More Evidence that Long-Term Keto Diets May Damage the Heart

I had previously written about evidence demonstrating the potential for negative health outcomes associated with long-term keto (high fat, low carb) dieting:

KETO DIETS: BEWARE OF POTENTIAL CARDIAC PROBLEMS

It should be stated that ketogenic diets (KDs) have been used as a treatment for epilepsy for several decades and have been used for patients with diabetes, Parkinson disease, and as adjuvant therapies in the setting of cancer. The increased levels of beta-hydroxybutyrate (BHB), the primary ketone produced by excess fatty acid oxidation, generated by KD has been shown to exert positive effects on life span in rodents. In addition, BHB has been shown to suppress oxidative stress and to exert anti-inflammatory effects. Thus, there are clear benefits to KD but caution related to composition and length of time on a KD needs to be taken into account.

Now there is more evidence that there could be serious health issues, specifically with respect to heart health, with the consumption of keto diets. Granted, although this latest report was carried out in laboratory animals, there is ample evidence that these types of studies can suggest similar outcomes in humans:

Ketogenic diets composed of long-chain and medium-chain fatty acids induce cardiac fibrosis in mice

The majority of fat consumed in the diet is triglyceride which is a molecule of glycerol (a 3-carbon alcohol) to which three fatty acids are attached. When endogenous fatty acids or dietary fatty acids circulate in the blood they are predominantly contained in triglycerides.

With respect to ketogenic diets the fatty acids in the triglycerides can be primarily long-chain length fatty acids (long-chain triglycerides, LCT) or they can be primarily medium-chain length fatty acids (medium-chain triglycerides, MCT), or they can be a combination of both. Numerous studies have demonstrated a higher level of benefit with the consumption of MCT versus LCT since in humans MCT result in higher levels of BHB and in mice MCT result in stronger anti-inflammatory effects.

The contribution of KD to potential cardiac pathology stems from the fact these diets are high in fatty acids and this leads to fatty acid accumulation in tissues and lipid accumulation in the heart is a common cause of heart disease. Fatty acid accumulation will lead to their increased oxidation to hydroxyl radicals, called lipid hydroperoxides. If the KD is high in omega-6 fatty acid this can lead to the accumulation of a particular form of lipid hydroperoxide that covalently binds to proteins altering their functions and also alters mitochondrial function. The lipid hydroperoxide-protein adducts in the heart have been shown to correlate with several cardiovascular diseases.

In this study the ketogenic diets used were designed such that the ratio of fat to carbohydrate was 8 to 1. For control purposes one group of animals was fed normal chow. The LCT diet was composed of mostly 16 carbon (C16) and C18 fatty acids. The MCT diet was a mix of 60% C8 and 40% C10 fatty acids. The LCT/MCT mixed diet was composed of 66% LCT and 34% MCT.

One of the findings from this study showed that both LCT and LCT/MCT diets resulted in significant increases in the levels of plasma BHB when compared to the standard chow diet. Both LCT and LCT/MCT diets also resulted similar body weight gain.

One significant finding was that the metabolic profiles of the LCT diet were distinctly different than those associated with the MCT diet. At the molecular level it was found that the LCT diet resulted in a significant reduction in expression of the gene that encodes the rate-limiting enzyme required for the utilization of ketones but resulted in a significant increase in the expression of one of the genes encoding a ketone synthesis enzyme. These results indicate that the heart is attempting to produce ketones on its own. Ketone synthesis is normally restricted to the liver.

With respect to cardiac pathology the LCT diet was associated with increased collagen fiber content in cardiac muscle, a process that contributes to fibrosis.

TAKE HOME: Various studies on the efficacy, or pathology, of ketogenic diets have begun to show that two critical factors need to be taken into account when choosing to utilize this diet regimen. The first is that the composition of the fatty acids in the diet needs to be carefully chosen. Polyunsaturated fatty acids (PUFA) are the best and omega-3 PUFA are superior to omega-6 PUFA. In addition medium-chain length fatty acids (MCT) are less likely to be associated with cardiac fibrosis than are long-chain fatty acids (LCT). The second consideration needs to be the length of time that one utilizes the KD since long-term use is more likely to be associated with pathologies such as cardiac and liver pathologies.