Quercetin

The dietary flavonoid quercetin increases VO(2max) and endurance capacity.
Davis JM, Carlstedt CJ, Chen S, Carmichael MD, Murphy EA.
Int J Sport Nutr Exerc Metab. 2010 Feb;20(1):56-62.

 Quercetin, a natural polyphenolic flavonoid substance present in a variety of food plants, has been shown in vitro and in animal studies to have widespread health and performance benefits resulting from a combination of biological properties, including antioxidant and anti-inflammatory activity, as well as the ability to increase mitochondrial biogenesis. Little is known about these effects in humans, however, especially with respect to exercise performance. The authors determined whether quercetin ingestion would enhance maximal aerobic capacity and delay fatigue during prolonged exercise in healthy but untrained participants. Twelve volunteers were randomly assigned to 1 of 2 treatments: (a) 500 mg of quercetin twice daily dissolved in vitamin-enriched Tang or (b) a nondistinguishable placebo (Tang). Baseline VO2max and bike-ride times to fatigue were established. Treatments were administered for a period of 7 days using a randomized, double-blind, placebo-controlled, crossover study design. After treatment both VO2max and ride time to fatigue were determined. Seven days of quercetin feedings were associated with a modest increase in VO2max (3.9% vs. placebo; p < .05) along with a substantial (13.2%) increase in ride time to fatigue (p < .05). These data suggest that as little as 7 days of quercetin supplementation can increase endurance without exercise training in untrained participants. These benefits of quercetin may have important implications for enhancement of athletic and military performance. This apparent increase in fitness without exercise training may have implications beyond that of performance enhancement to health promotion and disease prevention.
PMID: 20190352

  Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance.
Davis JM, Murphy EA, Carmichael MD, Davis B.
Am J Physiol Regul Integr Comp Physiol. 2009 Apr;296(4):R1071-7

 Quercetin is one of a broad group of natural polyphenolic flavonoid substances that are being investigated for their widespread health benefits. These benefits have generally been ascribed to its combination of antioxidant and anti-inflammatory activity, but recent in vitro evidence suggests that improved mitochondrial biogenesis could play an important role. In addition, the in vivo effects of quercetin on mitochondrial biogenesis exercise tolerance are unknown. We examined the effects of 7 days of quercetin feedings in mice on markers of mitochondrial biogenesis in skeletal muscle and brain, and on endurance exercise tolerance. Mice were randomly assigned to one of the following three treatment groups: placebo, 12.5 mg/kg quercetin, or 25 mg/kg quercetin. Following 7 days of treatment, mice were killed, and soleus muscle and brain were analyzed for mRNA expression of peroxisome proliferator-activated receptor-gamma coactivator (PGC-1alpha) and sirtuin 1 (SIRT1), and mitochondrial DNA (mtDNA) and cytochrome c. Additional mice underwent a treadmill performance run to fatigue or were placed in voluntary activity wheel cages, and their voluntary activity (distance, time, and peak speed) was recorded. Quercetin increased mRNA expression of PGC-1alpha and SIRT1 (P < 0.05), mtDNA (P < 0.05) and cytochrome c concentration (P < 0.05). These changes in markers of mitochondrial biogenesis were associated with an increase in both maximal endurance capacity (P < 0.05) and voluntary wheel-running activity (P < 0.05). These benefits of querectin on fitness without exercise training may have important implications for enhancement of athletic and military performance and may also extend to prevention and/or treatment of chronic diseases. PMID: 19211721

 Health effects of quercetin: from antioxidant to nutraceutical.
Boots AW, Haenen GR, Bast A.
Eur J Pharmacol. 2008 May 13;585(2-3):325-37

 Quercetin, a member of the flavonoids family, is one of the most prominent dietary antioxidants. It is ubiquitously present in foods including vegetables, fruit, tea and wine as well as countless food supplements and is claimed to exert beneficial health effects. This includes protection against various diseases such as osteoporosis, certain forms of cancer, pulmonary and cardiovascular diseases but also against aging. Especially the ability of quercetin to scavenge highly reactive species such as peroxynitrite and the hydroxyl radical is suggested to be involved in these possible beneficial health effects. Consequently, numerous studies have been performed to gather scientific evidence for these beneficial health claims as well as data regarding the exact mechanism of action and possible toxicological aspects of this flavonoid. The purpose of this review is to evaluate these studies in order to elucidate the possible health-beneficial effects of the antioxidant quercetin. Firstly, the definitions as well as the most important aspects regarding free radicals, antioxidants and oxidative stress will be discussed as background information. Subsequently, the mechanism by which quercetin may operate as an antioxidant (tested in vitro) as well as the potential use of this antioxidant as a nutraceutical (tested both ex vivo and in vivo) will be discussed. PMID: 18417116

  Quercetin reduces susceptibility to influenza infection following stressful exercise.
Davis JM, Murphy EA, McClellan JL, Carmichael MD, Gangemi JD.
Am J Physiol Regul Integr Comp Physiol. 2008 Aug;295(2):R505-9

 Exercise stress is associated with increased risk for upper respiratory tract infection. We have shown that exercise stress can increase susceptibility to infection. Quercetin, a flavonoid present in a wide variety of fruits and vegetables, has been reported to inhibit infectivity and replication of a broad spectrum of viruses and may offset the increase in susceptibility to infection associated with stressful exercise. This study examined the effects of quercetin feedings on susceptibility to the influenza virus A/Puerto Rico/8/34 (H1N1) following stressful exercise. Mice were randomly assigned to one of four treatment groups: exercise-placebo, exercise-quercetin, control-placebo, or control-quercetin. Exercise consisted of a run to fatigue (approximately 140 min) on a treadmill for 3 consecutive days. Quercetin (12.5 mg/kg) was administered via gavage for 7 days before viral challenge. At 30 min after the last bout of exercise or rest, mice (n=23-30) were intranasally inoculated with a standardized dose of influenza virus (0.04 hemagglutinating units). Mice were monitored daily for morbidity (time to sickness), symptom severity, and mortality (time to death) for 21 days. Exercise stress was associated with an increased susceptibility to infection [morbidity, mortality, and symptom severity on days 5-7 (P<0.05)]; quercetin offset the increase in susceptibility to infection [morbidity, mortality, and symptom severity on days 5-7 (P<0.05)] that was associated with stressful exercise. These data suggest that short-term quercetin feedings may prove to be an effective strategy to lessen the impact of stressful exercise on susceptibility to respiratory infection. PMID: 18579649

  The protective effect of quercetin on long-term alcohol consumption-induced
oxidative stress.
Kahraman A, Cakar H, Köken T.
Mol Biol Rep. 2011 Jun 15

 Long-term alcohol consumption can cause oxidative stress and cytokines induction, which are associated with free radicals. Quercetin, one of the most widely distributed flavonoids in plants, is a natural antioxidant. We investigated the hypothesis that quercetin could prevent the ethanol-induced oxidative stress and decreases tumor necrosis factor-α (TNF-α) and interferon-γ (INF-γ) as pro-inflammatory cytokines. Twenty-eight rats were randomly divided into control group (C), ethanol treatment group (EtOH) (~1 ml/day, 80%; 2 g/kg body wt), intragastrically (i.g.), quercetin treatment group (Q), (100 mg/kg-body wt per 3 days) i.g. and ethanol plus quercetin treatment group (EtOH + Q) (1 ml/day, 80% of ethanol and 100 mg/kg-body wt of quercetin per 3 days) i.g. for 30 days Plasma thiobarbituric acid reactive substance (TBARS) levels and protein carbonyl content were significantly higher in the EtOH group than the C group (P < 0.01). On the other hand, TBARS level and protein carbonyl content in the EtOH + Q group was decreased significantly by quercetin (P < 0.05, P < 0.01; respectively). While GSH levels in whole blood decreased in EtOH group compared to C group, they increased significantly by quercetin (P < 0.05). Plasma ALT, TNF-α and IFN-γ levels increased significantly in the EtOH group compared to control group (P < 0.05, P < 0.01, P < 0.01, respectively), but they decreased significantly in the EtOH + Q group in comparison with EtOH group (P < 0.05, P < 0.01, P < 0.01, respectively). Our results demonstrate that quercetin treatment may provide a protection as reflected by decreased plasma TBARS, protein carbonyls, TNF-α, INF-γ and ALT levels against ethanol-induced oxidative damage. PMID: 21674185

Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models.
Kleemann R, Verschuren L, Morrison M, Zadelaar S, van Erk MJ, Wielinga PY, Kooistra T.
Atherosclerosis. 2011 May 5

 Polyphenols such as quercetin may exert several beneficial effects, including those resulting from anti-inflammatory activities, but their impact on cardiovascular health is debated. We investigated the effect of quercetin on cardiovascular risk markers including human C-reactive protein (CRP) and on atherosclerosis using transgenic humanized models of cardiovascular disease. After evaluating its anti-oxidative and anti-inflammatory effects in cultured human cells, quercetin (0.1%, w/w in diet) was given to human CRP transgenic mice, a humanized inflammation model, and ApoE*3Leiden transgenic mice, a humanized atherosclerosis model. Sodium salicylate was used as an anti-inflammatory reference. In cultured human endothelial cells, quercetin protected against H(2)O(2)-induced lipid peroxidation and reduced the cytokine-induced cell-surface expression of VCAM-1 and E-selectin. Quercetin also reduced the transcriptional activity of NFκB in human hepatocytes. In human CRP transgenic mice (quercetin plasma concentration: 12.9±1.3μM), quercetin quenched IL1β-induced CRP expression, as did sodium salicylate. In ApoE*3Leiden mice, quercetin (plasma concentration: 19.3±8.3μM) significantly attenuated atherosclerosis by 40% (sodium salicylate by 86%). Quercetin did not affect atherogenic plasma lipids or lipoproteins but it significantly lowered the circulating inflammatory risk factors SAA and fibrinogen. Combined histological and microarray analysis of aortas revealed that quercetin affected vascular cell proliferation thereby reducing atherosclerotic lesion growth. Quercetin also reduced the gene expression of specific factors implicated in local vascular inflammation including IL-1R, Ccl8, IKK, and STAT3. Quercetin reduces the expression of human CRP and cardiovascular risk factors (SAA, fibrinogen) in mice in vivo. These systemic effects together with local anti-proliferative and anti-inflammatory effects in the aorta may contribute to the attenuation of atherosclerosis. PMID: 21601209. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  Antioxidant properties of quercetin.
Zhang M, Swarts SG, Yin L, Liu C, Tian Y, Cao Y, Swarts M, Yang S, Zhang SB, Zhang K, Ju S, Olek DJ Jr, Schwartz L, Keng PC, Howell R, Zhang L, Okunieff P.
Adv Exp Med Biol. 2011;701:283-9.

 Quercetin, a plant-derived aglycone form of flavonoid glycosides, has been used as a nutritional supplement and may be beneficial against a variety of diseases, including cancer. We examined the antioxidant properties of quercetin. The reduction potential of quercetin was measured at various pH values using voltammetric methods, and its total antioxidant capacity (TAC) was measured using the phosphomolybdenum method. The effect of quercetin on production of reactive oxygen species (ROS) and nitric oxide (NO) in LPS-stimulated human THP-1 acute monocytic leukemia cells was determined by flow cytometry using CM-H2DCFDA dye. The results were compared with curcumin, a natural product exhibiting a similar range of reported health benefits. Results: 1) Quercetin has a higher reduction potential compared with curcumin at three different pH settings and is comparable to Trolox at pH 7-9.5; 2) its TAC is 3.5 fold higher than curcumin; 3) it reduced LPS-induced ROS to near normal levels; 4) it reduced LPS-induced NO production. These data provide a physico-chemical basis for comparing antioxidants, with potential benefits individually or in combination. PMID: 21445799