The purpose of this study was to determine the effect of a 6-week ketogenic diet on maximal oxygen consumption (VO2max), high-intensity Wingate sprints, and work output during a 45-minute cycling bout. Twenty subjects were placed into either an intervention group (N=12) or a control group (N=8). Subjects in the dietary intervention group ingested a diet consisting of 61± 4% fat, 8± 3% carbohydrate, and 30± 5% protein while subjects in the control group were instructed to continue following their normal moderate carbohydrate diet. All subjects were instructed to maintain their current training status. On the first day subjects performed a VO2max test on an electronically braked cycle ergometer. On the second day subjects performed two 30-second Wingate sprints followed by a 30-minute rest. Following this subjects performed a 45-minute timed ride on a cycle ergometer set on isokinetic mode. Absolute VO2max decreased significantly (P<_ 0.05) in the ketogenic group while relative VO2max was unchanged. Rate of perceived exertion increased significantly at 9 and 11 minutes during the VO2max test. Absolute peak and mean power output during the first Wingate sprint was significantly less after the ketogenic diet compared with week 0. When analyzed relative to body weight, however, only peak power output was significantly decreased. Power output during the second sprint remained unchanged. Fat oxidation increased but work output decreased during the 45-minute cycling bout in the ketogenic group. The results of the present study suggest that a 6-week ketogenic diet results in metabolic adaptations that increase fat oxidation. However, the overall decreased performance during a VO2max test, 30-second Wingate sprints, and a 45-minute endurance test indicate that some aspect of the diet has an adverse effect on exercise performance. / School of Physical Education

Over the last decade, not only has the awareness of ASD increased dramatically, but the rates of children diagnosed with autism has increased as well. The Center of Disease Control (CDC) now estimates that autism affects approximately 1 in every 59 children, a 150% increase since 2000. Autism Spectrum Disorder is characterized by impaired social interactions and the presence of stereotyped behaviors that results in lifelong impaired functioning. There is significant clinical heterogeneity within ASD suggesting a multifactorial pathophysiology with contribution from both genetic and environmental risk factors. Given the complexity of ASD pathophysiology, existing treatments are directed at each clinical manifestation and are not considered curative. Antipsychotic medications have been shown to be efficacious in reducing the repetitive patterns of behavior, while behavioral therapy is effective in alleviating the social impairment associated with ASD. Notably, epilepsy occurs in approximately 33% of individuals with ASD. The high co-occurrence of epilepsy and autism has been hypothesized to be the result of a shared underlying pathophysiology. Current treatment guidelines for epilepsy include anti-epileptic medications with varying mechanisms of action, however approximately one-third of patients with epilepsy fail to achieve adequate seizure control with drug therapy. In these individuals with refractory epilepsy, studies have demonstrated that the ketogenic diet has proven efficacy in achieving seizure control. Numerous mouse models and several human trials have also evaluated the efficacy of the ketogenic diet in reversing the symptoms of autism, though these studies have largely been limited in generalizability, sample size, and randomization. This proposed study will be a randomized controlled study and will assess the utility of the ketogenic diet in reversing the core deficits of autism, social impairment and restricted, repetitive behaviors. Several assessment tools will be utilized to evaluate the behavioral response to the ketogenic diet. The applicability of the ketogenic diet to improve the symptoms of ASD can have a potentially profound impact on the financial burden of the disease. Additionally, it can reduce the need for both anti-epileptic and anti-psychotic medications, thus reducing both the side effects associated with those medications, while concurrently improving the symptoms of ASD.

No description available.

Thesis (M.S.)--University of Wisconsin--Madison, 1969. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

No description available.

Thesis--Ph. D., University of Hong Kong. / Mimeographed.

published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

Interest in the ketogenic diet and its potential to treat obesity and type 2 diabetes has been steadily growing in recent years. With a very limited amount of calories coming from carbohydrates (typically < 50 gm/day), and the majority of calories coming from fat, this diet leads to a states of physiological ketosis, in which ketone bodies replace glucose as the primary source of energy. Early clinical trials found this to lead to a spontaneous reduction in calories consumed, and it has been suggested that a state of ketosis has appetite suppressing properties. There are a few studies evaluating self-reported decrease in hunger while consuming a ketogenic diet, as well as the changes in hormone levels associated with appetite, but this evidence is limited. The primary determinant of weight change is the difference between calories consumed and calories burned, however there is some suggestion that the macronutrient composition of the ketogenic diet may have a specific metabolic advantage for weight loss separate from the total number of calories in deficit. Multiple diet comparison studies have found the ketogenic diet to be effective for weight loss in the short term, particularly when compared to low fat diets. It is questionable whether the ketogenic diet is sustainable in the long term, particularly without frequent nutritional counseling and monitoring. Still, there is preliminary evidence that the ketogenic diet can lead not only to a large amount of weight loss, but may also be effective in treating and reversing type 2 diabetes. Clinical trials have shown decreases in HbA1c, fasting glucose, and reduction of antiglycemic medication requirements, though it is unclear if these effects are primarily due to weight loss itself, or the specific composition of the ketogenic diet. These benefits need to be weighed against the risks, and a common criticism is its high fat content which can adversely affect serum lipid levels and thus risk of cardiovascular disease. Consuming a ketogenic diet with a high intake of saturated fat has been found to increase LDL cholesterol, however this effect can be mitigated by favoring polyunsaturated or monounsaturated fats instead. While the above findings provide a preliminary understanding of the effects of the ketogenic diet, more research is needed to further elucidate the effectiveness and safety of the diet for treating obesity and type 2 diabetes.

No description available.

Thesis advisor: Thomas N. Seyfried / Dietary therapy has been used since ancient times to treat the symptoms of disease and disorder. Dietary therapy has long captured the interest of the public in modern times, dating back to the mid-nineteenth century with Englishman William Banting's "Letter on Corpulence, Addressed to the Public", which addressed Banting's anecdotal use of a high-fat diet to treat obesity. High-fat diets became popular in the United States in the early twentieth-century to treat epilepsy. The utility of dietary therapy to treat diseases and disorder has not been embraced widely, as there is a paucity of standardized clinical trials that demonstrate robust safety and therapeutic efficacy for specific diseases and disorders. Additionally, preclinical studies of dietary therapy do not adhere to standardized guidelines, which can hinder cross-study interpretation and reproducibility. To that end, my dissertation updates diet implementation guidelines for preclinical studies that adhere to standardized experimental design and biomarker monitoring in mouse models in order to maximize therapeutic efficacy, diet regimen safety, and cross-study interpretability. With these guidelines, I explored the effect of various diets on circulating glucose and ketone bodies in mice, a measure of glycolytic flux, along with biomarkers of health. I found that calorie-restricted diets, regardless of macronutrient composition, lowers circulating glucose and increases circulating ketone levels, along with improving biomarkers of health, including lowering circulating triglyceride levels. In demonstrating the utility of dietary therapy to treat disease, I also explored the mechanisms on how dietary therapy can be used to treat epilepsy in a preclinical mouse model. I showed that reduced glucose utilization underlies the seizure-protective effects of dietary therapy in EL mice, a mouse model of idiopathic epilepsy. Lastly, I developed a novel tool, the Glucose Ketone Index Calculator, to track the progress of dietary therapy in brain cancer patients through a ratio of circulating glucose to circulating ketone bodies. Evidence is presented that demonstrates a low ratio of glucose to ketone bodies is associated with improved prognosis of brain cancer management in humans and mice. Overall, this dissertation demonstrates the utility of dietary therapy in treating disease using standardized guidelines, and suggests the use of a novel tool to apply and track the progress of dietary therapy in the clinical brain cancer population. / Thesis (PhD) — Boston College, 2014. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.