Design: In a 28-wk protocol, 12 patients in an active phase of multiple sclerosis were given 1200 mg elemental Ca/d along with progressively increasing doses of vitamin D3: from 700 to 7000 �g/wk (from 28 000 to 280 000 IU/wk).
Results: Mean (� SD) serum concentrations of 25(OH)D initially were 78 � 35 nmol/L and rose to 386 � 157 nmol/L (P < 0.001). Serum calcium concentrations and the urinary ratio of calcium to creatinine neither increased in mean values nor exceeded reference values for any participant (2.1�2.6 mmol/L and <1.0, respectively).
Liver enzymes, serum creatinine, electrolytes, serum protein, and parathyroid hormone did not change according to Bonferroni repeated-measures statistics, although parathyroid hormone did decline significantly according to the paired t test.
Disease progression and activity were not affected, but the number of gadolinium-enhancing lesions per patient (assessed with a nuclear magnetic brain scan) decreased from the initial mean of 1.75 to the end-of-study mean of 0.83 (P = 0.03).
Conclusions: Patients' serum 25(OH)D concentrations reached twice the top of the physiologic range without eliciting hypercalcemia or hypercalciuria. The data support the feasibility of pharmacologic doses of vitamin D3 for clinical research, and they provide objective evidence that vitamin D intake beyond the current upper limit is safe by a large margin.
Reference:"Higher levels of 25-hydroxyvitamin D are associated with a lower incidence of multiple sclerosis only in women," Kragt J, van Amerongen B, et al, Mult Scler, 2009; 15(1): 9-15. (Address: Department of Neurology, VU University Medical Center, Amsterdam, the Netherlands. E-mail: J. Killestein, [email protected] ).
Summary: In a study involving 103 patients with multiple sclerosis (MS) and 110 healthy controls, vitamin D was found to have a protective effect against MS in women, but not in men. In both subjects with MS and controls, serum levels of 25(OH)D and 1,25(OH)D were significantly higher during the summer, as compared to the winter. In women, for every 10 mmol/L increase in serum 25(OH)D, the odds of MS was reduced by 19% (OR=0.81), suggesting a protective effect. Moreover, an inverse association was found between score on the "Expanded Disability Status Scale" and 25(OH)D levels in women as well.
The authors conclude, "Our data suggest that higher circulating levels of 25(OH)D are associated with a lower incidence of MS and MS-related disability in women. This may imply clues to the pathogenesis of the sex difference in risk and to the nature of the environmental factors involved in MS."
The first evidence of how vitamin D deficiency and genetics interact to increase the risk of multiple sclerosis has been reported by researchers.
A UK and Canadian team found that vitamin D helps to control a gene known to increase MS risk, the PLoS Genetics journal reports.
It suggests that vitamin D supplements taken during pregnancy and early in life could prevent the disease.
More than 85,000 people in the UK are thought to have MS.
The condition results from the loss of nerve fibres and their protective myelin sheath in the brain and spinal cord, causing neurological damage.
Our study implies that taking vitamin D supplements during pregnancy and the early years may reduce the risk of a child developing MS in later life
Dr Sreeram Ramagopalan, study leader
It is not entirely clear what causes MS but other research has suggested vitamin D, produced in the body through exposure to sunlight, plays a part.
Specifically there is evidence that populations from Northern Europe have an increased risk of developing MS if they live in areas receiving less sunshine.
Various pieces of research have also pointed to genetic causes.
In the latest study, researchers at the University of Oxford and University of British Columbia looked at a section of the genome on chromosome six which had been shown to have the strongest effect on MS risk.
While one in 1,000 people in the UK is likely to develop MS, this number rises to around one in 300 among those carrying a single copy of the gene variant - known as DRB1*1501 - and one in 100 of those carrying two copies.
The researchers found that proteins activated by vitamin D in the body bind to a particular DNA sequence next to the gene, altering its function.
They believe that vitamin D deficiency in mothers or even in a previous generation may lead to altered expression of the gene in their offspring.
Immune system
Exactly how the gene-environment interaction alters MS risk is yet to be determined; one explanation could be an effect on the thymus - a part of the immune system which produces T cells to attack invaders such as bacteria and viruses.
It is thought that in people who carry the gene variant, a lack of vitamin D during early life might impair the ability of the thymus to delete rogue T cells, which then go on to attack the body, leading to a loss of myelin on the nerve fibres.
Co-author, Professor George Ebers, from the Wellcome Trust Centre for Human Genetics, at the University of Oxford, said it had been known for a long time that genes and the environment determine MS risk.
"Here we show that the main environmental risk candidate - vitamin D - and the main gene region are directly linked and interact."
Study leader, Dr Sreeram Ramagopalan, added: "Our study implies that taking vitamin D supplements during pregnancy and the early years may reduce the risk of a child developing MS in later life."
Simon Gillespie, chief executive of the MS Society, said: "These remarkable results tie together leading theories about the environment, genes and MS but they are only part of the jigsaw.
"This discovery opens up new avenues of MS research and future experiments will help put the pieces together."
The government already advises that pregnant and breastfeeding women make sure they get enough vitamin D, taking supplements if necessary. And it is also recommended that children under five take daily vitamin D supplements
Vitamin D Safety In MS Patients
Our study implies that taking vitamin D supplements during pregnancy and the early years may reduce the risk of a child developing MS in later life 
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