A ketogenic diet was safe, tolerable, and provided clinical benefits to people with relapsing multiple sclerosis (MS), a study found.
Relapsing MS patients enrolled in the 6-month prospective ketogenic intervention had significant reductions in fat mass and showed a nearly 50% decline in fatigue and depression scores, reported J. Nicholas Brenton, MD, of the University of Virginia in Charlottesville, at the American Academy of Neurology annual meeting, held in Seattle and online.
MS quality of life (QoL) physical health and mental health composite scores increased while participants were on the diet, and improvements were seen in Expanded Disability Status Scale (EDSS) scores, Brenton added. The findings were published simultaneously in the .
A ketogenic diet is high in fat, low in carbohydrates, and has adequate protein, and mimics a nutritional fasting state. It may reduce pro-inflammatory adipokines and raise anti-inflammatory adipokines. A ketogenic diet has been shown to improve seizure control in epilepsy, but hasn't been well studied in MS.
"We know that diet has the potential to impact the immune system in many ways," Brenton told . "The ketogenic diet, in particular, has neuroprotective properties that may positively impact MS pathobiology in addition to its clinical manifestations."
"This research takes the first step in objectively showing the feasibility of ketogenic diet studies in MS, provides important insight into laboratory and clinical metrics positively impacted by these diets, and identifies key obstacles and potential solutions for future clinical trials in MS diet research," Brenton added.
The study enrolled 65 relapsing-remitting MS patients who ate a ketogenic diet for 6 months, which allowed a maximum daily carbohydrate allowance of 20 g. Adherence was monitored with daily urine ketone testing. Most participants (91%) already were taking vitamin D at various doses at baseline, and were advised to continue as prescribed by their treating neurologist.
Fatigue, depression, QoL scores were obtained at baseline, in addition to fasting adipokines and MS-related clinical outcome metrics. These metrics were repeated at 3 and 6 months on the diet.
Overall, 83% of participants adhered to the ketogenic diet for the study duration. Median age was 40 and 86% were female; 63% were obese.
During the study period, fat mass percentage decreased from 44% to 40% of total body mass. MS QoL physical health (67 vs 79, P<0.001) and mental health (71 vs 82, P<0.001) composite scores increased.
EDSS scores improved (2.3 vs 1.9, P<0.001), as did scores on the 6-minute walk (1,631 vs 1,733 ft, P<0.001) and nine-hole peg test (21.5 vs 20.3 seconds, P<0.001). Serum levels of leptin, a pro-inflammatory adipokine, were lower (25.5 vs 14.0 ng/mL, P<0.001), while levels of adiponectin, an anti-inflammatory adipokine, were higher (11.4 vs 13.5 mcg/mL, P=0.002).
Among MS patients who completed the 6-month intervention, the most common side effects were constipation (43%), diarrhea (18%), nausea (9%), weight gain (9%), fatigue (5%), worsened depression or anxiety (5%), and acne (5%). Menstrual irregularities occurred in 27% of women. No participants showed signs of relapse.
A limitation of the study was its lack of a matched control group.
"Our study provides evidence that a ketogenic diet may indeed be safe and beneficial, reducing some symptoms for people with MS, when used over a 6-month period," Brenton noted. "However, more research is needed because there are potential risks associated with ketogenic diets such as kidney stones, digestive issues, and nutrient deficiencies."
Disclosures
The study was funded by the National Center for Advancing Translational Sciences through the iTHRIV Scholars Program, and supported by the ZiMS Foundation.
Brenton disclosed research funds from the NIH and the National Institute of Neurological Disorders and Stroke.
Primary Source
American Academy of Neurology
Brenton JN, et al "Ketogenic diet as a strategy for improved wellness and reduced disability in relapsing multiple sclerosis" AAN 2022.
Secondary Source
Journal of Neurology, Neurosurgery, and Psychiatry
Brenton JN, et al "Phase II study of ketogenic diets in relapsing multiple sclerosis: safety, tolerability and potential clinical benefits" J Neurol Neurosurg Psychiatry 2022; DOI:10.1136/jnnp-2022-329074.