Quercetin

Nutrient group: vitaminoids, plant extracts & active ingredients

Sources

Dietary sources

The flavonoid quercetin belongs to the group of substances known as polyphenols and occurs in nature as a yellow plant pigment, usually as a glycoside (e.g. in the form of rutin). Particularly high contents are found in some apple varieties, onions, parsley, sage, ginkgo biloba, but also in buckwheat (tea), green tea, black tea, grapes, dark cherries and berries. Since quercetin is mainly found in the fruit skin, the content in red wine is higher than in white wine.

Detailed information

Quercetin - the "king of bioflavonoids"

As a secondary plant substance, quercetin has strong antioxidant properties and is considered the most effective antioxidant in the substance class of flavonoids. This would put quercetin even above the anthocyanins from grapes (OPC) and the catechins from green tea (1). It is these antioxidant capacities that make quercetin of interest for human health, as they act as an effective free radical scavenger in the human organism after absorption through the digestive tract (2). Since free radicals are closely linked to numerous pathological processes (e.g., inflammatory reactions) in the body, reducing the body's oxidative load may have a positive effect on health (3)(4). Basic experiments have found that quercetin probably positively affects the antioxidant system in several ways at once:

- Direct neutralization of free radicals, thus reducing the burden of oxidative stress.
- ability to bind reactive metal ions and thus prevent the formation of further oxygen radicals
- inhibition of oxidation of LDL and thus lipid peroxidation
- Stimulation of glutathione production and consequent improvement of the body's antioxidant defenses
- Stimulation of antioxidant enzymes to strengthen activity (1).

Quercetin acts as a vitamin saver

The bioflavonoid quercetin has an antioxidant effect on vitamin C, i.e., it recycles oxidized vitamin C and therefore acts as a "vitamin saver" and "vitamin enhancer" (5). In nature, quercetin occurs mostly as a glycoside. The most common source of quercetin is rutin, where it is glycosylated with the sugar rutinose. Due to their antioxidant abilities, bioflavonoids also have anticarcinogenic, immunostimulatory (6), and anti-edematous effects.

Quercetin for sports, injuries and inflammations

Quercetin, as an antioxidant, may also help optimize athletic performance and physical recovery. In a placebo-controlled human study of 48 healthy amateur triathletes, twice-daily supplementation with 250 mg of the branded raw material Quercefit® (equivalent to 200 mg of quercetin per day) after exercise such as swimming, cycling and running maintained the physical resistance of the athletes in a statistically significant manner. This affected performance, triathlon duration, recovery, stress such as muscle discomfort and post-exercise cramps. Furthermore, oxidative stress was also significantly lower in those athletes taking Quercefit® with optimal tolerability without side effects (7). In addition, adjuvant use of quercetin is useful for injuries, inflammation and pain conditions due to its anti-inflammatory and antioxidant effects. Quercetin also shows analgesic effects in animal studies (8).

Quercetin for protection against hyperglycemic damage

Quercetin protects nervous and liver tissues from hyperglycemic stress in metabolic syndrome. In animal studies, quercetinaben has been shown to reduce oxidative stress induced by hyperglycemia, as evidenced by decreased lipid peroxidation and increased antioxidant parameters. Quercetin can also reverse organosomatic changes in liver and nervous tissue, as well as positively affect osmotic stress induced by hyperglycemia (9).

Anti-inflammatory properties of quercetin

Scientists believe that the anti-inflammatory effect of quercetin is partly due to its antioxidant potential. The underlying mechanism appears to be the deactivation of cofactors necessary for the function of the enzymes 12-lipoxygenase and cyclooxygenase-1 (arachidonic acid metabolism) (2). In addition, there is also evidence for a direct anti-inflammatory effect of quercetin, because while luteolin, which is almost structurally identical to quercetin, has a weaker antioxidant capacity, its anti-inflammatory effect is not reduced. This was observed in an in vitro experiment using inhibition of the signaling substance leukotriene B4, which is a downstream product of 5-lipoxygenase (10). In numerous basic experiments, a decrease in the proinflammatory signaling substances TNF α and NF κB was observed after quercetin administration (11). Both substances are reciprocally influenced by each other and are deeply intertwined with arachidonic acid metabolism. Moreover, they require free radicals for signal transduction for several metabolic pathways (12)(13)(14)(15).

Quercetin and its mast cell stabilizing effect in allergies and asthma

Quercetin has potential in its action against the most common allergic complaints and can increase the well-being of allergy sufferers and sensitive individuals. The flavonoid is able to inhibit histamine production and release in mast cells. In addition, quercetin appears to prevent diverse signaling substances involved in the IgE-associated allergic immune response from being active (16). In a pilot randomized controlled clinical trial, supplementation with 250 mg or 500 mg of Quercefit® daily (equivalent to 100 mg or 200 mg of quercetin per day) in 58 patients with mild to moderate asthma and rhinitis over a 30-day period showed a reduced frequency of symptoms by up to 50% during the day and up to 70% at night. Furthermore, respiratory function (peak expiratory flow) improved significantly with the use of Quercefit®. In addition, compared to standard therapy, the symptoms of rhinitis and the use of nasal drops were significantly reduced. The reduction of free radicals in the blood by Quercefit®, which was also measured, was considered to be the cause (17). In this context, a 2012 study compared the efficacy of the pharmacological mast cell stabilizer cromoglicic acid with quercetin in an in vitro study. This showed that quercetin was more effective than cromoglicic acid in inhibiting the release of the cytokines IL-8 and TNF in cultured human mast cells, both of which are released from mast cells during an immune response. In addition, quercetin blocked the activation of the protein NF-kB (nuclear factor 'kappa-light-chain-enhancer' of activated B-cells) and the increase in cytosolic calcium levels (18).

Antiviral properties of quercetin

Clinical studies show that quercetin ingestion can alleviate the symptoms of respiratory diseases. The immunomodularotic and anti-inflammatory effects of quercetin are probably at least partially responsible for this effect (19)(20). In addition, quercetin has antiviral properties, which are achieved by stabilizing the transcription factor NRF2 (21). This leads to the stimulation of endogenous antioxidant and antiviral metabolic processes that counteract viral replication. By decreasing the activity of NRF2 with older age and in the presence of various metabolic diseases such as diabetes, quercetin support is particularly promising in these cases (22). Another antiviral mechanism is opened up by the ionophoric ("ion-carrying") properties of quercetin, which are discussed particularly in relation to the disease COVID-19. Basic experiments show that zinc ions can inhibit replication of the novel coronavirus. Quercetin provides transport of zinc ions into the cell as an ionophore (23).

Quercetin in COVID-19

Diverse constituents in plants have the ability to modulate inflammatory and immune responses in individuals with respiratory symptoms. In patients with early-stage COVID-19, the branded raw material Quercefit® proved beneficial. In a randomized controlled clinical trial of 152 COVID-19 patients, the half of participants who received 1000 mg of Quercefit® (equivalent to 400 mg of quercetin) daily for 30 days in addition to their standard treatment showed less frequent (-68%) and shorter (-77%) hospitalizations, less (-93%) need for noninvasive oxygen therapy, less frequent ICU transfers, and fewer deaths, with a very good safety profile (24). In another randomized controlled clinical trial of 42 COVID-19 patients, half of the patients were given 1000-1500 mg of Quercefit® (equivalent to 400-600 mg of quercetin per day) for two weeks in addition to standard treatment. This showed significantly increased viral control with -73% fewer infected at 1 week, 0 infected at 2 weeks and significantly reduced symptomatology. After 1 week, 57% of participants were fully recovered. Accordingly, from a statistical perspective, quercetin shortened the duration to negative molecular test while reducing symptom severity and negative predictors of COVID-19 (25).

The bioavailability of quercetin

Although quercetin is found in abundance in plant foods, there are two factors that complicate the natural supply of antioxidant quercetin through diet. First, the substance in plant foods largely degrades within a few weeks due to transport and storage time) (26). On the other hand, the forms of quercetin contained in plants often show significantly lower antioxidant activity. In this regard, one study showed that the quercetin in onion extract was only 2% in the form of the unglycosylated parent substance algycon-quercetin, while the majority consisted of a glycosylated form, which, however, had a significantly reduced antioxidant capacity (2). For this reason, foods are of limited suitability for the effective supply of quercetin. Standardized extracts, on the other hand, allow not only a more accurate, but above all a higher dosage of quercetin. Due to the poor solubility of quercetin in water and the associated limited bioavailability of the substance, quercetin uptake from food is additionally hampered. However, one trial showed that the absorption of quercetin could be increased by 32-45% if the preparation was taken with a breakfast containing 4-15 g of fat (27). The special presentation of quercetin in the form of the branded raw material Quercefit® is shown to be significantly more effective. This is a quercetin extract from the Japanese cord tree (Sophora japonica) complexed with sunflower lecithin, which increases its water solubility and enhances its bioavailability. Compared with a standard preparation, the phytosome form was absorbed about twenty times as well, which corresponds to an increase in bioavailability of 2000%. This was shown in twelve healthy volunteers taking 500 mg of normal quercetin or 250 mg or 500 mg of quercetin (28).

Indications

Effect	Indication	Dosage
Physiological effects at a low intake	For prevention of radically associated diabetic late effects such as neuropathies, retinopathies, nephropathies or diabetic foot with diabetes- mellitus- Diseases	25 - 50 mg/d
	For enzyme therapy at injuries & burns in the acute phase (such as sprains, strains, bruises and after surgery)	100 - 300 mg/d
	For acute inflammation, colds & influenza or sport injuries	100 - 300 mg/d
	To support the regeneration of antioxidant micronutrients	10 - 20 mg/d
	To optimize athletic performance and physical recovery	100 - 200 mg/d
	For allergies and asthma	100 - 200 mg/d
	For COVID-19	400 - 600 mg/d

Administration

General mode of administration
When	Quercetin should be taken between meals.
Side effects
There are no known side effects to date.
Contraindications
There are no known contraindications to date.

Interactions

Interactions with drugs (according to Gröber)
None	There are no relevant interactions known to date.
Nutrient interactions
Enzymes	Bromelain seems to improve the anti-inflammatory effect of quercetin.

References

1) Yang, D. et al. 2020. Quercetin: Its Main Pharmacological Activity and Potential Application in Clinical Medicine. Oxid Med Cell Longev. 2020:8825387.
2) Lesjak, M. et al. 2018. Antioxidant and anti-inflammatory activities of quercetin and its derivatives. J Funct Foods. 40:68–75.
3) de Lavor, É. M. et al. 2018. Essential Oils and Their Major Compounds in the Treatment of Chronic Inflammation: A Review of Antioxidant Potential in Preclinical Studies and Molecular Mechanisms. Oxid Med Cell Longev. 2018:6468593.
4) Sharma, G. N. et al. 2018. A Comprehensive Review of Free Radicals, Antioxidants, and Their Relationship with Human Ailments. Crit Rev Eukaryot Gene Expr. 28(2):139–154.
5) Gröber, U. 2008. Orthomolekulare Medizin. Ein Leitfaden für Apotheker und Ärzte.
6) Watzl, B., Leitzmann, C. 1999. Bioaktive Substanzen in Lebensmitteln.
7) Riva, A. et al. 2018. Quercetin Phytosome® in triathlon athletes: a pilot registry study. Minerva Med. 109(4):285–9.
8) Kelly, G. S. 2011. Quercetin. Monograph. Altern Med Rev. 16(2):172–94.
9) Ramana, B.V. et al. 2006. Effect of quercetin on galactose-induced hyperglycaemic oxidative stress in hepatic and neuronal tissues of Wistar rats. Acta Diabetol. 43(4):135–41.
10) Loke, W. M. et al. 2008. Metabolic transformation has a profound effect on anti-inflammatory activity of flavonoids such as quercetin: Lack of association between antioxidant and lipoxygenase inhibitory activity.Biochem Pharmacol. 75(5):1045–1053
11) Wang, W. et al. 2016. The biological activities, chemical stability, metabolism and delivery systems of quercetin: A review. Trends Food Sci Technol. 56:21–38.
12) Das, U. N. 2018. Arachidonic acid in health and disease with focus on hypertension and diabetes mellitus: A review. J Adv Res. 11:43–55.
13) Chen, S. 2011. Natural Products Triggering Biological Targets – A Review of the Anti-Inflammatory Phytochemicals Targeting the Arachidonic Acid Pathway in Allergy Asthma and Rheumatoid Arthritis. Curr Drug Targets. 12(3):288–301.
14) Korbecki, J. et al. 2013. The effect of reactive oxygen species on the synthesis of prostanoids from arachidonic acid. J Physiol Pharmacol. 64(4):409–421.
15) Li, Y. et al. 2016. Quercetin, Inflammation and Immunity. Nutrients. 8(3):167.
16) Mlcek, J. et al. 2016. Quercetin and Its Anti-Allergic Immune Response. Molecules. 21(5):623
17) Cesarone, M. R. et al. 2019. Supplementary prevention and management of asthma with quercetin phytosome: a pilot registry. Minerva Med. 110(6):524–9.
18) Weng, Z. et al. 2012. Quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans. PLoS One. 7(3):e33805.
19) Di Pierro, F. et al. 2021. Possible Therapeutic Effects of Adjuvant Quercetin Supplementation Against Early-Stage COVID-19 Infection: A Prospective, Randomized, Controlled, and Open-Label Study. Int J Gen Med. 14:2359–2366.
20) Heinz, S. A. et al. 2010. Quercetin supplementation and upper respiratory tract infection: A randomized community clinical trial. Pharmacol Res. 62(3):237–242.
21) Manjunath, S. H., Thimmulappa, R. K. 2022. Antiviral, immunomodulatory, and anticoagulant effects of quercetin and its derivatives: Potential role in prevention and management of COVID-19. J Pharm Anal. 12(1):29–34.
22) Cuadrado, A. et al. 2020. Can Activation of NRF2 Be a Strategy against COVID-19? Trends Pharmacol Sci. 41(9):598–610.
23) Saakre, M. et al. 2021. Perspectives on plant flavonoid quercetin-based drugs for novel SARS-CoV-2. Beni Suef Univ J Basic Appl Sci. 10(1):21.
24) Di Pierro, F. et al. 2021. Possible Therapeutic Effects of Adjuvant Quercetin Supplementation Against Early-Stage COVID-19 Infection: A Prospective, Randomized, Controlled, and Open-Label Study. Int J Gen Med. 14:2359–66.
25) Di Pierro, F. et al. 2021. Potential Clinical Benefits of Quercetin in the Early Stage of COVID-19: Results of a Second, Pilot, Randomized, Controlled and Open-Label Clinical Trial. Int J Gen Med. 14:2807–16.
26) Wang, W. et al. 2016. The biological activities, chemical stability, metabolism and delivery systems of quercetin: A review. Trends Food Sci Technol. 56:21–38.
27) (21) Guo, Y. et al. 2013. Dietary fat increases quercetin bioavailability in overweight adults. Mol Nutr Food Res. 57(5):896–905.
28) Riva, A. et al. 2019. Improved Oral Absorption of Quercetin from Quercetin Phytosome®, a New Delivery System Based on Food Grade Lecithin. Eur J Drug Metab Pharmacokinet. 44(2):169–177.

References interactions
Stargrove, M. B. et al. Herb, Nutrient and Drug Interactions: Clinical Implications and Therapeutic Strategies, 1. Auflage. St. Louis, Missouri: Elsevier Health Sciences, 2008.
Gröber, U. Mikronährstoffe: Metabolic Tuning –Prävention –Therapie, 3. Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2011.
Gröber, U. Arzneimittel und Mikronährstoffe: Medikationsorientierte Supplementierung, 3. aktualisierte und erweiterte Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2014.