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New alkylresorcinol metabolites

identification, quantification and evaluation as dietary biomarkers

Wierzbicka, Roksana (2017). New alkylresorcinol metabolites. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., Acta Universitatis agriculturae Sueciae, 1652-6880 ; 2017:20
ISBN 978-91-576-8813-2
eISBN 978-91-576-8814-9
[Doctoral thesis]

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Abstract

Alkylresorcinols (AR) are amphiphilic phenolic lipids that are extensively metabolized in the liver and form metabolites that can be detected in plasma and urine. Two AR metabolites, 3,5-dihydroxybenzoic acid (DHBA) and 3-(3,5-dihydroxyphenyl)-propanoic acid (DHPPA), have been evaluated as urinary biomarkers of whole grain wheat and rye intake. AR metabolite concentrations are currently measured by chromatographic techniques but for samples from large epidemiological studies, immunoassay techniques are preferred due to rapid and cheap analysis. The aim of this thesis was to develop high-throughput analytical methods for the analysis of alkylresorcinol metabolites and to evaluate recently discovered putative metabolites 3,5-dihydroxycinnamic acid (DHCA), 5-(3,5-dihydroxyphenyl) pentanoic acid (DHPPTA), 3,5-dihydroxycinnamic acid amide (DHCA-amide) and 2-(3,5-dihydroxybenzamido) acetic acid (DHBA-glycine) as biomarkers of whole grain wheat and rye intake.

Polyclonal antibodies against DHBA and DHPPA were produced and characterized in terms of cross-reactivity, assay sensitivity, precision and accuracy. A developed ELISA method was used for analysis of urine samples and results were compared with GC-MS. A lack of agreement was found. Several putative AR metabolites were identified by LC-MS/MS, including DHPPTA, DHCA, DHBA-glycine and DHCA-amide. These compounds showed high cross reactivity in ELISA and likely explains the lack of agreement between the two methods.

The medium-term reproducibility and relative validity of DHCA, DHPPTA and DHBA-glycine were found to be moderate to excellent in 24h urine collections. Moreover, the reproducibility was good for these metabolites also in spot-urine samples. Age and sex were found to be important determinants besides whole grain intake. The results suggest that determination of AR metabolites in 24h urine and single or duplicate spot urine samples appear to be suitable medium to long-term biomarkers of whole grain wheat and rye intake. These findings need to be confirmed in other populations before using these biomarkers in epidemiological studies.

Authors/Creators:Wierzbicka, Roksana
Title:New alkylresorcinol metabolites
Subtitle:identification, quantification and evaluation as dietary biomarkers
Series/Journal:Acta Universitatis agriculturae Sueciae (1652-6880)
Year of publishing :2 February 2017
Volume:2017:20
Number of Pages:80
Papers/manuscripts:
NumberReferences
I.Wierzbicka, R., Eyer, L, Landberg, R., Kamal-Eldin, A. & Franek, M. (2014). Development of antibodies for determination of alkylresorcinol metabolites in human urine and elucidation of ELISA cross-reactivity. Journal of Immunological Methods 413, 12-24.
II.Wierzbicka, R., Wu, H., Franek, M., Kamal-Eldin, A. & Landberg, R. (2015). Determination of alkylresorcinols and their metabolites in biological samples by gas chromatography-mass spectrometry. Journal of Chromatography B, 1000, 120-9.
III.Wierzbicka, R., Zamaratskaia, G., Kamal-Eldin, A. & Landberg, R. Novel urinary alkylresorcinol metabolites as biomarkers of whole grain intake in free-living Swedish adults (submitted).
IV.Landberg, R., Wierzbicka, R., Shi, L., Nybacka, S., Kamal-Eldin, A., Hedblad, B., Lindroos, A.K., Winkvist, A. & Bertéus Forslund. H.New alkylresorcinol metabolites in spot urine as biomarkers of whole grain wheat and rye intake in a Swedish middle-aged population(manuscript).
Place of Publication:Uppsala
Publisher:Department of Molecular Sciences, Swedish University of Agricultural Sciences
ISBN for printed version:978-91-576-8813-2
ISBN for electronic version:978-91-576-8814-9
ISSN:1652-6880
Language:English
Publication Type:Doctoral thesis
Full Text Status:Public
Agris subject categories.:S Human nutrition > S01 Human nutrition - General aspects
Subjects:(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Immunology (Immunology in the medical area to be 30110)
Agrovoc terms:alkylresorcinols, metabolites, food intake, digestive absorption, grain, phenolic acids, antibodies, elisa, analytical methods
Keywords:Alkylresorcinol, ELISA, antibodies, dietary biomarker, AR metabolites, whole grain
URN:NBN:urn:nbn:se:slu:epsilon-e-3922
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-3922
ID Code:14017
Faculty:NJ - Fakulteten för naturresurser och jordbruksvetenskap
Department:(NL, NJ) > Department of Molecular Sciences
Deposited By: MSC Roksana Wierzbicka
Deposited On:03 Feb 2017 14:33
Metadata Last Modified:06 Feb 2017 12:07

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