INTRODUCTION

Accumulating evidence suggest that imbalanced macronutrient composition would increase the risk of chronic diseases. However, previous studies that predominantly focused on individual macronutrients often failed to thoroughly elucidate this complex association.

OBJECTIVES

This study aimed to comprehensively analyze the relationship between macronutrient clusters and all-cause mortality.

METHODS

The study included 26,615 adults aged 20-75 years from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. A three-dimensional cube method was employed to categorize clusters of macronutrients intake. The association between dietary macronutrient clusters and all-cause mortality was investigated using Cox proportional hazards modeling and restricted cubic spline (RCS) analysis.

RESULTS

Over a weighted median follow-up duration of 7.58 years, 3,998 deaths were recorded. After adjusting for potential confounders, compared with the reference Cluster , 4 specific Clusters were associated with reduced all-cause mortality: Cluster (HR: 0.79, 95 % CI: 0.67-0.92), Cluster (HR: 0.76, 95 % CI: 0.61-0.95), Cluster (HR: 0.86, 95 % CI: 0.75-0.97), and Cluster (HR: 0.73, 95 % CI: 0.60-0.89). Three-node RCS analysis revealed non-linear relationships between carbohydrate within Cluster and protein within Cluster and overall mortality. Subgroup and sensitivity analyses corroborated the robustness of these associations across different age, gender, and energy intake levels.

CONCLUSIONS

This study employed a three-dimensional cube approach to categorize the human macronutrients intake into 24 clusters. Cluster , Clusters , Cluster , and Cluster exhibited a lower mortality risk. Different clusters of macronutrients could be a precondition in nutrition intervene strategy.