Low-carbohydrate diets may affect LDL cholesterol differently from person to person. While some people experience little or no change, others may see a significant increase. New research suggests that genetics and saturated fat intake could help explain these varied cholesterol responses.
The study found that saturated fat, which can account for a substantial portion of some low-carbohydrate diets, may interact with a person’s genetic makeup to increase low-density lipoprotein (LDL) cholesterol. Often called “bad” cholesterol, elevated LDL cholesterol is a major risk factor for heart disease. These genetic differences may explain why people following similar diets can experience dramatically different cholesterol outcomes.
“Our findings suggest that some people may be more sensitive to the LDL cholesterol-raising effects of saturated fat because of their genetic background, particularly when following a low-carbohydrate diet,” said Alexa Barad, RDN, a postdoctoral fellow at Stanford University School of Medicine. Barad presented the findings at NUTRITION 2026, the American Academy of Nutrition’s annual scientific meeting.
“These findings highlight the significant differences in how individuals respond to dietary changes. Discussions about diet are sometimes oversimplified. One person may say that low-carbohydrate diets always raise LDL cholesterol, while another may report that their LDL levels did not change. Our findings suggest that both experiences may be accurate, at least in part because of genetic differences,” Barad said.
Why low-carbohydrate diets affect cholesterol differently
Previous research has shown that a healthy low-carbohydrate diet may help some people lose weight and improve blood sugar control. However, the effects of low-carb diets on LDL cholesterol have been inconsistent.
The researchers wanted to determine whether genetic information could help identify people who may benefit from reducing carbohydrate intake and those who may experience potentially harmful increases in LDL cholesterol.
The analysis used 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 difference between the two diets in terms of weight loss.
For the new analysis, researchers examined 431 DIETFITS participants who had genetic data available. They evaluated the relationship between genetic profile, saturated fat intake, diet type, and changes in LDL cholesterol from baseline to six months.
Genetic risk and saturated fat linked to higher LDL cholesterol
Among participants assigned to the low-carbohydrate diet, those with a genetic predisposition to high LDL cholesterol were more likely to experience an increase in LDL levels.
The researchers found that greater sensitivity to saturated fat appeared to contribute to this pattern. Participants with the highest genetic risk experienced the largest increases in LDL cholesterol when they consumed more saturated fat. The same relationship was not observed among participants following the low-fat diet.
Rather than examining individual genetic variants, as many earlier studies have done, the researchers combined thousands of genetic variations from across the genome to create a polygenic score. This score provided an estimate of each participant’s overall genetic tendency toward higher or lower LDL cholesterol.
Barad said polygenic risk scores could eventually help clinicians identify people who are more likely to experience unfavorable cholesterol changes after making specific dietary changes.
Cholesterol monitoring may be more useful than following a single diet rule
Genetic testing is not required to apply the practical lessons from this research. Because people can respond very differently to the same dietary changes, Barad emphasized the importance of monitoring individual cholesterol levels instead of assuming that one diet will produce identical results for everyone.
More research is needed to confirm the findings and determine whether they apply to larger and more diverse populations.
Current dietary guidelines generally recommend limiting saturated fat to less than 10% of daily calories and choosing unsaturated fats whenever possible. People following a low-carbohydrate diet may benefit from emphasizing heart-healthy fat sources, including nuts, seeds, olive oil, and avocados, instead of foods high in saturated fat, such as butter, tallow, fatty meats, and processed meats. These choices may help reduce the risk of an unfavorable LDL 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 Stanford Clinical Translational Science Award grant UL1TR001085 from the National Institutes of Health. Dr. Alexa Barad was supported by an 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 the abstracts presented at NUTRITION 2026 were evaluated and selected by a panel of experts but typically do not undergo the peer-review process required for publication in scientific journals. The findings should therefore be considered preliminary until they are published in a peer-reviewed journal.
Source: www.sciencedaily.com