Is There a Difference in the Clinical Efficacy of Diosmin and Micronized Purified Flavonoid Fraction for the Treatment of Chronic Venous Disorders? Review of Available Evidence.

Flavonoids are oral venoactive drugs frequently prescribed to relieve the symptoms of chronic venous disorders (CVD). Among venoactive drugs, diosmin is a naturally occurring flavonoid glycoside that can be isolated from various plant sources; it can also be obtained after conversion of hesperidin extracted from citrus rinds. Micronized purified flavonoid fraction (MPFF) is a preparation that contains mainly diosmin and a small fraction of hesperidin. We performed a state-of-the-art literature review to collect and analyze well-conducted randomized clinical studies comparing diosmin - also called non-micronized or hemisynthetic diosmin - 600 mg a day and MPFF, 1000 mg a day. Three clinical studies met the criteria and were included for this literature review. These clinical studies showed a significant decrease of CVD symptom intensity (up to approximately 50%) and global patient satisfaction after one-to-six-month treatment with diosmin or MPFF, without statistical differences between these two forms of diosmin. Both treatments were well tolerated with few mild adverse drug reactions reported. Overall, based on this literature review, there is no clinical benefit to increase the dose of diosmin beyond 600 mg per day, to use the micronized form, or to add hesperidin, since clinical efficacy on venous symptomatology is achieved with 600 mg per day of pure non-micronized diosmin. This challenges the status of diosmin - 600 mg a day - in guidelines for the management of CVD, which is currently categorized 2C (weak recommendations for use and poor quality of evidence), while the most widely used and assessed preparation MPFF is rated 1B (strong recommendation for use and moderate quality of evidence).

Anti-inflammatory and antiradical effects of a 2% diosmin cream in a human skin organ culture as model.

BACKGROUND: Diosmin, a naturally occurring flavonoid, is considered as a vascular-protective agent and is used orally to treat chronic venous insufficiency. It exhibits anti-inflammatory and free radical scavenging properties, but, like many other flavonoids, it is poorly absorbed in the small intestine. OBJECTIVE: Our aim was to investigate the skin protective effects of a diosmin-based cream, using skin organ culture as model. METHODS: Fragments of human skin explants, cultured ex vivo, were allocated to four treatment groups: no cream, no cream + stress, placebo cream + stress, and 2% diosmin cream + stress. Stress was induced by exposure to either substance P (anti-inflammatory effects' assessment) or UVB irradiation (free radical scavenging effects' assessment). Vascular dilation and the pro-inflammatory mediator IL-8 release were determined in the first model, whereas hydrogen peroxide level and the number of cyclobutane pyrimidine-positive cells were evaluated in the second model. RESULTS: In the substance P-induced inflammation model, 2% diosmin cream exhibited significant vasoconstrictive (proportion of dilated capillaries: -29%, capillary luminal area: -49% vs no cream + stress) and anti-inflammatory (IL-8 release: -36% vs no cream + stress) effects. In the UVB irradiation model, 2% diosmin cream significantly reduced hydrogen peroxide production and cyclobutane pyrimidine dimer formation (-45% and -36% vs no cream + stress, respectively). These effects were not observed with placebo cream. CONCLUSION: Diosmin administered topically may protect skin against the biological effects of various exogenous or endogenous stresses, such as those involved in chronic venous disease.