Alkylresorcinols As Biomarkers of Whole-Grain Intake
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University of Rhode Island DigitalCommons@URI Open Access Master's Theses 2016 Alkylresorcinols as Biomarkers of Whole-Grain Intake Michael Robert MacArthur University of Rhode Island, [email protected] Follow this and additional works at: https://digitalcommons.uri.edu/theses Recommended Citation MacArthur, Michael Robert, "Alkylresorcinols as Biomarkers of Whole-Grain Intake" (2016). Open Access Master's Theses. Paper 858. https://digitalcommons.uri.edu/theses/858 This Thesis is brought to you for free and open access by DigitalCommons@URI. It has been accepted for inclusion in Open Access Master's Theses by an authorized administrator of DigitalCommons@URI. For more information, please contact [email protected]. ALKYLRESORCINOLS AS BIOMARKERS OF WHOLE-GRAIN INTAKE BY MICHAEL ROBERT MACARTHUR A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE IN NUTRITION AND FOOD SCIENCES UNIVERSITY OF RHODE ISLAND 2016 MASTER OF SCIENCE THESIS OF MICHAEL ROBERT MACARTHUR APPROVED: Thesis Committee: Major Professor: Ingrid Lofgren Cathy English Angela Slitt Nasser H. Zawia DEAN OF THE GRADUATE SCHOOL UNIVERSITY OF RHODE ISLAND 2016 ABSTRACT Background: In order to attenuate the measurement error inherent in dietary recall methods, alkylresorcinols (ARs) have been proposed as a biomarker of whole-grain (WG) intake (1, 2). Although ARs have shown promise in experimental (3) and observational studies (4), most of this research has been conducted in Nordic populations that consume relatively high amounts of WG (5). Objectives: The objectives of this study were to assess the utility of plasma AR concentration as a WG intake biomarker and identify the primary dietary and non- dietary determinants of plasma AR concentration in a population that consumes relatively few WG. Methods: This ancillary study used data from first-year college students (n=122) who completed three interviewer-administered 24-hour recalls and had two fasting venous blood draws performed on non-consecutive days. Dietary data was compiled using the Nutrition Data System for Research (6). Blood lipids and glucose were determined via enzymatic assay and plasma AR concentrations were determined by gas chromatography-mass spectrometry (7). Correlation coefficients (rs) were calculated between plasma AR concentrations and dietary intake variables and cardiometabolic risk factors. One-way ANOVA and Tukey’s post-hoc test were used to assess group differences across plasma AR quartiles. Determinants of plasma AR concentration were assessed using multiple regression models. Statistical analyses were performed using R version 3.2.3. Results: Plasma AR concentration was significantly positively correlated with WG intake (rs = 0.24, p <0.01). The correlation was stronger in males (n=36, rs = 0.33, p < 0.05) than females (n=86, rs = 0.18, p = 0.08). One-way ANOVA across plasma AR quartiles was significant for fiber intake [F(3,118) = 8.58, p < 0.001] and Tukey’s HSD test showed that the mean daily fiber intake for the highest AR quartile was significantly greater than for the lowest (M = 20.2 ± 1.9 g, 14.7 ± 1.4 g respectively). The only cardiometabolic risk factor that was significantly associated with plasma AR concentration was triglycerides (rs = 0.27, p < 0.01). Multiple regression models including log-transformed dietary variables showed that WG bread was the only significant food-item predictor of plasma AR concentration (β = 0.54, p < 0.01). Conclusions: Although plasma AR concentration was significantly associated with WG and fiber intake, triglycerides were the primary determinant and the relationships were not strong enough to produce accurate WG intake prediction models. More research is needed on the use of AR as a quantitative biomarker in low WG- consuming populations. ACKNOWLEDGEMENTS I would like to thank my major advisor Ingrid Lofgren for everything over the past two years. I am grateful for all that you’ve taught me and for your support during tough times. I would also like to thank all the NFS grad students for the support and fun times. We pulled each other through and your friendship means a lot. Thanks to the Lipid Lab undergraduate researchers for showing me the ropes when I first got to URI and for the invaluable help on all our projects, from data entry to Cholestech. Finally, I’d like to thank my family for the unconditional love and support that has kept me going throughout the program. iv TABLE OF CONTENTS ABSTRACT .................................................................................................................. ii ACKNOWLEDGEMENTS ........................................................................................ iv TABLE OF CONTENTS ............................................................................................. v LIST OF TABLES ...................................................................................................... vi LIST OF FIGURES ................................................................................................... vii MANUSCRIPT ............................................................................................................. 1 INTRODUCTION ...................................................................................................... 1 MATERIALS AND METHODS ............................................................................... 2 RESULTS ................................................................................................................... 5 DISCUSSION ............................................................................................................ 8 CONCLUSION ........................................................................................................ 11 ACKNOWLEDGEMENTS ..................................................................................... 12 TABLES AND FIGURES ........................................................................................ 13 REFERENCES ......................................................................................................... 23 APPENDIX A: LITERATURE REVIEW ............................................................... 28 BIBLIOGRAPHY ...................................................................................................... 76 v LIST OF TABLES Table 1: Demographics, biochemical and dietary descriptives ............................ 13 Table 2: Metabolic syndrome characteristics ....................................................... 14 Table 3: Correlation coefficients (rs) between plasma AR concentration and various measures of WG intake. ........................................................................... 18 Table 4: Correlation coefficients (rs) between WG and AR by gender ................ 19 Table 5: Participant characteristics by plasma AR concentration quartile and WG intake quartile agreement with plasma AR concentration quartile ....................... 21 Table 6: Food determinants of plasma AR concentration .................................... 22 vi LIST OF FIGURES Figure 1: Average WG intake by source .............................................................. 15 Figure 2: Average Concentration of total AR and AR homologues ..................... 16 Figure 3: Log total WG intake vs log total plasma AR concentration ................. 17 Figure 4: Correlation coefficients (rs) between plasma AR concentrations and WG intake measures in males and females .................................................................. 20 vii MANUSCRIPT INTRODUCTION Although the inverse association between whole-grain (WG) intake and chronic disease risk is well-established (1-3), a number of challenges still exist in assessing WG intake. These include systematic and random measurement errors inherent in dietary reporting tools (4, 5), and consumer confusion in identifying WG products and evaluating serving sizes (6, 7). To deal with these challenges and improve the detection of relationships between WG intake and disease, alkylresorcinols (ARs) have been proposed as an objective biomarker of WG intake (8-10). Alkylresorcinols are phenolic lipids consumed almost exclusively from wheat and rye bran (11), and are absorbed and metabolized after consumption with a plasma half-life of ~5h (8, 12, 13). Intervention (14-18) and free-living (9, 19-22) studies have shown that plasma AR concentration is a valid, dose-responsive biomarker of WG intake and has moderate reproducibility up to 4 months. Correlation coefficients range from 0.24 – 0.56 for the relationship between plasma AR and total WG, WG wheat, WG rye and fiber intakes. The correlation between plasma AR and WG intake may be stronger in groups that consume more WG. This was shown with both acute consumption in a controlled feeding trial (14) and habitual consumption in observational and long-term intervention studies (16, 20). Many of the studies testing AR as a WG intake biomarker have been done in Nordic populations (9, 17, 19-21, 23, 24) which have relatively high habitual WG intake and consume more rye-based WG which has a higher AR content by weight than wheat (25, 26). 1 Few studies have tested plasma AR as a WG intake biomarker in American populations which consume relatively few WG, and those WG are primarily from wheat (27). To be a universally valid WG intake biomarker, plasma AR concentration should also reflect WG intake in populations that consume few WG from primarily non-rye sources. In this study, we examined the relationship