Intermittent Fasting in MS Leads to Immune Cell, Metabolic Changes

An eight-week calorie-restricted diet plan — known as intermittent fasting — led to immune and metabolic changes among people with multiple sclerosis (MS) in a small pilot clinical trial, data show.

The findings could underlie some of the proposed benefits of calorie restriction on MS disease course, the researchers noted, also pointing out that better outcomes were seen among patients on an intermittent fasting plan than a traditional weight loss diet.

Larger studies are needed to confirm these results and determine the role of such intermittent fasting in several aspects of the disease, according to the team.

The study, “Intermittent calorie restriction alters T cell subsets and metabolic markers in people with multiple sclerosis,” was published in eBioMedicine.

Diet has emerged as an important factor that may impact MS progression, potentially via “direct modulation of the immune system, via alterations to gut bacteria, or by changes to metabolism,” the scientists wrote.

In mouse models of the disease, intermittent calorie restriction or fasting — a diet plan that switches between significant calorie restriction and a normal diet on a pre-specified schedule — led to a less aggressive MS disease course and eased inflammation.

However, the effects of such a diet among MS patients have not been thoroughly explored.

Investigating intermittent fasting diet plans in humans

In a previous pilot trial, called Alternating the Timing and Amount of Calories in MS, or ATAC-MS (NCT02647502), researchers evaluated the effects of different types of calorie restrictive diets in people with relapsing-remitting MS.

The trial recruited 36 patients — 29 women and seven men, with an average age of 37.4 — at the Johns Hopkins MS Center, in Baltimore. Participants were randomly assigned to receive either a control diet, a calorie-restricted diet, or an intermittent fasting-like diet for eight weeks, or about two months. There were 12 patients in each of the three groups.

In the control diet, patients received 100% of their calorie needs every day, while those on a calorie-restricted diet got 78% of their calorie needs daily. Those assigned to the intermittent calorie-restricted diet received 100% of their calorie needs five days per week and 25% of calorie needs two days per week.

All meals were tailored to each individual’s caloric needs and delivered to participants’ homes twice weekly. A total of 31 patients (86%) completed the study.

Results showed that both an intermittent fasting diet and a traditional daily calorie-restricted plan were safe and feasible ways to achieve weight loss. Both diet plans also were associated with improvements in emotional health.

The team now aimed to expand on these findings by examining how these different diets influenced various facets of metabolism and immune function. They used blood samples collected at study’s start and at four and eight weeks.

Results showed that blood levels of leptin and adiponectin — two hormones involved in the regulation of body weight and responses to insulin — did not change with either calorie-restricted diet, but were significantly reduced with the control diet.

This was in contrast with “several previous studies implicating a link between fasting and lowering of leptin levels and increasing of adiponectin,” the researchers wrote. However, they added that this could be related to the small number of trial participants and the large variability in the levels of those in the control group.

Participants who intermittently fasted showed significant changes in multiple types of immune T-cells that are central to the abnormal immune responses and inflammation that drive MS.

Specifically, effector memory T-cells, those previously activated against a specific molecule or microbe and that are readily available to mount a faster immune reaction upon re-exposure, were decreased. Also lowered were T-helper 1 cells, which activate other immune cells. In turn, the levels of inactive T-cells were increased.

No notable immune cell changes were observed among individuals who received daily calorie restriction or a weight-maintaining diet.

Impact of diet plans on the body

Both calorie-restricted diets led to several changes in the blood levels of a range of metabolites — intermediate or end products of cellular metabolism — that play a role in the production, breakdown, or storage of fats in the body.

Among patients on the intermittent diet, larger reductions in two of these metabolites, called lysophospholipids and lysoplasmalogens, “were associated with larger reductions in memory T cell subsets and larger increases in naïve T cell subsets,” the researchers wrote.

Lysophospholipids are mediators of a range of cellular activities, including tissue regeneration and inflammation, while lysoplasmalogens are thought to actively participate in the inflammatory process.

As such, these links could be related to the ability of some fat metabolites to influence the composition or function of T-cells, the researchers suggested.

The findings suggest that metabolic and immune cell changes may interact to underlie the effects of calorie-restricted diets in MS.

In addition to its small sample size and variable adherence to the diet, another limitation of this study was its short duration.

“MS is a disease that evolves over decades, so it’s unclear whether what the long-term implications of our findings are,” the team wrote.

“Future larger studies are needed to replicate our findings as well as disentangle the underlying mechanisms,” the researchers concluded, adding, “This knowledge will improve our understanding of the long-term implications of [calorie restriction] in people with MS, including whether the noted biological changes are relevant to the inflammatory or neurodegenerative aspects of the disease course.”