A ketogenic diet may reduce disability and improve quality of life, fatigue, and depression in patients with multiple sclerosis (MS), new research suggests.

High-fat, low-carbohydrate ketogenic diets mimic a fasting state and promote a more efficient use of energy — and have previously been shown to affect immune regulation. The diet helps lower blood sugar in individuals with type 2 diabetes and has been used for years to improve seizure control in patients with epilepsy, researchers note.

Dr J. Nicholas Brenton

However, “there is a paucity of literature on the ketogenic diet in MS currently,” principal investigator J. Nicholas Brenton, MD, University of Virginia, Charlottesville, told Medscape Medical News.

“The current study demonstrates the safety, tolerability, and potential clinical benefits of a ketogenic diet over 6 months in patients with relapsing MS,” Brenton said.

The findings will be presented at the American Academy of Neurology (AAN) 2022 Annual Meeting in April.

Palatable, Beneficial

The open-label, uncontrolled study included 65 patients with relapsing MS who followed a ketogenic diet for 6 months. Investigators monitored adherence by daily urine ketone testing.

Patient-reported fatigue, depression, and quality-of-life scores were obtained at baseline, in addition to fasting adipokines and pertinent MS-related clinical outcome metrics. Baseline study metrics were repeated at 3 and/or 6 months while on the ketogenic diet.

Of the patient group, 83% adhered to the ketogenic diet for the full 6-month study period.

The ketogenic diet was associated with reductions in fat mass from baseline to 6 months (41.3 vs 32.0 kg; P < .001) and a significant decline in fatigue and depression scores, the investigators report.

MS quality-of-life physical and mental composite scores also improved while on the ketogenic diet (P < .001 for both).

A significant decrease from baseline to 6 months in Expanded Disability Status Scale scores, signifying improvement, was observed (2.3 vs 1.9; P < .001).

Improvements were also shown on the 6-minute walk (1631 vs 1733 feet; P < .001) and the nine-hole peg test (21.5 vs 20.3 seconds; P < .001).

At 6 months on the diet, fasting serum leptin was significantly lower (25.5 vs 14 ng/mL; P <.001), and adiponectin was higher (11.4 vs 13.5 μg/mL, P = .002).

Justifies Further Research

The current study builds on an earlier one Brenton and colleagues conducted in 2019 that showed that the ketogenic diet was feasible in patients with MS, as reported by Medscape Medical News.

“Our data justify the need for future studies of ketogenic diets as a complementary therapeutic approach to the treatment of MS,” Brenton said.

He noted that there may be multiple mechanisms of benefit when considering the ketogenic diet.

“One avenue is via reduction in total body fat. This is an important aspect as we continue to learn more about the role of obesity and fat-derived inflammation in MS,” Brenton said.

“Ketogenic diets also have immunomodulatory properties,” such as the capacity to reduce oxidative damage from metabolic stress, increase mitochondrial biogenesis, and reduce systemic inflammation, he added. “These intrinsic properties of the ketogenic diet make it appealing to study in immune-mediated diseases, such as MS.”

Brenton cautioned that the data demonstrate the diet’s safety over 6 months but that the study was not designed to assess its long-term implications in MS.

“Thus, while our results support the rationale for a larger-scale study of ketogenic diets as a complementary treatment for MS, our data does not support its widespread adoption outside of a clinical trial,” he said.

Remarkable Adherence

Commenting on the study for Medscape Medical News, Shaheen E. Lakhan, MD, PhD, a neurologist in Boston, Massachusetts, noted that “variations of the ketogenic diet have been popularized in the general population for weight loss and further studied for other medical conditions [that are] largely immune-related, including MS.”

He noted it was “remarkable” that the vast majority of study participants with MS adhered to the very regimented ketogenic diet for 6 months.

Seeing this translate into the real world “will be the next milestone, in addition to its impact on relapses and brain lesions as seen on MRI,” which are the classic markers of MS, said Lakhan, who was not involved with the research.

He cautioned that “even if one can follow the ketogenic diet, certain conditions can be made worse. This includes kidney stones, liver disease, reflux, constipation, and other metabolic disorders.”

The study was funded by the National Center for Advancing Translational Sciences of the National Institutes of Health and by the ZiMS Foundation. Brenton and Lakhan have reported no relevant financial relationships.

American Academy of Neurology (AAN) 2022 Annual Meeting: Abstract 622. To be presented April 7, 2022.

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