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Vitex agnus-castus

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)	No side effects over 8 weeks (6) No side effects over 3 months as compared to metformin (24)
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)
Strotan ® (each capsule contains 20 mg of VAC) (16)	No side effects observed with VAC (20 mg) over 3 months (16)

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
Dosing & administration	30 drops (as VAC extract – unspecified concentration) twice per day for 3 cycles
Outcomes	↓ breast pain intensity, mastalgia pain measured by VAS (10)(11)
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.