Zhiyuan Wu, PhD, is a postdoctoral research fellow at the Harvard T.H. Chan School of Public Health.

Zhiyuan Wu, PhD

Food Quality More Important Than Carbs or Fat for Preventing Heart Disease, With Zhiyuan Wu, PhD

 risk by dieting may depend on the quality of food more than the amount of carbohydrates or fat intake, according to a recent study.

Low-carb and low-fat diets are wildly popular in the US, despite little evidence existing to determine their long-term cardiovascular effects and the role of diet quality within the diet patterns. In this study, investigators aimed to prospectively examine the associations of these diets with coronary heart disease (CHD) risk among US individuals, as well as the objective metabolomic indices associated with the condition.

“Low-carb and low-fat diets are widely practiced in the US for weight control, glucose control, and metabolic health, but their effects on reducing heart disease risk is an ongoing debate, and one with mixed findings,” Zhiyuan Wu, PhD, a postdoctoral research fellow at the Harvard T.H. Chan School of Public Health and lead author of the present study, told 

 in an exclusive interview. “People follow their diets, but they can still choose unhealthy foods.”

Wu and colleagues collected data on 198,473 participants – 42,720 men from the Health Professionals Follow-Up Study (HPFS), 64,164 women in the Nurses’ Health Study (NHS), and 91,589 women from NHSII – to investigate CHD incidence. The team derived 5 low-carb diet and 5 low-fat diet indices based on food frequency questionnaires (FFQs). Each questionnaire emphasized different qualities and sources of macronutrients, including animal- versus plant-based foods, whole grains versus refined carbohydrates, and so on.

The team then assessed multimetabolite scores of low-carb and low-fat diet indices via elastic net regressions among 1146 healthy participants in lifestyle validation studies, which were embedded in NHS, NHSII, and HPFS. Patients were followed up for a total of 5,248,916 person-years, during which 20,033 CHD cases were documented.

Wu and colleagues compared individuals with the highest and lowest low-carb diet scores, determining a pooled multivariable-adjusted hazard ratio for CHD of 1.05 (95% CI, 1.01-1.1) for overall low-carb diets, 1.07 (95% CI, 1.02-1.12) for animal low-carb diets, 0.94 (95% CI, 0.9-0.99) for vegetable low-carb diets, 1.14 (95% CI, 1.09-1.2) for unhealthy low-carb diets, and 0.85 (95% CI, 0.82-0.89) for healthy low-carb diets.

For low-fat diets, the estimated hazard ratios were 0.93 (95% CI, 0.89-0.98) for overall low-fat diets, 0.94 (95% CI, 0.9-0.98) for animal low-fat diets, 0.87 (0.83-0.91) for vegetable low-fat diets, 1.12 (95% CI, 1.07-1.17) for unhealthy low-fat diets, and 0.87 (0.83-0.91) for healthy low-fat diets. The healthy versions of both diet patterns were also linked to lower triglycerides, higher HDL cholesterol, and lower high-sensitivity C-reactive protein levels. Additionally, both diets were associated with favorable metabolomic profiles, including decreased valine and increased 3-indolepropionic acid. Unhealthy patterns displayed opposite associations.

Investigators developed multimetabolite scores for both diet indices in the LVS and replicated in NHS, NHSII, and HPFS (

 = 0.21-0.38). These scores displayed associations with CHD risk, which were highly consistent with those obtained from the FFQ assessments.

Wu and colleagues did, however, note certain limitations of the study. These findings may not be generalizable to more extreme diets, such as ketogenic diets, and should be interpreted within the observed ranges of macronutrients. Additionally, dietary intake was fully self-reported by all patients enrolled in the study and thus was subject to measurement errors. The study findings might also have limited generalizability due to the patient population being health professionals, who presumably had higher health awareness and better access to care.

“For the public, we should still emphasize overall diet patterns rather than strict macronutrient restriction,” Wu said. “I think that focusing on overall diet quality should be an easy program for people to follow, compared with very extreme ways of cutting carbs or fat.”

Editor’s Note: Wu reports no relevant disclosures.

American College of Cardiology. Healthy versions of low-carb and low-fat diets linked to better cardiovascular and metabolic health. 

. February 11, 2026. Accessed February 11, 2026. 

https://www.eurekalert.org/news-releases/1115327

Wu Z, Liu B, Wang X, et al. Effect of low-carbohydrate and low-fat diets on metabolomic indices and coronary heart disease in U.S. individuals. JACC. Published online February 11, 2026. 

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Wu discusses his recent study spotlighting food source and quality as a more significant influence on CHD risk compared to simply cutting carbs or fat.

Zhiyuan Wu, PhD

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