Pycnogenol® and Centella asiatica in the management of asymptomatic atherosclerosis progression.

AIM: The aim of the study was to evaluate the effect of the nutritional supplements Pycnogenol® and total triterpenic fraction of Centella asiatica (TTFCA) on atherosclerosis progression in low-risk asymptomatic subjects with carotid or femoral stenosing plaques. METHODS: This was an observational pilot, substudy of the San Valentino epidemiological cardiovascular study. The study included 824 subjects aged 45-60 without any conventional risk factors who had a stenosing atherosclerotic plaque (>50-60%) in at least one carotid or common femoral bifurcation, allocated into 6 groups: Group 1 (Controls): management was based on education, exercise, diet and lifestyle changes. This same management plan was used in all other groups; group 2: Pycnogenol® 50 mg/day; group 3: Pycnogenol® 100 mg/day; group 4: Aspirin® 100 mg/day or ticlopidine 250 mg/day if intolerant to aspirin; group 5: Aspirin® 100 mg/day and Pycnogenol® 100 mg/day; group 6: Pycnogenol® 100 mg/day plus TTFCA 100 mg/day. The follow-up lasted 42 months. Plaque progression was assessed using the ultrasonic arterial score based on the arterial wall morphology and the number of plaques that progressed and on the number of subjects that had cardiovascular events. A secondary endpoint was to evaluate the changes in oxidative stress at baseline and at 42 months. RESULTS: The ultrasonic score increased significantly in groups 1, 2, and 4 (>1%) but not in groups 3, 5 and 6 (<1%) suggesting a beneficial effect of Pycnogenol® 100 mg. Considering the percent of patients that progressed from class V (asymptomatic) to VI (symptomatic) there was a progression of plaques in 48.09% of controls. In the Pycnogenol® 100 (group 3, 10.4%) and in the Aspirin®+ Pycnogenol® (group 5, 10.68%) progression was half of what observed with antiplatelet agent (group 4, 20.93%); in the TTFCA+ Pycnogenol®group (group 6) progression was 7.4 times lower than in controls; 3.22 times lower than in the antiplatelet agents group (4). Events (hospital admission, specialized care) were observed in 16.03% of controls; there were 8.83% of subjects with events with Pycnogenol® 50 mg and 8% in group 3 (Pycnogenol® 100 mg). In group 4 (antiplatelets), 8.52% of subjects had events; in group 5, 6.87% of subjects had events and in group 6 (TTFCA+ Pycnogenol®) only 4.41% had events (this was the lowest event rate; P<0.05). All treatment groups had a significantly lower event rate (P<0.05) in comparison with controls. Considering treatments groups 2, 3, 5, 6 had a lower number (P<0.05) of subjects in need of cardiovascular management in comparison with controls. The need for risk factor management was higher in controls and lower in group 6 (P<0.05). In groups 2 to 6 the need for risk factor management was lower than in controls (P<0.05). Including all events (hospital admission, need for treatment or for risk management) 51.9% of controls were involved. In the other groups there was a reduction (from a -9.28% reduction in group 2 to a -26% in group 6) (P<0.002). The most important reduction (higher that in all groups; P<0.05) was in group 6. At 42 months, oxidative stress in all the Pycnogenol® groups was less than in the control group. In the combined group of Pycnogenol® and TTFCA the oxidative stress was less than with Pycnogenol® alone (P<0.001). CONCLUSION: Pycnogenol® and the combination of Pycnogenol® +TTFCA appear to reduce the progression of subclinical arterial plaques and the progression to clinical stages. The reduction in plaque and clinical progression was associated with a reduction in oxidative stress. The results justify a large, randomized, controlled study to demonstrate the efficacy of the combined Pycnogenol® and TTFCA prophylactic therapy in preclinical atherosclerosis.

Meriva®, a lecithinized curcumin delivery system, in the control of benign prostatic hyperplasia: a pilot, product evaluation registry study.

INTRODUCTION: The aim of this registry evaluation study was to compare, in symptomatic BPH patients, two management plans based on a currently validated standard treatment [defined as the best standard management (BSM)] including or not curcumin (administered as Meriva®) as a further complementary adjuvant element. Signs and symptoms were evaluated using the International Prostate Symptom Score (IPSS). SUBJECTS, METHODS: The study was carried out on a total of 61 subjects. 33 subjects (mean age 58.6;5.3) completed the survey with at least 24 weeks of treatment with Meriva® in association with the BSM. The BSM-alone control group consisted of 28 volunteers of similar age (58.4 years;3.4) and severity of the condition. The range of inclusion age was 55-65. No other clinical or metabolic problems were present. Meriva® was administered at the dosage of 2 tablets/day (2 x 500 mg of Meriva®/day, corresponding to 2 x 100 mg curcumin/day) with a compliance values > 95% as evaluated by the number of tablets used according to medical recommendation. No other drugs or food supplement were used during the study. RESULTS: All IPSS scores, with the exception of the stream weakness score in the BSM group, were improved (p<0.05 vs. inclusion) in both groups. The overall results in the Meriva® group were significantly better than in the BSM-only group (p<0.05). No side effects were recorded. The quality of life improved in both groups, but was significantly better in the Meriva® group (p<0.01). There was also a significantly more important decrease in clinical and subclinical episodes of urinary infections and urinary block in the Meriva® group (p<0.01). COMMENTS: In patients with BPH, the addition of Meriva® to the standard treatment contributed to the reduction of signs and symptoms of the disease without causing any significant additional side effect. This pilot experience suggests a potential novel clinical application of curcumin, and further studies aimed at selecting the most appropriate dosages and length of treatment as well as the possibility to including longer treatments will, undoubtedly, validate and optimize the role of Meriva® in the management of BPH.

TECA (Titrated Extract of Centella Asiatica): new microcirculatory, biomolecular, and vascular application in preventive and clinical medicine. A status paper.

Plant-derived elements used for pharmacological applications constitute an increasing research field. Centella asiatica is widely used mainly as an extract (TECA). Triterpenic fractions, the primary constituents of Centella asiatica, produce a wide range of preventive and therapeutic effects. The modulation of collagen production and deposition in wound healing is of primary importance. TECA is also used to treat several microcirculatory problems, inflammatory skin conditions (leprosy, lupus, varicose ulcers, eczema, atopic dermatitis, psoriasis) and also intestinal problems, fever, amenorrhea and genitourinary conditions. Cognitive functions, anxiety and mental impairment may be also affected by TECA administration. New applications in neurology include nerve growth factor enhancement and applications in neurological degenerative conditions. Interaction with other products is also indicated in this document. The multiplicity of actions of TECA is associated to six important mechanisms, all inter-connected and modulating each other: 1) edema - and capillary filtration - control; 2) a strong antioxidant power, effective on several forms of oxidative stress associated to inflammation or infections and synergic with other antioxidant products; 3) an anti-inflammatory action; 4) a modulation of the collagen production avoiding slower scarring or faster, hyperthrophic scarring and cheloids; 5) a modulating action of local growth factors; 6) a modulation of angiogenesis. This "status" paper - resulting from an expert meeting held in Cobham, Surrey, indicates most of the therapeutic potential of TECA, still to be explored in further studies. The status paper constitutes the basis for a consensus document on TECA to be developed in the next future. This "status" paper opens a new window on an ancient but still partially unexplored product that may become an important value in prevention and treatment of several pre-clinical and risk conditions and in clinically significant disease both as a single products and in association with other 'natural' products.

Prevention of edema in long flights with Pycnogenol.

The aim of this study was to evaluate the prevention of edema during long-haul flights with an oral, anti-edema and antithrombotic agent (Pycnogenol, Horphag, Research Management SA, Geneva, Switzerland) in asymptomatic subjects. The assessment of edema was performed by evaluating an analogue scale, the rate of ankle swelling by strain-gauge derived rate of ankle swelling (RAS), and by assessing the ankle circumference variation. The study included 211 subjects; 169 completed the study (88 in the control group and 81 in the Pycnogenol group). There were no important differences between the two groups (comparable for age, gender, weight, body mass index, and pattern distribution). The edema score, the RAS, and the circumference at inclusion were also comparable. After the flight in those treated with Pycnogenol, the edema score was increased only by 17.9% (vs. an increase of 58.3% in the control group) (p<0.05). The RAS, evaluated in 22 subjects in the Pycnogenol group (age 44.5; SD 8) and in 23 in the control group (age 45; SD 9) was increased on average by 91% in the control group and 36% in the Pycnogenol group (p<0.05). The variation on circumference at the ankle was 6% in the Pycnogenol group (11% in the control group; p<0.05). These results indicate a positive effect of Pycnogenol on edema during long flights when considering subjective and objective data. No unwanted effects were observed.

Foam-sclerotherapy, surgery, sclerotherapy, and combined treatment for varicose veins: a 10-year, prospective, randomized, controlled, trial (VEDICO trial).

The study compared, by a prospective, randomized method, 6 treatment options: A: Sclerotherapy; B: High-dose sclerotherapy; C: Multiple ligations; D: Stab avulsion; E: Foam-sclerotherapy; F: Surgery (ligation) followed by sclerotherapy. Results were analyzed 10 years after inclusion and initial treatment. Endpoints of the study were variations in ambulatory venous pressure (AVP), refilling time (RT), presence of duplex-reflux, and number of recurrent or new incompetent venous sites. The number of patients, limbs, and treated venous segments were comparable in the 6 treatment groups, also comparable for age and sex distribution. The occurrence of new varicose veins at 5 years varied from 34% for group F (surgery + sclero) and ligation (C) to 44% for the foam + sclero group (E) and 48% for group A (dose 1 sclero). At 10 years the occurrence of new veins varied from 37% in F to 56% in A. At inclusion AVP was comparable in the different groups. At 10 years the decrease in AVP and the increase in RT (indicating decrease in reflux), was generally comparable in the different groups. Also at 10 years the number of new points of major incompetence was comparable in all treatment groups. These results indicate that, when correctly performed, all treatments may be similarly effective. "Standard," low-dose sclerotherapy appears to be less effective than high-dose sclero and foam-sclerotherapy which may obtain, in selected subjects, results comparable to surgery.