What is the history of the ketogenic diet for epilepsy?
History. The ketogenic diet is a mainstream dietary therapy that was developed to reproduce the success and remove the limitations of the non-mainstream use of fasting to treat epilepsy. Although popular in the 1920s and '30s, it was largely abandoned in favour of new anticonvulsant drugs.
What is a ketogenic diet?
Testing for ketone bodies in urine The ketogenic diet is a high- fat, adequate- protein, low-carbohydrate diet that in medicine is used mainly to treat hard-to-control (refractory) epilepsy in children. The diet forces the body to burn fats rather than carbohydrates.
What are the 15 health conditions that may benefit from ketosis?
15 Health Conditions That May Benefit From a Ketogenic Diet 1 Epilepsy. 2 Metabolic Syndrome. 3 Glycogen Storage Disease. 4 Polycystic Ovary Syndrome (PCOS) 5 Diabetes. 6 ... (more items)
Is the ketogenic diet effective for treating neurological disorders?
The ketogenic diet has been studied for potential therapeutic use in various neurological disorders other than epilepsy: Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), autism, headache, neurotrauma, pain, Parkinson's disease (PD) and sleep disorders.
What disease does keto diet Treat?
Very-low-carbohydrate ketogenic diets have been long been used to reduce seizure frequency and more recently have been promoted for a variety of health conditions, including obesity, diabetes, and liver disease. Ketogenic diets may provide short-term improvement and aid in symptom management for some chronic diseases.
What is the keto diet and what disease can it help and how?
The ketogenic diet is one of the medically accepted treatment for chronic seizures in epilepsy and other epileptic disorders, including Lennox-Gastaut syndrome and Dravet syndrome. [220]. Research has shown that it helps reduce the frequency of seizures in children.
Is ketogenic diet good for Parkinson's disease?
In conclusion, the ketogenic diet is feasible and safe for Parkinson's Disease and it showed greater improvements in both motor and non-motor symptoms in Parkinson's.
Who does the keto diet work for?
Interestingly, the keto diet has been around for a long time. Doctors first started using it, Ewoldt says, in the 1920s to treat kids with epilepsy, and it's still sometimes used for that. But today, it is gaining traction for weight loss or to fuel extreme endurance sports like marathon running and triathlons.
What is the pathophysiology of Parkinson's disease?
The primary pathophysiology in Parkinson disease (PD) is excitotoxic degeneration of dopaminergic neurons in the substantia nigra, leading to abnormalities of movement , and to an increasing extent, in cognition and other cortical functions. How could the KD benefit patients with PD? Based on the recognition that ketone bodies may bypass defects in mitochondrial complex I activity that have been implicated in PD, a small clinical study demonstrated that 5 of 7 affected patients showed improved scores on a standard PD rating scale (Vanitallie et al., 2005); however, given the small sample size, a placebo effect cannot be ruled out. In animal models of PD produced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), BHB administration ameliorated the mitochondrial respiratory chain damage that ordinarily results from that toxin (Kashiwaya et al., 2000). Additional evidence supporting the potential benefits of ketone bodies in PD is provided by in vitroexperiments demonstrating the protective effects of these substrates against mitochondrial respiratory chain dysfunction induced exogenously by complex I and II inhibitors rotenone and 3-nitropropionic acid, respectively (Kim do et al., 2010), and even anti-inflammatory actions of the KD on MPTP-induced neurotoxicity (Yang and Cheng, 2010). It would be of interest to determine whether commercially available treatments that augment ketonemia – e.g., the MCT-based formulation used in a recent Alzheimer’s clinical trial (Henderson et al., 2009) – might benefit patients with PD.
What are the effects of KD on the body?
Two hallmark features of KD treatment are the rise in ketone body production by the liver and a reduction in blood glucose levels. The elevation of ketones is largely a consequence of fatty acid oxidation. Specific polyunsaturated fatty acids (PUFAs) such as arachidonic acid, docosahexaenoic acid, and eicosapentaenoic acid, might themselves regulate neuronal membrane excitability by blocking voltage-gated sodium and calcium channels (Voskuyl and Vreugdenhil, 2001), reducing inflammation through activation of peroxisome proliferator-activated receptors (PPARs; Cullingford, 2008; Jeong et al., 2011), or inducing expression of mitochondrial uncoupling proteins which reduce reactive oxygen species (ROS) production (Bough et al., 2006; Kim do and Rho, 2008). Ketone bodies themselves have been shown to possess neuroprotective properties, by raising ATP levels and reducing ROS production through enhanced NADH oxidation and inhibition of mitochondrial permeability transition (mPT; Kim do et al., 2007). Along similar lines of improved bioenergetics, the KD has been shown to stimulate mitochondrial biogenesis, resulting in stabilized synaptic function (Bough et al., 2006).
Does KD help with mitochondrial dysfunction?
As mentioned above, given the growing evidence that the KD enhances mitochondrial functioning and biogenesis (Bough et al., 2006; Maalouf et al., 2009; Kim do et al., 2010), it is logical to ask whether patients with known mitochondrial cytopathies might derive a benefit from the KD and/or ketone bodies such as BHB. At the same time, it must be considered that inherent mitochondrial dysfunction might predispose individuals to adverse toxicities from high fatty acid loads that could overwhelm β-oxidation within the mitochondrial matrix. Experimental data described above attest to significant improvements in mitochondrial function, and many lines of evidence point to the rationale of therapeutically targeting mitochondrial bioenergetics for other disease states (Wallace et al., 2010), but is there any clinical evidence in patients with intrinsic mitochondrial disorders? Kang et al. (2007) reported that the KD was both safe and effective in 14 pediatric patients with established mitochondrial defects in complexes I, II, and IV, all of whom had medically intractable epilepsy. These authors observed that half of these patients became seizure-free on the KD, and only four patients failed to respond. Hence, these preliminary data suggest that the KD is not necessarily contraindicated in patients with mitochondrial respiratory chain abnormalities. However, KD treatment is not recommended in individuals with primary carnitine deficiencies [including mutations in carnitine palmitoyl transferase (CPT) I or II and mitochondrial translocase] and fatty acid β-oxidation abnormalities (e.g., medium-chain acyl dehydrogenase deficiency; Kossoff et al., 2009). Thus, it is critical to determine the specific mitochondrial defect when considering treatment with the KD, to avert clinical deterioration.
Does KD help with stroke?
To date, no clinical trials of the KD have been performed in patients with stroke, but several animal studies of hypoxia-ischemia support the potential beneficial effect of the diet. Most of these models entail pre-treatment with the KD (or with BHB), resulting in decreased structural and functional damage from the stroke. For example, Tai et al. (2008) utilized a cardiac arrest model in rats and found significantly reduced Fluoro-Jade staining in animals that underwent 25 days of pre-treatment with the KD. These investigators later determined that these effects were not due to involvement of plasmalemmal ATP-sensitive potassium channels (Tai et al., 2009), which have been implicated in ketone body action (Ma et al., 2007). Other researchers have hypothesized that the neuroprotective properties of ketone bodies might be related to up-regulation of hypoxia inducible factor (HIF1-α) which is important in angiogenesis and anti-apoptotic activity (Puchowicz et al., 2008). In that study, pre-treatment with BHB (via intraventricular infusion, followed by middle cerebral artery occlusion) led to significant increases in brain succinate content, as well as elevations in HIF1-α and Bcl-2, an anti-apoptotic protein. To be clinically meaningful, of course, a positive effect must be demonstrable after, and not before, an ischemic event. Nevertheless, such studies imply that biochemical alterations that favor energy metabolism would be protective against acute forms of severe brain injury.
Is KD good for brain tumors?
While clinical validation of this phenomenon is not yet forthcoming, there are several case reports suggesting that the KD may be efficacious in humans with brain tumors. Nebeling et al. (1995) reported beneficial effects of an MCT-based diet in two pediatric patients with advanced stage malignant astrocytomas. More recently, Zuccoli et al. (2010) described a case study of an elderly woman with glioblastoma multiforme who was treated with standard radiotherapy plus concomitant temozolomide therapy together with a calorie-restricted KD, and a complete absence of brain tumor tissue was noted on FDT–PET and MRI imaging after 2 months of treatment – results the authors attributed in part to the adjunctive dietary treatment. Further, in a pilot trial of the KD in 16 patients with advanced metastatic tumors, six individuals reported improved emotional functioning and less insomnia, indicating that in some instances, the KD may lead to improved quality of life (Schmidt et al., 2011). In contrast, a retrospective examination of five patients with tuberous sclerosis complex treated with the KD indicated either a lack of tumor suppression or further tumor growth (Chu-Shore et al., 2010). Thus, it may be that distinct tumor types within different organ systems may respond differently to the KD or other dietary treatments and that such differences may reflect variations in the metabolic vulnerability of specific tumor types, perhaps through intrinsic differences in the expression of metabolism-related genes (Stafford et al., 2010).
Does KD reduce tumor growth?
(2011) over the past decade has shown that animals with experimentally produced brain tumors placed on a KD exhibit markedly decreased tumor growth rates, and these remarkable effects appear to be a consequence of calorie restriction (i.e., reduced blood glucose levels) rather than KD-induced ketosis (i.e., fatty acid oxidation) as the principal mechanism. Other investigators have found similar effects of the KD in animal models. One group found that the KD reduces ROS production in malignant glioma cells, and gene microarray expression profiling demonstrated that the KD induces an overall reversion to patterns seen in non-tumor specimens and a reduction in the expression of genes encoding signal transduction pathways and growth factors known to be involved in glioma growth (Stafford et al., 2010). It is also interesting to note that PPARα-activated by nutrients such as fatty acids – is now a target for developing anti-cancer drugs that target mitochondrial metabolism (Grabacka et al., 2010).
Is AD related to epilepsy?
Recent studies have shown a closer linkage of AD to epilepsy. For example, animal models of AD exhibit neuronal hyperexcitability and enhanced propensity to seizures (Palop et al., 2007; Roberson et al., 2011); these models may ultimately allow for detailed analyses of both cognitive and anticonvulsant effects of the KD or other dietary manipulations such as calorie restriction. Transgenic AD mice fed 2DG demonstrated better mitochondrial function, less oxidative stress, and reduced expression of amyloid precursor protein and β-amyloid compared to control animals (Yao et al., 2011).
Which epileptic syndromes have good efficacy?
Other epileptic syndromes with good efficacy of KD are infantile spasms, Rett syndrome, tuberous sclerosis complex, Dravet syndrome, Doose syndrome, etc. But as most studies were reported from a single center or in single case series, reliable information on efficacy and adverse events of KD are sparse.
When was the first scientific report on the value of fasting in epilepsy published?
Until the 19th century, epilepsy was believed to be a disease of ‘eating too much’. Early in the 20th century, Guelpa and Marie, both French physicians, authored the first scientific report on the value of fasting in epilepsy (Guelpa and Marie, 1911). As simple fasting could not be maintained by epileptic patients for a sufficiently long period, ...
What is KD used for?
The KD has been used as a therapeutic alternative to antiepileptic drugs (AEDs) for the treatment of refractory epilepsy and usually reserved for young patients who have seizures that are difficult to control. Recently, KD is alternative treatment option in the treatment of super-refractory status epilepticus (SE) in many centers and the age of patients who are treated with KD is getting older (Cervenka et al., 2017). Also, KD can be used in the treatment of obese diabetes mellitus type II patients (Boden et al., 2005), or as an adjuvant treatment of some cancer therapies (Erickson et al., 2017). In the neurological field, many of neurodegenerative diseases or neuromuscular disorders such as mitochondrial diseases may be helped by KD as well (Paoli et al., 2014).
What is KD in medical terms?
KD is an old method of treating refractory epilepsy, but with an enormous recently published favorable clinical data. It is just beginning a broader application in the field of refractory epilepsy and super-refractory SE.
What is the ratio of fat to carbs in KD?
These different KDs are differ in the ratio of fat to carbohydrate and protein grams combined. A 4:1 ratio is more strict than a 3:1 ratio and is generally more effective but harder for patients to adhere to it. So a more strict regimen is used for the infants and children. As successful treatment of KD largely depends on the adherence of patient, cooperation among physician, dietician, family, and patient is utmost importance.
Is KD used for diabetes?
Also, KD can be used in the treatment of obese diabetes mellitus type II patients (Boden et al., 2005), or as an adjuvant treatment of some cancer therapies (Erickson et al., 2017).
Is KD a treatment option for super refractory SE?
KD as a treatment option in super-refractory SE needs additional comment. Although the number of patients with super-refractory SE treated with KD were not more than hundreds in the literature, the reported success rate is quite high and adverse events were not critical for most patients. Most of the patients were very refractory SE such as NORSE, encephalitis including immune-mediated encephalitis or epileptic encephalopathy. The evaluation of specific treatment in super-refractory SE is not easy because the patients already take more than 4–5 drugs including sedatives, but additional KD usually induces improvement in less than a week even with no additional treatment. As pointed out by Williams and Cervenka (2017), ICU setting affords good conditions to start, monitor, and maintain the diet. Therefore, adverse events can be detected earlier and the needed duration of maintaining KD is relatively short. Most of the patients treated in an ICU setting discontinued ventilatory support within two weeks.
Why is keto diet important?
Ketogenic diets are being considered for use in several disorders due to their beneficial effects on metabolic health and the nervous system.
What are the health benefits of keto?
Here are 15 health conditions that may benefit from a ketogenic diet. 1. Epilepsy. Epilepsy is a disease that causes seizures due to excessive brain activity. Anti-seizure medications are effective for some people with epilepsy. However, others don’t respond to the drugs or can’t tolerate their side effects.
How many people on keto diet can stop diabetes?
In a 16-week study, 17 of 21 people on a ketogenic diet were able to discontinue or decrease diabetes medication dosage. Study participants also lost an average of 19 pounds (8.7 kg) and reduced their waist size, triglycerides and blood pressure ( 28 ).
How much does a keto diet decrease HBA1C?
In a 3-month study comparing a ketogenic diet to a moderate-carb diet, people in the ketogenic group averaged a 0.6% decrease in HbA1c. 12% of participants achieved an HbA1c below 5.7%, which is considered normal ( 29 ).
What is glycogen storage disease?
People with glycogen storage disease (GSD) lack one of the enzymes involved in storing glucose (blood sugar) as glycogen or breaking glycogen down into glucose. There are several types of GSD, each based on the enzyme that is missing. Typically, this disease is diagnosed in childhood.
Does keto diet help with seizures?
The ketogenic diet may also have benefits on the brain beyond seizure control. For example, when researchers examined the brain activity of children with epilepsy, they found improvements in various brain patterns in 65% of those following a ketogenic diet — regardless of whether they had fewer seizures ( 9.
What is metabolic syndrome?
Metabolic syndrome, sometimes referred to as prediabetes, is characterized by insulin resistance.
Who was the first person to use keto?
The History and Evolution of the Keto Diet. The first mention. 1863 - William Banting . 1921 - the first use of the ketogenic diet for the treatment of epilepsy. 1927- Vilhjalmur Stefansson, a study of the Inuit tribe. 1951 - Alfred Pennington - Research for E. l. DuPont.
When was the first low carb diet?
The first documented mention of a low-carb diet dates back to 776 BC, which describes the diet of some athletes at the Olympic games-a minimum of carbohydrates and a lot of meat, as well as direct recommendations to avoid eating bread before performances. 1863 - William Banting.
What is the Atkins diet?
The Atkins diet restricts carbohydrate intake to switch metabolism from using glucose as an energy "fuel" to burning fat stored in the human body. This process, called ketosis (not to be confused with ketoacidosis, which has similar symptoms), is initiated by low insulin levels. In the normal state, the level of insulin is low when the blood glucose content is low (for example, before eating). With ketosis-lipolysis, excess lipids in the cells begin to gradually enter the blood and are used as a source of energy.
How many carbs are allowed on the Atkins diet?
In the old version of the Atkins diet, the consumption of carbohydrates is sharply reduced and at the first stage, the limit was set — to consume less than 5 g of carbohydrates.
Why didn't the low calorie diet work?
Its point was that the low-calorie diet didn't work because it didn't get rid of fat, because the bodies of obese people don't fully process carbs, and most of the carbs turn into fat. 1950-60 "Metabolic syndrome" (R. Mackarness, H. Taller) 1967 - The Stillman diet.
When did grains start to be eaten?
On a systematic basis, grains began to enter the diet at best 10-12 thousand years ago, but only in those regions that were predisposed to agriculture.
Does a low carb diet help you lose weight?
In his book "Dr. Atkins' Diet Revolution" Atkins put forward a thesis, unexpected at that time, that a low-carb diet provides a metabolic advantage for weight loss - since more calories are consumed for burning fat [than for burning carbohydrates], which means that the body loses more calories with this diet.
Who invented the keto diet?
In 1971, Peter Huttenlocher devised a ketogenic diet where 60% of the calories came from MCT oil, which allowed more protein and carbohydrates to be included compared with the original ketogenic diet, meaning parents could prepare more enjoyable meals for their children with epilepsy.
When did the keto diet start?
While the keto diet started as a lesser known diet in the 20s and 30s, to treat epilepsy, it did grow among the medical community to support other conditions.
How does fasting affect ketosis?
When you are fasting, you are inducing ketosis by restricting food and forcing your body to burn fat for fuel.
Why did people start fasting on keto?
For those people, especially children, the keto diet was reintroduced as a great way to reduce the number of seizures. It was around the 1050s that people also began to start fasting with a ketogenic diet, as this proved to be a very effective combination.
Why was the keto diet abandoned?
However, the ketogenic diet was eventually primarily abandoned due to the introduction of new anticonvulsant therapies.
How many parts fat are in a keto diet?
Classic Keto carries a 4:1 ratio, which means that there are four parts fat for every one part protein and carb.
Is the trendiest diet really good for fat loss?
That’s right, the newest, trendiest diet is actually an anti-inflammatory diet created by a doctor, and it just so happens to be incredibly useful for fat loss.
Abstract
The ketogenic diet (KD) is a high-fat, adequate-protein, and very-low-carbohydrate diet regimen that mimics the metabolism of the fasting state to induce the production of ketone bodies.
Types of the ketogenic diet
The KD is characterized as a high-fat, very-low-carbohydrate diet. Several variant KD that show similar efficacy to that of the original form has been developed to date, and offer flexibility to increase compliance with the regimens.
The impact of the ketogenic diet on metabolism
The metabolism of blood lipids during KD is often a concern. In the presence of oxygen, most cellular energy originates, through glycolysis, from glucose-metabolized pyruvate, which then undergoes oxidative phosphorylation within mitochondria. In the absence of glucose, cellular energy is produced by the degradation of fatty acids.
Function in endocrine and metabolic disorders
T2DM is characterized by chronic hyperglycemia with fasting plasma glucose concentrations ≥126 mg/dL and glycated hemoglobin (HbA1c) ≥6.5%. 90 As dietary carbohydrates are the major macronutrients that increase glycemic levels, 91 it is logical to reduce the dietary carbohydrate intake to treat T2DM.
Function in neurodegenerative diseases
Alzheimer’s disease (AD) affects ~50 million people worldwide and is characterized by cognitive impairment that is associated with a progressive decline in memory, impaired self-care, disorientation, and personality changes.
Function in cancer
Cancer is one of the greatest global public health challenges and is a leading cause of global mortality. Complementary approaches to significantly enhance the efficacy of standard anticancer therapies are scarce.
Function in cardiac diseases
Heart failure (HF) is characterized by metabolic abnormalities. Therefore, augmenting cardiac ATP production in a bioenergetically efficient manner is of significant interest to the HF field.
How long has fasting been used for epilepsy?
Fasting and other dietary regimens have been used to treat epilepsy since at least 500 BC. To mimic the metabolism of fasting, the ketogenic diet (KD) was introduced by modern physicians as a treatment for epilepsy in the 1920s. For two decades this therapy was widely used, but with the modern era of antiepileptic drug treatment its use declined dramatically. By the end of the twentieth century this therapy was available in only a small number of children ' s hospitals. Over the past 15 years, there has been an explosion in the use, and scientific interest in the KD. This review traces the history of one of the most effective treatments for childhood epilepsy.
Who wrote the book Epilepsy and cerebral localization?
Penfield W. Erickson TC. ( 1941) Epilepsy and cerebral localization: a study of the mechanism, treatment, and prevention of epileptic seizures. Charles C. Thomas, Baltimore . pp. 504 – 509 .
Is KD effective for epilepsy?
The KD has experienced a reemergence in recent years and modern clinical studies have established the treatment as significantly effective ( Freeman et al., 1998 ). The KD is now is available in over 45 countries ( Kossoff & McGrogan, 2005 ). However, physician perception still greatly affects when this therapy is utilized by pediatric neurologists. Two recent expert opinion surveys, one conducted in the United States and one conducted in Europe, revealed that the KD was the next-to-the-last or last choice for treatment of almost all childhood epilepsies. In addition, a recent survey of practicing child neurologists also ranked the KD as a therapy they typically used last, with many not using it at all ( Mastriani et al., 2008 ). Much work still needs to be done to improve the perception of the utility of the KD, a treatment that compares favorably with other new treatments that have been introduced to treat childhood epilepsy.
Is KD used for children?
Almost a century has passed since the KD was initially used, and many more therapies are now available for children with epilepsy. The KD has a rich history in the United States and continues to be utilized to treat refractory childhood epilepsy. It is available at almost all major children's hospitals. Our understanding of the scientific underpinnings of this unique therapy has evolved dramatically, culminating in this first international conference devoted to the KD. A better understanding of the scientific basis of this unique dietary therapy will continue to emerge with this renewed scientific interest, resulting in improved epilepsy care for all children. This will be a fitting legacy for the KD.
Is fasting good for epilepsy?
Fasting is the only therapeutic measure against epilepsy recorded in the Hippocratic collection . Five centuries later, fasting as a therapy for seizures was documented in Biblical times. In a quotation from the King James Version of The Bible, Mark relates the story of Jesus curing an epileptic boy ( Huisjen, 2000 ).