Keto Fuel for the Heart May Drive New CVD Therapies

The same ketones involved in diabetic ketoacidosis could have a protective role in cardiovascular disease (CVD), animal and human studies suggested.

Emerging evidence points to several cardiovascular benefits to these metabolites, according to B. Daan Westenbrink, MD, PhD, of University Medical Center Groningen in the Netherlands, and colleagues:

• Fuel for cardiac energetics: ketones act as ancillary fuel for the failing heart given that they require less oxygen per molecule of ATP generated
• Pleiotropic effects on other cellular processes: ketones are linked to improved endothelial function, protection from oxidative stress, direct targeting of inflammation, and slowdown of pathological cardiac remodeling
• Systemic effects on cardiovascular risk factors: ketones are associated with modest systolic blood pressure reduction and weight loss, although data are mixed for effects on blood glucose and lipid profile

Research from the heart failure space supports some of these benefits, Westenbrink’s group noted in their review paper published online in the Journal of the American College of Cardiology.

“Although metabolic perturbations in heart failure have been studied since the 1930s, it took more than 80 years before the metabolic switch toward increased ketone metabolism was discovered by two independent research groups in 2016,” he and his team said.

In addition, other groups have suggested that SGLT2 inhibitors may confer cardiovascular benefits in diabetic and nondiabetic patients alike through increases in circulating ketone bodies. However, such a causal link “remains controversial,” according to the review authors. Sympathetic nervous system dampening has also been proposed as a mechanism of action for SGLT2 inhibitors.

Ketone bodies are produced largely by the liver from fatty acids during periods of low food intake, prolonged intense exercise, alcoholism, or in untreated type 1 diabetes. They provide supplemental energy to multiple organs.

These metabolites can be achieved in several ways, though they all carry risk for provoking GI distress:

• “Keto diet” (very low in carbohydrates, high in fat)
• Ingestion of ketone precursors (e.g., 1,3-butanediol, medium-chain triglyceride)
• Supplementation with exogenous sources (e.g., ketone salts, ketone ester)

“While the keto diet has become increasingly popular, there are concerns about untoward effects on the heart. However, administration of ketones may be an alternative to a keto diet as a means of elevating ketone bodies for their protective effects,” Westenbrink suggested in a press release.

“Regardless of the pathway to achieve ketosis, ketone bodies have potential clinical applications that require further exploration, including new therapeutic approaches to harness the beneficial effect of ketosis. In the coming years, we will learn whether ketone bodies can be beneficial and optimized to be used in treatment and prevention of CVD,” his group concluded.