Horse Chestnut

Health Care Professional Information

Scientific Name
Aesculus hippocastanum
Common Name

Chestnut, marron europeen, escine, escin, aescin

Brand Name

Venastat™

Clinical Summary

Horse chestnut, a tree native to the Balkan Peninsula, has been used in traditional medicine for centuries. The seed extract is a popular dietary supplement used to support vascular functions. Horse chestnut should not be confused with sweet chestnut.

Escin, also known as Aescin, a natural mixture of triterpenoid saponins isolated from the seed of the horse chestnut and the major active principle, was shown to have anti-inflammatory (1), neuroprotective (1), antitumor effects (2) (3), and enhances the efficacy of gemcitabine (18). Data from clinical trials suggest efficacy of horse chestnut seed extract against chronic venous insufficiency (CVI) (4) (5). Conclusions from systematic reviews and meta analysis state that horse chestnut extract is a safe and well tolerated treatment for CVI (6) (7) (8).
Escin may also be effective in improving sperm quality in patients with varicocele-associated infertility (14).

Patients with compromised renal or hepatic function should not consume horse chestnut products.

Purported Uses
  • Circulatory disorders
  • Diarrhea
  • Hemorrhoids
  • Phlebitis
  • Varicose veins
Constituents
  • Coumarins: Aesculetin, fraxin, scopolin
  • Flavonoids: Flavonol (kaempferol, quercetin) glycosides including astragalin, isoquercetrin, rutin, and leucocyanidin
  • Saponins: Several saponins collectively referred to as aescin
  • Tannins
  • Other constituents: Allantoin, amino acids, choline, citric acid, phytosterol
    (2) (11)
Mechanism of Action

Anti-inflammatory actions have been documented for the saponins (aescin) found in horse chestnut. Aescin reduces transcapillary filtration of water and protein and increases venous tone by increasing the vasoconstrictor, prostaglandin F2 alpha. It stabilizes cholesterol-containing membranes of lysosomes and limits the release of enzymes, which is typically increased in chronic pathologic conditions of the vein. It also improves vascular resistance and aids toning of vein walls (10). The triterpene glycosides and steroid saponins decrease venous capillary permeability and appear to have a tonic effect on the circulatory system (11) while aesculetin (esculin), a hydroxycoumarin, may increase bleeding time. A synergistic inhibitory effect on human hepatocellular carcinoma SMMC-7721 cells observed with the combined administration of beta-aescin and 5-fluorouracil may be due to synergistic cell-cycle arrest, induction of apoptosis, activation of caspases-3, 8 and 9, and down-regulation of Bcl-2 expression (17).

Pharmacokinetics

Orally administered aescin has an absorption half-life of about 1 hour and an elimination half-life of about 20 hours. (12)

Warnings

Horse chestnut seed is classified by the FDA as an unsafe herb. The glycoside and saponin constituents are considered toxic.

Contraindications
  • Patients with hepatic or renal insufficiency should not consume horse chestnut.
Adverse Reactions

Toxicity: (Chestnut poisoning) Diarrhea, muscle twitching, dilated pupils, depression, and paralysis. (11) (14)
Case Report: Chestnut bezoar (well-defined, ovoid-shaped, intraluminal mass with mottled gas pattern) causing intestinal obstruction and abdominal pain was reported in a 68-year-old woman following consumption of excessive amounts of horse chestnut for several months. The bezoar was removed by surgery (15).
Case Report: Life-threatening kidney rupture was reported in a patient with angiomyolipoma (AML), a benign fat-containing mesenchymal tumor of the kidney, after taking horse chestnut seed extract for venous insufficiency. Her symptoms improved after an emergency embolization (16).

Herb-Drug Interactions
  • Anticoagulants / Antiplatelet agents: Horse chestnut may have an additive anticoagulant effect due to aesculin, a hydroxycoumarin (14).
Literature Summary and Critique

Pittler MH, Ernst E. Horse chestnut seed extract for chronic venous insufficiency. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD003230.
This review was conducted to determine the efficacy and safety of oral horse chestnut seed extract (HCSE) for the treatment of chronic venous insufficiency (CVI). Databases searched included the Cochrane Peripheral Vascular Diseases Review Group's Specialised Register (October 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library Issue 3, 2005, MEDLINE (January 1966 to October 2005), EMBASE (January 1980 to October 2005), Allied and Complementary Medicine (AMED) (inception to July 2005) and Phytobase (inception to January 2001) for randomized controlled trials (RCTs). Seventeen RCTs that compared oral HCSE mono-preparations with placebo, or reference therapy were included. The analysis indicated an improvement in CVI related symptoms such as leg pain, edema, and pruritus with HCSE compared to placebo. Adverse events were usually mild and infrequent.
The authors concluded that HCSE is an effective short-term treatment for CVI. However, larger well designed studies are needed to establish use of HCSE.

Dosage (Inside MSKCC Only)
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References
  1. Zhang L, Fu F, Zhang X et al. Escin attenuates cognitive deficits and hippocampal injury after transient global cerebral ischemia in mice via regulating certain inflammatory genes. Neurochem Int. 2010 May 11. [Epub ahead of print]
  2. Zhou XY, Fu FH, Li Z, et al. Escin, a natural mixture of triterpene saponins, exhibits antitumor activity against hepatocellular carcinoma. Planta Med. 2009 Dec;75(15):1580-5.
  3. Harikumar KB, Sung B, Pandey MK, et al. Escin, a pentacyclic triterpene, chemosensitizes human tumor cells through inhibition of nuclear factor-kappaB signaling pathway. Mol Pharmacol. 2010 May;77(5):818-27.
  4. Diehm C, Trampisch HJ, Lange S, Schmidt C. Comparison of leg compression stocking and oral horse-chestnut seed extract therapy in patients with chronic venous insufficiency. Lancet. 1996;347:292-4.
  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;21:188-92.
  6. 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. 2002 Dec;21(4):305-15.
  7. Pittler MH, et al.Horse-chestnut seed extract for chronic venous insufficiency. A criteria-based systematic review. Arch Dermatol. 1998;134:1356-60.
  8. Pittler MH, Ernst E. Horse chestnut seed extract for chronic venous insufficiency. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD003230. Review.
  9. Barnes J, Anderson LA, Phillipson JD. Herbal Medicines: A Guide for Health-Care Professionals. London: Pharmaceutical Press; 1996.
  10. Fetrow CW, Avila JR. Professional's Handbook of Complementary and Alternative Medicines. Philadelphia: Springjouse; 1999.
  11. Brinker F. Herb Contraindications and Drug Interactions, 2nd ed. Sandy (OR): Eclectic Med. Publications; 1998.
  12. Schulz V, et al. Rational Phytotherapy: A Physician's Guide to Herbal Medicine, 3rd ed. Berlin (Germany): Springer; 1998.
  13. Morrison D. Boehringer-Ingelheim Product Information Venastat™2001.
  14. Fang Y, Zhao L, Yan F, et al. Escin improves sperm quality in male patients with varicocele-associated infertility. Phytomedicine. 2010 Mar;17(3-4):192-6.
  15. Chen WT, Suk FM. Abdominal pain after consuming a chestnut. Diagnosis: Chestnut bezoar in the jejunum. Gastroenterology. 2011 Jun;140(7):e9-10.
  16. Snow A, Halpenny D, Mc Neill G, Torreggiani WC. Life-threatening rupture of a renal angiomyolipoma in a patient taking over-the-counter horse chestnut seed extract. J Emerg Med. 2011 Feb 9. [Epub ahead of print]
  17. Ming ZJ, Hu Y, Qiu YH, Cao L, Zhang XG. Synergistic effects of beta-aescin and 5-fluorouracil in human hepatocellular carcinoma SMMC-7721 cells.Phytomedicine. 2010;17(8-9):575-80.
  18. Wang YW, Wang SJ, Zhou YN, Pan SH, Sun B. Escin augments the efficacy of gemcitabine through down-regulation of nuclear factor-κB and nuclear factor-κB-regulated gene products in pancreatic cancer both in vitro and in vivo. J Cancer Res Clin Oncol. 2012 May;138(5):785-97.

Consumer Information

How It Works

Bottom Line: Horse chestnut was shown to be effective for treating chronic venous insufficiency but its long-term effects are not known.

Horse chestnut is a seed extract. One of its active components is aescin, which may reduce inflammation and increase the tone of veins. It also reduces the release of enzymes, which is typically increased in chronic diseases of the vein. Other compounds in horse chestnut generally increase the tone of blood vessels and decrease their permeability. Horse chestnut extract was shown in some studies to be effective against chronic venous insufficiency.
A compound called aesculetin may act as an anticoagulant and blood thinner, and is therefore often excluded from over-the-counter horse chestnut products.

Purported Uses
  • To treat circulatory disorders such as chronic venous insufficiency (a condition where a patient's veins are not capable of pumping blood back to their heart, resulting in blood collecting in the lower limbs and leg swelling)
    Several clinical trials support use of horse chestnut as a short-term treatment for CVI, but its long-term effects are unknown.
  • To treat diarrhea
    There is no scientific evidence to back this claim.
  • To treat hemorrhoids
    There are no data to support this.
  • To treat phlebitis
    No scientific evidence supports this use.
  • To treat varicose veins
    This claim is not backed by any evidence.
Research Evidence

Chronic venous insufficiency:
Researchers carried out a systematic review of randomized, controlled trials that used horse chestnut to treat chronic venous insufficiency. Overall, studies showed that patients who used horse chestnut had a significant decrease in symptoms of CVI compared to those who took placebo. The authors concluded that short-term use of this herb extract is relatively safe and effective. Long-term studies are needed.
 

Patient Warnings
  • Horse chestnut seed is classified by the FDA as an unsafe herb. Many of the compounds in horse chestnut are considered to be toxic.
Do Not Take If
  • You are taking warfarin, aspirin, or other blood thinners (Horse chestnut products that contain aesculin may increase the risk of bleeding. Check to make sure that your horse chestnut product is aesculin-free)
  • You have liver or kidney problems.
Side Effects
  • Stomach upset
  • Nausea and vomiting
  • Chestnut poisoning: Diarrhea, muscle twitching, dilated pupils, depression, and paralysis can occur after high doses of horse chestnut.
  • Case Reports:
    Chestnut bezoar (well-defined, ovoid-shaped mass) causing intestinal obstruction and abdominal pain was reported in a 68-year-old woman following consumption of excessive amounts of horse chestnut for several months. The bezoar was removed by surgery.
    Life-threatening kidney rupture was observed in a patient with angiomyolipoma (AML), a benign fat-containing tumor of the kidney, after taking horse chestnut seed extract for venous insufficiency. Her symptoms improved after an emergency embolization.
E-mail your questions and comments to aboutherbs@mskcc.org.