Certain traditional risk factors including severe high cholesterol, diabetes, hypertension and smoking may increase CV risk among those following a low-carbohydrate, high-fat “keto-style diet,” a speaker reported here.

In a population-based cohort study, regular consumption of a low-carbohydrate, high-fat diet was associated with elevated LDL cholesterol and apolipoprotein B levels, and an increased risk for incident major adverse coronary events (MACE), Iulia Iatan, MD, PhD, FRCPC, postdoctoral fellow in cardiovascular disease prevention, clinical lipidology and cardiometabolic health at the Centre for Heart Lung Innovation at the University of British Columbia, Vancouver, said during a presentation at the American College of Cardiology Scientific Session.

“Low-carbohydrate, high-fat diets, like ketogenic diets, have become increasingly popular due to the purported health benefits for a variety of conditions, including epilepsy, obesity and glycemic control for diabetes. This can be seen by the number of increasing publications in the last 10 years and monthly Google searches reaching up to 3.3 million results for ‘ketogenic diet.’ In fact, in 2021, approximately 16% of Americans and 14% of Canadians followed a low-carbohydrate dietary pattern in the previous year. These diets are generally characterized by restrictions of carbohydrates and a relative increase in the proportion of fat,” Iatan said.

However, Iatan said, “despite the patients who report subjective improvements in their wellbeing during these diets, a known risk of the diets is that they may trigger or exacerbate hypercholesterolemia.”

Impact on lipids, CV events

There remains limited data on the effect of low-carbohydrate, high-fat diet — or, keto-style diet — on overall lipid profile and risk for atherosclerotic CVD, Iatan said.

The researchers conducted a prospective, population-based cohort study, using the U.K. Biobank database to identify adults aged 40 to 69 years recruited from 2006 to 2010 who completed 24-hour dietary surveys.

The keto-style diet was defined as restricting daily intake of carbohydrates to less than 100 g and/or less than 25% of total daily energy intake and fat more than 45% total daily energy intake. A standard diet was defined as daily dietary parameters not meeting the criteria for the keto-style diet.

Iatan reported results from 305 participants who followed a keto-style diet and 1,220 who followed a standard diet who were not on lipid-lowering therapy. The mean age was 54 years, 73% were women and the majority were white.

At baseline, those following a keto-style diet were more likely to have diabetes, elevated BMI and obesity, according to the results. Based on self-reports, individuals who followed a keto-style diet consumed fewer total kcal per day and fewer carbohydrates, free sugars and plant proteins intake, but elevated intake of animal proteins and animal, plant and saturated fats, compared with those who followed a standard diet.

The primary endpoint was the impact of a keto-style diet on serum lipid levels. Those following a keto-style diet had significantly elevated levels of some lipids and ketone bodies, including:

• LDL cholesterol (3.8 vs. 3.64 mmol/L; P = .004);
• ApoB (1.09 vs. 1.04 g/L; P < .001);
• total cholesterol (6.08 vs. 5.85 mmol/L; P = .002);
• 3-hydroxybutyrate (0.14 vs. 0.06 mmol/L; P < .001);
• acetone (0.02 vs. 0.01 mmol/L; P < .001); and
• acetoacetate (0.02 vs. 0.01 mmol/L; P < .001).

The researchers reported lower levels of lipoprotein(a) (39.43 vs. 46.13 nmol/L; P = .041) and triglycerides (1.34 vs. 1.53 mmol/L; P = .001) with a keto-style diet.

The overall prevalence of severe hypercholesterolemia (> 5 mmol/L) was higher among individuals who followed a keto-style diet (11.1% vs. 6.2%; P < 001), Iatan told Healio.

The impact of a keto-style diet on incident MACE, including angina, MI, CAD, ischemic stroke, peripheral arterial disease, and coronary and carotid revascularization, was the study’s secondary endpoint. The proportion of the cohort that experienced an ASCVD event was higher among those who followed a keto-style (4.3% vs. 9.8%). Following adjustment for diabetes, hypertension, smoking and BMI, the risk for incident ASCVD events was more than twofold among patients following a keto-style diet compared with a standard diet (HR = 2.18; 95% CI, 1.39-3.43; P for all < .001), Iatan told Healio.

In a subgroup analysis, patients who followed a keto-style diet and had an LDL level of 5 mmol/L or more had a nearly sevenfold greater risk for ASCVD compared with those who followed a standard diet and had an LDL level less than 3.5 mmol/L (HR = 6.68; 95% CI, 2.62-17.09; P < .001), according to the results.

Hypercholesterolemia ‘should not be presumed to be benign’

“Based on our results for the primary and secondary endpoints, we show that in this population-based cohort of British descent, habitual consumption of a self-reported low-carb, high-fat diet was associated with increased LDL cholesterol and ApoB levels and increased risk of incident MACE,” Iatan concluded. “These findings highlight the potential CV risk of this dietary pattern and suggest that hypercholesterolemia during this low-carb high-fat diet should not be presumed to be benign.”

Editor’s Note: This article was updated on March 6, 2023, to reflect updated data.

Perspective

Alice H. Lichtenstein, DSc

The outcome of long-term consumption of a keto-style diet likely depends on the type of foods — hence, the type of fat — that predominates. If animal fat — meat and milk fat — predominates, high in saturated fat, it is not surprising the researchers reported a positive association with elevated CVD risk. Given LDL cholesterol levels were higher, that is likely the case in this study. If a person decides to follow a keto-style diet and gets their fats predominantly from plant sources, high in unsaturated fat such as plant oils — soybean, canola, corn, olive, nuts and seeds — it is very possible the results will be different.

There is a paper that recently came out in Diabetes Care in patients with type 2 diabetes that supports this premise (Hu Y, et al. Diabetes Care. 2023;doi:10.2337/dc22-2310).

Alice H. Lichtenstein, DSc

Gershoff Professor of Nutrition Science and Policy

Director and Senior Scientist, Cardiovascular Nutrition Laboratory

Tufts University

JM USDA Human Nutrition Research Center on Aging