Apigenin
Also known as: 4',5,7-Trihydroxyflavone, Chamomile Flavonoid, Apigenine, C.I. Natural Yellow 1
A dietary flavone (C15H10O5, MW 270.24) acting as a partial agonist at the benzodiazepine site of GABA-A receptors (Ki ~4 µM), a competitive CD38 inhibitor (IC50 ~7–10 µM), an aromatase/CYP19A1 inhibitor (IC50 ~2.7 µM), and an Nrf2 activator / NF-κB suppressor. Oral bioavailability is poor (~5–10%) with plasma Cmax of 0.2–0.4 µM after dietary intake.
Last reviewed: 2024-05-01 · 15 indexed studies
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Overview
Apigenin (4',5,7-trihydroxyflavone) is a dietary flavone abundant in chamomile (Matricaria chamomilla), parsley, celery, and thyme. It is best known as a natural sleep aid via GABA-A benzodiazepine-site modulation and has emerged as a CD38 inhibitor that helps preserve cellular NAD+. Popularized by Andrew Huberman as part of a sleep stack, isolated apigenin has strong mechanistic data but no published RCTs in humans — all clinical evidence to date uses chamomile extracts standardized to apigenin.
Mechanism & Function
Pale yellow crystalline flavonoid extracted from chamomile or parsley.
- Capsule
- Tablet
- Powder
Capsule is generally preferred for bioavailability or efficacy.
Mechanism of Action
Binds the central benzodiazepine site of the GABA-A receptor (selective for α1/α2 subunits), potentiating chloride influx with partial-agonist character — produces anxiolysis and mild sedation without the myorelaxant or anticonvulsant effects of full benzodiazepines. Competitively inhibits CD38 (the main age-related NAD+ glycohydrolase), elevating intracellular NAD+ and sirtuin activity. Inhibits aromatase (CYP19A1), reducing androgen→estrogen conversion. Suppresses NF-κB p65 nuclear translocation (↓ TNF-α, IL-1β, IL-6, COX-2, iNOS) and activates the Nrf2/HO-1/NQO1 antioxidant axis.
Physiological Role
Acts as a mild anxiolytic and sleep promoter via GABA-A modulation, a cellular NAD+ preserver via CD38 inhibition (relevant to mitochondrial function and aging), and a broad anti-inflammatory/antioxidant agent via NF-κB and Nrf2 pathways. Modest aromatase inhibition has implications for hormone-sensitive tissues.
Primary Pathways
Performance / Health Relevance
Primarily relevant for sleep quality, recovery, and pre-competition anxiety. CD38 inhibition and NAD+ preservation are mechanistically supportive of mitochondrial function and training recovery, though human performance data is absent. Not on the WADA prohibited list.
Evidence Review
Practical Use & Dosage
- Minimum Effective Dose
- 25–50mg isolated apigenin (or 220mg chamomile extract standardised to ≥1.2% apigenin)
- Optimal Range
- 50mg isolated apigenin 30–60 minutes before bed (Huberman protocol); 500–1,500mg/day chamomile extract for anxiety (Amsterdam RCTs)
- Upper / Caution Level
- 200mg/day isolated apigenin — no long-term human safety data above this range
- Timing
- 30–60 minutes before bed for sleep onset; split daytime dosing (with meals) when targeting anxiety with chamomile extracts
- Best Format
- 98%+ pure isolated apigenin capsule, or chamomile Phytosome® / ApigenSol™ for enhanced bioavailability
- Bioavailability
- Oral bioavailability of free apigenin is only ~5–10%; plasma Cmax after dietary intake is ~0.2–0.4 µM, well below the 5–50 µM needed for most in vitro effects. ~70% is metabolised by gut microbiota to smaller phenolic acids. Phytosome and self-emulsifying delivery systems (e.g. ApigenSol™) claim 10–25× absorption improvements.
- Absorption Considerations
- Highly lipophilic — take with a fat-containing snack. Tmax ~2–4 hours; half-life ~8–12 hours with enterohepatic recirculation. >97% plasma protein bound. Phase II metabolism is dominated by glucuronidation (UGT1A1/1A6/1A9) at the C-7 position.
Safety & Interactions
Side Effects
- •Mild next-day grogginess at higher doses
- •Mild sedation (desired effect)
- •Rare allergic reactions in Asteraceae-sensitive individuals (chamomile-derived sources)
Contraindications
- Pregnancy and lactation (emmenagogic / uterine-stimulant signals in animal models)
- Known Asteraceae/Compositae allergy (ragweed, chrysanthemum, marigold)
- Concurrent use with aromatase-inhibitor therapy (letrozole, anastrozole)
Drug Interactions
- •Benzodiazepines and other GABAergic sedatives (additive CNS depression)
- •Warfarin and other CYP2C9 substrates (theoretical ↑ INR / bleeding risk)
- •CYP1A2 substrates — caffeine, theophylline, clozapine, olanzapine
- •CYP3A4 substrates — statins, calcium-channel blockers, dasatinib (animal PK data)
- •Venlafaxine (↑ exposure in animal/in vitro models)
Who Should Avoid
- •Pregnant or breastfeeding women
- •Individuals on anticoagulants without medical supervision
- •Patients on narrow-therapeutic-index CYP1A2/2C9/3A4 drugs
- •People with hormone-sensitive cancers on aromatase inhibitors
Monitoring
No routine monitoring required at typical sleep-stack doses (50mg). Consider INR monitoring if combined with warfarin. Human dose-response data for isolated apigenin is essentially absent — all human RCT evidence uses chamomile extract.
Frequently Asked Questions
Auto-generated from indexed evidence — dosage, safety, interactions, and more.
When is Apigenin typically used or indicated?
Apigenin is most commonly used for: Sleep onset, Anxiety reduction, Cellular NAD+ support, Anti-inflammatory support, Estrogen modulation. Acts as a mild anxiolytic and sleep promoter via GABA-A modulation, a cellular NAD+ preserver via CD38 inhibition (relevant to mitochondrial function and aging), and a broad anti-inflammatory/antioxidant agent via NF-κB and Nrf2 pathways. Modest aromatase inhibition has implications for hormone-sensitive tissues.
How does Apigenin work?
Binds the central benzodiazepine site of the GABA-A receptor (selective for α1/α2 subunits), potentiating chloride influx with partial-agonist character — produces anxiolysis and mild sedation without the myorelaxant or anticonvulsant effects of full benzodiazepines. Competitively inhibits CD38 (the main age-related NAD+ glycohydrolase), elevating intracellular NAD+ and sirtuin activity. Inhibits aromatase (CYP19A1), reducing androgen→estrogen conversion. Suppresses NF-κB p65 nuclear translocation (↓ TNF-α, IL-1β, IL-6, COX-2, iNOS) and activates the Nrf2/HO-1/NQO1 antioxidant axis.
What is the recommended dose of Apigenin?
The optimal range is 50mg isolated apigenin 30–60 minutes before bed (Huberman protocol); 500–1,500mg/day chamomile extract for anxiety (Amsterdam RCTs). with a minimum effective dose of 25–50mg isolated apigenin (or 220mg chamomile extract standardised to ≥1.2% apigenin). Best taken: 30–60 minutes before bed for sleep onset; split daytime dosing (with meals) when targeting anxiety with chamomile extracts. Upper / caution level: 200mg/day isolated apigenin — no long-term human safety data above this range.
What are the side effects of Apigenin?
Reported side effects include: Mild next-day grogginess at higher doses; Mild sedation (desired effect); and Rare allergic reactions in Asteraceae-sensitive individuals (chamomile-derived sources). Monitoring: No routine monitoring required at typical sleep-stack doses (50mg). Consider INR monitoring if combined with warfarin. Human dose-response data for isolated apigenin is essentially absent — all human RCT evidence uses chamomile extract.
Does Apigenin interact with medications?
Known or theoretical interactions: Benzodiazepines and other GABAergic sedatives (additive CNS depression); Warfarin and other CYP2C9 substrates (theoretical ↑ INR / bleeding risk); CYP1A2 substrates — caffeine, theophylline, clozapine, olanzapine; CYP3A4 substrates — statins, calcium-channel blockers, dasatinib (animal PK data); and Venlafaxine (↑ exposure in animal/in vitro models). Always check with a clinician before combining with prescription medication.
Who should avoid Apigenin?
Apigenin is generally not recommended for: Pregnant or breastfeeding women; Individuals on anticoagulants without medical supervision; Patients on narrow-therapeutic-index CYP1A2/2C9/3A4 drugs; People with hormone-sensitive cancers on aromatase inhibitors; Pregnancy and lactation (emmenagogic / uterine-stimulant signals in animal models); Known Asteraceae/Compositae allergy (ragweed, chrysanthemum, marigold); and Concurrent use with aromatase-inhibitor therapy (letrozole, anastrozole).
How strong is the evidence for Apigenin?
Evidence level: Limited (overall score 42/100), based on 15 indexed studies on SuppIndex.
Research & References (15)
Key Studies
A randomized, double-blind, placebo-controlled trial of oral Matricaria recutita (chamomile) extract therapy for generalized anxiety disorder
First Phase II RCT showing chamomile extract (standardised to 1.2% apigenin) significantly reduces HAM-A scores vs placebo in GAD patients.
Chamomile (Matricaria chamomilla L.) extract therapy for generalized anxiety disorder: a randomized, double-blind, placebo-controlled trial of long-term safety and efficacy
Largest chamomile/apigenin RCT to date: 1,500mg/day chamomile extract for up to 38 weeks reduced GAD symptoms and prevented relapse vs placebo.
Therapeutic efficacy and safety of chamomile for state anxiety, generalized anxiety disorder, insomnia, and sleep quality: a systematic review and meta-analysis
Meta-analysis of 12 trials confirming chamomile's anxiolytic and sleep-improving effects.
Flavonoids and the CNS: apigenin as a benzodiazepine-site ligand
Seminal identification of apigenin as a central benzodiazepine receptor ligand isolated from Matricaria recutita.
Flavonoids, especially apigenin, inhibit CD38 in vitro and in vivo, increasing NAD+ and reversing diet-induced obesity
Escande et al. — landmark study establishing apigenin as a CD38 inhibitor that raises tissue NAD+ in vivo.
A randomized, double-blind, placebo-controlled trial of oral Matricaria recutita (chamomile) extract therapy for generalized anxiety disorder
First Phase II RCT showing chamomile extract (standardised to 1.2% apigenin) significantly reduces HAM-A scores vs placebo in GAD patients.
Chamomile (Matricaria chamomilla L.) extract therapy for generalized anxiety disorder: a randomized, double-blind, placebo-controlled trial of long-term safety and efficacy
Largest chamomile/apigenin RCT to date: 1,500mg/day chamomile extract for up to 38 weeks reduced GAD symptoms and prevented relapse vs placebo.
Chamomile therapy of generalized anxiety disorder with comorbid depression
Secondary analysis: chamomile extract attenuated both anxiety and depressive symptoms in GAD patients with comorbid depression.
Preliminary examination of the efficacy and safety of a standardized chamomile extract for chronic primary insomnia
Pilot RCT of chamomile extract in chronic primary insomnia — trends toward better daytime functioning, did not reach significance on PSQI.
Effect of chamomile tea on sleep quality and depression in postnatal women
Chamomile tea consumed for 2 weeks postpartum significantly improved sleep efficiency and depression scores vs control; benefits faded after withdrawal.
Therapeutic efficacy and safety of chamomile for state anxiety, generalized anxiety disorder, insomnia, and sleep quality: a systematic review and meta-analysis
Meta-analysis of 12 trials confirming chamomile's anxiolytic and sleep-improving effects.
Effects of chamomile on sleep: a systematic review and meta-analysis of randomised controlled trials
Updated 2024 meta-analysis confirming chamomile significantly improves sleep quality vs placebo, with strongest effects in postpartum and elderly populations.
The effects of chamomile consumption on glycemic markers: a systematic review and meta-analysis
Chamomile significantly reduced fasting blood glucose and HbA1c in diabetic populations.
Anti-inflammatory effects of chamomile (Matricaria chamomilla L.): a systematic review and meta-analysis of randomised controlled trials
Meta-analysis of RCTs showing chamomile significantly reduces CRP and IL-6 in humans.
Apigenin: a natural molecule at the intersection of sleep and aging
Comprehensive review of apigenin's GABA, CD38/NAD+, and aging-related mechanisms; calls for dedicated human RCTs of isolated apigenin.
Flavonoids and the CNS: apigenin as a benzodiazepine-site ligand
Seminal identification of apigenin as a central benzodiazepine receptor ligand isolated from Matricaria recutita.
Flavonoids, especially apigenin, inhibit CD38 in vitro and in vivo, increasing NAD+ and reversing diet-induced obesity
Escande et al. — landmark study establishing apigenin as a CD38 inhibitor that raises tissue NAD+ in vivo.
Inhibition of human aromatase by flavonoids
Kellis & Vickery — original demonstration that apigenin is among the most potent natural aromatase (CYP19A1) inhibitors.
Apigenin inhibits antiestrogen-resistant breast cancer cell growth via ER-α-dependent and -independent mechanisms
Preclinical evidence for apigenin's anti-proliferative effect in hormone-resistant breast cancer cell lines.
Apigenin and the role of neuroinflammation in neurodegenerative disease
Preclinical review of apigenin's NF-κB and NLRP3-inflammasome suppression in neuroinflammation models.
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Research Overview
Limited EvidenceCite this ingredient
One-click citation export in APA, MLA, Chicago, BibTeX, or HTML. The URL below is stable and safe to link.
Stable URL
https://thesuppindex.com/ingredients/apigenin
SuppIndex. (2026). Apigenin: Evidence summary, dosage and clinical studies. Retrieved October 23, 2026, from https://thesuppindex.com/ingredients/apigenin
Based on 15 indexed studies · Evidence level: Limited.
Goal Ratings
Stack Compatibility
Core component of the popularised Huberman sleep stack: 50mg apigenin + 300–400mg L-theanine + 145–200mg magnesium L-threonate/glycinate, taken 30–60 minutes before bed. Synergistic with ashwagandha (KSM-66) for stress/sleep. Avoid stacking with prescription sedatives or strong CNS depressants.
Products (3)
Momentous
Apigenin
Nootropics Depot
Apigenin 200mg Capsules
Double Wood Supplements
Apigenin 50mg