A small first-of-its-kind study from Johns Hopkins University found that intermittent calorie-restricted diets is associated with reduced memory T cell subsets in people with multiple sclerosis (MS).
The study was undertaken by Dr Kathryn Fitzgerald from the Division of Neuroimmunology at Johns Hopkins University and colleagues. Their research was published on medRxiv.org as a preprint and has not yet been peer reviewed.
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.
Limitations
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.
Study details
Intermittent calorie restriction alters T cell subsets and metabolic markers in people with multiple sclerosis
Kathryn Fitzgerald, Pavan Bhargava, Matthew Smith, Diane Vizthum, Bobbie Henry-Barron, Michael Kornberg, Sandra Cassard, Dimitrios Kapogiannis, Patrick Sullivan, David Baer, Peter Calabresi, Ellen Mowry
Posted on medRxiv on 12 January 2022
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. Patients were randomised to receive either: a daily CR diet (22% reduction in calories, 7 days/week), an intermittent CR diet (75% reduction, 2 days/week; 100%, 5 days/week), or a weight-stable diet (100%, 7 days/week). 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 CD4+ and CD8+ T cell subsets including effector memory, central memory, and naïve cells.
Results
31 (86%) completed the trial. Over time, individuals randomised to intermittent CR had significant reductions in CD4+CM -4.87%; 95%CI: -8.59%, -1.15%; p=0.01), CD4+EM (−3.82%; 95%CI: -7.44, – 0.21; p=0.04), and CD8+EM (−6.96%; 95%CI: -11.96, -1.97; p=0.006) with proportional increases in naïve subsets (CD4+Naïve: 5.81%; 95%CI: -0.01, 11.63%; p=0.05; CD8+Naïve: 10.11%; 95%CI: 3.30, 16.92%; p=0.006). 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.
Conclusions
In people with MS, an intermittent CR diet was associated with reduction in memory T cell subsets. The observed changes may be mediated by changes in specific classes of lipid metabolites.
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