Red Vine Leaf Extract: A Natural Remedy for Heavy Legs

Citable definition: Red vine leaf extract (standardized extract AS 195, derived from Vitis vinifera L. leaves) is a phytotherapeutic agent used for chronic venous insufficiency (CVI) — a condition in which leg veins fail to return blood efficiently to the heart, causing swelling, pain, and heaviness. A 2020 systematic review (Azhdari et al., Phytotherapy Research, PMID: 32754965) confirmed that AS 195 significantly reduces limb volume, ankle circumference, and subjective CVI symptoms in controlled clinical trials.

What Is Red Vine Leaf Extract?

Red vine leaf extract is obtained from the leaves of Vitis vinifera L. — the cultivated grapevine. In herbal medicine, the leaves used come specifically from so-called “Teinturier” varieties — such as Alicante Bouschet or Gamay Fréaux — which are exceptionally rich in anthocyanins, the red-violet pigments responsible for much of the therapeutic activity.

The European Medicines Agency (EMA) Committee on Herbal Medicinal Products (HMPC) community monograph for Vitis vinifera L. folium (adopted 2010, revised 2019) sets minimum quality standards: at least 0.20% anthocyanins and 4.0% total polyphenols in dry matter (Schneider et al., Planta Medica 2008, DOI: 10.1055/s-2008-1034370).

This plant extract has been used in Europe for several decades to relieve the symptoms of chronic venous insufficiency (CVI): heavy legs, ankle swelling, pain, and tingling. Today, its effectiveness is supported by rigorous clinical trials — not merely tradition.

For a broader overview of CVI and its management, see our article on chronic venous insufficiency.

What the Science Says: Solid Evidence

A Systematic Review Confirms Efficacy

A systematic review published in 2020 in Phytotherapy Research analyzed five clinical trials of the AS 195 extract. The conclusion: this extract significantly improves several key CVI parameters — limb volume, calf and ankle circumference, and subjective sensations of heaviness and tension (Azhdari et al., PMID: 32754965, DOI: 10.1002/ptr.6705).

The Landmark Trial: Rabe et al. 2011

The best-documented study is a randomized, double-blind, placebo-controlled trial conducted in 248 patients with CVI at CEAP stages 3 to 4a — meaning patients with established venous edema:

• Treatment: 720 mg/day of AS 195 for 12 weeks
• Primary outcome: reduction in lower limb volume of 19.9 ml on average versus placebo (p = 0.0268)
• Standardized effect size: 0.28 — considered clinically meaningful for this edema parameter (the patient-perceptible threshold for edema is lower than for other outcomes)
• Tolerability: similar to placebo, very few adverse events

(Rabe E. et al., European Journal of Vascular and Endovascular Surgery 2011, DOI: 10.1016/j.ejvs.2010.12.003)

An important limitation: the observation period (12 weeks) is short for a chronic condition that evolves over years. To date, no study has demonstrated a reduction in the risk of venous leg ulcers with AS 195. Data beyond three months are insufficient to draw conclusions about long-term benefits.

Evidence From Early-Stage Disease

An earlier randomized trial had already demonstrated the efficacy of 360 to 720 mg/day of AS 195 at CEAP stages I and II — the earliest stages of CVI — with significant edema reduction and subjective symptom improvement (Arzneimittelforschung 2000, PMID: 10719612).

Improvement of Skin Microcirculation

A crossover trial published in Drugs R&D (2004, PMID: 15293865) demonstrated objective improvement of skin microcirculation and transcutaneous oxygen supply in patients treated with AS 195 — two parameters directly correlated with CVI severity and venous ulcer risk.

How It Works: Four Complementary Mechanisms

Red vine leaf extract does not act through a single pathway, but through four complementary mechanisms:

1. Nitric Oxide Production

AS 195 stimulates nitric oxide synthase (NOS) in endothelial cells and red blood cells, increasing production of nitric oxide (NO). This natural vasodilator improves microcirculation and reduces excessive venous tone (Grau et al., Pharmacology Research & Perspectives 2016, DOI: 10.1002/prp2.213).

2. Antioxidant Protection

The extract reduces the production of free radicals (reactive oxygen species — ROS) and strengthens the antioxidant capacity of endothelial cells. This protection prevents vascular damage caused by chronic oxidative stress, which is common in CVI (Grau et al., 2016).

3. Reinforcement of the Endothelial Barrier

The flavonoids in red vine leaf — particularly quercetin glucuronide, isoquercitrin, and kaempferol — protect venous endothelium against activation by blood components (white blood cells, platelets). This action reduces vascular permeability and limits edema formation (Nees et al., Arzneimittelforschung 2003;53(5):330-341, DOI: 10.1055/s-0031-1297117).

4. Improved Red Blood Cell Deformability

The extract helps red blood cells pass through small capillaries more easily by improving their deformability — optimizing oxygen and carbon dioxide exchange in the tissues (Grau et al., 2016).

Chemical Composition: Polyphenols at Work

The therapeutic richness of red vine leaf comes from its complex polyphenolic composition. The main active compounds are:

DM = dry matter. Standards set by EMA HMPC monograph.

The exact composition varies depending on the grapevine variety, harvest date, and climate — which is why choosing standardized extracts such as AS 195 matters (Schneider et al., Planta Medica 2008).

How to Use It

Clinically Validated Dosage

The dose established in clinical trials is 720 mg/day of AS 195 extract, taken as two 360 mg tablets (morning and evening), preferably before meals.

Duration of Treatment

Significant benefits on edema and symptoms appear after 12 weeks of continuous treatment. A medical review is advisable at the end of this period.

Who Is This Treatment For?

Red vine leaf extract is particularly suited to patients with mild to moderate CVI (CEAP stages 1 to 3) who want a complementary treatment alongside elastic compression, or who find compression stockings difficult to tolerate.

Precautions

• Pregnancy and breastfeeding: not recommended as a precaution (insufficient safety data)
• Anticoagulants (warfarin, vitamin K antagonists, direct oral anticoagulants): consult your physician before use
• Allergy to plants of the Vitaceae family: contraindication

Overall tolerability is excellent in studies: adverse effects are rare, mild, and transient (mainly digestive) (Rabe et al., EJVES 2011; clinical review, Pharmazie 2019, PMID: 30940301).

Antistax®: Availability and Insurance Coverage

The AS 195 extract is the active ingredient in Antistax®, a traditional herbal medicinal product registered in France and across most European countries. It is available without a prescription at pharmacies, in film-coated tablets of 360 mg.

In Europe, Antistax® is sold over the counter under this name — it may be less familiar to patients in North America, where it is not widely marketed. If you are outside Europe, ask your pharmacist for a product standardized to AS 195 or an equivalent red vine leaf extract.

Insurance coverage: Antistax® is not reimbursed by French public health insurance (Assurance Maladie). Phytotherapeutic venotonics are classified as providing insufficient medical benefit (SMR insuffisant) by the French health authority (HAS), which excludes reimbursement. In the UK, US, and most other countries, it is similarly not covered by health insurance as it is a traditional herbal medicine rather than a prescription drug. The retail price in France is typically €10–15 for 30 tablets.

Compared to other venotonics: Micronized Purified Flavonoid Fraction (MPFF, e.g., Daflon®) has a higher level of evidence and a broader indication in the ESVS 2022 guidelines. Red vine leaf extract represents an interesting phytotherapeutic alternative — particularly for patients seeking a plant-based approach — but it does not replace validated drug treatments in severe CVI.

Place in the Overall Management of CVI

Red vine leaf extract belongs to the family of phytotherapeutic venotonics, alongside horse chestnut extract (aescin), Ginkgo biloba, and rutin. A review published in the Journal of Wound Care (Butcher, 2006, DOI: 10.12968/jowc.2006.15.9.26959) and recent European consensus data on veno-active nutraceuticals (Nutrients 2025, PMID: 41470775) confirm its value in the multimodal management of CVI.

It does not replace:

• Compression stockings (the reference treatment for CVI)
• Sclerotherapy or endovenous laser treatment for established varicose veins
• Regular medical follow-up with a vascular specialist

It can, however, complement these approaches — particularly to improve day-to-day comfort between consultations.

For more on CVI treatment options, see our guide to endovenous laser treatment.

Key Takeaways

• Red vine leaf extract (AS 195 — Antistax®) is a clinically validated phytotherapeutic treatment for mild to moderate chronic venous insufficiency
• The effective dose is 720 mg/day for 12 weeks; data beyond three months remain limited
• It acts through 4 mechanisms: nitric oxide, oxidative stress, endothelial barrier, and red blood cell deformability
• Tolerability is excellent, comparable to placebo in clinical trials
• It can complement elastic compression, without replacing it
• Not reimbursed by insurance; available over the counter at pharmacies
• Consult your physician or a vascular specialist before starting any new treatment

Medical Disclaimer: This article is produced by the Petit Veinard Editorial Board for informational and educational purposes only. It does not constitute medical advice, diagnosis, or treatment. Chronic venous insufficiency requires a medical diagnosis and regular follow-up. Always consult a qualified physician or vascular specialist before starting any treatment, including herbal medicines.

Also available in French on petitveinard.fr

Sources

1. Azhdari M, Zilaee M, Karandish M, et al. Red vine leaf extract (AS 195) can improve some signs and symptoms of chronic venous insufficiency, a systematic review. Phytotherapy Research. 2020;34(10):2577-2585. PMID: 32754965. DOI: 10.1002/ptr.6705

2. Rabe E, Stücker M, Esperester A, Schäfer E, Ottillinger B. Efficacy and Tolerability of a Red-vine-leaf Extract in Patients Suffering from Chronic Venous Insufficiency. European Journal of Vascular and Endovascular Surgery. 2011;41(4):540-547. DOI: 10.1016/j.ejvs.2010.12.003

3. Grau M, Bölck B, Bizjak DA, et al. The red-vine-leaf extract AS195 increases nitric oxide synthase–dependent nitric oxide generation and decreases oxidative stress. Pharmacology Research & Perspectives. 2016;4(1). DOI: 10.1002/prp2.213

4. Schneider E, von der Heydt H, Esperester A. Evaluation of Polyphenol Composition in Red Leaves from Different Varieties of Vitis vinifera. Planta Medica. 2008;74(5):565-572. DOI: 10.1055/s-2008-1034370

5. Butcher M. A review of evidence on red vine leaf extract in the prevention and management of venous disease. Journal of Wound Care. 2006;15(9):393-396. DOI: 10.12968/jowc.2006.15.9.26959

6. Schaefer E, Peil H, Ambrosetti L, Petrini O. Oedema Protective Properties of the Red Vine Leaf Extract AS 195 in the Treatment of Chronic Venous Insufficiency. Arzneimittelforschung. 2003;53(4):243-246. DOI: 10.1055/s-0031-1297103

7. Nees S, Weiss D, Reichenbach-Klinke E, et al. Protective Effects of Flavonoids Contained in the Red Vine Leaf on Venular Endothelium. Arzneimittelforschung. 2003;53(5):330-341. DOI: 10.1055/s-0031-1297117

8. Efficacy of orally administered extract of red vine leaf AS 195 in chronic venous insufficiency (stages I-II). Arzneimittelforschung. 2000. PMID: 10719612

9. Improvement of cutaneous microcirculation and oxygen supply in patients with chronic venous insufficiency by orally administered extract of red vine leaves AS 195. Drugs R D. 2004. PMID: 15293865

10. Therapeutic approach to chronic venous insufficiency — clinical benefits of red-vine-leaf-extract AS 195 (Antistax). Pharmazie. 2019. PMID: 30940301