Apigenin
The calming flavonoid in chamomile and parsley that binds the same brain receptors as benzodiazepines (far more gently), with moderate evidence for anxiety and sleep via chamomile and emerging interest in longevity.
At a Glance
- Best known for
- Mild anti-anxiety effect (via GABA-A receptor binding), Supports sleep onset and quality, Preserves NAD+ by inhibiting CD38
- Evidence
- Moderate
- Typical dose
- 50 mg isolated apigenin 30–60 min before bed
- Type
- Compound
What is Apigenin?
Apigenin is a yellow flavone found in high amounts in chamomile flowers, parsley, celery, and artichoke. It is the compound most responsible for chamomile's reputation as a gentle sleep aid and anxiety reliever. Chemically it is a flavone, a subclass of flavonoids distinct from the flavonols like quercetin, and it is one of the few plant compounds shown to bind directly to benzodiazepine sites on GABA receptors in the brain. More recently it has drawn interest from longevity researchers because it inhibits CD38, an enzyme that consumes NAD+ and rises with age.
Known Health Benefits
How It Works
Apigenin binds to the benzodiazepine site of GABA-A receptors, where it acts as a partial agonist, enhancing the calming effects of GABA without the strong sedation, tolerance, or dependence that benzodiazepine drugs produce. Its affinity is modest, which explains why chamomile relaxes rather than knocks out. Apigenin also inhibits monoamine oxidase to a small degree and modulates serotonin signaling. In the longevity context, it inhibits CD38, the main NAD+-degrading enzyme in aging tissues, which in animals raises NAD+ levels and improves metabolic function. Like most flavonoids it suppresses NF-κB and COX-2, reduces oxidative stress through Nrf2, and in cancer cell lines slows proliferation and triggers apoptosis.
What Research Says
Direct human trials of isolated apigenin are almost nonexistent; the clinical evidence comes from chamomile extracts standardized to apigenin. A 2009 randomized, double-blind, placebo-controlled trial of 57 people with generalized anxiety disorder found that chamomile extract (220–1100 mg daily, 1.2% apigenin) for 8 weeks produced a modest but significant reduction in anxiety scores compared with placebo. A larger 2016 follow-up study of 179 people found that continuing chamomile for 26 weeks reduced relapse of anxiety symptoms and was well tolerated. Sleep studies are smaller and mixed: a 2011 pilot in 34 people with insomnia found no significant difference in sleep latency with chamomile, while a 2017 trial in elderly nursing home residents reported improved sleep quality. The NAD+/CD38 findings are from mice only. Overall, apigenin via chamomile has reasonable support for mild anxiety, weaker support for sleep, and no human data yet for aging.
Active Compounds
Apigenin (4',5,7-trihydroxyflavone) and its glycoside apiin; in chamomile also found as apigenin-7-glucoside
Forms & Bioavailability
Apigenin in plants is mostly bound to sugars (as apiin or apigenin-7-glucoside), which must be split by gut bacteria before absorption, so absorption is slow and incomplete. Free apigenin is fat-soluble and is absorbed better with a meal containing some fat. Once absorbed it is quickly conjugated in the liver, and much is excreted within 24 hours, although it accumulates somewhat in fatty tissues with repeated dosing. Chamomile tea delivers only a few milligrams per cup, so its calming effects likely owe as much to warmth, ritual, and aroma as to apigenin itself.
Dosage Guidance
| Use Case | Dosage |
|---|---|
| Sleep support | 50 mg isolated apigenin 30–60 min before bed |
| Mild anxiety (chamomile extract) | 220–1100 mg extract daily (1.2% apigenin) |
| Chamomile tea | 1–3 cups daily |
| NAD+ / longevity (animal-based) | 50 mg daily |
Always consult a healthcare provider for personalized dosing.
Natural Food Sources
- Chamomile tea (richest common source — 3–5 mg per cup)
- Fresh parsley (about 215 mg per 100 g dried, far less fresh)
- Celery and celery seed
- Artichoke
- Oregano, thyme, peppermint
- Kumquats, oranges
Potential Side Effects
Drowsiness at higher doses; rare allergic reactions in people sensitive to ragweed, daisies, or chamomile
Who Should Avoid It
- Allergy to ragweed, chrysanthemums, marigolds, or daisies (cross-reactivity with chamomile)
- Concurrent use of benzodiazepines, zolpidem, or other sedatives (additive effect)
- Warfarin therapy (chamomile has coumarin content and apigenin inhibits CYP2C9)
- Driving or operating machinery after higher doses
Pregnancy & Lactation
Chamomile tea in moderate amounts (1–2 cups daily) is widely consumed in pregnancy, though some sources advise caution because of theoretical uterine effects of concentrated extracts. Isolated apigenin supplements have not been studied in pregnant or breastfeeding women and should be avoided in favor of weak chamomile tea if a calming beverage is wanted.
Known Drug Interactions
Additive sedation with benzodiazepines, sleep medications, and alcohol; inhibits CYP2C9 and CYP3A4 (warfarin, some SSRIs, calcium channel blockers); may enhance antiplatelet drugs
Evidence Classification
Supported by cohort studies, case-control studies, or multiple observational studies with consistent findings.
Frequently Asked Questions
Does apigenin work like a benzodiazepine for anxiety?
It binds the same receptor site but far more weakly and as a partial agonist, so the effect is a gentle calming rather than strong sedation. It does not cause the tolerance, dependence, or withdrawal that benzodiazepines do. For mild anxiety or winding down at night, chamomile extract has decent evidence; for diagnosed anxiety disorders, it should be seen as a complement to, not a replacement for, treatment.
Is 50 mg of apigenin the same as a cup of chamomile tea?
No — a cup of chamomile tea contains only about 3–5 mg of apigenin, and much of that is bound to sugar and poorly absorbed. A 50 mg isolated capsule delivers roughly 10–15 times more. That said, the clinical trials for anxiety used chamomile extract rather than isolated apigenin, so the extract has better evidence even though the capsule has more of the compound.
Can apigenin raise NAD+ levels?
In mice, apigenin inhibits CD38, an enzyme that destroys NAD+, and raises tissue NAD+ levels. This has made it popular in longevity stacks alongside NMN or nicotinamide riboside. No human study has yet shown that apigenin supplements raise NAD+ in people, so this use remains theoretical.
Why do some people feel nothing from apigenin for sleep?
Its effect is mild, absorption varies widely between people depending on gut bacteria, and sleep trials with chamomile have been inconsistent. People with significant insomnia often need more than apigenin alone. Pairing it with good sleep hygiene, magnesium, or glycine, and giving it a week or two of consistent use, improves the chances of noticing a benefit.
References
- A randomized, double-blind, placebo-controlled trial of oral Matricaria recutita (chamomile) extract therapy for generalized anxiety disorder. Amsterdam JD, Li Y, Soeller I, et al.. J Clin Psychopharmacol (2009)View study
- Long-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: a randomized clinical trial. Mao JJ, Xie SX, Keefe JR, et al.. Phytomedicine (2016)
- Chamomile. National Center for Complementary and Integrative Health. NCCIH Herbs at a Glance (2020)View study
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This entry is for educational purposes only. It is not medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement regimen, especially if you take medications or have health conditions.