Apigenin

Evidence Level
Preliminary
2 Clinical Trials
5 Documented Benefits
1/5 Evidence Score

Apigenin is a flavone abundantly found in parsley, chamomile, celery, and artichoke. It is best known as one of the compounds in chamomile, and it became popular in longevity supplement stacks after laboratory work showed it can block CD38, an enzyme that breaks down NAD+. That work was done in cells and in mice, not in people. In laboratory and animal tests apigenin also binds the benzodiazepine site of the GABA-A receptor and mildly inhibits the aromatase enzyme, and it is a frequent subject of cell-based cancer research. No published human trial of apigenin is cited on this page.

Studied Dose No human trial has established a dose for apigenin. Supplements are commonly sold at 50-100 mg per day, a range that comes from popular internet longevity protocols rather than from clinical testing. A cup of chamomile tea provides roughly 1-3 mg.
Active Compound Apigenin (4',5,7-trihydroxyflavone)

Benefits

CD38 Inhibition / NAD+ Preservation (Theoretical)

CD38 is an enzyme that breaks down NAD+. In a 2013 laboratory study, apigenin blocked CD38 in cells and raised NAD+ in the tissues of obese mice, which also showed better metabolic measurements. That is a mechanism finding in cells and animals. No human study has shown that taking apigenin raises NAD+ or affects aging in any way, and the concentrations that inhibit CD38 in the lab are far higher than the blood levels an oral supplement typically produces.

Anxiolytic / Calming Effects

In a 1995 laboratory and animal study, apigenin competed with the benzodiazepine drug flunitrazepam for binding at the GABA-A receptor and reduced anxiety-like behavior in mice on maze tests. Higher doses also cut the animals' movement by about 26 percent. This is the usual explanation for why chamomile feels calming. No human trial of apigenin for stress or anxiety is cited on this page, so a calming effect in people is unproven.

Sleep Support

Chamomile has a long traditional use as a bedtime tea, and a 2024 review discusses apigenin's GABA-A receptor activity as a possible reason for it. That review summarizes mostly cell and animal work. No human trial of apigenin itself for sleep is cited on this page, so any effect on how quickly you fall asleep or how well you sleep is unproven.

Anti-Inflammatory / Antioxidant

Inhibits NF-κB, COX-2 and iNOS in test tube studies, and it scavenges free radicals in laboratory assays. These are cell-based findings only. No study cited here measured inflammation, antioxidant status or any heart-related outcome in people taking apigenin.

Cancer Research (Laboratory and Animal Only)

Apigenin causes cancer cells to die in test tube experiments (breast, prostate, colon and lung cell lines) and slows tumor growth in some animal models. None of this has been tested in people, and no reference on this page is a human cancer study. Apigenin is not a treatment or a preventive for cancer and should never replace medical care.

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. It is far weaker at that site than prescription benzodiazepines. The calming effect was measured in mice, not in humans, and it is the usual explanation offered for chamomile's traditional calming reputation.

3

Aromatase Inhibition

Apigenin modestly inhibits aromatase enzyme (CYP19) — the enzyme that converts androgens to estrogens. What this means for people is unknown, because it has only been seen in laboratory tests and no cited study measured hormone levels in humans after taking apigenin. If you have a hormone-sensitive condition, ask your doctor before using a concentrated supplement.

4

NF-κB and Inflammatory Pathway Inhibition

Modulates NF-κB signaling, reduces COX-2 and iNOS expression in cell studies. Whether this changes inflammation in the human body has never been tested.

Clinical trials

1
Apigenin Receptor Binding and Anxiety Behavior in Mice (1995)

Laboratory and animal study published in Planta Medica in 1995, testing whether apigenin binds the brain's benzodiazepine receptor and whether it changes anxiety-like behavior in mice on the elevated plus maze and hole board tests.

Mice. No people were studied.

Apigenin competed with the benzodiazepine drug flunitrazepam for receptor binding (Ki about 4 micromolar) and reduced anxiety-like behavior in the mice. Higher doses cut the animals' movement by about 26 percent, which looks like sedation rather than calm. Because this was done in mice, it does not show that apigenin reduces anxiety in people.

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 blocked CD38 in cell experiments and raised NAD+ in the tissues of obese mice, and those mice showed better metabolic measurements. No human trial of apigenin for CD38 or NAD+ is cited on this page. Its popularity in longevity stacks comes from this cell and animal work, not from results in people.

Side effects and drug interactions

Common Potential side effects

No published human trial of apigenin supplements is cited here, so the side effect profile of concentrated doses is not well documented. Food amounts, such as parsley, celery and chamomile tea, have a long history of safe use.
Drowsiness or sedation at higher doses is reported by users, and higher doses reduced movement in mice by about 26 percent; this has not been measured in a human trial.
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. People take it for calm and sleep, and it is a common ingredient in longevity stacks. The research behind those uses is laboratory and animal work: apigenin binds a calming receptor in the brain of mice and blocks an enzyme called CD38 in cells. No human trial of apigenin is cited on this page.

Does apigenin help with sleep?

Apigenin is thought to be part of why chamomile is calming, because it binds receptors involved in relaxation, a finding from laboratory and mouse studies. It is widely sold in sleep and calm formulas, but no human study of apigenin on its own for sleep is cited here, so the honest answer is that nobody knows yet.

How much apigenin should I take?

No clinical trial has established a dose. Products are commonly sold at about 50 mg, often taken in the evening, but that figure comes from popular protocols rather than from testing in people. Chamomile tea is a traditional and gentler source. Follow the product label and talk to your doctor.

Is apigenin safe?

Apigenin in food amounts has a long history of safe use, but concentrated supplements have not been tested in any published human trial cited here, so long-term safety is unknown. Because it shows calming and hormone-related activity in laboratory tests, anyone who is pregnant or breastfeeding, taking sedatives or sleep medication, or living with a hormone-sensitive condition should check with a doctor first. People allergic to ragweed, daisies or marigolds may react to chamomile-derived products.

What is Apigenin?

Apigenin is a flavone abundantly found in parsley, chamomile, celery, and artichoke. It is best known as one of the compounds in chamomile, and it became popular in longevity supplement stacks after laboratory work showed it can block CD38, an enzyme that breaks down NAD+.

What is the recommended dosage of Apigenin?

The clinically studied dose is No human trial has established a dose for apigenin. Supplements are commonly sold at 50-100 mg per day, a range that comes from popular internet longevity protocols rather than from clinical testing. A cup of chamomile tea provides roughly 1-3 mg. 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: No published human trial of apigenin supplements is cited here, so the side effect profile of concentrated doses is not well documented. Food amounts, such as parsley, celery and chamomile tea, have a long history of safe use. 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 Preliminary (1 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: Mouse study: apigenin competitively inhibited flunitrazepam binding at central benzodiazepine receptors (Ki about 4 micromolar) and reduced anxiety-like behavior on the elevated plus maze and hole board, with higher doses reducing locomotor activity by 26 percent. Animal evidence only. It does not support any claim about anxiety or calm in people.
  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).