High-Quality Macronutrients Key to Cardiovascular Risk Reduction, Large Cohort Study Finds

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The quality of carbohydrates, fats, and proteins consumed as part of low-carbohydrate or low-fat diets may be more important for coronary heart disease (CHD) prevention than the macronutrient profile alone, according to data presented at the American Society for Nutrition's annual meeting, NUTRITION 2025.¹

Low-carbohydrate diets (LCD) and low-fat diets (LFD) have been widely touted for benefits like weight loss and better blood sugar and cholesterol. Yet, their effect on cardiovascular disease risk is still debated.¹

“We found that what you eat on low-carb or low-fat diets matters just as much as the diet itself,” presenting author Zhiyuan Wu, PhD, a postdoctoral research fellow at the Harvard T.H. Chan School of Public Health, said in a press release. “Healthy versions of these diets—those rich in plant-based foods and whole grains—were linked to better heart health outcomes and improved metabolic function. In contrast, low-carb and low-fat diets emphasizing unhealthy foods were associated with a higher risk of heart disease.”²

To examine how the quality and food sources within LCDs and LFDs affect CHD risk and shape metabolic profiles, Wu and colleagues followed 199 783 participants across 3 major US cohorts—the Health Professionals Follow-Up Study, Nurses’ Health Study, and Nurses’ Health Study II—for a combined total of more than 5.2 million person-years.¹

Investigators analyzed detailed questionnaires from the participants, assigning scores according to how healthy their food choices were within LFDs and LCDs. Healthy components included whole grains, fruits, vegetables, legumes, and nuts. Unhealthy components included refined grains, added sugars, and animal-derived fats and proteins.¹

In addition, associations between LCD/LFD indices and plasma metabolomics profiles were examined in 1146 participants, developing multi-metabolite scores using elastic net regression, according to the study abstract.¹ “This approach allowed us to better understand the biological effects of these diets and strengthened our findings,” Wu said in the press release.²

Researchers documented 19 407 cases of CHD and reported that healthy versions of both diet patterns were associated with reduced CHD risk, while unhealthy versions were associated with increased risk. Specifically, the hazard ratios (HRs) for CHD per 1-standard deviation increment in dietary scores were¹:

• 1.02 (95% CI 1.00-1.04) for overall LCD
• 0.94 (95% CI 0.93–0.96) for healthy LCD
• 1.05 (95% CI 1.04–1.07) for unhealthy LCD
• 0.94 (95% CI 0.93–0.96) for healthy LFD
• 1.04 (95% CI 1.03–1.06) for unhealthy LFD

“Spline regression revealed linear dose-response associations between the diet scores and CHD, except for the vegetable LCD (P = 0.03 for non-linearity),” researchers added in the study abstract.¹

Wu and colleagues also examined biomarker data from 1 146 participants in the Lifestyle Validation Study. Multimetabolite scores derived from plasma metabolomics showed consistent associations with CHD risk, further supporting the diet-disease relationships identified through dietary questionnaires.¹

“Our findings suggest that improving food quality is crucial for improving heart health,” Wu added in the press release. “Regardless of whether someone follows a low-carbohydrate or low-fat diet, emphasizing whole, minimally processed and plant-based foods and limiting refined grain, sugar and animal foods, can significantly reduce the risk of coronary heart disease.”²

Future research will aim to investigate how genetic predisposition, lifestyle behaviors, and other metabolic markers may influence individual responses to diet quality in relation to cardiovascular and other chronic disease outcomes.²

References:

1. Wu Z, Wang X, Hu Y, et al. Low-carbohydrate and low-fat diets, objective biomarker indices, and coronary heart disease in US men and women. Abstract P17-077-25. Presented at: NUTRITION; May 31-June 3, 2025; Orlando.

2. For heart health, food quality matters more than cutting carbs or fat. News release. American Society for Nutrition. June 1, 2025. Accessed June 2, 2025. https://www.eurekalert.org/news-releases/1084802