C9, and CYP3A4 enzymes - may increase plasma levels of warfarin, statins, and other substrates
- -May enhance anticoagulant effects of warfarin and other blood thinners - monitor INR closely
- -Anti-estrogenic properties may interfere with hormone replacement therapy or estrogen-sensitive medications
- -Synergistic NAD+ elevating effect when combined with NMN or NR - generally considered beneficial but monitor for additive effects
Cost & Where to Buy
Widely available as a standalone supplement or in combination NAD+ formulas; standalone 50-100mg capsules are inexpensive, while branded longevity stacks containing apigenin command premium pricing.
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