Ketogenic Diet Shows Potential for Modulating Immune Response in Multiple Sclerosis

Michael D. Kornberg, MD, PhD

(Credit: Johns Hopkins Medicine)

Findings from a new late-breaking study revealed that a ketogenic dietary approach, specifically the modified Atkins diet (MAD), may have significant immunomodulatory effects in patients with multiple sclerosis (MS). Presented at the 2025 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, held February 27 to March 1, in West Palm Beach, Florida, investigators observed notable changes in immune cell activity and metabolism after 6 months on the diet, highlighting its potential as an adjunctive strategy for managing MS.¹

In the analysis, the results showed that use of a MAD led to significant changes in both innate and adaptive immune responses. Authors noted that key findings included a reduction in proinflammatory myeloid cell phenotypes, a shift from memory to naïve CD8 T cells, and an increase in regulatory T (Treg) cells with enhanced suppressive function. Additionally, B-cell activation was reduced, which may suggest a broader dampening of inflammatory immune activity.

Presented by senior author Michael D. Kornberg, MD, PhD, associate director of the neurology residency program at Johns Hopkins Medicine, the study analyzed cryopreserved peripheral blood mononuclear cells and plasma from 39 patients with relapsing MS, who completed a previously-conducted phase 2 study of MAD for 6 months. Using a multi-omics approach, researchers assessed immune cell composition, gene expression, and metabolic shifts, revealing a broad range of anti-inflammatory effects in the findings.

Further supporting these immunological changes, investigators noted that the plasma analysis revealed decreased levels of inflammatory cytokines and chemokines, including IL-6 and CCL2. These molecules play a crucial role in driving inflammation in MS,² and their reduction suggests a systemic anti-inflammatory effect associated with the diet.

The research also examined how MAD influences immune cell metabolism. Previous studies have suggested that the balance between glycolysis (sugar metabolism) and fatty acid oxidation plays a role in immune cell function and inflammation.³ This study confirmed that 6 months on MAD promoted a shift from glycolysis to fatty acid oxidation across immune subsets.

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Plasma metabolomics data further supported these findings, showing reduced glycolytic byproducts such as lactate and pyruvate, along with increased fatty acid oxidation intermediates like acetylcarnitine. These metabolic adaptations may contribute to the observed reduction in inflammatory activity, as immune cells that rely more on fatty acid oxidation tend to exhibit anti-inflammatory characteristics.⁴

These findings build on a growing body of evidence suggesting that diet can influence immune function in MS. Although MAD has been successfully used to manage refractory epilepsy,⁵ its potential in MS treatment remains an emerging area of research. The study authors emphasized that these results justify larger, randomized trials to assess clinical outcomes and compare dietary strategies.

If further studies confirm these findings, dietary interventions like MAD could become a recommended adjunctive approach for patients with MS, alongside existing disease-modifying therapies. The ability to alter immune function through nutrition could provide patients with a nonpharmacological tool to help manage inflammation and disease progression.

For now, clinicians and researchers continue to explore the role of dietary strategies in MS, with the goal of establishing nutritional guidelines that could complement traditional treatments. The current study’s findings represent a promising step toward understanding how diet influences immune pathways in MS and offer a compelling case for further investigation.

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REFERENCES
1. Godfrey W, Moreau GB, Lehner-Gulotta D, et al. A Six-month Ketogenic Diet Alters The Immune And Metabolic Landscape In Multiple Sclerosis. Presented at ACTRIMS Forum 2025; February 27 to March 1; West Palm Beach, Florida. LB1.2.
2. Grunwald C, Krętowska-Grunwald A, Adamska-Patruno E, Kochanowicz J, Kułakowska A, Chorąży M. The Role of Selected Interleukins in the Development and Progression of Multiple Sclerosis-A Systematic Review. Int J Mol Sci. 2024;25(5):2589. Published 2024 Feb 23. doi:10.3390/ijms25052589
3. Hu T, Liu CH, Lei M, et al. Metabolic regulation of the immune system in health and diseases: mechanisms and interventions. Signal Transduct Target Ther. 2024;9(1):268. Published 2024 Oct 9. doi:10.1038/s41392-024-01954-6
4. Kemp F, Braverman EL, Byersdorfer CA. Fatty acid oxidation in immune function. Front Immunol. 2024;15:1420336. Published 2024 Jun 27. doi:10.3389/fimmu.2024.1420336
5. Sharma S, Jain P. The modified atkins diet in refractory epilepsy. Epilepsy Res Treat. 2014;2014:404202. doi:10.1155/2014/404202