Possible Benefits of Calorie Restriction in
Multiple Sclerosis

Abdullah Hashmi, MD, for Medscape

January 20, 2022

The study covered in this summary was published on medRxiv.org as a preprint and has not yet been peer reviewed. 

Key Takeaways

  • Intermittent caloric restriction is associated with reduced memory T cell subsets in people with multiple sclerosis (MS).

  • Changes in circulating levels of lipid metabolites, such as acyl carnitines and specific glycerophospholipids, may mediate the changes in specific T cell subsets. 

Why This Matters

  • Although previous studies have shown that calorie-restricted (CR) diets are safe in people with MS, this first-of-its-kind study helped determine underlying mechanisms for immune changes by changes in diet. These immune changes may be beneficial for inflammatory and neurodegenerative diseases such as MS. 

Study Design

  • Thirty-six people with MS were randomly assigned against controls to receive specific diets over 8 weeks. 

  • Using the patient population from the ATAC-MS study, patients aged 18-50 years from the Johns Hopkins MS Center, with a body mass index of at least 23 and stable weight, relapsing-remitting MS for less than 15 years, a new lesion or relapse in the past 2 years, Expanded Disability Status Scale score <6.0, and no changes to their MS therapy, were followed over 8 weeks.

  • Participants were randomly assigned to one of three diets: 1) a control diet in which the participant received 100% of caloric needs daily, 2) a daily CR diet in which the participant received 78% of caloric needs daily, or 3) an intermittent CR diet in which the participant received 100% of caloric needs 5 days per week and 25% of caloric needs 2 days per week.

  • Blood samples for outcomes from patients were collected during weeks 0, 4, and 8.  Intermediate outcomes included the adipokines plasma leptin and adiponectin, which were measured using enzyme-linked immunosorbent assay. Peripheral blood mononuclear cells were isolated and stained with antibodies. CD4+ and CD8+ cells were quantified as percent CD3. T cell subtypes including effector memory (TEM), central memory (TCM), and naïve cells (TNa ï ve) were identified, as well as Th2 and Th1 cells. A total of 670 metabolites were identified using untargeted metabolomics.

  • Mixed regression models showed that overall changes in intermediate outcomes (immune cell subtype, metabolites) were associated with CR diets. Enrichment analyses compared differences in biological states. 

Key Results

  • Participants receiving an intermittent CR diet had significant reductions in CD4+ CM (−4.87%; P = .01), CD4+ EM (−3.82%; P = .04), and CD8+ EM (−6.96%; P = .006), as well as significant proportional increases in naïve subsets (CD4+ Naïve: 5.81% [P = .05]; CD8+ Naïve: 10.11% [P = .006]). No changes were observed in those receiving the control diet or the daily CR diet.

  • Individuals undergoing intermittent calorie restriction also experienced reductions in Th1 cells (−4.26%, P = .02) and Th1/17 cells (−3.49%). 

  • No changes were observed in adipokine levels with calorie restriction over the 8-week period.

  • Changes in biologically relevant lipid metabolites, including increases in acyl carnitine metabolites and reductions in glycerophospholipids, were associated with proportional reductions in memory T cell subsets and naïve T cell subsets.


  • The study was 8 weeks in duration. Given that MS is a disease that evolves over decades, long-term implications of changes in diet were unable to be assessed.

  • The study included only 36 participants, of whom 31 (86%) completed the trial.

  • The feeding study conducted was remote, and adherence to the protocol was self-reported. 

  • Adherence to study diets differed across treatment arms, and although attempts were made to account for the differences analytically, confounding may have impacted the ability to detect changes in the biologic mediators. 


  • Kornberg has received consulting fees from Biogen Idec, Janssen Pharmaceuticals, Novartis, OptumRx, and TG Therapeutics. Calabresi has received consulting fees from Disarm, NervGen, and Biogen and is a principal investigator on grants from Genentech. Mowry has grants from Biogen, is a principal investigator on studies sponsored by Biogen and Genentech, and receives free medication for a clinical trial from Teva.

This is a summary of a preprint research study, "Intermittent calorie restriction alters T cell subsets and metabolic markers in people with multiple sclerosis," written by Kathryn Fitzgerald from the Division of Neuroimmunology at Johns Hopkins University and colleagues, on medRxiv, provided to you by Medscape. This study has not yet been peer reviewed.  The full text of the study can be found on medRxiv.org. 

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