Association between substituting macronutrients and all-cause mortality: a network meta-analysis of prospective observational studies

Sabina Wallerer; Theodoros Papakonstantinou; Jakub Morze; Julia Stadelmaier; Eva Kiesswetter; Lea Gorenflo; Janett Barbaresko; Edyta Szczerba; Manuela Neuenschwander; William Bell; Tilman Kühn; Szimonetta Lohner; Marta Guasch-Ferré; Georg Hoffmann; Joerg J Meerpohl; Sabrina Schlesinger; Adriani Nikolakopoulou; Lukas Schwingshackl

doi:10.1016/j.eclinm.2024.102807

Association between substituting macronutrients and all-cause mortality: a network meta-analysis of prospective observational studies

EClinicalMedicine. 2024 Sep 5:75:102807. doi: 10.1016/j.eclinm.2024.102807. eCollection 2024 Sep.

Authors

Sabina Wallerer¹, Theodoros Papakonstantinou², Jakub Morze^{3

4}, Julia Stadelmaier¹, Eva Kiesswetter¹, Lea Gorenflo^{1

5}, Janett Barbaresko⁶, Edyta Szczerba^{6

7}, Manuela Neuenschwander^{6

7}, William Bell⁸, Tilman Kühn^{8

9

10

11}, Szimonetta Lohner^{12

13}, Marta Guasch-Ferré^{14

15}, Georg Hoffmann⁹, Joerg J Meerpohl^{1

5}, Sabrina Schlesinger^{6

7}, Adriani Nikolakopoulou², Lukas Schwingshackl¹

Affiliations

¹ Institute for Evidence in Medicine, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany.
² Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany.
³ Department of Life Sciences, Chalmers University of Technology, Gothenburg, Sweden.
⁴ College of Medical Sciences, SGMK Copernicus University, Warsaw, Poland.
⁵ Cochrane Germany, Cochrane Germany Foundation, Freiburg, Germany.
⁶ Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at the Heinrich Heine University Düsseldorf, Germany.
⁷ German Center for Diabetes Research (DZD), Partner Düsseldorf, München-Neuherberg, Germany.
⁸ The Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Belfast, United Kingdom.
⁹ Department of Nutritional Sciences, University of Vienna, Vienna, Austria.
¹⁰ Center for Public Health, Medical University of Vienna, Vienna, Austria.
¹¹ Heidelberg Institute of Global Health (HIGH), Faculty of Medicine and University Hospital, Heidelberg, Germany.
¹² Cochrane Hungary, Medical School, University of Pécs, Pécs, Hungary.
¹³ Department of Public Health Medicine, Medical School, University of Pécs, Pécs, Hungary.
¹⁴ Department of Public Health and Novo Nordisk Center for Basic Metabolic Research, University of Copenhagen, Denmark.
¹⁵ Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA.

Abstract

Background: Suboptimal diet quality is a key risk factor for premature death. Assuming relatively stable energy intake among individuals, changes in nutrient intakes occur by exchanging different nutrients. Therefore we aimed to examine the association of isocaloric substitution of dietary (macro)nutrients with all-cause mortality using network meta-analysis (NMA).

Methods: For this systematic review and NMA of prospective observational studies MEDLINE, Embase, and Scopus were searched from inception to February 13th, 2024. Eligible studies reported substitution analyses for quantity and/or quality of macronutrients, including carbohydrates, proteins, and fatty acids on all-cause mortality. Random-effects NMA were used in order to evaluate the pooled hazard ratios (HR) and 95% confidence intervals (CI) of substituting each included nutrient with another. We assessed risk of bias with the ROBINS-E tool, and the certainty of evidence (CoE) using the Grading of Recommendations Assessment, Development and Evaluations (GRADE) approach. This study is registered with PROSPERO (CRD42023450706).

Findings: Thirty-nine studies with 1,737,644 participants, 395,491 deaths, 297 direct comparisons, and seven nutrient-specific networks were included. Moderate CoE was found for an association with lower mortality risk when replacing 5% of energy intake from carbohydrates with polyunsaturated fatty acids (PUFA; HR: 0.90; 95%CI: 0.84, 0.95), n-6 PUFA (0.85; 0.77, 0.94), n-3 PUFA (0.72; 0.59, 0.86), and plant monounsaturated fatty acids (MUFA; 0.90; 0.85, 0.95), and when replacing 5% of energy from saturated fatty acids (SFA) and trans-fatty acids (TFA), with PUFA, MUFA, and plant-MUFA (HR_range: 0.75 to 0.91). A lower mortality risk was additionally found when 5% of animal-MUFA was replaced with plant-MUFA, and when replacing animal protein, and SFA with plant protein (HR_range: 0.81 to 0.87, moderate CoE).

Interpretation: Our results provide practical knowledge for public health professionals and can inform upcoming dietary guidelines. The beneficial association of increasing PUFA (both n-3 and n-6) and (plant-) MUFA intake while reducing carbohydrates, SFA and TFA, along with replacing animal protein and animal-MUFA with plant-based sources of protein and fat (MUFA) on the all-cause mortality risk, underscores the importance of plant-based dietary recommendations.

Funding: None.

Keywords: Macronutrients; Mortality; Network meta-analysis; Replacement; Substitution.