Key Points:
- Quercetin reduced DNA damage after intense exercise
- Protection seen against both single- and double-strand breaks
- Core DNA repair genes were preserved with quercetin
- Cellular stress responses were more balanced
- Exercise-induced inflammatory shifts steadied
Overview of Study
Thirteen adults (ages 30-45) completed a randomized crossover study with both placebo and quercetin phases separated by a two- to three-week washout period.
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Quercetin First:
- 21 days of 1,000 mg/day quercetin, followed by 21 days of placebo
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Placebo First:
- 21 days of placebo, followed by 21 days of 1,000 mg/day quercetin
At the end of each supplementation phase, both groups completed the same high-intensity interval exercise (HIIE) session, designed to induce short-term oxidative and DNA stress.
Blood samples collected before and after exercise were used to measure DNA damage, repair signaling, antioxidant activation, and inflammatory markers.
"The supplement (or its placebo counterpart) was administered 1 hour before exercise, and blood samples were obtained immediately before supplementation and immediately post-exercise."
This image shows the study design: participants began with a HIIE workout, then repeated the workout after a single dose and again after 21 days of supplementation, before switching to the other (supplement or placebo) after a washout period.
Quercetin Reduced DNA Damage
High-intensity exercise increased DNA damage markers in both groups. However, participants supplemented with quercetin showed significantly lower DNA damage after exercise.
"DNA single-strand breaks increased post-exercise... Short-term (21-day) supplementation significantly decreased the post-exercise strand break."
Benefits were also observed for double-strand DNA breaks, both after a single dose and after 21 days of supplementation.
"DNA double-strand breaks increased post-exercise… Both acute and short-term quercetin supplementation resulted in lower strand breaks post-exercise."
"The significant decrease in DNA double-strand breaks post-exercise is noteworthy, as unresolved double-strand breaks can lead to genomic instability and senescence."
Research on cumulative DNA damage shows how repeated oxidative stress without efficient repair can drive long-term tissue dysfunction and age-associated disease risk.
This suggests that quercetin protectively limits the buildup of DNA damage during intense exercise and supports faster or more efficient repair.
Quercetin Stabilized Repair Systems
Quercetin was found to stabilize DNA repair systems during exercise, a period when these pathways typically show stress-driven shifts.
- Key repair enzymes SIRT6 and OGG1 increased instead of declining after exercise
- Stress-driven signals SIRT1 and PARP1 showed smaller post-exercise spikes
- RAD51 still increased appropriately, supporting essential double-strand repair
"RAD51, like SIRT1 and PARP1, significantly increased post-exercise, with no significant effects in quercetin… quercetin preserved SIRT6 and OGG1 expression."
In short, the placebo group responded to exercise-induced DNA damage with heightened stress signaling, while the quercetin group showed lower damage and a more controlled repair response.
Activation of Antioxidant and Nuclear Defense Pathways
Intense exercise usually triggers short-term swings in inflammation as the body reacts to stress. With quercetin, these markers stayed much more stable, suggesting the body handled exercise stress more smoothly.
"Post-exercise plasma glycan remodelling was observed in the placebo condition but not with quercetin supplementation, suggesting a stabilisation of glycosylation dynamics under oxidative stress."
Quercetin also increased in blood plasma, going into cells and reaching the nucleus. There, quercetin showed up in the same places as SIRT6, a key DNA repair protein, and helped activate Nrf2, a master regulator of antioxidant defenses.
"Quercetin accumulated in plasma and exhibited enhanced nuclear localisation post-exercise… increased the post-exercise SIRT6-quercetin nuclear colocalisation and Nrf2 nuclear translocation."
These changes support a coordinated response that links antioxidant protection, NAD+-dependent repair activity, and chromatin stability during oxidative stress.
Conclusion
These effects suggest that while high-intensity exercise temporarily increases oxidative DNA damage, quercetin helps cells recover with less disruption, supporting repair systems without shutting down normal stress adaptation.
Rather than blocking the beneficial stress signals of exercise, quercetin supported:
- Lower overall DNA damage
- Preservation of NAD+-linked, energy-efficient repair pathways
- More stable inflammatory and glycan aging markers
"[Quercetin] improved redox homeostasis and sustained DNA repair capacity… supplementation attenuated post-exercise DNA damage, including double and single-strand breaks… while preserving SIRT6 and OGG1 expression."
These findings position quercetin as a nutritional support compound that may help maintain cellular stability and resilience during periods of high physical demand or oxidative stress.
