Vitamin D is sub-optimal for most UK residents. In 2016 the Scientific Advisory Council on Nutrition recommended supplementation on a national scale to tackle vitamin D-deficiency and associated bone disease. Vitamin D also exerts extra-skeletal effects, and this may impact an array of common human diseases. The over-arching aim of my research is to mechanistically define a role for vitamin D in human health.
My group has identified new immunomodulatory effects of vitamin D mediated via localized intracrine/paracrine mechanisms independent of classical skeletal vitamin D endocrinology. We have shown that antibacterial and anti-inflammatory effects of vitamin D correlate better with serum levels of inactive 25-hydroxyvitamin D (25D) than active 1,25-dihydroxyvitamin D (1,25D). 25D is the major circulating form of vitamin D so that 25D status can potently influence immune function. Over the last 20 years, using human studies and mouse models, my group has been at the forefront of studies of vitamin D and immune function.
In the last five years this has included studies of vitamin D and COVID-19, but we have also pioneered new work on the role of vitamin D as a key regulator of immunometabolism, and the impact of vitamin D-deficiency on pregnancy outcomes, inflammatory bowel disease, rheumatoid arthritis and sarcopenia. Our work has provided researchers worldwide with the mechanistic rationale for the myriad clinical studies that have linked vitamin D-deficiency with human health problems.
The over-arching objective of our work is to answer a simple question: Is serum 25D concentration alone an accurate reflection of vitamin D function in vivo?
Our work has shown that the answer to this question is no. Instead, we now know that other health and disease pathways interface with vitamin D to provide a disease- or patient-specific profile for optimal vitamin D. Key factors, outlined above, that contribute to this profile are vitamin D binding protein (DBP), fibroblast growth factor 23 (FGF23), and tissue microbiota. Our recent work has also shown that our perspective on vitamin D is limited by the exclusive use of 25D as a marker of vitamin D function. We are now leading the world in demonstrating that the broader vitamin D ‘metabolome’ provides a more meaningful insight into vitamin D bioactivity. Our overall aim is to demonstrate that many health responses to vitamin D are not simply dependent on the basic building block of vitamin D function - serum 25D. A recent exciting example of this is our collaborative project with Prof. David Hodson at the University of Oxford that has identified a new role for DBP as a regulator of islet function and diabetes pathophysiology.
I am proud that my group at UoB is the leading vitamin D research team in the UK, with a huge global impact (my work has been cited nearly 50,000 times) and many productive collaborations to take our research legacy forward.
Research Centres and Groups
Centre for Musculoskeletal Ageing Research (CMAR) – Theme Lead