피크노제놀 (피부)
Pycnogenol (Skin)
📚 관련 논문 (16편)
1. Growth Horm IGF Res. 2002 Feb;12(1):34-40. doi: 10.1054/ghir.2002.0260. Kyolic and Pycnogenol increase human growth hormone secretion in genetically-engineered keratinocytes. Buz'Zard AR(1), Peng Q, Lau BH. Author information: (1)Department of Microbiology and Molecular Genetics, School of Me
1. Nutrients. 2025 Apr 30;17(9):1546. doi: 10.3390/nu17091546. Impact of a Dietary Supplementation with French Maritime Pine Bark Extract Pycnogenol(®) on Salivary and Serum Inflammatory Biomarkers During Non-Surgical Periodontal Therapy-A Randomized Placebo-Controlled Double-Blind Trial. Bayer J(1), Petersen NK(2), Hess JV(2), Jockel-Schneider Y(2), Högger P(1). Author information: (1)Institute of Pharmacy and Food Chemistry, University of Würzburg, 97074 Würzburg, Germany. (2)Department of Periodontology, University Hospital Würzburg, 97070 Würzburg, Germany. 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). DOI: 10.3390/nu17091546 PMCID: PMC12073762 PMID: 40362854 [Indexed for MEDLINE] Conflict of interest statement: This research was supported by an educational grant of Horphag Research to P.H. and Y.J.-S. The funders had no role in the design of the study; in the collection, analyses, or interpretation of the data; in the writing of the manuscript; or in the decision to publish the results. The authors declare no conflicts of interest.
2. BMC Complement Med Ther. 2025 Feb 22;25(1):71. doi: 10.1186/s12906-025-04819-9. Does supplementation with pine bark extract improve cardiometabolic risk factors? A systematic review and meta-analysis. Mohammadi S(1)(2), Fulop T(3), Khalil A(3), Ebrahimi S(4), Hasani M(5), Ziaei S(6), Farsi F(7), Mirtaheri E(8), Afsharianfar M(9), Heshmati J(10). Author information: (1)Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, 6135715794, Iran. shooka.mohammadi@gmail.com. (2)Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. shooka.mohammadi@gmail.com. (3)Department of Medicine, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Canada. (4)The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia. (5)Department of Nutritional Sciences, School of Health, Golestan University of Medical Sciences, Gorgan, Iran. (6)Department of Anesthesia, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran. (7)Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran. (8)Department of Biochemistry and Dietetics, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. (9)Department of Community Nutrition, School of Nutrition and Food Sciences, Isfahan University of Medical Sciences, Isfahan, Iran. (10)Department of Nutritional Sciences, School of Nutritional Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, 6715847141, Iran. javad.heshmati@gmail.com. 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). DOI: 10.1186/s12906-025-04819-9 PMCID: PMC11847364 PMID: 39987124 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
3. Phytother Res. 2021 Sep;35(9):5178-5188. doi: 10.1002/ptr.7187. Epub 2021 Aug 12. 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. Malekahmadi M(1)(2), Shadnoush M(3), Islam SMS(4), Shirvani A(5), Pahlavani N(6)(7), Gholizadeh Navashenaq J(8), Firouzi S(1), McVicar J(4), Nematy M(2), Zali MR(1), Moradi Moghaddam O(9), Norouzy A(2). Author information: (1)Department of Clinical Nutrition, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran. (2)Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. (3)National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran. (4)Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Melbourne, Victoria, Australia. (5)Virtual School of Medical Education and Management, Shahid Beheshti University of Medical Sciences, Tehran, Iran. (6)Health Sciences Research Center, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran. (7)Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran. (8)Student Research Committee, School of Medicine, Bam University of Medical Sciences, Bam, Iran. (9)Trauma and Injury Research Center, Critical Care Department, Rasoul-e-Akram Complex Hospital, Iran University of Medical Sciences, Tehran, Iran. 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. DOI: 10.1002/ptr.7187 PMID: 34382717 [Indexed for MEDLINE]
4. Skin Pharmacol Physiol. 2021;34(3):135-145. doi: 10.1159/000514323. Epub 2021 Mar 31. Oral Pycnogenol® Intake Benefits the Skin in Urban Chinese Outdoor Workers: A Randomized, Placebo-Controlled, Double-Blind, and Crossover Intervention Study. Zhao H(1), Wu J(2), Wang N(2), Grether-Beck S(3), Krutmann J(3), Wei L(4). Author information: (1)Department of Cosmetics, College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing, China. (2)Beijing EWISH Testing Technology Co., Ltd., Beijing, China. (3)IUF - Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany. (4)Air Force General Hospital, Beijing, China. 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. DOI: 10.1159/000514323 PMID: 33789311 [Indexed for MEDLINE]
5. Complement Ther Med. 2021 May;58:102689. doi: 10.1016/j.ctim.2021.102689. Epub 2021 Feb 18. 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. Navval-Esfahlan E(1), Rafraf M(2), Asghari S(3), Imani H(3), Asghari-Jafarabadi M(4), Karimi-Avval S(5). Author information: (1)Students' Research Committee, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran. (2)Nutrition Research Center, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: rafrafm@tbzmed.ac.ir. (3)Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran. (4)Road Traffic Injury Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. (5)Department of Endocrine and Metabolism, Sina Medical Research and Training Hospital, Tabriz University of Medical Sciences, Tabriz, Iran. 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. Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved. DOI: 10.1016/j.ctim.2021.102689 PMID: 33610726 [Indexed for MEDLINE]
6. Cochrane Database Syst Rev. 2020 Sep 29;9(9):CD008294. doi: 10.1002/14651858.CD008294.pub5. Pine bark (Pinus spp.) extract for treating chronic disorders. Robertson NU(1), Schoonees A(2), Brand A(2), Visser J(1). Author information: (1)Division of Human Nutrition, Stellenbosch University, Cape Town, South Africa. (2)Centre for Evidence-based Health Care, Division of Epidemiology and Biostatistics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. Update of Cochrane Database Syst Rev. 2012 Apr 18;(4):CD008294. doi: 10.1002/14651858.CD008294.pub4. 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 low for four, high for one and unclear for 22 studies. In adults with asthma, we do not know whether pine bark extract increases change in forced expiratory volume in one second (FEV1) % predicted/forced vital capacity (FVC) (mean difference (MD) 7.70, 95% confidence interval (CI) 3.19 to 12.21; one study; 44 participants; very low-certainty evidence), increases change in FEV1 % predicted (MD 7.00, 95% CI 0.10 to 13.90; one study; 44 participants; very low-certainty evidence), improves asthma symptoms (risk ratio (RR) 1.85, 95% CI 1.32 to 2.58; one study; 60 participants; very low-certainty evidence) or increases the number of people able to stop using albuterol inhalers (RR 6.00, 95% CI 1.97 to 18.25; one study; 60 participants; very low-certainty evidence). In children with ADHD, we do not know whether pine bark extract decreases inattention and hyperactivity assessed by parent- and teacher-rating scales (narrative synthesis; one study; 57 participants; very low-certainty evidence) or increases the change in visual-motoric coordination and concentration (MD 3.37, 95% CI 2.41 to 4.33; one study; 57 participants; very low-certainty evidence). In participants with CVD, we do not know whether pine bark extract decreases diastolic blood pressure (MD -3.00 mm Hg, 95% CI -4.51 to -1.49; one study; 61 participants; very low-certainty evidence); increases HDL cholesterol (MD 0.05 mmol/L, 95% CI -0.01 to 0.11; one study; 61 participants; very low-certainty evidence) or decreases LDL cholesterol (MD -0.03 mmol/L, 95% CI -0.05 to 0.00; one study; 61 participants; very low-certainty evidence). In participants with CVI, we do not know whether pine bark extract decreases pain scores (MD -0.59, 95% CI -1.02 to -0.16; one study; 40 participants; very low-certainty evidence), increases the disappearance of pain (RR 25.0, 95% CI 1.58 to 395.48; one study; 40 participants; very low-certainty evidence) or increases physician-judged treatment efficacy (RR 4.75, 95% CI 1.97 to 11.48; 1 study; 40 participants; very low-certainty evidence). In type 2 DM, we do not know whether pine bark extract leads to a greater reduction in fasting blood glucose (MD 1.0 mmol/L, 95% CI 0.91 to 1.09; one study; 48 participants;very low-certainty evidence) or decreases HbA1c (MD -0.90 %, 95% CI -1.78 to -0.02; 1 study; 48 participants; very low-certainty evidence). In a mixed group of participants with type 1 and type 2 DM we do not know whether pine bark extract decreases HbA1c (MD -0.20 %, 95% CI -1.83 to 1.43; one study; 67 participants; very low-certainty evidence). In men with erectile dysfunction, we do not know whether pine bark extract supplements increase International Index of Erectile Function-5 scores (not pooled; two studies; 147 participants; very low-certainty evidence). In women with sexual dysfunction, we do not know whether pine bark extract increases satisfaction as measured by the Female Sexual Function Index (MD 5.10, 95% CI 3.49 to 6.71; one study; 75 participants; very low-certainty evidence) or leads to a greater reduction of pain scores (MD 4.30, 95% CI 2.69 to 5.91; one study; 75 participants; very low-certainty evidence). In adults with osteoarthritis of the knee, we do not know whether pine bark extract decreases composite Western Ontario and McMaster Universities Osteoarthritis Index scores (MD -730.00, 95% CI -1011.95 to -448.05; one study; 37 participants; very low-certainty evidence) or the use of non-steroidal anti-inflammatory medication (MD -18.30, 95% CI -25.14 to -11.46; one study; 35 participants; very low-certainty evidence). We do not know whether pine bark extract increases bone alkaline phosphatase in post-menopausal women with osteopenia (MD 1.16 ug/L, 95% CI -2.37 to 4.69; one study; 40 participants; very low-certainty evidence). In individuals with traumatic brain injury, we do not know whether pine bark extract decreases cognitive failure scores (MD -2.24, 95% CI -11.17 to 6.69; one study; 56 participants; very low-certainty evidence) or post-concussion symptoms (MD -0.76, 95% CI -5.39 to 3.87; one study; 56 participants; very low-certainty evidence). For most comparisons, studies did not report outcomes of hospital admissions or serious adverse events. AUTHORS' CONCLUSIONS: Small sample sizes, limited numbers of RCTs per condition, variation in outcome measures, and poor reporting of the included RCTs mean no definitive conclusions regarding the efficacy or safety of pine bark extract supplements are possible. Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. DOI: 10.1002/14651858.CD008294.pub5 PMCID: PMC8094515 PMID: 32990945 [Indexed for MEDLINE] Conflict of interest statement: All authors: none known.
7. Trials. 2020 Feb 11;21(1):162. doi: 10.1186/s13063-019-4008-x. 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. Malekahmadi M(1)(2), Moradi Moghaddam O(3), Islam SMS(4), Tanha K(5), Nematy M(2)(6), Pahlavani N(1)(2), Firouzi S(1)(2), Zali MR(7), Norouzy A(8)(9). Author information: (1)Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran. (2)Nutrition Department, Faculty of Medicine, Mashhad University of Medical Sciences, Bahonar St, Mashhad, Iran. (3)Trauma and Injury Research Center, Critical Care Department, Rasoul-e-Akram Complex Hospital, Iran University of Medical Sciences, Tehran, Iran. (4)Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Melbourne, Australia. (5)Department of Biostatistics, School of Public Health, Iran University of Medical Sciences, Tehran, Iran. (6)Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. (7)Behbood Research Center for Gastroenterology and Liver Diseases, Tehran, Iran. (8)Nutrition Department, Faculty of Medicine, Mashhad University of Medical Sciences, Bahonar St, Mashhad, Iran. norouzya@mums.ac.ir. (9)Behbood Research Center for Gastroenterology and Liver Diseases, Tehran, Iran. norouzya@mums.ac.ir. 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. DOI: 10.1186/s13063-019-4008-x PMCID: PMC7014642 PMID: 32046747 [Indexed for MEDLINE] Conflict of interest statement: The authors declare that they have no competing interests.
8. Bratisl Lek Listy. 2019;120(12):941-944. doi: 10.4149/BLL_2019_158. Natural polyphenols improve erectile function and lipid profile in patients suffering from erectile dysfunction. Trebaticky B, Muchova J, Ziaran S, Bujdak P, Breza J, Durackova Z. OBJECTIVES: Erectile dysfunction (ED) is characterised as the inability to achieve or maintain an erection to complete sexual intercourse. ED may be considered as an early complication of diabetes mellitus (DM). The aim of this study was to assess the effect of registered food supplement, natural polyphenolic extract from the French maritime pine bark, Pycnogenol (PYC) on erectile function and lipid profile in ED patients. METHODS: 53 patients with ED were divided into two groups (32 with DM, 21 non-DM) in randomised, blinded and placebo-controlled study. During 3-month intervention with PYC or placebo and one month after the end of the intervention patients were investigated for ED with validated questionnaire International Index of Erectile Function-5 (IIEF-5); lipid profile, glycaemia was analysed in each group. RESULTS: In a randomised, blinded and placebo-controlled study, we found that natural polyphenolic extract, Pycnogenol improved erectile function in DM group by 45 % compared to the NDM group, where the improvement was also significant, but only by 22 %. Total cholesterol, LDL-cholesterol and glucose level was lowered by PYC in patients with DM. Glucose level was not affected by PYC in non-DM. Placebo showed no effect on monitored parameters in both groups. CONCLUSION: Administration of Pycnogenol leads in improvement of erectile function in patients with ED and diabetes (DM group) by 45 %, in NDM group by 22 %, in lowering of total-, LDL-cholesterol by 20 % and 21 % and glycaemia by 22 % in DM (Tab. 2, Fig. 2, Ref. 19). DOI: 10.4149/BLL_2019_158 PMID: 31855055 [Indexed for MEDLINE]
9. Pharmacol Res. 2019 Dec;150:104472. doi: 10.1016/j.phrs.2019.104472. Epub 2019 Oct 1. Effects of pycnogenol on cardiometabolic health: A systematic review and meta-analysis of randomized controlled trials. Malekahmadi M(1), Moradi Moghaddam O(2), Firouzi S(1), Daryabeygi-Khotbehsara R(3), Shariful Islam SM(3), Norouzy A(4), Soltani S(5). Author information: (1)Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran; Nutrition Department, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. (2)Trauma and Injury Research Center, Critical Care Department, Rasoul-e-Akram Complex Hospital, Iran University of Medical Sciences, Tehran, Iran. (3)Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Melbourne, Australia. (4)Nutrition Department, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: norouzya@mums.ac.ir. (5)Department of Nutrition, Faculty of Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Yazd Cardiovascular Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. Electronic address: s.soltani1979@yahoo.com. Comment in Pharmacol Res. 2020 Jan;151:104543. doi: 10.1016/j.phrs.2019.104543. Pharmacol Res. 2020 Jan;151:104544. doi: 10.1016/j.phrs.2019.104544. 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. Copyright © 2019 Elsevier Ltd. All rights reserved. DOI: 10.1016/j.phrs.2019.104472 PMID: 31585179 [Indexed for MEDLINE]
10. Pain Med. 2019 Jun 1;20(6):1236-1247. doi: 10.1093/pm/pnz040. Dietary Ingredients as an Alternative Approach for Mitigating Chronic Musculoskeletal Pain: Evidence-Based Recommendations for Practice and Research in the Military. Crawford C(1)(2), Boyd C(1)(2), Paat CF(3), Meissner K(4)(5), Lentino C(3), Teo L(3), Berry K(3), Deuster P(1). Author information: (1)Consortium for Health and Military Performance, Department of Military & Emergency Medicine, F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda, Maryland, USA. (2)The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA. (3)Thought Leadership and Innovation Foundation, McLean, Virginia, USA. (4)Division of Health Promotion, University of Applied Sciences Coburg, Coburg, Germany. (5)Institute of Medical Psychology, Ludwig Maximilian University of Munich, Munich, Germany. OBJECTIVE: Approximately 55-76% of Service members use dietary supplements for various reasons, including pain and related outcomes. This work evaluates current research on dietary ingredients for chronic musculoskeletal pain to inform decisions for practice and self-care, specifically for Special Operations Forces personnel. METHODS: A steering committee convened to develop research questions and factors required for decision-making. Key databases were searched through August 2016. Eligible systematic reviews and randomized controlled trials were assessed for methodological quality. Meta-analysis was applied where feasible. GRADE was used to determine confidence in the effect estimates. The committee made evidence-informed judgments and recommendations for practice and self-care use. RESULTS: Nineteen eligible dietary ingredients were assessed for quality, efficacy, and safety. Avocado soybean unsaponifiables, capsaicin, curcuma, ginger (as a food source), glucosamine, melatonin, polyunsaturated fatty acids, and vitamin D were conditionally recommended as their benefits outweighed risks, but there was still some uncertainty about the trade-offs. No recommendations were made for boswellia, ginger (as a dietary supplement), rose hip, or s-adenosyl-L-methionine. Recommendations were made against the use of collagen, creatine, devil's claw, l-carnitine, methylsulfonylmethane, pycnogenol, willow bark extract, and vitamin E. Research priorities were developed to address gaps precluding stronger recommendations. CONCLUSIONS: Currently the scientific evidence is insufficiently robust to establish definitive clinical practice guidelines, but processes could be established to track the impact of these ingredients. Until then, providers have the evidence needed to make informed decisions about the safe use of these dietary ingredients, and future research can address existing gaps. © 2019 American Academy of Pain Medicine. DOI: 10.1093/pm/pnz040 PMCID: PMC6544555 PMID: 30986309 [Indexed for MEDLINE]
11. J Sex Med. 2019 Feb;16(2):223-234. doi: 10.1016/j.jsxm.2018.12.002. The Potential Role of Arginine Supplements on Erectile Dysfunction: A Systemic Review and Meta-Analysis. Rhim HC(1), Kim MS(1), Park YJ(2), Choi WS(2), Park HK(2), Kim HG(2), Kim A(2), Paick SH(3). Author information: (1)Korea University, College of Medicine, Seoul, Korea. (2)Department of Urology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea. (3)Department of Urology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea. Electronic address: 20030010@kuh.ac.kr. Erratum in J Sex Med. 2020 Mar;17(3):560. doi: 10.1016/j.jsxm.2020.01.021. INTRODUCTION: The efficacy and safety of arginine supplements in erectile dysfunction (ED) remain debatable. AIM: To assess the potential role of arginine supplements on ED as alternatives to phosphodiesterase inhibitors. METHODS: Studies published up to April 2018 that evaluated the efficacy of arginine supplements were identified from multiple databases (Google Scholar, PubMed, Medline, Embase, Kiss, DBpia, and Cochrane databases). Studies comparing arginine supplements with placebo or no treatment; focusing only on patients with mild to moderate severity of ED; and presenting outcomes such as improvement rate, International Index of Erectile Function (IIEF) score, and adverse effects were included. Subgroup analysis for arginine alone and arginine in combination with other substances was further conducted to increase interpretability. MAIN OUTCOME MEASURE: The strength of the association between arginine supplements and ED was assessed using relative odds ratios and weighted mean differences with 95% CI. RESULTS: In total, 10 randomized controlled trials met the inclusion criteria, reporting the outcomes of 540 patients with ED. The analysis demonstrated that arginine supplements with dosage ranging from 1,500 to 5,000 mg significantly improved ED compared with placebo or no treatment (odds ratios, 3.37 [1.29, 8.77], P = .01, I2 = 44). Arginine supplements also caused significant improvements in the IIEF subdomain scores of overall satisfaction, intercourse satisfaction, orgasmic function, and erectile function, whereas the IIEF sexual desire score remain unchanged. The adverse effect rate in the arginine-treated group was 8.3%, and that in the placebo group was 2.3%, none of which were severe. CLINICAL IMPLICATIONS: Arginine supplements can be recommended to patients with mild to moderate ED. STRENGTH & LIMITATIONS: The strength of this study is that it is the first meta-analysis to assess the potential role of arginine supplements in ED compared with placebo or no treatment. A limitation is that the treatment dosage and duration varied among studies, which may have contributed to study heterogeneity. CONCLUSION: The results of our systematic review and meta-analysis provide evidence on the effectiveness of arginine supplements for mild to moderate ED. Rhim HC, Kim MS, Park Y-J, et al. The Potential Role of Arginine Supplements on Erectile Dysfunction: A Systemic Review and Meta-Analysis. J Sex Med 2019;16:223-234. Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.jsxm.2018.12.002 PMID: 30770070 [Indexed for MEDLINE]
12. Nutr J. 2019 Jan 5;18(1):1. doi: 10.1186/s12937-018-0428-9. The Australian Research Council Longevity Intervention (ARCLI) study protocol (ANZCTR12611000487910) addendum: neuroimaging and gut microbiota protocol. Simpson T(1), Deleuil S(1), Echeverria N(1), Komanduri M(1), Macpherson H(1)(2), Suo C(3), Gondalia S(1), Fard MT(1), Pipingas A(1), Scholey A(1), Stough C(4). Author information: (1)Centre for Human Psychopharmacology, Swinburne University of Technology, PO Box 218, Hawthorn, Victoria, Melbourne, Australia. (2)Institute for Physical Activity and Nutrition Research, Deakin University, Melbourne, Australia. (3)Brain and Mental Health Laboratory, Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences, Monash University, Melbourne, Australia. (4)Centre for Human Psychopharmacology, Swinburne University of Technology, PO Box 218, Hawthorn, Victoria, Melbourne, Australia. cstough@swin.edu.au. BACKGROUND: The Australian Research Council Longevity Intervention (ARCLI) was designed to investigate the effects of two active supplements, Pycnogenol and Bacopa monnieri (CDRI08) on cognitive performance in a cohort of elderly participants. An additional antioxidant supplement has been included into the trial. A neuroimaging component has also been added to the ARCLI study to investigate the neurochemical biomarkers of oxidative stress in vivo, as well as structural and functional changes associated with ageing and oxidative stress. Faecal biomarkers of gut microflora will also be analysed to investigate if gut microbiota are associated with domains of cognition (e.g., attention, processing speed, memory), mood or other ARCLI outcome variables. The aim of this paper is to update the published methods of the ARCLI clinical trial before it is completed, and data analysis commences. METHODS: ARCLI is a randomised, placebo controlled, double-blind, now 4-arm clinical trial including neuroimaging and gut microflora sub-studies. Along with the demographic, haematological, mood, cardiovascular and cognitive assessments described in the initial protocol, 80 eligible participants from the overall study pool of ~ 400 will be recruited into the neuroimaging study and undergo scans at baseline, 3 months and 12 months. Proton magnetic resonance spectroscopy, resting state functional connectivity and arterial spin labelled perfusion sequences are neuroimaging techniques included for each MRI visit in the study. Similarly, approximately 300 participants from the main study pool will be recruited to provide faecal samples at baseline, 3 months and 12 months so that the gut microbiome can be studied. DISCUSSION: ARCLI is 12-month intervention study, currently underway with a group of older adults, investigating a range of outcomes and their association with ageing. The additional measurements in the ARCLI trial will further the understanding of the underlying mechanisms associated with healthy ageing and may provide insights into novel preventative therapeutic strategies for maintaining cognitive and brain health into old age. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000487970 . DOI: 10.1186/s12937-018-0428-9 PMCID: PMC6321680 PMID: 30611275 [Indexed for MEDLINE] Conflict of interest statement: ETHICS APPROVAL AND CONSENT TO PARTICIPATE: This study was approved by the Swinburne University Human Ethics Research Committee which is a formally constituted ethics committee of the Australian National Health and Medical Research Committee. Ethics Number 2010/106. Informed written consent will be obtained from participants prior to enrolment. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors conduct studies on Bacopa monnieri that are funded by Soho Flordis-International-Research. Soho Flordis International-Reserach were not involved at any stage of the project including study design, analysis of results, or decision to publish. The same applies for Blackmores Australia and Horphag PUBLISHER’S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
13. Phytother Res. 2019 Feb;33(2):276-287. doi: 10.1002/ptr.6234. Epub 2018 Nov 19. The impact of pycnogenol supplementation on plasma lipids in humans: A systematic review and meta-analysis of clinical trials. Hadi A(1), Pourmasoumi M(1)(2), Mohammadi H(3), Javaheri A(4), Rouhani MH(5). Author information: (1)Halal Research Center of IRI, FDA, Tehran, Iran. (2)Gastrointestinal and Liver Diseases Research Center (GLDRC), Guilan University of Medical Sciences, Rasht, Iran. (3)Department of Clinical Nutrition, School of Nutrition and Food Science, Students' Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran. (4)Food Science, Technology and Business, Faculty of Engineering Technology, Technology Campus Ghent, Katholieke Universiteit Leuven, Leuven, Belgium. (5)Department of Community Nutrition, School of Nutrition and Food Science, Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. The effects of pycnogenol on plasma lipids are controversial. A systematic review and meta-analysis of clinical trials were conducted to obtain a conclusive result in humans. PubMed, Scopus, and Google Scholar were systematically searched until March 2018, to explore the clinical trials that examined the effect of pycnogenol supplementation on lipid parameters among adult human. Methodological quality of the eligible studies was evaluated using the Cochrane Collaboration's tool. To estimate the effect size, changes in blood lipids were implemented. Results were pooled using a random effects model. Potential sources of heterogeneity were explored by subgroup analysis. A systematic review and meta-analysis of 14 clinical trials with 1,065 participants suggested a significant increase in plasma concentration of high density lipoprotein cholesterol (HDL-C; 3.27 mg/dL; 95% CI [0.19, 6.36]; p = 0.038). In contrast, plasma levels of total cholesterol (TC; -4.45 mg/dL, 95% CI [-11.24, 2.34]; p = 0.199), triacylglycerol (TAG; -3.64 mg/dL; 95% CI [-17.89, 10.61]; p = 0.616), and low density lipoprotein cholesterol (LDL-C; -3.61 mg/dl; 95% CI [-8.76, 1.55]; p = 0.171) were not altered. Adjustment for confounding variables was poor in included studies. Also, these studies did not assess dietary lipid intake. The results indicate that pycnogenol supplementation improves levels of HDL-C; however, the changes in TC, TAG, and LDL-C were not clinically relevant. Since there are few phytochemicals that have a significant increasing effect on HDL-C levels, pycnogenol may have important role in prevention of cardiovascular diseases. © 2018 John Wiley & Sons, Ltd. DOI: 10.1002/ptr.6234 PMID: 30456865 [Indexed for MEDLINE]
14. BMC Complement Altern Med. 2017 Dec 16;17(1):537. doi: 10.1186/s12906-017-2044-1. Cellular pharmacodynamic effects of Pycnogenol® in patients with severe osteoarthritis: a randomized controlled pilot study. Jessberger S(1), Högger P(2), Genest F(3), Salter DM(4), Seefried L(3). Author information: (1)Institut für Pharmazie und Lebensmittelchemie, Universität Würzburg, Am Hubland C7, 97074, Würzburg, Germany. (2)Institut für Pharmazie und Lebensmittelchemie, Universität Würzburg, Am Hubland C7, 97074, Würzburg, Germany. petra.hoegger@uni-wuerzburg.de. (3)Department of Orthopedics, Universität Würzburg, Orthopedic Center for Musculoskeletal Research, Brettreichstraße 11, 97074, Würzburg, Germany. (4)Centre for Genomic and Experimental Medicine, University of Edinburgh, Osteoarticular Research Group, Crewe Road, Edinburgh, EH4 2XU, UK. BACKGROUND: The standardized maritime pine bark extract (Pycnogenol®) has previously shown symptom alleviating effects in patients suffering from moderate forms of knee osteoarthritis (OA). The cellular mechanisms for this positive impact are so far unknown. The purpose of the present randomized pilot controlled study was to span the knowledge gap between the reported clinical effects of Pycnogenol® and its in vivo mechanism of action in OA patients. METHODS: Thirty three patients with severe OA scheduled for a knee arthroplasty either received 100 mg of Pycnogenol® twice daily or no treatment (control group) three weeks before surgery. Cartilage, synovial fluid and serum samples were collected during surgical intervention. Relative gene expression of cartilage homeostasis markers were analyzed in the patients' chondrocytes. Inflammatory and cartilage metabolism mediators were investigated in serum and synovial fluid samples. RESULTS: The oral intake of Pycnogenol® downregulated the gene expression of various cartilage degradation markers in the patients' chondrocytes, the decrease of MMP3, MMP13 and the pro-inflammatory cytokine IL1B were statistically significant (p ≤ 0.05). Additionally, protein concentrations of ADAMTS-5 in serum were reduced significantly (p ≤ 0.05) after three weeks intake of the pine bark extract. CONCLUSIONS: This is the first report about positive cellular effects of a dietary supplement on key catabolic and inflammatory markers in patients with severe OA. The results provide a rational basis for understanding previously reported clinical effects of Pycnogenol® on symptom scores of patients suffering from OA. TRIAL REGISTRATION: ISRCTN10754119 . Retrospectively registered 08/10/2015. DOI: 10.1186/s12906-017-2044-1 PMCID: PMC5732384 PMID: 29246219 [Indexed for MEDLINE] Conflict of interest statement: ETHICS APPROVAL AND CONSENT TO PARTICIPATE: The study protocol was reviewed and approved (reference number 248/11) by the local Ethics Committee of the Medical Faculty of the University Würzburg. The procedures followed were in accordance with the ethical standards of the Ethics Committee and with the Helsinki Declaration of 1975, as revised in 2000. A total of 33 osteoarthritis patients were recruited for the study and gave written informed consent. CONSENT FOR PUBLICATION: Patients were informed that the results of the analysis of their blood, synovial fluid and cartilage tissue might be published after pseudonymization guaranteeing personal data security. The patients gave written informed consent. COMPETING INTERESTS: SJ declares no conflict of interests. PH, FG, DS and LS received research grants and/or travel support from Horphag Research, the producer of Pycnogenol®, within the past five years. PUBLISHER’S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
15. Br J Sports Med. 2018 Feb;52(3):167-175. doi: 10.1136/bjsports-2016-097333. Epub 2017 Oct 10. Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis. Liu X(1)(2), Machado GC(3), Eyles JP(1)(2)(4), Ravi V(1)(2), Hunter DJ(1)(2). Author information: (1)Department of Rheumatology, Royal North Shore Hospital, St Leonards, Australia. (2)Institute of Bone and Joint Research, The Kolling Institute, The University of Sydney, Sydney, New South Wales, Australia. (3)Sydney Medical School, The George Institute for Global Health, The University of Sydney, Sydney, New South Wales, Australia. (4)Department of Physiotherapy, Sydney Medical School, Royal North Shore Hospital, Sydney, New South Wales, Australia. OBJECTIVE: To investigate the efficacy and safety of dietary supplements for patients with osteoarthritis. DESIGN: An intervention systematic review with random effects meta-analysis and meta-regression. DATA SOURCES: MEDLINE, EMBASE, Cochrane Register of Controlled Trials, Allied and Complementary Medicine and Cumulative Index to Nursing and Allied Health Literature were searched from inception to April 2017. STUDY ELIGIBILITY CRITERIA: Randomised controlled trials comparing oral supplements with placebo for hand, hip or knee osteoarthritis. RESULTS: Of 20 supplements investigated in 69 eligible studies, 7 (collagen hydrolysate, passion fruit peel extract, Curcuma longa extract, Boswellia serrata extract, curcumin, pycnogenol and L-carnitine) demonstrated large (effect size >0.80) and clinically important effects for pain reduction at short term. Another six (undenatured type II collagen, avocado soybean unsaponifiables, methylsulfonylmethane, diacerein, glucosamine and chondroitin) revealed statistically significant improvements on pain, but were of unclear clinical importance. Only green-lipped mussel extract and undenatured type II collagen had clinically important effects on pain at medium term. No supplements were identified with clinically important effects on pain reduction at long term. Similar results were found for physical function. Chondroitin demonstrated statistically significant, but not clinically important structural improvement (effect size -0.30, -0.42 to -0.17). There were no differences between supplements and placebo for safety outcomes, except for diacerein. The Grading of Recommendations Assessment, Development and Evaluation suggested a wide range of quality evidence from very low to high. CONCLUSIONS: The overall analysis including all trials showed that supplements provided moderate and clinically meaningful treatment effects on pain and function in patients with hand, hip or knee osteoarthritis at short term, although the quality of evidence was very low. Some supplements with a limited number of studies and participants suggested large treatment effects, while widely used supplements such as glucosamine and chondroitin were either ineffective or showed small and arguably clinically unimportant treatment effects. Supplements had no clinically important effects on pain and function at medium-term and long-term follow-ups. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted. DOI: 10.1136/bjsports-2016-097333 PMID: 29018060 [Indexed for MEDLINE] Conflict of interest statement: Competing interests: None declared.
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