Red Vine Leaf
Vitis vinifera
Evidence Rating
C Moderate
Confidence Level
Moderate
Medium
Traditions
Western
Last Updated
2/9/2026
Summary
Red vine leaf extract (AS 195, marketed as Antistax) is a flavonoid-rich phytomedicine used for mild-to-moderate chronic venous insufficiency (CVI). Standardized to quercetin-3-O-beta-glucuronide, it has demonstrated significant edema reduction and symptom improvement in multiple RCTs at doses of 360-720 mg/day. The EMA/HMPC has granted traditional use status. It represents a well-tolerated option for early-stage CVI that has been marketed in France for over 70 years and is now available across multiple European countries.
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Drug Interactions
This herb has significant drug interactions. Do not use if you are taking medications without consulting a healthcare provider first. See detailed interaction information below.
Regulatory Status
| Regulatory Body | Status |
|---|---|
| Commission E (Germany) | âś“ Approved |
| ESCOP (European) | âś“ Approved |
| EMA/HMPC (EU) | âś“ Approved |
Metadata
| Field | Details |
|---|---|
| Common Names | Red vine leaf, Weinlaub (German), Feuille de vigne rouge (French), Foglia di vite rossa (Italian) |
| Botanical Name | Vitis vinifera L. |
| Plant Family | Vitaceae |
| Part Used | Leaf (Vitis viniferae folium) — specifically leaves of dark-red grape varieties harvested in autumn |
| Evidence Quality Rating | MEDIUM — Multiple RCTs with the specific AS 195 extract; systematic review; EMA/HMPC traditional use monograph |
Approved Indications
Commission E (Germany)
- No specific Commission E monograph for Vitis vinifera folium was issued during the Commission E era (1978-1994)
- The product entered the German market later than the Commission E monograph period for this indication
ESCOP Monograph
- No dedicated ESCOP monograph for red vine leaf at time of research [NEEDS-RESEARCH — may have been published since last check]
EMA/HMPC
- Traditional use registration: EMA published Assessment Report and European Union Herbal Monograph on Vitis vinifera L., folium
- Indication: Traditional herbal medicinal product for relief of symptoms of discomfort and heaviness of legs related to minor venous circulatory disturbances
- Traditional use recognized based on >70 years of use in France and subsequent marketing across EU
Agreement/Disagreement Between Bodies
- Red vine leaf is a newer entrant to the formal European phytotherapy system compared to horse chestnut or butcher’s broom
- The EMA/HMPC granted only traditional use status (not “well-established use”), meaning the clinical evidence, while positive, did not meet the higher regulatory threshold
- This is somewhat at odds with the available clinical trial data, which includes well-designed RCTs [CONTESTED]
Conditions Treated
Primary (evidence-based)
- Chronic venous insufficiency stages I-II (Widmer classification)
- Lower leg edema
- Feeling of heaviness and tiredness in legs
- Sensation of tension in legs
- Tingling in legs
- Pain associated with venous insufficiency
Secondary
- Improvement of cutaneous microcirculation
- Enhancement of transcutaneous oxygen supply in CVI patients
Mechanism of Action
Endothelial Barrier Preservation
- Active flavonoids accumulate in the venous intima (inner lining of veins)
- Preserve endothelial barrier function, preventing plasma leakage
- Inhibit the breakdown of the endothelial glycocalyx
Anti-inflammatory
- Inhibit the inflammatory cascade that drives CVI progression
- Reduce leukocyte adhesion to venous endothelium
- Anti-prothrombotic effects at the endothelial level
Microcirculation Enhancement
- Improve cutaneous microcirculation in affected legs
- Increase transcutaneous oxygen pressure (tcpO2) in CVI patients
- This mechanism has been demonstrated by laser Doppler fluxmetry in clinical trials
Anti-edematous
- Reduce capillary permeability (sealing effect)
- Decrease transcapillary filtration
- Clinically measured as reduced leg volume and circumference
Key Active Constituents
- Quercetin-3-O-beta-glucuronide: Main flavonoid — the primary marker compound for standardization
- Isoquercitrin (quercetin-3-O-beta-glycoside): Secondary flavonoid
- Additional flavonol glycosides and glucuronides
- The extract AS 195 is standardized to these flavonoid components
Clinical Evidence Summary
Pivotal RCT: Kiesewetter et al. (2000)
| Parameter | Details |
|---|---|
| Design | Randomized, double-blind, placebo-controlled |
| Population | CVI stages I and incipient stage II (Widmer classification) |
| Sample Size | Not specified in available abstracts; multi-center |
| Interventions | AS 195 360 mg once daily vs AS 195 720 mg once daily vs placebo |
| Duration | 12 weeks |
| Key Results | Both 360 mg and 720 mg doses significantly reduced lower leg edema and circumference vs placebo. Key CVI-related symptoms improved to a clinically relevant extent. |
| Safety | Both doses confirmed safe |
| Publication | Arzneimittelforschung. 2000;50(2):109-117 |
| [Source: pubmed.ncbi.nlm.nih.gov/10719612/] |
Microcirculation Study: Kalus et al. (2004)
| Parameter | Details |
|---|---|
| Design | Randomized, double-blind, placebo-controlled, crossover |
| Intervention | Orally administered AS 195 |
| Key Findings | Significant improvement of cutaneous microcirculation and transcutaneous oxygen supply in CVI patients |
| Significance | Provided mechanistic evidence for clinical efficacy — the extract genuinely improves tissue oxygenation in affected limbs |
| [Source: pubmed.ncbi.nlm.nih.gov/15293865/] |
Observational Study: Schneider et al. (2003)
| Parameter | Details |
|---|---|
| Design | 6-week observational clinical trial |
| Key Findings | Demonstrated edema-protective properties of AS 195 in routine clinical practice |
| Relevance | Confirmed that RCT findings translate to real-world clinical settings |
| [Source: pubmed.ncbi.nlm.nih.gov/12785119/] |
Efficacy and Tolerability RCT: Rabe et al. (2011)
- Double-blind, placebo-controlled study
- Confirmed efficacy for leg volume reduction and symptom improvement
- Well tolerated with adverse event profile similar to placebo [Source: sciencedirect.com, EJVES]
Systematic Review: Defined et al. (2020)
- Reviewed all available clinical evidence for AS 195
- Concluded: “Red vine leaf extract (AS 195) can improve some signs and symptoms of chronic venous insufficiency”
- Identified improvements in: lower leg volume, calf/ankle circumference, tired/heavy legs, tingling, pain, tension [Source: pubmed.ncbi.nlm.nih.gov/32314844/]
European vs US/Anglophone Consensus
| Aspect | European Position | US/Anglophone Position |
|---|---|---|
| Market presence | Antistax is a well-known OTC brand across Europe | Available in US as dietary supplement (Antistax brand); not widely known |
| Regulatory status | EMA/HMPC traditional use monograph; registered in multiple EU countries | Dietary supplement only |
| Clinical awareness | Known to pharmacists and some physicians as a CVI option | Virtually unknown to clinicians |
| Evidence perception | Accepted based on RCTs + long traditional use in France | Not in clinical consciousness |
| Historical context | Red vine leaves used in French traditional medicine for >70 years for “heavy legs" | "Heavy legs” is not a recognized clinical complaint in US medicine |
Safety Profile
Contraindications
- Known hypersensitivity to Vitis vinifera or any component of the extract
- No other specific contraindications identified in clinical trials
Drug Interactions
- No clinically significant drug interactions reported in clinical trials or post-marketing surveillance
- Theoretical: flavonoid content could theoretically interact with CYP450 substrates, but this has not been observed clinically
- The interaction profile is very favorable — one of the safest venoactive drugs
Side Effects
- Very well tolerated in clinical trials
- Adverse event rates similar to placebo
- Occasional: mild GI complaints
- Rare: headache, skin rash
- No serious adverse events reported in clinical trials
Pregnancy and Lactation
- Insufficient data — not recommended during pregnancy or lactation
- No specific safety studies in pregnant or lactating women
- Traditional use in France does not explicitly address pregnancy
Clinical Dosage
| Preparation | Dosage | Notes |
|---|---|---|
| AS 195 (Antistax) | 360 mg once daily | Minimum effective dose in RCTs |
| AS 195 higher dose | 720 mg once daily | Tested in RCTs; may provide additional benefit in some patients |
| Standard recommendation | 360-720 mg/day, taken as a single morning dose | Before breakfast with water |
| Duration | Minimum 6-12 weeks | Seasonal use common (spring through autumn in Europe) |
| Onset of effect | 2-4 weeks for measurable edema reduction | Subjective symptom improvement may occur earlier |
Key point: The evidence applies specifically to the AS 195 extract standardized to quercetin-3-O-beta-glucuronide. Generic “grape leaf extract” or “grape seed extract” products are NOT equivalent.
Sources
- EMA/HMPC Assessment Report on Vitis vinifera L., folium (Draft and Final versions)
- EMA European Union Herbal Monograph on Vitis vinifera L., folium
- Kiesewetter H et al. Efficacy of orally administered extract of red vine leaf AS 195 in chronic venous insufficiency (stages I-II). Arzneimittelforschung. 2000;50(2):109-117. [PubMed: 10719612]
- Kalus U et al. Improvement of cutaneous microcirculation and oxygen supply in patients with chronic venous insufficiency by orally administered extract of red vine leaves AS 195. Arzneimittelforschung. 2004;54(8):455-461. [PubMed: 15293865]
- Schneider M et al. Oedema protective properties of the red vine leaf extract AS 195 in the treatment of chronic venous insufficiency. Arzneimittelforschung. 2003;53(4):243-246. [PubMed: 12785119]
- Rabe E et al. Efficacy and Tolerability of a Red-vine-leaf Extract in Patients Suffering from Chronic Venous Insufficiency. EJVES. 2011;42(1):142-148.
- Defined M et al. Red vine leaf extract (AS 195) can improve some signs and symptoms of chronic venous insufficiency, a systematic review. Phytother Res. 2020;34(6):1243-1252. [PubMed: 32314844]
- Monsieur R, Van Snick G. Therapeutic approach to chronic venous insufficiency - clinical benefits of red-vine-leaf-extract AS 195 (Antistax). Pharmazie. 2019;74(4):193-200. [PubMed: 30940301]
Connections
- Compare with Horse Chestnut — stronger evidence base, different mechanism
- Compare with Butcher’s Broom — different mechanism (venoconstrictive vs anti-exudative)
- All three CVI herbs (horse chestnut, butcher’s broom, red vine leaf) represent the “venoactive drug” category