A nutraceutical formulation combined with sclerofoam-assisted laser treatment ameliorates chronic venous insufficiency

Chronic venous insufficiency (CVI) is a common condition with high impact on the healthcare system [1]. An epidemiological survey of 6009 patients, conducted in Belgium and Luxembourg, evidenced a high prevalence of CVI (61.3%) [2]. Prevalence will increase due to its main risk factors, including age, family history, obesity and necessity to stand at work [3]. For example, in a study including 541 Japanese women, 42% of subjects with varicose veins reported a positive family history compared with just 14% of women without disease; this difference is reduced with increasing age [4]. In the USA, the number of venous thromboembolism cases has been projected to increase from 1 million in 2010 to 1.8 million in 2050 [5], while varicose vein procedures are projected to increase by over 60% in the USA and Europe between 2013 and 2021 [6]. The CVI diagnosis is confirmed and classified with the Clinical, Etiologic, Anatomical, and Pathophysiological (CEAP) assessment (range: C0–C6) [7]. The CEAP classification for chronic venous disorders was developed in 1994 by an international ad hoc committee of the American Venous Forum, endorsed by the Society for Vascular Surgery, and incorporated into “Reporting Standards in Venous Disease” in 1995 [8]. Chemical endocavitary thermal treatments are a standard therapy due to low invasiveness, good efficacy and low complication rate [9]. Furthermore, they allow the patient to return to daily activities in a short time-frame post-treatment since CVI is cause of discomfort, pain, loss of working days, disability and reduction in quality of life [10‐12]. The sclerofoam-assisted laser treatment (SFALT) technique 13 is routinely used in Italy and combines intravenous sclerofoam injection (polidocanol 3% or sodium tetradecyl sulphate 3% according to Tessari’s method) followed by endothelium stripping with fibre optic (600µ)–coupled laser diode (1470 nm wavelength) delivered at 40 J/cm fluence [14, 15]. This instrumental treatment can be combined to pharmacological or nutraceutical therapy to reduce pain, edema, inflammation and fluid retention (common side effects of traditional varicose vein treatments) and to induce rapid functional restoration in CVI patients [16]. Other add-on therapies can include (1) leg elevation [1, 17], (2) pharmacological therapy using vasoactive drugs that include coumarins, flavonoids, saponosides and other plant extracts, whose action is to improve venous tone and capillary permeability [1, 17] and (3) exercise therapy to improve calf muscle function [18]. The emergent role of herbal therapy administered orally or topically to patients has also been highlighted [19‐21]. The advantage of herbal formulations is that multiple active principles are administered to the patient simultaneously, allowing synergistic action [22]. For this reason, the nutraceutical market in phlebology has sharply increased in the last 10 years [23]. Hence, in the current study, we evaluated the efficacy of SFALT combined with formulated compounds that display specific effects on the microcirculation of the operated leg.

All the patients complied with the treatment schedule without showing any adverse effects. Only 4 patients required the use of painkillers (acetaminophen or ibuprofen) in the first post-operative day. Limb volume measured by BIS was significantly decreased at T2 compared to baseline (p < 0.01) (Fig. 1A). Similarly, RES and REA measured by BIS were significantly increased at T2 compared to T0 (p < 0.0001 and p < 0.01, respectively) (Fig. 1B and C). A significant improvement in heaviness, paresthesia, pain, swelling and itch was observed (all p < 0.0001) while no changes in terms of diuresis were reported, as assessed by Doppler ultrasound, VAS and medical evaluation (Fig. 1D).

CVI has been treated with endovenous laser and radiofrequency in the last decade [15, 31]. However, these techniques are invasive and require multiple high-volume injections of tumescent anesthesia, which can lead to adverse effects, including post-operative pain, perivenous ecchymosis and hematoma in the treated areas, leading to patient’s dissatisfaction [32‐35]. On the other hand, the SFALT method is an innovative procedure that can overcome the limitations of conventional treatments [36]. The low temperature and the sclerofoam injection allows a great saphenous vein tract reduction, avoiding the use of high-volume tumescent anesthesia, typical of traditional procedures.

No clinical study beyond case reports comparing this SFALT technique to surgery has been published yet. However, clinical case reports indicate that 80 to 90% of saphenous trunks remain occluded after 3 years when treated using the SFALT method [36]. Furthermore, this technique includes other benefits such as optimal cosmetic results and cost-effectiveness. There is no downtime and patients can resume normal activity immediately. However, this technique should be avoided in patients with severe thrombophilia and carried out with prophylaxis in patients with less severe thrombophilia. In regard to the nutraceutical formulation that we employed in this study, extracts from the seed of the horse chestnut have traditionally been used to alleviate several symptoms including lower leg swelling. These effects are largely due to an inhibitory effect on the catalytic breakdown of capillary wall proteoglycans [37]. Several clinical trials in CVI patients and in patients affected by varicose veins demonstrated the effectiveness of Aesculus hippocastanum extracts through the objective measure of reduction in lower leg edema and the subjective alleviation of leg pain, heaviness and itching [38‐40]. In addition, Pinus pinaster Aiton administered as herbal supplement has been reported to have vasorelaxant activity, angiotensin-converting enzyme inhibiting activity, and the property to enhance the microcirculation by increasing capillary permeability [41]. Several clinical trials using red vine leaves (Vitis vinifera) confirmed improvement of microcirculation and oxygen supply, significant reduction of oedema and relevant improvement of leg pain, heaviness and tension [42‐44]. In addition, chondroitin sulphate or chondroitin-4-sulphate is a natural glycosaminoglycan which possesses anticoagulant and antithrombotic effects [45].

Furthermore, in the present preliminary trial, SFALT combined with nutraceutical administration improved the patients’ quality of life and allowed a faster return to work and routine activities. Our study has limitations, i.e. limited number of cases included, the absence of control groups receiving only nutraceutical or SFALT intervention and lack of a blinding approach. Nevertheless, this proof-of-concept study has shown that this approach has no side effects and gives a promising outcome. Further studies taking into consideration the above-mentioned limitations will be conducted in the future.