Doctor of Philosophy, The Ohio State University, 2021, Kinesiology

Although cognitive decline occurs at a higher rate in advancing age, a substantial number of cases are also attributed to poor metabolic health. A key component of brain plasticity and cognitive function is Brain Derived Neurotropic Factor (BDNF). BDNF is a neuronal protein that promotes the survival of neurons through growth and maturation. BDNF expression is decreased in conditions associated with cognitive decline as well as metabolic diseases. One novel strategy to naturally improve metabolic health and elevate BDNF is by increasing circulating ketones, achievable though a ketogenic diet and/or exogenous ketones. Increasing ketone concentrations, specifically Beta-Hydroxybutyrate (BHB), is associated with increased BDNF concentrations based primarily on in vitro and animal experiments, but the relevance in humans remains unclear. The overarching purpose of this dissertation is to elucidate how various methods of inducing ketosis influence plasma levels of BDNF in humans. This will be achieved by analyzing ketone and plasma BDNF concentrations from active and sedentary adults consuming ketogenic diets and/or exogenous ketones. Such information is expected to advance our understanding of the factors determining BDNF levels, which may prove useful in optimizing interventions aimed at preventing neurocognitive decline and/or potentially improving cognitive performance. Study 1: Ketone Salt and Caffeine Supplementation with Acute Exercise explored how acute ingestion of a ketone salt prior to high-intensity exercise influenced the metabolic response to exercise and performance in a group of healthy recreationally-trained adults who were habitually consuming either a mixed diet (Keto-Naive) or a ketogenic diet (Keto-Adapted). Acute exercise significantly increased BDNF concentrations immediately and 30-min postexercise in both groups, but there was no effect of the ketone salt despite significantly increasing BHB levels. Study 2: Prolonged Ketogenic Diet and Resistanc (open full item for complete abstract)

Committee: Jeff Volek (Advisor); Craig McElroy (Committee Member); Brian Focht (Committee Member); William Kraemer (Committee Member) Subjects: Kinesiology; Nutrition; Physiology

Master of Science, The Ohio State University, 2021, Kinesiology

Ketogenic diets (KDs) that elevate beta-hydroxybutyrate (BHB) promote weight and fat loss. Exogenous ketones, such as ketone salts (KS), also elevate BHB concentrations with the potential to protect against muscle loss during caloric restriction. Whether augmenting ketosis with KS impacts body composition responses to a well-formulated KD remains unknown. The primary goal of this study was to compare the effects of energy-matched, hypocaloric KD feeding (<50g carbohydrates/day; 1.5 g/kg/day protein), with and without the inclusion of KS, on weight loss and body composition responses. Overweight and obese adults were provided a precisely defined hypocaloric KD (~75% of energy expenditure) for six weeks. In a double-blind manner, subjects were randomly assigned to receive ~24 g/day of a racemic BHB-salt (KD+KS; n = 12) or placebo (KD+PL; n = 13). A matched comparison group (n = 12) was separately assigned to an isoenergetic/isonitrogenous low-fat diet (LFD). Body composition parameters were assessed by dual x-ray absorptiometry and magnetic resonance imaging. The KD induced nutritional ketosis (>1.0 mM capillary BHB) throughout the study (p < 0.001), with higher fasting concentrations observed in KD+KS than KD+PL for the first two weeks (p < 0.05). Significant losses were detected in body mass, whole body fat and lean mass, mid-thigh muscle cross-sectional area, and both visceral and subcutaneous adipose tissues (p < 0.001), but no group differences between the two KDs or with the LFD. Urine urea nitrogen excretion was significantly higher in KD+PL than LFD (p < 0.01) and trended higher in KD+PL compared to KD+KS (p = 0.076), whereas the nitrogen excretion during KD+KS was similar to LFD (p > 0.05). Energy-matched hypocaloric ketogenic diets favorably affected body composition but were not further impacted by administration of an exogenous BHB-salt that augmented ketosis. The attenuated nitrogen loss trend induced by the BHB-salt, if manifested over a longer period of (open full item for complete abstract)

Committee: Jeff Volek Dr. (Advisor); William Kraemer Dr. (Committee Co-Chair) Subjects: Kinesiology

Master of Science, The Ohio State University, 2020, Kinesiology

Background & Aims: The ketogenic diet (KD) has been shown to be effective at reversing manifestations of insulin resistance including non-alcoholic fatty liver disease (NAFLD). Whether KDs have an advantage over low-fat diets to decrease liver fat when matched for energy under controlled conditions remains unclear, as does the impact of exogenous ketone supplementation. The primary objective of this study was to compare composite liver fat responses to a precisely controlled hypocaloric ketogenic diet, with and without an exogenous ketone supplement, versus an energy-matched low-fat diet in overweight/obese adults. Approach and Results: Adults with excess weight and variable liver fat at baseline (mean 4.9%, range 0.5 to 23.0) were assigned to precisely controlled hypocaloric (75% of energy expenditure) 6 week diets that were ketogenic (KD+PL), ketogenic with ketone salt supplementation (KD+KS), or low fat (LFD). Weight loss was significant (P<0.001) but similar between groups (6.7 to 8.5% of initial body mass, p > 0.05). Composite liver fat assessed by magnetic resonance imaging decreased significantly (p=0.004) but was similar across KD+KS (-42%), KD+PL (-32%), and LFD (-52%) groups (p > 0.05). In the subset of individuals with NAFLD (liver fat >5%), the decreases in liver was of greater magnitude, but similar between the KD groups (-56%, n=7) and LFD (-60%, n=5). There were changes in serum albumin and alkaline phosphatase concentrations over time but no differences between groups. Neither AST nor ALT responses were significant. Conclusions: These results indicate that short-term hypocaloric KDs decrease liver fat independent of supplementation with exogenous ketones and to a similar extent as an energy-matched low-fat/high-carbohydrate diet.

Committee: Jeff Volek PhD, RD (Advisor); Orlando Simonetti PhD (Committee Member) Subjects: Nutrition; Physiology

Master of Science, The Ohio State University, 2018, Kinesiology

As research begins to broaden our understanding of the effects of low carbohydrate, high fat ketogenic diets to different populations, it is crucial to utilize empirical evidence associated with the metabolic and physiological adaptation of chronic implementation. Specific populations are finding that nutritional ketosis may prove advantageous to athletic or cognitive performance. Nutritional ketosis may be identified by an elevated plasma ketone concentration within the blood range > 0.5 to 5 mmol/L that resulted results from a chronic implementation of a ketogenic diet. Recently, science shows that ketones contribute to a vast range of therapeutic and performance benefits associated with nutritional ketosis, as a result, exogenous ketone supplements have become commercially available which have proven to induce acute nutritional ketosis without restriction of carbohydrate intake. However, as research increased for exogenous ketones on a mixed diet populationWe previously showed that a supplement cpontaining ketone salts and caffeine significantly increased performance in a non-ketoadapted population. , To date, there are no reports of whether ketone supplements have an ergogenic effect research has not shown what enhanced benefits may come from exogenous ketones in an already keto-adapted population. The primary purpose of this study was to replicate a previous study with exogenous ketones on a non-keto-adapted group of participants with a completely regulated keto-adapted groupdetermine the performance and metabolic effects of a supplement containing ketone salts and caffeine in a group of people habituated to a ketogenic diet. Twelve habitually ketogenic, recreationally trained individuals (3 female, 9 male: mean + SD age, 36.1 + 7.5 years; weight, 82.2 + 7.1 kilograms; height, 177.7 + 8.5 cm; VO2max 40.3 + 10.5 ml/kg/min). participated in two experimental sessions in a randomized and balanced order. Subjects consumed either a ketone-salt/caffeine supplement con (open full item for complete abstract)

Committee: Jeff Volek (Advisor); William Kraemer (Committee Chair); Carl Maresh (Committee Chair) Subjects: Kinesiology; Nutrition; Physiology