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Assessing Repeated Urinary Proline Betaine Measures as a Biomarker of Usual Citrus Intake during Pregnancy: Sources of Within-Person Variation and Correlation with Reported Intake.

ABSTRACT: Proline betaine (Pro-B) has been identified as a biomarker of dietary citrus intake, yet gaps remain in its validation as a quantitative predictor of intake during various physiological states. This study quantified sources of within-individual variation (WIV) in urinary Pro-B concentration during pregnancy and assessed its correlation with the reported usual intake of citrus fruit and juice. Pro-B concentrations were determined by ¹H-NMR spectroscopy in spot and 24-h urine specimens (n = 255) collected throughout pregnancy from women participating in the MARBLES cohort study. Adjusted linear or log mixed effects models quantified WIV and tested potential temporal predictors of continuous or elevated Pro-B concentration. Pearson or Spearman correlations assessed the relationship between averaged repeated biomarker measures and usual citrus intake reported by food frequency questionnaires. The proportion of variance in urinary Pro-B attributable to WIV ranged from 0.69 to 0.74 in unadjusted and adjusted models. Citrus season was a significant predictor of Pro-B in most analyses (e.g., adjusted β [95% CI]: 0.52 [0.16, 0.88] for non-normalized Pro-B), while gestational age predicted only non-normalized Pro-B (adjusted β [95% CI]: -0.093 [-0.18, -0.0038]). Moderate correlations (r_s of 0.40 to 0.42) were found between reported usual citrus intake and averaged repeated biomarker measurements, which were stronger compared to using a single measurement. Given the high degree of WIV observed in urinary Pro-B, multiple samples per participant are likely needed to assess associations between citrus consumption and health outcomes.

SUBMITTER: French CD

PROVIDER: S-EPMC10456298 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Assessing Repeated Urinary Proline Betaine Measures as a Biomarker of Usual Citrus Intake during Pregnancy: Sources of Within-Person Variation and Correlation with Reported Intake.

French Caitlin D CD Arnold Charles D CD Taha Ameer Y AY Engle-Stone Reina R Schmidt Rebecca J RJ Hertz-Picciotto Irva I Slupsky Carolyn M CM

Metabolites 20230802 8

Proline betaine (Pro-B) has been identified as a biomarker of dietary citrus intake, yet gaps remain in its validation as a quantitative predictor of intake during various physiological states. This study quantified sources of within-individual variation (WIV) in urinary Pro-B concentration during pregnancy and assessed its correlation with the reported usual intake of citrus fruit and juice. Pro-B concentrations were determined by <sup>1</sup>H-NMR spectroscopy in spot and 24-h urine specimens ...[more]

PMID: 37623848

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Project description:BackgroundNew food biomarkers are needed to objectively evaluate the effect of diet on health and to check adherence to dietary recommendations and healthy eating patterns.ObjectiveWe developed a strategy for food biomarker discovery, which combined nutritional intervention with metabolic phenotyping and biomarker validation in a large-scale epidemiologic study.DesignWe administered a standardized diet to 8 individuals and established a putative urinary biomarker of fruit consumption by using (1)H nuclear magnetic resonance (NMR) spectroscopic profiling. The origin of the biomarker was confirmed by using targeted NMR spectroscopy of various fruit. Excretion kinetics of the biomarker were measured. The biomarker was validated by using urinary NMR spectra from UK participants of the INTERMAP (International Collaborative Study of Macronutrients, Micronutrients, and Blood Pressure) (n = 499) in which citrus consumption was ascertained from four 24-h dietary recalls per person. Finally, dietary patterns of citrus consumers (n = 787) and nonconsumers (n = 1211) were compared.ResultsWe identified proline betaine as a putative biomarker of citrus consumption. High concentrations were observed only in citrus fruit. Most proline betaine was excreted < or =14 h after a first-order excretion profile. Biomarker validation in the epidemiologic data showed a sensitivity of 86.3% for elevated proline betaine excretion in participants who reported citrus consumption and a specificity of 90.6% (P < 0.0001). In comparison with noncitrus consumers, citrus consumers had lower intakes of fats, lower urinary sodium-potassium ratios, and higher intakes of vegetable protein, fiber, and most micronutrients.ConclusionThe biomarker identification and validation strategy has the potential to identify biomarkers for healthier eating patterns associated with a reduced risk of major chronic diseases. The trials were registered at clinicaltrials.gov as NCT01102049 and NCT01102062.

Project description:Hybridization to a PCR product derived from conserved betaine choline carnitine transporter (BCCT) sequences led to the identification of a 3.4-kb Sinorhizobium meliloti DNA segment encoding a protein (BetS) that displays significant sequence identities to the choline transporter BetT of Escherichia coli (34%) and to the glycine betaine transporter OpuD of Bacillus subtilis (30%). Although the BetS protein shows a common structure with BCCT systems, it possesses an unusually long hydrophilic C-terminal extension (169 amino acids). After heterologous expression of betS in E. coli mutant strain MKH13, which lacks choline, glycine betaine, and proline transport systems, both glycine betaine and proline betaine uptake were restored, but only in cells grown at high osmolarity or subjected to a sudden osmotic upshock. Competition experiments demonstrated that choline, ectoine, carnitine, and proline were not effective competitors for BetS-mediated betaine transport. Kinetic analysis revealed that BetS has a high affinity for betaines, with K(m)s of 16 +/- 2 microM and 56 +/- 6 microM for glycine betaine and proline betaine, respectively, in cells grown in minimal medium with 0.3 M NaCl. BetS activity appears to be Na(+) driven. In an S. meliloti betS mutant, glycine betaine and proline betaine uptake was reduced by about 60%, suggesting that BetS represents a major component of the overall betaine uptake activities in response to salt stress. beta-Galactosidase activities of a betS-lacZ strain grown in various conditions showed that betS is constitutively expressed. Osmotic upshock experiments performed with wild-type and betS mutant cells, treated or not with chloramphenicol, indicated that BetS-mediated betaine uptake is the consequence of immediate activation of existing proteins by high osmolarity, most likely through posttranslational activation. Growth experiments underscored the crucial role of BetS as an emerging system involved in the rapid acquisition of betaines by S. meliloti subjected to osmotic upshock.

Project description:BackgroundMaintaining thyroid homeostasis during pregnancy is essential for normal fetal growth and development. Growing evidence suggests that phthalates interfere with normal thyroid function. Few human studies have investigated the degree to which phthalates may affect thyroid hormone levels in particularly susceptible populations such as pregnant women.ObjectivesWe examined the associations between repeated measures of urinary phthalate metabolites and plasma thyroid hormone levels in samples collected at up to four time points per subject in pregnancy. Additionally, we investigated the potential windows of susceptibility to thyroid hormone disturbances related to study visit of sample collection.MethodsData were obtained from pregnant women (n = 439) participating in a nested case-control study of preterm birth with 116 cases and 323 controls. We measured 9 phthalate metabolite concentrations in urine samples collected at up to four study visits per subject during pregnancy (median = 10, 18, 26, and 35 weeks of gestation, respectively). We also measured a panel of thyroid function markers in plasma collected at the same four time points per subject during pregnancy.ResultsAlthough our results were generally null, in repeated measures analyses we observed that phthalate metabolites were largely inversely associated with thyrotropin and positively associated with free and total thyroid hormones. Cross-sectional analyses by study visit revealed that the magnitude and/or direction of these relationships varied by timing of exposure during gestation.ConclusionsThese results support previous reports showing the potential for environmental phthalate exposure to alter circulating levels of thyroid hormones in pregnant women. Citation: Johns LE, Ferguson KK, McElrath TF, Mukherjee B, Meeker JD. 2016. Associations between repeated measures of maternal urinary phthalate metabolites and thyroid hormone parameters during pregnancy. Environ Health Perspect 124:1808-1815; http://dx.doi.org/10.1289/EHP170.

Dataset Information

Assessing Repeated Urinary Proline Betaine Measures as a Biomarker of Usual Citrus Intake during Pregnancy: Sources of Within-Person Variation and Correlation with Reported Intake.

Publications

Assessing Repeated Urinary Proline Betaine Measures as a Biomarker of Usual Citrus Intake during Pregnancy: Sources of Within-Person Variation and Correlation with Reported Intake.

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