Edema and Micronized Purified Flavonoid Fraction: What the Evidence Says

Edema and Micronized Purified Flavonoid Fraction: What the Evidence Says

Laura Swoboda, DNP, APNP, FNP-C, FNP-BC, CWOCN-AP, WOCNF
December 1, 2023

Keywords

Edema

Lymphedema Management

Lymphedema

Venous Insufficiency

Venous Ulcers

Edema: What Tools Do We Have?

Lower extremity edema is a common comorbidity in wound patients with varying associated etiologies and contributing factors. Regardless of the etiology, edema is associated with delayed wound healing. The increased interstitial fluid volume that defines edema can contribute to the following depending on its extent^1-4:

Poor oxygenation
Pro-inflammatory metabolic waste products
Infection risk
Pain
Reduced mobility

While compression is the gold standard for managing edema, optimizing treatment for patients with phlebolymphedema often involves more than just compression.⁵ Furthermore, other interventions are of additional utility in managing patients who cannot tolerate therapeutic compression due to peripheral arterial disease, claustrophobia, heat intolerance, and skin reactions. These interventions can include⁵:

Dietary modifications
Supplements
Prescription medications
Weight reduction
Exercise therapies
Positional recommendations
Intermittent pneumatic compression devices

What is Micronized Purified Flavonoid Fraction (MPFF)?

Micronized purified flavonoid fraction (MPFF) is a venoactive drug (VAD) that is typically classified as a nutritional supplement in the US.^5,6 It is a ratio, or fraction, of different flavonoids. Flavonoids are natural plant secondary metabolites that are known to exert anti-inflammatory and additional favorable effects.⁷ The flavonoids present in MPFF include⁷:

Diosmin
Hesperidin
Diosmetin
Linarin
Isorhoifolin

These flavonoids are naturally present in the rind of a certain orange type and undergo minimal processing (micronized, purified) before oral consumption.⁷

How MPFF Can Be Used to Treat Certain Vascular Diseases

There has been significant research on the efficacy and effectiveness of MPFF, leading to its inclusion in many societal recommendations and guidelines.^5,6 Its use is common in the treatment and management of many vascular diseases⁶:

Venous insufficiency
Venous leg ulcers
Lymphedema
Post-phlebitic syndrome
Hemorrhoids

In phlebolymphedema, vascular leakage and stasis are often present. MPFF decreases red blood cell viscosity and exerts an anti-inflammatory effect. Contents within blood vessels normally flow in a laminar fashion, meaning the contents stay in the center of the vessel. Conditions that increase contact between vascular contents and the vessel lining contribute to inflammation of the blood vessel wall. The associated increased blood viscosity of stasis irritates the vascular endothelium, creating a positive feedback loop of inflammation that can ultimately lead to ulceration.⁸ MPFF reduces the effects of stasis by decreasing bradykinin-induced microvascular leakage and inappropriate leucocyte activation. A systematic review and meta-analysis of 7 randomized double-blind placebo-controlled trials including 1,692 patients identified MPFF significantly improved 9 leg symptoms including⁹:

Pain
Heaviness
Feeling of swelling
Cramps
Paresthesia
Burning sensation
Pruritus

In addition, the researchers also found decreased functional discomfort, ankle circumference, leg redness, and skin changes, as well as increased quality of life.⁹ MPFF’s use in microcirculatory disorders includes the adjunctive treatment of venous leg ulcers, where its use is strongly associated with both the ability to heal and accelerated healing. A meta-analysis has shown a 32% raised chance of ulcer healing and a 5-week shorter healing process.¹⁰

Conclusion

MPFF has a favorable safety profile and a wealth of evidence supporting its use in phlebolymphedema and venous leg ulcer healing. The product is available as a pharmaceutical in Europe, and usually as an over-the-counter supplement in the United States.

References

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Kakkos SK, Nicolaides AN. Efficacy of micronized purified flavonoid fraction (Daflon®) on improving individual symptoms, signs and quality of life in patients with chronic venous disease: a systematic review and meta-analysis of randomized double-blind placebo-controlled trials. Int Angiol. 2018;37(2):143-154. doi:10.23736/S0392-9590.18.03975-5
Coleridge-Smith P, Lok C, Ramelet AA. Venous leg ulcer: a meta-analysis of adjunctive therapy with micronized purified flavonoid fraction. Eur J Vasc Endovasc Surg. 2005;30(2):198-208. doi:10.1016/j.ejvs.2005.04.017