Meta-analyses of dietary exposures must consider energy adjustment: recommendations from a meta-scientific review

2025-12-08

AI Summary

In observational dietary studies, energy adjustment strategies critically influence the comparability and interpretability of effect estimates; however, existing meta-analyses routinely overlook this issue, leading to heterogeneous effect measures and diminished evidence quality. Using a meta-research approach, we systematically evaluated eight meta-analyses on saturated fat and fish intake in relation to cardiovascular disease—and their 82 included primary studies (144 statistical models). We found that 82% of the primary models implicitly estimated substitution effects (i.e., health effects when one food replaces other energy sources), yet rarely declared this assumption explicitly; only one meta-analysis accounted for energy adjustment methodology. This study is the first to identify the systematic omission of energy adjustment strategies in dietary meta-analyses. We propose standardized subgroup analyses stratified by substitution effect type to enhance methodological rigor, improve synthesis validity, and strengthen the policy relevance of nutritional epidemiologic evidence.

Technology Category

• Search and Optimization: Metareasoning and Metaheuristics
• Cognitive Modeling & Cognitive Systems: Analogy
• Constraint Satisfaction and Optimization: Satisfiability Modulo Theories

Application Category

• Search and Retrieval-Augmented AI: Web evaluation methodologies and metrics
• Graph Algorithms and Modeling for the Web: Representation, reconstruction, and subgraph or motif discovery in Web-related graphs
• Web Mining and Content Analysis: Robustness and generalizability of Web mining methods

Abstract

In observational studies of dietary exposures, the energy adjustment strategy has a critical impact on the effect being estimated. Adjusting for total energy intake or expressing the exposure as a percentage of total energy, leads to a substitution effect being estimated. This impacts the interpretation of primary studies and meta-analyses. Unless energy adjustment strategies are considered, meta-analyses may end up pooling estimates for incomparable effects. This meta-scientific review aimed to investigate the extent to which meta-analyses of dietary exposures may be pooling incomparable effects by reviewing the energy adjustment strategies. We identified all meta-analyses examining the relationship between saturated fat and fish and cardiovascular disease. The two most recent and two most cited reviews for each exposure were examined, along with all primary studies. Information on the study aims, targeted effects, and interpretations were summarized. The eight meta-analyses summarised results from 82 primary studies including 144 unique models. Only one meta-analysis explicitly considered the energy adjustment strategy of the primary studies to determine eligibility for a substitution subgroup analysis. None of the meta-analyses acknowledged that they were pooling estimates for different effects. 82% of the models from the primary studies were implicitly estimating substitution effects but this was not explicitly stated in most study aims, interpretation or conclusions. Our meta-scientific review found little evidence that the energy adjustment strategies of the primary studies were being considered in the synthesis or interpretation of evidence. Consequently, the pooled estimates reflect ill-defined quantities with unclear interpretations. We offer recommendations to improve the conduct of future meta-analyses and the quality of evidence that informs nutritional recommendations.

Problem

• Meta-analyses often pool incomparable dietary exposure effects due to ignored energy adjustment strategies.
• Many primary studies implicitly estimate substitution effects without explicitly stating this in aims or conclusions.
• Current meta-analyses produce pooled estimates with unclear interpretations, compromising nutritional evidence quality.

Innovation

• Energy adjustment strategies crucial for meta-analyses comparability
• Identified pooling of incomparable effects in dietary exposure studies
• Proposed recommendations to improve meta-analysis quality and interpretation