LYON, FRANCE—In blood samples drawn a median of nine years prior to multiple sclerosis (MS) onset, intermediate levels of retinol binding protein (RBP), a surrogate marker for vitamin A, were associated with a 55% decrease in MS risk compared with lower levels, researchers reported at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
“Vitamin A is needed for suppression of proinflammatory pathways, which may explain the association,” said Jonatan Salzer, MD, a doctoral student at Umeå University in Sverige, Sweden, and colleagues.
The investigators also conducted a post hoc analysis of younger participants and found that signs of inflammation, assessed using C-reactive protein (CRP) as a marker, were associated with a 61% decreased risk of MS.
Vitamin A and MS risk
To examine the link between vitamin A and MS, the researchers performed a nested case-control study of prospectively collected blood samples from 192 persons with MS and 37 pregnant mothers whose children had later developed MS. The 291,500 samples were identified in two biobanks in northern Sweden. From these biobanks, matched controls were also selected.
Measurements of RBP and CRP were performed with enzyme-linked immunosorbent assays (ELISAs), and the risk of MS was calculated with matched logistic regression. Because CRP levels could potentially distort the correlation between RBP and vitamin A, the study authors adjusted for CRP levels in multivariable analyses.
Results showed that RBP levels within the second quintile were associated with a lower risk of MS (odds ratio, 0.45) than those within the first quintile. The odds ratios of MS then increased toward 1.0 for quintiles three to five, describing a U-shaped pattern of MS risk over RBP quintiles. This suggests that both insufficient and excessive levels of RBP might be risk factors for MS.
In addition, an analysis of samples from pregnant mothers showed that gestational RBP and CRP levels had no effect on MS risk in the offspring. Adjustment for CRP levels did not change these results, noted the researchers.
Support for the Hygiene Hypothesis
Dr. Salzer and his coauthors focused on CRP levels in a post hoc analysis of young subjects, defined as those younger than the median age of 26.4 at sampling. In this analysis, CRP levels of 10 mg/L or greater were associated with a 61% decreased risk of MS (odds ratio, 0.39).
“This association between elevated CRP levels in young persons and a lower risk of MS supports the importance of the hygiene hypothesis in MS etiopathogenesis,” said Dr. Salzer. He added that previous epidemiologic research suggests that MS risk is largely established in young adulthood and that childhood infections might be linked to a decreased MS risk.
Dr. Salzer emphasized the need for other researchers to replicate his group’s findings. “If [the results are] replicated, further studies are needed that look into environment–environment and gene–environment interactions,” he told Neurology Reviews. “For example, high vitamin A levels may antagonize the beneficial effects of vitamin D, as they compete over the same nuclear receptor. This [factor] might explain why high RBP levels are associated with a higher MS risk, compared to intermediate [levels] in our material. Presumably, vitamin A may be of interest in all future studies investigating vitamin D and MS. We hope that the study will be an inspiration for future research, and that such research might help us understand the complex line of events that subsequently lead to MS.”