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New Insights Into Chaste Tree

by Kerry Bone, BSc (Hons), Dip. Phyto, FNIMH, FNHAA, MCPP

Chaste tree (Vitex agnus castus) is a Western herb with a long history of use for gynecological problems. In fact, when I was an herbal student, I was taught chaste tree was indicated for just about any kind of problem involving the female reproductive tract.

However, modern research suggests the herb has quite specific effects on hormonal regulation. While other aspects of its activity could still be revealed, these new insights reveal some new uses for chaste tree, as well as provide an explanation for the mechanism behind many of its traditional uses.

Mode of Action: Conventional Wisdom

The "conventional wisdom" of how chaste tree works was based on a German pharmacological study from the early 1960s. This was promoted and perpetuated through writings, papers and in promotional literature, especially in Germany, where chaste tree is widely used. The study found that low doses of chaste tree for 90 days in female guinea pigs decreased estrogenic and promoted progesterogenic effects. At 20 times this dose, pituitary, adrenal and uterine weights were all significantly decreased. Based on these findings, it was concluded that the site of action of chaste tree was the anterior pituitary. The effects at the lower dose were interpreted as a stimulation of LH and an inhibition of FSH. At the higher dose, all anterior pituitary activity was suppressed.1


According to a recent clinical trial, chaste tree caused a dose-dependent increase in melatonin secretion compared to placebo treatment.


New Research: Dopaminergic Activity

Recent research challenges this "conventional wisdom." It now is known that chaste tree has a dopaminergic activity,2 which also can explain its success in treating gynecological conditions (including PMS), many of which may be related to high prolactin levels. Dopamine and compounds of similar molecular structure inhibit prolactin secretion from the anterior pituitary. Increased prolactin inhibits corpus luteal development, thereby indirectly reducing the secretion of progesterone in the luteal phase of the menstrual cycle.

Therefore, chaste tree may increase progesterone by reducing prolactin secretion, rather than by increasing LH. Increased prolactin levels are associated with premenstrual mastalgia, corpus luteal insufficiency and infertility. In many cases, the hyperprolactinemia may not be constant and is referred to latent hyperprolactinemia, whereby prolactin is raised by stress and/or premenstrually.

This in vitro evidence of dopaminergic activity for chaste tree was supported by results of a randomized, placebo-controlled, double-blind study on 37 women with luteal phase defects due to latent hyperprolactinemia (LHP). With LHP, blood levels of prolactin may be only slightly raised, but there is an excessive response following IV injection of TRH (or to stress, etc., as noted above). The menstrual cycle is also abnormal: The luteal phase is much shorter, although the total length of the cycle is variable and can be normal. With chaste tree treatment, prolactin release after TRH injection was reduced significantly. Shortened luteal phases also were normalized and consequently, luteal phase progesterone deficiencies were corrected. There were no changes in any other hormones, except that luteal phase 17B-estradiol (i.e., estrogen) levels were higher in the chaste tree group. FSH and LH levels did not change. Two women receiving chaste tree became pregnant and PMS symptoms were reduced significantly in the chaste tree group.3


The diterpenes, rather than the flavonoids or iridoids, are thought to be responsible for the dopaminergic activity of chaste tree.


The active constituents thought to be responsible for the dopaminergic activity of chaste tree are the diterpenes (not the flavonoids [casticin] or the iridoids [agnuside]).4 New diterpenes are still being discovered, but to date, the most active of these are relatively nonpolar and probably cross the blood-brain barrier. If this is the case, chaste tree may be a beneficial adjunct in the treatment of patients with Parkinson's disease.

Implications for Autoimmune Diseases

Several autoimmune diseases have been linked to higher levels of prolactin in the blood, including systemic lupus erythematosus (SLE),5 rheumatoid arthritis (RA),6 Sjogren's syndrome7 and juvenile arthritis.8 For SLE, serum prolactin concentrations have been correlated with both clinical activity and remission.9 Studies on dopaminergic drugs such as bromocriptine suggest lowering elevated prolactin levels of pituitary origin can lead to clinical improvement in SLE,10 RA,11,12 psoriatic arthritis and Reiter's syndrome. (Prolactin also is produced peripherally in inflammatory diseases.) One study involving 79 patients with SLE, 23 with RA and 28 healthy controls, found significant elevations in approximately 40 percent of patients, in a pattern resembling LHP.13 In other words, the stress of taking the first blood sample significantly raised prolactin, which was lower in subsequent samples. This pattern was not observed in healthy controls.

New Research - Melatonin Release

Dioscorides, in his writing about chaste tree, stated: "It makes the menses come on earlier, detaches the embryo, attracts the milk, goes to your head and brings sleep." Although chaste tree is not commonly used to improve sleep, the results of a clinical trial published in 2003 may change this.14 In the open, placebo-controlled study, the effect of chaste tree administration on the circadian rhythm of melatonin secretion was measured. The 20 male participants were administered either placebo or one of three different doses of a chaste tree extract (corresponding to approximately 0.6-2.4 g/day of dried berries), given in divided doses three times daily.

Chaste tree caused a dose-dependent increase in melatonin secretion, especially during the night, when compared to placebo treatment. Total melatonin output was approximately 60-percent higher in the participants taking chaste tree and began approximately one hour after the lights were turned off. The authors observed that the promotion of sleepiness observed by some patients taking chaste tree during the trial might be a result of the stimulation of endogenous melatonin secretion.

Some Red Herrings

A number of investigative teams are examining chaste tree for possible estrogenic activity. One study identified the common fatty acid linoleic acid as an estrogenic compound from chaste tree15 and another identified the relatively common flavonoid apigenin as the most active phytoestrogen in this herb.16 Since these compounds are widely found in the plant kingdom, they can hardly explain the unique clinical applications of chaste tree recognized by most Western herbalists. No doubt this sort of research will lead to a mistaken belief among the misinformed that the therapeutic effects of chaste tree can be explained in terms of its possessing estrogenic properties.

Dosage Issues

The relevant dosage of chaste tree depends on the clinical application. Since herbal products come in various dosage forms, I would like to introduce the concept of dry herb equivalent (DHE) as a way of setting or comparing doses across these many forms. For example, for a 1:5 tincture (1 g dried herb extracted in 5 mL liquid), a DHE dose of 1 g is 5 mL. For a tablet containing 200 mg of a 5:1 concentrated dry extract, a DHE dose of 1 g is one tablet (or 200 mg of dry extract). For a capsule containing 500 mg of dried herb, a DHG dose of 1 g is two capsules (2 x 500 mg).

According to a survey of professional herbalists conducted in the U.K. in 1997, the average dose of chaste tree used was approximately 500 mg/day DHE.17 Clinical trials in PMS and mastalgia have used DHE of approximately 120 to 240 mg/day. For LHP, similar doses have been shown to be effective. However, doses used to influence melatonin levels were much higher (600 mg to 2.4 g DHE per day). Such doses can be used to treat insomnia, especially sleep maintenance insomnia. In conditions such as endometriosis and fibroids, for which a significant estrogen antagonist effect is needed, doses of at least 2 g/day DHE may be required and typically are used by professional herbalists. The use of chaste tree in the treatment of PCOS is controversial and may depend on the hormonal profile of each individual patient. It will be most indicated in cases in which prolactin is elevated and dosage will be influenced by the level of prolactin.

Acknowledgment: Thanks to Berris Burgoyne ND, for assisting with this article.


References

  1. Haller J. The effect of plant extracts on the hormonal interrelations between hypophysis and the ovary. An endocrinological study with animal experiments. Geburtshilfe Gynakol 1961;156:274-302.
  2. Sliutz G, et al. Horm Metab Res 1993;25(5):253-255. Cited in Mills S, Bone K. Principles and Practice of Phytotherapy: Modern Herbal Medicine. Churchill Livingstone, Edinburgh, 2000.
  3. Milewicz A, Gejdel E, Sworen H, et al. Vitex agnus castus - Extrakt zur Behandlung von Regeltempoanomalien infolge latenter Hyperprolaktinamie. Ergebnisse einer randomisierten Plazebo-kontrollierten Doppelblindstudie. Arzneim-Forsch 1993;43(7):752-756.
  4. Wuttke W, Jarry H, Christoffel V, et al. Phytomedicine 2003;10:348-357.
  5. Vera-Lastra O, Mendez C, Jara LJ, et al. Correlation of prolactin serum concentrations with clinical activity and remission in patients with systemic lupus erythematosus. Effect of conventional treatment. J Rheumatol 2003;30(10):2140-46.
  6. Ram S, Blumberg D, Newton P, et al. Raised serum prolactin in rheumatoid arthritis: genuine or laboratory artefact? Rheumatology (Oxford) 2004;43(10):1272-74.
  7. El Meidany YM, Ahmed I, Mooustafa H, et al. Hyperprolactinemia in Sjorgen's syndrome: a patient subset or a disease manifestation? Joint Bone Spine 2004;71(3):203-8.
  8. Picco P, Gattorno M, Buoncompagni A, et al. Interactions between prolactin and the proinflammatory cytokine network in juvenile chronic arthritis. Ann N Y Acad Sci 1999;876:262-65.
  9. Pacilio M, Migliaresi S, Meli R, et al. Elevated bioactive prolactin levels in systemic lupus erythematosus - association with disease activity. J Rheumatol 2001;28(10):2216-21.
  10. Walker SE. Bromocriptine treatment of systemic lupus erythematosus. Lupus 2001;10(10):762-8.
  11. Figueroa F, Carrion F, Martinez ME, et al. Effects of bromocriptine in patients with active rheumatoid arthritis. Rev Med Chil 1998;126(1):33-41.
  12. Mader R. Bromocriptine for refractory rheumatoid arthritis. Harefuah 1997;133(11):527-9
  13. Dostál C, Moszkorzová L, Musilová L, et al. Serum prolactin stress values in patients with systemic lupus erythematosus. Ann Rheum Dis 2003;62:487-488.
  14. Dericks-Tan JS, Schwinn P, Hildt C. Dose-dependent stimulation of melatonin secretion after administration of agnus castus. Experimental and Clinical Endocrinology & Diabetes 2003;111:44-46.
  15. 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.
  16. Jarry J, Spengler B, Porzel A, et al. Evidence of estrogen receptor B-selective activity of Vitex agnus-castus and isolated flavones. Planta Medica 2003;69:945-947.
  17. Christie S, Walker AF. Vitex agnus-castus L.: (1) A review of its traditional and modern therapeutic use: (2) Current use from a survey of practitioners. European Journal of Herbal Medicine 1997;3(3):29-45.
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