RESUMEN
Aims: Epidemiological studies that use dietary biomarkers to investigate the association between whole grain intake and the risk of obesity are sparse. We assessed the association between urinary alkylresorcinol metabolites including 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA) and 3,5-dihydroxybenzoic acid (DHBA), biomarkers of whole grain wheat and rye intake, and body fat measures. Methods: We measured urinary excretion of DHPPA and DHBA, body weight, height, and circumferences of the waist and hip at the baseline and again after 1-year in a representative sample of 306 community-dwelling adults in Huoshan, China. We also measured liver fat accumulation [indicated by the controlled attenuation parameter (CAP)] and other body composition after 1 year. Multivariate-adjusted linear models and linear mixed-effects models were used to analyze single measurement and repeated measurements, respectively. Results: Each 1 µg g-1 creatinine increase in urinary DHPPA levels was associated with 0.21%, 0.23%, 3.64%, and 4.80% decrease in body weight, body mass index (BMI), body fat mass (BFM) and visceral fat level (VFL), respectively (all P < 0.05). Higher DHBA levels were inversely associated with CAP (percentage difference per 1 µg g-1 creatinine increment: -1.98%, P < 0.05). Higher total urinary alkylresorcinol metabolite (DHPPA + DHBA) levels were associated with lower body weight, BMI, BFM, VFL, and CAP, with the percentage differences per 1 µg g-1 creatinine increment of -0.27%, -0.27%, -3.79%, -5.12%, and -2.24%, respectively (all P < 0.05). Conclusions: Our findings suggest that the intake of whole grain wheat and rye, reflected by urinary DHPPA and DHBA, is favorably associated with liver fat and other fat measures.
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Biomarcadores , Hígado , Resorcinoles , Secale , Triticum , Granos Enteros , Humanos , Secale/metabolismo , Triticum/metabolismo , Masculino , Femenino , Biomarcadores/orina , Persona de Mediana Edad , Resorcinoles/orina , Resorcinoles/metabolismo , Adulto , Hígado/metabolismo , Índice de Masa Corporal , China , Tejido Adiposo/metabolismo , Hidroxibenzoatos/orina , Hidroxibenzoatos/metabolismo , Propionatos/orina , Propionatos/metabolismo , Obesidad/metabolismo , Obesidad/orina , FenilpropionatosRESUMEN
High whole-grain consumption is related to better health outcomes. The specific physiological effect of these compounds is still unrevealed, partly because the accurate estimation of the intake of whole grains from dietary assessments is difficult and prone to bias, due to the complexity of the estimation of the intake by the consumer. A biomarker of whole-grain intake and type of whole-grain intake would be useful for quantifying the exposure to whole-grain intake. In this review, we aim to review the evidence on the potential biomarkers for whole-grain intake in the literature. We conducted a systematic search in Medline, Embase, Web of Science, and the Cochrane database. In total, 39 papers met the inclusion criteria following the PRISMA guidelines and were included. The relative validity, responsiveness, and reproducibility of these markers were assessed for short-, medium-, and long-term exposure as important criteria for the potential use of these biomarkers from a clinical and research perspective. We found three major groups of biomarkers: (1) alkylresorcinol, as well as its homologs and metabolites, assessed in plasma, adipose tissue biopsies, erythrocyte membranes, and urine; (2) avenacosides, assessed in urine samples; and (3) benzoxazinoid-derived phenylacetamide sulfates, assessed in blood and urine samples. The reviewed biomarkers may be used for improved assessment of associations between whole-grain intake and health outcomes.
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Benzoxazinas/sangre , Grano Comestible , Resorcinoles/sangre , Saponinas/orina , Granos Enteros , Adulto , Anciano , Avena , Benzoxazinas/orina , Biomarcadores/sangre , Biomarcadores/orina , Dieta , Fibras de la Dieta/administración & dosificación , Conducta Alimentaria , Femenino , Hordeum , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Resorcinoles/orina , Secale , TriticumRESUMEN
Resorcinol is a suspected endocrine disruptor that affects thyroid function by inhibiting thyroxin peroxidase. It may also have an impact on iodine uptake. Resorcinol has various uses; for example in the manufacture of rubber products and in wood adhesives, flame retardants, UV stabilizers, and dyes. It is also used in personal care products such as hair colorants, anti-acne preparations, and peels. The aim of this study was to assess both environmental background exposure and occupational exposure to resorcinol in Finland. We investigated occupational exposure in hairdresser work and in the manufacture of tyres, adhesive resins and glue-laminated timber by biomonitoring total resorcinol concentration in urine samples. The biomonitoring results were compared to the urinary levels of occupationally non-exposed volunteers, and to the biomonitoring equivalent (BE), which we estimated on the basis of the EFSA's acceptable daily intake (ADI) value for resorcinol. Almost all the urine samples (99%) of the non-occupationally exposed volunteers contained measurable amounts of resorcinol. The urinary resorcinol data were rather scattered, and the resorcinol concentrations among women (GM 84⯵g/l, 95th percentile 2072⯵g/l) were clearly higher than the respective concentrations among men (GM 35⯵g/l, 95th percentile 587⯵g/l). The reason for this difference remains unclear. Although the two highest results exceeded the BE of 4â¯mg/l calculated on the basis of the EFSA's ADI, the 95th percentile of the occupationally non-exposed volunteers' results remained well below the BE among both males and females. According to the results, hairdressers' exposure to resorcinol was at the same level as that of the reference population of occupationally non-exposed volunteers. All hairdresser's values remained below the BE for resorcinol. The urinary resorcinol levels of the industrial workers were also at the same level as those of the reference population. We observed slight increases in the post-shift and evening samples of those working in the manufacture of tyres and adhesive resins. The results of some workers in the tyre manufacturing company exceeded the 95th percentile of non-occupationally exposed males, which was used as a biological guidance value for occupational exposure. Moreover, in this case exposure was below the health-based biomonitoring equivalents. All the air samples collected in the companies contained very low resorcinol concentrations. It should be noted that the sample sizes for the male controls and industrial groups were small.
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Disruptores Endocrinos/orina , Exposición a Riesgos Ambientales , Salud Laboral , Resorcinoles/orina , Adulto , Anciano , Industria de la Belleza , Disruptores Endocrinos/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Monitoreo del Ambiente/métodos , Femenino , Finlandia , Humanos , Exposición por Inhalación/efectos adversos , Masculino , Industria Manufacturera , Persona de Mediana Edad , Exposición Profesional/efectos adversos , Reproducibilidad de los Resultados , Resorcinoles/efectos adversos , Medición de Riesgo , Urinálisis , Adulto JovenRESUMEN
BACKGROUND/OBJECTIVES: Studies on the health effects of whole grains typically use self-reported intakes which are prone to large measurement errors. Dietary biomarkers that can provide an objective measure of intake are needed. New alkylresorcinol (AR) metabolites (3,5-dihydroxycinnamic acid (DHCA), 2-(3,5-dihydroxybenzamido)acetic acid (DHBA-glycine) and 5-(3,5-dihydroxyphenyl) pentanoic acid (DHPPTA)) in 24 h urine samples have been suggested as biomarkers for whole grain (WG) wheat and rye intake but remain to be evaluated in spot urine samples. SUBJECTS/METHODS: The reproducibility of the new AR metabolites (DHCA, DHBA-glycine and DHPPTA) was investigated in 4 repeated samples over a period of 2 wk in spot urine from 40 Swedish men and women enroled in the SCAPIS-study, after adjustment of creatinine. Metabolite concentrations were correlated with total whole grain intake estimated during the same period. RESULTS: The medium-term reproducibility determined for DHCA, DHPPTA and DHBA-glycine varied from moderate to excellent (intra-class correlation coefficient = 0.35-0.67). Moreover, DHCA and DHBA-glycine were independently associated with self-reported total WG intake (ß = 0.18, P = 0.08 and ß = 0.18, P = 0.02, respectively) and all metabolites except for DHPPA were higher among women. CONCLUSIONS: This study supports the idea of using AR metabolites in one or several spot urine samples as biomarkers of whole grain intake. These findings need to be confirmed in different populations.
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Dieta , Fibras de la Dieta/administración & dosificación , Conducta Alimentaria , Resorcinoles/orina , Secale , Triticum , Granos Enteros , Biomarcadores/orina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , SueciaRESUMEN
SCOPE: Most studies on the role of whole grain for health rely on self-reported intake data, which are prone to measurement errors. There is a need for dietary biomarkers that can provide an objective measure of intake. Alkylresorcinols (AR) and their main metabolites 3,5-dihydroxybenzoic acid (DHBA) and 3-(3,5-dihydroxyphenyl)-propanoic acid (DHPPA) have been proposed as biomarkers for whole grain (WG) wheat and rye intake. METHODS AND RESULTS: The medium-term reproducibility and relative validity of four putative urinary AR metabolites (3,5-dihydroxycinnamic acid (DHCA), 5-(3,5-dihydroxyphenyl) pentanoic acid (DHPPTA), 2-(3,5-dihydroxybenzamido)acetic acid (DHBA-glycine) and 3,5-dihydroxycinnamic acid amide (DHCA-amide)) as biomarkers for WG intake were investigated. Three-day weighed food records and 24-h urine samples from two occasions 2-3 months apart were obtained from 69 Swedish adults. WG intake was calculated and urinary AR metabolites were analyzed. The medium-term reproducibility determined for DHCA, DHPPTA, and DHBA-glycine varied from moderate-to-excellent (intra-class correlation coefficient = 0.63-0.85). Moreover, DHCA and DHPPTA excretion correlated well with self-reported total WG intake (r = 0.55, p < 0.001 and r = 0.42, p < 0.001, respectively). CONCLUSION: DHCA or DHPPTA excretion in 24-h urine might be a suitable medium- to long-term biomarker of WG wheat and rye intake. These findings need to be confirmed in populations with low and infrequent WG intake.
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Cinamatos/orina , Fenilpropionatos/orina , Resorcinoles/farmacocinética , Granos Enteros , Adulto , Biomarcadores/orina , Femenino , Humanos , Hidroxibenzoatos/orina , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Resorcinoles/metabolismo , Resorcinoles/orina , Secale , Suecia , TriticumRESUMEN
Mounting evidence suggests that whole grain (WG) intake plays an important role in chronic disease prevention. However, numerous human studies have failed to produce clear-cut conclusions on this topic. Here, a combination of non-targeted and targeted metabolomics approaches, together with kinetic studies, was used to investigate biomarkers of WG wheat intake and further explore the diet-disease associations. Via these integrated approaches, forty-one compounds were identified as the most discriminating endogenous metabolites after WG versus refined grain (RG) wheat bread consumption. The corresponding biological assessment of these endogenous changes suggests that, in contrast to RG consumption, WG wheat consumption may facilitate antioxidant defense systems and moderate the risk factors of cancer, cardiovascular diseases, and other chronic diseases. A panel of urinary markers consisting of seven alkylresorcinol metabolites and five benzoxazinoid derivatives as specific biomarkers, as well as five phenolic acid derivatives, was also established to cover multiple time points and longer time periods for correctly and objectively monitoring WG wheat intake. Through these findings, we have established a comprehensive biomarker pool to better assess WG wheat consumption, and to monitor the endogenous changes that are linked to health effects of WG wheat consumption.
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Biomarcadores/orina , Dieta , Metabolómica/métodos , Triticum/metabolismo , Granos Enteros/metabolismo , Benzoxazinas/química , Benzoxazinas/metabolismo , Benzoxazinas/orina , Biomarcadores/metabolismo , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/orina , Enfermedad Crónica , Humanos , Hidroxibenzoatos/química , Hidroxibenzoatos/metabolismo , Hidroxibenzoatos/orina , Neoplasias/diagnóstico , Neoplasias/metabolismo , Neoplasias/orina , Resorcinoles/química , Resorcinoles/metabolismo , Resorcinoles/orinaRESUMEN
PURPOSE: Alkylresorcinols (AR) are phenolic lipids present in the bran of wheat and rye. Plasma AR and their urinary metabolites may be suitable biomarkers of whole-grain (WG) wheat and rye consumption. The objective of this study was to examine plasma AR and urinary AR metabolites in response to WG wheat consumption. METHODS: In a randomized crossover study, 19 subjects (10 males, 9 females; BMI 22.0 kg/m(2); age 26 years) incorporated either 3 servings (48 g) or 6 servings (96 g) of WG wheat daily into their regular diet for 1 week. Subjects completed a 2-week washout period, abstaining from all WG consumption, before each intervention. Fasting blood and 24-h urine were collected before and after each intervention. Plasma AR homologues (C19:0, C21:0, C23:0) were quantified by GC-MS after diethyl ether and solid phase extraction and derivatization. Urinary AR metabolites [3,5-dihydroxybenzoic acid and 3-(3,5-dihydroxyphenyl)-propanoic acid] were determined using HPLC with electrochemical detection after enzymatic deconjugation and ethyl acetate extraction. RESULTS: Urinary total AR metabolites were significantly higher after 6 compared with 3 servings of WG wheat (56 vs. 32 µmol/day, P < 0.001). This dose-response relationship was independent of age, sex, energy intake, and baseline urinary AR metabolite concentration. Plasma total AR tended to be higher after 6 compared with 3 servings of WG wheat (103.0 vs. 86.9 nmol/L), but this difference was not significant (P = 0.42). CONCLUSION: The results suggest that urinary AR metabolites from 24-h urine collections may be useful as biomarkers of compliance in intervention studies of WG wheat.
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Biomarcadores/sangre , Biomarcadores/orina , Dieta , Cooperación del Paciente , Resorcinoles/química , Granos Enteros , Adolescente , Adulto , Índice de Masa Corporal , Estudios Cruzados , Fibras de la Dieta/administración & dosificación , Femenino , Humanos , Hidroxibenzoatos/orina , Masculino , Fenilpropionatos/orina , Resorcinoles/orina , Secale , Triticum , Adulto JovenRESUMEN
Alkylresorcinols (ARs) are phytochemicals mainly associated with rye/wheat bran. Plasma ARs and their plasma and urine metabolites are considered as biomarkers for whole-grain rye/wheat intake. However ARs metabolite day and night variations have not been studied in prostate cancer patients yet. We investigated ARs metabolites 3, 5-dihydroxy-benzoic acid (DHBA), and 3-(3, 5-dihydroxyphenyl)-1-propanoic acid (DHPPA) in urine and plasma in prostate cancer patients and in control group. DHPPA in 12-h overnight urine correlated with the intake of rye bread and bread fiber across short time periods (3 days). Plasma DHPPA concentration was significantly greater in the prostate cancer group than in the control group. DHPPA and DHBA excretion was significantly higher in the overnight urine than in day urine in the prostate cancer group but not in the control group. DHPPA concentration in plasma in the prostate cancer group did not depend on the intake of rye bread in the previous day, suggesting an impaired metabolism of ARs metabolites in the prostate cancer group. The results of this study suggest DHPPA in 12-h overnight urine as a biomarker to estimate the intake of rye bread and bread fiber.
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Hidroxibenzoatos/sangre , Hidroxibenzoatos/orina , Fenilpropionatos/sangre , Fenilpropionatos/orina , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/orina , Resorcinoles/sangre , Resorcinoles/orina , Secale/metabolismo , Triticum/metabolismo , Anciano , Biomarcadores/sangre , Biomarcadores/orina , Pan , Estudios de Casos y Controles , Ritmo Circadiano , Fibras de la Dieta/metabolismo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Alkylresorcinols (ARs) are amphiphilic phenolic lipids and their two main metabolites, 3-(3,5-dihydroxyphenyl)-propanoic acid (DHPPA) and 3,5-dihydroxybenzoic acid (DHBA), can be used as biomarkers of whole grain wheat and rye intake. The aim of this study was to develop antibodies against DHBA and DHPPA for use in ELISA analysis. Good calibration curves were obtained for ELISA using alkaline phosphatase (AP) conjugates. The highest sensitivity for DHPPA was found using a reagent combination of anti-DHPPA-BSA and DHPAA-AP in a direct ELISA (IC50=1.5µmol/L), and for DHBA using a reagent combination of anti-DHBA-OV and DHBA-AP (IC50=1.3µmol/L). Calibration was conducted in the linear range (0.3-27.4µmol/L), with limit of detection (LOD) 0.1µmol/L. Intra and inter CVs was in the range of 0.7-7.2% and 5.1-11.5%, respectively, for DHPPA and 1.3-9.4% and 3.5-20%, respectively, for DHBA. Mean recovery was 104% for DHPPA and 102% for DHBA. The ELISA method developed was then used for analysis of 120 urine samples from free-living men and women that had previously been analysed by gas chromatography-mass spectrometry (GC-MS). ELISA produced several-fold higher values than GC-MS. Application of high-resolution Orbitrap mass spectrometry (HR Orbitrap MS) allowed several compounds, including novel putative AR metabolites, to be identified, synthesised and confirmed as compounds with high ELISA cross-reactivity.
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Anticuerpos/química , Carbohidratos de la Dieta/orina , Ensayo de Inmunoadsorción Enzimática/métodos , Hidroxibenzoatos/orina , Ácidos Fenilpirúvicos/orina , Resorcinoles/orina , Fosfatasa Alcalina/química , Animales , Calibración , Reacciones Cruzadas , Grano Comestible/metabolismo , Ensayo de Inmunoadsorción Enzimática/normas , Cromatografía de Gases y Espectrometría de Masas , Haptenos/química , Humanos , Límite de Detección , Conejos , Secale/metabolismo , Triticum/metabolismoRESUMEN
Biomarkers of dietary intake are prominent tools in nutritional research. The alkylresorcinol metabolites 3,5-dihydroxybenzoic acid (3,5-DHBA) and 3-(3,5-dihydroxyphenyl)propanoic acid (3,5-DHPPA) have been proposed as exposure biomarkers of whole-grain (WG) wheat and rye intake. However, the profile of alkylresorcinol metabolites is not fully understood. The aim of this study was to investigate the metabolism of alkylresorcinols in mice and in humans, while further determining urinary pharmacokinetics of the novel alkylresorcinol metabolites to explore their potential as biomarkers of WG wheat intake. Utilization of the liquid chromatography-mass spectrometry approach resulted in 10 alkylresorcinol metabolites identified in mice and in humans, including 3 phenolic acids and 7 of their phase II conjugates. Among them, 2 novel metabolites were discovered: 5-(3,5-dihydroxyphenyl)pentanoic acid (3,5-DHPPTA) and 2-(3,5-dihydroxybenzamido)acetic acid (3,5-DHBA glycine). The structures of these 2 metabolites were confirmed by comparing with authentic standards synthesized in-house. In the pharmacokinetic study, a group of 12 volunteers consumed a polyphenolic-restricted diet for 4 d before ingesting WG wheat bread containing 61 mg of alkylresorcinols. Urine samples were collected for 32 h, and alkylresorcinol metabolites were quantified with HPLC-coulometric electrode array detection. The mean urinary excretion rates and mean apparent half-life of 3,5-DHPPTA, 3,5-DHBA glycine, 3,5-DHBA, and 3,5-DHPPA at each time point were determined. Our results suggest that 3,5-DHPPTA and 3,5-DHBA glycine may be used in combination with 3,5-DHBA and 3,5-DHPPA as potential biomarkers to increase the accuracy of recording WG wheat and rye intake in epidemiologic studies. Further validation of 3,5-DHPPTA and 3,5-DHBA glycine as potential biomarkers is warranted.
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Biomarcadores/orina , Dieta , Preparaciones de Plantas/farmacocinética , Resorcinoles/orina , Secale , Triticum , Acetatos/metabolismo , Acetatos/orina , Adulto , Animales , Cromatografía Líquida de Alta Presión , Grano Comestible , Femenino , Humanos , Hidroxibenzoatos/metabolismo , Hidroxibenzoatos/orina , Masculino , Ratones , Ratones Endogámicos C57BL , Estructura Molecular , Ácidos Pentanoicos/metabolismo , Ácidos Pentanoicos/orina , Fenilpropionatos/metabolismo , Fenilpropionatos/orina , Preparaciones de Plantas/metabolismo , Polifenoles/administración & dosificación , Resorcinoles/metabolismo , SemillasRESUMEN
Alkylresorcinols (AR) have been established as short/medium-term biomarkers for whole grain (WG) wheat and rye intake; and AR metabolites, 3,5-dihydroxybenzoic acid and 3-(3,5-dihydroxyphenyl)-propanoic acid, have been suggested as complementary biomarkers to AR. The present study examined the medium-term reproducibility and relative validity of urinary AR metabolites as biomarkers for WG and cereal fibre intake. A total of sixty-six free-living Swedes completed 3 d weighed food records and provided single 24 h urine collections and morning urine spot samples on two occasions, 2-3 months apart. The medium-term reproducibility of urinary AR metabolites was moderate when assessed in 24 h collections and lower in creatinine (CR)-adjusted morning urine. Mean AR metabolite 24 h excretions correlated well with total WG (r(s) 0·31-0·52, P < 0·05) and cereal fibre (r(s) 0·46-0·58, P < 0·001) intake on both occasions. As expected, correlations with WG (r(s) 0·28-0·38, P < 0·05) and cereal fibre (r(s) 0·35-0·42, P < 0·01) were weaker for mean CR-adjusted AR metabolite concentrations in spot samples of morning urine, although the adjusted concentrations correlated well with 24 h urinary excretion (r(s) 0·69-0·73, P < 0·001). Adjustment for intra-individual variations substantially improved the correlations between intake and excretion. These findings suggest that urinary AR metabolites can successfully reflect the medium-term intake of WG and cereal fibre when adjusted for intra-individual variation in this population, where rye was the major contributor to high WG intake. The performance of urinary AR metabolites as medium-term biomarkers appears to be comparable to that of fasting plasma AR concentration in this population.
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Fibras de la Dieta/metabolismo , Grano Comestible/metabolismo , Resorcinoles/orina , Adulto , Algoritmos , Alquilación , Biomarcadores/orina , Creatinina/orina , Registros de Dieta , Fibras de la Dieta/administración & dosificación , Grano Comestible/química , Femenino , Manipulación de Alimentos , Humanos , Hidroxibenzoatos/metabolismo , Hidroxibenzoatos/orina , Masculino , Persona de Mediana Edad , Fenoles/metabolismo , Fenoles/orina , Fenilpropionatos , Propionatos/metabolismo , Propionatos/orina , Reproducibilidad de los Resultados , Resorcinoles/metabolismo , Secale/química , Suecia , Factores de TiempoRESUMEN
The urinary alkylresorcinol (AR) metabolites, 3,5-dihydroxybenzoic acid (DHBA) and 3-(3,5-dihydroxyphenyl)-propanoic acid (DHPPA), could potentially serve as biomarkers for intake of whole-grain (WG) wheat and rye. Excretion of AR metabolites is largely dependent on the intake of AR but may also be influenced by other factors. This study aimed to investigate the validity of free and conjugated AR metabolites as biomarkers for WG intake of wheat and rye and to identify potential determinants of AR metabolites in urine. We quantified free aglycones and conjugates of AR metabolites in 24-h urine collections from 52 free-living Swedish adults and calculated correlation coefficients between urinary AR metabolite excretion and self-reported WG intake. We used partial least-squares regression to identify possible determinants of urinary AR metabolites. Approximately 50% of urinary AR metabolites were found as conjugates. Excretions of individually quantified free and conjugated AR metabolites and their sums were correlated to self-reported intake of WG rye and wheat (r = 0.50-0.68; P < 0.001). Excretion of urinary AR metabolites was mainly dependent on intake of 2 major dietary AR homologs, C19:0 and C21:0. Sex, BMI, and vitamin C intake were identified as determinants of the proportion of free and glucuronidated DHPPA in the present study. Urinary AR metabolites may be useful in reflecting short-term to medium-term intake of WG, but urine samples should be deconjugated prior to quantification. Anthropometric and dietary factors affecting the proportion of conjugated AR metabolites in urine may to some extent influence AR elimination and thereby the performance of urinary AR metabolites as biomarkers.
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Resorcinoles/metabolismo , Resorcinoles/orina , Secale , Triticum , Adolescente , Adulto , Anciano , Ácido Ascórbico/administración & dosificación , Ácido Ascórbico/farmacología , Biomarcadores , Índice de Masa Corporal , Fibras de la Dieta , Femenino , Análisis de los Alimentos , Humanos , Masculino , Persona de Mediana Edad , Factores Sexuales , Suecia , Adulto JovenRESUMEN
Two alkylresorcinol (AR) metabolites, 3, 5-dihydroxybenzoic acid (DHBA) and 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), in urine have been suggested as biomarkers of whole grain (WG) and cereal fiber intake but the long-term reproducibility and correlation with habitual intake has not been determined. Therefore, we evaluated the long-term reproducibility of AR metabolites in spot urine samples and investigated their correlation with habitual WG and cereal fiber intake in U.S. women. AR metabolites were analyzed in 104 women participating in the Nurses' Health Study II and WG and fiber intakes were assessed using a FFQ. Long-term reproducibility was assessed by calculating the intra-class correlation coefficients (ICC) using samples taken 1-3 y (mean 1.8 y) apart. The observed Spearman correlation coefficients (r(s)) and r(s) adjusted for within-participant variation in the biomarker were calculated between WG and fiber intake and biomarkers. The long-term reproducibility was poor for DHBA [ICC = 0.17 (95% CI: 0.05, 0.43)] and modest for DHPPA [ICC = 0.31 (95% CI: 0.17, 0.51)]. The correlation between WG intake in 1995 and DHPPA measured 2 y later was 0.37 (P < 0.0001); the adjusted correlation was 0.60 (95% CI: 0.37, 0.76). Cereal fiber and WG intake were similarly correlated to the biomarkers. DHPPA in spot urine samples reflected WG intake despite relatively low intake of food sources of AR. The poor to modest reproducibility may limit the use of single measurements of these biomarkers in cohort studies in the US, where WG intake is relatively low and has changed over time. But DHPPA in repeated samples may be useful for validating WG intake and assessing compliance in WG intervention studies.
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Catecoles/orina , Fibras de la Dieta/administración & dosificación , Grano Comestible , Evaluación Nutricional , Ácidos Fenilpirúvicos/orina , Resorcinoles/orina , Adulto , Biomarcadores/orina , Índice de Masa Corporal , Química Clínica/normas , Femenino , Humanos , Hidroxibenzoatos , Reproducibilidad de los Resultados , Factores de Riesgo , Encuestas y Cuestionarios , Estados Unidos/epidemiologíaRESUMEN
Wholegrain cereals are reported to promote beneficial health effects. Wholegrain wheat and rye are almost exclusive sources of alkylresorcinols, and intact alkylresorcinols together with their plasma and urinary metabolites, 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA) and 3,5-dihydroxybenzoic acid (DHBA), have been proposed as biomarkers of the intake of these foods in humans. The pharmacokinetics of alkylresorcinols and their metabolites in plasma have been determined but not that of the urinary metabolites. We aimed to characterise the urinary pharmacokinetics of alkylresorcinol metabolites in humans to evaluate their potential as biomarkers of wholegrain wheat and rye. A group of fifteen volunteers followed a low-alkylresorcinol diet for 2 d before ingesting a single dose of rye bread, containing 100 mg alkylresorcinols. Urine was collected between baseline (0 h) and 25 h after administration. Thereafter alkylresorcinol metabolites were quantified by HPLC with coulometric electrode array detection. Maximum excretion rates were observed at 5-6 h for both metabolites, DHPPA being predominant over DHBA and also possessing a greater area under the curve0-25 h. Total urinary recovery between 0 and 25 h yielded 43 % of ingested alkylresorcinols, and at 25 h significant amounts of metabolites were still retained in the body, suggesting that even a spot urine sample may be sufficient to indicate whether or not wholegrain wheat or rye is a daily dietary component. These results support the use of urinary DHPPA and DHBA as biomarkers of wholegrain wheat and rye and enable new potential for studying the association between wholegrain intake and diseases, even in the absence of dietary data.
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Catecoles/farmacocinética , Catecoles/orina , Propionatos/farmacocinética , Propionatos/orina , Resorcinoles/farmacocinética , Secale/química , Adulto , Biomarcadores/orina , Pan/análisis , Catecoles/química , Catecoles/metabolismo , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Hidroxibenzoatos , Masculino , Fenoles , Fenilpropionatos , Propionatos/química , Propionatos/metabolismo , Resorcinoles/administración & dosificación , Resorcinoles/orina , Adulto JovenRESUMEN
Alkylresorcinols (AR) are amphiphilic compounds present at high concentrations in the outer parts of wheat and rye kernels. Due to their specificity to whole grain and bran products of these cereals, AR and their metabolites have been proposed as biomarkers for intake of such foods. Two alkylresorcinol metabolites, 3,5-dihydroxybenzoic acid (DHBA) and 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), have previously been quantified in human urine using two different methodologies: high-performance liquid chromatography coupled to a coulometric electrode array detector (HPLC-CEAD) and gas chromatography in combination with mass spectrometry (GC-MS). In this study, these two methodologies were compared by analysing 114 urine samples from free-living Swedish subjects consuming their habitual diet. Data were evaluated by graphical investigation of difference-plots and statistical inference of agreement was assessed by weighted Deming regression analysis. The median DHBA concentrations were 11 µM (GC-MS) and 13 µM (HPLC-CEAD), respectively. Both difference-plot and regression analysis showed a small but statistically significant additive bias, with HPLC-CEAD resulting in a slightly higher DHBA concentration than GC-MS. The median concentration of DHPPA was 18 µM for both methods. Examination of the difference-plot of DHPPA did not indicate any systematic difference between the methods, but regression analysis showed small but statistically significant constant and proportional biases. The conclusion was that the two methodologies are equally suitable for analysis of alkylresorcinol metabolites in human urine and that any small systematic differences observed are most likely of limited practical importance.
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Cromatografía Líquida de Alta Presión/métodos , Cromatografía de Gases y Espectrometría de Masas/métodos , Hidroxibenzoatos/orina , Propionatos/orina , Resorcinoles/orina , Dieta , Electroquímica/métodos , Electrodos , Femenino , Humanos , Hidroxibenzoatos/metabolismo , Masculino , Fenoles , Fenilpropionatos , Propionatos/metabolismo , Análisis de RegresiónRESUMEN
It has been demonstrated that intact plasma alkylresorcinols (AR) and urinary AR metabolites could be used as biomarkers of whole-grain intake. Thereafter, we developed the method for the plasma AR metabolites, which is more convenient and requires less sample pretreatment than the analysis of intact plasma AR. The aim of the present study is to evaluate whether AR metabolites measured in plasma, in the same population, could also be considered as useful biomarkers of cereal fibre. Fifty-six women were recruited in a cross-sectional and observational study. Dietary intake (5-d record) and plasma AR metabolites (3,5-dihydroxybenzoic acid, DHBA; 3-(3,5-dihydroxyphenyl)-1-propanoic acid, DHPPA) were measured. The relationship between plasma AR metabolites and cereal fibre intake was examined using partial correlation and stepwise regression. Cereal fibre intake correlated significantly with plasma DHBA (r 0.411; P = 0.002) and DHPPA (r 0.463; P = 0.000) even after adjustment for BMI and age. Thus, plasma AR metabolites correlate with cereal fibre intake as noted with plasma intact AR and urinary AR metabolites. We observed that plasma DHPPA was the independent predictor of cereal fibre intake, explaining 18 % of the variance (adjusted r(2) 0.176; P = 0.002). In epidemiological screening, it might be easier to obtain and to collect plasma than urine samples. In addition, the plasma AR metabolites half-life seems longer than those of intact plasma AR, and their measurements are more convenient, and faster. Thus, sum of plasma AR metabolites and more specifically plasma DHPPA seems to be good and specific biomarkers of cereal fibre intake.
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Fibras de la Dieta , Grano Comestible , Resorcinoles/sangre , Adulto , Biomarcadores/sangre , Biomarcadores/orina , Índice de Masa Corporal , Ingestión de Energía , Femenino , Frutas , Humanos , Persona de Mediana Edad , Propionatos/sangre , Propionatos/orina , Resorcinoles/orina , Secale , Triticum , VerdurasRESUMEN
BACKGROUND: Alkylresorcinols (ARs), phenolic lipids almost exclusively present in the outer parts of wheat and rye grains in commonly consumed foods, have been proposed as specific dietary biomarkers of whole-grain wheat and rye intakes. OBJECTIVE: The objective was to assess the dose response of plasma ARs and the excretion of 2 recently discovered AR metabolites in 24-h urine samples in relation to AR intake and to establish a pharmacokinetic model for predicting plasma AR concentration. DESIGN: Sixteen subjects were given rye bran flakes containing 11, 22, or 44 mg total ARs 3 times daily during week-long intervention periods separated by 1-wk washout periods in a nonblinded randomized crossover design. Blood samples were collected at baseline, after the 1-wk run-in period, and after each treatment and washout period. Two 24-h urine samples were collected at baseline and after each treatment period. RESULTS: Plasma AR concentrations and daily excretion of 2 urinary AR metabolites increased with increasing AR dose (P < 0.001). Recovery of urinary metabolites in 24-h samples decreased with increasing doses from approximately 90% to approximately 45% in the range tested. A one-compartment model with 2 absorption compartments with different lag times and absorption rate constants adequately predicted plasma AR concentrations at the end of each intervention period. CONCLUSION: Both plasma AR concentrations and urinary metabolites in 24-h samples showed a dose-response relation to increased AR intake, which strongly supports the hypothesis that ARs and their metabolites may be useful as biomarkers of whole-grain wheat and rye intakes.
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Fibras de la Dieta/administración & dosificación , Resorcinoles/administración & dosificación , Resorcinoles/farmacocinética , Secale/química , Triticum/química , Adulto , Biomarcadores/sangre , Biomarcadores/orina , Creatinina/orina , Estudios Cruzados , Dieta , Relación Dosis-Respuesta a Droga , Conducta Alimentaria , Femenino , Humanos , Masculino , Cooperación del Paciente , Resorcinoles/sangre , Resorcinoles/orinaRESUMEN
Alkylresorcinols (AR) could be good biomarkers of consumption of fiber-rich cereal products. The aim of this study was to examine the relationship between plasma ARs or urinary AR metabolites and cereal fiber intake in women consuming their habitual diet. Twenty-five postmenopausal and 31 premenopausal women were recruited. The subjects included also vegetarians (n = 20) to obtain a broad range of cereal intake. Dietary intake, plasma ARs, and urinary AR metabolites [3,5-dihydroxybenzoic acid and 3-(3,5-dihydroxyphenyl)-1-propanoic acid] were measured. Pearson's and Partial correlation tests were done between dietary fiber intake and plasma ARs or urinary AR metabolites. Cereal fiber intake correlated significantly with plasma AR C17:0 (r = 0.387), AR C19:0 (r = 0.350), AR C21:0 (r = 0.428), AR C23:0 (r = 0.409), AR C25:0 (r = 0.283), and total AR (r = 0.406) and with urinary AR metabolites DHBA (r = 0.359) and DHPPA (r = 0.402) even after adjustment for body mass index and age, which could be confounding variables. This is the first study to show a significant correlation between plasma ARs or urinary AR metabolites and cereal fiber intake during consumption of a habitual diet. These results indicate that assay of plasma ARs or urinary AR metabolites may be used as biomarkers in epidemiologic studies in free-living populations to evaluate the role of cereal fiber intake in various diseases.
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Fibras de la Dieta/metabolismo , Grano Comestible/metabolismo , Resorcinoles/sangre , Resorcinoles/orina , Biomarcadores/sangre , Biomarcadores/orina , Femenino , Finlandia , Humanos , Modelos Lineales , Persona de Mediana EdadRESUMEN
An RP-HPLC method for the determination of four phenolic compounds: gallic acid (GA), pyrogallol (PY), resorcinol (RE) and ellagic acid (EA), derived from hydrolysable tannins is reported. Separation was achieved on a SunFire C18 (250 x 4.6 mm id, 5 microm) column at 40 degrees C with gradient elution. UV detection at 280 nm was applied. The developed method was validated in terms of linearity, accuracy and precision. Satisfactory repeatability and between day precision were noticed with RSD values lower than 3%. Recoveries from different biological samples ranged from 91.50 to 105.25%. The LODs were estimated as 1.70 mg/L for PY, 1.68 mg/L for GA, 1.52 mg/L for RE and 0.98 mg/L for EA with a 20 microL injection volume. The method was applied for the determination of these compounds in oak leaves and in ruminal fluid and urine samples taken from beef cattle fed with oak leaves. The proposed method could be used in ruminant nutrition studies to verify the effect that a diet rich in tannins have on ruminal fermentation and to determine the toxicity of these compounds.