Dissertation Defence: Effects of Carbohydrate Restriction and Exogenous Ketosis on Cardiometabolic Health

Kaja Falkenhain, supervised by Dr. Jonathan Little, will defend their dissertation titled “Effects of Carbohydrate Restriction and Exogenous Ketosis on Cardiometabolic Health” in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Kinesiology.

An abstract for Kaja Falkenhain’s dissertation is included below.

Examinations are open to all members of the campus community as well as the general public. Registration is not required for in person defences.

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ABSTRACT

Ketosis, defined as a state of elevated ketone bodies in the blood, has regained attention for its potential to improve cardiometabolic health, particularly in individuals at risk for, or living with, chronic diseases such as obesity or type 2 diabetes (T2D). However, ketosis can be achieved endogenously (e.g., via means of a ketogenic diet) or exogenously via ingestion of oral ketone supplements; and the cardiometabolic effects thereof remain incompletely understood. This dissertation aims to (1) provide insight into the effects of a ketogenic diet on cardiometabolic health with a particular focus on blood lipids, and (2) advance the understanding of the effects of exogenously induced ketosis on glucose metabolism. To this end, we first conducted two systematic reviews and meta-analyses to critically evaluate the current state of the evidence on each topic. Subsequent chapters then present findings from randomized clinical trials examining how ketogenic interventions affect cardiometabolic health. Firstly, N = 155 adults with overweight or obesity were randomized to follow a 12-week dietary intervention delivered via an mHealth app promoting either a Mediterranean-style ketogenic diet or a low-fat calorie-restricted diet. Results showed significantly greater weight loss and improvements in aspects of cardiometabolic health (including glycaemic control and liver health) following the ketogenic diet intervention, with no detrimental effect on blood lipids. Secondly, adults with T2D completed two randomized placebo-controlled double-blind crossover trials to evaluate the effect of acute exogenous ketone supplement ingestion on plasma glucose concentration (N = 18), and the effect of 14-day thrice daily pre-meal exogenous ketone supplementation on free-living glycaemic control (N = 15). Results showed that oral ingestion of an exogenous ketone supplement did not reduce plasma glucose concentration when consumed acutely in a fasted state, and did not alter markers of glycaemic control across 14 days. Collectively, this dissertation highlights the potential of ketosis to improve some aspects of cardiometabolic health in adults living with chronic disease, thereby warranting further research on the differential health effects of endogenous and exogenous ketosis.