Alternate Names/Supplement Forms:
• Buckeye; Spanish Chestnut
Approach to the Patient
Standardized horse chestnut seed extract (HCSE) has been tested as a treatment for chronic venous insufficiency (CVI) in several double-blind, placebo-controlled trials conducted from the 1970s through the present.
Reasonably good evidence indicates that HCSE reduces objective measurements of lower leg edema and capillary leakage, and subjective complaints of pain, swelling, feelings of heaviness, fatigue, nocturnal calf spasms, and itching appear to improve as well. There is as yet no evidence that horse chestnut improves existing visible varicosities, although many patients may use horse chestnut for this purpose.
Like other treatments for venous insufficiency, such as oxerutins and diosmin/hesperidin, HCSE is thought to work by decreasing capillary leakage. HCSE appears to be safe when taken appropriately, and exhibits only minor side effects.
Many products marketed for venous insufficiency contain several supplements combined, each at an inadequate dose. Your patients may do better using a single-substance product that provides the dose found effective in double-blind trials. (See the article on Venous Insufficiency (Chronic) for several reasonably well-documented options.)
The use of raw horse chestnut is not safe; only properly prepared, enteric-coated extracts should be used.
Use of oral HCSE in patients with renal or hepatic dysfunction should be approached with caution.
(Higher numbers indicate stronger evidence; X modifier indicates contradictory results. See the Introduction for details of the rating scale.)
Chronic Venous Insufficiency +3
At least seven studies involving a total of almost 500 individuals have compared horse chestnut to placebo in the treatment of venous insufficiency. 1–7 In general, the results indicate that HCSE reduces leg volume and improves subjective symptoms such as pain and itching.
A 12-week, partially blinded study of 240 patients compared HCSE to placebo and compression stockings (use of the stockings could not be blinded). 8 The results showed that HCSE was just as effective as compression stockings, and superior to placebo.
Other Proposed Uses
Like other capillary stabilizers, horse chestnut or escin alone is sometimes used for edema following injuries such as sprains or surgery, 9 as well as for the treatment of hemorrhoids. In addition, based on its coumarin content, horse chestnut is sometimes administered along with standard therapy for phlebitis.
Mechanism of Action
The mechanism underlying the antiexudative actions of HCSE has been proposed to be related to reduced capillary permeability, a tonic effect on veins, inhibition of lysosomal glycosaminoglycan hydrolases involved in collagen breakdown, antiinflammatory activity, and increased activity of prostaglandins involved in venous contraction. 8
It has been suggested that the active constituent escin inhibits the hypoxia-induced activation of endothelial cells and the subsequent increased adherence of neutrophils. 13 Escin (250 ng/ml) was shown to strongly inhibit the adherence of neutrophil-like HL60 cells to hypoxic venous endothelium but not to normoxic venous endothelium. Adherence of activated neutrophils may lead to alterations in the venous wall related to what occurs in CVI. The clinical significance of these findings and others in vitro and animal studies is, of course, difficult to ascertain.
The most common dosage of HCSE in reported clinical trials is 300 mg standardized to 50 mg escin, given twice daily in a delayed-release formulation. The best HCSE preparations certify that the toxic substance esculin has been removed. Enteric formulations must be used to prevent gastrointestinal upset. See the Appendix for U.S. brand names of clinically tested products.
The saponins in horse chestnut extract irritate the gastrointestinal tract. This is the rationale for using controlled-release products, which reduce incidence of irritation to below 1%, even at higher doses. 8 Calf cramps and pruritis are occasionally reported. Pulse and blood pressure are not affected, even in long-term treatment.
Whole horse chestnut is classified as an unsafe herb by the FDA. Poisoning by ingestion of the nuts or a tea made from the leaves and twigs is characterized by nausea, vomiting, diarrhea, salivation, headache, hemolysis, convulsions, and circulatory and respiratory failure possibly leading to death. 14 However, typical European standardized extract formulations remove the most toxic substances (i.e., esculin) and standardize the quantity of escin.
Acute oral toxicity of HCSE and escin has been studied in several animal species. The “no effect” dose is approximately 8 times higher than the recommended human dose. Mutagenic and carcinogenic studies have not been published. 15
Use of oral HCSE in patients with renal or hepatic dysfunction should be approached with caution, as renal toxicity after high-dose oral escin has been reported. 16 In addition, acute renal failure has occurred in patients receiving intravenous escin at doses greater than 20 mg to prevent and treat postsurgical edema. 17 Drugs that displace escin from plasma-protein binding sites may also increase its nephrotoxic potential. 18
Hepatotoxicity and shock were reported in a patient receiving an intramuscular injection of an HCSE product, 19 but there are no reports of such events involving oral HCSE products.
Safety in Young Children and Pregnant or Lactating Women
Two trials reported use of HCSE in pregnancy-related varicose veins, with good tolerability. 4 However, as no formal safety evaluations have been reported, compression stockings should be recommended for pregnant women before HCSE.
Animal studies to date have not shown embryotoxicity or teratogenicity. 15
Maximum safe dosages for lactating women or young children have not been established.
Coumarins in HCSE could interfere with anticoagulant therapy; however, this has not been reported to date.
Escin is known to bind to plasma proteins and may thus compete with or displace drugs that are highly protein-bound. Drugs that displace escin from plasma-protein binding sites may also increase its nephrotoxic potential. 18
1. Bisler H, Pfeifer R, Kluken N, et al. Effects of horse-chestnut seed extract on transcapillary filtration in chronic venous insufficiency. Dtsch Med Wochenschr. 1986;111:1321-1329.
2. Lohr E, Garanin G, Jesau P, et al. Anti-edemic therapy in chronic venous insufficciency with tendency to formation of edema [translated from German]. MMW Munch Med Wochenschr. 1986;128:579-581.
3. Rudofsky G, Neiss A, Otto K, et al. Antiedematous effects and clinical effectiveness of horse chestnut seed extract in double blind studies [translated from German]. Phlebol Proktol. 1986;15:47-54.
4. Steiner M, Hillemanns HG. Investigation of the anti-edemic efficacy of Venostasin® retard [translated from German]. MMW Munch Med Wochenschr. 1986;128:551-552.
5. Diehm C, Vollbrecht D, Amendt K, Comberg HU. Medical edema protection—clinical benefit in patients with chronic deep vein incompetence. A placebo controlled double blind study. Vasa. 1992;21:188-192.
6. Friederich HC, Vogelsberg H, Neiss A. Evaluation of internally effective venous drugs [translated from German]. Z Hautkr. 1978;53:369-374.
7. Neiss A, Bohm C. Proof of the efficacy of horse chestnut seed extract in the treatment of varicose syndrome [translated from German]. MMW Munch Med Wochenschr. 1976;118:213-216.
8. Diehm C. The role of oedema protective drugs in the treatment of chronic venous insufficiency: a review of evidence based on placebo-controlled clinical trials with regard to efficacy and tolerance. Phlebology. 1996;11:23-29.
9. Wilhelm K, Feldmeier C. Thermometric investigations about the efficacy of Beta-escin to reduce postoperative edema [in German; English abstract]. Med Klin. 1977;72:128-134.
10. Hitzenberger G. The therapeutic effectiveness of chestnut extract [translated from German]. Wien Med Wochenschr. 1989;139:385-389.
11. Kreysel HW, Nissen HP, Enghofer E. A possible role of lysosomal enzymes in the pathogenesis of varicosis and the reduction in their serum activity by Venostasin®. Vasa. 1983;12:377-382.
12. Newall CA, Anderson LA, Phillipson JE. Herbal Medicines: A Guide for Health-Care Professionals. London, England: The Pharmaceutical Press; 1996:166-167.
13. Bougelet C, Roland IH, Ninane N, et al. Effect of aescine on hypoxia-induced neutrophil adherence to umbilical vein endothelium. Eur J Pharmacol. 1998;345:89-95.
14. Chandler RF. Horse chestnut. Can Pharm J. 1993;126:297-300, 306.
15. Hansel R, Keller K, Rimpler H, et al. Hagers Handbuch der Pharmazeutischen. Band 5: Drogen E-O. Berlin, Germany: Springer Verlag; 1993:108-122.
16. Grasso A, Corvaglia E. Two cases of suspected toxic tubulonephrosis due to escine [in Italian; English abstract]. Gazz Med Ital. 1976;135:581-584.
17. Reynolds JE, ed. Martindale: The Extra Pharmacopeia. 29th ed. London, England: The Pharmaceutical Press; 1989:1539-1540.
18. Rothkopf M, Vogel G, Lang W, et al. Animal experiments on the question of the renal toleration of the horse chestnut saponin aescin. Arzneimittelforschung. 1977;27:598-605.
19. Takegoshi K, Tohyama T, Okuda K, et al. A case of Venoplant-induced hepatic injury. Gastroenterol Jpn. 1986;21:62-65.
20. Alter H. Drug therapy of varicosis [translated from German]. Z Allgemeinmed. 1973;49:1301-1304.
21. Koch R. Comparative study of Venostasin and Pycnogenol in chronic venous insufficiency. Phytother Res. 2002;16 Suppl 1:S1-5.
Last reviewed September 2002 by EBSCO CAM Review Board
Please be aware that this information is provided to supplement the care provided by your physician. It is neither intended nor implied to be a substitute for professional medical advice. CALL YOUR HEALTHCARE PROVIDER IMMEDIATELY IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with any questions you may have regarding a medical condition.
Copyright (C) 2011 EBSCO Publishing. All rights reserved.