Benefits
Leg comfort, itching and lower-leg volume in vein studies
A review of 17 randomized trials in adults with leg vein problems found that six of seven placebo-controlled trials reported less leg pain with the extract, and several reported less itching. Pooling six trials (502 people) gave about 32 ml less lower-leg volume than placebo. Most trials were small, lasted 2 to 16 weeks and most used the same capsule extract.
Lower-leg volume in trials that also tested compression stockings
In a 12-week trial of 240 adults, lower-leg volume fell about 44 ml with the extract and 47 ml with compression stockings and rose about 10 ml with placebo. In a 16-week trial of 355 adults with more advanced vein disease, the extract (18 ml fall) did not differ significantly from placebo, while stockings (89 ml fall) did. In both trials the stocking group also took a diuretic in the first week.
Lower-leg swelling at rest and after a provocation test in vein studies
In a double-blind trial of 40 adults with weak deep leg vein valves, the extract reduced lower-leg volume more than placebo, both at rest and after a test designed to provoke swelling. Leg circumference and vein pressure readings trended the same way but were not the main measure.
Mechanism of action
Less fluid filtering out of small leg vessels
In a crossover trial of 22 women with leg vein problems, one dose of extract (100 mg aescin) cut the lower-leg capillary filtration coefficient by 22% at 3 hours, while it rose slightly after placebo. The EU monograph states that the exact mechanism is not known but that studies point to effects on vein tone and capillary filtration.
Laboratory effects on the vessel lining
In cell studies, aescin protected cultured vessel lining cells from low-oxygen and inflammatory stress, and in guinea pig tissue an extract closed gaps between the lining cells of small veins. The EU assessment notes that enzyme-blocking effects were seen only at concentrations probably above those reached in the body, so these findings are not proof of how the oral extract works.
Aescin and aesculin are different compounds
Aescin is a mixture of saponins in three main fractions; the beta fraction has hemolytic (red blood cell breaking) activity. Aesculin, a coumarin, occurs in other parts of the tree but not in the seed, according to the EU assessment. Raw seeds are still unsafe to eat (NCCIH); trials used processed extracts standardized to aescin.
Clinical trials
Cochrane systematic review of randomized trials of oral horse chestnut seed extract alone against placebo or reference treatments (rutosides, pine bark extract, compression), capsules for 2 to 16 weeks, all standardized to escin; 1,443 participants in total according to the EU assessment report, 11 of the 17 trials with fewer than 50 people. (Pittler et al. 2012, Cochrane Database Syst Rev)
Adults with chronic venous insufficiency in 17 randomized trials.
Six of seven placebo-controlled trials reported less leg pain; one trial gave a 42.4 mm difference on a 100 mm pain scale. Six trials (n = 502) gave 32.1 ml less leg volume than placebo (95% CI 13.49 to 50.72). One trial suggested the extract may be as effective as compression stockings. Adverse events were usually mild and infrequent. The authors called for larger definitive trials.
Randomized, partially blinded, placebo-controlled parallel trial with a hierarchical equivalence design; extract providing 50 mg aescin twice daily versus class II compression stockings versus placebo for 12 weeks. A later paper coauthored by a Klinge Pharma employee names the extract as the company's Venostasin retard; funding is not stated in the abstract. (Diehm et al. 1996, Lancet)
240 adults with chronic venous insufficiency.
Lower-leg volume of the worse leg fell 43.8 ml with the extract (n = 95) and 46.7 ml with stockings (n = 99), and rose 9.8 ml with placebo (n = 46). Both beat placebo (p = 0.005 and p = 0.002) and were equivalent to each other; the authors note that in this design compression could not be proven as the standard. No serious treatment-related events.
Randomized multicenter trial (company study report summarized in this paper), double-blind for extract versus placebo and open for compression; 50 mg aescin twice daily for 16 weeks after a 2-week placebo washout; the compression group took a diuretic for the first week. One author was an employee of the extract maker, Klinge Pharma, and the other received honoraria for preparing the manuscript. (Ottillinger et al. 2001, BMC Cardiovasc Disord)
355 adults with grade II or IIIa chronic venous insufficiency (143 extract, 142 compression, 70 placebo).
Lower-leg volume fell 89 ml with compression and 18 ml with the extract and rose 2 ml with placebo. Compression beat placebo (p < 0.001); the extract did not (p = 0.115), reaching significance only in the per-protocol group (p = 0.018). Grade II patients responded better than grade IIIa. Symptom scores did not differ significantly between extract and compression. Digestive side effects affected 15% on the extract, 7% on compression and 9% on placebo (p = 0.09).
Randomized, double-blind, placebo-controlled parallel trial measuring lower-leg volume by water displacement as the main outcome; the EMA assessment report lists its capsules as 75 mg aescin, two daily; funding is not stated in the abstract. (Diehm et al. 1992, Vasa)
40 adults with leg swelling from chronic deep vein valve incompetence.
The extract reduced leg volume significantly more than placebo, with the same result after a swelling provocation test. Leg circumference and vein pressure measures trended in the same direction. The abstract gives no adverse event rates.
Randomized, double-blind, placebo-controlled crossover trial; one dose of two Venostasin retard capsules (600 mg extract, 100 mg aescin) with measurement by venous occlusion plethysmography; published in German. (Bisler et al. 1986, Dtsch Med Wochenschr)
22 women with confirmed chronic venous insufficiency.
Three hours after the extract, the lower-leg capillary filtration coefficient fell 22%, while it rose slightly after placebo (p = 0.006). Lower-leg blood volume fell 5% more than with placebo, which was not statistically significant. A one-dose physiology study.
Open, controlled comparison of 600 mg/day horse chestnut seed extract (Venostasin) versus 360 mg/day Pycnogenol for 4 weeks, with no placebo group; funding not stated in the abstract. (Koch 2002, Phytother Res)
40 adults with chronic venous insufficiency.
Horse chestnut extract reduced lower-leg circumference moderately but not significantly and marginally improved symptoms, while the pine bark extract group improved significantly. The abstract gives no adverse event rates for either group. Open design and small size limit the result.