Chaste Tree

Scientific Name(s): Vitex agnus-castus L. Family: Verbenaceae

Common Name(s): Chaste tree , agnus castus , chasteberry , gattilier , Indian spice , lilac chaste tree , Monk's pepper , sage tree hemp , wild pepper , vitex

Uses

Chaste tree extract has been used to manage symptoms related to premenstrual syndrome (PMS) and cyclic mastalgia and may be a suitable alternative to standard pharmacological management. Although the Complete German Commission E Monographs supports its use for PMS and cyclic mastalgia, there are limited clinical trials to support these uses. Limited evidence exists for its use in menopause.

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Dosing

Daily doses of chaste tree fruit extract are typically 20 to 40 mg.

Contraindications

Patients who have an allergy to or are hypersensitive to V. agnus-castus or patients who are pregnant or breast-feeding should avoid use. Safe use in children has not been established.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. However, chaste tree may have estrogenic, progesterogenic, and/or uterine stimulant activity and should be avoided in pregnancy and while breast-feeding.

Interactions

None well documented.

Adverse Reactions

Generally regarded as safe; mild and reversible adverse effects include GI reactions, itching, rash, headache, fatigue, acne, and menstrual disturbances.

Toxicology

Information is limited and safety has not been determined in children.

Botany

The chaste tree is a small (6 to 7 m) tree or shrub native to river banks in southern Europe and the Mediterranean region. The plant is cultivated in China. It blooms in summer, developing light purple flowers and palm-shaped leaves. The dark brown to black fruits are the size of peppercorns. These fruits have a pepperish aroma and flavor and are collected in autumn. 1 , 2

History

The dried, ripe fruit is used in traditional medicine. The plant has been recognized since antiquity and has been described in works by Hippocrates (AD 460), Dioscorides (AD 40), and Theophrastus (AD 372). In Homer's epic The Iliad , the plant was featured as a symbol of chastity, capable of warding off evil. Early physicians recognized its effect on the female reproductive system, suggesting its use in controlling hemorrhages and expelling the placenta after birth. Monks have chewed it to decrease sexual desire. 2 , 3 , 4

Chemistry

V. agnus-castus contains iridoids, flavonoids, diterpenoids, progestins, essential oils, and ketosteroids. Iridoid glycosides have been isolated from the leaves and fruit of the plant and include agnuside and aucubin. Flavonoid content (including kaempferol, quercetagetin, and casticin) has been identified in chaste tree leaves, flowers, and fruits. Flavonoids were isolated from the root bark.

The alkaloid vitricine is present in the plant. Vitexlactam A, a labdane diterpene, has been isolated from the fruit of V. agnus-castus . In vitro studies show that labdane diterpenes have dopamine receptor affinity.

Clerodadienols are potent inhibitors of prolactin release. Although present in only trace amounts, progesterone, hydroxyprogesterone, testosterone, and androstenedione have been isolated from the leaves and flowers of V. agnus-castus . Numerous fatty acids also have been found. 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16

Uses and Pharmacology

Mastalgia/Cyclic breast pain
Animal data

The widespread use of chaste tree extracts and the relatively safe profile of the preparations make data from animal studies largely irrelevant. The plant has been approved for this condition by the Complete German Commission E Monographs . 17

In vitro experimental studies suggest dopaminergic activity of the plant's diterpenes, similar to bromocriptine, may result in decreases in serum prolactin. Additionally, estrogen receptor binding by phytoestrogens or linoleic acid from the fruits has been postulated as a possible mechanism for effect. 18 , 19 , 20

Clinical data

A limited number of controlled clinical trials have been conducted, and reviews of these trials are concordant in finding a benefit for treatment with V. agnus-castus . Decreased pain and shorter durations of pain have been demonstrated when chaste tree preparations are used for at least 3 cycles. 18 , 20 , 21

Menopause
Animal data

The widespread use of chaste tree extracts and the relatively safe profile of the preparations make data from animal studies largely irrelevant. With regard to menopausal symptoms, effects of chemical constituents of chaste tree on dopamine receptors, opioid receptors, and melatonin were described in animal experiments and in vitro studies. 21 , 22 , 23 , 24 , 25

Clinical data

Few controlled clinical trials have evaluated the efficacy of V. agnus-castus as a single agent in the management of menopausal symptoms. 21 Chaste tree was evaluated in combination with other natural products in the Herbal Alternatives for Menopause Trial. Other observational studies and pharmacological experiments suggest V. agnus-castus may be a suitable alternative to standard management, such as hormone replacement therapy, but quality clinical trials are required to support a definitive role in therapy. 21

Premenstrual syndrome
Animal data

The widespread use of chaste tree extracts and the relatively safe profile of the preparations make data from animal studies largely irrelevant. The plant has been approved for this condition by the Complete German Commission E Monographs . 17

Clinical data

A limited number of high-quality, controlled clinical trials have evaluated the efficacy of V. agnus-castus preparations in treating symptoms associated with PMS (moderate to severe), 26 , 27 , 28 , 29 , 30 , 31 with most conducted in Germany and China. 32 Despite a large placebo response observed in these trials (approximately 50%) and heterogeneity in trial conditions, a systematic review found that chaste tree extract demonstrated an overall benefit in reducing adverse physical symptoms and poor mood. 18 , 33 The number needed to treat for improvement in global symptoms score in 1 person was determined to be “4” in a quality controlled trial involving 104 women followed for at least 3 menstrual cycles. 18 , 26 Chaste tree has also been favorably compared with fluoxetine in the management of depression associated with PMS. 31 The clinical studies have found the preparations to be well tolerated with few adverse effects, although data from larger controlled trials are still needed. 18 , 32 , 33

Other effects
Amenorrhea/Infertility

There have been case reports for the reinstatement of regular cycles in amenorrhea; however, information from controlled clinical trials is lacking. 18 , 21 , 34

Cancer

Ethanol extracts from the fruit of V. agnus-castus have shown in vitro cytotoxic activity against various human cancer cell lines, including cervical, ovarian, breast, and gastric cancer, and small cell lung carcinoma. Numerous mechanisms of action may be involved in inducing apoptosis. 20 , 35 , 36

Immune system

Experimental studies suggest immunomodulatory effects of chaste tree flavonoids, diterpenes, and other chemical constituents. 10 , 11 , 12 , 15

Orchiectomy

Inhibition of testosterone in rats and bone-sparing effects in castrated rats have been demonstrated by extracts of chaste tree. 37 , 38

Dosage

The effect of chaste tree extract on hormones in women may be dose-dependent. Some studies suggest lower doses result in increases in prolactin and estrogen as well as decreases in progesterone, while higher doses decrease prolactin levels. 18

Daily doses of chaste tree fruit extract are typically 20 to 40 mg, although dosages of up to 1,800 mg/day have been used. 18 Chaste tree fruit is available in several different extracts standardized to casticin or agnuside content. 3 , 39 , 40

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. However, chaste tree may have estrogenic, progesterogenic, and/or uterine stimulant activity and should be avoided in pregnancy. 18 , 41 , 42 , 43

No consensus exists regarding the efficacy of extracts in increasing milk production. 18 , 44 When analyzed chemically, human breast milk revealed no compositional changes after chaste tree use. 45 Despite low toxicity and a lack of evidence that chemical constituents pass into the milk, chaste tree products should be avoided during breast-feeding because safety has not been established. 18 , 43

Interactions

Case reports are lacking; however, chaste tree has dopamine agonist activity. An interaction with dopamine agonists (eg, bromocriptine, levodopa), dopamine receptor antagonists, and fertility and contraceptive drugs may be theoretically possible. 45 , 46 , 47 , 48

Adverse Reactions

Chaste tree administration is generally regarded as safe for use because it has not been associated with any major adverse reactions. Minor and reversible adverse effects reported in clinical trials and surveillance include GI reactions, pruritus, rash, headache, fatigue, acne, and menstrual disturbances. 18 , 48

Toxicology

Information is limited. The safety of the plant's use in children has not been determined. 49

Bibliography

1. Vitex agnus-castus . USDA, NRCS. 2011. The PLANTS Database ( http://plants.usda.gov , 14 March 2011). National Plant Data Team, Greensboro, NC 27401-4901 USA.
2. Chevallier A. Encyclopedia of Medicinal Plants . New York, NY: DK Publishing; 1996:149.
3. Christie S, Walker A. Vitex agnus-castus L.: (1) a review of its traditional and modern therapeutic use; (2) current use from a survey of practitioners. Eur J Herbal Med . 1998;3:29-45.
4. Hobbs C. The chaste tree: Vitex agnus castus . Pharm Hist . 1991;33(1):19-24.
5. Kuruüzüm-Uz A, Ströch K, Demirezer LO, Zeeck A. Glucosides from Vitex agnus-castus . Phytochemistry . 2003;63(8):959-964.
6. Hirobe C, Qiao ZS, Takeya K, Itokawa H. Cytotoxic flavonoids from Vitex agnus-castus . Phytochemistry . 1997;46(3):521-524.
7. Hoberg E, Orjala J, Meier B, Sticher O. Diterpenoids from the fruits of Vitex agnus-castus . Phytochemistry . 1999;52(8):1555-1558.
8. Liu J, Burdette JE, Sun Y, et al. Isolation of linoleic acid as an estrogenic compound from the fruits of Vitex agnus-castus L. (chaste-berry). Phytomedicine . 2004;11(1):18-23.
9. Ono M, Eguchi K, Konoshita M, et al. A new diterpenoid glucoside and two new diterpenoids from the fruit of Vitex agnus-castus . Chem Pharm Bull (Tokyo) . 2011;59(3):392-396.
10. Ahmad B, Azam S, Bashir S, Khan I, Adhikari A, Choudhary MI. Anti-inflammatory and enzyme inhibitory activities of a crude extract and a pterocarpan isolated from the aerial parts of Vitex agnus-castus . Biotechnol J . 2010;5(11):1207-1215.
11. Choudhary MI, Azizuddin, Jalil S, et al. Antiinflammatory and lipoxygenase inhibitory compounds from Vitex agnus-castus . Phytother Res . 2009;23(9):1336-1339.
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19. Tamagno G. Are changes of prolactin levels the effectors of Vitex agnus castus beneficial effects on the pre-menstrual syndrome? Maturitas . 2009;63(4):369.
20. Carmichael AR. Can Vitex agnus castus be used for the treatment of mastalgia? What is the current evidence? Evid Based Complement Alternat Med . 2008;5(3):247-250.
21. van Die MD, Burger HG, Teede HJ, Bone KM. Vitex agnus-castus (Chaste-Tree/Berry) in the treatment of menopause-related complaints. J Altern Complement Med . 2009;15(8):853-862.
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26. Schellenberg R. Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study. BMJ . 2001;322(7279):134-137.
27. Berger D, Schaffner W, Schrader E, Meier B, Brattström A. Efficacy of Vitex agnus castus L. extract Ze 440 in patients with pre-menstrual syndrome (PMS). Arch Gynecol Obstet . 2000;264(3):150-153.
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30. Ma L, Lin S, Chen R, Zhang Y, Chen F, Wang X. Evaluating therapeutic effect in symptoms of moderate-to-severe premenstrual syndrome with Vitex agnus castus (BNO 1095) in Chinese women. Aust N Z J Obstet Gynaecol . 2010;50(2):189-193.
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32. Freeman EW. Therapeutic management of premenstrual syndrome. Expert Opin Pharmacother . 2010;11(17):2879-2889.
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34. Gerhard I, Patek A, Monga B, Blank A, Gorkow C. Mastodynon bei weiblicher Sterilität. Forsch Komplementarmed . 1998;5(6):272-278.
35. Ohyama K, Akaike T, Imai M, Toyoda H, Hirobe C, Bessho T. Human gastric signet ring carcinoma (KATO-III) cell apoptosis induced by Vitex agnus-castus fruit extract through intracellular oxidative stress. Int J Biochem Cell Biol . 2005;37(7):1496-1510.
36. Imai M, Kikuchi H, Denda T, Ohyama K, Hirobe C, Toyoda H. Cytotoxic effects of flavonoids against a human colon cancer derived cell line, COLO 201: a potential natural anti-cancer substance. Cancer Lett . 2009;276(1):74-80.
37. Nasri S, Oryan S, Rohani AH, Amin GR. The effects of Vitex agnus castus extract and its interaction with dopaminergic system on LH and testosterone in male mice. Pak J Biol Sci . 2007;10(14):2300-2307.
38. Sehmisch S, Boeckhoff J, Wille J, et al. Vitex agnus castus as prophylaxis for osteopenia after orchidectomy in rats compared with estradiol and testosterone supplementation. Phytother Res . 2009;23(6):851-858.
39. Huddleston M, Jackson EA. Is an extract of the fruit of agnus castus (chaste tree or chasteberry) effective for prevention of symptoms of premenstrual syndrome (PMS)? J Fam Pract . 2001;50(4):298.
40. Loch EG, Selle H, Boblitz N. Treatment of premenstrual syndrome with a phytopharmaceutical formulation containing Vitex agnus castus . J Womens Health Gend Based Med . 2000;9(3):315-320.
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42. Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG . 2002;109(3):227-235.
43. 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-e79.
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