Adapted Ketogenic Diet and Neuroprotective Benefits in Multiple Sclerosis

Using single molecule array assay, researchers examined sNfL levels of patients with MS who were either on a common diet or ketogenic diet or fasting.

An adapted ketogenic diet (AKD) reduced serum neurofilament light chain (sNfL) levels at 6 months in patients with relapsing-remitting multiple sclerosis (MS), according to study findings published in Neurology Neuroimmunology & Neuroinflammation.

Effective therapeutic strategies and biomarkers would help evaluate drug efficacy and disease course for MS. Prior research has indicated sNfL could be a reliable biomarker of neuroaxonal damage and change in MS and that caloric restriction (CR) and AKD could influence neuroinflammation in MS. Single molecule assays (SiMoA) have measured NfL after axonal injury. The objective of the current study was to determine whether AKD and CR instead of common diet (CD) affects neurodegeneration and whether that could be measured with sNfL levels.

Researchers conducted a three-armed parallel group clinical trial in which they utilized the NF-Light Advantage Kit (Quanterix) SiMoA HD-1 to measure sNfL. They compared patients following a common diet, a 7-day CR (200-350 kcal/d) followed by 3-day stepwise reintroduction to isocaloric common diet, and AKD for 6 months from study outset.

SNfL was associated with age (r = 0.347 P <.05) and disease duration (r = 0.313 P <.05) and inversely correlated with Multiple Sclerosis Functional Composite (MSFC) 2 (r = -0.298) and 3 (r = -0.298 P <.05 for both). SNfL and Paced Auditory Serial Addition Test 3 (r = -0.298 P <.005) were inversely correlated.

Among the 17 individuals in the AKD group, sNfL decreased from 8.5 at baseline to 7.1 pg/mL at 6 months (mean difference -1.307 95% CI -2.256 to -0.357 P <.05), while it remained similar from baseline to 6 months in the CR group (n=14) and CD group (n=9). At 6 months, SNfL levels had decreased significantly more in the AKD group compared with the CD group ((adjusted difference -2.145 ± 0.615 95% CI -3.393 to -0.897; P =.001).

Three relapses in the CD group, 2 in the CR group, and 1 in the AKD group occurred during the study.

SNfL significantly increased among all groups at month 3 and remained elevated in an analysis that excluded patients with relapse activity.

Study limitations included short observation time, lack of MRI, limited power, and undefined extent of variation indicating meaningful change in sNfL.

“Overall, our study suggests that an AKD offers an avenue to impact sNfL levels, which seems to be a promising biomarker in neuroinflammatory diseases, supporting the use of dietary interventions as a treatment tool for MS,” stated the researchers. “These findings are of urgent medical interest because such dietetic strategies exhibit few unwanted side effects.”


Bock M, Steffen F, Zipp F, et al. Impact of dietary intervention on serum neurofilament light chain in multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. Published online November 11, 2021. doi: 10.1212/NXI.0000000000001102