Quercetin

Summary (The Good, The Bad, and all other Essential Benefits/Effects/Facts Information)

Quercetin is a Bioflavonoids found in fruits and vegetables, but highest levels are found in apples and onions.

Like many other bioflavonoids, Quercetin has anti-oxidant, anti-artherogenic, and anti-carcinogenic properties. Quercetin is also neuroactive, with some of the same abilities as Caffeine but less potent.

There is a divide between the effects seen in quercetin in in vitro (cell cultured) studies and in vivo (in living) studies, with cell studies showing great results that are not that amazing in humans or animals. This is mostly due to quercetin having low oral bioavailability (low percentage of the compound is absorbed and put to use), but could also be due to in vitro studies using a form of quercetin called 'quercetin aglycone' whereas this particular form is never found in the blood, even after ingested, as it it gets changed in the liver.

Many studies also note a high range of differences between people who ingest the same amount of quercetin, suggesting a large degree of variability is possible with supplementation.

Quercetin has GRAS (Generally Recognized As Safe) status, and no side-effects have yet been noted in doses of a few grams a day in either humans or animals.

Also Known As

Apple extract, 3,4,5,7-pentahydroxylflavone

Is a Form of

• Bioflavonoids
• Health Support

Goes Well With

• Other Bioflavonoids such as Genistein and Resveratrol, due to AMPK activation (in the cell) or by increasing bioavailability (in the gut)

• Green Tea due to catechol-o-methyl transferase inhibition, and increasing bioavailability of Green Tea Catechins

• Apigenin in regards to reducing Aromatase transcription

How to Take (recommended dosage, active amounts, other details)

Dosages of quercetin used are in the range of 12.5 to 25mg per kg body weight, which translates to a range of 1,136-2,272mg daily consumption of quercetin when in isolation.

It is suggested to supplement with other Bioflavonoids such as Resveratrol, Genistein, or Green Tea Catechins to increase the potency synergistically and theoretically get the benefits at a reduced level of intake.

When looking for quercetin, the form of dihydrate has the apparent best bioavailability followed by glycosides, aglycone, and finally rutinoside.

Things to Note

• Quercetin can block adenosine receptors. In the brain this would induce wakefulness (although transport is an issue) and in systemic may be a fat burning augmenter.

• Quercetin is highly water-soluble

• Quercetin is yellow colored

Caution Notice (just some FYI - if needed)

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Detailed Summary

1. Sources and Structure
   1. Sources
2. Pharmacology
   1. Absorption and the Intestines
   2. Hepatic (Liver)
   3. Circulating Quercetin
   4. Neurology
3. Notable Enzymatic/Receptor Interactions
4. Effects on Neurology and Neuroprotection
5. Effects on Exercise Performance
6. Interactions with Hormones
   1. Testosterone
7. Nutrient-Nutrient and Nutrient-Drug Interactions
   1. Yerba Mate

Edit1. Sources and Structure

1.1. Sources

Quercetin is one of the most prominent bioflavonoid compounds in plants, being found in:

• Euonymus alatus, 23mg per 20g ethanol extract^[1][2]

• Lagerstroemia^[3]

• Nelumbo Nucifera^[4]

• Tilia Americana var. Mexicana^[5]

• Onions^[6] and Wine/Grapes^[7]

• Myrica Rubra^[8]

• Ginkgo Biloba^[9]

Edit2. Pharmacology

2.1. Absorption and the Intestines

After oral ingestion of quercetin, it is taken up from the gut into the liver. The conjugate of quercetin influences its absorption rates. At least intestinally, quercetin glycosides (food source) were found to have a 52+/-15% uptake, quercetin rutinoside (tea) has a 17+/-15% uptake, and supplemental quercetin aglycone had a 24+/-9% uptake.^[10]

Quercetin is a potent inhibitor of intestinal sulfurotransferases, and has some activity on hepatic sulfurotransferases as well.^[11] This mechanism may increase bioavailability of compounds that undergo extensive intestinal metabolism via this method, like Resveratrol.^[12]

2.2. Hepatic (Liver)

After the liver, quercetin exists in the blood solely as quercetin glucuronides.^[13] Regardless of initial source, all forms of quercetin undergo hydrolysis and get glucuronidated in the liver before being released into systemic circulation.

2.3. Circulating Quercetin

Quercetin has been measured in the blood 15-30 minutes after ingestion of 250-500mg, with peak levels 120-180 minutes after ingestion and returns to baseline levels in humans 24 hours after ingestion. Additional ingestion of quercetin dose-dependently increases plasma quercetin glucoronides.^[14] Accumulation of quercetin has been noted in many tissues including kidneys, colon, liver, brain, lung and muscle.

Systemically, resting quercetin levels are highly variable. The previous study noted resting quercetin levels (from food intake) ranging from 30-163uM/L. After supplementation of 50,100,and 150mg quercetin dihydrate serum ranges increased to 95.9-255, 164-497, and 240-1292 respectively. These concentrations are much larger than neural concentrations.^[15]

However, those are general ideas as quercetin bioavailability seems contradictory in many studies, possibly due to large differences between individuals and quercetin supplementation^[16]

2.4. Neurology

In pigs, feeding of quercetin aglycone at 50mg/kg BW increased neurological concentrations to 0.02uM,^[17] while another study noted levels of 0.22uM with a dosage of 500mg/kg BW.^[18]

Quercetin is a highly polar (water-soluble) compound, but seems to be able to cross models of the blood brain barrier.^[19][20] Mixed onion flavanoids (of which Quercetin comprises a large amount) appear to have around a 60% efficacy in crossing the BBB.^[21]

Edit3. Notable Enzymatic/Receptor Interactions

Like some other Bioflavonoids, quercetin has the ability to inhibit the xanthine oxidase enzyme^[22]

Quercetin, like Caffeine, is also an adenosine receptor antagonist^[23] although at a dose equivalent to 200mg caffeine quercetin failed to have caffeine like effects.

Quercetin has its antioxidant potential reduced via the enzyme catechol-o-methyl transferase^[24] which is strongly inhibited by Green Tea Catechins.

Edit4. Effects on Neurology and Neuroprotection

In vitro studies at 25-100uM show that quercetin is able to protect PC-12 neurons from oxidative stress induces from toxins and peroxides^[25][26] as well as inhibiting formation of beta-amyloid pigmentation.^[27] Protective effects against some ROS has been reported as low as 0.5uM of quercetin-3-glucuronide, which may be the only effects notable with basic quercetin supplementation due to low oral bioavailability and brain concentrations.^[28]

On the other side of things, quercetin can be a potential neurotoxic substance in supraphysiological levels. Quercetin has been noted in some studied to initially protect the neuron and later act as a toxin in in vitro studies.^[29] Quercetin seems to, in pure in vitro neuronal cultures, to induce toxicity at a concentration of 1-10uM^[30] but is protected to a degree in vivo by metabolization by glial cells around neurons.^[31] Inducing supraphysiological concentrations of quercetin in the range of 30uM-100uM in cultures with glia cells shows no signs of toxicity and increased survivial of neurons, however the effectiveness of the quercetin per unit is reduced by the protecting metabolization.^[32][33]

In regards to neuroinflammation, quercetin is able to act as an anti-inflammatory in the brain (and thus protectant of Alzheimers and Parkinsons, of which inflammation is an exacerbating factor) by increasing heme-oxygenase-1 expression which suppresses nitric oxide release induced from an inflammation response at concentrations as low as 10uM.^[34][35] Suppression of other pro-inflammatory markers, TNF-alpha and IL-1alpha, occurred with quercetin (and resveratrol) at concentrations as low as 0.1uM.^[36]

Edit5. Effects on Exercise Performance

Effects on exercise performance look promising on a molecular level, but studies done on an applicative level are mixed.

Quercetin has been found to increase cardiovascular performance in untrained men compared to a placebo dosed at 500mg twice a day^[37] and mice studies note positive effects on exercise performance and mitochondrial biogenesis at doses between 12.5 and 25mg/kg BW.^[38] Quercetin has also been noted to increase exercise output in trained cyclists at 300mg, but was studied in conjunction with Green Tea Catechins (300mg) and caffeine(45mg) along many vitamins.^[39]

In the above study, the catechins and anti-oxidants alone increased performance but the addition of quercetin added to said increase. This may be due to possible synergism between many Bioflavonoids compounds (of which Green Tea Catechins are a subset).

On the negative side of things, quercetin failed to increase performance in repeated sprint intervals when dosed at 1000mg/day (in 2 doses) of quercetin-3-glucoside^[22] and did not increase performance time trials on an erg bike at an acute dose of 2g^[40]

So although the effects of Quercetin on exercise performance look promising, there is not enough conclusive evidence to state whether supplementation will increase performance.

Edit6. Interactions with Hormones

6.1. Testosterone

Quercetin, at 20mg/kg bodyweight, can prevent testicular damage from Dioxins and thus prevent a decline in testosterone levels;^[41] the mechanism seems to be through being an anti-oxidant present in the testes^[42] as it is the same mechanism by which quercetin protects the kidneys from Dioxins.^[43] Quercetin may also protect against physical injuries, as evidenced by rotating rat testicles 720 degrees clockwise.^[44]

Quercetin can increase aromatase activity 4x at a concentration of 100uM,^[45] but possesses inhibitory actions at a lower dosage (0.026uM).^[46] It shows some suppressive effects on mRNA transcription of aromatase in the corpus luteum^[47] and in a seemingly dose dependent manner, with 10uM being more potent than 100nM. Quercetin shows synergism with Apigenin in this regard.^[47] In intestinal cells, they do not influence mRNA levels but induce aromatase activity.^[48]

Using onion juice, a good source of Quercetin, testosterone levels can increase in rats after 4g/kg bodyweight daily for 20 days.^[49]

Edit7. Nutrient-Nutrient and Nutrient-Drug Interactions

7.1. Yerba Mate

Yerba Mate is a form of tea with a caffine content and a relatively unique blend of polyphenolic compounds. The saponin content of Yerba Mate synergistically works with Quercetin to suppress inflammation via NO and PGE(2).^[50]

Scientific Support & Reference Citations

The multiple faces of quercetin in neuroprotection

References

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2. Jeong EJ, et al. Inhibitory constituents of Euonymus alatus leaves and twigs on nitric oxide production in BV2 microglia cells. Food Chem Toxicol. (2011)
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4. Goo HR, Choi JS, Na DH. Simultaneous determination of quercetin and its glycosides from the leaves of Nelumbo nucifera by reversed-phase high-performance liquid chromatography. Arch Pharm Res. (2009)
5. Aguirre-Hernández E, et al. HPLC/MS analysis and anxiolytic-like effect of quercetin and kaempferol flavonoids from Tilia americana var. mexicana. J Ethnopharmacol. (2010)
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25. Protective Effects of Quercetin and Vitamin C against Oxidative Stress-Induced Neurodegeneration
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Last Updated: Apr 6, 2012 07:35:37