Supplementation with a lecithin-based delivery form of Boswellia serrata extract (Casperome®) controls symptoms of mild irritable bowel syndrome.

OBJECTIVE: Irritable Bowel Syndrome (IBS) is a chronic, gastrointestinal disorder in which abdominal pain or discomfort is associated with defecation or changes in bowel habits. Its multifactorial pathophysiology leads to a variety of available treatments, mainly aimed at controlling symptoms. The management of IBS patients could be optimized by individualized strategies, including non-pharmaceutical approaches. In this study, we evaluated the efficacy and safety of a novel delivery form of Boswellia serrata extracts (BSE) (Casperome®) in patients with IBS. PATIENTS AND METHODS: 71 otherwise healthy subjects with idiopathic IBS were recruited. Participants were assigned to the following management strategies: hyoscine butylbromide; papaverine hydrochloride + A. belladonna extract; supplementation with Casperome®. Predominant IBS symptoms were evaluated at inclusion and at the end of the observational period (4 weeks). The numbers of subjects who needed rescue medication or medical attention/hospital admission were recorded. Adverse events were also evaluated. RESULTS: In all groups, the IBS symptoms investigated, namely abdominal pain, altered bowel movements, meteorism and cramps improved during the observational period. Of note, the number of subjects who needed medical attention significantly decreased only in Casperome®-supplemented group. In addition, Casperome® supplementation was related to a lower incidence of side effects (mainly stypsis). CONCLUSIONS: This preliminary study suggests that Casperome® supplementation could represent a promising alternative approach to manage symptoms associated with IBS in otherwise healthy subjects.

Effects of a curcumin-based supplementation in asymptomatic subjects with low bone density: a preliminary 24-week supplement study.

OBJECTIVE: Osteopenia is a chronic bone condition characterized by decreased calcification, density, or bone mass that, if untreated, can lead to osteoporosis and bone fractures. Although its increasing prevalence, nowadays osteopenia is not adequately prevented and managed. In this study, we evaluated the efficacy, in term of changes in bone density, and safety of an oral formulation based on turmeric phytosome (Meriva®), in subjects suffering from low bone density. PATIENTS AND METHODS: 57 otherwise healthy subjects with low bone density were enrolled in this pilot, supplement study. Informed participants freely decided to follow either a standard management (SM) to control low bone density (control group=28) or SM associated with a curcumin-based oral supplementation (supplement group=29). The bone densities of heel, small finger and upper jaw were evaluated at inclusion and at different time points during the observational period (4, 12 and 24 weeks), in all subjects. RESULTS: The bone density of the heel measured by the Sahara densitometer remarkably improved in the Meriva®-supplemented group, with a significant decrease of ultrasounds transmission values at week 12 (-18.4%) and at week 24 (-21.0%), compared with baseline values. The bone densities of small finger and upper jaw also significantly increased during the study in supplemented subjects, reaching +7.1% and +4.8%, respectively, at week 24, with respect to values at inclusion. Noteworthy, no significant changes of heel, small finger and upper jaw densities were observed in the control group. Last, no safety and tolerability issues were reported during the observational period. CONCLUSIONS: This preliminary study suggests that a curcumin-based supplementation in combination with an appropriate lifestyle could be beneficial in the prevention and management of osteopenia.

Influence of Sensory Stimulation on Exhaled Volatile Organic Compounds.

The real-time exhaled volatile organic compounds (VOCs) have been suggested as a new biomarker to detect and monitor physiological processes in the respiratory system. The VOCs profile in exhaled breath reflects the biochemical alterations related to metabolic changes, organ failure, and neuronal activity, which are, at least in part, transmitted via the lungs to the alveolar exhaled breath. Breath analysis has been applied to investigate cancer, lung failure, and neurodegenerative diseases. There are by far no studies on the real-time monitoring of VOCs in sensory stimulation in healthy subjects. Therefore, in this study we investigated the breath parameters and exhaled VOCs in humans during sensory stimulation: smell, hearing, sight, and touch. Responses sensory stimulations were recorded in 12 volunteers using an iAQ-2000 sensor. We found significant effects of sensory stimulation. In particular, olfactory stimulation was the most effective stimulus that elicited the greatest VOCs variations in the exhaled breath. Since the olfactory pathway is distinctly driven by the hypothalamic and limbic circuitry, while other senses project first to the thalamic area and then re-project to other brain areas, the findings suggest the importance of olfaction and chemoreception in the regulation lung gas exchange. VOCs variations during sensory activation may become putative indicators of neural activity.

Robuvit® and endurance in triathlon: improvements in training performance, recovery and oxidative stress.

AIM: The aim of this registry study was to evaluate the effects of supplementation with Robuvit® (Quercus robur wood extract, or "QR") on performance and endurance in triathlon by evaluating amateur athletes in a period of 2 weeks of training. Supplementation with QR may improve training efficiency (by decreasing post-triathlon, muscular pain, cramps and by improving recovery time). Robuvit® should decrease post-training plasma free radicals (PFR). METHODS: Sixty-one subjects (age range 30-40) were included in the study. Subjects followed a free diet. An isotonic saline drink was suggested to all subjects. RESULTS: After 2 weeks there were 27 subjects using the supplement and 27 without supplementation. The groups were comparable. All subjects improved in training considering the 3 events (swim, biking, run). The improvement was greater with Robuvit® (P<0.05) for the swim and biking (P<0.05); the running time decreased by 12.32% in subjects using Robuvit® (3.6% in controls; P<0.05). The improvement the total triathlon time was -10.56% with Robuvit® in comparison to -3.41% in controls. SAFETY: no side effects or tolerance problems were reported; all QR capsules were used as indicated. CONCLUSION: In conclusion, the -10.56% shorter total trioathlon time was considered as very good improvement, considering that for this type of athletes being almost at the top of their form it is difficult to improve even further without severe training. Training was considered better (on an analogue scale) in the QR group (P<0.05). Postrun muscular pain, cramps, localized pain, straining and the recovery time, were all considered better with QR (P<0.05). Plasma free radical (PFR) values 1 hour after the final run were, on average,16.98% higher in controls (P<0.05), indicating a higher level of oxidative stress. Higher levels of PFR are associated with a slower recovery. All routine blood tests were normal at inclusion and after the final triathlon. After the final test run triathlon athletes using QR had a lower increase of UBR and LDH (indicator of hemolysis). These two tests were significantly increased in controls (P<0.05) but not in the Robuvit® group. Robuvit® supplementation improved training, results and decreased hemolysis.

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.

Improvement in symptoms and cochlear flow with pycnogenol in patients with Meniere's disease and tinnitus.

AIM: The aim of this supplement registry was to evaluate the efficacy of the Pycnogenol® in improving cochlear flow and symptoms in a 6-month follow-up for patients with Meniere's disease (MD), tinnitus and cochlear hypoperfusion. METHODS: Main signs/symptoms were considered: Spontaneous vertigo, positional vertigo, hearing loss, tinnitus, pressure in the ear, unsteady gait, associated clinical problems, alterations in daily life. All subjects were managed with the best available management (BM); one group used the supplement Pycnogenol (150 mg/day). Cochlear flow and tinnitus were also evaluated. Out of 120 patients incuded in the registry, 55 used Pycnogenol and 52 (controls) were managed only with BM. RESULTS: There was a more significant improvement in all registry items at 3 and 6 months in the Pycnogenol group (P<0.05). The number of lost working days was lower in the Pycnogenol group. At 3 months, 45.4% of subjects using Pycnogenol were completely asymptomatic in comparison with 23.07% of controls. At 6 months 87.3% of the Pycnogenol subjects were asymptomatic compared with 34.6% of controls. Cochlear flow velocity was significantly better (higher flow, higher diastolic component) in the Pycnogenol group (P<0.05). The subjective tinnitus scale decreased in both groups (P<0.05); the decrease was more significant in Pycnogenol subjects (P<0.05) at 3 and 6 months. CONCLUSION: Symptoms of Meniere's disease, flow at cochlear level and tinnitus improved in Pycnogenol subjects in comparison with best management.

Evaluation of the effects of supplementation with Pycnogenol® on fitness in normal subjects with the Army Physical Fitness Test and in performances of athletes in the 100-minute triathlon.

AIM: The aim of this registry study was to evaluate the effects of Pycnogenol® (French pine bark extract) on improving physical fitness (PF) in normal individuals using the Army Physical Fitness Test (APFT). The study evaluated the efficacy of Pycnogenol, used as a supplement, in improving training, exercise, recovery and oxidative stress. METHODS: The study was divided into 2 parts. In PART 1 (Pycnogenol 100 mg/day), the APFT was used to assess an improvement in PF during an 8-week preparation and training program. In PART 2 (Pycnogenol 150 mg/day), the study evaluated the effects of Pycnogenol supplementation in athletes in training for a triathlon. RESULTS: PART 1. There was a significant improvement in both males and females in the 2-mile running time within both groups, but the group using Pycnogenol (74 subjects) performed statistically better than controls (73 subjects). The number of push-ups was improved, with Pycnogenol subjects performing better. Sit-ups also improved in the Pycnogenol group. Oxidative stress decreased with exercise in all subjects; in Pycnogenol subjects the results were significantly better. PART 2. In the Pycnogenol group 32 males (37.9; SD 4.4 years) were compliant with the training plan at 4 weeks. In controls there were 22 subjects (37.2;3.5) completing the training plans. The swimming, biking and running scores in both groups improved with training. The Pycnogenol group had more benefits in comparison with controls. The total triathlon time was 89 min 44 s in Pycnogenol subjects versus 96 min 5 s in controls. Controls improved their performing time on average 4.6 minutes in comparison with an improvement of 10.8 minutes in Pycnogenol subjects. A significant decrease in cramps and running and post-running pain was seen in the Pycnogenol group; there were no significant differences in controls. There was an important, significant post-triathlon decrease of PFR one hour after the end of the triathlon with an average of -26.7, whereas PFR in controls increased. In Pycnogenol subjects there was a lower increase on oxidative stress with a faster recovery to almost normal levels (<330 for these subjects). These variations in PFR values were interpreted as a faster metabolic recovery in subjects using Pycnogenol. CONCLUSION: This study opens an interesting new application of the natural supplementation with Pycnogenol that, with proper hydration, good training and nutritional attention may improve training and performances both in normal subjects and in semi-professional athletes performing at high levels in difficult, high-stress sports such as the triathlon.

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.

Improvement in cochlear flow in patients with tinnitus with the complex supplement Acustop: a product evaluation.

AIM: Patients with tinnitus constitute a very large group without a real, specific therapeutic solution. With noninvasive, color duplex it is possible to measure flow in the cochlear artery and to follow duplex flow changes due to treatments in most patients. The aim of this preliminary evaluation was to study flow variations in patients with "mild-to-moderate" tinnitus, possibly associated to cochlear hypo-perfusion, after administration of Acustop (used as a food supplement). The aim was to improve cochlear flow decreasing the level of tinnitus. METHODS: Patients with "mild-to-moderate", "idiopathic", monolateral tinnitus, present for at least 4 weeks were included; no vertigo or important hearing loss had been observed. The origin of tinnitus had been sudden (hours or days). The tinnitus was associated to a decrease in cochlear flow measured by color Duplex at the affected ear. A group of 42 patients was evaluated; 25 used Acustop; there were 17 controls (follow-up only). Groups were comparable for their clinical problem and other details. The average duration of treatment was 4 weeks. RESULTS: No side effects were observed and no drop-outs were recorded. Flow velocity at the level of the affected inner ear was significantly lower (both the diastolic and systolic components; P<0.05) in comparison with the other ear. This was considered an indication of the vascular origin of the tinnitus. With Acustop treatment there was a significant improvement in systolic (P<0.05) and diastolic flow velocity (P<0.05). The increase in flow velocity was not significant in controls. An analogue scale line was used to measure symptoms in the Acustop group: it was 8.2;2 at inclusion; it decreased to 3.1;1.5 at 4 weeks (P<0.05). The score was 8.4;2 in controls at inclusion; at 4 weeks the score was 7.1;2.2 (not significant). Tinnitus scale: the value at inclusion of the tinnitus scale in the Acustop group a was 8.5;1.1 versus 8.3;1.2 in controls. After 4 weeks the score was 3.1;1.1 (P<0.05) in the Acustop group vs 7.2 in controls; the difference between the two groups was significant; P<0.025). CONCLUSION: In conclusion, these results suggest that in selected patients with tinnitus and altered inner ear perfusion Acustop appears to be effective in relieving tinnitus possibly by improving cochlear flow. More studies should be planned to evaluate better the potential applications of Acustop in this very interesting field. This clinical problem affects a large number of patients, without a real therapeutic solution at the moment, decreasing their quality of life and their performing abilities.

Improvement in cochlear flow with Pycnogenol® in patients with tinnitus: a pilot evaluation.

AIM: The aim of this preliminary evaluation was to study the efficacy of Pycnogenol in improving cochlear flow in patients with mild-to-moderate tinnitus present for at least two weeks (without vertigo or important hearing loss), possibly associated with cochlear hypo-perfusion. METHODS: Patients with mild-to-moderate, idiopatic, monolateral tinnitus present for at least 2 weeks were included; no vertigo or important hearing loss had been found in a specific examination. The origin of tinnitus had been sudden (hours or days). Fifty-eight patients used Pycnogenol: 24 used 150 mg/day (group A; mean age 43.2+/-4.3) and 34 patients 100 mg/day (group B: mean age 42.4+/-3.8). Controls included 24 patients (mean age 42.3+/-4.5). The groups were comparable for their clinical problem and age and sex. The average duration of treatment was 34.3+/-3.1 days. No side effects were observed and no drop-outs occurred. RESULTS: The variations in cochlear flow velocity (in cm/s at the cochlear artery), at inclusion and after four weeks of treatment indicated that flow velocity at the level of the affected ear was significantly lower (both the diastolic and systolic components; P<0.05) in comparison with the other ear. The treatment favored an improvement in systolic (P<0.05) and diastolic flow velocity (P<0.05) in the two treatment groups A+B. The increase in flow velocity was very limited and not significant in controls. CONCLUSION: These results suggest that in selected patients with tinnitus and altered perfusion, Pycnogenol is effective in a short period of time in relieving tinnitus symptoms by improving cochlear blood flow. The effect is more pronounced with higher Pycnogenol dosage. More studies should be planned to better evaluate the pathology and potential applications of Pycnogenol in a larger number of patients who are currently without a real therapeutic solution.

Improvement of signs and symptoms of chronic venous insufficiency and microangiopathy with Pycnogenol: a prospective, controlled study.

The aim of this study was to evaluate the clinical efficacy of standardized French maritime pine bark extract Pycnogenol in patients with severe chronic venous insufficiency (CVI). 98 subjects with symptomatic CVI and edema were randomly assigned to one group treated with 150 mg Pycnogenol a day only, another group with stockings only and a third group with both Pycnogenol and elastic stockings. The average ambulatory venous pressure (AVP) at inclusion was 58+/-7 mm Hg (range 48-60 mm Hg) with a refilling time (RT)<12 s (average 7+/-2 s). The duration of the disease was on average 6.0+/-3.1 years. There were no differences in AVP or RT among the 3 groups at inclusion and microcirculatory and clinical evaluations were comparable. After 8 weeks treatment there was a significant decrease of rate of ankle swelling, resting flux, transcutaneous pO(2) and clinical symptom scores in all groups with significantly better results for the combination treatment. Pycnogenol alone was more effective than compression alone for all parameters (p<0.05). No side-effects were observed; compliance and tolerability were very good. This study corroborates a significant clinical role for Pycnogenol in the management, treatment and control of CVI also in combination with compression.

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.

Pycnogenol may alleviate adverse effects in oncologic treatment.

AIM: A large variety of adverse reactions are well known to frequently occur during chemotherapy and radiotherapy in oncology. Specific medications exist to target individual side effects. The aim of this study was to explore in a pilot trial whether supplementation with French maritime pine bark extract Pycnogenol could alleviate side effects and improve patient's quality of life. METHODS: Cancer patients who previously underwent surgery and who were in view of their pathology in relatively good condition, both physically and psychologically, were recruited for this study and divided into two groups. These patients received their first cycle of radiotherapy or chemotherapy, which lasted from 10 days up to 1 month. Then one group of patients received 150 mg Pycnogenol, the control group comparable placebo in a single-blinded fashion. The authors studied the occurrence of side effects and made attempts to judge their severity on a semi-quantitative visual analogue scale over a 2 months period starting after patients completed their first cycle of chemo- or radiotherapy, respectively. RESULTS: Twenty five radiotherapy patients receiving Pycnogenol showed a decreased frequency of essentially all investigated side-effects as compared to 21 patients receiving placebo, though in many categories the difference was limited. The most apparent improvements of acute side effects related to decreased soreness and ulceration in the mouth and throat as well as less dryness of the mouth and the eyes. A decreased incidence of nausea /vomiting, diarrhoea, edema and weakness was noticed, which was reflected by semi-quantitative evaluation suggesting that severity was only half or even less pronounced than in the control group. Only one case of deep vein thrombosis occurred in the Pycnogenol group whereas 2 cases of superficial vein thromboses and one case of deep vein thrombosis occurred in the control group (2.9% vs 10%). Thirty four chemotherapy patients were supplemented with Pycnogenol and another 30 patients were in the control group. For all patients this was the first chemotherapy treatment period. The Pycnogenol group presented with a lowered incidence of all investigated side effects as compared to the control group, though in many cases to a limited extent. The most prominent improvements were found for nausea, vomiting, diarrhoea and weight loss. Semi-quantitative evaluation showed that here again symptom severity was half or less pronounced than in the control group. Various further symptoms improved such as cognitive impairment and also cardiotoxicity and neutropenia. Effects on anemia could not be investigated as several patients received erythrocyte transfusion. In the Pycnogenol group one case of superficial vein thrombosis was indentified while 3 cases of superficial vein thromboses and one deep vein thrombosis were detected in the control group (4% vs 19%). In both chemotherapy and radiotherapy patients Pycnogenol lowered the requirement for medication to address side effects. This was reflected by less days of hospitalisation the patients required. The authors did not investigate a possible interference with the anti-neoplastic efficacy of chemo- and radiotherapy. This possibility requires attention in future studies with Pycnogenol. From their previous clinical experience the authors suggest that alleviation of side effects described in this study results from Pycnogenol activities related to endothelial protection, and anti-inflammatory anti-edema activities. CONCLUSION: The results of this pilot trial warrant further prospective studies with larger number of patients to validate benefits more specifically with regard to type of malignancy and treatment regimen.

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.

Jet-lag: prevention with Pycnogenol. Preliminary report: evaluation in healthy individuals and in hypertensive patients.

This study was conducted with the aim of showing the effects of Pycnogenol on controlling jet-lag symptoms. Oral Pycnogenol, 50 mg tablets 3 times/die, for 7 days starting 2 days prior to the flight was used. The study was divided into two separate parts. In study 1 the most common complaints of patients with jet-lag were evaluated with a rating scale consisting in of a scoring system. In study 2 a brain CT scan was performed after the flight in order to assess minimal brain edema (MBE) in association with typical signs and symptoms, observed in previous published flight studies. Study one included 38 subjects treated with Pycnogenol and 30 controls. The symptomatic jet-lag related total score was significantly lower (indicating a lower level of jet-lag) in the Pycnogenol group. The average duration of any jet lag symptom following the flight was significantly reduced from 39.3 (SD=0.8) hours in controls to an average of 18.2 (SD=3.3) hours in the Pycnogenol group (P<0.05). Study 2 included 34 subjects treated with Pycnogenol and 31 controls. The main observation was the brain CT scan performed within 28 hours after the end of the flight. The difference between the Pycnogenol and the control groups was statistically significant (P<0.05) for all items assessed including the cerebral edema score obtained by CT scan. The short-term memory was significantly altered in the control group and associated to edema and swelling of the lower limbs. The score (and the level of edema) was comparatively higher in a subgroup of hypertensive subjects in the control group. Minor alterations of cardiac function were observed in association with de-stabilisation of blood pressure. Fatigue was also significantly higher in the control group in comparison with the Pycnogenol group. A number of spontaneously reported symptoms was also scored and there was a statistically significant difference (P<0.05) between the Pycnogenol and control groups. In conlusion, Pycnogenol was useful to control jet-lag and minimal brain edema.

LINFAVENIX: improvement of signs and symptoms of chronic venous insufficiency and microangiopathy.

The aim of this independent study was to demonstrate the rapidity of the efficacy of an oral venotropic compound (Linfavenix, including natural elements) in patients with chronic venous insufficiency (CVI). Two groups of patients with chronic venous insufficiency (CVI) ankle swelling) were treated with Linfavenix or with below-knee elastic compression. The average ambulatory venous pressure (AVP) at inclusion (both groups)was 56.2 (range 48-55) with a refilling time (RT) shorter than 10 seconds. These parameters indicated a severe level of venous hypertension. There were no significant differences in AVP and RT between the two groups. The two groups of subjects with CVI were comparable; in the Linfavenix group there were 14 patients (age 44.5; sd 4; range 34-55; 7 females); in the elastic compression group there were 12 patients (45.4;5; range 36-56; 7 females). The clinical picture and microcirculatory parameters at inclusion were comparable. RF was comparable at inclusion in the two groups. At two weeks, the differences in RF (between goups) were not significant (the flux decreased in both groups, indicating improvement) while at 4 weeks the difference was larger (but non significant between the two groups) with a significant decrease in RF in the Linfavenix group. The RAS was also comparable at inclusion. Both groups had a significant decrease at 2 and 4 weeks. The decrease produced by Linfavenix after 4 weeks in RF was larger and significant (p<0.05) in comparison with the elastic compression group. Also the differences observed in ASLS were significant in both groups with an important, significant difference in favour of Linfavenix at 4 weeks (op<0.05) visibile as edema reduction. The decrease in edema was relevant in both groups at 2 (p<0.05) and 4 weeks (p<0.05) with a minimal but significant difference (p<0.05) between the Linfavenix and the elastic compression group. These variations in microcirculatory parameters indicate that the treatment with Linfavenix is, in its microcirculatory efficacy, at least comparable than elastic compression with is considered a standard therapeutic option in these patients. A significant level of improvement was reached with Linfavenix, in most patients (10/14) at 2 weeks for RF, at 7 days for the RAS and also at 2 weeks in almost all patients (13/14) considering ASLS and edema. No side effects due to treatment were observed. Compliance and tolerability were very good (no patient had to stop treatment; there were no drop-outs). In conclusion venous microangiopathy and edema were improved by the treatment with Linfavenix (better in comparison with compression) in a few days.

Rapid relief of signs/symptoms in chronic venous microangiopathy with pycnogenol: a prospective, controlled study.

The aim of this study was to investigate the clinical efficacy of oral Pycnogenol (Horphag Research Ltd, UK) in patients with severe chronic venous insufficiency. Patients with severe venous hypertension (chronic venous insufficiency, ankle swelling) and history of venous ulcerations were treated with Pycnogenol. Patients received oral Pycnogenol (50 mg capsules, 3 times daily for a total of 150 mg daily) for 8 weeks. A group of 21 patients was included in the treatment group and 18 equivalent patients were observed as controls (no treatment during the observation period). All 21 patients (age 53 years; range, 42-60 years; M:F=11:10) in the treatment group completed the 8-week study. Also the 18 controls completed the follow-up period. There were no drop-outs. The average ambulatory venous pressure was 59.3 (SD 7.2; range 50-68) with a refilling time shorter than 10 seconds (average 7.6; SD 3). There were no differences in ambulatory venous pressure or refilling time between the treatment and control patients. The duration of the disease-from the first signs/symptoms-was on average 5.7 years (SD 2.1). At 4 and 8 weeks, in all Pycnogenol-treated subjects, microcirculatory and clinical evaluations indicated a progressive decrease in skin flux, indicating an improvement in the level of microangiopathy; a significant decrease in capillary filtration; a significant improvement in the symptomatic score; and a reduction in edema. There were no visible effects in controls. In conclusion, this study confirms the fast clinical efficacy of Pycnogenol in patients with chronic venous insufficiency and venous microangiopathy. The study indicates the significant clinical role of Pycnogenol in the management, treatment and control of this common clinical problem. The treatment may be also useful to prevent ulcerations by controlling the level of venous microangiopathy.

Improvement of diabetic microangiopathy with pycnogenol: A prospective, controlled study.

The aim of this study was to investigate the clinical efficacy of oral Pycnogenol (Horphag Research Ltd, United Kingdom) in patients with diabetic microangiopathy. Patients without a history of diabetic ulcerations were treated with Pycnogenol. Patients received oral Pycnogenol (50 mg capsules, 3 times daily for a total of 150 mg daily for 4 weeks). A group of 30 patients was included (severe microangiopathy); 30 comparable patients were observed as controls (no treatment during the observation period). All patients (age, 59 years; range, 55-68 years; male:female = 18:12) included in the treatment group completed the 4-week study. Also, all controls completed the follow-up period. There were no drop-outs. All included subjects had signs and symptoms of diabetic microangiopathy. The duration of diabetes-from the first signs/symptoms--was on average 7.5 years (SD = 3). After 4 weeks, microcirculatory and clinical evaluations showed a progressive decrease in skin flux at rest in the foot (indicating an improvement in the level of microangiopathy), a significant decrease in capillary filtration, and a significant improvement in the venoarteriolar response in all treated subjects. There were no visible effects in controls except a slight reduction in skin flux at rest in the foot. Treatment was well tolerated in both groups. In conclusion, this study confirms the clinical efficacy of Pycnogenol in patients with diabetic microangiopathy. The study indicates the clinical role of Pycnogenol in the management, treatment, and control of this common clinical problem. The treatment may be also useful to prevent diabetic ulcerations by controlling the level of microangiopathy.

Diabetic ulcers: microcirculatory improvement and faster healing with pycnogenol.

Diabetic microangiopathy leads to lower limb ulcers that are very slow to heal. Pycnogenol was evaluated on diabetic ulcers in a controlled trial. Ulcer medications were used in 4 groups (30 patients): (1) systemic Pycnogenol and local application; (2) local Pycnogenol only; (3) oral Pycnogenol; and (4) medications only (control group). Ulcerated areas and symptom scores were more reduced with the combined oral and local treatment (P < .05). Oral and local treatment were less effective, but still improved compared with the controls. Combined treatment produced 89% complete healing at 6 weeks versus 84% with local treatment and 85% with oral treatment; healing in controls was 61%. The combined treatment group and oral only group had better microcirculation after the combined treatment. Combined local and systemic application of Pycnogenol may offer a new treatment of diabetic ulcers. Local treatment also speeds ulcer healing.

Comparison of Pycnogenol and Daflon in treating chronic venous insufficiency: a prospective, controlled study.

The aim of this study was to investigate the clinical efficacy of oral Pycnogenol (Horphag Research Ltd., UK) in patients with severe chronic venous insufficiency (CVI) in comparison to the combination of diosmin and hesperidin (Daflon, Servier, France). A group of 86 patients with severe chronic venous insufficiency (CVI), venous hypertension, ankle swelling) and previous history of venous ulcerations received either oral Pycnogenol (capsules) 150 mg or 300 mg daily for 8 weeks or Daflon, 1,000 mg/day. All patients completed the study without dropouts. At the end of the study, microcirculatory results indicated: a progressive decrease of skin flux at rest (RF); a significant decrease in capillary filtration (RAS); an improvement in the symptomatic venous score (ASLS); a reduction in edema; a significant improvement (increase) in pO(2) and a decrease in pCO(2) in the Pycnogenol group. A significant level of improvement was reached after 4 weeks of treatment in most patients (p < .05) of the Pycnogenol group while clinical improvement was significant only in 6 subjects in the Daflon group. The positive effects of treatment with Pycnogenol after 8 weeks were significantly larger in comparison with the Daflon group. In conclusion, this study confirms the fast clinical efficacy of Pycnogenol in patients with chronic venous insufficiency and venous microangiopathy and its superiority-considering the evaluated parameters-to the combination of diosmin and hesperidin.