Safety evaluation of a soluble granular food containing quercetin glycosides for healthy adults: A randomized controlled trial

Quercetin glycosides (QG), enzymatically modified isoquercitrin derivatives, are widely used in functional foods for their antioxidant, antihypertensive, and lipid metabolism benefits. Previous safety studies have confirmed tolerability at intake levels up to 480 mg/day for four weeks. However, Japanese regulatory guidelines require overdose safety evaluations at approximately five times the effective dose (110 mg/day), and data on higher intake levels remain limited. To evaluate the safety of daily consumption of a food product containing 550 mg/day of QG approximately five times the effective dose for four weeks in healthy adults. A randomized, double-blind, placebo-controlled, parallel-group trial was conducted at a single clinical site in Japan. Healthy adults aged 20–64 years with BMI 18.5–29.9 kg/m 2 were enrolled and randomized (1:1) to receive either soluble granular food containing QG (550 mg/day) or placebo for four weeks. Randomization was stratified by sex, age, and BMI using blocked allocation. Both participants and investigators were blinded to group assignments. The primary endpoint was the incidence of adverse reactions. Secondary endpoints included the incidence of adverse events and changes in physiological and clinical parameters. Safety assessments were performed at baseline, week 2, and week 4. Of 149 screened individuals, 48 were randomized and 47 completed the study(QG group: n = 23, control group: n = 24). No adverse reactions attributable to the test food occurred. Ten adverse events were reported (QG: 4 events in 4 participants, placebo: 5 events in 4 participants), all mild and unrelated to the intervention. In addition, no abnormal changes were observed in clinical test values. In the QG group, minor intragroup changes in biochemical parameters were noted, but all values remained within standard ranges. Also, no significant intergroup differences were detected. Daily intake of 550 mg/day QG for four weeks was safe in healthy adults, with no adverse reactions or clinically meaningful changes in safety parameters. These findings support the safety of QG at doses exceeding previously tested levels. Further research is needed to assess long-term safety and higher dosages. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation. Trial registration: The clinical trial was registration with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR, UMIN ID: UMIN000053632); https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000061206 . The consumption of food containing 550 mg/day quercetin glycosides for four weeks is safe for healthy adults.