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Higher consumption of oily fish such as tuna and salmon or lean fish like cod and perch is associated with a reduced risk for disability progression in patients with multiple sclerosis (MS), a new study confirmed.

Investigators observed the positive associations across three different disability measures, suggesting that diets high in fish may offer benefits across different disease stages.

While the benefit was greater in people who consistently ate more fish over time, the risk for disability progression was lower even among those who added more fish to their diet years after their MS diagnosis.

The reduced risk is likely due to the anti-inflammatory and neuroprotective properties of nutrients such as omega 3 fatty acids and taurine found in fish, investigators noted.

“The results underscore the potential role of diet, particularly fish consumption, as a modifiable factor that could complement existing therapeutic strategies for MS,” lead investigator, Eva Johansson, Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden, and colleagues wrote.

The findings were published online on February 25 in the Journal of Neurology, Neurosurgery and Psychiatry.

Progression Push Back?

Previous research has linked higher fish consumption to more favorable disability outcomes in MS. However, robust longitudinal studies examining the impact of fish consumption on progression of MS-related disability were lacking.

Despite advancements in disease-modifying therapies, which significantly reduce relapse rates and slow progression for some patients, preventing disease progression remains a major challenge.

The current analysis included 2719 Swedish patients with MS (mean age at diagnosis, 38 years) from the Epidemiologic Investigation of Multiple Sclerosis, who were recruited between April 2005 and June 2015 and followed for up to 15 years through the Swedish MS Registry.

For fish consumption, participants reported their average consumption of lean and oily fish. Oily fish species was defined as those with a fat content > 3%, such as herring, mackerel, tuna, salmon, and trout. Lean fish was defined as species with a fat content < 3%, such as cod, pollock, haddock, whiting, pike, and perch.

Researchers recorded responses about fish consumption as never/seldom, 1-3 times/month, or weekly. They summed the responses, yielding a value between 2 (lowest exposure) and 6 (highest exposure).

Outcomes included confirmed disability worsening (CDW) as defined by an increase in the expanded disability status scale (EDSS) score by at least 1 point from baseline and sustained between two follow-up visits separated by no < 6 months, and time to progression to EDSS 3 and EDSS 4.

The analyses controlled for age, sex, disease phenotype, disease duration, and treatment.

Compared with never/seldom fish consumption, the highest consumption was associated with a 44% lower risk for CDW (adjusted hazard ratio [aHR], 0.66; 95% CI, 0.51-0.86), a 45% lower risk for progression to EDSS 3 (aHR, 0.55; 95% CI, 0.53-0.79), and a 43% lower risk for progression to EDSS 4 (aHR, 0.57; 95% CI, 0.33-0.96).

Consistent Benefit

Consistent associations across disability measures suggests higher fish consumption “may exert a stable beneficial impact across different stages of MS progression,” the investigators wrote.

Participants were asked to complete a follow-up questionnaire in 2021, capturing lifestyle habits from the time of diagnosis. Of the 1719 patients who completed the questionnaire, 24% had altered their fish consumption frequency.

The study showed those who consistently consumed high levels of fish over time had a more pronounced inverse association.

“This consistency might be important because the anti-inflammatory and neuroprotective benefits of nutrients found in fish may accumulate over time, leading to sustained improvements in health outcomes,” the investigators wrote.

Individuals who increased their fish consumption from a frequency score of 2-3 to a score of 5-6 within 5 years after MS diagnosis had a significantly reduced risk for CDW (HR, 0.80; 95% CI, 0.63-0.99) compared with those whose fish consumption remained low.

The authors noted omega-3 fatty acids found in oily fish are well-known for their anti-inflammatory properties, and the beneficial effects from lean fish consumption might be due to taurine, an amino acid found in significant amounts in fish and seafood.

Taurine has diverse cellular functions, including cytoprotective actions through antioxidative and anti-inflammatory effects, making it a potential therapeutic agent for neurological disorders, the researchers noted.

Diet also affects gut microbiota, which has been shown to influence the production and metabolism of fatty acids with potential immunomodulatory effects, they added.

“Therefore, the beneficial impact of fish consumption on MS progression might also be mediated through favorable modifications of gut microbiota composition and function,” the investigators wrote.

Supplementary analyses found results were similar after adjusting for physical activity, body mass index, smoking, alcohol, sun exposure, and vitamin D levels, suggesting “vitamin D may not be the primary factor driving the observed benefits of fish consumption on disability progression in MS,” they observed.

A sensitivity analysis focused on participants enrolled between 2007-2011 showed that the association between high fish consumption and risk for disease worsening remained consistent (HR, 0.67; 95% CI, 0.46-0.97), and the trend of decreasing risk for CDW with increasing consumption of fish was maintained (HR, 0.93; 95% CI, 0.87-1.00).

Questions Remain

Commenting through the nonprofit UK Science Media Centre (SMC), Aravinthan Varatharaj, PhD, clinical lecturer in neurology, University of Southampton, Southampton, England, noted UK guidelines recommend eating at least two portions of fish per week, with at least one being oily fish, although most people in the UK eat less than this and only a minority regularly eat oily fish.

“People with multiple sclerosis already know the importance of a healthy balanced diet, and this study is another bit of evidence to say that eating more fish is good for you,” said Varatharaj.

That people who began eating more fish later still benefited “goes to show that making a lifestyle change after diagnosis can have a positive impact,” Varatharaj added.

But the study didn’t look at whether people who ate less fish were also less well-off, said Varatharaj. “Fish can be expensive, so this could be a factor. We know that people with lower incomes have worse health outcomes — for multiple sclerosis and many other conditions.”

The apparent consistent dose-response relationship between fish consumption and MS severity “is the first time this has been reliably described,” noted Ruth Dobson, PhD, clinical senior lecturer in neurology, Queen Mary University of London, London, England, in the SMC statement.

The same is true for physical activity and smoking behavior, but this has been shown before, she added.

“I don’t think this (study) fully answers the question about whether it is fish consumption directly that influences MS (although this is completely plausible), whether it is synergistic with other lifestyle traits (I think this is most likely), or whether it is purely acting as a surrogate for other lifestyle traits (less likely),” she said.

Although the authors adjusted for a number of factors, residual confounding remains a concern in all studies like this, said Dobson.

This study was supported by grants from the Swedish Research Council, Swedish Research Council for Health, Working Life and Welfare, Swedish Brain Foundation, Swedish Medical Research Council, Margaretha af Ugglas Foundation, Swedish Foundation for MS Research, and NEURO Sweden. Johansson reported no relevant disclosures. Disclosures for other authors are included in the original article. Varatharaj is involved in trials of disease-modifying treatments for progressive MS, is an investigator on the UK MS Register, and has received funding from Roche, which makes pharmaceuticals for MS. Dobson had no relevant conflicts of interest.