A ketogenic diet involves consumption of foods with high fat (80%), moderate protein (15%), and low carbohydrates (5%). Consistent intake of high fat, moderate protein foods, with simultaneous avoidance of carbohydrates, allows the body to transition from using glucose (sugar) as a primary source of fuel, to using ketone bodies (commonly called “ketones”). During ketosis, many people experience significant weight loss, and a report a variety of neurophysiological changes.
Ketogenic diets have long been prescribed as a natural intervention for the management of epilepsy. The therapeutic potential of ketogenic diets was discovered in the 1920s when it was noted that fasting (going for a period of time without food) significantly reduced seizures. During fasting, the body breaks down stores of fat and uses the fatty acids to generate ATP (adenosine triphosphate).
As new anticonvulsant drugs were developed, many individuals resorted to popping a pharmaceutical pill for epilepsy rather than adhering to a strict, arguably bland ketogenic diet. Despite an initial fallout in popularity, the ketogenic diet has regained some popularity as a safe and effective modality of managing epilepsy. In fact, many epilepsy sufferers have found the ketogenic diet to be equally as effective as medication, without unpleasant side effects and/or deleterious long-term effects.
How a Ketogenic Diet Prevents Seizures (Possible Mechanisms)
There are numerous theories regarding the anticonvulsant properties of the ketogenic diet. Many professionals simply accept that the ketogenic diet is an effective treatment for various cases of epilepsy, but cannot fully elucidate how it works. In a study published in 2007, researchers attempt to decipher the mechanisms by which a ketogenic diet inhibits seizure activity.
GABA increases: Researchers noted that chronic ketosis is thought to alter the Krebs cycle (tricarboxylic acid cycle), promoting synthesis of the neurotransmitter GABA within the brain. GABA is known to elicit inhibitory effects, thus attenuating excess neuroelectrical activity. Further, it is suspected that ketosis limits free radical generation and enhances the production of energy within brain tissue – possibly indirectly contributing to seizure reduction.
Hyperpolarization of neurons: Those adhering to ketogenic diets also experience increases in levels of polyunsaturated fatty acids (PUFAs) which facilitate the expression of neuronal uncoupling proteins, increase activation of metabolic genes, and aid in the production of new mitochondria via biogenesis. Due to restricted glucose levels and increases in oxidative phosphorylation, neurons become hyperpolarized or change in their electrical charge. In addition, a ketogenic diet is thought to activate ATP-sensitive potassium channels.
Glutamate processing: Collectively, the neural alterations resulting from a ketogenic state may contribute to stabilization of synapses and ultimately reduce likelihood of seizures. Researchers in later studies speculate that the ketogenic diet alters the processing of glutamate, an excitatory neurotransmitter. It accomplishes this in by increasing the concentrations of GABA in multiple ways, which inhibits seizure activity.
Benzodiazepine receptor binding potential: Later research used a PET (positron emission technology) scan to analyze the brains of individuals with intractable epilepsy. They scanned brains prior to the individuals going on a ketogenic diet, and following adherence to a ketogenic diet. The PET scans suggested that a ketogenic diet may control seizures as a result of directly (or indirectly) enhancing benzodiazepine receptor binding potential.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/17241207
- Source: http://www.ncbi.nlm.nih.gov/pubmed/14769486
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22352031
- Source: http://www.ncbi.nlm.nih.gov/books/NBK98219/
Eating A Ketogenic Diet for Epilepsy (Scientific Research)
The ketogenic diet has been utilized as a treatment for epilepsy since the 1920s. Since its inception as a therapeutic intervention for epilepsy, it has been subject to extensive scientific research. A majority of the research suggests that a ketogenic diet is a clinically effective intervention for seizure reduction among those diagnosed with intractable epilepsy.
2013: A publication from 2013 suggests that ketogenic diets were historically used as a “last resort” modality of treatment for intractable epilepsy. Those with intractable epilepsy tend to first pursue antiepileptic medications and sometimes opt for surgery before they’ll try a ketogenic diet. Authors of this report suggest that a ketogenic diet should be pursued as an earlier line of treatment rather than after many medications and/or surgery.
In fact, they go as far as to suggest that a ketogenic diet should be recommended as a first-line treatment for those with intractable epilepsy. It makes a lot of sense to try a ketogenic diet which isn’t associated with significant side effects nor adverse long-term effects before ingesting exogenous pharmaceutical compounds or pursuing surgical procedures. Only individuals with medical contraindications (e.g. primary carnitine deficiency) are recommended to avoid the ketogenic diet.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/23515149
2013: A report published in 2013 noted that a ketogenic diet is among the most effective interventions for drug-resistant epilepsy. Authors of the study suggest that increased dietary intake of medium-chain triglycerides (C:6, C:8, C:10, C:12) to fuel a ketogenic diet may be superior to a standard ketogenic diet for seizure reduction. They note that with increased MCTs as opposed to LCTs (long-chain triglycerides), individuals are able to consume more proteins and carbohydrates without disruption of ketosis and the associated neurological benefits among those with epilepsy.
This may be advantageous for children and/or adults with intractable epilepsy that would like to get the therapeutic benefits of ketone bodies without extreme dietary compromise. Authors suggest that MCT oil benefits among individuals with epilepsy may be therapeutically significant, despite some potential MCT oil side effects (e.g. diarrhea). Consuming copious amounts of MCT oil may enhance the efficacy of ketogenic efforts for the treatment of epilepsy.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/23515148
2012: A review of evidence was published in 2012 to determine the effects of a ketogenic diet among those diagnosed with epilepsy. For this review, researchers included randomized controlled trials (RCTs) spanning from 1948 to 2011, selecting trials of ketogenic diets (or similar diets) being used to treat epilepsy. They collected 4 randomized-controlled trials including a total of 289 participants; all were children or adolescents.
None of the studies were considered “blinded,” which could have skewed the results. That said, the researchers noted that the studies were of “good quality.” The review of evidence discovered that among children with epilepsy, ketogenic diets provide short-term to medium-term seizure control.
They noted that a long-term study suggested that efficacy of the diet was reduced over time. In other words, there may be diminishing returns of the ketogenic diet when used over an extended period of time. In addition, many of the children had a tough time tolerating the diet, minimizing adherence rates.
Authors note that a ketogenic diet is a feasible intervention among those with intractable epilepsy, however tolerability remains suboptimal. Perhaps modifications can be made to maximize adherence rates and improve tolerability of a ketogenic diet for children with epilepsy. Further research is warranted to elucidate a ketogenic diet’s efficacy for seizure control.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22419282
2010: While the ketogenic diet has long been used as an intervention for children diagnosed with epilepsy, less investigation has been conducted among adults. A study published in 2010 analyzed the efficacy, safety, and compliance rates among adults diagnosed with refractory epilepsy. This was considered an open-label, pilot study and a ketogenic diet was used as an adjunct (as opposed to a standalone) treatment.
Researchers assessed seizure frequency at baseline (a 4 month period) and then during the addition of a ketogenic diet (for 4 additional months). The ketogenic diet prescribed was one that incorporated a 3:1 ratio of fat to protein and carbohydrates (as opposed to a 4:1 ratio used in children). On average, using a ketogenic diet as an adjunct for epilepsy significantly reduced frequency of seizures.
On average, those eating a ketogenic diet experienced an approximate 40% seizure freqeuncy reduction in the first two phases of the experiment. It was reported that four participants experienced up to an 85% reduction in seizure frequency. Significant increases in the number of individuals that were “seizure free” after implementation of a ketogenic diet were also observed.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/20937568
2006: A study published in 2006 reviewed the effect of a long-term ketogenic diet among 28 children diagnosed with epilepsy. A total of 15 boys and 13 girls (7 to 23 years old) were documented by Johns Hopkins Hospital as having adhered to a ketogenic diet for at least 6 years. Baseline seizure activity during the early phase of the ketogenic diet was noted as “630” on a scale from 1 to 1400.
After 6+ years of adherence to the ketogenic diet, 24 of the children experienced seizure reduction exceeding 90%. A total of 22/28 children were satisfied with the effectiveness of the ketogenic diet for seizure reduction. Researchers noted that tolerability and efficacy of the ketogenic diet for seizure reduction was maintained over a long-term with modest side effects.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/17109786
2006: A meta-analysis was conducted to determine the efficacy of the ketogenic diet among pediatric patients with epilepsy. A total of 19 studies fit the inclusion criteria set by researchers and incorporated a total of 1084 participants. Results indicated that participants experienced up to 50% reduction in seizures.
Some individuals discontinued the diet for a variety of reasons including: inadequate seizure reduction, the restrictive nature of the diet, and miscellaneous side effects (or illness). The meta-analysis also suggested that those who experience significant seizure reduction from the diet tend to exhibit greater long-term adherence. It was difficult to determine the precise efficacy of the ketogenic diet among pediatric patients based on this meta-analysis.
Authors noted that future studies should consider the ketogenic diet’s effect on specific seizure subtypes and seek to better understand its long-term efficacy. They also note that more information needs to be collected to understand dietary adherence (or lack thereof).
- Source: http://www.ncbi.nlm.nih.gov/pubmed/16901419
2006: A study published in 2006 stated that the ketogenic diet has been employed for over 80 years as an alternative to anticonvulsant medications among those with refractory epilepsy. Researchers noted that a specific type of epilepsy classified as “myoclonic-astatic” is often resistant to pharmaceutical treatment. The basis for their study was to determine the efficacy and tolerability of the ketogenic diet among those with myoclonic-astatic epilepsy.
Evidence was gathered from 30 patient records spanning from 1990 to 2004 – all of whom had been diagnosed with myoclonic-astatic epilepsy. A total of 11 of the 30 patients were adjusted to a ketogenic diet, following the “Hopkins protocol.” These individuals were monitored for a period of 18 months to determine the efficacy of the ketogenic diet for seizure reduction.
Results indicated that only 6 of the 11 patients stayed on the diet for 18 months. Among the 6 patients adhering to the ketogenic diet, 2 had no seizures, 2 experienced a decrease in seizure frequency exceeding 75%, and the other 2 experienced a 50% to 74% reduction in seizure activity. Researchers concluded that the ketogenic diet is an effective intervention for children diagnosed with myoclonic-astatic epilepsy, noting that it should be used as a first-line treatment rather than after all other options have been pursued.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/16793577
2006: A paper published in 2006 highlighted the fact that fasting is an effective treatment for seizures, and has been considered such for centuries. Authors note that the ketogenic diet elicits similar biochemical effects to fasting, and is also an effective intervention for the treatment of seizures. While the diet hasn’t always been historically popular, in recent years it has gained a resurgence of attention on a worldwide scale.
It was mentioned that there are various versions of the ketogenic diet that may be modified to increase adherence, tolerability, and improve long-term outcomes among those diagnosed with epilepsy. Those with epilepsy may want to explore variations of the ketogenic diet to determine which variation is likely to minimize seizure frequency and maximize tolerability.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/16822355
2002: A study published in 2002 investigated the “breath acetone” to measure degree of ketosis among children with epilepsy. Results from the study suggested that children on ketogenic diets had significantly greater levels of fasting breath acetone (2530 mmol/L) compared to those not on a ketogenic diet with epilepsy (19 mmol/L and a group of healthy controls (21 mmol/L). Evidence indicates that measures of breath acetone could be taken among individuals on a ketogenic diet for seizure control to determine whether they are in ketosis.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/12193682
2000: A review of evidence was published in 2000 discussing the efficacy of the ketogenic diet among children with refractory epilepsy. Researchers focused specifically one the degree to which the diet reduced seizure frequency. Inclusion criteria for the review involved studies that documented the degree of seizure reduction from a ketogenic diet among children with refractory epilepsy.
All of the studies were considered “uncontrolled” and 11 trials fit inclusion criteria for the review. The review documented that all of the studies discovered significant therapeutic benefit derived from a ketogenic diet among children with refractory epilepsy. Adherence to a ketogenic diet reduced seizure frequency to a significant extent, which authors note was unlikely due to a placebo effect.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/10742367
2000: A study from 2000 investigated whether the type of fat used in a ketogenic diet could influence the efficacy of a ketogenic diet for seizure prevention. Researchers used a group of rats and fed them either: lard, butter, MCTs, flaxseed oil, or a mix of butter / MCTs / flaxseed oil. The effects of the ketogenic diet were monitored for a period of 98 days and seizure susceptibility was recorded with a maximal electroshock (MES) or pentylenetetrazole (PTZ) tests.
Results suggested that MCTs induced ketosis the quickest, followed by the blend (butter / MCTs / flaxseed oil), flaxseed oil, lard, and butter. The PTZ test suggested that 50% of the rats on the ketogenic diet had decreased susceptibility to seizures, whereas the MES test suggested no benefit. This study suggests that variations to the ketogenic diet fail to provide additional anti-seizure benefit.
It is difficult to determine whether these results are replicable in humans. In other words, would humans have the same response to different types of fats in the ketogenic diet for seizure susceptibility. It may be worth investigating whether certain types of fats in the ketogenic diet result in greater tolerability, seizure reduction, and dietary adherence among individuals diagnosed with epilepsy.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/11077453
Benefits of a Ketogenic Diet for Epilepsy & Seizures
There are many benefits that can be derived from a ketogenic diet for the treatment of epilepsy. Perhaps the most prominent benefit is that a ketogenic diet can significantly reduce seizure frequency, and is relatively well-tolerated with less side effects than a pharmaceutical anticonvulsant. Moreover, ketogenic diets can be maintained over a long-term and provide additional miscellaneous benefits (e.g. neuroprotection).
- Adjunct treatment: In many cases, a ketogenic diet can be used as an adjunct treatment for epilepsy along with an anticonvulsant medication. Those that aren’t able to attain full seizure reduction with a pharmaceutical drug may derive synergistic benefit from adhering to a ketogenic diet. In other cases, someone on a ketogenic diet may wish to add a pharmaceutical to the equation to get therapeutic relief greater than either intervention in isolation.
- Adults: There is some evidence to suggest that a ketogenic diet can be used to reduce the frequency of seizures among adults. While most literature is heavily concentrated on analyzing the efficacy of a ketogenic diet among children with epilepsy, preliminary evidence suggests benefit for adults. The mechanisms associated with therapeutic seizure reduction are likely not subject to significant variation between adults, adolescents and children.
- Children: There is substantial research that has been conducted among children and adolescents with epilepsy to determine the efficacy of a ketogenic diet. The diet appears to be safe, and well-tolerated among children with a modest side effect profile. Strict adherence to a ketogenic diet among children appears to reduce seizure frequency, and this reduction may increase over longer-terms (i.e. 6+ months).
- Drug alternative: Many people don’t respond to anticonvulsant medications, don’t tolerate medications, and/or dislike the side effects associated with their medications. For these individuals, a ketogenic diet may serve as a viable alternative. The ketogenic diet tends to have minimal side effects and may be highly effective even when an individual doesn’t respond to pharmaceutical drugs.
- Effective: While more evidence is necessary to understand the efficacy of a ketogenic diet for the treatment of epilepsy, most trials document efficacy. None of the studies investigating a ketogenic diet suggest that it is ineffective. It is unknown as to how effective a ketogenic diet is compared to an anticonvulsant drug due to lack of comparison studies, but it should be highlighted that many people who don’t respond to drugs still respond to a ketogenic diet.
- Minimal side effects: Although some side effects are common on a ketogenic diet, most are modest and well-tolerated. Examples of some side effects associated with a ketogenic diet include: constipation, diarrhea, fatigue, and kidney stones. In many cases the side effects of a ketogenic diet are favorable to those associated with traditional anticonvulsant treatment.
- Miscellaneous health benefits: The ketogenic diet may provide miscellaneous health benefits unrelated to seizure reduction. These additional benefits can include: weight loss, increased HDL cholesterol, reduced blood sugar, lower blood pressure, and may even improve certain aspects of cognitive function. Some studies hypothesize a potential neuroprotective effect associated with ketosis.
- Safe: Most professionals regard a ketogenic diet as being “safe.” Some would argue that the safety associated with a ketogenic diet is based off of the quality of the fats consumed. For example, consuming MCT oil, high quality olive oil, and grass-fed butter are likely significantly safer than consuming canola oil, standard butter, and vegetable oils. Assuming an individual consumes only the healthiest fats, a ketogenic diet is likely safe.
- Surgery alternative: Those with refractory epilepsy or seizures that are not responsive to medications often decide to pursue surgery. Surgical procedures can alter the structure of the brain and may lead to unexpected, long-term functional impairments. In many cases, a ketogenic diet provides substantial seizure reduction and may be a therapeutic alternative to brain surgery.
Limitations associated with Ketogenic Diets for Epilepsy Research
There are many limitations to consider regarding the scientific research of ketogenic diets for epilepsy. The most prominent limitation is that most studies conducted were not well-designed in that they were not randomized, double-blind, nor placebo controlled. Moreover, many are of small sample sizes and utilize children rather than other age groups – making it difficult to interpret the efficacy of this diet for other ages.
- Adherence: It is often difficult to get people (especially children) to adhere to a ketogenic diet. A ketogenic diet involves eating mostly fats, limited protein, and minimal carbohydrates. Most children naturally gravitate towards sugary, foods packed with simple carbohydrates. In many studies, lack of dietary diversity on a ketogenic diet and “sweets” make for difficult adherence, which in turn leads to high drop-out rates in trials.
- Children-centric: Much of the research is children-centric, meaning young children are tested on a ketogenic diet rather than adults. While the diet appears to be effective in children, there is a need for more trials incorporating individuals of other ages (e.g. teenagers and adults). It is important to note whether age influences the efficacy of a ketogenic diet for epilepsy.
- Comparative efficacy: Research does not compare the efficacy of a ketogenic diet for epilepsy to antiepileptic (anticonvulsant) medications and/or surgery. It would be interesting to understand whether a ketogenic diet is more or less effective than first-line pharmaceutical options for various types of epilepsy. Assuming a ketogenic diet is more or less effective than pharmaceutical interventions, it would be interesting to know whether the difference in efficacy is of therapeutic significance.
- Ketogenic modifications: Several studies have suggested that modifications to the ketogenic diet may be more effective than a standard 80% fats, 15% protein, and 5% carbohydrates for seizure reduction. In addition, these modified versions of the ketogenic diet may have greater adherence and/or slight differences in overall efficacy. For example, a ketogenic diet comprised heavily of MCT oil may have a quicker onset of efficacy compared to one with a high intake of lard. Understanding the subtle differences and/or health implications associated with the specific types of fats consumed may prove useful.
- Short-term trials: Most trials of a ketogenic diet for epilepsy are fairly short-term and longer-term trials are less feasible for a variety of reasons. Despite difficulties with longer-term feasibility, especially in double-blind, placebo-controlled, randomized designs – it would be interesting to learn whether seizure reduction increases and/or decreases among those on a long-term ketogenic diet. Some studies suggest that efficacy diminishes over the long-term, while others suggest that efficacy is amplified.
- Seizure types: The efficacy of the ketogenic diet should be determined specifically based on types of seizures a person experiences as well as subtypes of epilepsy. For example, those with myoclonic seizures may find superior relief from the ketogenic diet from another type (e.g. tonic). There could be potential differences in efficacy based specifically on the underpinnings associated with the subtype of epilepsy being targeted.
- Small samples: Another major problem with the research of ketogenic diets among those with epilepsy is that most studies incorporate extremely small samples. Of the small samples, only a few participants actually adhere to the diet for the full “assigned” term, making it difficult to assess the efficacy of the intervention. Larger-scale trials would help researchers better understand efficacy and adherence difficulties associated with a ketogenic diet.
- Study designs: It is difficult to design a “placebo controlled” and “double blind” study involving consumption of a ketogenic diet, but this could be accomplished via the blending of food. Most people know whether they’re eating a lot of carbohydrates or extensive amounts of fat. It is difficult to fool them with placebo controlled, double-blind designs. However, assuming individuals were assigned to receive fully blended “liquid” meals, this could allow for more robust study designs.
Are there any drawbacks associated with a ketogenic diet for epilepsy?
Perhaps the most obvious drawback associated with using a ketogenic diet for epilepsy is a restriction of food. Many people love (and crave) their sweets and carbohydrates, and without them, they experience temporary sugar withdrawal symptoms as well as gluten withdrawal symptoms. These withdrawal symptoms can include intense cravings, headaches, and other potent psychological disturbances spanning for several weeks.
Once a person has adapted to the ketogenic diet, consuming minimal carbohydrates is difficult in social settings and in the midst of a cultural evolution (over the past few centuries) that has promoted heavy consumption of carbohydrates. Assuming an individual can survive the withdrawals and resist savvy marketing of food manufacturing conglomerates, the ketogenic diet has potential to work. That said, another major concern is if a person has any health contraindications such as metabolic and/or mitochondrial disorders; these individuals will not be able to stay on the diet.
Some nutritionists speculate that health benefit can be derived from ketogenic diets, but many people do not consume any fruits – making them miss out on vital antioxidants. In addition, there may be health concerns for remaining in ketosis for prolonged periods, especially if an individual is consuming toxic fats such as canola oil or vegetable oil. For this reason, it is important to be highly selective of the types of fats that are consumed.
Finally, it is important to understand that not everyone with epilepsy will derive significant benefit from ketogenic diets. Some people may try a ketogenic diet and find that they provide little to no actual benefit in terms of seizure reduction. Therefore, it is important to avoid the extreme ideology that a ketogenic diet is optimal for all cases of epilepsy.
Have you tried a ketogenic diet for epilepsy?
If you’ve tried a ketogenic diet for epilepsy, or are on a ketogenic diet to manage seizures, share your experience with it in the comments section below. Discuss whether the ketogenic diet has been effective (or ineffective) for your seizure management. If it has been effective, mention how you determined the efficacy, and the extent to which it has reduced your seizures.
To help others get a better idea of your situation, mention the type of epilepsy you were diagnosed with, how long you’ve been on the diet, and how long it took you to get into ketosis. Do you use the ketogenic diet as a standalone management strategy for epilepsy or as an adjunct to a pharmaceutical medication? Highlight whether the benefits of being on a ketogenic diet for epilepsy outweigh the drawbacks (e.g. side effects, restriction of foods, etc.).