Safety Profile
Known Safety Concerns
- Raw/non-standardized product: esculin toxicity
- Nephrotoxicity reported
- Antiplatelet and anticoagulant interactions
- Hypoglycemic effect -- drug interactions
Contraindications
- Raw/non-standardized product: esculin toxicity
- Nephrotoxicity reported
Interactions
Information not yet available for this ingredient profile.
Evidence and Scientific Findings
Ingredient Overview
Horse chestnut seed extract (HCSE) containing standardized aescin has strong evidence for chronic venous insufficiency. Raw horse chestnut seeds contain esculin, a toxic compound removed in standardized extracts. Nephrotoxicity has been reported.
Biological and Chemical Classification
- Scientific Name
- Aesculus hippocastanum (seed extract)
Mechanism of Action
Information not yet available for this ingredient profile.
Clinical Evidence of Effectiveness
Information not yet available for this ingredient profile.
Pharmacokinetics
Information not yet available for this ingredient profile.
Recommended Dosage
Information not yet available for this ingredient profile.
SETI — Scientific Evidence Transparency Index
Executive Summary — Ingredient Assessment
- 10 studies reviewed
- 0 high-quality studies (meta-analysis or RCT)
- Main clinical benefit observed: Botanical
- Evidence consistency: High consistency across studies (100%)
- Raw/non-standardized product: esculin toxicity
- Nephrotoxicity reported
- Antiplatelet and anticoagulant interactions
- Hypoglycemic effect -- drug interactions
The available scientific evidence for Horse Chestnut indicates notable safety signals that warrant caution. Use should be considered carefully and monitored, particularly in sensitive populations or alongside other medications.
Total SETI Score
High risk| Evidence quality | 10/40 |
| Evidence consistency | 20/20 |
| Safety signals | 0/20 |
| Study recency | 10/10 |
| Evidence transparency | 10/10 |
Evidence Summary
- 10 studies reviewed
- 0 high-quality studies (meta-analysis or systematic review)
- 0 studies identified benefits or no safety concern (GREEN)
- 10 studies reported limited or advisory safety evidence (YELLOW)
Evidence Policy
Only peer-reviewed scientific literature indexed in PubMed or comparable databases is included in this evaluation. Commercial websites, blogs, and marketing materials are excluded. All references include direct traceable links to source documents.
Last updated: 25 მარ 2026, 22:39
Evidence Distribution
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Observational / other LOW evidence YELLOWModulation of Wnt/u03b2-Catenin Pathway by Aesculus hippocastanum Extract Enhances Temozolomide Sensitivity in Glioblastoma Cells. ↗Scuderi SA et al.. Modulation of Wnt/u03b2-Catenin Pathway by Aesculus hippocastanum Extract Enhances Temozolomide Sensitivity in Glioblastoma Cells.. J Cell Mol Med. 2026. PMID:41693444.PMID 41693444 ↗Journal J Cell Mol MedYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41693444/
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Observational / other LOW evidence YELLOWAnnual Dynamics of Mycobiota in Symptomatic Century-Old Trees of Aesculus hippocastanum, Fagus sylvatica, Populus alba, and Quercus robur. ↗Spetik M et al.. Annual Dynamics of Mycobiota in Symptomatic Century-Old Trees of Aesculus hippocastanum, Fagus sylvatica, Populus alba, and Quercus robur.. J Fungi (Basel). 2026. PMID:41590462.PMID 41590462 ↗Journal J Fungi (Basel)Year 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41590462/
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Observational / other LOW evidence YELLOWLatvian herbal medicines under the infrared lens: An FTIR-ATR dataset. ↗Vu012btoliu0146a UL et al.. Latvian herbal medicines under the infrared lens: An FTIR-ATR dataset.. Data Brief. 2026. PMID:41510503.PMID 41510503 ↗Journal Data BriefYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41510503/
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Observational / other LOW evidence YELLOWAesculus hippocastanum Extract Exerts Neuroprotective Effects in an MPP(+)-Induced Parkinson's Disease Model via PPARu03b3 Activation. ↗Scuderi SA et al.. Aesculus hippocastanum Extract Exerts Neuroprotective Effects in an MPP(+)-Induced Parkinson's Disease Model via PPARu03b3 Activation.. J Cell Mol Med. 2026. PMID:41492840.PMID 41492840 ↗Journal J Cell Mol MedYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41492840/
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Observational / other LOW evidence YELLOWFoliar Illumination Affects the Severity of Cameraria ohridella Damage Among Horse Chestnut Species. ↗Bogoutdinova LR et al.. Foliar Illumination Affects the Severity of Cameraria ohridella Damage Among Horse Chestnut Species.. Plants (Basel). 2025. PMID:41515031.PMID 41515031 ↗Journal Plants (Basel)Year 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41515031/
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Observational / other LOW evidence YELLOWDelphi Consensus on the Role of Venoactive Nutraceuticals in the Management of Chronic Venous Disease: A Position Statement of the Italian Society… ↗Buso G et al.. Delphi Consensus on the Role of Venoactive Nutraceuticals in the Management of Chronic Venous Disease: A Position Statement of the Italian Society of Angiology and Vascular Medicine (SIAPAV).. Nutrients. 2025. PMID:41470775.PMID 41470775 ↗Journal NutrientsYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41470775/
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Observational / other LOW evidence YELLOWExfoliated Graphite as a Solid Sorbent in Ultrasound-Assisted Dispersive Micro-Solid-Phase Extraction for Determination of Chromium and Vanadium in Herbs. ↗Osiu0144ska M et al.. Exfoliated Graphite as a Solid Sorbent in Ultrasound-Assisted Dispersive Micro-Solid-Phase Extraction for Determination of Chromium and Vanadium in Herbs.. Foods. 2025. PMID:41376013.PMID 41376013 ↗Journal FoodsYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41376013/
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Observational / other LOW evidence YELLOWExtraction-Dependent Antioxidant Activity of Red Horse Chestnut (Aesculus u00d7 carnea, Family Sapindaceae) Plant Parts. ↗Florkowska K et al.. Extraction-Dependent Antioxidant Activity of Red Horse Chestnut (Aesculus u00d7 carnea, Family Sapindaceae) Plant Parts.. Molecules. 2025. PMID:41375147.PMID 41375147 ↗Journal MoleculesYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41375147/
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Observational / other LOW evidence YELLOWAntiradical and Antioxidant Activity and Stimulation of Pancreatic Lipase by Extracts Obtained from Saponin-Rich Raw Materials: Experimental and In Silico Study. ↗Sroka Z et al.. Antiradical and Antioxidant Activity and Stimulation of Pancreatic Lipase by Extracts Obtained from Saponin-Rich Raw Materials: Experimental and In Silico Study.. Int J Mol Sci. 2025. PMID:41226295.PMID 41226295 ↗Journal Int J Mol SciYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41226295/
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Observational / other LOW evidence YELLOWMultidisciplinary Bioanalytical Approach to Assess the Anti-Aging Properties of Flower Petals-A Promising Sustainable Cosmetic Ingredient. ↗Ivkoviu0107 u0110 et al.. Multidisciplinary Bioanalytical Approach to Assess the Anti-Aging Properties of Flower Petals-A Promising Sustainable Cosmetic Ingredient.. Plants (Basel). 2025. PMID:41012020.PMID 41012020 ↗Journal Plants (Basel)Year 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41012020/
Score Transparency
0 of 10 approved references (score saturates at 10). More peer-reviewed studies = stronger evidence base.
Method: Q = number of approved references ÷ 10 (capped at 1.0)
Limited — mostly case reports or animal studies
Method: L = mean study-level weight across approved references. Level 1 (meta-analysis / systematic review) = 1.0; Level 2 (RCT) = 0.8; Level 3 (cohort/case-control) = 0.6; Level 4 (case report) = 0.4; Level 5 (animal / in-vitro) = 0.2.
Mixed or neutral — roughly equal benefit and risk signals
Method: D = (sum of risk-scored references − sum of benefit-scored references) ÷ total evidence score, then scaled from [−1, 1] to [0, 1]. 0.0 = pure benefit; 0.5 = neutral; 1.0 = pure risk.
One or more monitoring-level safety signals active
Method: S = 0.5 (neutral baseline) + sum of active signal severity deltas ÷ 10. Severity deltas: Critical = +2.0, High = +1.5, Moderate = +1.0, Low = +0.5. Capped at 1.0.
Final GIRI Score for Horse Chestnut. Risk level thresholds: Low 0–3.0 · Moderate 3.0–5.5 · High 5.5–7.5 · Critical 7.5–10.
Full methodology & data sources
The GIRI Score is computed entirely from structured data — no editorial scoring or subjective weighting is applied at any step.
- References: Only approved references are counted. Each reference is assigned an evidence level (L1–L5) and a direction (risk / neutral / benefit) by the reference manager or AI classifier.
- Safety Signals: Sourced from regulatory agencies (FDA, EMA, Health Canada, TGA, and others) and pharmacovigilance databases. Only active signals count toward the score.
- Formula version: GIRI Score v3.7.0 — Q × L × D × S × 10.
- Limitations: The score reflects published evidence and recorded signals as of the last update date. It is not a clinical risk assessment and should not replace advice from a qualified healthcare professional.
Risk Level Classification
Based on available regulatory signals and scientific evidence, this ingredient presents a moderate safety concern. Caution is advised, particularly at high doses or in sensitive populations.
0–3.0
3.0–5.5
5.5–7.5
7.5–10
The score pin shows exactly where this ingredient falls on the fixed risk scale.
What drove the Moderate classification for Horse Chestnut
A score of 4.0 places this ingredient in the Moderate band. Thresholds: Low 0–3.0 · Moderate 3.0–5.5 · High 5.5–7.5 · Critical 7.5–10.
0 approved references.
Limited — mostly case reports or animal studies (Level 4–5).
Neutral or mixed — benefit and risk signals roughly balanced.
No active signals — S component is at neutral baseline (0.5), contributing no extra risk weight.
No major regulatory restrictions or advisories recorded across monitored jurisdictions (FDA, EMA, Health Canada, TGA, and others).
How are the Low / Moderate / High / Critical thresholds defined?
The four risk levels are fixed score bands. A score is assigned to exactly one level based on where it falls:
| Level | Score | Meaning |
|---|---|---|
| LOW | 0.0 – 2.9 | Sparse or predominantly beneficial evidence. No active safety alerts. |
| MODERATE | 3.0 – 5.4 | Mixed signals — some risk alongside benefit. Caution at high doses or in sensitive groups. |
| HIGH | 5.5 – 7.4 | Multiple studies or regulatory alerts documenting adverse effects. Professional oversight recommended. |
| CRITICAL | 7.5 – 10 | Regulatory restrictions in one or more major jurisdictions. Serious documented harm. Avoid without specialist supervision. |
Thresholds are fixed constants (GIRI_Score_Utils::LEVEL_THRESHOLDS). They do not change per ingredient and are never subject to editorial adjustment.