Specific macronutrient clusters associated with lower mortality risk: Evidence from NHANES 1999-2018

Jiaying Yu; Yang Chen; Defang Li; Lan Zhang; Yuting Zhang; Jiaqi Zhang; Jiayu Zhu; Zican Li; Hongxin Fu; Dongwei Guan; Runan Zhang; Liyan Liu; Cheng Wang; Changhao Sun; Rennan Feng

doi:10.1016/j.jare.2025.02.019

Specific macronutrient clusters associated with lower mortality risk: Evidence from NHANES 1999-2018

J Adv Res. 2025 Dec:78:533-542. doi: 10.1016/j.jare.2025.02.019. Epub 2025 Feb 14.

Authors

Jiaying Yu¹, Yang Chen¹, Defang Li¹, Lan Zhang¹, Yuting Zhang¹, Jiaqi Zhang¹, Jiayu Zhu¹, Zican Li¹, Hongxin Fu¹, Dongwei Guan¹, Runan Zhang¹, Liyan Liu¹, Cheng Wang², Changhao Sun³, Rennan Feng⁴

Affiliations

¹ Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, PR China; Key Laboratory of Precision Nutrition and Health of Ministry of Education, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, PR China.
² Department of Environmental Hygiene, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, PR China. Electronic address: wangchenghlj@163.com.
³ Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, PR China; Key Laboratory of Precision Nutrition and Health of Ministry of Education, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, PR China. Electronic address: sunchanghao@ems.hrbmu.edu.cn.
⁴ Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, PR China; Key Laboratory of Precision Nutrition and Health of Ministry of Education, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, PR China; Key Laboratory of Science and Engineering for the Multi-modal Prevention and Control of Major Chronic Diseases, Ministry of Industry and Information Technology, PR China. Electronic address: fengrennan@yeah.net.

Abstract

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 _Pm:Fm:Cmh, 4 specific Clusters were associated with reduced all-cause mortality: Cluster _Pm:Fm:Cm (HR: 0.79, 95 % CI: 0.67-0.92), Cluster _Pm:Fmh:Cml (HR: 0.76, 95 % CI: 0.61-0.95), Cluster _Pm:Fmh:Cm (HR: 0.86, 95 % CI: 0.75-0.97), and Cluster _Pl:Fm:Cmh (HR: 0.73, 95 % CI: 0.60-0.89). Three-node RCS analysis revealed non-linear relationships between carbohydrate within Cluster _Pm:Fm:Cm and protein within Cluster _Pl:Fm:Cmh 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 _Pm:Fm:Cm, Clusters _Pm:Fmh:Cml, Cluster _Pm:Fmh:Cm, and Cluster _Pl:Fm:Cmh exhibited a lower mortality risk. Different clusters of macronutrients could be a precondition in nutrition intervene strategy.

Keywords: All-cause mortality; Dietary protein, fat and carbohydrate intake; Macronutrient; Three-dimensional cube method.

MeSH terms

Adult
Aged
Diet*
Female
Humans
Male
Middle Aged
Mortality*
Nutrients*
Nutrition Surveys
Proportional Hazards Models
Risk Factors
Young Adult

Substances

Nutrients