Low-Carb Diets Raise LDL Cholesterol Risk by Genetics

If you suspect a health complaint traces back to what is happening in your gut or your bloodstream, a low-carb, high-fat diet like keto is one of the most common places people start experimenting. It is also, according to a new analysis of the UK Biobank, one of the diets most likely to quietly push cholesterol into dangerous territory in a specific subset of people: those whose genes already predispose them to high LDL. The catch is that most people never find out which group they are in until after the fact.

Key Takeaways

• In a UK Biobank cohort, people on a low-carb, high-fat (LCHF) diet had higher LDL cholesterol and a roughly two-fold higher risk of a major cardiovascular event over nearly 12 years of follow-up than matched peers on a standard diet.
• The cholesterol jump was not evenly spread: it was concentrated almost entirely in people who already carried a high genetic risk score for elevated LDL, while people with an average genetic score barely budged.
• The study is observational, based on self-reported diet, so it cannot prove the diet directly caused the heart events, but the pattern held up across several sensitivity checks.
• The authors suggest genetic testing could eventually help identify who should think twice, or at least monitor cholesterol closely, before going low-carb.

Low-Carb, High-Fat Diets Were Linked to Higher LDL and More Heart Events

Researchers found that adults following a low-carbohydrate, high-fat (LCHF) diet, defined as under 25% of daily calories from carbohydrates and over 45% from fat, had significantly higher LDL cholesterol (LDL-C, the "bad" cholesterol that builds up in artery walls) and apolipoprotein B (apoB, a protein tag on LDL and related particles that many cardiologists consider an even more precise risk marker) than people eating a standard diet. In the most tightly matched group, 305 people on an LCHF diet and 1,220 matched people on a standard diet who had both a same-day diet questionnaire and blood draw, average LDL-C was 3.81 mmol/L versus 3.64 mmol/L, and apoB was 1.10 g/L versus 1.04 g/L. Over a mean follow-up of 11.8 years, 9.8% of the LCHF group had a major adverse cardiovascular event (MACE, meaning heart attack, unstable angina, stroke, peripheral artery disease, or a revascularization procedure) compared with 4.3% of the standard-diet group, a difference that held at more than double the risk (adjusted hazard ratio 2.18) after accounting for diabetes, smoking, hypertension, and body mass index. The findings, published in the journal JACC: Advances, come from the UK Biobank, a long-running health study of roughly half a million UK adults.

The Risk Was Concentrated in People With a High Genetic Cholesterol Score

Not everyone on a low-carb diet saw their cholesterol move. The researchers used a polygenic risk score (PRS, a single number combining the effect of many genetic variants that individually barely nudge LDL but collectively predict a person's baseline tendency toward high cholesterol) to sort participants into those in the top 20% for genetic LDL risk and everyone else. Among people with that elevated PRS, LDL-C on an LCHF diet averaged 4.38 mmol/L versus 3.85 mmol/L on a standard diet, and severe hypercholesterolemia (LDL-C above 5.0 mmol/L, a level generally flagged for closer monitoring) was nearly three times more common on the low-carb diet, 32.3% versus 10.6%. Among people without that elevated genetic score, the diet made essentially no difference: 3.55 mmol/L versus 3.56 mmol/L, a gap the researchers said was not statistically meaningful. A formal interaction test confirmed the diet's effect on LDL-C was significantly stronger in the high-PRS group than the rest of the cohort. This matters most for anyone with a family history of high cholesterol or heart disease, since a polygenic predisposition to high LDL, not a single "cholesterol gene," is what the researchers say is driving the split.

Researchers Tracked Over 10,000 UK Biobank Participants for Nearly 12 Years

The study drew on the UK Biobank, matching each low-carb dieter to four people on a standard diet by age and sex. The main analysis included 2,034 people who had completed at least one 24-hour dietary questionnaire and reported an LCHF pattern, matched against 8,136 standard-diet controls, with cardiovascular outcomes tracked through hospital admission records to late 2021. A stricter subset of 305 LCHF participants, whose dietary questionnaire was completed on the same day as their blood draw, allowed the researchers to compare diet and lipid levels at the same point in time rather than relying on a diet reported months or years before or after a blood test. The researchers also checked participants' DNA for rare mutations that cause familial hypercholesterolemia (a single-gene disorder that causes very high LDL from birth) and found none in the low-carb group, ruling out that explanation and pointing instead to the cumulative, polygenic genetic score as the driver.

What This Means if You Are Already Following a Low-Carb Diet

The study does not say low-carb diets are unsafe for everyone, and it does not establish that carbohydrate restriction itself, rather than something else about the people who choose it, caused the extra heart events. What it does suggest is that if you are on or considering an LCHF or ketogenic diet, checking a full lipid panel, including apoB or an LDL-C reading, after a few months is a reasonable step, especially if you have a personal or family history of high cholesterol or early heart disease. The researchers found that severe hypercholesterolemia on this diet was not explained by rare single-gene mutations, so a "normal" family history does not fully rule out an outsized response; a polygenic risk score, not yet standard in routine care, would be needed to flag it in advance. Anyone whose LDL-C climbs into the range flagged in this study, above 5.0 mmol/L (about 193 mg/dL), is worth discussing with a doctor rather than assuming the numbers will settle on their own.

The Study Cannot Prove the Diet Caused the Extra Heart Events

Because this is an observational cohort, not a randomized trial, the researchers cannot rule out that other differences between people who choose a low-carb diet and those who do not are driving part of the result. People on the LCHF diet in this study were more likely to already have diabetes (4.9% versus 1.7%) and obesity (26.3% versus 19.8%) at the start of the study, both of which independently raise cardiovascular risk. The association with heart events held up even after statistically excluding participants with diabetes, but residual confounding, meaning risk factors the researchers could not fully measure or adjust for, cannot be excluded. Diet was also assessed with a 24-hour recall questionnaire, a validated tool but one prone to recall error and a poor substitute for tracking what someone eats over months or years. The cohort was also predominantly of White British descent, so it is unclear whether these findings generalize to other populations.

Genetic Screening Could Eventually Shape Diet Advice

The study's authors say their next step is refining how a genetic risk score for LDL could be used in clinical practice, potentially flagging in advance who is likely to see a sharp cholesterol spike on a low-carb diet before they start one, rather than discovering it months later on a blood test. That kind of routine genetic screening is not yet standard in primary care, and the authors themselves call for further research, including the American Heart Association's 2021 scientific statement on popular dietary patterns, which already places very-low-carbohydrate and ketogenic diets in its lowest alignment tiers for heart health, partly for the same saturated-fat concerns this study highlights.

Common Questions

Does this mean keto causes heart disease? The study cannot prove causation because it is observational. It found a strong association between an LCHF diet and both higher LDL cholesterol and more cardiovascular events, an association that persisted after adjusting for several known risk factors, but a randomized trial would be needed to establish cause and effect.

How do I know if I have a high genetic risk score for LDL cholesterol? Polygenic risk scores for LDL are not yet part of routine clinical checkups. For now, a personal or family history of high cholesterol or early heart disease, combined with a standard lipid panel before and after starting a low-carb diet, is the most accessible way to gauge your own risk.

Is apoB a better test than standard cholesterol? Many cardiologists consider apolipoprotein B (apoB) a more precise measure of artery-clogging particles than LDL-C alone, since it counts every particle capable of contributing to plaque, not just the cholesterol they carry. This study measured both and found both were elevated on the low-carb diet.

Should I stop a low-carb diet based on this study? The researchers do not recommend stopping outright. They suggest closer cholesterol monitoring, particularly for people with a family history of high cholesterol, and note the American Heart Association already ranks very-low-carbohydrate diets lower for cardiovascular alignment than patterns like Mediterranean or DASH.

References

Iulia Iatan, Kate Huang, Diana Vikulova, Shubhika Ranjan, Liam R. Brunham (2024). Association of a Low-Carbohydrate High-Fat Diet With Plasma Lipid Levels and Cardiovascular Risk. JACC: Advances. https://doi.org/10.1016/j.jacadv.2024.100924