What is the impact of Vitamin D on the complicated course of MS?

Some general neurologists get away with not having to think too much about multiple sclerosis (MS). This is because they have an ‘MSologist‘ at hand to refer all their patients with ‘demyelination‘. Many general neurologists however care for people with MS because they do not have a ‘fallback guy‘ to do the heavy lifting for them. This therefore makes it imperative for neurologists to keep up with everything about this often disabling and distressing disorder.

MS prevalence map. By AdertOwn work and [1], CC BY-SA 3.0, Link
The management of MS is however very tricky, and it is challenging to get a grip of it all. This is partly because the clinical course is varied, and the diagnostic process tortuous. The patient first goes through an onerous retinue of tests which include an MRI, a lumbar puncture, evoked potentials, and a shedload of blood tests. This is all in a bid to secure the diagnosis and to exclude all possible MS mimics.

MRI scan. NIH Image Galley on Flikr. https://www.flickr.com/photos/nihgov/30805879596

Then comes the head-scratching phase of determining if the patient actually fulfils the diagnostic criteria for MS, or if they just have clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS). To secure the diagnosis of MS, the neurologist turns to the McDonald criteria which stipulate dissemination in time and place of inflammatory events. As simple as this should be, this is no easy task at all. This is because, at different times, the criteria have meant different things to different people. The guidelines have also gone through several painful, and often confusing, iterations. Indeed the McDonald criteria have only recently been re-revised-to the delight of MSologists but the chagrin of the general neurologist!

Steampunk Time and Space Machine. Don Urban on Flikr. https://www.flickr.com/photos/donpezzano/3230179951

Once the diagnosis of relapsing remitting MS (RRMS) is reasonably established, the patient is taken through a guided tour of the ever-expanding available treatment options. These are typically to prevent relapses, but more recently to prevent disease progression as well. People with mild to moderate MS are nudged towards interferons, glatiramer acetate, dimethylfumarate, or terifluonamide. Those with more aggressive disease, on the other hand, are offered a menu of fingolimod, natalizumab, or alemtuzumab. Other newer agents include daclizumab and cladribine. And, just stepping into the arena, there is ocrelizumab for primary progressive (PPMS). Whichever option is chosen, the course of treatment is long, and it is fraught with risks such as infections and immune suppression.

https://pixabay.com/en/syringe-pill-bottle-morphine-small-1884784/

Once the bigger questions have been settled, the neurologist then braces for the ‘minor’ questions her enlightened patients will ask. The easier questions relate to the treatment of symptoms, and some of the most vexing concern the role of Vitamin D deficiency. Such questions include, ‘Is vitamin D deficiency a cause of MS?‘, ‘Do people who are vitamin D deficient experience a worse outcome?‘, and ‘Should patients with MS be on Vitamin D supplementation?‘.

Pandora’s box. Michael Hensman on Flikr. https://www.flickr.com/photos/mycael/3664900435

To attempt to resolve these questions I plunged into some of the literature on Vitamin D and MS. And this is like opening Pandora’s box. Here are some of the things I found.

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Is MS associated with Vitamin D deficiency?

It therefore appears that there is an association of vitamin D deficiency with MS, but it is far from certain that this is a causative relationship. One hypothesis is that vitamin D deficiency is the outcome, rather than the cause, of MS. The deficiency presumably results becuase the very active immune system in people with MS mops up the body’s Vitamin D. This so-called reverse causation hypothesis asserts that vitamin D deficiency is a consumptive vitaminopathy

Sunshine Falls. Dawn Ellner on Flikr. https://www.flickr.com/photos/naturesdawn/4299041739

Does Vitamin D deficiency worsen MS progression?

There is therefore no single answer to this question, but the emerging consensus is that Vitamin D deficiency adversely affects the course of MS. 

Milk splash experiment. Endre majoros on Flikr. https://www.flickr.com/photos/boneball/24597145866

Should people with MS be on Vitamin D supplementation?

Even if Vitamin D deficiency doesn’t cause MS, the evidence suggests that it negatively influences the course of the disease.

Salmon salad nicoise. Keith McDuffee on Flikr. https://www.flickr.com/photos/gudlyf/3609052894

What to do?

This is the million dollar question eloquently posed by a recent editorial in the journal Neurology titled Preventing multiple sclerosis: to (takevitamin D or not to (takevitamin D? The reasonable consensus is to encourage vitamin D replenishment to prevent MS, starting from preconception. It is also generally agreed that people with MS should be on vitamin D supplementation in the expectation that it will slow the disease activity.

A practical approach to Vitamin D replacement is the Barts MS team vitamin D supplementation recommendation. This is to start with 5,000IU/day vitamin D, and aim for a plasma level of 100-250 nmol/L. Depending on the level, the dose is then adjusted, up or down, to between 2-10,000IU/day. They also advise against giving calcium supplementation unless there is associated osteoporosis.

What is a general neurologist to do? To follow the prevailing trend, and hope it doesn’t change direction too soon!

Vitamin D Pills. Essgee51 on Flikr. https://www.flickr.com/photos/sg51/5224823967

 

MS risk factors: the top 6

Before day 2 commences, a quick word on a wonderful symposium on Multiple Sclerosis (MS).

 

"Journal.pone.0057573.g005" by Veela Mehta, Wei Pei, Grant Yang, Suyang Li, Eashwar Swamy, Aaron Boster, Petra Schmalbrock, David Pitt - Mehta V, Pei W, Yang G, Li S, Swamy E, et al. (2013) Iron Is a Sensitive Biomarker for Inflammation in Multiple Sclerosis Lesions. PLoS ONE 8(3): e57573. doi:10.1371/journal.pone.0057573. http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057573#pone-0057573-g005. Licensed under CC BY 2.5 via Wikimedia Commons.
Journal.pone.0057573.g005” by Veela Mehta, Wei Pei, Grant Yang, Suyang Li, Eashwar Swamy, Aaron Boster, Petra Schmalbrock, David Pitt – Mehta V, Pei W, Yang G, Li S, Swamy E, et al. (2013) Iron Is a Sensitive Biomarker for Inflammation in Multiple Sclerosis Lesions. PLoS ONE 8(3): e57573. doi:10.1371/journal.pone.0057573. http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057573#pone-0057573-g005. Licensed under CC BY 2.5 via Wikimedia Commons.

 

MS epidemiologists and researchers dissected the topic Causes/Triggers of MS. Speakers were David Hafler, Alberto Aschiero, Lisa Barcellos and Larry Steinman. And the top 6 are

  • Genetics
  • Tobacco smoking

 

smoking

  • Vitamin D deficiency

 

milk-33603_1280

 

  • EBV infection
  • Overweight in early age
  • High salt intake

 

salt-653072_1280

 

 

I suggested to David we should only be looking for correlation rather than causation (an idea I picked up from a great book Big Data).


He strongly disagreed! He believes genome wide association studies (GAS) have confirmed the cause for MS. I think the search for a definite cause is probably futile but we define cause flexibly. Alberto made the point that even if all the known risk factors were eliminated, MS will still be very prevalent