Ketosis may benefit cardiometabolic health in CVD

February 23, 2021

2 min read


Westenbrink and Yurista report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

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Ketosis, as achieved via ketogenic diet or supplements, may improve cardiometabolic health in patients with CVD, particularly HF, according to a review published in the Journal of the American College of Cardiology.

“We found that data from experimental and human studies suggest ketone bodies exert protective effects on patients with heart disease. As heart disease remains the leading killer worldwide, determining new ways to offer cardiac protection is vital to this patient population,” B. Daan Westenbrink, MD, PhD, cardiologist and translational scientist at University Medical Center Groningen in the Netherlands, said in a press release. “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.”

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Ketone bodies and the heart

According to the review, ketone bodies are produced by the liver, particularly during prolonged fasting, insulin deprivation and extreme exercise, and act as an efficient substrate for cardiac metabolism because they require less oxygen per adenosine triphosphate (ATP) molecule generated. In the early stages of structural heart disease, substrate utilization switches from fatty acids to glucose utilization and oxidative metabolism is reduced, which sets the stage for myocardial energy starvation and the development of HF, researchers reported. In HF, the heart may reprogram metabolism to increase reliance on ketone bodies, according to the study.

“Separate studies demonstrated that circulating ketone concentrations and cardiac ketone utilization are increased in a variety of clinical conditions, including heart failure with reduced ejection fraction and HF with preserved ejection fraction,” Salva R. Yurista, MD, PhD, of the department of cardiology at University Medical Center Groningen, and colleagues wrote. “Plasma beta-hydroxybutyrate and cardiac utilization thereof are also increased in patients with diabetes and arrhythmogenic cardiomyopathy, suggesting that the ketogenic shift is a universal cardiac response to stress.”

Option for supplementation

According to the review, ketosis can be achieved by raising the body’s levels of circulating beta-hydroxybutyrate by supplementation with:

  • 1,3-butanediol, which can raise beta-hydroxybutyrate to 0.3 mmol/L to 0.8 mmol/L but has a bitter taste, may cause gastrointestinal distress and a low state of alcohol intoxication;
  • medium-chain triglyceride, which can raise beta-hydroxybutyrate to 0.3 mmol/L to 1 mmol/L but has a bitter taste and may cause gastrointestinal distress;
  • ketone salts, which can raise beta-hydroxybutyrate to 1 mmol/L to 3 mmol/L but may cause cation overload and gastrointestinal distress; and
  • ketone ester, which can raise beta-hydroxybutyrate to 2 mmol/L to 6 mmol/L but has a bitter taste and may cause gastrointestinal distress.

Prior research in animals demonstrated that ketone bodies may also lower BP, body weight and blood glucose and improve the lipid profile in mice and rats. Further research is needed in humans, according to the researchers.

“The keto diet has become extremely popular, both within and outside of the medical arena. The keto diet consists of a very low-carbohydrate and high-fat diet that forces the body into endogenous ketosis,” the researchers wrote. “Although sustained keto diet can raise blood beta-hydroxybutyrate to 2 to 4 mmol/L, long-term compliance is low, often due to gastrointestinal distress.”

“With numerous pathways to achieve ketosis, ketone bodies have potential clinical implications that require further study,” Westenbrink said in the press release. “Further exploration of therapeutic approaches to harness the beneficial effects of ketosis are necessary. I believe in the coming years we will have a much better grasp on whether ketone bodies can be optimized and used in the treatment and prevention of heart disease.”

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