People have long been using diet modifications to improve their health and treat disease. In particular, the ketogenic diet is an interesting example of how a specific diet has been used to treat a serious neurological condition.

The ketogenic, or “keto”, diet was originally developed to treat epilepsy, and has recently become a household name due to its popularity as a weight-loss diet.

What is a ketogenic diet?

The ketogenic diet consists of a very low level of carbohydrates in concert with adequate protein and  healthy fats. This combination changes the way the body uses energy stores. When carbohydrates are broken down by the body, they are converted into glucose, which is the main energy source for the body’s tissues. In the absence of glucose, the body uses fat for fuel, specifically ketone bodies, which are made when dietary fat is metabolized or when fat deposits in the body are broken down.

How did the ketogenic diet become a treatment for epilepsy?

Epilepsy is a common neurological disease that causes unprovoked, recurring seizures. Today, people with epilepsy have access to anticonvulsant medications, but these do not work for everyone, leaving many without a treatment option.

The use of a ketogenic diet for epilepsy can be traced back to the Hippocratic collection. In modern times, fasting to treat epilepsy was first documented in 1911 by Parisian physicians Gulep and Marie, who found that starvation reduced the severity of epileptic seizures in a group of 20 adults and children.

In the 1920s, another pair of physicians, Drs. Stanley Cobb and W.G. Lennox investigated the effectiveness of starvation as a treatment for epilepsy and found that after 2-3 days of no food, seizures improved. This research progressed in 1921 when Dr. Russel M. Wilder proposed implementing a ketone-producing diet high in fats for people with epilepsy and found that such a diet had comparable results to fasting and was maintained over time.

These early investigators observed that fasting or low-carb, high-fat diets that improved epileptic seizures also resulted in high levels of circulating and excreted ketone bodies, suggesting that the body had altered its metabolism. They hypothesized that these effects could be replicated using dietary strategies, and thus, the ketogenic diet was born.

Grilled bacon and avocado, fried eggs with spinach and cherry tomatoes in cast-iron pan. Gray concrete background. Top view. Ketogenic diet. Low carb high fat breakfast. Healthy food concept
Similar to fasting, a low-carb, high-fat diet was successful in reducing seizures in 1920 experiments. This is where the ketogenic diet comes from.

Following these initial findings, the ketogenic diet was refined and more widely used to treat epilepsy under the observation and guidance of healthcare professionals. There are multiple versions of the diet, with the classic makeup consisting of a ratio of 4 grams of healthy fat to 1 gram of protein plus carbohydrate (4:1 ratio), but this can be reduced to 3:1 if increased protein or carbohydrate intake is desired.

The growth of anticonvulsant medications has slowed the use of this dietary intervention for the treatment of epilepsy, but to this day, more than one-third of people with epilepsy do not respond to anticonvulsants and are considered refractory, leaving use of the ketogenic diet as a viable treatment option.

Why does the ketogenic diet work for seizures?

The mechanisms by which the ketogenic diet are thought to improve epilepsy symptoms are multifold and still being elucidated. The major metabolic byproduct of the ketogenic diet is the generation of ketone bodies, which enter the bloodstream and are circulated to organs throughout the body, including the brain, where they are used as alternative energy sources in the absence of glucose. Although the evidence is not clear, there is interest in understanding whether ketone bodies themselves have a direct anti-seizure effect.

It is also thought that the ketogenic diet has a neuroprotective effect through increases in mitochondrial numbers and improvements in mitochondrial function. Overall, this stabilizes energy production and makes neurons more resilient during seizure events, which reduces cellular stress and lowers levels of reactive oxygen species. A ketogenic diet may also increase the concentration of GABA (gamma-aminobutyric acid) in the brain, an inhibitory neurotransmitter that lowers excitation and may prevent seizures.

Finally, recent data from mice have also pointed to a strong link between ketogenic diet-induced changes in the gut microbiome and anti-seizure effects. The ketogenic diet alters composition of the gut microbiome and therefore, the metabolic by-products that are produced by the sum of the bacteria species present in the gut. In particular, the abundance of A. muciniphila and Parabacteroides were associated with seizure protection in this study.

The ketogenic diet for migraines

Given the success of the ketogenic diet in epilepsy, there has also been a lot of interest in understanding whether this dietary strategy can be effective for the treatment of migraines.

Use of the ketogenic diet for migraines was first reported in 1928 due to the mistaken idea that migraines were a less severe form of epilepsy. Additional case studies have been reported in small numbers of patients in the intervening decades showing general improvement of migraine symptoms and severity with use of the ketogenic diet.

Woman suffering from painful headache massaging temples
The ketogenic diet may reduce the energy deficit in the brains of people with migraines and reduce overall inflammation.

Migraine is a neurological condition characterized by the occurrence of severe headaches that may last up to three days and are often accompanied by nausea, or sensitivity to light or sound. For those who suffer from migraines, there are few treatment options, partially driven by the uncertainty around how migraines are caused.

However, there is some evidence that increased oxidative stress is associated with migraine pathology and that high levels of ketone bodies, particularly D-β-hydroxybutyrate, combat high oxidative stress and increase the efficiency of energy production in the brain.

Why is the ketogenic diet effective for migraines?

The brains of people with migraines are in a continuous energy deficit compared to the brains of healthy people. The metabolism of ketones produces more energy compared with the metabolism of glucose and thus, the ketogenic diet could also contribute to decreasing energy deficits in people with migraines. Moreover, ketogenic diet-induced increases in mitochondrial numbers and improvements in mitochondrial function could offer protection against migraines by optimizing waste removal of products that could damage mitochondria and by optimizing energy production in the brain.

The ketogenic diet may also help improve blood sugar control and increase insulin sensitivity, which may reduce overall inflammation and lead to fewer migraine attacks. Ketone bodies like D-β-hydroxybutyrate also seem to have an anti-inflammatory effect.

The positive effects of a ketogenic diet on headaches can be seen within four weeks! A 2019 randomized double-blind, cross-over study reported that obese people with migraines who alternated between a very low calorie ketogenic diet ( ≥75 g/day of protein; 30–50 g of carbs/day; 20 g/day of fats- maily olive oil) and a very low calorie non-ketogenic diet (≅ 50 g of prtein/day; ≥70 g of carbs/day; 20 g of fats/day mainly from olive oil) had fewer migraine days during their 4 weeks on the ketogenic diet, with almost 75% of partipicants having at least a 50% reduction in headache days. In this study, the anti-migraine effect seems to be the result of carb restriction and ketosis, as weight loss was similar in both groups.

Given the positive results of the few studies investigating the effectiveness of the ketogenic diet for the treatment of migraine and epilepsy, the use of a ketogenic diet for the treatment of those conditions seems promising. However, it may be hard to stick to a keto diet long-term. Even just reducing carb intake seems to help with reducing migraine attacks, as well as avoiding the most common migraine triggers, such as chocolate, cheese, and citrus fruit.

The above is not medical advice. Prior to changing your diet, you are encouraged to consult a qualified health professional.


Emily Poulin, PhD

As a cancer biologist and science communicator, I have always been fascinated by the simple, yet incredibly complex nature of biology. How just four DNA letters and two cells develop into an entirely unique person, unlike anyone else in the world. Or how our incredibly stalwart cells become hijacked by their own DNA to form a deadly tumor. On my LIFE APPS blog, “What’s the Deal?” I explore how biological systems work through the lens of health-related topics like cancer. Join me to learn how diseases like cancer work and how to better understand all that stuff in the news.

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