News report bylines cite cancer protective, cholesterol lowering, muscle building, and many other health enhancing attributes for chemicals derived from food. What gets lost in translation, however, is that many of these studies do not take into account the role of digestion and absorption of these agents from food, in other words bioavailability. Quercetin, a widely distributed flavonoid with numerous reports in the scientific literature on its biological activities in cell systems has a bioavailability (as % excreted dose) of 6% in humans fed onions (Simons et al. 2010). These authors reported bioavailability for genistein (soymilk) and hesperitin (grapefruit) each at 7%, naringenin (orange) at 3%, whereas daidzein (soymilk) was 43%. Genistein’s flavonoid analogue, apigenin, has bioavailability of < 3% in rats exposed to a major form of apigenin in foods, apigenin-7-glucoside (Hanske et al., 2009). Anthocyanins from strawberries were 2% bioavailable (Carkeet et al., 2008). In contrast, coffee phenolic acids were almost 50% bioavailable (Stalmach et al., 2009).
Many flavonoids and phenolic acids show promising biological activity in cell systems when tested as aglucons but not in the form the intact human would experience (Manach et al. 2005). Plant phenolics (phenolic acids, flavonols, flavonones, isoflavones) occur in food as glucosides. During digestion, they may be deglucosylated by human or microbial glucosidases. Apparently, only aglucons are absorbed and immediately biotransformed to make glucuronide or sulfate conjugates in the intestinal mucosa, with additional biotransformation by the liver, kidney and other organs before excretion. The absorbed phenolics are excreted in the urine or in the bile where they are deconjugated in the lower intestine by microbes and reabsorbed with concomitant biotransformation. More than 90% of plasma circulating forms are glucuronides or sulfates (Zhang et al. 2003). These forms that the cells interact with need much more study, but seem to be much less bioactive than the aglucon phenolics that they are derived from, as shown for isoflavone glucuronides (Zhang et al. 1999). Most plant phenolics are catabolized by gut microflora (Hendrich 2002). The great variety of these gut microbial metabolites is not well characterized yet for their bioactivities. Additionally, most plant phenolics and their metabolites do not accumulate in tissues but are rather rapidly excreted, most within a day after intake.
Thus, reports on the biological activity of interesting phytochemicals need to be interpreted in terms of the assay system, i.e., how closely it mimics intact digestion, absorption, and circulation, and the form of the phytochemical, i.e., is the chemical form the one circulating in plasma that cells will actually experience?
Patricia A. Murphy and Suzanne Hendrich
Iowa State University
Carkeet, C., Clevidence, B.A., Novotny, J.A. Anthocyanin Excretion by Humans Increases
Linearly with Increasing Strawberry Dose1 J. Nutr. 2008, 138: 897–902.
Hanske, L., Loh, G., Sczesny, S., Blaut, M., Braune, A. The Bioavailability of Apigenin-7-Glucoside Is Influenced by Human Intestinal Microbiota in Rats. J. Nutr. 2009, 139: 1095–1102.
Hendrich, S. Bioavailability of isoflavones. J Chromatog. B 2002, 777: 203-210.
Manach C, Williamson G, Morand C, Scalbert A, Rémésy C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr. 2005 Jan;81(1 Suppl):230S-242S.
Simons, A., Renouf, M., Murphy, P., Hendrich, S. Greater apparent absorption of flavonoids is associated with lesser human fecal flavonoid disappearance rates. J. Agric. Food Chem. 2010, 58, 141-147.
Stalmach, A. , Mullen, W. Denis Barron, D., Uchida, K., Yokota, T., Cavin, C., Steiling, H., Williamson, G., Crozier, A. Metabolite Profiling of Hydroxycinnamate Derivatives in Plasma and Urine after the Ingestion of Coffee by Humans: Identification of Biomarkers of Coffee Consumption. Drug Metab. Dispos. 2009, 37:1749-1758.
Zhang, Y., Song, T. T., Cunnick, J. E., Murphy, P. A., Hendrich, S. Daidzein and genistein glucuronides in vitro are weakly estrogenic and activate human natural killer cells in nutritionally relevant concentrations. J. Nutr. 1999, 129: 399-405.
Zhang, Y., Murphy, P. A., Hendrich, S. Glucuronides are the main isoflavone metabolites in women. J. Nutr. 2003, 133: 399-404.