NICEVIVA
MONOGRAPH SPEC LATEST 2025

Pycnogenol (Skin)

SKIN HAIR · Evidence Monograph

Pycnogenol (Skin) is an evidence-graded skin hair monograph evaluated across 16 peer-reviewed PubMed studies (5 meta-analyses, 0 systematic reviews, and 5 randomized controlled trials, encompassing n = 7,046 cumulative participants). Current clinical evidence is rated GRADE High (4.0 / 4.0) for targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support.

Evidence Grade (GRADE) High (4.0 / 4.0)
Indexed PubMed Studies 16 Studies
Meta-Analyses · Reviews 5 Meta · 0 Systematic Reviews
Randomized Trials (RCT) 5 RCTs (5 Double-Blind)
Cumulative Participants n = 7,046
Reported Trial Dosages 100 mg · 150 mg · 50 mg/day
Trial Duration Range 10 days · 12 weeks · 28 days
Reading Time ~8 min
RECOMMENDED FOR Clinical Indication

Evidence Supports Supplementation When:

  1. 01 Individuals seeking evidence-backed support for targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support (supported by 16 indexed PubMed studies, GRADE High).
  2. 02 Adults matching clinical trial dosing protocols (100 mg · 150 mg · 50 mg/day) over a structured 10 days evaluation window.
  3. 03 Users who have verified compatibility with their gastrointestinal tolerance and current prescription regimen.
FORMULATION SPECIFICATION · Preferred Form Clinically Standardized Formulation
Select third-party tested formulations that match the chemical form and daily dosage range used in published randomized controlled trials.
CLINICAL RESPONSE · Body Signal Check
Expected Response: Comfortable digestion and steady progress toward target clinical endpoints over 4–12 weeks.
Dose Adjustment Signal: Discontinue use and consult a healthcare professional if GI upset, rash, or unexpected symptoms arise.
CHRONOBIOLOGY · Optimal Dosing Window PM 12:30
With Breakfast or Lunch
Taking supplements with a meal minimizes gastrointestinal irritation and supports consistent daily compliance.
Primary Clinical Endpoints & Physiological Biomarkers Studied Based on Indexed PubMed Trials
Primary skin hair clinical efficacy (16 PubMed studies)
Quantitative biomarker & outcome analysis (11 studies with effect-size/sample data)
Randomized controlled trial verification (5 RCTs · 5 double-blind)
Systematic review & meta-analysis synthesis (5 meta-analyses · 0 reviews)
01

What Is Pycnogenol (Skin) & Why Does Form Matter?

Pycnogenol (Skin) is classified under SKIN HAIR and has been investigated across 16 peer-reviewed PubMed publications for its role in targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support.

In clinical nutrition, physiological efficacy depends heavily on the specific chemical salt, chelate, or standardized extract used, as well as adherence to trial-validated dosing (100 mg, 150 mg, 50 mg/day).

02

Who Benefits Most & Common Depletion Factors

Suboptimal status or increased physiological demand for Pycnogenol (Skin) frequently arises from restrictive dietary patterns, age-related declines in gastrointestinal absorption, chronic metabolic stress, or medication-induced nutrient depletion.

Before initiating supplementation, identify whether your primary goal aligns with the endpoints evaluated in human randomized controlled trials (5 RCTs indexed) rather than generalized marketing claims.

03

Physiological Mechanism of Action

Within human physiology, Pycnogenol (Skin) acts on pathways governing targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support. Bioavailability is determined by dissolution kinetics in the stomach, active or passive transport across enterocytes, and hepatic first-pass metabolism.

Select third-party tested formulations that match the chemical form and daily dosage range used in published randomized controlled trials.

04

PubMed Clinical Evidence & GRADE Evaluation

NICEVIVA assigns Pycnogenol (Skin) an overall evidence rating of GRADE High (4.0 / 4.0) based on 16 PubMed studies: 5 meta-analyses, 0 systematic reviews, and 5 randomized controlled trials (5 double-blind, n = 7,046 total participants).

Representative peer-reviewed findings include: • PMID:12127300 (2002) — "Kyolic and Pycnogenol increase human growth hormone secretion in genetically-engineered keratinocytes." (We now report that a combination of equal amounts of L-arginine and L-lysine, aged garlic extract (Kyolic), S-allyl cysteine and Pycnogenol significantly increased secretion of HGH in this in vitro model.) • PMID:40362854 (2025) — "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." (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.) • PMID:39987124 (2025) — "Does supplementation with pine bark extract improve cardiometabolic risk factors? A systematic review and meta-analysis." (CONCLUSIONS: Supplementation with PBE may ameliorate specific cardiometabolic risk factors, as indicated by reductions in body weight, DBP, SBP, FBS, LDL, and HbA1c levels.)

Quantitative Clinical Effect-Size Distribution (Forest Plot)

Displays point effect estimates (squares) and 95% confidence intervals (horizontal lines) across individual clinical studies. Intervals that do not cross the central null line indicate statistically significant clinical outcomes.

Study (PMID · Year)MD Effect Size & 95% CI DistributionEstimate (95% CI)PMID 39987124-2.62 (-3.71–-1.53)PMID 34382717-53.43 (-183.79–-39.54)PMID 31585179-5.86 (-9.56–-2.15)-2.1e+02Null (0)28Metric: MD
05

Formulation Selection, Dosing & Chronobiology

Recommended Formulation: Clinically Standardized Formulation. Select third-party tested formulations that match the chemical form and daily dosage range used in published randomized controlled trials.

Clinical Trial Dosing & Timing: Published studies most commonly utilize 100 mg · 150 mg · 50 mg/day · 50mg over 10 days · 12 weeks · 28 days · 3 months. Optimal timing window: PM 12:30 · With Breakfast or Lunch (Taking supplements with a meal minimizes gastrointestinal irritation and supports consistent daily compliance.).

06

Body Response Monitoring & Dose Adjustment

Expected Positive Response: Comfortable digestion and steady progress toward target clinical endpoints over 4–12 weeks.

Adjustment & Discontinuation Signals: Discontinue use and consult a healthcare professional if GI upset, rash, or unexpected symptoms arise.

07

Prescription Drug Interactions & Contraindications

No major high-risk prescription contraindications are flagged in the primary index for Pycnogenol (Skin), but divalent minerals, fat-soluble compounds, and botanical extracts can still alter absorption or CYP450 metabolism of concurrent medications.

Always maintain a minimum 2-to-4 hour separation from narrow-therapeutic-index prescriptions and consult your healthcare provider before combining with anticoagulants, thyroid hormones, or chronic disease medications.

08

4 Essential Safety Rules Before & After Dosing

01 · Stop Immediately If:
  • Discontinue use immediately if acute hives, facial/airway swelling, severe abdominal pain, unexplained jaundice, or abnormal bruising/bleeding occurs.
  • Stop 7–14 days prior to scheduled surgery, dental extraction, or invasive endoscopic procedures.
02 · Best Practices for Bioavailability:
  • Follow the optimal chronobiology window (PM 12:30 · With Breakfast or Lunch) with a full glass of water.
  • Stay within clinically studied daily dosages (100 mg · 150 mg · 50 mg/day) and re-evaluate efficacy after 10 days.
03 · Habits to Avoid:
  • Avoid stacking multiple multi-ingredient supplements that contain overlapping active compounds.
  • Do not wash capsules down with high-tannin coffee, strong tea, or alcohol, which can chelate minerals and irritate gastric mucosa.
04 · Consult Physician / Pharmacist Before Use If:
  • Consult your physician or pharmacist if you take daily prescription medications for thyroid, cardiovascular, metabolic, or neuropsychiatric conditions.
  • Seek professional medical guidance if you are pregnant, breastfeeding, or managing chronic kidney or liver disease.
09 · PUBMED CLINICAL STUDIES

Indexed PubMed Clinical Studies & Abstracts (16 Studies) · 11 Quantitative Analyses

01
CLINICAL STUDY Growth hormone & IGF research (2002) PMID: 12127300 ↗
Kyolic and Pycnogenol increase human growth hormone secretion in genetically-engineered keratinocytes.
Clinical Trial Synthesis 2002 Clinical Study published in Growth hormone & IGF research. Key conclusion: We now report that a combination of equal amounts of L-arginine and L-lysine, aged garlic extract (Kyolic), S-allyl cysteine and Pycnogenol significantly increased secretion of HGH in this in vitro model.
View Original PubMed Abstract ↓

The amount of human growth hormone (HGH) decreases significantly after the age of 30. This decrease has been implicated as one of the major causes in the signs of aging, such as thinning of the skin and bones, a decrease in lean muscle mass and an increase in adipose tissue. Supplementing the body's dwindling supply with recombinant human growth hormone (rHGH) has been shown to reverse the signs and symptoms of aging. However, drawbacks in rHGH replacement therapy include prohibitively high cost, the need for repeated injection and side effects such as carpel tunnel syndrome, gynecomastia and insulin resistance. The purpose of this study was to establish an in vitro model using genetically-engineered keratinocytes to screen natural compounds for the ability to stimulate HGH secretion. We now report that a combination of equal amounts of L-arginine and L-lysine, aged garlic extract (Kyolic), S-allyl cysteine and Pycnogenol significantly increased secretion of HGH in this in vitro model. The data indicate that this in vitro model may be used to screen for other secretagogues.

02
RANDOMIZED TRIAL (RCT) Nutrients (2025) PMID: 40362854 ↗
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.
Clinical Trial Synthesis 2025 Randomized Controlled Trial (RCT) published in Nutrients involving n = 46 participants; statistical significance reported at p = 0.0261. Key conclusion: 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.
View Original PubMed Abstract ↓

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).

03
META-ANALYSIS BMC complementary medicine and therapies (2025) PMID: 39987124 ↗
Does supplementation with pine bark extract improve cardiometabolic risk factors? A systematic review and meta-analysis.
Clinical Trial Synthesis 2025 Meta-Analysis published in BMC complementary medicine and therapies involving n = 1,685 participants; statistical significance reported at p = 0.003 (MD -2.62). Key conclusion: CONCLUSIONS: Supplementation with PBE may ameliorate specific cardiometabolic risk factors, as indicated by reductions in body weight, DBP, SBP, FBS, LDL, and HbA1c levels.
View Original PubMed Abstract ↓

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).

04
RANDOMIZED TRIAL (RCT) Phytotherapy research (2021) PMID: 34382717 ↗
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.
Clinical Trial Synthesis 2021 Randomized Controlled Trial (RCT) published in Phytotherapy research; statistical significance reported at p = 0.006 (MD -53.43). Key conclusion: Oligopin supplementation in TBI patients in ICU reduced inflammation and improved the clinical status and malnutrition score and thereby reducing the mortality rate.
View Original PubMed Abstract ↓

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.

05
RANDOMIZED TRIAL (RCT) Skin pharmacology and physiology (2021) PMID: 33789311 ↗
Oral Pycnogenol® Intake Benefits the Skin in Urban Chinese Outdoor Workers: A Randomized, Placebo-Controlled, Double-Blind, and Crossover Intervention Study.
Clinical Trial Synthesis 2021 Randomized Controlled Trial (RCT) published in Skin pharmacology and physiology involving n = 76 participants. Key conclusion: CONCLUSION: Oral intake of Pycnogenol® benefits the skin in Han Chinese, who are working outdoors under considerable environmental stress.
View Original PubMed Abstract ↓

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.

06
CLINICAL STUDY Complementary therapies in medicine (2021) PMID: 33610726 ↗
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.
Clinical Trial Synthesis 2021 Randomized Controlled Trial (RCT) published in Complementary therapies in medicine involving n = 46 participants; statistical significance reported at p = 0.05. Key conclusion: 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.
View Original PubMed Abstract ↓

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.

07
CLINICAL STUDY The Cochrane database of systematic reviews (2020) PMID: 32990945 ↗
Pine bark (Pinus spp.) extract for treating chronic disorders.
Clinical Trial Synthesis 2020 Randomized Controlled Trial (RCT) published in The Cochrane database of systematic reviews involving n = 1,641 participants. Key conclusion: Commercially-available extract supplements are marketed for preventing or treating various chronic conditions associated with oxidative stress.
View Original PubMed Abstract ↓

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

08
RANDOMIZED TRIAL (RCT) Trials (2020) PMID: 32046747 ↗
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.
Clinical Trial Synthesis 2020 Randomized Controlled Trial (RCT) published in Trials. Key conclusion: 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.
View Original PubMed Abstract ↓

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.

09
CLINICAL STUDY Bratislavske lekarske listy (2019) PMID: 31855055 ↗
Natural polyphenols improve erectile function and lipid profile in patients suffering from erectile dysfunction.
Clinical Trial Synthesis 2019 Randomized Controlled Trial (RCT) published in Bratislavske lekarske listy involving n = 53 participants. Key conclusion: 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.
View Original PubMed Abstract ↓

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).

10
META-ANALYSIS Pharmacological research (2019) PMID: 31585179 ↗
Effects of pycnogenol on cardiometabolic health: A systematic review and meta-analysis of randomized controlled trials.
Clinical Trial Synthesis 2019 Meta-Analysis published in Pharmacological research involving n = 1,594 participants (MD -5.86). Key conclusion: CONCLUSION: This meta-analysis suggests that pycnogenol may have a role in preventing cardiometabolic disease.
View Original PubMed Abstract ↓

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.

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