Polyphenolic flavonoids are among a wide variety of phytochemicals present in the human diet. Basic research, animal model, and human studies suggest flavonoid intake may reduce the risk of several age-related chronic diseases. The vast number of flavonoids and mixtures of their subclasses, including flavonols, flavones, and flavanones, and the variety of agricultural practices that affect their concentration in foods have presented a challenge to the development of adequate food composition databases for these compounds. Nonetheless, dietary assessments have been applied to cohort and case-control epidemiological studies, and several reveal an inverse association with risk of some forms of cancer, cardiovascular disease, and other chronic conditions. Those observational studies that have examined these relationships with regard to flavonols, flavones, and flavanones are reviewed. The requirement for caution in interpreting these studies is discussed with regard to the limited information available on the bioavailability and biotransformation of these flavonoids. As the totality of the available evidence on these flavonoids suggests a role in the prevention of cancer and cardiovascular disease, further research is warranted, particularly in controlled clinical trials.

Dietary intervention with anthocyanins may confer benefits in brain function, including vision. Research to date indicates that animals have only a limited capacity to absorb anthocyanins, compared to other types of flavonoids. Pigs, which are a suitable model for human digestive absorption, were used to examine the deposition of anthocyanins in tissues including the liver, eye, and brain tissue. Pigs were fed diets supplemented with 0, 1, 2, or 4% w/w blueberries ( Vaccinium corymbosum L. 'Jersey') for 4 weeks. Prior to euthanasia, pigs were fasted for 18-21 h. Although no anthocyanins were detected in the plasma or urine of the fasted animals, intact anthocyanins were detected in all tissues where they were sought. LC-MS/MS results are presented for the relative concentration of 11 intact anthocyanins in the liver, eye, cortex, and cerebellum. The results suggest that anthocyanins can accumulate in tissues, including tissues beyond the blood-brain barrier.

Quercetin and quercetin glycosides from food or dietary supplements appear in body tissues almost exclusively as glucuronated, sulfated, and methylated quercetin conjugates, suggesting that the in vivo bioactivity of quercetin may be due to its metabolites. In this study, pre- and postabsorptive metabolism of orally ingested quercetin was examined by comparing the metabolite pattern in gastrointestinal (GI) tissues, contents, and internal tissues. F344 rats (n = 6) were fed for 6 wk a diet containing 0.45% quercetin and the metabolite patterns were determined in the tissues and contents of stomach, small intestine, cecum, and colon and in liver, kidney, and plasma using LC-MS/MS. GI contents contained predominantly unmetabolized quercetin at 94-100%, whereas quercetin in GI tissues was present as 11 different sulfated, glucuronated, and methylated metabolites at 32% in stomach, 88% in small intestine, 27% in cecum, and 46% in colon. Quercetin was further metabolized postabsorption and found in liver, kidney, and plasma almost exclusively as sulfated methyl-quercetin glucuronide. The unique pattern of quercetin metabolites in each GI tissue indicates extensive biotransformation before absorption and distribution in rats.

Epidemiological studies suggest that consumption of flavonol-rich diets decreases the risk of developing heart disease and certain cancers. Recent studies have detected flavonol conjugates in blood and urine following various dietary interventions. To assess to what extent flavonols also accumulate in tissues, where they might be expected to exert anti-carcinogenic and anti-atherogenic effects, [2-(14)C]quercetin-4'-glucoside was synthesized and fed to rats. After 60 min, 93.6% of the ingested radioactivity was recovered from the intestine, incorporated into 18 metabolites that had undergone deglycosylation followed by varying degrees of glucuronidation, methylation, and/or sulfation. [(14)C]Quercetin, the aglycon of the radiolabeled substrate, was present in the intestine and in trace amounts in the liver but was not detected in the plasma and kidneys. The original [2-(14)C]quercetin-4'-glucoside was detected exclusively in the intestine, where it accounted for only 26.2% of the radioactivity. The remainder of the recovered radioactivity was located mainly in the plasma, liver, and kidneys as (14)C-labeled metabolites. However, compared to the quantities in the gastrointestinal tract, the levels of metabolites in plasma and body tissues were very low, indicating only limited absorption into the blood stream. The data demonstrate that quercetin-4'-glucoside, which is a major flavonol in onions, undergoes rapid and extensive metabolism in the intestine, and this appears not to be associated to any extent with transport across the gut wall into the blood stream.