Quercetin supplement benefits and side effects, drug interactions, influence on allergy

Quercetin is one of the most abundant natural flavonoids. It is one of a broad group of natural polyphenolic flavonoid substances that are being investigated for their widespread health benefits. These benefits are most likely due to its combination of anti-oxidant and anti-inflammatory activity, but recent in vitro evidence suggests that improved mitochondrial biogenesis could play an important role.

Quercetin in foods, dietary intake
Quercetin is one of the most prominent dietary antioxidants. It is widely present in foods including vegetables, fruit, tea and wine as well as countless food supplements. It is abundant in apples and onions.

Dietary supplements over the counter
There are a number of nutritional supplement companies that sell quercetin, some by itself, others combined with bromelain, vitamin C, or other nutrients.

Quercetin 500 mg per 2 capsules (Dimorphandra mollis) (fruit). It is not clear from the supplement fact panel of this product whether it has 500 mg of quercetin per two capsules or whether it has 500 mg of the fruit with some of it being quercetin.
500 mg, 120 capsules
500 mg 60 tablets.

Health benefit
Quercetin, a member of the bioflavonoids family, has anti-inflammatory, anti-atherogenic, and anti-hypertensive properties leading to the beneficial effects against cardiovascular diseases. Epidemiological studies report that this antioxidant flavonol found in apples, berries, and onions, is associated with reduced risk of coronary heart disease and stroke.

Athletic competition
Quercetin does not appear to provide much of a benefit in athletic competition.

Oral quercetin supplementation and blood oxidative capacity in response to ultramarathon competition.
Int J Sport Nutr Exerc Metab. 2008; Quindry JC, Hosick P, Dumke C, McAnulty LS, Henson D, Morrow JD, Nieman D. Dept. of Health, Leisure, and Exercise Science, Appalachian State University, Boone, NC, USA.
Previous research indicates that ultramarathon exercise can result in blood oxidative stress. The purpose of this investigation was to examine the efficacy of oral supplementation with quercetin, a naturally occurring compound with known antioxidant properties, as a potential countermeasure against blood oxidative stress during an ultramarathon competition. In double-blind fashion, 63 participants received either oral quercetin (250 mg, 4x/day; 1,000 mg/day total) or quercetin-free supplements 3 weeks before and during the 160-km Western States Endurance Run. Quercetin supplementation did not affect race performance. In response to the ultramarathon challenge, aqueous-phase antioxidant capacity (ferric-reducing ability of plasma) was similarly elevated in athletes in both quercetin and quercetin-free treatments and likely reflects significant increases in plasma urate levels. Alternatively, trolox-equivalent antioxidant capacity was not altered by exercise or quercetin. Our findings suggest that oral quercetin supplementation does not alter blood plasma lipid or aqueous-phase antioxidant capacity or oxidative damage during an ultramarathon challenge.

Blood pressure
Those with hypertension may consider adding quercetin supplements to their regimen.

Quercetin reduces blood pressure in hypertensive subjects.
J Nutr. 2007. Edwards RL, Lyon T, Litwin SE, Rabovsky A. Division of Nutrition, University of Utah, Salt Lake City, UT, USA.
Quercetin supplementation reduces blood pressure in hypertensive rodents. The efficacy of quercetin supplementation to lower blood pressure in hypertensive humans has never been evaluated. We tested the hypothesis that quercetin supplementation reduces blood pressure in hypertensive patients. We then determined whether the antihypertensive effect of quercetin is associated with reductions in systemic oxidant stress. Men and women with prehypertension and stage 1 hypertension were enrolled in a randomized, double-blind, placebo-controlled, crossover study to test the efficacy of 730 mg quercetin/d for 28 d vs. placebo. Blood pressure at enrollment was 137/86 in prehypertensives and 148/96 in stage 1 hypertensive subjects. Blood pressure was not altered in prehypertensive patients after quercetin supplementation. In contrast, reductions in systolic (-7 mm Hg), diastolic (-5 mm Hg), and mean arterial pressures (-5 mm Hg) were observed in stage 1 hypertensive patients after quercetin treatment. However, indices of oxidant stress measured in the plasma and urine were not affected by quercetin. These data are the first to our knowledge to show that quercetin supplementation reduces blood pressure in hypertensive subjects. Contrary to animal-based studies, there was no quercetin-evoked reduction in systemic markers of oxidative stress.

Cancer prevention
Quercetin has anti-proliferative effects in many cancer cell lines. Rodent studies have shown that dietary administration of this flavonol prevents chemically induced carcinogenesis, especially in the colon, while epidemiological studies have indicated that an intake of quercetin may be associated with the prevention of lung cancer.

Quercetin-induced apoptotic cascade in cancer cells: Antioxidant versus estrogen receptor alpha-dependent mechanisms.
Mol Nutr Food Res. 2009.Galluzzo P, Martini C, Bolli A, Pallottini V, Marino M. Department of Biology, University Roma Tre, Rome, Italy.
We studied the molecular mechanisms of quercetin committed to the generation of an apoptotic cascade in cancer cells devoid or containing transfected estrogen receptor alpha (ERalpha; i.e., human cervix epitheloid carcinoma HeLa cells). Although none of tested quercetin concentrations increase reactive oxygen species (ROS) generation in HeLa cells, quercetin stimulation prevents the H(2)O(2)-induced ROS production both in the presence and in the absence of ERalpha. However, this flavonoid induces the activation of p38/MAPK, leading to the pro-apoptotic caspase-3 activation and to the poly(ADP-ribose) polymerase cleavage only in the presence of ERalpha. Notably, no down-regulation of survival kinases (i.e., AKT and ERK) was reported. Taken together, these findings suggest that quercetin results in HeLa cell death through an ERalpha-dependent mechanism involving caspase- and p38 kinase activation. These findings indicate new potential chemopreventive actions of flavonoids on cancer growth.

Heart and cardiovascular health
Dietary flavonoids improve endothelial function and ultimately lead to beneficial cardiovascular effects. Together with its blood thinning and anti-inflammatory effects, the latter mainly mediated through the inhibition of cytokines and nitric oxide, quercetin is a good supplement choice for those who wish to improve their blood vessel and heart health.

Quercetin reduces niacin flush
A quercetin containing supplement reduces niacin-induced flush in humans.
Int J Immunopathol Pharmacol. 2008; Kalogeromitros D, Makris M, Aggelides X, Kempuraj D, Theoharides TC. Allergy Clinical Research Center, Allergy Section, Attikon Hospital, University of Athens Medical School, Athens, Greece.
Coronary artery disease is associated with increased serum levels of cholesterol, triglycerides and LDL, but low levels of HDL. The most potent agent capable of reversing this trend is the vitamin nicotinic acid (niacin). However, compliance even with extended-release preparations and addition of acetylsalicylic acid (ASA) is hampered by the development of a feeling of erythema and burning ("flush"), especially on the face. We recently showed that the natural flavonoids quercetin and luteolin can eliminate "flush", as well as inhibit both niacin-induced plasma prostaglandin D2 (PGD2) and serotonin increase in an animal model. We conducted a pilot clinical study in humans. Four normal male subjects received (a) 1 g immediate release niacin either alone or after (b) the dietary formulation (Algonot-plus) containing 150 mg quercetin per capsule. Subjects completed a visual scale symptom assessment. Erythema and burning sensation scores were were reduced. Quercetin also inhibited methylnicotinate-induced human mast cell PGD2 release. These preliminary results suggest that quercetin could reduce niacin-induced flush in humans.

Absorption
Quercetin is readily absorbed from the intestinal tract and blood levels rise as the dosage of the quercetin supplement increases. Quercetin is commonly present as a glycoside and is converted to glucuronide / sulfate conjugates during intestinal absorption and conjugated metabolites are found in circulating blood.

Quercetin and drug interactions
Quercetin influences activities of several drug metabolizing enzymes including CYP1A2, CYP2A6, NAT2 and XO.

Short-term effect of quercetin on the pharmacokinetics of fexofenadine, a substrate of P-glycoprotein, in healthy volunteers.
Eur J Clin Pharmacol. 2009. Department of Clinical Pharmacology and Toxicology, Anam Hospital, Korea University College of Medicine, Sungbuk-gu, Seoul, Korea.
The aim of the present study was to assess whether quercetin exhibited any inhibitory effect on P-glycoprotein (P-gp)-mediated drug disposition in humans using fexofenadine as a P-gp substrate. Twelve healthy subjects were enrolled in the study and treated daily for 7 days with 500 mg quercetin or placebo 3 times a day. On day 7, a single dose of 60 mg fexofenadine was administered orally. Plasma and urinary fexofenadine concentrations were measured, and pharmacokinetic differences between placebo and quercetin phases were assessed. The mean plasma concentrations of fexofenadine were significantly increased after quercetin treatment compared to those of the placebo phase. The results of the present study showed that short-term use of quercetin elevated the plasma concentrations of fexofenadine, probably by the inhibition of P-gp-mediated efflux in humans.

Animal studies

Antioxidant
Quercetin protects against oxidative stress-related renal dysfunction by cadmium in rats.
Exp Toxicol Pathol. 2009. Renugadevi J, Milton Prabu S. Department of Zoology, Annamalai University, Annamalainagar, Tamil Nadu, India.
The aim of this study was to investigate the possible protective role of the dietary flavonoid quercetin on cadmium (Cd)-induced nephrotoxicity using biochemical and histopathological approaches. In experimental rats oral administration of CdCl(2) for 4 weeks significantly induced renal damage which was evident from the increased levels of serum urea, uric acid and creatinine with a significant decrease in creatinine clearance. Cd also significantly decreased the levels of urea, uric acid and creatinine in urine. Cd-induced oxidative stress in kidney tissue was indicated by the increased levels of renal lipid peroxidation markers (thiobarbituric acid reactive substances and lipid hydroperoxides) and protein carbonyl content with a significant decrease in non-enzymatic (total sulphydryl group, reduced glutathione, vitamin C and vitamin E) and enzymatic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) and glucose 6-phosphate dehydrogenase (G6PD)). Moreover the kidneys of Cd-treated rats showed tubular necrosis, degeneration, dilation, desquamation, thickening of basement membrane and luminal cast formation. Quercetin treatment markedly attenuated the cadmium induced biochemical alterations in serum, urine and renal tissue. Quercetin also ameliorated the Cd-induced pathological changes when compared with Cd-alone-treated group. These data indicate that the natural dietary antioxidant quercetin might have protective effect against cadmium induced nephrotoxicity and oxidative stress in rats.

Asthma
Quercetin inhalation inhibits the asthmatic responses by exposure to aerosolized-ovalbumin in conscious guinea-pigs.
Arch Pharm Res. 2008; Division of Pathophysiology and Pharmacology, College of Pharmacy, Seoul, Korea.
Effects of quercetin inhalation on immediate, late-phase and late late-phase asthmatic responses by exposure to aerosolized-ovalbumin were studied in conscious guinea-pigs sensitized. Quercetin inhalation for 2 mininutes significantly decreased histamine and protein contents, PLA2 activity, and recruitments of leukocytes in BALF and also improved slightly infiltration of eosinophils and neutrophils in histopathological survey. Its anti-asthmatic activity was similar to cromolyn sodium and dexamethasone.

In vitro studies

Allergy
Role of quercetin (a natural herbal compound) in allergy and inflammation.
J Biol Regul Homeost Agents. 2006. Department of Medicine, Section of Infectious Diseases, Boston University School of Medicine, Boston, MA, USA.
Quercetin has an antioxidant and anti-inflammatory activity and prevents cancer. Quercitin inhibits the growth of certain malignant cells in vitro, and histamine and most cyclin-dependent kinases and also displays unique anticancer properties. Quercetin is a natural compound that blocks substances involved in allergy and is able to act as an inhibitor of mast cell secretion, causes a decrease in the release of tryptase, MCP-1 and IL-6 and the down-regulation of histidine decarboxylase (HDC) mRNA from few mast cell lines. Quercetin is a safe, natural therapy that may be used as primary therapy or in conjunction with conventional methods.

Blood thinning
Interactions of gallic acid, resveratrol, quercetin and aspirin at the platelet cyclooxygenase-1 level. Functional and modelling studies.
Thromb Haemost. 2009. Research Laboratories Catholic University, Campobasso, Italy.
While resveratrol and quercetin possess antiplatelet activity, little is known on the effect of gallic acid on platelets. We studied the interactions of these three different polyphenols among themselves and with aspirin, at the level of platelet cyclooxygenase-1 (COX-1). Both functional (in vitro and in vivo) and molecular modelling approaches were used. All three polyphenols showed comparable antioxidant activity; however, resveratrol and quercetin, but not gallic acid, inhibited AA-induced platelet aggregation. Gallic acid, similarly to salicylic acid, the major aspirin metabolite, prevented inhibition of AA-induced platelet function by aspirin but, at variance with salicylic acid, also prevented inhibition by the other two polyphenols.Experiments in mice showed that gallic acid administered before aspirin, resveratrol or quercetin fully prevented their inhibitory effect on serum TxB(2). Finally, a mixture of resveratrol, quercetin and gallic acid, at relative concentrations similar to those contained in most red wines, did not inhibit platelet aggregation, but potentiated sub-inhibitory concentrations of aspirin. Gallic acid interactions with other polyphenols or aspirin at the level of platelet COX-1 might partly explain the complex, and possibly contrasting, effects of wine and other components of the Mediterranean diet on platelets and on the pharmacologic effect of low-dose aspirin.

Quercetin accumulates in mitochondria, the energy factories of cells
Mitochondria accumulate large amounts of quercetin: prevention of mitochondrial damage and release upon oxidation of the extramitochondrial fraction of the flavonoid.
J Nutr Biochem. 2009. Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino "Carlo Bo",Urbino, Italy.
Intramitochondrial quercetin appears to be functional for prevention of mitochondrial damage as well as for redistribution to the cytosol, when the fraction of the flavonoid therein retained is progressively consumed either by cell-permeant oxidants or by activation of plasma membrane oxidoreductases.

Interactions
Graviola herb - We have not seen any studies regarding the combination of quercetin and graviola herb.

Emails
After taking both Swansons 650mg quercetin and coconut oil capsule 1000 mg for only 4 days at 2 doses a day, I have developed a mild but obvious case of Lichen planus. I have recently been diagnosed with Hepatitis C and suspect I had it for 25 years but have never had lichen planus before. My mother developed lichen planus after chemotherapy, I believe it is an immune response? I stopped taking the supplements 2 days ago the symptoms have lessened. Could you please advise me on this complication as I am trying to heal myself from HCV.
    We have not had any feedback from other users of this product that it has caused an allergy or skin condition. A review of Medline in 2010 does not show any reports of such association.