Within the well-known DIETFITS trial at Stanford University, a new look at 431 adults who had genetic data available shows that people carrying more LDL-raising gene variants had far larger cholesterol increases on a healthy low-carb diet than participants without that genetic profile. The signal was strongest in dieters who ate the most saturated fat. Nothing similar showed up in the low-fat arm.
The analysis was presented on July 27, 2026 at NUTRITION 2026, the American Society for Nutrition's annual meeting at the Gaylord National Resort in National Harbor, Maryland. It draws on data from DIETFITS, a 12-month randomized controlled trial of more than 600 overweight adults originally published in JAMA in 2018, which found low-carb and low-fat diets produced similar average weight loss.
What the polygenic score changes
Instead of looking at one or two well-known cholesterol genes, the Stanford team built a polygenic score by combining thousands of common gene variants across the genome. That score estimates a person's overall inherited tendency toward higher or lower LDL cholesterol, the type of cholesterol linked to heart disease risk.
Over six months, participants in the top of that genetic risk range who ate a low-carb, saturated-fat-rich diet saw the biggest LDL jumps. Low-fat dieters with the same genetic risk did not show that pattern, according to the Stanford-led analysis reported by ScienceDaily.
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"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.
Why two low-carb dieters can end up in different places
The finding helps explain a familiar argument in low-carb circles. One dieter reports crashing LDL numbers. Another watches their reading climb. Barad said the data suggest both experiences can be real, and that inherited biology helps decide which camp a person falls into. Because this is an observational analysis inside a randomized trial, not a separate intervention targeting people by genotype, the results point to a link rather than proof of cause.
The practical takeaway lines up with mainstream cardiology advice. The American Heart Association recommends keeping saturated fat to less than 6% of daily calories and flags fatty cuts of red meat, butter, coconut oil and full-fat dairy as major sources to watch. In March 2026, the American College of Cardiology, the AHA and nine other groups issued an updated dyslipidemia guideline that again emphasized replacing saturated fat with unsaturated fat to lower LDL.
What to do if you eat low-carb
For readers who want to stay on a low-carb pattern, Barad's advice was to shift the fat mix. She recommended emphasizing "healthier fat sources such as nuts, seeds, olive oil and avocado over foods high in saturated fat such as butter, beef tallow, fatty cuts of meat and processed meats" to reduce the risk of an adverse cholesterol response. A recent two-year walnut trial fits the same picture, with the most harmful LDL particles falling in participants who added walnuts to their usual diet.
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Anyone with a family history of high cholesterol or heart disease who wants to try a low-carb or ketogenic pattern has a reason to check LDL before starting and again within a few months. Standard lipid panels are inexpensive and widely available, and reference ranges by age make it easier to spot a change that matters. If LDL climbs sharply, a clinician can weigh whether the fat mix, a genetic factor or a lipid disorder such as familial hypercholesterolemia is driving the shift.
Barad said clinical polygenic testing for diet response is not yet routine. "In the future, clinicians could potentially use polygenic scores to help identify people who are more likely to experience adverse LDL cholesterol responses to certain dietary modifications," she said.
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This article is made and published by Jesper Bengtson, who may have used AI in the preparation.