Sunday, November 14, 2021

What is Ketogenic diet ?


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.

Normally carbohydrates in food are converted into glucose, which is then transported around the body and is important in fueling brain function. But if little carbohydrate remains in the diet, the liver converts fat into fatty acids and ketone bodies, the latter passing into the brain and replacing glucose as an energy source. An elevated level of ketone bodies in the blood (a state called ketosis) eventually lowers the frequency of epileptic seizures. 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 after discontinuing the diet. Some evidence shows that adults with epilepsy may benefit from the diet and that a less strict regimen, such as a modified Atkins diet, is similarly effective. Side effects may include constipation, high cholesterol, growth slowing, acidosis, and kidney stones.

The original therapeutic diet for pediatric epilepsy provides just enough protein for body growth and repair, and sufficient calories to maintain the correct weight for age and height. The classic therapeutic ketogenic diet was developed for treatment of pediatric epilepsy in the 1920s and was widely used into the next decade, but its popularity waned with the introduction of effective anticonvulsant medications. This classic ketogenic diet contains a 4:1 ketogenic ratio or ratio by weight of fat to combined protein and carbohydrate. This is achieved by excluding high-carbohydrate foods such as starchy fruits and vegetables, bread, pasta, grains, and sugar, while increasing the consumption of foods high in fat such as nuts, cream, and butter. Most dietary fat is made of molecules called long-chain triglycerides (LCTs). However, medium-chain triglycerides (MCTs)—made from fatty acids with shorter carbon chains than LCTs—are more ketogenic. A variant of the classic diet known as the MCT ketogenic diet uses a form of coconut oil, which is rich in MCTs, to provide around half the calories. As less overall fat is needed in this variant of the diet, a greater proportion of carbohydrate and protein can be consumed, allowing a greater variety of food choices.

In 1994, Hollywood producer Jim Abrahams, whose son's severe epilepsy was effectively controlled by the diet, created the Charlie Foundation for Ketogenic Therapies to further promote diet therapy. Publicity included an appearance on NBC's Dateline program and ...First Do No Harm (1997), a made-for-television film starring Meryl Streep. The foundation sponsored a research study, the results of which—announced in 1996—marked the beginning of renewed scientific interest in the diet.

Possible therapeutic uses for the ketogenic diet have been studied for many additional neurological disorders, some of which include: Alzheimer's disease, amyotrophic lateral sclerosis, headache, neurotrauma, pain, Parkinson's disease, and sleep disorders.

Epilepsy

Epilepsy is one of the most common neurological disorders after migraine and stroke, affecting around 50 million people worldwide. It is diagnosed in a person having recurrent, unprovoked seizures. These occur when cortical neurons fire excessively, hype synchronously, or both, leading to temporary disruption of normal brain function. This might affect, for example, the muscles, the senses, consciousness, or a combination. A seizure can be focal (confined to a specific part of the brain) or generalized (spread widely throughout the brain and leading to a loss of consciousness). Epilepsy can occur for a variety of reasons; some forms have been classified into epileptic syndromes, most of which begin in childhood. Epilepsy is considered refractory (not yielding to treatment) when two or three anticonvulsant drugs have failed to control it. About 60% of patients achieve control of their epilepsy with the first drug they use, whereas around 30% do not achieve control with drugs. When drugs fail, other options include epilepsy surgery, vagus nerve stimulation, and the ketogenic diet.

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 favor of new anticonvulsant drugs. Most individuals with epilepsy can successfully control their seizures with medication. However, 25–30% fail to achieve such control despite trying a number of different drugs. For this group, and for children in particular, the diet has once again found a role in epilepsy management.

Fasting

Physicians of ancient Greece treated diseases, including epilepsy, by altering their patients' diet. An early treatise in the Hippocratic Corpus, On the Sacred Disease, covers the disease; it dates from c. 400 BC. Its author argued against the prevailing view that epilepsy was supernatural in origin and cure, and proposed that dietary therapy had a rational and physical basis. In the same collection, the author of Epidemics describes the case of a man whose epilepsy is cured as quickly as it had appeared, through complete abstinence of food and drink. The royal physician Erasistratus declared, "One inclining to epilepsy should be made to fast without mercy and be put on short rations." Galen believed an "attenuating diet" might afford a cure in mild cases and be helpful in others.

The first modern study of fasting as a treatment for epilepsy was in France in 1911. Twenty epilepsy patients of all ages were "detoxified" by consuming a low-calorie vegetarian diet, combined with periods of fasting and purging. Two benefited enormously, but most failed to maintain compliance with the imposed restrictions. The diet improved the patients' mental capabilities, in contrast to their medication, potassium bromide, which dulled the mind.

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.

Conklin's fasting therapy was adopted by neurologists in mainstream practice. In 1916, a Dr McMurray wrote to the New York Medical Journal claiming to have successfully treated epilepsy patients with a fast, followed by a starch- and sugar-free diet, since 1912. In 1921, prominent endocrinologist Henry Rawle Geyelin reported his experiences to the American Medical Association convention. He had seen Conklin's success first-hand and had attempted to reproduce the results in 36 of his own patients. He achieved similar results despite having studied the patients for only a short time. Further studies in the 1920s indicated that seizures generally returned after the fast. Charles P. Howland, the parent of one of Conklin's successful patients and a wealthy New York corporate lawyer, gave his brother John Elias Howland a gift of $5,000 to study "the ketosis of starvation". As professor of pediatrics at Johns Hopkins Hospital, John E. Howland used the money to fund research undertaken by neurologist Stanley Cobb and his assistant William G. Lennox.

Diet

In 1921, Rollin Turner Woodyatt reviewed the research on diet and diabetes. He reported that three water-soluble compounds, β-hydroxybutyrate, acetoacetate, and acetone (known collectively as ketone bodies), were produced by the liver in otherwise healthy people when they were starved or if they consumed a very low-carbohydrate, high-fat diet. Dr. Russell Morse Wilder, at the Mayo Clinic, built on this research and coined the term "ketogenic diet" to describe a diet that produced a high level of ketone bodies in the blood (ketonemia) through an excess of fat and lack of carbohydrate. Wilder hoped to obtain the benefits of fasting in a dietary therapy that could be maintained indefinitely. His trial on a few epilepsy patients in 1921 was the first use of the ketogenic diet as a treatment for epilepsy.

Wilder's colleague, paediatrician Mynie Gustav Peterman, later formulated the classic diet, with a ratio of one gram of protein per kilogram of body weight in children, 10–15 g of carbohydrate per day, and the remainder of calories from fat. Peterman's work in the 1920s established the techniques for induction and maintenance of the diet. Peterman documented positive effects (improved alertness, behaviour, and sleep) and adverse effects (nausea and vomiting due to excess ketosis). The diet proved to be very successful in children: Peterman reported in 1925 that 95% of 37 young patients had improved seizure control on the diet and 60% became seizure-free. By 1930, the diet had also been studied in 100 teenagers and adults. Clifford Joseph Barborka, Sr., also from the Mayo Clinic, reported that 56% of those older patients improved on the diet and 12% became seizure-free. Although the adult results are similar to modern studies of children, they did not compare as well to contemporary studies. Barborka concluded that adults were least likely to benefit from the diet, and the use of the ketogenic diet in adults was not studied again until 1999.

Anticonvulsants and decline

During the 1920s and 1930s, when the only anticonvulsant drugs were the sedative bromides (discovered 1857) and phenobarbital (1912), the ketogenic diet was widely used and studied. This changed in 1938 when H. Houston Merritt, Jr. and Tracy Putnam discovered phenytoin (Dilantin), and the focus of research shifted to discovering new drugs. With the introduction of sodium valproate in the 1970s, drugs were available to neurologists that were effective across a broad range of epileptic syndromes and seizure types. The use of the ketogenic diet, by this time, restricted to difficult cases such as Lennox–Gastaut syndrome, declined further.

MCT diet

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). MCTs are more efficiently absorbed and are rapidly transported to the liver via the hepatic portal system rather than the lymphatic system. 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. The MCT diet replaced the classic ketogenic diet in many hospitals, though some devised diets that were a combination of the two.

Revival

The ketogenic diet achieved national media exposure in the US in October 1994, when NBC's Dateline television programme reported the case of Charlie Abrahams, son of Hollywood producer Jim Abrahams. The two-year-old suffered from epilepsy that had remained uncontrolled by mainstream and alternative therapies. Abrahams discovered a reference to the ketogenic diet in an epilepsy guide for parents and brought Charlie to John M. 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. A multicentre prospective study began in 1994, the results were presented to the American Epilepsy Society in 1996 and were published[17] in 1998. There followed an explosion of scientific interest in the diet. In 1997, 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 2007, 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.

Adverse effects

The ketogenic diet is not considered a benign, holistic, or all-natural treatment. As with any serious medical therapy, it may result in complications, although these are generally less severe and less frequent than with anticonvulsant medication or surgery. Common but easily treatable short-term side effects include constipation, low-grade acidosis, and hypoglycaemia if an initial fast is undertaken. Raised levels of lipids in the blood affect up to 60% of children and cholesterol levels may increase by around 30%. This can be treated by changes to the fat content of the diet, such as from saturated fats towards polyunsaturated fats, and if persistent, by lowering the ketogenic ratio. Supplements are necessary to counter the dietary deficiency of many micronutrients.

Long-term use of the ketogenic diet in children increases the risk of slowed or stunted growth, bone fractures, and kidney stones. The diet reduces levels of insulin-like growth factor 1, which is important for childhood growth. 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. About one in 20 children on the ketogenic diet develop kidney stones (compared with one in several thousand for the general population). 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. The stones are treatable and do not justify discontinuation of the diet. Around half of clinics gives oral potassium citrate supplements empirically to all ketogenic diet patients, with some evidence that this reduces the incidence of stone formation. However, has not been tested in a prospective controlled trial. Kidney stone formation (nephrolithiasis) is associated with the diet for four reasons:

Excess calcium in the urine (hypercalciuria) occurs due to increased bone demineralisation with acidosis. Bones are mainly composed of calcium phosphate. The phosphate reacts with the acid, and the calcium is excreted by the kidneys.

Hypocitraturia: the urine has an abnormally low concentration of citrate, which normally helps to dissolve free calcium.

The urine has a low pH, which stops uric acid from dissolving, leading to crystals that act as a nidus for calcium stone formation.

Many institutions traditionally restricted the water intake of patients on the diet to 80% of normal daily needs; this practice is no longer encouraged.

In adolescent and adults, common side effects reported include weight loss, constipation, dyslipidemia, and in women, dysmenorrhea.

Implementation

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 or the low-glycaemic index treatment diet, because they find the difficulties too great.

Sample meal plan for one day



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