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The Condition of Ketosis Ketosis is the abnormal accumulation of ketone bodies in the blood as a result of excessive breakdown of fats caused by a deficiency or inadequate use of carbohydrates. A ketone is a chemical structure where oxygen is double-bonded to carbon and is between at least two other carbons. Our body produces three kinds of ketone bodies: acetone, acetoacetate and beta-hydroxybutyrate.1When our body runs out of glucose which is our body’s primary energy source or when glucose levels are low, our liver can generate fatty acids from fat and select amino acids and turn them into ketone bodies so that our body can still function effectively. Fatty acids can not cross the blood brain barrier and therefore this is the reason for which fatty acids are converted to ketone bodies which can cross the barrier. Ketone bodies then become the main source of energy for the body instead of glucose. Ketosis can be seen in starvation, and occasionally in pregnancy if the intake of protein and carbohydrates is inadequate, and most frequently in diabetes mellitus.2Ketosis only becomes life threatening in the case of diabetes. If a diabetic fails to receive insulin, they go into a state of starvation. They may have glucose, but without insulin which helps cells uptake glucose, the glucose cannot get into the cells. The body will begin to make ketone bodies out of fat which will continue to build up and will not stop because diabetics can not produce insulin. PH imbalances begin to occur when levels reach 15 to 25 mMand this can result in other metabolic disorders and in severely ill persons. Nutritional ketosis however, is not necessarily fatal.3 • Positive Effects: • Low-carbohydrate/ high-fat diets consumed for more than 7 days decreases muscle glycogen content and carbohydrate oxidation, which is compensated by increased rates of fat oxidation.1 • When muscle glycogen levels are low, the increase in the ability of skeletal muscle to oxidize fat after a low-carbohydrate diet fails to alter or enhance exercise ability.1 • If enhanced fat utilization is combined with increased carbohydrate availability, this would be beneficial for endurance performance, especially in extremely long exercises such as marathon running, where glycogen stores are likely to become minimal, and we can turn to fat as being our primary energy source.1 • The body adapts to using a different energy source after a week.1 • The capacity for fat oxidation and muscle glycogen sparing does not go away when carbohydrates are introduced back into a person’s diet.1 • For example, if someone is training for a marathon and tried a ketogenic diet for awhile, but then carbohydrate loaded before their actual marathon, their body would still be able to use ketone bodies as an efficient fuel source.1 • Chronic low-carbohydrate/high-fat diets induce powerful metabolic adaptations to enhance fat oxidation. When combined with short periods of carbohydrate intake, these adaptations have been shown to produce superior results compared with other dietary strategies to enhance exercise performance, especially for ultra-endurance exercise.1 • Some of the metabolic and enzymatic changes are still unclear, but enzymatic adaptations are thought to involve muscle fiber-type specificity and to depend on the increase in dietary fat.1 • Fat-adaptation increases resting muscle triglyceride stores and resting AMPK-α1 and -α2 activity.5 • This results in higher rates of whole body fat oxidation, reduced muscle glycogenolysis, and attenuated the exercise-induced rise in AMPK-α1 and AMPK-α2 activity compared with high-carbohydrate diets.5 • This demonstrates that AMPK-α1 and AMPK-α2 activity and fuel selection in skeletal muscle in response to exercise can be manipulated by diet and/or the interactive effects of diet and exercise training.5 • Negative Effects: • Patients following low carbohydrate diets usually complain about lightheadedness, weakness, and fatigue. • The participants from the elite gymnast study testing the effect of the ketogenic diet versus high-carbohydrate diet done were unable to continue and thrive off of the low carbohydrate diet for more than 2 weeks, but most maintained their low-carbohydrate diets for at least 7 days.6 This shows that a ketogenic diet may not be beneficial for athletes whose sport requires short bursts of energy. • Examining the results of Stephen Phinney’s two ketogenic diet performance studies together indicated that both groups experienced a lag in performance across the first week or two of carbohydrate restriction, after which both peak aerobic power and sub-maximal (60–70% of VO2max) endurance performance were fully restored.8 • There are no studies in today’s research that carefully examine the optimum length of this “keto-adaptation” period, but it is longer than one week and likely will advanced within 3–4 weeks.6 • The adaptation process does not appear to happen any faster in highly trained athletes than in overweight or untrained individuals. This adaptation process also appears to require consistent adherence to carbohydrate restriction. People who intermittently consume carbohydrates while attempting a ketogenic diet report subjectively reduced exercise tolerance.6 • These negative results in the scientific literature can be explained by the cultures that traditionally lived by hunting. • Therapeutic use of ketogenic diets should not require constraint of most forms of physical labor or recreational activity, with the one exception that anaerobic (ie, weight lifting or sprint) performance is limited by the low muscle glycogen levels induced by a ketogenic diet. This would strongly discourage its use under most conditions of these types of competitive athletics.7 Fat For Fuel:Ketogenic Diet and Athletic PerformanceDepartment of Health Sciences: DieteticsNutrition 482: Nutrition and Metabolism Fall 2013 KetogenicDiet Nutritional ketosis is the result of a ketogenicdiet, which is a high fat, adequate protein, and low carbohydrate diet. A low carbohydrate diet means a daily consumption of fewer than 50 grams of carbohydrate, regardless of fat, protein or caloric intake.4Switching to a ketogenic diet is something that should be done gradually. Keto-adaptation is achieved through slowly reducing the amount of carbohydrates in a diet so that the body can begin to learn to rely on fat. The person will go from “glucocentric” (getting their primary fuel source from glucose) to “adipocentric” (getting their primary fuel source from fat/ketone bodies). On a ketogenic diet, fatty acids are derived from dietary fat or adipose tissue if the diet does not meet necessary daily caloric requirements. Ketone bodies mediate glucose sparing effects by serving as the preferred energy source for active tissues, such as in the heart and muscle. KetogenicDiet and Exercise There are always athletes out there trying to get the edge in their training, whether it be through steroids, supplements, or some laboratory procedure (blood doping). All of these methods are ways to become a more efficient athlete who can perform at higher levels. What if there was a way to do this by just simply changing the diet that one consumes? It is known that for endurance athletes, a higher percentage of fat is burned during exercise for energy instead of carbohydrates. So in theory, if an athlete trains their body to burn fat more efficiently, fat stores will burn for a longer period of time and glucose stores will be saved for later use. Therefore, scientific research has been done on athletes to test if a ketogenic diet can be beneficial to athletic performance. There have been other studies performed that counteract the positive aspects showing that athletes have had side effects hindering training and performance. Positive and negative effects of a ketogenic diet on athletic performance are as follows. Corey Crowe ‘14 Amanda Sperry ‘14 Jocelyn Tomsic ‘14 Brittany Shannon ‘14 Fig. 1. Simplified illustration of hepatic and cerebral metabolism of relevant substrates in ketosis. 10