Genetic makeup may determine whether low-carb diets raise LDL cholesterol
核心洞察
A new analysis of the DIETFITS trial suggests genetic predisposition interacts with saturated fat intake to drive LDL cholesterol increases on low-carb diets.
Researchers combined thousands of genetic variants into a polygenic score to estimate each participant's overall tendency toward higher or lower LDL cholesterol.
Among low-carb dieters, those with the highest genetic risk showed the largest LDL increases when consuming more saturated fat, a pattern not seen on low-fat diets.
New research suggests that whether a low-carbohydrate diet sends your cholesterol soaring may depend on your genes. The findings indicate that saturated fat, which can make up a larger share of some low-carb diets, may interact with a person's genetic makeup to raise low-density lipoprotein (LDL) cholesterol (搜索), a major contributor to heart disease (搜索) risk. This genetic influence could help explain why two people following 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, because of their genetic background," said Alexa Barad, PhD, RDN, a postdoctoral scholar at Stanford University School of Medicine. Barad presented the findings at NUTRITION 2026, the flagship annual meeting of the American Society for Nutrition (搜索), held July 25–28 in National Harbor, Maryland.
"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.
Why Low-Carb Diets Affect People Differently
Earlier research has found that healthy low-carbohydrate diets can help some people lose weight and improve blood sugar control. Their impact on LDL cholesterol, however, has been inconsistent. The researchers wanted to determine whether genetic information could help identify people who are more likely to benefit from eating fewer carbohydrates and those who may instead experience a potentially dangerous rise in LDL cholesterol.
The analysis used data from DIETFITS, a randomized controlled trial involving more than 600 adults who followed either a healthy low-carb 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 were available, examining how genotype, saturated fat consumption, diet type, and changes in LDL cholesterol from baseline to 6 months were related.
Genetics and Saturated Fat Linked to LDL Increases
Among participants assigned to the low-carb diet, those who were genetically predisposed to higher LDL cholesterol were more likely to experience an increase. The researchers found that greater sensitivity to saturated fat appeared to drive this pattern. Participants with the highest genetic risk showed the largest LDL increases when they consumed more saturated fat. The same relationship was not observed among people following the 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 that polygenic scores could eventually help clinicians identify people who are more likely to experience unfavorable cholesterol changes after certain dietary modifications.
Monitoring Cholesterol May Matter More Than Following One 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, making it important to monitor how an individual's body responds rather than assuming a particular diet will produce the same results for everyone.
Current dietary guidance generally recommends keeping saturated fat below 10% of daily calories and choosing unsaturated fats when possible. For people who follow a low-carbohydrate diet, Barad suggested emphasizing sources such as nuts, seeds, olive oil, and avocado rather than foods rich in saturated fat, including butter, beef tallow, fatty cuts of meat, and processed meats. Doing so may help lower the risk of an unfavorable cholesterol response.
Additional research will be needed to confirm the results and determine whether they apply broadly across more diverse populations. The abstracts presented at NUTRITION 2026 were evaluated and selected by a committee of experts but have not generally undergone the same peer review process required for publication in a scientific journal, so the findings should be considered preliminary until a peer-reviewed publication is available.
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).