A study suggests that genetic factors may explain why LDL cholesterol rises sharply in some people who follow a low-carbohydrate, high-fat diet.
Two people can follow the same low-carbohydrate diet and experience very different changes in cholesterol. One may see little difference, while the other develops a sharp increase in low-density lipoprotein (LDL) cholesterol. New findings suggest that inherited genetic differences may help explain why.
Low carbohydrate diets often include substantial amounts of saturated fat, which can raise LDL cholesterol, an important contributor to heart disease risk. The study indicates that genetic predisposition can influence how strongly someone responds to that saturated fat, helping account for the conflicting results reported by people following similar diets.
“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, PhD, RDN, a postdoctoral scholar at Stanford University School of Medicine. Barad will present the findings at NUTRITION 2026, the flagship annual meeting of the American Society for Nutrition, held July 25–28 in National Harbor, Maryland, just outside Washington, D.C.
“These findings highlight that there is real heterogeneity in how people respond to diet. 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,” said Barad.
A major diet trial tests vulnerability
Previous research has found that healthy low-carbohydrate diets may help some people lose weight and manage blood sugar. Their effects on LDL cholesterol, however, have varied considerably. The researchers wanted to determine whether they could identify who might benefit from this type of diet and who could experience a potentially dangerous cholesterol increase.
They turned to data from DIETFITS, a randomized controlled trial involving more than 600 adults who followed either a healthy low-carbohydrate diet or a healthy low-fat diet for one year. The original trial found no significant advantage for either approach in terms of weight loss.
For the latest analysis, the researchers focused on 431 participants whose genetic information was available. They examined how genotype, saturated fat consumption, and assigned diet related to changes in LDL cholesterol between the beginning of the study and the six-month mark.
Genetic risk magnifies saturated fat response
Among people assigned to the low carbohydrate diet, those with a stronger genetic tendency toward high LDL cholesterol were also more likely to experience an increase during the study.
The pattern appeared to reflect heightened sensitivity to saturated fat. Participants with greater genetic risk recorded the largest LDL increases when their diets contained more saturated fat. The researchers did not observe the same relationship among participants following the low-fat diet.
The results suggest that saturated fat intake alone may not fully predict how LDL cholesterol will change. A person’s genetic background may also shape the magnitude of that response.
Genetic scores could guide diet choices
Earlier studies have often examined individual genetic variants one at a time. In this analysis, the researchers combined information from thousands of variants across the genome to create a polygenic score, which estimates a person’s overall inherited tendency toward higher or lower LDL cholesterol.
Barad said such scores could eventually help clinicians identify patients who may be especially likely to experience an unfavorable LDL response after changing their diet. That information could support more individualized dietary guidance rather than applying the same recommendation to everyone.
Genetic testing is not required to act on the study’s broader message. Barad emphasized that responses to dietary changes vary, making it important for people to monitor what happens in their own bodies instead of assuming that a particular eating pattern will produce identical results for everyone.
Additional research will be needed to confirm the findings and determine whether they apply across more diverse populations. Current dietary guidance generally recommends keeping saturated fat below 10% of daily calories and choosing unsaturated fats more often.
For people who prefer a low carbohydrate diet, Barad noted that the source of dietary fat may matter. Nuts, seeds, olive oil and avocado provide alternatives to foods higher in saturated fat, including butter, beef tallow, fatty cuts of meat and processed meats. Favoring those unsaturated sources may help lower the likelihood of an adverse cholesterol response.
Meeting: Nutrition 2026
The DIETFITS trial was funded by grant 1R01DK091831 from the National Institute of Diabetes and Digestive and Kidney Diseases; grants 1K12GM088033 and T32HL007034 from the National Heart, Lung, and Blood Institute; and the Stanford Clinical and Translational Science Award, grant UL1TR001085 from the National Institutes of Health. Dr. Alexa Barad was supported by the American Heart Association Postdoctoral Fellowship (26POST1542318).
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