Diosmin is a flavonoid derived from citrus plants. There have been many studies evaluating the efficacy of diosmin as a dietary treatment for managing chronic venous insufficiency, among other maladies, but likely none as noted as the RE LIEF (Reflux assEssment and quaLity of lIfe improvEment with micronized Flavonoids) study published in Angiology in May, 2002.¹

The study followed 4,527 patients in 23 countries for two years who were diagnosed with varying degrees of chronic venous insufficiency (CVI). Some had venous reflux disease, others did not. Each was treated with micronized purified flavonoid fraction (MPFF), which consisted of 450mg of micronized diosmin and 50mg of hesperidin. These patients were assigned to classes C0 to C4 on the basis of CEAP clinical classification, and were split into two comparative groups, depending on whether or not they were presenting with venous reflux. At two-month checkup intervals, patients were assessed on the parameters of symptoms, including swelling, cramps, leg heaviness, pain, edema, disease severity and quality of life. At the conclusion of the study, the researchers reported a reduction in the clinical scores of all symptoms for both groups, with the greatest improvements reported within the first two months of treatment and continuous improvements reported throughout the study.

It is widely reported that diosmin was first isolated in 1925 and first introduced in Europe in 1969 as a therapeutic agent. A quick search on the Internet will yield pages of results claiming the flavonoid contains properties that protect the vascular system and treat CVI, hemorrhoids and other venous and non-venous maladies. With this come advertisements for diosmin-related products that can be sold online and over the counter in vitamin shops throughout the U.S. Its accessibility is owed to the fact that the flavonoid is generally considered a dietary supplement in the States and therefore falls under the Dietary Supplement Health and Education Act of 1994. The same cannot be said in certain parts of Europe, where diosmin and its related products must be prescribed.

One particular product has sparked conversations within the medical field: Vasculera. It consists of a specially formulated proprietary blend of micronized, highly purified diosmin glycoside, alkaline granules and alka4-complex. It differs from its counterparts because it is classified as a prescription medical food product and adheres to a specific formulation process. It is also intended for patients receiving ongoing medical supervision for a specific disease or condition for which distinctive nutritional requirements are established by medical evaluation.2 As a physician considering or researching diosmin as a therapy for patients with CVI, this classification can add peace of mind that the product being prescribed will have a formulation consistency not found in its naturally occurring food state. It will also provide the ability to monitor patients’ improvements as they progress with their treatment.

In the literature for Vasculera, it states that it manages the oxidative and inflammatory factors induced by venous hypertension, and manages venous tone by increasing smooth muscle contractility. The manufacturer also states that it improves lymphatic contractility and drainage, thereby helping to mobilize edema. Its alka4-complex is said to counter local acidosis produced in venous insufficiency and works with diosmin to manage venous inflammation, which may be an added benefit to Vasculera’s formulation.

Given that the most common reported side effects to taking diosmin are stomach pain and diarrhea, Vasculera’s proprietary alka4-complex may mitigate these side effects for a larger majority of patients. The company states that in acid dissolution studies alka4-complex has been shown to release alkalizing salts in two gradual steps. Starting at a pH of 2, alka4-complex takes approximately 15 minutes to raise the solution pH to 6, whereas this occurs in seconds with bicarbonate. A further increase to a pH of 7 occurs over the next 60-90 minutes. This biphasic, slow release gives alka4-complex seven times more pH neutralizing capacity compared to the same concentration of sodium bicarbonate. The molecular protection afforded by the proprietary matrix allows the alka4-complex to enter the intestinal tract where it is absorbed. Compared to bicarbonate ions, hydroxyl ions present in alka4-complex have been shown to be better absorbed by the intestinal lumen.

The accepted methods for treating CVI have proven themselves effective, but given the multitude of studies surrounding diosmin as an effective treatment for CVI, a closer inspection of Vasculera as an additional therapy for your CVI patients may provide an additional tool in your arsenal for treating this debilitating disease.

For more information on Vasculera, please contact Primus Pharmaceuticals, (480) 483-1410, www.vasculera.com

1. On behalf of the RELIEF Study Group (Reflux assEssment and quaLity of life improvEment with micronized Flavonoids).
Scientific Advisor and Corresponding Author: G. Jantet, MB, FRCS; Immediate Past President, Union Internationale de Phlebologie, 14 rue Duroc, 75007, Paris, France
Relief Study Group: International coordinators: Prof J. Jimenez Cossio and Prof J. Ulloa
National Coordinators: J. R. Baron, S. Baktiroglu, S. Cheng, Y. Abd Wahab, M. Dhobb, Imam Nassef, M. Lajos, F. Lozano Sanchez, Ming Keng Teoh, C. Maduro, W. Noszczyk, E. T. Ona, M. Paramo Diaz, H. Partsch, R. Pinjala, M. E. Renno de Castro Santos, V. S. Saveljev, R. Simkin, A. H. Sheriffdeen, J. Strejcek, V. Strvtinova
Participating countries: Argentina, Austria, Brazil, Brunei, Colombia, Czech Republic, Egypt, Greece, Hong Kong, Hungary

2.http://www.fda.gov/regulatoryinformation/legislation/federalfooddrugandcosmeticactfdcact/significantamendmentstothefdcact/orphandrugact/default.htm