Therapeutic response to mechanical compression for chronic venous insufficiency is often less than expected because of poor compliance. For this reason, an oral therapy would be desirable. Horse-chestnut seed extract has been studied mainly in Europe as a possible oral therapy for chronic venous insufficiency. It may work by preventing leukocyte activation, which is considered a pathophysiologic mechanism of chronic venous insufficiency. Pittler and Ernst conducted a literature review to evaluate the evidence for or against the use of this compound for venous insufficiency.

The authors found 13 randomized controlled trials of horse-chestnut seed extract: eight were placebo-controlled trials and five were controlled against reference medications. The number of subjects in the placebo-controlled trials ranged from 20 to 226, and the studies lasted from 20 days to eight weeks. In the five trials controlled against reference medications, the size of the studies ranged from 30 to 240 subjects, and the studies lasted from four to 12 weeks.

The findings of the placebo-controlled trials suggested that treatment with horse-chestnut seed extract produced a decrease in lower-leg volume and calf and ankle circumference. Edema provocation before and after the treatment period revealed protective effects against edema. One study demonstrated a 22 percent decrease in the capillary filtration rate in patients who received horse-chestnut seed extract. Similarly, all five of the randomized control trials against reference medications demonstrated evidence for the effectiveness of horse-chestnut seed extract in the treatment of chronic venous insufficiency. One trial that compared the herbal medication to compression stockings suggested a therapeutic equivalence, but the authors noted that this trial was not properly blinded, so bias may have affected the results.

Data from the studies showed that therapeutic benefit was derived from doses of horse-chestnut seed extract standardized to 100 to 150 mg of escin daily. (Escin is the active component of the extract.) In two of the placebo-controlled studies, daily doses of 100 mg of escin resulted in a significant reduction in the mean leg volume after two weeks of therapy. In another study, the effects of treatment were noted to persist: at the end of a six-week follow-up period the mean leg volume was not significantly different from that immediately after treatment.

The authors note that many experts remain skeptical about the effectiveness of horse-chestnut seed extract for chronic venous insufficiency. Most of the studies the authors analyzed were from German investigators. Further trials are needed. If further studies substantiate the benefits of horse-chestnut seed extract, its postulated mechanism of action might generate interest in other forms of drug therapy. Escin has been shown in vitro to inhibit the activity of elastase and hyaluronidase. Both of these substances are involved in enzymatic proteoglycan degradation, which is part of the capillary endothelium and the main component of the extravascular matrix. Horse-chestnut seed extract may prevent vascular leakage by shifting the equilibrium between the degradation and synthesis of proteoglycans.