Ingredient review —Vitex agnus-castus
What is it?
Description
Vitex agnus-castus (VAC) is also commonly known as chaste tree or chasteberry. The plant’s main constituents include vitexin, casticin, agnuside, p-hydroxybenzoic acid, alkaloids, and diterpenoids. The fruit consists of flavonoids, terpenoids, neolignans, phenolic compounds, and glycerides. (20) Its main flavonoids include casticin, vitexin, and orientin. (8) Standardized extracts typically measure the iridoid or flavonoid content where aucubin (iridoid glycoside) or agnuside is used as the reference material. (9)
Main uses
Premenstrual syndrome
Regulation of hormonal balance
Formulations
Form
Safety
Agnolyt ® (100 g of tincture provides 9 g of VAC with 1:5 ratio. A capsule contains dried extract of VAC fruit [9.58–11,5 : 1] 3.5–4.2mg) (5)
Considered as safe with no serious adverse events; 12 of 85 patients reported mild GI distress, skin manifestations or headaches, while 5 reported similarly in B6 group (13)
Agnucaston ® - BNO 1095 (70% ethanol, 30% H2O extract; 4 mg of extract equivalent to 40 mg of dry weight (10:1 ratio) VAC) (2) (25)
No adverse events over 3 menstrual cycles (12)
Agnugol ® (3.2-4.8 mg dried fruit extract ) (6)
Prefemin® - Ze 440 (60% ethanol m/m, fruit extract ratio 6-12:1 standardized for casticin; 20 mg of extract equivalent to 120-240 mg of dry weight VAC) (22)
Equal instances (~5%) of reported adverse events between VAC (20 mg per day) and placebo groups with good tolerability over 3 cycles (22)
No serious adverse events with VAC (20 mg per day) over 3 cycles
(18)
20/50 reported 37 adverse events, none serious in nature (20 mg per day) over 8 cycles (3)
Physicians suspected adverse events in 1% of patients with no serious effects. 94% of patients describe tolerance as good or very good (14)
Dosing & administration
Bone fractures
General outcomes from A-level evidence
No data currently available.
Dosing & administration
4 mg (as Agnugol® dried fruit extract) per day for 8 weeks
Outcomes
alkaline phosphatase, serum VEGF (6)
Class of evidence
b
Cyclical mastalgia
General outcomes from A-level evidence
No data currently available.
Dosing & administration
3.2–4.8 mg (as dried fruit extract) for two months
Outcomes
breast pain intensity and length (days) in VAC and placebo, but significantly greater extent in VAC (17)
Class of evidence
b
Hyperprolactinemia
General outcomes from A-level evidence
No data currently available.
Dosing & administration
20 mg (as Strontan®) per day for 3 months
Outcomes
prolactin release
luteal phase: to normal length, progesterone synthesis, 17 beta-estradiol (16)
Class of evidence
c
Polycystic ovarian syndrome (PCOS)
General outcomes from A-level evidence
No data currently available.
Dosing & administration
One capsule (as standardized fruit extract to 2, 1-3 and 3 mg of aucubin) per day for 3 months
Outcomes
serum DHEA-S; normalized 60% of participants’ (with oligomenorrhea or amenorrhea) menstrual cycle duration (7)
Class of evidence
b
Postmenopausal hot flashes
General outcomes from A-level evidence
No data currently available.
Dosing & administration
40 drops per day (as standardized extract - unspecified concentration) for 8 weeks
Outcomes
frequency of hot flashes (1)
Class of evidence
b
Premenstrual syndrome (PMS)
General outcomes from A-level evidence
No data currently available.
Dosing & administration
20 mg tablet (as ZE 440 fruit extract) per day for 3 cycles
Outcomes
visual analog scale (VAS) compared with placebo (22)
Class of evidence
b
Dosing & administration
8 mg, 20 mg or 30 mg (as ZE 440 fruit extract) per day for 3 cycles
Outcomes
total symptom score. 30 mg did not improve effects observed in 20 mg (23)
Class of evidence
b
Dosing & administration
40 mg (as BNO 1095 extract) per day for 3 cycles
Outcomes
PMSD score, PMTS score (12)
*note: 50% placebo effect
Class of evidence
b
Dosing & administration
40 mg (as BNO 1095 extract) per day for 3 cycles
Outcomes
PMSD score, negative affect score & water retention score (15)
Class of evidence
b
Dosing & administration
40 drops (extract added to fruit juice - unspecified concentration) per day for 6 days prior to menstruation for 6 cycles
Outcomes
mean VAS in VAC and placebo, but to a significantly greater extent by VAS (26)
Class of evidence
b
Adverse effects
Vitex agnus-castus does not pose serious health risks and is considered safe. However, it is recommended that pregnant and lactating women avoid its use due to limited safety data in these states. Commonly reported side effects include nausea, headache, gastrointestinal disturbances, menstrual disorders, acne, pruritus, and erythematous rash. However, these side effects are mild and reversible. (4)(5)
Pharmacokinetics
The pharmacokinetics of VAC have been scarcely studied.
Absorption
- In mice, the oral bioavailability of agnuside was 0.7% with peak plasma concentrations achieved within 30-45 minutes of administration. (21)
- In vitro, BNO 1095 (a VAC extract) solubility and permeability was improved once it was nano-emulsified, suggesting the possibility for improved bioavailability. (19)
Distribution
- In mice, agnuside was found in the highest amounts in the intestine, kidney, liver, spleen, brain, lungs and heart. (21)
Metabolism
- No data is currently available.
Excretion
- No data is currently available.
References
- Abbaspoor, Z. (2011). Effect of Vitex agnus-castus on menopausal early symptoms in postmenopausal women: A randomized, double blind, placebo –controlled study. British Journal of Medicine and Medical Research,1(3), 132-140. ()
- Bachman, C. (2011). Mönchspfeffer bei prämenstruellem syndrom. Fortbildung,25-26. Retrieved from https://www.rosenfluh.ch/media/arsmedici-dossier/2011/10/Moenchspfeffer_bei_PMS.pdf. ()
- Berger, D., Schaffner, W., Schrader, E., Meier, B., & Brattström, A. (2000). Efficacy of Vitex agnus castus L. extract Ze 440 in patients with pre-menstrual syndrome (PMS). Archives of Gynecology and Obstetrics,264(3), 150-153. ()
- Carmichael, A. R. (2008). Can Vitex agnus castus be used for the treatment of mastalgia? What Is the current evidence? Evidence-Based Complementary and Alternative Medicine,5(3), 247-250. ()
- Daniele, C., Coon, J. T., Pittler, M. H., & Ernst, E. (2005). Vitex agnus castus: A systematic review of. adverse events. Drug Safety,28(4), 319-332. ()
- Eftekhari, M. H., Rostami, Z. H., Emami, M. J., & Tabatabaee, H. R. (2014). Effects of “vitex agnus castus” extract and magnesium supplementation, alone and in combination, on osteogenic and angiogenic factors and fracture healing in women with long bone fracture. Journal of Research in Medical Sciences,19(1), 1-7. ()
- Ghahremaninasab, P. , Shahnazi, M., Khalili, A. F., & Hamdi, K. (2016). The effects of combined low-dose oral contraceptives and Vitex agnus on the improvement of clinical and paraclinical parameters of polycystic ovarian syndrome: A triple-blind, randomized, controlled clinical trial. Iranian Red Crescent Medical Journal,18(12). ()
- Hajdú, Z., Hohmann, J., Forgo, P., Martinek, T., Dervarics, M., Zupkó, I., . . . Máthé, I. (2007). Diterpenoids and flavonoids from the fruits of Vitex agnus-castus and antioxidant activity of the fruit extracts and their constituents. Phytotherapy Research,21(4), 391-394. ()
- Hajimehdipoor, H., Shekarchi, M., Hamedani, M. P., Abedi, Z., Zahedi, H., Shekarchi, M., & Gohan, A. R. (2011). A Validated HPTLC-Densitometric Method for Assay of Aucubin in Vitex agnus-castus L. Iranian Journal of Pharmaceutical Research, 10(4), 705-710. ()
- Halaska, M., Beles, P., Gorkow, C., & Sieder, C. (1999). Treatment of cyclical mastalgia with a solution containing a Vitex agnus castus extract: Results of a placebo-controlled double-blind study. Ceska Gynekologie,8(4), 175-181. ()
- Halaska, M., Raus, K., Beles, P., Martan, A., & Paithner, K. G. (1998). Treatment of cyclical mastalgia using an extract of Vitex agnus castus extract: Results of a double-blind comparison with a placebo. Ceska Gynekologie,63(5), 388-392. ()
- He, Z., Chen, R., Zhou, Y., Geng, L., Zhang, Z., Chen, S., . . . Lin, S. (2009). Treatment for premenstrual syndrome with Vitex agnus castus: A prospective, randomized, multi-center placebo controlled study in China. Maturitas,63(1), 99-103. ()
- Lauritzen, C., Reuter, H., Repges, R., Böhnert, K., & Schmidt, U. (1997). Treatment of premenstrual tension syndrome with Vitex agnus castus controlled, double-blind study versus pyridoxine. Phytomedicine, 4(3), 183-189. ()
- Loch, E., Selle, H., & Boblitz, N. (2000). Treatment of premenstrual syndrome with a phytopharmaceutical formulation containing Vitex agnus castus. Journal of Womens Health & Gender-Based Medicine, 9(3), 315-320. ()
- Ma, L., Lin, S., Chen, R., & Wang, X. (2010). Treatment of moderate to severe premenstrual syndrome with Vitex agnus castus (BNO 1095) in Chinese women. Gynecological Endocrinology,26(8), 612-616. ()
- Milewicz, A., Gejdel, E., Sworen, H., Sienkiewicz, K., Jedrzejak, J., Teucher, T., & Schmitz, H. (1993). Vitex agnus castus extract in the treatment of luteal phase defects due to latent hyperprolactinemia. Results of a randomized placebo-controlled double-blind study. Arzneimitell-Forschung, 43(7), 752-756. ()
- Mirghafourvand, M., Mohammad-Alizadeh-Charandabi, S., Ahmadpour, P., & Javadzadeh, Y. (2015). Effects of Vitex agnus and Flaxseed on the menstrual bleeding: A randomized controlled trial. Journal of Zanjan University of Medical Sciences and Health Services,23(100), 90-95. ()
- Momoeda, M., Sasaki, H., Tagashira, E., Ogishima, M., Takano, Y., & Ochiai, K. (2014). Efficacy and safety of Vitex agnus-castus extract for treatment of premenstrual syndrome in japanese patients: A prospective, open-label study. Advances in Therapy, 31(3), 362-373. ()
- Piazzini, V., Monteforte, E., Luceri, C., Bigagli, E., Bilia, A. R., & Bergonzi, M. C. (2017). Nanoemulsion for improving solubility and permeability of Vitex agnus-castus extract: Formulation and in vitro evaluation using PAMPA and Caco-2 approaches. Drug Delivery,24(1), 380-390. ()
- Rafieian-Kopaei, M., & Movahedi, M. (2017). Systematic review of premenstrual, postmenstrual and infertility disorders of Vitex agnus castus. Electronic Physician,9(1), 3685-3689. ()
- Ramakrishna, R., Bhateria, M., Singh, R., Puttrevu, S. K., & Bhatta, R. S. (2016). Plasma pharmacokinetics, bioavailability and tissue distribution of agnuside following peroral and intravenous administration in mice using liquid chromatography tandem mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis,125, 154-164. ()
- Schellenberg, R. (2001). Treatment for the premenstrual syndrome with agnus castus fruit extract: Prospective, randomised, placebo controlled study. Bmj,322(7279), 134-137. ()
- Schellenberg, R., Zimmermann, C., Drewe, J., Hoexter, G., & Zahner, C. (2012). Dose-dependent efficacy of the Vitex agnus castus extract Ze 440 in patients suffering from premenstrual syndrome. Phytomedicine,19(14), 1325-1331. ()
- Shayan, A., Masoumi, S. Z., Shobeiri, F., Tohidi, S., & Khalili, A. (2016). Comparing the effects of agnugol and metformin on oligomenorrhea in patients with polycystic ovary syndrome: A randomized clinical trial. Journal Of Clinical And Diagnostic Research,10(12), QC13-QC16. ()
- Wuttke, W., Jarry, H., Christoffel, V., Spengler, B., & Seidlová-Wuttke, D. (2003). Chaste tree (Vitex agnus-castus) – Pharmacology and clinical indications. Phytomedicine,10(4), 348-357. ()
- Zamani, M., Neghab, N., & Torabian, S. (2012). Therapeutic effect of Vitex agnus castus in patients with premenstrual syndrome. Acta Medica Iranica,50(2), 101-106. ()