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Published by Rohit Vishal Kumar

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Published by: Rohit Vishal Kumar on Sep 29, 2008
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ELSEVIERNutrition esearchVol. 18. No. 2. pp. 402416.1998Copyright@1998 Elsevier cience nc.F’rintedn theUSA. All tights eserved0271-5317m $19.00 + .oo
PI1 s0271-5317(98)00030-x
Asuri N. Prasad', M.D.MRCP(UK), FRCPCCarl E. Stafstrom'M.D., Ph.D.From the Division of Pediatrics (Neurology), The Charles A. Janeway ChildHealth Centre, St.John's, Newfoundland, Canada, and the Division of PediatricNeurology', The Floating Hospital for Children at New England Medical Center,Tufts University School of Medicine, 750 Washington Street, Boston, MA.ABSTRACTFrom aserendipitousobservation thatfastingtemporarilysuppresses epileptic seizures, arose the idea that a diet wouldmimic the metabolic effects of ketosis.The so named "ketogenicdiet“ has enjoyed a renewal of interest amongst physicians and thepublic in recent years, partly because of dramatic proclamation bythe media that a miracle cure has been long ignored by the medicalestablishment. The efficacy of the ketogenic diet until recentlyhas not been rigorously examined through scientific trials. Weexamine the historical precedent to the use of the ketogenic dietastreatment for epileptic seizures,and critically reviewprevious andcurrent researchregarding its efficacyandmechanisms of action. Despite the efficacy of the diet in a widevariety of difficult to treat epileptic seizures in children andadults, there remain several limitations. Although a metabolicadaptation within the brain is thought to be responsible for itsaction, the precise mechanisms at a cellular level remain poorlyunderstood.Further research on the ketogenic diet needs to focuson precisely defining indications,mechanisms of action, safetyand impact on quality of life in epilepsy.0 *998ElsNicrsdaIcxInc.Keywords: Ketone bodies, epilepsy, myoclonicseizures, Diettherapy, side effects, Antiepileptic drugs.'Address for correspondence and reprint requests to:Dr. Asuri N. Prasad at the Division of Pediatrics (Neurology)The Charles A. Janeway Child Health CentreSt.John's, Newfoundland, Canada. AlAlR8
INTRODUCTIONThroughout history, persons withepilepsyhavebeen persecuted,castigated and stigmatized.Not only have they had to deal with the dramaticand unpredictable nature of their seizures,but also with society's reactionto their mysterious ailment.Individuals with epilepsy and their physicianshave resorted to all sorts of therapiesin their attempts to tame thiscondition. As noted by Ternkin( some such therapies are now consideredbizarre(e.g powdered human skull, liver of a recently slain gladiator).Othertreatments that might seem strange at first glance are finding their way intoconventional epilepsy treatment regimens (e.g. vagal nerve stimulation).When considered against this historical backdrop, dietary approaches totherapy cannot be considered all that unusual, and indeed, an epilepsy dietmight provide an attractive alternativeto standard antiepileptic drugs andtheir attendant side effects.The concept that we might be able to controlepileptic seizures simply by altering nutritional intake is a radical one, yetdeeply rooted in medical history. As we enter the new millennium, dietaryapproaches are likely to emerge as important and increasingly used therapeuticadjuncts in our battle against epilepsy.In this article, we review the state of our current knowledge about thebest known dietary treatment for epilepsy, the ketogenic diet.Although theketogenic diet has proven efficacy, its mechanism of action remains unknown.Suffice it to say, considerable more research isneeded to clarify themechanisms,indications and consequences of this treatment modality.HISTORICAL PERSPECTIVEDietary manipulations to treat epilepsy were used as early as the 5t"century BC when Hippocrates described a man whose seizures were completelycured by total abstinence from food and drink. Galen suggested a role fordiet in the etiology of epilepsy, and recommended an "attenuating diet" forsome patients. In biblical times, Jesus cast demons out of epileptic childrenand told his followers that a cure would come through prayer and fasting. Inthe8th century, the renowned physician Avicenna recommended a seizuretreatment consistingmainly ofavoidance of certain foods. The earliestattemptsto induce ketosis for treatment of seizures are not preciselyestablished,but the impetus appears to have come from the observation thatseizures temporarily remitted during fasting(2-4).Geyelin suggested that the beneficial results of fasting might be due toacidosis which develops(3). Wilder (5)first speculated that a diet with a highfat content and low percentages of protein and carbohydrate would mimic theeffect of fasting in producing ketosis, but could be maintained for muchlonger periods than could fasting. He and others showed subsequently that sucha diet was indeed useful for control of seizures (5-10). Dietary therapybecame less popular with the advent of effective antiepileptic drugs.Although the ketogenic diet's use continued over the years, its popularity asa therapeutic option has until recently taken a back seat to drug therapy.However,increasing concerns about side effects of antiepileptic drugs, inparticular the effects of antiepileptic medication on cognitive function, haveprompted physicians to evaluate alternative therapies. Recent researchpublications and media interest have renewed much debate on the merits of theketogenic diet(2, 4, 11).Several questions remain unanswered, despite several decades ofexperience with the ketogenic diet: How does the diet work? What are theoptimal indications for use? In which seizure types is it most effective?
Should it be used as a first or second line therapy for some seizure disordersin childhood? What are the effects of the diet on cognitive function? Arethere any significant long-term side effects? None of the available clinicalstudies satisfactorily answer these questions.The very nature of the dietprecludes a blinded trial design. Attempts to study the efficacy of the dietthroughprospective randomizedtrials have not been possible untilrecently(l2, 13).DEVELOPMENT OF THE DIETBased on the assumption that fasting improved seizure control throughthe twin changes of ketosis and acidosis, Wilder devised a diet that wouldmimic the biochemical changes of fasting. This ketogenic diet consisted of ahigh proportion of fatscombined with small amounts ofcarbohydrate andprotein. While fat was "ketogenic" the other two components tend to be"antiketogenic".Wilder's calculations indicated that a ratio of the foodsproducing a ketogenic effect to the foods producing an antiketogenic effectshould be of the order of 1.5:1 or higher(5).Subsequent studies showed thatthe optimum seizure control was achieved when the diet had a ketogenicpotential of 3 or higher, thus giving rise to the current nomenclature of a3:l or 4:l diet. Modifications of the "classic diet" include the medium chaintriglyceride (MCT) diet, and a "modified" MCT diet(l4, 15).INDICATIONS FOR USETwo broad indications for the use of the ketogenic diet have foundgeneral acceptance among neurologists and their patients, namely: 1) seizuresrefractory to drug therapy, and 2) drug toxicity. The diet seems to have thegreatest beneficial effects in young children,who produce and utilize ketonesmorerapidly (2 -3 days), and whose dietary intake can be more closelysupervised.In older children, it is more difficult (though not impossible)to prepare a palatable diet with the appropriate ratio of fat, carbohydrateand protein necessary to produce the desired level of ketosis(l1).Also,older children usually have well-established dietary likes and dislikes, andthese can become a limiting factor in compliance, which must be strict.Thediet has traditionally been used in the treatment of refractory epilepsy,where conventional antiepileptic medications have failed.The role of thediet as a first or second line treatment againstnewly diagnosed seizuredisorders remains to be evaluated.KETOGENIC DIET PROTOCOLSThe early ketogenic diets recommended by Wilder (5)and Livingston (16)were based on the consumption of a high percentage long-chain saturated fatswith a fat to carbohydrate ratio of 4:l. Some consider the classical diet tobe relatively unpalatable,which may lead to poor compliance.A modificationof the standard ketogenic diet was proposed by Huttenlocher and colleagues(14).Table 1 compares some of the features of the classic and the MCTketogenic diets.The specific details of day to day dietary adjustments must be worked outbetween the parents and the dietitian.Indeed the collaboration of aninterested and experienced dietitian is essential if the ketogenic diet is tosucceed. Parental education requires constant attention to ensure the

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