ACTRIMS 2023: Intermittent fasting shows potential to lessen MS severity

Small RRMS trial also finds cognitive benefits with twice weekly restricted diet

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Limiting calorie intake over two days of each week for three months led to beneficial immune and metabolic changes, as well as improvements in cognitive function, among people with relapsing-remitting multiple sclerosis (RRMS), a study found.

A restrictive diet also promoted a better body composition, namely a reduction in body fat.

These findings suggest that intermittent calorie restriction, or intermittent fasting, is “safe and feasible in [people with MS], and can ameliorate metabolic, immunologic and cognitive profiles,” the researchers wrote in the abstract “Randomized Clinical Trial of Intermittent Calorie Restriction in People with Multiple Sclerosis: Effects on Immunometabolic and Cognitive Measures.

Laura Piccio, MD, PhD, a neurologist and professor of neurology at Washington University in St. Louis, Missouri, and the University of Sydney, presented study findings at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2023, held Feb. 23-25 in San Diego.

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Research suggests restrictive diet can promote anti-inflammatory changes

Obesity in childhood and adolescence has been linked to a higher risk of developing multiple sclerosis (MS) in adulthood. While the mechanisms underlying this relationship are complex, adipose, or fat tissue, is a key factor, according to Piccio.

That tissue secretes hormones and other signaling molecules, collectively referred to as adipokines, that can have direct effects on immune cells. Some adipokines like leptin have pro-inflammatory effects, while others, such as adiponectin, are anti-inflammatory.

Obesity can alter adipokine production and “shift the balance towards a more pro-inflammatory milieu,” which may promote autoimmunity, Piccio noted.

A growing body of evidence also suggests that a calorie restrictive diet can lead to metabolic, hormonal, and immune system changes that are anti-inflammatory.

Piccio’s team previously reported that dietary restrictions — either through daily or intermittent fasting — significantly eased disease severity in an MS mouse model, in addition to lowering inflammatory T-cells levels and altering the composition of microbes in the gut.

A pilot trial by a separate research team found that eight weeks of calorie restriction or intermittent fasting safely led to weight loss in MS patients, and resulted in altered levels of adipokines, immune cell subsets, and other molecules in their blood.

To extend these findings, Piccio’s team launched a clinical trial (NCT03539094) evaluating 12 weeks of intermittent calorie restriction in MS patients. The study, funded by the National MS Society, involved 42 adults with RRMS who were randomly assigned to a calorie restricted group or to a control group on a regular diet.

The intermittent fasting diet involved a lower calorie intake — about 400-500 calories per day — two days each week with a normal die for the other five days. On low-calorie days, the diet consisted of one to two salads consisting of “fresh, steamed or roasted” nonstarch vegetables and a light dressing.

This intermittent diet was chosen, Piccio said, because it may be more feasible for patients than fasting, or avoiding food entirely.

Adherence to the study was high, with 81% of participants or 34 people continuing until its end.

The trial met its main goal, that of lowering through diet blood levels of leptin, a hormone that helps to control appetite. Lower leptin levels were noted after six weeks among those following the calorie restrictive diet, and their leptin levels were significantly lower than control group levels at six and 12 weeks.

An increase in adiponectin levels also was observed with intermittent fasting after six and 12 weeks.

A group of lipids, or fat molecules, in the blood called lysophospholipids were significantly elevated with calorie restriction, while no changes were found in the control group. Notably, most of the lipids that changed with the calorie restriction positively correlated with adiponectin levels.

“We are now trying to understand what would be the underlying mechanism through which calorie restriction would modulate these lipids and what could be the biological meaning,” Piccio said.

Higher levels of protective regulatory T-cells seen with intermittent fasting

Changes also were observed in certain immune cell subsets with the intermittent fasting diet. Specifically, this diet was associated with reductions in inflammatory immune T-cell subsets and increases in regulatory T-cells, which play a protective role in MS.

People on the intermittent fasting diet saw significant reductions in proxy and direct measures of body fat compared with the study’s start, whereas no significant changes in body composition were seen among control group patients.

Cognitive performance, assessed with the Symbol Digit Modalities Test (SDMT), also improved with the calorie restriction diet, with patients performing significantly better than controls by week 12.

“We are aware that these results need to be taken with caution because there are multiple factors that can drive this change, but it’s definitely interesting and encouraging,” Piccio said.

A number of patient-reported outcomes, including fatigue levels and physical and psychological well-being, also improved with the calorie restriction diet.

Analyses are ongoing to assess diet-related changes in the gut microbiome, the collection of microbes living in the gut, Piccio said. A dysregulated gut microbiome has been implicated in MS diseases processes.

Note: The Multiple Sclerosis News Today team is providing in-depth coverage of the ACTRIMS Forum 2023 Feb. 23–25. Go here to see the latest stories from the conference. Follow along on Facebook, Twitter, and Instagram for live updates using the hashtag #actrims2023.