The ketogenic diet, first conceived as a last-ditch method to relieve severe epilepsy, has been adopted by many as a viable option for weight loss. A ketogenic diet is extremely low in carbohydrates and forces the body to burn fats instead of carbohydrates for energy. This works because the human body has evolved to be able to burn fat as a stopgap measure to stay alive during periods of starvation until its preferred food, carbohydrate, becomes available again. But is sustained eating of such a diet safe?
Burning fat for energy, or to put this more precisely, the oxidation of fatty acids, causes the production of ketone bodies by the liver which end up in the bloodstream and reach other areas of the body. Ketone bodies include acetoacetate, beta-hydroxybutyrate and acetone, with beta-hydroxybutyrate being the most abundant. Early studies suggested that low-carbohydrate diets such as the keto diet might decrease cardiovascular incidents and mortality. Recent studies however no longer support this hypothesis (1,2,3). On the contrary, higher levels of beta-hydroxybutyrate in the body are now being linked to poor heart health and have been implicated in atrial fibrillation (an irregular and often rapid heart rate that can increase the risk of stroke, heart failure and other heart-related complications) and in the development of other types of cardiovascular disease (CVD). Indeed, long-term consumption of a keto diet may not be safe at all (4).
Many animal studies are bringing to light the fact that long-term exposure to a ketogenic diet has adverse effects on the heart. For example, a 2020 study on rats found that the ketogenic diet increased blood pressure, oxidative stress, inflammation and the incidence of fibrosis of the heart (abnormal thickening of the heart muscle with impaired heart function). (5)
A study from 2021 also examined keto diet effects, this time in rats and humans. The keto diet in rats was once again associated with cardiac fibrosis as well as to a decrease in the number of mitochondria in cells of the heart. Mitochondria are the powerhouses of cells where food is turned into energy. The keto threat to mitochondria was linked to the activation of an enzyme, SIRT7, by beta-hydroxybutyrate that inhibits mitochondria production. When the researchers of this study looked at human patients with atrial fibrillation, the level of the ketone body beta-hydroxybutyrate was found to be 3.3 times higher on average than in patients with normal heart rhythm. Increased SIRT7 levels were observed and numbers of mitochondria were reduced in the humans as well. (4)
Research from 2019 analyzed the health records of almost 14,000 people looking for a relationship between carbohydrate intake and atrial fibrillation. Results showed that low-carbohydrate diets were associated with increased atrial fibrillation risk regardless of the type of protein or fat used to replace the carbohydrate. (6)
A 2013 systematic review and meta-analysis looked at seventeen high-quality, long-term population-based studies of people originating from multiple nations that had investigated low-carbohydrate diets and their long-term effects on mortality and the incidence of CVD. Results revealed that low-carbohydrate diets were associated with a 53% higher risk of death from any cause and observed that they offered no benefits for cardiovascular health. In fact, long-term consumption of low-carbohydrate diets low in nutritional quality seemed to cause cardiovascular harm. Low-carbohydrate diets such as the keto diet tend to be deficient in fiber and fruit and high in protein from animal sources as well as in cholesterol and saturated fat, all aspects that are risk factors for CVD and mortality. These diets simply contain a lower content of healthful components such as bioactive compounds (including phytochemicals and antioxidants), fiber, minerals and vitamins. When dietary sub-groups were analyzed in this review, low-carbohydrate diets consisting of animal-based foods were associated with increased risk of mortality and CVD while low-carbohydrate diets concentrating on plant-based foods were linked to decreased risk of mortality and CVD. The researchers concluded that the possible short-term benefits of low-carbohydrate diets for weight loss may well be irrelevant because of their potential for increasing the risks of chronic diseases and that such diets should no longer be recommended (7).
More research is required on this topic. Animal studies can only point out possible effects that might carry over to human beings and the research using human subjects so far shows mostly associations of low-carbohydrate diets with adverse effects on the heart, and not cause and effect. What is needed now are randomized controlled trials performed in humans. However, there already exist more than enough published trials sending out the warning that eating a diet very low in carbohydrates might well be damaging the heart.
There’s no need to jump on the keto diet bandwagon anyway. The BROAD study from New Zealand, published in 2017, demonstrates a better path to follow. It examined 65 overweight or obese participants (BMI greater than 25), with a diagnosis of one of type-2 diabetes, ischemic heart disease or the cardiovascular risk factors of hypertension or hypercholesterolemia. Participants were randomized to either an intervention group who received standard medical care plus a diet improvement program, or a control group who received standard medical care only. Intervention participants were encouraged to eat whole grains, legumes, vegetables and fruits along with starches such as potatoes, sweet potatoes, bread, cereal and pasta to satisfy the appetite. They were also instructed to avoid refined oils and animal products (meat, fish, eggs and dairy) and to limit intake of high-fat plant foods (nuts, avocados) and highly processed foods. They were told that they could eat as much of the allowed foods as they desired and were counselled to avoid counting calories. (8)
The result? The intervention group displayed an average reduction in BMI of 4.4 at 6 months and of 4.2 at 12 months along with a weight loss average of 27 pounds at 6 months and 25 pounds at 12 months. The control group showed no significant reductions in BMI at 3 or 6 months and only small losses of weight. In other words, significant weight loss was achieved in the intervention group and maintained for at least a year. The BROAD study intervention participants also enjoyed significant improvements in cholesterol and other health risk factors. The researchers concluded with this statement. “To the best of our knowledge, this research has achieved greater weight loss at 6 and 12 months than any other trial that does not limit energy intake or mandate regular exercise.” (8)
In a 2018 interview, Dr. Kim Williams, an eminent US cardiologist and former president of the American College of Cardiology, stated that no one should adopt a ketogenic diet over the long term (9). Instead, consider embracing a sustainable diet consisting of unprocessed plant-based foods including fruits, vegetables, legumes, whole grains, nuts and seeds. Such a way of eating is well supported by evidence as being the best chance to realize the goal of a long, healthy and vibrant life.
1 Lagiou, P., Sandin, S., Lof, M., Trichopoulos, D., Adami, H.-O., Weiderpass, E. Low carbohydrate-high protein diet and incidence of cardiovascular diseases in Swedish women: prospective cohort study. BMJ. 2012 Jun 26; 344:e4026. Doi: 10.1136/bmj.e4026.
2 Trichopoulou, A., Psaltopoulou, T., Orfanos, P., Hsieh, C.-C., Trichopoulos, D. Low-carbohydrate-high-protein diet and long-term survival in a general population cohort. Eur J Clin Nutr. 2007 May; 61(5): 575-581. Doi: 10.1038/sj.ejcn.1602557.
3 Lagiou, P., Sandin, S., Weiderpass, E., Lagiou, A., Mucci, L., et al. Low carbohydrate-high protein diet and mortality in a cohort of Swedish women. J Intern Med 2007. 261: 366–374.
4 Xu, S., Tao, H., Cao, W. et al. Ketogenic diets inhibit mitochondrial biogenesis and induce cardiac fibrosis. Sig Transduct Target Ther. 2021; 6(54). Doi.org/10.1038/s41392-020-00411-4.
5 You, Y., Guo, Y., Jia, P. et al. Ketogenic diet aggravates cardiac remodeling in adult spontaneously hypertensive rats. Nutr Metab (Lond) 17, 91 (2020). https://doi.org/10.1186/s12986-020-00510-7.
6 Zhuang, X., Zhang, S., Zhou, H., Du, Z. and Liao, X. U-Shaped Relationship between Carbohydrate Intake and incident Atrial Fibrillation. J Am Coll Cardiol. 2019 Mar. 73 (9_Supplement_2).
7 Noto, H., Goto, A., Tsujimoto, t., Noda, M., Manzoli, L. Low-Carbohydrate Diets and All-Cause Mortality: A Systematic Review and Meta-Analysis of Observational Studies. PLoS One. 2013; 8(1): e55030. Doi: 10.1371/journal.pone.0055030
8 Wright, N., Wilson, L., Smith, M., Duncan, B., McHugh, P. The BROAD study: A randomised controlled trial using a whole food plant-based diet in the community for obesity, ischaemic heart disease or diabetes. Nutr Diabetes. 2017;7(3):e256.