Following the Mediterranean diet was associated with a significantly lower risk for multiple sclerosis (MS), with the impact especially strong in people aged 45 years or younger and among nonsmokers, results of a large prospective study showed.

Investigators found that even small dietary changes showed positive benefits, with each 1-point increase in the Mediterranean Diet Score yielding a decrease in MS risk of 14% overall, 26% among nonsmokers, and 23% among people younger than 45 years.

“As the decreased MS risk is particularly evident among younger adults, we have to encourage healthy dietary habits early on [as] this can decrease the risk of disease onset,” lead author Sara Ratti, Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy, told Medscape Medical News.

Doctors should look at “the big picture,” she added. “We need a comprehensive approach to lifestyle counseling that includes both nutrition and smoking cessation, in addition to physical activity and other lifestyle habits.”

The findings were published online on December 15 in Multiple Sclerosis Journal.

Expanding the Scope of Research

A chronic disease of the central nervous system, MS is characterized by myelin loss, inflammation, and neurodegeneration. Smoking and age are key factors influencing the disease, the onset of which typically occurs between ages 20 and 45.

The Mediterranean diet, which emphasizes fruits, vegetables, grains, olive oil, and omega-3 fatty acids, is linked to a reduced risk for Alzheimer’s and Parkinson’s diseases, potentially due to the diet’s antioxidant and anti-inflammatory effects.

Previous research suggested adhering to this diet may also lower the risk for MS, but the scope of those studies was limited. For one thing, said Ratti, they mostly had a case-control design, which can involve recall bias.

The new study included 41,428 participants without MS (mean age, 52 years; 74.5% female) from the Swedish National March Cohort (SNMC) who had completed an extensive questionnaire on lifestyle and medical history. The authors noted that Sweden has one of the highest MS prevalence rates in the world, at 215 per 100,000.

Almost one third (32.1%) of the participants were aged 45 years or younger, and 61% were nonsmokers.

Researchers assessed dietary intake using a validated 85-item semiquantitative Food Frequency Questionnaire. Participants reported their average consumption for each food and beverage item during the previous year.

Small Changes, Big Difference

The authors assessed adherence to the Mediterranean diet using the Mediterranean Diet Score, which ranges from 0 to 9. Participants get 1 point for consuming more than the average of healthy items (vegetables, fruits, nuts, legumes, grains, fish, and unsaturated to saturated fat ratio) and for eating below the average of unhealthy items (dairy and meat).

Researchers categorized adherence into low (0-3 points, reference), medium (4-5 points), and high (6-9 points). They adjusted for sex, smoking status, BMI, education level, physical activity, energy intake, and levels of vitamin D and vitamin B12.

Ratti noted that previous studies didn’t always account for intake of such vitamins, which are known to influence neurodegenerative diseases.

During a mean follow-up of 17.6 years, 89 participants developed MS, identified through diagnostic codes.

The study showed each 1-point increase in the Mediterranean Diet Score was associated with a 14% lower risk for MS (adjusted hazard ratio [HR], 0.86; P = .03).

When examining low, medium, and high categories, there was no reduction in risk for the medium- vs low-adherence group. And although the high-adherence group showed a lower risk than the low-adherence group, this difference was not statistically significant.

The lack of significance is likely due to the heterogeneity within the medium-adherence group and very limited cases in some subgroups (the high-risk group had only 16), said Ratti. She stressed that because MS is considered a rare disease, statistical power is often constrained when analyzing specific categories.

Even small dietary changes can make a difference, commented Ratti. “You don’t necessarily need to follow the diet 100% to see a difference in risk. Every single point is associated with a 14% reduction in MS risk,” she noted.

With its prospective design, the study may hold more weight than previous research. “We collected dietary data at baseline, before any symptoms appeared,” said Ratti. “So we were able to establish a clear temporal sequence: The diet came first, and the disease potentially followed.”

Toxic Effect of Tobacco

Smoking status affected associations between diet adherence and MS risk. While there was no statistically significant association among smokers, there was a 26% risk reduction per 1-point increase in score (HR, 0.74; P = .002) among nonsmokers.

This is consistent with evidence indicating that smoking “triggers systematic inflammation and oxidative stress, which are key factors for MS pathogenesis and progression,” said Ratti. “In this case, the toxic, proinflammatory effect of tobacco use may be so dominant that it overwhelms the neuroprotection the diet can provide.”

Age, too, affected associations. Higher adherence to the Mediterranean diet lowered the risk for MS among those aged 45 years or younger (HR per 1-unit increase in Mediterranean Diet Score, 0.77; P = .008), but there was no significant association among older participants.

Ratti noted that older participants are more likely to have comorbidities, which could counteract the benefits of the diet.

To minimize the risk for reverse causation, researchers conducted a sensitivity analysis excluding MS cases diagnosed in the first 2 years of follow-up. Associations between Mediterranean diet adherence and MS risk remained mostly unchanged.

Discussing the potential mechanism underlying the findings, Ratti noted the Mediterranean diet has proven neuroprotective, anti-inflammatory, and antioxidant properties, along with cardio, renal, and metabolic benefits.

In addition to there being only 89 identified MS cases, which limited statistical power, the findings may not be generalizable to younger people at risk for MS. Another potential study limitation is that diet was assessed only at baseline, which prevented the examination of dietary changes over time.

Big Caveat

Commenting on the findings for Medscape Medical News, Michael D. Kornberg, MD, PhD, associate professor of neurology, Division of Neuroimmunology and Neurological Infections, Johns Hopkins University, Baltimore, highlighted the large initial population that was studied.

“The Swedish patient database is very sophisticated and very accurate. And so from an epidemiology standpoint, I think this is stronger than many prior studies,” said Kornberg, who was not part of the study.

However, because it’s still not a randomized trial, “you can’t definitively establish causation,” he added. “There are probably many other healthy habits that people who adhere to the Mediterranean diet have that could also impact MS risk.”

Kornberg noted that diet was assessed only once at baseline, and that assessment was based on patient reporting. Another big caveat, he said, was that with a mean age of 52 years, the study population was older than most people at risk for MS.

Also reached for comment, Barbara Giesser, MD, Pacific Neuroscience Institute, Santa Monica, California, said the study adds to current knowledge about the impact of the Mediterranean diet on MS.

“There’s a growing body of evidence that the Mediterranean diet has benefits for people already diagnosed with MS, and this study adds to current information suggesting that the diet may lower the risk of MS as well,” Giesser told Medscape Medical News.

Clinicians can now “confidently recommend” the diet to people with MS, “and this may be a mitigating strategy for those thought to be at increased risk,” added Giesser, who was not part of the research.

Gloria Dalla Costa, MD, research scientist, Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, agreed that the study “ provides valuable prospective evidence” that adherence to the Mediterranean diet may reduce MS risk and reinforces “that dietary counseling should be part of comprehensive lifestyle modification — alongside smoking cessation,” said Costa, who also was not part of the study. 

And she noted the findings complement emerging evidence on ultraprocessed foods and MS activity that suggest that “what we eat matters both for disease risk and progression.”

Open access funding was provided by Karolinska Institute. The SNMC was supported by ICA Gruppen AB; Telefonaktiebolaget LM Ericsson; the Swedish Cancer Society; and the Strategic Research Area Health Care Science, Karolinska Institute. Ratti, Kornberg, Giesser, and Costa reported having no relevant conflicts of interest.