'Keto-like' Diet Linked to Doubling of Heart Disease Risk

March 07, 2023

Consumption of a low-carbohydrate, high-fat diet, dubbed a "keto-like" diet, was associated with an increase in LDL levels and a twofold increase in the risk for future cardiovascular events, in a new observational study.

"To our knowledge this is the first study to demonstrate an association between a carbohydrate-restricted dietary platform and greater risk of atherosclerotic cardiovascular disease," said study investigator Iulia Iatan, MD, PhD, University of British Columbia, Vancouver, Canada.

"Hypercholesterolemia occurring during a low-carb, high-fat diet should not be assumed to be benign," she concluded.

Iatan presented the study March 5 at the American College of Cardiology (ACC) Scientific Session/World Congress of Cardiology (WCC) 2023.

The presentation received much media attention, with headlines implying a causal relationship with cardiac events based on these observational results. But lipid expert Steven Nissen, MD, Cleveland Clinic, Cleveland, Ohio, warned against paying much attention to the headlines or to the study's conclusions.

To theheart.org | Medscape Cardiology, Nissen pointed out that the LDL increase in the "keto-like" diet group was relatively small and "certainly not enough to produce a doubling in cardiovascular risk."

"The people who were on the 'keto-like' diet in this study were different to those who were on the standard diet," he commented. "Those on the 'keto-like' diet were on it for a reason — they were more overweight, they had a higher incidence of diabetes, so their risk profile was completely different. Even though the researchers tried to adjust for other cardiovascular risk factors, there will be unmeasured confounding in a study like this."

He said he doesn't think this study "answers any significant questions in a way that we want to have them answered. I'm not a big fan of this type of diet, but I don't think it doubles the risk of adverse cardiovascular events, and I don't think this study tells us one way or another." 

For the study, Iatan and colleagues defined a low-carbohydrate, high-fat diet as consisting of no more than 25% of total daily energy from carbohydrates and more than 45% of total daily calories from fat. This is somewhat higher in carbohydrates and lower in fat than a strict ketogenic diet but could be thought of as a 'keto-like' diet.

They analyzed data from the UK Biobank, a large-scale prospective database with health information from over half a million people living in the United Kingdom who were followed for at least 10 years.

On enrollment in the Biobank, participants completed a one-time, self-reported 24-hour diet questionnaire and, at the same time, had blood drawn to check their levels of cholesterol. The researchers identified 305 participants whose questionnaire responses indicated that they followed a low-carbohydrate, high-fat diet. These participants were matched by age and sex with 1220 individuals who reported eating a standard diet.

Of the study population, 73% were women and the average age was 54 years. Those on a low carbohydrate/high fat diet had a higher average body mass index (27.7 vs 26.7) and a higher incidence of diabetes (4.9% vs 1.7%).

Results showed that compared with participants on a standard diet, those on the "keto-like" diet had significantly higher levels of both LDL cholesterol and apolipoprotein B (ApoB).

Levels of LDL were 3.80 mmol/L (147 mg/dL) in the keto-like group vs 3.64 mmol/L (141 mg/dL) in the standard group (P = .004).  Levels of ApoB were 1.09 g/L (109 mg/dL) in the keto-like group and 1.04 g/L (104 mg/dL) in the standard group (P < .001).

After an average of 11.8 years of follow-up, 9.8% of participants on the low-carbohydrate/high-fat diet vs 4.3% in the standard diet group experienced one of the events included in the composite event endpoint: angina, myocardial infarction, coronary artery disease, ischemic stroke, peripheral arterial disease, or coronary/carotid revascularization.

After adjustment for other risk factors for heart disease — diabetes, hypertension, obesity, and smoking — individuals on a low-carbohydrate, high-fat diet were found to have a twofold risk of having a cardiovascular event (HR, 2.18; P < .001).

"Closer Monitoring Needed"

Senior author Liam Brunham, MD, University of British Columbia, commented to theheart.org | Medscape Cardiology: "Our results have shown, I think for the first time, that there is an association between this increasingly popular dietary pattern and high LDL cholesterol and an increased future risk of cardiovascular events. This is concerning as there are many people out there following this type of diet, and I think it suggests there is a need for closer monitoring of these people."

He explained that while it would be expected for cholesterol levels to rise on a high-fat diet, "there has been a perception by some that this is not worrisome as it is reflecting certain metabolic changes. What we've shown in this study is that if your cholesterol does increase significantly on this diet then you should not assume that this is not a problem.

"For some people with diabetes this diet can help lower blood sugar and some people can lose weight on it," he noted, "but what our data show is that there is a subgroup of people who experience high levels of LDL and Apo B and that seems to be driving the risk."

He pointed out that overall the mean level of LDL was only slightly increased in the individuals on the low-carb/high-fat diet but severe high cholesterol (more than 5 mmol/L or 190 mg/dL) was about doubled in that group (10% vs 5%). And these patients had a sixfold increase in risk of cardiovascular disease (P < .001).   

"This suggests that there is a subgroup of people who are susceptible to this exacerbation of hypercholesterolemia in response to a low-carb/high-fat diet."

Brunham said his advice would be that if people choose to follow this diet, they should have their cholesterol monitored, and manage their cardiovascular risk factors.

"I wouldn't say it is not appropriate to follow this diet based on this study," he added. "This is just an observational study. It is not definitive. But if people do want to follow this dietary pattern because they feel there would be some benefits, then they should be aware of the potential risks and take steps to mitigate those risks."

Jury Still Out

Nissen said in his view "the jury was still out" on this type of diet. "I'm open to the possibility that, particularly in the short run, a 'keto-like' diet may help some people lose weight and that's a good thing. But I do not generally recommend this type of diet."

Rather, he advises patients to follow a Mediterranean diet, which has been proven to reduce cardiovascular events in a randomized study, the PREDIMED trial.

"We can't make decisions on what type of diet to recommend to patients based on observational studies like this where there is a lot of subtlety missing. But when studies like this are reported, the mass media seize on it. That's not the way the public needs to be educated," Nissen commented. 

"We refer to this type of study as hypothesis-generating. It raises a hypothesis. It doesn't answer the question. It is worth looking at the question of whether a ketogenic-like diet is harmful. We don't know at present, and I don't think we know any more after this study," he added.

The authors of the study report no relevant financial relationships.

American College of Cardiology (ACC) Scientific Session/World Congress of Cardiology (WCC) 2023. Late-Breaking Clinical Trials. Presented March 5, 2023.

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