Sun Exposure, Vitamin D, and MRI Measures in MS
Demographic and clinical characteristics of the patient population are summarised in Table 1.
We first assessed the relative importance of candidate predictors of deseasonalised vitamin D metabolite levels in regression analyses that corrected for age and sex and the individual predictor of interest. Our candidate list of predictors included: BMI, skin colour, eye colour, multivitamin supplementation in the preceding 3 months, use of vitamin D supplements or calcium plus vitamin D supplements in the preceding 3 months, present use of interferon β, and summer and winter sun exposure in the preceding 2 years. Levels of 25 hydroxy vitamin D3, 1, 25 dihydroxy vitamin D3 and 24, 25 dihydroxy vitamin D3 metabolites were individually assessed as dependent variables. Table 2 shows the partial correlations and corresponding p values for the predictors. The results from the individual analyses indicated that multivitamin supplementation, BMI, summer sun exposure and eye colour had the strongest associations with vitamin D3 metabolite levels. The results from stepwise regression models were similar (data not shown).
Figure 1A compares the relative contributions of multivitamin supplements to vitamin D or calcium plus vitamin D supplements in the preceding 3 months. The group that reported taking multivitamin supplements had an increase in deseasonalised 25 hydroxy vitamin D3 levels. Vitamin D or calcium plus vitamin D supplements did not increase deseasonalised 25 hydroxy vitamin D3 levels in the group also taking multivitamin supplements.
(Enlarge Image)
Figure 1.
(A) Dependence of deseasonalised 25-hydroxy vitamin D3 levels (in ng/ml on the left axis and nmol/l on the right axis) on the presence or absence of multivitamin consumption in the preceding 3 months. The dark gray (blue in online version of figure) bars correspond to the group that did not take vitamin D or calcium plus vitamin D supplements and the light gray (green in online version of figure) bars correspond to the group that took vitamin D or calcium plus vitamin D supplements. (B) Dependence of deseasonalised 25-hydroxy vitamin D3 levels (in ng/ml on the left axis and nmol/l on the right axis) on the quartile of summer sun exposure in the preceding 2 years in the absence (dark gray bars/blue bars in online version of figure) or presence (lighter gray bars/green bars in online version of figure) of multivitamin consumption. The bars represent the mean values and error bars are SEs. Access the article online to view this figure in colour.
Figure 1B compares the relative contributions of multivitamin supplements for different quartiles of summer sun exposure. A pattern of increasing deseasonalised 25 hydroxy vitamin D3 levels with increasing quartile of summer sun exposure was found. The higher quartiles of summer sun exposure exhibited a more marked increasing trend in those not taking multivitamin supplements.
The results from the two stage statistical analyses are summarised in Table 2. T2-LV and T1-LV were not associated with sun exposure. The dependence of GMV and WBV for different quartiles of summer sun exposure is shown in figure 2A and B, respectively. Increased summer sun exposure was associated with increased GMV and WBV after correcting for EDSS. Additional analyses with an interaction term between EDSS and summer sun exposure were conducted and did not support a significant interaction. In the second stage of the analysis, the inclusion of vitamin D did not substantially affect the positive associations between sun exposure and GMV and WBV. Interaction analysis between sunlight and 25-hydroxy vitamin D3 is not included given the non-significant main effects for vitamin D. We also separately assessed the associations of sunlight in the subsets of MS patients with relapsing disease and those with progressive disease (secondary progressive or primary progressive MS). The findings are summarised in the online supplementary data.
(Enlarge Image)
Figure 2.
(A) Dependence of normalised grey matter volume (GMV) and (B) normalised whole brain volume (WBV) of multiple sclerosis (MS) patients on the quartile of summer sun exposure in the preceding 2 years. (C) Dependence of GMV and (D) WBV of healthy controls on the quartile of summer sun exposure in the preceding 2 years. The lower quartiles of sun exposure are in darker shades of gray (green in online version) and the highest quartile is lighter shades of gray (more yellow in online version). The bars represent the mean values and error bars are SEs. Access the article online to view this figure in colour.
We had sun exposure and MRI data on 69 controls (mean age 43.7±SD 11.7 years, 55% female). In regression analyses that corrected for sex and age, we found a trend between increased sun exposure and increased normalised GMV (rp=0.21, p=0.087, figure 2C). WBV was not associated (p=0.45, figure 2D).
Results
Demographic and clinical characteristics of the patient population are summarised in Table 1.
Environmental Determinants of Vitamin D Metabolites
We first assessed the relative importance of candidate predictors of deseasonalised vitamin D metabolite levels in regression analyses that corrected for age and sex and the individual predictor of interest. Our candidate list of predictors included: BMI, skin colour, eye colour, multivitamin supplementation in the preceding 3 months, use of vitamin D supplements or calcium plus vitamin D supplements in the preceding 3 months, present use of interferon β, and summer and winter sun exposure in the preceding 2 years. Levels of 25 hydroxy vitamin D3, 1, 25 dihydroxy vitamin D3 and 24, 25 dihydroxy vitamin D3 metabolites were individually assessed as dependent variables. Table 2 shows the partial correlations and corresponding p values for the predictors. The results from the individual analyses indicated that multivitamin supplementation, BMI, summer sun exposure and eye colour had the strongest associations with vitamin D3 metabolite levels. The results from stepwise regression models were similar (data not shown).
Figure 1A compares the relative contributions of multivitamin supplements to vitamin D or calcium plus vitamin D supplements in the preceding 3 months. The group that reported taking multivitamin supplements had an increase in deseasonalised 25 hydroxy vitamin D3 levels. Vitamin D or calcium plus vitamin D supplements did not increase deseasonalised 25 hydroxy vitamin D3 levels in the group also taking multivitamin supplements.
(Enlarge Image)
Figure 1.
(A) Dependence of deseasonalised 25-hydroxy vitamin D3 levels (in ng/ml on the left axis and nmol/l on the right axis) on the presence or absence of multivitamin consumption in the preceding 3 months. The dark gray (blue in online version of figure) bars correspond to the group that did not take vitamin D or calcium plus vitamin D supplements and the light gray (green in online version of figure) bars correspond to the group that took vitamin D or calcium plus vitamin D supplements. (B) Dependence of deseasonalised 25-hydroxy vitamin D3 levels (in ng/ml on the left axis and nmol/l on the right axis) on the quartile of summer sun exposure in the preceding 2 years in the absence (dark gray bars/blue bars in online version of figure) or presence (lighter gray bars/green bars in online version of figure) of multivitamin consumption. The bars represent the mean values and error bars are SEs. Access the article online to view this figure in colour.
Figure 1B compares the relative contributions of multivitamin supplements for different quartiles of summer sun exposure. A pattern of increasing deseasonalised 25 hydroxy vitamin D3 levels with increasing quartile of summer sun exposure was found. The higher quartiles of summer sun exposure exhibited a more marked increasing trend in those not taking multivitamin supplements.
Relationships to MRI Outcomes
The results from the two stage statistical analyses are summarised in Table 2. T2-LV and T1-LV were not associated with sun exposure. The dependence of GMV and WBV for different quartiles of summer sun exposure is shown in figure 2A and B, respectively. Increased summer sun exposure was associated with increased GMV and WBV after correcting for EDSS. Additional analyses with an interaction term between EDSS and summer sun exposure were conducted and did not support a significant interaction. In the second stage of the analysis, the inclusion of vitamin D did not substantially affect the positive associations between sun exposure and GMV and WBV. Interaction analysis between sunlight and 25-hydroxy vitamin D3 is not included given the non-significant main effects for vitamin D. We also separately assessed the associations of sunlight in the subsets of MS patients with relapsing disease and those with progressive disease (secondary progressive or primary progressive MS). The findings are summarised in the online supplementary data.
(Enlarge Image)
Figure 2.
(A) Dependence of normalised grey matter volume (GMV) and (B) normalised whole brain volume (WBV) of multiple sclerosis (MS) patients on the quartile of summer sun exposure in the preceding 2 years. (C) Dependence of GMV and (D) WBV of healthy controls on the quartile of summer sun exposure in the preceding 2 years. The lower quartiles of sun exposure are in darker shades of gray (green in online version) and the highest quartile is lighter shades of gray (more yellow in online version). The bars represent the mean values and error bars are SEs. Access the article online to view this figure in colour.
We had sun exposure and MRI data on 69 controls (mean age 43.7±SD 11.7 years, 55% female). In regression analyses that corrected for sex and age, we found a trend between increased sun exposure and increased normalised GMV (rp=0.21, p=0.087, figure 2C). WBV was not associated (p=0.45, figure 2D).
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