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

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.