Plain English Summary
Background and study aims
Regular exercise is an important part of a healthy lifestyle. However, all forms of exercise cause some oxidative stress which can lead to cell damage. Moderate exercise produces healthy amounts of reactive chemicals (such as reactive oxygen), which is beneficial. However, prolonged vigorous exercise, particularly in hot environments (e.g. prolonged running in the sun), may produce a lot of reactive chemicals and result in damage to muscles and vital organs. Evidence suggests that a diet rich in foods that are naturally high in antioxidants is beneficial for health. Antioxidants reduce the effects of oxidative stress by mopping up (neutralizing) reactive chemicals when they develop, preventing the cell damage. We want to investigate whether short-term antioxidant supplementation can influence the ability of enzymes to protect muscle cells when oxidative stress is caused by exercise in the heat. The supplements we will use are Quercetin and Vitamin C. Quercetin is one of the most abundant type of antioxidants called flavonoids, present in many plants and foods, such as red wine, onions, green tea, apples and berries. Vitamin C (also known as ascorbic acid) is a water-soluble vitamin and a powerful antioxidant. It is abundant in fruits and vegetables, especially citrus fruits. We want to know whether supplementation with these antioxidants (in tablet form) could be used to improve exercise performance in hot environments.
Who can participate?
Male volunteers aged 18 to 48 years, who are active (exercise more than 20 minutes per day, at least 3 times per week), non-smokers, not taking any supplementation and who do not suffer from any disease.
What does the study involve?
Participants are asked to attend a preliminary visit before the experimental trial. When there, anthropometric measurements are taken (height, body mass and percentage of body fat). They then perform two separate tests on a motorized treadmill, one for determining the relationship between running speed and their oxygen uptake and the other to measure peak oxygen uptake (their maximum ability to deliver oxygen to the muscles - VO2max). From the results of these two tests, we can work out how hard each participant should be asked to run in the actual experimental trial. Participants are then asked to run in the heat at 70% VO2max (that is, at 70% of their peak oxygen uptake) for 60 minutes where the temperature is kept at 33°C and with 40% relative humidity to familiarise themselves with the test. For the actual trials, each participant is randomly assigned to receive either a dummy tablet (CON), Quercetin (Q), or Quercetin plus vitamin C (QC). They are all asked to take a 1000 mg tablet 14 hours (that is, the night before) the study begins, then to take a further tablet of 500 mg two hours before they start the experimental trial. Before they start the exercise, their body mass is recorded. They are then asked to do a warm up on a motorized treadmill for 5 minutes (at 50% VO2max) before running at 70% VO2max (33°C, 40% relative humidity) for one hour. Expired gases and blood samples are taken during the last minute of the warm up and then every 20 minutes during the trial and then one hour after they have stopped the exercise. Heart rate, temperature and the participants’ perceptions on how tired and hot they are recorded every 10 minutes. After collection of exhaled gases, the participants are given plain water and whatever tablet they have been allocated to take. Each participant is weighed after they have finished exercising. A muscle biopsy sample is collected 2 days before and 2 days after the experimental trial. Participants do have the option of saying no to this if they wish. The participants are asked to do the experimental trial on three occasions. They are assigned to a different tablet on each occasion and all participants will take all three tablets. There is a seven-day break between each trial.
What are the possible benefits and risks of participating?
At the end of the study, each participant will be given a copy of their results and personalised feedback on their fitness level, diet, blood results (including haemoglobin, total antioxidant status and plasma volume) and body composition analysis (percentage body fat and muscle mass). During the VO2max test participants will reach their maximal ability to take up oxygen and this will require maximum effort for 1-2 minutes. However, they will decide when they can no longer maintain this level of exercise and, therefore, when the test ends. They should recover fully in around 5 minutes. The blood samples taken might cause minor discomfort and bruising. The muscle biopsies may cause bleeding and a little soreness afterwards. Participants will be given a sheet that lists the possible complications, including those that are more severe (e.g. intramuscular bleeding, infection). These complications are very rare, however, and the risks are minimised by following best practice. Exercise in the heat can endanger health and impair exercise performance. However, during the 1 hour run on the treadmill, participants will be asked to drink an appropriate beverage at the start of, every 20 minutes and at the end of the exercise bout to prevent dehydration. Participants will also be asked to stop exercising and will be removed from the heat if their body core temperature exceeds 39.5°C. All participants will be asked to wear minimal clothing. Importantly, volunteers are free to withdraw from the study at any point.
Where is the study run from?
The Exercise Physiology Laboratory within the Department for Health at the University of Bath (UK).
When is the study starting and how long is it expected to run for?
November 2014 to November 2015.
Who is funding the study?
1. Malaysian Higher Education Authority (Malaysia)
2. University of Bath (UK)
Who is the main contact?
Dr James Bilzon
Dr James Bilzon
University of Bath
c/o James Bilzon
Department for Health
Influence of antioxidant supplementation on oxidative stress and thermal tolerance during exercise heat stress
It is hypothesised that antioxidant supplementation will significantly influence the responses of antioxidant enzymes and intramuscular heat shock proteins (HSPs) and enhance endurance capacity during exercise in the heat. The null hypothesis is that there will be no difference in the responses of antioxidant enzymes and HSPs between the antioxidant supplementation group and the control group.
NRES Committee South West of England - Frenchay, 26/06/2014, ref: 14/SW/0098.
Randomised cross-over design
Primary study design
Secondary study design
Randomised cross over trial
Patient information sheet
Not available in web format yet, please use the contact details below to request a patient information sheet.
Antioxidant supplementation, Oxidative Stress, Heat Shock Protein (HSPs), Antioxidant Enzyme.
Main Experimental Trials: Participants will be randomly assigned to either consume a tablet of 1000 mg Quercetin (Q), Quercetin plus vitamin C (QC) or placebo control (CON) 14 hours (the night before the trial). 2 hours before exercise, participants will consume a tablet of 500 mg Quercetin, Quercetin plus vitamin C or placebo control.
Participants will be asked to run on a motorized treadmill at 70% VO2max (33°C, 40% relative humidity) for one hour. The motorized treadmill will be remained flat. At 10 minute intervals during the trial, heart rate, rectal temperature, rating of perceived exertion and thermal discomfort will be recorded. Expired air and blood samples will be obtained every 20 minutes during the trial and after one hour post-exercise. Following the collection of expired air, participants will be asked to consume 3 ml.kg-1 body weight of plain water with tablet of either Quercetin, Quercetin plus vitamin C or placebo. Post-exercise nude body weight will be also recorded.
Additionally, a muscle biopsy sample will be taken 2 days before and 2 days after the actual experimental trials from willing participants.
Each trial will be separated by at least 7 days. For the second and third trial, the study protocol will be identical to the first trial.
Quercetin, Vitamin C
Primary outcome measures
Oxidative stress blood markers and intramuscular heat shock protein (HSPs) following each experimental trial.
Blood antioxidant measurements: quercetin, ascorbic acid, urate, oxidised/reduced glutathione (GSSG-GSH) ratio, total antioxidant capacity and oxidative stress biomarkers (lipid peroxidation (MDA) and protein carbonyl).
All these outcomes will be measured before warm-up, immediately after warm-up, every 20 minutes during the one hour exercise bout and post one hour exercise.
Secondary outcome measures
Intramuscular heat shock proteins (HSP 70 and HSP60).
These outcomes will be measured 2 days pre-exercise and 2 days post-exercise
Overall trial start date
Overall trial end date
Participant inclusion criteria
2. Aged between 18-48 years
3. Individuals free from cardiovascular, metabolic or joint disease as determined by a standard health questionnaire
5. Not taking any mineral or vitamin supplement (other than those provided) or any other antioxidant supplements for 2 weeks before and during the study
Target number of participants
Participant exclusion criteria
1. Individuals taking vitamin supplements
2. Any bleeding disorder or taking medication which impacts blood coagulation
3. Known tendency towards keloid scarring
4. Known sensitivity or allergy to any local anaesthetic medicines
5. Any reported use of substance which may pose undue personal risk to participants or introduce bias into the experiment
6. Any other condition or behaviour deemed either to pose undue risk to participants or introduce bias into the experiment
7. A known renal dysfunction
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
University of Bath
Malaysian Higher Education Authority (Malaysia)
Funding Body Type
Funding Body Subtype
University of Bath (UK)
Funding Body Type
private sector organisation
Funding Body Subtype
Results and Publications
Publication and dissemination plan
To be confirmed at a later date
Intention to publish date
Participant level data
Not expected to be available
Results - basic reporting