Low-fat diet may help reduce fatigue in MS, new trial analysis suggests

A low-fat diet may help reduce fatigue in multiple sclerosis (MS) by altering how the body processes lipids, or fats, and amino acids, which serve as the building blocks of proteins, a small study by U.S. researchers suggests.

These scientists analyzed data from a small clinical trial involving adults with MS that evaluated the effects of starting a low-fat eating plan versus continuing the usual diet. This follow-up analysis specifically focused on potential links between changes in fatigue and metabolism — the full range of chemical reactions whereby the body converts food into energy.

The trial’s participants had experienced a reduction in fatigue after following the low-fat diet. This analysis found decreases in fat mass and low-density lipoprotein (LDL) cholesterol, known as bad cholesterol, among these individuals.

Still, the researchers noted that the small size of the trial limits any real takeaways.

“These findings highlight lipid and amino acid pathways as candidates for future investigation in MS fatigue,” the scientists wrote, adding that larger studies are needed to confirm these benefits and to better understand how dietary changes can ease symptoms.

The study, “Low-fat diet reduces fatigue and alters serum metabolomic pathways in people with multiple sclerosis: a sub-study of a randomized controlled trial,” was published in the journal Multiple Sclerosis and Related Disorders.

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Fatigue is one of the most common symptoms of MS, a disease that occurs when the immune system mistakenly attacks the protective covering of nerve fibers in the brain and spinal cord. Although dietary changes may help reduce fatigue, the biological pathways involved are not fully understood.

Here, the research team conducted an exploratory analysis of data from a four-month, single-center clinical trial (NCT03322982) that evaluated the effects of starting a low-fat diet against continuing the usual diet among adults with MS.

After trial data showed the low-fat diet was associated with a significant reduction in fatigue, the scientists took a look at possible links between changes in metabolism and fatigue.

Looking beyond a low-fat diet into body metabolism

The new analyses covered 27 trial participants — 16 in the low-fat diet group and 11 in the control group — who had paired fatigue and blood metabolomic data at the study’s start and after four months. The researchers also examined several other measures, including patients’ dietary intake and body composition, as well as physical activity.

Fatigue was assessed using the Modified Fatigue Impact Scale (MFIS), a questionnaire that measures how fatigue affects physical activity, cognition, and social and emotional life. After four months, scores dropped — indicating improvements — significantly in both groups, by 12.9 points in the low-fat diet group and 8.5 points in the control group. Still, the difference between groups failed to reach statistical significance, meaning it could be due to chance.

People in the low-fat diet group reduced the percentage of calories from fat by 15.2%, while the others showed almost no change, resulting in a significant group difference. They also consumed significantly less saturated and trans fats, which are linked to heart and blood vessel diseases, and significantly more fiber.

Compared with the individuals who continued their usual diet, those in the low-fat diet group also experienced significantly greater reductions in fat mass, total cholesterol, and LDL cholesterol, as well as marking a significant increase in physical activity.

When the researchers looked at blood levels of metabolites, or the molecules produced when the body processes food and other materials, they found 847 metabolites of known identity across samples. Slightly more than half were involved in lipid pathways, while 20% were part of amino acid pathways.

To our knowledge, this is the first study to associate [easing of] fatigue following a low-fat dietary intervention with … [metabolism-related] changes in people with MS.

Importantly, greater changes in MFIS scores were linked to changes in lipid and amino acid pathways, the researchers noted. Examples included octadecenedioylcarnitine and cis-4-decenoate (involved in lipid metabolism) and phenol sulfate and phenylpyruvate (involved in amino acid metabolism).

For instance, acylcarnitines, which help transport fatty acids (a type of fatty molecule) for energy production, decreased by 1.76% to 6.47% in the low-fat diet group but increased by 5.48% to 39.56% in the group of patients who continued their usual diet. According to the researchers, this may reflect changes in mitochondrial fatty acid beta-oxidation, the process in which mitochondria, the cells’ powerhouses, break down fats to release energy.

Also, phenol sulfate, a gut-derived metabolite, increased by 30.88% in the low fat-diet group and decreased by 4.64% in the control group.

Overall, the findings suggest that a low-fat diet may lessen fatigue in MS by altering lipid and amino acid metabolism. However, the study involved few patients, and individual responses varied. Because the difference in fatigue between groups was not statistically significant, larger studies are needed to confirm these preliminary findings, the scientists noted.

“To our knowledge, this is the first study to associate [easing of] fatigue following a low-fat dietary intervention with [blood] metabolomic changes in people with MS,” the researchers wrote.

Still, “replication in larger, longitudinal [studies] with mechanistic validation will be critical to confirm these findings and explore their potential as biomarkers or therapeutic targets,” the team noted.