Summary of Findings
- Multiple Sclerosis (MS) is more common in Northern parts of the world which have less sunlight. (106)
- Studies have shown that the risk of MS is decreased by exposure to sunlight in childhood. (106)
- Epidemiology data suggests that Vitamin D deficiency in the last three months of pregnancy is particularly harmful to the fetus and raises the risk of MS in later life. (111)
- Nurses who took 400IU per day of Vitamin D as part of a multivitamin demonstrated a 40% reduced risk of developing MS. (107)
- Professor Ebers of Oxford University has shown that vitamin D interacts with a specific region of a gene, which is known to exert a direct influence on the risk of developing MS. (118)
- Only 16% of MS patient experienced a relapse when treated with 14,000IU per day of Vitamin D for twelve months compared to 40% of patients treated with only 1000IU. (American Academy of Neurology April 2009)
- For every 10ng increase in Vitamin D level, 32% less brains lesions were detected by MRI in MS patients (176)
- Each 4 nanogram increase in Vitamin D level reduced relapse rate in MS patients by 13.7 % (177)
Multiple Sclerosis and Vitamin D3
MS is believed to be an autoimmune disease in which part of the immune system (T cells) become activated, enabling it to attack normal tissue. Such an attack produces inflammation and progressive damage. T cells are known to have Vitamin D receptors (VDR) and activation of these receptors results in suppression of the cell’s activity. Hence, a lack of Vitamin D allows these cells to act unchecked. Vitamin D influences the immune system in several ways, and animal models of these mechanisms have shown that Vitamin D deficiency suppresses the system while correcting the deficiency results in dramatic improvements. (109). It has long been known that Multiple Sclerosis (MS) is more common in Northern parts of the world which have less sunlight. At least two studies have shown that the risk of MS is decreased by exposure to sunlight or higher intakes of Vitamin D in childhood. (106,) (111) Epidemiology data suggests that Vitamin D deficiency in the last three months of pregnancy is particularly harmful to the fetus. (111)
The incidence of MS in Scotland is one of the highest in the world where as many as 1:300 people suffer from the disease. This is a least twice the rate seen farther south in England. (110) Scotland is exposed to at least 50% less UV radiation than Southern regions of the UK, resulting in significantly lower Vitamin D levels.
This strongly suggests that an environmental factor rather than genetics are the primary cause of this condition. Studies in identical twins show that it is highly unlikely that both twins will develop the condition, which also is a strong argument against a genetic cause for MS. (111) Additional studies conducted in Australia support the connection between MS and Vitamin D deficiency. Northern regions of Australia have a prevalence of the disease six times higher than in Southern areas. (113) In addition, migration studies show that moving to a sunny part of the world and working out of doors reduces the risk of developing MS. (114) In the Nurses Health Study I and II, 200,000 women were followed up for 30 years with a questionaire every 4 years on their Vitamin D intake. The incidence of MS decreased with increasing Vitamin D intake. It was 33% lower among women in the highest quintile versus the lowest, and there was evidence of a dose effect with incidence of MS being 40% lower among women taking at least 400IU/day. (107) Furthermore, in MS patients the number of classic MS lesions in the brain has been shown to decrease in the summer when Vitamin D levels are highest. (116) Several small clinical studies have suggested that symptoms are improved by treatment with Vitamin D. (117) The use of high doses of Vitamin D in MS has become common place. In 2007 the results of a phase I study were published that explored the safety of these higher doses. Doses up to the equivalent of 40,000IU per day were used in patients suffering from Multiple Sclerosis (MS). (143)
In this study 12 patients with MS were given weekly doses of Vitamin D3 and the dose escalated every few weeks. The table below shows the dosing regimen:
Study WeekDose of D3/IU/week
The highest dose given equates to 40,000IU of Vitamin D3 per day. None of the patients developed hypercalcemia and no adverse events were seen in any patient throughout the 28 week trial. The mean serum Vitamin D levels at the start of the study was 31ngs/ml and at completion of the trial were 154ngs/ml.
While this publication showed the results of the first 28 weeks of therapy it has been reported that the study continued for twelve months and no adverse effects were seen.
At the annual meeting of the American Academy of Neurology (April 2009) the results of using high doses in patients were presented. The study compared the effects of 1000IU vis 14,000IU of Vitamin D daily for a year in patients with mild relapsing MS.
During the year of treatment 40% of patients on the low dose of Vitamin D experienced a relapse. Only 16% of those on the high dose experienced a relapse. When each treatment group was compared to their relapse rate in the year prior to receiving Vitamin D, those taking the high dose had 41% fewer relapses than they experienced in the prior year, compared to only a 17% reduction in episodes in those taking the low dose.
High dose Vitamin D appears to suppress the autoimmune responses thought to cause MS. In patients given high dose Vitamin D, T-cell activity was reported to drop significantly. The investigator reported that it appears MS patients do best with levels in excess of 40ng/ml which is in the same range that experts on Vitamin D have recommended in other conditions.
Professor Ebers of Oxford University has shown that Vitamin D interacts with a specific region of a gene, which is known to exert a direct influence on the risk of developing MS. (118) The authors of this paper concluded that taking Vitamin D supplements during pregnancy and the early years of life may significantly reduce the risk of developing MS later in life. These recent findings led to great excitement in the media and calls for the recommendations of daily Vitamin D supplements to be updated. In April 2012 a study was published showing that for every 10ng increase in vitamin D level, 32% less brains lesions were detected by MRI. This was a five year longitudinal MS cohort study conducted at the University of California, San Francisco. (176)
Participants had clinical evaluations, brain MRI, and blood draws annually. From the overall cohort, patients were evaluated with clinically isolated syndrome or relapsing-remitting MS at baseline. In univariate and multivariate (adjusted for age, sex, ethnicity, smoking, and MS treatments) repeated measures analyses, annual 25-hydroxyvitamin D levels were evaluated for their association with subsequent new T2-weighted and gadolinium-enhancing T1-weighted lesions on brain MRI, clinical relapses, and disability (Expanded Disability Status Scale [EDSS]). 2,362 3T brain MRI scans were acquired from 469 subjects.
In multivariate analyses, each 10 ng/mL higher 25-hydroxyvitamin D was associated with a 15% lower risk of a new T2 lesion (incidence rate ratio [IRR]= 0.85, 95% CI [0.76, 0.95], p=0.004) and a 32% lower risk of a gadolinium-enhancing lesion (IRR=0.68, 95% CI [0.53, 0.87], p=0.002).
Each 10 ng/mL higher vitamin D level was associated with lower subsequent disability (-0.047, 95% CI [-0.091, -0.003], p=0.037).
Higher vitamin D levels were associated with lower, but not statistically significant, relapse risk.
Except for the EDSS model, all associations were stronger when the within-person change in vitamin D level was the predictor.
Conclusion: Vitamin D levels are inversely associated with MS activity on brain MRI.
Just a months later another study suggested the relapse rate in MS patients is reduced by 14 percent for each 4 ng increase in Vitamin D level. (177)
In this observational, uncontrolled study, vitamin D3 supplementation (3010 IU/day on average) was given to 156 consecutive patients with relapsing–remitting multiple sclerosis, under first-line immunomodulatory therapy and with initial 25-OH-D serum level lower than 100 nmol/l (40 ng/ml). Relapses were determined for 29.1 ± 8.4 months during vitamin D and 29.8 ± 10.1 months before supplementation. The 25-OH-D level was measured before supplementation and several times during supplementation. The incidence rate of relapses before and during supplementation was estimated using negative binomial regression models with follow-up durations as offset terms. The incidence rate and incidence rate ratio of relapses at various 25-OH-D levels were also calculated using negative binomial regression models.
In 76 patients, immunomodulatory therapy preceded vitamin D supplementation (by 4.2 ± 2.7 years) and in 80 patients both treatments were started simultaneously. Under supplementation, the 25-OH-D level increased from 49 ± 22 nmol/l to 110 ± 26 nmol/l on average. Pooling data collected before and during supplementation, found a significant strong inverse relationship between the relapse incidence rate and the 25-OH-D level(p < 0.0001), suggesting that vitamin D did indeed influence the relapse rate. Results of univariate, bivariate and multivariate analyses were analogous: in the multivariate model adjusted for age, disease duration and previous use of immunomodulatory therapy, every 10 nmol increase in 25-OH-D level was associated with a reduction in the relapse incidence rate of 13.7%. Dividing iteratively the population made up of pooled periods into two subgroups according to the 25-OH-D levels, the relapse incidence rate ratio decreased as the 25-OH-D level increased up to 110 nmol/l, but a plateau effect was observed beyond this limit.
In summary the study found:
•3100 IU reduced MS relapse rate
•Each 4 nanogram increase in vitamin D level reduced relapse rate by 13.7 %
•Started at 20 nanograms, Plateau at 44 nanograms
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