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19-05-2015

Venous insufficiency, a chronic, progressive disease

veinotonics 30% of the population suffer from venous insufficiency – four times as many women as men. To prevent this chronic, progressive disease from getting worse, it is important to take action from the moment symptoms appear. Diet, and in particular, nutritional supplements with plant extracts such as horse chestnut, grape seed and ginkgo biloba, as well as essential nutrients like vitamin E, seem to play an important role in mitigating its onset and development.

The term venous insufficiency covers any condition which is the result of a pooling of blood in the veins (stasis) - from feelings of heaviness in the legs, through to skin complications and thrombosis, and including oedema, night cramps, spontaneous bruising, restless leg syndrome, varicose veins and phlebitis.

What causes venous insufficiency?

Some literature suggests it is caused by a primary weakness of the vein wall which is responsible for dilation and stasis. According to other sources, it may originate from excessive pressure due to standing.

Various epidemiological arguments suggest the typical Western diet is a key risk factor, while other predisposing, triggering or aggravating factors include heredity, pregnancy, sedentarism, standing for long periods, excess weight and hormone imbalances. Nutritional shortcomings mean the vein wall becomes sensitive to the effects of venous pressure or blood stasis, with the potential for frequent but undetected thromboses.

Symptoms

Chronic superficial venous insufficiency may be completely painless or it may present as a sensation of heavy, tired legs, and generalised or localised burning. Such problems normally affect part of the leg or the ankles.
Venous disease can be said to have three stages: in the first, there is moderate dilation of the vein. Legs feel heavy and a little swollen at the end of the day and there are possibly a few, visible varicose veins. Venous return is problematic but does occur. In the absence of any treatment, the condition will develop, more or less rapidly, to the second stage where varicose veins are apparent and often require surgical treatment such as scleropathy or echoscleropathy, stripping or de-veining. At the third stage, complications develop where varicose veins are long-standing but untreated.

Mechanism

Venous stasis is responsible for damage to the vein wall which causes ischaemic processes in endothelial cells, together with activation of substances in plasma such as coagulation factors. Local cell ischaemia results in production of arachidonic acid which is released by phospholipase. Prostaglandins are responsible for vasodilation and oedematous effects. Phospholipase A2 initiates aggregation of polymorphonuclear neutrophils and blood platelets. In chronic inflammation, polymorphonuclear neutrophils generate oxygenated free radicals.

Role of vitamin E

Research into dietary factors suggests that sub-deficiency in vitamin E, aggravated by conditions such as pregnancy, plays a key role. In populations with a vitamin E-rich diet, venous insufficiency appears to be less common. Vitamin E may have an effect via its action on coagulation, fibrinolysis and the vein wall.
According to an article published in the French journal Phlébologie1, “The plethora of published studies on vitamin E has convinced many doctors to recommend daily supplementation with the vitamin and an increasing number of phlebologists prescribe it for its effects on blood platelets and for its vascular-protective properties for the arteries and veins”.
A number of experimental and clinical studies have examined vitamin E’s effects on blood platelets, vein walls and blood vessels, as well as on inflammation and the impact of free radicals.
In one human and cell culture study2, subjects given 600mg of vitamin E a day were found to produce less hydrogen peroxide and have less platelet aggregation. Cell studies also showed reduced platelet aggregation and less thromboxane, a component known to promote blood clot formation.
Two doctors who carried out a review3 of clinical, epidemiological and experimental research into vitamin E highlighted, in particular, how vitamin E inhibits proliferation of smooth muscle cells which would otherwise increase, impairing circulation in veins and blood vessels. Vitamin E also has an inhibitory effect on blood clot-formation.
In one study4 on cell cultures, scientists tested vitamin E’s effects on adhesion molecules which encourage monocytes to stick to blood vessel walls. They also examined its effect on nuclear factor kB (NF-kB), known to stimulate genes involved in inflammation – which in turn activates adhesion molecules. Results showed that vitamin E inhibits some types of adhesion molecules and seems to reduce activity of the factor responsible for pro-inflammatory gene induction.

Horse chestnut extract

Horse chestnut extract works by reducing the number and size of the small pores of capillary membranes, thus stemming the leakage of fluid into surrounding tissue. This ‘plugging’ effect improves blood flow in veins and reduces swelling in the small vessels in the legs. A study5 published in The Lancet investigated 240 patients with severe leg oedema caused by chronic venous insufficiency. After 12 weeks’ treatment with a horse chestnut extract, the amount of fluid in the legs decreased by around 43.3 ml while in a placebo group, fluid retention rose by 9.8ml.
A clinical trial of 35 patients with chronic venous insufficiency measured subjects’ foot volume while lying down and standing up. Horse chestnut proved to be effective against foot oedema in both positions, without reducing potassium levels, as is the case with diuretics.
Another study on leg oedema concluded that it offered clinical benefit whatever the patient’s position (moving, sitting or standing).

Horse chestnut extract helps restore vein tone, that is the ability of the vein to contract dynamically to the correct size for any given venous pressure. It also helps correct increased capillary permeability. Injecting rats with an inflammatory stimulus causes permeability of the lympho-plasmatic barrier to increase, doubling the lymphatic flow. Escin, the key ingredient in horse chestnut, counters this effect, normalising the permeability of the lympho-plasmatic barrier.
In addition, horse chestnut inhibits two key stages in the degenerative cascade triggered by hypoxia, the decrease in ATP content and the increased activity of phospholipase (A2), a pro-inflammatory enzyme. Furthermore, escin prevents neutrophils from adhering to hypoxic cells on the internal vein wall. Finally, horse chestnut combats the damaging effects of oxygenated free radicals, helps stabilise connective tissue and maintains the integrity of the extracellular matrix. It inhibits enzymes which break down proteoglycans, these being essential for the stability and function of connective tissue.

Gotu Kola or Centella asiatica

Centella asiatica is a tropical plant which has long been used for medicinal purposes. Its efficacy in treating varicose veins and venous insufficiency has been demonstrated in a number of studies. It works by strengthening the connective integrity of tissues and improving capillary permeability. A vacuum suction chamber, which produces swelling when applied to the skin of the ankle, has been employed in some gotu kola studies to evaluate the rate of fluid leakage in venous insufficiency. When leg veins are losing a lot of fluid, this swelling takes longer to disappear. A study of subjects with venous insufficiency showed that two weeks’ treatment with gotu kola extract was enough to eradicate swelling. A placebo-controlled study of 52 patients with venous insufficiency compared the effects of gotu kola extract at daily doses of 180mg and 90mg against placebo. After four weeks’ treatment, researchers observed improvements in various measurements of vein function in all treated patients, but not in the placebo group. Local application of gotu kola extract also improves vein tone. When applied three times a day to patients with various circulation disorders, including haemorrhoids and varicose veins, subjective and objective improvements were reported in clinical symptoms.

The flavonoids diosmin, hesperidin and troxerutin

Several randomised, controlled trials have demonstrated that two flavonoids, diosmin and hesperidin, are effective at treating varicose veins and haemorrhoids when combined in a specific ratio of 9:1.
They have been shown to boost vein tone and elasticity, and strengthen the veins, improving their overall health. Good vein tone reduces the likelihood that stagnant blood will accumulate in the veins and thus lowers the risk of varicose veins and haemorrhoids.
A paper7on the use of diosmin and hesperidin for treating various-cause oedema reviewed three studies on chronic venous insufficiency, with 200, 320 and 30 subjects. In all three studies, patients received 1000mg/day of the flavonoids for between six and eight weeks. In each study, the treatment produced a significant reduction in oedema.
A double-blind study8of 120 participants suffering from haemorrhoids highlighted the efficacy of taking 1000mg/day of these flavonoids for two months, compared with a placebo. The treated group suffered fewer episodes of haemorrhoids than the placebo group (40% against 70%), duration was shorter (2.6 days against 4.6 days), and on a scale of 1 to 3, severity of attacks in the supplemented group was 1.1 as opposed to 1.6 in the placebo group. Another study9 of 100 patients suffering an acute episode of haemorrhoids, evaluated the effect of this combination of flavonoids at an initial dose of 1500mg three times a day for four days, then 1000mg twice a day for the next three days, compared with a placebo. Those taking the supplement experienced greater improvement – their attacks were shorter in duration and less severe. In patients (aged 71 on average) with venous leg ulcers, administration10 of 1000mg of diosmin/hesperidin for two months, in conjunction with conventional treatment, notably accelerated complete healing of their ulcers. 32% of patients in the supplemented group saw their ulcers heal compared with 14% of the placebo group. A Polish study11 similarly examined chronic venous insufficiency patients suffering with leg ulcers. They were given standard compression treatment either alone or combined with diosmin/hesperidin supplements. In the latter case, patients were more likely to experience complete healing of their ulcers compared with those receiving only the compression. This study shows that healing of ulcers is accelerated when conventional therapies such as compression are accompanied by flavonoid supplementation.

In research conducted at the Technical University of Munich, 16 healthy volunteers 12 were given a placebo for two weeks, followed by 500mg of troxerutin twice a day for the next three weeks. At the beginning of the study and each week thereafter, oedema was incited in the subjects. Administration of troxerutin was found to produce a progressive reduction in the oedema. Given that the subjects were healthy with no sign of venous insufficiency, these results suggest a protective effect for troxerutin. Another double-blind, placebo-controlled study, 13 of 133 subjects showed that troxerutin, combined with compression therapy, was more effective than the latter alone. A six month course of troxerutin at 900mg/day given to 102 subjects aged over 65 improved cramps, heaviness and restlessness in the legs. In research involving 97 haemorrhoidal pregnant women15who received 1000mg/day of troxuretin or a placebo, improvements in symptoms - measured at two and four weeks of treatment - were greater in the supplemented group than in those given a placebo. Side-effects were mild and temporary.

Proanthocyanidins

The flavonoid group of proanthocyanidins are mainly extracted from maritime pine bark (pycnogenol), grapeseed or blueberries. First recognised for their antioxidant properties, they were subsequently also found to inhibit hyaluronidase, elastase and collagenase. These enzymes break down connective structures in tissue resulting in vascular permeability. Proanthocyanidins preferentially bind to areas with a high glycosaminoglycan content, such as capillary walls, a characteristic which enables them to reduce vascular permeability and boost capillary resistance, vascular function and peripheral circulation.
In vitro research showed that, in the presence of proanthocyanidins, fibroblasts and smooth muscle cells in pig skin attached themselves to elastin fibres. By increasing elastin resistance to enzymatic degradation and boosting interaction between fibres and cells, proanthocyanidins promote healthy function of vascular walls. The addition of 1mg/ml of proanthocyanidins to a human cell culture of diseased vein walls resulted in a 34% decrease in levels of hyaluronic acid, suggesting a potential counter-effect for these flavonoids against veino-lymphatic oedema - thought to be linked to increased levels of hyaluronic acid. Varicose vein walls differ from normal vein walls in that they have less collagen and more proteoglycans, particularly hyaluronic acid. This reduction in collagen content is believed to be due to increased activity by the protein- and collagen-destructive enzyme as well as to free radicals. Anthocyanosides are also powerful antioxidants that can combat the damaging effects of free radicals. A large number of clinical studies have been conducted in France using grapeseed extracts to treat capillary fragility and varicose veins. In one double-blind study16, 71 patients with venous insufficiency were given 300mg/day of grapeseed anthocyanidins or a placebo. A significant reduction in functional symptoms was observed in 75% of the supplemented patients against 41% of those given a placebo. Research17 showed that administration of a single, 150mg dose of anthocyanidins increased vein tone in patients with widespread varicose veins. In another clinical trial18, a group of geriatric patients with poor capillary resistance was treated with 100-150mg of anthocyanidins or a placebo. After two weeks’ treatment, half the supplemented patients showed an improvement in capillary resistance.
Human studies have shown that pycnogenol, extracted from French maritime pine bark, reduces platelet aggregation. One study19 evaluated pycnogenol’s efficacy in treating chronic venous insufficiency. Initially, researchers gave 20 subjects a placebo or 100mg of pycnogenol three times a day for two months. In a second phase of the study, 20 additional volunteers received the same dose of pycnogenol.
The first phase produced a 60% reduction in feelings of heaviness in the legs and a 74% reduction in subcutaneous oedema in the supplemented patients. In the second phase, the heaviness and oedema decreased by 44% and 54% respectively. Venous pressure was also significantly reduced following pycnogenol supplementation. Clinically, capillary leakage, perivascular inflammation and subcutaneous oedema were all reduced.
In another double-blind, randomised study, 40 venous insufficiency patients with varicose veins were given either 100mg of pycnogenol three times a day or a placebo, for two months. The pycnogenol supplements were found to induce significant reductions in subcutaneous oedema, and in heaviness and pain in the legs after 30 and 60 days’ treatment. In almost 60% of those given the pycnogenol, oedema and pain had completely gone by the end of the treatment. All patients reported a reduction in heaviness in the legs, and for 33%, it disappeared completely.


References

1 «Vitamine E en phlébologie », Phlébologie, 1999,52, n°53, 341-345
2 Pignatelli P, Pulcinelli FM, Lenti L et al., «Vitamin E inhibit collagen-induced platelet activation by blunting hydrogen peroxide», Arterioclerosis, Thrombosis and Vascular Biology, 1999;2542-2547.
3 Emmert DH et Kirchner JT, «The role of vitamin E in the prevention of heart disease», Archives of Family Medicine, 1999 ;8 :537-542
4 Islam KN, Devaraj S, Jialal I. «Alpha-tocopherol enrichment off monocytes decreases agonist-induced adhesion to human endothelial cells”, Circulation, 1998;98:2255-2261.
5 Diehm C, et al. “Comparison of leg compression stocking and oral horse-chestnut seed extract therapy in patients with chronic venous insufficiency”, Lancet, 1996;3;347(8997):292-4
6 Allegra C, Pollari G, Criscuolo A et al., « Centella asiatica extract in venous disorders of the lower limbs. Comparative clinico-instrumental studies with a placebo”, Clin. Ter, 1981;88:507-513.
7 Oiszewski W. “Clinical efficacy of micronized purified flavonoid fraction in edema”, Angiology, 2000;51(1)25-9.
8 Godeberge P, “Daflon 500 mg in treatment of flavonoids pertaining to inflammation”, Angiology, 1994;45:574-8.
9 Cospite M « Double-blind, placebo-controlled evaluation of clinical activity and safety of Daflon 500 mg in the treatment of acute hemorrhoids », Angiology, 1994 ; 45 (6 Pt 2) :566-73.
10 Guihou JJ, Fevrier F, et al. « Benefit of a 2-month treatment with a micronized, purified flavonoidic fraction on venous ulcer healing. A randomised, double-blind, controlled versus placebo trial”, Int J Microcirc Clin Exp, 1997; 17 sipple 1:21-6
11 Glinski W, Chodynicka Bet al., “ Effectiveness of a micronized purified flavonoid fraction in the healing process of lower limb ulcers,.” Minerva Cardioangiol. , 2001;49:107-14.
12 Rehn D, et al. «Time course of the anti-oedematous effect of O-(beta-hydroxyethyl)-rutosides in healthy volunteers”, Eur. J Clin. Pharmcol., 1991;40(6):625-7.
13 Unkauf M et al, “Investigation of the efficacy of oxerutins compared to placebo in patients with chronic insufficiency treated with compression stockings”, Azneimittelforschung 1996;45(5):483-7.
14 McLennan WL, et al. « Hydroxyethylrutosides in elderly patients with chronic venous insufficiency : it efficacy and tolerability”, Gerontology,1994;40(1):45-52.
15 Wijayanegar H et al. “A clinical trial of Hydroxyethylrutosides in the treatment of hemorrhoids of pregnancy”, J. Int. med. Res. 1992;20(1):54-60.
16 Thebaut JF, Thebaut P, Vin F, « Study of Endotelon in functional manifestation of peripheral venous insufficiency. Results of a double blind study of 92 patients” Gaz. Med; France, 1985;92:96-100.
17 Royer RJ, Schmidt CL,, «Evaluation of venotropic drugs by venous gap plethysmography. A study of procyanidolic oligomers”. Sem. Hop, 1981;57:2009-2013.
18 Dartenuc JY, Marache P, Choussat H, «capillary resistance in geriatry. A study of a microangioprotector Endotelon”, Bor Med, 1980;13:903-907.
19 Petrassi C, Mastromarino A, Spartera C, “Pycnogenol in chronic venous insufficiency”, Phytomedicine, 2000 7(5) :383-8.
Order the nutrients mentioned in this article
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Improves blood circulation in the legs

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Centella asiatica 60 mg

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Taxifolin

Natural taxifolin (dihydroquercetin) supplement for the circulation

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Lymphatonic 20 mg

Melilotus officinalis extract standardised 18% coumarin
Protects and thins the lymphatic system

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Natural E 400

400 IU Alpha Tocopherol (natural Vitamin E) 

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