Intermittent calorie restriction alters T cell subsets and metabolic markers in people with multiple sclerosis

Kathryn C Fitzgerald; Pavan Bhargava; Matthew D Smith; Diane Vizthum; Bobbie Henry-Barron; Michael D Kornberg; Sandra D Cassard; Dimitrios Kapogiannis; Patrick Sullivan; David J Baer; Peter A Calabresi; Ellen M Mowry

doi:10.1016/j.ebiom.2022.104124

Intermittent calorie restriction alters T cell subsets and metabolic markers in people with multiple sclerosis

EBioMedicine. 2022 Aug:82:104124. doi: 10.1016/j.ebiom.2022.104124. Epub 2022 Jul 8.

Affiliations

¹ Division of Neuroimmunology and Neurological Infections, Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, United States. Electronic address: fitzgerald@jhmi.edu.
² Division of Neuroimmunology and Neurological Infections, Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, United States.
³ Institute for Clinical and Translational Research, Johns Hopkins School of Medicine, Baltimore, MD, United States.
⁴ Department of Cellular and Molecular Neuroscience, National Institute on Aging, Baltimore, MD, United States.
⁵ Beltsville Human Nutrition Research Center, United States Department of Agriculture, Beltsville, MD, United States.

Abstract

Background: Intermittent fasting or calorie restriction (CR) diets provide anti-inflammatory and neuroprotective advantages in models of multiple sclerosis (MS); data in humans are sparse.

Methods: We conducted a randomised-controlled feeding study of different CR diets in 36 people with MS over 8 weeks. Participants were randomised to 1 of 3 diets: 1) a control diet, in which the participant received 100% of his or her calorie needs 7 days per week, 2) a daily CR diet, in which the participant received 78% of his or her calorie needs 7 days per week, or 3) an intermittent CR diet, in which the participant received 100% of his or her calorie needs on 5 days per week and 25% of his or her calorie needs 2 days per week (i.e., a "5:2" style diet). Untargeted metabolomics was performed on plasma samples at weeks 0, 4 and 8 at Metabolon Inc (Durham, NC). Flow cytometry of cryopreserved peripheral blood mononuclear cells at weeks 0 and 8 were used to identify CD3⁺;CD4⁺ (CD4⁺) and CD3⁺;CD4^- (as a proxy for CD8⁺) T cell subsets including effector memory, central memory, and naïve cells.

Findings: 31 (86%) completed the trial. Over time, individuals randomised to intermittent CR had significant reductions in effector memory (for CD4^-_EM: -3.82%; 95%CI: -7.44, -0.21; for CD4^-: -6.96%; 95%CI: -11.96, -1.97) and Th1 subsets (-4.26%; 95% CI: -7.11, -1.40) and proportional increases in naïve subsets (for CD4^-: 10.11%; 95%CI: 3.30, 16.92%). No changes were observed for daily CR or weight-stable diets. Larger within-person changes in lysophospholipid and lysoplasmalogen metabolites in intermittent CR were associated with larger reductions in memory T cell subsets and larger increases in naïve T cell subsets.

Interpretation: In people with MS, an intermittent CR diet was associated with reduction in memory T cell subsets and certain biologically-relevant lipid markers.

Funding: National MS Society, NIH, Johns Hopkins Catalyst Award.

Keywords: Diet; Immunophenotyping; Intermittent fasting; Multiple sclerosis.

Publication types

Randomized Controlled Trial

MeSH terms

CD4-Positive T-Lymphocytes
Caloric Restriction*
Energy Intake
Female
Humans
Leukocytes, Mononuclear
Male
Multiple Sclerosis*
T-Lymphocyte Subsets

Grants and funding

UL1 TR001079/TR/NCATS NIH HHS/United States