The Cardioprotective Effects of Nutritional Ketosis: Mechanisms and Clinical Implications

Abstract

Cardiovascular diseases (CVDs) persist as the primary cause of death worldwide, accounting for roughly 17.9 million fatalities each year. The prevalence of obesity, metabolic syndrome, and type 2 diabetes (key risk factors for CVD) continues to escalate at an alarming rate, necessitating novel therapeutic strategies to address this global health crisis. Nutritional ketosis, induced through ketogenic diets, modified fasting, intermittent fasting, and medium-chain triglyceride (MCT) oil consumption, has garnered attention for its potential cardioprotective effects. Ketosis is a metabolic state in which the body, due to a significantly reduced intake of carbohydrates, shifts its primary energy source from glucose to ketone bodies, i.e., beta-hydroxybutyrate (BHB), acetoacetate, and acetone, which are produced in the liver from fatty acids. This review examines the mechanisms by which ketone bodies, particularly BHB, mitigate cardiovascular risk. We focus mainly on the anti-inflammatory and antioxidative properties of BHB and summarize recent evidence to highlight the clinical relevance of ketosis in cardiometabolic health.

Keywords: beta-hydroxybutyrate; cardiovascular risk; inflammation; ketogenic diet; obesity.

Figure 1

The central role of visceral adipose tissue (VAT) in obesity-related cardiometabolic risks. VAT dysfunction contributes to insulin resistance, increased lipolysis, and free fatty acid (FFA) release, disrupting lipid and glucose metabolism. As an endocrine organ, VAT secretes adipokines such as leptin, adiponectin, and resistin, but in obesity, this balance shifts, with decreased beneficial adipokines and increased harmful ones. VAT also drives systemic inflammation by releasing pro-inflammatory cytokines like TNF-α and IL-6 and recruiting macrophages. These processes link VAT dysfunction to the development of type 2 diabetes, atherosclerosis, and coronary artery disease (CAD). Arrows indicate the pathways connecting VAT to these systemic effects.

Figure 2

Mechanisms of cardioprotection of nutritional ketosis. The ketone bodies acetoacetate, D-β-hydroxybutyrate, and L-β-hydroxybutyrate, depicted in the center, have pleiotropic effects that act through different mechanisms. Ketone bodies can modulate inflammatory and oxidant states, lipid metabolism, and endothelial function. A subset or combination of these mechanisms underlies the beneficial effects of ketone administration in the setting of cardiometabolic health.