Genetic makeup may determine how low-carb diets influence cholesterol levels

Low-carbohydrate diets have surged in popularity in recent years, yet their impact on cholesterol remains highly variable. While some individuals see minimal changes, others experience significant increases. Emerging research points to genetics as a possible explanation for these differences.

The study indicates that saturated fat, which often comprises a larger portion of certain low-carb eating patterns, may interact with an individual’s genetic profile to elevate low-density lipoprotein (LDL) cholesterol, a key contributor to cardiovascular risk. This genetic component could account for why two people following comparable diets can experience markedly different cholesterol outcomes.

“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.

“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 well-formulated low-carbohydrate diets can support weight loss and improve blood sugar control in some individuals. Their effect on LDL cholesterol, however, has been inconsistent across studies.

The research team sought to determine whether genetic information could help identify individuals more likely to benefit from reduced carbohydrate intake, as well as those who might experience a potentially harmful rise in LDL cholesterol.

The analysis drew on 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 12 months. The original trial found no significant difference between the two diets in terms of weight loss.

For the new analysis, the researchers focused on 431 DIETFITS participants for whom genetic data were available. They examined how genotype, saturated fat consumption, diet type, and changes in LDL cholesterol from baseline to six months were interrelated.

Genetics and Saturated Fat Linked to LDL Increases

Among participants assigned to the low-carbohydrate diet, those with a genetic predisposition to higher LDL cholesterol were more likely to experience an increase.

The researchers found that heightened sensitivity to saturated fat appeared to drive this pattern. Participants with the highest genetic risk scores showed the largest LDL increases 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 in isolation, as many prior studies have done, the researchers aggregated thousands of variants across the genome to construct a polygenic score. This approach allowed them to estimate each participant’s overall genetic likelihood of having higher or lower LDL cholesterol.

Barad noted that polygenic scores could eventually help clinicians identify individuals more likely to experience unfavorable cholesterol changes following specific dietary modifications.

Monitoring Cholesterol May Matter More Than Adhering to a Single Rule

Genetic testing is not necessary to draw a practical takeaway from the findings. Barad emphasized that individuals can respond very differently to the same dietary changes, making it essential to monitor how each person’s body reacts rather than assuming any one diet will produce uniform results.

Further research is needed to confirm the results and assess whether they apply broadly across more diverse populations.

Current dietary guidelines generally recommend limiting saturated fat to less than 10% of daily calories and favoring unsaturated fats whenever possible. For individuals following a low-carbohydrate diet, Barad recommended emphasizing sources such as nuts, seeds, olive oil, and avocado over foods high in saturated fat, including butter, beef tallow, fatty cuts of meat, and processed meats. This approach may help reduce the risk of an unfavorable cholesterol response.

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