Horse Chestnut Seed Extract for Venous Insufficiency
Horse Chestnut Seed Extract for Venous Insufficiency
By Lynn Keegan, RN, PhD, HNC-BC, FAAN, Dr. Keegan is Director, Holistic Nursing Consultants, Port Angeles, WA; she reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study.
Venous insufficiency is a disabling condition in which the blood has problems being moved back up the lower extremities from the legs to the heart. Vein valves usually push the flow of blood toward the heart. When these valves are damaged, the blood leaks and pools in the legs and feet. The condition may also be caused by a deep vein thrombosis. Chronic venous insufficiency (CVI) is a long-term condition that occurs because of partial vein blockage or blood leakage around the valves of the veins. Symptom generally include swelling of the legs; dull aching, heaviness, or cramping in legs; pain that worsens when standing; and pain that lessens when raising the legs. Persons with CVI also may have skin color changes around the ankles, redness of legs and ankles, thickening of the skin on legs and ankles, and ulcers on the legs and ankles.1
Impairment of the cutaneous microcirculation is a major predisposing factor in inflammation and ulceration in patients with CVI. Increase of capillary filtration rate predisposes to the formation of edema, and local lymphedema, a complication of CVI, is often under diagnosed.2 Venous leg ulceration (VLU) is the most serious consequence of CVI and is responsible for almost 70% of chronic leg ulcers.3 Chronic leg ulcers are extremely common and account for a large proportion of all lower extremity ulcers. The relatively high prevalence of chronic leg ulcers impacts health care costs and affects patients' lives significantly.4 Progress has been made in understanding the pathophysiology, clinical features, and diagnosis of these ulcers, but the basic principles of care have remained consistent for almost 50 years (see box below).4
The standard of care for venous ulcer treatment is compression therapy to reverse the effect of venous hypertension and occlusive dressings to maintain a moist wound-healing environment and treat ulcer bed abnormalities. The treatment with the highest level of evidence for venous ulcers is the use of multilayered elastic bandages for compression in patients with normal arterial flow. Treating the ulcer bed with cadexomer iodine dressings is also supported by evidence from randomized controlled trials, whereas newer dressings provide fewer well-proven alternative opportunities to speed the healing of venous ulcers.1 The Association for the Advancement of Wound Care (AAWC) Government and Regulatory Task Force developed a content-validated venous ulcer guideline based on best available evidence supporting each aspect of venous ulcer care. After compiling all-inclusive lists of elements in venous ulcer algorithms published before August 2002, the Task Force objectively rated and summarized up to five best references from MEDLINE, CINAHL, and EMBASE literature searches covering each aspect of care. Sixteen multidisciplinary wound care professionals and educators used judgment quantification to content validate all steps. A 2004 e-mail survey of AAWC members (n = 1,514) clarified effects of under-reimbursement on evidence-based venous practice. The Venous Ulcer Guideline containing all elements with A-level evidence plus those with a Content Validity Index > 0.75 now resides on the AAWC and the Agency for Healthcare Research and Quality National Guideline Clearinghouse web sites. However, a review of U.S. health care environment components, including reimbursement policies, and the results of the survey identified many barriers to implementation of A-level evidence supported steps (sustained graduated high compression, autolytic debridement, and moist wound environments) in practice. Sufficient evidence supports improved venous ulcer care in the United States but inadequate and/or inconsistent reimbursement policies impede quality evidence-based venous ulcer practice, delaying healing and increasing the burden of venous ulcers on society.2 Treatment of microcirculatory dysfunction can be done by pharmacologic intervention or compression therapy or using a combination of both.3 References 1. Sackheim K, et al. Compression modalities and dressings: Their use in venous ulcers. Dermatol Ther 2006;19:338-347. 2. Bolton L, et al; Government and Regulatory Task Force, Association for the Advancement of Wound Care. Development of a content-validated venous ulcer guideline. Ostomy Wound Manage 2006;52:32-48. 3. Wollina U, et al. A review of the microcirculation in skin in patients with chronic venous insufficiency: The problem and the evidence available for therapeutic options. Int J Low Extrem Wounds 2006;5:169-180. |
History and Traditional Use
The use of extracts from the seed of the horse chestnut (Aesculus hippocastanum L.) is the most promising alternative therapy for treating CVI and the resulting leg ulcers. Horse chestnut seed extract (HCSE) traditionally has been used to treat patients with CVI and to alleviate its associated symptoms, including lower leg swelling.5
The horse chestnut tree belongs to the same family as the sweet chestnut and Ohio buckeye trees. The fruit of the sweet chestnut is edible; the fruits of the Ohio buckeye trees are toxic. Native to Greece and Albania, the tree was introduced in the United States in the 1740s as a shade tree. It grows up to 35 meters high and bears long clusters of white flowers in May and a prickly fruit in the fall. The fruit contains three large seeds; the extract of these seeds has been used in Europe since the 1800s as an oral remedy for various venous diseases.
Mechanism of Action
The efficacy of HCSE preparations is believed to be due to an inhibitory effect on the catalytic breakdown of capillary wall proteoglycans.
The anti-inflammatory effects of Japanese horse chestnut (Aesculus turbinata) seeds were examined in vivo and in vitro.6 The extract inhibited croton oil-induced swelling of the mouse concha. HCSE inhibited cyclooxygenase (COX)-1 and COX-2 activities, but had no effect on 15-lipoxygenase and phospholipase A2 activities. Inhibition of COX-2 occurred at a lower concentration of HCSE than for COX-1. Japanese horse chestnut seeds contain coumarins and saponins, but these chemicals did not inhibit COX activities. These results suggest that the anti-inflammatory effect of Japanese horse chestnut seeds is caused, at least partly, by the inhibition of COX. The inhibitor of COX in this seed may be a chemical other than coumarins and saponins.
Contraction forces generated by non-muscle cells such as fibroblasts play important roles in determining cell morphology, vasoconstriction, and/or wound healing. However, few factors, such as lysophosphatidic acid and thrombin, that induce cell contraction forces are known. Another Japanese study analyzed various plant extracts for ingredients that induce generation of cell contraction forces in fibroblasts populating collagen gels.7 The researchers found that HCSE induced such contraction forces in fibroblasts.
Clinical Trials
The primary treatment of choice for VLU is compression therapy; however, serious clinical issues demand the development of new treatments.
Four clinical trials in patients with CVI and one study in patients with varicose veins demonstrated HCSE's effectiveness in reducing lower-leg edema and the subjective alleviation of leg pain, heaviness, and itching. In these trials HCSE proved to be safe, well-tolerated, and acceptable to patients with mild-to-moderate venous insufficiency.5
HCSE's clinical feasibility in VLU was explored in an Australian two-stage trial.8 The second stage was a descriptive survey exploring current opinion and utilization of natural therapies, venotonics, and HCSE in VLU. A questionnaire mailed to 122 district nurses, 73 medical practitioners, and 53 patients with VLU resulted in a response rate of 32%, 31.5%, and 81%, respectively. The authors found that natural therapy and HCSE use for VLU was minimal in all groups. Half of the groups supported venotonics, with a similar proportion of nurses and clients utilizing venotonics in practice. However, medical practitioners were less likely to utilize venotonics for VLU. Although clinicians indicate that clinical evidence may influence the utilization of HCSE in clinical practice, the evidence currently does not exist. Positive findings from well-designed trials may ameliorate the integration of natural medicine into mainstream practice.
Another Australian study evaluated the clinical efficacy of orally administered HCSE for treating VLUs.9 In a prospective, triple-blind, randomized placebo-controlled trial, 54 patients with VLUs from a large South Australian community nursing service were randomly allocated to receive HCSE (n = 27) or placebo (n = 27) for 12 weeks. Ulcers were assessed at weeks 0, 4, 8, and 12 utilizing a wound assessment tool and the Alfred/Medseed Wound Imaging System. The difference between groups in the number of healed leg ulcers and change in wound surface area, depth, volume, pain, and exudate was not statistically significant. However, HCSE had a significant effect on the percentage of wound slough over time and on the number of dressing changes at week 12.
To determine whether an alternative venous ulcer treatment using HCSE and conventional therapy involving dressings and compression was more cost-effective than using conventional therapy alone, a 12-week cost-benefit analysis of HCSE therapy was conducted.10 The study, using data from a 12-week prospective, randomized, placebo-controlled trial conducted in South Australia in 2002-2004, involved 54 patients with venous ulceration. Taking into account the cost of HCSE, dressing materials, travel, staff salaries, and infrastructure for each patient, HCSE therapy combined with conventional therapy was found to be more cost-effective than conventional therapy alone. This study confirms that dressing change frequency has a significant impact on the total cost of wound care and suggests that district nursing service operation efficiency may be enhanced by HCSE use.
One of the more significant studies—a systematic review from the Cochrane Library—reviewed the efficacy and safety of oral HCSE vs. placebo or reference therapy for treating CVI.11 Following a search of the Cochrane Peripheral Vascular Diseases Review Group's Specialized Register, the Cochrane Central Register of Controlled Trials, Medline, Embase, Allied and Complementary Medicine, and Phytobase for randomized controlled trials of HCSE for CVI, trials were included if they compared oral HCSE mono-preparations with placebo or reference therapy in people with CVI. Trials assessing HCSE as one of several active components in a combination preparation, or as a part of a combination treatment, were excluded.
There seemed to be an improvement in CVI-related signs and symptoms with HCSE compared to placebo. Leg pain was assessed in seven placebo-controlled trials. Six reported a significant reduction of leg pain in the HCSE groups compared with the placebo groups, while another reported a statistically significant improvement compared with baseline. One trial suggested a weighted mean difference of 42.4 mm measured on a 100 mm visual analogue scale. Leg volume was assessed in seven placebo-controlled trials. Meta-analysis of six trials (n = 502) suggested a weighted mean difference of 32.1 mL in favor of HCSE compared to placebo. One trial indicated that HCSE may be as effective as treatment with compression stockings. Adverse events usually were mild and infrequent. The evidence presented implies that HCSE is an efficacious and safe short-term treatment for CVI.
Side Effects
Standardized HCSE generally is considered to be safe in adults at recommended doses for short periods of time. Stomach upset, muscular (calf) spasm, headache, dizziness, nausea, and itching have been reported. Contact skin irritation (dermatitis) has been reported following application of HCSE to the skin.
HCSE may cause an allergic reaction in patients with known allergy to horse chestnuts, esculin, or any of its ingredients (flavonoids, biosides, trisides of quertins, and oligosaccharides, including 1-ketose and 2-ketose). Anaphylactic shock has been reported with intravenous use.12
There is not enough scientific evidence to recommend use of horse chestnut in children. Deaths have been reported in children who ate raw horse chestnut seeds or tea made from horse chestnut leaves and twigs. Unprocessed horse chestnut seeds, flowers, branch bark, and leaves have not been shown effective for any indication. These contain esculin and have been associated with significant toxicity and death. Symptoms of HCSE poisoning may include vomiting, diarrhea, headache, confusion, weakness, muscle twitching, poor coordination, coma, or paralysis. HCSE standardized to escin content should not contain significant levels of esculin, and should not have the same risks.
HCSE may cause lowered blood sugar, so caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Serum glucose levels may need to be monitored by a qualified health care provider, and medication adjustments may be necessary.
In theory, HCSE may increase the risk of bleeding. Caution is advised in patients with bleeding disorders or taking drugs that may increase the risk of bleeding. Monitoring is recommended and dosing adjustments may be necessary. Liver and kidney toxicity has been associated with HCSE. Aflatoxins, considered to be cancer-causing agents, have been identified in commercial skin products containing horse chestnut, but not in HCSE.12
Dosage and Formulation
Dosage and formulation information is available in the following table.
Summary and Conclusion
Although standard care for CVI consists largely of compression treatment, this often causes discomfort and has been associated with poor compliance.11 Treatment of CVI is multifactorial. Compression, interventional and operative approaches, along with possible systemic treatments, are available. The efficacy of systemic venotonic medications, mostly phytotherapeutic agents, is controversial. Nonetheless, in a number of clinical and laboratory studies, an effect was seen after use for 8-12 weeks. When administered appropriately, venotonic agents can show anti-edematous, anti-inflammatory, antioxidative, and proteolytic effects as well as reduce capillary leakage. Furthermore, they increase vein tone and lymph flow. Venotonic agents should be considered if compression therapy alone is insufficient, contraindicated, or intolerable.13
When taken for short periods of time in recommended dosage and form, HCSE seems to offer a viable alternative for those seeking relief from the discomfort and disability of chronic venous insufficiency.
References
1. National Library of Medicine, National Institutes of Medicine. Medical encyclopedia: Venous insufficiency. Available at: www.nlm.nih.gov/medlineplus/ency/article/000203.htm. Accessed Jan. 10, 2007.
2. Wollina U, et al. A review of the microcirculation in skin in patients with chronic venous insufficiency: The problem and the evidence available for therapeutic options. Int J Low Extrem Wounds 2006;5:169-180.
3. Abbade LP, et al. A sociodemographic, clinical study of patients with venous ulcer. Int J Dermatol 2005;44:989-992.
4. Reichenberg J, Davis M. Venous ulcers. Semin Cutan Med Surg 2005;24:216-226.
5. Suter A, et al. Treatment of patients with venous insufficiency with fresh plant horse chestnut seed extract: A review of 5 clinical studies. Adv Ther 2006;23:179-190.
6. Sato I, et al. Antiinflammatory effect of Japanese horse chestnut (Aesculus turbinata) seeds. J Vet Med Sci 2006;68:487-489.
7. Fujimura T, et al. Horse chestnut extract induces contraction force generation in fibroblasts through activation of rho/rho kinase. Biol Pharm Bull 2006;29:1075-1081.
8. Leach MJ. The clinical feasibility of natural medicine, venotonic therapy and horsechestnut seed extract in the treatment of venous leg ulceration: A descriptive survey. Complement Ther Nurs Midwifery 2004;10:97-109.
9. Leach MJ, et al. Clinical efficacy of horsechestnut seed extract in the treatment of venous ulceration. J Wound Care 2006;15:159-167.
10. Leach MJ, et al. Using horsechestnut seed extract in the treatment of venous leg ulcers: A cost-benefit analysis. Ostomy Wound Manage 2006;52:68-70, 72-74, 76-78.
11. Pittler MH, Ernst E. Horse chestnut seed extract for chronic venous insufficiency. Cochrane Database Syst Rev 2006;(1):CD003230.
12. MayoClinic.com. Drugs & Supplements: Horse chestnut (Aesculus hippocastanum L.). Available at: www.mayoclinic.com/health/horse-chestnut/NS_patient-Horsechestnut. Accessed Jan. 7, 2007.
13. Reich S, et al. Systemic therapy of chronic venous diseases. Hautarzt 2006;57:9-10, 12-18.
Keegan L. Horse chestnut seed extract for venous insufficiency. Altern Ther Women's Health 2007;9(4):25-29.Subscribe Now for Access
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