From Medscape Medical News > Neurology
Pauline Anderson
February 7, 2011 — A new study appears to cement the suspected link between sun exposure and lower rates of multiple sclerosis (MS).
The Australian case-control study found that past and current sun exposure and serum vitamin D levels are independently associated with a reduced risk for a central nervous system (CNS) first demyelinating event (FDE). The association remained after adjusting for potential confounders and did not vary by study region, sex, or type of demyelination.
The study is unique in several ways, said one of the study authors, Anne-Louise Ponsonby, PhD, professor at the Murdoch Children's Research Institute in Melbourne, Australia. For example, it included more than 1 site, enrolled people with a demyelinating event who had not yet been diagnosed as having MS, and investigated both sun and vitamin D levels simultaneously.
"The study raises the question of whether sun exposure itself is important, separate from vitamin D," said Dr. Ponsonby. She acknowledged that although the sun is believed to have direct immune effects in addition to providing vitamin D, the sun exposure effect found in the study could simply reflect longer-term vitamin D status. "In any case, it's important to study both vitamin D and sun exposure to understand the effects on immune function and MS."
The Autoimmune Study is published in the February 8 issue of Neurology.
Varying Latitudes
The study included 282 patients from 4 regions of Australia with varying latitudes (Brisbane City, Newcastle, Geelong City and Western Districts of Victoria, and the island of Tansmania) who had a first clinical diagnosis of CNS demyelination within the study period. Of these, 16 had a distinct event during the study period, whereas others may have had a previous event. The study also included 542 controls randomly selected from the Australian Electoral Roll, 395 of whom were matched to an eligible FDE case.
Inclusion of subjects with an FDE rather than established MS minimized changes in behavior, said Dr. Ponsonby. "It means it was before they introduced any disease-related changes to their lifestyle." About 60% of people presenting with a demyelinating event will progress to MS within 10 years, she said.
The multisite nature of the study allowed the researchers to compare various latitudes. "We designed the study so we could not only look at sun exposure and vitamin D but also see how much of that was accounted for by latitude gradient," said Dr. Ponsonby.
Through questionnaires, researchers collected information on sun exposure during leisure time (weekends and holidays) in summer and winter for different periods of life (6-10 years, 11-15 years, 16-20 years, and last 3 years). With this information, the researchers were able to examine past sun exposure before the onset of MS.
Determining sun exposure before the age of 6 years would have been too problematic, said Dr. Ponsonby. "At least by the age of 6 or 10 years, people have anchoring events like going to primary school, so they might have some recall of their sun exposure."
Researchers also gathered data on subjects' propensity to tan or burn, their number of freckles as a teenager, smoking history, educational level, physical activity, diet, and use of vitamin D supplements. As well, they noted each patient's eye and skin color and grades of actinic skin damage and collected blood samples for DNA and vitamin D analysis.
Accumulated Sun Exposure
The study showed that both sun exposure and current vitamin D levels contributed independently to reduced FDE risk. Accumulated leisure time sun exposure, defined as the dose per 1000 kJ/m2 at the age of 6 years to present, had an adjusted odds ratio (AOR) of 0.70 (95% confidence interval [CI], 0.53 – 0.94) for each UV dose increment of 1000 kJ/m2.
For vitamin D, the AOR for decreased FDE risk was 0.93 (95% CI, 0.86 – 1.00) per 10-nmol/L increase in serum 25-hydroxyvitamin D (25[OH]D) levels.
As well, fair skin and a higher nevus count were associated with increased FDE risk. The AOR for actinic skin damage score (>3 grade vs ≤3) was 0.42 (95% CI, 0.26 – 0.70).
The study authors determined that the differences in leisure time sun exposure, serum 25(OH)D levels, and skin type additively accounted for a 32.4% increase in FDE incidence from the low to high latitude regions.
"We've got fewer FDE cases in Queensland and more in Tasmania, and for a long time, people said that this might reflect sun exposure," said Dr. Ponsonby. "We found in this study that yes, indeed, sun exposure and low vitamin D did explain the gradient but only part of it, only a third of it."
The results were similar for the larger group, who may have had a previous demyelinating event, and the smaller, "purer" group, whose first event definitely occurred during the study period, said Dr. Ponsonby. "This helps to indicate that there wasn't any history of disease problems causing them to change their sun exposure or vitamin D."
Risk Persisted After Adjustments
The FDE risk persisted after adjusting for factors thought to be associated with MS, including freckles, exercise, diet, smoking, and eye color. "Particularly important was adjusting for skin type," said Dr. Ponsonby, who pointed out that whites are more prone to sun damage and tend to have higher risk for MS.
"We thought it was important to make sure that low vitamin D and sun exposure weren't just a marker for any of those other things," she said. "These other factors didn't explain in any way the pattern between low sun exposure and vitamin D."
Also implicated in MS is genetic predisposition, a history of infectious mononucleosis, and Epson-Barr virus infection, she added.
The findings suggest that vitamin D supplements alone may be a less effective prevention intervention than has been implied in previous epidemiology studies, said the study authors.
How might UV and vitamin D affect MS rates? According to the study authors, both independently stimulate T-regulatory cells and secretion of interleukin 10, reduce levels of the proinflammatory cytokine interleukin 17, and dampen TH1 immune function. This, they said, provides "biological plausible pathways to reduced MS risk."
The researchers were only able to adjust for 1 of the 3 genes recently identified in a genome-wide association study as determining serum 25(OH)D levels. However, the combined effect of these genetic variants was apparently not large because only 1% to 4% of the variation in serum 25(OH)D was attributed to their combined effect, they write.
Growing Evidence
Approached for a comment on these findings, Lily Jung Henson, MD, medical director of Neurology Clinic, Swedish Medical Group, Seattle, Washington, said there's nothing really new or different about this study.
"It just adds to the growing evidence we have that vitamin D deficiency, potentially associated with lack of sun exposure, can contribute to MS," she said.
R. M. Lucas, PhD, receives research support from Multiple Sclerosis Research Australia, The Royal Australasian College of Physicians, and the National Health and Medical Research Council of Australia. Dr. Ponsonby receives research support from Multiple Sclerosis Research Australia and the National Health and Medical Research Council of Australia. For further disclosures, see original article.
Neurology. 2011;76:540-548.
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