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Supplement

Apigenin

A flavonoid (chamomile, parsley) with affinity for the GABA-A/benzodiazepine receptor; the anxiolytic and sedative principle of chamomile. Popular as an isolated supplement for its role in sleep and as a sirtuin activator for longevity.
Category
Scientific evidence
Low
Number of findings
1
Sources
Our own summaries · Cited studies
Recommended dose and how to use
25–75 mg/day at night. In chamomile studies the equivalent is approx. 1.2% apigenin in 500–1,500 mg of extract.

How to take it

25–75 mg/day at night. In chamomile studies the equivalent is approx. 1.2% apigenin in 500–1,500 mg of extract.

Safety

Well tolerated; cross-allergy with Asteraceae. May potentiate sedatives. Caution with anticoagulants (additive effect). Human evidence for the isolated flavonoid is limited; the solid evidence is for the whole chamomile extract.

Effect by goal · level of evidence

Anxiety and sleep (via chamomile)

improves Moderate RCT in chamomile (AA)
Via extract

Apigenin is mainly responsible for the anxiolytic effect of chamomile, backed by randomized trials in GAD and sleep quality. As an isolated flavonoid, human evidence is scarce.

View the study (RCT) →

Longevity (autophagy, sirtuins)

association Low preclinical (A)
Preclinical

Studies in animal/cell models: modulates sirtuins and autophagy. No human longevity trials; extrapolation is still premature.

Cancer (chemoprevention)

association Low preclinical (A)
No human RCTs

In vitro and animal-model evidence on prostate, breast and colon. There are no human RCTs. Promising but speculative.

In depth

⏱ 3 min read

Apigenin is a flavonoid found in many edible and medicinal plants (parsley, celery, chamomile, artichoke), largely responsible for the characteristic calming effect of chamomile infusions and of several other traditional uses in Mediterranean herbal medicine; in the last decade it has moved from the niche of relaxing tea to the geroprotection laboratory, because several studies have shown that it inhibits CD38, an enzyme that consumes NAD+ and whose increasing activity with age is one of the proposed mechanisms for the decline in NAD+ that defines mitochondrial aging.

This double life (traditional calming agent and emerging geroprotector) makes it one of the most interesting compounds of the moment: the traditional evidence on anxiety and sleep is consolidated by centuries of safe use, while the geroprotective evidence is in the early phases of clinical research but points to solid mechanisms on which longevity science is actively working.

Sleep and anxiety: the legacy of chamomile

The most established use of apigenin (via chamomile) is as a mild anxiolytic and sleep aid: several randomized trials with standardized chamomile extract rich in apigenin (typically 220-1,500 mg/day for 8 weeks) have shown significant improvements in mild to moderate generalized anxiety and in sleep quality, especially sleep latency and the morning feeling of rest, with an excellent safety profile.

The most plausible mechanism combines binding to GABA-A receptors (similar to but milder than that of benzodiazepines, with no documented tolerance or dependence) with modulation of other neurotransmission systems; the effect is modest but subjectively noticeable, especially in people with mild anxiety and trouble falling asleep who do not want to turn to pharmacological hypnotics.

The connection with NAD+ and sirtuins

The most interesting discovery of recent years is that apigenin potently inhibits CD38, a glycohydrolase that consumes NAD+ and whose expression increases with age in multiple tissues; this inhibition raises cellular levels of NAD+ available to sirtuins (the aging-regulating enzymes that depend on NAD+ to function), and preclinical studies show effects on mitochondrial function, immune function, and body composition in aged animals.

David Sinclair and other researchers have popularized the use of apigenin as part of NAD+ optimization protocols alongside precursors such as NMN or nicotinamide riboside, on the logic that increasing production while reducing consumption (via CD38 inhibition) may be more efficient than either strategy alone; clinical evidence in humans remains preliminary, but the preclinical data are reasonable.

Other effects: inflammation, cancer, and metabolism

In preclinical studies and animal models, apigenin shows well-documented anti-inflammatory properties, modest antitumor effects in several types of cancer (especially prostate and breast, where it could modulate hormone receptors), and some effect on insulin sensitivity and hepatic lipogenesis; translation to humans remains limited, and pure apigenin supplements have not been tested at scale in formal clinical trials.

How to take it and precautions

Apigenin as an isolated supplement is sold in capsules of 50 to 100 milligrams, and the doses used by longevity enthusiasts are 50-100 mg/day taken with meals (its oral bioavailability is modest and improves with dietary fat); it can also be obtained from regular consumption of chamomile tea (two to three cups daily) or from standardized chamomile extract, both options with an excellent safety profile and supported by the traditional evidence on sleep and anxiety.

It is generally very well tolerated; adverse effects are rare and mild (some daytime drowsiness at high doses, occasionally allergic reactions in people sensitive to the Asteraceae family); people taking anticoagulants should be cautious because of a possible mild antiplatelet effect at high doses, and apigenin may inhibit some hepatic cytochrome P450 enzymes, which could theoretically alter the metabolism of several drugs if combined at high doses over long periods.

References

  1. Amsterdam, J.D. et al. (2009). A randomized, double-blind, placebo-controlled trial of oral Matricaria recutita (chamomile) extract therapy for generalized anxiety disorder. J Clin Psychopharmacol 29, 4. doi:10.1097/JCP.0b013e3181ac935c
  2. Mao, J.J. et al. (2016). Long-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: a randomized clinical trial. Phytomedicine 23, 14. doi:10.1016/j.phymed.2016.10.012
  3. Escande, C. et al. (2013). Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome. Diabetes 62, 4. doi:10.2337/db12-1139
  4. Ali, F. et al. (2017). Health functionality of apigenin: a review. Int J Food Prop 20, 6. doi:10.1080/10942912.2016.1207188
  5. Salehi, B. et al. (2019). The therapeutic potential of apigenin. Int J Mol Sci 20, 6. doi:10.3390/ijms20061305

Information, not medical advice. Scientific evidence reflects the quality of the studies.

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