Alkylresorcinol metabolites as potential biomarkers for whole-grain rye intake and the effect of rye bread intake on plasma low-density lipoproteins

Nestled in the research field exploring the protective mechanisms of whole grains against cardiovascular disease (CVD), this thesis focuses on two novel candidate biomarkers for whole-grain rye/wheat intake and the effect of rye bread intake on plasma low-density lipoproteins (LDLs). A special emphasis is on alkylresorcinols, which are rye- and wheat bran-associated phytochemicals. Alkylresorcinols are absorbed in humans, and their plasma concentration is suggested to serve as a biomarker for whole-grain rye/wheat intake. Following absorption, alkylresorcinols are metabolized in the liver to 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA) and 3,5-dihydroxy-benzoic acid (DHBA), which have been identified in plasma and urine. \n\nHere, we have determined the kinetic parameters for DHPPA and DHBA in plasma and urine from 15 humans after ingesting a single serving of rye bread (6 slices, 198 g). We showed that DHPPA and DHBA possess good biomarker properties with longer half-lives (t1/2) than intact alkylresorcinols. This can result in higher fasting plasma concentrations than those for alkylresorcinols, which is advantageous when blood samples from low-to-moderate whole-grain rye consumers are being analyzed. \n\nAlkylresorcinols possess antioxidant activity in in vitro assays, although human data are lacking. Because LDL particles serve as carriers of alkylresorcinols in human circulation, and oxidative modification of LDL has been linked to atherogenesis, we aimed to study the potential of alkylresorcinols to protect LDL particles against oxidation. We also determined the efficacy of added plant sterols (PSs) in rye bread to lower LDL cholesterol (LDL-C), a known risk factor for CVD. \n\nWe explored with a dietary intervention the effects of rye bread intake on plasma LDL by varying the rye bread dose from 0 g/d (baseline) to 99 g/d, and finally to 198 g/d. Rye bread was consumed without (n=31, controls) or with added PSs (n=32). Intake of 198 g/d of rye bread significantly (P PIENEMPI 0.001) increased oxidation resistance and alkylresorcinol contents of LDL from baseline. However, alkylresorcinol concentration did not correlate with the oxidation resistance of LDL. Therefore, alkylresorcinols are presumably not the major causative antioxidants in LDL, and their role remains unclear. Compared with controls, the PS group exhibited similar improvements in the oxidation resistance of LDL, but showed a significant decrease in LDL-C and some other lipid risk factors, suggesting that PS enrichment further increased the health benefits of whole-grain rye. \n\nIn summary, this thesis characterizes the kinetics of DHPPA and DHBA and supports their suitability as biomarkers for whole-grain rye intake. Moreover, rye bread intake was shown to significantly increase in vitro oxidation resistance of LDL, and, when enriched with PSs, to also lower plasma LDL-C, providing a promising dietary means for prevention of CVD.

Topic: Food composition and properties
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences