Evaluation of Pine Bark Extract for Anti-fatigue Ergogenic Properties

This research proposal aims to elucidate the physiological responses to pine bark extract supplementation during a single bout of high-intensity cycling exercise at 70% VO₂max and the subsequent recovery phase. Specifically, the study seeks to investigate the underlying mechanisms by which pine bark extract modulates exercise-induced fatigue and metabolic fitness, and to determine whether such supplementation may enhance endurance performance in the post-recovery period.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Other: Placebo (Placebo trial); Other: PBE (PBE trial)

Detailed Description

The primary active component of natural pine bark extract (PBE) is proanthocyanidins, which possess antioxidant, anti-inflammatory, and endothelial function-enhancing properties. These attributes suggest its potential as an ergogenic aid to improve exercise performance. In this study, 14 healthy participants will be randomly assigned to receive either 300 mg/day of PBE or a placebo for 4 consecutive days. Following supplementation, participants will consume a low-calorie meal (300 kcal) accompanied by either the placebo or PBE and rest for one hour. One hour after capsule ingestion, participants will perform a 60-minute cycling exercise at 70% VO₂max. Upon completion of the exercise challenge, they will consume a post-exercise meal adjusted to body weight. After a 3-hour recovery period, subjects will undergo an anaerobic power test followed by an endurance test at 75% VO₂max to volitional exhaustion. Gas exchange and blood samples will be collected at multiple time points: pre- and post-initial cycling session, during the recovery phase, and following the exhaustive endurance test. Gas samples will be analyzed to determine rates of fat and carbohydrate oxidation. Blood biomarkers will be assessed for glucose, superoxidase dismutase (SOD), malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), creatine kinase (CK), lactate dehydrogenase (LDH), and uric acid (UA).

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taichung, Taiwan
    • China Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• A minimum of three years of regular exercise habits.

Exclusion Criteria:

• Have smoking and drinking habits.
• People who feel unwell due to other reasons during the experiment.
• Individuals with respiratory disorders.
• Severe lower limb musculoskeletal injuries within the past six months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Containing edible yellow No. 4, edible yellow No. 5, sucrose, silica, talc, oxidized starch, gelatin, magnesium stearate, and palm wax.	Other: Placebo (Placebo trial); The Placebo capsule supplement was taken for 4 days (3 capsules per day); Other: PBE (PBE trial); The PBE capsule supplement was taken for 4 days, with a daily dosage of 300 mg of PBE (equivalent to 3 capsules per day, each containing 100 mg of PBE).
Experimental: PBE; Each capsule containing 100 mg of Pycnogenol®, Taiwan	Other: Placebo (Placebo trial); The Placebo capsule supplement was taken for 4 days (3 capsules per day); Other: PBE (PBE trial); The PBE capsule supplement was taken for 4 days, with a daily dosage of 300 mg of PBE (equivalent to 3 capsules per day, each containing 100 mg of PBE).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Exhaustion (TTE)	The total duration (in minutes) from the start of the graded exercise test until the participant reaches volitional exhaustion or can no longer maintain the required cadence of 60 RPM. Unit of Measure: Minutes	Baseline and at the end of the 4-week crossover period.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Tumor Necrosis Factor-alpha (TNF-alpha) Concentration	A pro-inflammatory cytokine measured in serum using a commercial ELISA kit (BioLegend) to evaluate the inflammatory response.Unit of Measure: Picograms per milliliter (pg/mL)	7 time points (Baseline, START, END, 0 min, 60 min, 120 min, 180 min in two ergometer trials) during each crossover trial.
Superoxide Dismutase (SOD) Activity	biomarker used to evaluate total antioxidant capacity. Serum SOD activity is measured using a commercial colorimetric assay kit and read with an ELISA plate reader.Unit of Measure: Units per milliliter (U/mL).	7 time points (Baseline, START, END, 0 min, 60 min, 120 min, 180 min in two ergometer trials) during each crossover trial.
Blood Glucose Levels	Estimated from blood using the glucometer to assess glycemic response during the trials.	7 time points (Baseline, START, END, 0 min, 60 min, 120 min, 180 min in two ergometer trials) during each crossover trial.
Uric Acid (UA) Levels	Measured in serum as a marker of metabolic stress and muscle damage using commercial analytical reagents. Unit of Measure: Milligrams per deciliter (mg/dL).	7 time points (Baseline, START, END, 0 min, 60 min, 120 min, 180 min in two ergometer trials) during each crossover trial.
Lactate Dehydrogenase (LDH) Activity	Description: A biomarker of muscle damage measured in serum using an automated clinical chemistry analyzer (Beckman Coulter AU5800). Unit of Measure: Units per Liter (U/L)	7 time points (Baseline, START, END, 0 min, 60 min, 120 min, 180 min in two ergometer trials) during each crossover trial.
Serum Interleukin-6 (IL-6) Concentration	A pro-inflammatory cytokine measured in serum using a commercial ELISA kit (BioLegend) to evaluate the inflammatory response. Unit of Measure: Picograms per milliliter (pg/mL)	7 time points (Baseline, START, END, 0 min, 60 min, 120 min, 180 min in two ergometer trials) during each crossover trial.
Malondialdehyde (MDA) Levels	A standard biomarker of lipid peroxidation. Serum MDA levels are determined using a commercial ELISA kit to assess oxidative stress status. Unit of Measure: micromolar (μM)	7 time points (Baseline, START, END, 0 min, 60 min, 120 min, 180 min in two ergometer trials) during each crossover trial.
Serum Creatine Kinase (CK) Concentration	A biomarker of muscle damage measured in serum using an automated clinical chemistry analyzer (Beckman Coulter AU5800). Unit of Measure: Units per Liter (U/L)	7 time points (Baseline, START, END, 0 min, 60 min, 120 min, 180 min in two ergometer trials) during each crossover trial.
Carbohydrate (CHO) Oxidation Rate	Determined using VO 2 and VCO 2 data collected during the cycling challenge. Calculated using the equation: 4.585×VCO2 -3.226×VO2 . Unit of Measure: grams per minute (g/min)	7 time points (Baseline, START, END, 0 min, 60 min, 120 min, 180 min in two ergometer trials) during each crossover trial.
Fat Oxidation Rate	Determined using VO 2 and VCO 2 data collected during the cycling challenge. Calculated using the Frayn equation: 1.695×VO 2 -1.701×VCO 2 . Unit of Measure: grams per minute (g/min)	7 time points (Baseline, START, END, 0 min, 60 min, 120 min, 180 min in two ergometer trials) during each crossover trial.
Respiratory Exchange Ratio (RER)	Calculated as the ratio of carbon dioxide production ($VCO_2$) to oxygen consumption ($VO_2$). It reflects the relative contribution of carbohydrates and fats to energy metabolism. Unit of Measure: Ratio (Unitless)	7 time points (Baseline, START, END, 0 min, 60 min, 120 min, 180 min in two ergometer trials) during each crossover trial.
Maximal Oxygen Consumption (VO2max)	Measured using a graded exercise test on a stationary ergometer. VO2max is defined as the plateau in oxygen uptake despite an increase in workload, confirmed when at least two of the following criteria are met: (1) RER > 1.10, (2) VO2 plateau (< 2 ml/kg/min change), or (3) attainment of age-predicted maximum heart rate. Unit of Measure: ml/kg/min	Baseline and at the end of the 4-week crossover period.
Profile of Mood States (POMS) - Vigor Subscale Score	A subscale of the POMS brief version used to evaluate the positive mood state of vigor. It consists of specific adjectives scored on a 5-point scale (1-5). Higher scores indicate higher levels of vigor. Unit of Measure: Units on a scale	Measured immediately after each cycling challenge at baseline and at the end of the 4-week crossover trial.
Profile of Mood States (POMS) - Self-esteem Subscale Score	A subscale of the POMS brief version used to evaluate the mood state of self-esteem. Scored on a 5-point scale (1-5). Higher scores indicate higher levels of self-esteem. Unit of Measure: Units on a scale	Measured immediately after each cycling challenge at baseline and at the end of the 4-week crossover trial.
Profile of Mood States (POMS) - Tension Subscale Score	A subscale of the POMS brief version used to evaluate the negative mood state of tension. Scored on a 5-point scale (1-5). Higher scores indicate higher levels of tension. Unit of Measure: Units on a scale	Measured immediately after each cycling challenge at baseline and at the end of the 4-week crossover trial.
Profile of Mood States (POMS) - Confusion Subscale Score	A subscale of the POMS brief version used to evaluate the negative mood state of confusion. Scored on a 5-point scale (1-5). Higher scores indicate higher levels of confusion. Unit of Measure: Units on a scale	Measured immediately after each cycling challenge at baseline and at the end of the 4-week crossover trial.
Profile of Mood States (POMS) - Anger Subscale Score	A subscale of the POMS brief version used to evaluate the negative mood state of anger. Scored on a 5-point scale (1-5). Higher scores indicate higher levels of anger. Unit of Measure: Units on a scale	Measured immediately after each cycling challenge at baseline and at the end of the 4-week crossover trial.
Profile of Mood States (POMS) - Fatigue Subscale Score	A subscale of the POMS brief version used to evaluate the negative mood state of fatigue. Scored on a 5-point scale (1-5). Higher scores indicate higher levels of fatigue. Unit of Measure: Units on a scale	Measured immediately after each cycling challenge at baseline and at the end of the 4-week crossover trial.
Profile of Mood States (POMS) - Depression Subscale Score	A subscale of the POMS brief version used to evaluate the negative mood state of depression. Scored on a 5-point scale (1-5). Higher scores indicate higher levels of depression. Unit of Measure: Units on a scale	Measured immediately after each cycling challenge at baseline and at the end of the 4-week crossover trial.

Collaborators and Investigators

• Sponsor: China Medical University Hospital
• Collaborators: China Medical University, Taiwan; National Science and Technology Council, Taiwan
• Investigators: Study Chair: Jung-Piao Tsao, China Medical University, China

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2023
• Primary Completion (Actual): October 1, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: July 27, 2025
• First Submitted That Met QC Criteria: February 26, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 26, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: exercise performance; pine bark extract; Maximal oxygen consumption
• Other Study ID Numbers: CMUH111-REC2-173

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No