Pycnogenol® supplementation to relieve symptoms after hemorrhoidectomy.

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.

Pycnogenol® prevents skin hyperpigmentation following sclerotherapy.

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.

Periostial and cartilage morphology in knee osteoarthritis: beneficial effects of supplementation with Pycnogenol® + Centellicum®.

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.

Prevention and control of jet lag symptoms and temporary impairment of cognitive function with Pycnogenol® in healthy individuals and in hypertensives.

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).

Intestinal fat absorption shifting by polyglucosamine biopolymer: control of lipids and reduction of progression of early subclinical atherosclerosis.

BACKGROUND: Atherosclerosis progression is possible in subjects with limited alteration of body weight, lipid profile, and oxidative stress. The ultrasound carotid thickness (IMT) and arterial wall modification (granulation and bubbles) are evident signs of the disease. Intestinal fats absorption shifting (IFAS) is expected to prevent or reduce the arterial damage. The aim of the registry was to evaluate the effects of a mild diet in association with lifestyle modifications (standard management [SM]) and SM+ a polyglucosamine biopolymer (BP) shifting the intestinal absorption of dietary fats. METHODS: The present is a two-year registry comparing two groups of otherwise healthy subjects, respectively 150 (SM) and 144 (SM+BP). BP was administered at the dosage of 3g/day. IMT and relative arterial damages were measured together with lipid profile, oxidative stress, anthropometric and vital measures. RESULTS: The two groups at the baseline were comparable for all variables: 8 cases of drop out were found limited to SM. Compliance with BP was optimal (>97%) and no side effect were observed. IMT showed a significant decrease in thickness (P<0.05) using BP+SM, while increased in SM group. Intimal granulations and lipid wall bubbles were also significantly decreased with BP in comparison to SM only (P<0.05). BMI significantly decreased with BP (P<0.05) as well as BW, fat mass, lipid profile and oxidative stress in comparison to SM only. A positive variation in blood pressure and heart rate (P<0.05) was also observed. CONCLUSIONS: BP allows IFAS to improve early subclinical arterial lesions that tend to progress to plaques and clinical events. The long-term and safe treatment of BP is effective on IMT, lipids, BW, and early lesions of the arterial wall structure in subjects with subclinical conditions. BP also reduces oxidative stress which contributes to lipid oxidation and deposition into the arterial wall layer in areas of high dynamic stress (arterial bifurcations).

Borderline hyperlipidemia preventive management with Berberine PL in asymptomatic prevention of early atherosclerosis.

BACKGROUND: The aim of this pilot, efficacy supplement registry was to use a supplementary management with berberine to control hyperlipidemia. The supplement Berberine (Berbevis™ as Sophy® tablets) was used to control lipids and to evaluate (as a natural, preventive management) the early evolution of subclinical atherosclerosis in subjects (otherwise healthy, not using drugs) with borderline hyperlipidemia. METHODS: The registry involved two groups of subjects not using drugs for a total of 50 subjects and three months of supplementation. RESULTS: The registry groups using standard management (SM) or SM and supplement were resulted comparable. No side effects were observed during the three months of berberine supplementation. No tolerability problems were reported. All subjects managed with berberine completed the three-month registry. Compliance was >97% (% of correctly used tablets). Total cholesterol was significantly decreased with berberine (P<0.05) and HDL was significantly improved (P<0.5) with supplementation. Triglycerides decreased in the berberine groups (P<0.05) and the levels of CoQ10 remained within normal values in supplemented subjects. Oxidative stress - measured in Carr units - was significantly decreased with berberine (P<0.05). Routine blood tests remained within normal values during the registry. Body weight was significantly more decreased (P<0.05) with berberine in comparison with standard management. The fat proportion also decreased (P<0.05) with berberine supplementation and the abdominal fat thickness (in the peri-umbilical area) was significantly decreased after berberine supplementation (P<0.05). CONCLUSIONS: This pilot registry indicates that berberine administration is effective in reducing lipids (decreasing weight, fat percentage and abdominal fat) in otherwise healthy subjects not using drugs. A longer study, with more advanced hyperlipidemic subjects is suggested. Predictive analytics according to Siegel suggests that a six-month study with 60 patients, in more advanced hyperlipidemic, also evaluating the intima-media thickness for the analysis of vascular benefits, may produce a stronger evaluation for this product.

Xerostomia and prevention of dryness with a Pycnogenol® mouth spray: a pilot study.

BACKGROUND: The aim of this pilot, supplement study was the evaluation of primary, idiopathic mucosal mouth dryness (xerostomia or dry mouth) in subjects without systemic diseases. METHODS: Subjects with xerostomia were managed either with standard management (SM) or with SM and a Pycnogenol® mouth spray (Hankintatukku Oy, Karkkila, Finland), at the dosage of 60 mg/day in 30 spurts, for 2 weeks. RESULTS: A total of 50 subjects were included in the study: 25 controls using only standard management (SM) and 25 subjects using the Pycnogenol® mouth spray. No side effects and no tolerability problems were observed with the Pycnogenol® mouth spray. The groups were comparable for characteristics and symptoms at baseline. These otherwise healthy subjects had a BMI<26. After 2 weeks, salivary flow and salivary oxidative stress (in Carr Units) were improved significantly with Pycnogenol® mouth spray as compared to controls (P<0.05), whereas minimal improvements in salivary flow were seen with SM. The subjective symptomatic dry mouth score and the number of mucosal breaks and ulcerations (all minimal, <1 mm in length or diameter) were significantly decreased with the Pycnogenol® mouth spray supplement compared to SM controls (P<0.05). The Pycnogenol® mouth spray led to significant improvement in salivary lysozyme levels, compared to controls (P<0.05). CONCLUSIONS: Based on these preliminary results, Pycnogenol® mouth spray could be a new supplementary option for the management of primary xerostomia.

Positive effects of Pycnogenol®-Centellicum® on venous elasticity: an ex-vivo concept study.

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.

Intestinal fat absorption shifting: polyglucosamine biopolymer controls lipids and weight and reduces the progression of subclinical atherosclerosis.

BACKGROUND: Intestinal fat absorption shifting (IFAS) can be obtained in hyperlipidemic subjects with polyglucosamine biopolymer (BP) able to segregate most metabolic fats in the gut, making them unavailable for intestinal interaction (shift). The aim of this study was to evaluate the effects of a SM (standard management) for hyperlipidemia in asymptomatic subjects for primary cardiovascular prevention focusing on arterial wall morphology (IMT thickness) in comparison to SM associated to the administration of the BP. METHODS: Two groups of comparable subjects (SM and SM+oral BP, 3 g/day) were considered; subjects were managed - in a supplement, pilot registry - for a year. Weight, fat mass, lipid profile, oxidative stress, IMT (carotids), the presence of granulations at the internal arterial layers and "near wall low density 'bubbles' were observed and compared at 1 year of management. A non-parallel, comparable group of subjects (102) using a statin for the same conditions was used as a reference population. RESULTS: Two hundred eighty-four subjects completed one year (140 in the SM group and 144 in the SM+BP group). Compliance was optimal with (96.3% of the table correctly used) with no side effects. BMI, fat mass and oxidative stress decreased more in the SM+BP group (P<0.05). Cholesterol and triglycerides levels were significantly improved with BP (P<0.05). IMT measurements were significantly decreased (P<0.05) in the SM+BP group (as for the intimal granulation/bubbles) with minimal variations in the comparative SM group. In the statin group, the lipid profile was modified (P<0.05) but not the IMT and the rate of drop outs was higher (15.7%); these patients stopped the management; in 23% of these subjects muscular pain not seen with BP, was observed. CONCLUSIONS: These results indicate positive effects of IFAS due to BP on IMT and arterial wall morphology and weight after 12 months. Fat shifting at intestinal level and the reduction of oxidative stress limit lipid oxidation/deposition into the arterial wall.

Robuvit® reduces fatigue after chemotherapy for colon cancer. A pilot registry study.

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.

Anthocran® Phytosome®: Prevention of Recurring Urinary Infections and Symptoms after Catheterization.

In this preliminary pilot registry study, we investigated the effects of the oral supplementation of a standardized cranberry extract (Anthocran® Phytosome®, Indena) delivered by a lecithin-based system, for the prophylactic management of recurrent-urinary tract infections (R-UTIs). We included 64 otherwise healthy subjects who underwent a surgical procedure and required post-surgical urinary catheterization for high-risk UTIs or a previous history of R-UTIs. Patients were given supplementation with the standardized cranberry extract at the dose of either 120 mg/day (n = 12) or 240 mg/day (n = 12) or assigned to a control group consisting of standard management (SM; n = 18) or nitrofurantoin administration (n = 22) for 4 weeks. After 4 weeks, patients receiving the standardized cranberry supplementation reported to have a more effective reduction in UTI symptoms, as assessed on the visual analogue scale, compared with patients in the SM or nitrofurantoin groups. The occurrence of hematuria and urine bacterial contamination were decreased among patients treated with the supplement compared with controls (p < 0.05). The cranberry extract was also superior to the control management in terms of recurrence of signs/symptoms, with none of the patients in this group suffering from a R-UTI in the 3 months following the study end (p < 0.05). The supplementation showed an optimal safety profile, with no significant adverse events and no drop-outs in the supplement group. This registry shows that this cranberry extract is effective as a supplementary, preventive management in preventing post-operative, post-catheter UTIs; the product has a good tolerability profile.

Correction to: Intestinal fat absorption shifting: polyglucosamine biopolymer controls lipids and weight and reduces the progression of subclinical atherosclerosis.

This article was published in Volume 69, issue 1 of publishing year 2023, with a mistake in Table I. The correct Table I is the one included in this erratum.

Effects of Robuvit® on the progression of non-alcoholic fatty liver disease.

BACKGROUND: The aim of this study was to evaluate the effects of Robuvit® in preventing the progression of chronic hepatitis (CH) in non-alcoholic fatty liver disease (NAFLD) which encompasses the entire spectrum of fatty liver disease, from isolated steatosis to non-alcoholic steatohepatitis (NASH). METHODS: One group of patients followed the Standard management (SM) and were assigned as controls while the supplementation group followed the SM and additionally took 2 Robuvit® capsules daily for 3 months (200 mg/day). RESULTS: 34 subjects with NAFLD were included in the study. The two groups completing 90 days were comparable at baseline with 18 being supplemented with Robuvit® and 16 in the control group. The tolerability was very good, and no side effects were observed with the supplement. Fasting glucose levels were significantly lower after 3 months with Robuvit® (P<0.05) compared to controls. The increased serum aspartate aminotransferase levels (AST), considered the key metabolic value in these patients, decreased significantly with Robuvit® (P<0.05) compared to controls. Serum alanine aminotransferase levels (ALT) also decreased significantly with the supplement compared to controls (P<0.05). Platelet count and albumin levels improved significantly with Robuvit® (P<0.05) in comparison to standard management. No other significant changes were observed. The APRI score (the AST/platelet ratio index) was also decreased with the supplementation compared to controls (P<0.05). A high APRI score provides an estimate of the possibility of the liver to develop fibrosis and eventually cirrhosis. After Robuvit® supplementation, the ultrasound characterization showed a significant decrease in the size of the liver in association with a lower echogenicity, which represents less fibrotic changes due to collagen accumulation. CONCLUSIONS: Robuvit® improved liver function in NAFLD and prevented progression to liver fibrosis by improving hepatic metabolism in a relatively short period of time. Numerous people are affected by NAFLD, many of them with subclinical symptoms. But to date, there are no specific, definite treatment options. Prolonged evaluations of Robuvit® in a larger group of subjects is suggested.

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

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