Quercetin and your skin
Lipolysis, blood circulation support, skin irritation, cellulite
Quercetin is a flavonoid found in many herbs, vegetables and fruits and is well researched for its antioxidant action and circulation supporting benefits. It has also been found to be a PDE4 inhibitor and therefore acts as a lipolytic. Finally, quercetin is well-known for its anti-irritation / anti-histamine action. Quercetin is therefore of great importance as an active ingredient in anti-cellulite, leg wellness, contouring and under-eye creams [the Celluence® creams are the only leg wellness / cellulite creams in the world with high concentrations of 95%+ pure quercetin, encased in liposomes, plus 39x other natural anti-cellulite actives].
Quercetin: The science
Quercetin PREVENTS mitochondria-related health dysfunction...
...by protecting mitochondria from oxidative stress, by helping regulate mitochondrial metabolism and biogenesis, and by modulating cell apoptosis due to mitochondrial dysfunction [Source: Dietary Polyphenols and Mitochondrial Function: Role in Health and Disease]
Glycation: the silent assassin of youth
Glycation refers to the damage of proteins, lipids and DNA/RNA by sugars and by high temperature cooking.
Increased consumption of sugars, especially fructose, sucrose/sugar, and high fructose corn syrup, as well as high temperature cooking, leads to the creation of advanced glycation end products (AGEs).
AGEs cause widespread damage to all tissues of the body, from blood vessels to skin to organs, by increasing inflammation, oxidative damage and collagen cross linking.
Skin is particularly prone to glycation damage, with loss of elasticity and firmness and an unhealthy grey complexion usually indicating damage by AGEs. Glycation is also an important cause of cellulite.
According to the authors of this review, "elevated circulating AGEs are associated with increased risk of developing many chronic diseases that disproportionally affect older individuals".
Fighting glycation on all fronts
Following a diet high in vegetables, herbs and spices (with the exception of chilli), avoiding high temperature grilling and frying and avoiding sugary foods, are the best things you can do to avoid glycation damage on your skin, blood vessels and other tissues.
Chlorogenic acid (found in green coffee), carnosine (found in meat) and quercetin (found in citrus fruits) are the most well-known natural compounds that can fight glycation.
All three natural chemicals can also be used topically in the form of anti-ageing / anti-cellulite creams.
Drugs that aim to inhibit or break AGEs are also being developed. Existing drugs known to fight glycation include aminoguanidine (pimagedine) and alagebrium chloride (ALT-711), with neither of them being commercially available.
- Paper: Does accumulation of advanced glycation end products contribute to the aging phenotype?
- Abstract: BACKGROUND: Aging is a complex multifactorial process characterized by accumulation of deleterious changes in cells and tissues, progressive deterioration of structural integrity and physiological function across multiple organ systems, and increased risk of death. METHODS: We conducted a review of the scientific literature on the relationship of advanced glycation end products (AGEs) with aging. AGEs are a heterogeneous group of bioactive molecules that are formed by the nonenzymatic glycation of proteins, lipids, and nucleic acids. RESULTS: Humans are exposed to AGEs produced in the body, especially in individuals with abnormal glucose metabolism, and AGEs ingested in foods. AGEs cause widespread damage to tissues through upregulation of inflammation and cross-linking of collagen and other proteins. AGEs have been shown to adversely affect virtually all cells, tissues, and organ systems. Recent epidemiological studies demonstrate that elevated circulating AGEs are associated with increased risk of developing many chronic diseases that disproportionally affect older individuals. CONCLUSIONS: Based on these data, we propose that accumulation of AGEs accelerate the multisystem functional decline that occurs with aging, and therefore contribute to the aging phenotype. Exposure to AGEs can be reduced by restriction of dietary intake of AGEs and drug treatment with AGE inhibitors and AGE breakers. Modification of intake and circulating levels of AGEs may be a possible strategy to promote health in old age, especially because most Western foods are processed at high temperature and are rich in AGEs.
The salads of the future
Edible flowers have been used throughout the centuries as "glamorous" ingredients for salads and food/dessert decoration. However, what most people do not know is that flowers can be sources of valuable nutrients, carotenoids and polyphenols.
In these two studies, the nutritional properties of several flowers have been analysed: dahlias, roses, marigolds, mountain cornflower, elderflower, french honeysuckle and mallow.
Scientists have found that:
- most flowers are rich in fibre, natural sugars, organic acids, polyunsaturated fats (especially linoleic acid) and also small amounts of protein
- calendula/marigold is rich in tocopherol (vitamin E) and carotenoids (vitamin A precursor)
- elderflower has high levels of the antioxidants rutin and quercetin and the highest overall antioxidant activity, with cornflower being a close runner-up
- mallow can help keep high blood glucose and weight in check, by inhibiting the absorption of carbohydrates
- additionally, elderflower has the strongest activity against lipid peroxidation, one of the causes of cardiovascular disease
The Instagram-able superfoods
Typically plant pigments represent healthful "antioxidants" (carotenoids and polyphenols), and most flowers are appreciated for their vibrant colours. This means that flowers are an undiscovered treasure trove of wholesomeness for our plate.
Only a tiny sample of the abundance of deeply colourful flowers available has being investigated by these two studies, so we expect in future studies more beneficial effects to be discovered
Edible flowers are clearly an amazing source of taste, decoration, colour, glamour and nutrients for our plate, and clearly there is huge potential in marketing them as salad ingredients as well as nutritional supplements.
Flowers could become the salads of the future, and many of them can easily attain superfood status, due to their high micronutrient and low calorie profile - not to mention the Instagram factor!
- Paper 1: Nutritional and chemical characterization of edible petals and corresponding infusions: Valorization as new food ingredients
- Abstract 1: Edible flowers provide new colours, textures and vibrancy to any dish, and apart from the “glam” factor, they can constitute new sources of bioactive compounds. In the present work, the edible petals and infusions of dahlia, rose, calendula and centaurea, were characterized regarding their nutritional value and composition in terms of hydrophilic and lipophilic compounds. Carbohydrates were the most abundant macronutrients, followed by proteins and ash. Fructose, glucose and sucrose were identified in all the petals and infusions. Rose petals and calendula infusions gave the highest content of organic acids, mainly due to the presence of malic and quinic acids, respectively. Polyunsaturated fatty acids predominated over saturated fatty acids, mainly due to the contribution of linoleic acid. Calendula presented the highest content in tocopherols, with α-tocopherol as the most abundant. These results highlight the interest of edible petals “as” and “in” new food products, representing rich sources of bioactive nutrients. Highlights: Edible petals can be included in a daily diet as nutrients source. Edible petals can be also used in infusions providing soluble sugars and organic acids. Rose petals gave the highest content of organic acids and sugars. Calendula petals presented the highest content in tocopherols.
- Paper 2: Edible Flowers: A Rich Source of Phytochemicals with Antioxidant and Hypoglycemic Properties
- Abstract 2: Edible flowers are receiving renewed interest as rich sources of bioactive compounds. Ethanol extracts of eight edible flowers were phytochemically characterized and investigated for their bioactivity. Rutin, quercetin, luteolin, kaempferol, and myricetin were selected as standards and quantified by HPLC. The fatty acid profile was analyzed by GC and GC-MS. Antioxidant properties were evaluated by using different in vitro tests. The hypoglycemic effects were investigated via the inhibition of α-amylase and α-glucosidase. Sambucus nigra exhibited the highest radical-scavenging activity (IC50 of 1.4 μg/mL), followed by Hedysarum coronarium (IC50 of 1.6 μg/mL). Both species contained high quercetin and rutin contents. S. nigra extract exerted the highest activity in preventing lipid oxidation. Malva sylvestris extract inhibited both α-amylase and α-glucosidase with IC50 values of 7.8 and 11.3 μg/mL, respectively. These findings support the consumption of edible flowers as functional foods and their use as sources of natural antioxidants by the food industry.
- Quercetin, one of the most versatile and healthful flavonoids, found in citrus fruits, onions and herbs like parsley, has been found in a study published this week to inhibit glycation and advanced glycation end-products (AGE)
- Glycation is a major cause of metabolic syndrome/diabetes, cardiovascular disease, skin ageing and overall body ageing and involves the damage of proteins by sugars
- Glycation is caused by the ingestion of excess carbohydrates, especially sugars. Heavily roasting food increases the amounts of glycation, while boiling produces no glycation.
- In this study, quercetin was compared to vitamin C, green tea extract, Padma Circosan (an ancient Tibetan multi-herbal formula) and, most especially, aminoguanidin (the standard with which anti-glycation agents are compared to).
- Quercetin was found to have the highest overall anti-glycation effect (60.5% reduction), higher than aminoguanidin itself, and to exert the highest high molecular weight AGE reduction (79.5% reduction)!
- Padma Circosan was found to inhibit lower molecular weight AGE more (74.9% reduction), while vitamin C had the best antioxidant effect.
- This study shows that glycation can be inhibited by widely available foods, supplements and anti-ageing cream actives, with the aim to fight whole body and skin ageing and deterioration cause by lifestyle factors.
- Source: Inhibitory actions of selected natural substances on formation of advanced glycation endproducts and advanced oxidation protein products.
- Abstract: BACKGROUND: Advanced glycation endproducts (AGE) and advanced oxidation protein products (AOPP) arise as a result of excessive glycation and oxidation processes of proteins in hyperglycemia and oxidative stress conditions respectively, both in vivo and in vitro. In vivo these processes are especially intensified in patients with diabetes, and the adverse effects of AGE and AOPP are particularly unfavorable for the pathogenesis and aggravate the biochemical disturbances and clinical complications of diabetes. Total AGE and AOPP (T-AGE and T-AOPP) are heterogeneous groups of compounds, and they can be divided into two main fractions: high- and low-molecular-weight, i.e. HMW-AGE and HMW-AOPP as well as LMW-AGE and LMW-AOPP. Therefore it is important to find natural substances that will prevent formation of total AGE and AOPP and their high- and low-molecular-weight fractions and thereby reduce their adverse effects on tissues and organs. METHOD: Selected natural substances and dietary supplements such as vitamin C, aminoguanidine, quercetin and green tea as well as the multicompound formulations Padma Circosan and Padma 28 were tested in an in vitro model using bovine serum albumin (BSA). Fluorescence of T-, HMW- and LMW-AGE and concentration of T-, HMW- and LMW-AOPP were measured after incubation with these substances. RESULTS: In the examined concentrations quercetin showed the greatest degree of inhibition for T-AGE (60.5 %) as well as for HMW-AGE (79.5 %), while in the case of LMW-AGE the greatest degree of glycation inhibition was shown by Padma Circosan (74.9 %). T-AOPP and HMW-AOPP were best inhibited by vitamin C (87.3 and 89.1 % respectively). The results obtained for LMW-AOPP are atypical, but the lowest concentration was observed in a sample with Padma 28. CONCLUSION: The results show that all tested natural compounds have inhibitory activity towards the formation of total and low- and high-molecular-weight forms of AGE and AOPP in vitro. That suggest a possible role in the prevention of diabetic complications, especially the multiherbal compound Padma preparations, which are especially effective in lowering the most dangerous, i.e. LMW fractions.
- Quercetin, found n onions, parsley, citrus fruits, berries and apples, protects from heart disease by fighting inflammation and atherosclerotic plaque formation
- Quercetin attenuates atherosclerotic inflammation and adhesion molecule expression by modulating TLR-NF-κB signaling pathway.
- Abstract: Adhesion molecules expressed by activated endothelial cells play key role in regulating leukocyte trafficking to sites of inflammation. The present study attempted to explore whether the polyphenolic flavonoid quercetin influence leukocyte endothelial attraction and the involvement of TLR-NF-κB signaling pathway in the expression of adhesion molecules involved in the early development of atherosclerosis. Quercetin at 25μM concentration significantly reduced the HUVEC expression of VCAM-1 and ICAM-1 evidently enhanced by oxLDL. In addition, quercetin significantly downregulated the mRNA expression of MCP-1 and alleviated the nuclear translocation of NF-κB p65 subunit in oxLDL induced HUVECs. Western blot and PCR analyses revealed that quercetin significantly attenuated the expression of both protein and mRNA expression of TLR2 and TLR4. Quercetin supplementation significantly decreased the inflammatory mediators like COX, 5-LOX, MPO, NOS, CRP and the mRNA expression of the cytokine IL-6 in hypercholesterolemic diet (HCD) fed atherosclerotic rats. The results demonstrate that quercetin is effective to regulate the atherosclerotic inflammatory process by inhibiting oxLDL induced endothelial leukocyte adhesion by attenuating the TLR-NF-κB signaling pathway in endothelial cells and decrease the inflammatory process induced by HCD in rats. Therefore, quercetin acts as anti-inflammatory and anti-atherogenic agent, which may have implications for strategies attenuating endothelial dysfunction-related atherosclerosis.
- Source: Quercetin, not caffeine, is a major neuroprotective component in coffee.
- Abstract: Epidemiologic studies indicate that coffee consumption reduces the risk of Parkinson's disease and Alzheimer's disease. To determine the factors involved, we examined the protective effects of coffee components. The test involved prevention of neurotoxicity to SH-SY5Y cells that was induced by lipopolysaccharide plus interferon-γ or interferon-γ released from activated microglia and astrocytes. We found that quercetin, flavones, chlorogenic acid, and caffeine protected SH-SY5Y cells from these toxins. They also reduced the release of tumor necrosis factor-α and interleukin-6 from the activated microglia and astrocytes and attenuated the activation of proteins from P38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa light chain enhancer of activated B cells (NFκB). After exposure to toxin containing glial-stimulated conditioned medium, we also found that quercetin reduced oxidative/nitrative damage to DNA, as well as to the lipids and proteins of SH-SY5Y cells. There was a resultant increase in [GSH]i in SH-SY5Y cells. The data indicate that quercetin is the major neuroprotective component in coffee against Parkinson's disease and Alzheimer's disease.
- Source: The berry constituents quercetin, kaempferol, and pterostilbene synergistically attenuate reactive oxygen species: involvement of the Nrf2-ARE singling pathway,
- Abstract: Quercetin, kaempferol, and pterostilbene are abundant in berries. The anti-oxidative properties of these constituents may contribute to cancer chemoprevention. However, their precise mechanisms of action and their combinatorial effects are not completely understood. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) regulates anti-oxidative stress enzymes and Phase II drug metabolizing/detoxifying enzymes by binding to antioxidant response element (ARE). This study aimed to investigate the anti-oxidative stress activities of quercetin, kaempferol, and pterostilbene individually and in combination, as well as the involvement of the Nrf2-ARE signaling pathway. Quercetin, kaempferol, and pterostilbene all exhibited strong free-radical scavenging activity in the DPPH assay. The MTS assay revealed that low concentration combinations we tested were relatively non-toxic to HepG2-C8 cells. The results of the DCFH-DA assay and combination index (CI) indicated that quercetin, kaempferol, and pterostilbene attenuated intracellular reactive oxygen species (ROS) levels when pretreated individually and had synergistic effects when used in combination. In addition, the combination treatment significantly induced ARE and increased the mRNA and protein expression of Nrf2-regulated genes. Collectively, our study demonstrated that the berry constituents quercetin, kaempferol, and pterostilbene activated the Nrf2-ARE signaling pathway and exhibited synergistic anti-oxidative stress activity at appropriate concentrations.
- Source: Response of keloid fibroblasts to Vitamin D3 and quercetin treatment - in vitro study
- Summary: Keloid scars continue to pose a challenge to clinicians as the treatment armamentarium lacks a formidable agent to tackle them. We have undertaken an in vitro study based on the mechanism of action of Vitamin D3 and quercetin on isolated keloid fibroblasts. Dose-dependent action on the reduction of cellular proliferation, collagen synthesis and induction of apoptosis by Vitamin D3 and quercetin are analyzed and probable mechanism of action is elaborated. This study thus opens up newer avenues in tackling keloid scars effectively.
- Source: Phytochemicals in regulating fatty acid β-oxidation: Potential underlying mechanisms and their involvement in obesity and weight loss.
- Abstract: Excessive accumulation of fat as the result of more energy intake and less energy expenditure is known as obesity. Lipids are essential components in the human body and are vital for maintaining homeostasis and physiological as well as cellular metabolism. Fatty acid synthesis and catabolism (by fatty acid oxidation) are normal part of basic fuel metabolism in animals. Fatty acids are degraded in the mitochondria by a biochemical process called β-oxidation in which two-carbon fragments are produced in each cycle. The increase in fatty acid oxidation is positively correlated with body mass index. Although healthy life style, avoiding Western diet, dieting and strenuous exercise are the commonly used methods to lose weight, they are not considered a permanent solution in addition to risk attenuation of in basal metabolic rate (BMR). Pharmacotherapy offers benefits of weight loss by altering the satiety and lowering absorption of fat from the food; however, its side effects may outweigh the benefits of weight loss. Alternatively, dietary phytochemicals and natural health products offer great potential as an efficient weight loss strategy by modulating lipid metabolism and/or increasing BMR and thermogenesis. Specifically, polyphenols such as citrus flavonoids, green tea epigallocatechin gallate, resveratrol, capsaicin and curcumin, have been reported to increase lipolysis and induce fatty acid β-oxidation through modulation of hormone sensitive lipase, acetyl-coA carboxylase, carnitine acyl transferase and peroxisome proliferator-activated receptor gamma coactivator-1. In this review article, we discuss selected phytochemicals in relation to their integrated functionalities and specific mechanisms for weight loss.
- Source: Mood, stress and longevity: convergence on ANK3.
- Abstract: Antidepressants have been shown to improve longevity in C. elegans. It is plausible that orthologs of genes involved in mood regulation and stress response are involved in such an effect. We sought to understand the underlying biology. First, we analyzed the transcriptome from worms treated with the antidepressant mianserin, previously identified in a large-scale unbiased drug screen as promoting increased lifespan in worms. We identified the most robust treatment-related changes in gene expression, and identified the corresponding human orthologs. Our analysis uncovered a series of genes and biological pathways that may be at the interface between antidepressant effects and longevity, notably pathways involved in drug metabolism/degradation (nicotine and melatonin). Second, we examined which of these genes overlap with genes which may be involved in depressive symptoms in an aging non-psychiatric human population (n=3577), discovered using a genome-wide association study (GWAS) approach in a design with extremes of distribution of phenotype. Third, we used a convergent functional genomics (CFG) approach to prioritize these genes for relevance to mood disorders and stress. The top gene identified was ANK3. To validate our findings, we conducted genetic and gene-expression studies, in C. elegans and in humans. We studied C. elegans inactivating mutants for ANK3/unc-44, and show that they survive longer than wild-type, particularly in older worms, independently of mianserin treatment. We also show that some ANK3/unc-44 expression is necessary for the effects of mianserin on prolonging lifespan and survival in the face of oxidative stress, particularly in younger worms. Wild-type ANK3/unc-44 increases in expression with age in C. elegans, and is maintained at lower youthful levels by mianserin treatment. These lower levels may be optimal in terms of longevity, offering a favorable balance between sufficient oxidative stress resistance in younger worms and survival effects in older worms. Thus, ANK3/unc-44 may represent an example of antagonistic pleiotropy, in which low-expression level in young animals are beneficial, but the age-associated increase becomes detrimental. Inactivating mutations in ANK3/unc-44 reverse this effect and cause detrimental effects in young animals (sensitivity to oxidative stress) and beneficial effect in old animals (increased survival). In humans, we studied if the most significant single nucleotide polymorphism (SNP) for depressive symptoms in ANK3 from our GWAS has a relationship to lifespan, and show a trend towards longer lifespan in individuals with the risk allele for depressive symptoms in men (odds ratio (OR) 1.41, P=0.031) but not in women (OR 1.08, P=0.33). We also examined whether ANK3, by itself or in a panel with other top CFG-prioritized genes, acts as a blood gene-expression biomarker for biological age, in two independent cohorts, one of live psychiatric patients (n=737), and one of suicide completers from the coroner's office (n=45). We show significantly lower levels of ANK3 expression in chronologically younger individuals than in middle age individuals, with a diminution of that effect in suicide completers, who presumably have been exposed to more severe and acute negative mood and stress. Of note, ANK3 was previously reported to be overexpressed in fibroblasts from patients with Hutchinson-Gilford progeria syndrome, a form of accelerated aging. Taken together, these studies uncover ANK3 and other genes in our dataset as biological links between mood, stress and longevity/aging, that may be biomarkers as well as targets for preventive or therapeutic interventions. Drug repurposing bioinformatics analyses identified the relatively innocuous omega-3 fatty acid DHA (docosahexaenoic acid), piracetam, quercetin, vitamin D and resveratrol as potential longevity promoting compounds, along with a series of existing drugs, such as estrogen-like compounds, antidiabetics and sirolimus/rapamycin. Intriguingly, some of our top candidate genes for mood and stress-modulated longevity were changed in expression in opposite direction in previous studies in the Alzheimer disease. Additionally, a whole series of others were changed in expression in opposite direction in our previous studies on suicide, suggesting the possibility of a "life switch" actively controlled by mood and stress.
- In this study quercetin has been found to not only counter the effects of hypoxia in fat cells, but but actually to overcompensate those effects and improve fat tissue oxygenation
- Hypoxia is a key cause of cellulite and quercetin proves once again a valuable tool in the fight against cellulite, warranting it's use in anti-cellulite creams and also in nutritional supplements
- In addition quercetin has been found to boost the levels of irisin and PAI-1, which fight adipogenesis and fibrosis, respectively
- Quercetin Impacts Expression of Metabolism- and Obesity-Associated Genes in SGBS Adipocytes.
- Abstract: Obesity is characterized by the rapid expansion of visceral adipose tissue, resulting in a hypoxic environment in adipose tissue which leads to a profound change of gene expression in adipocytes. As a consequence, there is a dysregulation of metabolism and adipokine secretion in adipose tissue leading to the development of systemic inflammation and finally resulting in the onset of metabolic diseases. The flavonoid quercetin as well as other secondary plant metabolites also referred to as phytochemicals have anti-oxidant, anti-inflammatory, and anti-diabetic effects known to be protective in view of obesity-related-diseases. Nevertheless, its underlying molecular mechanism is still obscure and thus the focus of this study was to explore the influence of quercetin on human SGBS (Simpson Golabi Behmel Syndrome) adipocytes' gene expression. We revealed for the first time that quercetin significantly changed expression of adipokine (Angptl4, adipsin, irisin and PAI-1) and glycolysis-involved (ENO2, PFKP and PFKFB4) genes, and that this effect not only antagonized but in part even overcompensated the effect mediated by hypoxia in adipocytes. Thus, these results are explained by the recently proposed hypothesis that the protective effect of quercetin is not solely due to its free radical-scavenging activity but also to a direct effect on mitochondrial processes, and they demonstrate that quercetin might have the potential to counteract the development of obesity-associated complications.
- 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).