OBJECTIVE OF THE STUDY

The primary end point was to evaluate the efficacy of a tablet nutraceutical, composed of phytotherapeutic active ingredients, in reducing symptomatology and CEAP class in female patients with mild-to-moderate venous insufficiency symptoms. The second end point was to evaluate the tolerability and therapeutic sustainability of treatment with such a nutraceutical for 3 months.

FOREWORD

In the hottest summer months, a feeling of deep leg fatigue occurs in a great many individuals due to poor blood return from the peripheral districts to the heart. During the summer period all these compensatory mechanisms are made less efficient: in fact, the heat, by causing an increase in vasodilation, leads to the appearance of heavy legs, itching and swelling of the ankles, which are the main symptoms of venous insufficiency. An unhealthy lifestyle can also contribute to an aggravation of this symptomatology: overweight, obesity, water retention, use of oral contraceptives, constipation, cigarette smoking, and carrying out a profession, which forces one to stand and be immobile for many hours, are among the main predisposing causes of venous insufficiency. The Dr. Alfredo Sabato, planned to monitor, with the support of territorial doctors., patients with mild-to-moderate venous insufficiency symptoms in the lower limbs: swelling, heaviness, pain, itching, burning, hyperpigmentation, stasis dermatitis.

Introduction by Dr. ALFREDO SABATO

We can say that venous insufficiency is a condition in which the venous system has difficulty returning blood from the periphery back to the heart. We have a load of fluid that is contained in vessels that do NOT have a muscular wall like arteries which are able to give active propulsion, but are vessels with a wall without muscle fibers and which have some valves: the ascent of the blood back to the heart must take place on the one hand by the muscle pump, and for this it is necessary to walk, and on the other hand by the tightness of the valves that the veins possess. So if there is a problem to the ascent back to the heart, a stasis of the blood column is formed, which causes transudation of the finest capillaries and edema of the tissue. Failure to take action can result in progressive worsening of the situation. Venous insufficiency is a chronic and progressive disease.

As for causes, first of all there is a family predisposition and it is more prevalent in the female sex: there are girls even young girls who have the same problems as mothers and grandmothers; there are also causes due to behaviors or wrong lifestyle or even physical problems such as excess weight or sedentary lifestyle, working in static orthostatism. Excessive environmental temperature, excessive exposure to the sun causing vasodilation, taking oral estroprogestinics, hormonal imbalances.

In particular, the pregnancy is a temporary cause but is important for those who already have a family predisposition and for those who gain a lot of weight, because in addition to a physical obstruction of venous return there is the weight of the fetus pressing on the veins that are most important for venous return and there is also a physiological increase in progesterone. The progesterone Is a powerful vasodilator. Other causes may be unbalanced diets or even alterations in plantar support. There may also be footwear that affects optimal venous return, such as shoes that are too high or too low. Incongruous sports activities can also have a negative effect on venous return.

The most frequent symptoms are very common and the first is edema of the lower limbs with a feeling of tired and heavy legs, paresthesias, tingling, diffuse and localized heat in the limbs, night cramps, restlessness of the limbs (so-called restless legs syndrome) may present. Orthostatic phlebodynia may also present.

Other symptoms may be visual, considered more as “conditions,” which may be asymptomatic with or without pain: these are truncular varices, of telangiectasias to phlebostatically based skin ulcers in more advanced states. Clinical classification is made through the CEAP classification which has been used for 25 years now and is based on four parameters: clinical, etiological, anatomical and pathophysiological and is used to describe the different relative clinical patterns of onset and evolution of chronic venous disease.

Venous insufficiency is a chronic aggravating condition for which complications arise as the condition progresses but are treatable and containable through proper management of the patient taking into account his or her general clinical picture and social and family status.

Among the milder complications we highlight the following edema in the lower limbs, the varicophlebitis but more serious that affect not the quality of life but life itself: deep vein thrombosis of the popliteal vein, femoral vein where it is necessary to do therapy with low molecular weight heparins, wear a curative elastic brace, and study the patient from the point of view of potential genetic abnormalities that may predispose to thrombophilia.

Then there are also deep vein thromboses of paraneoplastic origin, tumors with necrosis factors that can trigger the process of coagulation within the vessel. Deep vein thrombosis is a pathological condition severe which must be managed carefully as it can cause pulmonary embolism.

There are other complications due to the chronicity of this condition and they are the varices ingravescence, i.e., the inordinate increase of varices in the lower limbs due to which pigment leaks out with dystrophies and skin discolorations that can lead to phlebostatic-based skin ulceration that prefers the inner malleolar area of the leg and ankle.

SCIENTIFIC RATIONALE

Wikenfarma found that a nutraceutical, composed of active phytotherapeutic ingredients such as micronized Diosmin, Hesperidin, Melilot, Horse Chestnut, and Rutin, is particularly effective in reducing symptoms related to venous insufficiency and improving the CEAP membership class commonly used to classify chronic venous disorders.

DESCRIPTION OF THE ACTIVE INGREDIENTS OF THE NUTRACEUTICAL

La DIOSMINE is a phytotherapeutic that can be found in drug or supplement form in a micronized form that ensures maximum bioavailability and thus optimal efficacy.

The properties of Diosmin are innumerable:

• Increases vessel tone by inhibition of COMTs and reduction of norepinephrine metabolism
• decreases capillary permeability
• neutralizes pro-inflammatory molecules such as thromboxane A2 by reducing leukocyte activation and expression of adhesion molecules by vascular endothelium with reduction of inflammatory process and edema
• Improves the dynamic balance between coagulation and fibrinolysis
• Optimizes lymphatic drainage by preventing extravascular fluid accumulation
• Reduces the compression of edema on nerve structures and thus the pain symptoms.

Using a combination with other phytotherapeutics creates a synergy to intervene more effectively on mediators of inflammation, to reduce vascular permeability, to increase venous tone, and to achieve good control of the hemostatic balance by stimulating tissue fibrinolysis by reducing edema.

The substances that go best in association with Diosmin are theHesperidine which improves the permeability and fragility of capillary walls by increasing their resistance, and the Rutin which acts directly on the permeability and trophism of capillaries and has antihemorrhagic and antiedemigenous action.

L’Horse Chestnut is characterized by its high content of l’Escin which increases tone, reduces capillary permeability, exerts anti-inflammatory action and has fibrinolytic action so it reduces the risk of edema becoming chronic and is also very useful in lymphatic edema.

The Melilotus has anti-inflammatory, anti-edemigenous action and has a high titer of Coumarins, which are anticoagulant substances. Coumarol is the most representative molecule in this category. These substances decrease prothrombin synthesis and have a great anticoagulant effect.

Therefore, the synergy of the different phytotherapeutic active ingredients, shortens the therapy time and improves the symptomatology quickly.

INCLUSION AND EXCLUSION CRITERIA

Female patients aged 18 to 79 years with a diagnosis of mild to moderate venous insufficiency were recruited into the study. Symptomatic patients with clinical and instrumental signs of venous insufficiency

Patients with severe cardiovascular or renal function comorbidities and patients on antihypertensive therapy with calcium antagonists

PROCEDURE

The experimental study was carried out through a controlled clinical trial. At the first visit, the volunteer was evaluated by the researcher. Having met the inclusion criteria, the volunteer was enrolled in the study. After signing the informed consent, therapy was prescribed and the patient returned for follow-up visit after 3 months: clinical examination was performed and self-assessment questionnaire was completed.

MATERIALS AND METHODS

The nutraceutical FLEBOKEN 30cpr® was used in the study for 3 months, with the following dosage: 2 tablets daily for the first 15 days and then 1 tablet daily.

The multicenter study involved 147 patients. Court enrollment of patients lasted 30 days from June 1, 2021, the study lasted 3 months and ended on September 30, 2021.

The composition of the nutraceutical FLEBOKEN 30cpr® with which the study was done is as follows:

• Micronized diosmin 300mg
• Hesperidine 70mg
• Rutin 50mg
• Sweet Clover 50mg
• Horse chestnut 150mg