A person’s genetic makeup may determine whether a low-carb diet raises LDL cholesterol sharply, according to preliminary research presented at a major nutrition conference, with saturated fat appearing to drive the effect in those already genetically predisposed to higher cholesterol levels.
The work was presented by Alexa Barad, PhD, RDN, a postdoctoral scholar at Stanford University School of Medicine, at EurekAlert!-covered NUTRITION 2026, the flagship annual meeting of the American Society for Nutrition, held 25–28 July in National Harbor, Maryland. The findings, which have not yet undergone peer review for journal publication, attempt to explain one of the more persistent puzzles in dietary research: why people following seemingly identical diets end up with very different cholesterol results.
The low-carb diet LDL cholesterol puzzle
Low-carbohydrate diets have attracted considerable interest as a tool for weight management and blood sugar control. Their effect on low-density lipoprotein (LDL) cholesterol (a major contributor to heart disease risk) has been far less predictable. Some people see little movement; others experience a substantial rise. For years, those divergent outcomes were largely attributed to differences in what individuals actually ate, or how strictly they followed the diet.
Barad’s analysis points toward genetics as an important additional variable. ‘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,’ she said. Rather than contradicting each other, she argued, the people who say low-carb diets always raise their LDL and those who report no change at all may simply be responding in accordance with their own genetic profiles.
What the data actually show
The analysis drew on DIETFITS, a randomised controlled trial that assigned more than 600 adults to either a healthy low-carb or a healthy low-fat diet for one year. The original trial found no meaningful advantage for either approach on weight loss. For this new analysis, the researchers worked with data from 431 DIETFITS participants for whom genetic information was available, examining how genotype, saturated fat intake, and diet type related to changes in LDL cholesterol from baseline to six months.
Rather than isolating individual genetic variants, as many earlier studies have done, the researchers combined thousands of variants across the genome into what is known as a polygenic score: an estimate of each participant’s overall genetic tendency towards higher or lower LDL. Among those assigned to the low-carb diet, participants with the highest genetic risk showed the largest LDL increases when they consumed more saturated fat. The same pattern was not observed in those following the low-fat diet.
Barad said polygenic scores could eventually help clinicians identify patients likely to experience unfavourable cholesterol changes after dietary modifications. Whether that translates into routine clinical practice remains an open question, not least because the findings are preliminary and will require replication in more diverse populations before any firm conclusions can be drawn.
A practical note on saturated fat
Genetic testing is not a prerequisite for drawing something useful from this research. Current dietary guidance, including recommendations from the National Institutes of Health‘s constituent bodies, generally suggests keeping saturated fat below 10% of daily calories and preferring unsaturated fats. Barad’s practical advice aligns with that: people following a low-carbohydrate diet may reduce their risk of an adverse cholesterol response by prioritising nuts, seeds, olive oil, and avocado over butter, beef tallow, fatty cuts of meat, and processed meats.
The broader point, and the one that makes this research worth watching even at the abstract stage, is the insistence on individual variation. ‘These findings highlight that there is real heterogeneity in how people respond to diet,’ Barad said. ‘Dietary conversations can sometimes become overly simplified.’ Monitoring how an individual’s cholesterol actually responds to a dietary change, rather than assuming a universal outcome, appears to be the more defensible approach.
The DIETFITS trial was funded 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, all under the NIH umbrella. Barad was supported by an American Heart Association Postdoctoral Fellowship. The research team notes that the content does not necessarily represent the views of any of the funders. Peer-reviewed publication, when it comes, will be the test of how well these preliminary findings hold up.
