Effects of ketone bodies on energy expenditure, substrate utilization, and energy intake in humans

The potential of ketogenic approaches to regulate energy balance has recently gained attention since ketones may influence both energy expenditure and energy intake. In this narrative review, we summarized the most relevant evidence about the role of ketosis on energy expenditure, substrate utilization, and energy intake in humans. We considered different strategies to induce ketosis, such as fasting, dietary manipulation, and exogenous ketone sources. In general, ketosis does not have a major influence on energy expenditure but promotes a shift in substrate utilization towards ketone body oxidation. The strategies to induce ketosis by reduction of dietary carbohydrate availability (e.g., ketogenic diets) do not independently influence energy intake, being thus equally effective for weight loss as diets with higher carbohydrate content. In contrast, the intake of medium-chain triglycerides and ketone esters induces ketosis and appears to increase energy expenditure and reduce energy intake in the context of high carbohydrate availability. These latter strategies lead to slightly enhanced weight loss. Unfortunately, distinguishing the effects of the various ketogenic strategies per se from the effects of other physiological responses is not possible with the available human data. Highly controlled, inpatient studies using targeted strategies to isolate the independent effects of ketones are required to adequately address this knowledge gap.