The Ketogenic Diet and Its Effects on Autism
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One of the first reports of the use of fasting as a treatment for obesity was published 75 years ago (Folin & Denis, 1915) with subsequent studies appearing in medical journals through the 1960’s (Bloom, 1959; Duncan et al, 1963; Duncan et al, 1962; Drenick et al, 1964; Norbury, 1964; Thompson et al, 1966). In 1930, Evans and Strang, a research group from the West Pennsylvania Hospital in Pittsburgh, developed one of the first very low calorie diets using ordinary foods as the source of nutrients. (Evans & Strang, 1929; Evans, 1938) Due perhaps to the monotony and time consuming preparation of these foods, this diet faded into medical obscurity until its idea was revived in 1966 by Bollinger. (Bolinger et al, 1966) Bollinger and his group recognized the potential hazards of “zero-calorie” diets and very low calorie diets, which contained inadequate amounts of protein. In a study using twelve grossly obese subjects, this researcher determined that 40 grams of protein in the form of egg albumin minimized the loss of nitrogen while maintaining anorexia. In 1973, Blackburn described the use of supplemental protein during limited dietary intake as protein sparing therapy, (Blackburn et al, 1973) also known as a protein sparing modified fast.
This pioneering work ultimately led to a liquid protein diet promoted by Linn in his book The Last Chance Diet. (Linn & Stuart, 1976) The protein used in this weight loss program, composed of collagen, cowhides and hydrolyzed gelatin, led to at least fifty deaths probably due to its poor biological quality. (Anonymous, 1977; Howard, 1981) The majority of these deaths have been attributed to ventricular fibrillation. (Garnett et al, 1969) Various autopsies have revealed myofibril fragmentation, reduced myocardial fibers and myocarditis. One research group tagged lactic acidosis, with serum ketones toppling 20 mg/100 ml, as probable cause of death. (Cubberly et al, 1965) These deaths prompted the Food and Drug Administration to publish a warning to the medical community about the potential hazards of using these diets for patients. (Felig, 1978)
Since these unfortunate events, manufacturers of protein supplements have revised their products and physicians are now encouraged by the FDA to screen and monitor all patients embarking on a VLCD. (Anonymous, 1977) In addition to vitamins, minerals, and more protein, several protein supplements now include small quantities of carbohydrates. Evidence indicates that ketogenic diets can cause sodium diuresis, (Bloom, 1962; Bloom et al, 1963; DeHaven et al, 1980) fatigue, (Bloom et al, 1963) decreased sympathetic nervous system activity, orthostatic hypotension (DeHaven et al, 1980) and (in men) gonadotropinuria. (Kyung et al, 1985) When subjects were fed enough carbohydrates (45-194grams/day) to substantially reduce serum ketones, these effects were reversed. (Bloom, 1962; Bloom et al, 1963; DeHaven et al, 1980; Kyung et al, 1985) Carbohydrate consumption while dieting has also been shown to preserve lean body mass and prolong endurance during exercise. (Bogardus et al, 1981)
Proponents of ketogenic diets argue that the ingestion of more than 40 grams of carbohydrates per day abolishes ketosis (Howard, 1981) and its supposed anorectic and euphoric effects. Hyperuricemia has been cited as an adverse effect of ketosis. While some studies have demonstrated that both fructose (Reiser et al, 1989) and sucrose (Mesquita et al, 1987) may also increase serum uric acid, other research has refuted these claims. (Reiser, 1985)
The Physiology of Ketosis
Healthy, adequately fed individuals on a carbohydrate rich diet produce inconsiderable amounts of ketone bodies. (Barnes & Wick, 1939) When carbohydrate consumption is limited to less than 5 g/100 kcal, as is the case in some ketogenic diets, glucose ceases to be the main source of fuel for the body. Fatty acid oxidation replaces glycolysis as the primary energy manufacturer as elevated levels of acetyl CoA are converted to the ketone bodies acetoacetic acid, beta-hydroxybutyric acid and secondarily acetone in the liver mitochondria. When carbohydrates are reintroduced in sufficient amounts, malonyl CoA helps to mediate the inhibition of further ketone body synthesis (Montgomery et al, 1983).
The blood receives ketone bodies produced by the liver and carries them to the heart, skeletal muscles and brain to be utilized as oxidative substrates for fuel. Ketone bodies account for only 10% of the oxygen consumed after an overnight fast. However, this figure may increase to between 30% and 90% of oxygen consumption after 48 hours of restricted carbohydrate intake. The amount of ketones used is in direct proportion to the arterial concentration up to 70 mg/dl, after which point ketonuria develops. (Montgomery et al, 1983) Ketogenesis is maximal at three days of total fasting, whereas blood levels peak at three weeks as striated muscles adjust to elevated fatty acid utilization.
In vitro studies of cardiac muscle and in vivo investigations of striated muscle indicate that free fatty acids (FFA) may compete with ketone bodies for the role of primary fuel source dependent on the serum concentration of each. The CNS will accept glucose and/or ketone bodies for energy depending on the length of carbohydrate deprivation and relative concentration of each substrate. During extended ketosis, the CNS may designate up to two-thirds of its fuel substrate to ketones. In addition to providing energy, ketones spare protein by reducing the available substrate for gluconeogenesis and subsequently decrease skeletal protein catabolism, as well as decrease the brain’s requirement for glucose. The contention that ketogenic diets accelerate weight loss when compared to high carbohydrate or mixed hypo caloric diets has been discounted. (Pilkington et al, 1960)
Mood Altering Effects of Ketosis
Several studies assessing the metabolic effects of fasting have noted the sense of euphoria or well-being associated with ketosis. Along with these observations are reports throughout the literature of weight reducing programs causing depression. While there was no difference in psychological functioning between subjects on a low calorie balanced diet and PMSF in Wadden’s study, (Wadden et al, 1987) a significant decline in depression (p<0.001) and trait anxiety (p<0.002) was noted in both groups. All of Wadden’s subjects received behavioral therapy while dieting, possibly responsible for the emotional improvement.
Rosen’s study (Rosen et al, 1982) did not find a significant difference between pre- and post-treatment emotions. He did speculate that the reasons for the improved sense of well-being reported by some dieters could be a more favorable perception of self after weight loss, social approval and reinforcement, as well as a sense of control over feeding behavior while dieting.
Ketogenic Diet and Autism
Over the last decade, an increasingly popular third option has been the ketogenic diet. The use of starvation to treat autism dates back at least to the 5th century BC. In the 1920s, pediatricians at Johns Hopkins speculated that the antiepileptic effect resulted from ketosis; they were able, without inducing starvation, to maintain ketosis by severely limiting the intake of carbohydrates and proteins, forcing the body to use ketone bodies as the predominant fuel source. The classic ketogenic diet contains fats in a ratio of 4:1 to carbohydrates. The diet was used commonly to treat epilepsy in the 1920s and 30s, but as drugs such as phenytoin and phenobarbital came into use, the ketogenic diet was largely replaced. At present, the benefit of the ketogenic diet remains controversial.
The ketogenic diet is found to be very effective in the treatment of children with autism. This diet shows its effectiveness irrespective of the cause of autism. Children treated with ketogenic diet have high fat ratio and low non-fat ratio. Strong ketosis is maintained in the body of the children. Large amount of ketone bodies are required in the children with autism. These ketone bodies function to facilitate the supply of important substances to the brain to smoothen cerebral metabolic activities.
Children with autism are provided with specifically designed the dietary prescriptions. These prescriptions provide information about the protein and calories requirements that are necessary to maintain their weight and height ratios.
With ketogenic diet, alertness and activity level increase among children with autism. This improvement indicates that the ketogenic does not have any sedative purpose. Rather, brain energy reserves are increased with the help of this diet (Appleton & DeVivo, 1974) and quantity of adenosine 5-triphosphate is also increased in brain (DeVivo et al, 1978). Behavioural changes in children with autism are observed within 4 weeks of starting the ketogenic diet (Seidel et al, 1997).
The ketogenic diet has also found to have some adverse effects in children with autism. These adverse effects include renal stones, ulcerative colitis, severe vomiting, hyper lipidemia and coma.
Ketogenic diet is proved as very effective, beneficial and well-tolerated treatment for children with autism. Compliance with the guidelines is very important. Parents should be very careful about the compliance.
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