People can follow similar low-carb diets and see very different changes in their LDL cholesterol. Preliminary research suggests part of that variation may be related to genetics, particularly when a low-carb diet includes more saturated fat.
The findings come from a secondary analysis of the DIETFITS randomized clinical trial and were presented at NUTRITION 2026, the annual meeting of the American Society for Nutrition. Because the analysis has not yet been published in a peer-reviewed journal, the results should be considered preliminary.
Researchers studied 431 adults with overweight or obesity who had been assigned to follow either a healthy low-carbohydrate diet or a healthy low-fat diet. They examined participants’ genetic tendency toward higher LDL cholesterol, changes in saturated fat intake and changes in LDL cholesterol after six months.
LDL cholesterol is commonly associated with increased cardiovascular risk, although an individual’s overall risk depends on more than a single laboratory measurement.
The researchers found that greater saturated fat intake and higher genetic risk were each associated with larger increases in LDL cholesterol in both diet groups. However, genetics appeared to make a greater difference among participants following the low-carb diet.
“Our findings suggest that some individuals may be more sensitive to the LDL cholesterol-raising effects of saturated fat, particularly in the context of a low-carbohydrate diet, because of their genetic background,” said Alexa Barad, a postdoctoral scholar at Stanford University School of Medicine.
Among people in the low-carb group, the relationship between saturated fat and LDL cholesterol became stronger as genetic risk increased. Participants in the highest third for genetic risk experienced an estimated 10.5 mg/dL greater rise in LDL cholesterol for each standard-deviation increase in saturated fat intake. The estimate was 5 mg/dL in the middle group. In the lowest-risk group, the association was small and statistically uncertain.
The study does not mean that everyone with a genetic tendency toward higher LDL cholesterol will experience a major increase on a low-carb diet. It also does not show that low-carb diets are inherently harmful.
Instead, the findings suggest that the kinds of foods used to replace carbohydrates may matter, and that people may respond differently even when following the same general eating pattern.
Low-carb diets can vary widely. Some emphasize vegetables, nuts, seeds, fish, avocado and olive oil. Others rely more heavily on butter, fatty cuts of meat, processed meats and other foods high in saturated fat.
That distinction may help explain why studies of low-carb diets have reported mixed effects on LDL cholesterol.
“These findings highlight that there is real heterogeneity in how people respond to diet,” Barad said. “Dietary conversations can sometimes become overly simplified. One person may say, ‘Low-carb diets always raise LDL cholesterol,’ while another says, ‘My LDL cholesterol did not change at all.’ Our findings suggest that both experiences can be true, depending, at least in part, on the individual’s genetic makeup.”
The researchers used a polygenic score, which combines information from many genetic variants, to estimate each participant’s inherited tendency toward higher LDL cholesterol.
Such scores are mainly research tools and are not routinely needed to make decisions about diet. The study did not test whether giving people genetic results helped them choose a better diet or avoid an increase in LDL cholesterol.
It also did not examine heart attacks, strokes or other clinical outcomes. The researchers measured changes in LDL cholesterol, not whether those changes led to disease.
The analysis was limited to adults ages 18 to 50 with overweight or obesity, and the findings may not apply to older adults, people at lower weights or populations with different genetic backgrounds. Only participants with complete genetic, diet and cholesterol data were included, which reduced the sample from the original DIETFITS trial.
Still, the results offer a practical reason to avoid assuming that a popular eating pattern will affect everyone in the same way.
People who make a major dietary change, especially one that increases foods high in saturated fat, may want to have their cholesterol checked and discuss the results with a health care professional. Someone whose LDL cholesterol rises may be able to adjust the diet by choosing more unsaturated fats from foods such as nuts, seeds, olive oil and avocado.
The findings do not establish an ideal low-carb diet or suggest that genetic testing is necessary. They instead reinforce a simpler message: individual responses matter and measuring those responses can provide more useful information than relying on another person’s experience.
The DIETFITS trial was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute and the Stanford Clinical and Translational Science Award from the National Institutes of Health. Barad was supported by an American Heart Association postdoctoral fellowship.