2-(3,4-dihydroxyphenyl)-3,5,7,trihydroxy-4H-1-benzopyran-4-one; 3,3′,4′,5,7-pentahydroxyflavone; Flavan-3,4-diols; Vitamin P
Actions & Pharmacology
Quercetin may have antioxidant, antineoplastic, anti-inflammatory, and antiviral activity. As an anticancer agent, quercetin interrupts cell cycles, ATPase activity, signal transduction, and phosphorylation. Some activity had been found against viral reverse transcriptases.
Inhibition of liver glutathione-S-transferase activity has been demonstrated. This enzyme plays an important part in the development of resistance to various cancer chemotherapy agents (Pickett & Lu, 1989; Das et al, 1986). Quercetin is also a potent inhibitor of p-form phenolsulfotransferase, an enzyme used to sulfonate various drugs and environmental chemicals. (Walle et al, 1995).
Low-density lipoproteins are oxidatively modified by macrophages in the formation of foam cells and atherosclerotic plaque. Quercetin inhibited oxidative modification with an effective dose concentration 50% of about 2 mmol/liter. Based on the results of several studies, it appears that quercetin donates an electron to enzyme-bound alpha tocopherol, preventing LDL oxidation (Frankel et al, 1993a, Frankel et al, 1993b, De Walley et al, 1990).
Quercetin, like most flavonoids, modified acute inflammatory responses by suppressing macrophage phagocytosis. Quercetin also decreased the release of oxidants by phagocytosizing neutrophils and by macrophages phagocytosizing latex particles, and activation of mast cells (Daniel et al, 1988; Busse et al, 1984). A specific anti-inflammatory response may be more complicated since many of quercetin's functions are biphasic with lymphocyte proliferation and function stimulated at low doses but inhibited at larger doses (Formica & Regelson, 1995). Quercetin inhibits both lung and intestinal mast cell reactivity to histamine release (Middleton & Ferriola, 1988; Pearce et al, 1984).
Antiviral activity has been demonstrated. Quercetin's antiviral activity may be related to its ability to bind viral protein coat and to interfere with viral nucleic acid synthesis (DNA) (Formica & Regelson, 1995).
Effects with Iron
Quercetin acts as an iron-chelating agent (Sestili et al, 1998). This was demonstrated in an iron-loaded preparation of rat hepatocytes. Quercetin prevented lipid peroxidation and enzyme leakage in this preparation (Morel et al, 1993). Quercetin has a pro-oxidant effect and will increase the iron-dependent DNA damage induced by bleomycin. Quercetin may reduce iron to the ferrous state, which allows bleomycin to complex more readily with oxygen and produce more efficient DNA damage (Laughton et al, 1991). A biphasic pro-oxidant effect with bleomycin has been demonstrated. At low concentrations increased DNA damage was noted, and at higher doses less DNA damage was noted.
Lymphocyte protein kinase phosphorylation was inhibited by quercetin in 9 of 11 cancer patients in a phase I clinical trial. Fifty-one patients with microscopically confirmed cancer not amenable to standard therapies and with a life expectancy of at least 12 weeks participated in this trial. The patients had not received any other form of chemotherapy, immunotherapy, or radiotherapy for 3 to 6 weeks (depending on the agent). The patients were treated at 3-week intervals at the beginning of the study. Quercetin was administered intravenously as quercetin dihydrate and administered at a concentration of 50 mg/mL for doses up to 945 mg/m2, and at 100 mg/mL for doses above this. The maximum allowed dose was reached when 2 of 3 patients on each dose schedule reached grade 3 or 4 general toxicity, or grade 2 renal toxicity, cardiac toxicity, or neurotoxicity. Phosphorylation was inhibited at 1 hour and persisted for 16 hours. In one patient with ovarian cancer refractory to cisplatin, CA 125 fell from 295 to 55 units/mL after treatment with two courses of quercetin (totaling 420 mg/m2). Also in this group of study patients, a hepatoma patient had serum alpha-fetoprotein fall (Ferry et al, 1996).
Epidemiological studies suggest that quercetin protects against cardiovascular disease. Long-term flavone and flavonol dietary intake was strongly inversely proportional to thrombotic stroke. One study involved a cohort of 552 middle-aged men without history of stroke. The men were divided into quartiles of flavonol and flavone intake and followed for 15 years. During these years, 42 men had a first stroke. The association was not affected by other risk factors. In the top quartile, those that were taking over 30 mg daily had about one-third the risk of stroke (Hertog & Hollman, 1996).
Quercetin improved symptoms of benign prostatic hyperplasia in a small double-blind, placebo-controlled study. Thirty men with category IIIa and IIIb chronic pelvic pain were randomized to receive placebo or 500 mg quercetin twice daily for a month. All of the patients in the quercetin group finished the study while 2 of the 15 placebo subjects withdrew due to increased symptoms. Improvement was measured on the NIH symptom score. Twenty percent of patients taking placebo and 67% of those taking the quercetin had symptom improvement of at least 25% (p=0.003) (Shoskes et al, 1999).
Indications & Usage
Quercetin may protect against the development of cardiovascular disease and alleviate the symptoms of prostatitis.
Precautions & Adverse Reactions
Side effects include pain, flushing, dyspnea, and emesis after intravenous injection.
Nephrotoxicity has been a dose-limiting side effect of quercetin administration in humans.
Cyclosporine: Concomitant use may reduce cyclosporine effectiveness. Clinical Management: Monitor serum concentrations of cyclosporine and signs and symptoms of loss of efficacy in patients taking quercetin and cyclosporine.
Floroquinolones: Concomitant use may reduce effectiveness of fluoroquinolones. Clinical Management: Patients taking fluoroquinolones and quercetin concomitantly should be monitored for signs of decreased activity of fluoroquinolones.
Mode of Administration
Intravenous solution in ethanol or DMSO, capsule, tablet, food and drink.
400 to 500 mg orally 3 times daily is recommended by practitioners of natural medicine. If the water soluble quercetin chalcone is used the dose is reduced to about 250 mg 3 times daily.
Prostatitis: 500 mg orally of quercetin twice daily.
Cancer (quercetin dihydrate in ethanol or DMSO): An intravenous bolus dose of 1400 mg/m2 given at 3-week intervals (from a phase 1 study) (Ferry et al, 1996).
Quercetin tablets and capsules should be stored at room temperature, away from heat, moisture, and direct light.