A new study suggests six months of a modified Atkins diet offers the capacity to reprogram immune cell metabolism and promote anti-inflammatory phenotypes. Researchers said their findings support the immunomodulatory potential of ketogenic diets in multiple sclerosis. 

A large body of preclinical research supports the immunomodulatory effects of diet, and dietary strategies for MS remain of major interest to clinicians and people with the disease. Ketogenic diets produce anti-inflammatory effects in animal models of MS and other autoimmune disorders, but whether these diets produce similar effects in humans remains unknown. 

The modified Atkins diet is a less restrictive ketogenic diet that is easier to sustain and has an established clinical use for the treatment of refractory epilepsy, making it an ideal dietary intervention to investigate in MS. Johns Hopkins University researchers set out to use a multi-omics approach to broadly characterize the immunologic and immunometabolic effects of a six-month modified Atkins diet intervention in people with MS. 

Researchers analyzed preserved peripheral blood mononuclear cells and plasma at a baseline and after six months of modified Atkins diet in 39 patients with relapsing MS who completed a previously published phase 2 study of modified Atkins diet. Samples were analyzed as matched pairs, comparing samples obtained at baseline and six months on-diet from each subject.

They found that six months of modified Atkins diet produced substantial changes in the profiles of peripheral immune subsets linked to both innate and adaptive immunity. These changes included reduced proinflammatory phenotypes in myeloid cells, a shift from memory to naïve CD8 cells, increased abundance and suppressive activity of regulatory T cells, and decreased B cell activation. Further analysis revealed that modified Atkins diet significantly reduced plasma levels of proinflammatory cytokines and chemokines, such as IL-6 and CCL2. 

As a low carbohydrate/high fat diet, researchers hypothesized that the modified Atkins diet might shift the balance between glycolysis and fatty acid oxidation, pathways previously identified as determinants of immune cell fate. As predicted, gene and protein expression patterns revealed metabolic reprogramming from glycolysis to fatty acid oxidation across immune subsets. These changes were corroborated by plasma metabolomics, which demonstrated a decrease in glycolytic products such as lactate and pyruvate and an increase in fatty acid oxidation intermediates, such as acetylcarnitine. 

The researchers said their findings support the immunomodulatory potential of ketogenic diets in MS, demonstrating the capacity of modified Atkins diet to reprogram immune cell metabolism and promote anti-inflammatory phenotypes. These results provide a rationale for larger, randomized studies comparing dietary interventions and evaluating clinical outcomes, with a goal of establishing nutritional guidelines as an adjunctive approach to MS therapy.

The study was presented at ACTRIMS 2025.