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Horse Chestnut

Plant Part Used

Seed

Active Constituents

Saponins (including aescin or escin), coumarin glycosides (aesculin and aesculetin), condensed tannins (proanthocyanidins).(1),(2)

[span class=alert]This section is a list of chemical entities identified in this dietary supplement to possess pharmacological activity. This list does not imply that other, yet unidentified, constituents do not influence the pharmacological activity of this dietary supplement nor does it imply that any one constituent possesses greater influence on the overall pharmacological effect of this dietary supplement.[/span]

Introduction

The horse chestnut tree was introduced into Northern Europe from the Near East in the sixteenth century. The French used extracts of horse chestnut seed for the treatment of hemorrhoidal problems as early as the 1800's. Germany has been using extracts of horse chestnut seed for chronic venous insufficiencies for a few decades with great success, and it’s actually one of the most prescribed pharmaceuticals in Germany. Also, in Germany prescriptions for oral, standardized horse chestnut seed extract are written more than any other anti-edema venous agent.(3)

Interactions and Depletions

Interactions

Dosage Info

Dosage Range

300mg (standardized extract), 1-2 times a day, 1/2 hour before or 1 hour after meals.

Topically: Apply a 2% escin gel, 1-2 times daily to affected area(s).

Most Common Dosage

300mg (standardized extract), 2 times a day, 1/2 hour before or 1 hour after meals.

Topically: Apply a 2% escin gel, 2 times daily to affected area(s).

Standardization

[span class=doc]Standardization represents the complete body of information and controls that serve to enhance the batch to batch consistency of a botanical product, including but not limited to the presence of a marker compound at a defined level or within a defined range.[/span]

The most current available medical and scientific literature indicates that this dietary supplement should be standardized to 50mg triterpene glycosides, calculated as anhydrous escin (16%).

Uses

Frequently Reported Uses

  • Varicose Veins
  • Venous Insufficiencies Or Enlarged Veins
  • Improves Capillary Fragility And Permeability
  • Leg Fatigue, Lower Extremity Edema
  • Deep Vein Thrombosis

Other Reported Uses

  • Hemorrhoids
  • Soft Tissue Injuries
  • Decreases Platelet Aggregation, Improves Blood Flow

Toxicities & Precautions

General

Generally well-tolerated in recommended dosages.(4)

Do not apply topical extracts to broken skin.

Health Conditions

Based on pharmacology, individuals with kidney or liver problems should not take horse chestnut.(4)

Based on pharmacology, use with caution in individuals with bleeding disorders.(5)

Due to the possibility that standardized horse chestnut seed extract may increase the absorption of magnesium, use with caution in patients with hypermagnesemia.(6)

Side Effects

May cause minor side effects, such as stomach upset or rash in rare uses.(7)

Pregnancy/ Breast Feeding

If pregnant or nursing, consult a physician before use.

Age Limitations

Do not use in children under 2 years of age unless recommended by a physician.

Pharmacology

Venous Insufficiency

Over the past few decades, a number of studies have been done to test the efficacy of horse chestnut in the treatment of chronic venous insufficiencies, most performed in Germany.(8),(9) Many of the trials were objectively measured by the volume reduction in the leg, as well as subjectively, in the treatment of such symptoms as pain, tiredness, tension and swelling in the leg, itching, and the tendency towards edema. Horse chestnut seed extract is reported to be useful for the treatment or prevention of venous insufficiency.(10),(11),(12),(31)

The saponins of the horse chestnut extract (aescin) are hemolytic and can be toxic when injected, but when ingested orally, they are harmless and often aid the absorption of other constituents. Aescin, also written as escin, is the saponin constituent comprised of b-escin and a-escin fractions with effects on the vascular system.(13) It is reported to be 100 times more powerful than the bioflavonoids as an anti-inflammatory, and reduces local edema by reducing capillary permeability to water, thereby decreasing the flow of fluid into intercellular spaces.(14) Other mechanisms proposed regarding the anti-exudative actions of horse chestnut seed extract include a tonic effect on veins, inhibition of lysosomal glycosaminoglycan hydrolases involved in collagen breakdown, and increased activity of prostaglandins involved in venous contraction.(15),(16) The coumarin glycosides (aesculin and aesculetin) may improve lymphatic drainage, decrease edema, and act as an anti-inflammatory.(17) However, aesculin is commonly removed in most European horse chestnut seed products. Oral doses reportedly slow the onset of platelet coagulation, but it is not a true anticoagulant because bleeding and prothrombin times do not change; however use with caution.(18)

Several clinical studies have been reported in the literature regarding the effectiveness of standardized preparations of horse chestnut seed extract in chronic venous insufficiencies using human subjects.(3) The effect of a standardized horse chestnut seed extract was assessed in a randomized placebo-controlled crossover double-blind trial of 22 patients with proven chronic venous insufficiency by measuring the capillary filtration coefficient and the intravascular volume of the lower leg by venous-occlusion plethysmography.(19) Three hours after taking two capsules of a standardized preparation (600 mg; each capsule containing 50 mg aescin), the capillary filtration coefficient had decreased by 22%, whereas after administration of a placebo capsule it rose slightly over three hours. The difference in the effect of standardized horse chestnut seed extract and placebo is statistically significant. The authors concluded that a standardized preparation of horse chestnut seed has an inhibitory effect on edema formation via a decrease in transcapillary filtration and thus improves edema-related symptoms in venous diseases of the legs.

A case observation study involving over 800 general practitioners and more than 5,000 patients with chronic venous insufficiency who were treated with standardized horse chestnut seed extract showed that horse chestnut may be considered an economical alternative to compression stocking therapy.(20) In a randomized placebo controlled parallel double blind study on 40 patients suffering from venous edema in chronic deep vein incompetence, the edema-reducing effect of horse chestnut seed extract was compared to placebo.(21) The horse chestnut seed extract was effective in reducing edema in everyday situations (in movement as well as on sitting or standing), and may be a useful adjunct to compression therapy. However, another study determined that an extract of horse chestnut seed was inferior to compression stocking, although the compression stocking in the study was not superior to placebo.(22)

A criteria based, systematic review performed in 1998 assessed the effectiveness of horse-chestnut seed extract (HCSE) as a symptomatic treatment of chronic venous insufficiency.(23) Double-blind, randomized controlled trials of oral HCSE for patients with chronic venous insufficiency were included, where the HCSE was reported by all placebo-controlled studies to be effective. The therapeutic usefulness of HCSE includes a decrease of the lower-leg volume and a reduction in leg circumference at the calf and ankle, along with decreasing symptoms such as leg pain, pruritus, and a feeling of fatigue and tenseness. Five comparative trials against the reference medication indicate that HCSE and O-(beta-hydroxyethyl)-rutosides (commonly used in Europe for the treatment of venous insufficiency) are equally effective. Adverse effects were found to be usually transient and infrequent. The authors concluded that the data found in these studies report that HCSE is superior to placebo and as effective as reference medications in alleviating the objective signs and subjective symptoms of chronic venous insufficiency.

A horse chestnut seed gel product containing 2% escin was successful in a recent non-controlled multi-center trial for six weeks on 71 patients with chronic venous insufficiency and edema.(24) Ankle circumference was reduced by a statistically significant 0.7 cm and the symptoms score was reduced by approximately 60% as determined by physicians and patients.

A study examined a mixture of the saponin fraction (escins) isolated from horse chestnut seed on magnesium absorption from the gastrointestinal tract in laboratory mice.(25) Samples were fed orally to fasted mice before loading of MgSO4 (10 mL/kg, p.o.). The saponin fraction (12.5-100 mg/kg) significantly enhanced the magnesium absorption 30, 60, 120 and 240 min after administration, with maximum enhancement by 48.3% at 50 mg/kg. Pretreatment of the animals with insulin or indomethacin did not reduce the effects. The authors concluded that the results may imply that neither the sympathetic nervous system nor endogenous inhibition of prostaglandins is involved, and that the involvement of the parathyroid hormone and/or the metabolism of vitamin D should be considered as a mechanism of increasing magnesium absorption. A more recent study by the authors reported that nitric oxide formation may play an important role in the mechanism of escins on magnesium absorption.(6) It remains to be studied clinically if standardized horse chestnut seed extract has this effect on magnesium absorption.

A 2006 Cochrane Database System review of clinical trials using horse chestnut seed extract (HCSE) for chronic venous insufficiency (CVI) found that overall there appears to be an improvement in CVI related signs and symptoms with HCSE compared with placebo.(32) One trial reviewed in the study indicated that HCSE may be as effective as treatment with compression stockings.

Clinical studies also support the use of HSCE in the treatment of venous leg ulcers when combined with conventional therapies.(33)

Other Uses

The saponins contained in horse chestnut seed have been reported in laboratory animal studies to be inhibitory on gastric emptying and accelerate gastrointestinal transit times.(26) The method of the effects of gastric emptying inhibition was determined to involve the capsaicin-sensitive sensory nerves, the central nervous system (involvement of dopamine and dopamine receptors), and endogenous prostaglandins (PG's).(27) Another study reported that nitrous oxide formation and prostaglandin inhibition may be involved in acceleration of the gastrointestinal tract transit.(28) Some of the saponin compounds inhibited glucose absorption by suppressing the transfer of glucose from the stomach to the small intestine and by inhibiting the glucose transport system at the small intestinal brush border.(29)

Beta-escin has been reported in laboratory studies to have anti-cancer effects, inducing apoptosis and decreasing cell proliferation in various human cancer cell lines.(34),(35)

A 3% escin horse chestnut gel formulation was applied topically to the skin around the eye three times daily for nine weeks to 40 healthy female volunteers.(36) After six weeks, significant decreases in the wrinkle scores at the corners of the eye or in the lower eyelid skin were observed compared with controls. After nine weeks, similar results were obtained, suggesting a potential use of topical horse chestnut get as an anti-wrinkling agent. Horse chestnut extract induces contraction force generation in fibroblasts through activation of Rho/Rho kinase.(37)

As stated, escin is comprised of a-escin and b-escin fractions. As determined in laboratory animal studies, the bioavailability of escin is about 10 to 15%, with a half-life of 10 to 19 hours.(3) Maximum plasma level after a single capsule of delayed release horse chestnut is 20 to 30 ng/ml after 2 to 3 hours. In a study of the bioavailability of b-escin in a delayed release formulation versus a normal release preparation, both standardized to 50 mg escin, area under the curve for the normal release product was reported to be 30% higher and time to maximum concentration greater.(30)

References

  1. View Abstract: Yoshikawa M, Murakami T, Yamahara J, et al. Bioactive Saponins and Glycosides. XII. Horse chestnut. (2): Structures of Escins IIIb, IV, V, and VI and Isoescins Ia, Ib, and V, Acylated Polyhydroxyoleanene Triterpene Oligoglycosides, from the Seeds of Horse Chestnut Tree (Aesculus hippocastanum L., Hippocastanaceae). Chem Pharm Bull (Tokyo). Nov1998;46(11):1764-9.
  2. Farnsworth NR, et al. A Review of Some Biologically Active Compounds Isolated from Plants as Reported in the 1974-1975 Literature. Lloydia. 1976;39:420-55.
  3. Schulz V, et al. Rational Phytotherapy. Berlin: Springer-Verlag; 1998:129-138.
  4. Newall CA, et al. Herbal Medicines: A Guide for Health Care Professionals. London: The Pharmaceutical Press; 1996:166-67.
  5. View Abstract: Heck AM, et al. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm. Jul2000;57(13):1221-7.
  6. View Abstract: Li Y, Matsuda H, Wen S, et al. Enhancement by Escins Ib and IIb of Mg(2+) Absorption from Digestive Tract in Mice: Role of Nitric Oxide. Eur J Pharmacol. Jan2000;387(3):337-42.
  7. PDR for Herbal Medicines, 2nd ed. Montvale, NJ: Medical Economics Company; 2000:405.
  8. Simini B. Horse-chestnut Seed Extract for Chronic Venous Insufficiency. Lancet. Apr1996;347(9009):1182-83.
  9. Vayssairat M, et al. Horse-chestnut Seed Extract for Chronic Venous Insufficiency. Lancet. Apr1996;347(9009):1182.
  10. View Abstract: Greeske K, et al. Horse Chestnut Seed Extract--An Effective Therapy Principle in General Practice. Drug Therapy of Chronic Venous Insufficiency. Fortschr Med. May1996;114(15):196-200.
  11. View Abstract: Pittler MH, Ernst E. Horse chestnut seed extract for chronic venous insufficiency. Cochrane Database Syst Rev. 2002;(1):CD003230.
  12. View Abstract: Siebert U, Brach M, Sroczynski G, Berla K. Efficacy, routine effectiveness, and safety of horsechestnut seed extract in the treatment of chronic venous insufficiency. A meta-analysis of randomized controlled trials and large observational studies. Int Angiol. Dec2002;21(4):305-15.
  13. View Abstract: Annoni F, Mauri A, Marincola F, et al. Venotonic Activity of Escin on the Human Saphenous Vein. Arzneimittelforschung. 1979;29(4):672-5.
  14. View Abstract: Rothkopf M, et al. New findings on the efficacy and mode of action of the horse chestnut saponin escin. Arzneim-Forsch/Drug Res. 1976;26(2):225-35.
  15. Dworschak E, et al. Medical Activities of Aesculus Hippocastaneum (Horse-chestnut) Saponins. Adv Exp Med Biol. 1996;404:471-74.
  16. View Abstract: Guillaume M, et al. Veinotonic Effect, Vascular Protection, Anti-inflammatory and Free Radical Scavenging Properties of Horse Chestnut Extract. Arzneim-Forsch/Drug Res. 1994;44(1):25-35.
  17. View Abstract: Berti F, et al. The Mode of Action of Aescin and the Release of Prostaglandins. Prostaglandins. Aug1977;14(2):241-49.
  18. View Abstract: Akopov SE, et al. Mechanisms of Platelet-induced Angiospastic Reactions: Potentiation of Calcium Sensitivity. Can J Physiol Pharmacol. Jul1997;75(7):849-52.
  19. View Abstract: Bisler H, Pfeifer R, Kluken N, et al. Effects of Horse-chestnut Seed Extract on Transcapillary Filtration in Chronic Venous Insufficiency. Dtsch Med Wochenschr. Aug1986;111(35):1321-9.
  20. View Abstract: Diehm C. Comparison of Leg Compression Stocking and Oral Horse-chestnut Seed Extract Therapy in Patients with Chronic Venous Insufficiency. Lancet. 1996;347(8997):292-94.
  21. View Abstract: Diehm C, Vollbrecht D, Amendt K, et al. Medical Edema Protection--Clinical Benefit in Patients with Chronic Deep Vein Incompetence. A Placebo Controlled Double Blind Study. Vasa. 1992;21(2):188-92.
  22. View Abstract: Lange S, Freitag G, Trampisch HJ. Practical Experience with the Design and Analysis of a Three-armed Equivalence Study. Eur J Clin Pharmacol. Sep1998;54(7):535-40.
  23. View Abstract: Pittler MH, Ernst E. Horse-chestnut Seed Extract for Chronic Venous Insufficiency. A Criteria-based Systematic Review. Arch Dermatol. Nov1998;134(11):1356-60.
  24. Geissbühler S, Degenring FH. Treatment of Chronic Venous Insufficiency with Aesculaforce Vein Gel. Schweiz Zschr Ganzheits Medizin. 1999;11:82-87.
  25. View Abstract: Li Y, Matsuda H, Wen S, et al. Structure-related Enhancing Activity of Escins Ia, Ib, IIa and IIb on Magnesium Absorption in Mice. Bioorg Med Chem Lett. Sep1999;9(17):2473-8.
  26. View Abstract: Matsuda H, Li Y, Murakami T, et al. Effects of Escins Ia, Ib, IIa, and IIb from Horse Chestnuts on Gastric Emptying in Mice. Eur J Pharmacol. Mar1999;368(2-3):237-43.
  27. View Abstract: Matsuda H, Li Y, Yoshikawa M. Possible Involvement of Dopamine and Dopamine2 Receptors in the Inhibitions of Gastric Emptying by Escin Ib in Mice. Life Sci. Nov2000;67(24):2921-7.
  28. View Abstract: Matsuda H, Li Y, Yoshikawa M. Roles of Endogenous Prostaglandins and Nitric Oxide in Inhibitions of Gastric Emptying and Accelerations of Gastrointestinal Transit by Escins Ia, Ib, IIa, and IIb in Mice. Life Sci. 2000;66(3):PL41-6.
  29. View Abstract: Matsuda H, Murakami T, Li Y, et al. Mode of Action of Escins Ia and IIa and E,Z-senegin II on Glucose Absorption in Gastrointestinal Tract. Bioorg Med Chem. Jul1998;6(7):1019-23.
  30. View Abstract: Schrader E, Schwankl W, Sieder C, et al. Comparison of the Bioavailability of Beta-aescin After Single Oral Administration of Two Different Drug Formulations Containing an Extract of Horse-chestnut Seeds. Pharmazie. Sep1995;50(9):623-7.
  31. Suter A, Bommer S, Rechner J. Treatment of patients with venous insufficiency with fresh plant horse chestnut seed extract: a review of 5 clinical studies. Adv Ther. Jan-Feb 2006;23(1):179-190.
  32. Pittler MH, Ernst E. Horse chestnut seed extract for chronic venous insufficiency. Cochrane Database Syst Rev. 25 Jan 2006;(1):CD003230. Review.
  33. Leach MJ, Pincombe J, Foster G. Using horsechestnut seed extract in the treatment of venous leg ulcers: a cost-benefit analysis. Ostomy Wound Manage. Apr 2006;52(4):68-70,72-74,76-78.
  34. Wang XH, Xu B, Liu JT, Cui JR. Effect of beta-escin sodium on endothelial cells proliferation, migration and apoptosis. Vascul Pharmacol. Oct-Dec 2008;49(4-6):158-165. Epub 2008 Jul 30.
  35. Patlolla JM, Raju J, Swamy MV, Rao CV. Beta-escin inhibits colonic aberrant crypt foci formation in rats and regulates the cell cycle growth by inducing p21(waf1/cip1) in colon cancer cells. Mol Cancer Ther. Jun 2006;5(6):1459-1466.
  36. Fujimura T, Tsukahara K, Moriwaki S, Hotta M, Kitahara T, Takema Y. A horse chestnut extract, which induces contraction forces in fibroblasts, is a potent anti-aging ingredient J Cosmet Sci. Sep-Oct 2006;57(5):369-376.
  37. Fujimura T, Moriwaki S, Hotta M, Kitahara T, Takema Y. Horse chestnut extract induces contraction force generation in fibroblasts through activation of Rho/Rho kinase. Biol Pharm Bull. Jun 2006;29(6):1075-1081.

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