Low-Carb Diets May Raise LDL More in Genetically Susceptible People, Study Suggests

Low-carbohydrate diets can produce very different cholesterol responses from one person to another. While some people experience little change in LDL cholesterol, others see substantial increases. New research suggests that inherited differences may help explain some of that variation, particularly when a low-carbohydrate diet contains more saturated fat.

The analysis, presented at NUTRITION 2026, the annual meeting of the American Society for Nutrition, found that people with a greater genetic predisposition to elevated LDL cholesterol tended to experience larger LDL increases on a low-carbohydrate diet as saturated fat intake increased. The findings are preliminary and have not yet undergone full peer review.

Genetics may shape cholesterol response

The analysis was led by Alexa Barad, a postdoctoral scholar and registered dietitian at Stanford University School of Medicine. Barad and her colleagues investigated whether genetic predisposition to higher LDL cholesterol could help predict differences in cholesterol responses to a low-carbohydrate eating pattern.

The researchers used data from DIETFITS, a randomized clinical trial that enrolled more than 600 adults and assigned them to follow either a healthy low-carbohydrate diet or a healthy low-fat diet for one year.

Earlier results from DIETFITS found no significant difference in 12-month weight loss between the healthy low-fat and healthy low-carbohydrate groups. However, individuals varied in their responses to the diets, providing researchers with an opportunity to investigate factors that might contribute to those differences.

For the new analysis, the researchers examined 431 participants for whom genetic data were available. Rather than focusing on a single genetic variant, they calculated a polygenic score incorporating many genetic variants associated with LDL cholesterol. The score was intended to represent each participant’s inherited predisposition toward higher LDL levels.

Saturated fat may interact with genetic risk

Among participants assigned to the healthy low-carbohydrate diet, a higher genetic predisposition to elevated LDL was associated with greater increases in LDL cholesterol, particularly as saturated fat intake increased.

The largest LDL increases were observed among participants who combined higher genetic risk with greater saturated fat consumption. This suggests that inherited susceptibility and the composition of a low-carbohydrate diet may interact in determining an individual’s cholesterol response.

The same pattern was not observed in the healthy low-fat group. This indicates that genetic predisposition did not influence LDL responses in the same way under the two dietary conditions.

However, the findings should not be interpreted as showing that low-carbohydrate diets themselves inevitably increase LDL cholesterol or cardiovascular risk. Low-carbohydrate eating patterns can differ substantially in their food composition, including the amount and sources of saturated and unsaturated fats.

Similarly, the analysis does not establish that saturated fat alone explains every large LDL increase observed during low-carbohydrate diets. Genetic predisposition appears to be one potential contributor to substantial individual variation in response.

What the findings could mean for personalized nutrition

The results contribute to growing interest in understanding why people can respond differently to similar dietary interventions.

Polygenic scores combine information from numerous genetic variants to estimate an individual’s genetic predisposition to a particular trait. In this study, such a score helped identify differences in LDL response among participants consuming a low-carbohydrate diet.

In the future, genetic information could potentially contribute to more individualized dietary recommendations. However, this study does not establish that polygenic testing should currently be used to determine whether someone should follow a low-carbohydrate or low-fat diet.

The analysis also remains preliminary because it was presented at a scientific conference rather than published as a full peer-reviewed research paper. Additional studies, including research in more diverse populations, will be needed to determine how reproducible and clinically useful the findings are.

What it means for people following low-carb diets

Genetic testing is not required to determine whether a particular diet is affecting a person’s LDL cholesterol. Blood testing before and after a substantial dietary change can provide direct information about an individual’s response.

This may be particularly relevant for people following very-low-carbohydrate or ketogenic eating patterns containing substantial amounts of saturated fat. Someone may lose weight or experience improvements in certain metabolic measures while simultaneously experiencing an unfavorable change in LDL cholesterol.

Dietary guidance generally recommends limiting saturated fat and replacing it with unsaturated fats where appropriate. For people following a lower-carbohydrate diet, sources of unsaturated fats can include nuts, seeds, olive oil, avocado and fish, while foods such as butter, fatty meats and some full-fat dairy products can contribute larger amounts of saturated fat.

The study does not mean that these foods must universally be eliminated, nor does it identify a single low-carbohydrate diet appropriate for everyone. Instead, the findings reinforce the importance of considering both the overall composition of a diet and an individual’s biological response.

More research is needed

Barad and her colleagues hope that further research will clarify whether genetic information can eventually help clinicians identify eating patterns that support both weight management and cardiometabolic health.

Studies involving broader and more diverse populations will also be important because the predictive performance of polygenic scores can vary across populations depending on how those scores were developed and validated.

For now, the results offer a possible explanation for why apparently similar dietary changes can produce markedly different LDL responses. Genetics may be part of the picture, but diet composition — particularly saturated fat intake — also appears to matter.

The findings therefore support an individualized approach rather than treating all low-carbohydrate diets, or everyone who follows them, as metabolically equivalent. Monitoring LDL cholesterol and other relevant health markers can help determine how a particular eating pattern is affecting an individual over time.

The DIETFITS trial received funding from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute and the National Institutes of Health. Barad’s work was supported by an American Heart Association postdoctoral fellowship. Because the new analysis was presented as conference research, its conclusions should be considered preliminary until the full findings undergo peer review.