Quercetin: Difference between revisions

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In plants, quercetin serves as a protective substance, defending against microbial infections and environmental stress. For humans, it’s predominantly obtained through the consumption of foods such as onions, apples, berries, and teas. Its biological roles in human health are vast, with studies suggesting benefits ranging from anti-aging and anti-inflammatory effects to potential protective roles against various diseases.
In plants, quercetin serves as a protective substance, defending against microbial infections and environmental stress. For humans, it’s predominantly obtained through the consumption of foods such as onions, apples, berries, and teas. Its biological roles in human health are vast, with studies suggesting benefits ranging from anti-aging and anti-inflammatory effects to potential protective roles against various diseases.


== Chemical and Physical Properties ==
== Natural Occurrence and Derivatives==
 
'''Quercetin''' is naturally found in various plants, primarily as glycosides, where the quercetin molecule is bound to a sugar molecule, enhancing its solubility and transport within the plant. These glycosides are metabolized to free quercetin in the human digestive system when consumed through the diet. Notable sources of quercetin include onions, apples, berries, and tea, among others. The presence of quercetin in these forms in plants underscores its relevance in plant physiology, particularly in providing protection against oxidative stress and contributing to the pigmentation in plant tissues.
 
Quercetin is one of the most abundant dietary flavonoids,<ref name="lpi">{{cite web|url=http://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/flavonoids|title=Flavonoids|publisher=Micronutrient Information Center, Linus Pauling Institute, Oregon State University, Corvallis, OR|date=November 2015|access-date=1 April 2018}}</ref><ref name="usda">{{cite web|url=http://www.ars.usda.gov/SP2UserFiles/Place/12354500/Data/Flav/Flav_R03.pdf|title=USDA Database for the Flavonoid Content of Selected Foods, Release 3|year=2011|publisher=U.S. Department of Agriculture}}</ref> with an average daily consumption of 25–50 [[wikipedia:Milligram|milligrams]].<ref name="pmid8847003">{{cite journal|vauthors=Formica JV, Regelson W|title=Review of the biology of quercetin and related bioflavonoids|journal=Food and Chemical Toxicology|volume=33|issue=12|pages=1061–80|year=1995|pmid=8847003|doi=10.1016/0278-6915(95)00077-1}}</ref>
{| class="wikitable sortable"
!Foods
! data-sort-type="number" |Quercetin,
mg / 100 g
|-
|[[wikipedia:Capers|capers]], raw
|234<ref name="usda" />
|-
|[[wikipedia:Capers|capers]], canned
|173<ref name="usda" />
|-
|[[wikipedia:Lovage|lovage]] leaves, raw
|170<ref name="usda" />
|-
|[[wikipedia:Rumex|dock]] like [[wikipedia:Sorrel|sorrel]]
|86<ref name="usda" />
|-
|[[wikipedia:Radish|radish]] leaves
|70<ref name="usda" />
|-
|[[wikipedia:Carob|carob]] fiber
|58<ref name="usda" />
|-
|[[wikipedia:Dill|dill]] weed, fresh
|55<ref name="usda" />
|-
|[[wikipedia:Coriander|coriander]]
|53<ref name="usda" />
|-
|[[wikipedia:Hungarian_wax_pepper|yellow wax pepper]], raw
|51<ref name="usda" />
|-
|[[wikipedia:Fennel|fennel]] leaves
|49<ref name="usda" />
|-
|[[wikipedia:Red_onion|onion, red]]
|32<ref name="usda" />
|-
|[[wikipedia:Radicchio|radicchio]]
|32<ref name="usda" />
|-
|[[wikipedia:Watercress|watercress]]
|30<ref name="usda" />
|-
|[[wikipedia:Kale|kale]]
|23<ref name="usda" />
|-
|[[wikipedia:Chokeberry|chokeberry]]
|19<ref name="usda" />
|-
|[[wikipedia:Vaccinium_uliginosum|bog blueberry]]
|18<ref name="usda" />
|-
|[[wikipedia:Buckwheat|buckwheat]] seeds
|15<ref name="usda" />
|-
|[[wikipedia:Cranberry|cranberry]]
|15<ref name="usda" />
|-
|[[wikipedia:Lingonberry|lingonberry]]
|13<ref name="usda" />
|-
|[[wikipedia:Black_plum|plums, black]]
|12<ref name="usda" />
|-
|}
<ref name="pmid21229237">{{cite journal|vauthors=Petrus K, Schwartz H, Sontag G|title=Analysis of flavonoids in honey by HPLC coupled with coulometric electrode array detection and electrospray ionization mass spectrometry|journal=Analytical and Bioanalytical Chemistry|volume=400|issue=8|pages=2555–63|date=Jun 2011|pmid=21229237|doi=10.1007/s00216-010-4614-7|s2cid=24796542}}</ref>
 
In red onions, higher concentrations of quercetin occur in the outermost rings and in the part closest to the root, the latter being the part of the plant with the highest concentration.<ref>{{cite journal|vauthors=Slimestad R, Fossen T, Vågen IM|title=Onions: a source of unique dietary flavonoids|journal=Journal of Agricultural and Food Chemistry|volume=55|issue=25|pages=10067–80|date=December 2007|pmid=17997520|doi=10.1021/jf0712503}}</ref> One study found that [[wikipedia:Organic_farming|organically grown]] [[wikipedia:Tomato|tomatoes]] had 79% more quercetin than non-organically grown fruit.<ref name="pmid17590007">{{cite journal|vauthors=Mitchell AE, Hong YJ, Koh E, Barrett DM, Bryant DE, Denison RF, Kaffka S|title=Ten-year comparison of the influence of organic and conventional crop management practices on the content of flavonoids in tomatoes|journal=Journal of Agricultural and Food Chemistry|volume=55|issue=15|pages=6154–9|date=Jul 2007|pmid=17590007|doi=10.1021/jf070344+}}</ref> Quercetin is present in various kinds of [[wikipedia:Honey|honey]] from different plant sources.
== Chemical and Physical Properties==


'''Quercetin''' possesses distinct chemical and physical properties, integral to its bioactivity and its interaction within biological systems.
'''Quercetin''' possesses distinct chemical and physical properties, integral to its bioactivity and its interaction within biological systems.


* '''Molecular Structure:''' Quercetin has a molecular formula of C<sub>15</sub>H<sub>10</sub>O<sub>7</sub> and is composed of two phenyl rings (A and B) bonded to a heterocyclic ring (C) containing one oxygen atom, forming a structure typical of flavonoids. Its full chemical name is 3,3',4',5,7-pentahydroxyflavone.
*'''Molecular Structure:''' Quercetin has a molecular formula of C<sub>15</sub>H<sub>10</sub>O<sub>7</sub> and is composed of two phenyl rings (A and B) bonded to a heterocyclic ring (C) containing one oxygen atom, forming a structure typical of flavonoids. Its full chemical name is 3,3',4',5,7-pentahydroxyflavone.
 
*'''Solubility and Stability:''' Quercetin has limited solubility in water but is soluble in organic solvents like ethanol. It is relatively stable in acidic conditions but is susceptible to degradation in basic conditions and under exposure to light and heat. Its stability is crucial for its absorption and bioavailability, as well as its effectiveness in various formulations.


* '''Solubility and Stability:''' Quercetin has limited solubility in water but is soluble in organic solvents like ethanol. It is relatively stable in acidic conditions but is susceptible to degradation in basic conditions and under exposure to light and heat. Its stability is crucial for its absorption and bioavailability, as well as its effectiveness in various formulations.
*'''Molecular Weight:''' The molecular weight of quercetin is approximately 302.24 g/mol, a factor that influences its distribution and metabolism within the body.


* '''Molecular Weight:''' The molecular weight of quercetin is approximately 302.24 g/mol, a factor that influences its distribution and metabolism within the body.


== Pharmacological Properties ==
==Pharmacological Properties==


The pharmacological properties of '''Quercetin''' have sparked extensive research due to its potential therapeutic applications. Here we explore its absorption, metabolism, elimination, and mode of action within the body.
The pharmacological properties of '''Quercetin''' have sparked extensive research due to its potential therapeutic applications. Here we explore its absorption, metabolism, elimination, and mode of action within the body.


=== Absorption and Bioavailability ===
===Absorption and Bioavailability===
Quercetin's bioavailability is complex, influenced largely by its poor water solubility, which results in low absorption and extensive metabolism, hence reducing its availability to exert biological effects. It is predominantly found in foods as glycosides, bound to sugar molecules, which impacts its absorption and subsequent bioavailability.
Quercetin's bioavailability is complex, influenced largely by its poor water solubility, which results in low absorption and extensive metabolism, hence reducing its availability to exert biological effects. It is predominantly found in foods as glycosides, bound to sugar molecules, which impacts its absorption and subsequent bioavailability.


Quercetin, when consumed, undergoes an absorption process primarily in the small intestine. The glycosidic form of quercetin needs to be hydrolyzed by β-glucosidase to its aglycone form before absorption. Once hydrolyzed, it is absorbed through enterocytes via passive diffusion or through active transport mechanisms. The overall absorption of quercetin is estimated to be relatively low, varying between individuals and dependent on dietary matrix and presence of other flavonoids.
Quercetin, when consumed, undergoes an absorption process primarily in the small intestine. The glycosidic form of quercetin needs to be hydrolyzed by β-glucosidase to its aglycone form before absorption. Once hydrolyzed, it is absorbed through enterocytes via passive diffusion or through active transport mechanisms. The overall absorption of quercetin is estimated to be relatively low, varying between individuals and dependent on dietary matrix and presence of other flavonoids.


=== '''Enhancing Bioavailability''' ===
==='''Enhancing Bioavailability'''===
Due to inherent limitations in bioavailability, several strategies have been explored to enhance the absorption and stability of quercetin. These include the development of various formulations and delivery systems such as:
Due to inherent limitations in bioavailability, several strategies have been explored to enhance the absorption and stability of quercetin. These include the development of various formulations and delivery systems such as:


{| class="wikitable"
{| class="wikitable"
|-
|-
!Formulation!!Alternative Names!!Enhancement in Bioavailability!!Notes
!Formulation!!Alternative Names !!Enhancement in Bioavailability!! Notes
|-
|-
|Quercetin Phytosomes|| Quercetin-Phospholipid||Up to 20 times ||Significantly increases oral bioavailability compared to unformulated quercetin.
|Quercetin Phytosomes||Quercetin-Phospholipid||Up to 20 times||Significantly increases oral bioavailability compared to unformulated quercetin.
|-
|-
|Nanoparticle Formulations||Nanoquercetin, Quercetin Nanocapsules|| Several-fold increase||Includes liposomal encapsulations; increased solubility and cellular uptake.
|Nanoparticle Formulations||Nanoquercetin, Quercetin Nanocapsules||Several-fold increase||Includes liposomal encapsulations; increased solubility and cellular uptake.
|-
|-
|Complexation with Cyclodextrins|| Quercetin-β-Cyclodextrin Complex||Up to 10 times||Improves water solubility significantly, enhancing therapeutic effects.
|Complexation with Cyclodextrins||Quercetin-β-Cyclodextrin Complex||Up to 10 times||Improves water solubility significantly, enhancing therapeutic effects.
|-
|-
|Co-administration with Piperine||Bioavailability Enhanced Quercetin, Piperine-Quercetin Combination||Approximately 20%||Inhibits metabolism of quercetin, improving its bioavailability.
|Co-administration with Piperine||Bioavailability Enhanced Quercetin, Piperine-Quercetin Combination||Approximately 20%|| Inhibits metabolism of quercetin, improving its bioavailability.
|}
|}


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Once absorbed, quercetin undergoes extensive first-pass metabolism in the liver and intestines, where it is converted into various metabolites through glucuronidation, sulfation, and methylation. The extensive metabolism significantly reduces the concentrations of free quercetin in the plasma, limiting its bioavailability. The metabolites, however, may retain some biological activity and contribute to the overall effects of quercetin in the body.
Once absorbed, quercetin undergoes extensive first-pass metabolism in the liver and intestines, where it is converted into various metabolites through glucuronidation, sulfation, and methylation. The extensive metabolism significantly reduces the concentrations of free quercetin in the plasma, limiting its bioavailability. The metabolites, however, may retain some biological activity and contribute to the overall effects of quercetin in the body.


=== Implications of Low Bioavailability===
===Implications of Low Bioavailability===
The low bioavailability of quercetin raises questions about the clinical relevance of its potential health benefits observed in vitro and in animal studies. It necessitates the need for effective delivery systems and formulations to realize its therapeutic potential in humans. Additionally, understanding the biological activities of its metabolites is crucial, as they are the predominant forms present in systemic circulation.
The low bioavailability of quercetin raises questions about the clinical relevance of its potential health benefits observed in vitro and in animal studies. It necessitates the need for effective delivery systems and formulations to realize its therapeutic potential in humans. Additionally, understanding the biological activities of its metabolites is crucial, as they are the predominant forms present in systemic circulation.


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The antioxidant activity of quercetin is attributed to its ability to neutralize free radicals and reduce oxidative stress, potentially mitigating aging-related cellular damage and dysfunction. Its antioxidant properties are linked to a reduction in the risk of chronic conditions such as cancer and neurodegenerative diseases.
The antioxidant activity of quercetin is attributed to its ability to neutralize free radicals and reduce oxidative stress, potentially mitigating aging-related cellular damage and dysfunction. Its antioxidant properties are linked to a reduction in the risk of chronic conditions such as cancer and neurodegenerative diseases.


===Impact on Cellular Senescence===
===Impact on Cellular Senescence ===
Research has indicated that quercetin may delay cellular senescence by modulating senescence-associated signaling pathways and reducing the accumulation of senescent cells, potentially impacting aging processes and age-related diseases.
Research has indicated that quercetin may delay cellular senescence by modulating senescence-associated signaling pathways and reducing the accumulation of senescent cells, potentially impacting aging processes and age-related diseases.


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Several clinical trials and studies have been conducted to assess the safety and efficacy of quercetin supplementation in age-related conditions. The data, however, are still inconclusive, necessitating further well-designed studies to establish its therapeutic benefits in aging and longevity comprehensively.
Several clinical trials and studies have been conducted to assess the safety and efficacy of quercetin supplementation in age-related conditions. The data, however, are still inconclusive, necessitating further well-designed studies to establish its therapeutic benefits in aging and longevity comprehensively.


===Role as an NAD+ Booster===
=== Role as an NAD+ Booster===
Quercetin has been identified as a potential NAD+ booster, which is significant as NAD+ is a crucial coenzyme involved in numerous biological processes, including energy metabolism, DNA repair, and aging. The depletion of NAD+ is associated with aging and several age-related diseases.
Quercetin has been identified as a potential NAD+ booster, which is significant as NAD+ is a crucial coenzyme involved in numerous biological processes, including energy metabolism, DNA repair, and aging. The depletion of NAD+ is associated with aging and several age-related diseases.


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Exploring the optimal dosage and various administration forms is crucial for leveraging the potential benefits of '''Quercetin'''. Given the variances in individual responses and bioavailability, establishing the right dosage is paramount.
Exploring the optimal dosage and various administration forms is crucial for leveraging the potential benefits of '''Quercetin'''. Given the variances in individual responses and bioavailability, establishing the right dosage is paramount.


=== Recommended Dosages===
===Recommended Dosages===
Typical supplemental dosages of quercetin range from 500 to 1000 mg per day, usually divided into multiple doses. However, optimal dosages may vary based on individual health conditions, goals, and sensitivities, and consultation with a healthcare provider is advised for personalized recommendations.
Typical supplemental dosages of quercetin range from 500 to 1000 mg per day, usually divided into multiple doses. However, optimal dosages may vary based on individual health conditions, goals, and sensitivities, and consultation with a healthcare provider is advised for personalized recommendations.


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In some individuals, quercetin supplementation can lead to side effects such as headaches, stomach pain, and tingling of the extremities. Rarely, it may cause kidney damage at high doses.
In some individuals, quercetin supplementation can lead to side effects such as headaches, stomach pain, and tingling of the extremities. Rarely, it may cause kidney damage at high doses.


=== Interactions with Medications and Other Supplements===
===Interactions with Medications and Other Supplements===
Quercetin has the potential to interact with various medications, including antibiotics and blood pressure medications, potentially altering their effects. Additionally, its interaction with other supplements, particularly those with similar biological effects, needs careful consideration to avoid cumulative effects or imbalances.
Quercetin has the potential to interact with various medications, including antibiotics and blood pressure medications, potentially altering their effects. Additionally, its interaction with other supplements, particularly those with similar biological effects, needs careful consideration to avoid cumulative effects or imbalances.


===Safety Precautions and Contraindications===
=== Safety Precautions and Contraindications===
Individuals with kidney conditions, pregnant or breastfeeding women, and those on specific medications should consult healthcare providers before starting quercetin supplementation. Proper dosage and adherence to safety precautions are crucial to minimize the risk of adverse reactions.
Individuals with kidney conditions, pregnant or breastfeeding women, and those on specific medications should consult healthcare providers before starting quercetin supplementation. Proper dosage and adherence to safety precautions are crucial to minimize the risk of adverse reactions.


==Conclusions and Future Directions ==
==Conclusions and Future Directions==


'''Quercetin''' has garnered substantial attention in the realm of longevity and health due to its multifaceted biological activities, including antioxidant, anti-inflammatory, and potential anti-aging properties.
'''Quercetin''' has garnered substantial attention in the realm of longevity and health due to its multifaceted biological activities, including antioxidant, anti-inflammatory, and potential anti-aging properties.


===Summary of Key Findings===
=== Summary of Key Findings===
Quercetin’s diverse pharmacological properties, such as modulation of inflammatory pathways, neutralization of free radicals, and potential impact on cellular senescence, offer promising avenues for addressing age-related conditions and promoting health and longevity. However, the conclusive benefits and optimal dosages in humans are yet to be firmly established.
Quercetin’s diverse pharmacological properties, such as modulation of inflammatory pathways, neutralization of free radicals, and potential impact on cellular senescence, offer promising avenues for addressing age-related conditions and promoting health and longevity. However, the conclusive benefits and optimal dosages in humans are yet to be firmly established.


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While quercetin’s therapeutic potential is evident from preclinical and some clinical studies, significant gaps persist in our understanding of its precise mechanisms of action, long-term safety, and efficacy in humans. Further well-designed clinical trials and comprehensive studies are imperative to bridge these gaps and validate quercetin's roles in human health and longevity.
While quercetin’s therapeutic potential is evident from preclinical and some clinical studies, significant gaps persist in our understanding of its precise mechanisms of action, long-term safety, and efficacy in humans. Further well-designed clinical trials and comprehensive studies are imperative to bridge these gaps and validate quercetin's roles in human health and longevity.


===Future Directions and Potential Implications===
=== Future Directions and Potential Implications===
The ongoing and future research on quercetin is poised to explore novel formulations and delivery methods to improve its bioavailability and therapeutic efficacy. The elucidation of its molecular targets and mechanisms will facilitate the development of targeted interventions for age-related diseases and conditions, potentially impacting healthcare approaches and strategies for healthy aging.
The ongoing and future research on quercetin is poised to explore novel formulations and delivery methods to improve its bioavailability and therapeutic efficacy. The elucidation of its molecular targets and mechanisms will facilitate the development of targeted interventions for age-related diseases and conditions, potentially impacting healthcare approaches and strategies for healthy aging.


Quercetin remains a compelling subject in the longevity and health science field, with its future promising to unveil deeper insights into its biological activities and therapeutic potentials, possibly leading to innovative solutions for aging and age-associated ailments.
Quercetin remains a compelling subject in the longevity and health science field, with its future promising to unveil deeper insights into its biological activities and therapeutic potentials, possibly leading to innovative solutions for aging and age-associated ailments.