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administration routes to determine the bioavailability of a compound

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To evaluate the potential effects of SDG on human health, it is critical to determine its bioavailability. As mentioned above, due to its relative stability in biological fluids, EL is commonly used as a biomarker for determining SDG bioavailability [49]. Several reported bioavailabilitystudies are worth examining. First, SDG bioavailability was investigated in healthy human subjects who consumed 30 g milled flaxseeds (equivalent to 90 mg SDG lignan) daily for 4 weeks. This study reported that the total EL concentration was about 513 nM, and average END and ENL concentrations were 209 nM and 304 nM, respectively [49,50]. Another human study investigated the possible effects of different types of flaxseed products (whole flaxseed, crushed flaxseed, and ground flaxseed) on SDG lignan bioavailability. In this study, the total EL concentration of ELs was approximately 270 nM, and average concentrations of END and ENL were 103 nM and 167 nM, respective, following the consumption of about 20 g ground flaxseed (equivalent to 60 mg lignan) [51]. The latter study also reported that plasma EL concentrations following the consumption of crushed flaxseed and whole flaxseed were lower than those observed in the ground flaxseed group. Data showed that the relative bioavailability of ELs from whole flaxseed was about 28% that of ground flaxseed, whereas the relative bioavailability of ELs from crushed flaxseeds was about 43% [51]. Although a number of studies have clearly shown that the intake of lignan-rich foods leads to increased plasma EL levels in most subjects, there are growing concerns that the bioavailability of ELs may be significantly influenced by food matrix, gut microbial action, and other factors, thereby being subject to large interpersonal, foodstuff-derived, and other variations. For examples, a continuous increase serum EL concentration was observed over a 4-month intervention with flaxseed (33, 52, and 70 nM at baseline and after 2 and 4 months, respectively) [52]. In another study, a dose-response urinary excretion of SDG metabolites was reported (with no plateau) after the daily consumption of 5, 15, and 25 g flaxseed products for 7 days [53]. These data indicate that the amount of ELs produced by intestinal bacteria may increase linearly, but that blood levels of ELs may largely depend on an individual-specific threshold, caused by adaption to metabolic and excretory mechanisms.