Calorie Restriction Diets Associated With Reduction in Memory T Cell Subsets in Multiple Sclerosis


Investigators conducted a study to assess the effects of CR diet on immune cell subsets, concluding that observed changes could be mediated by changes in classes of lipid metabolites.

Kathryn Cauley Fitzgerald, ScD, assistant professor of neurology, Johns Hopkins University School of Medicine, in Baltimore, Maryland

Kathryn Cauley Fitzgerald, ScD

Intermittent calorie restriction (CR) diets were associated with reduction in memory T cell subsets in patients with multiple sclerosis, a recent study found. According to data presented at Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2022, February 24-26, in West Palm Beach, Florida, these changes have potential to be mediated by changes in certain classes of lipid metabolites.1

Investigators, led by Kathryn Cauley Fitzgerald, ScD, assistant professor of neurology, Johns Hopkins University School of Medicine, in Baltimore, Maryland, initially included 36 patients with MS, conducting a controlled feeding study of 3 CR diets over an 8-week period. Patients were randomized to either a daily CR diet, including a 22% daily reduction in energy needs; an intermitted CR diet, including a 75% reduction in calorie needs for 2 days each week, with 100% of daily needs for 5 days each week; or a weight-stable diet, including 100% of daily calorie needs.

Thirty-one patients (86%) completed the trial. Those who underwent intermittent CR had significant reductions in memory T cell subsets, including CD4+EM(–5.00%; 95% CI, –8.73% to –1.28%; P = .008), CD4+CM (–3.84%; 95% CI, –7.45 to –0.23; P = .04), and CD8+EM (–7.08%; 95% CI, –12.10 to –2.06; P = .006). These patients also had concomitant increases in naïve subsets, including CD4+Naïve (5.93%; 95% CI, 0.10-11.77; P = .05) and CD8+Naïve (10.32%; 95% CI, 3.47-17.17; P = .003).

Investigators did not observe notable changes in T cell subsets for patients randomized to daily CR or weight stable diets. Larger within person change in phospholipids and phosphoethanolamine metabolites were associated with larger reductions in memory T cell subsets, as well as increases in naïve T cell subsets for those in the intermittent CR group.

READ MORE: Significance and Role of B-Cell Depleting Medications for Multiple Sclerosis

“Intermittent fasting or calorie restriction (CR) diets may provide additional anti-inflammatory and neuroprotective advantages beyond the benefits obtained from weight loss alone,” Fitzgerald et al wrote.“In models of multiple sclerosis (MS), fasting delays the onset of the disease, reduces pro-inflammatory cytokines and promotes regeneration of oligodendrocytes. However, data in humans are lacking.”

Plasma was obtained through morning blood samples provided by participants at baseline and weeks 4 and 8. Additionally obtained via blood samples were peripheral blood mononuclear cells (PBMCs) at baseline and week 8. Those in the intermittent CR group had samples at weeks 4 and 8 collected after a 25% calorie-needs day. CD4+ and CD8+ T cells and memory subsets, including effector memory (TEM: CCR7‐ CD45RO+), central memory (TCM: CCR7+ CD45RO+), and naïve cells (TNaive: CCR7+ CD45RO‐) were identified from PBMCs.

The effect of diet has been explored in additional studies in MS, including the ketogenic diet, the Wahls diet, and the Swank diet. Findings from the WAVE study evaluation the Wahls and Swank elimination diet were presented at the 2021 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC), October 25-28, with data suggesting significant reductions for both groups in fatigue and cognitive dysfunction.2 Additional findings from the WAVE study are also being presented at this year’s ACTRIMS Forum.

Ultimately, at 12 weeks, the Swank diet group (n = 38) reported total Perceived Deficits Questionnaire (PDQ) scores of 25.1 (±2.00), compared with 32.4 (±2.36) at baseline, while the Wahls group (n = 39) reported total scores of 29.1 (±2.71), compared with 35.9 (±2.16) at baseline, both being a significant improvement (P ≤.05). At 24 weeks, those scores remained significant at 26.1 (±2.14) and 25.1 (±3.03), respectively (P ≤.05).

For more coverage of ACTRIMS Forum 2022, click here.

1. Fitzgerald K, Bhargava P, Smith MD, et al. Calorie restriction diets and changes in T cell subsets in people with multiple sclerosis. Presented at 2022 ACTRIMS Forum; February 24-26; West Palm Beach, FL and Virtual. Poster P093.
2. Titcomb T, Eyck PT, Hoth KF, Snetselaar L, Wahls T. Effect of the Swank and Wahls elimination diets on perceived fatigue and cognitive dysfunction in relapsing-remitting multiple sclerosis: a randomized parallel-arm trial. Presented at: CMSC 2021; October 25-28; Paper 7210.

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