Two flavonoids derived from citrus were found to improve vein health including varicose veins

Restore Healthy, Youthful-Looking Legs

Two flavonoids derived from citrus were found to improve vein health including varicose veins, and chronic venous insufficiency.

Scientifically reviewed by: Amanda Martin, DC, in June 2024. Written by: Laurie Mathena.

About half of all people have chronic venous abnormalities.

This can mean cosmetic concerns like varicose veins, which affect about 10% to 30% of the population, with greater prevalence in older populations.

Venous disease can also extend to chronic venous insufficiency, which can cause painful swollen legs, changes in skin appearance such as discoloration or rashes, and even ulcerations.1,2

A flavonoid, diosmin, found in citrus, has been widely studied to improve the health of veins, including varicose veins and chronic venous insufficiency.

Chronic Venous Disease

The job of the veins in the legs is to return deoxygenated blood from the lower extremities to the heart. These leg veins contain one-way valves that are supposed to prevent blood from flowing back to the feet.

When those valves become damaged, blood can flow backward and collect in the leg veins. This condition is called chronic venous disease (CVD).

Over time, chronic venous disease damages the venous wall and leads to health concerns and cosmetic issues like varicose veins, ankle swelling, painful ulcers, and skin pigmentation.1

It can also cause your legs to feel heavy, tired, or achy.

Chronic venous disease is associated with deep vein thrombosis, a condition that can cause potentially life-threatening blood clots.5

There are different stages of chronic venous disease, classified according to the severity of symptoms and signs. Treatment options vary for different stages and may include lifestyle modifications, laser ablation, and surgical interventions.1

Improved Symptoms in 30 Days

In a study of patients with chronic venous insufficiency who were not on medical treatment, supplementation with a citrus bioflavonoid called diosmin improvement of edema, pain, and leg discomfort/tightness in over 80% of the participants as early as 30 days. There was also improvement in symptom- severity classification of the disease.6

Measurable Reduction in Leg Swelling

In a clinical study of patients suffering from chronic venous insufficiency/disease, participants received 600 mg of diosmin two times per day for three months. They were evaluated for cardiovascular disease based on clinical symptoms and blood markers of vascular health before and after the study.

After three months, there was significant improvement in pain and swelling. Blood markers revealed improvements in endothelial and inflammatory health markers.7

Another study found that within two months of receiving 500 mg of diosmin 2 times a day, participants with venous edema without skin changes and symptoms (pain, tension, heaviness, and restless legs) saw their ankle and calf circumferences shrink by more than half a centimeter. Overall leg volume decreased by an average of 78 cubic centimeters along with significant improvement in other symptoms.8

A review and analysis of 10 randomized controlled trials found that Micronized Purified Flavonoid Fraction diosmin helps significantly reduce pain and swelling in the lower legs.9

Another analysis of five randomized controlled trials on participants with venous ulcers found that treatment with Micronized Purified Flavonoid Fraction along with conventional therapy increased chances of ulcer healing by 32% after six months as compared to conventional therapy alone.10

Citrus Extracts and Venous Health

Diosmin can be derived as a metabolite of the flavonoid hesperidin from citrus rinds.3

To aid intestinal absorption, diosmin is often micronized; particles are milled down to a fine grade.

The resulting product is referred to as Micronized Purified Flavonoid Fraction (MPFF), and often contains diosmin and hesperidin in a 9:1 ratio.3

Micronized Purified Flavonoid Fraction products have been widely used and studied in Europe for the treatment of varicose veins and chronic venous disease.3,4

This Micronized Purified Flavonoid Fraction has been found, in several clinical trials, to improve vein and leg health, resulting in improved leg appearance and quality of life, including:4

  • improved healing of venous ulcers,
  • reduced leg swelling (edema) and feelings of heaviness in the legs,
  • Improved changes in skin appearance associated with venous disease,
  • Reduced leg cramping, and
  • Improved symptom scores for venous disease and venous insufficiency.

Improved Clinical Outcomes for Varicose Veins

The damaged valves that cause varicose veins allow for backflow of blood toward the feet, which can cause hypertension in the veins. This can damage the venous wall and contribute to the appearance of varicose veins.1

In addition, prolonged untreated venous insufficiency is associated with vascular endothelial dysfunction, leakage, and inflammation. This can lead to venous leg ulcers.

In an animal study, treatment with micronized diosmin showed protective effects on vascular endothelium, improved vascular tone, reduced venous leakage, and alleviated inflammatory response; it also helped maintain overall vascular health.11

A review of human studies of micronized diosmin showed that it improved ulcer healing in more advanced stage venous disease when used in addition to multilayer compression bandaging, and in individuals undergoing standardized local care of leg ulcers.12

Post thrombotic syndrome is a frequent and disabling complication of deep vein thrombosis and may involve swelling, chronic pain, and heaviness of affected limb.

A clinical study randomized participants with a history of deep vein thrombosis into a control group that received standard care with rivaroxaban (Xeralto®) for six months and compression stockings for 12 months, or the experimental group that received diosmin 600 mg with standard care. It was found that the group that received diosmin had a 14% decreased risk of post-thrombotic syndrome along with complete vein recanalization (seen on ultrasound), and low vascular disease progression as compared to control group.13

In a clinical trial, patients undergoing a surgical procedure for varicose vein disease were given micronized diosmin 1,000 mg/day for two weeks before and for 30 days after surgery. Compared to those not taking diosmin, these individuals achieved a measurable reduction in postoperative hematomas, pain severity, and limb heaviness. They also saw better exercise tolerance and improved quality-of-life scores.14


Micronized diosmin, or Micronized Purified Flavonoid Fraction, can be used alone as a dietary supplement, or in combination with standard treatment such as compression stockings, for chronic venous disease.

It has been shown to be effective for improving cosmetically unattractive venous disorders, including varicose veins, leg ulcers, swelling, and edema.

In patients suffering from chronic venous insufficiency, diosmin can provide significant relief from pain, heavy legs, and cramps, particularly when complemented with standard conservative treatment such as leg elevation and compression stockings.

If you have any questions on the scientific content of this article, please call a Life Extension Wellness Specialist at 1-866-864-3027.


  1. Available at: Accessed March 25, 2024.
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