Exploiting genomics to understand the role of vitamin D in human health and metabolism

Vitamin D is essential to human health. It is crucial for bone and muscle health and it is important for protection against many diseases including hypertension, infection, autoimmune diseases, diabetes and cancer.

Vitamin D deficiency is widespread among the population and is a major public health concern in the UK and many other countries worldwide. Vitamin D3 (cholecalciferol) is the natural form that is made by our skin when exposed to ultraviolet B (UVB) radiation in sunlight and obtained from some animal-derived foods, while vitamin D2 (ergocalciferol) is obtainable from supplements and some artificially fortified foods and is generally manufactured by UV-irradiating mushrooms.

At the latitude of the UK there is only sufficient UVB radiation from sunlight between the months of April and September and therefore it is recommended that we take vitamin D3 supplements between October and March. The new government guidelines (July 2016) are that we take 10 micrograms vitamin D per day.

Our over-arching aim of this project was to understand how vitamin D supplementation influences gene expression in humans.

To do this researchers analysed genome-wide expression in whole human blood across time following vitamin D supplementation. The study was undertaken with healthy white European and South Asian women, the latter to explore whether there may be ethnic differences in the response to elevated levels of vitamin D in the body. The team investigated the global influence of the two different forms of vitamin D: D2 and D3. Vitamin D2 is generally used by vegans, vegetarians and Muslims.

This work was supported by DRINC, a partnership between BBSRC, the Engineering and Physical Sciences Research Council (EPSRC), the Economic and Social Research Council (ESRC), the Medical Research Council (MRC), and a consortium of leading food and drink companies.

Vitamin D3 was found to be significantly better at raising serum total 25-hydroxyvitamin D (25(OH)D) levels than vitamin D2; The concentration of 25(OH)D is used as a measure of how efficiently vitamin D is assimilated in the body. The results of our initial genomic analysis are striking.

Significantly, researchers discovered that the two forms of vitamin D influence expression of different cellular pathways, where vitamin D3 influences far more genes than D2. This raised the intriguing possibility that vitamin D2 may not be exerting the same biological influence in humans. The interpretation and further validation of these findings is ongoing.

The results of the study aimed ultimately to influence national and international guidelines on the fortification of foods with vitamin D2.

Publications

Tripkovic, L., Wilson, L., Hart, K., Johnsen, Sig, de Lusignan, Simon, Smith, Colin, Bucca, Giselda, Penson, S., Chope, G.and Elliott, R. (2017) Daily supplementation with 15 µg vitamin D2 compared with vitamin D3 to increase wintertime 25-hydroxyvitamin D status in healthy South Asian and white European women: a 12-wk randomized, placebo-controlled food-fortification trial. American Journal of Clinical Nutrition, 106 (2). pp. 481-490. ISSN 0002-9165

Tripkovic, L., Wilson, L., Hart, K., Elliott, R., Smith, Colin, Bucca, Giselda, Penson, S., Chope, G., Hypponen, E., Berry, J. and Lanham-New, S. (2015) The D2-D3 Study: a randomised, double-blind, placebo-controlled food-fortification trial in women, comparing the efficacy of 15 microgram/d vitamin D2 vs vitamin D3 in raising serum 25OHD levels. In: Proceedings of the Nutrition Society, Summer Meeting, Carbohydrates in health: friends or foes, UK, 2014.

Wilson, L., Hart, K., Elliott, R., Smith, Colin, Bucca, Giselda, Penson, S., Chope, G., Hypponen, E., Berry, J. and Lanham-New, S. (2015) The D2-D3 Study: comparing the efficacy of 15 microgram/d vitamin D2 vs. D3 in raising vitamin D status in both South Asian and Caucasian women, and the ethical implications of placebo treatment. In: Proceedings of the nutrition society (2015), Carbohydrates in health: friends or foes, UK.