The impact of vitamin D on auto-immune disease

A recent prospective study has shown that vitamin D supplementation has a “strongly positive effect” in reducing the incidence of rheumatoid arthritis, Martin Hewison, Professor of Molecular Endocrinology, explains.

The recognition that low vitamin D levels were linked with increased risks of a variety of health issues, including common cancers and autoimmune disease, prompted calls for prospective, randomised, controlled trials of vitamin D supplementation. The rationale for this was that systematic supplementation with vitamin should reduce the risk of developing such diseases. Such studies need to be continued for long periods and may fail to show any effects if the participants are vitamin D-replete at the outset rather than vitamin D deficient.

“Essentially, many of the trials have been null studies – they haven’t really shown any specific effect of vitamin D. Sometimes in subgroups, for example, if you look at people who are …… vitamin D deficient at start versus those who [have] sufficient that’s where you may see in an effect of vitamin D – in the vitamin D-deficient people”, explains Professor Hewison.

However, the VITAL trial,¹ has recently shown that “there is some potential for vitamin D protecting against autoimmune disease”, he says.

The trial involved nearly 26,000 participants. The treatment group received vitamin D 2000 IU per day over a five-year period. The initial results showed that vitamin D supplementation had no effect on cardiovascular disease or common cancers but when the incidence of autoimmune disease was examined, a different picture emerged.  “Over the first three years there was no real difference between the vitamin D arm and the placebo arm, in terms of effects on prevention of autoimmune disease, but once it went beyond the three years you did see a very strongly significant effect. There’s actually something like a 22 percent decrease …. in the reports of autoimmune disease in these individuals”, says Professor Hewison.

The trial targeted an older age group (over 50 years of age) and so provided no information about younger people who might be at risk of type 1 diabetes or multiple sclerosis.  “But nevertheless, this was a very strongly positive effect showing that vitamin D can help to potentially prevent the onset of autoimmune disease in a more elderly population. So, the message was really, if you can increase your vitamin D level when you get a bit older then you have the potential to protect against some forms of autoimmune disease”, he says.

“It’s interesting to know that when they broke down the autoimmune diseases into the different types …… it was primarily rheumatoid arthritis that vitamin D in this study protected against so it has most positive effect on that particular form of autoimmunity”, he adds.

The next important question will be whether vitamin D has any benefits in established auto-immune disease, i.e. as a treatment to reduce inflammation. This is likely to present a number of challenges.  Professor Hewison explains:

“We know that once autoimmune disease sets in the immune system almost tries to circumvent the effects of vitamin D. We know, for example, that memory immune cells that are produced in autoimmunity, in your synovial joints for example, are less sensitive to vitamin D than T-cells, immune cells ….. in your general circulation. So, the idea is that when the autoimmune disease sets in, it almost makes it harder for agents like vitamin D to work. So, you need higher levels of vitamin D to achieve an effect once the diseases become established. So, that’s another problem that we have to face … if somebody already has autoimmune disease do we have to increase vitamin D levels still further in order to get a positive effect?”

Reference

1. Hahn J et al. Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial. BMJ 2022;376:e066452

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