Pycnogenol® improves cognitive function in post-stroke patients: a 6 month-study.

BACKGROUND: This pilot study in post-stroke patients evaluated the effects of supplementation with Pycnogenol® on alterations in cognitive functions (COFU) over a period of 6 months, starting 4 weeks after the stroke. METHODS: The effects of supplementation - possibly acting on residual brain edema, on global cognitive function, attention and on mental performance - were studied. A control group used standard management (SM) and the other group added Pycnogenol®, 150 mg daily to SM. RESULTS: 38 post-stroke patients completed the 6-month-study, 20 in the Pycnogenol® group and 18 in the control group. No side effects were observed with the supplement. The tolerability was very good. The patients included into the two groups were comparable for age, sex and clinical distribution. There were 2 dropouts in the control group, due to non-medical problems. Main COFU parameters (assessed by a cognitive questionnaire) were significantly improved (all single items) with the supplement compared to controls (P<0.05). Additional observations indicate that Pycnogenol® patients experienced significantly less mini-accidents (including falls) than controls (P<0.05). The incidences of (minor) psychotic episodes or conflicts and distress and other problems including rare occurrence of minor hallucinations, were lower with the supplementation than in controls (P<0.05). Single observations concerning daily tasks indicated a better effect of Pycnogenol® compared to controls (P<0.05). Plasma free radicals also decreased significantly with the supplement in comparison to controls (P<0.05). Globally, supplemented subjects had a better recovery than controls. CONCLUSIONS: In post-stroke subjects, Pycnogenol® supplementation resulted in better recovery outcome and faster COFU 'normalization' after the stroke in comparison with SM; it can be considered a safe, manageable post-stroke, adjuvant management possibly reducing local brain edema. Nevertheless, more patients and a longer period of evaluation are needed to confirm these results.

Positive effects of Pycnogenol®-Centellicum® on venous elasticity: an ex-vivo concept study.

BACKGROUND: The aim of this ex-vivo study was to evaluate the efficacy of Pycnogenol®-Centellicum® oral supplementation on vein segments, retrieved from graft harvesting or from vein surgery. The parameters assessed were elasticity and recovery after dynamic tests: 1) an enlargement stress; 2) an elongation stress; and 3) elasticity after torsion. The tests were made in standardized conditions, less than 3 hours after explant, at 22 °C by the same operator with surgical and microsurgical experience. METHODS: Veins of 59 subjects were included in the study: 17 subjects with normal veins with a planned bypass graft and 42 subjects with varicose veins. Of the subjects with normal veins, 8 subjects followed standard management (group 1) and 9 took Pycnogenol®-Centellicum® for 4 weeks before surgery (group 2). In the group with varicose veins, 22 subjects served as controls (group 3) and 20 were supplemented with Pycnogenol®-Centellicum® for 4 weeks before surgery (group 4). No side effects or tolerability problems were observed in the supplementation period before surgery and veins harvesting. The full return to initial shape/sizes after dynamic stress was evaluated in 1 min after removing the stress. RESULTS: In group 1, 4 out of 8 vein segments recovered their size after forced enlargement vs. 7/9 in the Pycnogenol®-Centellicum® group 2 (P<0.05). In the elongation test, 3/8 normal control vein segments recovered their length (group 1) vs. 7/9 in the supplement group (group 2) (P<0.05). In the torsion test, 4/8 (group 1) veins recovered their shape after torsion vs. 9/9 veins in Pycnogenol®-Centellicum®-pretreated segments (group 2) (P<0.05). Only 45.8% of normal, control vein segments (group 1) recovered their shape/size in comparison with 85.2% of normal vein segments in the supplement group (group 2) (P<0.05). In group 3 and 4 (segments of varicose veins), the proportion of vein segments with enlargements, elongation and torsion were significantly lower at the end of the test (P<0.05) in the Pycnogenol®-Centellicum® group 4 with 51.7% of the vein segments recovering their shape in the Pycnogenol®-Centellicum® vs. 16.6% of the vein segments recovering their shape in control segments (P<0.05). Results show that Pycnogenol®-Centellicum® supplementation allows vein segments to better return to their original shape/size after a morphological alteration of shape (in different directions). This could be an expression of an improved wall tone and elasticity of the veins. No vein was teared or damaged during the 59 tests indicating that all stresses were well within the normal wall tensile characteristics of the veins. CONCLUSIONS: In this study, Pycnogenol®-Centellicum® improved vein elasticity in subjects with normal and varicose veins as vein segments were more elastic (able to recover length and shape) and less passively dilated by high pressure or dynamic stresses. This study indicates that the protective effects of Pycnogenol®-Centellicum® may partially stop passive dilatation of veins to varicose veins over time by improving vein elasticity. Pycnogenol®-Centellicum® managed vein segments return more rapidly back to the initial dimensions, shapes and diameters after a dynamic stress.

Pycnogenol® supplementation prevents inflammation and symptoms in recurrent, non-severe urinary infections.

BACKGROUND: The aim of this pilot, registry study was to evaluate the prophylactic effects of oral supplementation with Pycnogenol® (150 mg/day) in subjects with previous history of recurrent (urinary tract infections (UTI) in a 2-month open follow-up. METHODS: subjects with recurrent-UTIs, defined by: 1) at least three symptomatic UTIs over the past year; 2) two episodes of UTI's in the past six months; 3) symptoms of UTIs with urinalysis without bacterial presence, were included in the study. Pycnogenol® was supplemented at the dose of 150 mg/day for 2 months. RESULTS: The two groups of subjects (supplement and controls, each including 25 subjects) were demographically and clinically comparable at baseline. No side effects or tolerability problems were observed. The registry evaluated the number of recurrent UTIs in two months; there was a limited decrease in the rate of recurrent UTIs, in comparison with the period before inclusion of 9.93% in the standard management group in comparison with a more important decrease in the Pycnogenol® group (-50.1%; P<0.05). The number of episodes decreased from 3.22±0.4 to 2.9±0.3 in the control group in 2 months versus a decrease from 3.1±0.5 to 1.6±0.6 in the Pycnogenol® group. The number of infection-free subjects at the end of the two-month registry study was significantly higher with the supplement (P<0.05) than in controls. Oxidative stress measured as plasma free radicals at inclusion was 388±22 Carr units in the control group and resulted unchanged (not significant) at the end of the study (379±21 Carr units). In the supplement group, there was a significant decrease in oxidative stress from 389±24 to 227±14 Carr units at the end of the study (P<0.05). CONCLUSIONS: This pilot registry indicates that prophylaxis with Pycnogenol® decreases the occurrence of UTIs both in men and women without side effects and with a good tolerability. The effects of Pycnogenol® in these patients - including the control of oxidative stress - may be very important, particularly when a predominantly inflammatory component (UTI without infection or with a minimal bacterial component due to bacterial fragments) is present and maintains the inflammatory process.

Chronic venous insufficiency and venous microangiopathy: management with compression and Pycnogenol®.

BACKGROUND: The aim of this prospective supplement summer registry study was to evaluate the efficacy of Pycnogenol® in controlling symptoms of chronic venous insufficiency (CVI) and microcirculatory parameters: venous hypertension and microangiopathy. Pycnogenol® (Horphag Research) is the standardized extract of the bark of Pinus Pinaster. METHODS: During the summer period between June and August 142 patients were split into three groups: 1) Pycnogenol® 150 mg/day; 2) compression stockings; 3) and compression + Pycnogenol®. RESULTS: Venous pressure (ambulatory venous pressure, AVP) and refilling time (RT), microcirculatory and clinical measurements were comparable at inclusion. At 8 weeks variations in skin flux (RF), rate of ankle swelling (RAS), skin PO2-PCO2, Analogue Symptomatic Score (ASLS), Venous Disability and severity Scores and local oxidative stress (OS) indicated a statistically significant improvement by Pycnogenol® both as a single supplement and in association with compression in comparison with baseline. Pycnogenol® significantly improved the microcirculation in comparison with compression (P<0.05). The combined effects of Pycnogenol+compression produced the best results in most measurements. The summer study penalized compression - in a very hot summer - with many drops out. No side effects due to supplementation were observed; tolerability was optimal. The tolerability to stocking was less than optimal (70% of compression not correctly used). Pycnogenol® alone was more effective than compression alone. The increase (P<0.05) in skin O2 and the decrease in PCO2 were associated with the decrease in skin flux. The variations in capillary filtration (RAS) were the most important microcirculation changes. RAS is directly associated with swelling, the hallmark of CVI. Pycnogenol® in both Pycnogenol groups significantly improved RAS in comparison with compression only (P<0.05). The decrease in OS in both Pycnogenol® groups was significant in comparison with compression only (P<0.05). A lower OS is an important micro-metabolic indication of a better capillary bed with better nutritional, perfusional exchanges. The clinical measurements followed the patterns of the microcirculation with the supplement groups performing statistically better (P<0.002) than the compression-only. CONCLUSIONS: This "summer registry" study confirms the clinical and microcirculatory efficacy of Pycnogenol in CVI and venous microangiopathy. The study indicates the significant clinical role of Pycnogenol® (both as a single treatment and in association with compression) in the management, treatment and control of this common clinical problem.

Robuvit®: improvement of fatigue in medical convalescence.

BACKGROUND: The aim of this registry study was the evaluation of symptoms of fatigue following supplementation with an oak wood extract (Robuvit®) after disappearance of acute symptoms. Robuvit®, with established antioxidant-antifatigue activity, has been successfully used in hepatic failure and in chronic fatigue syndrome: these conditions are characterized by weakness and fatigue and are broadly comparable to convalescence that is associated to increased oxidative stress. METHODS: The registry study lasted 3 weeks. After a period (7-10 days) of flu, during the post-disease period (3 days without disease) subjects were included into the study. One group of subjects was supplemented with Robuvit® (300 mg/day) in addition to a standard management (SM) plan, another group of patients was treated with the standard management only. RESULTS: The SM and the supplement group were comparable in all convalescence parameters at inclusion. Weakness and heart rate were significantly reduced with Robuvit® in comparison with the controls (P<0.05) at 10 days and at 3 weeks; Attention and sleep patterns improved significantly at 3 weeks with Robuvit® (P<0.05) in comparison to controls. Recovery after efforts was normalized at 10 days in the supplement group, significantly better versus controls (P<0.05). O2 saturation increased significantly with Robuvit® at 10 days in comparison to controls (P<0.05). The alterations in working/concentration capacity were better improved with the supplement (P<0.05). Oxidative stress was significantly decreased (P<0.05) in comparison to controls. The improvement of health according to the Karrnofsky Scale was significantly more pronounced in the Robuvit® group (P<0.05). The supplement was well tolerated. CONCLUSIONS: The causative relations between Robuvit® supplementation, oxidative stress, vigor and fatigue in convalescence need more specific evaluations in a larger number of subjects. This preliminary study may indicate a possible supplementation in convalescence.

Prevention of recurrent venous thrombosis and post-thrombotic syndrome.

BACKGROUND: This retrospective registry study evaluated different managements on the development of post-thrombotic syndrome (PTS) and recurrent deep venous thrombosis (R-DVT). The effects of aspirin (100 mg/day), added to the "standard management" (SM) (IUA consensus), were observed in patients after a proximal DVT. METHODS: The study started after the anticoagulant period. Comparable groups used the mild-antithrombotic agent Pycnogenol® (200 mg/day), ticlopidine (250 mg/day) or sulodexide (500 ULS/day). RESULTS: The groups were comparable for sex and age distribution and clinical pictures. In the SM group, 222 patients completed the follow-up (72 months). With SM, the percentage of patients with R-DVT (requiring anticoagulants) was 17.2%; 19.8% of SM patients had a PTS. In the aspirin group (202 subjects), R-DVT was observed in 14.8% of patients; 17.32% had a PTS. The reduction in R-DVT and PTS with aspirin was significant (P<0.05) vs. the SM. There was no tolerability problem in subjects using Pycnogenol® (137 patients); they had a much lower incidence of R-DVT (5.8%) and PTS (6.5%) vs. SM and aspirin (P<0.05). Ticlopidine (121 patients) reduced the incidence of R-DVT (12.4%) and PTS (19.8% of patients) (P<0.05 vs. SM). With sulodexide the incidence of R-DVT was 6.7% (P<0.05 vs. SM); the incidence of PTS was 16.6% (P<0.05 vs. SM). The combined R-DVT+PT syndrome was observed in 14.9% of subjects using SM and in 12.9% of subjects using aspirin (P<0.05 vs. SM), in 3.6% of subjects managed with Pycnogenol® (<0.05% vs. aspirin and all other managements). The incidence was 10.74% with ticlopidine and 6.7% with sulodexide (both significantly lower than SM). CONCLUSIONS: Interaction between PTS and R-DVT are complex; recurrences cause more PTSs, and a post-thrombotic limb is prone to R-DVT. Aspirin, for patients that can tolerate it, reduces the occurrence of PTS and R-DVT. In addition, ticlopidine and sulodexide are effective. Pycnogenol® is the most effective and safe for R-DVT and particularly PTS. Its full range of anti-thrombotic activity is now under evaluation.

Centella asiatica (Centellicum®) facilitates the regular healing of surgical scars in subjects at high risk of keloids.

BACKGROUND: Formation of scars after surgical incisions requires the proper appositions of elements contributing to the scarring process. The structural rebuilding of damaged tissues is essential in producing a linear scar. The excess of blood, foreign particles, exuberant sutures, necrotic tissue, possible infective agents, as well as the ongoing inflammatory process may produce a non-linear, sometimes painful keloidal scar. Centella asiatica (CA) extracts have been used topically since ancient times for preventing keloids (i.e. after extensive burns) and for other applications including ulcer healing. The aim of this registry study was to evaluate the effect of supplementation with Centellicum® (Horphag Research Ltd.) on the healing of surgical wounds in subjects with previous hypertrophic or keloid scars, and to identify with ultrasound the collagen components of the scar in order to assess the quality (or linearity) of surgical wounds. METHODS: Subjects with history of hypertrophic scars or keloid following previous surgery were included in this registry. Short term antibiotic prophylaxis was used as per surgical standards with cephalosporins for three days maximum after surgery. Only patients receiving abdominal or knee surgery were included. A total of 129 patients were included: 64 in the control group treated only with standard management, and 65 in the active treatment group where CA supplementation with Centellicum® was used at the dose of two 225 mg capsules/day from the 2nd to 6th week after surgery. RESULTS: A total of 64 scars were analyzed within the control group and 65 in the supplement group. The tolerability to Centellicum® was overall good, and no side effects were reported. Compliance to treatment was optimal, with >98% of the CA capsules correctly used. The ultrasound-assessed scar tissue regularity was on average lower in controls than in supplemented subjects (P<0.05). Scars also appeared to be significantly more homogeneous in CA patients than in controls. CONCLUSIONS: Supplementation with Centellicum® is safe and does not interfere with other concomitant treatments. It is well tolerated and compliance to treatment is optimal.

Pycnogenol® and Centella asiatica to prevent asymptomatic atherosclerosis progression in clinical events.

BACKGROUND: The aim of this study was to evaluate the effect of the nutritional supplements Pycnogenol® and Centella asiatica (CA) on atherosclerosis progression in low-risk, asymptomatic subjects with carotid or femoral stenosing plaques. METHODS: The study included subjects aged 45-60 with stenosing atherosclerotic plaques (50-60%) in at least one carotid or common femoral bifurcation. Subjects were allocated into 3 groups. In Group 1 (controls), management was based on education, exercise, diet and lifestyle changes. This same management plan was used in the other two groups: Group 2 used Pycnogenol® (100 mg/day), while Group 3 used Pycnogenol® 100 mg/day plus CA (100 mg/day). The follow-up lasted 4 years. Plaque progression was assessed using the ultrasonic arterial score based on arterial wall morphology, considering plaque characteristics and the number of subjects that had cardiovascular events. Oxidative stress was also measured. RESULTS: Of the 413 individuals that were admitted, 391 individuals completed 4 years. Group distribution was comparable. The rate of progression of ultrasound arterial score was significantly lower in the two supplement groups (P<0.05) in comparison with controls suggesting a beneficial effect of Pycnogenol® with a significant difference in favor of the combination (P<0.05). There was a reduction in plaques progression in the supplement groups with the best effects obtained by the combination, considering maximum plaque thickness and length and echogenicity (grey scale median) (P<0.05). Plaques became generally dense (more echogenic) achieving a mixed echogenicity. The occurrence of anginal events was less than 3% in the two supplement groups (in comparison with 6.25% in controls) (P<0.05) with the best results obtained by the combination (P<0.05). The occurrence in myocardial infarctions was significantly lower for the combination (P<0.05). Minor transient ischemic attacks were also less frequent with the supplements with the best results observed with the combination (P<0.05). Events in controls - requiring hospital admission - were globally seen in 16.4% of subjects (minor events) in comparison with 8.9% of subjects using Pycnogenol® and only 3.3% of patients using the combination. At 4 years, oxidative stress in the supplement groups was lower than in controls (P<0.05, with no significant difference between groups 2 and 3). CONCLUSIONS: Pycnogenol® and the combination of Pycnogenol® plus CA reduce the progression of arterial plaques and the progression to clinical stages. The reduction in plaques and clinical progression was associated with a reduction in oxidative stress. The results justify a larger study to define the efficacy of the combination of Pycnogenol® plus CA as a prophylaxis in preclinical atherosclerosis.

Carotid plaque stabilization induced by the supplement association Pycnogenol® and centella asiatica (Centellicum®).

BACKGROUND: Aim of this registry study was the evaluation of the stability of carotid plaques by ultrasound in asymptomatic subjects with high oxidative stress following supplementation with a combination of the extract from bark of Pinus pinaster, Pycnogenol®, with an extract from Centella asiatica leaves, Centellicum®. METHODS: 50 patients, mean age 61.5 years, with carotid plaques (<50% stenosis) and high oxidative stress were included in this 3 months registry study. 26 patients received the combination of Pycnogenol® and Centellicum® and standard management, a control group received standard management only. The 2 groups were comparable. RESULTS: The combination of Pycnogenol® and Centellicum® reduced significantly (p<0.05) plaque height and length as well as the number of plaques relative to controls. The plaque stability index, based on the echogenicity in the ultrasound picture of the "white" components of the plaque, increased significantly (p<0.01) in the verum group, no changes were observed in the controls. Plasma free radicals were significantly (p<0.05) decreased by the combination product, whereas the levels of plasma free radicals remained unchanged in the control group. No unwanted effects or abnormal laboratory tests were recorded. CONCLUSIONS: This registry study revealed a significant increase in stability of plaques, indicated by an enhanced density of the plaques, following supplementation with the combination of Pycnogenol® and Centellicum®. As size and number of plaques was simultaneously reduced, the combination of the two plant extracts could be a safe option for prevention of cardiovascular events for patients with carotid plaques.

A controlled study of a lecithinized delivery system of curcumin (Meriva®) to alleviate the adverse effects of cancer treatment.

A proprietary lecithin delivery system of curcumin (Meriva) was evaluated in a controlled study to assess its efficacy in alleviating the side effects of cancer chemo- and radiotherapy in 160 patients undergoing these treatments. In both cases, a semi-quantitative evaluation of the side effects was carried out using a visual analogue scale, assessing also the plasma free radical status in all patients. Results showed that lecithinized curcumin might alleviate the burden of side effects associated to chemo- and radiotherapy, suggesting that the anecdotal use of various preparations of curcumin as a supportive agent for cancer treatment is well worth a systematic investigation in larger scale clinical trials. The capacity of curcumin to upregulate anti-oxidative responses and downregulate inflammatory pathways could explain its beneficial effect in tempering the prolonged and systemic oxidative and inflammatory effects of cancer treatment, and the beneficial effects observed in the plasma oxidative status in all patients of the treatment group support this view.

The LONFLIT4-VENORUTON study: a randomized trial prophylaxis of flight-edema in normal subjects.

This study evaluated the protective effects of Venoruton on the development of flight edema in normal subjects travelling in economy in long-haul flights (8-9 hours). Edema is a relevant aspect of long-haul flights affecting both venous patients and normal subjects. Edema and flight microangiopathy were studied in a group of 164 subjects randomized (after informed consent) into two groups to evaluate prophylaxis in 8- to 9-hour flights. The treatment group received Venoruton (hydroxyethyl rutosides) 1 g twice daily for 3 days (2 days before the flight and the day of the flight). The control group received comparable placebo. Edema was evaluated with a composite edema score based on the edema tester, on the measurements of ankle circumference, volume measurements, subjective swelling, and on a discomfort score. Items 1, 4, and 5 are based on an analogue scale line (1 to 10) directly defined by the subjects before and after the flights. Of the included subjects, 151 completed the study. Dropouts were due to poor compliance, travelling, or connection problems. Age and gender distribution were comparable in the two groups as were risk factor distributions. The level of edema at inclusion was comparable in the two groups of subjects. After the flight there was an average score of 6.7 (SD 1.7) in the control group, while in the Venoruton group the score was on average 3 (SD 1.1) (p < 0.05). In the control group 77% of the subjects had an evident increase in ankle circumference and volume, which was clearly visible at inspection and associated with discomfort. In the Venoruton group, edema was clearly present only in 8% of subjects (associated with discomfort rated between 3 and 6 on the analogue scale line) and it was mild, not associated with symptoms. Therefore the control of flight edema with Venoruton was clear both considering parametric data (circumference and volume) and non-parametric (analogue scale lines) measurements. The combined evaluation of the edema score is significantly favorable for subjects under prophylaxis with Venoruton.