A physician traces one boy’s story and unpacks the research
Six years ago on a spring day in Indiana, suddenly and without warning, Will had his first seizure. Shortly thereafter, the previously healthy 5-year-old was diagnosed with generalized epilepsy. Despite starting treatment, Will’s epilepsy continued to worsen.
His mother, Sarah Ackerman, recalls, “We tried medicine after medicine, upping the doses and combining it with others only to see his condition drastically decline. He went from having just a few generalized myoclonic seizures to over 100 a day within the first two months. His numbers continually increased as the months went on with no reprieve.”
Will’s epilepsy was preventing him from focusing and learning in kindergarten. Sometimes he had so many seizures in a row that he would pass out. When medical treatments for epilepsy fail, doctors often recommend surgery on the affected part of the brain. However, such a procedure was not offered to Will because his seizures were occurring in multiple areas of the brain rather than one specific location.
With surgery off the table and his medication choices running out, Will and his family made the two-hour drive to Cincinnati Children’s Hospital, one of the largest in the country. There, he was evaluated by a neurologist who recommended trying an alternative treatment approach called the ketogenic diet.
The ketogenic diet is named after ketones, products of the fat metabolism that occurs when the body is running low on other sources of energy, namely carbohydrates and proteins. Ketones are able to cross the blood-brain barrier, acting as a substitute for glucose to supply the brain with essential energy. The goal of the keto diet, as it relates to treating epilepsy, is to mimic a fasting state so that the brain is fueled by ketones rather than glucose.
But could this alternative energy source actually help treat Will’s seizures? Ackerman remembers feeling uncertain. “When the doctors explained the keto diet to us, I don’t know that I would say we were confident it would work,” she says. “We just knew that we had no other choice. This was not the quality of life we wanted for our son, and we would do anything to help him get back what the seizures had stolen from him.”
The concept of fasting to treat epilepsy is far from new. In fact, the only method of treating seizures recorded in the manuscripts of the ancient physician Hippocrates was fasting. One-hundred fifty years later, another Greek doctor, Erasistratus, followed the same protocol. Fast forward to early 20th-century Paris. It was there in 1911 that physicians Gulep and Marie documented reduced severity of seizures in 20 fasting subjects.
It was not until 1921, however, that Dr. Russel Wilder of the Mayo Clinic proposed that ketone production occurring in the fasting state could also be achieved through an alteration in diet — thus coining the term “ketogenic diet.” This diet would be high in fat, moderate in protein, and low in carbohydrates.
Current versions of the keto diet follow the same principles established by Wilder and generally fall into one of four categories.
- In the classic ketogenic diet, 80% to 90% of calories come from fat, 10% or less come from protein, and the rest are from carbohydrates — preferably fruits or vegetables. The diet is often further described in terms of the ratio of fats to other calories (i.e. proteins and carbs). For example, the ratio might be 4:1, 3:1, or 2:1. The classic keto diet is the most frequently recommended dietary treatment for epilepsy in children.
- Another version of the keto diet also recommended for children is the medium-chain triglyceride, or MCT, diet. This diet utilizes MCT oils that occur naturally in palm and coconut oil as well as human, cow, and goat milk. The MCT diet allows for a few more carbohydrates but still compares favorably to the classic keto diet in terms of efficacy. On initiation of either the MCT or the classic ketogenic diet, children and their families receiving treatment for epilepsy traditionally stay three to four days in the hospital for lab testing and dietary teaching.
- The modified Atkins diet is less restrictive than the classic ketogenic diet. Experts more frequently recommend it for adolescents and adults due to a greater likelihood of adherence in this demographic. However, positive results have been seen in children as well. In their most recently published recommendations, the International Ketogenic Diet Study Group addressed both the modified Atkins diet and the low glycemic index diet (below) commenting, “They tend to require less time for meal calculations and allow more parental independence.”
- The low glycemic index diet allows for more carbohydrates as long they have a low glycemic index, meaning they don’t raise the body’s blood sugar too quickly. Strawberries, lentils, and whole-grain breads, for example, are well-suited — as opposed to pineapple, potatoes, or white bread, which have a high glycemic index.
I first became aware of the ketogenic diet during my residency training from 2011–2015, coincidentally, also in Cincinnati, Ohio. I recall caring for children who were admitted to the hospital in order to begin the diet. At that time, the idea that the keto diet could effectively treat epilepsy was emerging from the shadows of expert opinion into the light of evidence-based medicine.
Our team monitored patients’ seizure activity, glucose levels, urine ketones, electrolyte measurements, and observed for potential side effects of the diet. As I was completing my final year of training at Cincinnati Children’s, Will’s experience with the ketogenic diet was just starting.
Ackerman recalls how Will’s treatment began. “Under the supervision of the hospital as an inpatient, we immediately reduced all his medications, except one, and began the process.” The team of hospital staff supervising Will included pharmacists, nurses, medical trainees, pediatricians, and neurologists — all working together to care for Will, but none of them more essential than the dietitians.
Tara Finnerty is a board-certified ketogenic nutrition specialist at Primary Children’s Hospital in Salt Lake City, Utah. For the past eight years and counting, she has cared for many individuals looking to improve their health through the keto diet, including children suffering from epilepsy.
Finnerty was open-minded when she first learned of the ketogenic diet. “I really had no reason to doubt the effectiveness of the diet,” she says. However, it took observing the changes in her patients firsthand to fully solidify her belief in the treatment approach. She expresses a feeling of amazement as she witnessed the transformation of a patient suffering from significant lethargy as a side effect of anti-epileptic drugs. Finnerty portrays the child, now on the keto diet, as tracking, smiling, and essentially coming back to life.
The goal of the keto diet, as it relates to treating epilepsy, is to mimic a fasting state so that the brain is fueled by ketones rather than glucose.
While success stories from experts like Finnerty are compelling, some may wonder what scientific research has to say. The answer is encouraging for keto enthusiasts who, over the past few years, have witnessed a robust advancement of scientific literature on the topic.
A Cochrane review published in 2020 analyzed nearly 1000 patients with epilepsy from 13 studies. The majority of participants were children. Its authors concluded that children on the ketogenic diet were three times more likely to be seizure-free and six times more likely to have a 50% reduction in seizure frequency when compared to usual dietary care.
The same review showed that over 50% of children on the classic keto diet became seizure-free after three months and 85% saw a significant reduction in seizures. In comparison, 25% of children who implemented the less-restrictive modified Atkins diet achieved seizure freedom while 60% saw a reduction in seizure activity.
Findings were less dramatic for adult patients but significant nonetheless. Because adults typically pursue a less-restrictive treatment approach, the majority of data in the review evaluated the modified Atkins diet. While there were no reports of seizure freedom, adult subjects were up to five times more likely to have a 50% reduction in seizure frequency.
Despite strong evidence of its efficacy, a mechanism to clearly explain the keto diet’s benefit remains elusive. Research indicates that ketones are able to reduce the excitability of neurons and stabilize synapses in the brain, but how?
Finnerty replied frankly when asked. “Honestly, I still don’t think we have clear answers,” she admits. Experts have put forth numerous theories. Some say the effect is directly related to ketones in the blood while others postulate it is due to elevated fatty acids, glucose stabilization, increased activation of potassium channels, or even elevated brain amino acids.
Finnerty proposes that the diet’s level of effectiveness is likely related to the underlying cause of epilepsy which varies for each patient. She has observed that a portion of patients must attain significant ketosis in order to see positive results, whereas another portion does not. For example, some individuals on less restrictive diets, such as the low glycemic index diet, are able to find success despite having few or no measurable ketones, which supports the theory of glucose stabilization. In contrast, Finnerty notes, “I have other patients who can only achieve seizure control on the classic 4:1 ratio where we push ketone levels to high therapeutic ranges which indicates the ketones themselves offer the benefit.”
Though much is left to be uncovered about how the diet works for epilepsy in general, the picture becomes more clear by looking at specific epilepsy syndromes. For a few rare diagnoses such as glucose transporter deficiency, Dravet syndrome, and pyruvate dehydrogenase deficiency, the keto diet is becoming the treatment of choice.
Finnerty explains: “Glucose-transporter deficiency is where the person lacks the transporter responsible for carrying glucose into the cells of the brain to be used for energy. It results in severe neurological impairment, gross motor delays, and often seizures. The only treatment for this diagnosis is the ketogenic diet, which offers another fuel source for the brain.”
She continues, “Within 24–48 hours of elevating ketones in the brain, we see a reduction in seizures, whereas other etiologies of epilepsy may or may not respond as well and often can take a full two to three months of being in ketosis.” Recovery in these patients is a joy for Finnerty to witness. “I just love seeing this transformation that almost presents as a miracle for these patients. Seeing the relief in the parent is so rewarding. I can’t tell you how many times I hear the parent comment that they can see their child come to life for the first time, or how they are so excited because their child actually looked at them and responded to their name for the first time. It’s pretty awesome.”
Upon initiating the keto diet, Will and his family hoped to realize a similar success story but were prepared by their dietitian and other members of their care team that the road ahead would not always be easy.
His mother, Sarah, remembers, “We were told that most families abandon this treatment option after the first month because of the challenges: time constraint to prep the food, the emotional stress it puts on the child to not eat what others are eating, having such small portions, the extra fat intake, and the desire to cheat. I think knowing this ahead of time helped us cope and stay on track during the years to come.”
As they start keto, patients typically continue at least one of their anti-epileptic medications. This was the case for Will. Additionally, because liquid children’s medications are compounded using syrups high in carbohydrates, patients’ seizure drugs are usually changed to a carbohydrate-free preparation. Vitamin supplements are regularly prescribed including a multivitamin with selenium, calcium, vitamin D, and potassium citrate to reduce the likelihood of kidney stones.
Will started his keto journey in the hospital on the modified Atkins diet. Ackerman describes a rocky start. “He was not taking to the change,” she says, “so he wasn’t eating much of anything. Within the first day, Will experienced ketosis. That was when we discovered that his body went into ketosis quicker than most. We stayed on the modified Atkins diet for about two weeks and weren’t seeing much change.”
The modified Atkins diet, as well as other forms of the ketogenic diet, can often take two to three months to produce an effect, but two weeks into the new diet Will and his caretakers were already looking for something they could do to improve his chances of a favorable outcome. They opted to increase the portion of dietary fats, shifting his regimen towards the classic ketogenic diet. A day’s worth of meals looked something like this:
- Breakfast: scrambled eggs mixed with heavy whipping cream and butter, with a side of bacon and strawberries
- Lunch: tortilla, pepperoni, mozzarella cheese, and a side of lettuce and ranch/grape-seed oil/butter mixed together
- Dinner: a small portion of chicken nuggets and salad topped with a mixture of ranch/oil/butter, cheese, and bacon
- Snacks: celery with a mixture of peanut butter and butter and a side of strawberries
Even with the increase in fats, Will tolerated the change. “We began steadily increasing his ratio and discovered that at 2.5:1 his seizures completely disappeared,” Ackerman recounts.
Not only did the keto diet effectively treat Will’s epilepsy, but its success was sustained over the long term. Will’s neurologist and nurses were impressed with his results. According to Ackerman, he looked to them like a completely different boy compared to when he was in the hospital. Will maintained the same 2.5:1 ratio on the keto diet for the next few years.
Maintaining dietary changes over time can be challenging with any type of diet, and keto is no exception. Finnerty teaches patients and parents that the ketogenic diet is about replacing not restricting foods. “One has to relearn how to cook, measure, and prepare foods differently,” she says. “It’s not necessarily harder to do, just different.”
She emphasizes the importance of advance planning and discourages processed foods. “People who spend time prepping meals and snacks for the week tend to do the best. It is difficult to sustain the diet if you get caught hungry and without any food to eat,” Finnerty says. “Focusing on fresh, whole foods is still important and will help sustain the diet. The ketogenic diet has become so popular now that we are seeing a lot of processed and packaged keto convenience foods in the market. Although these can still sometimes be incorporated, and helpful in certain situations, they can sometimes interfere with outcomes and success of the diet.”
In addition to becoming a proven treatment for epilepsy, evidence is building that the ketogenic diet may be helpful for a number of other medical conditions as well. The most well-developed data suggest a benefit for patients with Type 2 diabetes as well as glioblastoma multiforme, a type of aggressive brain cancer.
Investigations into many other disorders are on the horizon. “Conditions such as metabolic syndrome, non-alcoholic fatty liver disease, obesity, chronic migraines, traumatic brain injury, dementia, Parkinson’s, autoimmune disorders, mental health, polycystic ovarian syndrome, and so much more have been studied, are being studied, and are anecdotally helping so many people,” Finnerty explains.
The keto diet is gaining popularity in healthy individuals too. Yet, it is important to note the keto diet is not without risk or monetary cost. “It is critical to have medical and dietary guidance for using the ketogenic diet to treat a medical condition,” Finnerty cautions. Although patients are now more frequently initiating the ketogenic diet outside the hospital setting, side effects such as kidney stones, low bone density, weight loss, low blood sugar, and gastrointestinal symptoms may occur. Certain rare metabolic disorders can even be made worse on the ketogenic diet. So, close supervision from experts remains a necessity.
For Will and his family, the ketogenic diet was a breakthrough, but his story didn’t end there. There was one more perk to discover. Remarkably, the success of the ketogenic diet has been shown to extend beyond its duration. One such study demonstrated that 80% of patients who were seizure-free after two years of keto remained seizure-free even after discontinuing the diet. Would this effect pan out for Will? According to his mother, “After a little over three years, we began the slow process of stair-stepping him down on his ratio while keeping his medicine in place. Will is now completely off keto and taking two doses of his seizure medicine each day. Besides a few small hiccups, he has been seizure-free ever since.”
As a practicing physician in the fields of internal medicine and pediatrics, a significant portion of my job is spent prescribing medication. I’m constantly accounting for the potential side-effects and interactions of various pharmaceutical agents. It is both fascinating and encouraging to me when a non-medical intervention like a change in diet proves durably helpful to manage a chronic condition. Learning how individuals in the modern world are benefiting from a diet rooted in ancient medicine leaves me hopeful about the future. So much is left to be discovered about how nutrition affects the brain and body — we have only scratched the surface.