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Apigenin and calmness: grade C

Limited evidence. Direction: No effect.

Evidence maturity: EmergingSubjective outcome only

Educational guidance, not medical advice

Why this grade

Rubric condition met: A state-anxiety meta-analysis of 3 RCTs was null; the placebo-controlled positive trials are in diagnosed generalized anxiety disorder, and a 2024 review counted 9 of 10 trials positive without pooling; C with direction none

A 2019 meta-analysis of 3 randomized trials found no difference in state anxiety (SMD -0.15). In adults with diagnosed generalized anxiety disorder, an 8-week trial of 57 people found a greater fall in anxiety ratings than placebo (P = 0.047), and a 26-week continuation trial found lower symptom scores but no significant difference in time to relapse, its primary outcome. These are clinical populations, so they cannot lift the grade for healthy adults above C, and the pooled state-anxiety result was null. Slug note: the evidence uses anxiety scales, not the Bond-Lader calmness subscale (see gaps).

How sure are we?

Evidence maturity: Emerging The pooled state-anxiety analysis of 3 RCTs was null; positive trials are in generalized anxiety disorder.

Tested as: Chamomile extract or tea

Who paid for the studies
Not stated (treated as not independent)
Risk of bias
Some concerns
Trial registry check
Not checked yet
Outcome measured
A test score, rating scale or performance measure
Who was studied
Mixed healthy and clinical, pooled
Material tested
As chamomile extract or tea, not isolated apigenin
Doses used in studies
Chamomile extract or tea; apigenin content not stated in the trials
Rules applied
Population cap (logged, no further change): Mixed healthy and clinical populations; Form does not transfer (logged, no further change): Chamomile results do not transfer to isolated apigenin
  • As isolated apigenin: D Preliminary, no effect found Evidence maturity: Mechanistic only No trial of isolated apigenin; the plausibility evidence is benzodiazepine-receptor binding and calming effects in mice.
  • Could rise: Would move to C benefit with a preregistered chamomile RCT in healthy adults positive on a calmness primary.
  • Could fall: Would move to N with two adequately sized null RCTs in healthy adults.

Science is provisional. This grade reflects the evidence we found as of . Next review: .

Maturity sits beside each grade. The grade says what the evidence shows; maturity says how much of it there is and how well it is confirmed.

Established
many trials from several independent teams, including at least one registered in advance
Emerging
two or more trials, or one large registered trial, not yet independently confirmed
Early signal
one trial, small pilots, or results only on secondary outcomes
Mechanistic only
lab, animal or biomarker data, or uncontrolled reports; no controlled human results
Traditional use only
a traditional-use monograph and nothing else

How we grade evidence

Studies this grade rests on

EffectMixedNo effectSize shows participants (n)20052010201520202025Meta-analysisRCTMao 2016, 2016: RCT, n = 179, result not recordedAmsterdam 2009, 2009: RCT, n = 57, result not recordedSaadatmand 2024, 2024: meta-analysis, n not recorded, result not recordedHieu 2019, 2019: meta-analysis, n not recorded, result not recorded
each study this grade rests on, by publication year and design. Solid: effect versus the comparator; half-filled: mixed; hollow: no effect; dashed: result not recorded yet. Larger marks had more participants.
Show the numbers
StudyYearDesignParticipantsResult
Amsterdam 20092009RCT57result not recorded
Mao 20162016RCT179result not recorded
Hieu 20192019meta-analysisnot recordedresult not recorded
Saadatmand 20242024meta-analysisnot recordedresult not recorded

The Effect of Oral Chamomile on Anxiety: A Systematic Review of Clinical Trials.

Saadatmand S, Zohroudi F, Tangestani H. The Effect of Oral Chamomile on Anxiety: A Systematic Review of Clinical Trials Clin Nutr Res, 2024. PMID 38784853

Result not recorded
Design
Systematic review of 10 clinical trials (no meta-analysis)
Population
Trials of oral chamomile and anxiety (mixed populations)
Funding
Bushehr University of Medical Sciences (Crossref funder)

Long-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: A randomized clinical trial.

Mao JJ, Xie SX, Keefe JR. Long-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: A randomized clinical trial Phytomedicine, 2016. PMID 27912875

Result not recorded
Design
12-week open-label phase, then 26-week randomized, double-blind, placebo-substitution trial
Sample
n = 179
Population
Adults with moderate-to-severe generalized anxiety disorder (clinical population)
Funding
NIH/NCCIH R01 AT005074 and NIH/NCI P30 CA008748; study product supplied by the Swedish Herbal Institute

A randomized, double-blind, placebo-controlled trial of oral Matricaria recutita (chamomile) extract therapy for generalized anxiety disorder.

Amsterdam JD, Li Y, Soeller I. A randomized, double-blind, placebo-controlled trial of oral Matricaria recutita (chamomile) extract therapy for generalized anxiety disorder J Clin Psychopharmacol, 2009. PMID 19593179

Result not recorded
Design
Randomized, double-blind, placebo-controlled trial, 8 weeks
Sample
n = 57
Population
Outpatients with mild to moderate generalized anxiety disorder (clinical population)
Funding
NIH grants (NCCIH, NIMH, NCI) per PubMed grant list

Therapeutic efficacy and safety of chamomile for state anxiety, generalized anxiety disorder, insomnia, and sleep quality: A systematic review and meta-analysis of randomized trials and quasi-randomized trials.

Hieu TH, Dibas M, Surya Dila KA. Therapeutic efficacy and safety of chamomile for state anxiety, generalized anxiety disorder, insomnia, and sleep quality: A systematic review and meta-analysis of randomized trials and quasi-randomized trials Phytother Res, 2019. PMID 31006899

Result not recorded
Design
Systematic review and meta-analysis of 12 randomized and quasi-randomized trials
Population
Mixed: state anxiety, generalized anxiety disorder, insomnia and sleep-quality trials
Funding
Joint Usage/Research Center on Tropical Disease, Nagasaki University; Institute of Allied Health Sciences, National Cheng Kung University (PubMed grant list)

Search and history

Search (): chamomile[ti] AND (anxiety[tiab] OR mood[tiab] OR depress*[tiab]) AND randomized controlled trial[pt]

  • Graded C (awaiting approval)
  • C to C (approved): Editor sign-off November 13, 2026: grade matches the editor-approved final page
  • C to C (approved) (maturity: emerging): Re-appraisal November 14, 2026: no RCT of isolated apigenin on sleep or calm exists; chamomile results do not transfer to isolated apigenin. Maturity, bias summary and re-check date added