Chasteberry

NutraPedia - Evidence-Based Supplement Research

Back to Table of Contents
Health Goals: mood stress skin

Research Overview

Across the provided abstracts, chasteberry (Vitex agnus-castus) appears most studied or discussed in two broad contexts: (1) endocrine-related indications in veterinary medicine—specifically equine pituitary pars intermedia dysfunction (PPID)—and (2) symptom-focused use in humans, particularly women’s health (e.g., PMS and menopausal symptoms) and mental health outcomes such as anxiety/depression (including potential relevance to cancer populations). However, the human literature summarized here is largely framed as “promising” rather than definitive, and in women’s health the review explicitly notes that rigorous clinical trials for PMS botanicals (including chasteberry) have not been done, despite common use and proposed hormonal/estrogenic mechanisms.

The strongest evidence in these abstracts is negative evidence in equine PPID: an evidence-based guideline using GRADE concludes that chasteberry has no effect on ACTH concentrations and provides no benefit when added to pergolide therapy. In contrast, for human anxiety/depression, a review of single-herb randomized trials across multiple botanicals identifies chasteberry among those considered “promising,” with a portion of studies reporting positive findings and generally fewer adverse effects than conventional medications; however, this conclusion is not specific to cancer patients and is presented as preliminary, with outcomes not always being primary endpoints and with an emphasis on the need for better trials.

Key research gaps highlighted by these abstracts include the need for well-designed, larger randomized controlled trials to establish efficacy and safety for psycho-oncologic applications (and more generally for anxiety/depression), and more rigorous clinical trials in women’s health indications where use is common but evidence is limited (e.g., PMS; menopausal symptoms where estrogenic activity is proposed). Additionally, the veterinary guideline underscores that, at least for PPID, chasteberry does not improve core endocrine markers (ACTH) and does not enhance standard therapy, suggesting future work—if pursued—should clarify whether any clinically meaningful benefits exist beyond ACTH modulation and should be evaluated against established treatments with clinically relevant endpoints.

1. What conditions has Chasteberry been studied for?

  • Equine pituitary pars intermedia dysfunction (PPID; “equine Cushing’s disease”): evaluated as a management/treatment option, including as an add-on to pergolide therapy.

  • Premenstrual syndrome (PMS): multiple randomized controlled trials (RCTs) of Vitex agnus-castus extracts.

  • Premenstrual dysphoric disorder (PMDD): RCTs comparing Vitex with fluoxetine or placebo/other comparators.

  • Latent hyperprolactinaemia (including cyclic mastalgia and luteal phase abnormalities): RCTs assessing prolactin-related endpoints and symptoms.

  • Anxiety and/or depressive symptoms: included among “promising” single-herb RCTs in a broad review (not limited to women’s health and not necessarily cancer-specific trials).

  • Osteoarthritis in the context of iron overload (preclinical): cardamonin, described as a substance found in the fruit of the chasteberry plant, studied in mouse and cell models.

  • Menopausal symptoms (discussion/mechanistic context): chasteberry is listed among botanicals with potential estrogenic activity proposed for menopausal symptom relief, but the provided abstract emphasizes controversy and does not present chasteberry-specific RCT outcomes.

2. Does it work in treating those conditions? Summarize the evidence.

  • PMS: A systematic review of randomized controlled trials found that 7 of 8 PMS trials reported Vitex extracts were superior to comparators, including placebo (5 of 6 studies), pyridoxine (1), and magnesium oxide (1). The review notes methodological quality was generally moderate-to-high but with limitations (e.g., some small samples and heterogeneity).

  • PMDD: Evidence is mixed. In the systematic review, one trial reported Vitex equivalent to fluoxetine, while another found fluoxetine outperformed Vitex.

  • Latent hyperprolactinaemia/cyclic mastalgia: In the systematic review, one trial found Vitex superior to placebo for reducing TRH-stimulated prolactin secretion and for improving reproductive hormone-related measures (e.g., normalizing shortened luteal phase and increasing mid-luteal progesterone and 17β-estradiol). Another trial found Vitex comparable to bromocriptine for reducing serum prolactin and improving cyclic mastalgia.

  • Anxiety/depression symptoms: A review of single-herb RCTs (1996–2016) concluded chasteberry is “promising” for anxiety or depression symptom mitigation and that across included herbs/studies 45% reported positive findings with fewer adverse effects than conventional medications. However, this evidence is indirect for chasteberry specifically because the abstract does not quantify chasteberry-only outcomes, and symptoms were not always primary endpoints.

  • Equine PPID: An evidence-based equine guideline concluded chasteberry has no effect on ACTH concentrations and that there is no benefit to adding chasteberry to pergolide therapy for PPID management.

  • Osteoarthritis with iron overload (preclinical): In a mouse model and in vitro chondrocytes, cardamonin (from chasteberry fruit) reduced cartilage degeneration and chondrocyte apoptosis, and reduced NLRP3 inflammasome signaling via a SIRT1–MAPK pathway; effects were blocked by a SIRT1 inhibitor. This is mechanistic/preclinical evidence and does not establish clinical efficacy in humans.

  • Menopausal symptoms: The provided abstracts describe chasteberry among botanicals proposed to have estrogenic activity, but also state that clinical trial data for botanicals are controversial; no chasteberry-specific efficacy result is provided here.

3. What health benefits does it have?

  • Reduction of PMS symptoms: The systematic review of RCTs suggests Vitex extracts can improve PMS compared with placebo and some active comparators in most trials.

  • Possible benefit for PMDD in some patients: One RCT found equivalence to fluoxetine, though another found fluoxetine superior (so benefit is plausible but not consistently demonstrated).

  • Prolactin-related benefits (latent hyperprolactinaemia): Trials reported reductions in prolactin measures and improvements in cyclic mastalgia and luteal phase/hormonal parameters (e.g., mid-luteal progesterone and 17β-estradiol in one study).

  • Potential mood symptom support (uncertain strength): A broad RCT review suggests chasteberry may help mitigate anxiety/depressive symptoms with a favorable risk-benefit profile, but the abstract does not provide chasteberry-specific effect sizes or consistency.

  • Anti-inflammatory/chondroprotective potential (preclinical): Cardamonin (not necessarily equivalent to typical Vitex supplements) showed anti-inflammatory pathway effects and cartilage protection in iron-overload osteoarthritis models; clinical relevance remains unproven.

4. Does it have any downsides or side effects?

  • Generally mild, infrequent adverse events in RCTs: The systematic review reports adverse events with Vitex were mild and generally infrequent.

  • Uncertainty about interactions/toxicities for women’s health botanicals: A women’s health review cautions that botanicals (including those used for hormonal symptoms) are often perceived as “natural” but may not be rigorously tested for toxic effects or drug/botanical interactions. (This is a general caution; the abstract does not list specific chasteberry interactions.)

  • Lack of benefit in equine PPID and risk of inappropriate substitution: In horses with PPID, chasteberry showed no effect on ACTH and no added benefit with pergolide; using ineffective therapies could delay effective treatment (the guideline emphasizes welfare risks from inappropriate lifelong therapy decisions, though this point is made broadly about diagnostic/treatment decisions rather than chasteberry toxicity).

  • Product variability and evidence gaps: Across the abstracts, limitations include heterogeneity of conditions, varying comparators, and calls for better-designed trials; these issues can translate into uncertain dosing/standardization and unpredictable results.

5. Is it beneficial or harmful for any genetic variations (pharmacogenomics)?

No pharmacogenomic findings are provided in the supplied abstracts. None of the abstracts report differential efficacy or adverse effects of chasteberry/Vitex based on genetic variants (e.g., CYP450 polymorphisms, serotonin transporter variants, dopamine receptor variants, or estrogen receptor genotypes). Therefore, based on these sources, there is insufficient evidence to say chasteberry is beneficial or harmful for any specific genetic variation.

References

  1. BEVA primary care clinical guidelines: Diagnosis and management of equine pituitary pars intermedia dysfunction.
    Nicola J Menzies-Gow, Heidi E Banse, Aimi Duff, Nicholas Hart, Joanne L Ireland, Edward J Knowles, Dianne McFarlane, David Rendle (2024) - Equine veterinary journal
  2. Herbal medicine for depression and anxiety: A systematic review with assessment of potential psycho-oncologic relevance.
    K Simon Yeung, Marisol Hernandez, Jun J Mao, Ingrid Haviland, Jyothirmai Gubili (2018) - Phytotherapy research : PTR
  3. Botanicals and Their Bioactive Phytochemicals for Women's Health.
    Birgit M Dietz, Atieh Hajirahimkhan, Tareisha L Dunlap, Judy L Bolton (2016) - Pharmacological reviews
  4. Cardamonin protects against iron overload induced arthritis by attenuating ROS production and NLRP3 inflammasome activation via the SIRT1/p38MAPK signaling pathway.
    Shaocong Li, Qi He, Baihao Chen, Jiaxu Zeng, Xiangyun Dou, Zhaofeng Pan, Jiacong Xiao, Miao Li, Fanchen Wang, Chuyi Chen, Yuewei Lin, Xintian Wang, Haibin Wang, Jianfa Chen (2023) - Scientific reports
  5. Vitex agnus-castus extracts for female reproductive disorders: a systematic review of clinical trials.
    M Diana van Die, Henry G Burger, Helena J Teede, Kerry M Bone (2013) - Planta medica
  6. Botanical modulation of menopausal symptoms: mechanisms of action?
    Atieh Hajirahimkhan, Birgit M Dietz, Judy L Bolton (2013) - Planta medica
  7. Efficacy and Safety of Nutraceutical on Menopausal Symptoms in Post-Menopausal Women: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.
    Teerapong Rattanatantikul, Mart Maiprasert, Pansak Sugkraroek, Akkarach Bumrungpert (2022) - Journal of dietary supplements
  8. Stimulatory effect of dietary chasteberry (Vitex agnus-castus) extract on immunity, some immune-related gene expression, and resistance against Aeromonas hydrophila infection in goldfish (Carassius auratus).
    Maedeh Rashmeei, Seyed Pezhman Hosseini Shekarabi, Mehdi Shamsaie Mehrgan, Hamed Paknejad (2020) - Fish & shellfish immunology
  9. Efficacy of Cimicifuga racemosa, Hypericum perforatum and Agnus castus in the treatment of climacteric complaints: a systematic review.
    Elena Laakmann, Donata Grajecki, Katja Doege, Christine zu Eulenburg, Kai J Buhling (2012) - Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology
  10. Evaluation of the anti-obesity effect of
    Şeyma Ulusoy, Ebrar İnal, Esra Küpeli Akkol, Mahmut Çiçek, Murat Kartal, Eduardo Sobarzo-Sánchez (2024) - Frontiers in pharmacology
  11. Herbal supplement use among reproductive-aged women in an academic infertility practice.
    Julie Friedman, Jeanelle Sheeder, Aaron Lazorwitz, Alex Joel Polotsky (2023) - F&S reports
  12. Quality Assessment of Medicinal Product and Dietary Supplements Containing Vitex agnus-castus by HPLC Fingerprint and Quantitative Analyses.
    Mami Sogame, Yoko Naraki, Takahiro Sasaki, Masaharu Seki, Kazuyoshi Yokota, Sayaka Masada, Takashi Hakamatsuka (2019) - Chemical & pharmaceutical bulletin
  13. Computational analysis for hepatic safety signals of constituents present in botanical extracts widely used by women in the United States for treatment of menopausal symptoms.
    Yun-Jan Wang, Jinhui Dou, Kevin P Cross, Luis G Valerio (2011) - Regulatory toxicology and pharmacology : RTP
  14. Vitex Agnus-Castus for the Treatment of Cyclic Mastalgia: A Systematic Review and Meta-Analysis
    Soo Liang Ooi, Stephanie Watts, Rhett McClean, Sok Cheon Pak (2020)
  15. The effects of Vitex agnus-castus on menstrual bleeding: A systematic review and meta-analysis.
    Sanaz Mollazadeh, Mojgan Mirghafourvand, Nafiseh Ghassab Abdollahi (2019) - Journal of complementary & integrative medicine
  16. REMEDIAL INTERVENTION OF FERTILITY AGENT AND GENE 35 ON INDUCED CYSTIC OVARY IN RATS.
    M Almozie'l, A Khudhair, F Shari (2024) - Georgian medical news
  17. [Evaluation of the efficacy of a new nutraceutical product in the treatment of postmenopausal symptoms].
    V Cappelli, G Morgante, A Di Sabatino, M G Massaro, V De Leo (2015) - Minerva ginecologica
  18. Kampo Prescriptions for Premenstrual Syndrome and Premenstrual Dysphoric Disorder: A Secondary Analysis of Nationwide Survey by JSOG Women's Health Care Committee.
    Takashi Takeda, Kana Yoshimi, Fumi Inoue, Tamami Odai, Nahoko Shirato, Zen Watanabe, Tempei Otsubo, Masakazu Terauchi (2025) - The Tohoku journal of experimental medicine


Want personalized supplement recommendations based on your genetics?
Upload Whole Genome Sequencing (WGS) raw DNA data today!
Or upload raw DNA data to get started with your free analysis!