Yamada S, Shirai M, Inaba Y, Takara T. Effects of repeated oral intake of a quercetin-containing supplement on allergic reaction: a randomized, placebo-controlled, double-blind parallel group study. Eur Rev Med Pharmacol Sci. 2022:26(12):4331-4345.
Randomized, placebo-controlled, double-blind trial
Phytosome quercetin significantly reduced several important pollinosis symptoms during pollen season in these Tokyo residents across 4 weeks of use.
The study included 66 subjects (aged 22–78 years) with allergic symptoms of pollinosis during a high-pollen season in Tokyo, Japan. Ninety adults consented to participate in the study and 66 qualified and were enrolled in the study. Three subjects were later excluded and another three left the study. In the end, 60 subjects were included in the analysis. There were 18 women and 12 men in the treatment arm, and 15 women and 15 men in the placebo arm. The authors state there were no significant differences at baseline; however, high-density lipoprotein (HDL) was lower in the placebo group compared to the treatment group (P=0.02).
Inclusion Criteria: These included those with a relatively high score on the Japanese Rhino-Conjunctivitis Quality of Life Questionnaire (JRQLQ).
Exclusion Criteria: Excluded were patients with prior cancers, heart failure, myocardial infarction; pacemaker or defibrillator; receiving treatment for arrhythmia, liver dysfunction, kidney dysfunction, cerebrovascular disorders, rheumatoid arthritis, diabetes, dyslipidemia, hypertension, and other chronic illnesses; ingesting functional foods or beverages; continuous use of drugs for allergic eye and nose symptoms; using herbs or supplements; allergic to quercetin and lecithin; unable to follow directions; planning to travel during the study period; practicing nose gurgling (nasal lavage); pregnant, lactating or planning to become pregnant during the study period; in a clinical trial in the prior 3 months or planning to be in another clinical trial during the study period; and judged inappropriate by the principal investigator for this trial.
Study Parameters Assessed
Investigators assessed JRQL questionnaire, height, weight, body mass index (BMI), body-fat ratio, blood pressure, heart rate, complete blood count (CBC), aspartate aminotransferase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT), lipid panel, glucose, hemoglobic A1c (HbA1c), complete urine analysis (UA), virology and immunoserological tests for hepatitis C, human immunodeficiency virus (HIV), and Treponema pallida for all subjects. Primary end point was the JRQLQ score, and secondary end points were allergic symptoms, nasal discharge, and a homemade questionnaire.
Investigators called the intervention a food because the quercetin was in the phytosome form with lecithin accessed from Indena S.p.A, Milan, Italy. The study dose was 50 mg quercetin per tablet, 2 tablets twice daily, at breakfast and supper. The placebo was the same quantity of vehicle per tablet, also at 2 tablets twice daily, at breakfast and supper. The investigators determined that it was impossible to distinguish between the test and placebo foods by taste or external appearance.
Changes in the JRQLQ scores
JRQLQ total scores were lower in the treatment arm at 4 weeks in the total score (P=0.04), quality-of-life total score (P=0.02), and sleep and physical scores (P=0.00). In the detailed JRQLQ score breakdown at 4 weeks versus baseline, the treatment arm was significantly better in sneezing (P=0.04), mental focus (P=0.01), ability to participate in outdoor activities (P=0.01), improved sleep (P=0.01), reduction in fatigue (P=0.02); and facial swelling (P=0.03).
The authors declared no conflicts of interest. Funding for the study as stated by the authors: “This study was conducted under assignment from Indena Japan Co., Ltd. and Indena S.p.A. at the cost of the assignors.” Indena S.p.A. is the maker of the quercetin phytosome.
Rhinitis is a type-1 allergic reaction associated with mast cell degranulation from excess immunoglobulin E (IgE) response to the allergen, histamine release, mucus release, ocular conjunctivitis, hives and eczema, angioedema, asthma, and even anaphylaxis.1,2 The population incidence can be up to 2% for anaphylaxis, is increasing in younger populations, and in North America may be as high as 20% to 30%.2 In Tokyo the primary causes are Japanese cedar, sugi, Cryptomeria japonica pollen (48.8% of population), other allergens, air pollution, and infections.
Quercetin, a bioflavonoid with extensive research, works by inhibiting mast cell activation, reducing histamine release and the ensuing inflammation from eosinophil activation, inhibiting lipopolysaccharide-induced tumor necrosis factor alpha (TNF-α), and inhibiting lipid peroxidation, platelet aggregation, capillary permeability, and stimulated mitochondrial biogenesis, among its multiple actions.3 It was identified in 1957 from oaks (Quercus) and is yellow.3 Dietary intake from fruits and vegetables can range from 4 to 500 mg/d with low oral bioavailability of 2% to 17%.3 Vitamin C, folate, and intake of other flavonoids simultaneously can increase absorption rates.4 Absorption takes place in the small intestine; half-life studies show a range of 3.5 to 28 hours, with excretion primarily via the kidneys.4
Vitamin C, folate, and intake of other flavonoids simultaneously can increase absorption rates.
The phytosome formulation was quercetin, from Sophora japonica, and sunflower lecithin in a 1:1 ratio, standardized to 40% quercetin.5 In a single-dose trial in healthy adults aged 18 to 50 years, based on 12 blood samples from baseline to 24 hours postingestion and 3 doses of either quercetin 500 mg, quercetin phytosome 250 mg, or quercetin phytosome 500 mg, the area under the curve was 4,774.9 ng/mL, 50,401.5 ng/mL, and 96,163.8 ng/mL, respectively, or a 105-fold increase between 500 mg quercetin and 500 mg quercetin phytosome.5
In a 3-month study on prevention of Covid-19 in 120 healthcare workers (60 placebo, 60 treatment) using quercetin phytosome 250 mg twice daily, there was less Covid-19 in the treatment group and faster recovery. At 5 months, Covid-free survival was 99.8% in the treatment group versus 96.5% in the control group for a 14% greater protection factor for not contracting SARS-CoV-2 infection.6 A trial using a combination product of 500 mg vitamin C, 500 mg quercetin, and 50 mg bromelain over 3 months in healthcare workers found that 1 worker in the treatment group contracted Covid-19, whereas 9 of 42 (21.4%) in the control group contracted the SARS-CoV-2 infection.7 The possible mechanisms in these trials likely include immune activation, counteracting cytokine storms, and counteracting senescent cells.6
My clinical experience with quercetin has usually involved 500 mg of quercetin with 500 mg of vitamin C in a twice daily or thrice daily prescription for allergies and early infections with good success, especially if initiated 7 to 14 days prior to onset of the local allergy/pollen season, confirming the above findings. Having not had access to quercetin phytosome, I cannot speak to how it compares, although it appears potentially more effective. The determining factor for my use in patients will be the cost versus presumed greater benefit.