Nete MunkNielsen, Researcher, Department of Epidemiology Research, Statens Serum Institut, Copenhagen, DenmarkNMN@ssi.dk
Kassandra L. Munger, Boston; Egon Stenager, Odense, Denmark; Alberto Ascherio, Boston
Submitted April 27, 2017
In response to our article, [1] Dr. Zhargami suggests that clinical trials are necessary to compare the efficacy and cost-benefit of vitamin D supplementation vs sun exposure in pregnancy. Unfortunately, such trials are not feasible because of the relatively low frequency of multiple sclerosis (MS) and the long interval between any intervention in pregnancy and the observation of its potential effect on MS risk in offspring. We agree, nevertheless, that judicious sun exposure provides an alternative approach for the correction of vitamin D deficiency in regions with levels of ultraviolet-B radiation high enough to support year-round vitamin D production. This is not the case in countries like Denmark, where winter sunlight cannot produce sufficient vitamin D levels. [2]
Xia et al. suggest that long-term cumulative effects of 25(OH)D may be more important than short term exposures. We agree and acknowledge that our findings may be indicative of longer-term vitamin D exposure if high levels of 25(OH)D in the dried blood spots samples (DBSS) were a marker for higher longer-term 25(OH)D exposure. However, our findings suggested that exposure to vitamin D deficiency in utero may contribute to MS risk in addition to exposures later in life, [1] the effect of which have been demonstrated. [3-5] Although prevalence of parental MS was higher among cases, the majority of individuals with MS do not have parental history of MS; [1] therefore, there no evidence supports the conclusion suggested by Xia et al. that our results apply to individuals with parental history of MS.
1. Nielsen NM, Munger KL, Koch-Henriksen N, et al. Neonatal vitamin D status and risk of multiple sclerosis: A population-based case-control study. Neurology 2017;88:44-51.
2. Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr 2004;79:362-371.
3. Munger KL, Zhang SM, O'Reilly E, et al. Vitamin D intake and incidence of multiple sclerosis. Neurology 2004;62:60-65.
4. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 2006;296:2832-2838.
5. Salzer J, Hallmans G, Nystrom M, et al. Vitamin D as a protective factor in multiple sclerosis. Neurology 2012;79:2140-2145.
For disclosures, please contact the editorial office at journal@neurology.org.
In response to our article, [1] Dr. Zhargami suggests that clinical trials are necessary to compare the efficacy and cost-benefit of vitamin D supplementation vs sun exposure in pregnancy. Unfortunately, such trials are not feasible because of the relatively low frequency of multiple sclerosis (MS) and the long interval between any intervention in pregnancy and the observation of its potential effect on MS risk in offspring. We agree, nevertheless, that judicious sun exposure provides an alternative approach for the correction of vitamin D deficiency in regions with levels of ultraviolet-B radiation high enough to support year-round vitamin D production. This is not the case in countries like Denmark, where winter sunlight cannot produce sufficient vitamin D levels. [2]
Xia et al. suggest that long-term cumulative effects of 25(OH)D may be more important than short term exposures. We agree and acknowledge that our findings may be indicative of longer-term vitamin D exposure if high levels of 25(OH)D in the dried blood spots samples (DBSS) were a marker for higher longer-term 25(OH)D exposure. However, our findings suggested that exposure to vitamin D deficiency in utero may contribute to MS risk in addition to exposures later in life, [1] the effect of which have been demonstrated. [3-5] Although prevalence of parental MS was higher among cases, the majority of individuals with MS do not have parental history of MS; [1] therefore, there no evidence supports the conclusion suggested by Xia et al. that our results apply to individuals with parental history of MS.
1. Nielsen NM, Munger KL, Koch-Henriksen N, et al. Neonatal vitamin D status and risk of multiple sclerosis: A population-based case-control study. Neurology 2017;88:44-51.
2. Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr 2004;79:362-371.
3. Munger KL, Zhang SM, O'Reilly E, et al. Vitamin D intake and incidence of multiple sclerosis. Neurology 2004;62:60-65.
4. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 2006;296:2832-2838.
5. Salzer J, Hallmans G, Nystrom M, et al. Vitamin D as a protective factor in multiple sclerosis. Neurology 2012;79:2140-2145.
For disclosures, please contact the editorial office at journal@neurology.org.