BARCELONA, Spain — Ultraprocessed foods (UPFs) may worsen multiple sclerosis (MS), providing compelling evidence for diet’s role in inflammatory disease exacerbation, new research suggested.

Over a 5-year follow-up, patients in the highest quartile of UPF consumption had a 30% greater risk for relapse than those in the lowest quartile (P = .01).

Within 2 years, high UPF consumers also showed more new active lesions on imaging (P = .05) and a greater increase in T2 lesion volume (P = .036), even after controlling for other prognostic factors.

On the basis of these data, “ultraprocessed food appears to function as a chronic inflammatory accelerant increasing the risk of relapse and other evidence of disease activity,” said study investigator Gloria Dalla Costa, MD, neurologist and researcher in the Department of Nutrition at the Harvard T.H. Chan School of Public Health, Boston.

The findings were presented at the Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2025.

UPFs and Increased MS Activity

UPFs have not only been linked to inflammatory conditions but also been linked to long-term health risks, including cardiovascular disease, cancer, and increased all-cause mortality.

A recent meta-analysis of more than 1.1 million participants showed that for every 10% increase in UPFs in the diet, the risk for mortality significantly increased (P < .001).

To explore the potential influence of UPFs on MS, researchers turned to the well-characterized Betaferon/Betaseron in Newly Emerging MS for Initial Treatment trial cohort.

This study originally examined whether early interferon beta-1b treatment after a clinically isolated syndrome (CIS) could slow progression to MS, reduce relapses, and improve MRI outcomes. After 15 years of follow-up, results confirmed an advantage for an early start with interferon beta-1b.

Dalla Costa’s study is a secondary analysis of this cohort, examining how UPF intake relates to MS disease activity over time. For the analysis, the investigators analyzed data from 451 patients randomly assigned to interferon beta-1b or placebo and followed for 5 years.

They applied a previously published UPF metabolomic signature to baseline plasma samples to derive individual UPF scores. Study outcomes included time to clinically definite MS (CDMS) or MRI-based MS, relapse rates, and MRI lesion metrics. The investigators adjusted for age, sex, treatment allocation, baseline disease burden, BMI, vitamin D levels, and smoking.

Plasma and urine collection was included in the protocol, allowing analysis of metabolites, an accurate approach to quantifying UPF exposure. Specifically, the goal was to evaluate a validated UPF-related metabolomic score in relation to MS activity, Dalla Costa said.

The metabolomic signature included 39 metabolites, 17 of which were positively associated with UPF exposure. Over the first 5 years, 208 patients with CIS converted to CDMS, while 243 did not.

Robust Data

At this timepoint, UPF scores did not differ between those who converted and those who did not, suggesting that UPF dietary exposure may not trigger MS onset, Dalla Costa said.

However, among patients who developed CDMS, those with higher UPF intake had significantly greater T1 hypointense lesion volume (P = .022) and lower Multiple Sclerosis Functional Composite Scores (P = .036) than those with lower UPF intake.

The greater number of relapses, the greater number of new active lesions, and the cumulative new active lesions in those in the highest quartile of UPFs all trended toward, or reached statistical significance, after adjustment for age, sex, treatments, baseline disease burden, BMI, vitamin D level, and smoking.

Dalla Costa acknowledged that confirmatory studies are needed. However, she believes the data are robust and applicable to clinical practice.

“I would recommend avoiding ultraprocessed foods as a valuable supporting strategy for early MS management,” she said.

Beyond their proinflammatory activity, Dalla Costa outlined several additional ways UPFs could directly or indirectly contribute to greater MS activity. These include substances within UPFs that may impair central nervous system defenses or cause metabolic stress that hinders repair.

The proinflammatory effects of UPFs — industrially formulated and designed foods — have been well documented in multiple studies. A 2024 review in Nature Reviews linked several mechanisms of immune dysregulation to synthetic ingredients and to processing methods such as hydrogenation and extrusion.

Dalla Costa added that the degree of ultraprocessing can be quantified using the Nova food classification system, developed more than a decade ago.

Clinically Relevant Findings

When asked whether a prospective randomized trial is planned to confirm the study’s findings, Dalla Costa noted that a randomized trial would be costly and complex, given the well-known challenge of recruiting participants who will maintain long-term dietary changes.

However, Liliana Patrucco, MD, co-director of the Multiple Sclerosis Center of Buenos Aires, Buenos Aires, Argentina, who was not involved in the study, said that finding ways to strengthen the evidence is still worthwhile. She noted that, even beyond UPFs, a growing body of research has linked proinflammatory diets to worsening MS and other inflammatory diseases.

“This is an association that is very clinically relevant and a potentially important way to modify risk of MS activity and progression,” Patrucco said.

Given the broader evidence of adverse health effects from UPFs, she suggested that patients might be encouraged to reduce their intake now, even if additional research is needed to confirm a disease-modifying effect in MS.

This study received funding from Bayer. Dalla Costa reported having no relevant financial relationships. Patrucco reported having financial relationships with Avanir, Bayer, Biogen, Merck, Novartis, and Teva.