Recommendations for the medical management of chronic venous disease: The role of Micronized Purified Flavanoid Fraction (MPFF)

Phlebology. 2017 Apr;32(1_suppl):3-19. doi: 10.1177/0268355517692221.


Scope A systematic review of the clinical literature concerning medical management of chronic venous disease with the venoactive therapy Micronized Purified Flavonoid Fraction was conducted in addition to an investigation of the hemodynamics and mechanism of chronic venous disease. Methods The systematic review of the literature focused on the use of Micronized Purified Flavonoid Fraction (diosmin) which has recently become available in the US, in the management of chronic venous disease. The primary goal was to assess the level of evidence of the role of Micronized Purified Flavonoid Fraction in the healing of ulcers, and secondarily on the improvement of the symptoms of chronic venous disease such as edema. An initial search of Medline, Cochrane Database for Systematic Reviews and Google Scholar databases was conducted. The references of articles obtained in the primary search, including a Cochrane review of phlebotonics for venous insufficiency, were reviewed for additional studies. Studies were included if patients had a diagnosis of chronic venous disease documented with Doppler and Impedance Plethysmography. Studies excluded were those that had patients with arterial insufficiency (Ankle Brachial Index < .6), comorbidity of diabetes, obesity, rheumatological diseases, or if other causes of edema were present (congestive heart failure, renal, hepatic or lymphatic cause), or if the patient population had recent surgery or deep vein thrombosis, or had been using diuretics (in studies of edema). Other elements of the study design were to note specifically the type of compression therapy used in conjunction with Micronized Purified Flavonoid Fraction. Results The literature review yielded 250 abstracts, 65 of which met criteria for further review and 10 papers were selected for consideration in the systematic review. Conclusion In summary, the general level of evidence supports the recommendation that the use of medical therapy with Micronized Purified Flavonoid Fraction has beneficial outcomes without serious adverse events. In the United States, diosmiplex is the only available prescription formulation of Micronized Purified Flavonoid Fraction. It is derived from the rinds of oranges and is categorized as a medical food and not as a drug; and may be a particularly attractive therapy for many chronic venous disease patients because of its favorable safety profile. The Working Group for chronic venous disease concurs with previous guidance by the International European Society for Vascular Surgery in 2015 which recommended the use of Micronized Purified Flavonoid Fraction for the healing of venous ulcers, alone and adjunctive to compression therapy, and for the reduction in symptoms of chronic venous disease such as edema.

Keywords: Chronic venous disease; Micronized Purified Flavonoid Fraction; chronic venous insufficiency; diosmin; diosmiplex; flavonoids; leg ulcers; varicose veins; venous disease; venous insufficiency; venous ulcers.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Animals
  • Capillaries / cytology
  • Cardiology / methods
  • Chronic Disease
  • Edema / therapy
  • Flavonoids / therapeutic use*
  • Hemodynamics
  • Humans
  • Hypertension
  • Leukocytes / cytology
  • Permeability
  • Quality of Life
  • Varicose Ulcer / epidemiology
  • Varicose Ulcer / physiopathology
  • Vascular Diseases / drug therapy*
  • Vascular Diseases / epidemiology*
  • Vascular Diseases / physiopathology
  • Veins / physiopathology
  • Venous Insufficiency / epidemiology
  • Venous Insufficiency / physiopathology
  • Venous Thrombosis / drug therapy
  • Venous Thrombosis / epidemiology


  • Flavonoids