The ketogenic diet has been studied in at least 14 rodent animal models of seizures. It is protective in many of these models and has a different protection profile than any known anticonvulsant. Conversely, fenofibrate, not used clinically as an antiepileptic, exhibits experimental anticonvulsant properties in adult rats comparable to the ketogenic diet.[58] This, together with studies showing its efficacy in patients who have failed to achieve seizure control on half a dozen drugs, suggests a unique mechanism of action.[56]

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In the 1960s, medium-chain triglycerides (MCTs) were found to produce more ketone bodies per unit of energy than normal dietary fats (which are mostly long-chain triglycerides).[15] MCTs are more efficiently absorbed and are rapidly transported to the liver via the hepatic portal system rather than the lymphatic system.[16] The severe carbohydrate restrictions of the classic ketogenic diet made it difficult for parents to produce palatable meals that their children would tolerate. In 1971, Peter Huttenlocher devised a ketogenic diet where about 60% of the calories came from the MCT oil, and this allowed more protein and up to three times as much carbohydrate as the classic ketogenic diet. The oil was mixed with at least twice its volume of skimmed milk, chilled, and sipped during the meal or incorporated into food. He tested it on 12 children and adolescents with intractable seizures. Most children improved in both seizure control and alertness, results that were similar to the classic ketogenic diet. Gastrointestinal upset was a problem, which led one patient to abandon the diet, but meals were easier to prepare and better accepted by the children.[15] The MCT diet replaced the classic ketogenic diet in many hospitals, though some devised diets that were a combination of the two.[10]

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Metabolic Syndrome Limited research, including a study published in November 2017 in the journal Diabetes & Metabolic Syndrome: Clinical Research & Reviews, has suggested that adults with metabolic disease following keto shed more weight and body fat compared with those on a standard American diet, which is heavy in processed food and added sugars. (6)

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The ketogenic diet has recently been investigated a great deal for how it may help prevent or even treat certain cancers. One study found that the ketogenic diet may be a suitable complementary treatment to chemotherapy and radiation in people with cancer. This is due to the fact that it would cause more oxidative stress in cancer cells than in normal cells.
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.[17] The parents attend classes over the first three full days, which cover nutrition, managing the diet, preparing meals, avoiding sugar, and handling illness.[19] The level of parental education and commitment required is higher than with medication.[44]

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Wondering what fits into a keto diet — and what doesn’t? “It’s so important to know what foods you’ll be eating before you start, and how to incorporate more fats into your diet,” says Kristen Mancinelli, RD, author of The Ketogenic Diet: A Scientifically Proven Approach to Fast, Healthy Weight Loss, who is based in New York City. We asked her for some guidelines.

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After initiation, the child regularly visits the hospital outpatient clinic where they are 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.[9] A period of minor adjustments is necessary to ensure consistent ketosis is maintained and to better adapt the meal plans to the patient. This fine-tuning is typically done over the telephone with the hospital dietitian[19] and includes changing the number of calories, altering the ketogenic ratio, or adding some MCT or coconut oils to a classic diet.[18] Urinary ketone levels are checked daily to detect whether ketosis has been achieved and to confirm that the patient is following the diet, though the level of ketones does not correlate with an anticonvulsant effect.[19] This is performed using ketone test strips containing nitroprusside, which change colour from buff-pink to maroon in the presence of acetoacetate (one of the three ketone bodies).[45]

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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.[19] On admission, only calorie- and caffeine-free fluids[37] are allowed until dinner, which consists of "eggnog"[Note 8] restricted to one-third of the typical calories for a 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.[19]

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The possible benefits of the diet are impressive, but there are a few potential downsides to note. One is it’s tough to stick to. In fact, in a review of 11 studies involving adults on the keto diet, which was published in January 2015 in the Journal of Clinical Neurology, researchers calculated a 45 percent compliance rate among participants following the approach with the aim of controlling epilepsy. (13) “The diet is pretty hard to follow because it’s a complete shift from what you’re used to,” Nisevich Bede says. Slashing your intake of carbs can also make you feel hungrier than usual — a feeling that can last until you’re three weeks in.
The ketogenic diet is a high-fat, adequate-protein, low-carbohydrate diet that in medicine is used primarily to treat difficult-to-control (refractory) epilepsy in children. The diet forces the body to burn fats rather than carbohydrates. Normally, the carbohydrates contained in food are converted into glucose, which is then transported around the body and is particularly important in fueling brain function. However, if little carbohydrate remains in the diet, the liver converts fat into fatty acids and ketone bodies. The ketone bodies pass into the brain and replace glucose as an energy source. An elevated level of ketone bodies in the blood, a state known as ketosis, leads to a reduction in the frequency of epileptic seizures.[1] Around half of children and young people with epilepsy who have tried some form of this diet saw the number of seizures drop by at least half, and the effect persists even after discontinuing the diet.[2] Some evidence indicates that adults with epilepsy may benefit from the diet, and that a less strict regimen, such as a modified Atkins diet, is similarly effective.[1] Potential side effects may include constipation, high cholesterol, growth slowing, acidosis, and kidney stones.[3]

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Metabolic Syndrome Limited research, including a study published in November 2017 in the journal Diabetes & Metabolic Syndrome: Clinical Research & Reviews, has suggested that adults with metabolic disease following keto shed more weight and body fat compared with those on a standard American diet, which is heavy in processed food and added sugars. (6)

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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. Some evidence of synergistic benefits is seen 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.[18]
A survey in 2005 of 88 paediatric neurologists in the US found that 36% regularly prescribed the diet after three or more drugs had failed, 24% occasionally prescribed the diet as a last resort, 24% had only prescribed the diet in a few rare cases, and 16% had never prescribed the diet. Several possible explanations exist for this gap between evidence and clinical practice.[34] One major factor may be the lack of adequately trained dietitians who are needed to administer a ketogenic diet programme.[31]
Sleep enough – for most people at least seven hours per night on average – and keep stress under control. Sleep deprivation and stress hormones raise blood sugar levels, slowing ketosis and weight loss a bit. Plus they might make it harder to stick to a keto diet, and resist temptations. So while handling sleep and stress will not get you into ketosis on it’s own, it’s still worth thinking about.

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Ketosis has been shown to have anti-inflammatory properties while also assisting with pain relief. Reducing glucose metabolism influences pain, so this could be one potential mechanism of action. In the review The Nervous System and Metabolic Dysregulation: Emerging Evidence Converges on Ketogenic Diet Therapy the authors look at numerous ways that a ketogenic diet can assist with pain and inflammation.

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Because some cancer cells are inefficient in processing ketone bodies for energy, the ketogenic diet has also been suggested as a treatment for cancer.[59][60] A 2018 review looked at the evidence from preclinical and clinical studies of ketogenic diets in cancer therapy. The clinical studies in humans are typically very small, with some providing weak evidence for anti-tumour effect, particularly for glioblastoma, but in other cancers and studies, no anti-tumour effect was seen. Taken together, results from preclinical studies, albeit sometimes contradictory, tend to support an anti-tumor effect rather than a pro-tumor effect of the KD for most solid cancers.[61]

Around this time, Bernarr Macfadden, an American exponent of physical culture, popularised the use of fasting to restore health. His disciple, the osteopathic physician Dr. Hugh William Conklin of Battle Creek, Michigan, began to treat his epilepsy patients by recommending fasting. Conklin conjectured that epileptic seizures were caused when a toxin, secreted from the Peyer's patches in the intestines, was discharged into the bloodstream. He recommended a fast lasting 18 to 25 days to allow this toxin to dissipate. Conklin probably treated hundreds of epilepsy patients with his "water diet" and boasted of a 90% cure rate in children, falling to 50% in adults. Later analysis of Conklin's case records showed 20% of his patients achieved freedom from seizures and 50% had some improvement.[10]
Children who discontinue the diet after achieving seizure freedom have about a 20% risk of seizures returning. The length of time until recurrence is highly variable, but averages two years. This risk of recurrence compares with 10% for resective surgery (where part of the brain is removed) and 30–50% for anticonvulsant therapy. Of those who 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 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 children with tuberous sclerosis who achieve seizure freedom could remain on the ketogenic diet indefinitely.[46]

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