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Articles

Carbon Dioxide Is the Major Metabolite of Quercetin in Humans^{1 ,2}

Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425

³To whom correspondence should be addressed. E-mail: wallet{at}musc.edu.

A previous study in ileostomy patients indicated that dietary glucosides of the flavonoid quercetin are hydrolyzed efficiently in the intestinal lumen, followed by absorption of a large fraction of the quercetin aglycone. To determine the fate of quercetin, we administered 1.85 MBq (50 µCi) of ¹⁴C-quercetin both orally (100 mg, 330 µmol) and intravenously (iv; 0.3 mg, 1 µmol) to healthy volunteers. Serial plasma samples, urines and stools were collected for 72 h. Total radioactivity was determined by liquid scintillation spectrometry directly in plasma and urine and after repeated methanol extraction of stool homogenate samples. The oral absorption, based on total radioactivity, was surprisingly high, ranging from 36.4 to 53.0%. The biological half-life was very long, ranging from 20 to 72 h. The urinary recovery of total radioactivity ranged from 18.4 to 26.8% after the iv dose and from 3.3 to 5.7% after the oral dose. The corresponding fecal recoveries were only 1.5–5.0% and 1.6–4.6%, respectively. Thus, the total recovery of the ¹⁴C-quercetin doses, in particular after oral administration, was very low. In search for the unaccounted for fraction of the ¹⁴C-quercetin dose, we performed ¹⁴CO₂ recovery studies in three volunteers (3 iv and 3 oral doses). At timed intervals, ¹⁴CO₂ in expired air was trapped in hyamine hydroxide/thymolphthalein and analyzed for radioactivity. As much as 23.0–81.1% of the quercetin dose was recovered as ¹⁴CO₂ in the expired air from these volunteers, after both oral and iv doses. The disposition of quercetin in humans is thus highly complex, requiring further studies.

KEY WORDS: • quercetin • intestinal absorption • enterohepatic recirculation • carbon dioxide formation • flavonoids • humans

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