# The controversial role of linoleic acid in cardiometabolic health: from molecular pathways to human studies

**Authors:** Loni Berkowitz, Paloma Araneda, Glenda Cofré, Daniela Sara, Mariano Olsen, Isadora Urzúa, Druso Pérez, Attilio Rigotti

PMC · DOI: 10.3389/fnut.2025.1728865 · Frontiers in Nutrition · 2026-01-14

## TL;DR

This paper reviews the ongoing debate about linoleic acid's effects on heart and metabolic health, concluding that it likely has benefits but depends on diet and genetics.

## Contribution

The paper provides a comprehensive analysis of the evolving scientific and clinical understanding of linoleic acid's role in cardiometabolic health.

## Key findings

- Most human studies associate linoleic acid with beneficial cardiometabolic outcomes.
- The effects of linoleic acid depend on dietary context, genetic background, and metabolic status.
- Conflicting guidelines stem from evolving biochemical insights and experimental approaches.

## Abstract

Unhealthy diets are major contributors to the global burden of non-communicable diseases, particularly cardiovascular disease and metabolic syndrome, where dietary fat quality plays a critical role. Among dietary fats, linoleic acid (LA)—the predominant omega-6 polyunsaturated fatty acid—has been at the center of a long-standing and evolving controversy. Initially promoted for its cholesterol-lowering properties, LA later became the focus of debate due to hypotheses suggesting pro-inflammatory and oxidative effects, which led to conflicting interpretations of its metabolic impact and inconsistent dietary guidelines over time. This review traces the origins and progression of this controversy, examining how shifts in biochemical understanding, experimental design, and population dietary patterns have shaped current perspectives on LA and cardiometabolic health. By integrating evidence from biochemical, preclinical, and human studies, we clarify the mechanistic and clinical bases underlying LA’s actions and re-evaluate its role in lipid metabolism, inflammation, and glucose regulation. Overall, most human evidence supports beneficial associations between LA exposure and cardiometabolic outcomes, though heterogeneity across studies underscores the relevance of dietary context, genetic background, and metabolic status. Understanding how the controversy emerged and evolved is essential to refine current recommendations for dietary fat and disease prevention.

## Linked entities

- **Chemicals:** linoleic acid (PubChem CID 5280450)
- **Diseases:** cardiovascular disease (MONDO:0004995), metabolic syndrome (MONDO:0000816)

## Full-text entities

- **Diseases:** cardiovascular disease (MESH:D002318), metabolic syndrome (MESH:D024821), inflammation (MESH:D007249)
- **Chemicals:** glucose (MESH:D005947), lipid (MESH:D008055), omega-6 polyunsaturated fatty acid (-), LA (MESH:D019787), cholesterol (MESH:D002784)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

111 references — full list in the complete paper: https://tomesphere.com/paper/PMC12846940/full.md

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Source: https://tomesphere.com/paper/PMC12846940