Less Sunlight Means More Risk of Relapse, Disability, Studies Assert

Reduced exposure to sunlight, previously reported as a risk factor for developing multiple sclerosis (MS), also seems to increase the risk for relapse and worsening disability, data from two clinical studies suggest.

The beneficial effects of sunlight exposure were linked to increased levels of vitamin D, but also modulation of immune pathways, including the type I interferon response.

The study “Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity” was published in the journal PNAS.

Low exposure to ultraviolet-B (UV-B) radiation from sunlight, which results in a defective synthesis of vitamin D, have been suggested to increase the risk for developing MS. However, it remains a matter of debate whether sunlight and vitamin D levels also influence disease severity and progression.

In this study, researchers in Germany assessed the impact of two independent measures of sunlight exposure — vitamin D levels and latitude — on MS disease severity. (Decreasing latitude is linked with an increase of sunlight that reaches the Earth’s surface.)

Also, they assessed whether the effects of sunlight exposure were modulated by medication or variations in the gene coding for the melanocortin 1 receptor (MC1R) gene, which plays an important role in the color of the skin and, consequently, sensitivity to sunlight. MC1R signaling also has immunosuppressive functions and a protective effect in mouse models of MS.

The team reviewed data from patients previously enrolled in two studies, the German National MS cohort and the French BIONAT cohort (NCT00942214) studies.

Overall, the group from the MS study included 908 patients with clinically isolated syndrome (CIS) or relapsing remitting MS (RRMS), who had not received prior treatment. The BIONAT group included 808 MS patients, the majority of whom had received treatment. The most common treatment, given to more than half of patients, was interferon-beta.

In both groups, researchers confirmed that patients living in lower latitude areas had higher levels of vitamin D. In agreement with prior reports, patients in the BIONAT group treated with interferon-beta had higher levels of vitamin D compared to those who had no therapy.

In the German National MS cohort, higher latitude (hence lower sun exposure) was linked to significantly worse disease severity, as measured with the MS severity score (MSSS). The risk for gadolinium (Gd)-enhancing lesions also increased by 8.31% for every degree increase in latitude.

Gd-enhancing lesions, which are visible on MRI scans of the brain, indicate areas of damage in the central nervous system.

In the BIONAT study, higher levels of vitamin D were linked with lower MSSS disability scores. However, in a first analysis no link was found for an increase in latitude and MSSS scores, as observed in patients from the German National MS cohort.

Since certain patients in in the BIONAT study were given interferon-beta therapies, researchers assessed whether the missing effect of latitude was due to the confounding effect of such treatments on vitamin D levels.

Indeed, further analysis showed that the effect of latitude on disability depended on the interferon-beta treatment status. Increasing latitudes were associated with worsening disability in patients given therapies other than interferon-beta, while this association was not present among interferon-beta-treated patients.

Researchers then looked at whether vitamin D and latitude affected the risk for relapses and disability accumulation, as measured by the expanded disability status scale (EDSS).

The analysis revealed that higher vitamin D levels were associated significantly with reduced risk for relapses and disability accumulation. Lower latitude also was linked with a reduced disability worsening, but not associated with the risk of relapse.

The researchers then analyzed whether patients carrying genetic variants that lower the activity of the MC1R gene — hence, an increased sensitivity toward sunlight – modified the sunlight impact on MS severity.

For patients carrying a genetic variant that increased their sensitivity toward sunlight, the risk for Gd-enhancing lesions increased by 20.5% for every degree decrease in latitude, while that risk decreased by 11.6% in non-carriers.

In an exploratory analysis, they went on to evaluate how phototherapy with UV radiation exposure modulated gene activity in immune cells. The cells had been collected from blood samples of MS patients that participated in a pilot study.

UV radiation induced vitamin D production and activated type 1 interferon genes, providing a protective effect.

Overall, “our study suggests beneficial effects of sun exposure on established MS, as demonstrated by a correlative network between the three factors: Latitude, vitD [vitamin D], and disease severity,” the researchers wrote.

However, for photosensitive patients, such as those carrying certain genetic variants in the MC1R gene, “sun exposure might be detrimental,” the study concluded.