Assessing the role of vitamin D metabolism in ageing
Carl Jenkinson, University of Birmingham
The aim of this project will be to undertake a collaborative project with the ANZAC Research Institute (ARI) (Sydney, Australia) to investigate the link between vitamin D status and metabolism in health and disease in an ageing population. The health risks of vitamin D-deficiency extend beyond its actions on the skeleton, notably its potent activity as a regulator of immune function and muscle strength and function. Vitamin D-deficiency is therefore not only associated with the bone disease osteoporosis, but also linked to increased risk of infection, inflammation and autoimmune disease. It is therefore hypothesized that vitamin D deficiency or elevated inactive vitamin D metabolites could be linked with increased risk of certain health risks within older populations.
I am aiming to use this grant to measure vitamin D levels in an ageing male population established at the ARI using samples from the Concord Health and Ageing in Men Project (CHAMP) observational cohort. The objectives of this project are to:
- Measure active and inactive forms of vitamin D metabolites using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the CHAMP cohort.
- Compare vitamin D metabolite concentrations with health data from the CHAMP database to establish novel vitamin D biomarkers in ageing.
Two novel analytical methods were developed using liquid chromatography tandem mass spectrometry (LC-MS/MS) to measure multiple phase I and phase II vitamin D metabolites. The methods aimed to expand analysis of vitamin D to incorporate active and inactive mono and di-hydroxyvitamin D forms. Analysis also incorporated sulfate and glucuronide conjugate forms of vitamin D to understand their metabolism pathways in the circulation. The key challenging aspect of method development projects was achieving the detection limits required to routinely quantitate metabolites at circulating concentrations. Derivatization was used to improve ionisation and lower limits of quantitation.
These LC-MS/MS methods were validated and applied to the analysis of samples from the Concord Health and Ageing in Men Project (CHAMP), consisting of 1700 community dwelling males aged over 70 in the Sydney inner west. The aim of this analysis was to determine whether vitamin D and its deficiency is associated with health implications in ageing. This also included characterising metabolism profiles of vitamin D beyond the routinely measured 25-hydroxyvitamin D form.
The findings from the analysis revealed that the active hormonal form of vitamin D; 1,25-dihydroxyvitamin D was a significant marker of bone health and density in older males. However other metabolites of vitamin D, including 25-hydroxyvitamin D did not associate with bone density. Analysis also revealed that sulfated forms of vitamin D, including 25-hydroxyvitamin D-sulfate circulates in high abundance and often match its unconjugated form. The high proportions of 25-hydroxyvitamin D sulfate suggest this analyte may be acting as a biological and storage reservoir from for hydrolysis at localised tissue sites.
The findings from this project have revealed important metabolism profiles and biomarkers of vitamin D for bone health in ageing that have not previously been observed by isolated unconjugated 25-hydroxyvitamin D measurements.
Grant awarded: £2,000.00