Ketones-enriched Diet May Boost Motor, Cognitive Function in Youth

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by Patricia Inacio PhD |

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A diet enriched with a nutritional formula supplemented with ketones — natural metabolites that arise from the breakdown of fat — may improve fine motor skills, memory, and cognition in children with Angelman syndrome, according to the results from a small trial.

Funded by the Foundation for Angelman Syndrome Therapeutics (FAST), this study supports the potential for a dietary intervention to help manage the symptoms of the complex neurological disorder.

“The results from this early safety and tolerability study are promising for individuals living with Angelman syndrome,” Allyson Berent, FAST’s chief science officer, said in a press release.

The ketogenic diet, which involves eating very few carbohydrates (sugars and starches) and consuming more fats, is known to help manage and control seizures that are resistant to medication.

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How Can the Ketogenic Diet Help My Child With Angelman Syndrome?

While cells in the body will preferentially use carbohydrates — particularly glucose — as an energy source, when carbohydrates are not available the body will use fat for energy in a process called ketosis. This process, in turn, generates molecules called ketones: natural metabolites produced by the body that can replace sugar as the main source of fuel, with particular effects on the brain.

“There is robust data showing the benefit of modified ketogenic diets positively impacting individuals with seizures and other neurodevelopmental delays, and finding a medical food that would manage the metabolic aspects of these symptoms, while not having to be on prohibitively restrictive diets, would dramatically improve the quality of life of those living with Angelman syndrome,” Berent said.

Dietary supplementation with ketones was shown to significantly decrease the frequency of seizures in a mouse model of Angelman syndrome. The ketones-enriched diet also improved the animal’s behavior, learning, memory, and overall function.

These findings suggest that dietary ketone supplementation in humans may hold the potential to help manage Angelman symptoms.

The Nutritional Formulation for Angelman Syndrome (FANS) trial (NCT03644693) enrolled 13 children, ages 4-11, who had genetically confirmed Angelman syndrome and a variety of dietary backgrounds.

Instead of going on a ketogenic diet, participants were randomly assigned to take a nutritional formulation containing exogenous ketones, commercialized by trumacro Nutrition, or a placebo dietary supplement for 16 weeks, or about four months.

According to FAST, the ketogenic formulation lessened constipation among the participants. Constipation is common among Angelman patients and a symptom that often correlates with the severity of other symptoms, including seizures, aberrant behaviors, and sleep quality.

Children fed the ketogenic formulation showed an early trend for improvements in fine motor skills — the ability to make movements using the small muscles in the hands and wrists — according to the Vineland Adaptive Behavior Scales.

Additionally, they showed improvements in memory and cognition, as shown by a reduction in delta brain waves on electroencephalography (EEG) and auditory event-related potentials (AERP).

Of note, brainwaves are produced by electrical pulses from neurons communicating with each other. They are divided into different bandwidths that change according to what an individual is doing and feeling.

Delta brain waves have been reported to mediate the weakening of memory and promote forgetting.  The brain’s automatic responses to sounds, measured through auditory event-related potentials, or ERPs, can be used to investigate alterations in cognition.

The ketogenic formulation was well-tolerated over the 16 weeks.

The results from this small study, although preliminary, are promising and now require confirmation in larger studies, the researchers noted.

“While more studies are needed, we are excited about the prospect of use of this formulation to improve the quality of life of individuals with Angelman syndrome, as it may offer the opportunity to safely liberalize very restrictive low carbohydrate diets to ensure the same benefit even with the introduction of preferred foods,” said Jessica Duis, MD, assistant professor of pediatrics at the University of Colorado School of Medicine, where the trial was conducted. Duis noted this was the first trial in this age range.