Compound
    Moderate Evidence

    Apigenin

    Apigenin (4',5,7-trihydroxyflavone)

    TL;DR

    Apigenin is a chamomile flavonoid that binds benzodiazepine sites weakly and is taken at 50 mg before bed for calm and sleep. Human trials are scarce.

    Ideal For

    • Adults wanting a gentle wind-down supplement
    • People who respond to chamomile tea and want a concentrated form
    • Those avoiding melatonin but seeking evening calm

    Avoid If

    • You are pregnant or breastfeeding
    • You take sedatives or benzodiazepines
    • You are allergic to ragweed, daisies or chrysanthemums
    • You take tamoxifen or other hormone-sensitive therapy

    Frequently Asked Questions

    Overview

    Apigenin is a flavone found in chamomile, parsley, celery and several herbs. It has become popular as an evening supplement largely on the strength of its mechanism — partial binding at the benzodiazepine site of the GABA-A receptor — and on chamomile trials rather than on trials of isolated apigenin itself.

    That distinction matters. Chamomile extract standardised to apigenin has been tested in generalised anxiety disorder, where 1500 mg/day over eight weeks reduced anxiety scores, and in insomnia, where results are modest and inconsistent. Isolated apigenin at the typical 50 mg dose has almost no direct human sleep data. Preclinical work is broader — CD38 inhibition raising NAD+, anti-inflammatory effects, and effects on proliferation in cell models — but none of that has been confirmed in people at supplemental doses.

    Apigenin is a reasonable, low-risk part of an evening routine. It is not a substitute for sleep hygiene or for treatment of a diagnosed sleep disorder, and the honest summary is that mechanism currently outruns evidence.

    How It Works

    • Binds the benzodiazepine site of GABA-A receptors as a weak partial agonist
    • Inhibits CD38, which in preclinical models slows NAD+ degradation
    • Suppresses NF-kB signalling and downstream inflammatory cytokines
    • Antioxidant activity through direct radical scavenging and Nrf2 signalling
    • Weak monoamine oxidase inhibition in vitro

    Quick Facts

    • Promotes calmness and sleep
    • Neuroprotective effects
    • Anti-inflammatory action
    • May enhance longevity pathways
    • Supports NAD+ metabolism

    Supporting Research
    4 studies

    Ethnobotany, Phytochemistry and Bioactivity of the Genus Turnera (Passifloraceae) with a Focus on Damiana - Turnera diffusa

    Score: 5/10
    2014
    systematic_review

    Szewczyk K, Zidorn C

    Damiana contains flavonoids (notably apigenin derivatives), terpenoids and arbutin with aphrodisiac, anxiolytic and PDE-5 inhibitory activity demonstrated almost exclusively in animal and in vitro models.

    View source

    Long-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: a randomized clinical trial

    Score: 7/10
    2016
    rct
    n=93

    Mao JJ, Xie SX, Keefe JR +3 more

    Long-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: a randomized clinical trial.

    View source

    A randomized, double-blind, placebo-controlled trial of oral Matricaria recutita (chamomile) extract therapy for generalized anxiety disorder

    Score: 6/10
    2009
    rct
    n=57

    Amsterdam JD, Li Y, Soeller I +3 more

    A randomized, double-blind, placebo-controlled trial of oral Matricaria recutita (chamomile) extract therapy for generalized anxiety disorder.

    View source

    Apigenin: a natural molecule at the intersection of sleep and aging

    Score: 4/10
    2024
    systematic_review

    Kramer DJ, Johnson AA

    Apigenin: a natural molecule at the intersection of sleep and aging.

    View source

    Safety Information

    Potential Side Effects

    Very few reported at typical doses. Mild drowsiness, and allergic reactions in people sensitive to related plants. Long-term safety at concentrated doses has not been studied.

    Contraindications

    Cross-reactive allergy is the main practical risk for people sensitive to the Asteraceae family. Additive sedation with other CNS depressants. Theoretical oestrogenic activity means caution in hormone-sensitive conditions.

    Drug Interactions

    • Benzodiazepines and Z-drugs — additive sedation
    • Warfarin — chamomile preparations have case reports of raised INR
    • CYP1A2 and CYP3A4 substrates — apigenin inhibits these enzymes in vitro
    • Tamoxifen — theoretical competition at oestrogen receptors

    Pregnancy & Breastfeeding

    Pregnancy: likely_unsafe

    Breastfeeding: insufficient_data

    Dosage Guidelines

    Dosage Used in Studies

    50-200 mg

    Best Time to Take

    30-60 minutes before bed

    Best Form

    Chamomile extract standardised to apigenin where the goal is anxiety, since that is where the human evidence sits

    Bioavailability

    Flavonoid with low bioavailability. Found in chamomile, parsley, celery. May have anxiolytic and sleep-promoting effects. Anti-inflammatory properties. CYP450 enzyme interactions possible.

    Forms Compared

    Isolated apigenin

    Chamomile extract standardised to apigenin

    Liposomal or phospholipid apigenin

    Food & Timing

    With a small amount of dietary fat, which helps absorption of this poorly soluble flavone

    Medical Disclaimer

    The information provided on this website is for educational and informational purposes only and is not intended as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any supplement regimen.

    Individual results may vary. The statements on this website have not been evaluated by the Food and Drug Administration. Products and information are not intended to diagnose, treat, cure, or prevent any disease.