UK Biobank Analysis: Self-reported LCHF Diet May be Linked to Cardiac Events

By Gerry Chi on

Key Points:

  • In spite of the increase popularity of low-carbohydrate high-fat diet due to purported benefit in a variety of conditions, there is limited data on the effect of LCHF diet on overall lipid profile and risk of ASCVD
  • Compared to the standard diet, regular consumption of a self-reported low-carbohydrate, high-fat diet was associated with elevated levels of total cholesterol (6.08 vs. 5.85 mmol/L; p=0.002), LDL cholesterol (3.80 vs. 3.64 mmol/L; p=0.004), and apolipoprotein B (1.09 vs. 1.04 g/L; p<0.001).
  • At 11 years, LCHF diet was associated with a two-fold risk of incident major adverse cardiac event (MACE; defined as the composite of angina, myocardial infarction, coronary artery disease, ischemic stroke, peripheral arterial disease, or coronary/carotid revascularization) compared to standard diet (9.8% vs. 4.3%; p<0.001).
  • Other covariates linked to a greater MACE risk included diabetes (HR=3.37), current smoking (HR=2.44), and hypertension (HR=1.89).

Regular consumption of low-carbohydrate, high-fat keto-like diet is linked to increased levels of low-density lipoprotein (LDL) cholesterol and a greater risk of cardiovascular disease, according to the analysis of the UK Biobank presented by Iulia Iatan, MD, PhD at the ACC.23/WCC.


Carbohydrates are the primary fuel source for the human body and provide energy for various physiological processes.  Low-carbohydrate, high-fat (LCHF) diets, including the ketogenic diet, limit the intake of carbohydrates such as grains, baked goods, and fruits, and replace them with high-fat sources.  This dietary modification forces the body to utilize fat as a fuel source in the absence of carbohydrates.  The metabolic process of breaking down fat in the liver results in the production of ketones, which serve as alternative energy substrates for the body.  Advocates of the ketogenic diet typically recommend restricting carbohydrate intake to 10% of total daily caloric intake, while consuming 60% to 80% of daily caloric intake from fat.  Furthermore, protein is frequently advised to be maintained within the range of 20% to 30% of daily caloric intake.  Ketogenic diet has gained popularity due to its potential benefits in weight loss and blood sugar control; however, previous studies have demonstrated an association with elevated LDL cholesterol in some populations.


In this observational study, Iatan and colleagues defined an LCHF diet as one consisting of no more than 25% of total daily energy or calories from carbohydrates and more than 45% of total daily calories from fat. The researchers examined data from the UK Biobank, a large prospective population-based dataset with health information from more than 500,000 individuals in the UK who were followed for at least 10 years.  The primary endpoint was the impact of LCHF diet on serum lipid levels; and the secondary endpoint was to investigate the association between LCHF dietary patterns and incident major adverse cardiovascular events. A total of 70,684 participants, completed a one-time self-reported 24-hour diet questionnaire and had blood drawn to check their lipid panels.  Of these participants, 305 were identified as consuming an LCHF diet, mean age 53 and mostly women (73.3%)> They were matched by age and sex with 1,220 individuals who reported consuming a standard diet. The results showed that, compared with those consuming a standard diet, individuals consuming an LCHF diet had significantly higher levels of LDL cholesterol and apolipoprotein B.  Furthermore, after an average follow-up of 11.8 years, those on an LCHF diet had a more than two-fold higher risk of experiencing incident major adverse cardiac events (MACE; defined as the composite of angina, myocardial infarction, coronary artery disease, ischemic stroke, peripheral arterial disease, or coronary/carotid revascularization), even after adjusting for other risk factors. Limitations to the study include the observational nature, the fact that the diet pattern was self-reported, the relatively small sample size.


The study suggests that people considering an LCHF diet should be aware of the potential increase in their levels of LDL cholesterol and consult with a healthcare provider before starting the diet.  During the diet, individuals should have their cholesterol levels monitored and address other risk factors for heart disease or stroke, such as diabetes, hypertension, physical inactivity, and smoking.  The findings also indicate that not everyone responds to an LCHF diet in the same way and that identifying specific characteristics or genetic markers predictive of response to this LCHF diet is an area for future research.


It is essential to note that the study was observational and cannot establish causality between LCHF diet and an increased risk of major cardiac events.  Additionally, the participants provided dietary information at only one time point, which may limit the interpretation of the study findings.  Nevertheless, given that approximately 1 in 5 Americans report following a low-carb, keto-like, or full keto diet, the results highlight the importance of further research in prospectively designed studies to confirm these findings.