Research recap: Modified Atkins diet and health-related quality of life - Dr. Magnhild Kverneland

Reported by Joy Mazur, Epigraph intern | Edited and produced by Nancy Volkers

Cite this article: Mazur J. Research recap: Modified Atkins diet and health-related quality of life - Dr. Magnhild Kverneland. Epigraph 2023; 25(3): 58-62.

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Diet treatments are often used with the aim of reducing seizure frequency and severity — but they may have other benefits as well. Joy Mazur spoke with Dr. Magnhild Kverneland about the possible effect of dietary treatments on emotional symptoms and their correlation with health-related quality of life. 

Sharp Waves episodes are meant for informational purposes only, and not as clinical or medical advice.

Podcast Transcript

Joy Mazur: A 2023 study published in Epilepsia found that dietary treatments may have effects beyond seizure frequency, and that health-related quality of life may also be considered as an indicator of successful diet treatments in the future.

The study used a 12-week diet intervention among adults with epilepsy to compare self-reported health-related quality of life scores. Some participants followed the modified Atkins diet, while others maintained their usual diet.

Sharp Waves spoke to the first author about the results and implications of the study.

Magnhild Kverneland: My name is Magnhild Kverneland and I work as a leading dietician at the National Centre for Epilepsy in Norway. I work in the adult’s department and my main task is to teach and follow adults with drug- resistant epilepsy that are treated with the ketogenic diet.

Joy Mazur: So why did you want to study the health-related quality of life in people following the modified Atkins diet for epilepsy?

Magnhild Kverneland: Well here in the National Centre for Epilepsy in Norway, people with drug resistant epilepsy are admitted from all over the country. And in 2010, we wanted to start offering ketogenic dietary treatment to our adult patients. At that time, we knew that the dietary treatment among children with severe epilepsies had shown excellent results. It was documented by a randomized controlled trial from Great Ormond Street in the United Kingdom, published in 2008.

However, for adults, such documentation was lacking. And therefore, we decided to set up a randomized controlled trial at that time. And it is important to emphasize that our group of patients is a refractory group who generally have suffered from epileptic seizures for many years and who have tried on average nine to 10 different anti-seizure drugs.

A considerable share of the patients had been evaluated for epilepsy surgery. Twenty percent had undergone surgery and about half had or had had vagus nerve stimulators. Our neurologists always look for new and complementary treatments for these severely diseased patients. And in 2010, also, quite a few of our patients or next of kins had asked for a possibility to try dietary treatment in our hospital.

So in our randomized controlled trial, firstly, we wanted to examine seizure frequency. These results were published in Epilepsia in 2018. Participation was limited to those diagnosed with focal and multifocal epilepsies and for seizure frequency, we detected a moderate benefit in the diet group compared to controls, and a large variation between individuals.

Health-related quality of life was a secondary measure in our randomized controlled trial. So, health-related quality of life can absolutely be as important as seizure frequency for these patients. So, we thought it was very important to publish these results as well.

Joy Mazur: Can you tell me more about the methods used to collect the data?

Magnhild Kverneland: When we set up the randomized control trial in 2010, we decided to use the Quality of Life in Epilepsy Inventory 89. It's abbreviated to QOLIE-89. This is a questionnaire originally validated in the United States, specifically to detect health-related quality of life in epilepsy.

This questionnaire was translated into and validated for the Norwegian language in 1999. And compared to other validated epilepsy-specific inventories, the QOLIE-89 is, I think, to date the most comprehensive.

We actually invited and interviewed a lot of patients: 277 were invited. And of those, there were 75 who fulfilled the inclusion criteria and wanted to participate. 37 were randomized into diet group and 38 to a control group. Of these, 24 in the diet group and 32 in the control group were available for analysis after the intervention.

Those who participated in the randomized control trial, around 35% were diagnosed with intellectual disability of varying severity. And since the QOLIE-89 questionnaire has not been adapted for persons with intellectual disability, we could not get the answers from all the participants.

Participants randomized to control group continued eating their habitual diet for the 12-week intervention period. During the project period, we contacted them twice by telephone to ensure that they were eating their normal diet and registering the seizures. They were admitted to our hospital for short stays immediately before and after the 12-week project period, and during these short hospital stays, they filled in the QOLIE-89 questionnaire. All control group participants were offered dietary treatments afterwards using exactly the samedietary protocol as for the diet group.

Those in the diet group started the dietary treatment at home after a short admittance to our hospital. They were told to follow a modified Atkins diet with 16 grams of carbohydrates per day.

This implies a radical dietary change, with no starch-based staples like bread, potatoes, rice, pasta, and fruits. Some vegetables low in carbohydrates can be eaten, and protein sources like eggs, meat, fish, and cheese are allowed in normal portions.

Intakes of fatty food, like plant oils, margarine, avocado, mayonnaise, nuts, fatty dairy products, like for instance, butter, sweet and sour cream, and so on were increased. And, of course, sweets, biscuits, cakes, chocolate and sugary foods and drinks had to be excluded from the diet 100%.

The participants measured urine ketones on a daily basis at home, and we conducted follow-up and evaluation visits to our hospital after four and 12 weeks of the intervention. No changes to medications or adjustments to vagus nerve stimulators were allowed.

Joy Mazur: Can you tell me what the results were and what the implications of those results are as well?

Magnhild Kverneland: After 12 weeks of treatment in the diet group, the mean total score of the QOLIE-89 increased by six points, starting at 64 points. In the control group, there was a mean decline of four points, starting at 62 points.

Comparing the two groups revealed a more favorable outcome in the diet group than in the control group with a difference of 10 points, which was statistically significant with a p-value of 0.002. When it comes to the other sub scores on emotional wellbeing, health discouragement, language, role limitations due to physical problems, and social support also improved significantly in the diet group compared to the control group.

Implications of the results? Well, the improvement in health-related quality of life among our participants is modest, but it is clear, I think. However, this study is too small to be able to draw any firm conclusions, unfortunately.

Joy Mazur: Is a six-point increase on the QOLIE-89, is that a large increase?

Magnhild Kverneland: The scale of the QOLIE-89 runs from 0 to 100, and an improvement of 10 points in the QOLIE-89 is considered clinically relevant. So, six points is smaller than 10, but the six-point improvement that we discovered is a modest change. And we see that the tendency of improvement of health- related quality life from the dietary treatment is very clear in our material when comparing the diet group with the control group. So, we think that this is an important result.

However, in addition to seizures, a large and important part of health-related quality of life is psychiatric health. And in the epilepsy population, we know that there is an increased occurrence of psychiatric disorders. And a meta- analysis by Scott and coworkers from 2017 reported a prevalence of anxiety and depression among people with epilepsy of 20.2% and 22.9% respectively, versus 8.2% and 9.4% in the general population.

But that means that among people with epilepsy, the occurrence of depression and anxiety is double compared to healthy people.

We would expect that the health-related quality of life in a group of patients with epilepsy compared to healthy people would be impaired.

Joy Mazur: Are you able to speculate a bit about the results of this study? Do you believe the quality of life improved because of the diet improving mood? Was it the diet reducing seizures in some way? Was it both? Were there other factors going on?

Magnhild Kverneland: It is an apparent question whether the improvement is caused by the dietary treatment independent of results in seizure frequency. And among clinicians, there is a common perception that dietary treatment has beneficial effects beyond seizure reduction, which I think maybe is supported by our results. In our study, the effect on seizure frequency was modest, but we did discover an association between changes in seizure frequency and the QOLIE-89 results when we lowered the seizure frequency cutoff to 40%, not 50%.

So, there was some connection between the reduction in seizure frequency and the improvement in quality of life. But we also speculate that the dietary treatment might give an additional effect, for example, by improving the energy situation in the brain.

It is also worth mentioning that some of our patients recovered faster from seizures. And that may be very important for the individual and a good reason to continue the dietary treatment, even if the seizure frequency is unchanged. Also, if you think about how demanding such a diet is for the participant and the people around him or her, I find the results remarkable and extremely interesting because one could expect that to start such a demanding treatment could reduce the perceived quality of life when you're not able to eat your favorite foods, et cetera. But our results are in accordance with the results of previous studies indicating diet-induced improvements in mood, alertness, memory, sleep, and attention.

And longer treatment duration correlates also with perceived reduction of depressive and anxiety symptoms by others. And our findings on emotional wellbeing, such as feeling nervous, calm, sad, happy, suggest that the dietary treatment may have a normalizing effect on such symptoms.

The explanations are manyfold, both organic and psychosocial elements may contribute to this.

Joy Mazur: What do you consider the strengths of your study? And were there any limitations as well?

Magnhild Kverneland: Strengths of the study are the randomized controlled design, and also the use of the QOLIE-89. As I mentioned, compared to other validated epilepsy specific inventories of health-related quality of life, the QOLIE-89 is the most comprehensive.

Our study has limitations, such as the relatively short duration of intervention and a small sample size. Moreover, we were not able to assess health-related quality of life among all participants, excluding some of those with intellectual disability.

Joy Mazur: Do you have any plans for future studies on this topic as well?

Magnhild Kverneland: Currently for an individual, the only way to find out whether the diet is effective against seizures, is to eat a ketogenic diet for at least three months. However, this is very demanding and to start such a diet, both for the patient and other caretakers. Many people are often involved in planning, purchasing, preparing, and serving the food. And healthcare personnel spend a lot of time guiding, teaching, calculating recipes, evaluating the results of the treatment. Therefore, I think it's very important to be able to predict whomay get effect from the treatment, not having to try the diet.

So, in the future studies, what we would like to look for is biomarkers that may be associated with the response to the ketogenic dietary treatment. There is a lot of research going on in the area of ketogenic dietary treatment for epilepsy and especially about knowledge on how the mechanisms of the ketogenic dietarytreatment reduce seizure frequency and potentially how it affects other neurological functions.

We want to study changes in the metabolome caused by the ketogenic dietary treatment. Current research suggests that several mechanisms act together, and one may speculate that mechanisms may vary from person to person, and when we get closer to understanding the mechanisms, the ketogenic diet may becomepart of an individual's individualized treatment for epilepsy in the future.

Joy Mazur: Great, thank you. Is there anything else you would like to add?

Magnhild Kverneland: I would like to thank the participants of the study who made a great effort to implement the diet and to complete the study participation. I'm very, very grateful for their efforts. I also would like toacknowledge all my coworkers in the study and my colleagues at the National Centre for Epilepsy in Norway who contributed to the study.

And also, I would like to thank those who supported our research.