Clinic speak: vitamin D levels as a predictor of MS disease activity

Chicken or egg: low vitamin D levels and MS. #MSBlog #MSResearch #ClinicSpeak

"Chicken or egg? Vitamin D and MS is another conundrum in need of a solution. We know  that low vD levels are a susceptibility factor for MS and  that MS incidence (number of new cases per year) and prevalence (total number of cases in the population) are strongly associated with latitude (distance from the equator) and in particular annual ultraviolet B light exposure (UVB). UVB is the spectrum of light required by your skin to synthesize vD. For  these reasons we believe that low vD levels are part of the causal pathway that leads to the development of MS. However, what happens once you have MS? Will low vD levels increase your chances of having a poor prognosis? Will vD supplements improve your disease course? The study below addresses the former; CISers with low vD levels were more likely to do poorly over the next 5-years than CISers/MSers with high vD levels. This study, however, does not show causation. It is possible that low vD levels are simply a marker of a more active disease. In other words inflammation consumes vD and hence the more inflammation you have the lower your vD levels are. This could be untangled by an adequate double-blind placebo controlled trial of vD supplementation trial in CIS. If vD supplements reduces MS disease activity then vD is a DMT. If on the contrary vD supplements don't reduce MS disease activity then low vD levels are likely to be a consequence of MS disease activity." ]

"The problem with treatment trials is that we in the field have yet to settle on what is an appropriate dose. Most vD experts suggest that you need to take enough vD to raise your blood levels above 100 nmol/L. At the moment this is much higher than the upper limit of the normal range. Why so high? At present the normal range is based on the vD levels in the normal population. If a large number of the normal population are vD deficient, or insufficient, then the normal range will be artificially low. They base their assumption on the vD levels of people living in outdoor environments with unlimited sun exposure, for example hunter-gatherers in Africa, farmers, life-guards, etc. These sorts of people have year round levels above 100 nmol/L. As we evolved as a species in these environments it is likely that these levels are physiological or normal. At present most studies are testing fixed doses of vD levels of 10,000U per day or lower. This may not be enough for MS. Some commentators suggest we need to adjust doses and  treat to a target blood level. Too late. There are several ongoing vD supplementation trials, which to the best of my knowledge are using a fixed-dose. Let's hope they provide answers."

"Should we treat low vD levels in MSers? Yes, I do. Why? Not because I think vD supplements will reduce MS disease activity; we don't have the evidence for this at present. I supplement low vD levels to maximise bone health. MSers are known to have thin bones, aka osteopaenia, and as a result are at increased risk of falls and fractures. Therefore, I recommend vD supplements to all the MSers under my care and I also recommend it to their family members. There is a theoretical possibility that by keeping your children and siblings vD replete that you will reduce their chances of getting MS."

"What now? We need to wait for the Australian CIS vD supplementation trial to report. It may show that vD supplements are disease-modifying. However, we still need to remind MSers that vD may be linked to MS disease activity and therefore there is a good reason to keep yourself vD replete, i.e. with a blood level of >100nmol/L. Do this you need to take more vD than the RDA. We recommend 5,000U vD3 per day for children older than 10 years and adults. This recommendation is based on the guidelines of the Vitamin D Council. For children less than 2 years of age we recommend 600U per day and for children 2-10 years of age 2,000U per day."

"Do I practice what I preach? Yes, I do. I personally take 5,000U per day as well as my family. The problem I have is getting my family to adhere to the supplements. That is the elephant in the room. It is easy to say take this, or do that, it is much more difficult to get people to take your advice and stick to it in the long-term. I hope having MS, or not wanting to have MS, is a big enough incentive not to forget your supplements." 

Epub: Ascherio et al. Vitamin D as an Early Predictor of Multiple Sclerosis Activity and Progression. JAMA Neurol. 2014 Jan.

IMPORTANCE: It remains unclear whether vitamin D insufficiency, which is common in individuals with multiple sclerosis (MS), has an adverse effect on MS outcomes. 

OBJECTIVES: To determine whether serum concentrations of 25-hydroxyvitamin D (25[OH]D), a marker of vitamin D status, predict disease activity and prognosis in patients with a first event suggestive of MS (clinically isolated syndrome). 

DESIGN, SETTING, AND PARTICIPANTS: The Betaferon/Betaseron in Newly Emerging multiple sclerosis For Initial Treatment study was a randomized trial originally designed to evaluate the impact of early vs delayed interferon beta-1b treatment in patients with clinically isolated syndrome. Serum 25(OH)D concentrations were measured at baseline and 6, 12, and 24 months. A total of 465 of the 468 patients randomized had at least 1 25(OH)D measurement, and 334 patients had them at both the 6- and 12-month (seasonally asynchronous) measurements. Patients were followed up for 5 years clinically and by magnetic resonance imaging. 

MAIN OUTCOMES AND MEASURES: New active lesions, increased T2 lesion volume, and brain volume on magnetic resonance imaging, as well as MS relapses and disability (Expanded Disability Status Scale score). 

RESULTS: Higher 25(OH)D levels predicted reduced MS activity and a slower rate of progression. A 50-nmol/L (20-ng/mL) increment in average serum 25(OH)D levels within the first 12 months predicted a 57% lower rate of new active lesions (P <001), 57% lower relapse rate (P = .03), 25% lower yearly increase in T2 lesion volume (P< .001), and 0.41% lower yearly loss in brain volume (P = .07) from months 12 to 60. Similar associations were found between 25(OH)D measured up to 12 months and MS activity or progression from months 24 to 60. In analyses using dichotomous 25(OH)D levels, values greater than or equal to 50 nmol/L (20 ng/mL) at up to 12 months predicted lower disability (Expanded Disability Status Scale score, -0.17; P = .004) during the subsequent 4 years. 

CONCLUSIONS AND RELEVANCE: Among patients with MS mainly treated with interferon beta-1b, low 25(OH)D levels early in the disease course are a strong risk factor for long-term MS activity and progression.

Labels: , , ,