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Danish study of a Modified Atkins diet for medically intractable epilepsy in children: Can we achieve the same results as with the classical ketogenic diet?

Open ArchivePublished:December 02, 2010DOI:https://doi.org/10.1016/j.seizure.2010.11.010

      Abstract

      Modified Atkins diet (MAD) is a less restrictive variety of the classical ketogenic diet (KD), used for treating patients with medically resistant epilepsy. There are only few reports comparing the two types of diets in terms of seizure reduction and tolerability. We compared the effect of a MAD evaluated prospectively on 33 consecutive children with medically resistant epilepsy, with a group of 50 patients, previously treated with KD. Patients who had >50% seizure reduction were considered responders. After 3 months on the MAD, 17 patients (52%) were responders, including 14 (42%) who had >90% seizure reduction. After 6 months, 13 patients (39%) were responders. Seventeen patients (52%) remained on the MAD at least 12 months with excellent overall tolerance and compliance, including 9 patients (27%) who were responders, 4 of them (12%) having >90% seizure reduction. Although there was a trend for higher incidence of responders in the KD group, this failed to reach the level of significance: after 6 months 39% on MAD and 60% on KD were responders. However, this trend was not observed when the two groups were adjusted for difference in age (patients in the MAD group were older than the KD group). In conclusion, our experience suggests that the MAD is similarly effective as the KD in reducing seizure frequency in children with medically resistant epilepsy.

      Keywords

      1. Introduction

      Approximately 25% of all children with epilepsy do not respond sufficiently to antiepileptic drugs (AEDs) and are considered medically intractable. Classical ketogenic diet (KD), a low carbohydrate, low-to-adequate protein and high fat diet, has been applied to many of those children, especially over the last 2 decades in Europe.
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      However, KD has been known and used for nearly a century.
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      KD results in >50% seizure reduction in at least 50% of the children. Approximately 10% will eventually become completely seizure-free and even medicine-free.
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      The modified Atkins diet (MAD) is a less restrictive alternative ketogenic diet, based on the same principles as classical KD.
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      The modified Atkins diet.
      The MAD is a diet where carbohydrates are initially restricted to 10 g per day, but otherwise free intake of protein, fat and calories is allowed, and high fat intake is encouraged.
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      A modified Atkins diet is effective for the treatment of intractable pediatric epilepsy.
      The MAD ratio of fat/protein and carbohydrates is on average 1:1, while KD ratios are most often 3–4:1, yet both diets induce ketosis (average occidental foods are 0.3:1). The MAD was developed in the US at the Johns Hopkins hospital in early 2000s,
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      based and inspired on the well-known Atkins diet, widely used in the US for obesity management.
      In the last 7 years, since the first report appeared,
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      A modified Atkins diet is effective for the treatment of intractable pediatric epilepsy.
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      Modified Atkins diet to children and adolescents with medical intractable epilepsy.
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      • et al.
      A pilot trial with modified Atkins’ diet in adult patients with refractory epilepsy.
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      • et al.
      Comparison of seizure reduction and serum fatty acid levels after receiving the ketogenic and modified Atkins diet.
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      and 1 review
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      The modified Atkins diet.
      have been published. Two of the reports were on adults.
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      • Rowley H.
      • Sinha S.R.
      • Vining E.P.
      A prospective study of the modified Atkins diet for intractable epilepsy in adults.
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      • Raedt R.
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      • et al.
      A pilot trial with modified Atkins’ diet in adult patients with refractory epilepsy.
      A few of the previous publications suggested that the MAD has an efficacy close to the KD. However, randomised studies comparing the efficacy of MAD and KD have not been performed yet. The MAD can be used as a diet of first choice in a child with intractable epilepsy or as a way of liberalizing the classical KD treatment.
      • Kossoff E.H.
      • Dorward J.L.
      The modified Atkins diet.
      In Denmark, treatment of severe and medically intractable epilepsies is mostly centralized at The Danish Epilepsy Centre where the majority of Danish patients (children and adults) receiving KD are treated too. After the first Danish experience with a few patients treated with MAD,
      • Weber S.
      • Mølgaard C.
      • Karen taudorf
      • Uldall P.
      Modified Atkins diet to children and adolescents with medical intractable epilepsy.
      we standardized the MAD protocol and began to offer MAD regularly to drug-resistant patients in our Institution, in addition to classical KD. MAD has been used since June 2007 as a standard treatment offered to a great proportion of patients referred or considered candidates for KD but where a liberalized type of diet was deemed more suitable; i.e. most children older than 4–5 years (some younger) with the exception of patients with gastrostomy. This study summarizes the Danish protocol for MAD, describes the first 38 patients treated since June 2007, the efficacy in terms of seizure control, compliance, side effects, as well as induction of ketosis, impact on blood fat parameters (cholesterol and triglycerides), and the global impression of change, as reported by the parents, based on changes in attention, behaviour and sleep. Lastly, we compared the efficacy of MAD in these patients with the KD in 50 consecutive children previously treated at our Institution.

      2. Patients and methods

      2.1 Patients

      From the 1st June 2007 until the 31st March 2009 (22 months), 38 children, aged (at diet start) 1.1–15.6 years (mean 8.1 years) were offered and accepted treatment with MAD, whilst in the same time period 33 were started on KD, for their medically intractable epilepsy. Children were referred to the ketogenic diet team at the Danish Epilepsy Centre, either from our own Centre or from another paediatric neurology clinic in Denmark, for diet treatment of their epilepsy. After a first visit with one of the paediatric neurologists at the KD team (MM), parents and doctor together decided which diet, MAD or classical KD was more suitable for their child and the family (i.e. selection of candidates for MAD was made on individual basis). Parents were counselled on the advantages and disadvantages of the diets. Parents of the older children opted more often for the MAD, because they also doubted their children would comply with the stricter regimen of the KD. Parents of the younger children weighed less the compliance issue (younger children only eat what they are given) and opted more often for the KD because the more robust evidence for the efficacy of this type of diet. Parents were also advised that they could switch from one diet to the other in case of side effects or lack of efficacy.
      All diet candidates had more than 1 seizure per week, and had tried at least 3 AEDs without achieving acceptable seizure control. Three (out of 38) changed their minds after the first 2 outpatient visits with doctor and dietician respectively, and never started dietary treatment. Additionally 2 children were on the diet for less than 1 month and were therefore excluded from the study. Thirty-three children (15 males and 18 females) started the MAD, and have been on the MAD between 2 and 22 months (mean 8.7 months) at time of analysis.
      With respect to their epilepsy diagnosis, 23 had focal/multifocal (symptomatic/cryptogenic) epilepsies, 6 Dravet Syndrome, 2 myoclonic absences and 2 myoclonic astatic epilepsy (MAE).
      The interval between epilepsy onset and diet treatment was 7.3 years (15.5–1). Patients had tried a median of 7 (13–3) medications before the diet. Patient details are shown in Table 1.
      Table 1Patient characteristics (MAD).
      Pt. nr./genderEpilepsy onset Age (y)Epilepsy typeEtiology/syndromeAge MAD (years) startMAD duration: monthsAED tried (n)AED at start of MD
      1/F0.4P/sGLissencephaly6.5226LEV, NTZ
      2/M4P/sG CSWSPerinatal stroke/CSWS91180
      3/F7P/sGBand heterotopia15.425CBZ
      4/M0.8P/sGCongenital CMV4.398LEV, ZNS, PGB
      5/M0.8P/sGStroke (arteria carotis malf.)5.81012VPA, PGB
      6/F0.4G (abs, GTC, my)Dravet Syndrome (S) spectrum (SCN1A−)2.3225TPM, LEV
      7/M0.5GMyoclonic absences10.9185LTG
      8/M8.6GIdiopathic/unknown10.236TPM, LEV
      9/F0.6SpasmsMCD (cortical dysplasia bilateral)2.81510LEV
      10/F0.5G (abs, GTC, my)Dravet S (SCN1A+)15.639VPA, LTG, CZP, VNS
      11/M1SpasmsMCD (cortical dysplasia bilateral)3.4710ZNS, CLB
      12/F7.5P/sGCryptogenic Focal13.44.54LEV
      13/F2.4P/sG CSWSPerinatal stroke/CSWS8.325LEV, STM
      14/M2.8P/sG CSWSCryptogenic CSWS6135STM
      15/F0.4P/sGMCD (CC hypoplasia)12.51360
      16/F0.08P/sGUnknown9.3813LEV
      17/M2.8GMAE/LGS idiopat/cryptogenic7.9139TPM, CLB
      18/M6.1P/sGEncephalitis sequelae12.810CLB
      19/F2.5P/sGDravet S (SCN1A−)9.41011STIR, CLB, ZNS
      20/M3.8GMyoclonic absences4.6211LEV, ESM
      21/F0.25PMCD (cortical dysplasia bilateral)5.81260
      22/M2.1P/sGMCD9.9810FELB, STM
      23/F8P/sGPerinatal cerebral haemorrhage13.847PGB, VPA, CBL, TPM
      24/M0.4GDravet S (SCN1A+)1.183LEV
      25/M7P/sGFrontal lobe epilepsy (cryptogenic)1085TPM, CBZ
      26/F0.3P/sGCorpus callosum dysgenesis7.829LEV, ZNS, CLB
      27/F0.25GDravet/GEFS+ (SCN1A+)4.178LEV, PGB
      28/F0.4GDravet S (SCN1A+)4.725OXC, CLB, TPM
      29/M0.8SpasmsAutism (cryptogenic)6.6550
      30/M0.3P/sGLissencephaly (LIS1+)7.446LEV, VPA
      31/F1.4PMCD2.7490
      32/F3P/GFrontal lobe epilepsy (cryptogenic)9.825TPM, LEV
      33/F0.4GMAE15.32210LEV
      CC: corpus callosum; CMV: cytomegalovirus; CSWS: encephalopathy with continuous spike and waves during slow sleep. G: generalised epilepsy; GEFS+: generalised epilepsy with febrile seizures plus; LGS: Lennox–Gastaut Syndrome; malf.: malformation; MAE: myoclonic astatic epilepsy; MCD: malformation of cortical development; Mo: months; my: myoclonia; P: partial epilepsy; sG: secondary generalised; and y: years.

      2.2 Modified diet protocol

      All patients referred to our Centre with medically intractable epilepsy, and who are not considered surgery candidates or whose parents chose not to pursue surgical treatment, are typically offered diet treatment. During a first consultation with paediatric neurologist, diet treatment is discussed. Once decided to try MAD following the considerations mentioned above, a second appointment is made with the nurse and the dietician. In the meantime, blood samples are taken in order to rule out carnitine deficiency/beta-oxidation defects. If no contraindication for the diet is found, families are introduced to the MAD principles and all practical issues during this 2-h consultation with the dietician and the nurse. After that, families go home and start the diet. A gradual increase in fat intake is recommended (throughout the first days) to avoid side effects. We start with 10 g carbohydrates per day and otherwise free calories, protein and mealtimes whilst high fat intake is encouraged. For our own control, as we just were starting offering MAD, we asked for standard weekly measurements on blood glucose, blood ketosis and urine ketosis during the first 4 weeks. Liberalizing the 10-g carbohydrate (often increasing but a few times reducing the intake) was allowed after the first 3 months, depending on acceptance, tolerance and effect. Families come to our keto-clinic for clinical control and blood samples, every 3 months. Families can however contact their keto-team nurse and dietician at any time if any problem occurs or with any question about the diet, medicines or any issues related to their child's epilepsy. The MAD protocol is summarized in Table 2.
      Table 2Modified Atkins diet protocol at the Danish Epilepsy Centre.
      I – At enrolment
       • Doctor consultation: considerations about diet treatment, pros and cons, diet type
       • Nurse consultation – further information
       • Blood samples: haematology, lipids, lever, electrolytes, Ca, Mg, P, selenium, metabolic screening, carnitine profile
      II – At start of the diet
      Prior to start:
        • Two hour consultation with nurse & dietician: parent education on the diet
      Recommendations:
        • Carbohydrates restricted to 10 g/day for the first 3 months (both children and adults), thereafter 15-20 g/day if good seizure control
        • Fat intake free, but high intake necessary and encouraged: Recommended vegetable fat rather than animal fat, whenever possible
        • Protein intake free, moderate intake suggested
        • Carbohydrate conversion table provided:
       ✓ 100 g ingredient/x g carbohydrate = y gram ingredient (equals 1 g carbohydrate intake)
        • Carbohydrate list provided; uses only if no description of contents in the foods
        • Unrestricted mealtimes
        • No calorie restriction
        • No liquid restriction (use of light soft drinks allowed)
        • Supplement of a low-carbohydrate multivitamin and calcium daily
        • Booklet of a few calculated recipes provided
        • List of suggestions for uncalculated recipes provided
        • Weekly-report leaflets provided
      III – After initiation of the diet: during the first 3 months and after 3, 6, 9 and 12 months
      Controls:
        • Urine ketones twice weekly
        • Blood ketones and blood glucose 3 times daily for 2 days for the first 4 weeks and later if needed.
        • 3-days-food-diary after 2 and 8 weeks, to be evaluated by the dietician for optimizing the diet
        • Telephone consultation with the nurse after 5 and 10 weeks for support
        • Outpatient clinic consultation with doctor after 3, 6, 9 and 12 months
        • Blood samples after 3, 6, 9 and 12 months

      2.3 Global impression of change in quality of life

      Every 3 months, parents responded to a simple questionnaire developed by the authors (not validated), regarding the global effect of the diet on attention, behaviour and sleep, as (subjectively) experienced by parents/caregivers. Parents answered the questions during the consultation with a doctor at 3, 6 and 12 months after diet start. We asked the parents 6 questions to which they could answer: (1) no change from before diet; (2) little/moderate improvement; (3) definite improvement. Questions were on every day life situations: (1) play (could they maintain interest in playing? Could they play for a longer time?); (2) eating situation (could they keep sitting at the table while eating? Could they eat by themselves better than before?); (3) school/homework – when relevant for the age (concentration and attention on homework as required for the age); (4) interaction with parents and siblings (did they show more interest in contact with near persons/more attention in contact); (5) alertness (more alert, longer time per day); (6) sleep (more quiet nights, less awakenings) compared with the situation before the diet. Based on these a global impression of change, as experienced by parents and/or caregivers (in the case of both there had to be agreement) were registered and scored (1–3 for each question). The maximum score was 18. A score of 15 or more was considered as global improvement.

      2.4 Statistical analysis

      The efficacy between MAD and KD groups was compared using chi-square test. The patients in the MAD group were older than in the KD group. Therefore multiple regression analysis for categorical and continuous predictors (age, type of diet, efficacy) was done.

      3. Results

      3.1 Seizure reduction on MAD

      Three months after the start of diet, 52% of patients (17/33) were responders, i.e. had at least 50% seizure reduction. Out of these 14 (42%) had >90% seizure reduction after 3 months (including the 5 patients who were seizure-free). Some responders lost effect with time and eventually returned to the pre-diet situation (Table 3). However 17 patients (52%) remained on the MAD at least 12 months (at evaluation time) and out of these 9 patients (27% of the 33 enrolled patients) had >50% seizure reduction. Four of these patients (12%) continued having >90% seizure reduction (were seizure-free in some periods). Details on seizure reduction are shown in Table 3.
      Table 3Seizure reduction in children actively receiving the MAD at each time point.
      Time MAD3 months (n = 33)6 months (n = 33)12 months (n = 17)
      >50% seizure reduction
      Total figures in bold.
      17 (52%)13 (39%)9 (27%)
      50–90% seizure reduction3 (9%)7 (21%)5 (15%)
      >90% seizure reduction9 (27%)6 (18%)4 (12%)
      Seizure-free5 (15%)00
      All percentages are calculated from the total of patients (n = 33).
      * Total figures in bold.

      3.2 Global impression of change in quality of life

      24/33 (73%) reported definite improvement (15 or more of the 18 total points), reflecting a global improvement in daily life. The most consistent effects were that parents and caregivers experienced more alert children during the day, and more quiet nights, i.e. with fewer awakenings.

      3.3 Medication

      AEDs were not changed in the first 2 months in order to evaluate the effect of the diet. List of medications tried before the diet and during the first 2 months are listed in Table 1. Children were receiving on the average 2 (0–4) AEDs at the start of the diet. Overall, no significant reductions in medications were performed during diet treatment despite the effect of MAD. However, 6 children (18%) benefited from medicine reductions (4 were reduced from 2 to 1 medication, 1 child was withdrawn from medication and additionally 1 child could be reduced in medicine dose). None of them resulted in increased seizure frequency.

      3.4 Ketosis and blood-glucose

      Measurements of blood glucose, blood ketosis and urine ketosis were made regularly in the first 4 weeks. All patients achieved ketosis within the first week and regular urine ketosis measurements throughout the treatment revealed ketosis from 8 to 16 mmol/L in >90% of measurements in 26/33 patients. Twenty-three out of 33 patients completed blood measurements as described in Table 2 (weekly measurements in the first 4 weeks). Mean blood ketosis was 2.5 mmol/L (0.8–4.4) and blood glucose was very stable with >90% of completed measurements between 3.5 and 4.8 mmol/L at any time of the day (before breakfast, before evening meal, before bedtime).

      3.5 Tolerance and side effects

      Tolerance was excellent, and practically all families coped well with the MAD. No patients had to stop the diet because of hyperketosis, vomiting, extreme fatigue or dislike of the foods. Subtle side effects such as slight fatigue were reported in the first month by 1/3 of the patients. Continuous support of the families was decisive for maintaining the diet. Only lack or insufficient effect was the cause of stopping the diet in all but 1 patient. This child (patient no. 17) had a bone fracture and stopped the diet; the patient had epilepsy since 1 month of age and had tried 13 medications during 9 years; however, the child experienced >50% seizure reduction on the diet.

      3.6 Serum lipid profile

      Measurements of free cholesterol, triglycerides, cholesterol-LDL and cholesterol-HDL, in the MAD-group revealed no significant increases above the laboratory references in these parameters in 31/33 children. Only in 2 patients was cholesterol measured higher than 8 mmol/L (upper limit in our lab) on one occasion, subsequently falling below 8 mmol/L in the next measurement. Cholesterol results mean on measurements while on the diet were found to be 4.5 mmol/L (9.8–3.1). Triglycerides mean was found to be 0.8 mmol/L (2.1–0.3).
      In the KD-group, one child had cholesterol higher than 8 mmol/L on one occasion (1 month after initiation of the diet). Three children had elevated triglycerides sporadically (1 or 2 occasions) and only 1 patient had elevated triglycerides in several measurements after 1 month of initiation of the diet.

      3.7 Comparison with KD (MAD vs. KD)

      Data from these 33 consecutive patients treated with MAD were compared with 50 consecutive patients previously treated by KD in our Institution (Table 4). KD patients had participated in a previous study.
      • Beniczky S.
      • Jose Miranda M
      • Alving J.
      • Heber Povlsen J.
      • Wolf P.
      Effectiveness of the ketogenic diet in a broad range of seizure types and EEG features for severe childhood epilepsies.
      The time point for comparison was 6 months after the start of the diet. Responders were defined as those who had more than 50% seizure-reduction at 6 months after the start of the diet.
      Table 4Analysis comparing 33 MAD and 50 KD patients. Seizure-reduction data are at 6 months after start of diet.
      MADKDp
      Demographic and clinical data
       Male/female18/1527/230.9
       Age: mean (SD)8.25 (0.7)4.6 (0.4)<0.001
       Seizure frequency before the start of diet: mean (SD)124 (51)80 (15)0.4
       Symptomatic/cryptogenic, localization-related epilepsies31 (94%)44 (88%)0.4
       Idiopathic focal epilepsies1 (3%)3 (6%)0.5
       Idiopathic generalised epilepsies1 (3%)3 (6%)0.5
      Seizure-reduction (all patients)
       <50%20 (61%)20 (40%)0.06
       >50%13 (39%)30 (60%)
       50–90%7 (21%)13 (26%)0.62
       >90%6 (18%)17 (34%)0.11
      Seizure-reduction (age-matched MAD: mean age = 6.1; n = 23; vs. KD; p = 0.1)
       <50%13 (56%)20 (40%)0.19
       >50%10 (43%)30 (60%)
       50–90%5 (22%)13 (26%)0.69
       >90%5 (21%)17 (34%)0.29
      Side-effects
       Nausea/vomiting1 (3%)5 (10%)0.23
       Hyperketosis (first week)1 (3%)2 (4%)0.82
       Fatigue (prolonged beyond the first week)7 (21%)8 (16%)0.55
       Constipation treatment needed (preventive)33 (100%)50 (100%)1
       No significant side effects described beyond the first week25 (75%)39 (78%)0.81
      Lipids
       Increased total cholesterol (1 month after initiation of the diet or later) (>8 mmol/L)2 (6%)1 (2%)0.33
       Increased triglycerides (like above) (>2.5 mmol/L)0 (0%)3 (6%)0.15
      We did not find any statistically significant difference between the responder-rates in the 2 groups, although there was a strong trend for higher incidence of responders in the KD group (MAD 39% vs. KD 60%, p = 0.06).
      The age of the patients in the MAD was significantly higher than in the KD group. To assess if our results could be biased by this difference, we performed two additional analyses. First we did a sub-group analysis where in the MAD group we excluded the patients older than 10 years. The age of this subgroup (<10-years-old) was not different from the KD group. When this analysis was performed, there was not even a trend towards significance in results (Table 4). Subsequently, when both types of diet (KD vs. MAD) and age were included into the multiple regression analysis for categorical and continuous predictors, their effect became non-significant (type of diet: beta = −0.16, p = 0.18; age: beta = 0.15, p = 0.19).

      4. Discussion

      Our data suggest that MAD is a highly well tolerated diet in a mixed group of difficult-to-treat epilepsy children. More than half of the children had a higher than 50% seizure reduction after 3 months, and more than 1/4 of the patients had more than 90% seizure reduction after 3 months, which is comparable to most classical KD clinical studies. At 12 months follow up, 9/33 children (27%) on MAD had been responders, including the 4 children (12%) with >90% seizure reduction and periods of seizure freedom. These results are also comparable to most KD studies.
      • Henderson C.B.
      • Filloux F.M.
      • Alder S.C.
      • Lyon J.L.
      • Caplin D.A.
      Efficacy of the ketogenic diet as a treatment option for epilepsy: meta-analysis.
      • Freeman J.M.
      • Vining E.P.
      • Pillas D.J.
      • Pyzik P.L.
      • Casey J.C.
      • Kelly L.M.
      The efficacy of the ketogenic diet-1998: a prospective evaluation of intervention in 150 children.
      Furthermore, at 6 months after start of diet the results of MAD were similar to the KD, though there was trend for higher incidence of responders in the KD group (39% vs. 60%). However, the patients in the KD group were significantly younger than the patients in the MAD group. This likely reflects the higher use of the KD in younger patients, many of whom were formula-fed (infants or gastrostomy tube fed) only. When we adjusted the 2 groups for the difference in age, the trend disappeared. The young children have been previously reported in the literature as having higher levels of seizure reduction and compliance.
      • Kossoff E.H.
      • McGrogan J.R.
      • Freeman J.M.
      Benefits of an all-liquid ketogenic diet.
      • Hosain S.A.
      • La Vega-Talbott M.
      • Solomon G.E.
      Ketogenic diet in pediatric epilepsy patients with gastrostomy feeding.
      We feel that for older, solid-food eating children the results are largely similar and either diet is therefore acceptable.
      Similarly to KD and to AEDs, some patients lose the initial effect in spite of good compliance, while another group (12%) maintains the good effect over time. Studies targeting the identification of different patient categories may have future implications for choosing appropriate diet-candidates, both for KD and MAD.
      We find it remarkable in this study that a supportive group of healthcare professionals is needed for achieving the high compliance and good effect in this liberal type of diet, where families are very much “on their own” compared to the strict dietician control required for the KD. Networking between families is important too. In a few children (ex. patients 7, 27, 30), dietician support for keeping a high fat intake and ketosis was crucial for achieving seizure freedom/>90% seizure reduction. Parents of those 3 children (patients 7, 27, 30) reported seizure-freedom related to the amount of fat intake and the level of ketosis. Each of these families had found the most suitable level for their child. We have thus practiced the concept of “patient-tailored diet” with success. We have experienced that in the group with >90% seizure reduction over time, this was the best approach. Some of these children have now been on the diet for nearly 2 years where compliance is still very high combined with very much freedom in every-day life as reported by these parents. The most striking case is patient number 7, who by the time of MAD start had epilepsy with few GTCs and subsequently frequent myoclonic absences (numerous seizures every day), over almost 10 years, regardless of AEDs. The parents found the precise amount of fat and ketosis level on which their child was completely seizure-free, not depending so much on the precise amount of carbohydrates. The amount of fat intake seems to be important for some children.
      The main message of our study is that a more liberal, less restrictive and more palatable type of diet, in the setting of a dedicated team, yields high compliance and similar effectiveness as a classical, more restrictive KD. This may have important implications as many more children might benefit from diet treatment earlier in the course of their epilepsies, avoiding long lasting and often ineffective medicine trials. As the MAD is less restrictive than the KD, it may present a more attractive option to families and neurologists previously reluctant to use dietary treatments.
      To the best of our knowledge, this is one of the first studies comparing the effectiveness of a classical and a modified Atkins type of diet. We acknowledge the limitations of this study; especially as the KD experience was retrospective and there was a bias towards older children starting the MAD. A randomised trial prospectively comparing both types of diets on similar patients would be highly informative. However, this might be a very difficult task as it is well recognised that even patients with comparable diagnoses may respond differently to the KD and now after almost 10 years of use of the MAD many parents have strong personal opinions about which diet they wish their child to start. Only understanding the variety of mechanisms of action of ketogenic diets in different epilepsy types will eventually lead to the accurate choice of treatment. It would also be useful to understand which children respond better to the KD, and therefore switched to that when/if the MAD is unsuccessful.
      In conclusion, we found that MAD, a less restrictive type of ketogenic diet, is a very well-tolerated diet, with high compliance and very few side effects. Furthermore, MAD was similarly effective as the classical KD in reducing seizure frequency in children with medically resistant epilepsy. Continued use of this alternative diet appears warranted.

      Acknowledgements

      We would like to thank Dr. Szabolcs Kéri for the help with the statistical analysis and Dr. Ivana Rosenzweig for the linguistic revision.

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