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Background: Centellicum ® , a standardized Centella Asiatica extract, has been used orally for fibrosis and scar prevention. The main aim of this 2-month registry pilot study was the reduction of visible, significant scars and keloids after suturing traumatic wounds with irregular edges (lacerations), using Centellicum ® ., Methods: The effects of oral Centellicum ® (450 mg/day; 2 capsules) and a standard management (SM) on wound healing were compared with the effects of a control group that used only the standard management., Results: Forty-eight otherwise healthy male subjects with lacerations requiring suturing were included in the study. 25 took Centellicum ® in addition to the standard management and 24 followed the standard management only. No side effects were observed with the supplement. Centellicum ® supplementation showed very good tolerability and compliance with 98% of the capsules correctly used. The two groups of otherwise healthy male subjects with lacerations were considered comparable at inclusion and there were no dropouts. No infections were observed. At 60 days, the scar dimensions were significantly smaller in the supplemented group (P<0.05). The elevation of the scar above the surrounding, non-affected skin, was also significantly reduced in the Centellicum ® group compared to controls (P<0.05). Local pain levels were significantly lower (P<0.05) in the supplement group at 60 days. Additionally, the scar redness score was significantly lower in the supplement group compared to controls (P<0.05) by the end of the study. The incidence of initial keloid formation was significantly lower in the supplemented subjects at 60 days, as determined by finger-point pressure palpation and high-resolution ultrasound (P<0.05). Skin flux, as measured by laser Doppler flowmetry (indicating hypervascularization due to local inflammation) was lower (P<0.05) with Centellicum ® at the end of the study. Inflammation, assessed via thermography (hot spots on the healing skin) was less visible and reduced in most areas in the supplement group (P<0.05) in comparison with the control group. Plasma oxidative stress was significantly lower in the Centellicum ® group at the end of the study (P<0.05)., Conclusions: Oral Centellicum ® intake over 2 months improved healing of lacerations and reduced scarring, fibrosis and keloids at the level of the lesions. A larger study setup with more patients and with a prolonged study duration is needed to confirm these initial results.

Background: The aim of this registry study was to evaluate the effects of Pycnogenol ® and Centellicum ® (PYCE) on skin perfusion and skin elasticity in healthy women over a period of 4 weeks., Methods: The supplemented women used 150 mg of Pycnogenol ® and 450 mg of Centellicum ® daily. The supplemented group used the combination PYCE daily for 4 weeks and followed the standard management (SM) in addition. A control group used only the SM. SM for all subjects included a healthy diet (low levels of NaCl, low sugar, low calories), vitamin supplementation (C, E, B), daily mild outdoors exercise, regular washing with neutral soap; the same non-clinical, non-specific hydrating cream (Nivea) was used once daily., Results: Sixty-three women completed the registry study. Thirty women using the PYCE combination and 33 women in the control group. The groups were comparable at baseline. No clinical condition was observed during the registry; no drug was used. There were no side effects or tolerability problems with the supplements. After 4 weeks, ultrasound elastosonography showed that skin elasticity significantly improved with the PYCE combination (P<0.05) without significant changes in the control group. In parallel, transcutaneous skin PO2 increased significantly with PYCE compared to controls and transcutaneous skin PCO2 decreased significantly compared to controls (P<0.05). This showed that skin oxygenation and nutrition improved with PYCE. Skin hydration also significantly improved with PYCE (P<0.05) in comparison with controls. Skin flow, indicating skin blood perfusion (thermoregulatory flow), assessed by laser Doppler flowmetry significantly improved over 4 weeks compared to controls (P<0.05). More specifically, the most superficial part of the flow, in the most superficial layer of the skin, corresponding to the nutritional blood flow, significantly improved with the combination PYCE compared to controls (P<0.05). Skin and tissue elasticity are crucial in surgery for healing, scarring, and wound closure. Reduced elasticity can lead to irregular or delayed healing. This preliminary concept study suggests that PYCE supplementation enhances skin elasticity, perfusion, and nutrition, with visible effects seen in just 4 weeks., Conclusions: This preliminary, concept study indicates that skin elasticity, skin perfusion, and skin nutrition improved with the supplementation of PYCE and the effects of PYCE were visible after only 4 weeks. A longer observation period should be considered in future studies. In conclusion, this pilot concept study shows a significant activity of the combination Pycnogenol ® and Centellicum ® on skin elasticity over a short period of supplementation.

Background: The aim of this 4-week pilot registry, supplement study was to assess the effects of Pycnogenol ® compared to a standard management on hand osteoarthritis associated with pain. As Pycnogenol ® decreases inflammation and pain, chronic use of drugs, causing side effects may be reduced., Methods: The registry patients included suffered finger pain associated with hand osteoarthritis All subjects used a standard management (SM). A supplementary group additionally used 150 mg Pycnogenol ® per day. In addition, a retrospective group with 40 comparable subjects using oral diclofenac was used for comparison. Forty-two subjects with hand osteoarthritis completed the study. The registry patients were former sport professionals, fishermen and subjects working with their hands in a common manual activity. 22 subjects took Pycnogenol ® in addition to standard management and 20 subjects followed the standard management only and served as controls., Results: The two groups were comparable at inclusion. No subject had to stop supplementation or the SM. No side effects were observed. After 4 weeks, spontaneous pain in the morning and pain after work were significantly reduced with Pycnogenol ® supplementation compared to controls (P<0.05). Residual pain at rest in the evening was significantly improved after 4 weeks with the supplement compared to controls (P<0.05). The number of subjects requiring pain medication during the 4-week study period was significantly lower in the supplement group (2/22) compared to controls (8/20) (P<0.05). Hand dynamometry results show significant improvement in hand-finger strength (due to decreased pain and stiffness) with the supplement compared to controls (P<0.05). At inclusion, all subjects presented hyperthermic joints, 2°C higher than the surrounding tissues as shown by thermography. After 4 weeks, the number of subjects with hyperthermic joints was lower in the Pycnogenol ® group than in controls (P<0.05). Both nonspecific markers of inflammation (ESR and C-reactive protein levels in blood) were significantly lower after 4 weeks in the Pycnogenol ® group than in controls (P<0.05). Other routine blood tests were normal at inclusion and at the end of the study. Within 4 weeks, plasma oxidative stress decreased by 14.4% (P<0.05) in the Pycnogenol ® group vs. 5.5% in the control group. The retrospective comparison with a group of 40 comparable subjects using oral diclofenac showed that after 4 weeks, the efficacy of Pycnogenol ® on improving pain in the morning, after work and in the evening, on hand-finger strength and on decreasing C-reactive protein was significantly higher (P<0.05) than in the diclofenac group (comparable, non-parallel group, CNPG)., Conclusions: In conclusion, supplementation with Pycnogenol ® was well tolerated and effectively controlled pain while improving grip strength in patients with hand osteoarthritis. All supplement subjects showed an improved operativity.

Background: The aim of this supplement registry study was to evaluate the efficacy of Pycnogenol ® in controlling signs and symptoms of chronic venous insufficiency (CVI), diabetic microangiopathy and microcirculatory parameters - in diabetic patients with CVI and microangiopathy. These CVI patients are eligible for medical procedures as their incompetent superficial veins can be treated with repeated sclerotherapy and or local surgery according to needs., Methods: During this registry study, only non-interventional managements were used. The effects of the use of elastic compression with standard management (SM) was compared to Pycnogenol ® intake (150 mg/day) and SM, without using elastic compression for 8 weeks., Results: Fifty-eight diabetic patients with CVI completed the study with 28 subjects supplemented with Pycnogenol ® and 30 in the control group. The two groups completing 8 weeks were comparable at baseline. After 8 weeks, no side effects were observed; the compliance was optimal with >98.5% of the supplement capsules correctly used. The tolerability to stockings was lower (73% of stockings were not fully used for the whole day). There were no dropouts. Venous pressures were comparable in the two groups at baseline. Microcirculatory and clinical measurements of the patients were comparable at inclusion. After 8 weeks, the differences between Pycnogenol ® and elastic compression were statistically significant for skin resting flux (RF), rate of ankle swelling (RAS), transcutaneous PO2 and PCO2 indicating a significant improvement in microcirculatory perfusion with Pycnogenol ® in comparison with elastic compression. In parallel, clinical symptoms assessed by the Composite Symptom Score (CSS), the venous Clinical severity Score (VCSS) and the Venous Disability Score (VDS), were significantly lower in the Pycnogenol ® group than in the compression group, indicating a significant clinical effect of Pycnogenol ® compared to elastic compression (P<0.05). Pycnogenol ® showed important antioxidant properties and lowered oxidative stress as seen also in previous studies., Conclusions: This registry study confirms the clinical and microcirculatory efficacy of Pycnogenol ® in CVI in diabetics. The study indicates the significant supplementary, clinical role of Pycnogenol ® in the management of this common clinical condition over a short period of time, possibly preventing ulcerations.

Background: Chronic venous insufficiency (CVI) is the consequence of venous valve reflux and/or venous flow obstruction and resulting venous hypertension in the lower extremities. The aim of this prospective supplement registry study was to evaluate the efficacy of compression stockings or Pycnogenol ® in controlling symptoms and edema in CVI and their efficacy on microcirculatory parameters., Methods: Two comparable groups of 30 subjects with CVI were observed for 4 months., Results: Elastic compression was less tolerated than Pycnogenol ® with 12 subjects being unable to follow the compression routine. No side effects due to supplementation were observed; tolerability of the supplementation was optimal. Ambulatory venous pressure (AVP) and refilling time (RT) at inclusion indicated a significant increase in venous pressure and reflux (refilling time <16 seconds). AVP and RT did not change after 4 months. Microcirculatory and clinical measurements were comparable at inclusion between the 2 groups. After 4 months, skin resting flux (RF) and skin PO2-PCO2 were significantly improved with Pycnogenol ® compared to compression (P<0.05). The significant increase in skin PO2 and the decrease in PCO2 after Pycnogenol ® intake were ascribed to the decrease in the abnormally high skin resting flux, a sign of better perfusion and skin nutritional supply. Pycnogenol ® reduced leg volume, on average by 18.3% in the evening compared to 4.4% of reduction with compression (P<0.05) showing an important effect on edema. The venous Clinical Severity Score (VCSS) and the composite symptom score (CSS) decreased significantly in the Pycnogenol ® group compared to compression, indicating a better improvement in microcirculatory perfusion and nutritional supply produced by the supplementation of Pycnogenol ® in comparison with compression. Pycnogenol ® significantly improved microcirculation and clinical symptoms in comparison with compression. The decrease in local oxidative stress (OS) at the distal perimalleolar region with Pycnogenol ® was significant in comparison with compression (P<0.05). A lower local OS is an important metabolic indication of a better capillary perfusion with better nutritional exchanges. At the end of the registry study, four small ulcerations and skin breaks in four limbs (between 3 and 5 mm of maximum diameters) were observed in the compression group. No ulcerations or skin breaks were observed in the Pycnogenol ® group., Conclusions: Pycnogenol ® relieved edema, improved microcirculation in CVI patients and reduced stationary, interstitial fluid in comparison with compression. Most symptoms of CVI are associated with interstitial water retention; the presence of extra fluid in limb tissues alters perfusion and nutrient supply. Pycnogenol ® supplementation reduced water and fluid accumulation in CVI limbs and improved microcirculation and local oxidative stress thus showing important anti-edema effects.

Background: Hemorrhoids are a common problem associated with symptoms, like swelling, local thrombosis and generally with a decreased quality of life, often in otherwise healthy subjects. Hemorrhoids can be classified by grades (I to IV) according to their severity. In this registry study subjects treated with excisional hemorrhoidectomy (EH) for the first time, were included. After surgery, edema tends to complicate surgical areas causing relevant symptoms. Most hemorrhoids symptoms are related to alterations in bowel habits. Increase in diet fibers to avoid constipation, exercise, and limiting straining reduce recurrence after surgery., Methods: The aim of the registry study was to evaluate the effects of Pycnogenol ® (Horphag Research, Geneva, Switzerland) on relieving postoperative symptoms following hemorrhoidectomy. Pycnogenol ® 150 mg/day was used between one month before surgery up to one month after surgery. The main postoperative symptoms were scored., Results: Thirty-eight subjects completed the 60-day supplement registry study. Eighteen subjects were supplemented with Pycnogenol ® in addition to the standard management (SM) and 20 subjects only received SM and were considered as controls. The two groups were comparable for age, sex and main symptoms distribution and for their clinical characteristics at inclusion. No other disease was present. The scores for pain, discomfort, and constipation were significantly lower with the supplement compared to controls (P<0.05) 10 and 30 days after surgery. In addition, the quality-of-life score was higher with Pycnogenol ® (P<0.05) while bleeding (minimal, not clinically evaluable) and a possible residual anal stenosis (requiring a longer period of observation) were barely observed. A satisfactory return to activity was observed 30 days after surgery in the 18 subjects using Pycnogenol ® , and in only 15 out of 20 patients (75%) in the control group (P<0.05). All Pycnogenol ® subjects were able to drive and perform daily tasks in comparison with 14 out of 20 subjects in the control group. The proportion of patients that took pain medication from day 10 to 30 post-surgery was significantly lower in the Pycnogenol ® group than in controls (P<0.05)., Conclusions: In this post-surgical pilot, registry study, Pycnogenol ® was effective in preventing and controlling postoperative symptoms after hemorrhoidectomy. To confirm the results, more cases are needed, including different surgical methods and clinical conditions. Mucosal and cutaneous edema and perianal swelling - generally seen after surgery - seem to be clearly reduced with Pycnogenol ® and the supplement intake was associated with a more regular and pain-controlled convalescence and healing.

Background: The aim of this registry supplement study was to evaluate the effects of the oral supplement Pycnogenol ® on possible skin discolorations or other minor skin changes after varicose vein sclerotherapy in comparison with a standard management (SM)., Methods: One hundred sixty-one subjects completed the study. 84 took Pycnogenol ® from the day before sclerotherapy for 12 weeks and followed SM. 77 followed SM only and served as controls. 420 injection sites were followed-up in the Pycnogenol ® group and 431 in the control group. The number of injected veins (using only Aetoxysklerol) was on average 4-8 veins/patient. No side effects were observed for the SM or for supplementation. Pycnogenol ® supplementation showed a good tolerability. The two management groups were comparable for age, sex and veins distribution at inclusion., Results: After 12 weeks, skin discoloration assessed by a skin staining score was generally significantly lower and less frequent (P<0.05) with Pycnogenol ® with a score of 0.4±0.2 compared to controls (with a score of 2.1±0.4). In addition, the number of stains per treated vein was significantly lower in the Pycnogenol ® group than the control group., Conclusions: Varicose vein sclerotherapy is a minimally invasive procedure almost without complications. Pycnogenol ® intake appears to improve healing and prevent skin discolorations after injection of the sclerosing agent. To verify this effect of Pycnogenol ® , more studies for a longer period are needed.

Background: The aim of this registry study was to evaluate the efficacy of Pycnogenol ® in controlling signs/symptoms and temporary impairment of cognitive function (COFU) associated with jet lag. Previous flight studies have shown a decrease in the level of jet lag symptoms with Pycnogenol ® . The control of jet lag signs/symptoms appeared to be correlated with flight-related microangiopathy and peripheral edema. Pycnogenol ® - a standardized extract from the bark of French maritime pine - has significant antiedema, anti-inflammatory and antioxidant properties., Methods: A group of subjects flying east in economy class for 10-12 hours used Pycnogenol ® 150 mg/day and a similar group without supplementation served as controls. A subgroup of mild hypertensive subjects using a single ACE inhibitor was also included., Results: One hundred twenty-seven subjects completed the study. Of the participants, 48 were aviation professionals like pilots, flight attendants or air company staff - 24 of them took Pycnogenol ® and 24 served as controls. Forty-seven study participants were frequent flyers and non-staff professionals, 25 of which took Pycnogenol ® and 22 served as controls. In addition, a group of 32 subjects with mild hypertension was included, 16 took Pycnogenol ® and 16 served as controls. No side effects and a good tolerability were observed. The registry groups were comparable for baseline characteristics. Eastbound flights' duration was 11.22±0.4 hours in supplemented subjects and 11.14±0.32 in controls. Dropouts were due to logistical problems. Post flight Visual Analogue Scale (VAS) scores were significantly lower in all Pycnogenol ® groups, including hypertensives for all signs and symptoms of jet lag compared to controls, showing prevention and improvement of jet lag symptoms. The duration of any sign/symptom of jet lag with Pycnogenol ® intake was significantly shorter (P<0.05) post-flight compared to controls (P<0.05). The number of nights of altered/disturbed sleep was also lower in the Pycnogenol ® groups compared to controls. Leg edema was present in almost all subjects with different degrees especially in the hypertensive group. The increase in ankle circumference before and after flight was significantly lower with Pycnogenol ® compared to controls (P<0.05). After the flight, average scores of the single COFU tasks were significantly higher in the Pycnogenol ® groups compared to controls, showing preserved cognitive function., Conclusions: In conclusion, in this registry study Pycnogenol ® was effective in preventing jet lag-related symptoms and preserving cognitive functions without tolerability problems. These observations should be tested in a larger group of subjects including complex individuals prone to edema (i.e. diabetics, hypertensive or older patients).

Background: The aim of this registry study was to evaluate the progress of osteoarthrosis (OA) symptoms after the intake of a new standardized supplement combination (Pycnogenol ® + Centellicum ® , both Horphag Research) in a group of subjects with OA., Methods: Supplemented subjects took daily 150 mg Pycnogenol ® + 450 mg Centellicum ® for 6 months. Another comparable group of subjects using only standard management (SM) was included as a reference., Results: Forty-five subjects with a mean age of 42 years completed the study, 25 in the supplemented group and 20 in the SM group. There were no safety problems or tolerability issues with the supplements. The two groups, SM and SM + Pycnogenol ® + Centellicum ® were comparable for age and clinical characteristics at inclusion. The two main ultrasound characteristics of cartilage, its thickness and surface-irregularity were more improved with the supplements. Pain scores, C reactive protein, the level of fitness and the use of extra pain killers (as rescue medication) were all significantly improved at 6 months with the supplement combination compared to SM (P<0.05). Plasma free radicals, pain-free walking distance on treadmill and erythrocyte sedimentation rate (ESR) were significantly improved with the supplements compared to SM., Conclusions: The morphological improvement - visible with ultrasound - correlates with a decrease in clinical symptoms and with a more efficient ambulation without pain. SM along with the Pycnogenol ® Centellicum ® combination are useful to avoid drug treatments that may expose patients to some side effects over time.

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

Background: The aim of this pilot registry study was to evaluate the efficacy of Robuvit ® (oak wood extract) on residual fatigue due to convalescence in otherwise healthy subjects within one month after surgery and chemotherapy for colon cancer. Robuvit ® has been clinically tested in subjects with fatigue (chronic fatigue syndrome), post-traumatic stress disorder, convalescence and burnout., Methods: One group of patients followed the standard management (SM) and was designated as control group while the supplementation group followed the SM and additionally took two Robuvit ® capsules daily for six weeks (200 mg/day).The main study endpoints were the Karnofsky performance scale index, handgrip strength in kg, fitness test score on a treadmill, self-assessed work ability, fatigue score, oxidative stress and carcinoembryonic antigen (CEA) plasma levels. In addition, the mood of the patients was assessed using the 'brief mood introspection scale', BMIS., Results: Fifty-one subjects with fatigue linked to convalescence within 1 month after chemotherapy for colon cancer completed the study, 29 in the Robuvit ® group and 22 as controls. The two management groups were comparable for age and sex distribution. The main investigation parameters were also comparable at inclusion. No side effects or tolerability problems were observed in the six weeks of follow-up. Occasional use of painkillers, antinausea medication or anti-inflammatory agents was accepted. After six weeks, Robuvit ® supplementation significantly improved the Karnofsky performance scale index compared to controls. Hand grip strength (dynamometry), treadmill fitness test score and the self-assessed work ability were significantly improved with Robuvit ® as well. The fatigue score after six weeks was significantly improved with Robuvit ® (P<0.05) in comparison with SM controls. Mood was significantly improved after 6 weeks in the Robuvit ® patients compared to the control group. The examined study parameters improved in the patients of the control group as well, during a normal postchemotherapy convalescence, but in a lesser extend when compared to the supplementation group. Oxidative stress was high at inclusion in both groups. The decrease in oxidative stress - as plasma free radicals - was significantly higher with the supplementation (P<0.05). CEA values were within the normal values from inclusion and in the 6 weeks of the registry in all subjects., Conclusions: In conclusion, Robuvit ® helps to reduce fatigue after chemotherapy and improves strength, performance, fitness, work ability and mood in these patients, without exposing them to the risk of side effects.

Background: The aim of this open, pilot supplement registry study was to evaluate the protective, preventive effects of Robuvit ® on professional-related fatigue symptoms and on aspects of cognitive functions, professional attitudes and decision-making in healthy nurses under professional stress and with increased oxidative stress., Methods: In total, 40 subjects, aged 30-37, completed the 4-week registry study. A control group of 20 subjects used only the standard management (SM) and one group of 20 subjects took 300 mg Robuvit ® in addition. Safety and tolerability of Robuvit ® were optimal. The two registry groups were comparable at inclusion., Results: The overall scores of the real daily life and tasks questionnaire after 4 weeks were significantly higher in the Robuvit ® group (P<0.05) as compared to controls. It increased from 4.3±0.4 at baseline to 6.78±0.8 after 4 weeks of Robuvit ® intake and from 4.2±0.5 to 5.12±1.0 in the control group. The supplementation significantly improved the subjective perception of fatigue in comparison with controls (P<0.05). A practical professional score evaluation provided an indication of professional attitude and stamina, in difficult, stressful working conditions under continuous pressure. The results showed that after 4-week supplementation, all assessed parameters improved significantly and the difference with controls was statistically significant (P<0.05). Furthermore, oxidative stress as plasma free radicals decreased significantly in the Robuvit ® group (P<0.05) but not in the control group., Conclusions: Robuvit ® supplementation appears to improve most symptoms related to work-induced fatigue, stress and cognitive function and supports stamina. Further evaluations need to be planned according to the concept of this pilot registry in a field that requires more attention.

Background: The aim of this open supplement study was to evaluate the effects of Pycnogenol ® in comparison with controls on symptoms of post-COVID-19 syndrome and in improving endothelial function, microcirculation, inflammatory markers and oxidative stress over 3 months in symptomatic subjects recovering from COVID-19., Methods: Sixty subjects recovering from symptomatic COVID-19 were included. One group of 30 followed a standard recovery management while 30 comparable subjects received a supplement of 150 mg Pycnogenol ® daily (in 3 doses of 50 mg) in addition to standard management., Results: Two groups of selected subjects were comparable at baseline. The groups progressively improved both with the SM (standard management) and with the SM in combination with the supplement. Patients, supplemented with Pycnogenol ® showed significantly better improvement compared to the control group patients. No side effects from the supplementation were observed; tolerability was optimal. The progressive evolution over time was visible in all target measurements. Physiological tests: endothelial function, low in all subjects at inclusion was assessed by flow mediated dilation (FMD) and finger reactive hyperemia in the microcirculation (laser Doppler measurements) after the release of an occluding suprasystolic cuff. It was significantly improved in the Pycnogenol ® group after one month and after 3 months (P<0.05 vs. controls). The rate of ankle swelling (RAS) by strain gauge decreased significantly in the supplemented group (P<0.05) in comparison with controls showing an improvement of the capillary filtration rate. At inclusion, the kidney cortical flow velocity indicated a decrease in perfusion (lower systolic and diastolic flow velocity) in all patients. Kidney cortical flow velocity increased significantly with the supplement (P<0.05) in comparison with controls with improvement in systolic velocity and in diastolic component. High sensitivity CRP (hs-CRP) and Il-6 plasma levels decreased progressively over 3 months with a significant more pronounced decrease in the supplement group (P<0.05). The number of patients with normal plasma IL-6 levels at the end of the study was higher (P<0.05) with the supplement. ESR followed the same pattern with a progressive and a more significant decrease in the supplemented subjects (P<0.02). Oxidative stress decreased significantly in the supplemented group (P<0.05) compared with the control group. Systolic blood pressure was significantly lower in the supplemented group (P<0.05) at the end of the study. Finally, the scores of Quality-of-life, mood and fatigue questionnaire and the Karnofsky Scale Performance Index significantly improved in the supplement group (P<0.05) compared to controls after 1 and 3 months. All other blood parameters (including platelets and clotting factors) were within normal values at the end of the study., Conclusions: In conclusion, Pycnogenol ® may offer a significant option for managing some of the signs and symptoms associated with post-COVID-19 syndrome. This pilot evaluation offers some potential rationale for the use of Pycnogenol ® in this condition that will have significant importance in the coming years.

Background: The aim of this study was to evaluate the combination of Pycnogenol ® (150 mg/day) (Horphag Research, London, UK) and Centella asiatica (Centellicum ® 3×225 mg/day; Horphag Research) (PY-CE) for 8 months in subjects with sequelae of idiopathic interstitial pneumonia (IIP). Recently, post-COVID-19 lung disease is emerging with large numbers of patients left with chronic lung conditions. Considering the antifibrotic activity of the combination PY-CE, we also tested this supplementary management in post-COVID-19 lung patients., Methods: Nineteen subjects with idiopathic interstitial pneumonia (IIP) were included in the study. High Resolution CT scans at inclusion confirmed the presence of lung fibrosis: 10 patients were treated with the Pycnogenol ® Centellicum ® combination and 9 subjects with standard management (SM) served as controls. Oxidative stress that was very high in all subjects at inclusion, decreased significantly in the supplement group (P<0.05). The Karnofsky Performance Scale Index significantly improved in the supplement group in comparison with controls (P<0.05). The symptoms (fatigue, muscular pain, dyspnea) were significantly lower after 8 months in supplemented patients (P<0.05) as compared with controls., Results: At the end of the study, the small cystic lesions (honeycombing) and traction bronchiectasis were stable or in partial regression in 4 subjects in the supplemented group (vs. none in the control group) with a significant improvement in tissue edema in the supplemented subjects. On ultrasound lung scans the white (more echogenic) fibrotic component at inclusion was 18.5±2.2% in the images in controls vs. 19.4±2.7% in the supplement group. At the end of the study, there was no improvement in controls (18.9±2.5%) vs. a significant improvement in supplemented subjects (16.2±2.1%; P<0.05). In addition, 18 subjects with post-COVID-19 lung disease were included in the study; 10 patients were treated with the Pycnogenol ® Centellicum ® combination and evaluated after 4 weeks; 8 patients served as controls. Preliminary results show that symptoms associated with post-COVID-19 lung disease after 4 weeks were significantly improved with the supplement combination (P<0.05). Oxidative stress and the Karnofsky Performance Scale Index were significantly improved in the supplements group as compared with controls (P<0.05)., Conclusions: According to these observations, Pycnogenol ® controls and decreases edema and Centellicum ® by modulating the apposition of collagen, slows down the development of irregular cicatrization, the keloidal scarring and fibrosis. More time is needed to evaluate this effect in a larger number of post-COVID-19 patients with lung disease. This disease has affected millions of subjects worldwide, leaving severe consequences. Pycnogenol ® and Centellicum ® may improve the residual clinical picture in post-COVID-19 lung disease (PCL) patients and may reduce the number of subjects evolving into lung fibrosis. The evolution from edema to fibrosis seems to be slower or attenuated with this supplement combination both in Idiopathic pulmonary fibrosis (IPF) and in PCL patients.

Background: Neck/shoulder, sudden pain, or muscular pain (not associated to structural or bone/joints components), due to fascial or muscular strain is common in active subjects, in non-professional athletes and sports performers. The aim of this supplement registry was the evaluation of a cream based on natural, active ingredients for topical application in supporting the improvement of pain and improving head/neck mobility, possibly minimizing the use of systemic drugs., Methods: The cream includes standardized active ingredients of natural origin as an extract of Harpagophytum procumbes, an extract from Boswellia serrata, a CO2 extract of ginger and escin. Subjects were divided into three groups, all using the standard management (SM) in combination with the Sport Cream or in addition to Flector (diclofenac) patch., Results: The groups were comparable and homogeneous at the baseline. No side effects or skin tolerability issues were observed with the Sport Cream nor with the SM or diclofenac patches. Subjects receiving sport cream + SM reported a significant improvement in pain, stiffness, altered mobility and altered working capacity, with a reduced need for rescue medication (diclofenac) compared to subjects in the other two groups., Conclusions: Finally, subjects receiving sport cream + SM reported a more remarkable decrease in skin temperature in the affected area associated to an improvement in clinical symptoms.

Background: The aim of this supplement registry study was the evaluation of possible benefits of Robuvit® (oak wood extract) as a standardized supplement (in an 8-week registry) in stable, mild, heart failure patients., Methods: All subjects received the standard management (SM) for this condition. Otherwise healthy subjects with mild, initial symptoms (mild shortness of breath and/or angina) and slight limitation during their normal daily activity were included. This corresponds to the New York Heart Association (NYHA) Functional Classification class II., Results: Forty subjects were included in the study. The two groups completing 8 weeks were comparable at baseline with 20 subjects managed with SM and 20 subjects supplemented with Robuvit® in addition to SM. Tolerability and compliance were optimal (with more than 95% of the capsules correctly used). The age and symptoms of the supplemented patients and the controls were comparable at baseline. There were no dropouts. At 8 weeks, systolic-diastolic pressure, heart rate, respiratory rate were minimally (non-significantly) lowered with the supplement without differences in controls. Ultrasound-derived ejection fraction was significantly increased in the supplement group (P<0.05) while there were minimal, non-significant differences in controls. Walking distance on treadmill was also significantly increased in the supplement group (P<0.05) and significantly less in controls. The microcirculation (laser Doppler parameters and transcutaneous PO2, PCO2) improved significantly in the Robuvit® group (P<0.05) in comparison with the non-supplemented controls. Oxidative stress was significantly decreased (P<0.05) with the supplement while there were minimal, non-significant changes in controls., Conclusions: In conclusion in this pilot, supplement registry Robuvit® seems to help and improve patients with mild heart failure and should be considered for larger studies.

Background: The aim of this open registry study was to evaluate the effects of Robuvit® in subjects with hangover after acute alcohol consumption also measuring changes in levels of oxidative stress. A group using standard management (SM) and a group using SM and Robuvit® 300 mg/day for 3 days were compared., Methods: Nineteen male subjects with hangover were included in the SM group and 22 in the Robuvit® + SM group., Results: The groups were comparable at baseline. No side effects were observed. Fatigue scores - as the main observable symptom in these subjects, in both groups - were significantly lower in the group using Robuvit® (P<0.05) than in the control group after 24 hours. The scores of other symptoms like weakness, thirst, headache, muscle aches and body pain were significantly lower at 24 hours (P<0.05) with the supplement than in the control group. The scores of residual gastrointestinal symptoms (nausea, vomiting and stomach pain) were also significantly lower at 24 hours with Robuvit® (P<0.05). Sleep and rest were significantly better with Robuvit® (P<0.05). Sensory symptoms and cognitive functions were also significantly better with supplementation in comparison with SM only (P<0.05). Finally, scores of mood, concentration, depression, anxiety, irritability were significantly lower (P<0.05) with Robuvit® though these symptoms need a more specific and complete evaluation. Signs of sympathetic activity, tremor, sweating, increased heart rate improved significantly better with the supplement at 24 hours (P<0.05). Oxidative stress was increased at inclusion in all subjects; in the Robuvit® group, oxidative stress decreased significantly (P<0.05) at 24 hours; in controls (SM) oxidative stress showed minimal changes at 24 hours and it remained elevated above normal values (>330 CU). Most symptoms almost disappeared at 24 hours in the Robuvit® group. Significant symptoms were still observed in 11 out of 19 subjects in the SM group in comparison with four of 22 subjects using the supplementation with Robuvit® (P<0.05). Blood tests were normal in all subjects (hematocrit and kidney and liver functional test at 24 hours)., Conclusions: In conclusion, Robuvit® supplementation appears to improve hangover and relieved symptoms faster. More studies are needed to confirm this association between acute alcohol consumption and a possible hepatic dysfunction.

Background: The aim of this study was to evaluate the effects of the standardized supplement Robuvit® (oak wood extract) in defined diffuse, minimal lymphatic "retention" (DMLR)., Methods: Robuvit® has already been investigated in both primary and secondary (post-surgical, post chemo-radiotherapy) lymphatic insufficiency. This registry included subjects with diffuse, minimal lymphatic "retention" (DMLR). The registry management groups included women with mild-moderate limb swelling using standard management (SM) as controls. A second, comparable group used prevention with Robuvit® at the dosage of 3 cp/day (300 mg/day) for 4 weeks., Results: No tolerability problems or side effects were observed with the preventive supplementation. The management groups (34 women in total), including 18 women in Robuvit® and 16 in SM were comparable in age and baseline evaluations. After 4 weeks, in the Robuvit® group, edema scale values derived from ultrasound observations decreased significantly (P<0.05) at all measurement's sites, from the proximal (inguinal) level to the more distal (ankle-foot) level. No significant changes in edema were observed in control subjects. Generally, in areas with higher level of edema (distal areas at the foot and ankle), the edema decrease was larger than in more proximal, ultrasound measurement sites., Conclusions: Preventive Robuvit® supplementation appears to be safe and effective in controlling DMLR in subjects without significant or apparent clinical conditions. This preventive, concept study should be extended to a larger population for more meaningful observations.

Background: The aim of this pilot study was the supplementary management of minimal, residual symptoms of systemic Lupus (SLE) with vasculitis (LV) in remission phases, using a natural, anti-inflammatory, antioxidant agent (Pycnogenol®) extracted from French maritime pine bark. Pycnogenol® has a significant clinical anti-inflammatory activity; it is a standardized supplement with a high-safety profile., Methods: Subjects with Lupus vasculitis were included in the study. The standard management (SM) was used in all subjects for 8 weeks; one group added Pycnogenol® (150 mg/day) to SM., Results: The two groups completing 8 weeks were comparable at baseline with 12 subjects managed with SM and 14 subjects supplemented with Pycnogenol®. No side effects due to Pycnogenol® were observed; Pycnogenol® was associated with an optimal tolerability. The proportion of patients with photosensitivity, oral ulcers, renal-associated hematuria (minimal), leukopenia, lymphopenia, thrombocytopenia, positive anti-DNA and positive antiphospolipids tests were significantly lower in the Pycnogenol® group (P<0.05) at 8 weeks in comparison with controls. No difference in activity between SM and supplementation was observed for rash, serositis, anemia, neurological symptoms (all mild at inclusion) and anti-Smith. Considering additional clinical parameters such as the need for corticosteroids, peripheral ischemia, oxidative stress, the effects of Pycnogenol® appeared to be superior to SM alone (P<0.05). The decrease in oxidative stress was significantly higher with Pycnogenol® (P<0.05) compared to SM. This is particularly interesting as it has not been observed before in LV. Considering microvascular parameters, the number of subjects with 'cold' hypoperfused thermographic areas was significantly lower in the supplement group (P<0.05) and distal flux (laser Doppler) was higher with the supplement (P<0.05) at 8 weeks., Conclusions: This pilot registry indicates that Pycnogenol® can be safely used in subjects with LV with mild symptoms (in remission) possibly avoiding some drug treatments that may cause side effects. A larger study in progress is evaluating the effects of Pycnogenol® on recurrent symptoms in subjects in remission.

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

Background: This 'concept' registry study evaluated the efficacy of Pycnogenol® and the combination Pycnogenol® and Centella Asiatica (Centellicum®) in controlling over 12 months the increasing number of arterial/cardiac calcifications in subjects with asymptomatic atherosclerosis., Methods: The study included 3 groups of 30 males with asymptomatic coronary calcifications. Group one was followed with standard management (SM); group 2 used SM and Pycnogenol® (150 mg/day); group 3 used the combination Pycnogenol® (150 mg/day) + Centellicum® (450 mg/day). All subjects took cardioaspirin (Bayer, 100 mg/day)., Results: No dropouts, no clinical events were observed in 12 months. The 3 groups had comparable demographic and medical characteristics at baseline. No tolerability problems and no side effects from supplementation were reported. After 12 months, oxidative stress was significantly decreased (P<0.05) in both groups taking Pycnogenol®. The evaluation of the number of calcifications >1 mm indicated a trend in controls using SM towards a progressive increase in calcifications. At 12 months the decrease in the number of calcifications with the combined supplements (Pycnogenol® and Centellicum®) (group 3) was -9.952% and thus significantly better that in the other two groups (P<0.05). Pycnogenol® alone was more effective than SM alone in controlling the variation in calcifications (P<0.05). Considering a 34.88% increase in SM subjects, the total absolute difference between SM (34.8%) and the decrease observed in group 3 (-9.95%) was 44.75% (P<0.02). This indicates that supplementation with the combined supplements blocks the increase in calcified areas and, possibly, in time may decrease the number of calcified spots., Conclusions: This study shows that there is a significant activity of the complex Pycnogenol®+ Centellicum® in reducing the progressive diffusion of central cardiovascular calcifications-associated with advanced plaques - in a relatively short period of time. Longer studies - focusing also on events - may better evaluate the efficacy of these standardized supplements combination on the evolution of atherosclerosis.

Background: In association with standard management, natural pharmaceutical standard (PS) supplements may play an important role in managing and preventing mild-to-moderate symptoms of asthma, a significant health issue that impacts patients and the healthcare system. Quercetin is a natural flavonoid with important biological properties (anti-inflammatory, antihistamine and anti-oxidative actions)., Methods: In this pilot registry, we evaluated the effects of quercetin formulated with the Phytosome® delivery system (Quercefit™, QFit)+standard management (SM) in otherwise healthy subjects with mild-moderate asthmatic attacks and rhinitis. Subjects used either QFit 1 or 2 tabs/day in association with SM or SM only (control group). After 30 days of management, we evaluated the presence of the main signs/symptoms of asthma according to the GINA classification system also considering the need of rescue medication, nasal drops, the use of inhalers, the rhinitis score and oxidative stress., Results: QFit+SM showed superior results compared with SM alone in controlling, preventing and reducing daily and night symptoms, in maintaining higher peak expiratory flow (PEF) and in decreasing PEF variability. The supplementary use of QFit improved additional measures of asthma management, decreasing the use of inhalers, nasal drops, rescue medications and improving the rhinitis score. QFit produced a significantly more evident reduction in oxidative stress compared with SM; Qfit showed a very good safety profile., Conclusions: This preliminary supplement, concept registry shows a potential protective and preventive effect of quercetin on attacks frequency and in controlling the most common signs/symptoms of asthma in the milder cases of the disease.

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

Background: The aim of this pilot study was the evaluation of primary, idiopathic mucosal dryness (xerostomia or dry mouth) in subjects without cancer., Methods: A group of non-diabetic subjects and a group of diabetics were managed with standard management (SM) or with SM+Pycnogenol® (150 mg/day) for 2 weeks., Results: In total, 48 subjects were included in the study; 24 diabetics and 24 non-diabetics. 12 diabetics and 12 non-diabetics took Pycnogenol® and 12 diabetics and 12 non-diabetics were followed up with standard management only and served as controls. No side effects and no tolerability problems were observed with Pycnogenol®. The registry groups were comparable for characteristics and symptoms at baseline. All otherwise healthy subjects had a BMI<26 kg/m2. In 2 weeks, salivary flow and oxidative stress improved significantly in both groups of subjects (non-diabetics and diabetics) with 150 mg/day Pycnogenol® (P<0.05), while minimal improvements in salivary flow were seen with SM. The subjective score and the number of mucosal breaks and ulcerations, all minimal (<1 mm in length or diameter), were significantly decreased with Pycnogenol® supplementation (P<0.05) with minimal variations in the SM controls. Finally, the mean lysozyme level in parotid saliva samples was significantly increased in the Pycnogenol® group (P<0.05) both in diabetics and non-diabetics., Conclusions: Based on these preliminary results, Pycnogenol® could be a new, valid option for the treatment of xerostomia.

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

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

Background: In this study we aimed to evaluate the efficacy of Pycnogenol® supplementation in controlling oxidative stress levels and in reducing the frequency and severity of side effects of levothyroxine (LT4) treatment in patients who had recently started this therapy., Methods: The registry included 60 females affected by primary hypothyroidism with multi-nodular goiter. LT4 was administered at the dosage of 100 μg/day.The registry study included only subjects under initial treatment, and followed up for a period of at least 30 days. A group took 150 mg Pycnogenol® daily and another served as control., Results: The global occurrence of symptoms during the 30-day period was significantly lower with the supplement (P<0.05)., Conclusions: Pycnogenol® may represent a useful tool to reduce LT4- related side effects in patients treated with hormone replacement therapy for hypothyroidism.

Background: The aim of this study is to evaluate the use of Aspirin, Pycnogenol®, ticlopidine, and sulodexide to reduce the incidence of new RTV (retinal vein thrombosis) after a first episode. Pycnogenol® is an anti-inflammatory, anti-edema, mild antiplatelet-antithrombotic agent., Methods: The registry study evaluated the number of repeated episodes of RVT in 12 months. Possible managements were: standard management (SM); SM + Aspirin (100 mg/once day; if there were no tolerability problems); SM + Pycnogenol (100 mg/day); SM and ticlopidine (200 mg/day); SM + sulodexide (500 ULS/day). The number of subjects age and sex, distribution, the percent of smokers, the vision were comparable at inclusion., Results: 307 subjects completed the study, 44 in the SM group, 90 in the Pycnogenol® group, 90 in the aspirin group, 45 in the ticlopidine group and 38 in the sulodexide group. At 12 months, recurrent RVT was documented in 22.7% of controls (SM), 3.3% of Pycnogenol® subjects (P<0.05 vs. SM; 19.4% difference). There were RVTs in 15.5% subjects using Aspirin (-7.2% vs. SM). Ticlopidine also reduced (P<0.05) the incidence of RVT in comparison with SM (-9.1%). Sulodexide reduced the occurrence of new RVT (-9.5% vs. SM). Edema was better controlled with the supplement than with all other treatments (P<0.05) (edema present in only 5.5% of the Pycnogenol® subjects). Pycnogenol® had a very good tolerability and safety profile (no patient had to stop treatment)., Conclusions: Pycnogenol® is the only product able to control edema and this may reduce the incidence of recurrent RVT. This retrospective registry indicates that Aspirin, Pycnogenol®, ticlopidine an sulodexide reduce recurrent RVT without side effects. Larger studies should be planned to involve a wider range of conditions, diseases and risk factors associated with RVT and to its recurrence.

Background: The purpose of this study was to evaluate the long-term efficacy and the safety of a lecithin-based delivery form of boswellic acids from Boswellia serrata (Casperome®) for the prevention of symptoms in otherwise healthy subjects with mild irritable bowel syndrome (IBS)., Methods: The study included 69 otherwise healthy participants with a mild form of IBS who completed a 6-month follow-up period. In total, 34 subjects were assigned to the standard management (SM) group: diet and, if needed, hyoscine butylbromide (Buscopan®) or papaverine hydrochloride + 10 mg of Atropa belladonna extract; 35 subjects were assigned to supplementation with the Boswellia serrata lecithin-based delivery form (one tablet/day; Casperome®). IBS signs and symptoms were evaluated at inclusion (T0), after 3 (T1) and 6 months (T2). The numbers of patients who needed rescue medication were recorded. Adverse events were also evaluated., Results: At baseline, the groups were comparable in terms of demographic and clinical characteristics. At follow-up, compared with the SM group, the Boswellia group showed lower mean score values for almost all self-assed IBS symptoms. A significantly lower need for rescue medications and consultations or medical evaluation/admissions was found in the Boswellia group compared with the SM group. The incidence of minimal adverse events - mainly stipsis - was significantly higher in the SM group. Oxidative stress at T2 was significantly decreased in Boswellia-supplemented subjects., Conclusions: Boswellia serrata lecithin-based delivery form (Casperome®) appears to be effective and safe in improving signs and symptoms in IBS subjects who are otherwise healthy, particularly in comparison with symptomatic drug treatment that may cause side effects and stiptis.

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

Background: In this pilot non-interference clinical study we evaluated possible interactions between Quercetin Phytosome® (Quercefit™), an innovative delivery form of quercetin, and antiplatelet agents, anticoagulants, and anti-diabetic therapy in otherwise healthy subjects., Methods: Interaction with antiplatelet therapy was assessed through the bleeding time (BT) test in 30 patients treated with acetylsalicylic acid, ticlopidine or clopidogrel before and after 10 days of supplementation with Quercetin Phytosome®. Interaction with anticoagulants was evaluated by measuring the International Normalized Ratio (INR) in 20 patients using warfarin or dabigatran before and after 20 days of supplementation with Quercetin Phytosome®. Lastly, glycaemia and glycated hemoglobin were measured in 12 diabetic patients treated with metformin and restricted diet before and after 20 days of supplementation with Quercetin Phytosome®., Results: After 10 days of supplementation no significant difference was observed in mean BT in patients treated with acetylsalicylic acid, ticlopidine or clopidogrel at standard dosages. Similarly, after 20 days of supplementation, the INR level among patients assuming warfarin or dabigatran was not statistically different from baseline. Lastly, no statistically significant difference in mean levels of glycaemia and glycated hemoglobin was reported before and after 20 days of complementary administration of Quercetin Phytosome® in diabetic patients treated with metformin and restricted diet., Conclusions: Quercetin Phytosome® does not alter the antiplatelet activity of the most common antiplatelet agents, has no impact on the INR values in stable patients treated with warfarin or dabigatran, and does not influence the metabolic control of diabetic patient treated with metformin.

Background: This registry study evaluated the effects of G3 Sports supplement drink (G3) on performance and endurance in triathlon in amateur athletes in a period of 2 weeks of training. G3 is composed of a proprietary fruit juice blend high in carotenoid compounds as well as 100 mg of standardized French oak (Quercus robur) wood extract, Robuvit®, per 50 mL bottle. The antioxidant and anti-inflammatory actions of the compounds in G3 may improve training efficiency (decreasing post-triathlon muscular pain, cramps and improve recovery time) and decrease post-training plasma free radicals (PFR)., Methods: We selected 50 healthy subjects available to follow the registry plan (age 30-40). No clinical or risk condition were present; no medications were used. Subjects followed a free diet. None used sport supplements (aminoacids or anabolic products). The use of rehydrating drink (Polase) was suggested to all subjects. The only other admitted beverage was Gatorade for use by the control group only. Triathlon total time as well as objective markers of oxidative stress, measured as plasma concentration of free radicals (PFR), and intravascular hemolysis (hemoglobin, serum ferritin, unconjugated bilirubin (UBR) and lactate dehydrogenase (LDH) were measured., Results: Fifty subjects were included: 25 using the supplement; 25 subjects did not use the supplement and acted as controls. Routine blood tests were normal at inclusion and after the final triathlon. The two groups were comparable considering men and women performances at inclusion and age distribution. Drinking and training regimens were comparable between the groups. No side effects or tolerance problems were reported; all G3 drinks were used as indicated. The final "measurement" run was not competitive but chronometric. All subjects completed the test. All subjects performances improved with training. The improvements were seen in parallel both in men and women. The improvement was significantly greater with G3 (P<0.05). The final variation in time was superior with G3 vs. controls (P<0.05). Oxidative stress (PFR), assessed 1 h after the final run, was higher in controls (P<0.05). The higher level of PFR may be associated to a slower recovery time after training and after the test run. After the final test run triathlon, there were no significant changes in hemoglobin or serum ferritin in both groups. Athletes using G3 had a lower variation in UBR and LDH; however, both were significantly increased in controls (P<0.05)., Conclusions: G3 supplementation significantly improved exercise performance in two weeks training time and appeared to significantly decrease oxidative stress and hemolysis resulting from exercise.

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

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

Background: The aim of this comparative registry study was to evaluate the supplementation with Pycnogenol® in subjects with Behçet syndrome (BS) with symptoms impairing their quality of life despite being in a remitting phase of the disease., Methods: Thirty-four patients with a confirmed diagnosis of BS were divided into the control group (without supplement) or the active group, in this specific case using Pycnogenol® (Horphag Research LTD) supplement at the daily dose of 150 mg (50 mg tid) for 4 weeks., Results: All subjects receiving Pycnogenol® reported a significant decrease in symptoms, such as burning/pain due to dryness and ulcerations (P<0.05). In addition, Pycnogenol® showed important anti-inflammatory activity by decreasing ESR, leucocytosis and Pathergy Test response., Conclusions: Pycnogenol® may be a useful supplementation for the management of BS.

Background: Oxidative stress is associated with delayed recovery and higher risk of post-training pain in triathlon athletes. Therefore, supplementation with antioxidant compounds may have a role in enhancing recovery. Quercetin presents marked antioxidant activity. In this pilot registry study, we evaluated the effects of the supplementation with a novel proprietary delivery form (phytosome®) of quercetin in amateur triathlon athletes., Methods: We employed a specific study model of triathlon according to the "Sprint" distance. The individual triathlon training included repetition of the run 8 times in 14 days. A group of athletes used quercetin phytosome® supplementation (one tablet of 250 mg quercetin phytosome® twice daily). A control group did not use supplementation. All subjects attended a baseline measurement run and a second final measurement run at day 14. At the end of the study, subjective performance, post-training pain, cramps, time to full recovery and oxidative stress were measured., Results: In total, 23 subjects used the supplement and 25 did not. No side effects were reported. The improvement of time to complete the run was greater in subjects on quercetin supplementation compared with the control group (-11.3% vs. -3.9%; P<0.05). Training was considered more valuable in the quercetin group compared with controls (P<0.05). Similarly, post-run muscular pain, cramps, localized pain and the post-exercise recovery time were all considered better with the supplementation (P<0.05). Oxidative stress was also reduced (P<0.05)., Conclusions: This pilot study suggests that the oral supplementation with quercetin phytosome® may result in improved training and performance in amateur triathlon athletes.

Background: The aim of this study was to evaluate the efficacy of Pycnogenol® supplementation in terms of safety and tolerability in the setting of preclinical or borderline, initial symptoms of benign prostatic hyperthrophy (BPH), in otherwise healthy subjects, using Pycnogenol® over a period of 60 days., Methods: Seventy-five healthy men with symptoms and signs of initial BPH were included. The subjects were divided into three groups: 1) control group using only the standard management (SM); 2) a group using SM plus Pycnogenol® 150 mg/day; 3) a group using standard pharmacological management., Results: BPH symptoms like emptying, frequency, intermittency, urgency, weak flow, straining, nocturia, were all significantly improved with Pycnogenol® (P<0.05) and the difference with both control groups was statistically significant (P<0.05)., Conclusions: Pycnogenol® may be an important option for self-management of BPH in otherwise healthy men.

Background: Post-mastectomy lymphedema is one of the most significant, non-life-threatening complications following breast cancer surgery and radiotherapy. Post-mastectomy post-radiotherapy (PMPR) lymphedema is related to damages to lymphatics and/or veins during/after axillary surgery and radiotherapy. The management of this condition is very challenging; the comprehensive decongestive therapy (CTD), which combines physiotherapy, self-management, and hygiene, and is currently considered the standard management (SM). The aim of this registry study was to evaluate whether the supplementation with Robuvit® as a lymphedema controlling agent added to CTD over a 2-month period could be more effective than CTD alone., Methods: A group of 65 patients with PMPR lymphedema was included in this registry study and followed up for 2 months; 33 were treated with current SM only (control group), and 32 were also supplemented with 600 mg/day of Robuvit® (active treatment group)., Results: At 1- and 2-month follow-up, the decrease in volume was significantly greater in the supplement group (P<0.05), with a final reduction in volume after two months of 654±21 mL (-19.82%) versus 433±23 mL (-12.81%) in the control group. A more significant decrease in skin thickness and symptoms was also observed in the Robuvit® group. No side effects were reported., Conclusions: CTD, combined with self-management, can effectively control the excess of limb volume in post-mastectomy lymphedema. Supplementation with Robuvit® is useful to further reduce limb volume. Later stages of lymphedema seem to be more difficult to manage and may require surgery or more invasive treatments.

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

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

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

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

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

Background: This registry study evaluated the effects of Pycnogenol® on edema and thrombotic complications in long-haul flights; jet lag was also evaluated., Methods: Four hundred and fifty subjects at different risk levels for thrombosis, flying in economy class twice a week for more than 8 hours, were included; 295 completed the registry study and were subdivided in 3 groups according to their risk level - low, moderate, or high. The high-risk group also received Aspirin®. A standard management (SM) was used in all groups. In each risk category, three groups were made according to patient management: a Pycnogenol group, a SM group (control), and a stockings group. The groups were comparable at inclusion. No side effects were observed., Results: In the low risk group edema were reduced more (P<0.05) with Pycnogenol and stockings compared to control. Ankle circumference was smaller with Pycnogenol (P<0.05). No thrombosis was detected. D-dimer was negative in Pycnogenol subjects; one subject in the control group had increased values, as did two of the 36 subjects in the stockings group. In the group with moderate risk, edema and ankle circumference were lower in the Pycnogenol group (P<0.05). One deep vein thrombosis (DVT) and one minimal superficial vein thrombosis (SVT) were seen in controls. D-dimer was normal in the Pycnogenol group. In high-risk subjects, edema, and ankle circumference were significantly reduced in the Pycnogenol group (P<0.05). There were no SVT or DVT in the Pycnogenol group. One minimal DVT and one SVT were observed in controls. D-dimer was negative in all Pycnogenol subjects (P<0.05); three post-flight values increased in controls and in four of the 32 subjects in the stockings group. The jet lag score was lower in low-, medium-, and high-risk Pycnogenol subjects (P<0.05)., Conclusions: This registry study indicates that Pycnogenol supplementation reduces edema and may control some thrombotic events.

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

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