Effect of mixed flavonoids, n-3 fatty acids, and vitamin C on oxidative stress and antioxidant capacity before and after intense cycling


Journal Title (Medline/Pubmed accepted abbreviation): Int. J. Sport Nutr. Exerc. Metab.
Year: 2011
Volume: 21
Page numbers: 328-337

Summary of background and research design:

Background: The flavonoids compose a family of antioxidants that include quercetin.  Quercetin is thought to have anti-inflammatory properties against exercise-induced oxidative stress.  Because of different mechanisms of action, it is thought that particular combinations of anti-inflammatory supplements (ex. omega-3 fatty acids, vitamin C, etc.) may be able to optimally reduce inflammation.

F2 isoprostanes- compounds similar in structure to those in the inflammation pathway that are markers of oxidative stress

Hypothesis: Does a quercetin-containing supplement, with or without epigallocatechin gallate (EGCG), isoquercetin (another flavonoid), omega-3 fatty acids, and vitamin C, affect exercise-induced inflammation?  Does it matter if the supplement is consumed once or daily for 2 wks?

Subjects: Trained cyclists- 32 male and 7 female, age about 25-30 y

Experimental design: randomized, double-blind, placebo-controlled

Treatments:  A supplement was produced in chew form (including sugars, gums, flavors, etc.).  Three varieties of chew were produced:

  1. Quercetin + vitamin C (QC, n = 13): 250 mg quercetin, 250 mg vitamin C, 10 mg niacin, 200 µg folic acid.
  2. Quercetin + other flavonoids and omega-3’s (QFO, n = 14): the contents of QC plus 100 mg isoquercetin, 30 mg epigallocatechin gallate (EGCG), and 100 mg omega-3 fatty acids (55 mg eicosapentaenoic acid, EPA, and 45 mg docosahexaenoic acid, DHA).
  3. Placebo: citric acid to mimic the taste of vitamin C and color (reddish-purple) in order to mimic the active treatments.

During the supplementation period, the participants consumed 4 chews/day, divided into 2 doses, for 14 days.

Protocol:  Participants were first familiarized with the protocol and evaluated for VO2max, ventilation rates, and heart rate on a cycle ergometer.  The testing protocol was followed after the supplementation period (2 wks) which included 3 consecutive days of intense cycling; the participants cycled from 3:00-6:00 pm at about 57% of their previously determined Wmax.  Blood samples were collected before supplementation (fasted), after 14 days of supplementation but before the exercise sessions (fasted), immediately after the third exercise session (not fasted), and 14 hrs after the third exercise session (fasted).  A standardized lunch (63 kJ/kg = 6.8 kcal/lb or about 1020 kcal for a 150 lb. person) was consumed before the afternoon cycling session.  Supplementation continued during the 3 days of testing.  Blood was assessed for concentration of active compounds, F2 isoprostanes, and total plasma antioxidant potential.


Summary of research findings:
  • Quercetin supplementation caused an increase in quercetin concentration in plasma for both GC and QFO, showing that the quercetin effectively was absorbed.
  • Supplementation with QC and QFO attenuated the level of F2 isoprostanes after exercise (p ≤ 0.01).  Supplementation caused a decrease in these levels after the 2 wks of supplementation before exercise and the morning after the third day of cycling, but these results were not statistically significant. 
  • The antioxidant properties of the blood were not different between treatments, as measured by FRAC or ORAC.  Interestingly, FRAP values were increased after exercise and ORAC values were decreased after exercise.  Both of these assays measure antioxidant potential and are usually correlated.  This seemingly contradictory finding might be explained by the opposing activities taking place: exercise (typically increases oxidative stress) and antioxidant supplementation (typically increases antioxidant potential) or the nature of the assays.
  • Vitamin C plasma concentrations were significantly increased after the third exercise session for all treatment groups.
Key practice applications:

The quercetin-based supplement was effective at reducing exercise-induced stress and the effect was more pronounced when it was combined with additional immune-modulating compounds.  Unfortunately, there were many confounding factors:
  • When comparing the quercetin supplements to the placebo, it is unknown whether it was the acute dose (the dose taken during the exercise bout) or the chronic dose of the supplement that caused the results.
  • When comparing QC and QFO, it is unknown whether it was the increased amount of antioxidants or identity of the antioxidants that made a difference.
  • Within the supplement cocktail, it is unknown which compounds/groups of compounds were efficacious.

The authors declare that, because there was no difference in F2-isoprostanes or antioxidant potential in the blood after an overnight fast after the 12 wks of supplementation, it must have been the acute dose during exercise that led to physiological changes.  However, there could have changes in tissues other than the blood that affected how the body responded to exercise.  Moreover, it would have been interesting if the authors measured cycling performance.

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