Vitamin D genetic risk scores in multiple sclerosis.

BACKGROUND: Low serum 25(OH)D3 (vD) is an environmental risk factor for multiple sclerosis (MS). Lower vD levels during early disease may be associated with long-term disability. Determinants of serum vD levels in healthy individuals include supplementation behaviour and genetic factors. These determinants have been less well studied in people with MS (pwMS). METHODS: We developed a vD-weighted genetic risk score (GRS) and validated this in 373,357 UK Biobank participants without MS. We measured serum 25(OH)D3 and genotyped six vD-associated SNPs (rs12785878, rs10741657, rs17216707, rs10745742, rs8018720, rs2282679) in a cohort of pwMS (n = 315) with age and geographically matched controls (n = 232). We then assessed predictors of serum vD concentration in this cohort. RESULTS: The GRS was strongly associated with vD status in the Biobank cohort (p < 2 × 10-16). vD supplementation, having MS, lower BMI, increased age and supplementation dose were associated with higher vD levels (false discovery rate, FDR < 5%). In multivariable models adjusting for supplementation, BMI, age, sex, and MS status, the GRS was strongly associated with vD level (p = 0.004), but not in those who supplemented (p = 0.47). CONCLUSIONS: Our findings suggest that vD supplementation is the major determinant of vD level in pwMS, with genetic determinants playing a far smaller role.

Digesting science: Developing educational activities about multiple sclerosis, prevention and treatment to increase the confidence of affected families.

BACKGROUND: The majority of information sources for children of people with multiple sclerosis (MS) are paper, or text, based and require high levels of literacy. OBJECTIVE: To develop educational activities to inform children who have a parent with MS about a number of aspects around MS and to improve the confidence levels of both parents and children to discuss MS. METHODS: A structured interactive event, Digesting Science (DS), was developed. This covers the effect MS can have on: vision, bladder function, walking, the mechanisms of action of disease-modifying treatments, the potential importance of vitamin D supplementation, and risk factors for developing MS. Qualitative and semi-quantitative feedback and other data were collected from event questionnaires and a follow-up online survey. RESULTS: In total, 86 DS events have been delivered internationally, reaching approximately 345 families affected by MS. Confidence ratings around discussing MS improved in 57/77 families (74%; 95% CI: 62.6-83.1) following a DS event. 39/87 (45%) families who attended DS events reported taking vitamin D prior to the event, and 48/87 (55%) were not supplementing. Of those not taking vitamin D supplements, 71% now take vitamin D supplements, 6% have not changed their behaviour, and the remainder were unsure. CONCLUSION: Educational activities that explain complex neurological diseases to children can be developed and successfully implemented at an international level. These activities give families the confidence to discuss the impact of MS on their lives and also have the potential to change health-related behaviour. IMPLICATIONS FOR PRACTICE: Creative approaches to health behaviour communication can inform children of parents with MS and may affect their behaviour with the aim of potentially reducing their risk of developing MS in the future. Now more than ever, we need educational resources that can facilitate conversations within families that can respond to health information needs in a timely manner.

Remote testing of vitamin D levels across the UK MS population-A case control study.

OBJECTIVE: The association between vitamin D deficiency and multiple sclerosis (MS) is well described. We set out to use remote sampling to ascertain vitamin D status and vitamin D supplementation in a cross-sectional study of people with MS across the UK. METHODS: People with MS and matched controls were recruited from across the UK. 1768 people with MS enrolled in the study; remote sampling kits were distributed to a subgroup. Dried blood spots (DBS) were used to assess serum 25(OH)D in people with MS and controls. RESULTS: 1768 MS participants completed the questionnaire; 388 MS participants and 309 controls provided biological samples. Serum 25(OH)D was higher in MS than controls (median 71nmol/L vs 49nmol/L). A higher proportion of MS participants than controls supplemented (72% vs 26%, p<0.001); people with MS supplemented at higher vD doses than controls (median 1600 vs 600 IU/day, p<0.001). People with MS who did not supplement had lower serum 25(OH)D levels than non-supplementing controls (median 38 nmol/L vs 44 nmol/L). Participants engaged well with remote sampling. CONCLUSIONS: The UK MS population have higher serum 25(OH)D than controls, mainly as a result of vitamin D supplementation. Remote sampling is a feasible way of carrying out large studies.

Vitamin D supplementation.

Vitamin D testing and supplementation is of great interest to neurologists and their patients. Recommended nutritional intakes of vitamin D in the UK remain focused on bone health, despite increasing evidence for a role outside this area. Here we discuss how neurologists might approach vitamin D testing and supplementation, focusing on two conditions associated with vitamin D deficiency that have an increased risk of downstream complications resulting from these: multiple sclerosis and epilepsy. We set out a rationale for testing serum 25-hydroxyvitamin D concentrations and discuss our personal practice in terms of supplementation, with evidence where available.

The difficulties with vitamin B12.

A 22-year-old woman presented with progressive sensory ataxia and optic neuropathy. Previous investigation by her general practitioner had found a low serum vitamin B12, which had been corrected with oral supplementation. Neurological investigations showed raised plasma homocysteine and methylmalonic acid towards the upper limit of normal with a low serum vitamin B12 MRI showed an extensive cord lesion in keeping with subacute combined degeneration of the spinal cord. We treated her with high dose parenteral vitamin B12 and she has made a partial recovery. We discuss the management of patients who present with neurological manifestations of vitamin B12 deficiency; highlighting the fact that parenteral replacement is needed in such cases, even if the serum vitamin B12 level appears to be normal. We also discuss ancillary investigations that should be performed in patients with suspected vitamin B12 deficiency.

The effect of vitamin D-related interventions on multiple sclerosis relapses: a meta-analysis.

Observational studies have shown an association between lower vitamin D levels and higher risk of relapse among people with multiple sclerosis (MS). This has raised interest in potential clinical benefits of vitamin D supplementation in the management of MS. The objectives were to examine the effect of vitamin D based interventions on the relative risk of relapse in MS. Any randomised controlled trial assessing the effect on the relative risk of relapse of any formulation or dose of vitamin D, in participants with MS, was eligible. The inverse variance with random effects model in Review Manager 5.1 was used to calculate the odds ratio of relapses in high dose vitamin D treated patients vs. controls. Five studies were published as of September 2012, yielding a total of 129 high-dose vitamin D-treated patients and 125 controls. We found no significant association between high-dose vitamin D treatment and risk of MS relapse (OR 0.98, 95% CI 0.45-2.16). In conclusion, although no significant association between high-dose vitamin D treatment and risk of MS relapses was found, the studies were limited by several methodological limitations. Further larger, more prolonged studies are merited.

Vitamin D deficiency--do we follow our own advice?

Over the last few years, vitamin D deficiency has emerged as a risk factor for many diseases. Public awareness of the importance of the 'sunshine vitamin' is increasing, however deficiency remains an ongoing problem. Is an awareness of the importance of vitamin D enough to promote healthy people to take supplements or is a different approach required? In this article the importance of vitamin D is discussed and data showing that knowledge of this is not sufficient to encourage people to take supplements are presented.