The neuron is unable to fire again for a short time known as the refractory period , which is mediated by another potassium channel. Don't rely on their nine lives to get them out of trouble, kitten insurance can provide a peace of mind for your new little buddle of fluff. Two pounds per week is considered the most you should shoot for, and even half a pound per week is a success. Cederquist who has over 10 years of clinical experience in weight management. Some dairy products can be used in moderation, such as heavy whipping cream and most cheeses. Glucose Transporter Type 1 Deficiency Syndrome. There is some evidence of synergistic benefits when the diet is combined with the vagus nerve stimulator or with the drug zonisamide , and that the diet may be less successful in children receiving phenobarbital.
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Abrahams discovered a reference to the ketogenic diet in an epilepsy guide for parents and brought Charlie to John Freeman at Johns Hopkins Hospital , which had continued to offer the therapy. Under the diet, Charlie's epilepsy was rapidly controlled and his developmental progress resumed. This inspired Abrahams to create the Charlie Foundation to promote the diet and fund research.
There followed an explosion of scientific interest in the diet. In , Abrahams produced a TV movie, First Do No Harm , starring Meryl Streep , in which a young boy's intractable epilepsy is successfully treated by the ketogenic diet.
By , the ketogenic diet was available from around 75 centres in 45 countries, and less restrictive variants, such as the modified Atkins diet , were in use, particularly among older children and adults.
The ketogenic diet was also under investigation for the treatment of a wide variety of disorders other than epilepsy. Early studies reported high success rates: These studies generally examined a cohort of patients recently treated by the physician what is known as a retrospective study and selected patients who had successfully maintained the dietary restrictions. However, these studies are difficult to compare to modern trials.
One reason is that these older trials suffered from selection bias , as they excluded patients who were unable to start or maintain the diet and thereby selected from patients who would generate better results.
In an attempt to control for this bias, modern study design prefers a prospective cohort the patients in the study are chosen before therapy begins in which the results are presented for all patients regardless of whether they started or completed the treatment known as intent-to-treat analysis.
Another difference between older and newer studies is that the type of patients treated with the ketogenic diet has changed over time. When first developed and used, the ketogenic diet was not a treatment of last resort; in contrast, the children in modern studies have already tried and failed a number of anticonvulsant drugs, so may be assumed to have more difficult-to-treat epilepsy. Early and modern studies also differ because the treatment protocol has changed. Concerns over child health and growth led to a relaxation of the diet's restrictions.
A study with an intent-to-treat prospective design was published in by a team from the Johns Hopkins Hospital  and followed-up by a report published in The study enrolled children. Those who had discontinued the diet by this stage did so because it was ineffective, too restrictive or due to illness, and most of those who remained were benefiting from it.
During this period the most common reason for discontinuing the diet was because the children had become seizure-free or significantly better. Those remaining on the diet after this duration were typically not seizure-free but had had an excellent response.
It is possible to combine the results of several small studies to produce evidence that is stronger than that available from each study alone—a statistical method known as meta-analysis. One of four such analyses, conducted in , looked at 19 studies on a total of 1, patients. A systematic review in found and analysed seven randomized controlled trials of ketogenic diet in children and young people with epilepsy.
A systematic review in looked at sixteen studies on the ketogenic diet in adults. It concluded that the treatment was becoming more popular for that group of patients, that the efficacy in adults was similar to children, the side effects relatively mild. However, many patients gave up with the diet, for various reasons, and the quality of evidence inferior to studies on children.
Health issues include high levels of low-density lipoprotein LDL , high total cholesterol , and weight loss. The ketogenic diet is indicated as an adjunctive additional treatment in children and young people with drug-resistant epilepsy.
Some clinicians consider the two less restrictive dietary variants—the low glycaemic index treatment and the modified Atkins diet—to be more appropriate for adolescents and adults. These include Dravet syndrome , infantile spasms , myoclonic-astatic epilepsy and tuberous sclerosis complex. There are several possible explanations for this gap between evidence and clinical practice. Because the ketogenic diet alters the body's metabolism, it is a first-line therapy in children with certain congenital metabolic diseases such as pyruvate dehydrogenase E1 deficiency and glucose transporter 1 deficiency syndrome ,  which prevent the body from using carbohydrates as fuel, leading to a dependency on ketone bodies.
The ketogenic diet is beneficial in treating the seizures and some other symptoms in these diseases and is an absolute indication. On the ketogenic diet, their body would consume its own protein stores for fuel, leading to ketoacidosis , and eventually coma and death. The ketogenic diet is usually initiated in combination with the patient's existing anticonvulsant regimen, though patients may be weaned off anticonvulsants if the diet is successful.
There is some evidence of synergistic benefits when the diet is combined with the vagus nerve stimulator or with the drug zonisamide , and that the diet may be less successful in children receiving phenobarbital.
As with any serious medical therapy, the ketogenic diet may have complications. Long-term use of the ketogenic diet in children increases the risk of slowed or stunted growth, bone fractures and kidney stones.
Like many anticonvulsant drugs, the ketogenic diet has an adverse effect on bone health. Many factors may be involved such as acidosis and suppressed growth hormone. A class of anticonvulsants known as carbonic anhydrase inhibitors topiramate , zonisamide are known to increase the risk of kidney stones, but the combination of these anticonvulsants and the ketogenic diet does not appear to elevate the risk above that of the diet alone.
In adolescent and adults, common side effects reported include weight loss, constipation, dyslipidemia and, in women, dysmenorrhea.
The ketogenic diet is a medical nutrition therapy that involves participants from various disciplines. Team members include a registered paediatric dietitian who coordinates the diet programme; a paediatric neurologist who is experienced in offering the ketogenic diet; and a registered nurse who is familiar with childhood epilepsy. Additional help may come from a medical social worker who works with the family and a pharmacist who can advise on the carbohydrate content of medicines.
Lastly, the parents and other caregivers must be educated in many aspects of the diet for it to be safely implemented.
Implementing the diet can present difficulties for caregivers and the patient due to the time commitment involved in measuring and planning meals. Since any unplanned eating can potentially break the nutritional balance required, some people find the discipline needed to maintain the diet challenging and unpleasant.
Some people terminate the diet or switch to a less demanding diet, like the modified Atkins diet MAD or the low-glycaemic index treatment LGIT diet, because they find the difficulties too great. The Johns Hopkins Hospital protocol for initiating the ketogenic diet has been widely adopted.
At the initial consultation, patients are screened for conditions that may contraindicate the diet. A dietary history is obtained and the parameters of the diet selected: The day before admission to hospital, the proportion of carbohydrate in the diet may be decreased and the patient begins fasting after his or her evening meal.
The following breakfast and lunch are similar, and on the second day, the "eggnog" dinner is increased to two-thirds of a typical meal's caloric content. By the third day, dinner contains the full calorie quota and is a standard ketogenic meal not "eggnog". After a ketogenic breakfast on the fourth day, the patient is discharged. Where possible, the patient's current medicines are changed to carbohydrate-free formulations. When in the hospital, glucose levels are checked several times daily and the patient is monitored for signs of symptomatic ketosis which can be treated with a small quantity of orange juice.
Lack of energy and lethargy are common but disappear within two weeks. Variations on the Johns Hopkins protocol are common. The initiation can be performed using outpatient clinics rather than requiring a stay in hospital.
Often there is no initial fast fasting increases the risk of acidosis and hypoglycaemia and weight loss. Rather than increasing meal sizes over the three-day initiation, some institutions maintain meal size but alter the ketogenic ratio from 2: If the diet does not begin with a fast, the time for half of the patients to achieve an improvement is longer two weeks but the long-term seizure reduction rates are unaffected.
After initiation, the child regularly visits the hospital outpatient clinic where he or she is seen by the dietitian and neurologist, and various tests and examinations are performed. These are held every three months for the first year and then every six months thereafter. Infants under one year old are seen more frequently, with the initial visit held after just two to four weeks.
This fine-tuning is typically done over the telephone with the hospital dietitian  and includes changing the number of calories, altering the ketogenic ratio, or adding some MCT or coconut oils to a classic diet. A short-lived increase in seizure frequency may occur during illness or if ketone levels fluctuate. The diet may be modified if seizure frequency remains high, or the child is losing weight. Even "sugar-free" food can contain carbohydrates such as maltodextrin , sorbitol , starch and fructose.
The sorbitol content of suntan lotion and other skincare products may be high enough for some to be absorbed through the skin and thus negate ketosis. This is done by lowering the ketogenic ratio until urinary ketosis is no longer detected, and then lifting all calorie restrictions. When the diet is required to treat certain metabolic diseases, the duration will be longer. The total diet duration is up to the treating ketogenic diet team and parents; durations up to 12 years have been studied and found beneficial.
The length of time until recurrence is highly variable but averages two years. Of those that have a recurrence, just over half can regain freedom from seizures either with anticonvulsants or by returning to the ketogenic diet. Recurrence is more likely if, despite seizure freedom, an electroencephalogram EEG shows epileptiform spikes, which indicate epileptic activity in the brain but are below the level that will cause a seizure.
Recurrence is also likely if an MRI scan shows focal abnormalities for example, as in children with tuberous sclerosis. Such children may remain on the diet longer than average, and it has been suggested that children with tuberous sclerosis who achieve seizure freedom could remain on the ketogenic diet indefinitely. The ketogenic diet is calculated by a dietitian for each child. Age, weight, activity levels, culture and food preferences all affect the meal plan.
Highly active children or those with muscle spasticity require more calories than this; immobile children require less. The ketogenic ratio of the diet compares the weight of fat to the combined weight of carbohydrate and protein. This is typically 4: The quantity of fat in the diet can be calculated from the overall energy requirements and the chosen ketogenic ratio.
Lastly, the amount of carbohydrate is set according to what allowance is left while maintaining the chosen ratio. Any carbohydrate in medications or supplements must be subtracted from this allowance.
The total daily amount of fat, protein and carbohydrate is then evenly divided across the meals. A computer program such as KetoCalculator may be used to help generate recipes. Only low-carbohydrate fruits and vegetables are allowed, which excludes bananas, potatoes, peas and corn. Suitable fruits are divided into two groups based on the amount of carbohydrate they contain, and vegetables are similarly divided into two groups. Foods within each of these four groups may be freely substituted to allow for variation without needing to recalculate portion sizes.
For example, cooked broccoli, Brussels sprouts, cauliflower and green beans are all equivalent. Fresh, canned or frozen foods are equivalent, but raw and cooked vegetables differ, and processed foods are an additional complication. The child must eat the whole meal and cannot have extra portions; any snacks must be incorporated into the meal plan. A small amount of MCT oil may be used to help with constipation or to increase ketosis.
The classic ketogenic diet is not a balanced diet and only contains tiny portions of fresh fruit and vegetables, fortified cereals and calcium-rich foods. In particular, the B vitamins , calcium and vitamin D must be artificially supplemented.
This is achieved by taking two sugar-free supplements designed for the patient's age: Normal dietary fat contains mostly long-chain triglycerides LCT. Medium-chain triglycerides are more ketogenic than LCTs because they generate more ketones per unit of energy when metabolised.
Their use allows for a diet with a lower proportion of fat and a greater proportion of protein and carbohydrate,  leading to more food choices and larger portion sizes. The classical and modified MCT ketogenic diets are equally effective and differences in tolerability are not statistically significant.
First reported in , the idea of using a form of the Atkins diet to treat epilepsy came about after parents and patients discovered that the induction phase of the Atkins diet controlled seizures. The ketogenic diet team at Johns Hopkins Hospital modified the Atkins diet by removing the aim of achieving weight loss, extending the induction phase indefinitely, and specifically encouraging fat consumption.
Compared with the ketogenic diet, the modified Atkins diet MAD places no limit on calories or protein, and the lower overall ketogenic ratio approximately 1: The MAD does not begin with a fast or with a stay in hospital and requires less dietitian support than the ketogenic diet. Like the ketogenic diet, the MAD requires vitamin and mineral supplements and children are carefully and periodically monitored at outpatient clinics. The low glycaemic index treatment LGIT  is an attempt to achieve the stable blood glucose levels seen in children on the classic ketogenic diet while using a much less restrictive regimen.
The hypothesis is that stable blood glucose may be one of the mechanisms of action involved in the ketogenic diet,  which occurs because the absorption of the limited carbohydrates is slowed by the high fat content. Like the modified Atkins diet, the LGIT is initiated and maintained at outpatient clinics and does not require precise weighing of food or intensive dietitian support. Both are offered at most centres that run ketogenic diet programmes, and in some centres they are often the primary dietary therapy for adolescents.
The data coming from one centre's experience with 76 children up to the year also indicate fewer side effects than the ketogenic diet and that it is better tolerated, with more palatable meals. Infants and patients fed via a gastrostomy tube can also be given a ketogenic diet. Parents make up a prescribed powdered formula, such as KetoCal, into a liquid feed. It is used to administer the 4: The formula is available in both 3: There are theoretically no restrictions on where the ketogenic diet might be used, and it can cost less than modern anticonvulsants.
However, fasting and dietary changes are affected by religious and cultural issues. A culture where food is often prepared by grandparents or hired help means more people must be educated about the diet.
When families dine together, sharing the same meal, it can be difficult to separate the child's meal. In many countries, food labelling is not mandatory so calculating the proportions of fat, protein and carbohydrate is difficult. In some countries, it may be hard to find sugar-free forms of medicines and supplements, to purchase an accurate electronic scale, or to afford MCT oils.
In Asia, the normal diet includes rice and noodles as the main energy source, making their elimination difficult. Therefore, the MCT-oil form of the diet, which allows more carbohydrate, has proved useful. In India, religious beliefs commonly affect the diet: The Indian ketogenic diet is started without a fast due to cultural opposition towards fasting in children. The low-fat, high-carbohydrate nature of the normal Indian and Asian diet means that their ketogenic diets typically have a lower ketogenic ratio 1: However, they appear to be just as effective.
In many developing countries, the ketogenic diet is expensive because dairy fats and meat are more expensive than grain, fruit and vegetables. The modified Atkins diet has been proposed as a lower-cost alternative for those countries; the slightly more expensive food bill can be offset by a reduction in pharmaceutical costs if the diet is successful. The modified Atkins diet is less complex to explain and prepare and requires less support from a dietitian.
The brain is composed of a network of neurons that transmit signals by propagating nerve impulses. The propagation of this impulse from one neuron to another is typically controlled by neurotransmitters , though there are also electrical pathways between some neurons.
A neuron that releases inhibitory neurotransmitters from its terminals is called an inhibitory neuron, while one that releases excitatory neurotransmitters is an excitatory neuron.
When the normal balance between inhibition and excitation is significantly disrupted in all or part of the brain, a seizure can occur. The GABA system is an important target for anticonvulsant drugs, since seizures may be discouraged by increasing GABA synthesis, decreasing its breakdown, or enhancing its effect on neurons.
The nerve impulse is characterised by a great influx of sodium ions through channels in the neuron's cell membrane followed by an efflux of potassium ions through other channels. The neuron is unable to fire again for a short time known as the refractory period , which is mediated by another potassium channel. The flow through these ion channels is governed by a "gate" which is opened by either a voltage change or a chemical messenger known as a ligand such as a neurotransmitter.
These channels are another target for anticonvulsant drugs. There are many ways in which epilepsy occurs. Examples of pathological physiology include: Although many hypotheses have been put forward to explain how the ketogenic diet works, it remains a mystery. Disproven hypotheses include systemic acidosis high levels of acid in the blood , electrolyte changes and hypoglycaemia low blood glucose.
The lack of understanding in this area is similar to the situation with many anticonvulsant drugs. On the ketogenic diet, carbohydrates are restricted and so cannot provide for all the metabolic needs of the body. Instead, fatty acids are used as the major source of fuel. These are used through fatty-acid oxidation in the cell's mitochondria the energy-producing parts of the cell.
Humans can convert some amino acids into glucose by a process called gluconeogenesis , but cannot do this by using fatty acids. This could pose a problem for the brain, since it is normally fuelled solely by glucose, and most fatty acids do not cross the blood—brain barrier. These ketone bodies enter the brain and partially substitute for blood glucose as a source of energy. The ketone bodies are possibly anticonvulsant; in animal models , acetoacetate and acetone protect against seizures.
The ketogenic diet results in adaptive changes to brain energy metabolism that increase the energy reserves; ketone bodies are a more efficient fuel than glucose, and the number of mitochondria is increased. This may help the neurons to remain stable in the face of increased energy demand during a seizure, and may confer a neuroprotective effect.
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