Clinical studies with Pycnogenol in venous insufficiency

Efficacy of Pycnogenol in patients with venous insufficiency has been proven in eight double-blind studies with approx. 600 patients compared to placebo, or the reference (the most commonly used).prescription drug

The four-day consumption, reduced leg swelling

The effect of Pycnogenol on capillaries was studied in 27 patients who were treated with 180 mg/day Pycnogenol or placebo for 4 days in a d ouble-blind , placebo-controlled study. The increase in leg volume was measured by means of water displacement in supine and sedentary position (for 2 hours). In sedentary position gravitation causes leakage of fluid into the leg tissues. The four-day Pycnogenol treatment significantly reduced the increase in leg volume in sedentary position. In the placebo group, no such effect was observed (Schmidtke & Schoop, 1984).

The two-month consumption of Pycnogenol reduced the subjective symptoms of venous insufficiency

Forty patients with chronic venous insufficiency were treated with 3 X 100 mg Pycnogenol per day or placebo for two months. The subjective symptoms of venous insufficiency (heavy legs, swelling, pain) were studied using a standard questionnaire. The symptom score was calculated at baseline and at the end of the first and second month.

As soon as at the end of the first month many patients in the Pycnogenol group became asymptomatic. At the end of the second month, the majority of patients became free of pain and swelling, and the tolerability was excellent. No effect was observed in the placebo group (Arcangelli, 2000).

The four-week treatment with Pycnogenol was more effective in relieving symptoms than the horse chestnut extract

The aim of this study was to compare the efficacy of Venostasin (horse chestnut seed extract) and Pycnogenol (French maritime pine bark extract) in the treatment of chronic venous insufficiency (CVI). In an randomized, controlled study 40 patients with diagnosed chronic venous insufficiency (CVI) were treated either with 600 mg chestnut seed extract per day or 360 mg Pycnogenol per day over a period of 4 weeks. The following parameters were investigated before the start of treatment and after 2 and 4 weeks of treatment: circumference of the lower legs (to measure leg swelling) and rating of subjective symptoms (scores) of pain, cramps, night-time swelling, feeling of "heaviness", and reddening of the skin. In addition, blood levels of cholesterol LDL and HDL were determined before and at the end of treatment. Pycnogenol significantly reduced the circumference of the lower limbs and significantly improved subjective symptoms. Furthermore, Pycnogenol significantly decreased cholesterol and LDL values in the blood, whereas HDL remained unaffected. Venostasin only moderately but not significantly, reduced the circumference of the lower limbs and marginally improved symptoms. Venostasin had no influence on the determined lipid values. Both medications were equally well tolerated. In conclusion, Pycnogenol was found to be more efficacious than Venostasin for the treatment of CVI.

The eight-week Pycnogenol therapy was more effective than the standard prescription diosmin-hesperidine combination

PYC= Pycnogenol, D+H = diosmin+hesperidine, RF= resting flux ,RAS= rate of ankle swelling, ASLS= Analogue Scale Line Score, PO2 = (Parcial) Oxygen concentration, pCO2= (Partial) carbon dioxide concebtration

Change of Treatment Parameters of Pycnogenol 150 and 300 mg/day vs. diosmin +hesperidine 1000 mg

Difference (%)
Difference (%)
150 mg Pycnogenol
300 mg Pycnogenol
Resting flux
Rate of ankle swelling (capillary filtration)
Symptom score
pO2 (oxygen concentration)
pCO2(carbon dioxidw concentration)

Italian researchers ( L'Aquila University) compared the efficacy of daily 150 mg or 300 mg Pycnogenol vs. 1000 mg diosmin -hesperidine combination (Daflon, Detralex) administered for eight weeks, to 86 patients with with severe chronic venous insufficiency, venous hypertension, and ankle swelling. In addition to the measurement of ankle swelling, questionnaires were used to determine the score of the subjective symptoms (pain, restless legs, redness of the skin).

A significant level of improvement was reached after 4 weeks of treatment in most patients (p < .05) of the Pycnogenol group while clinical improvement was significant only in 6 subjects in the diosmin - hesperidine group.

After e ight weeks of treatment ankle swelling decreased by 35% in the Pycnogenol group and 19% of the diosmin -hesperidine group. The decrease in the symptom score (pain, restless legs, tired legs, skin lesions) was 64% in the Pycnogenol group, and half of that, 32% in the diosmin -hesperidine group.

In addition, Pycnogenol significantly increased oxygen, and decreased the carbon dioxide concentration in the skin of the leg, thus improving blood flow to the leg. The diosmin -hesperidine did not affect significantly tissue oxygenation, therefore did not improve the blood circulation in the legs. Pycnogenol improved oxygen concentrations five times, and decreased carbon dioxide concentration 15 times better, than diosmin -hesperidine.

The higher dose of Pycnogenol (300 mg) did not have not significantly better effects than the lower dose (150 mg), except for the total symptom score values.

The study concluded that Pycnogenol had better efficacy on the investigated parameters in chronic venous insufficiency compared to the standard diosmin -hesperidine combination (Cesarone et al, 2006)

Summary : the evidence of Flavogard (Pycnogenol) treament of chronic venous insufficiency

  • strengthening the vein and capillary walls, efficacy in the fast reduction of feet and leg swelling;
  • a higher ( "attack") dose is particularly useful for reducing leg swelling which can enhance patient/consumer compliance;
  • efficacy in alleviating the subjective symptoms of venous insufficiency (pain, muscle cramps, heavy legs);
  • enables restoration of the functions of the small veins through inhibition of the production of inflammatory agents;
  • reducing platelet aggregation without increasing bleeding time, therefore it may help in preventing the complications of platelet aggregation ( ex. deep vein thrombosis, DVT);
  • all natural ingredients; mild gastric/intestinal discomfort reported in rare cases, which can be avoided if Flavogard is taken with or after meals.


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  • Vinciguerra G és mtsai: Cramps and muscular pain: prevention with pycnogenol in normal subjects, venous patients, athletes, claudicants and in diabetic microangiopathy. Angiology 2006 May-Jun;57(3):331-339.

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