Restless legs syndrome: prevention with Pycnogenol® and improvement of the venoarteriolar response.

BACKGROUND: The aim of this registry study was to evaluate the preventive efficacy of Pycnogenol® (French maritime pine bark, standardized extract), an anti-inflammatory and antioxidant supplement, previously used for muscular pain and cramps, in otherwise healthy subjects with restless legs syndrome (RLS). METHODS: Two management groups were formed: one using the standard management (SM) and one using SM and Pycnogenol® 150 mg/day for 4 weeks. RESULTS: Forty-five subjects were included in the study, 21 took Pycnogenol® and 24 were in the SM group. After 4 weeks no side effects or tolerability problems were observed. Compliance was optimal. The two groups were comparable at baseline. Limb sensations were assessed with a Visual Analogue Scale Line (0 to 4). There was a statistically non-significant improvement with SM in all subjects. Improvement with Pycnogenol® supplementation was significant (P<0.05) for all assessed parameters with important clinical meanings as 19 out of 21 supplemented subjects reported a clear benefit from supplementation. Resting flux - slightly elevated at inclusion - was normalized in the supplemented group (P<0.05) as seen by a decrease in flux. The venoarteriolar response - affected at inclusion in all subjects with RLS - was improved with the supplement, indicating a better axon-axon reflex response and a lower level of subclinical neural alteration. The need for pain managements was significantly reduced (P<0.05) with supplementation after 4 weeks, as only 4/21 supplemented subjects vs. 16/24 in the SM-only group had to use analgesics. Thermography of the leg did not reveal any significant asymmetry of perfusion. Oxidative stress as plasma free radicals (PFR) was significantly improved (reduced) (P<0.05) in subjects using Pycnogenol®. Likewise, minimal edema, measured with the edema tester, was significantly decreased with Pycnogenol®. CONCLUSIONS: Pycnogenol® prevents or relieves symptoms associated with restless leg syndrome and positively affects the venoarteriolar response. Future studies in this condition, including more complex subjects may indicate the role of Pycnogenol® in this common and still obscure syndrome and in subclinical muscular and neurological alterations.

Primary benign back pain: supplementation with Pycnogenol®.

BACKGROUND: Back pain (BP) is one of the most common problems seen by general practitioners. The aim of this pilot registry study was to evaluate the effects of Pycnogenol® (French Maritime Pine Bark extract) on pain, mobility and muscle spasm in patients with recurring episodes of back pain without any other clinical condition. METHODS: The registry follow-up lasted 3 weeks. Subjects used either SM (standard management), including mild exercise and 3 days of resting or immobilization - or SM+Pycnogenol® 200 mg/day (4 cps/day). RESULTS: Eighty-two subjects were included in the study, 23 took Pycnogenol® and 59 were in the SM group. No safety problems or tolerability problems were observed with Pycnogenol® or with the SM. The two groups, SM and SM+Pycnogenol®, were comparable at inclusion. A prevalent localization to the lower part of the back/spine was observed in all patients of both groups. The improvement in Karnofsky performance status Scale - expressing the global physical capacity of the individuals - during the 3 weeks of follow-up was significantly higher and faster in the Pycnogenol® group (P<0.05) compared to SM. Patients were able to restart physical training in 3 weeks with Pycnogenol® (in comparison with 4.5 weeks with SM only). The decrease in back pain score (VASL score) was faster and more pronounced with Pycnogenol® (P<0.05) compared to SM. Oxidative stress was significantly reduced in subjects using Pycnogenol® (P<0.05) while it remained elevated in the control group. The use of the rescue medication doses (ibuprofen) was significantly higher in the SM only (P<0.05) in comparison with SM+Pycnogenol®. CONCLUSIONS: Pycnogenol® appears to be an effective and safe supplementary management in healthy subjects with idiopathic BP. Mobility, pain, general physical capacity and oxidative stress improved in only a week with further improvements up to 4 weeks in most patients; results appear to be better and faster with Pycnogenol® supplementation than with SM alone.

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.

Delayed progression of atherosclerosis and cardiovascular events in asymptomatic patients with atherosclerotic plaques: 3-year prevention with the supplementation with Pycnogenol®+Centellicum®.

BACKGROUND: The aim of this study was the evaluation of the progression of atherosclerosis and the occurrence of cardiovascular events in asymptomatic patients with atherosclerotic plaques (Class IV and V) and arterial wall atherosclerotic lesions and intima-media thickening (IMT). METHODS: Progression of atherosclerotic lesions, oxidative stress and IMT were measured in a 3-year concept, pilot registry study. All subjects were followed with standard management (SM) - including diet and exercise - to control cardiovascular risk factors.The target measurements were: the rate of progression of the atherosclerotic lesions (the passage of subjects from one atherosclerotic class to the next class); the occurrence of "hard" cardiovascular events (i.e. myocardial infarction or strokes; angina was not considered a "hard" event). The study included 3 groups: 1) SM): 2) subjects using cardioaspirin (100 mg/day) and SM; 3) subjects following SM, taking cardioaspirin and supplemented with Pycnogenol® (150 mg/day)+Centellicum® (450 mg/day). RESULTS: The groups were comparable for age and baseline evaluations. 54 subjects completed the 3 year study with standard management only, 74 with aspirin and 56 with aspirin and Pycnogenol®+Centellicum®. The BMI of all subjects was <26. No side effects and no tolerability problems were observed with the supplements. Progression was defined by the passage of the atherosclerotic lesions from one class to the next more advanced class. Progression in the supplement group was observed in 5.3% of the subjects in comparison with a progression >20% in the other groups (P<0.05). In comparison with the SM group and the cardioaspirin group the rate of 'hard' cardiovascular events, requiring hospital admissions were <4% with the combined supplement in comparison with a value >12% in the other two groups (22.22% event rate in the SM group). The reduction produced by the aspirin only was significantly lower (P<0.05) in comparison with supplemented patients. Antiplatelet management appears to reduce a significant number of events (P<0.05) without a real effect on progression of atherosclerotic lesions. The additional parameters of carotid IMT and oxidative stress were also lower (P<0.05) with the supplements. CONCLUSIONS: In conclusion, this study indicates that the combined supplementation with Pycnogenol®+Centelicum® appears to control both the progression of atherosclerosis and the occurrence of cardiovascular events in this 3 year study. Larger studies, in a wider population with more complex and less standardized conditions may be needed.

Pycnogenol®+Centellicum®, post-stent evaluation: prevention of neointima and plaque re-growth.

BACKGROUND: The aim of this study was to evaluate the regrowth and progression of within-stent neointima after stenting as a model of accelerated atherosclerosis and the potential effects of the combination Pycnogenol® and Centellicum® in 12 months' follow-up. METHODS: Progression was defined as the passage from one arterial risk class to next, more advanced risk class in 12 months of follow-up. Each class corresponds to a different risk of cardiovascular events and progression. Three management groups were formed, treated with either standard management (SM), Pycnogenol® 150 mg/day, or a combination of Pycnogenol® 150 mg/day and Centellicum® 450 mg/day. RESULTS: No side effects or tolerability problems were observed. 82 subjects with stented arteries in class 2 were evaluated for the passage into class 3 over 12 months. This group included 82 subjects; there were no dropouts. The management subgroups were comparable at baseline. At 12 months 66.7% of subjects in the SM subgroup progressed to class 3, versus 10.7% in the Pycnogenol® group; progression was seen in 6.7% (P<0.05) of subjects supplemented with the combination. In the second section of the registry study (78 subjects with stented arteries in class 3) we evaluated the percentage of patients passing into class 4. At 12 months 53.6% of subjects using the SM progressed versus 26.9% in the subgroup using Pycnogenol® (P<0.05) and 11.5% in the Pycnogenol®+Centellicum® group (P<0.05). Across all 160 subjects in the three management groups, progression of the stented artery at 12 months was seen in 59.6% of subjects in the SM group versus 18.5% (P<0.05) in the group managed with Pycnogenol® only. The Pycnogenol®+Centellicum® combination further decreased progression down to 8.9% (P<0.05). Oxidative stress was significantly reduced (P<0.05) in the two supplement groups. CONCLUSIONS: In conclusion, the combination Pycnogenol®+Centellicum® appears to reduce the rate of progression of the neointima after stenting.

Management of mild, primary Raynaud Syndrome: supplementation with Pycnogenol®.

BACKGROUND: Raynaud syndrome (RS) is associated with vasospasm of the hand and fingers as a response to cold or stress. RS may cause discomfort and color changes (pallor, cyanosis, erythema, as single symptoms, but usually in combination, localized to one or more fingers). The aim of this 4-week registry study was the evaluation of subjects with mild, primary RS and their treatment with a standard management (SM) plan in comparison with SM associated with supplementation with Pycnogenol®. METHODS: A group of 67 females with mild, primary RS was included. All subjects were working in shops with refrigerators. No skin lesions were present. The age range was between 30 and 40; the vasospastic changes were symmetrical; no other physical findings were present. RESULTS: The two groups, receiving standard management (N.=33) or SM+Pycnogenol®, 100 mg/day, (N.=34) were comparable at inclusion. Considering the main symptoms, the decrease in coldness, burning pain, paresthesias and irregular color changes was more significant with Pycnogenol® (P<0.05) at 4 weeks. At thermography, low temperature areas and discrepancies in temperature and color were decreased with Pycnogenol® more than in controls (P<0.05). In the Pycnogenol® group, one subject (2.94%) decided to use drug treatment (PGE1) in 4 weeks in comparison with 5 controls (15.15%). The lowest finger temperature improved from 20.3° C at inclusion to 26.4° C at 4 weeks (+30.04%) with Pycnogenol® in comparison with lower values (from 20.5 to 23.1 [+12.7%] in controls [P<0.05]). The fingertip skin flux increased significantly (+ 1.55 flux units) with Pycnogenol® (P<0.05), in controls just by +0.14 (ns). Supplementation with Pycnogenol® decreased oxidative stress and increased transcutaneous oxygen pressure (TcPO2) more than in controls. Compliance and tolerability were optimal. CONCLUSIONS: This pilot registry study suggests that Pycnogenol® may be used with significant advantages in primary, mild RS. Subjects using Pycnogenol® may control their symptoms and may avoid the need for more complex and, potentially dangerous or expensive treatments.

Temporary kidney dysfunction: supplementation with Meriva® in initial, transient kidney micro-macro albuminuria.

BACKGROUND: The aim of this registry was to evaluate the efficacy of Meriva® in subjects with temporary kidney dysfunction (TKD) and increased oxidative stress levels. TKD was a casual finding on urinary tests after reported side effects following drug consumption, a clinical event or dehydration. METHODS: Patients followed either standard management (SM) or SM plus Meriva® (Curcumin Phytosome®) supplementation (3 capsules/day, corresponding to 1.5 g of Meriva® containing 300 mg of curcumin in a bioavailable delivery form). The follow-up period lasted 4 weeks. Subjects were divided according to macroalbuminuria (>300 mg albumin on 24 hours) or microalbuminuria (<300 mg/day albuminuria). RESULTS: Albuminuria decreased in all subjects, with a statistically significant improvement in the supplement group compared with controls (P<0.05). Oxidative stress level was high in all microalbuminuria subjects at inclusion; it was significantly more reduced in the supplement group (P<0.05) after 4 weeks. During follow-up blood pressure values were controlled; all subjects were under one single antihypertensive. Blood and urinary tests at 4 weeks were normalized in all subjects. Fatigue was significantly decreased or disappeared in most supplemented subjects at 4 weeks, with better results than in controls. Compliance and tolerability to Meriva® were good. CONCLUSIONS: This registry study indicates that albuminuria - marker of TKD - is safely ameliorated with the standardized supplement Meriva®. Studies are needed to evaluate the effect of Meriva® in subjects with more significant clinical conditions (i.e. diabetics) or risk factors.

Pycnogenol®: supplementary management of symptomatic osteoarthritis with a patch. An observational registry study.

BACKGROUND: The aim of the present observational registry study was to evaluate the efficacy of a thin polycarbonate patch of Pycnogenol® in alleviating symptoms of knee arthrosis, in comparison to the standard management usually applied to treat osteoarthritis (OA). METHODS: A total of 67 subjects were included in the registry: 34 formed the control group, and 33 entered the active management group in which the Pycnogenol® patch was used. Two Pycnogenol® patches were used every day for three weeks. Each patch contains 110 mg Pycnogenol®. All patients included in this registry suffered from osteoarthritis of the knee. RESULTS: Results from this study show that Pycnogenol® patch allows faster improvement in OA symptoms, with a decrease in the use of non-steroidal anti-inflammatory drugs and other painkillers. Pycnogenol® patch significally reduced C reactive protein and ESR. CONCLUSIONS: Pycnogenol® patch was effective in controlling mild to moderate pain and inflammations and its related symptoms in subjects with knee OA over a period of three weeks.

Postpartum stretchmarks: repairing activity of an oral Centella asiatica supplementation (Centellicum®).

BACKGROUND: This registry study evaluates the effects of oral Centellicum®, a new preparation of Centella asiatica (CA) on cutaneous stretchmarks (SMs) on the lower abdominal wall in comparison with the topical treatment with a specific antistretch cream. This cream is used for pregnancy SMs. The aim of the management was to give back to the structurally damaged skin areas (apparent as SMs) a normal elasticity and resistance and improving the local microcirculation. METHODS: We selected 78 healthy women with SMs at least 6 months postpartum available to follow the registry plan. The subjects were evaluated in three treatment groups: Clarins, stretch mark minimizer, the hydrating control cream and Centellicum® 3X225 mg/day for 6 weeks. RESULTS: The three registry groups of otherwise healthy subjects were comparable at inclusion and 6 weeks: 25 women used the SMs cream 1 (mean age 34.4;3.2); 28 control women (age 35.2;2) used the hydrating control cream. The third group (25 women; mean age 35.3;1.5) used the hydrating control cream and oral Centellicum® as a supplementary management. Standard management was used in all groups. As for the safety issue, no allergy, no side effects and no tolerability problems were observed. The compliance was very good and there were no drop outs. No other drug or treatment was used during the registry period. Skin thickness (ultrasound, measuring at the edge of at the largest visible stretchmark) increased significantly more at 6 weeks with Centellicum® in comparison with both controls (P<0.05). Skin thickness at the center of the SM (skin was less dense at this level) was also increased more with the supplement in comparison with the other managements (P<0.05). The grey scale median improved more (increased) with Centellicum at 6 weeks (P<0.05). The skin included more collagen components and become whiter or denser at ultrasound. Skin perfusion measured by laser Doppler showed a higher improvement with Centellicum® (P<0.05). Skin temperature, considered a function of nutritional and thermoregulatory dermal perfusion, improved more with the supplement (P<0.05). Elasticity (measured by elastosonography) was improved more with the supplement (P<0.05). The subjective evaluation with an analogue score resulted better (the SMs were less visible and the score decreased) with Centellicum® (P<0.05). The number of visible SMs was decreased more with Centellicum® (P<0.05). CONCLUSIONS: Oral supplementation with Centellicum® appears to improve SMs in a relatively short period of time. Larger studies are needed to evaluate the protective and repairing potentials of CA.

Efficacy of Pycnogenol® supplementation in remission phases of Sjögren syndrome.

BACKGROUND: The aim of this study was to evaluate the effects of Pycnogenol® supplementation in otherwise healthy subjects with Sjögren syndrome (SS) in a remission phase, who experienced persisting symptoms impairing their quality of life. METHODS: The control group receiving only standard treatment was composed of 14 subjects, the supplement group included 16 subjects who used Pycnogenol® supplementation. RESULTS: ESR and oxidative stress levels were high in all subjects at inclusion; both decreased significantly with supplementation (P<0.05). Pycnogenol® significantly improved the majority of symptoms (dry eyes and mouth dryness), diminishing the need for corticosteroids and other treatments. CONCLUSIONS: Pycnogenol® supplementation in patients with SS in a remission phase may be effective to control inflammation and reduce symptoms.

Supplementation with Robuvit® in post-traumatic stress disorders associated to high oxidative stress.

BACKGROUND: Post-traumatic stress disorder (PTSD) is associated to recurrent, obsessive recollection of severe traumatic events. This condition is still not completely understood. Elective treatment of PTSD is psychotherapy. Standardized supplements, used for improving chronic fatigue syndrome (i.e. Robuvit®, Horphag Research Ltd) can also be used to control some of the symptoms associated to PTSD, as well as to control the associated increased oxidative stress, present in many of these patients. The aim of this open registry was to evaluate the effects of supplementary Robuvit® 300 mg/day, added to standard management (SM), in subjects with PTSD over a period of 4 weeks, both on the psychological and the inflammatory level. METHODS: Otherwise healthy individuals with a diagnosis of PTSD were included in this registry. A clear main traumatic event occurred with different modalities in all subjects during or just after major earthquakes in Central Italy. SM included exposure therapy and psychotherapy. Supportive psychotherapy was used in all affected subjects. Subjects autonomously decided which group to enter (either SM or SM + Robuvit®), without any pre-defined group allocation or randomization. No placebo was used. RESULTS: The two groups were comparable: 18 subjects (11 females; age range 25-49) were included in the SM group, and 16 subjects (8 females; age range 26-52) using SM in combination with Robuvit® supplementation. BMI of all subjects was below 25 kg/m2. After 4 weeks, the percentages of subjects with recurrent memories and dreams, transient walking-dissociative states and reactive flashbacks/hallucinations, alarm reactions and intense emotional distress, emotional numbness, social disinterest and detachment were significantly lower in the subjects treated with Robuvit® (P<0.05%). Sleeping problems, irritability, and fatigue were also significantly reduced with supplementation. CONCLUSIONS: The results of our preliminary, pilot registry show that symptoms of PTSD as well as the high oxidative stress-related to the condition can be controlled and improved using Robuvit® as a supplementary management. The improvement with Robuvit® is faster and larger than that seen with standard management only. Supplementation is safe and well tolerated and may represent an important option in PTSD treatment.

Improvement in mood, oxidative stress, fatigue, and insomnia following supplementary management with Robuvit®.

BACKGROUND: Oxidative stress (OS) plays a substantial role in inflammatory and neurodegenerative diseases, causing cellular damage and mitochondrial dysfunction. OS also contributes to aging and severe neural disorders such as Alzheimer's and Parkinson's diseases. Previous registries have documented a reduction in OS levels with Robuvit® (Horphag Research, Ltd.), an extract from wood of the French oak (Quercus robur) that provides a decrease of OS as well as relief from chronic fatigue syndrome. The aim of the present registry was to investigate the influence of Robuvit® on a group of subjects presenting with mood disorders, oxidative stress, fatigue, and insomnia. METHODS: Forty patients were recruited from a selection of patients with high OS levels as assessed with the d-ROMs test. Twenty-two subjects formed the control group following the standard management plan. The remaining 18 subjects formed the Robuvit® supplementation group. They received three capsules of Robuvit® 100 mg per day, for 8 weeks. RESULTS: Tolerability to the supplementation with Robuvit® was overall good, and no safety concerns were raised. Mood tests showed a significant general improvement in 13 out of 16 items of the BMIS (P<0.05) in the active treatment group. Oxidative stress levels decreased significantly with Robuvit® supplementation after 4 and 8 weeks. Fatigue and insomnia score were also significantly better in supplemented subjects (P<0.05). No changes were observed in controls. CONCLUSIONS: The observed decrease in OS levels in our patients is probably the result of the antioxidative activity of Robuvit®, and, more precisely, of its active metabolites, the urolithins and ellagic acid.

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.

Temporary kidney dysfunction: Robuvit® supplementation in initial, transient kidney insufficiency and micro-macro albuminuria.

BACKGROUND: The aim of this study was to evaluate the efficacy of Robuvit® (French oak extract, Horphag Research) in improving kidney function in subjects with temporary kidney dysfunction (TKD) and increased oxidative stress levels. METHODS: Fifty-seven subjects with TKD were included in the registry. Subjects were divided into two goups according to albumin levels in the urine. Plasma free radicals were measured in order to evaluate a possible connection with alterations in kidney function. Robuvit® was used at the dose of three capsules/day (300 mg/day) for 4 weeks. RESULTS: Subjects with micro-albuminuria treated with Robuvit® improved significantly more than controls treated with standard management, achieving a full normalization of albumin levels in the urine (P<0.05). In subjects with macroalbuminuria, the decrease in albumin loss was also significant after four weeks, with better overall results in Robuvit® supplemented patients (P<0.05) than in controls. CONCLUSIONS: Albuminuria, as a significant marker of TKD, can be significantly and safely improved with Robuvit® supplementation.

Pycnogenol® supplementation in minimal cognitive dysfunction.

BACKGROUND: Impairments in cognitive function are difficult to evaluate and measure. In most cases, subjects do not perceive any alteration in their own status, particularly in case of mild cognitive impairment. In case of minimal alterations of cognitive function, no real treatment exists at the moment. Functional and/or temporary alterations in the cerebral microcirculation may be involved in cognitive impairment, and some aspects of MCI may be theoretically caused by perfusional problems. Metabolic problems and sleep disturbances can also be associated to cognitive impairment. Pycnogenol® (Horphag) is a natural compound extracted from the bark of French maritime pine, and it is a highly standardized supplement. The aim of this registry was to evaluate the effects of supplementation with Pycnogenol® over a two-month-period in otherwise healthy individuals with minimal cognitive impairment and initial cognitive dysfunction selected on the basis of their MMSE score. METHODS: Eighty-seven healthy subjects with a MMSE score ranging from 18 to 23 (mild impairment) were included. Their BMI was <26 kg/m2, and no metabolic disorders were present. Participants were divided into two groups: one group was treated with standard management (SM) only (N.=44), whereas the other group received Pycnogenol® supplementation (150 mg/day) in addition to SM (N.=43). RESULTS: In the Pycnogenol® group MMSE score at inclusion was on average 21.64±1.5; after 8 weeks of supplementation, the average MMSE score increased significantly to 25.64±1.4 (P<0.05). In controls, the initial MMSE score was 22.43±1.2, comparable to the supplement group; however, in these subjects it did not show significant improvement after 8 weeks (average after treatment: 23.00±1.3). The median increase was 18% with Pycnogenol® vs. 2.48% in the SM group (P<0.05). CONCLUSIONS: Pycnogenol® has shown a large number of positive effects in subjects with initial cognitive impairment, due to its effects on oxidative stress levels. The safety and tolerability of Pycnogenol® are good, and thus the supplementation regimen should be tested in larger studies with a longer follow-up.

Phytoproflex®: supplementary management of osteoarthrosis: a supplement registry.

BACKGROUND: Curcumin is a powerful anti-oxidant that can be used to treat inflammation and pain in chronic conditions such as osteoarthrosis (OA). Phytoproflex® is characterized by an innovative delivery system that improves bioavailability of curcuminoids and could be useful in the management of OA. METHODS: This 4-week registry included 56 patients with knee OA treated according to the best standard management for symptomatic OA. On top of that, 24 patients used Phytoproflex® supplement preparation (an extract containing boswellic acid 90%, curcumin 20% and valeric acid 0.8%). Patients' control of symptoms and functional capacity were evaluated through the Karnofsky Scale and standardized treadmill test, together with measurement of oxidative stress levels and use of rescue medication. RESULTS: No problems of tolerability or safety were reported among subjects using the supplement. After 4 weeks, patients treated with the supplement reported a significant decrease in pain (P<0.05), and a significant improvement in the fitness scale (P<0.05), indicating that subjects were able to perform normal daily tasks. Less subjects in the supplement group had to use rescue medication (P<0.05), while oxidative stress levels, which were high at inclusion, significantly decreased in both groups (P<0.05). Moreover, the variation in pain-free walking distance and the Karnofsky Scale were significantly more improved (P<0.05) in patients taking the supplement compared to controls. CONCLUSIONS: This preliminary registry study indicates that Phytoproflex® can be safely used as an effective, supplementary management in most OA patients.

Supplementation with Robuvit® in subjects with burnout associated to high oxidative stress.

BACKGROUND: This supplement registry study evaluated the effect of supplementation with Robuvit® on the burnout syndrome (BOS) of patients with significant fatigue and high oxidative stress. Robuvit® (French oak wood extract) is a standardized supplement, effective in treating chronic fatigue syndrome (CFS), post-traumatic stress disorder (PTSD) and convalescence. METHODS: A group of 108 subjects with BOS, consisting of a subgroup of 42 young surgeons in training and a subgroup of 66 managers, were studied. Subjects followed a standard management (SM); one half of the subjects received 300 mg/day of Robuvit® for 4 weeks in addition to SM. RESULTS: Robuvit® was (P<0.05) more effective compared to SM in improving parameters evaluated with the aid of Maslach Burnout Inventory: dealing with patients problems, improving the relationship with patients, decreasing emotional drainage and intolerance (P<0.05). The feeling of a positive influence improved. The decrease in strain from interactions at work, the decrease in the lack of care feeling, the improved levels in interest were all positively affected with Robuvit (P<0.05) in comparison with SM. The need for giving up decreased, the level of satisfaction improved and the regrets for being in the profession decreased. BOS symptoms were positively affected by the supplement (P<0.05). Oxidative stress (388;24 Carr Units decreased to 344;22 with Robuvit®; P<0.05), SM had no influence on oxidative stress. Robuvit® was also more effective in professionals with burnout syndrome than the SM only in in decreasing emotional drainage, fatigue and intolerance (P<0.05). Robuvit® significantly improved the feeling of having a positive influence (P<0.05). Also, Robuvit® significantly decreased the strain resulting from interactions at work and improved the care for colleagues/customers (P<0.05). Interest and enthusiasm were significantly increased in subjects taking Robuvit® in comparison with controls with standard management alone (P<0.05). The mean score of the desire to give up was decreased with Robuvit® in comparison with SM (P<0.05) and job satisfaction was significantly improved (P<0.05). The feeling of regrets of being in the profession was significantly reduced with the supplement in comparison to SM (P<0.05). Robuvit® reduced oxidative stress (P<0.05) from 397;33 to 323;29 Carr Units in comparison with a low decrease with SM (from 396;19 vs. 378;27) at 4 weeks. CONCLUSIONS: In conclusion, in this registry study on BOS, Robuvit® by controlling fatigue (the primary symptom) and oxidative stress, relieves the most important 'symptoms' associated with BOS. The effects are comparable in young surgeons not accustomed to stress, as well as in professionals in management positions who are used to control stress.

Normalization of cardiovascular risk factors in peri-menopausal women with Pycnogenol®.

BACKGROUND: The aim of the study was the evaluation of the efficacy of Pycnogenol® in peri-menopausal women in controlling homocysteine and C-reactive protein (CRP) levels, borderline cardiovascular risk factors, oxidative stress (OS) and symptoms associated to menopausal transition (MT). METHODS: Pycnogenol®, 100mg/day, was used as a supplement for 8 weeks by a group of 35 women. A comparable group of 35 women with identical cardiovascular risk factors was included as the control group. All women were instructed to participate in a best management plan of menopause. RESULTS: The two groups were comparable. All women completed the eight weeks study. Only minor deviations from the best management plan were observed. At inclusion, both groups were similar in respect to risk factors. Supplementation with Pycnogenol® decreased the slightly elevated cholesterol and triglycerides after 8 weeks (P<0.05). Also the fasting glucose levels were normalized (P<0.05). The borderline increased blood pressure was reduced to normal values at 8 weeks (P<0.05). Plasma free radicals dropped significantly by 22% (P<0.05). Homocysteine and CRP levels decreased sharply by 43% and 60%, respectively (P<0.05). No significant changes of these risk factors were noted in the control group. Almost all menopausal symptoms, scored by The Menopausal Symptoms Questionnaire 34, improved significantly following supplementation with Pycnogenol®. The supplementation was well tolerated. CONCLUSIONS: The supplementation with Pycnogenol® improved the quality of life of perimenopausal women and normalized a series of cardiovascular risk factors, especially factors connected to cardiovascular events, as homocysteine and CRP.

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.

Supplementary management of functional, temporary alcoholic hepatic damage with Robuvit® (French oak wood extract).

BACKGROUND: The aim of this registry study was to evaluate Robuvit® (French oak wood extract) supplementation in the evolution of moderate functional hepatic failure (MTHF) due to alcohol. Recent studies have indicated the protective effect of oak wood (QR) extracts on liver injury. This registry included patients with MTHF characterized by: decreased albumin levels; increased total bilirubin, altered hepatic functions enzymes, increased oxidative stress, negative viral hepatitis markers. METHODS: The two groups resulted divided into a best management (BM) group and a comparative group (BM + Robuvit®): 23 Robuvit® patients and 21 comparable controls completed the 12-week registry. At inclusion, blood parameters in the two groups were comparable. RESULTS: During the observation period, the increase in albumin levels was significantly (P<0.05 at 6 weeks) faster and higher in the Robuvit® group in comparison with controls. The decrease in ALT-SGPT and AST-ASAT were significantly more important in the supplement group (P<0.05 at 6 and 12 weeks). Alkaline phosphatase was significantly lower at 6 and 12 weeks in Robuvit® patients; (Robuvit® group's values were significantly better; P<0.05). Total bilirubin improved more in Robuvit® subjects at 6 weeks. Results were statistically significant in comparison with controls (P<0.05). Also, direct bilirubin values were higher in the Robuvit® group at 6 and 12 weeks (P<0.05). Gamma GT values were normalized at 6 and 12 weeks in the Robuvit® group. There was a less important decrease in controls (P<0.05) without normalization at 12 weeks. Plasma free radicals, high at inclusion, showed a more significant decrease in Robuvit® subjects (at 6 and 12 weeks), with normalization at 12 weeks. Persisting high values in controls were observed even at 12 weeks (P<0.05). Erythrocytes sedimentation rate (ESR) decreased in both groups with a more important decrease in the Robuvit® group (P<0.05). Hepatitis markers were negative when repeated at 6 and 12 weeks. CONCLUSIONS: In conclusion, observations from this pilot, supplement registry study indicate a significant protective activity of the supplementation with Robuvit®, associated with a very good safety profile, in patients with temporary alcoholic hepatic failure. The activity of Robuvit® seems to be mediated by its anti-inflammatory activity associated to its important action on oxidative stress.