Scientists carrying out an observational study concluded that following a keto-like low-carbohydrate, high-fat diet, is linked to an increase in LDL levels and a twofold increase in the risk for future cardiovascular events, although an expert was sceptical of their findings.
“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 Dr Iulia Iatan, PhD, University of British Columbia, Vancouver.
“Hypercholesterolemia occurring during a low-carb, high-fat diet should not be assumed to be benign,” she added.
Iatan presented the study at the recent American College of Cardiology (ACC) Scientific Session/World Congress of Cardiology (WCC) 2023.
However, lipid expert Dr Steven Nissen of Cleveland Clinic, Ohio, warned against paying much attention to the study’s conclusions.
He said that the LDL increase in the “keto-like” diet group was relatively small and “certainly not enough to produce a doubling in cardiovascular risk”.
“Those on the keto-like diet in this study were different from 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 and 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 did not 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 ‘keto-like’.
They analysed data from the UK Biobank, a large-scale prospective database with health information from more than half a million people living in the United Kingdom who were followed for at least 10 years.
On enrolment in the Biobank, participants completed a one-time, self-reported 24-hour diet questionnaire and had blood drawn to check their cholesterol levels. The researchers identified 305 participants whose responses indicated they followed a low-carbohydrate, high-fat diet, and they were matched with 1 220 individuals who followed a standard diet.
Of the study population, 73% were women and the average age was 54. 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, ischaemic stroke, peripheral arterial disease, or coronary/carotid revascularisation.
After adjustment for other risk factors for heart disease – diabetes, hypertension, obesity, and smoking – those 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 Dr Liam Brunham, University of British Columbia, said: “Our results have shown… an association between this increasingly popular dietary pattern and high LDL cholesterol and an increased future risk of cardiovascular events. This is concerning as many people out there follow this type of diet, and it suggests there is a need for closer monitoring.”
While it would be expected for cholesterol levels to rise on a high-fat diet, “there has been a perception that this is not worrisome as it is reflecting certain metabolic changes”.
“What we’ve shown is that if your cholesterol does increase significantly on this diet then you should not assume 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, but our data show that a subgroup experienced high levels of LDL and Apo B and that seems to be driving the risk.”
He said overall, the mean level of LDL was only slightly increased in those 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 a subgroup of people is susceptible to this exacerbation of hypercholesterolemia in response to a low-carb/high-fat diet.”
This was just an observational study and was not definitive, he said. But if people want to follow this dietary pattern because they feel there would be some benefits, they should be aware of the potential risks and take steps to mitigate those.”
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, this kind of diet may help some people lose weight. But I do not generally recommend it.”
Rather, he advises patients to follow a Mediterranean diet, which has been proven to reduce cardiovascular events.
“We can’t make decisions on what type of diet to recommend based on observational studies like this where there is a lot of subtlety missing.
“We refer to this type of study as hypothesis-generating. 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.”
Study details
Association of A Low-carbohydrate High-fat (Ketogenic) Diet with Plasma Lipid Levels and Cardiovascular Risk In A Population-based Cohort
Iulia Iatan, Kate Huang, Diana Vikulova, Shubhika Ranjan, Liam Brunham.
Presented at The American College of Cardiology (ACC) Scientific Session/World Congress of Cardiology (WCC) 2023 on 5 March 2023.
Background
Low-carbohydrate high-fat (LCHF) or ketogenic diets (KDs) have attracted interest because of their purported health benefits for a variety of conditions, including obesity and diabetes. These dietary patterns typically involve a high intake of saturated fats and restriction of carbohydrates in order to induce ketogenesis. In some individuals, LCHF diets can lead to hypercholesterolemia. However, there are limited data on the effect of KDs on the risk of atherosclerotic cardiovascular disease.
Methods
We examined the association between a LCHF diet and lipids as well as incident major adverse cardiovascular events in the UK Biobank. In this population-based cohort study, serum lipids and nuclear magnetic resonance metabolomic markers were collected at baseline in 70,714 participants. Dietary patterns were assessed using a 24-hour online food questionnaire completed at enrolment. We defined a LCHF diet as consumption of <100 grams of carbohydrates per day. We matched each case on a KD with age- and sex-matched individuals on a standard diet (SD) in a 1:4 ratio.
Results
In total, 3048 controls and 762 subjects on a LCHF diet were included in the analysis. Mean age (55.1±7.81) and sex distribution (79.8% females) were similar in both groups. Body mass index was 27.2 and 26.6 kg/m2 in patients on a KD and SD, respectively (p=0.005). Patients on the LCHF diet had significantly higher levels of βhydroxybutyrate, acetoacetate and acetone (p<0.001). Levels of low-density lipoproteincholesterol (LDL-C) and apolipoprotein B were significantly increased in individuals on a KD as compared to controls (p<0.001). After a mean of 11.3 years of follow-up, rates of incident cardiovascular events were significantly greater in participants reporting a LCHF diet compared to controls (8.7% vs 5.5%, p=0.0017). In Cox regression analyses, this difference was statistically significant after adjustment for diabetes, smoking, hypertension and obesity (hazard ratio 1.54; 95% confidence interval 1.16 to 2.05, p=0.003).
Conclusion
In a large population-based cohort, consumption of a LCHF diet was associated with increased LDL-C and apolipoprotein B and a greater risk of incident cardiovascular events.
Medscape article – ‘Keto-like’ diet linked to doubling of heart disease risk (Open access)
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