Apigenin is the plant compound most often credited with chamomile's calming reputation. Animal and laboratory studies show it acts on the brain, and trials of chamomile extract report modest improvements in how people rate their sleep. No randomised trial has yet tested isolated apigenin for sleep in humans, so the case for it rests on chamomile research and on mechanism.
That is the honest summary. The rest of this article goes through what apigenin is, what the studies found, and what we still do not know.
What is apigenin?
Apigenin is a flavone, one of the families of flavonoids that plants make. In food it is almost always bound to a sugar, as a glycoside, and not present as the free molecule (Salehi et al., 2019).
The richest sources are dried chamomile flowers and dried parsley. Dried chamomile contains roughly 5,000mg of apigenin glycosides per 100g, and dried parsley around 1,200 to 1,350mg per 100g (Hostetler, Ralston and Schwartz, 2017). Citrus contains it too, in smaller amounts: grapefruit has up to about 4.9mg per 100g, and citrus juices carry apigenin glycosides such as vicenin-2 and rhoifolin (Gattuso et al., 2007; Hostetler, Ralston and Schwartz, 2017).
Most people eat very little of it. Estimated flavone intake in European adults is between 0.7 and 9mg a day (Hostetler, Ralston and Schwartz, 2017).
How might apigenin affect sleep?
The GABA story, and why it is contested
The usual explanation is that apigenin binds to the benzodiazepine site on GABA-A receptors, the brain's main "slow down" system. That idea comes from a 1995 study in which apigenin competed for that binding site and reduced anxiety-like behaviour in mice without sedating them. At ten times the dose it produced mild sedation (Viola et al., 1995).
Later work complicated the picture:
- In rats, apigenin reduced movement but showed no anti-anxiety effect, and the researchers concluded the sedation could not be put down to the benzodiazepine site (Avallone et al., 2000).
- A second rat study found the sedative effect was not reversed by flumazenil, a drug that blocks that site (Zanoli, Avallone and Baraldi, 2000).
- On human GABA-A receptors in the lab, apigenin on its own reduced GABA responses, although it enhanced the effect of diazepam when the two were combined (Campbell, Chebib and Johnston, 2004).
- In cultured neurons, apigenin also dampened NMDA receptor activity, which is part of the brain's excitatory signalling. The authors suggested this lowering of overall excitability may explain its calming effect better than GABA does (Losi et al., 2004).
So apigenin does appear to quiet neural activity in animals. How it does so is still debated, and "works like a gentle benzodiazepine" is too simple (Wasowski and Marder, 2012).
Sleep in animals
In mice, apigenin lengthened sleep induced by pentobarbital and increased chloride influx in nerve cells (Kim et al., 2012). That shows it can strengthen an existing sleep signal. It does not show that it produces sleep by itself.
Apigenin and ageing
Apigenin inhibits an enzyme called CD38 and raises levels of NAD+ in cells and in mice (Escande et al., 2013). Because NAD+ declines with age, one review has proposed this as a link between apigenin, ageing and sleep (Kramer and Johnson, 2024). It is an interesting hypothesis built on mouse data, and that review was funded by a longevity supplement company, so treat it as an idea to be tested.
What human studies show
Almost all human evidence comes from chamomile, which contains apigenin alongside many other compounds.
Chronic insomnia. A four-week pilot trial gave 34 adults with insomnia 270mg of chamomile extract twice a day, supplying roughly 15 to 23mg of apigenin daily. There were no significant differences from placebo on any sleep diary measure, although time to fall asleep and night-time awakenings leaned in chamomile's favour (Zick et al., 2011).
Older adults. In 60 people aged 60 and over, 200mg of chamomile extract twice daily for 28 days improved sleep quality scores compared with a placebo capsule (Adib-Hajbaghery and Mousavi, 2017). The trial was single-blind.
New mothers. Among 80 postnatal women, two weeks of chamomile tea improved some sleep and mood scores, but the difference had gone four weeks later (Chang and Chen, 2016).
Anxiety. In 57 people with generalised anxiety disorder, eight weeks of chamomile extract standardised to 1.2% apigenin reduced anxiety scores more than placebo (Amsterdam et al., 2009).
Pooled results. A meta-analysis of 12 trials found chamomile improved sleep quality but found no significant effect on insomnia severity, based on a single trial (Hieu et al., 2019). A later meta-analysis of 10 trials and 772 participants reported better overall sleep scores, fewer awakenings and faster sleep onset in most studies, with no improvement in sleep duration or sleep efficiency. Results varied widely between trials and none used objective sleep measurement (Kazemi et al., 2024).
Diet. In a study of 1,936 Italian adults, people who ate more apigenin were less likely to report poor sleep quality (Godos et al., 2020). This is an association, not proof of cause.
The authors of the main review on apigenin and sleep say plainly that it is hard to be certain chamomile's effects are due to apigenin (Kramer and Johnson, 2024).
Chamomile tea versus an apigenin supplement
The chamomile trials above delivered somewhere between about 3 and 25mg of apigenin a day. A supplement dose of 50 to 150mg is several times higher.
A higher number on the label is not the whole story, because absorption matters. In a human study, apigenin taken as the free molecule was poorly absorbed, with about 0.5% of the dose recovered in urine. From chamomile tea, where apigenin is bound to glucose, the figure was 34% (Borges et al., 2022). Absorption from parsley was also low and varied a great deal between people (Meyer et al., 2006).
This means milligrams of apigenin in a capsule and milligrams in a cup of tea are not directly comparable, and research on how best to deliver apigenin is still developing.
How much, and when?
There is no clinically established dose of isolated apigenin for sleep. Supplements typically provide 50 to 150mg. OFFLINE Sleep contains 150mg, from a bitter orange extract, taken 30 to 45 minutes before bed alongside four other ingredients.
In the human absorption study, apigenin metabolites from chamomile tea peaked in the blood at about two hours (Borges et al., 2022), which is one reason to take it in the evening and not at the moment you turn the light off.
Safety and who should avoid it
Chamomile has been used in trials for up to several months with side effects similar to placebo (Amsterdam et al., 2009; Zick et al., 2011). Long-term safety data for isolated apigenin at supplement doses are limited.
Points to know:
- Medicines. In laboratory studies apigenin inhibits the liver enzymes CYP3A4 and CYP2C9, which process many drugs, including warfarin (Si et al., 2009; Kimura et al., 2010). One case report describes bleeding in a woman on warfarin who used chamomile heavily (Segal and Pilote, 2006). If you take prescription medicine, speak to your doctor or pharmacist first.
- Hormones. Apigenin inhibits the enzyme aromatase in the test tube (Jeong et al., 1999). This effect was not seen in an animal study (Ye et al., 2012) and there are no human data.
- Pregnancy and breastfeeding. One observational study linked regular chamomile use in pregnancy with a higher risk of pre-term delivery and lower birth weight (Trabace et al., 2015). There are no safety data for isolated apigenin, so it is best avoided.
- Allergy. People allergic to plants in the daisy family can react to chamomile (McKay and Blumberg, 2006).
Frequently asked questions
Is apigenin the same as chamomile? No. Apigenin is one compound found in chamomile. Chamomile contains many others, and the human trials tested the whole extract.
Does apigenin make you drowsy the next day? Chamomile trials did not report more side effects than placebo, and one meta-analysis found no change in daytime functioning (Kazemi et al., 2024). Isolated apigenin has not been tested for this.
Can I get enough from tea? Tea delivers a small amount in a well-absorbed form. Supplements deliver far more in a form that may be absorbed less well. Neither has been compared head to head for sleep.
Is apigenin proven to help sleep? Not as an isolated ingredient. The supporting evidence is animal research and chamomile trials showing modest improvements in self-rated sleep quality.
The bottom line
Apigenin is a plausible calming compound with a long history of use through chamomile and real biological activity in the lab. The human evidence is indirect and modest, and the trial that would settle it has not been run. We include it in OFFLINE Sleep as one of five ingredients, and we would sooner tell you where the science stands than oversell it.
This article is for general information and is not medical advice. Food supplements are not a substitute for a varied diet. If you have ongoing sleep problems, speak to your GP.
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