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
Affiliations
Kathryn C. Fitzgerald
Division of Neuroimmunology and Neurological Infections, Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, United States; Corresponding author at: Departments of Neurology and Epidemiology, Johns Hopkins University School of Medicine, Pathology 627, 600 N. Wolfe St. Baltimore, MD 21287, United States.
Pavan Bhargava
Division of Neuroimmunology and Neurological Infections, Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, United States
Matthew D. Smith
Division of Neuroimmunology and Neurological Infections, Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, United States
Diane Vizthum
Institute for Clinical and Translational Research, Johns Hopkins School of Medicine, Baltimore, MD, United States
Bobbie Henry-Barron
Institute for Clinical and Translational Research, Johns Hopkins School of Medicine, Baltimore, MD, United States
Michael D. Kornberg
Division of Neuroimmunology and Neurological Infections, Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, United States
Sandra D. Cassard
Division of Neuroimmunology and Neurological Infections, Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, United States
Dimitrios Kapogiannis
Department of Cellular and Molecular Neuroscience, National Institute on Aging, Baltimore, MD, United States
Patrick Sullivan
Beltsville Human Nutrition Research Center, United States Department of Agriculture, Beltsville, MD, United States
David J. Baer
Beltsville Human Nutrition Research Center, United States Department of Agriculture, Beltsville, MD, United States
Peter A. Calabresi
Division of Neuroimmunology and Neurological Infections, Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, United States
Ellen M. Mowry
Division of Neuroimmunology and Neurological Infections, Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, United States
Summary: 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.
