Epilepsy diets are medical treatments used to control seizures. These diets are high in fat, adequate in protein, and low in carbohydrates. The ketogenic diet, in particular, has been used to treat children with epilepsy for almost a century. Ketones, the byproducts of fats, are produced by the liver when there is an inadequate supply of carbohydrates. Unlike most other organs in the body, the brain can utilize ketones as an alternative source of energy. Ketones can be produced with prolonged fasting, and these diets are intended to induce these changes-stably reducing carbohydrates and driving the production of ketones, or ketosis-in a sustainable manner.
Understanding the Modified Atkins Diet (MAD)
The modified Atkins diet (MAD) is a liberalized form of the ketogenic diet (KD) utilized in the treatment of epilepsy [1]. The MAD is a practical option for older children and teenagers who may benefit from diet therapy for seizure control. Compared to the traditional ketogenic diet, MAD is less restrictive. The food is measured with household measurements like tablespoons, cups, or servings rather than on a food scale. Carbohydrates are limited to about 20 g net carbs a day (net = total carbs - fiber). There is no fluid restriction or limitation. Foods can be eaten in restaurants and outside the home. MAD is mostly used for patients who still have frequent seizures despite anti-seizure medications.
The modified Atkins diet (often abbreviated in the literature as “MAD”) is a change to the traditional “classic” ketogenic diet to make it less restrictive. Its history goes back to the early 2000s. Some families who had used the ketogenic diet for many years eventually stopped weighing and measuring foods. They had noticed that ketones still remained high and seizures stayed under control. It was first formally studied in children and adults who had never tried the ketogenic diet at Johns Hopkins Hospital by Dr. Eric Kossoff and colleagues in 2002. The first paper on this diet was published in 2003. This diet is now over 14 years old with greater than 500 patients published to date.
How MAD Works
The classic ketogenic diet was developed in 1921. It was designed originally to mimic the ketotic effect of fasting, resulting in an anti-epileptic effect; however, it likely works through effects on mitochondria. Most of the time, the brain uses carbs for energy. The MAD forces the body to use fat to make ketones for energy instead. It can take a few weeks to months to see just how the MAD will affect seizures. If the MAD is helping seizures, your child will likely stay on the diet for 2 to 3 years.
The classic ketogenic diet is the strictest of the epilepsy diets. It is calculated based on a fixed ratio of fat to carbohydrates plus protein. Typically, a regular diet has a ratio of 0.3:1. Ketogenic diets range from 1:1 to 4:1. It is calorie controlled, and food is weighed on a gram scale. The MAD is a more liberalized version of the classical ketogenic diet. It provides unrestricted protein, a carb restriction of 10 to 20 grams per day and fat with every meal and snack.
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Implementing the Modified Atkins Diet
Typically, the amount of daily carbohydrate in the Modified Atkins diet (MAD) is restricted to 10-20 g from the beginning of the therapy. However, some patients may find it difficult to lower the carbohydrate content abruptly. It is possible to gradually reduce the daily carbohydrate amount to this target to increase acceptability of the diet.
A recent survey among the UK dietitians reported 72% of the centers advised patients to make initial dietary modifications (reducing dietary intake of high sugar foods and overall carbohydrates, over a 4- to 6-week period, before commencing a modified KD [3]. All UK centers (n = 18) provided a specific carbohydrate target (15-30 g per day) based on a predetermined weight in 67% of centers or 5% of the estimated total energy requirements in 28% of centers. One center calculated carbohydrates to provide between 10% and 20% of estimated total energy [3]. This means, for an older child requiring 1500 calories per day, daily carbohydrate would be 37.5-75 g. Authors from South Korea reported a different method of implementing the MAD: carbohydrates were restricted to 10 g per day initially, but were allowed to be increased by 5 g per day to a maximum of 10% carbohydrates per day by weight at intervals of at least 1 month, depending on tolerance [4]. One adult study reported the use of 50 g carbohydrate in their protocol for the MAD [5]. An inpatient protocol from Australia reduces carbohydrate over 2 weeks [6].
Gradual Carbohydrate Reduction: A Liberalized Approach
Rapid lowering of daily carbohydrate intake can be difficult to implement in some patients on a MAD. A more gradual reduction in the amount of carbohydrates can be undertaken over days to weeks depending on individual tolerability and resultant seizure control. This is similar to the practice of gradual initiation of the classic KD [7,8]. Variable amount of medium chain triglyceride oil can be added to any type of diet to increase the ketogenic potential [10].
A flexible patient-specific approach is often suggested, choosing an individualized treatment based primarily on specific dietary and lifestyle requirements, rather than on a rigid diet protocol. This can utilize one specific type of diet, but alternatively can use the principles of different or all forms of ketogenic therapies [9]. Ontario provincial guidelines for the management of drug-resistant epilepsy mention the use of individualized modifications to diet therapy [10].
Case Study: MAD with Slow Carbohydrate Reduction in GLUT-1 Deficiency
We report the use of the MAD with slow carbohydrate reduction in a patient with Glucose Transporter 1 Deficiency, including results of neuropsychological assessments. A two-and-one-half-year-old boy presented with two convulsive episodes of unresponsiveness and associated body stiffness lasting 2-3 min. During one of the seizures, he was incontinent of urine. He also had two episodes with dystonic posturing of the right-sided limbs lasting several seconds with retained awareness. Subsequently, he developed multiple daily seizures with staring and unresponsiveness lasting up to 5-15 s. These episodes were not associated with automatisms or eye blinking. There was no history of exertional dystonia. Birth history was unremarkable. He walked independently at 18 months, but he was often described as “off balance.” There was no family history of epilepsy. His neurological examination was normal except for a clumsy gait. His head circumference was 52 cm. EEG showed frequent generalized and bifrontal epileptiform discharges. Brain MRI did not reveal any parenchymal abnormalities and chromosomal microarray analysis was normal. Metabolic investigations were also normal.
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In 2015, a next generation epilepsy genetic sequencing panel revealed a de novo heterozygous mutation in SCLC2A1 gene (p.Asp461_Ile463del), confirming the diagnosis of GLUT-1 deficiency. Following an assessment by our registered dietitian, blood investigations, and an ECG, the patient was initiated on a liberalized form of the KD as an outpatient in October of 2015. We used the principles of the MAD [1]: there were no restrictions of fat intake but minimum daily recommendations were provided. The appropriate amount of carbohydrate per day was prescribed. Initially, we decreased daily carbohydrate to 86 g (two-thirds of the pre-diet consumption). The patient was encouraged to increase the fat and protein intake, with minimum recommendations of 105-g fat and a maximum protein recommendation of 70 g per day. The patient was supplemented with vitamin D, calcium, and multivitamins. At the first stage, his home blood ketone levels were 1.3-3.1 mmol/L. One episode of hypoglycemia (2.9 mmol/L) was identified and responded readily to supplemental treatment with juice. After 2 weeks, the daily carbohydrate prescription was further reduced to 50 g, and suggestions were provided to increase recommended fat intake to maintain weight stability. It was recommended that daily carbohydrate intake be spaced out evenly throughout the day. Patient became seizure-free at this stage. A 3-day food record analysis showed an average intake of 47 g carbohydrate, 78.5 g protein, and 125.5 g fat per day. The calculated average ratio was 1:1. The 6-month blood investigations revealed low blood levels of selenium and zinc, which were corrected with supplementation. The patient developed six episodes of absence seizures within the next year; hence, the carbohydrate intake was further limited to 45 g per day. The patient remains seizure-free since then, with resolution of headache (Table 1). Home blood ketone levels ranged 0.5-1.5 mmol/L. Recent food record analysis data are as follows: 45-47 g carbohydrate per day (spread throughout the day), and average fat of 190 g per day with an estimated ratio of 1.2:1. Most recent lipid profile was normal. The patient has been off all anti-seizure medications for 10 months and the parents stopped home blood ketone level monitoring. No seizures from Oct 28, 2015-Aug 2016.
Neuropsychological Assessments
Neuropsychological assessment was done in September 2015 prior to diet initiation, and repeated in April 2016 and May 2019 to monitor cognitive development. At baseline, overall intellectual ability was below the 1st percentile, but the patient had a relative personal strength in his verbal reasoning skills, which were intact and age-appropriate. At follow-up, although still a relative strength, his verbal reasoning skills were more in line with the rest of his cognitive profile (i.e., very low). Parental consent was obtained for this publication.
Implications of the Case
This case suggests seizure freedom can be achieved at higher than standard carbohydrate levels by following an individualized approach to gradual carbohydrate reduction when compared to the traditional MAD, which allows only for 10-20 g of carbohydrate per day. It is unclear what level of ketosis is required in a patient with GLUT-1 deficiency. The classic KD is highly restrictive, which affects compliance. The MAD is increasingly being used in adolescents and adults with epilepsy. A 50-90% improvement in seizure control has been reported in four out of five children with trace to zero ketosis while following the MAD [1]. Though reasonable blood ketone levels were obtained during home monitoring, subsequent blood ketone levels were only modest. Nonetheless, the patient remained seizure-free. We suggest that in patients with seizures, seizure freedom could be a clinical marker for achieving the appropriate carbohydrate level of diet therapy as opposed to the amount of ketosis. In our patient, we combined the principles of the MAD and gradual titration method [1,[6], [7], [8]]. By this liberalized method, we were able to achieve seizure control at higher than standard daily carbohydrate intake. Slow reduction of carbohydrate in the MAD will allow the dietary team to identify the appropriate level of carbohydrate required for each patient.
The clinical phenotype of our patient was consistent with GLUT-1 deficiency. Missing the mutation in the earlier genetic test was related to a reporting error by the laboratory. Patients with GLUT-1 deficiency in general require long-term treatment with the KD, and therefore the MAD may be an ideal option. A survey among families of children with GLUT-1 deficiency reported 31% of the patients were on the MAD [11], which is increasingly being used in GLUT-1 deficiency [12,13]. Many reports suggest at least some improvement in cognitive function following the KD [14]; however, a case series examining the cognitive outcome at 25 months reported no improvement in measures of the corresponding intelligence quotient [15]. Cognitive outcome may be related to earlier institution of KD as a therapy [14]. In our patient, the neurocognitive status was already compromised at baseline but his adaptive functioning never declined and his subjective alertness and attention improved. Diet therapy was started at a later age of 7 years old in our patient, which may be the reason for lack of cognitive improvement.
MAD in Developing Countries
Epilepsy remains a significant problem of public health in emerging countries. At least 50 million people in the world have epilepsy and approximately 85% of them live in developing countries1,2,3. Besides the high frequency of epilepsy, treatment in emerging countries is also a problem. Compounding this issue, many anti-convulsant drugs are also not available. Moreover, these drugs are not affordable for many patients as most people in developing countries lack health insurance. The direct costs of epilepsy are thus important, but indirect costs are also considerable due to loss of opportunities and productivity.
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On the other hand, there has been a tendency in developing countries to use traditional therapies such as plants or special diets. There is also a current trend throughout the world of using non-pharmacological therapies8,9. However, the diet can be difficult to adhere to as significant amounts of fats with limited proteins, carbohydrates and fluids have to be used. It is not available in many countries as it requires traditionally a 3-4 day hospitalization with specialized neurologist and dietitian consultation. Though the KD is less expensive than many anticonvulsants, the prices of foods used are relatively high, as even in some developed countries occasional financial difficulties with the diet are reported11. Recently, less restrictive diets have been developed. Among these, the Modified Atkins Diet (MAD) has many advantages, primarily that its efficacy appears in studies to date to be very similar to the classical KD11,12. In MAD, approximately 65% of calories are from fat sources. It is less restrictive, while still requiring decreased intakes of carbohydrates but with no protein, calorie, or fluid restrictions. Another key difference is that the, MAD does not require hospitalization and can be started as an out-patient without fasting. Another point is that the caregiver or the patient in MAD has to calculate only carbohydrates that should be less than 10 grams per day for children and less than 20 grams for adults, while the KD, calculation is difficult as proteins, fats, carbohydrates and even calories should all be taken into account using computer programs. Another advantage of MAD is that it can be easily adapted to local dishes and traditional recipes.
For all these reasons, we think that dietary therapies, especially MAD, should be encouraged as a therapeutic option in developing countries, not only for drug resistant epilepsy, but also potentially as a first line therapy when medical or surgical treatment isn't available or can't be afforded. MAD is probably the most appropriate in this specific context as its efficacy is similar to the ketogenic diet, but with a better tolerability, ease to use, and less costs. Currently, the diet is used worldwide for the treatment of epilepsy though it was challenging to introduce it in some countries, like Asian countries were customary diets contain less fat than western diets16.
Potential Risks and Side Effects
The MAD is not a good fit for everyone. The MAD can be a big lifestyle change. Some people may get high cholesterol when they start the MAD. This should get better over time and will go back to normal after they stop the diet. The diet may increase acid in the body. This is called acidosis. Routine visits to the Neurology Clinic are needed every 3 to 6 months. At each visit, the dietitian will look at growth and nutrition. Blood work will be done to see how your child is doing with the diet.
There are cases in which the diet can be dangerous: there are metabolic syndromes that impact the ability to break down fats effectively, such as with fatty acid oxidation disorders, or otherwise do not tolerate fasting well, and in these cases children can decompensate quickly. The diet certainly has its risks for side effects: It often worsens gut motility and can lead to constipation, nausea and other GI issues. Prolonged use puts children at risk for osteoporosis, kidney stones and hyperlipidemia.
The Importance of Professional Guidance
Information on epilepsy diets has exploded online, and more and more families have expressed an interest in it, but starting an epilepsy diet without proper support often impacts the effectiveness and sustainability of the treatment and may even increase the risk of side effects. Because of these risks, we strongly encourage families to not start the diet on their own - they really need to work with a registered dietitian, optimally as part of a ketogenic diet program.
We have a team approach to treat epilepsy in the GW diet clinic. Once you start the diet, blood and urine will be monitored every 3 months. Once the team determines the MAD diet is right for you, the dietitian will review your diet history and provide a personalized diet “prescription”.
First visit is likely to be scheduled on a Friday and last from the morning into the afternoon. After the visit you can join other new dietary therapy patients at a teaching session presented by the Adult Epilepsy Diet Center team that introduces you to the diet. Once you start on the diet, it is important to not change your seizure medications immediately so that we can gauge the effects of the diet on your seizures. After starting the diet, you can schedule 30-minute follow-up visits with our Center.
After parents submit the child’s medical information, our team reviews it carefully to determine if a ketogenic diet is an appropriate treatment, and which version may work best for each child. New patients take part in a 3-day orientation (Monday through Wednesday) that starts the child on the diet and provides education for the family.
Conclusion
A liberalized form of MAD with slow reduction of carbohydrate may be a therapeutic option in children with epilepsy. This case report illustrates that a liberalized form of MAD with slow reduction of carbohydrate may be a therapeutic option in some children with epilepsy. This case suggests seizure freedom can be achieved at higher than standard carbohydrate levels by following an individualized approach to gradual carbohydrate reduction when compared to the traditional MAD, which allows only for 10-20 g of carbohydrate per day. By this liberalized method, we were able to achieve seizure control at higher than standard daily carbohydrate intake. Slow reduction of carbohydrate in the MAD will allow the dietary team to identify the appropriate level of carbohydrate required for each patient.
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