Diosmin and Hesperidin Dosing in Chronic Venous Insufficiency Studies
Dosing Regimen in the Comparative Trial
The micronized formulation (Daflon 500 mg) used 450 mg of diosmin plus 50 mg of hesperidin per tablet, administered as two tablets daily (total: 900 mg diosmin + 100 mg hesperidin per day), while the comparator arm received an equivalent dose of non-micronized diosmin (900 mg daily). 1
Study Design and Administration
The randomized, double-blind, multicenter trial enrolled 90 patients with chronic venous insufficiency who received either two tablets of Daflon 500 mg or an equivalent dose of non-micronized diosmin, divided into two doses daily for two months. 1
Each Daflon 500 mg tablet contained a micronized purified flavonoidic fraction consisting of 450 mg diosmin and 50 mg hesperidin, formulated to enhance gastrointestinal absorption. 1
Clinical Outcomes with This Dosing
The micronized formulation at 900 mg diosmin + 100 mg hesperidin daily produced statistically superior improvements in all clinical symptoms and plethysmographic parameters (maximum venous volume increase at 60 mmHg and total emptying time) compared to 900 mg non-micronized diosmin alone. 1
Patient satisfaction was significantly higher with the micronized formulation (95%) versus non-micronized diosmin (80%, p < 0.01), despite similar clinical and laboratory safety profiles in both groups. 1
Evidence Challenging Higher Doses
More recent evidence suggests that 600 mg daily of pure non-micronized diosmin achieves equivalent clinical efficacy to the 1000 mg daily MPFF formulation (900 mg diosmin + 100 mg hesperidin), questioning whether doses above 600 mg or the addition of hesperidin provide additional clinical benefit. 2
Three well-conducted randomized clinical studies comparing diosmin 600 mg daily versus MPFF 1000 mg daily showed significant decreases in chronic venous disorder symptom intensity (up to approximately 50%) and high global patient satisfaction after one-to-six months of treatment, with no statistical differences between the two formulations. 2
Both the 600 mg non-micronized diosmin and 1000 mg MPFF formulations were well tolerated with few mild adverse reactions, suggesting no clinical advantage to increasing the dose beyond 600 mg per day, using micronization, or adding hesperidin. 2