The janus face of ketone bodies in hypertension

Abstract

Hypertension is the most important risk factor for the development of terminal cardiovascular diseases, such as heart failure, chronic kidney disease, and atherosclerosis. Lifestyle interventions to lower blood pressure are generally desirable prior to initiating pharmaceutical drug treatments, which may have undesirable side effects. Ketogenic interventions are popular but the scientific literature supporting their efficacy is specific to certain interventions and outcomes in animal models and patient populations. For example, although caloric restriction has its own inherent difficulties (e.g. it requires high levels of motivation and adherence is difficult), it has unequivocally been associated with lowering blood pressure in hypertensive patients. On the other hand, the antihypertensive efficacy of ketogenic diets is inconclusive, and this is surprising, given that these diets have been largely helpful in mitigating metabolic syndrome and promoting longevity. It is possible that side effects associated with ketogenic diets (e.g. dyslipidemia) aggravate the hypertensive phenotype. However, given the recent data from our group, and others, reporting that the most abundant ketone body, b-hydroxybutyrate, can have positive effects on endothelial and vascular health, there is hope that ketone bodies can be harnessed as a therapeutic strategy to combat hypertension. Therefore, we conclude this review with a summary of the type and efficacy of ketone supplements. We propose that ketone supplements warrant investigation as low-dose antihypertensive therapy that decreases total peripheral resistance with minimal adverse side effects.

Compositional alterations of the gut microbiota in acute myocardial infarction patients with type 2 diabetes mellitus

“…In addition, a ketogenic diet can improve cardiac energy expenditure and reduce oxygen use to improve cardiovascular diseases, such as high blood pressure ( 37 ). This might be because β-hydroxybutyric acid exerts a protective effect on the endothelium and blood vessels ( 37 - 39 ).…”

Calponin 2 regulates ketogenesis to mitigate acute kidney injury

“…From the perspective of cellular localization, Hmgcs2 is specifically expressed in proximal tubules ( Figure 4 ). Its functions, other than systemic ketone provision, likely include antiinflammation and anti–oxidative stress ( 36 , 37 ). In circumstances where damaged proximal tubules are unable to fully recover, it could cause a metabolic switch along with AKI progression ( 38 ).…”

Genome-wide characterization of circulating metabolic biomarkers

“…The discovery regarding this potential causal relationship between acetone and hypertension is noteworthy, since the data on the role of ketogenic diets in hypertension are suggestive but inconclusive 58,59 and ketone bodies have also emerged as potential therapeutic agents for coronary disease 60 . This finding concords with preclinical and human studies that link interventions that alter levels of ketone bodies, such as ketogenic diets and ketone salt supplementation, with changes in blood pressure 61,62 , leading to suggestions that ketone bodies could be a promising potential therapeutic strategy for hypertension and other cardiovascular diseases 60,63 . The mechanisms by which ketone bodies influence risk of hypertension are currently unclear, with both indirect (for example, obesity and diabetes) and direct (for example, sympathetic nervous system activity, vasodilation and cardiac endothelial cell proliferation) pathways being suggested [64][65][66] .…”