Ketogenic diets could modify the immune response and thus change the course of MS. Animal experiments confirm this, but what about humans?
Obesity is a known risk factor for MS and diet is a potentially modifiable factor that could influence disease progression. Recent studies suggest a link between eating habits and the degree of disability or symptom severity suffered (sources 1 and 2). In a large cross-sectional study, the quality of diet and an active lifestyle were also associated with lower fatigue, depression, cognitive impairment, and less pain.
Ketogenic diets mean a lot of fat with few carbohydrates and thus imitate a state of fasting. There is a shift in metabolism away from energy production by glycolysis towards beta-oxidation of fatty acids as the primary energy source, resulting in ketone bodies. We do not want to make a metabolic physiology lecture out of it, but only name some essential mechanisms through which a ketogenic diet could have a beneficial effect:
In the mouse model of experimental autoimmune encephalitis, a ketogenic diet led to the reversal of motor disability, improved learning, and memory, higher hippocampal volumes, and remyelination of periventricular lesions (source 3). This was associated with suppressed production of inflammatory cytokines and increased neuronal repair processes.
The results of a small pilot study (source 2) in 20 patients with relapsing-remitting MS were published in July 2019 in Neurology, the official journal of the American Academy of Neurology (AAN). Adherence to a modified Atkins diet was verified by a daily ketone test in urine. After 6 months, a decrease in body fat and BMI (p < 0.0001) and an improvement in the scores for fatigue (p = 0.002) and depression (p = 0.003) were observed. After 3 months, leptin concentrations in serum (a proinflammatory adipokine) had decreased significantly (p < 0.0001).
There is growing evidence that neurodegeneration plays an important role in MS in addition to neuroinflammation, even if there is no consensus as to whether neurodegeneration triggers inflammation or vice versa - or whether both mechanisms exist in parallel. Mitochondrial dysfunction appears to be central to the neurodegenerative component of MS pathogenesis. This results in lower availability of ATP, which could promote axonal atrophy and degeneration. In vitro and animal studies, a ketogenic diet has been shown to improve mitochondrial function and thus promote axonal survival by promoting ATP production and mitochondrial biogenesis, bypassing disturbed processes within mitochondria, increasing levels of antioxidants, and reducing oxidative damage (source 4).
Various studies have reported significant differences in the concentration, diversity, and composition of intestinal bacteria in MS patients and their influence on immune regulation. After approximately 3 months on a ketogenic diet, this condition also improved in MS patients (source 5).
There is still very little evidence of this in humans, but we can look forward to further, hopefully, larger and more controlled studies.
Sources:
1. Fitzgerald, K. C. et al. Diet quality is associated with disability and symptom severity in multiple sclerosis. Neurology 90, e1-e11 (2018).
2. Brenton, J. N. et al. Pilot study of a ketogenic diet in relapsing-remitting MS. Neurol Neuroimmunol Neuroinflamm 6, (2019).
3. Kim, D. Y. et al. Inflammation-mediated memory dysfunction and effects of a ketogenic diet in a murine model of multiple sclerosis. PLoS ONE 7, e35476 (2012).
4. Storoni, M. & Plant, G. T. The Therapeutic Potential of the Ketogenic Diet in Treating Progressive Multiple Sclerosis. Mult Scler Int 2015, 681289 (2015).
5. Swidsinski, A. et al. Reduced Mass and Diversity of the Colonic Microbiome in Patients with Multiple Sclerosis and Their Improvement with Ketogenic Diet. Front Microbiol 8, 1141 (2017).