There is a large body of circumstantial evidence to suggest that a lack of vitamin D plays a large part in the development of MS. The risk of developing MS involves complex interactions between our genes and environmental factors, possibly including low levels of vitamin D. However, once MS is established, the role of vitamin D in disease progression is not well understood. Here we highlight three Australian studies exploring relationships between vitamin D, MS risk, MS onset and wellbeing in MS.
In the human body, vitamin D comes from sunlight (UV rays) and nutrition. Exposure to sunlight activates the conversion of cholesterol to cholecalciferol (25-hydroxyvitamin D or vitamin D3). Vitamin D consumed in our diet is also converted to vitamin D3.
Vitamin D3 then travels to the liver, where it is converted to an intermediary called calcidiol. This is then transported to the kidneys for conversion to an activated form of vitamin D called calcitriol. This activated form of vitamin D is released to the bloodstream, where it binds to proteins on the cells’ surface, known as vitamin D receptors (VDR). This then gets internalised into the cell, where it affects the genes that cell uses.
But why is this important? Better understanding of the metabolism of vitamin D might help researchers find additional effective treatments for MS.
In the 1970s, vitamin D deficiency was proposed to be a risk factor for MS. Since then, a body of epidemiological data has sustained this hypothesis.
Over time, researchers discovered that vitamin D acts as a hormone involved with the immune and nervous system. It drives the specialisation and growth of different types of immune cells, and a number of these cells have vitamin D receptors on their surface. These immune cells are important in MS as they are involved in mounting an immune response, which in MS can lead to the damage of myelin in the brain and spinal cord. Potentially explaining some of the links between vitamin D and MS.
MS Research Australia funded researchers at the Westmead Institute for Medical Research, who have examined vitamin D and the epigenetics of the vitamin D receptor on immune cells. Epigenetics is the science of how cells chemically modify their DNA to switch specific genes “on” or “off”. When genes are switched off, the protein they encode is no longer produced in the cell. In this study, the researchers analysed chemical modification of the vitamin D receptor gene to determine whether it was switched on or off in specific immune cells.
The research, led by Dr Lawrence Ong and Dr Grant Parnell, suggests that not enough exposure to vitamin D early in life is a potential factor increasing the chance of developing MS. They showed that vitamin D has minor effects on the epigenetics of some immune cells, or there was only minor changes in the chemical modification of the DNA in these cells. The researchers also found significant epigenetic changes when comparing cells from children to those of adults, and many that normally respond to the presence of vitamin D. This suggests vitamin D exposure at critical periods of immune system development may contribute to differences in autoimmune disease risk.
Another group of Australian scientists based in Melbourne, led by Dr Steve Simpson-Yap, has been exploring whether people with MS feel better after taking vitamin D.
Dr Simpson-Yap surveyed 1,401 people with MS about their sun exposure levels and whether they took vitamin D supplements, along with standardised questions to determine people’s physical and mental quality of life.
They found that self-reported vitamin D supplement use, sun exposure, and wearing sun-related attire were associated with higher physical and mental quality of life. This study shows that vitamin D supplementation is well tolerated, and people do feel better for it. Of course, this study wasn’t blinded (i.e. people were aware they were taking Vitamin D), which may induce a placebo effect. The study did not examine why people feel better or whether it was associated with a physical change.
MS Research Australia is in the final stages of its world-first vitamin D MS Prevention Trial called PrevANZ. This study aims to see whether vitamin D supplementation can delay the onset of MS. In this gold standard double-blind placebo-controlled trial, people who had experienced their first MS-like episode and were diagnosed with CIS (clinically isolated syndrome) were recruited. They were then randomised into different groups, given either a mock treatment (placebo) or different doses of vitamin D and then observed for 12 months.
202 people were enrolled in the trial, and the last participant has just finished the 12-month observation period. Statisticians and clinicians are now busy compiling the results, and we look forward to releasing the results in mid-2021.
It is important to note that excessive vitamin D consumption can lead to a build-up of toxic levels of vitamin D. Symptoms include nausea, vomiting, constipation and more. Any supplementation should be done in consultation with a healthcare professional.