Background: Several environmental and lifestyle factors relating to sunlight/vitamin D, body mass index (BMI), and smoking are associated with the risk of developing multiple sclerosis (MS). However, their relation to disease progression, particularly age at symptomatic onset, remains inconsistent, which may be the result of significant changes in human-environment interactions over the last century. This study investigates historical trends in the association between common MS environmental risk factors and age at disease onset.

Methods: Using a narrative approach, we evaluated the current literature for published studies assessing the association between vitamin-D, BMI, and tobacco smoking exposures with the risk of early/pediatric-onset MS and direct correlations with age at MS onset using MEDLINE, EMBASE, and Web of Science. Measures were plotted by the average calendar year of disease onset for each cohort to examine trends over time. In total, 25, 9, and 11 articles were identified for vitamin D, BMI, and smoking-related exposures, respectively.

Results: Higher sun exposure habits and residential solar radiation were associated with older age at onset. On the contrary, two studies observed a negative correlation between age at onset and serum 25-hydroxyvitamin D (25(OH)D) levels. Higher adolescent BMI was generally associated with younger age at onset, although genetic susceptibility for childhood obesity was not significantly associated. Tobacco smoking was associated with later disease onset, despite being a risk factor for MS. Association with age at onset was inflated for more recent studies relating to smoking, while often weaker for serum vitamin D and BMI.

Conclusions: Current findings indicate a likely association between age at onset and environmental risk factors, such as sun exposure, adolescent BMI, and tobacco smoking, in certain populations. However, findings are often inconsistent and assessment of the relationships and potential changes over time require further investigation.