Supplement
Apigenin
Longevity · Chamomile flavonoid
Apigenin is a flavone from chamomile, parsley and celery. In the longevity scene it is regarded as a sleep aid and as a brake on CD38, the enzyme that breaks down NAD+. Both ideas have a real basis in the laboratory, but isolated apigenin has barely been studied in humans.
In brief
Apigenin binds to the same site in the brain as benzodiazepines and, in cell culture and in mice, inhibits the NAD+-degrading enzyme CD38. The human data on anxiety and sleep come almost entirely from chamomile extract, which contains apigenin: in a placebo-controlled study it reduced the symptoms of generalized anxiety disorder, and meta-analyses show better subjective sleep quality. For isolated apigenin, there is no published randomized trial. Isolated apigenin is moreover an unauthorized novel food in the EU.
What it is
Apigenin belongs to the flavones, a subgroup of the flavonoids. In plants it is mostly bound to sugar, in parsley for example as apiin. Chamomile flowers, parsley, celery and artichokes are the best-known sources. The body does not need apigenin; it is not a nutrient but a secondary plant compound.
How much of it reaches the blood was measured in a study of 11 healthy adults. They ate a single large portion of blanched parsley. The peak concentration in the blood averaged 127 nmol/l and was reached only after 7.2 hours, with large differences between individuals. After 28 hours, nothing was detectable any more. In the urine, 0.22 percent of the ingested amount was found. So a small part reaches the circulation; most of it is converted in the gut and the liver.
As a product, apigenin is sold as an isolated, highly purified substance in capsules, usually obtained from chamomile. To be distinguished from this are chamomile extracts, which contain apigenin alongside many other substances. This distinction matters for the whole page, because almost all human data concern chamomile and not the pure substance.
How it is supposed to work
The first mechanism concerns the brain. In 1995, a research group isolated apigenin from chamomile flowers and showed that it binds to the central benzodiazepine binding site of the GABA-A receptor. The binding strength was a Ki of 4 µM, that is, considerably weaker than that of classic benzodiazepines. In mice, apigenin had an anxiety-relieving effect without causing tiredness or relaxing the muscles. Only the 10-fold dose reduced locomotor activity, by 26 percent. This fits the traditional use of chamomile tea in the evening.
The second mechanism is the reason apigenin is so popular in the longevity scene. According to animal data, CD38 is the most important NAD+-degrading enzyme in mammals. A study showed in 2013 that apigenin inhibits CD38. In cell culture, the NAD+ content rose as a result. Overweight mice had more NAD+ on apigenin, and their sugar and fat metabolism improved. This gave rise to the idea of combining apigenin with NAD+ precursors such as NMN or NR.
Both mechanisms have been cleanly shown in the laboratory. Whether the amounts that reach the blood and the brain after intake are sufficient for them, nobody has measured in humans.
Chamomile is not the same as apigenin
Anyone taking apigenin for sleep is relying on data that were almost all generated with chamomile extract. In a study with 80 menopausal women, the extract was standardized to apigenin; there it improved hot flashes, but not psychological or physical quality of life. Whether the pure substance has the same effects, weaker or stronger ones, nobody knows. Chamomile flowers have an EU monograph for traditional use, but for gastrointestinal complaints, colds and inflammation, not for sleep or anxiety.
What is well supported
In humans, chamomile extract, which contains apigenin, is best studied for anxiety. In a double-blind trial with 57 patients with mild to moderate generalized anxiety disorder, anxiety scores fell more over 8 weeks on chamomile than on placebo. In a larger follow-up study, 93 of 179 participants responded in the open phase and continued the study. Those who then took chamomile for a further 26 weeks had lower anxiety symptoms than the group that was switched to placebo without knowing it.
For sleep, two meta-analyses show a similar picture. An analysis of 12 randomized trials found better sleep quality (SMD -0.73). A more recent analysis of 10 studies with 772 participants arrived at a score 1.88 points lower on the Pittsburgh Sleep Quality Index, on which lower scores mean better sleep. Night-time awakening in particular improved in several studies. The laboratory findings on the benzodiazepine binding site and on CD38 inhibition have been reproduced and give these observations a plausible basis.
What the studies show
Chamomile in generalized anxiety disorder 2009
61 outpatients were enrolled and 57 randomized: 28 received chamomile extract, 29 placebo, each for 8 weeks. The anxiety score on the Hamilton scale fell more on chamomile; the difference was narrowly significant (P = 0.047). All secondary outcomes pointed in the same direction. In each group, 1 person dropped out because of side effects. The authors speak of a modest anxiety-relieving effect that needs to be replicated.
Relapse prevention over 26 weeks 2016
179 people with moderate to severe anxiety disorder first took chamomile extract openly. 93 responded and were allocated double-blind to chamomile or placebo. 7 of 46 on chamomile and 12 of 47 on placebo had a relapse. This gave a hazard ratio of 0.52 but was not significant (P = 0.16); the primary endpoint was missed. Symptoms, however, remained markedly lower on chamomile (P = 0.0032), and side effects were rare in both groups.
Meta-analysis on sleep 2024
The analysis covers 10 studies with 772 participants, healthy and sick adults. Only the sleep quality index from 5 studies was pooled: minus 1.88 points, with very large inconsistency between the studies (I² 88.4 percent). Falling asleep and night-time awakening improved in most individual studies, sleep duration did not. Only 1 study had checked how much active ingredient the products actually contained.
Flavonoid mixture after colorectal cancer 2008
In a German study, 31 patients took a mixture of apigenin and the green tea compound EGCG after surgery for colorectal cancer or polyps; 56 served as comparison. After 3 to 4 years, among the operated cancer patients, 1 of 14 with the mixture and 7 of 15 without it had a new growth. The study was not randomized and very small; a planned randomized follow-up study with 382 patients has been suspended.
Where the data stop
The central gap is easy to name: for isolated apigenin, there is no published randomized trial on sleep, anxiety, NAD+ or aging. The only registered study with the pure substance examined 20 older sepsis patients, was completed in 2024 and has not published any results to this day. Everything known in humans about anxiety and sleep comes from chamomile extract. It contains apigenin, but also many other substances, so the effect cannot be attributed to a single molecule.
Even for chamomile itself, the data are limited. In a pilot study with 34 people with chronic insomnia, it did not change a single value in the sleep diary. Sleep duration did not lengthen in the meta-analysis either. CD38 inhibition and the rise in NAD+ have only been shown in cell culture and in mice; there is no measurement of NAD+ after apigenin in humans. The popular practice of combining it with NAD+ precursors is thus based solely on animal data.
Status, approval and legal
Isolated apigenin from chamomile with a purity of at least 98 percent was classified in the EU as a novel food following a request to the Czech authority and is not authorized. The entry in the European Commission’s novel food catalogue dates from January 22, 2026. As a food supplement, the pure substance is therefore not marketable in the EU, whereas chamomile as a plant is. There is no approved medicinal product containing apigenin. For chamomile flowers there is an EU monograph for traditional use in mild gastrointestinal complaints, colds and inflammation of the skin and mucous membranes; sleep and anxiety are not among them. There are no authorized health claims. Apigenin is not on the WADA Prohibited List. Biohacking Kompakt gives neither a purchase recommendation nor a dosage for apigenin.
Safety
The safety of isolated, high-dose apigenin has not been systematically studied in humans; there is no upper limit from EFSA, BfR or NIH. Chamomile extract was well tolerated in studies of up to 26 weeks, with side effect rates similar to placebo. Anyone allergic to chamomile or other members of the daisy family should also avoid apigenin from chamomile; the EMA lists this allergy as a contraindication for chamomile preparations. In the laboratory, apigenin inhibits the liver enzyme CYP2C9, which breaks down losartan and warfarin, among others. Whether this is relevant in humans has not been studied. Chamomile tea prolonged blood clotting time by 0.7 seconds in a study with 8 healthy people, and not at all in another over 7 days. Anyone taking anticoagulants, sedatives or sleeping pills should clarify intake with a physician. There are no data for pregnancy, breastfeeding and children.
BK-Score Not studied in humans
| Human evidence | 1 | |
|---|---|---|
| Mechanism | 3 | |
| Safety data | 2 | |
| Hype gap | 1 | |
| Track record of use | 4 |
No robust human evidence was found for isolated apigenin as a food supplement. What is cited as evidence are studies on chamomile extract – which contains apigenin, but also much else; a causal conclusion about the single substance cannot be drawn from them. The GABA-A binding comes from receptor studies in cell culture and animals in the 1990s. Systematic safety data for the isolated, high-dose form do not exist, nor does an assessment by a public authority.
The score rates the state of knowledge, not the substance. “Safety data 9” means well studied – not harmless.
Subjective assessment by Biohacking Kompakt based on published scoring rules – not a scientific rating and not a medical recommendation. Rules and all ratings (German)
Frequently asked questions about apigenin
Does apigenin help you fall asleep?
For isolated apigenin, there is no published placebo-controlled study on this. Chamomile extract, which contains apigenin, improved subjective sleep quality in meta-analyses but did not lengthen sleep. In chronic insomnia, a small pilot study showed no effect.
Does apigenin raise NAD levels?
In cell culture and in overweight mice, apigenin inhibited the enzyme CD38 and thereby raised NAD+. This has never been measured in humans. The combination with NAD precursors is therefore based solely on animal data.
Is apigenin the same as chamomile tea?
No. Chamomile tea contains apigenin, but in small amounts and together with many other plant compounds. The positive human studies on anxiety and sleep were done with chamomile extract, not with the isolated pure substance.
Is apigenin allowed in Germany?
Isolated, highly purified apigenin from chamomile is considered an unauthorized novel food in the EU and is therefore not marketable as a food supplement. Chamomile itself is available as a food and as a traditional medicinal product. There is no approved apigenin medicinal product.
Does apigenin act like a sedative?
In the laboratory, apigenin binds to the same site of the GABA-A receptor as benzodiazepines, but much more weakly. In mice it had an anxiety-relieving effect; only the tenfold dose caused tiredness. Whether this happens to any meaningful extent in humans has not been studied.
Does apigenin have side effects or interactions?
Systematic safety data for the pure substance are lacking. In the laboratory, apigenin inhibits a liver enzyme that breaks down some blood pressure and anticoagulant drugs. People with an allergy to the daisy family and anyone taking anticoagulants or sedatives should clarify this with a physician.
Related
- Works together withNMN
- Works together withResveratrol
- Works together withMagnesium
- Works together withMelatonin
- Same categoryFisetin
- Same categoryNicotinamide riboside (NR)
- Related topicGlycine
Sources
- Viola et al., Planta Med 1995
- Escande et al., Diabetes 2013
- Meyer et al., Ann Nutr Metab 2006
- Amsterdam et al., J Clin Psychopharmacol 2009
- Mao et al., Phytomedicine 2016
- Kazemi et al., Complement Ther Med 2024
- Zick et al., BMC Complement Altern Med 2011
- Hoensch et al., World J Gastroenterol 2008
- European Commission, novel food status (catalogue)
- EMA, EU monograph Matricariae flos
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Information only, not medical advice and not a usage or dosage recommendation. Prescription-only and unapproved substances belong in the hands of a physician. Last updated: 2026-10-04.