Plasma levels of polyunsaturated fatty acids and multiple sclerosis susceptibility in a US case-control study

Background: There are plausible mechanisms, yet mixed evidence, that higher polyunsaturated fatty acids (PUFAs) levels reduces the risk of multiple sclerosis (MS). Prior studies relied on dietary surveys to estimate levels. Objective: We tested associations between plasma levels of n-3 and n-6 PUFAs and likelihood of MS onset or clinically isolated syndrome (CIS) using data from the MS Sunshine Study, a case-control study conducted in the United States. Methods: Case participants (n = 589) aged ≥ 18 years and matched control participants (n = 630) were recruited between 2011 and 2015. Plasma phospholipid fatty acid profiling was conducted by gas-liquid chromatography. We used logistic regression to report odds ratios, testing for interactions, adjusting for covariates and correcting for multiple comparisons. Results: There was a 6 % lower probability of MS/CIS per unit increase in total n-6 PUFA level, expressed as a percentage of total plasma phospholipid fatty acids (odds ratio = 0.94; 95 % confidence interval = 0.90,0.98; p = 0.012). We found no statistically significant association between individual or total plasma levels of n-3 PUFAs and probability of MS/CIS; however, plasma levels of n-3 PUFAs were low across the cohort. No other individual or aggregate PUFA levels were significantly associated with MS/CIS. Conclusion: A higher total n-6 PUFA level may be beneficial in terms of MS susceptibility. Further research is needed to determine whether n-3 PUFAs may be beneficial only above a threshold that is achievable by supplementation.