Quercetin And Uric Acid Levels: Human Trial Summary

The study “Quercetin Lowers Plasma Uric Acid in Pre-hyperuricaemic Males: A Randomised, Double-Blind, Placebo-Controlled, Cross-Over Trial” by Yuanlu Shi et al. (2016) tested whether quercetin supplementation could lower plasma uric acid in men whose levels were at the higher end of the normal range. The study included twenty-two healthy male volunteers who took 500 mg quercetin per day or a placebo tablet for four weeks, with a four-week washout period in between. The authors measured plasma uric acid, fasting glucose, 24-hour urinary uric acid, and resting blood pressure before and during each phase. They report that quercetin lowered plasma uric acid without changing fasting glucose or blood pressure and describe the results as evidence that this dose of quercetin, roughly equal to the bioavailable quercetin in about 100 g of red onions, was linked with lower plasma uric acid in this specific group. This page simply summarizes and paraphrases the published scientific study and is not intended as treatment advice.

The authors describe hyperuricaemia as a major risk factor for gout, an inflammatory arthritis linked with urate crystal deposition. The paper also discusses associations between higher uric acid and cardiometabolic conditions such as obesity, insulin resistance, type 2 diabetes, and hypertension. The study notes diet-related influences on uric acid, including purines, alcohol, and fructose, and describes pathways by which sustained fructose exposure may increase uric acid production.

Uric acid is produced in the body by an enzyme called xanthine oxidoreductase (XO), also known as xanthine oxidase or xanthine dehydrogenase. Inhibition of xanthine oxidoreductase is the target of drugs such as allopurinol, a standard uric acid–lowering medicine used in gout. Quercetin is a dietary flavonoid found at relatively high levels in foods such as onions, apples, and black tea, and previous laboratory and animal work has shown that quercetin and some quercetin metabolites can inhibit xanthine oxidoreductase and affect uric acid metabolism in non-human models.

However, before this trial, it was still unclear whether similar effects would appear in humans. The authors therefore designed a controlled human study to test the hypothesis that four weeks of quercetin supplementation might reduce plasma uric acid in men with “non-optimal” but still normal uric acid levels.

The scientific paper reports a randomized, double-blinded, placebo-controlled, crossover human trial. The researchers recruited twenty-two healthy male volunteers aged 19 to 65 years. At baseline, the men had:

• Mean age about 29.9 years
• Mean body mass index (BMI) around 24.8 kg/m²
• Plasma uric acid in the higher, but still healthy, range with a mean of about 339 µmol/L

Volunteers were non-smokers, not heavy drinkers, and did not have diagnosed gout, kidney stones, or significant intestinal disorders. Those with plasma uric acid below 300 µmol/L were excluded.

The study followed a crossover design with two treatment periods of four weeks each, separated by a four-week washout period. In one period, participants took one tablet per day containing quercetin dihydrate (label claim 500 mg quercetin, measured content about 544 ± 45 mg aglycone) from a commercial supplement. In the other period, they took a matching placebo tablet containing lactose and excipients but no quercetin. The order of treatments was randomized, and both participants and researchers were blinded to assignment.

Blood and 24-hour urine samples were collected at day 0, day 14, and day 28 of each period. The main outcome was plasma uric acid concentration after two and four weeks. Secondary outcomes were fasting plasma glucose, 24-hour urinary excretion of uric acid, and resting blood pressure.

Uric acid in plasma and urine was measured using an enzymatic colorimetric assay, and plasma glucose was assessed with a hexokinase-based method. The authors performed power calculations beforehand and estimated that at least seventeen participants would be needed to detect a 10 percent difference in plasma uric acid with 80 percent power. In the end, twenty-two participants completed the study and were included in the analyses.

The authors report that plasma uric acid fell progressively during the quercetin phase. From baseline to four weeks, the mean reduction reached −26.5 µmol/L (95% confidence interval −45.5 to −7.6, P=0.008), which the authors report as statistically significant.

During the placebo phase, plasma uric acid did not change in a significant way at either two or four weeks, and there were no differences between baseline values at the start of each phase. The authors note that the average reduction in plasma uric acid with quercetin was roughly 8 percent of the baseline value. They also point out that the dose used is similar in bioavailable quercetin to what would be obtained from about 100 g of fresh red onion.

The study also tracked fasting blood glucose and blood pressure. According to the results, quercetin supplementation did not significantly change fasting glucose or systolic blood pressure in this group of pre-hyperuricaemic males. There was a small trend toward a decrease in diastolic blood pressure (about −2.0 mm Hg, P=0.07) during the quercetin phase, but this did not reach the usual threshold for statistical significance. The authors report no statistically significant changes in BMI, fasting blood glucose, or blood pressure in this small study, and no adverse effects were reported during the study periods.

To explore potential mechanisms, the study measured 24-hour urinary uric acid. The authors did not find a significant change in total 24-hour urinary uric acid excretion after quercetin compared with placebo. One interpretation offered in the paper is that the lower plasma uric acid may reflect reduced production, such as inhibition of xanthine oxidoreductase, rather than increased excretion through the kidneys, although the paper notes that several mechanisms could be involved.

In the discussion, the authors mention that quercetin and some of its conjugates inhibit xanthine oxidoreductase in vitro with inhibitory constants in the micromolar range, and they compare these values with those of allopurinol. They also consider possible effects on renal transporters that handle uric acid, but the urinary data in this study did not show a clear change in excretion.

The authors report that no serious adverse events occurred and that participants did not report notable side effects related to quercetin or placebo intake. Based on tablet counts, self-reported adherence, and urinary quercetin measurements, the study classifies all participants as compliant with the protocol. This describes study tolerability for 500 mg quercetin per day over four weeks in this research setting.

Within the limits of this small, short-term study, the authors report that 500 mg quercetin daily for four weeks was associated with lower plasma uric acid in healthy males whose baseline levels were at the higher end of the normal range. The paper reports no statistically significant changes in fasting glucose, BMI, 24-hour urinary uric acid excretion, or blood pressure during the quercetin phase compared with placebo.

The discussion links these findings to prior in vitro and animal work and proposes possible mechanisms, including xanthine oxidoreductase inhibition. The paper also notes that human evidence remains limited and calls for additional research in different populations, over longer durations, and with varying doses.

All of the implications described here come directly from the published scientific paper. This summary does not extend those conclusions beyond what the authors reported and does not suggest quercetin use for disease treatment, cure, or prevention. Any decisions about supplements or treatment should be made with a qualified health professional.

In this randomized, double-blinded, placebo-controlled, crossover trial, four weeks of quercetin supplementation at 500 mg was associated with an average reduction of about 26.5 µmol/L in plasma uric acid in pre-hyperuricaemic healthy males. No statistically significant changes were reported in fasting glucose, blood pressure, or urinary uric acid excretion. The authors interpret the findings as evidence that this dose, described as roughly comparable in bioavailable quercetin to about 100 g of red onions, was linked with lower plasma uric acid in this specific research setting. This page paraphrases the original scientific paper and does not replace medical advice.