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Rvl5.4
Red Vine Leaf Extract Research
Too few graded studies
12 peer-reviewed studies
What the evidence says
Too few graded studies
Red Vine Leaf Extract doesn't have enough studies with structured effect-size data yet to pool a verdict. Browse the studies below for individual findings.
Most evidence is from medium-quality meta-analyses and randomised trials published 2000–2026 with a typical study size of 71 participants.
Based on 12 studies · 1 meta-analysis · 3 RCTs · 745 total participants
Confidence
Moderate confidence
By outcome
Chronic venous insufficiencyModest reduction in lower-leg swelling and calf circumference in chronic venous insufficiency, with less leg pain in one trial. Not studied for heart or arterial outcomes · 6-12 weeks
Too few graded studies10 studies
Microcirculation & endothelium
Too few graded studies4 studies
Safety profile
Too few graded studies4 studies
Steady research
2 studies in the last 5 years · Latest meta-analysis: 2026
200020132026
1RCTCited 47×n=248 · medium study2011
In plain English: After 12 weeks, AS195 significantly reduced lower limb volume by a mean of 19.9 standard error (SE) 8.9 ml over placebo (95% confidence interval (CI): -37.5, -2.3; p = 0.0268; analysis of covariance, ANCOVA).
Rabe E et al. · Eur J Vasc Endovasc Surg (2011)
Registered (NCT00855179) randomised, double-blind, placebo-controlled multicentre trial of 720 mg/day for 12 weeks in people with CEAP C3 to C4a chronic venous insufficiency and moderate to severe symptoms. The full-analysis set was 248 (122 placebo, 126 extract)
Lower limb volume fell by about 20 ml more than placebo (95% CI -37.5 to -2.3 ml, p = 0.0268), a standardised effect size of 0.28
Leg pain fell 6.6 mm more than placebo on a 100 mm scale (p = 0.047). Other symptoms showed no significant change
In plain English: In contrast, for patients treated with AS 195, lower leg volume decreased, and after 12 weeks of treatment, the difference in mean lower leg volume between the active treatment groups and the placebo group was -75.9 g (95% CI: -106.1 to -45.8 g) and -99.9 g (95% CI: -130.3 to -69.6 g) for the group treated with 360-mg AS 195 (N = 86) and 720-mg AS 195 (N = 84), respectively.
Kiesewetter H et al. · Arzneimittelforschung (2000)
Randomised, double-blind, placebo-controlled multicentre trial in 260 outpatients with stage I to incipient stage II chronic venous insufficiency, not using compression stockings: placebo, 360 mg or 720 mg once daily for 12 weeks
Lower leg volume (water displacement) rose 33.7 g with placebo at 12 weeks and fell with the extract, a difference versus placebo of -75.9 g at 360 mg and -99.9 g at 720 mg (p < 0.001)
Calf circumference fell versus placebo at both doses. Ankle circumference fell in the same direction but less markedly
In plain English: After 6 weeks of treatment the leg circumference was decreased (ankle level: by -0.39 +/- 0.09cm versus +0.29 +/- 0.09cm; p < 0.0001; calf level: by -0.54 +/- 0.05cm versus +0.14 +/- 0.05cm; p < 0.0001).
Kalus U et al. · Drugs R D (2004)
Randomised, double-blind, placebo-controlled crossover trial in 71 people with stage I or II chronic venous insufficiency: 360 mg once daily or placebo for 6 weeks, a 4-week washout, then the other treatment
Cutaneous microvascular blood flow at the ankle rose with the extract and fell with placebo (p < 0.0001), and transcutaneous oxygen pressure rose 1.35 mmHg versus a 7.27 mmHg fall with placebo (p < 0.0001)
Ankle circumference fell 0.39 cm versus a 0.29 cm rise with placebo, and calf circumference fell 0.54 cm versus a 0.14 cm rise (both p < 0.0001)
In plain English: Red vine leaf extract significantly improved numbers of outcomes (lower leg volume, calf and ankle circumference, tired, heavy legs, tingling sensation, pain, the sensation of tension in the legs, cutaneous microcirculation, and transcutaneous oxygen pressure) in only some trials.
Azhdari M et al. · Phytother Res (2020)
Systematic review that screened 56 studies and included 5 trials of the extract in chronic venous insufficiency. No pooled estimate is reported
Leg volume, calf and ankle circumference, heaviness, tension, tingling and pain improved in only some of the trials
In plain English: Red vine leaf extract (RR = 0.62; 95% CI: 0.44 - 0.87) was significantly associated with fewer adverse events.
Nguyen AN et al. · Phlebology (2026)
Network meta-analysis of 51 randomised trials (6,800 patients) of drug treatments for chronic venous disease
Red vine leaf extract was associated with fewer adverse events than control (RR 0.62, 95% CI 0.44 to 0.87)
The abstract names only calcium dobesilate as significantly reducing pain, and calcium dobesilate and Centella asiatica as reducing heaviness. It does not report a significant pain or heaviness benefit for red vine leaf extract
In plain English: No consensus was reached for ruscus, horse chestnut, hydroxyethylrutosides, red vine leaf extract, anthocyanosides, or β-arbutin in monotherapy.
Buso G et al. · Nutrients (2025)
Three-round Delphi consensus of 21 Italian vascular specialists on venoactive nutraceuticals in chronic venous disease
The panel reached no consensus on using red vine leaf extract on its own
A multi-ingredient combination that included a Vitis vinifera extract was judged a reasonable first-line conservative option, which is expert opinion rather than trial evidence for this extract alone
In plain English: At the end of the study, all subjective symptoms of CVI (tired, heavy legs, sensation of tension in the legs, tingling sensations in the legs, pain in the legs) were statistically significantly improved.
Schaefer E et al. · Arzneimittelforschung (2003)
Open-label, uncontrolled multicentre study in 65 people aged 25 to 82 with grade I or II chronic venous insufficiency, 360 mg once daily for 42 days
Tired and heavy legs, tension, tingling and leg pain all improved significantly from baseline, with no placebo group for comparison
Six people had adverse events possibly related to the extract, four of them gastrointestinal
In plain English: Quality of life according to the CIVIQ2 questionnaire, in spite of continuing hormone therapy, improved from 42.03±7.634 to 30.36±8.646 (p=0.000001).
Tsukanov IuT et al. · Angiol Sosud Khir (2014)
Uncontrolled six-month study of 360 mg/day in 62 women with orthostatic leg venous symptoms while on long-term hormone replacement therapy, 59 of whom completed it
Calf circumference fell from 36.77 to 35.98 cm in the first 3 months (p = 0.001) and stayed stable for the next 3 months. Ankle circumference fell less clearly
Venous symptoms and CIVIQ2 quality-of-life scores improved from baseline. Mild adverse events in 3 women (5.08%) resolved on their own
9In VitroCited 13×2003
In plain English: These findings identify for the first time the venular endothelium as a possible important therapeutic target in certain vascular diseases, chronic venous insufficiency being perhaps the most prominent example.
Nees S et al. · Arzneimittelforschung (2003)
Laboratory study on cultured venular endothelial cell layers exposed to products released by activated platelets and white cells, which sharply raise endothelial leakiness
The standardised red vine leaf extract, rich in quercetin-3-O-glucuronide and isoquercitrin, prevented that rise in leakiness and helped already-damaged endothelium recover
Cell-culture evidence only, which proposes a mechanism and does not show a clinical effect
In plain English: Surprisingly, the component contents in the health foods were different even within a same lot in a same brand.
Masada S, Takahashi Y, Goda Y, Hakamatsuka T · Chem Pharm Bull (Tokyo) (2016)
Laboratory analysis by LC/MS of over-the-counter drug products and health food products containing red vine leaf extract, across different lot numbers, by a national health sciences institute
Multivariate analysis showed the composition of the health food products was highly variable compared with the drug products, and differed even within one lot of the same brand
Flavonol and stilbene contents were kept constant in the drug products but not in the health food products
In plain English: The calf volume decreased on average by 26.3 ml after 2 weeks (t=-5.37 p<0.001), 29.8 ml after 4 weeks (t=-6.44 p<0.001) and 32.7 ml after 6 weeks (t=-7.67<0.001).
Monsieur R et al. · Praxis (Bern 1994) (2006)
Open, uncontrolled observational study in 39 people with grade I or II chronic venous insufficiency, 180 mg twice daily (360 mg/day) for 6 weeks
Calf volume fell from baseline by 26.3 ml at 2 weeks and 32.7 ml at 6 weeks (p < 0.001)
Heaviness and leg pain scores fell by about 2.2 to 2.6 points from baseline, with no placebo group for comparison
In plain English: Red-vine-leaf extract AS195 increases NOS activation and decreases oxidative stress.
Grau M et al. · Pharmacol Res Perspect (2016)
Laboratory study on human umbilical vein endothelial cells and red blood cells from healthy volunteers
The extract increased nitric oxide synthase activation and antioxidant capacity, reduced induced reactive oxygen species, and limited the loss of red blood cell deformability under oxidative stress
Cell-culture evidence only, offered as a possible explanation for the microcirculation changes seen in patients