Low-carb diets have become increasingly popular, but their effects on cholesterol are far from uniform. Some people see little change, while others experience a substantial increase. New research suggests genetics may help explain why.
The findings indicate that saturated fats, which may make up a larger proportion of some low-carbohydrate diets, may interact with a person’s genetic makeup to increase low-density lipoprotein (LDL) cholesterol, a major contributor to heart disease risk. This genetic influence could help explain why two people who eat similar diets can have very different cholesterol responses.
“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, due to their genetic background,” said Alexa Barad, PhD, RDN, a postdoctoral researcher at Stanford University School of Medicine. Barad presented the findings at NUTRITION 2026, the flagship annual meeting of the American Society for Nutrition.
“These findings highlight that there is real heterogeneity in how people respond to diet. Diet conversations can sometimes be oversimplified. One person may say, ‘Low-carb diets always raise LDL cholesterol,’ while another says, ‘My LDL cholesterol didn’t change at all.’ Our findings suggest that both experiences may be true, depending, at least in part, on the individual’s genetic makeup,” Barad said.
Why low-carb diets affect people differently
Previous research has found that healthy low-carb diets can help some people lose weight and improve blood sugar control. However, its impact on LDL cholesterol has been inconsistent.
The researchers wanted to determine whether genetic information could help identify people who are most likely to benefit from eating fewer carbohydrates and those who may instead experience a potentially dangerous increase in LDL cholesterol.
The analysis used data from DIETFITS, a randomized controlled trial involving more than 600 adults who followed a healthy low-carbohydrate diet or a healthy low-fat diet for one year. The original trial found no significant advantage for either diet when it came to weight loss.
For the new analysis, the researchers focused on 431 DIETFITS participants for whom genetic data was available. They examined how genotype, saturated fat intake, diet type, and changes in LDL cholesterol were related from baseline to 6 months.
Genetics and saturated fats linked to increases in LDL
Among participants assigned to the low-carbohydrate diet, those who were genetically predisposed to having higher LDL cholesterol were more likely to experience an increase.
The researchers found that greater sensitivity to saturated fat seemed to drive this pattern. Participants with the highest genetic risk showed the greatest increases in LDL when they consumed the most saturated fat. The same relationship was not seen among people who followed a low-fat diet.
Instead of examining only individual genetic variants, as many previous studies have done, the researchers combined thousands of variants from across the genome (creating what is known as a polygenic score). This allowed them to estimate each participant’s overall genetic tendency toward higher or lower LDL cholesterol.
Barad said polygenic scores could eventually help doctors identify people who are more likely to experience unfavorable changes in cholesterol after certain dietary modifications.
Controlling Cholesterol May Be More Important Than Following a Rule
Genetic testing is not required to draw a practical lesson from the findings. Barad noted that people can respond very differently to the same dietary change, so it’s important to monitor how an individual’s body responds rather than assuming that a particular diet will produce the same results for everyone.
Additional research will be needed to confirm the results and determine whether they apply widely to more diverse populations.
Current dietary guidelines generally recommend keeping saturated fats below 10% of daily calories and choosing unsaturated fats when possible. For people following a low-carb diet, Barad suggested emphasizing sources like nuts, seeds, olive oil, and avocado instead of foods high in saturated fats, like butter, beef tallow, fatty cuts of meat, and processed meats. Doing so can help reduce the risk of an unfavorable cholesterol response.
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 Sciences Award, grant UL1TR001085 from the National Institutes of Health. Dr. Alexa Barad was supported by the American Heart Association Postdoctoral Fellowship (26POST1542318). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other funders.
Please note that abstracts presented at NUTRITION 2026 were evaluated and selected by a committee of experts but have generally not undergone the same peer review process required for publication in a scientific journal. As such, the findings presented should be considered preliminary until a peer-reviewed publication is available.