Effects of exercise and quercetin on DNA integrity
| ISRCTN | ISRCTN34136514 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN34136514 |
| Secondary identifying numbers | REC/23/0020 |
- Submission date
- 20/02/2025
- Registration date
- 26/02/2025
- Last edited
- 10/04/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Genetic Diseases
Plain English Summary
Background and study aims
As we get older, our risk of developing diseases like cancer, heart disease, and brain disorders increases. Exercise is known to help slow down ageing by making positive changes to our DNA. This study aims to see how high-intensity exercise (HIE) and a natural supplement called quercetin affect DNA and the ageing process in healthy males.
Who can participate?
Healthy males aged 30-45 years who live in the UK or Ireland are invited to take part in the study.
What does the study involve?
Participants will first undergo fitness testing at Ulster University Belfast, where their height, weight, and fitness levels will be measured. They will then perform high-intensity exercise and provide blood samples before and after exercise and supplementation. Participants will take either quercetin or a placebo for 21 days, with a one-week break between treatments.
What are the possible benefits and risks of participating?
Participants will contribute to important research on ageing and may gain insights into their own fitness levels. Risks include muscle injury, heart issues, nausea, fainting, infections, and discomfort from blood sampling. The research team has taken steps to minimize these risks.
Where is the study run from?
The study is conducted at the Human Performance Lab at Ulster University Belfast (UK)
When is the study starting and how long is it expected to run for?
September 2022 to May 2025
Who is funding the study?
DoNotAge.org
Ulster University (UK)
Who is the main contact?
Ciara Juan, PhD Researcher (Juan-CA@ulster.ac.uk)
Prof. Gareth Davison, Chief Investigator (gw.davison@ulster.ac.uk)
Contact information
Public, Scientific
York St
Belfast
BT15 1ED
United Kingdom
 ORCID ID |
0000-0001-5308-7021 |
|---|---|
| Phone | +44 7944006251 |
| juan-ca@ulster.ac.uk |
Principal Investigator
York Street
Belfast
BT15 1ED
United Kingdom
| ORCID ID |
0000-0002-2002-2253 |
|---|---|
| Phone | + 44(0)28 9536 5212 |
| gw.davison@ulster.ac.uk |
Study information
| Study design | Single-center interventional double-blind randomized placebo-controlled crossover trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised cross over trial |
| Study setting(s) | University/medical school/dental school |
| Study type | Prevention |
| Participant information sheet | 46877_PIS.pdf |
| Scientific title | Exercise and quercetin in ageing-associated DNA repair and epigenetic modifications |
| Study hypothesis | Exercise and quercetin, individually and in combination, activate DNA repair pathways |
| Ethics approval(s) |
Approved 30/12/2022, Ulster University Research Ethics Committee (UREC) (York Street, Belfast, BT15 1ED, United Kingdom; +44 (0)28 95365028; e.bell2@ulster.ac.uk), ref: REC/23/0020 |
| Condition | Prevention of genome instability in healthy middle-aged men |
| Intervention | All participants completed a three-week intervention with an oral quercetin supplement (1000 mg per day) and another three-week intervention with a placebo, separated by a 1-2 weeks washout period. Laboratory technicians generated random numbers using the R programming language, ensuring that each participant had an equal chance of being placed in any group, minimising bias in the study design. Blinding was unknown to the PhD student who gathered data. |
| Intervention type | Supplement |
| Primary outcome measure | Current primary outcome measures as of 10/04/2025: The primary outcome measures are assessed at baseline before quercetin, baseline before placebo, after 3 weeks of quercetin, after 3 weeks of placebo, after exercise with quercetin, and after exercise without quercetin, except where stated otherwise: 1. DNA strand breaks measured using single-cell gel electrophoresis 2. Oxidised purines measured using single-cell gel electrophoresis with formamidopyrimidine DNA glycosylase (FPG) enzyme incubation 3. DNA double-strand breaks measured using immunofluorescence for γH2AX and 53BP1 foci 4. Lipid damage measured using the spectrophotometric lipid hydroperoxide assay 5. DNA repair gene expression (SIRT1, SIRT6, PARP1, RAD51, OGG1, XRCC1, etc.) measured using RT-qPCR 6. Telomere length measured using qPCR at baseline before quercetin, baseline before placebo, after 3 weeks of quercetin, and after 3 weeks of placebo 7. Plasma quercetin levels using HPLC-mass spectrometry Previous primary outcome measures: The primary outcome measures are assessed at baseline before quercetin, baseline before placebo, after 3 weeks of quercetin, after 3 weeks of placebo, after exercise with quercetin, and after exercise without quercetin, except where stated otherwise: 1. Total DNA damage measured using single-cell gel electrophoresis 2. Single-strand break DNA damage measured using single-cell gel electrophoresis with formamidopyrimidine DNA glycosylase (FPG) enzyme incubation 3. Double-strand break DNA damage measured using dual staining immunohistochemistry for γH2AX and 53BP1 foci 4. Lipid damage measured using the spectrophotometric lipid hydroperoxide assay 5. DNA repair gene expression (SIRT1, SIRT6, PARP1, RAD51, OGG1, XRCC1, etc.) measured using RT-qPCR 6. Telomere length measured using qPCR at baseline before quercetin, baseline before placebo, after 3 weeks of quercetin, and after 3 weeks of placebo |
| Secondary outcome measures | There are no secondary outcome measures |
| Overall study start date | 30/09/2022 |
| Overall study end date | 30/05/2025 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 30 Years |
| Upper age limit | 45 Years |
| Sex | Male |
| Target number of participants | 10 |
| Total final enrolment | 13 |
| Participant inclusion criteria | 1. Male: Menstrual cycle-related hormonal variations in women are known to affect the molecular pathways associated with the DNA damage repair response. 2. Lightly active: Having a VO2max of <50ml/kg/min. Athletes and very fit individuals tend to have a blunted response to exercise which may be due to genetic factors or exercise training effects. 3. Of normal weight: Having a BMI of 18.5 to 24.9. Overweight/obese participants also have a blunted response to exercise partly due to impaired blood flow. 4. Omnivore: Vegans have a differential SIRT1 response to acute exercise (Potthast et al., 2020) which may be due to their blood and cell antioxidant status. 5. Non-smoker: Smokers are known to have differential hormonal, antioxidant, and inflammatory status that may affect the exercise and supplementation response. 6. Not a heavy drinker: Not exceeding 14 units of alcohol per week. Heavy drinkers are also known to have differential hormonal, antioxidant, and inflammatory status. 7. Not on any medication or supplementation affecting response to exercise. |
| Participant exclusion criteria | 1. Smoking: Smokers are known to have differential hormonal, antioxidant, and inflammatory status that may affect the exercise and supplementation response. 2. Exceeding 14 units of alcohol per week: Heavy drinkers are also known to have differential hormonal, antioxidant, and inflammatory status. 3. Working in night shift: SIRT1 regulates circadian rhythm and vice versa. 4. Having an infection: Respiratory tract infections, gastrointestinal issues, or any changes in inflammatory status affect the exercise response. 5. Having cardiovascular or metabolic disorders: These diseases are associated with impaired blood flow that affects exercise response. 6. Taking a clinically prescribed medicine: Medication can interfere with the associated molecular pathways. 7. Being an athlete or overly fit (VO2max >50ml/kg/min). |
| Recruitment start date | 01/08/2023 |
| Recruitment end date | 30/03/2024 |
Locations
Countries of recruitment
- Northern Ireland
- United Kingdom
Study participating centre
Belfast
BT15 1ED
United Kingdom
Sponsor information
University/education
York Street
Belfast
BT15 1ED
Northern Ireland
United Kingdom
| Phone | +44 7944006251 |
|---|---|
| e.bell2@ulster.ac.uk | |
| Website | https://www.ulster.ac.uk/departments/research/research-governance |
"ROR" |
https://ror.org/01yp9g959 |
Funders
Funder type
Charity
No information available
Government organisation / Universities (academic only)
- Alternative name(s)
- University of Ulster, Ulster, Ulster Uni, UU
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/05/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request, Published as a supplement to the results publication |
| Publication and dissemination plan | Publication in peer-reviewed journal |
| IPD sharing plan | For each participant, his own unique, individual dataset generated during and/or analysed during the current study, such as values for telomere length and DNA damage and repair, are/will be available to him upon request from Ciara Juan juan-ca@ulster.ac.uk beginning March 2025 onwards through the participant’s email. The datasets generated and/or analysed as a group during the current study will be published as a supplement to the results publication without identifying the participants. All participants consented to the use of their data for research purposes. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | 24/02/2025 | No | Yes |
Additional files
Editorial Notes
10/04/2025: The following changes were made:
1. The overall study start date was changed from 30/12/2022 to 30/09/2022.
1. The overall study end date was changed from 30/03/2024 to 30/05/2025.
3. The primary outcome measures were updated.
24/02/2025: Study's existence confirmed by Ulster University Research Ethics Committee (UREC).
