Flavonoid
Apigenin
Emerging EvidenceThe sedative and anxiolytic mechanism is well described preclinically and apigenin is the compound behind chamomile's reputation, but controlled human trials of isolated apigenin are scarce - hence Emerging rather than a higher rating.
Recommended Dose
50 mg daily
Timing
30 min before bed
Mechanism of Action
Binds to benzodiazepine sites on GABA-A receptors as a positive allosteric modulator, providing anxiolytic effects. Also inhibits CD38 enzyme, potentially preserving NAD+ levels.
Side Effects & Safety
Well-tolerated. Mild sedation intended. Theoretical concerns about muscle relaxation at very high doses. May interact with sedatives.
Do not use / talk to a doctor first
- Taking any narrow-therapeutic-index drug cleared by CYP3A4, without checking with a pharmacist
- Scheduled surgery or a general anaesthetic, given the sedative effect and CYP involvement in anaesthetic clearance
Interactions
Drugs cleared by CYP3A4
Apigenin reversibly inhibits CYP3A4, which clears a large share of prescription medicines - statins, many benzodiazepines, several immunosuppressants and calcium-channel blockers among them. Inhibition raises the drug's levels. This is the interaction that matters most on this page
Source: Saric Mustapic 2018, Molecules (PMID 30301254)
Drugs cleared by CYP1A2
Apigenin is a potent CYP1A2 inhibitor. Caffeine, theophylline, clozapine and olanzapine are cleared this way
Source: Shimada 2010, J Biochem Mol Toxicol (PMID 20806393)
P-glycoprotein substrates
Apigenin inhibits P-glycoprotein, which can raise absorption of drugs that rely on it for efflux. Demonstrated in animal pharmacokinetic work with imatinib and dasatinib
Source: PMC3863468; PMC9964503 - animal pharmacokinetics
Sedatives, benzodiazepines and alcohol
Additive sedation - apigenin acts at benzodiazepine binding sites, and the mild sedation is the intended effect here
Source: mechanistic
Pregnancy & breastfeeding
Not adequately studied as an isolated supplement in pregnancy or breastfeeding. Not recommended without medical advice.
Who should avoid / see a doctor
Anyone taking prescription medication should check with a pharmacist first. This is the one compound on this page whose main risk is not its own toxicity but what it does to OTHER drugs: apigenin inhibits CYP3A4, CYP1A2, CYP2A6 and P-glycoprotein, and CYP3A4 alone handles clearance of a large fraction of prescription medicines. Most of that evidence is in vitro or in animals, which makes the size of the effect in people uncertain - not the direction.
Synergies
Used in These Stacks
See Apigenin inside a full protocol — the stack pages cover when and why to combine it.
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References
- 1.Saric Mustapic 2018, Molecules — Apigenin showed reversible inhibition of CYP3A4 among tested flavonoid aglycones. (in vitro)
- 2.Shimada 2010, Journal of Biochemical and Molecular Toxicology — Apigenin is a potent inhibitor of human CYP1A2, by a mechanism distinct from genistein's. (in vitro)
- 3.Flavonoid aglycones and CYP activity, PMC6749521 — Effects of flavonoid aglycones on CYP1A2, CYP2A6, CYP2C8 and CYP2D6 activity. (in vitro)
