Pine Bark Extract (Pycnogenol)

Background: Gingival inflammation is highly prevalent and may impact systemic health. While professional mechanical plaque removal (PMPR) is the standard treatment, dietary interventions may provide additional benefits. The French maritime pine bark extract Pycnogenol® has anti-inflammatory and antioxidant properties, but its impact on inflammatory biomarkers in saliva and serum has not been studied in a controlled clinical trial. Methods: In this randomized, double-blind, placebo-controlled clinical trial, 91 participants received Pycnogenol® (100 mg twice daily; n = 46) or a placebo (n = 45) following PMPR. Saliva and serum samples were collected at baseline, and after two and three months. Inflammatory biomarkers (IL-1β, IL-6, MMP-8, and MMP-9) and polyphenol concentrations were analyzed using ELISA and LC-MS/MS. Results: Pycnogenol® supplementation significantly reduced salivary MMP-8 levels (p = 0.0261), and serum IL-6 levels compared to placebo (p = 0.0409). Additionally, ferulic acid, caffeic acid, and the gut microbial metabolite 5-(3,4-dihydroxyphenyl)-γ-valerolactone (M1) significantly increased in saliva following Pycnogenol® intake. A correlation analysis revealed a significant inverse association between bleeding on probing and M1 concentration in saliva (r = -0.3476, p = 0.0167). Conclusions: Dietary supplementation with Pycnogenol® significantly reduced key inflammatory biomarkers and increased polyphenol concentrations in saliva, suggesting a potential anti-inflammatory effect of Pycnogenol® on gingival inflammation. Trial registration: ClinicalTrials.gov (NCT05786820).

Complete surgical resection with clear margins remains the mainstay of therapy for localised fibrosarcomas. Nevertheless, metastatic fibrosarcomas still represent a therapeutic dilemma. Commonly used chemotherapeutic agents like doxorubicin have proven to be effective in <30% of all cases of disseminated fibrosarcoma. Especially elderly patients with cardiac subdisease are not suitable for systemic chemotherapy with doxorubicin. Therefore we tested the apoptotic effects of the well-tolerated pine bark extract pycnogenol and its constituents on human fibrosarcoma cells (HT1080). Ten healthy subjects (six females, four males, mean age 24.8 ± 6 years) received a single dose of 300 mg pycnogenol orally. Blood plasma samples were obtained before and 6 h after intake of pycnogenol. HT1080 cells were treated with these plasma samples. Additionally, HT1080 were incubated separately with catechin, epicatechin and taxifolin that are known as the main constituents of pycnogenol. Vital, apoptotic and necrotic cells were quantified using flow cytometric analysis. Gene expression was analyzed by RNA microarray. The results showed that single application of taxifolin, catechin and epicatechin reduced cell viability of HT1080 cells only moderately. A single dose of 300 mg pycnogenol given to 10 healthy adults produced plasma samples that led to significant apoptotic cell death ex vivo whereas pycnogenol-negative serum displayed no apoptotic activity. Microarray analysis revealed remarkable expression changes induced by pycnogenol in a variety of genes, which are involved in different apoptotic pathways of cancer cells [Janus kinase 1 (JAK1), DUSP1, RHOA, laminin γ1 (LAMC1), fibronectin 1 (FN1), catenin α1 (CTNNA1), ITGB1]. In conclusion, metabolised pycnogenol induces apoptosis in human fibrosarcoma cells. Pycnogenol exhibits its pro-apoptotic activity as a mixture and is more effective than its main constituents catechin, epicatechin and taxifolin indicating that the metabolised components interact synergistically. These results provide experimental support for in vivo trials assessing the effect of the pine bark extract pycnogenol.

BACKGROUND: Supplementation with pine bark extract (PBE) may improve risk factors associated with cardiometabolic syndrome (CMS). The effects of PBE supplementation on cardiometabolic risk factors were evaluated in this systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: A comprehensive search of various databases was performed to identify relevant RCTs published up to September 2024. A random-effects model was employed for the meta-analysis, which included 27 RCTs with 1,685 participants. RESULTS: The findings indicated that PBE supplementation significantly reduced systolic blood pressure (SBP) (weighted mean difference (WMD): -2.26 mmHg, 95% confidence interval (CI): -3.73, -0.79; P = 0.003), diastolic blood pressure (DBP) (WMD: -2.62 mmHg, 95% CI: -3.71, -1.53; P < 0.001), fasting blood sugar (FBS) (WMD: -6.25 mg/dL, 95% CI: -9.97, -2.53; P = 0.001), hemoglobin A1c (HbA1c) (WMD: -0.32%, 95% CI: -0.54, -0.11; P = 0.003), body weight (WMD: -1.37 kg, 95% CI: -1.86, -0.88; P < 0.001), and low-density lipoprotein (LDL) cholesterol (WMD: -5.07 mg/dL, 95% CI: -9.21, -0.94; P = 0.016) in the PBE-treated group compared to their untreated counterparts. However, no significant impact of PBE was observed on waist-to-hip ratio (WHR), body mass index (BMI), waist circumference (WC), or serum levels of insulin, high-density lipoprotein (HDL) cholesterol, triglycerides (TG), and total cholesterol (TC). CONCLUSIONS: Supplementation with PBE may ameliorate specific cardiometabolic risk factors, as indicated by reductions in body weight, DBP, SBP, FBS, LDL, and HbA1c levels. This approach can be regarded as an adjunct therapeutic strategy for CMS management. Further high-quality trials with larger sample sizes and longer durations are required to validate these findings. © 2025. The Author(s).

OBJECTIVES: High blood pressure (BP) is a major risk factor for cardiovascular disease and prevalence rates continue to rise with ageing populations. Polypharmacy remains a burden among the ageing, thus alternative effective strategies are warranted. This study investigated the effects of a polyphenols rich dietary supplement containing Pinus massoniana bark extract (PMBE) for modulating BP in healthy Australian adults. DESIGN: This study is a secondary analysis of data from a double-blinded, placebo-controlled clinical trial. METHODS: Sixty-two healthy adults aged 55-75 years were randomized to receive 50 mL dietary supplement containing placebo (0 mg PMBE) or PMBE (1322 mg PMBE) daily for 12 weeks. Seated systolic BP (SBP) and diastolic (DBP) were measured at baseline, 6 weeks and 12 weeks. Effects of PMBE on modulating BP was also explored in this study stratified for SBP status (optimal v high) as well as by SBP medication status. Mixed effect regression modelling was employed involving fixed categorical effects for elapsed time, treatment assignment and their interaction as well as random subject-level intercept to account for within-subject correlations resulting from repeated measurements. Significant models were further examined by addition of covariates and power calculations were performed since this study was a secondary analysis. RESULTS: SBP significantly reduced (-3.29 mmHg, p = 0.028) after PMBE at 12 weeks compared to baseline. SBP in individuals with normal-high SBP (>120 mmHg) in the PMBE group reduced by - 6.46 mmHg (p = 0.001) at 12 weeks compared to baseline. No significant changes were reported for individuals with optimal (≤120 mmHg) SBP nor did DBP significantly change in either study groups. In individuals with non-medicated normal-high SBP, SBP significantly reduced by - 7.49 mmHg (p = 0.001) and DBP by - 3.06 mmHg (p = 0.011) at 12 weeks compared to baseline after PMBE. Cross-group comparisons were not statistically different. CONCLUSIONS: A polyphenol-rich dietary supplement derived from PMBE led to a clinically and statistically significant reduction in SBP in adults. Future studies to investigate the effects of PMBE-polyphenol suppl

Inflammation plays an important role in the pathophysiology of traumatic brain injury (TBI). Based on the anti-inflammatory properties of French maritime pine bark extract and the neuroprotective effects, we aimed to evaluate the effects of its supplementation on TBI. Sixty-seven TBI patients admitted to the intensive care units (ICUs) were enrolled. After stabilizing the hemodynamic status, the intervention group received 150 mg of French maritime pine bark extract supplementation (Oligopin) with enteral nutrition for 10 days. The control group received a placebo. Inflammatory status and oxidative stress markers were measured three times. Also, clinical and nutritional statuses were assessed. Supplementation, significantly decreased IL-6 (β = -53.43 pg/ml, 95% confidence interval [CI] = -91.74, -15.13, p = .006), IL-1β (β = -111.66 pg/ml, 95% CI = -183.79, -39.5402, p = .002) and C-reactive protein (β = -19.99 mg/L, 95% CI = -27.23, -12.76, p ˃ .001) in the intervention group compared to control group after 10 days. Clinical scores including acute physiology and chronic health evaluation II and sequential organ failure assessment were reduced (β = -3.72, 95% CI = -5.96, -1.49, p = .001and β = -2.07, 95% CI = -3.23, -0.90, p < .001, respectively), and Nutric score was reduced compared to control group (β = -.60, 95% CI = -1.08, -0.12, p = .01). The survival rate was higher by 15% in the intervention group compared to control group. Oligopin supplementation in TBI patients in ICU reduced inflammation and improved the clinical status and malnutrition score and thereby reducing the mortality rate. © 2021 John Wiley & Sons Ltd.

BACKGROUND: Oral supplementation with a standardized extract from the bark of the French pine (Pycnogenol®) has been reported to benefit the skin. It might thus represent an easy-to-use strategy to improve the skin health of individuals who are exposed to considerable environmental stress in large urban areas. OBJECTIVE: We investigated if oral intake of Pycnogenol® can benefit the skin of Han Chinese working outdoors in Beijing, China. METHODS: In a monocentre, double-blind, randomized, placebo-controlled, and crossover study, the effects of Pycnogenol® intake (2 × 50 mg/day for a total of 12 weeks) on a variety of skin physiological parameters was studied in Chinese subjects (n = 76), from spring to autumn, who were working outdoors in Beijing, China. RESULTS: During the intervention period, study subjects were constantly exposed to increased levels of particulate matter (PM)2.5 as well as seasonal changes in humidity and temperature. Despite this environmental stress, Pycnogenol® intake prevented (i) a decrease in the skin hydration, (ii) transepidermal water loss (TEWL), and (iii) skin darkening during the dry autumn season. In addition, Pycnogenol® intake improved (iv) viscoelastic skin properties such as gross elasticity and elastic recovery irrespective of the season. These beneficial effects were not observed if the same subjects were supplemented with placebo. CONCLUSION: Oral intake of Pycnogenol® benefits the skin in Han Chinese, who are working outdoors under considerable environmental stress. © 2021 S. Karger AG, Basel.

OBJECTIVE: The RADIANT study aimed to investigate the efficacy and safety of a complementary medicine supplement combination in people with hand osteoarthritis (HOA). METHOD: This was an internet-based, double-blind, randomised, placebo-controlled trial. Participants aged over 40 years with symptomatic HOA with radiographic confirmation (Kellgren Lawrence grade ≥ 2) throughout Australia were recruited and randomly assigned (1:1) to receive either a supplement combination composed of Boswellia serrata extract 250 mg/day, pine bark extract 100 mg/day, methylsulfonylmethane 1,500 mg/day and curcumin 168 mg/day or placebo for 12 weeks. The primary outcome was change in hand pain assessed using a visual analogue scale (VAS 0-100) from baseline to week 12. A range of secondary outcomes and additional measures were recorded. Adverse events were monitored weekly. RESULTS: One hundred and six participants were included with mean age 65.6 years and 81% were women. 45% of the participants were graded as KLG 4, 40% KLG three and 39 (37%) had erosive OA. There was no significant difference in pain VAS reduction between groups. The adjusted between group difference in means (95%CI) was 5.34 (-2.39 to 13.07). Five participants (10%) in the supplement combination group discontinued study treatment due to AE vs four participants (7%) in the placebo group. CONCLUSION: There were no significant differences in symptomatic relief between the two groups over 12 weeks. These findings do not support the use of the supplement combination for treating hand pain in people with HOA. REGISTRATION: Prospectively registered (Australian New Zealand Clinical Trials Registry ACTRN12619000835145, 31/05/2019).

OBJECTIVES: This study investigated the effect of French maritime pine bark extract (PBE) supplementation on metabolic parameters, vascular cell adhesion molecule 1 (VCAM-1), urinary albumin-to-creatinine ratio (UACR), and anthropometric indexes in patients with type 2 diabetes (T2DM) and microalbuminuria. DESIGN: This randomized, double-blind, placebo-controlled clinical trial was conducted on 46 patients with T2DM and the evidence of microalbuminuria aged 30-65 years. SETTING: Patients were recruited from the endocrinology clinic of Sina hospital (Tabriz, Iran) from March 2018 to April 2019. INTERVENTIONS: The subjects were randomly assigned to receive two capsules/day each containing 50mg of PBE or placebo for eight weeks. MAIN OUTCOME MEASURES: Glycemic parameters, serum VCAM-1 and lipid profile, UACR, and anthropometric indexes were measured for all patients at baseline and the end of the study. RESULTS: PBE supplementation significantly reduced glycosylated hemoglobin, VCAM-1, total cholesterol, UACR, waist circumference, and waist-to-height ratio compared to the placebo group at the end of the study (all P < 0.05). Changes in fasting blood glucose, insulin, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were not significant between the two groups (all P > 0.05). CONCLUSIONS: The study findings demonstrated some favorable effects of PBE supplementation on glycemic control, serum VCAM-1 and total cholesterol levels, and microalbuminuria, as well as abdominal obesity in patients with T2DM.

The purpose of this study was to investigate the complementary effects of polyphenolic compounds from pine bark extract (PE) as a strong antioxidative substrate on the symptoms of inattention and impulsivity in children with attention-deficit hyperactivity disorder (ADHD). This was a randomized, double-blind, crossover, placebo-controlled study that included two experimental units (4 weeks with PE supplementation and 4 weeks with placebo supplementation) separated by a 2-week washout period. ADHD participants were supplemented with 25 mg or 50 mg PE. We recruited 20 participants (17 boys and 3 girls) with a mean age of 10.0 ± 2.1 years. PE supplementation caused a significant reduction in the inattention and hyperactivity-impulsivity items of SNAP-IV. During the period of PE supplementation, the item of commissions in the Continuous Performance Test III (CPT III) significantly decreased, which was used to evaluate the symptoms of inattention and impulsivity. In addition, the erythrocytic reduced glutathione/oxidized glutathione ratio significantly increased, and the plasma TBARs level significantly decreased after 4 weeks of PE supplementation. However, there was no significant correlation between CPT III (commission) and antioxidative status indictors. PE supplementation may have potential effects of ameliorating inattention and impulsivity, and elevating the antioxidative status in children with ADHD. © 2021 John Wiley & Sons, Ltd.

BACKGROUND: Evidence indicates a close association between oxidative stress and the etiopathogenesis of osteopenia. In vitro and animal studies report that Oligopin®, an extract of French maritime pine bark extract, has beneficial effects on oxidative stress. PURPOSE: Here, we aimed to determine whether supplementation with Oligopin® affects bone turnover markers, antioxidant enzymes, and oxidative stress markers in these patients. METHODS: Forty-three postmenopausal women with osteopenia were randomized in a placebo-controlled, double-blind clinical trial to receive either 150 mg/day Oligopin® (n = 22) or placebo (n = 21) for 12 weeks. Plasma levels of bone turnover markers; osteocalcin (OC), type I collagen cross-linked C-telopeptide (CTX-1), OC/CTX1 ratio along with total antioxidant capacity(TAC), malondialdehyde (MDA) concentration, protein carbonyl, and total thiol contents in plasma, activities of manganese superoxide dismutase (MnSOD) and catalase in both peripheral blood mononuclear cells (PBMCs) and plasma as well as mRNA expression of MnSOD, catalase, and Nrf2 in PBMCs were measured at the baseline and the end of the intervention. RESULTS: Oligopin® supplementation significantly increased OC levels and the ratio of OC to CTX1 in women with osteopenia compared to placebo intervention after 12 weeks. Oligopin® significantly decreased plasma protein carbonyl content in postmenopausal women compared with the after placebo treatment. Moreover, Oligopin® intervention significantly increased plasma total thiol content, TAC, plasma activity of both MnSOD and catalase, and the transcript level of Nrf2, MnSOD, and catalase in comparison with the placebo group. CONCLUSION: Supplementation with 150 mg/day Oligopin® for 12 weeks exerts beneficial effects in postmenopausal osteopenia through improving the antioxidant defense system in the plasma and PBMCs that was accompanied by an increase in indicators of bone turnover.

BACKGROUND: Pine bark (Pinus spp.) extract is rich in bioflavonoids, predominantly proanthocyanidins, which are antioxidants. Commercially-available extract supplements are marketed for preventing or treating various chronic conditions associated with oxidative stress. This is an update of a previously published review. OBJECTIVES: To assess the efficacy and safety of pine bark extract supplements for treating chronic disorders. SEARCH METHODS: We searched three databases and three trial registries; latest search: 30 September 2019. We contacted the manufacturers of pine bark extracts to identify additional studies and hand-searched bibliographies of included studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating pine bark extract supplements in adults or children with any chronic disorder. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility, extracted data and assessed risk of bias. Where possible, we pooled data in meta-analyses. We used GRADE to evaluate the certainty of evidence. Primary outcomes were participant- and investigator-reported clinical outcomes directly related to each disorder and all-cause mortality. We also assessed adverse events and biomarkers of oxidative stress. MAIN RESULTS: This review included 27 RCTs (22 parallel and five cross-over designs; 1641 participants) evaluating pine bark extract supplements across 10 chronic disorders: asthma (two studies; 86 participants); attention deficit hyperactivity disorder (ADHD) (one study; 61 participants), cardiovascular disease (CVD) and risk factors (seven studies; 338 participants), chronic venous insufficiency (CVI) (two studies; 60 participants), diabetes mellitus (DM) (six studies; 339 participants), erectile dysfunction (three studies; 277 participants), female sexual dysfunction (one study; 83 participants), osteoarthritis (three studies; 293 participants), osteopenia (one study; 44 participants) and traumatic brain injury (one study; 60 participants). Two studies exclusively recruited children; the remainder recruited adults. Trials lasted between four weeks and six months. Placebo was the control in 24 studies. Overall risk of bias was

INTRODUCTION: Hand osteoarthritis (HOA) is a highly prevalent disabling joint disease. The current management regimens are limited. Potentially as a consequence, many people turn to complementary and alternative medicines for symptomatic relief. A combination of two or more supplements is common in clinical practice; however, evidence for the efficacy of this approach is lacking. The aim of this study is to investigate the efficacy of a supplement combination for treating symptomatic HOA in comparison to placebo. METHODS AND ANALYSIS: The RADIANT study is an internet-based, parallel, superiority, double-blind, placebo-controlled, randomised, two-arm clinical trial. A participatory design is used to facilitate the study procedures. One hundred and six participants aged over 40 years with painful HOA and structural change on X-ray (Kellgren and Lawrence grade (KLG) ≥2) will be recruited from the community and randomly allocated to receive either a supplement combination composed of: (1) combined supplement containing Boswellia serrata extract, pine bark extract and methylsulfonylmethane and (2) curcumin or placebo for 12 weeks. The primary outcome will be 12-week change in hand pain on a visual analogue scale (VAS). Main secondary outcomes include adverse events, change in hand function, patient global assessment of disease activity and quality of life. A range of additional measures will be recorded, and an individual patient placebo response will be performed. The primary analysis will be conducted using an intention-to-treat approach. Adverse events will be monitored weekly throughout the study. ETHICS AND DISSEMINATION: This protocol has been approved by the University of Sydney Human Research Ethics Committee (HREC No. 2018/766). Dissemination will occur through conferences, social media, scientific publications and PhD thesis. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12619000835145); Pre-results. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

BACKGROUND: Traumatic brain injury (TBI) is one of the major health and socioeconomic problems in the world. Immune-enhancing enteral formula has been proven to significantly reduce infection rate in TBI patients. One of the ingredients that can be used in immunonutrition formulas to reduce inflammation and oxidative stress is pycnogenol. OBJECTIVE: The objective of this work is to survey the effect of pycnogenol on the clinical, nutritional, and inflammatory status of TBI patients. METHODS: This is a double-blind, randomized controlled trial. Block randomization will be used. An intervention group will receive pycnogenol supplementation of 150 mg for 10 days and a control group will receive a placebo for the same duration. Inflammatory status (IL-6, IL- 1β, C-reactive protein) and oxidative stress status (malondialdehyde, total antioxidant capacity), at the baseline, at the 5th day, and at the end of the study (10th day) will be measured. Clinical and nutritional status will be assessed three times during the intervention. The Sequential Organ Failure Assessment (SOFA) questionnaire for assessment of organ failure will be filled out every other day. The mortality rate will be calculated within 28 days of the start of the intervention. Weight, body mass index, and body composition will be measured. All analyses will be conducted by an initially assigned study arm in an intention-to-treat analysis. DISCUSSION: We expect that supplementation of 150 mg pycnogenol for 10 days will improve clinical and nutritional status and reduce the inflammation and oxidative stress of the TBI patients. TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov (ref: NCT03777683) at 12/13/2018.

OBJECTIVES: Dietary supplements are increasingly used by people with osteoarthritis. Boswellia serrata extract, curcumin, pine bark extract and methylsulfonylmethane have been identified as having the largest effects for symptomatic relief in a systematic review. It is important to understand whether any pharmacokinetic interactions are among the major constituents of these supplements so as to provide information when considering the combination use of these supplements. The aim of this study was to investigate the pharmacokinetics of the constituents alone and in combination. METHODS: This study was a randomized, open-label, single-dose, four-treatment, four-period, crossover study with 1-week washout. The pharmacokinetics of the constituents of these supplements when dosed in combination with methylsulfonylmethane were compared to being administered alone. Plasma samples were obtained over 24 h from 16 healthy participants. Eight major constituents were analysed using a validated ultra-high-performance liquid chromatography-tandem mass spectrometry assay. KEY FINDINGS: The pharmacokinetics of each constituent was characterized, and there were no significant differences in the pharmacokinetic profiles of the constituents when administered as a combination, relative to the constituents when administered alone (P > 0.05). CONCLUSIONS: These data suggest that interactions between the major constituents of this supplement combination are unlikely and therefore could be investigated to manage patients with osteoarthritis without significant concerns for possible pharmacokinetic interactions. © 2019 Royal Pharmaceutical Society.

AIM: Clinical trials on the effect of pycnogenol supplementation on cardiometabolic health have been controversial. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the potential effect of pycnogenol supplementation on cardiometabolic profile. METHODS: PubMed, Scopus, and ISI Web of Science databases were searched until October 2018. RCTs that evaluated the effects of pycnogenol on cardiometabolic parameters were included. DerSimonian and Laird random-effect models were used to compute the weighted mean differences (WMDs) and 95% confidence intervals (CIs). RESULTS: Twenty-four RCTs including 1594 participants were included in the meta-analysis. Pycnogenol significantly reduced fasting blood glucose (WMD: -5.86 mg/dl; 95% CI: -9.56, -2.15), glycated hemoglobin (WMD = -0.29%, 95%CI: -0.56, -0.01), systolic blood pressure (WMD: -2.54 mmhg; 95% CI: -4.08, -0.99), diastolic blood pressure (WMD: -1.76 mmhg; 95% CI: -3.12, -0.41), body mass index (WMD: -0.47 kg/m2; 95% CI: -0.90, -0.03), LDL cholesterol (WMD: -7.12 mg/dl; 95% CI: -13.66, -0.58) and increased HDL cholesterol (WMD: 3.27 mg/dl; 95% CI: 0.87, 5.66). CONCLUSION: This meta-analysis suggests that pycnogenol may have a role in preventing cardiometabolic disease. However, further well-designed RCTs are recommended to evaluate its long-term effects and explore the optimal duration of use and dosage.

French maritime pine bark extract (FMPBE; Oligopin®), a dietary supplement, is rich in procyanidin. The objective of this study was to determine the effects of FMPBE on bone remodeling in postmenopausal osteopenic women. This randomized, double-blinded, placebo-controlled clinical trial was conducted on 40 postmenopausal osteopenic women. Individuals were randomly assigned to either FMPBE (250 mg/day, n = 21) or placebo (250-mg starch/day, n = 19) for 12 weeks. Biochemical indices, including bone remodeling marker, were assessed before and after the intervention. After the 12-week intervention, that is, FMPBE supplementation, a significant increase in bone alkaline phosphatase (BAP), procollagen type 1 amino-terminal propeptide (P1NP) levels and a significant decrease in C-terminal telopeptide of type I collagen (CTx1) were observed. Compared with the control group, FMPBE supplementation resulted in a significant increase in P1NP (0.015), BAP levels (0.001), and BAP/CTx1 ratio (p = 0.001) and a significant decrease in CTx1 levels (0.006). FMPBE supplementation for 12 weeks in postmenopausal osteopenic women produced favorable effects on bone markers. Meanwhile, further research is needed to determine whether FMPBE supplements can be used as a preventive strategy for bone loss in postmenopausal osteopenic women. © 2019 John Wiley & Sons, Ltd.

INTRODUCTION: In the pre-therapeutic stage of osteopenia or clinically stable osteoporosis dietary supplements are frequently used, but often evidence for benefits and risks is sparse. The French maritime pine bark extract Pycnogenol® has anti-inflammatory and antioxidative effects. Although beneficial impact on various health conditions has been recorded, no data regarding the impact on quality of life and safety of Pycnogenol® supplementation in osteopenia and stable osteoporosis is available yet. METHODS: In a randomized, double-blind, placebo-controlled clinical trial, 67 women received Pycnogenol® (100 mg twice daily; n = 33) or placebo (n = 34) for 3 months, after which all participants took Pycnogenol® for additional 3 months in an active-treatment extension phase. The quality of life was assessed by two validated questionnaires and biochemical safety indicators, including blood count, liver and kidney function, markers of inflammation and mineral metabolism were analyzed. RESULTS: During the randomized placebo-controlled phase, the SF-36v2 bodily pain score improved in the Pycnogenol® group while remaining unchanged under placebo. This effect persisted after adjustment for baseline values (p = 0.0106). A comparable difference was observed for vitality (p = 0.0282). The total QUALEFFO-41 score did not differ between the groups. In the QUALEFFO-41 pain domain, scores were lower after 6 months in the group treated continuously with Pycnogenol® than in the group switched from placebo (p = 0.0231). During the intake of Pycnogenol®, the activities of the liver enzymes aspartate aminotransferase

INTRODUCTION: Osteoporosis is a highly prevalent health concern both in terms of disability to an individual and costs to society. While antiresorptive drugs are the standard treatment, nutritional supplementation may offer additional advantages, particularly in the pre-therapeutic stage of osteopenia or clinically stable osteoporosis. The French maritime pine bark extract Pycnogenol® exhibits antioxidant and anti-inflammatory properties, but its influence on bone turnover has not been investigated in humans yet. METHODS: In this randomized, placebo-controlled, double-blind clinical trial, 67 women received either Pycnogenol® (100 mg twice daily; n = 33) or placebo (n = 34) during a 3-month placebo-controlled phase, followed by a 3-month active-treatment extension, in which all participants took Pycnogenol®. The primary endpoint included changes in the bone resorption marker C-terminal telopeptide of type I collagen (CTX-1) and bone formation marker procollagen type I N propeptide (P1NP) in serum. Secondary endpoints comprised other bone turnover markers (N-terminal telopeptide of type I collagen, NTX-1; tartrate-resistant acid phosphatase 5b, TRAP5b; bone sialoprotein, BSP), an inflammatory marker (interleukin-6, IL-6), the microbial metabolite 5-(3',4'-dihydroxyphenyl)-γ-valerolactone (M1), and in vitro dif

The endothelial glycocalyx (GCX) is a major contributor to endothelial cell function and vascular integrity. GCX damage has been linked to atherosclerosis promotion and other pathophysiologic states. The dietary supplement Pycnogenol®, a standardized extract from the bark of Pinus pinaster, has shown beneficial impact on cardiovascular and endothelial health in various clinical studies, but the underlying effect mechanism is not fully understood. The purpose of the present investigation was to explore the influence of human serum collected before and after Pycnogenol® supplementation on the properties of the endothelial GCX under basal, osmotic and inflammatory conditions. Since static cell culture poorly reproduces a physiologically relevant GCX, while controlled flow systems are technically demanding, a suitable cell culture model was to be established. A dynamic culture model using a rocking shaker was successfully implemented. Visualization of endothelial GCX structures using lectin-based staining with wheat germ agglutinin (WGA) revealed significantly increased WGA intensity (approximately 60%) under dynamic compared to static culture conditions. Under dynamic conditions, endothelial cell viability and proliferation were significantly enhanced as well as the functional responsiveness to TNF-alpha and sodium chloride exposure. When cells were dynamically incubated with serum samples obtained from healthy volunteers before and after intake of Pycnogenol®, the WGA signal intensity per cell significantly increased across all conditions. Endothelial monolayer permeability as determined with labelled dextran decreased by up to 48% after incubation with serum obtained after intake of Pycnogenol®. Moreover, the GCX shedding markers syndecan-4 an

OBJECTIVE: To describe the distribution and day-to-day variability of EuroQol Visual Analogue Scale (EQ-VAS) values and to estimate a minimal important difference (MID) in adults with post-COVID-19 condition (PCC). DESIGN: Secondary analysis of pooled EQ-VAS data from both arms of a 12-week randomised, placebo-controlled trial (PYCNOVID) of Pycnogenol (200 mg/day) versus placebo in adults with PCC. SETTING: Single centre study in Switzerland between June 2023 and July 2024. PARTICIPANTS: Adults with PCC with at least one of the following symptoms: fatigue, post-exertional malaise, dyspnoea or brain fog. MAIN OUTCOME MEASURE: EQ-VAS ratings over 7 consecutive days before baseline (randomisation) and at follow-up (after 12 weeks). Weekly mean EQ-VAS values and within-person SDs (wpSD) were calculated. The MID was estimated using distribution-based and anchor-based methods with prespecified correlation criteria, using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) instrument as the primary anchor, along with additional anchors. RESULTS: Among 153 participants, baseline EQ-VAS values were low, with a median of 48.7 on a 0-100 scale. Day-to-day variability was considerable, with a median wpSD of 6.4. Distribution-based MID estimates ranged from 5.9 to 8.9 points. FACIT-Fatigue was the only anchor meeting the correlation threshold (ρ≥0.30), yielding an anchor-based MID of 8.96 points. Triangulation of these estimates supported a final MID estimate of 8 EQ-VAS points. CONCLUSIONS: Adults with PCC reported

BACKGROUND: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome associated with liver dysfunction and remains a major cause of mortality among patients with advanced liver disease. This study aimed to evaluate the protective effects of Pycnogenol in a rat model of thioacetamide-induced hepatic encephalopathy. METHODS: Thirty-two rats were assigned to four groups: control, HE (TAA), and two treatment groups receiving Pycnogenol at 5 mg/kg and 10 mg/kg. HE was induced by intraperitoneal administration of TAA at 200 mg/kg for three consecutive days. Pycnogenol was administered orally for 14 days prior to and during TAA exposure. Behavioral tests (locomotor activity, elevated plus maze), histopathological evaluations, biochemical parameters, immunohistochemical staining, and gene expression analyses (qPCR) were performed. RESULTS: Pycnogenol administration resulted in significant improvements in locomotor activity, reductions in oxidative stress marker

Acrolein (AC) is a potential environmental contaminant that poses a serious threat to human health and the environment. Studies on human diseases that can result from AC have rapidly increased in recent years. Pycnogenol (PYC), a natural phenolic compound, has therapeutic and protective potential against some cancers. Currently, there is insufficient data on the potential effects of AC and PYC on pancreatic cells or on their interaction. Because toxicological effects of AC and interactions between AC and PYC in human pancreatic cells have not yet been investigated, we evaluated the toxicological profile of AC and possible protective effect of PYC on healthy human pancreatic cells (hTERT-HPNE). Our results showed that AC (25, 50, and 100 µM) increased cytotoxicity and oxidative stress, induced apoptosis and DNA single- and double-strand breaks, whereas it decreased mitochondrial membrane potential and antioxidant parameters in human pancreatic cells. Combined treatments with AC and PYC (100 µg/mL) improved these parameters compared to AC treatment alone. Therefore, our results suggest that PYC may have a protective effect against AC-induced damage. Our results may also be particularly important for identifying the factors involved in the pathogenesis of mitochondrial diseases, which have rapidly increased in recent years, and for providing preventive solutions. © 2026 Wiley Periodicals LLC.

BACKGROUND: Peripheral nerve injuries frequently lead to incomplete functional recovery, largely due to secondary oxidative stress and neuroinflammation that impede regeneration. Pycnogenol®, a standardized French maritime pine bark extract rich in procyanidins, exhibits potent antioxidant and anti-inflammatory activities, suggesting potential neuroregenerative benefits. This study aimed to comprehensively evaluate the neuroregenerative potential of Pycnogenol® in a rat sciatic nerve crush model using an integrated assessment of histopathological, biochemical, and functional electrophysiological outcomes. METHODS: In a randomized, blinded, controlled study, 20 male Wistar rats underwent sciatic nerve crush injury. Animals were allocated to receive either intraperitoneal Pycnogenol® (20 mg/kg/day) or an equivalent volume of saline vehicle for 28 days. Functional recovery was assessed by measuring the motor threshold current (MTC) at baseline and day 28. Histopathological evaluation of nerve s

The preservation of beef products, particularly thawed beef, presents significant challenges due to the rapid growth of spoilage organisms and oxidative processes. This study introduces a novel water-resistant bilayer film. The active inner layer was composed of Artemisia sphaerocephala Krasch gum (ASKG) integrating gliadin nanoparticles loaded with Pycnogenol (PGNPs), and was cast onto a pre-formed film made of a blend of chitosan and gelatin. Compared to single-layer, the bilayer film exhibited significantly enhanced physical properties. The film showed a tensile strength of 13.22 MPa and an elongation at break of 204.99%. More importantly, it demonstrated excellent barrier performance, with water vapor permeability of 11.14 × 10-10 g·m-1·s-1·Pa-1 and oxygen permeability of 3.26 × 10-9 g·mm·m-2·s-1·Pa-1. When applied to thawed beef during refrigerated storage, this bilayer film effectively inhibited quality deterioration. Key improvements included inhibited moisture loss, appearance changes, protein and fat oxidation, and odor changes in thawed beef. These results demonstrate that the bilayer film presented a highly promising solution for thawed beef preservation.

Erratum in Cureus. 2025 Nov 18;17(11):c379. doi: 10.7759/cureus.c379. Rhabdomyolysis can cause complications such as acute kidney injury (AKI), with common etiologies including strenuous exercise, trauma, medications, and toxins. Given that creatine kinase (CK) levels of about 100,000 U/L are rare, this level of elevation may indicate the presence of an underlying contributor, such as excessive Pycnogenol intake, emphasizing the importance of taking a thorough patient history to identify factors that may otherwise be overlooked. We present a case of a 35‑year‑old previously healthy male who presented with diffuse myalgia, soreness, and tea‑colored urine two days after lifting furniture for a friend. The physical examination revealed mild tenderness and edema in his upper extremity muscles. Laboratory studies showed an initial CK of 154,000 U/L, aspartate aminotransferase (AST) of 2,400 U/L, alanine aminotransferase (ALT) of 700 U/L, and normal renal function (creatinine: 0.7-0.8 mg/dL throughout admission). Urine toxicology, viral serologies, and antinuclear antibody (ANA) were negative. During a subsequent interview, the patient disclosed consuming over-the-counter French maritime pine bark extract (Pycnogenol) in excess of the labeled recommendations. On day six of the patient's admission, the CK level declined to 7,874 U/L; transaminase levels decreased to AST of 252 U/L and ALT of 468 U/L with aggressive IV hydration. There was no evidence of kidney injury during the hospital course. This case suggests a potential association between excessive Pycnogenol consumption and severe rhabdomyolysis triggered by minimal physical activity, supported by a Naranjo score of 3. Clinicians should inquire about dietary supplement use when CK le

Pycnogenol, a standardized French maritime pine bark extract, is known for its antioxidant, anti-inflammatory, and neuroprotective properties. This study evaluated its therapeutic potential in sciatic nerve regeneration following crush injury in female Sprague Dawley rats. Twenty-one rats were assigned to Sham, Control, and Pycnogenol (100 mg/kg/day) groups. After standardized nerve injury, Pycnogenol was administered for 28 days. Functional recovery was assessed using the Sciatic Functional Index (SFI), pinprick, and cold allodynia tests. Histopathology, muscle weight, and ELISA for nerve growth factor (NGF) were evaluated post-euthanasia. By Day 14, the Pycnogenol group showed significantly better SFI scores (83.60 ± 2.26 vs. 89.81 ± 2.42, p < 0.001), with continued improvement through Day 28 (49.42 ± 3.0 vs. 62.95 ± 2.93, p < 0.001). Histological analysis revealed enhanced muscle regeneration, increased fiber area, and improved myelination. EL

Nosocomial infections caused by Pseudomonas aeruginosa (P. aeruginosa) have become increasingly common, particularly among immunocompromised individuals, who experience high mortality rates and prolonged treatment durations due to the limited availability of effective therapies. In this study, we screened for anti-ExoS compounds targeting P. aeruginosa and identified pycnogenol (PYC) as a potent inhibitor of the type III secretion system (T3SS), a major virulence mechanism responsible for the translocation of effectors such as ExoS. Using ELISA, western blotting, and real-time PCR analyses in both P. aeruginosa and infected H292 cells, we found that PYC significantly reduced T3SS activity. Mechanistically, PYC suppressed the transcription of T3SS-related genes by downregulating exsA expression in P. aeruginosa. Furthermore, pretreatment with PYC attenuated the cytotoxic effects and reduced the expression of proinflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-18 (IL-18), in P. aeruginosa-infected H292 cells. These effects were associated with the in

BACKGROUND: The aim of this pilot registry study was to investigate the use of Pycnogenol® (French maritime pine bark, standardized extract) in subjects 2 weeks after an episode of sudden loss of vision (SLV). METHODS: Visual acuity, retinal edema, vasospasms, distal retinal circulation and blood flow at the Zinn-Haller circle (distal optic nerve) were examined over 4 weeks. In addition, symptoms of neurological alterations (ION: ischemic optic neuritis) associated with retinal flow decrease were monitored. One registry group used only the standard management (SM, control group), a second group used SM+ 150 mg Pycnogenol®/day (Pycno150) and another group used SM+100 mg Pycnogenol® /day (Pycno100). RESULTS: Sixty subjects completed the study. 18 in the control group, 20 in the Pycno150 group and 22 subjects in the Pycno100 group. The registry groups were comparable at inclusion. No dropouts were observed in the two Pycnogenol® groups whereas 2 dropouts occurred in the SM group (due to the occurrence of a new, minor visual loss episode). No side effects or tolerability problems were observed during the registry study. After 4 weeks, the visual acuity score of the affected eye was significantly higher in t

BACKGROUND: The aim of this pilot supplement registry study was to investigate the efficacy of the anti-inflammatory supplement Pycnogenol® in subjects with history of Lyme disease and persistent symptoms with no active bacteria present (Stage 2 and 3 of Lyme disease), on the reduction of inflammation and the relieve of the main symptoms. There is currently no specific treatment for this condition. METHODS: The subjects were divided into two groups: one group received 150 mg/day of Pycnogenol® alongside standard management, while the control group received only standard management. The observation period lasted for six months. RESULTS: Forty subjects with history of Lyme Disease and persistent symptoms completed the study: 20 in the Pycnogenol® group, 20 in the control group. No side effects from the supplementation were observed. The tolerability was optimal as no supplemented subject had to stop management and compliance was optimal with 97% of the Pycnogenol® capsules correctly used. The two groups were comparable for sex, age distribution and for their main clinical findings and signs/symptoms at inclusion. During the study, corticosteroids at low dose were used on demand in 10% of subjects using Pycnogenol® and significantly more, in 45% of the control patients (P<0.05). After 6 months, the number of patients experiencing symptoms was significantly lower in the Pycnogenol® group compared to the control group across all symptoms (P<0.05). After

BACKGROUND: A mancozeb, belonging to a pesticide, can induce testicular injury via free radical generation and antioxidant suppression. Pinus pinaster extract (Pycnogenol®) and L. carnitine have potent antioxidant properties. AIM: This study aimed to compare and evaluate the therapeutic roles of P. pinaster extract (Pycnogenol®) and L. carnitine in eliminating and/or reducing the testicular toxicity of mancozeb in male rats, emphasizing their combined antioxidant. METHODS: Testicular toxicity was induced by oral administration of mancozeb (MCZ) at a dose of 313.6 mg/Kg for 4 weeks. Fifty male rats were allocated randomly into 5 groups, each group contained 10 rats. The first group (control group; C), second group (mancozeb group; MCZ) was orally administered 313.6 mg/Kg of mancozeb as a single dose/day for 4 weeks, third group (MCZ+PPE) received MCZ as the second group then administered P. pinaster extract (Pycnogenol®) at dose 40 mg/ Kg/day/ orally for 4 weeks, fourth group (MCZ+LC) was treated as the second group then administered L. carnitine at dose 200 mg/Kg/day/orally for 4 weeks. The fifth group (MCZ+PPE+LC) was treated as the second group and then received PPE and LC at the same doses mentioned in the third and fourth groups for 4 weeks. RESULTS: Testicular follicle-stimulating hormone receptor (FSHr) and luteinizing hormone receptor (LHr) gene expression was significantly upregulated in rats that received PPE + LC+ MCZ compared with the experimental rats. The seminal fluid quality was significantly elevated while abnormal morphology significantly declined in the MCZ+PPE, MCZ+LC, and MCZ+PPE+LC groups compared with the MCZ group. The serum F

BACKGROUND: This study investigated the potential use of a food supplement, Pycnogenol® (French maritime Pine Bark Extract) as an anti-inflammatory management during the remission phases of four conditions with a vasculitis component: systemic lupus erythematosus, Behçet's disease, Sjögren Syndrome and polyarteritis nodosa. Symptoms were minimal but persisting and the subjects did not use any chronic drug treatment. METHODS: The aim of this pilot registry study was to evaluate the safety and the preventive effects of oral Pycnogenol® on the residual symptoms of the inflammatory conditions and possible effects on the recurrence of symptoms in a 4-week, open, supplement registry study. RESULTS: The registry study included 124 otherwise healthy subjects, suffering from one of the vasculitis conditions with 63 patients taking Pycnogenol® 150 mg per day and 61 serving as controls. There were no dropouts. Symptom distribution was comparable in the control and in the supplement groups at baseline. No side effects of Pycnogenol® supplementation were observed. The symptom scores that ranged from 0 to 10, decreased significantly in all the Pycnogenol® groups after 4 weeks compared to controls (P<0.05). After 4 weeks ESR values decreased significantly in all Pycnogenol® groups compared to controls (P<0.05). The proportion of subjects with high IL-6 (>5.9 pg/mL) decreased significantly after 4 weeks in the Pycnogenol® group compared to controls. The proportion of subjects th

Background: This study aims to elucidate the potential protective effects of Pycnogenol® against noise-induced hearing (NIHL) loss in a rat model. Methods: This study employed a randomized controlled design to investigate the potential protective effects of Pycnogenol® against NIHL in a rat model. Twenty-five male Wistar albino rats were randomly assigned to 5 groups (n=5 per group): a control group receiving saline administration, a noise exposure group, a noise+saline receiving group, only Pycnogenol® receiving group, and finally, a Pycnogenol® treatment group receiving daily oral administration of Pycnogenol® at 40 mg/kg/day via gavage for 7 days following noise exposure. All groups were subjected to auditory brainstem response assessments at 4 time points: pre-exposure (baseline), post-exposure day 1, day 7, and day 21. Both noise exposure and the Pycnogenol® treatment groups were exposed to 4 kHz narrowband noise at 120 dB SPL for 4 hours. Following sacrifice, histological and immunohistochemical evaluations were conducted on cochlear tissues. Statistical analyses were performed using SPSS software version 25 to determine significant differences between groups and across time points. Results: Outcome of this research shows that the auditory brainstem response thresholds and cochlear morphology between the experimental and control groups are significantly different from each other, suggesting that

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. Microcircul

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 PO<inf>2</inf> increased significantly with PYCE compared to controls and transcutaneous skin PCO<inf>2</inf> decreased significantly compared to controls (P<0.05). T

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 cont

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 PO<inf>2</inf>-PCO<inf>2</inf> were significantly improved with Pycnogenol® compared to compression (P<0.05). The significant increase in skin PO<inf>2</inf> and the decrease in PCO<inf>2</inf> after Pycnogenol® intake were ascribed to the decrease in

BACKGROUND: A significant proportion of the global population has been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at some point since the onset of the pandemic. Although most individuals who develop coronavirus disease 2019 (COVID-19) recover without complications, about 6% have persistent symptoms, referred to as post-COVID-19 condition (PCC). Intervention studies investigating treatments that potentially alleviate PCC-related symptoms and thus aim to mitigate the global public health burden and healthcare costs linked to PCC are desperately needed. The PYCNOVID trial investigates the effects of Pycnogenol®, a French maritime pine bark extract with anti-inflammatory and antioxidative properties, versus placebo on patient-reported health status in people with PCC. METHODS: This is a single-center, placebo-controlled, quadruple blind, randomized trial. We aim to randomly assign 150 individuals with PCC (1:1 ratio) to receive either 200 mg Pycnogenol® or placebo daily for 12 weeks. Randomization is stratified for duration of PCC symptoms (≤ 6 months versus > 6 months) and presence of symptomatic chronic disease(s). The primary endpoint is perceived health status at 12 weeks (EuroQol-Visual Analogue Scale) adjusted for baseline values and stratification factors. Secondary endpoints include change in self-reported PCC symptoms, health-related quality of life, symptoms of depression and anxiety, cognitive function, functional exercise capacity, physical activi

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

Pycnogenol® French maritime pine bark extract is a well-known and thoroughly studied patented extract from the bark of Pinus pinaster Ait. ssp. Atlantica. In 39 randomized double-blind, placebo-controlled (RDP) human clinical trials including 2,009 subjects, Pycnogenol® French maritime pine bark extract supplementation for two weeks to six months has been shown to beneficially affect cardiovascular health, chronic venous insufficiency, cognition, joint health, skin health, eye health, women's health, respiratory health and allergies, oral health and sports performance. The mechanisms of action that can explain the respective effects on different conditions in the human body are discussed as well. As investigated in several in vitro, in vivo and in clinical studies, Pycnogenol® French maritime pine bark extract showed antioxidative effects, anti-inflammatory abilities, beneficial effects on endothelial function and reinforcing effects on the extracellular matrix. The present review aims to give a comprehensive overview of currently available "gold standard" RDP trials of Pycnogenol®'s benefits across various health domains compared to placebo. In addition, some of the processes on which the presented effects of Pycnogenol® French maritime pine bark extract are based will be elucidated and discussed. This broad overview of RDP studies on Pycnogenol® in different health domains can be used as a basis for further research on applications and mechanisms of this unique French maritime pine bark extract.