Evidence Level
Limited
2 Clinical Trials
5 Documented Benefits
2/5 Evidence Score

Apigenin is a flavone abundantly found in parsley, chamomile, celery, and artichoke. Most known for chamomile's calming effects, apigenin has gained attention as a senolytic and CD38 inhibitor — Bryan Johnson and longevity protocols feature it for putative NAD+ preservation. Active at GABA-A benzodiazepine receptor (anxiolytic mechanism), inhibits aromatase, and shows broad antioxidant effects. Also studied for cancer chemoprevention research.

Studied Dose 50-100 mg/day common in longevity stacks (Bryan Johnson protocol uses 50 mg/day); chamomile-based supplementation provides ~1-3 mg per cup of tea
Active Compound Apigenin (4',5,7-trihydroxyflavone)

Benefits

CD38 Inhibition / NAD+ Preservation (Theoretical)

CD38 enzyme degrades NAD+ — apigenin inhibits CD38 in vitro and in animal models, theoretically preserving NAD+ levels. Component of longevity protocols seeking to maintain age-related NAD+ decline. Clinical translation in humans not definitively established.

Anxiolytic / Calming Effects

Apigenin binds GABA-A benzodiazepine receptor with modest affinity — basis for chamomile's traditional calming use. trial of chamomile (containing apigenin) showed modest anxiolytic benefit in generalized anxiety disorder vs placebo.

Sleep Support

Chamomile traditionally used for sleep; apigenin contributes via GABA-A receptor activity and circadian effects. Modest sleep onset latency reduction in some trials. Zick et al. 2011 chamomile trial found modest, largely non-significant effects on sleep in adults.

Anti-Inflammatory / Antioxidant

Inhibits NF-κB, COX-2, iNOS in vitro — broad anti-inflammatory profile. Free radical scavenging activity. Component of multi-mechanism cardiovascular and longevity supplementation.

Cancer Chemoprevention Research

Extensive in vitro evidence for apoptosis induction in cancer cell lines (breast, prostate, colon, lung); animal models show tumor growth inhibition. Human clinical translation limited; not established cancer therapy.

Mechanism of action

1

CD38 Inhibition (NAD+ Pathway)

CD38 is the major NAD+-degrading enzyme; CD38 expression increases with age, contributing to NAD+ decline. Apigenin inhibits CD38 in vitro and animal studies — theoretical NAD+ preservation. Mechanism makes apigenin popular in NMN/NR/longevity stacks. Note: in vitro CD38 IC50 is in micromolar range; achievable plasma levels with oral supplementation are typically nanomolar — clinical CD38 inhibition uncertain.

2

GABA-A Benzodiazepine Receptor Modulation

Apigenin is a ligand at the benzodiazepine site of the GABA-A receptor — mild positive allosteric modulator. Lower potency than pharmaceutical benzodiazepines but contributes to anxiolytic/calming effects. Basis for chamomile's traditional calming use.

3

Aromatase Inhibition

Apigenin modestly inhibits aromatase enzyme (CYP19) — the enzyme that converts androgens to estrogens. Theoretical implications for hormone-sensitive conditions; clinical relevance modest at typical supplemental doses.

4

NF-κB and Inflammatory Pathway Inhibition

Modulates NF-κB signaling, reduces COX-2 and iNOS expression. Broad anti-inflammatory profile basis for chronic inflammation contexts.

Clinical trials

1
Chamomile (Apigenin-Containing) for GAD

Clinical trial of standardized chamomile extract vs placebo in patients with mild-to-moderate generalized anxiety disorder for 8 weeks.

57 patients with GAD.

Chamomile extract significantly reduced anxiety scores (Hamilton Anxiety Rating Scale) vs placebo. Effect modest. Apigenin contributes to but is not solely responsible for chamomile's effects.

2
Apigenin CD38 Inhibition / NAD+ Animal Studies

Multiple preclinical studies of apigenin's CD38 inhibition and NAD+ preservation effects in cell culture and animal models.

Cell culture and rodent models.

Apigenin inhibits CD38 in vitro and increases NAD+ in tissues of treated animals. Translates to improved metabolic markers. Human clinical trials testing CD38 inhibition / NAD+ preservation with apigenin specifically are limited — popularized largely from preclinical mechanism plus longevity protocols.

Side effects and drug interactions

Common Potential side effects

Generally well-tolerated.
Drowsiness / sedation at higher doses (consistent with GABA-A activity).
Allergic reactions — chamomile (and possibly apigenin) cross-reactive with ragweed, daisy, marigold (Asteraceae family); contact dermatitis possible.
GI distress at high doses uncommon.
Hypotension in sensitive individuals.

Important Drug interactions

Benzodiazepines (alprazolam, lorazepam, diazepam) — additive CNS depression via GABA-A activity; theoretical concern.
Sedatives, sleep aids — additive CNS depression.
Anticoagulants (warfarin) — chamomile (and possibly apigenin) may modestly affect coagulation; theoretical interaction.
Cyclosporine — chamomile may reduce levels via CYP3A4 effects; theoretical.
Tamoxifen — apigenin's modest aromatase inhibition is theoretically relevant but unlikely clinically significant at typical supplement doses; consult oncologist.
Hormone-sensitive conditions — theoretical caution due to aromatase effects.

Frequently asked questions about Apigenin

What is apigenin used for?

Apigenin is a flavonoid found in chamomile, parsley, and celery. It is studied for calming and sleep support (it interacts with relaxation-related brain receptors), as well as antioxidant activity and cellular health.

Does apigenin help with sleep?

Apigenin is thought to be part of why chamomile is calming, as it can bind to receptors involved in relaxation. It is increasingly used in sleep and calm formulas, though direct human studies on isolated apigenin are limited.

How much apigenin should I take?

Isolated apigenin supplements are often dosed around 50 mg, sometimes taken in the evening for sleep. Chamomile tea is a traditional, gentler source. Follow product labeling.

Is apigenin safe?

It is generally well tolerated. As a flavonoid with mild calming and hormone-related activity, those who are pregnant, on sedatives, or with hormone-sensitive conditions should check with a doctor before using concentrated supplements.

What is Apigenin?

Apigenin is a flavone abundantly found in parsley, chamomile, celery, and artichoke. Most known for chamomile's calming effects, apigenin has gained attention as a senolytic and CD38 inhibitor — Bryan Johnson and longevity protocols feature it for putative NAD+ preservation.

What is the recommended dosage of Apigenin?

The clinically studied dose is 50-100 mg/day common in longevity stacks (Bryan Johnson protocol uses 50 mg/day); chamomile-based supplementation provides ~1-3 mg per cup of tea Always follow the product label and check with a healthcare provider for personal advice.

Is Apigenin safe, and does it have side effects?

For most healthy adults, Apigenin is well tolerated at studied doses. Reported effects can include: Generally well-tolerated. Drowsiness / sedation at higher doses (consistent with GABA-A activity). It may also interact with some medications. Apigenin is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Apigenin interact with any medications?

Possible interactions include: Benzodiazepines (alprazolam, lorazepam, diazepam) — additive CNS depression via GABA-A activity; theoretical concern. Sedatives, sleep aids — additive CNS depression. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Apigenin?

NutraSmarts rates the evidence for Apigenin as Limited (2 out of 5). It is backed by 2 clinical trials and 3 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(3 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Viola H, Wasowski C, Levi de Stein M, Wolfman C, Silveira R, Dajas F, Medina JH, Paladini AC Apigenin, a component of Matricaria recutita flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects Planta Medica. 1995;61(3):213-6. doi: 10.1055/s-2006-958058.PubMedUsed to support: Preclinical study demonstrating apigenin binds central benzodiazepine receptors with anxiolytic effects in animal models; backs 'Anxiolytic / Calming Effects' (animal/in vitro evidence only — no human RCT data available for this mechanism).
  2. Escande C, Nin V, Price NL, Capellini V, Gomes AP, Barbosa MT, O'Neil L, White TA, Sinclair DA, Chini EN Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome Diabetes. 2013;62(4):1084-93. doi: 10.2337/db12-1139.PubMedUsed to support: In vitro and animal study establishing apigenin as a CD38 inhibitor that raises cellular NAD+ levels and improves metabolic parameters in obese mice; backs 'CD38 Inhibition / NAD+ Preservation (Theoretical)' (preclinical evidence only — not yet established in human trials).
  3. Kramer DJ, Johnson AA Apigenin: a natural molecule at the intersection of sleep and aging Frontiers in Nutrition. 2024;11:1359176. doi: 10.3389/fnut.2024.1359176.PubMedUsed to support: Review synthesizing the evidence for apigenin's roles in sleep regulation and aging biology, including GABA-A receptor modulation and longevity-related pathways; backs 'Sleep Support', 'Anxiolytic / Calming Effects', and 'Anti-Inflammatory / Antioxidant' (review of mostly preclinical literature).