Keto Diets: Beware of Potential Cardiac Problems

Well before the keto diet weight loss craze, low-carbohydrate, high-fat diets (the ketogenic diet) had been used successfully to treat a number of pathological conditions. Ketogenic diets have been in clinical use for over 70 years. The longest use of ketogenic diets has been in patients with medically intractable epilepsy. Infants who inherit a non-functional glucose transporter 1 (GLUT1) have severely impaired energy generation in the brain due to a lack of glucose transport. These infants are effectively treated with a ketogenic diet given that the ketones, acetoacetate and beta-hydroxybutyrate (BHB) freely enter the brain and can be used for energy production. Ketogenic diets have also been used in the clinical treatment of diabetes, cancer, Alzheimer disease, and Parkinson disease.

The current non-clinical setting for ketogenic diets is in the area of weight loss diets. However, a certain level of caution must be understood certain given that several lines of clinical evidence have correlated ketogenic diets with cardiovascular health. For example, the concentration of BHB in heart tissues is significantly higher in patients who suffer from atrial fibrillation. In addition, increased circulating levels of BHB has been independently associated with adverse cardiovascular events in patients undergoing hemodialysis. In individuals practicing the ketogenic diet the occurrence of cardiovascular disease of unknown etiology has been frequently found. A major study also showed that in a 25-year follow-up study of a large population of participants found that a low-carbohydrate diet was statistically associated with increased mortality. It is clear from all these studies that the long-term consumption of a ketogenic diet should be carefully considered.

A study published in 2021 in Signal Transduction and Targeted Therapy clearly demonstrates that increase levels of ketones in the body are associated with the potential for cardiac pathology:

Ketogenic diets inhibit mitochondrial biogenesis and induce cardiac fibrosis

Although this study was primarily carried out using laboratory animals there were correlative studies in humans and with human cardiac cells in culture. The findings of the study demonstrated that long term exposure to BHB results in cardiomyocyte (heart muscle cells) apoptosis (programmed cell death) and the onset of cardia fibrosis. Importantly, these observation were exclusive to BHB and not the other major ketone body, acetoacetate. A contributory factor in the induction of apoptosis and cardiac fibrosis was finding that BHB impairs the biogenesis of mitochondria, the energy producing organelle of the cell.

Within the contest of this finding it is important to understand that, BHB can be used as an alternative fuel in pathological conditions such as in the failing human heart and that the excitation-contraction cycle is improved by BHB during hypoxic conditions. However, it appears that these benefits are likely to be lost in the context of long term ketogenic diet consumption.

What is the TAKE-HOME from this study: Whereas, there is ample evidence to indicated there are benefits to the ketogenic diet, such as weight loss and in pathological states, too much of a good thing may actually turn out to be detrimental to your health.