Daily Variation and Effect of Dietary Folate on Urinary Pteridines


Introduction: Urinary pteridines are putative molecular biomarkers for noninvasive cancer screening and prognostication. Central to their translational biomarker development is the need to understand the sources and extent of their non-epidemiological variation. Objectives: This study was designed to characterize the two primary sources of urinary pteridine variance: daily variation and the effect of dietary folate. Methods: Daily variation was studied by collecting urine specimens (n = 81) three times daily for 3 days. The effect of dietary folate was investigated in a treatment study in which urine specimens (n = 168) were collected daily during a control week and a treatment week during which participants received dietary folate supplements. Measurements of six urinary pteridines were made using high-performance liquid chromatography–tandem mass spectrometry. Coefficients of variation were calculated to characterize daily variance between and within subjects, while nearest neighbor non-parametric analyses were used to identify diurnal patterns and measure dietary folate effects. Results: Daily variance was approximately 35 % RSD for both within-day and between-day periods for most pteridines. Diurnal patterns in response to circadian rhythms were similarly observed for urinary pteridines. Folate supplementation was shown to alter urinary pteridine profiles in a pathway dependent manner, suggesting that dietary folate may regulate endogenous neopterin and biopterin biosynthesis. Conclusions: Urinary pteridine levels were found to be responsive to both daily variation and folate supplementation. These findings provide new insights into pteridine biosynthesis and regulation as well as useful information for the design of future clinical translational research.



Keywords and Phrases

6 Carboxypterin; Biopterin; Folic Acid; Isoxanthopterin; Neopterin; Pteridine; Pterin; Unclassified Drug; Vitamin; Xanthopterin; Adult; Circadian Rhythm; Controlled Study; Daily Variation; Data Processing; Diet; Diet Supplementation; Female; Freeze Thawing; High Performance Liquid Chromatography; Human; Limit Of Detection; Limit Of Quantitation; Male; Normal Human; Questionnaire; Relative Density; Signal Transduction; Tandem Mass Spectrometry; Urinalysis

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Article - Journal

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© 2016 Springer New York, All rights reserved.

Publication Date

01 May 2016