Effect of Acute and Chronic Ingestion of Exogenous Ketone Supplements on Blood Pressure: A Systematic Review and Meta-Analysis

Abstract

Exogenous ketone supplements have been suggested to have potential cardiovascular benefits, but their overall effect on blood pressure is unclear. Our objective was to perform a systematic review and meta-analysis on the effects of exogenous ketone supplements on blood pressure (BP) and concomitant changes in resting heart rate (HR). Five databases were searched on January 27^th, 2023, for randomized and non-randomized studies. A random-effects model meta-analysis was performed including all studies jointly and separately for acute and chronic ingestion of ketone supplements. Out of 4012 studies identified in the search, 4 acute and 6 chronic studies with n = 187 participants were included. Pooled results (n = 10) showed no change in systolic (SMD [95% CI]= −0.14 [−0.40; 0.11]; I²= 30%; p = 0.17) or diastolic BP (−0.12 [−0.30; 0.05]; I²= 0%; p = 0.69), with a potential tendency observed toward increased resting heart rate (0.17 [-0.14; 0.47]; I²= 40%; p = 0.10). Similar results for systolic and diastolic BP were observed when assessing separately the effect of acute and chronic ingestion of ketone supplements (p ≥ 0.33). Supplement dosage was found to modulate the increase in resting heart rate (0.019 ± 0.006; p = 0.013; R²=100%), suggesting that higher supplement doses lead to a higher resting heart rate. Based on currently available data, acute or prolonged ingestion of ketone supplements does not seem to modulate BP. However, a tendency for HR to increase after acute ingestion was observed, particularly with higher doses. Higher quality studies with appropriate standardized measurements are needed to confirm these results.

Keywords:

• BHB
• hemodynamic response
• β-hydroxybutyrate
• ketosis
• β-OHB
• Vascular function

Authors contribution

The conceptualization of the study was performed by every author. Literature search, selection of the studies, and full scrutiny of full article by A.M-C and R.T Independent reviewers K.F and E.R arbitrated any disagreements in the study inclusion; Quality assessment using the Cochrane Bias tool (ROB-2 and ROBINS-I) was done by A.M.C, R.T and K.F; Statistical analysis was done by K.F as well as an independent statistician; Original writing and preparation was done by A.M-C under the supervision of J.L and E.R. All authors have read and agreed to the published version of this manuscript.

Competing interests

JPL is volunteer Chief Scientific Officer for the not-for-profit Institute for Personalized Therapeutic Nutrition. JPL holds founder shares in Metabolic Insights Inc., a for-profit company that developed noninvasive metabolic monitoring devices.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was not supported by any grant. A.M.C was supported by the Frederick Banting Charles Best CIHR doctoral scholarship, R.T. was supported by the CIHR master’s graduate scholarship. E.R. co-holds a Research Chair for a successful aging and J.L. was supported by a Michael Smith Foundation for Health Research (MSFHR) Scholar Award (16890).

Notes on contributors

Alexis Marcotte-Chénard

Alexis Marcotte-Chénard, is a PhD candidate at the University of Sherbrooke, investigating the effects of non-pharmaceutical approaches on the management of cardiovascular diseases.

Renaud Tremblay

Renaud Tremblay, is a master student at the University of Sherbrooke, investigating the effects of high-intensity interval training and resistance exercises on metabolic disorders, particularly on cardiovascular health.

Kaja Falkenhain

Kaja Falkenhain, is a PhD student at the University of British Columbia, investigating the effects of endogenous and exogenous ketosis on cardiometabolic health.

Jonathan P. Little

Jonathan P. Little, is Professor in the School of Health and Exercise Sciences at the University of British Columbia. He leads the Exercise, Metabolism, and Inflammation Laboratory and conducts research with the goals of optimizing exercise and diet interventions for the prevention, treatment, and reversal of type 2 diabetes.

Eléonor Riesco

Eléonor Riesco, is Professor at the Faculty of physical activity sciences at the University of Sherbrooke and researcher at the Research Center on Aging, CIUSSS de l’Estrie – CHUS. She conducts research on the effects of exercise on chronic diseases in the elderly, metabolism, immunity and health outcomes.