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Metabolic profiling strategy for discovery of nutritional biomarkers: proline betaine as a marker of citrus consumption
Open accessAbstract
Background New food biomarkers are needed to objectively evaluate the effect of diet on health and to check adherence to dietary recommendations and healthy eating patterns.Objective We developed a strategy for food biomarker discovery, which combined nutritional intervention with metabolic phenotyping and biomarker validation in a large-scale epidemiologic study.Design We 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.Results We 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.Conclusion The 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.
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“Metabolites such as S-methyl-L-cysteine sulfoxide or proline betaine as biomarkers of cruciferous vegetables or citrus fruit, respectively, could be identified in NMR studies on the basis of their characteristic chemical shifts (Table 3) (80,84).”
From The food metabolome: a window over dietary exposure (2014) · cites this paper as [80]
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“For example, many studies have been conducted with oranges (Table 3), but a broad coverage of all citrus and many other fruit as well as kinetic studies have been necessary to interpret proline betaine as a short-term marker of citrus that is dominated by orange and orange juice intake (80).”
From The food metabolome: a window over dietary exposure (2014) · cites this paper as [80]
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Choi, P. M., Tscharke, B. J., Donner, E., O'Brien, J. W., Grant, S. C., Kaserzon, S. L., Mackie, R., O'Malley, E., Crosbie, N. D., Thomas, K. V., et al. (2018) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2018.06.004 · Cited by 486
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Metadata
- Authors
- Heinzmann, S. S., Brown, I. J., Chan, Q., Bictash, M., Dumas, M.-E., Kochhar, S., Stamler, J., Holmes, E., Elliott, P., & Nicholson, J. K.
- Affiliations
- Northwestern University (US)
- Corresponding author
- Elliott, Paul
- Nicholson, Jeremy K
- ORCID
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2010-08
- Volume
- 92
- Issue
- 2
- Pages
- 436-443
- ISSN
- 0002-9165 (ISSN-L)
- PMC
- PMC2904656
- OpenAlex
- W2120929142
- Cited by
- 271
- References
- 53
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 14 · 2023: 10 · 2022: 13 · 2021: 19 · 2020: 26 · 2019: 18 · 2018: 22 · 2017: 29 · 2016: 16 · 2015: 16 · 2014: 22 · 2013: 18 · 2012: 18
- FWCI
- 14.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL050490, R01HL50490, R01HL084228)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Health Sciences › Medicine › Biochemistry (medical) › Phytochemicals and Antioxidant Activities
- Keywords
- proline betaine, citrus consumption, urinary biomarkers, metabolic phenotyping, dietary adherence, excretion kinetics, dietary habits, fruit consumption, INTERMAP, healthy eating patterns
- MeSH terms
- Adult, Citrus, Diet, Female, Fruit, Humans, Male, Middle Aged, Magnetic Resonance Spectroscopy, Nutritional Status, Proline, Biomarkers, Multivariate Analysis, Plant Preparations
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