Reviewed: Eftekhari MH, Rostami ZH, Emami MJ, Tabatabaee HR. 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. J Res Med Sci. January 2014;19(1):1-7.
Broken or fractured bones are a common injury, but complications may delay the healing process. Vascular endothelial growth factor (VEGF) has been shown to induce angiogenesis (i.e., increased blood circulation to a tissue or organ), which may facilitate bone repair. Chaste tree (Vitex agnus-castus, Lamiaceae) fruit has been used traditionally for female reproductive system problems,1,2 and recent in vivo research indicates that it may aid bone healing as well. This randomized, double-blind, placebo-controlled trial investigated the impact of chaste tree and magnesium (an essential mineral for bone formation and repair) supplementation on premenopausal women with long bone fractures.
In total, 64 women (aged 20 to 45 years) who received surgical treatment for their fractures were enrolled in the study. Patients were excluded if they were pregnant or lactating, smokers, postmenopausal, had a chronic disease, used alcohol, were taking pharmaceuticals to speed bone healing, or using diuretics, hormones, vitamins, minerals, or botanical supplements known to contain phytoestrogens.
The eight-week treatment consisted of 4 mg/day dried chaste tree fruit extract (Agnugol; Goldaru Pharmacy Company; Isfahan, Iran), 250 mg/day magnesium oxide (Nature Made®; Pharmavite, LLC; Mission Hills, California), or placebo (two forms of placebo were given to match the Agnugol capsules and the magnesium tablets; both consisted of lactose, starch, and “maintaining substances,” procured from the Shiraz University of Medical Sciences School of Pharmacy; Shiraz, Iran). The authors did not provide an adequate description of the extract, but the manufacturer’s website states that each Agnugol tablet contains 3.2 to 4.8 mg V. agnus-castus dried extract, equivalent to 0.42 to 0.58 mg aucubin.
Included patients were assigned randomly to one of four groups. Group one received chaste tree and magnesium, group two received chaste tree and placebo, group three received magnesium and placebo, and group four received both placebos. Compliance was assessed every two weeks by phone, and those who did not take the treatment for more than six days were excluded.
At baseline, fracture history was taken, and participants’ pre-fracture exercise levels were assessed as light, moderate, or severe. A food frequency questionnaire (FFQ) was used to assess nutritional intake, with phytoestrogen intake rated as high (twice per day), moderate (two to seven times per week), or low (once per week to once per month). Fasting blood samples were collected at the beginning and end of the study to assess VEGF and serum levels of the osteogenesis markers alkaline phosphatase (ALP) and osteocalcin (OCN). Also, at baseline and endpoint, participants were X-rayed to detect and measure the formation of calluses, an indication of fracture healing.
Of the 64 patients enrolled, 51 finished the protocol. In group one, six patients were excluded due to non-compliance, loss to follow-up, or transportation problems. In group two, one patient was lost to follow-up; in group three, four patients were excluded due to non-compliance, loss to follow-up, or personal causes; and in group four, two patients were excluded for non-compliance or transportation issues. Despite these issues, overall compliance in the trial was 95.45%.
The participants’ fractures were caused by accidents (62.7%) or falls (37.3%). The fractures occurred in the tibia (52.9%), femur (25.5%), humerus (13.7%), and radius and ulna (7.8%). There were no significant differences among groups in age, fracture etiology, location of fracture, or consumption of phytoestrogens, magnesium, calcium, zinc, or vitamins C, D, and K.
The total change in ALP concentration from baseline to endpoint was not significantly different among groups; however, in group two (chaste tree and placebo), the increase in ALP concentration approached significance (P=0.05). Osteocalcin levels were significantly higher in group one (chaste tree and magnesium) as compared to groups two and four (P=0.01). Although there were no significant differences in VEGF changes among groups, VEGF significantly increased in group two from baseline to endpoint (P=0.01). The average callus formation was 80.0% for group one, 71.4% for group two, 50.0% for group three, and 53.5% for group four, but the differences among groups were not significant. No adverse effects were reported.
Overall, participants consuming chaste tree extract alone or with magnesium had significant changes in VEGF and OCN levels respectively, suggesting the potential use of this botanical to promote bone fracture healing. The authors hypothesize that these effects may be due to the phytoestrogens present in chaste tree, although the potency of these phytoestrogens has been disputed2 and was not measured in the extract tested. As some endpoints approached significance, the authors speculate that dosage may be an important factor. Further study is needed to confirm the efficacy of chaste tree extract for treating bone fractures and to assess the contribution of its different constituents.
—Amy C. Keller, PhD
- Blumenthal M, Goldberg A, Brinckmann J, eds. Herbal Medicine: Expanded Commission E Monographs. Austin, TX: American Botanical Council and Newton, MA: Integrative Medicine Communications; 2000.
- Upton R, ed. Chaste Tree Fruit (Vitex agnus-castus). Scotts Valley, CA: American Herbal Pharmacopoeia; 2001.