Keto Diet, Exercise, Effective First-line Tx for Narcolepsy

HELSINKI — A ketogenic diet and regular physical exercise appear to be effective first-line treatments for narcolepsy, new research suggested.

Results of a randomized, controlled trial on the impact of physical exercise and a ketogenic diet on narcolepsy showed both exercise and the diet improved excessive daytime sleepiness (EDS) in narcolepsy type 1.

“When we have a closer look at the European guidelines on narcolepsy, especially in the patient opinion section, there is a request for more non-pharmacological treatment options. And you will see that there is no specific guidance regarding physical activity or nutrition,” said study investigator Frederike Tepel, Centre for Narcolepsy and Hypersomnia, Witten/Herdecke University, Witten, Germany.

EDS was improved by both interventions “to a point where the results were clinically relevant and in the range of those seen with drug treatment,” Tepel added.

Both also improved fatigue and physical and mental quality of life, while the ketogenic diet additionally led to significant weight loss compared with best clinical practice, “and these interventions are available everywhere and quite inexpensive, and we couldn’t document any adverse effects,” said Tepel.

She went on to explain that patients anecdotally report improvements in narcolepsy with low-carbohydrate diets, and the current study — while limited by the small size of only 44 patients who completed the trial — is “to our knowledge, the biggest sample size [to study this] up to now.”

The results were presented here at the Congress of the European Academy of Neurology (EAN) 2024.

Clinically Significant

For the study, 60 adult patients (41 women) with type 1 narcolepsy (NT1) and a mean age of 34 years were randomly assigned to receive either regular physical activity (n = 20), a ketogenic diet (n = 20), or a control group of best clinical practice (n = 20) for 10 weeks.

Participants had to have a diagnosis of NT1, be over 18 years of age, and have a body mass index > 20. The latter was because the advising nutritionist “guessed that a lot of subjects would lose weight in the trial,” Tepel noted.

Patients were excluded if they had severe cardiovascular disease, were participating in a weight loss program, were in training for any intensive sporting competition, or were taking sodium oxybate or any other medications that have a potential influence on ketogenic mechanisms.

A total of 44 patients completed the study. Three dropped out due to health issues (fracture of the foot or viral infections), and 13 withdrew from the study due to personal reasons or noncompliance. Dropout rates were comparable between the groups (25% for the sports group, 25% for the keto group, and 30% for the control group). There were no adverse effects associated with the interventions.

The primary outcome was EDS as measured by the Epworth Excessive Sleepiness Scale (ESS), and secondary outcomes included sleep quality, quality of life, well-being, cataplexy frequency, and fatigue, as measured by various pre- and post-study questionnaires including the Pittsburgh Sleep Quality Index (PSQI) and the short-form 12.

The exercise group performed a power walking test before and after the intervention to help monitor compliance and were advised to participate in three sports sessions a week. Their daily step count was also logged as was the number of training minutes.

The ketogenic diet group had nutritional counseling before the start of the study and had to stick to the eating plan for 10 weeks, with weekly measures of capillary ketone bodies to determine compliance, as well as monitoring of weight and waist circumference.

“The most important finding was that the sports group experienced a decrease of 2.9 points on the ESS from 13.9 to 11 points (P P

The sports group also significantly improved their sleep quality as measured by the PSQI after the intervention (P

Likewise, there “was a huge improvement in well-being in the sports and keto groups, while the control group remained stable,” noted Tepel.

Asked to comment, session co-chair Rolf Fronczek, MD, PhD, of the Sleep-Wake Center SEIN, the Netherlands, agreed that many narcolepsy patients have “described that if they eat less carbs, they feel better, so I think it’s very good to study it.” And with the ketogenic diet, “you can also test whether people are complying with it by measuring ketosis,” he noted.

“But I think more practical advice…is to follow a low-carb diet because adopting a ketogenic diet is very tough and expensive too. I see it more that we should add guidance to incorporate a low-carb diet to the behavioral advice that we already give in narcolepsy, but it’s good to prove it with this study,” Fronczek told Medscape Medical News.

Tepel agreed that sticking to a keto diet is challenging. “I talked with the study participants in the keto group a lot before and after the study, and they told me it was really difficult to stick to the routine because…if you go out with friends to a restaurant, it’s almost impossible to stay in nutritional ketosis,” she said.

The average weight reduction in the keto group in the trial was 6 kg over 10 weeks, “and I can also remember that 3 subjects lost more than 10 kg in 10 weeks, which is a huge amount,” Tepel said. She noted that if a low-carb diet, rather than a keto one, is to be recommended, “it’s good to stick to a maximum of 50 g of carbohydrate a day.”

Tepel and Fronczek reported no conflicts of interest.