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Horse Chestnut

Horse Chestnut (Aesculus hippocastanum) is a plant extract with a group of molecules known as aescins, which are beneficial to circulatory health. Supplementation of horse chestnut appears to be beneficial for varicose veins and veinous insufficiency.

Our evidence-based analysis on horse chestnut features 70 unique references to scientific papers.

Kamal Patel
Research analysis led by Kamal Patel.
All content reviewed by the Examine.com Team. Published:
Last Updated:

Things To Know & Note

Primary Function:

Also Known As

Aesculus hippocastanum, Conker tree, Rosskastanie, venostasin

Goes Well With

  • Glucocorticoids (Horse chestnut augments the antiinflammatory properties of glucocorticoids)

Caution Notice

Examine.com Medical Disclaimer

  • It may be possible to be allergic to the β-aescin component of horse chestnut extract

How to Take Horse Chestnut

Recommended dosage, active amounts, other details

Horse chestnut tends to be taken in the 400-600mg range, although it seems that the overall dose is less important than the standardization for aescin which should ultimately reach 100-150mg daily.

Supplementation tends to be divided into two daily doses divided by 12 hours (so, a morning and evening dose at 8am and 8pm as an example), which is due to the active components (aescins) requiring about 12 hours to reach baseline concentrations.

Human Effect Matrix

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects horse chestnut has on your body, and how strong these effects are.
Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
grade-b Chronic Venous Insufficiency Notable Very High See all 3 studies
Due to the venotrophic effects of aescin supplementation, disease states associated with blood pooling in extremities are significantly and fairly reliably treated with horse chestnut.
grade-b Leg Swelling Notable Very High See all 3 studies
Symptoms of leg swelling and varicose veins appear to be fairly reliably reduced with the recommended oral doses of horse chestnut supplementation.
grade-b Pain Minor - See study
The pain associated with chronic venous insufficiency may be alleviated when that condition is treated by horse chestnut extract.
grade-c Hemorrhoids Minor - See study
Preliminary evidence suggests that the classical usage of horse chestnut for the treatment of hemorrhoids may be relevant to oral supplementation, with benefits within a week of usage.
grade-d HDL-C - - See study
No significant influence on HDL-C levels associated with horse chestnut extract supplementation.
grade-d LDL-C - - See study
No detectable influence on LDL cholesterol concentrations associated with horse chestnut extract.

Studies Excluded from Consideration

  • Confounded with troxerutin[1]

Scientific Research on Horse Chestnut

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1Sources and Composition

1.1Sources

Aesculus hippocastanum (of the family hippocastanaceae[2]) is a plant commonly referred to as Horse Chestnut or Conker Tree. It is widely spread across the world due to having large environmental resiliance and the bark of branches, fruits, and seeds are usually used medicinally (the leaves are at times, but this is much less common[3]) while the bright white, yellow, or red flowers are mostly aesthetic. The oil extract of the fruits is sometimes used for neuralgic and rheumatic conditions specifically.[4]

The 'seeds' themselves are medicinally referred to as semen hippocastani and they are covered by a large spiky husk[5] which is commonly referred to as the horse chestnut or buckeye.[6] The term buckeye actually refers to all seeds of the hippocastanaceae family, whereas actual chestnuts belong to the castanea genus.

Aesculus hippocastanum is a tree which bears seeds in spiky husks that are known as horse chestnuts. The seeds are the main part of the plant used medicinally, although it appears all parts of the plant have at times been investigated or used for medicinal purposes

Traditionally, the seeds have been mostly used medicinally for the treatment of hemorrhoids and circulatory health.[2] Lesser known uses include the treatment of rheumatism, bladder and gastrointestinal disorders, fever, and leg cramps (possible secondary to the circulatory effects).[2]

Traditional usage of horse chestnut appears to be for hemorroids and circulatory health, particularly against blood pooling

1.2Composition

Horse chestnut (seeds) tends to contain:

  • Aescin, which is a series of triterpenoid glycosides broken into two subsets of β-aescins (main ones, known as aescin Ia and aescin Ib[2]) and the α-aescins (two aesceins known as isoaescin Ia and isoaescin Ib[2]). These glycosides are based off the protoaescigenin and barringtogenol C molecules.

  • The coumarin structures Aesculetin[2] and its glycoside Aesculin[2]

  • Scopoletin and its glycoside Fraxin[2] 

  • Procyanidin A2[2]

  • Leucocyanidine[6]

  • Quercetin and its glycosides[2][7]

  • Kaempferol and its glycosides[2][7]

  • Tamarixetin as 3-O-β-d-glucopyranosyl(1→3)-O-β-d-xylopyranosyl-(1→2)-O-β-d-glucopyranoside[6]

Whereas the leaves are known to contain:

  • Coumarins scopoletin (0.41% dry weight), aesculetin (0.13%), and fraxetin (0.05%)[3]

  • Kaempferol as the glycosides 3-O-α-arabinofuranoside, 3-O-β-glucopyranoside, 3-O-α-rhamnopyranoside, and 3-O-α-rhamnopyranosyl(1→6)-O-β-glucopyranoside[8]

  • Quercetin as the glycosides 3-O-α-arabinofuranoside, 3-O-β-glucopyranoside, and 3-O-α-rhamnopyranosyl(1→6)-O-β-glucopyranoside[8]

The fruits consist of:

  • Oil (8.1% of fruit weight[4]) which is comprised of oleic acid (65.3%), linoleic (20.2%), palmitic (4.8%), and stearic (2.1%) acids[4][9] with trace linolenic[9]

  • Phospholipids (0.3%[4]) which are 36.9% Phosphatidylcholine and 13.2-13.9% phosphatidylethanolamine and phosphatidylinositol[4]

  • Sterols (1.2%[4]) with a sitosterol and stigmasterol content[10][11] with the majority (73.2% of sterols) being β-Sitosterol[4]

  • Vitamin E (627mg/kg[4]) mostly γ-Tocopherol (59%) and α-Tocopherol (40%) with trace tocotrienols[4]

The four molecules collectively refered to as aescins (and the two referred to as β-aescins in particular) are the main bioactives in horse chestnut supplements. The coumarins, particular aesculin, are also thought to be somewhat bioactive

Total flavonoids in horse chestnut seed powder (used for supplements) are up to 0.88%[6] or 0.3%[7] of the dry weight; the low contentration seen here may be due to losses in wastewater during processing, which can reach up to 2.58%.[6]

The flavonoids are likely in too low quantities to really contribute significantly to the effects of a seed based supplement

1.3Structures and Properties

The α and β subsets of aescin can be differentiated by their melting point, specific rotation, haemolytic index and solubility in water while the α-aescins can be converted into β-aescins by heating at 100C.[2] β-aescin has a molar mass of 1137.3g.[12]

'Aescin' refers to the mixture of four steroidal saponins, where 'α-aescin' and 'β-aescin' both refer to two of the four saponins. The individual saponins in the α-aescin group are the two isoaescins (Ia and Ib) while the two in the β-aescin group are the aescins (Ia and Ib)

1.4Variants and Formulations

There is a brand name known as Emospid which contains leucocyanidin from Horse Chestnut (100mg), various anthocyanins from bilberry (80mg bilberry standardized to 36% anthocyanins), and triterpenoids from Centella asiatica (30mg) for the treatment of venous disorders such as chronic venous insufficiency and acute hemorroidal crisis.[13]

2Pharmacology

2.1Absorption

It was initially reported that the bioavailability of aescin was 12.5%[14] although subsequent studies in rats have reported bioavailabilities of less than 0.25%.[15] 

Aescins from horse chestnut appear to be poorly absorbed

The differences in absorption rates and values with Aescorin® (standard form of horse chestnut with 50mg β-aescin) and Venostasin® (a delayed release formulation with 50mg β-aescin) is not significant.[16]

2.2Serum

In rats, both isolated aescin Ia and isoaescin Ia are absorbed at an oral intake of 4mg/kg (to max values of 7.1ng/mL and 43.8ng/mL, respectively).[15]

Supplementation of 50mg β-aescin from horse chestnut reaches a Tmax value in just under three hours (2.3-2.9h) reaching an average Cmax of 16.9-17.3ng/mL with an AUC24h of 247.4-258.5ng/h/mL.[16]

The exact peaks in plasma appear to be subject to a wide degree of interpersonal variability.[17]

Twice daily supplementation of β-aescin (50mg) separated by 12 hours is enough to maintain a serum level of above 5ng/mL for 24 hours, as it appears to require 12 hours for the spike in serum β-aescin to reach baseline.[16]

2.3Metabolism

Aescin Ia is known to be extensively metabolized by lactobacillus brevis and intestinal microflora into various metabolites including Isoaescin Ia, protoaescigenin, desacylescin I, and 21β-O-tigloylprotoaescigenin.[18]

Aescin Ia is able to convert into Isoaescin Ia in vitro[2] and in the rat, and while the reverse reaction may also occur it is at a lower rate.[15]

2.4Elimination

Aescin Ia and Isoaescin Ia appear to have a half-life in the 6-8 hour range.[15][2]

2.5Mechanisms

β-aescin has been confirmed to increase the sensitivity of cells to calcium permeability which seems to apply to all tested cells including cardiac cells,[19] bronciol cells,[20] neurons,[21] skeletal muscle cells.[22][23]

3Cardiovascular Health

3.1Mechanisms

In endothelial cells subject to hypoxia (lack of oxygen), the expected decrease in cellular ATP concentrations and the increase in phospholipase A2 activity appears to be attenuated with 100ng/mL (88nM) aescin, with maximal effects at 750ng/mL (660nM).[24] 250ng/mL aescin (220nM) is also effective in reducing a hypoxia-induced immune cell adherence to the endothelium.[25]

The adverse effects of hypoxia (lack of oxygen) on blood vessel cells appears to be reduced when there is aescin circulating around the cell at the time of hypoxia

While aescin does not inherently modify the relaxing effects of acetylcholine on the endothelium, the impairment seen with pyrogallol is reversed in a manner that is again prevented by L-NAME (aescin was unable to preserve relaxation in the presence of pyrogallol and L-NAME).[26] As pyrogallol produces superoxide radicals and reduces nitric oxide bioavailability[27] while L-NAME outright prevents synthesis,[28] these protective effects may be secondary to preserving nitric oxide, which is common for antioxidants (which horse chestnut has been implicated in previously[29]).

Aescin appears to stimulate nitric oxide production from the endothelium in vitro at 1µM[26] and it has been hypothesized[28] that the increased endothelial cell permeability to calcium seen with aescin[20] can cause an increase in endothelial nitric oxide synthase (eNOS) activity, since eNOS is a calcium dependent enzyme.[30]

Aescin may be able to sensitize endothelial cells to calcium influx, which results in an increase in nitric oxide production

Aescin does not modify contractile responses by adrenaline[26] although aescin itself appears to be capable of contracting rabbit portal veins[31] as well as dog[29] and human[32][33] saphenous veins, and the potency in humans appears to be a variable EC50 in the 10-30µM range.[32][33] Although the magnitude of contraction at maximal efficacy is comparable to 100nM adrenaline,[26] the concentrations may be too high to be relevant to oral supplementation.

Aescin has the potential to increase blood pressure, but this requires concentrations in the blood which are orders of magnitude greater than what is seen in the blood with supplementation of Horse chestnut; this information likely does not apply to supplementation in humans

Aescin appears to induce PGF2α, an arachidonic acid prostaglandin.[34][31]

3.2Chronic Venous Insufficiency

Chronic venous insufficiency (CVI) is a condition where the veins are unable to adequately pump blood back to the heart, which tends to result in itching and discoloration as well as edema of the legs.[35][36] Chronic venous insufficiency is the condition which varicose veins are associated with,[37] and CVI is both an aesthetic and medical complication.

Studies that assess the efficacy of horse chestnut extract against placebo note that it is significantly more effective when taken over a period of 1-3 months in reducing symptoms of chronic leg insufficiency.[38][39][40][41] While there appear to be significantly more trials in existence according to meta-analysis,[42] they are not available online due to being conducted in German. Said meta-analysis was able to assess 17 trials conducted on horse chestnut extract for the treatment of chronic venous insufficiency and noted significant reductions in leg pain, edema, leg volume (32.10mL with a 95% CI of 13.49-50.72mL) and both ankle (4.71mm with a 95% CI of 1.13-8.28mm) and calf (3.51mm with a 95% CI of 0.58-6.45mm) width as well as itching relative to placebo.[42]

Relative to placebo, horse chestnut extract at the standard oral doses appears to be effective in reducing all symptoms of chronic venous insufficiency

Supplementation of a seed extract containing 50mg aescin twice daily for 12 weeks in persons with chronic venous insufficiency noted that supplementation was associated a greater reduction in edema relative to placebo (9.8mL in placebo, 43.8mL with the supplement)[39] yet was a potency comparable to compression therapy (stockings or wraps to physically compress the legs[43]). Other comparative studies have noted that horse chestnut (600mg) is less effective than pycnogenol (360mg) in reducing overall symptoms and leg volume[44] and relative to O-ß-hydroxyethyl rutosides (synthetic analogies of rutin for the usage of chronic venous insufficiency[45]) they appear to be comparable according to reviews[42][46] (both trials conducted in German and not available online).

Based on limited evidence, the potency of horse chestnut extract for the treatment of chronic venous insufficency appears to be comparable or lesser than pycnogenol and comparable to compression therapy

4Inflammation and Immunology

4.1Mechanisms

It has been noted that while the antiinflammatory effects of aescin are dependent on the adrenal glands, supplementation does not inhernetly increase circulating corticosterone levels.[47] This led to the hypothesis that aescin is enhancing the effects of already present glucocorticoids[48] as the mechanisms attributed to aescin (Phospholipase A2 suppression,[24] NF-kB inhibition,[49] and reduction of cell adhesion factors[50]) are also seen with glucocorticoids.[51][52][53]

In vitro, aescin and corticosterone can both inhibit macrophage activation (3ng/mL for corticosterone and 10µg/mL for aescin) while the combination appears to be synergistic, reducing secretion of nitric oxide (34.8%), TNF-α (24%), and IL-1β (46.7%) at concentrations of 1ng/mL (corticosterone) and 100ng/mL (aescin).[54]

2mg/kg aescin injected three hours after inflammation was induced in rats (carrageenan) appears to be insufficient to reduce inflammation, and while 1mg/kg corticosterone was also ineffective the combination reduced edema caused by the inflammation by 52.86%[54] and the combination has been used elsewhere synergistically in rats experiencing retinal barrier breakdown (a consequence of inflammation).[55]

Aescin appears to have antiinflammatory properties, and while they are inhernetly weak they appear to be able to enhance the antiinflammatory effects of corticosteroids at reasonable concentrations. This is likely relevant to oral supplementation

4.2Allergies

Type I hypersensitivities (allergic rhinitis, allergic conjunctivitis, allergic asthma, food allergies and anaphylaxis) are immune responses mostly mediated by mast cells and eosinophils where IgE binding to the FcεRI receptor causes a fairly rapid immune responses;[56][57][58] it is divided into an early phase (IgE binding to FcεRI) and a later phase (mediated by the cytokines released from the mast cells, which are degraded after the early phase) and these inflammatory responses (called allergies) tend to be treated with corticosteroids, anti-histamines and mast cell stabilizers.

In a passive cutaneous anaphylaxis model (type I hypersensitivity model for the early phase[59]) and ovalbumin-induced airway inflammation (late phase[60]), intraperitoneal injections of β-Aescin (1.5-3mg/kg) is as effective as the reference drug of 3mg/kg dexamethasone in reducing allergic skin responses while it is slightly less effective at reducing lymphocyte infiltration of the lungs.[12] Anti-allergic effects have been noted elsewhere against compound 48/80 with oral aescin.[61]

β-Aescin appears to have potent anti-allergic effects, and is effective following oral ingestion. While injections are equally effective as corticosteroids, this relative potency may not accurately reflect oral supplementation (since β-Aescin is poorly absorbed)

5Interactions with Organ Systems

5.1Ears

In conditions of circulatory insufficiency in the ears (inner ear disturbances), supplementation of 25mg aescin (although confounded with 450mg troxerutin) five times daily for six weeks was associated with significant improvements in hearing and outperformed the reference drug of 600mg pentoxifylline.[1]

Thought to be beneficial for inner ear disorders as they are related to poor blood flow in veins, but the only study is confounded with another agent

5.2Intestines

The treatment of hemorrhoids is one of the traditionally recommended uses of horse chestnut, mainly as they are congestion of of veins around the anal canal and horse chestnut is known to alleviate congestion of veins.[5]

It has been reported (via a review,[5] primary text here[62]) that two months supplementation of a thrice daily 40mg aescin supplement was associated with significant improvements in endoscopic evaluation, symptoms, and bleeding (82% response with the supplement relative to 32% in placebo) with benefits within a week of supplement usage.

Horse chestnut is traditionally recommended for hemorrhoids. While there is not a lot of evidence actually looking into this issue, the lone study noted significant benefits associated with supplementation

6Interactions with Aesthetics

6.1Skin

A side-effect of chronic veinous insufficient (of which horse chestnut is seen as therapeutic) is varicose veins, and thus the usage of horse chestnut is sometimes recommended for varicose veins[5][63] due to the aescin content.[26]

One study (mentioned in a review[64] and not accessible online) that used oral therapy of 20mg aescin thrice daily in addition to topical application of 4.4mL cream (2% aescin) over eight weeks reported improvements in leg blueness, size, and edema relative to placebo.

Due to its role in chronic venous insufficiency, horse chestnut supplementation is thought to help with varicose veins (which are a common side-effect during mid to late disease stage); very limited evidence on the topic, but it suggests that it is effective

7Safety and Toxicology

7.1General

The meta-analysis on chronic venous insufficiency (2006 version)[42] noted that the most commonly reported side-effects associated with horse chestnut consumption were gastrointestinal complaints, dizziness, nausea, headache, and pruritis. Usually, these side-effects did not differ from placebo (aside from gastrointestinal compliants which sometimes were significant).[42]

Short term usage of horse chestnut extract is thought to be generally safe, although there may be more gastrointestinal side-effects assocaited with horse chestnut relative to placebo

7.2Case studies

The component aesculetin is thought to be present in sufficient quantities to adversely interact with warfarin in regards to blood thinning.[65]

Due to the anticoagulating effects of aesculetin and the blood flow enhancement with aescins, it is thought that horse chestnut can potentially interact (adversely) with pharamceutical blood thinners such as Warfarin

In a person with angiomyolipoma (renal tumor thought to be present in 0.13%[66] of the population) which is known to be predisposed to aneurysm and hemorrhage,[67] the usage of an over-the-counter horse chestnut extract was thought to contribute to an observed rupture of said angiomyolipoma.[68]

A case study has associated horse chestnut extract with a rupture of a form of renal tumor; causation was not placed and this topic is not well explored as it applies to horse chestnut extract

The β-aescin component has been implicated in instances of contact urticaria (skin hives associated with itching and reddening)[69] and occupational asthma,[70] suggesting that it may be an allergin.

It appears to be possible to be allergic to β-aescin

References

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This page features 70 references. All factual claims are followed by specifically-applicable references. Click here to see the full set of references for this page.

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