Structure-degradation relationships of flavonoids and their correlation to human bioavailability

The chemical structure of flavonoids greatly influences the rate of degradation by human gut microflora and their overall bioavailability. Daidzein, genistein and glycitein were incubated in fecal fermentation mixtures consisting of brain heart infusion media (BHI) and fresh feces in vitro from 12 human subjects for 24 hours. Genistein, which possesses a hydroxyl group in the 5 position, degraded most rapidly compared to daidzein and glycitein in all subjects.; To further determine the relationship between other flavonoids with hydroxyl groups in the 5 position and gut microbial degradation, 14 flavonoids, flavone, apigenin, chrysin, naringenin, kaempferol, genistein, daidzein, daidzin, puerarin, 7,4'-dihydroxyflavone, 6,4'-dihydroxyflavone, 5,4'-dihydroxyflavone, 5,3'-dihydroxyflavone and 4'-hydroxyflavone, were fermented in fecal fermentation mixtures from 11 human subjects. The degradation rates of 5,7,4' -trihydroxyl-flavonoids, apigenin, genistein, naringenin and kaempferol, were significantly faster compared to flavonoids with other structural motifs (p < 0.0001).; The bioavailability of flavonoids that are rapidly degraded by the gut microflora may be significantly reduced compared to flavonoids that are slowly degraded. The bioavailability of the rapidly degraded flavonoids, genistein, naringenin, quercetin and hesperetin with an average k = 5.8 +/- 1.9% were significantly lower than daidzein with an average k = 42.6 +/- 15.9% (p = 0.02) expressed as the amount of flavonoid excreted in urine as a percentage of ingested dose in 5 men and 5 women. Subjects with low genistein degrader phenotypes (average k = 0.11 +/- 0.07 h-1, n = 4) based on average linkage cluster analysis, experienced a higher genistein bioavailability (11.5 +/- 8.0%) compared to the lower genistein bioavailability (3.6 +/- 1.9%, p = 0.007) experienced by subjects with high genistein degrader phenotypes (average k = 1.28 +/- 0.45 h-1 , n = 3).; The data from the in vitro fecal fermentation studies reveal that the chemical structure of flavonoids greatly influences the gut microbial degradation rate. Flavonoids with 5,7,4'-trihydroxyl-flavonoid structures were rapidly degraded by the human intestinal microflora, which in turn, resulted in lesser apparent absorption and excretion in urine over 24 h. Therefore, the chemical structure of flavonoids is a strong determinant of the human bioavailability of flavonoids.