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Chasteberry

Plant Part Used

Berry

Active Constituents

Iridoid glycosides (agnuside, aucubin and eurostosid) and flavonoids, including casticin and vitexin; diterpenes.(1)

[span class=alert]This section is a list of chemical entities identified in this dietary supplement to possess pharmacological activity. This list does not imply that other, yet unidentified, constituents do not influence the pharmacological activity of this dietary supplement nor does it imply that any one constituent possesses greater influence on the overall pharmacological effect of this dietary supplement.[/span]

Introduction

The Chasteberry tree finds its origins in the Mediterranean. Its fruit is harvested and dried for medicinal purposes. It has a long folk history of use in women’s health. Chasteberry (commonly know as Vitex) has been recommended for use in mild to moderate complaints, especially in endometriosis, menopause, and PMS symptoms.

Interactions and Depletions

Interactions

Dosage Info

Dosage Range

200-400mg (standardized extract) daily, preferably on an empty stomach, either 1 hour before or 2 hours after breakfast.

OR

4mg daily of a 6% standardized product.

Most Common Dosage

400mg (standardized extract) daily, preferably on an empty stomach, either 1 hour before or 2 hours after breakfast.

OR

4mg daily of a 6% standardized product

Standardization

[span class=doc]Standardization represents the complete body of information and controls that serve to enhance the batch to batch consistency of a botanical product, including but not limited to the presence of a marker compound at a defined level or within a defined range.[/span]

The most current available medical and scientific literature indicates that this dietary supplement should be standardized to 0.5% agnuside and 0.6% aucubin per dose.

Uses

Frequently Reported Uses

  • Hormonal imbalances, including PMS, Menstrual Irregularities and Menopausal And Postmenopausal Symptoms
Other Reported Uses
  • Acne Vulgaris
  • Hyperprolactinemia
  • Infertility Associated With Corpus Luteum Deficiency
  • Insufficient Lactation

Toxicities & Precautions

General

Chasteberry has been reported safe in recommended dosages.

Side Effects

May cause minor side effects such as stomach upset or rash in rare instances. (2)

Pregnancy/ Breast Feeding

Based on pharmacology, do not use in women of child-bearing age, women trying to conceive or in pregnant women.(3) Iridoid glycosides are found in Chasteberry. Structural modifications to them have demonstrated in vitro implantation preventing activity in animal cell lines.(4) In vitro studies have reported phytoestrogenic, emmenagogue and uterine stimulant activity.(23)

Age Limitations

To date, the medical literature has not reported any adverse effects specifically related to the use of this dietary supplement in children. Use with caution.

Pharmacology

Orally, Chasteberry is used for menstrual irregularities including dysmenorrhea, secondary amenorrhea, metrorrhagia, oligomenorrhea, and polymenorrhea.(24) Chasteberry is also used for symptoms of menopause, for symptoms of premenstrual syndrome (PMS) including cyclical mastalgia, luteal-phase dysfunction (corpus luteum insufficiency), and other symptoms. It is also used orally for treating female infertility, preventing miscarriage in patients with progesterone insufficiency, controlling postpartum bleeding, aiding in expulsion of the placenta, increasing lactation, and treating fibrocystic breasts.(25) It is used for promoting urination, treating benign prostatic hyperplasia (BPH), and reducing sexual desire. Chasteberry is also used for acne.

The actual activity of the constituents of Chasteberry is not fully established at this time. Studies have reported Chasteberry to have a significant effect on the pituitary.(5),(6) Studies point to a progesterone-like component and effect as well.(7),(8) Studies report that Vitex stimulates luteinizing hormone (LH) and inhibits follicle stimulating hormone (FSH).(9),(10),(26) Chasteberry may also possess estrogenic activity as evidenced by in vitro up-regulation of the estrogen-inducible gene, pS2 (presenelin-2) in S30 breast cancer cells.(11) Because of this activity, Vitex has been recommended for a variety of female complaints, such as PMS, amenorrhea, menopausal symptoms, endometriosis and hyperprolactinemia.(12),(13),(14) Studies have reported beneficial effects of Vitex on female-related disorders,(15),(16) with several clinical studies reporting beneficial results when using Chasteberry in treating women with infertility associated with corpus luteum deficiency.(17) Chasteberry may also be of benefit in acne, as human data reports increasing healing while using a Chasteberry preparation.(3)

A multicentric noninterventional trial (open study without control) was conducted to study the efficacy and tolerance of Chasteberry extract in 1,634 patients suffering PMS. Four major symptoms of PMS were monitored including depression, anxiety, craving, and hyperhydration. After a treatment period of three menstrual cycles, 93% of patients reported a decrease in the number of symptoms or even cessation of PMS complaints. Mastodynia was still present after 3 months of therapy but was generally less severe than before treatment.(18) However, a recent double-blind, placebo controlled study in two parallel groups (each 50 patients) reported that use of Vitex was useful in the treatment of cyclical breast pain in women.(19)

In a prospective, multi-center trial, the efficacy of a Vitex extract was studied in 50 patients with PMS.(20) At the conclusion of the study, PMS-related symptoms were reduced by treatment. Although the symptoms gradually returned after treatment cessation, a 20% difference from baseline remained up to 3 cycles thereafter. At baseline, the VAS score (visual analogue scale; self evaluated) was elevated in the late luteal phase and low at the follicular phase, as expected by the authors. During treatment, the VAS score decreased in the late luteal phase (47.2%) and remained 21.7% below baseline after 3 cycles post-cessation of treatment, with the low VAS score within the follicular phase remaining unchanged over the whole observation period. In the patient's assessment, 38 judged the global efficacy moderate to excellent with 5 patients indicating no global efficacy. The number of day’s patient’s sustained PMS symptoms was reduced slightly from 7.5 to 6, with the resting levels of blood prolactin remaining within the physiological range throughout the study. No differences were seen between patients on or off oral contraceptives. Twenty patients reported 37 transient adverse events with no serious adverse reactions reported. One patient withdrew after four days of treatment due to fatigue and headache. The authors concluded that patients with PMS can be treated successfully with Vitex preparations as indicated by a clear improvement in the main effect parameter during treatment and the gradual return after cessation of treatment. The main response to treatment seems related to symptomatic relief rather than to the duration of the syndrome.

A randomized, double blind, placebo controlled, parallel group comparison study of 178 women taking a standardized Vitex product (1 tablet daily) reported improvement in PMS symptoms (over three menstrual cycles) when compared to placebo.(21) Improved symptoms included mood alteration, anger, headache, breast fullness and bloating, where improvement rates were 52% and 24% for Vitex and placebo, respectively.

The pharmacological effects of an ethanolic extract of Vitex was studied regarding its effects on dopamine-D2 and opioid (mu and kappa subtype) receptors.(22) A relative potent binding inhibition was observed for dopamine-D2 and the opioid receptors. Binding to the histamine-H1, benzodiazepine, OFQ receptor, and the binding-site of the serotonin (5-HT) transporter, was significantly inhibited. The lipophilic fractions of the Vitex extract contained the diterpenes which exhibited inhibitory actions on dopamine-D2 receptor binding. While binding inhibition to mu and kappa opioid receptors was most pronounced in lipophilic fractions, binding to delta opioid receptors was inhibited mainly by an aqueous fraction. The authors concluded that the data indicates a dopaminergic effect of Vitex extracts and suggests additional pharmacological actions via opioid receptors. Due to this dopaminergic activity, it has been postulated that Chasteberry may be used in the management of Parkinson’s disease, although no clinical research has been performed to support that theory.(6)

A combination of Chasteberry and St. John’s wort (Hypericum perforatum) was found in a double-blind, randomized, placebo-controlled parallel trial to be superior to placebo for total PMS-like scores including anxiety.(27)

Other Uses

Laboratory studies have reported to constituents in Chasteberry may have antitumor activity through apoptosis induction and cytotoxic activity.(28)

References

  1. Kondo Y, et al. Studies on the Constituents of Vitex rotundifolia L. fil. Chem Pharm Bull. (Tokyo). 1986; 34(11):4829-32.
  2. PDR for Herbal Medicines, 2nd ed. Montvale, NJ: Medical Economics Company; 2000:176.
  3. Newall CA, et al. Herbal Medicines: A Guide for Health Care Professionals. London: The Pharmaceutical Press;1996:19-20.
  4. View Abstract: Misra AP, Mathad VT, Raj K, Bhaduri AP, Tiwari R, Srivastava A, et al. Modified iridoid glycosides as anti-implantation agents. Inhibition of cell adhesion as an approach for developing pregnancy interceptive agents. Bioorg Med Chem. Nov 2001;9(11):2763-72.
  5. Amann W. Amenorrhea. Favorable Effect of Agnus castus (Agnolyt) on Amenorrhea. ZFA. (Stuttgart). 1982;58(4):228-31.
  6. View Abstract: Sliutz G, et al. Agnus castus Extracts Inhibit Prolactin Secretion of Rat Pituitary Cells. Hormone and Metabolic Research. 1993;25:253-55.
  7. Amann W. Elimination of Obstipation with Agnolyt. Ther Gegenew. 1965;104(9):1263-65.
  8. View Abstract: Makwana HG, et al. General Pharmacology of Vitex leucoxylon Linn Leaves. Indian J Physiol Pharmacol. 1994;38(2):95-100.
  9. View Abstract: Milewicz A, et al. Vitex Agnus castus Extract in the Treatment of Luteal Phase Defects Due to Latent Hyperprolactinemia. Results of a Randomized Placebo-controlled Double-blind Study. Arzneim Forsch/Drug Res. 1993;43(7):752-56.
  10. View Abstract: Bhargava SK. Antiandrogenic Effects of a Flavonoid-rich Fraction of Vitex Negundo Seeds: A Histological and Biochemical Study in Dogs. J Ethnopharmacol. 1989;27(3):327-39.
  11. View Abstract: Liu J, Burdette JE, Xu H, Gu C, van Breemen RB, Bhat KP, et al. Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms. J Agric Food Chem. May 2001;49(5):2472-9.
  12. Hillebrand H. The Treatment of Premenstrual Aphthous Ulcerative Stomatitis with Agnolyt. Z Allgemeinmed. 1964;40(36):1577.
  13. McGibbon D. Premenstrual Syndrome. CMAJ. 1989;141(11):1124-25.
  14. View Abstract: Jarry H, et al. In Vitro Prolactin But Not LH and FSH Release Is Inhibited by Compounds in Extracts of Agnus castus: Direct Evidence for a Dopaminergic Principle by the Dopamine Receptor Assay. Exp Clin Endocrinol. 1994;102(6):448-54.
  15. Amann W. Premenstrual Water Retention. Favorable Effect of Agnus castus (Agnolyt) on Premenstrual Water Retention. ZFA. (Stuttgart). 1979;55(1):48-51.
  16. Snow JM. Vitex agnus-castus L. (Verbenaceae). Protocol Journal of Botanical Medicine. 1996;1(4): 20-23.
  17. Propping D, et al. [Diagnosis and Therapy of Corpus Luteum Deficiency in General Practice]. Therapiewoche. 1988;38:2992-3001.
  18. View Abstract: Loch EG, et al. Treatment of premenstrual syndrome with a phytopharmaceutical formulation containing Vitex agnus-castus. J Women's Health Gend Based Med. 2000;9(3):315-320.
  19. View Abstract: Halaska M, Raus K, Beles P, Martan A, Paithner KG.[Treatment of cyclical mastodynia using an extract of Vitex agnus castus: results of a double-blind comparison with a placebo]. Ceska Gynekol. Oct1998;63(5):388-92.
  20. View Abstract: Berger D, Schaffner W, Schrader E, Meier B, Brattstrom A. Efficacy of Vitex agnus castus L. extract Ze 440 in patients with pre-menstrual syndrome (PMS). Arch Gynecol Obstet. Nov2000;264(3):150-3.
  21. View Abstract: Schellenberg R. Treatment for the Premenstrual Syndrome with Agnus castus Fruit Extract: Prospective, Randomised, Placebo Controlled Study. BMJ. Jan2001; 322:134-137.
  22. View Abstract: Meier B, Berger D, Hoberg E, Sticher O, Schaffner W. Pharmacological activities of Vitex agnus-castus extracts in vitro. Phytomedicine. Oct2000;7(5):373-81.
  23. Dugoua JJ, Seely D, Perri D, Koren G, Mills E. Safety and efficacy of chastetree (Vitex agnus-castus) during pregnancy and lactation. Can J Clin Pharmacol. 2008;15(1):e74-79. Epub 2008 Jan 18. Review.
  24. He Z, Chen R, Zhou Y, Geng L, Zhang Z, Chen S, Yao Y, Lu J, Lin S. Treatment for premenstrual syndrome with Vitex agnus castus: A prospective, randomized, multi-center placebo controlled study in China. Maturitas. 20 May2009 ;63(1):99-103. Epub 2009 Mar 9.
  25. Döll M. [The premenstrual syndrome: effectiveness of Vitex agnus castus] Med Monatsschr Pharm. May 2009;32(5):186-191. Review. German.
  26. Hu Y, Hou TT, Zhang QY, et al. Evaluation of the estrogenic activity of the constituents in the fruits of Vitex rotundifolia L. for the potential treatment of premenstrual syndrome. J Pharm Pharmacol. Sep 2007;59(9):1307-1312.
  27. Van Die MD, Bone KM, Burger HG, Reece JE, Teede HJ. Effects of a combination of Hypericum perforatum and Vitex agnus-castus on PMS-like symptoms in late-perimenopausal women: findings from a subpopulation analysis. J Altern Complement Med. Sep 2009;15(9):1045-1048.
  28. Zhou Y, Liu YE, Cao J, et al. Vitexins, nature-derived lignan compounds, induce apoptosis and suppress tumor growth. Clin Cancer Res. 15 Aug 2009;15(16):5161-5169. Epub 2009 Aug 11.

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