OPTIMAL-D · Development and Application of Mass Spectrometry Methods for Analysis of Optimal Vitamin D
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-10-15 → 2023-04-15
- EU contribution
- €277,940
- Participants
- 2
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Development and Application of Mass Spectrometry Methods for Analysis of Optimal Vitamin D
Vitamin D deficiency is highly prevalent across European communities and globally. Deficiency of vitamin D is linked with multiple health and social issues across all communities, including bone health and immune functions. Despite the clear importance of optimal vitamin D levels, analysis of vitamin D status and deficiency has continued to rely on measurements of a single inactive vitamin D precursor metabolite; 25-hydroxyvitamin D as the sole biomarker. However, vitamin D undergoes complex metabolism, transport and distribution with many metabolites formed throughout its metabolic pathways that have varying biological actions, or unknown actions. OPTIMAL-D aims to establish state-of-the art mass spectrometry analytical methods to characterise vitamin D status in human populations across different health settings, and identify unique biomarkers of vitamin D linked with health and disease. The project outcomes are expected to lead to important benefits for society by reducing the possible health implications of vitamin D deficiency. The outputs from OPTIMAL-D include the development of novel liquid chromatography tandem mass spectrometry methods to simultaneously measure multiple vitamin D metabolites across different biological sample matrices. Translational applications of these methods to health and population studies have achieved novel reference levels and provided context to under investigated vitamin D pathways. This includes analysis revealing that conjugated forms of vitamin D, including 25-hydroxyvitamin D circulate at high concentrations that may have important biological storage and reservoir functions. The application of mass spectrometry methods to observational cohorts have revealed differences in circulating vitamin D metabolism following supplementation of vitamin D. Furthermore, different associations have been found between individual vitamin D metabolites and skeletal health during ageing. The overall conclusions from these findings have highlighted the complex metabolic pathways and the impact of vitamin D sufficiency and deficiency across different population groups and health settings. Further conclusions are that the biological impact of vitamin D can be more accurately assessed by integrating multiple metabolite measurements beyond 25-hydroxyvitamin D. The developed and validated analytical methods established from this project are expected to contribute towards future healthcare tools to monitor vitamin D and guide future policies for supplementation strategies for reducing deficiency and to optimise vitamin D treatment in individuals.
Data: CORDIS, © European Union
Project objective
Vitamin D has well-recognised actions on the skeleton, but also exerts potent effects on extra-skeletal tissues. Current approaches to measure vitamin D almost exclusively rely on measuring a single, inactive vitamin D metabolite – 25-hydroxyvitamin D. However, vitamin D undergoes complex metabolism that may strongly influence the physiological impact of vitamin D. This is particularly important for extra-skeletal responses to vitamin D, where tissue-specific metabolites appear to be a crucial component of vitamin D activity. Hence, to better understand the broader role of vitamin D in human health there is an urgent need for new analytical methods that more accurately define optimal levels of vitamin D. The current project will develop state-of-the-art mass spectrometry methods for more comprehensive measurement of vitamin D metabolism in blood and solid tissues. Studies during the outgoing phase of the project will establish more comprehensive LC-MS/MS methods for analysis of classical vitamin D metabolism pathways, as well as alternative metabolic pathways. LC-MS/MS methods will also be developed to measure polymorphic variants of the serum vitamin D binding protein, and thereby enable clearer definition of the bioavailability of vitamin D metabolites. These new methods will initially be validated using a large human cohort at the outgoing phase. Finally, novel MALDI mass spectrometry imaging methods will be developed to visualise vitamin D metabolites in solid tissues. Translational application of each new analytical method will be tested on the return phase of the project through studies of large patient cohorts with both serum and tissue samples (placenta and skin tissues). Further enhancement of analytical methods will be achieved through an industrial secondment that will provide access to cutting-edge equipment. The project will establish an entirely new philosophy and methodology for the measurement of vitamin D biomarkers in health and disease.
Original text from CORDIS.
Participants
- THE UNIVERSITY OF BIRMINGHAM · BirminghamCoordinatorUnited Kingdom
- ANZAC HEALTH AND MEDICAL RESEARCH FOUNDATION · Concord NswAustralia
Links
- View on CORDIS
- DOI: 10.3030/840567
- https://www.birmingham.ac.uk/staff/profiles/metabolism-systems/jenkinson-carl.aspx
Data: CORDIS, © European Union
