The ketogenic diet as epilepsy treatment

The Red Tea Detox


Newswise — While ketogenic diets have been used to deal with epilepsy for the final 100 years, they’re now discovering a resurgence of curiosity. The diets shift the physique’s power supply from glucose to ketones, mimicking the physiological results of fasting; Hippocrates famous that fasting may cut back seizure frequency (see timeline beneath).

A boy named Charlie and a sea change

The traditional ketogenic diet gained reputation within the 1920s and 1930s, however its presence pale with the provision of extra anti-seizure medicines, which had fewer life-style restrictions. As not too long ago as 25 years in the past, the ketogenic diet was hardly ever used as a treatment for epilepsy.

At that point, Johns Hopkins (USA) was one of many few establishments providing the traditional ketogenic diet (90% of energy from fats, 7% from protein and solely three% from carbohydrates) as treatment for pediatric epilepsy. They met with households from many areas of the nation—and around the globe—who couldn’t discover a native doctor to supply the diet.

“There were many doctors who told families they didn’t believe in it and that it was too hard,” mentioned Eric Kossoff, professor of neurology and pediatrics on the Johns Hopkins University School of Medicine.

But households had began to hunt therapies for refractory epilepsy that may enhance seizure management, and maybe with fewer antagonistic results than medicines. Neurologists started to steadily settle for the ketogenic diet as a sound treatment choice in these conditions. Much of the shift hinged on the publicity surrounding a single affected person: Charlie Abrahams, a 2-year-old boy with drug-resistant epilepsy and cognitive decline.

Charlie was handled with the ketogenic diet in 1994. He turned seizure free inside a month, spent a number of years on the diet and by no means had one other seizure. (He is now 28.) Charlie’s father, Jim Abrahams, fashioned The Charlie Foundation to extend consciousness of the ketogenic diet, and in 1994 Charlie’s story was featured on a US tv program known as NBC Dateline, which resulted in 1000’s of telephone calls to the Charlie Foundation from mother and father in search of extra info for his or her youngsters with drug-resistant epilepsy.

Abrahams additionally directed a movie depicting the household’s expertise, First Do No Harm (1997), and the Charlie Foundation supported the first potential trial of the traditional ketogenic diet, which was printed in 1998.

Since then, ketogenic diets have turn into more and more studied and accepted as a pillar of epilepsy treatment. “The ketogenic is mainstream, it is everywhere,” mentioned Eric Kossoff, professor of neurology at Johns Hopkins. “It’s one of the four major ways we treat epilepsy, along with medication, surgery and nerve stimulation.”

Some skepticism stays, nonetheless, mentioned Kossoff. “There are some neurologists who are not as familiar with it, or who are not willing to prescribe it.”

Types of ketogenic diets

Due to its very excessive fats requirement, the classical KD will be troublesome to keep up. Less restrictive options seem like almost as efficient whereas offering extra meals alternative. These options embody the modified Atkins diet (MAD; additionally known as the modified ketogenic diet), the medium-chain triglyceride (MCT) diet, and low glycemic index remedy (LGIT) (see desk).

Do the diets work?

Published in 1998, the primary KD trial included 51 youngsters who had been enrolled at 7 websites. Eighty-eight p.c of the youngsters remained on the diet after three months, 69% remained on it at 6 months, and 47% remained on it at 1 yr. Three months after initiating the diet, 54% of youngsters had at the very least a 50% lower in seizure frequency. At 1 yr, 10% of sufferers had been seizure free.

Another 1998 research adopted 150 youngsters between age 1 and 16. Collectively, they averaged 410 seizures per 30 days. Three months after beginning the diet, 32% of the youngsters had at the very least a 90% lower in seizures. After a yr, 55% of youngsters had been nonetheless on the diet; of these, 27 % had at the very least a 90% lower in seizures.

Since then, different research have collectively proven that as much as 55% of youngsters obtain seizure freedom with classical KD after three months, and 85% obtain seizure discount. The first randomized medical trial, printed in 2008, included 145 youngsters randomized to dietary treatment or ordinary care . After three months, 38% of the diet group had better than a 50% seizure discount, in contrast with 6% within the usual-care group, and seven% of the diet group had a 90% or better discount in seizures, in contrast with zero% within the management group. “This study justifies consideration of the KD alongside any other anti-epileptic drug (AED) in the treatment of drug resistant epilepsy,” wrote the authors.

Though few research have in contrast the varied diet varieties, a latest randomized trial discovered that in 158 youngsters, median seizure reductions had been 66% on classical KD, 45% on Modified Atkins diet (MAD) and 54% on low-glycemic-index treatment (LGIT) after 24 weeks. Similar numbers of youngsters throughout the three therapies skilled at the very least a 50% discount in seizures.

The trial additionally confirmed that modifications in seizure burden had been extra gradual with LGIT than with the opposite two diets, however the fee of antagonistic results was lowest within the LGIT group. LGIT is taken into account the least restrictive diet of the three, which can make long-term adherence extra possible.

“There is increasing evidence that the ketogenic diet, in whatever form may be most practical for the individual, may be effective where drugs have failed across the age range,” mentioned Helen Cross, The Prince of Wales’s Chair of Childhood Epilepsy and Head of Programme in Clinical Neurosciences on the Great Ormond Street Institute of Child Health at University College London, and senior writer of the 2008 randomized trial.

Who is a candidate for a ketogenic diet?

Ketogenic diets have been proven efficient in youngsters as younger as 6 weeks, on up by way of maturity. In common, anybody who can tolerate the diet safely is a candidate to attempt it (see Table for checklist of contraindicators).

Certain teams could profit greater than others, nonetheless. For sure circumstances, proof exhibits ketogenic diet is extremely useful and must be used early in affected person administration. These circumstances are:

  • Angelman syndrome
  • Complex 1 mitochondrial problems
  • Tuberous sclerosis advanced
  • Dravet syndrome
  • Doose syndrome
  • GLUT-1 deficiency syndrome*
  • Infantile spasms
  • Febrile infection-related epilepsy syndrome (FIRES, now thought-about a subset of NORSE)
  • Solely formula-fed infants or youngsters with drug-resistant seizures
  • Ohtahara syndrome
  • Pyruvate dehydrogenase deficiency*
  • Super refractory standing epilepticus (SRSE)

*A ketogenic diet is the treatment of alternative for this situation.

For different circumstances—together with childhood absence epilepsy, cortical malformation, juvenile myoclonic epilepsy, Lennox-Gastaut syndrome, and Rett syndrome—a KD has been reported as reasonably useful. For extra element, see the suggestions from the International Ketogenic Diet Study Group.

Starting the diet

Traditionally, initiating the ketogenic diet required a brief hospital keep, throughout which the diet was safely began, ketones are monitored, and the particular person is examined for hypoglycemia or different metabolic points. The Johns Hopkins program admits sufferers for 3 days, gives training and recipe/meal planning to households, after which schedules follow-up visits each one to 3 months.

Common antagonistic results of the ketogenic diets embody constipation, vomiting and diarrhea. Constipation is the most typical facet impact, however often tapers off over time or will be managed with medicine, mentioned Natasha Schoeler, analysis dietitian in Clinical Neurosciences on the Great Ormond Street Institute of Child Health at University College London.

“Generally, side effects seem to be consistent across the various types of diet,” said Schoeler. “We do sometimes see higher rates in individuals on the classic KD compared with the other forms of diet, but the differences are not striking.”

Other short-term negative effects can embody lethargy, irritability, starvation, lack of urge for food, exacerbation of reflux, and elevated susceptibility to respiratory tract infections. Schoeler famous that many of those negative effects are frequent within the common inhabitants and are additionally seen in management teams of KD trials.

If the diet is efficient, tapering of AEDs can happen, mentioned Schoeler. “Usually if someone is experiencing a very good response to the KD, at least at the three-month mark, or even before, we can start tapering off medications,” she mentioned. “Many people do come off medication completely, but others don’t, so it has to be what works best for each person.”

What are the drawbacks?

Besides the diet’s potential negative effects, ketogenic diets will be costly. “Medications can be expensive, but insurance will cover them,” mentioned Kossoff. “On the diet, families buy more meat, dairy, eggs—and insurance companies don’t pay for groceries. There are ways to make it less expensive, but it’s definitely a cost issue for some families.”

These diets additionally infiltrate all points of day by day life and will be troublesome for households to keep up. Meals for social occasions, schooldays and holidays have to be rigorously deliberate. Such planning requires constant effort and time, as effectively as buy-in from prolonged members of the family, buddies and faculty directors and academics. A meta-analysis of 12 research together with 270 adults on the ketogenic diet discovered the compliance fee for the classical KD was 38%, and for the modified Atkins diet it was 56%. The authors cited attainable negative effects, psychosocial components and the restrictiveness of the diets as attainable causes for the low compliance.

“Even if you’re doing the low-glycemic-index treatment or the modified Atkins diet, you’re still radically changing the way someone eats,” mentioned Kossoff. “It’s pretty easy for a month or so, and then it gets old.”

Is it a lifelong remedy?

For youngsters with circumstances for which a KD is the treatment of alternative, and for many adults with epilepsy who discover success with a KD, the diet is mostly a lifelong dedication. But for others, after two years on the diet it’s attainable to return to a much less restrictive approach of consuming.

“Around the 2-year mark, we have a discussion with each family as to whether it’s the right time to discontinue the diet,” mentioned Schoeler. “There are data showing that 75% to 80% of people who are seizure free on the diet will maintain it off the diet.”

Less clear is what occurs to those that have decreased seizures however not seizure freedom, she mentioned. “We don’t know if they maintain that response after going off the diet. And of course, there is a risk in anyone that seizures will return.”

How does it work?

We actually don’t perceive how the diet could profit some individuals and a few circumstances. A latest assessment listed at the very least 12 mechanisms at play, together with results on neurotransmitters, mitochondria, intestine microbiota, DNA methylation, ion channels, irritation, and G-protein coupled receptors.

“It’s extremely complex,” mentioned Kossoff. “I don’t think there will ever be a pill that could completely replicate what the diet does.”

But some teams try to tease out the important thing mechanisms of the KD in hopes of offering at the very least a partial “ketogenic diet in a tablet.” Several compounds are in improvement, together with 2-deoxyglucose (2-DG), a glucose analogue that may be taken up by cells, however not used for power. Instead, it partially blocks cell metabolism exercise. 2-DG has been used (as fluorodeoxyglucose) in PET scans to establish areas of glucose uptake, such as in tumor cells. Some research have proven that 2-DG has anti-seizure exercise, whereas others present the other.

A 2018 animal research confirmed that the ketogenic diet’s results are dependent upon the intestine microbiome, and recognized two kinds of micro organism that proliferated within the guts of mice given KD. Changes within the intestine micro organism led to modifications within the biochemistry of the intestine, which affected neurotransmitters within the mind.
Ketogenic diets additionally inhibit adenosine kinase, leading to elevated ranges of adenosine. “Abnormally low levels of adenosine are a hallmark of the epileptic brain,” mentioned Detlev Boison, who spoke about metabolic therapies for epilepsy on the 2020 North American Virtual Epilepsy Congress. Boison, professor of neurosurgery at Rutgers University’s Robert Wood Johnson Medical School, mentioned that inhibiting adenosine kinase could not solely cut back seizures, but additionally forestall epileptogenesis. Work by his group has proven that systemic treatment with an adenosine kinase inhibitor (5-iodotubercidin) stops the event of epilepsy in a mouse mannequin.

The ketogenic diet for standing epilepticus

Based on present proof, the International Ketogenic Diet Study Group already recommends the ketogenic diet for treating tremendous refractory standing epilepticus (SRSE) and febrile infectious refractory epilepsy syndrome (FIRES), a subset of new-onset refractory standing epilepticus (see checklist of circumstances wherein the KD is very useful, above).

The KD additionally could also be efficient for standing epilepticus (SE). A 2019 systematic assessment of 17 articles (four observational research, 10 case studies, and three case sequence) discovered that KD led to the cessation of SE in 82% of grownup sufferers. And a latest research of pediatric sufferers on a KD seen within the emergency division discovered considerably decrease charges of standing epilepticus in youngsters who had been on the diet for at the very least six months, in contrast with these following it for much less time.

Because the ketogenic diet is at the moment one of many final choices tried in SE—whether it is tried in any respect—there’s a threat of the diet being administered too rapidly and interacting with different therapies, mentioned Schoeler. Care have to be taken to keep away from beginning the diet in sufferers on propofol, as propofol infusion syndrome is a uncommon however typically deadly consequence.

The ketogenic diet for different circumstances

The ketogenic diet is being acknowledged in all kinds of different circumstances, such as dementia, mind tumors and a few metabolic ailments, mentioned Cross.

Indeed, within the first 10 months of 2020, greater than 300 research had been printed on the ketogenic diet for different ailments and circumstances, together with weight reduction, most cancers, sort 2 diabetes, cognitive impairment, coronary heart failure, autism, bipolar dysfunction, athletic efficiency, Alzheimer’s illness, and COVID-19.

The ketogenic diet in 2020

Today, a number of components make ketogenic diets simpler to comply with in high-resource areas. Besides the much less restrictive options to the classical KD, there are also ketogenic formulation, snacks, shakes, and ready-to-eat meals out there. Much of the product explosion stems from the elevated reputation of “going keto” as a method for weight reduction or insulin management.

There is also extra skilled assist for the diet than up to now. “There’s still some cynicism, but very few doctors don’t believe it works, though they may not recommend it high on their list of options,” mentioned Kossoff. But happening a ketogenic diet remains to be an endeavor.

“The diet still requires a hospital admission most of the time, and weighing and measuring,” he mentioned. “It’s still easier to take a pill. We need to find ways to make the diets easier and more accessible.”

Resources

Ketogenic diet pointers for infants with refractory epilepsy (2016): van der Louw et al, European Journal of Paedatric Neurology DOI:10.1016/j.ejpn.2016.07.009

Optimal medical administration of youngsters receiving dietary therapies for epilepsy: Updated suggestions of the International Ketogenic Diet Study Group (2018): Kossoff et al, Epilepsia Open DOI:10.1002/epi4.12225

Systematic assessment of ketogenic diet use in grownup sufferers with standing epilepticus (2019): Mahmoud et al, Epilepsia Open  DOI: 10.1002/epi4.12370

International Centers: List of worldwide ketogenic diet facilities

Ketogenic formulation and merchandise (as of 2014)

YES Webinar: Ketogenic diet October 2020

En español

Dieta Cetogénica, Conceptos básicos

Dieta cetogénica: Información common y enlaces

Video: Descripción de la dieta cetogénica (Epilepsy Foundation)

Training alternatives

Johns Hopkins Medicine coaching for worldwide physicians: 1- or 2-week periods.

The Charlie Foundation coaching seminars at medical facilities; since 2006, they’ve supplied coaching in 11 nations. The medical middle ought to have a longtime treatment staff together with a dietitian, doctor, nurse, and pharmacist. The coaching contains sensible info for establishing a program and medical pointers for managing sufferers from pre-diet workup by way of cessation of remedy.

Matthew’s Friends KetoCollege – 11-session video tutorial for well being professionals. Videos cowl all points of the diets, from the kinds of diets, affected person choice, diet initiation and discontinuation, and the ketogenic diet for adults. There is a price, which varies by nation.

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Founded in 1909, the International League Against Epilepsy (ILAE) is a worldwide group with greater than 120 nationwide chapters.

Through selling analysis, training and coaching to enhance the prognosis, treatment and prevention of the illness, ILAE is working towards a world the place no particular person’s life is proscribed by epilepsy.

ILAE web site (out there in a number of languages) | Facebook | Instagram 

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