French Maritime Pine Bark Extract Research Articles

Pycnogenol® French maritime pine bark extract in randomized, double-blind, placebo-controlled human clinical studies.

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.

Review of the pharmacokinetics of French maritime pine bark extract (Pycnogenol®) in humans.

The French maritime pine bark extract Pycnogenol® is a proprietary product from Pinus pinaster Aiton. It complies with the quality specifications in the United States Pharmacopeia monograph "Pine extract" in the section of dietary supplements. Pycnogenol® is standardized to contain 65-75% procyanidins which are a variety of biopolymers consisting of catechin and epicatechin monomeric units. The effects of Pycnogenol® have been researched in a multitude of human studies. The basis for any in vivo activity is the bioavailability of constituents and metabolites of the extract. General principles of compound absorption, distribution, metabolism and elimination as well as specific data from studies with Pycnogenol® are summarized and discussed in this review. Based on plasma concentration profiles it can be concluded that low molecular weight constituents of the extract, such as catechin, caffeic and ferulic acid, taxifolin are readily absorbed from the small intestine into systemic circulation. Procyanidin oligomers and polymers are subjected to gut microbial degradation in the large intestine yielding small bioavailable metabolites such as 5-(3',4'-dihydroxyphenyl)-γ-valerolactone. After intake of Pycnogenol®, constituents and metabolites have been also detected in blood cells, synovial fluid and saliva indicating a substantial distribution in compartments other than serum. In studies simultaneously investigating concentrations in different specimen, a preferential distribution of individual compounds has been observed, e.g., of ferulic acid and 5-(3',4'-dihydroxyphenyl)-γ-valerolactone into synovial fluid compared to serum. The main route of elimination of constituents and metabolites of the French pine bark extract is the renal excretion. The broad knowledge accumulated regarding the pharmacokinetics of compounds and metabolites of Pycnogenol® constitute a rational basis for effects characterized on a cellular level and observed in human clinical studies.

Effect of pine bark extract and its phenolic compounds on selected pathogenic and probiotic bacterial strains.

Inflammatory bowel disease (IBD) comprises a heterogeneous group of chronic diseases as ulcerative colitis (UC) and Crohn's disease (CD). IBD is the result of a dysregulation of intestinal homeostasis with a host's loss of tolerance toward normal enteric microflora. Plant-based extracts as phenolic compounds can play a role by modulating the intestinal inflammation response. The in vitro antimicrobial activity of French maritime pine bark extract (PBE) and its phenolic constituents has been investigated in this study. Furthermore, the ability of PBE and phenolic compounds (caffeic acid, chlorogenic acid, ferulic acid, gallic acid and taxifolin) to modulate the microbiota has been assessed. Phenolic compounds and PBE showed a great inhibitory effect on the pathogens growth at the highest concentration assessed (1.25 mg/mL). The growth of E. sakazakii and E. faecalis were affected by the effect of caffeic acid and ferulic acid. Taxifolin showed a very strong activity against Listeria sp. (with a reduction ~98%). Gallic acid revealed antibacterial effect on S. aureus at different concentrations. The inhibitory effect of PBE was highly significant on the growth of E. coli O157:H7. PBE, caffeic acid and chlorogenic acid seem to provide the greatest beneficial effect on the probiotic bacteria. However, the highest concentrations of taxifolin may have impaired the growth of beneficial microbiota. Present findings could be of interest for considering PBE and/or its phenolic constituents as protectors against gastrointestinal disturbances which lead to ulcerative colitis and Crohn's disease.

An oral French maritime pine bark extract improves hair density in menopausal women: A randomized, placebo‐controlled, double blind intervention study

Female pattern hair lossaffects females of all ages with a trend to increase after menopause. This disorder may have significant psychological impact and lead to anxiety and depression. In a single center, double blind, randomized, placebo-controlled study, the effects of oral Pycnogenol® intake (3 × 50 mg/day for a total of 6 months) on hair density, scalp microcirculation, and a variety of skin physiological parameters was studied in Han Chinese menopausal women (N = 76) in Shanghai, China. Measurements were taken at the beginning and after 2and 6months, respectively. Hair density was determined by digital photographs and further evaluated by Trichoscan software. Transepidermal water loss was measured by a humidity sensor in a closed chamber on the skin surface. Changes in microcirculation were detected as resting flux on the scalp by reflection photoplethysmography. Pycnogenol® intake significantly increased hair density by 30% and 23% after 2and 6months of treatment, respectively, as detected by Trichoscan® evaluation of digital photographs. Interestingly, photoplethysmography revealed that this beneficial effect was associated with a decrease in resting flux of the scalp skin, which might indicate an improvement of microcirculation. None of these effects were observed in the placebo taking group. In addition, a significant transient decrease of transepidermal water loss was observed in scalp skin under Pycnogenol,®but not placebo treatment. Oral intake of Pycnogenol® might have the potential to reduce hair loss in postmenopausal women.

Targeting Inflammation in the Diagnosis, Management, and Prevention of Cardiovascular Diseases.

Inflammation plays an important role in the development and progression of cardiovascular diseases (CVDs). Hypertension and hyperlipidemia are the key risk factors of CVDs and induce inflammation in the heart and vessels. Unhealthy diet, infection, and smoking coupled with genetic factors lead to the development of CVDs as well as induce inflammation. Risk factors of CVDs such as hypertension and hyperlipidemia along with diabetes activate nuclear factor kappa B, which regulates the transcription of immunoglobulin free light chain (FLC) κ in B cells and the production of multiple inflammatory molecules, leading to inflammation. FLCs are novel biomarkers of inflammation, and their levels have been associated with overall mortality in a general population and with cardiovascular outcomes. In this review, the role of inflammation in the pathogenesis of CVDs, new biomarkers of inflammation, and dietary options counterbalancing inflammatory processes, such as the polyphenol-rich French maritime pine bark extract Pycnogenol, are discussed.

Clinical Investigation of French Maritime Pine Bark Extract on Attention-Deficit Hyperactivity Disorder as compared to Methylphenidate and Placebo: Part 1: Efficacy in a Randomised Trial

Graphical abstract with the main results of the clinical trial • Assessing the value of French Maritime Pine Bark Extract (PBE) in ADHD therapy as compared to methylphenidate (MPH) and placebo in a 10-week randomised trial; • Teachers reported significant improvement of total and hyperactivity/impulsivity ADHD-RS scores (primary outcome) by PBE and MPH after 10 weeks compared to placebo; • Adverse effects reported five times more frequently for MPH than for PBE; • PBE is a valuable treatment option in paediatric ADHD especially for those not willing to take standard medication or experiencing side effects. Determine the effect of French Maritime Pine Bark Extract (PBE; Pycnogenol®) on Attention-Deficit Hyperactivity Disorder (ADHD) behaviour and co-morbid physical/psychiatric symptoms, compared to placebo and the medicine MPH, and to assess its tolerability. Behaviour (measured by the ADHD-Rating Scale (ADHD-RS) and Social-Emotional Questionnaire (SEQ)) and physical complaints were evaluated in weeks 5 and 10. Eighty-eight paediatric ADHD patients (70 % male, mean age 10.1 years) were randomised to placebo (n = 30), PBE (n = 32) or MPH (n = 26). Teachers reported significant improvement of total and hyperactivity/impulsivity ADHD-RS scores by PBE and MPH after 10 weeks compared to placebo. MPH also improved inattention. SEQ ratings support ADHD-RS results. Adverse effects were reported five times more frequently for MPH than for PBE. PBE appears a good alternative for MPH in paediatric ADHD and especially in the primary school environment, a fortiori when considering its almost complete lack of adverse effects.

Clinical Investigation of French Maritime Pine Bark Extract on Attention-Deficit Hyperactivity Disorder as compared to Methylphenidate and Placebo: Part 2: Oxidative Stress and Immunological Modulation

To evaluate the effect of French Maritime Pine Bark Extract (PBE; Pycnogenol®) on immune, oxidative stress and neurochemical biomarkers in paediatric Attention-Deficit Hyperactivity Disorder (ADHD) as compared to methylphenidate (MPH) and placebo. Paediatric ADHD patients (n = 88, 70 % male, mean age 10.1 years) were randomised (placebo (n = 30), PBE (n = 32) and MPH (n = 26)) receiving 20 mg/day if < 30 kg or 40 mg/day if ≥ 30 kg PBE, or 20 mg/day if < 30 kg or 30 mg/day if ≥ 30 kg MPH for 10 weeks. In the oxidative stress pathway, catalase (CAT) activity was nominally significant different in the PBE group with a p-value of 0.025 whereas the immunity biomarkers IgA and IgG2 were nominally significant different after MPH treatment with a p-value of 0.028 and 0.017 respectively, compared to baseline. Serum Neuropeptide Y (NPY) levels and weight were significantly lower after 10-weeks MPH. Loss of appetite and weight loss was observed for MPH, whereas no differences in NPY concentrations and a significant weight gain, which is to be an expected physiological process in this age group, was noticed for PBE. Firm evidence that PBE increases antioxidant levels, reduces oxidative damage and improves immune status in general as compared to placebo or MPH could not be obtained.

Pycnogenol® supplementation alleviates symptoms of Parkinson's disease with mild cognitive impairment.

The aim of this pilot registry study was to assess the preventive effect of an 8-week Pycnogenol® (French maritime pine bark extract) supplementation on symptoms, such as cognitive and motor aspects, in subjects with Parkinson's disease (PD). The study was based on five types of observations: a. Karnofsky performance scale index; b. oxidative stress markers in plasma (plasma free radicals, PFR); c. the main signs and symptoms, evaluated by a physician; d. face motion and expressions and their symmetry, recorded with a high-speed video camera. A total of 79 patients were included in the study: 39 controls using only standard management (SM) and 40 subjects supplemented with Pycnogenol® 150 mg/day. At inclusion, the two groups (SM and SM+Pycnogenol®) were comparable for age, symptoms, Karnofsky performance scale rating and for the management of PD. Likewise, oxidative stress and the presence of peripheral edema were also comparable between the two groups. No side effects of supplementation were observed. There were no tolerability problems. At the end of the study after 8 weeks, the Karnofsky performance index was significantly (P<0.05) higher with Pycnogenol® compared to controls. Also, the proportion of patients with a clinically visible peripheral edema decreased significantly over 8 weeks with Pycnogenol® compared to controls (P<0.05). Plasma oxidative stress was significantly lower with Pycnogenol® (P<0.05). The scores of PD main signs/symptoms like tremor, bradykinesia, alterations in cognitive functions, rigidity and speech impairment were significantly lower in the Pycnogenol® group compared to controls (P<0.05). Face expression evaluation showed a marked asymmetry at inclusion. Over 8-week supplementation, facial expression scores for visible and subliminal asymmetry, altered facial responses, altered shoulder motion and altered emotional pattern improved significantly in the Pycnogenol® group compared to controls (P<0.05) where the scores did not change significantly. In conclusion, according to this pilot registry study, Pycnogenol® supplementation helps patients with moderate, well-controlled PD - under stable treatment - to attenuate most signs and symptoms and life-relational aspects associated with Parkinson-related cognitive impairment.

Primary benign back pain: supplementation with Pycnogenol®.

Back pain (BP) is one of the most common problems seen by general practitioners. The aim of this pilot registry study was to evaluate the effects of Pycnogenol® (French Maritime Pine Bark extract) on pain, mobility and muscle spasm in patients with recurring episodes of back pain without any other clinical condition. The registry follow-up lasted 3 weeks. Subjects used either SM (standard management), including mild exercise and 3 days of resting or immobilization - or SM+Pycnogenol® 200 mg/day (4 cps/day). Eighty-two subjects were included in the study, 23 took Pycnogenol® and 59 were in the SM group. No safety problems or tolerability problems were observed with Pycnogenol® or with the SM. The two groups, SM and SM+Pycnogenol®, were comparable at inclusion. A prevalent localization to the lower part of the back/spine was observed in all patients of both groups. The improvement in Karnofsky performance status Scale - expressing the global physical capacity of the individuals - during the 3 weeks of follow-up was significantly higher and faster in the Pycnogenol® group (P<0.05) compared to SM. Patients were able to restart physical training in 3 weeks with Pycnogenol® (in comparison with 4.5 weeks with SM only). The decrease in back pain score (VASL score) was faster and more pronounced with Pycnogenol® (P<0.05) compared to SM. Oxidative stress was significantly reduced in subjects using Pycnogenol® (P<0.05) while it remained elevated in the control group. The use of the rescue medication doses (ibuprofen) was significantly higher in the SM only (P<0.05) in comparison with SM+Pycnogenol®. Pycnogenol® appears to be an effective and safe supplementary management in healthy subjects with idiopathic BP. Mobility, pain, general physical capacity and oxidative stress improved in only a week with further improvements up to 4 weeks in most patients; results appear to be better and faster with Pycnogenol® supplementation than with SM alone.

The effect of French maritime pine bark extract supplementation on inflammation, nutritional and clinical status in critically ill patients with traumatic brain injury: A randomized controlled trial.

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.

Invitro effect of pine bark extract on melanin synthesis, tyrosinase activity, production of endothelin-1, and PPAR in cultured melanocytes exposed to Ultraviolet, Infrared, and Visible light radiation.

French maritime pine bark (Pinus pinaster) extract (PBE), the registered trade name of which is Pycnogenol® , has been studied for its depigmenting action due to its antioxidant, anti-inflammatory, and anti-melanogenic activity. However, the mechanisms through which PBE are still not fully clear. Evaluate the impact of PBE on four in vitro parameters closely associated with cutaneous pigmentation, including melanin synthesis, tyrosinase activity, endothelin-1 (ED1), and production of peroxisome proliferator-activated receptor α, δ, and γ (PPAR α, δ, and γ), by studying the modulation of action of ultraviolet radiation A (UVA)/ultraviolet radiation B (UVB), infrared-A (IR-A), visible light (VL), and association of UVA/UVB, IR-A, and VL (ASS). Human melanocytes were incubated in a dry extract solution of PBE, exposed to UVA/UVB, IR-A, VL, and ASS for subsequent quantification of melanin, ED1, and PPAR α, δ, and γ. The effects of PBE on inhibition of tyrosinase activity were also performed by monophenolase activity assay. UVA/UVB, IR-A, VL, and ASS radiation caused significant increases in the synthesis of melanin, ED1, and PPAR α, δ, and γ when compared to baseline control. However, PBE significantly reduced the production of melanin, ED1, and PPAR α, δ, and γ, as well as reducing about 66.5% of the tyrosinase activity. PBE reduces in vitro melanin production by downregulating tyrosinase and reducing pigmentation-related mediators, such as ED1 and PPAR α, δ, and γ, therefore contributing to the inhibition of pathways associated with skin hyperpigmentation.

A Placebo-Controlled, Pseudo-Randomized, Crossover Trial of Botanical Agents for Gulf War Illness: Curcumin (Curcuma longa), Boswellia (Boswellia serrata), and French Maritime Pine Bark (Pinus pinaster).

This report is part of a larger study designed to rapidly and efficiently screen potential treatments for Gulf War Illness (GWI) by testing nine different botanicals. In this placebo-controlled, pseudo-randomized, crossover clinical trial of 20 men with GWI, we tested three botanical agents with putative peripheral and central anti-inflammatory actions: curcumin (Curcuma longa), boswellia (Boswellia serrata), and French maritime pine bark extract (Pinus pinaster). Participants completed 30 +/− 3 days of baseline symptom reports, followed by 30 +/− 3 days of placebo, 30 +/− 3 days of lower-dose botanical, and 30 +/− 3 days of higher-dose botanical. Participants then repeated the process with a new botanical until completing up to three botanical cycles. Data were analyzed using linear mixed models. Curcumin reduced GWI symptom severity significantly more than placebo at both the lower (p < 0.0001) and higher (p = 0.0003) dosages. Boswellia was not more effective than placebo at reducing GWI symptoms at either the lower (p = 0.726) or higher (p = 0.869) dosages. Maritime pine was not more effective than placebo at the lower dosage (p = 0.954) but was more effective than placebo at the higher dosage (p = 0.006). This study provides preliminary evidence that curcumin and maritime pine may help alleviate symptoms of GWI. As a screening study, a final determination of the efficacy of these compounds for all individuals with GWI cannot be made, and further studies will need to be conducted to determine strength and durability of effects, as well as optimal dosage. These results suggest that GWI may, at least in part, involve systemic inflammatory processes. This trial was registered on ClinicalTrials.gov (NCT02909686) on 13 September 2016.

Effect of French maritime pine bark extract supplementation on metabolic status and serum vascular cell adhesion molecule-1 levels in patients with type 2 diabetes and microalbuminuria

ObjectivesThis 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. DesignThis randomized, double-blind, placebo-controlled clinical trial was conducted on 46 patients with T2DM and the evidence of microalbuminuria aged 30–65 years. SettingPatients were recruited from the endocrinology clinic of Sina hospital (Tabriz, Iran) from March 2018 to April 2019. InterventionsThe subjects were randomly assigned to receive two capsules/day each containing 50mg of PBE or placebo for eight weeks. Main outcome measuresGlycemic parameters, serum VCAM-1 and lipid profile, UACR, and anthropometric indexes were measured for all patients at baseline and the end of the study. ResultsPBE 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). ConclusionsThe 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.

Oligopin® Supplementation Mitigates Oxidative Stress in Postmenopausal Women with Osteopenia: A Randomized, Double-blind, Placebo-Controlled Trial

BackgroundEvidence 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. PurposeHere, we aimed to determine whether supplementation with Oligopin® affects bone turnover markers, antioxidant enzymes, and oxidative stress markers in these patients. MethodsForty-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. ResultsOligopin® 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. ConclusionSupplementation 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.

Phlebotonics for venous insufficiency.

Chronic venous insufficiency (CVI) is a condition in which veins are unable to transport blood unidirectionally towards the heart. CVI usually occurs in the lower limbs. It might result in considerable discomfort, with symptoms such as pain, itchiness and tiredness in the legs. Patients with CVI may also experience swelling and ulcers. Phlebotonics are a class of drugs often used to treat CVI. This is the second update of a review first published in 2005. To assess the efficacy and safety of phlebotonics administered orally or topically for treatment of signs and symptoms of lower extremity CVI. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and Clinicaltrials.gov trials register up to 12 November 2019. We searched the reference lists of the articles retrieved by electronic searches for additional citations. We also contacted authors of unpublished studies. We included randomised, double-blind, placebo-controlled trials (RCTs) assessing the efficacy of phlebotonics (rutosides, hidrosmine, diosmine, calcium dobesilate, chromocarbe, Centella asiatica, disodium flavodate, French maritime pine bark extract, grape seed extract and aminaftone) in patients with CVI at any stage of the disease. Two review authors independently extracted data and assessed the quality of included RCTs. We estimated the effects of treatment by using risk ratios (RRs), mean differences (MDs) and standardized mean differences (SMDs), according to the outcome assessed. We calculated 95% confidence intervals (CIs) and percentage of heterogeneity (I2). Outcomes of interest were oedema, quality of life (QoL), assessment of CVI and adverse events. We used GRADE criteria to assess the certainty of the evidence. We identified three new studies for this update. In total, 69 RCTs of oral phlebotonics were included, but only 56 studies (7690 participants, mean age 50 years) provided quantifiable data for the efficacy analysis. These studies used different phlebotonics (28 on rutosides, 11 on hidrosmine and diosmine, 10 on calcium dobesilate, two on Centella asiatica, two on aminaftone, two on French maritime pine bark extract and one on grape seed extract). No studies evaluating topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the inclusion criteria. Moderate-certainty evidence suggests that phlebotonics probably reduce oedema slightly in the lower legs, compared with placebo (RR 0.70, 95% CI 0.63 to 0.78; 13 studies; 1245 participants); and probably reduce ankle circumference (MD -4.27 mm, 95% CI -5.61 to -2.93 mm; 15 studies; 2010 participants). Moderate-certainty evidence shows that phlebotonics probably make little or no difference in QoL compared with placebo (SMD -0.06, 95% CI -0.22 to 0.10; five studies; 1639 participants); and similarly, may have little or no effect on ulcer healing (RR 0.94, 95% CI 0.79 to 1.13; six studies; 461 participants; low-certainty evidence). Thirty-seven studies reported on adverse events. Pooled data suggest that phlebotonics probably increase adverse events slightly, compared to placebo (RR 1.14, 95% CI 1.02 to 1.27; 37 studies; 5789 participants; moderate-certainty evidence). Gastrointestinal disorders were the most frequently reported adverse events. We downgraded our certainty in the evidence from 'high' to 'moderate' because of risk of bias concerns, and further to 'low' because of imprecision. There is moderate-certainty evidence that phlebotonics probably reduce oedema slightly, compared to placebo; moderate-certainty evidence of little or no difference in QoL; and low-certainty evidence that these drugs do not influence ulcer healing. Moderate-certainty evidence suggests that phlebotonics are probably associated with a higher risk of adverse events than placebo. Studies included in this systematic review provided only short-term safety data; therefore, the medium- and long-term safety of phlebotonics could not be estimated. Findings for specific groups of phlebotonics are limited due to small study numbers and heterogeneous results. Additional high-quality RCTs focusing on clinically important outcomes are needed to improve the evidence base.

French maritime pine bark extract (pycnogenol) in association with triple combination cream for the treatment of facial melasma in women: a double-blind, randomized, placebo-controlled trial.

Melasma can be recalcitrant to treatment, and relapses are common. Pycnogenol has been reported to be effective in treating melasma. To compare the efficacy, safety and tolerability of 75mg pycnogenol taken orally twice a day vs. a placebo, in association with the triple combination and broad-spectrum sunscreen for the treatment of facial melasma. A randomized, double-blind, parallel, placebo-controlled study was conducted on 44 women with facial melasma in a single centre from May 2019 through November 2019. Patients with melasma were randomly assigned to orally take 75mg pycnogenol (PYC) or a placebo (PLAC) twice a day for 60days. Both groups also received tinted sunscreen [Sun Protection Factor (SPF) 50; Persistent Pigment Darkening (PPD) 17] for daytime use and a topical triple combination at bedtime. The primary outcome was a change from the baseline Modified Melasma Area Severity Index (mMASI) score. Secondary outcomes were improvements in the patients' quality of life (MELASQoL), colorimetric indices and Global Aesthetic Improvement Scale (GAIS). All participants completed the trial. The mean (SD) age of the participants was 39 (7) years, and 91% were phototypes III-IV. Both groups exhibited a reduction in mMASI scores, MELASQoL scores and colour contrast (P<0.01). The mean (CI 95%) reductions of the mMASI scores were 49% (36-61%) for PYC and 34% (16-47%) for PLAC. The reductions in mMASI scores and colorimetric contrast were superior for the PYC group (P<0.05). The analysis of GAIS resulted in an improvement of 86% (CI 95%: 68-96%) for the participants in the PYC group and 55% (CI 95%: 32-73%) for those in the PLAC group. There were no adverse effects related to oral treatment. Pycnogenol is well-tolerated and increases the effectiveness of broad-spectrum sunscreen and the triple combination in the treatment of facial melasma in women.

083 The Effect of Ristela Supplementation on Female Sexual Function in Women Taking Antidepressants: An Open Label Trial

Impaired sexual desire, arousal, and orgasm are common in women taking antidepressants. Ristela® is a hormone-free supplement that has been shown to improve female sexual function in three randomized controlled trials. Comprised of Pycnogenol® (French Maritime Pine Bark extract), L-Arginine, L-Citrulline, and a proprietary rose hip extract, Ristela is formulated to increase nitric oxide production, blood flow, and delivery of nutrients and oxygen to tissues including the reproductive organs and brain.

Evaluation of the effects of pycnogenol (French maritime pine bark extract) supplementation on inflammatory biomarkers and nutritional and clinical status in traumatic brain injury patients in an intensive care unit: A randomized clinical trial protocol

BackgroundTraumatic 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.ObjectiveThe objective of this work is to survey the effect of pycnogenol on the clinical, nutritional, and inflammatory status of TBI patients.MethodsThis 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.DiscussionWe 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 registrationThis trial is registered at clinicaltrials.gov (ref: NCT03777683) at 12/13/2018.

Physiologically relevant screening of polyphenol-rich commercial preparations for bioactivity in vascular endothelial cells and application to healthy volunteers: A viable workflow and a cautionary tale

This study describes the screening of 13 commercially-available plant extracts for pharmacological activity modulating vascular function using an endothelial cell model. A French maritime pine bark extract (FMPBE) was found to have the greatest effect upon nitric oxide availability in control (181% ± 36% of untreated cells) and dysfunctional cells (132% ± 8% of untreated control cells). In healthy volunteers, the FMPBE increased plasma nitrite concentrations 8 h post-consumption compared to baseline (baseline corrected median 1.71 ± 0.38 (25% IQR) and 4.76 (75% IQR) µM, p < 0.05). This was followed by a placebo-controlled, healthy volunteer study, which showed no effects on plasma nitrite. It was confirmed that different batches of extract had been used in the healthy volunteer studies, and this second batch lacked bioactivity, assessed using the in vitro model. No difference in plasma catechin levels was seen at 8 h following supplementation between the studies (252 ± 194 nM versus 50 ± 64 nM, p > 0.05), however HPLC-UV fingerprinting showed that the new batch had a 5–15% in major constituents (including procyanidins A2, B1 and B2) compared to the original batch. This research describes a robust mechanism for screening bioactive extracts for vascular effects. It also highlights batch variability as a significant limitation when using complex extracts for pharmacological activity, and suggests the use of in vitro systems as a tool to identify this problem in future studies.

Effects of French maritime pine bark extract (Oligopin®) supplementation on bone remodeling markers in postmenopausal osteopenic women: A randomized clinical trial.

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 (250mg/day, n=21) or placebo (250-mg starch/day, n=19) for 12weeks. 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 12weeks 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.