Why Are Flavonoids Recommended for the Treatment of Chronic Venous Insufficiency?

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Recent medical advancements have widened the horizons when it comes to treating chronic venous insufficiency (CVI). For instance, pharmacologic therapy is now recommended in the form of venoactive drugs to be consumed not only in conjunction with conservative management of CVI but also alongside intervention procedures.

So why are flavonoids recommended for the treatment of chronic venous insufficiency? Flavonoids are naturally occurring compounds that offer a multitude of health benefits. Certain types of venoactive flavonoid drugs such as diosmin and micronized purified flavonoid fraction are proven to significantly improve vein integrity, lymph drainage, and capillary function, which are influential factors in the pathology of chronic venous disease.

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What You Need to Know About Chronic Venous Insufficiency

Chronic venous disease affects approximately 60 million individuals in the United States, with 2% of the national healthcare being allocated for the treatment of this ailment, with a 17% chance of incidence in males and a 40% chance in females. Western countries appear to have a higher overall prevalence of the disease than non-western countries.

Chronic venous insufficiency (CVI) or chronic venous disease is a cardiovascular condition wherein the one-way venous valves that are supposed to maintain a unidirectional flow of blood from the lower extremities to the heart and prevent blood reflux are weakened and fail to do so. Valvular incompetence leads to complications within the deep and superficial veins of the legs. Severe cases left untreated can lead to a loss of productivity and worse quality of life.

In 1994, the CEAP which stands for clinical, etiological, anatomical, and pathophysiological classifications was devised in order to create an international consensus on the diagnosis and treatment of chronic venous disease. It outlines the stages of symptom progression, causes, and the underlying pathological mechanisms that result in CVI.

1) Causes

Chronic vein sufficiency is a cardiovascular ailment that is primarily caused by venous reflux and venous obstruction due to thrombosis (excessive blood clotting). There are a few risk factors associated with the development of these venous disorders. Chances are, you have a greater probability of contracting CVI if you:

  • Have a medical history of deep vein thrombosis (DVT)
  • Have a family medical history of cardiovascular diseases and chronic venous disorders (e.g., hypertension, varicose veins)
  • Are obese
  • Are pregnant
  • Are smoking tobacco cigarettes
  • Prolonged standing or sitting
  • Are lacking in physical activity or exercise
  • Are over 50 years of age

The etiological classification of chronic venous insufficiency outlines three major types of CVI based on causes: primary, secondary, and congenital chronic venous insufficiency.

  • Primary chronic venous insufficiency: Primary CVI is idiopathic, with more uncertain causes in which the incidence of chronic venous disease is intrinsic without a prior precipitating disorder.
  • Secondary chronic venous insufficiency: Secondary CVI is caused by a prior disorder or external influencing factor affecting vein functioning, venous integrity, and blood pressure. The most common premeditating condition is deep vein thrombosis (DVT), which is characterized by the accumulation of blood clots within the deep veins.
  • Congenital chronic venous insufficiency: Congenital CVI is caused by genetic factors that contribute to inborn valvular incompetence and diminished vein integrity. The most common type of congenital CVI is the Klippel-Trenaunay syndrome.

2) Symptoms

The set of symptoms experienced by individuals affected by chronic venous disease differs according to which stage it is being experienced. As outlined in the clinical classifications of the CEAP, below is the symptom progression according to CVI stages:

  • Stage C0: Healthy and normal venous functioning
  • Stage C1: Appearance of spider vein (<1mm) and reticular vein (1-3mm)
  • Stage C2: Appearance of varicose vein (deep veins within the legs at least 3 mm wide)
  • Stage C3: Venous edema, or swelling due to accumulation of fluid within leg tissue
  • Stage C4: Skin discoloration and hardening/thickening of skin texture; appearance of venous stasis dermatitis or venous eczema 
  • Stage C5: Venous ulceration healing naturally
  • Stage C6: Severe venous leg ulcer requiring wound treatment

While symptoms vary based on stage, it’s still important to recognize early signs of congenital venous insufficiency: Here are some of the most common observable signs and symptoms you can notice at the early stages of chronic venous disease:

  • Leg pain
  • Leg heaviness
  • Leg swelling
  • Swollen veins
  • Tingling sensation in the legs, i.e., “pins and needles sensation”
  • Reddish-brown skin discoloration
  • Open sores near the ankles and lower legs
  • “Leathery” appearance of skin in your legs

3) Treatments

Chronic venous disease, as mentioned, is principally driven by valvular incompetence, weakened vein functioning, obstructive blood clots, and decreased blood flow. Thus, a combination of conservative management therapy and vascular surgery are administered to treat chronic venous disease. Some of the most effective treatment methods for chronic venous disease include:

a) Compression Therapy

Compression therapy is the most commonly used and recommended treatment method by vein specialists to treat chronic venous disease. Compression therapy, as the name implies, applies compressive force onto the legs to promote blood flow within the leg veins and alleviate leg swelling and discomfort.

b) Sclerotherapy

Sclerotherapy employs the use of sclerosing agents such as 23.4% sodium chloride to fully obstruct and dehydrate the affected vein, triggering its collapse, after which blood is redirected to unaffected veins.

c) Manual Lymphatic Drainage

Manual lymphatic drainage (MLD) is a treatment commonly used to treat lymphedema (accumulation of lymph fluid within the tissue). Recent studies have proven the effectiveness of MLD as a conservative treatment for preventing and alleviating symptoms of chronic venous disease, thus making it also an effective varicose vein treatment.

MLD works through a skin-stretching massage that promotes lymph flow within lymphatic vessels, inducing lymph drainage within the affected areas, balancing pressure differences between capillary filtration and lymph drainage, and alleviating CVI symptoms such as edema and venous ulcer. The lymphatic system network of vessels runs in parallel with cardiovascular vessels. 

d) Pharmacological Therapy

Another non-invasive treatment used for chronic venous disease is the prescription of venoactive drugs. A venoactive drug has properties promoting the strength of venous tone, regulation of blood coagulation, the efficiency of capillary filtration, and improvement of inflammatory response. These drugs are useful in alleviating leg pain and leg swelling, as well as in promoting venous leg ulcer healing.

What are Flavonoids?

Flavonoids are phytochemical substances found in many fruits and vegetables. Some common flavonoid-rich food includes tea, grapes, onion, strawberry, banana, and red wine. They are polyphenolic water-soluble molecules containing 15 carbon atoms and two benzene rings joined together by a three-carbon chain. 

Polyphenols have been widely used in Ayurvedic medicine, as well as in Chinese medicine, and are associated with antioxidant benefits, skin protection, brain function, and blood pressure regulation. 

Pharmaceutical Properties of Flavonoids

Research heavily attests to the benefits of flavonoids in many physiological aspects. Below are some of the pharmaceutical properties of flavonoids that are beneficial to the body:

  • Antibacterial: Several types of flavonoids serve as bactericidal agents by destroying the cytoplasmic membrane and inhibiting nucleic synthesis and energy metabolism of pathogenic bacteria.
  • Antifungal: Flavonoid-rich leaves such as aquilaria are often used as alternatives for antifungal drugs that have side effects and are affected by the development of resistance.
  • Antiviral: Many drugs are currently synthesized from medicinal plants with flavonoids that are effective against influenza, herpes simplex-1, and human immunodeficiency-1 viruses.
  • Anti-inflammatory: Many flavonoid-rich plant species are found to be effective in inhibiting several enzymes that are involved in inflammatory pathways.
  • Antioxidant: The natural molecular structure of flavonoids enables them to be effective antioxidants. Flavonoids serve as antioxidants by forming less reactive oxygen species to prevent cellular membrane damage caused by reactive oxygen species’ interaction with lipids, nucleic acids, and proteins.

While flavonoids promise a multitude of significant health benefits, patients should also be made known of certain drugs with flavonoid interaction. Some of these are the enzyme cytochrome P450 and P-glycoprotein. Flavonoid is also known to prevent cellular uptake of ascorbic acid or vitamin C, which is why many experts recommend avoiding food rich in flavonoids when taking vitamin C.

Flavonoid Treatments for Chronic Venous Insufficiency

Flavonoids are proven by recent studies to contain properties that promise significant improvements in the alleviation of chronic venous disease symptoms. Thus, the pharmacological treatment of CVI is presently encouraged as an adjunctive therapy method alongside conservative management and interventional procedures such as sclerotherapy.

Thus, the role of flavonoid-based pharmaceutical treatment for chronic venous insufficiency shows significant promise. The most common flavonoid-based venoactive drugs prescribed for CVI are micronized purified flavonoid fraction (MPFF) and diosmin.

1) Micronized purified flavonoid fraction (MPFF)

Micronized purified flavonoid fraction or MPFF is the most widely-used venoactive drug in Europe. It possesses strong anti-inflammatory properties, reduction of endothelial activation and vascular incompetence, and stronger capillary resistance, making MPFF treatment a potent treatment in all stages of CVI. MPFF is also effective in treating postthrombotic syndrome (PTS), or chronic venous disease precipitated by deep venous thrombosis. 

A study from 2021 attests to the effectiveness of MPFF treatment in decreasing venous reflux, inhibiting inflammation, alleviating capillary hyperpermeability,  and promoting venal recanalization. MPFF treatment also improves venous tone through hormonal regulation and protects against valve inflammation by inhibiting blood clots formed from leukocyte-endothelial interaction, improving capillary resistance, decreasing venous hypertension, and promoting lymphatic drainage, as attested by a prior 2016 study.

MPFF treatment is recommended as an adjunctive treatment alongside lifestyle change and conservative management of CVI. It’s also proven to reduce preprocedural pain and bleeding, which is why it’s also recommended for treatment during the recovery periods after vascular surgery treatments such as sclerotherapy and vein ablation.

2) Diosmin

Diosmin is a flavonoid naturally occurring in many plant sources, mainly in citrus fruits. It has long been used as a venoactive drug treatment for chronic venous disease. It’s also known to strengthen the venous tone, improve the lymphatic profile, and stabilize capillary permeability. Diosmin composes 90% of MPFF, with hesperidin comprising the remaining 10%. Many studies claim that MPFF treatment is a more potent treatment for CVI.

Other medicinal plants rich in flavonoids are also becoming topics of curiosity in CVI treatment. For instance, a 2013 study reviewed clinical trial studies on Centella asiatica (Gotu Kola), and provided insights on its benefits in alleviating CVI symptoms, although more rigid research is needed.

A 2021 study further outlines other benefits of flavonoids to chronic venous insufficiency treatment which include:

  • Prevention against vascular pathology
  • Reduction of vein responsiveness of mesenteric blood vessels
  • Regularization of venous tone
  • Prevention of varicose veins

Other Benefits of Flavonoids

  • Cardiovascular health: According to a 1995 study, consumption of flavonoids can account for 25% of the difference in mortality rates due to coronary heart disease and cancer. It also lowers the risk of atherosclerosis and improves blood vessel walls, lowering as well the risk for chronic venous disorders.
  • Diabetes prevention: A 2013 study has shown a significant improvement in vascular function among men with type 2 diabetes after they consumed flavonoid-rich spice mix.
  • Cancer treatment: Flavonoid consumption is also associated with a lower risk of gastric cancer and breast cancer.
  • Neurodegenerative disease prevention: Flavonoids are able to regulate neuronal signal cascade caused by cell apoptosis. Some flavonoids such as hesperidin are known for their neuroprotective, antidepressant, and memory-improving benefits. Thus, flavonoids are also effective in preventing dementia, Alzheimer’s disease, and Parkinson’s disease.

The Best Outpatient Vein Treatment Procedures at Vein Center Doctor

Chronic venous disorders can lead to more severe physiological irregularities when left untreated, decreasing quality of life and productivity. At Vein Center Doctor our team is always dedicated to providing patient-centered services through our advanced medical equipment and trusted medical professionals. 

Get the best vein treatment therapy you deserve at Vein Center Doctor. You can reach us by contacting 862-227-1143 (NJ) or 862-227-1054 (NY) for your free consultation.

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