Pycnogenol® supplementation improves health risk factors in subjects with metabolic syndrome.

This open, controlled study evaluated the effects of 6 month supplementation with Pycnogenol® maritime pine bark extract on health risk factors in subjects with metabolic syndrome. Pycnogenol® was used with the aim of improving risk factors associated with metabolic syndrome, central obesity, elevated triglycerides (TG), low HDL cholesterol, high blood pressure and fasting blood glucose. Sixty-four subjects (range 45-55 years) presenting with all five risk factors of metabolic syndrome were included, and Pycnogenol® was administered for 6 months. A group of 66 equivalent subjects were followed up as controls. In the 6-month study Pycnogenol® supplementation 150 mg/day decreased waist circumference, TG levels, blood pressure and increased the HDL cholesterol levels in subjects. Pycnogenol lowered fasting glucose from baseline 123 ± 8.6 mg/dl to 106.4 ± 5.3 after 3 months and to 105.3 ± 2.5 at the end of the study (p < 0.05 vs controls). Men's waist circumference decreased with Pycnogenol from 106.2 ± 2.2 cm to 98.8 ± 2.3 cm and to 98.3 ± 2.1 after 3 and 6 months. Women's waist decreased from 90.9 ± 1.6 cm to 84.6 ± 2.1 cm and to 83.6 ± 2.2 cm after 3 and 6 months. Both genders waist circumference reduction was significant as compared to controls at both time points. In addition, plasma free radicals decrease in the Pycnogenol group was more effective than in the control group (-34.6%; p < 0.05). In conclusion, this study indicates a role for Pycnogenol® for improving health risk factors in subjects with metabolic syndrome.

Lady Prelox® improves sexual function in generally healthy women of reproductive age.

AIM: This supplement study evaluates the Female Sexual Function Index (FSFI) of 100 healthy women (37 to 45 years) with moderate sexual dysfunction who underwent a management program of lifestyle, diet, exercise, and stress control. In association with the management program a group of these women also used the supplement Lady Prelox® in tablets (20 mg Pycnogenol® pine bark extract, 200 mg L-arginine, 200 mg L-citrulline and 50 mg Rosvita® rose hip extract) for eight weeks. METHODS: One group of women was supplemented with Lady Prelox® for 8 weeks. The nine-item FSFI questionnaire was used for evaluation of women's sexual function at inclusion (baseline), after four weeks, and after eight weeks of management and supplementation. Variation in oxidative stress was also evaluated by measuring plasma free radicals. RESULTS: Following supplementation with Lady Prelox® the mean total FSFI scores increased from 14.96±2.68 to 28.25±2.35 after four weeks and 33.91±2.7 after eight weeks. Treatment values were significantly higher than in controls (who used only the management plan) with baseline values of 17.92±2.32 and scores of 23.45±1.82 after four weeks and to 23.52±2.20 after eight weeks. Women in the Lady Prelox® group had an initial value of plasma free radicals (PFR) of 398±29 Carr units: this value decreased to 344:28 at 4 weeks (P<0.05) and 332:31 at 8 weeks (P<0.05). Lower changes were observed in controls with an initial value of 389±33, decreasing to 377±32 (P<0.05) at 4 weeks and to 365; 33 (P<0.05) at 8 weeks (value significantly higher in controls not using Lady Prelox®). The supplementation was well tolerated; no unwanted effects occurred and no women had to stop the supplementation. CONCLUSION: The study suggests that supplementation with Lady Prelox significantly improves sexual function across all domains evaluated by the FSFI in healthy women of late reproductive age. The improvement in FSFI is also associated with a significant decrease in oxidative stress.

[Severe intermittent claudication: PGE1 treatment. A 40-week registry, efficacy and costs]. / Claudicatio intermittens severa: trattamento con PGE1. Registry, follow up (40 settimane), efficacia e costi.

AIM: Intermittent claudication (IC) in peripheral vascular disease is characterized by lower limb pain appearing on effort. Treatment with PGE1 has been successfully used to manage IC patients. This registry has evaluated safety and costs of PGE1 in the management of IC. METHODS: In this study a long-term treatment protocol (LTP), a short-term protocol (STP) and an outpatient (OP), "on-demand" treatment have been compared. A treadmill effort test has been used to evaluate walking distance. The follow up for these three protocols was 40 weeks. PGE1 treatment was associated to a risk reduction plan and to an exercise program. RESULTS: The final analysis has included 252 LTP patients, 223 STP patients and 284 OP patients (total 659 valid cases). A group of 171 comparable patients not treated with PGE1 was used for a parallel comparison. Cardiovascular mortality and morbidity has been evaluated in 731 PGE1 patients completing 24 months of follow up. All protocols have been well tolerated. No side effects were observed. The lower cost has been observed for OP patients. In the long term, mortality and morbidity were lower in patients treated with PGE1 in comparison with patients not treated with PGE1. CONCLUSION: Considering costs and results (increase in walking distance) and improvement in Karnofsky scale the STP plan appears to be better than LTP for IC patients. The OP, "on-demand" treatment offers further improvements. This last treatment plan is simpler; the plan allows better timing for exercise. The treatment can be used even in non-specialized centers.

Pycnogenol® Supplementation Prevents Recurrent Urinary Tract Infections/Inflammation and Interstitial Cystitis.

This open pilot registry study aimed to evaluate and compare the prophylactic effects of Pycnogenol® or cranberry extract in subjects with previous, recurrent urinary tract infections (UTI) or interstitial cystitis (IC). Methods. Inclusion criteria were recurrent UTI or IC. One subject group was supplemented with 150 mg/day Pycnogenol®, another with 400 mg/day cranberry extract, and a group served as a control in a 2-month open follow-up. Results. 64 subjects with recurrent UTI/IC completed the study. The 3 groups of subjects were comparable at baseline. All subjects had significant symptoms (minor pain, stranguria, repeated need for urination, and lower, anterior abdominal pain) at inclusion. In the course of the study, the subjects reported no tolerability problems or side effects. The incidence of UTI symptoms, in comparison with the period before inclusion in the standard management (SM) group, decreased significantly; there was a more pronounced decrease in the rate of recurrent infections in the Pycnogenol® group (p < 0.05). The improvement in patients supplemented with Pycnogenol® was significantly superior to the effects of cranberry. At the end of the study, all subjects in the Pycnogenol® group were infection-free (p < 0.05vs. cranberry). Significantly, more subjects were completely symptom-free after 2 months of management with Pycnogenol® (20/22) than with SM (18/22) and cranberry (16/20). Conclusions. This pilot registry suggests that 60 days of Pycnogenol® supplementation possibly decrease the occurrence of UTIs and IC without side effects and with an efficacy superior to cranberry.

A natural pharma standard supplement formulation to control treatment-related toxicity and oxidative stress in genitourinary cancer: a preliminary study.

OBJECTIVE: Oncological treatments are associated with toxicities that may decrease compliance to treatment in most genitourinary cancer patients. Supplementation with pharmaceutical-standardized supplement may be a supplementary method to control the side effects after chemo- and radiotherapy and the increased oxidative stress associated to treatments. This registry study evaluated a natural combination of supplements containing curcumin, cordyceps, and astaxanthin (Oncotris™) used as supplementary management in genitourinary cancer patients who had undergone oncological therapy. PATIENTS AND METHODS: Patients with genitourinary cancers (prostate or bladder malignancies) who had undergone and completed cancer treatments (radiotherapy, chemotherapy or intravesical immunotherapy with increased oxidative stress and residual symptoms) were recruited in this registry, supplement study. Registry subjects (n = 61) freely decided to follow either a standard management (SM) (control group = 35) or SM plus oral daily supplementation (supplement group = 26). Evaluation of severity of treatment-related residual side effects, blood count test, prostate-specific antigen (PSA) test and plasma free radicals (oxidative stress) were performed at inclusion and at the end of the observational period (6 weeks). RESULTS: Two patients dropped out during the registry. Therefore, the analysis included 59 participants: 26 individuals in the supplementation group and 33 in the control group. In the supplement group, the intensity of signs and symptoms (treatment-related) and residual side effects significantly decreased at 6 weeks: minimal changes were observed in controls. Supplementation with Oncotris™ was associated with a significant improvement in blood cell count and with a decreased level of plasmatic PSA and oxidative stress. CONCLUSIONS: Naturally-derived supplements, specifically Oncotris™ (patent pending), could support the body to overcome the treatment-related toxicities - and the relative oxidative stress in cancer patients.

Management of Varicose Veins and Chronic Venous Insufficiency in a Comparative Registry with Nine Venoactive Products in Comparison with Stockings.

The aim of this registry study was to compare products used to control symptoms of CVI. Endpoints of the study were microcirculation, effects on volume changes, and symptoms (analogue scale). Pycnogenol, venoruton, troxerutin, the complex diosmin-hesperidin, Antistax, Mirtoselect (bilberry), escin, and the combination Venoruton-Pycnogenol (VE-PY) were compared with compressions. No safety or tolerability problems were observed. At inclusion, measurements in the groups were comparable: 1,051 patients completed the registry. Best performers : Venoruton, Pycnogenol, and the combination VE-PY produced the best effects on skin flux. These products and the combination VE-PY better improved PO 2 and PCO 2 . The edema score was decreased more effectively with the combination and with Pycnogenol. Venoruton; Antistax also had good results. Considering volumetry, the best performers were the combination PY-VE and the two single products Venoruton and Pycnogenol. Antistax results for edema were also good. The best improvement in symptoms score were obtained with Pycnogenol and compression. A larger decrease in oxidative stress was observed with Pycnogenol, Venoruton, and with the VE-PY combination. Good effects of Antistax were also observed. Parestesias were lower with Pycnogenol and with Antistax. Considering the need for interventions, the best performers were Pycnogenol, VE-PY, and compression. The efficacy of Pycnogenol and the combination are competitive with stockings that do not have the same tolerability in warmer climates. A larger and more prolonged evaluation is suggested to evaluate cost-efficacy (and non-interference with drugs) of these products in the management of CVI. The registry is in progress; other products are in evaluation.

Bilberry extracts are not created equal: the role of non anthocyanin fraction. Discovering the "dark side of the force" in a preliminary study.

OBJECTIVE: Several experimental studies and clinical trials support the potential of bilberry (Vaccinium myrtillus L) extracts in promoting eye health and circulation. Many active ingredients have been isolated from the berries and leaves of the bilberry plant. However, anthocyanins represent the most widely studied bioactive compounds in this plant. PATIENTS AND METHODS: The aim of this registry, supplement study was to evaluate the effects of Mirtoselect® (standardized in 36% anthocyanins and obtained by an industrial extraction process that preserves the full range of the non-anthocyanin components, mainly natural sugars and polyphenols) in different types of retinal vasculopathies. In total, 140 patients with different types of retinopathy spontaneously decided to join one of the following groups: standard management (SM) only (n=38); SM associated with Mirtoselect® supplementation (n=47); SM associated with a generic bilberry extract supplementation (n=55). Retinal circulatory parameters and flow measurements of the retinal vessels were evaluated at the inclusion and after 6-months supplementation. RESULTS: Overall, significant improvements in several retinal circulatory parameters such as retinal blood flow velocity, with respect to the values at inclusion, were observed in both supplementation groups, especially in Mirtoselect® supplementation group. However, at 6 months, inter-group comparison revealed a statistical advantage in all tested parameters for Mirtoselect® supplementation groups. No side effects or tolerability concerns were reported. CONCLUSIONS: Our registry study suggests that Mirtoselect® supplementation could represent an effective and safe integrated approach for the treatment of different retinopathies.

Managing ulcerative colitis in remission phase: usefulness of Casperome®, an innovative lecithin-based delivery system of Boswellia serrata extract.

OBJECTIVE: Boswellia serrata extracts (BSE) have been traditionally used for the treatment of several inflammatory diseases. The aim of this study was to evaluate the efficacy of a novel delivery form of BSE (Casperome®) in Ulcerative Colitis (UC) during minimally symptomatic remission phase. PATIENTS AND METHODS: In this open-label, observational, registry study, informed participants with UC in remission phase (n = 43) freely decided to receive the oral daily Casperome® supplementation (n = 22) or no supplementation (n = 21) for 4 weeks. Several parameters associated with minimally symptomatic UC in remission were evaluated at the inclusion and the end of the study. RESULTS: A significant beneficial effect of Casperome® was observed for all the parameters evaluated, namely: diffuse intestinal pain, evident and occult blood in stools, bowel movements and cramps, watery stools, malaise, anemia, rectal involvement, number of white blood cells as well as need for concomitant drugs and medical attention. Faecal concentration of calprotectin, a marker of bowel inflammation, resulted ameliorated in Casperome® supplemented patients. CONCLUSIONS: Our study showed that Casperome® supplementation attenuates symptoms associated with mild UC in remission, reducing the use of drugs and medical consultations. Therefore, our study suggests that Casperome® supplementation could represent a promising alternative approach to manage minimally symptomatic UC and maintain the remission phase.

A novel lecithin based delivery form of Boswellic acids (Casperome®) for the management of osteo-muscular pain: a registry study in young rugby players.

OBJECTIVE: Several experimental studies and clinical trials support the potential of Boswellia serrata extracts (BSE) for the treatment of various inflammatory diseases. The aim of this registry study was to assess the safety and the efficacy of a novel lecithin-based delivery form of Boswellia serrata extract (Casperome®) in the supportive management of osteo-muscular pain. PATIENTS AND METHODS: 52 healthy young rugby players with acute knee pain and inflammation were recruited. Informed participants freely decided to follow either a standard management (SM) to control joint pain (control group = 27) or SM associated with oral daily supplementation with Casperome® (supplement group =25). Parameters associated with osteo-muscular pain and inflammation, and measurements of joint health and functions were assessed at the inclusion and after a 4-week supplementation. RESULTS: A significant beneficial effect of Casperome® vs SM alone was observed for all the parameters evaluated, namely: local pain on effort; pain-free walking distance (treadmill test); minimal joint effusion; structural damage (joint, tendons, muscles) and intramuscular hematomas; thermal imaging of the anterior knee; Visual Analog Scale for Pain (VAS Pain); need for concomitant drugs and medical attention; measurement of inflammatory biomarkers. CONCLUSIONS: Our registry study suggests that Casperome® supplementation could represent an effective and safe, integrated approach for the treatment of osteo-muscular pain and inflammation.

Phyto-relief CC: prevention of cold episodes. Control of signs/symptoms and complications.

The aim of this supplement, registry study was to evaluate the effects of the use of standardized, oral supplement (Phyto-Relief CC, Alchem). Phyto-Relief CC includes anti-inflammatory, anti-oxidant and anti- edema natural compounds. Increased salivation produced by ginger is useful in the prevention of cold episodes and on signs and symptoms associated to the episodes by increasing saliva and its content (i.e. lysozyme). Main targets of the study were the evaluation of the occurrence of episodes and the reduction of signs/symptoms, the reduction of days of disease, the reduction in the use of other treatments and the control of cold-related complications. RESULTS: The two resulting registry groups were comparable. There were 5 full episodes (lasting at least 3 days) of cold in 61 registry subjects (8.1%) in comparison with 17 cases in 63 subjects (26.98%) in controls. Phyto-Relief CC subjects - even in this time-limited and small study population registry - had 30.1% of the episodes of the control group with a reduction of 69.88% of the cold episodes (p<0.0221). Also in the following, continuation, third week only 3 episodes of cold were recorded in the Phyto- Relief CC group vs 6 (50% reduction) observed in controls. All the other chosen parameters were better in the supplement group (p<0.05). Affected days (2.9;1.1 vs 4.6; 1.2 in controls), lost working days (0.58;0.5 vs 1.02;0.43 in controls. The use of any other OTC product, nasal drops, aspirin, Vit C, antihistamines, aerosols, the number of complications after 4 days were better in the Phyto-Relief CC group. Disease 'extension' (to >4 days), particularly tracheal and bronchial extension were significantly less frequent (p<0.05) with the supplement. No safety or tolerability problem was observed. In conclusion this preliminary study shows that Phyto-Relief CC may help the evolution of cold if used early, when initial symptoms could be identified. More specific evaluations and larger prevention studies are needed.

Management of osteoarthritis (OA) with the pharma-standard supplement FlexiQule (Boswellia): a 12-week registry.

This registry study assessed the pharma-standard supplement FlexiQule (Boswellia extract in capsules) in the management of symptoms associated to osteoarthritis (OA) also managed with the 'standard management' (SM) in comparison with a group of patients managed only with SM. The 12- week registry included patients with symptomatic knee arthrosis. They were able to walk on a treadmill for a walking test and to complete the WOMAC questionnaire. RESULTS: 32 patients used the supplement and 34 acted as controls (SM). No safety problems were observed. At 12 weeks, the Karnofsky scale was significantly improved in both groups: the variation was higher (p<0.05) in the supplement group. The WOMAC score was decreased significantly more in the supplement+SM group in comparison with controls considering pain, stiffness and physical functions (p<0.05). For social and emotional functions the decrease in score was also more evident in the supplement group (p<0.05). Both groups improved in pain-free and total walking distance at 12 weeks. Pain-free walking distance (treadmill) was higher (p<0.05) with the supplement (from 93.4;11.6 m to 271.3;19.3 m) than in controls (from 90.5;13.5 m to 158.3;22.3)(p<0.05). The improvement in total walking distance was also higher in the supplement group (p<0.05) (from 164.3;23.2 to 322.3;22.3 m) in comparison with the SM- only group ( from 158.3;18,4 to 240.2;19.3 m). The need for concomitant drugs and medical attention during the registry was reduced more in the supplement group (p<0.05). In conclusion the difference between SM and the Flexiqule+SM was in favor of the management with the supplement for all target measurements. The product is safe and well tolerated.

Management of functional, hepatic damage after chemotherapy with Liverubin (pharma-standard silymarin).

Mild, temporary hepatic failure (MTHF) after chemotherapy is a common clinical problem; in case of repeated episodes MTHF may cause chronic impairment. This registry has evaluated post- chemotherapy (PC)-MTHF in subjects using Liverubin (standardized Silymarin) for 8 weeks (3 capsules/day). METHODS: PC-MTHF was evaluated in a registry study. Hepatitis markers were negative at inclusion and at end-registry. In the final registry there were results concerning 18 Liverubin-supplemented patients and 19 controls completing the 8-week period. Signs/symptoms. The distribution of the most common symptoms and signs with ultrasound scans were comparable. Symptoms were mostly minimal or subclinical. Most symptoms observed at inclusion were completely disappeared or greatly attenuated after 8 weeks. The improvement produced by Liverubin induced a better and faster disappearance of symptoms. The results of the blood tests (at inclusion and at 8 weeks showed the increase in albumin, significantly (P<0.05) faster with the final values higher in the supplement group. Total bilirubin was reduced with the supplement better than in controls (P<0.05). Direct bilirubin values improved more in the supplement (P<0.05) group. The decrease in SGPT and AST-ASAT was more evident with the supplement (P<0.05). Improvement in controls was more limited. Alkaline phosphatase was significantly lower (than in controls) with Liverubin at 8 weeks (p<0.05). Gamma GT also decreased more and faster with the supplement. The ESR (erythrocytes sedimentation rate) was decreased in both groups, more in the Liverubin group (P<0.05). There was a more limited decrease in controls with persisting higher values at 8 weeks. The white cell count was also better at 3 months (with a larger decrease with the supplement; P<0.05). Oxidative stress. Plasma free radicals (PFR) were elevated in both groups at inclusion. A more significant decrease in the supplement group was observed at 8 weeks. Persisting elevation in values was seen in controls (P<0.05). Platelets values improved better with Liverubin (P<0.05). Safety and tolerability were optimal (no side effect was registered). In conclusion, results from this pilot registry indicate a significant activity of Liverubin associated with a very good safety profile, in patients with post-chemotherapy hepatic failure. The recovery of hepatic function is faster and more effective with Liverubin in comparison with the best "standard" management.

Supplementary management of benign prostatic hypertrophy with Prostaquil. An 8-week registry.

The aim of this registry was to evaluate the management of initial symptoms of benign prostatic hyperthrophy (BPH) in otherwise healthy subjects, using Prostaquil® (Alchem) in a 8-week registry. Prostaquil was used at the dosage of 200 mg/day. The product includes Pygeum extract (100 mg) and Saw palmetto oil (35 mg). The two resulting groups standard management and supplement) were comparable. RESULTS: No side effects or comparability problems were observed and compliance was optimal with more than 95% of the capsules correctly used. Empting, frequency, intermittency, urgency, weak flow, straining, nocturia were all significantly improved with Prostaquil (p<0.05) and the improvement - globally and evaluating any single item - was significantly superior to the one observed in controls (p<0.05). Quality of life with the supplement was also significantly better in comparison with controls (p<0.05). The residual vescical volume was 94.7;5,8 ml in the supplement group at inclusion and decreased to 39.3;5 ml (p<0.05) at 8 weeks. This decrease was equivalent to a reduction of 58.5%(vs a decrease of 27.9% in controls)(p<0.05; ANOVA). In conclusion, the most common symptoms of BPH are controlled by Prostaquil a new standardized supplement including Pygeum.

Miraqule-C and mild heart failure: an 8-week registry.

The aim of this registry study was the evaluation of possible benefits of a supplement including CoenzymeQ10 and a grape seed combination (MiraQule C, Alchem) in stable, moderate, heart failure patients. RESULTS: The mean age of the 18 supplemented patients was 60.1;2 years (the age of the 22 controls was 61.1;2.2). The two groups were comparable. There were no dropouts in the two groups. In the 8 weeks of the registry, all supplemented patients remained in the NYHA class while 7 out of 22 in controls increased the level of heart failure passing into Class III. Systolic- diastolic pressure, heart rate, respiratory rate were minimally (non significantly lowered) with the supplement without differences controls. Ultrasound-derived ejection fraction was increased by supplementation (median of 2.7%) in the CoQ10 group (p<0.05) while there were minimal, non- significant differences in controls. Walking distance on treadmill was also significantly increased with the supplement (p<0.05) and only marginally in controls. The microcirculation (laser Doppler parameters and transcutaneous PO2, PCO2) improved significantly in the MQ-C group (p<0.05) and only marginally in controls. Oxidative stress was significantly decreased (p<0.05) with the CoQ10 preparation while there were minimal. Non-significant changes were observed in in controls. Tolerability and compliance were optimal (with more than 95% of the capsules correctly used). In conclusion in this supplement registry Miraqule-C seem to help patients with moderate heart failure and should be considered for larger studies.

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.

Robuvit® (Quercus robur extract) supplementation in subjects with chronic fatigue syndrome and increased oxidative stress. A pilot registry study.

AIM: The aim of this registry study was to evaluate the effects of supplementation with Robuvit® (French Quercus robur extract) capsules in subjects with Chronic Fatigue Syndrome (CFS) associated with an increased oxidative stress. Robuvit is a wood extract from Quercus robur (Horphag Research) used to improve liver dysfunction and chronic fatigue. After excluding any disease, subjects observed a defined management plan to improve CFS. Signs/symptoms had been present for more than 6 months in association with an increase in oxidative stress (measured as plasma free radicals). Blood tests were within normal values. METHODS: The registry study included 38 CFS subjects and 42 comparable controls. There were no dropouts in the 4 weeks of follow-up; the subjects were evaluated for a further period of 6 months. The management plan included: improved/increased sleep; reduction/abolition in smoking and alcohol or any other agent that may have affected them; control of diet, increase in dietary proteins; good hydration; rest (1/2-1 h/day) and exercise (at least 30 min/day); planned relaxation time; increased time in open spaces. In the Robuvit® supplementation group 300 mg/day of Robuvit® was used. RESULTS: Symptoms improved in both groups with a significantly more important improvement in the supplement group (P<0.05). The single items in the Multidimensional Assessment of Fatigue (MAF) questionnaire were statistically better improved (P<0.05) in the supplement group. A parallel improvement in oxidative stress was observed in the supplemented subjects. In the follow up, at 6 months no organic disease was discovered or disease markers found. CONCLUSION: This preliminary registry indicates that supplementation with Robuvit® improves CFS in otherwise healthy subjects with no presence of clinical disease or risk conditions. The effects of Robuvit® in CFS may be partially mediated by a clear reduction of plasma free radicals and oxidative stress.

Effects of Pycnogenol® on endothelial dysfunction in borderline hypertensive, hyperlipidemic, and hyperglycemic individuals: the borderline study.

AIM: This registry study aimed to evaluate the effects of supplementation with pycnogenol on altered endothelial function (EF) in borderline hypertensive, hyperlipidemic and hyperglycemic subjects without atherosclerotic changes in their main arteries and no coronary artery disease. METHODS: Flow mediated dilatation (FMD) and endothelium-independent (EID) dilatation were measured with brachial ultrasound after occlusion. Also, after occlusion, laser Doppler (LDF) flux and distal straingauge flow were measured. Oxidative stress (oxstress) was evaluated at 8 and 12 weeks. 93 subjects with borderline symptoms were enrolled into the study: 32 hypertensives, 31 hyperlipidemics, 30 hyperglycemics. All participants were instructed to follow the best available management to control their symptoms. In addition to best management, half of the subjects in each group used 150 mg/day Pycnogenol(®). 31 normal subjects were included as control. RESULTS: After 12 weeks metabolic values and blood pressure were back to normal in all subjects. Values were slightly better under Pycnogenol(®). FMD increased after 8 weeks from an average 5.3;3.4% to 8.2;2.2% with a further increase to 8.8;3.1% (P<0.05) at 12 weeks. No effects were found in controls and normal subjects. EID of normal subjects was consistently higher with 26%. LDF skin flux increased with Pycnogenol(®) at 8 weeks and 12 weeks. The final flux increase was not different from normal values. In controls flux after occlusion was not improved at 8 weeks; there was a significant but minor increase at 12 weeks. Flux increases were superior in all Pycnogenol(®) subjects. In Pycnogenol(®) subjects, limb flow after occlusion increased at 8 weeks with a further increase at 12 weeks. In controls inclusion flow after occlusion was comparable at 8 and 12 weeks. Oxidative stress was significantly decreased in Pycnogenol(®) subjects at 8 and 12 weeks. Minor differences were observed in controls. CONCLUSION: This open registry study indicates that Pycnogenol(®) improves EF in preclinical, borderline subjects in a macro-microcirculatory model. This observation may suggest an important preventive possibility for borderline hypertensive, hyperglycemic and hyperlipidemic subjects.

Supplementary management of functional, hepatic damage with Liverubin (pharma-standard Silymarin). A 3-month registry.

Mild, temporary hepatic failure (MTHF) is a common clinical problem; in case of repeated episodes MTHF may cause chronic liver impairment. This registry has evaluated MTHF in subjects using Liverubin (standardized Silymarin) for 8 weeks. METHODS: MTHF was evaluated in a registry study. In all subjects viral hepatitis markers were negative at inclusion. Different possible causes of MTHF had been considered. In these subjects alcohol was not a main factor. The registry included MTHF patients with decreased albumin levels, increased total bilirubin, altered hepatic function enzymes, increased oxidative stress. Two management groups were created: a standard management (SM) group and a SM+Liverubin group; 32 Liverubin patients and 33 SM subjects completed the registry. Liverubin was used at the dosage of two tablets (each equivalent to 140 mg) daily. RESULTS: Distribution of symptoms, blood test values and ultrasound results were comparable. Symptoms observed at inclusion disappeared at 3 months in both groups. The increase in albumin levels was significantly (P<0.05 at 4 weeks) faster and the final blood tests improved more with Liverubin. Total bilirubin was reduced with the supplement (better than in controls; P<0.05). Direct bilirubin values improved more in the supplement group at 3 months (P<0.05). The decrease of SGPT and AST- ASAT was more evident in the supplement group (P<0.05). Alkaline phosphatase value was normalized at in Liverubin patients; values decreased less in controls (P<0.05). Gamma GT decreased more with Liverubin. ESR was decreased in both groups (significantly more with Liverubin: P<0.05). There was a less important decrease in controls at 3 months. The white cell count was also better with the supplement group; P<0.05). Plasma free radicals - significantly elevated in both groups at inclusion - decreased more with the supplement at 3 months. All other blood tests (including hematocrit, renal function tests) were within the normal range at inclusion and at 3 months in both groups. Hepatitis markers were negative at inclusion and at end-registry. Safety and tolerability were optimal (no side effect was registered). CONCLUSION: In conclusion, data from this pilot, registry study indicate a significant activity of Liverubin associated with a very good safety profile, in patients with temporary hepatic failure. The recovery of hepatic function is faster and more effective with Liverubin compared to the best "standard" management.

Recurrence of retinal vein thrombosis with Pycnogenol® or Aspirin® supplementation: a registry study.

AIM: The aim of this study was to use Pycnogenol® to reduce the recurrence of retinal vein thrombosis (RVT) after a first episode. Pycnogenol® is an anti-inflammatory, anti-edema and an antiplatelet agent with a "mild" antithrombotic activity. The registry, using Pycnogenol® was aimed at reducing the number of repeated episodes of RVT. METHODS: Possible management options--chosen by patients--were: standard management; standard management + oral Aspirin® 100 mg once/day (if there were no tolerability problems before admission); standard management + Pycnogenol® two 50 mg capsules per day (for a total of 100 mg/day). Number of subjects, age, sex, distribution, percentage of smokers, and vision were comparable. RESULTS: Recurrent RVT was seen in 17.39% of controls and in 3.56% of subjects supplemented with Pycnogenol® (P<0.05 vs. controls). There was RVT in 15.38% of the subjects using Aspirin®. The incidence of RVT was 4.88 times higher with standard management in comparison with the supplement group and 4.32 lower with Pycnogenol® supplementation in comparison with Aspirin®. Vision level was better with Pycnogenol® (20/25 at nine months; P<0.05). With Pycnogenol®, edema at the retinal level was also significantly reduced compared to the other groups. Pycnogenol® has a very good safety profile. In the Aspirin® group 26 completed 9 months and 6 subjects dropped out for tolerability problems. In the Aspirin® group, 2 minor, subclinical, retinal, hemorrhagic episodes during the follow-up were observed (2 subjects out of 26, equivalent to 7.69%). This pilot registry indicates that Pycnogenol® seems to reduce the recurrence of RVT without side effects. It does not induce new hemorrhagic episodes that may be theoretically linked to the use of Aspirin® (or other antiplatelets). CONCLUSION: Larger studies should be planned involving a wider range of conditions, diseases and risk factors associated to RVT and to its recurrence.

Cranberry supplementation in the prevention of non-severe lower urinary tract infections: a pilot study.

OBJECTIVE: Cranberry extracts have been tested as a nutritional supplementation in the prevention of recurrent lower-urinary tract infections (R-UTIs), with mixed results. This pilot, registry study evaluates the prophylactic effects of oral supplementation with a new well-standardized cranberry extract in patients with R-UTI, over a 2-month follow-up. PATIENTS AND METHODS: All subjects were suggested to take one capsule containing a cranberry extract (Anthocran™) for 60 days and were also given lifestyle advice. Clinical outcomes were compared between patients on cranberry extracts and those who don't take this supplementation. RESULTS: In total, 22 subjects completed the study in each of the two groups. In the cranberry group, the reduction in the frequency of UTI episodes during the study period compared with the two months before the inclusion was 73.3% (p < 0.05). This figure was 15.4% in the control group (p < 0.05; p = 0.012 vs cranberry group). Seven (31.8%) subjects in the cranberry group were symptom-free; no patient was symptom-free in the control group (p < 0.05). The mean duration of UTI episodes was 2.5 ± 1.3 days in the cranberry group, compared with 3.6 ± 1.7 days in subjects not on cranberry (p < 0.05). Three subjects (13.6%) in the cranberry group and 8 (36.3%) in the control group required medical consultation for UTI symptoms (p < 0.05). Urine evaluation was completely negative in 20/22 subjects in the Cranberry group (90.9%) and in 11 control subjects (50.0%; p < 0.005). No adverse events were observed. CONCLUSIONS: These preliminary results, obtained in a field-practice setting, indicates the effectiveness and safety of a well-standardized cranberry extract in the prevention of R-UTI.