22 Nov 2017 --- Maintaining sufficient vitamin D levels may help to prevent the onset of inflammatory diseases like rheumatoid arthritis, research led by the University of Birmingham in the UK has discovered. The research also found that vitamin D is not as effective once inflammatory disease is established because diseases such as rheumatoid arthritis lead to vitamin D insensitivity.

Another key finding of the research was that the impact of vitamin D on inflammatory disease cannot be predicted using cells from healthy individuals or even from the blood of patients with inflammation, as cells from the diseased tissue are very different.

The researchers concluded that if vitamin D is to be used in patients with rheumatoid arthritis, clinicians may need to prescribe much higher doses than the ones that are currently used or provide a treatment that also corrects the vitamin D insensitivity of immune cells within the joint.

True representation of vitamin D benefits
In addition to its well-established actions on the skeleton, vitamin D is a potent modulator of the immune system. In particular, vitamin D can suppress inflammation in autoimmune diseases such as rheumatoid arthritis. Patients with rheumatoid arthritis are frequently vitamin D deficient and may receive vitamin D supplementation.

The study, published in the Journal of Autoimmunity, involved using paired peripheral blood and synovial fluid from the inflamed joints of patients with rheumatoid arthritis.

“Our current understanding of vitamin D and rheumatoid arthritis is based on studies of patient blood which may not truly represent the situation at the site of inflammation – the joints,” says Professor Martin Hewison of the University of Birmingham’s Institute of Metabolism and Systems Research. “We, therefore, investigated responses to the active form of vitamin D in immune cells from the inflamed joints of patients with rheumatoid arthritis.”

“Compared to blood from the same patients, the inflamed joint immune cells were much less sensitive to active vitamin D,” Professor Hewison notes. “This appears to be because immune cells from the joints of rheumatoid arthritis patients are more committed to inflammation, and therefore less likely to change, even though they have all the machinery to respond to vitamin D.”

“Our research indicates that maintaining sufficient vitamin D may help to prevent the onset of inflammatory diseases like rheumatoid arthritis,” says Dr. Louisa Jeffery, also of the University of Birmingham.

“However, for patients who already have rheumatoid arthritis, simply providing vitamin D might not be enough,” Dr. Jeffery continues. “Instead, much higher doses of vitamin D may be needed, or possibly a new treatment that bypasses or corrects the vitamin D insensitivity of immune cells within the joint.”

Senior author Professor Karim Raza, also of the University of Birmingham, says the findings were unexpected: “We initially thought that cells from the inflamed rheumatoid joint would respond just as well to vitamin D as cells from the blood. The fact that they don’t have important implications for how we think about using vitamin D to treat inflammation.”

“Unlike previous studies, we isolated different immune cell types from the actual site of disease to determine whether specific subsets of immune cells (specific T cell groups) have equal sensitivity to vitamin D,” Raza adds.

The study, carried out in collaboration with Professor David Sansom at University College London, is part of an ongoing research project which first began in 2011. It is the first research of its kind to describe the effects of vitamin D in both peripheral blood and inflamed joints of patients with inflammatory disease.

The university notes that it now hopes to embark on new research to determine why rheumatoid arthritis leads to vitamin D insensitivity, how it can be overcome and whether this effect is seen in other inflammatory diseases.

“In rheumatoid arthritis patients, the immune cells associated with inflammation of joints are known as memory T cells,” Professor Hewison tells NutritionInsight. “In blood these cells are less abundant because blood also has naïve T cells (those that have yet to encounter an immune ‘challenge’). We are currently investigating what is different about memory T cells that makes them less able to utilize vitamin D.”

“In addition to our studies of arthritis, we are also looking at how vitamin D may benefit other inflammatory disorders such as Crohn’s disease (inflammatory bowel disease),” Professor Hewison adds. “We think that the immune cells from the intestine of patients with Crohn’s disease may be similar to those from the inflamed joints of arthritis patients and may therefore also be insensitive to vitamin D.”

“In this case, we are exploring how different forms of vitamin D may help to overcome this insensitivity, and also how probiotics may help the actions of vitamin D,” Professor Hewison speculates.

By Paul Creasy