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Your brain on ketones: Does a ketogenic diet affect cognition, sleep, and mood?

Ketogenic diets affect nerves; that's why they're an effective treatment for some seizure disorders. But how these diets affect mood and cognition is less clear.

Study under review: Three consecutive weeks of nutritional ketosis has no effect on cognitive function, sleep, and mood compared with a high-carbohydrate, low-fat diet in healthy individuals: a randomized, crossover, controlled trial.

Introduction

Witnessing an epileptic seizure is heartbreaking. You want to try and help, do anything that might stop the aggressive convulsions, but after having turned the patient to their side, moved any potential hazards away, and noted the start time of the episode, the only thing you can do is to wait, and since there isn’t much to do once a seizure starts, preventive measures are some of the best options for reducing episodes.

This means there are some things that can be done to prevent seizures from happening in the first place. One example is fasting, which is the first documented[1] therapy for epilepsy reported in the Hippocratic collection, which served as a precursor for the ketogenic diet, since fasting reduces carbohydrate intake, alongside everything else. Researchers have known that a diet composed primarily of fats can suppress seizures since the 1920s[2]. While the mechanism isn’t exactly clear, putative mechanisms[3] suggest that a nutritional state of ketosis and the elevation of circulating ketone bodies (free fatty acid metabolites) reduce neuronal excitation by correcting discrepancies between excitatory (e.g. glutamate) and inhibitory (e.g. GABA) neurotransmitters and by inhibiting neuronal machinery (i.e. channels, receptors) related to excess excitation. An (oversimplified!) illustration of this possible mechanism is shown in Figure 1.

While inhibiting neurons can be helpful for reducing seizure risk, inhibition can also have downsides. One concern regarding this reduction in neuronal excitation is whether it might negatively influence cognitive function. This is especially important since the ketogenic diet has entered mainstream media and is now frequently used for weight loss[4] and management of chronic disease[5], as well as other conditions. If ketosis impacts cognition, that’s a side effect that people should be made aware of. However, the research concerning ketosis’ effects on cognition is, as of now, conflicting.

Some studies[6][7] report a decline in cognitive function following consumption of a high fat diet, while other studies report enhancements in memory[8] and overall cognitive function[9], as well as associations[10] of greater total fat and polyunsaturated fatty acid intake with faster reaction time. The conflicting results are likely due to use of different sample populations (e.g. obese or elderly people), the fact that weight loss in several of these studies can be accompanied by various other physiological benefits, and the lack of control for a state of nutritional ketosis. To address these concerns with past research, the authors of the study under review designed a relatively simple experiment that focused on ensuring a state of nutritional ketosis in healthy participants during a ketogenic diet. They then evaluated changes in cognitive function before and after the diet, in comparison to a high carbohydrate, low fat diet.

Researchers have known that the ketogenic diet can reduce neuronal excitation for about a century. However, whether the induced changes in neuronal excitation influences cognitive function is still unclear as studies demonstrate conflicting results, likely due to variations in sample population, control, and confounding variables. The authors of the study under review closely monitored a group of healthy participants to ensure they were in a state of nutritional ketosis during a ketogenic diet and evaluated changes in cognitive function in comparison to a high carbohydrate, low fat diet.

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