Mediterranean-style diet may be linked to lower odds of developing MS

Following a Mediterranean-style diet may be associated with lower odds of multiple sclerosis (MS) onset, and diet-related differences in biological processes that regulate gene activity may partly help explain the association, a study in Australia has found.

Specifically, differences in DNA methylation were estimated to account for up to about one-third of the association between Mediterranean diet scores and MS onset. DNA methylation is a biological process that helps regulate whether genes are switched on or off. Notably, the methylation sites identified by the researchers were linked to genes involved in immune function.

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The findings offer new insights into the biological mechanisms that may link diet to MS risk “and inform future research,” the researchers wrote. However, they cautioned that further studies are needed to clarify the relationships.

The study, “DNA methylation partially mediates the associations of Mediterranean diet scores with MS onset-risk: Results from the Ausimmune case–control study,” was published in Multiple Sclerosis Journal.

MS is a chronic disorder in which the immune system mistakenly attacks myelin, the protective coating around nerve fibers in the brain and spinal cord. These attacks cause inflammation and damage that disrupt nerve signaling. While a person’s genetic makeup is known to affect MS risk, environmental and lifestyle factors are also thought to influence the likelihood of developing the disease.

Diet affects overall health and has been linked to several chronic diseases, including MS. Among the dietary patterns studied, the Mediterranean diet — rich in fruits, vegetables, whole grains, fish, and healthy fats — has attracted particular attention because of its well-established health benefits.

Some studies suggest that closer adherence to a Mediterranean-style diet may be associated with lower odds of developing MS. Exactly how diet might influence MS risk, however, remains unclear.

Researchers have explored a variety of possible mechanisms underlying this association, including inflammation, cellular stress, changes in fat metabolism and alterations to the gut microbiome — the community of microorganisms living in the digestive tract. Another possible explanation lies in epigenetics, a group of biological processes that regulate gene activity within cells without changing the DNA sequence itself.

One of the most-studied epigenetic mechanisms is DNA methylation, in which small chemical tags called methyl groups are added at specific sites along the DNA. These tags can influence the activity of certain genes, helping regulate specific cell functions.

Researchers examine DNA methylation as a possible link

To investigate whether DNA methylation might help explain the relationship between diet and MS, researchers analyzed data from 201 people with MS and 342 matched people without the disease who had participated in the Ausimmune Study. The study, conducted between 2003 and 2007 across four regions of Australia, aimed to identify environmental triggers of MS.

Participants completed food frequency questionnaires (FFQ) describing how often they had consumed 101 foods and drinks during the previous year. Researchers used the responses to calculate several scores reflecting how closely each person’s eating habits matched particular dietary patterns.

Overall, higher scores on aMED-Red — a modified version of the Alternative Mediterranean Diet score that awards a point for above-median consumption of unprocessed red meat — were significantly associated with lower odds of MS onset. Higher Healthy diet scores, reflecting diets richer in foods such as fish, poultry, eggs, vegetables and legumes, were also significantly associated with lower odds of MS onset.

These associations remained significant after accounting for multiple factors known to influence MS risk. The original aMED score showed a similar trend, but the association did not reach statistical significance.

The researchers next assessed whether diet scores were associated with patterns of DNA methylation. They examined 2,432 methylation sites identified in an earlier analysis of the same Ausimmune dataset as being associated with a first episode of central nervous system demyelination, which can be an early sign of MS. The sites were grouped into five clusters, called DNA methylation modules.

Immune-related DNA methylation pattern emerges

Both aMED and aMED-Red scores were significantly associated with higher scores on one methylation cluster, called the A5 module. These associations did not differ significantly according to the two common genetic variants linked to MS risk that were examined, suggesting that the “functional mechanisms by which Mediterranean diet intake may act upon MS … may be broadly generalisable among people with MS,” the researchers wrote.

Analyses showed that the A5 module contained 35 DNA methylation sites linked to 35 genes. These genes were involved in pathways regulating immune activity, including the activation and development of T cells and B cells, which participate in the immune responses involved in MS.

Statistical analyses further estimated that the A5 module accounted for about 30% of the association between aMED scores and MS onset and about 22% of the association for the aMED-Red scores.

“While further investigations are required to clarify these relationships, [the DNA methylation patterns] represent plausible modes by which the Mediterranean diet may affect MS risk via modulation of immune and cellular pathways,” the researchers concluded.