Pauline Anderson

October 12, 2012

October 12, 2012 — A new study has uncovered a significant inverse relationship between sun exposure and multiple sclerosis (MS) among residents of Italy and Norway, with the strongest effect being in early childhood in Italy and in late adolescence in Norway.

The results indicate that in terms of MS risk, both early childhood and late adolescence are stages of life that are sensitive to lack of sun exposure, an indirect measure of vitamin D insufficiency, said study author Kjetil Lauvland Bjørnevik.

The association also appeared to differ seasonally. Whereas in Norway the association was significant only in summer, in Italy, a more southerly country, the association existed in both summer and winter.

The results further support the importance of vitamin D in relation to MS risk, said Dr. Bjørnevik.

He presented the data here at the e He 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

EnvMS Study

The data are from the EnvIMS study, a large multinational case-control study investigating environmental risk factors, including infections, diet, smoking, and sun exposure, and the risk for MS in Norway, Sweden, Canada, Serbia, and Italy. At the meeting here, Dr. Bjørnevik presented the results on early-life sun exposure from Italy and Norway.

The analysis included 733 cases and 1438 population-based controls from Italy and 959 cases and 1718 population-based controls from Norway. Study participants completed questionnaires estimating the amount of time they spent outdoors, selecting from categories ranging from "no outdoor activity" to "being outside most of the time," during both winter and summer months at different ages (up to 6 years, 7 to 12 years, 13 to 15 years, 19 to 24 years, and 25 to 30 years).

They also answered questions about the use of sunscreen. To help jog their memory about early-life sun exposure, they were encouraged to get help from their parents.

The researchers found that after adjustment for sex, the inverse association between sun exposure and MS in Norway was strongest with little sun exposure in the summer between age 16 and 18 years (odds ratio [OR], 1.79; 95% confidence interval [Cl], 1.28 - 2.52), whereas the period from age 0 to 5 years showed the strongest effect in Italy (OR, 1.57; 95% Cl, 1.17 - 2.12).

The findings suggest a possible age variation related to latitude in the risk for MS due to vitamin D insufficiency. Sicily, where most Italian study participants resided, has a latitude of 41 degrees north, while the latitude of Norway varies and can be as high as 71 degrees north.

The study also found a statistically significant inverse association between MS risk and sun exposure in the winter in Italy (OR, 1.45; 95% Cl, 1.05 - 2.00), but not in Norway.

In addition, high use of sunscreen in early childhood (up to age 6 years) was associated with an increased risk for MS in Norway (OR, 1.59; 95% Cl, 1.23 - 2.04) after adjustment for sun exposure during the same period.

Session co-chair, George Ebers, MD, professor, Nuffield Department of Clinical Neurosciences (Clinical Neurology), University of Oxford, United Kingdom, commented that the current widespread policy to advocate for sun screen use is "misguided" in that although such behavior might affect skin cancer risk, it can also produce "unwanted biological effects."

"I think it's going to turn out to be one of the most embarrassing chapters in public health," he said in an interview.

Dr. Ebers also said that vitamin D can induce epigenetic changes and that sun exposure of mothers might help explain the variation in the effect of sun exposure on MS risk in Italy and in Norway.

"If the sun exposure in the offspring has an effect, it's quite possible that sun exposure in the parent might also have an effect," he said.

BMI and MS Risk

Another analysis using the EnvIMS data found that being overweight, especially for young Norwegian men, is a risk factor for developing MS, although body weight didn't seem to be much of a factor among the Italian population.

"A large body size in early adulthood seems to be risk factor for MS for both men and women," said lead author, Kristin Wesnes, a researcher at the University of Bergen, Norway, and PhD candidate. "The highest risk is among men aged 25 and although it's lower for women in Norway, they still have an increased risk."

The study included 959 cases (286 men, 673 women) and 1718 controls (462 men, 1256 women) in Norway and 732 cases (261 men, 471 women) and 1439 controls (471 men, 968 women) in Italy. The participants identified current and past (at age 5, 10, 25, and 30 years) body size from a choice of 9 body silhouettes ranging from 1 to 9, with 9 representing the largest; 3 was the reference body size. Researchers used body mass index (BMI) to validate body size.

In Norway, a large body size (silhouettes 6 to 9) at age 25 was associated with an increased risk for MS in men and women; the risk at age 20 was less pronounced but significant.

Table. Large Body Size (Silhouettes 6 to 9) and MS Risk by Sex and Age

Group Hazard Ratio (95% CI) P Value for Trend
Age 20 y 1.55 (0.71 - 3.36) .001
Age 25 y 2.20 (1.14 - 4.24) .003
Age 20 y 1.16 (0.72 - 1.88) .01
Age 25 y 1.62 (1.04 - 2.53) .0005


There was no significant trend in Italy. Results were similar after adjustment for smoking and education.

However, in both countries, the slimmest body sizes (silhouettes 1 and 2) had a protective effect in all age groups compared with body size 3.

The results makes some sense, said Wesnes, in that vitamin D is stored in the fat of overweight people, leaving less available to circulate throughout the body. In addition, obesity is related to chronic inflammation and so may be an immune trigger that sets the stage for MS.

She pointed out that other studies, including 2 recent ones from Canada and Sweden, have shown that low vitamin D levels are related to obesity and that a large body size in young adults may increase the risk for MS.

The reason the association is much less strong in Italy might be due to the different cuisine (the Mediterranean diet is rich in fresh, low-fat fruits, vegetables, and fish) or because Italians, living in a more southerly clime, are exposed to more sunlight, Wesnes speculated.

She also noted that on average, the Italian participants had much lower BMIs than the Norwegian participants and, in their northern neighbor, weight differed little between those with MS and the controls without MS.

"Very little separates the cases from the controls in Italy," said Wesnes. "But in Norway, for men and for women, there is a significant difference between cases and controls with larger controls up to 25 years, and then at current ages, cases are thinner than controls."

She also noted that young people in Norway today eat much less fish than their ancestors, and this could contribute to increased body size and the risk for MS, she speculated.

The study was supported by FISM and the Western Norway Regional Health Authority. Kristin Wesnes has disclosed no relevant financial relationships.

28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis. Abstract #64, P253. Presented October 11, 2012.