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 post-menopausal women.

AIM: The aim of this pilot, single-blinded study was to evaluate the efficacy of a proprietary, dietary supplement Lady Prelox® for supporting and improving sexual function in generally healthy, post-menopausal women. METHODS: The Lady Prelox® and placebo control groups were comparable at inclusion with regard to the total Female Sexual Function Index (FSFI) score, as well as for the six individual FSFI domains, with 40 women (50.1 ± 3.1 years) and 43 women (51.2 ± 2.3 years), respectively. RESULTS: At baseline the women in the verum group presented with a mean total FSFI score of 44.6 ± 24.1 which increased significantly already after four weeks treatment with Lady Prelox® to 70.9 ± 18.5 and further increased to 71.7 ± 23.9 after completion of the eight-week trial period. In the control group the mean total FSFI was 44.1 ± 22.8 at inclusion and non-significantly increased to 45 ± 21.4 after four weeks and 47.4 ± 21.8 after eight weeks, respectively. The treatment with Lady Prelox® was comparatively significantly more effective than placebo after both four and eight weeks of treatment (P<0.05). The individual six FSFI domains related to desire, arousal, lubrication, orgasm, satisfaction and pain did all respond favourably to treatment with Lady Prelox®; however, with only marginable higher scores in the placebo group. Four women in each group dropped out because of inabilities to attend scheduled check-ups. No adverse effects were reported. CONCLUSION: This study opens an interesting perspective for women experiencing moderate sexual function impairment and suggests a promising new treatment option. Further studies with larger numbers of women, including also premenopausal and perimenopausal women are warranted.

Lady Prelox® improves sexual function in post-menopausal women.

AIM:he aim of this pilot, single-blinded study was to evaluate the efficacy of a proprietary, dietary supplement Lady Prelox® for supporting and improving sexual function in generally healthy, post-menopausal women. METHODS: The Lady Prelox® and placebo control groups were comparable at inclusion with regard to the total Female Sexual Function Index (FSFI) score, as well as for the six individual FSFI domains, with 40 women (50.1±3.1 years) and 43 women (51.2±2.3 years), respectively. RESULTS:At baseline the women in the verum group presented with a mean total FSFI score of 44.6±24.1 which increased significantly already after four weeks treatment with Lady Prelox® to 70.9±18.5 and further increased to 71.7±23.9 after completion of the eight-week trial period. In the control group the mean total FSFI was 44.1±22.8 at inclusion and non-significantly increased to 45±21.4 after four weeks and 47.4±21.8 after eight weeks, respectively. The treatment with Lady Prelox® was comparatively significantly more effective than placebo after both four and eight weeks of treatment (P<0.05). The individual six FSFI domains related to desire, arousal, lubrication, orgasm, satisfaction and pain did all respond favourably to treatment with Lady Prelox®; however, with only marginable higher scores in the placebo group. Four women in each group dropped out because of inabilities to attend scheduled check-ups. No adverse effects were reported. CONCLUSION: This study opens an interesting perspective for women experiencing moderate sexual function impairment and suggests a promising new treatment option. Further studies with larger numbers of women, including also premenopausal and perimenopausal women are warranted.

Venoruton®: post thrombotic syndrome. Clinical improvement in venous insufficiency (signs and symptoms) with Venoruton®. A five-year, open-registry, efficacy study.

AIM: This registry evaluation was conducted in post-thrombotic syndrome (PTS) patients (with a minimum five-year follow up). The study evaluated: 1) variations in peripheral edema with an analogue scoring system; 2) ankle circumference at the PTS limb in comparison with the normal contralateral limb. METHODS: The difference was expressed in percent increase in circumference measured at the PTS limb; 3) other end-points were observed in a five-year follow-up that created a specific PTS registry. Subjects could follow a management system including: 1) compression; 2) compression and Venoruton® (1 g/day); 3) compression and Venoruton® (2 g/day). RESULTS: The groups of patients with chronic venous insufficiency (CVI) resulted comparable. The occurrence of a new deep venous thrombosis (DVT) episode was considered a drop out. At five years there were four new DVTs (in 90 patients) in the compression group. There was one case (90 patients included) in the compression and HR (1 g) group and no DVT in group 3. The outcome in groups 2 and 3 was significantly better (0.05) than in group 1. The need for surgery or sclerotherapy (for larger varicose veins), the occurrence of lipodermatosclerosis and ulcerations were significantly lower in the HR groups with a better outcome in the higher dose group (P<0.05). The number of ulcerations were also significantly reduced in the HR groups. The difference in ulcerations was significantly better in the higher dose group in comparison with the other groups (P<0.05). The edema score was significantly reduced at five years in the HR groups (P<0.05) in comparison with the compression group. The higher dose resulted more effective in controlling edema. Both edema score and ankle circumference at five years were significantly lower (P<0.05) in the HR-treated groups with a significant decrease in edema score and ankle circumference in the higher dosage group. CONCLUSION: The study confirms the long-term efficacy of HR in PTS, CVI patients. Controlling signs/symptoms and edema in CVI with HR prevents the most severe complications of CVI including lipodermatosclerosis and venous ulcerations. An early therapeutic program including exercise, risk factor controls, compression an edema-controlling treatment with HR is effective in decreasing the classic complications of PTS syndrome. The important restrictions and difficulties to the use of elastic stockings (in regions with warmer climates) are not applicable to HR that is well tolerated and can be used all the time alone or in association with compression.

Potential role of curcumin phytosome (Meriva) in controlling the evolution of diabetic microangiopathy. A pilot study.

AIM: The aim of the present study was to evaluate the improvement of diabetic microangiopathy in patients suffering from this condition since at least five years, and whose disease was managed without insulin. METHODS: Curcumin, the orange pigment of turmeric, has recently received increasing attention because of its antioxidant properties, mediated by both direct oxygen radical quenching and by induction of anti-oxidant responses via Nrf2 activation. This aspect, combined with the beneficial effects on endothelial function and on tissue and plasma inflammatory status, makes curcumin potentially useful for the management of diabetic microangiopathy. To further evaluate this, Meriva, a lecithinized formulation of curcumin, was administered at the dosage of two tablets/day (1 g Meriva/day) to 25 diabetic patients for four weeks. A comparable group of subjects followed the best possible management for this type of patients. RESULTS: All subjects in the treatment and control group completed the follow-up period; there were no dropouts. In the treatment group, at four weeks, microcirculatory and clinical evaluations indicated a decrease in skin flux (P<0.05) at the surface of the foot, a finding diagnostic of an improvement in microangiopathy, the flux being generally increased in patients affected by diabetic microangiopathy. Also, a significant decrease in the edema score (P<0.05) and a corresponding improvement in the venoarteriolar response (P<0.05) were observed. The PO2 increased at four weeks (P<0.05), as expected from a better oxygen diffusion into the skin due to the decreased edema. These findings were present in all subjects using Meriva, while no clinical or microcirculatory effects were observed in the control group. CONCLUSION: Meriva was, in general, well tolerated, and these preliminary findings suggest the usefulness of this curcumin formulation for the management of diabetic microangiopathy, opening a window of opportunities to be evaluated in more prolonged and larger studies. The molecular mechanisms involved in the beneficial effects of curcumin on microcirculation and edema are also worth investigation.

Supplementation with Pycnogenol® improves signs and symptoms of menopausal transition.

AIM: The aim of this study was to evaluate the efficacy of Pycnogenol® standardized pine bark extract for alleviation of signs and symptoms associated with menopausal transition. METHODS: Pycnogenol® was used by 38 women as daily supplement in a dosage of 100 mg over an eight week period and menopausal symptoms were evaluated by means of a scoring system, based on a total number of 33 common signs and symptoms. A parallel control group of 32 comparable women was also followed up for the same period. Pycnogenol® was well tolerated, no side effects were reported and the compliance was very good with 98.6% of tablets used as prescribed. A range of 33 menopausal symptoms were evaluated using a scoring system with values ranging from zero (absent) to maximum 4 (very serious). RESULTS: A subset of six most common symptoms comprising hot flushes, night sweats, mood swings, irregular periods, loss of libido and vaginal dryness showed a decrease from average 2.67/4 to 1.45/4 after 8 weeks supplementation with Pycnogenol®. The control group of women showed no change from initial average 2.72/4 to 2.73/4 after eight weeks. The improvement of symptoms was statistical significant compared to the control group. Further symptoms related to fatigue, sleeping disorders, concentration and memory problems, dizziness, depression and irritability all improved significantly with Pycnogenol® compared to baseline values but did not reach statistical significance compared to the control group of women. The sensation of pain related to headaches, breast pain, the feeling of "electric shocks", tingling extremities, burning tongue and itchy skin all improved significantly after intake of Pycnogenol® for eight weeks compared to baseline. Specifically the sensation of "electric shocks" and digestive problems improved significantly with Pycnogenol® as compared to women in the control group. The presence of elevated oxidative stress in women was investigated measuring capillary blood plasma free radicals. Oxidative stress was significantly lowered after four weeks (P<0.05) and eight weeks (P<0.022) in the Pycnogenol® group while no significant changes were observed in the control group at any time. CONCLUSION: Pycnogenol® significantly contributed to reduce signs and symptoms associated with menopausal transitions in women investigated in this study. Furthermore, Pycnogenol® improved the quality of life of most women and these benefits may be at least in part attributed to decreased oxidative stress levels.

Pycnogenol® improvements in asthma management.

AIM: The simplification of the management of asthma in the different clinical phases of this common chronic inflammatory disorder is the main goal of therapy. Pycnogenol®, a standardized extract of French maritime pine bark, inhibits expression of 5-lipoxygenase and consequently decreases leukotriene levels in asthmatic patients. Pycnogenol® anti-inflammatory activities may be supportive when taken in addition to inhalation corticosteroid (ICS), putatively allowing for a reduction in dosage and frequency of ICS administration. METHODS: This study evaluated the efficacy of Pycnogenol® during a period of six months for improving allergic (mite in house dust) asthma management in patients with stable, controlled conditions. Pycnogenol® was used at a daily dosage of 100 mg, distributed as 50 mg in the morning at 9 am and again in the evening at 9 pm). An individual patient's asthma condition was graded in five steps based on the daily dosage of inhaled fluticasone propionate with step 1 indicating 0 µg and step 5 the maximum dose of 500 µg ICS twice daily. RESULTS: A total 76 patients were enrolled for this study. The group taking Pycnogenol® in addition to ICS and the group taking only ICS were comparable for age, gender and clinical characteristics including FEV1. The analysis of therapeutic ranking steps showed that 55% of patients taking Pycnogenol® improved as judged by passing to a lower ICS dose step. In comparison, only 6% of patients depending exclusively on ICS progressed to a lower (ICS dose) therapeutic step. No deterioration (passage to a higher ICS therapeutic step) was observed in the Pycnogenol® group, whereas in 18.8% of patients depending exclusively on corticosteroids a deterioration requiring a higher dosage step was observed. The passage to different therapeutic steps was statistical significant between groups (P<0.05). Drop-outs were associated entirely to irregularities in follow-up and not due to medical reasons. No serious adverse events were observed in both groups and tolerability of Pycnogenol® was very good. The levels of asthma control in the 6 interventional months as compared to the same period in the previous year were compared. In the Pycnogenol® group, night-awakenings were less frequent, the number of days with PEF<80% were decreased, days with asthma score >1 were lower, requirement for salbutamol and additional asthma medication less frequent, and consultation of general practitioner and specialist required less commonly. All these parameters were statistical significantly improved in Pycnogenol® + ICS group versus the ICS control group where no considerable changes were observed. Various common signs and symptoms were evaluated by visual analog scale, (dry) cough, severity of chest symptoms, wheezing, dyspnea and daytime symptoms. In the ICS-only group values did not improve while they did improve significantly in the ICS + Pycnogenol® group (P<0.05 vs. ICS only group). A decrease by 15.2% of the specific IgE titer was found in the Pycnogenol® + ICS group, whereas the titer increased by 13.4% in the ICS-only group, while IgG1 and IgG4 remained unchanged in both groups. CONCLUSION: Pycnogenol® administration was effective for better control of signs and symptoms of allergic asthma and reduced the need for medication.

Osteoporosis of the jaw. Product evaluation: mf Odontovis Calcium®.

AIM: The aim of this study was to test mf Odondovis Calcium® as a food supplement in a 3-month product evaluation study measuring how the low jaw bone density, could be improved. The upper jaw density was tested with an ultrasound method, evaluating the grey scale median of the images (GSM). METHODS: Seventy nine subjects were enrolled; 22 normal subjects (group A) and 57 with upper jaw osteoporosis (according to DEXA values). Patients were divided into 2 groups (group B and C, respectively 28 and 29 cases). These subjects were treated with what was considered the' best treatment' and in the group B only was added mf Odontovis Calcium®, consisting of calcium salts, Vitamin D and physiological modulators with antioxidant activity. This treatment continued for 3 months. RESULTS: The GSM of osteoporotic patients was significantly lower in comparison with GSM in normal subjects. No changes were observed (between the inclusion and 3 month values) in normal subjects and minimal, non-significant changes were observed in control osteoporosis patients. Before-after treatment values of GSM in treatment patients showed a significant increase (P<0.022) at 3 months. The increase in GSM in these patients was significantly higher (P<0.05) in comparison with control patient with osteoporosis. The Tolerability of the product was very good and the compliance corresponded to 98%. CONCLUSION: the jaw density in patients with osteoporosis is increased in only 3 months with supplementation with mf Odontovis Calcium®. Long-term clinical implications should be observed in more prolonged studies.

Variations in C-reactive protein, plasma free radicals and fibrinogen values in patients with osteoarthritis treated with Pycnogenol.

In a previous, double-blind, placebo-controlled study we evaluated the efficacy of a 3-month treatment with Pycnogenol for 156 patients with osteoarthritis of the knee. Pycnogenol significantly decreased joint pain and improved joint function as evaluated using the WOMAC score and walking performance of patients on a treadmill. In this study, we further investigated the anti-inflammatory and antioxidant activity of Pycnogenol in a subset of the osteoarthritis patients presenting with elevated C-reactive protein (CRP) and plasma-free radicals. Elevated CRP levels have been suggested to be associated with disease progression in osteoarthritis. In our study, 29 subjects of the Pycnogenol group and 26 patients in the placebo group showed CRP levels higher than 3 mg/l at baseline. Comparison of blood specimens drawn at baseline and after 3-month treatment showed that Pycnogenol significantly decreased plasma free radicals to 70.1% of baseline values. Plasma CRP levels decreased from baseline 3.9 mg/l to 1.1 mg/l in the Pycnogenol group whereas the control group had initial values of 3.9 mg/l which decreased to 3.6 mg/l. The CRP decrease in the Pycnogenol was statistical significant as compared to the control group (P < 0.05). Fibrinogen levels were found to be lowered to 62.8% of initial values (P < 0.05) in response to Pycnogenol. No significant changes for plasma free radicals, CRP and fibrinogen were found in the placebo-treated group. The decrease of systemic inflammatory markers suggests that Pycnogenol may exert anti-inflammatory activity in osteoarthritic joints and patients did not present with other ailments or infections. The nature of the anti-inflammatory effects of Pycnogenol with regard to CRP warrants further investigation.

Treatment of osteoarthritis with Pycnogenol. The SVOS (San Valentino Osteo-arthrosis Study). Evaluation of signs, symptoms, physical performance and vascular aspects.

The aim of this double-blind, placebo-controlled study was to evaluate the efficacy of 100 mg Pycnogenol daily (oral capsules) in a 3 month study in patients with osteoarthritis (OA). OA symptoms were evaluated by WOMAC scores, mobility by recording their walking performance (treadmill). Treatment (77 patients) and placebo group (79) were comparable for age, sex distribution, WOMAC scores, walking distances and use of antiinflammatory drugs. The global WOMAC score decreased by 56% (p < 0.05) in the treatment group versus 9.6% in the placebo group. Walking distance in the treadmill test was prolonged from 68 m at the start to 198 m after 3 months treatment (p < 0.05), under placebo, from 65 m to 88 m (NS). The use of drugs decreased by 58% in the treatment group (p < 0.05) versus 1% under placebo. Gastrointestinal complications decreased by 63% in the treatment group, but only 3% under placebo. Overall, treatment costs were reduced significantly compared with placebo. Foot edema was present in 76% of the patients of the treatment group at inclusion and in 79% of the controls. After 3 months edema decreased in 79% of Pycnogenol patients (p < 0.05) vs 1% in controls. In conclusion, Pycnogenol offers an option for reduction of treatment costs and side effects by sparing antiinflammatory drugs.

Management of uncomplicated ankle sprains with topical or oral ketoprofen treatment. A registry study.

Ankle sprains mainly caused by accidents or strenuous sport activities can often be quite painful and impair motility. If not treated immediately and correctly, sprains may lead to severe complications. The aim of the present study was to compare the efficacy and safety of topically applied ketoprofen versus orally administered ketoprofen in 20 patients with grade I ankle sprain and 34 patients with grade II sprain. The patients were divide into in two treatment groups and received either topically applied ketoprofen treatment (ketoprofen 10% spray-gel; Prontoflex; 360 mg/die) or orally administered ketoprofen treatment (ketoprofen tablets; 3x50 mg/die). Treatment duration was one week. After 3 and 7 days of treatment, reduction of spontaneous pain and pain on active movement in the Prontoflex group was significantly bigger greater in the oral treatment group, irrespective of sprain severity. Regarding secondary parameters as mobility impairment and ankle swelling topically applied ketoprofen treatment turned out to be significantly superior to orally administered ketoprofen treatment. Additionally, Prontoflex was well tolerated, whereas ketoprofen tablets caused gastrointestinal side effects in some patients. The good efficacy in pain reduction and absence of side effects in the present study distinguished the topically applied ketoprofen as a favorable treatment for patients with accidental or sport soft tissue injuries.

Management of superficial vein thrombosis and thrombophlebitis: status and expert opinion document.

Superficial vein thrombosis is characterized by clotting of superficial veins (ie, following direct trauma) with minimal inflammatory components. Superficial thrombophlebitis is a minimally thrombotic process of superficial veins associated with inflammatory changes and/or infection. Treatments generally include analgesics, elastic compression, anti-inflammatory agents, exercise and ambulation, and, in some cases, local or systemic anticoagulants. It is better to avoid bed rest and reduced mobility. Topical analgesia with nonsteroidal, anti-inflammatory creams applied locally to the superficial vein thrombosis/superficial thrombophlebitis area controls symptoms. Hirudoid cream (heparinoid) shortens the duration of signs/symptoms. Locally acting anticoagulants/antithrombotics (Viatromb, Lipohep, spray Na-heparin) have positive effects on pain and on the reduction in thrombus size. Intravenous catheters should be changed every 24 to 48 hours (depending on venous flow and clinical parameters) to prevent superficial vein thrombosis/superficial thrombophlebitis and removed in case of events. Low molecular weight heparin prophylaxis and nitroglycerin patches distal to peripheral lines may reduce the incidence of superficial vein thrombosis/superficial thrombophlebitis in patients with vein catheters. In case of superficial vein thrombosis/superficial thrombophlebitis, vein lines should be removed. In neoplastic diseases and hematological disorders, anticoagulants may be necessary. Exercise reduces pain and the possibility of deep vein thrombosis. Only in cases in which pain is very severe is bed rest necessary. Deep vein thrombosis prophylaxis should be established in patients with reduced mobility. Antibiotics usually do not have a place in superficial vein thrombosis/superficial thrombophlebitis unless there are documented infections. Prevention of superficial vein thrombosis should be considered on the basis of patient's history and clinical evaluation.

Topical heparin: new observations.

Topical effects of heparins on the skin need deeper investigations. The lack of evidence is mainly due to the lack of large investments in this field. Three main local actions of heparin on the skin can be defined: (a) the anticoagulant action, (b) the microcirculatory-modulatory action determining important control of the microcirculation in case of excessive vasoconstriction or vasodilatation, and (c) the 'facilitatory action' on skin permeability allowing other drugs to diffuse better and faster into the skin (producing a therapeutic effect). These aspects have to be evaluated more extensively in both experimental and clinical conditions. Recent experimental studies demonstrate these effects of locally applied heparin. Therefore, key questions on local heparin administration such as skin penetration and the action on the local thrombi have promising answers. These observations suggest important clinical applications for local liposomal heparin. Both the potentials of local applications of heparin, particularly with new formulations, and some new aspects in the management of superficial vein thrombosis (SVT) can focus on locally applied heparin. SVT is an important clinical condition considering its frequency and the potentially heavy use of local heparin in this clinical problem. Results from new studies and observations presented in this issue of Angiology could be a window for suggesting new significant clinical applications and therapeutic solutions.