Quercetin fights inflammation and free radical damage

  • Quercetin is known for it's antioxidant, anti-inflammatory and immune modulating activity, and due to those properties it is a valuable anti-cellulite active 
  • Source: Well-Known Antioxidants and Newcomers in Sport Nutrition: Quercetin
  • Abstract: Quercetin (3,4,5,7-pentahydroxylflavone) is a natural bioactive flavonoid found in a wide variety of natural foods, such as nuts, grapes, apples, berries, onions, broccoli and black tea (Boots et al. 2008, Kelly 2011). In vitro and animal studies indicate that quercetin has many biological effects such as antioxidant, antiinflammatory, anticarcinogenic, antiviral, psychostimulant, cardioprotective, neuroprotective, antipathogenic, immune regulatory and increasing mitochondrial biogenesis (Davis et al. 2009a). Antioxidant properties of quercetin are attributed to its chemical structure, particularly the presence and location of the hydroxyl (-OH) substitutions. The beneficial effects of quercetin largely depend on its bioavailability after oral administration. Although initial reports indicated that bioavailability of quercetin was limited, recent evidence suggests that quercetin can be detected in plasma within 15–30 min of ingestion of a 250 or 500 mg quercetin chew preparation, reaching a peak concentration at approximately 120–180 min, returning to baseline levels at 24 h in humans (Boots et al. 2008, Davis et al. 2009a). Quercetin also has been shown to reach and accumulate in various tissues such as the colon, kidney, liver, lung, muscle and brain, though the tissue distribution has not yet been studied in humans (de Boer et al. 2005, Harwood et al. 2007). Quercetin supplementation studies in athletes have focused on the potential effects of exercise-induced inflammation, oxidative stress, immune dysfunction and exercise performance (Nieman et al. 2012). The available evidence for a beneficial effect of quercetin on exercise performance, while encouraging, is limited by the lack of sophisticated clinical trials. The first human exercise study investigating quercetin supplementation was published in 2006 (MacRae and Mefferd 2006), with many more published in the past few years and continuing to be published. When athletes are studied, most of the researches have failed to find an ergogenic effect (Quindry et al. 2008, Utter et al. 2009), in contrast to that of a study of elite cyclists, who exhibited an improvement of their aerobic performance (MacRae and Mefferd 2006). MacRae and Mefferd (2006) indicated that administration of quercetin (1200 mg) for 6 weeks resulted in performance improvement in cyclists. Davis et al. (2010) examined the effects of 7 days of quercetin (1000 mg) supplementation on both VO2max and time to fatigue on a bicycle ergometer in healthy untrained men and women. Increases in both VO2max (3.9%) and time to fatigue (13.2%) were found. In a recently published meta-analysis (Pelletier et al. 2013), it has been demonstrated that quercetin supplementation improves endurance performance by 0.74 ± 1.04% compared with placebo. However, no relationship was found between quercetin duration and percentage changes in endurance performance between groups. In this meta-analysis, it was demonstrated that quercetin confers an increase in performance which is much less than this efficacy threshold, thereby indicating that it is unlikely to confer any ergogenic value, at least within the length of supplementation used and quercetin doses provided by the actual studies. The authors concluded that quercetin is unlikely to improve performance, independent of the training state. Athletes may hope to benefit from use of a sport nutrition supplement during out of doors, real-world exercise conditions, if it produces an effect under laboratory-controlled exercise conditions that is 1.3–1.6% (Hopkins et al. 1999, Hopkins and Hewson 2001) greater than the effect of the placebo. In a study by Dumke et al. (2009), no effect of quercetin supplementation (1000 mg·day–1) was observed on cycling time trial performance in elite cyclists. Quindry et al. (2008) reported that quercetin supplementation (1000 mg·day–1 for 3 weeks) had no effect on race performance at the Western States 100-mile race. A single, very high dose of quercetin (2 g) was also shown not to increase exercise performance in moderately fit military personnel during exercise in the heat (Cheuvront et al. 2009). Supplementation with quercetin and vitamin C for 8 weeks did not improve exercise performance but reduced muscle damage and body fat percent in athletes (Askari et al. 2012). Sharp et al. (2012) demonstrated that supplementation with quercetin (1000 mg·day–1 for 9 days) did not improve aerobic capacity, aerobic performance, steady state load carriage exercise and change the metabolic or perceptual responses to exercise. In a recent study, Casuso et al. (2013) suggested that quercetin supplementation showed no effect on VO2peak, speed at VO2peak or endurance time to exhaustion after 6 weeks of quercetin supplementation. Some studies (MacRae and Mefferd 2006, Davis et al. 2010, Nieman et al. 2010) reported an improvement in exercise performance in humans after ingestion of quercetin, whereas most others failed to find statistically significant benefits in exercise capacity (Cureton et al. 2009, Utter et al. 2009, Bigelman et al. 2010, Ganio et al. 2010, Sharp et al. 2012, Askari et al. 2013). The most important novel effect of quercetin related to a possible benefit on endurance performance comes from two recent in vitro and rodent studies (Rasbach and Schnellmann 2008, Davis et al. 2009b) that show a benefit on mitochondrial function. Davis et al. (2009b) found that quercetin feedings (12.5 and 25 mg·kg–1day–1) for 7 days improve running time to fatigue by stimulation of mitochondrial biogenesis, including peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and sirtuin 1 (SIRT1) gene expression, mitochondrial DNA (mtDNA) and cytochrome c enzyme concentration in both the brain and soleus muscle of rats. However, this effect has not yet been observed in humans. A study investigating markers of mitochondrial biogenesis in humans after quercetin administration (1000 mg·day–1 for 2 weeks) observed trends towards increased markers of mitochondrial biogenesis such as cytochrome c oxidase and muscle mtDNA but failed to reach statistical significance (Nieman et al. 2010). Possible reasons for the inconsistent findings among these studies may include the range of subject fitness levels, differences in plasma quercetin concentration obtained via the various supplementation protocol/supplement types and differences in research design. In accordance with anti-inflammatory properties, it has been shown that quercetin modulates intracellular signalling pathways, including the inflammatory signalling cascade, by inhibiting activation proinflammatory transcription factor and nuclear factor-kappa B (NF-κB) (Harwood et al. 2007). Strenuous exercise is capable of damaging muscle and initiating an inflammatory response. Nieman et al. (2007a,b,c) examined the effect of quercetin upon inflammation after three consecutive days of cycling and following an ultralong endurance run. Except for an attenuation of interleukin (IL)-8 and IL-10 mRNA in blood leukocytes following the cycling bouts, quercetin failed to attenuate any of the measured markers of muscle damage, inflammation, increases in plasma cytokines and alterations in muscle cytokine mRNA expression. Recently, Overman et al. (2011) reported that quercetin decreased expression of inflammatory cytokine TNF-α, interferon-γ, IL-6 and IL-1β transcripts in cultured human macrophages, which are known to be contributors to secondary muscle damage. O’Fallon et al. (2012), McAnulty et al. (2008) and Abbey and Rankin (2011) demonstrated no effect of quercetin supplementation on the markers of muscle damage and no effect of quercetin or eccentric exercise on biological markers of systemic inflammation (IL-6 and C-reactive protein) in untrained and trained individuals. Konrad et al. (2011) reported that ingestion of a quercetin-based supplement (1000 mg) 15 min before the 2 hours of treadmill run did not attenuate exercise-induced inflammation or immune changes or improve performance. In a study, quercetin feedings reduced self-reported symptoms of upper respiratory tract infection (URTI) following 3 days of exhaustive exercise (Nieman et al. 2007c). In this study, highly trained cyclists ingesting 1000 mg·day–1 of quercetin during a 3-week period experienced a significantly lower incidence of URTI during the 2-week period following the 3 days of intensified training. However, there was no beneficial effect of quercetin on any of the immune components measured, including natural killer (NK) cell lytic activity, polymorphonuclear respiratory burst or phytohaemagglutinin-stimulated lymphocyte proliferation, despite the reduced incidence of URTI symptoms that were observed after quercetin feedings. However, in a similar study, Henson et al. (2008) reported no benefit on illness rates following the Western States Endurance Run. Davis et al. (2008) reported that quercetin supplementation (12.5 mg·kg–1·day–1) for 7 days reduces susceptibility to influenza infection following stressful exercise in rats. No effects of quercetin were found on leukocyte subset counts, granulocyte respiratory burst activity and salivary immunoglobulin A following quercetin supplementation for 3 weeks before and 2 weeks after the Western States Endurance Run (Henson et al. 2008). Another interesting property of quercetin which may enhance mental and physical performance is its caffeine-like psychostimulant effect. Psychostimulants, like caffeine, can delay fatigue during endurance exercise, because of their ability to block adenosine receptors in the brain, which results in an increase in dopamine activity (Davis et al. 2003). A psychostimulant effect of quercetin has also been reported in vitro (Alexander 2006) in a manner similar to that of caffeine (Ferré 2008), but this effect was not found in human subjects (Cheuvront et al. 2009).