Your friend cuts carbs, loses weight, feels better, and their cholesterol stays steady. You follow a similar plan, but your LDL cholesterol spikes. The difference might not be willpower or discipline. It might be partly written into your DNA.
A new analysis of a yearlong clinical trial suggests genetics may help explain why people’s cholesterol responds differently to dietary changes. Among participants following a low-carb diet, increases in saturated-fat intake were linked to larger rises in LDL cholesterol in those with a stronger inherited tendency toward high LDL. In the lower saturated fat group, genetic risk did not appear to amplify the relationship between saturated-fat intake and LDL changes in the same way.
The caveat matters: The findings have so far appeared only in a conference abstract, a common way to share new research. The results remain preliminary until a full, peer-reviewed paper assesses them.
The analysis drew on genetic data from 481 people who completed the 2018 DIETFITS clinical trial, a major study that compared healthy low-carb and healthy low-fat diets over a year. It found that, on average, both approaches led to similar weight loss.
In the DIETFITS study, “healthy” meant emphasizing vegetables and minimally processed foods while limiting added sugars, refined flour, and trans fats. The low-carb group cut back on grains and starchy foods; the low-fat group reduced oils, fatty meats, and full-fat dairy.
Researchers examined LDL changes over six months, reported saturated-fat intake, and a polygenic score, which is essentially a genetic risk report card that adds up thousands of small DNA differences linked to LDL cholesterol. It’s like a weighted average of many small genetic nudges, some pushing LDL up, and some down.
On average, participants substantially reduced carbohydrates without significantly increasing saturated fat intake. However, among those with a greater genetic tendency toward high LDL cholesterol, participants who ate more saturated fat experienced larger LDL increases. The abstract does not identify which foods accounted for the differences in saturated fat intake.
Genes: Just One Piece of the Puzzle
Not every expert is convinced the polygenic score is ready for personal use. Jonny Bowden, a board-certified nutrition specialist, said genetics can help shape how we may respond to dietary fat. However, he questioned whether the genetic score used in this study is useful to guide someone’s personal diet choices.
“In consultations, we look at the clinically relevant genes, not thousands of them,” he told The Epoch Times. “Two people can eat essentially the same low-carb, higher-saturated-fat diet and have dramatically different lipid responses because of their underlying genetics.”
No single gene test can determine the best fats for you to eat or whether your LDL cholesterol will rise after a diet change. Lucia Aronica, a nutrition scientist who lectures at the Stanford University School of Medicine on personalized nutrition, said genetic research may eventually help make dietary guidance more personal, but for now it cannot dictate what an individual should eat.
“Dietary response is highly individualized,” Aronica told The Epoch Times, adding that genetic risk is only one factor. Metabolic health, body composition, sex, weight changes, and the foods used to replace carbohydrates can also shape a person’s cholesterol response. For now, Aronica views genetics as “a promising research tool rather than a validated way to predict an individual’s LDL response.”
One gene that comes up is ApoE, which helps transport fats through the blood. “There are people who, genetically, because they have a copy of the ApoE4 gene, are likely to have trouble with saturated fat,” Bowden said. APOE comes in four different types. The highest risk variant is having any copies of E4 from either parent.
Study results vary, though, so having the APOE gene alone cannot reliably predict whether a person’s LDL will rise on a low-carb diet higher in saturated fat.
Some rare cases should not be overlooked. Familial hypercholesterolemia is an inherited condition that causes very high LDL cholesterol from birth and, without treatment, can lead to early heart disease. “Familial hypercholesterolemia can profoundly affect LDL levels and cardiovascular risk and should be identified and managed appropriately,” Aronica said.
Look Beyond LDL
The DIETFITS measured LDL cholesterol and total cholesterol. Those are important tests, but neither gives a complete picture of heart-disease risk.
“I do not think any single marker tells the whole story,” Aronica said. For people on a low-carb diet, she also watches triglycerides and HDL cholesterol, since cutting carbs tends to improve both.
In plain terms, cutting carbs often lowers triglycerides—a type of blood fat—and raises HDL, the “good” cholesterol that helps clear excess cholesterol from the bloodstream. But that doesn’t automatically erase concern about a large or lasting LDL rise. She finds ApoB especially useful. “Each atherogenic lipoprotein particle contains one ApoB molecule, so it provides an estimate of the number of circulating particles capable of entering the arterial wall,” she said.
LDL tells you how much cholesterol is being carried; ApoB tells you how many particles are carrying it. Bowden put the limits of LDL simply: “It’s a marker. It’s not the risk.”
Aronica also considers more test markers than cholesterol measures alone. “Ultimately, I integrate the lipid profile with blood pressure, glycemic status, insulin resistance, family history, and other clinical risk factors,” she said.
She also considers non-HDL cholesterol and lipoprotein(a), or Lp(a), an inherited cholesterol-carrying particle in the blood that can add to heart-disease and stroke risk if high. U.S. guidelines recommend measuring Lp(a) at least once in adulthood, since, unlike LDL, it’s largely determined by genetics rather than diet.
Not All Low-Carb Diets Look Alike
“Low-carb” only describes what a person eats less of. It does not say what foods they eat instead.
One low-carb diet may include olive oil, avocado, nuts, seeds, fatty fish, eggs, non-starchy vegetables, and minimally processed proteins. Another may lean heavily on butter, cream, bacon, sausage, cheese, coconut oil, and highly processed keto snack foods.
Both qualify as low in carbohydrates. But, nutritionally, they can be worlds apart in fiber, processing, and the types of fat they contain.
“I’m not making the case that that study is wrong, or that saturated fat is wonderful for everybody. Things have to be looked at in context,” Bowden said.
That context matters for interpreting this analysis too: Participants substantially cut carbohydrates without significantly increasing the total amount of saturated fat they ate.
“I would not interpret that finding to mean that saturated fat is irrelevant or that everyone will respond the same way,” Aronica said. The preliminary abstract does not specify which foods drove the changes in saturated fat intake the researchers observed.
What to Do If Your LDL Rises
If LDL rises substantially after starting a low-carb diet, Aronica would first change the diet’s fat sources rather than automatically abandon carbohydrate restriction.
“I would shift some of the fat toward extra-virgin olive oil, avocado, nuts, seeds, and fatty fish, while reducing reliance on butter, cream, and fatty processed meats,” she said.
She also recommends non-starchy vegetables, minimally processed foods, and adequate fiber within a person’s carbohydrate target—then repeating blood tests to see if the numbers move.
Bowden takes a wider view, looking at ApoB, fasting insulin, inflammation, triglycerides, HDL cholesterol, blood pressure, waist size, sleep, stress, and physical activity. “Risk is a picture. It’s a puzzle with lots of pieces,” he said.
If questions remain after repeat testing and clinical assessment, imaging can sometimes add clarity. Coronary artery calcium scanning can identify calcified plaque in coronary arteries, while carotid ultrasound can look for plaque in neck arteries.
“Biomarkers help us estimate risk,” Aronica said, “but imaging can sometimes help us determine whether atherosclerosis [plaque buildup in the arteries] is actually present.”
The preliminary DIETFITS finding does not show that low-carb diets are inherently harmful or that saturated fat affects everyone in the same way. It suggests that genes, metabolic health, and food choices can all affect how any one person’s cholesterol responds to cutting carbs.
“The question is not simply whether low-carb diets are good or bad,” Aronica said. “It is which version of a low-carb diet, for which person, and with what measurable response.”
Genes alone do not determine your health outcomes. But they may be one more reason a one-size-fits-all approach to diet doesn’t work—and one more argument for personalizing your diet.