1. R.M. Lucas, PhD,
2. A.-L. Ponsonby, PhD,
3. K. Dear, PhD,
4. P.C. Valery, PhD,
5. M.P. Pender, MD,
6. B.V. Taylor, MD,
7. T.J. Kilpatrick, MD,
8. T. Dwyer, MD,
9. A. Coulthard, FRANZCR,
10. C. Chapman, FRACP,
11. I. van der Mei, PhD,
12. D. Williams, PhD and
13. A.J. McMichael, PhD
From the National Centre for Epidemiology and Population Health (R.M.L., K.D., A.J.M.), The Australian National University, Canberra; Murdoch Childrens Research Institute (A.-L.P., T.D.), Melbourne; Queensland Institute of Medical Research (P.C.V.), Brisbane; The University of Queensland and Royal Brisbane and Women's Hospital (M.P.P., A.C.), Brisbane; Menzies Research Institute (B.V.T., I.v.d.M.), Hobart; Centre for Neuroscience (T.J.K.), The University of Melbourne, Melbourne; Department of Neurology (C.C.), Barwon Health, Geelong; and Department of Neurophysiology (D.W.), John Hunter Hospital, Newcastle, Australia.
Address correspondence and reprint requests to Dr. Robyn Lucas, National Centre for Epidemiology and Population Health, The Australian National University, Canberra 0200, Australia Robyn.Lucas at anu.edu.au
Objectives: To examine whether past and recent sun exposure and vitamin D status (serum 25-hydroxyvitamin D [25(OH)D] levels) are associated with risk of first demyelinating events (FDEs) and to evaluate the contribution of these factors to the latitudinal gradient in FDE incidence in Australia.
Methods: This was a multicenter incident case-control study. Cases (n = 216) were aged 18–59 years with a FDE and resident within one of 4 Australian centers (from latitudes 27°S to 43°S), from November 1, 2003, to December 31, 2006. Controls (n = 395) were matched to cases on age, sex, and study region, without CNS demyelination. Exposures measured included self-reported sun exposure by life stage, objective measures of skin phenotype and actinic damage, and vitamin D status.
Results: Higher levels of past, recent, and accumulated leisure-time sun exposure were each associated with reduced risk of FDE, e.g., accumulated leisure-time sun exposure (age 6 years to current), adjusted odds ratio (AOR) = 0.70 (95% confidence interval [CI] 0.53–0.94) for each ultraviolet (UV) dose increment of 1,000 kJ/m2 (range 508–6,397 kJ/m2). Higher actinic skin damage (AOR = 0.39 [95% CI 0.17–0.92], highest grade vs the lowest) and higher serum vitamin D status (AOR = 0.93 [95% CI 0.86–1.00] per 10 nmol/L increase in 25(OH)D) were independently associated with decreased FDE risk. Differences in leisure-time sun exposure, serum 25(OH)D level, and skin type additively accounted for a 32.4% increase in FDE incidence from the low to high latitude regions.
Conclusions: Sun exposure and vitamin D status may have independent roles in the risk of CNS demyelination. Both will need to be evaluated in clinical trials for multiple sclerosis prevention.
Study funding: Supported by the National Multiple Sclerosis Society of the United States of America, the National Health and Medical Research Council of Australia, the ANZ William Buckland Foundation, and Multiple Sclerosis Research Australia.
AOR; adjusted odds ratio
CI: confidence interval
EAE: experimental allergic encephalomyelitis
FCD: first clinical diagnosis of CNS demyelination
FDE: first demyelinating event
MS: multiple sclerosis
OR: odds ratio
PPMS: primary progressive multiple sclerosis
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- 30% less likely to get MS for UV increase of 1000 kJ/m2
- 7% less likely to get MS for each 4 ng increase in vitamin D level in blood