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Michelle Orengo-McFarlane, MD University of California at San Francisco Family and Community Medicine. Horse chestnut seed for chronic venous insufficiency. Chronic venous insufficiency (CVI) affects 10-15% of men and 20-25% of women

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Horse chestnut seed for chronic venous insufficiency

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Michelle Orengo-McFarlane, MD

University of California at

San Francisco

Family and Community Medicine

Horse chestnut seed for chronic venous insufficiency

Chronic venous insufficiency (CVI) affects 10-15% of men and 20-25% of women

Characterised by chronic inadequate drainage of venous blood and venous hypertension, which results in

leg edema (swelling)‏

dermatosclerosis (hardening of

the skin)

Feelings of pain, fatigue and tenseness in the lower extremities

May be complicated by

skin ulceration

chronic (and potentially life-threatening) infections of the lower extremities


Conservative therapy consists largely of compression treatment

This often causes discomfort and has been associated with poor compliance

Oral drug treatment is an attractive option, but no drugs in the standard US pharmacopoeia provide this

horse chestnut aesculus hippocastanum

Native to the Balkan Peninsula

Grown throughout the northern hemisphere

Related to Aesculus californica, the California buckeye

Traditionally used in European herbal medicine for circulatory disorders and ulcer treatment

The “most widely prescribed oral antiedema venous remedy in Germany”

Horse chestnut (Aesculus hippocastanum)‏
goals of meta analysis

To “review the evidence from rigorous clinical trials assessing the efficacy and safety of HCSE versus placebo, or reference therapy, for the symptomatic treatment of CVI.”

Goals of meta-analysis

Inclusion criteria:

Randomised controlled trials (RCTs)‏

Study participants = patients with CVI

Oral preparations containing HCSE as the only active component (mono-preparation) compared to placebo or reference therapy

HCSE was standardised to escin which is the primary active constituent

Clinical outcome measures:

CVI-related symptoms (leg pain, pruritus, edema), leg volume, circumference at ankle and calf, and adverse events


2 of the authors (Pittler and Ernst) selected trials and extracted data

Quality of studies was assessed using the Jadad scale, giving each study a score of 1-5 (higher scores indicate better study quality)‏

Concealment of treatment allocation was scored: A = clearly concealed, B = unclear if concealed, C = clearly not concealed, D = concealment of allocation was not used.

Only RCTs were included


29 randomized controlled clinical trials were identified, and 17 trials met inclusion criteria

All RCTs except one were doubleblinded

All scored at least one out of five points on the Jadad scale

8 good quality

5 intermediate

3 poor

3 trials scored A and 14 trials scored B for the method of allocation concealment

Dose range: 100-150mg escin

15 100mg daily (50 BID)

2 150mg daily (75 BID)

Duration: 2-16 weeks

Most 3-8 weeks


10 were placebo controlled

2 compared HCSE with compression stockings + placebo

5 were controlled against reference medication

4 = O-ß-hydroxyethyl rutosides (HR)‏ - a plant-derived flavonoid

1 = pycnogenol – a flavonoid-containing water extract of the bark of the French maritime pine

results leg pain

Seven placebo-controlled trials

Six studies (n = 543) reported a statistically significant reduction (P < 0.05) of leg pain compared with placebo

One reported an improvement compared with baseline

Studies which compared HCSE with HR, pycnogenol or compression reported no significant difference

Results: leg pain
Six placebo-controlled trials

Five trials (n = 491) reported a statistically significant reduction of edema compared with placebo

Results: edema
One study reported that HCSE was inferior to pycnogenol

One reported no significant differences compared with compression

Results: edema
results pruritis

8 placebo-controlled trials

4 trials (n = 407) suggested a statistically significant reduction of pruritus compared with placebo (P < 0.05)‏

One found no significant difference compared with compression

Results: pruritis
results leg volume

7 placebo-controlled trials

All of these studies used water displacement

plethysmometry to measure this outcome

Meta-analysis of 6 (n = 502) suggested a WMD of 32.1ml (95% CI 13.49 to 50.72) vs placebo (pooled standardised mean difference 0.34; 95% CI 0.15 to 0.52)‏

One suggested HCSE was not significantly different then HR

One suggested that it may be as efficacious as treatment with compression stockings (WMD -2.90 ml; 95% CI -30.42 to 24.62)‏

Results: leg volume
results leg volume17

3 studies, all using 100 mg escin daily, reported a statistically significant reduction of mean leg volume after two weeks of tx vs placebo (P < 0.01)

Persistence of treatment effects was suggested by one study - at the end of a six week follow-up period, mean leg volume was similar to post-treatment values

Results: leg volume
results limb circumference

7 placebo controlled trials

5 (n = 172) suggested a statistically significant reduction at the ankle, 3 (n = 112) at the calf vs placebo

Ankle: meta-analysis of 3 trials w/ adequate data suggested a statistically significant reduction vs placebo (WMD 4.71 mm; 95% CI 1.13 to 8.28;

pooled standardised mean difference 0.60; 95% CI 0.15 to 1.05).

Calf: pooled analysis of three trials suggested a statistically significant reduction vs placebo (WMD 3.51 mm; 95% CI 0.58 to 6.45; pooled standardised mean difference 0.42; 95% CI -0.04 to 0.88).

Results: limb circumference
results adverse effects

14 studies

4 reported no treatment-related adverse events

6 reported GI complaints, dizziness, nausea, headache and pruritus; frequency 1-36% of treated patients.

4 reported good tolerability

Results: adverse effects

Limited data on adherence - only 3 trials reported that adherence was monitored

Most studies had a small sample size

Drop-out rates ranged 0-19.5%

Insufficient data on effect size top assess heterogeneity for most studies, though the data on leg volume appear fairly homogenous


Did effect vary by quality of studies? – was not evaluated

Were all relevant studies included? - unknown

Evidence of unreported negative studies - not evaluated

Was effect size clinically significant?

Objective measures were significantly positive, though there was limited data on effect size for subjective outcomes


HCSE appears to be a safe and well-tolerated treatment for CVI

Objective measures were significantly positive and most studies were good quality

More data is needed to establish long-term safety and efficacy

Caution is advised in recommending any US-manufactured supplement, as they are minimally regulated under DSHEA

Identify reputable supplement companies


A Modern Herbal:



Schulz V, et al. Rational Phytotherapy. Berlin: Springer-Verlag; 1998:129-138.

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