Researchers defined intermittent fasting as 500-calorie fasting twice a week and determined it to be a safe and effective dietary strategy in patients with relapsing-remitting multiple sclerosis. A study on this by Ghezzi and colleagues has been published in the Journal of Neurology Neurosurgery and Psychiatry. A small randomized trial showed reductions in the proinflammatory adipokine leptin, which correlated with improvements in cognitive processing speed and immune function. The results implicate dietary interventions as ancillary to the management of MS symptoms and a reduction in disease activity.

Multiple sclerosis is a chronic autoimmune disorder characterized by inflammation and neurodegeneration in the central nervous system. Diet is of considerable interest to a large proportion of patients with MS, although there is little evidence for its effect on the course of the disease. Leptin represents an adipokine released by adipose tissue and is involved in MS pathology; its levels are increased in the cerebrospinal fluid and serum of patients with MS. Because it has proinflammatory properties and is associated with the risk of MS, the researchers investigated whether intermittent calorie restriction might reduce leptin levels and if this would improve clinical outcomes in relapsing-remitting MS.
This study was carried out at the Washington University School of Medicine in St. Louis from 2018 to 2021 and enrolled 42 patients with relapsing-remitting MS who were randomized to either an intermittent fasting group or a control group. Thirty-four patients completed the trial: 17 in each group. The primary outcome measure was a reduction in leptin levels in the serum at 12 weeks.
Those in the intermittent fasting arm were asked to restrict their daily caloric intake to 500 or fewer calories on two consecutive days a week. On days of actual fasting, participants were permitted to take non-starchy vegetables, non-caloric beverages, and a very small amount of oil. On non-fasting days, the subjects were encouraged to maintain their usual diet but with portion size recommendations. The participants in the control arm were asked to maintain their usual diet but were further advised to eat vegetables every day to ensure that the two groups consumed similar amounts of vegetables.
Key Findings
• In the intermittent fasting group, after 12 weeks, the level of leptin was significantly reduced to the control group, adding to a positive metabolic-inflammatory profile in patients with MS.
• At 12 weeks, the fasting group had higher scores on the Symbol Digit Modality Test, indicative of faster cognitive processing.
• It also showed a 6-week increase in CD45RO+ regulatory T-cells in the fasting group, which may be related to some immune benefits of the diet.
• The adherence to the fasting regimen was very good, with the participants following it 99.5% of the time for the first 6 weeks and 97.2% during the second 6 weeks.
• There were no grade 3 or higher adverse events reported. Mild headache and fatigue noted on fasting days did not lead to discontinuation.
The findings enhance the current knowledge base on the role of diet as an adjunctive strategy for MS. Intermittent-fasting was associated with reductions in the pro-inflammatory marker circulating leptin, pointing to the potential for even moderate dietary changes to exert changes in disease pathways in MS. While small, the trial showed high compliance and positive effects on cognitive function and immune markers. A current clinical trial, FOOD for MS, is underway, which will ascertain potential benefits in more detail, including longer-term outcomes, such as MRI findings and thorough functional assessment.
In sum, the authors demonstrate in this study that intermittent fasting represents a feasible and probably beneficial dietary strategy for patients with relapsing-remitting MS. By lowering proinflammatory markers and improving cognitive and immune functions, IF might become a useful addendum to MS therapies available today. However, larger and longer studies are needed to confirm such findings and flesh out the broader implications of dietary interventions in MS management.
Reference:
Ghezzi, L., Tosti, V., Shi, L., Cantoni, C., Mikesell, R., Lancia, S., Zhou, Y., Obert, K., Dula, C., Sen, M. K., Ge, A., Tolentino, M., Bollman, B., Don, A. S., Matarese, G., Colamatteo, A., La Rocca, C., Lepore, M. T., Raji, C. A., … Piccio, L. (2024). Randomised controlled trial of intermittent calorie restriction in people with multiple sclerosis. Journal of Neurology, Neurosurgery, and Psychiatry, jnnp-2024-333465. https://doi.org/10.1136/jnnp-2024-333465