Cardiovascular disease (CVD) is the leading cause of death in the United States. Age is a primary risk factor for the development of CVD and middle-age is a vulnerable period where risk factors for the disease begin to exceed diagnostic thresholds. Interest has increased for the use of low carbohydrate high fat (LCHF) ketogenic diets due to their reported improvements for cardiometabolic health. Supplementation with exogenous ketone esters (KE) has been shown to increase plasma β-hydroxybutyrate (BHB) and mimic the metabolic effects of LCHF ketogenic diets. Evidence suggests elevated concentrations of plasma BHB may lower blood pressure, improve vascular function, attenuate hyperglycemic responses, and enhance cognitive function. The majority of research has been conducted in preclinical models, and whether exogenous KE supplementation has similar improvements in humans of any ages remains relatively unanswered. To address this we conducted a randomized, placebo controlled, crossover design study in healthy, sedentary, middle to older aged adults who received the exogenous KE (or placebo), and consumed the supplement for 2-weeks (3x/day, 15 minutes prior to each meal; breakfast, lunch, and dinner). Our first hypothesis was to test that KE supplementation would improve vascular function by increasing flow-mediated dilation, reducing arterial stiffness, and lowering blood pressure. Secondly, we hypothesized that KE supplementation would attenuate the glycemic response to an oral glucose tolerance test, improve glycemic variability, and show reductions in postprandial glucose levels. Thirdly, we tested the hypothesis that KE supplementation would improve cognitive performance by showing improvements in processing speed, memory, attention control, and executive functions. In support of our first hypotheses, KE supplementation increased flow-mediated dilation (8.1 ± 1.3 vs. 7.7 ± 1.2%, p = 0.023), but it did not show any difference in arterial stiffness or blood pressure. In contrast to our second hypotheses, following the KE supplementation intervention there were no significant difference from the placebo in terms of glycemic response, variability or mean 2-hour post-meal glucose. In support of our third hypotheses, we found a significant improvement in measures of working memory (7.55 ± 0.93 vs. 7.27 ± 0.29, p = 0.026) and inhibitory control (80 ± 38 vs. 87 ± 32ms, p = 0.035) following the 14-day KE supplementation. More research is needed to elucidate the effects of KE on cardiometabolic health and cognition. / Doctor of Philosophy / Recently there has been an increase in the popularity of low carbohydrate high fat (LCHF) ketogenic diets, with advocates for the diet claiming increased benefits in weight loss and blood glucose control, therefore leading to an increased interest for its use in the treatment for cardiovascular disease, obesity, and diabetes. As more evidence has accumulated much of the impact LCHF ketogenic diets are said to have, has been attributed to a state known as nutritional ketosis, which occurs in response to the restriction of carbohydrates from the diet. Ketone esters (KE) have been shown to effectively elevate ketone bodies (alternative energy produced by the body during times when glucose stores are low) without the need of altering one's own diet, however, this method of inducing ketosis is still lacking evidence for its impact on cardiometabolic health in humans. The purpose of these studies is to determine the effect of having sustained elevations of ketone bodies on our health and cognition in humans. Study 1 included healthy, sedentary middle to older aged adults who consumed a KE for 2-weeks (3x/day, prior to each meal) and a placebo. Following supplementation participants completed test to assess our vascular health and blood sugar control. Study 2 included healthy, sedentary middle to older aged adults who consumed a KE for the same 2-weeks (3x/day, prior to each meal) and a placebo. Participants underwent a series of tests to assess cognitive performance. Overall, after a 2-week supplementation period we found significant improvements in our blood vessel function and with cognitive performance where we saw improvements in working memory, and inhibitory control.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/111147 |
| Date | 06 July 2022 |
| Creators | Reid, Glen Robertson |
| Contributors | Human Nutrition, Foods and Exercise, Davy, Kevin P., Hedrick, Valisa E., Katz, Benjamin D., Davy, Brenda M. |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Language | English |
| Detected Language | English |
| Type | Dissertation |
| Format | ETD, application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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