Chronic Venous Disease: Varicose Veins And Venous Insufficiency
Diosmin. Diosmin is a naturally occurring flavonoid found in many plants, primarily citrus fruits. Diosmin, a phlebotonic, improves vein integrity and reduces inflammation and risk of blood clotting; it also promotes lymphatic drainage (Gohel 2009; Gohel 2010; MacKay 2001). Diosmin comprises 90% of the European drug Daflon, which is one of the most studied preparations for the treatment of varicose veins and chronic venous disease (Szymanski 2016; Gohel 2009; MacKay 2001).
A 2016 review and analysis of randomized controlled trials found that a 90% diosmin preparation significantly reduced leg and ankle edema and lower leg pain (Martinez-Zapata 2016). In another analysis of five randomized controlled trials involving over 700 subjects with venous ulcers, treatment with the diosmin preparation combined with conventional therapy increased the chances of ulcer healing by 32% at six months compared with conventional therapy alone (Coleridge-Smith 2005).
Numerous animal and clinical studies have established that the diosmin-containing preparation micronized purified flavonoid fraction, which is the preparation used in most studies, is safe and well tolerated. Adverse effects are rare and usually mild, and there are no contraindications to its use (MacKay 2001).
Clinical practice guidelines issued by the Society for Vascular Surgery and the American Venous Forum endorse the use of diosmin. Diosmin is recommended in conjunction with compression therapy to treat pain, swelling, and ulcers due to chronic venous disease (Gloviczki 2011).
Horse chestnut seed extract (Aesculus hippocastanum). Horse chestnut seed extract (Aesculus hippocastanum) is a traditional herbal remedy for swelling and inflammation used extensively in Europe to treat venous disorders. A review and analysis of randomized controlled trials concluded that horse chestnut seed extract is an effective and safe short-term treatment for chronic venous insufficiency (Pittler 2012; Yu 2013; AMR 2009).
The benefits of horse chestnut seed extract in chronic venous insufficiency have been attributed to anti-inflammatory and anti-edema properties. Horse chestnut seed also improves the tone of vein walls, resulting in improved blood flow and decreased blood congestion in the venous system (Dudek-Makuch 2015).
While horse chestnut seed extract contains flavonoids such as quercetin and proanthocyanidins, most of its benefit in venous disorders is attributed to its main active component, escin (Dudek-Makuch 2015; AMR 2009).
In a review of 17 randomized controlled trials, supplementation with horse chestnut seed extract in people with chronic venous insufficiency resulted in marked improvement in leg pain, swelling, and itching. Horse chestnut seed extract compared favorably to compression stockings for treatment of leg pain. Adverse effects were mild and infrequent (Pittler 2012).
Pycnogenol. Pycnogenol is a standardized extract of French maritime pine bark. Clinical studies have shown that pycnogenol improves symptoms of chronic venous insufficiency, promoting healing of venous ulcers and reducing leg edema and the risk of blood clots during long flights (Gulati 2014; Toledo 2017). Pycnogenol has strong anti-inflammatory, vasodilating and anti-clotting properties, which are due largely to active constituents called procyanidins (Gulati 2014). Supplementation with pycnogenol in early stages of varicose veins may slow progression to chronic venous insufficiency (Belcaro 2014).
In one study, supplementation with pycnogenol at 100 mg/day for eight weeks reduced venous leg edema by 40% (Belcaro 2015). In another trial, 150 mg per day of pycnogenol for eight weeks reduced a composite score by nearly 24%; the score included edema, pain, restless limbs, and skin changes and redness associated with venous insufficiency (Cesarone 2006).
Nattokinase. Chronic venous disease increases the risk of a blood clot in a deep leg vein; this is known as deep vein thrombosis (Shaydakov 2016). Nattokinase, a protein-digesting enzyme extracted from natto, a traditional Japanese food made from fermented soybean, has been shown in several laboratory studies to reduce the risk of blood clot formation and break up existing blood clots (Kurosawa 2015; Xu 2014; Jang 2013; Chandrasekaran 2015; Fujita 1995; Sumi 1990).
Nattokinase works in part by directly degrading fibrin, the fibrous protein that forms the matrix of blood clots. It also breaks down fibrinogen, the protein precursor to fibrin, and other clotting factors, while increasing concentrations of anti-clotting factors (Kurosawa 2015; Jang 2013; Rottenberger 2013; Dabbagh 2014).
In a clinical trial, oral ingestion of nattokinase for two months significantly reduced plasma levels of the clotting factors fibrinogen, factor VII, and factor VIII—all risk factors for cardiovascular disease. Nattokinase treatment was safe and similarly effective in both healthy volunteers and patients with cardiovascular disease (Hsia 2009). In another study, a single dose of nattokinase (2000 fibrinolytic units) significantly increased the breakdown of fibrin and fibrinogen and enhanced anti-coagulation activity in the blood of healthy male subjects (Kurosawa 2015).
Centella asiatica. Centella asiatica (C. asiatica), also called Gotu kola, is a tropical plant with a long history of use as a traditional medicine in Southeast Asia. C. asiatica is rich in carotenoids and vitamins C and B complex (Chandrika 2015; MacKay 2001). A rigorous review of randomized controlled clinical trials found evidence that C. asiatica likely exerts beneficial effects on the signs and symptoms of chronic venous insufficiency (Chong 2013).
Natural plant compounds called triterpenes are important constituents of C. asiatica. Animal studies have shown that triterpenes derived from C. asiatica exhibit anti-inflammatory and antibacterial activity. These compounds also promote wound healing by stimulating synthesis of collagen and the formation of new blood vessels (angiogenesis) (Chandrika 2015; Chong 2013).
In a randomized controlled trial in patients with venous hypertension, C. asiatica extract significantly improved edema-related symptoms in patients with venous hypertension as well as ankle edema (De Sanctis 2001).
In another randomized controlled trial in 94 patients with venous insufficiency, treatment with an extract of C. asiatica significantly reduced edema and heaviness in the legs. In addition, C. asiatica treatment resulted in markedly better overall self-evaluation of symptoms by the patients. C. asiatica also improved the capacity of veins to stretch or dilate (Pointel 1987).
Vitamin E. Vitamin E is a fat-soluble vitamin and free radical scavenger (Higdon 2015). Studies have shown that vitamin E inhibits blood clots, which are a potential complication of chronic venous disease (Murohara 2004; Eberhardt 2014).
In the Women’s Health Study that followed nearly 40 000 women, 600 IU of supplemental vitamin E on alternate days, over approximately 10 years, reduced the risk of venous thromboembolism by 21% and pulmonary embolism by 28% compared with placebo. In women genetically predisposed to venous thromboembolism, vitamin E supplementation was even more protective, cutting the risk by about half (Glynn 2007).
Grape seed extract. Proanthocyanidins, active components of grape seeds, inhibit enzymes that degrade collagen and elastin, which provide structure and resilience to blood vessel walls (Wali 2002). This activity of proanthocyanidins may play a role in their efficacy in enhancing vascular function and circulation (MacKay 2001).
In a double-blind study in patients with peripheral venous insufficiency, symptoms were significantly reduced in 75% of participants who received 300 mg of grape seed proanthocyanidins daily. Another study reported increased venous tone in patients with extensive varicose veins following a single administration of 150 mg proanthocyanidins (MacKay 2001).
Vitamin C. Vitamin C is an important scavenger of free radicals that also contributes to venous dilation. Vitamin C is necessary for the synthesis of collagen, a crucial structural protein in blood vessels; and vitamin C has an important role in wound healing. Vitamin C deficiency leads to degradation of collagen-rich connective tissue in blood vessel walls (Calderon Mdel 2015; Kishimoto 2013; Grossmann 2001; Wali 2002; May 2013).
In one study, plasma levels of vitamin C were lower in patients with chronic leg ulcers than in patients without leg ulcers (Lazareth 2007). In another study in patients with venous ulcers, supplementation with 500 mg of vitamin C and topical application of a type of antimicrobial honey resulted in complete healing of all ulcers (Sherlock 2010; Calderon Mdel 2015).
Butcher’s broom (Ruscus aculeatus). Extracts of the herb butcher’s broom (Ruscus aculeatus) have been used traditionally to treat varicose veins, and contemporary scientific research helps explain the mechanisms behind this efficacy (MacKay 2001; AMR 2001).
The primary active constituents of butcher’s broom are compounds called ruscogenins. Ruscogenins from extracts of butcher’s broom inhibit elastase enzymes, which degrade the elastin protein that imparts flexibility to veins. Butcher’s broom also reduces vascular permeability, which contributes to edema (AMR 2001; Scallan 2010).
Several controlled clinical trials have found that butcher’s broom improved venous function and reduced symptoms of chronic venous insufficiency including itching, cramping, and swelling (AMR 2001; MacKay 2001).
Standardized red vine leaf extract (AS 195). Red vine leaf extract is derived from the leaves of the wine grape plant (Vitis vinifera). It contains activated forms of quercetin, the powerful flavonoid present in many plants. Clinical trials in patients with chronic venous insufficiency have found that red vine leaf extract (AS 195) reduces leg edema, enhances blood flow, and improves symptoms such as pain and sensation of heaviness and swelling (Stucker 2016; Rabe 2013; Rabe 2011; Fernandes 2013).
The anti-inflammatory properties of red vine leaf flavonoids are believed to be responsible for much of the clinical benefit of red vine leaf extract, including the normalization of venous permeability (Stucker 2016; Rabe 2013). Red vine leaf extract (AS 195) appears to increase production of nitric oxide, a potent vasodilator, and decrease oxidative stress, contributing to improved circulation (Grau 2016; Shu 2015).
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