Mercola J. Historical rise of cancer and dietary linoleic acid: Mechanisms and therapeutic strategies. World J Clin Oncol 2025; 16(9): 110686 [PMID: 41024837 DOI: 10.5306/wjco.v16.i9.110686]
Corresponding Author of This Article
Joseph Mercola, Researcher, Midwestern University, 555 31st Street, Downers Grove, IL 60515, United States. drm@mercola.com
Research Domain of This Article
Oncology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Oncol. Sep 24, 2025; 16(9): 110686 Published online Sep 24, 2025. doi: 10.5306/wjco.v16.i9.110686
Historical rise of cancer and dietary linoleic acid: Mechanisms and therapeutic strategies
Joseph Mercola
Joseph Mercola, Midwestern University, Downers Grove, IL 60515, United States
Author contributions: Mercola J was the sole author responsible for study conception and design, data acquisition and interpretation, manuscript preparation and revision, final approval of the version to be published, and agrees to be accountable for the integrity of the work in all respects.
Conflict-of-interest statement: The author reports no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Joseph Mercola, Researcher, Midwestern University, 555 31st Street, Downers Grove, IL 60515, United States. drm@mercola.com
Received: June 12, 2025 Revised: July 14, 2025 Accepted: August 20, 2025 Published online: September 24, 2025 Processing time: 103 Days and 11.3 Hours
Abstract
Over the past century, dietary intake of linoleic acid (LA), an essential omega-6 fatty acid, has risen markedly in industrialized regions, largely due to industrial seed oils (e.g., soybean oil). This trend parallels increased cancer incidence, though causality remains unestablished. LA’s susceptibility to oxidation may generate reactive species, such as 4-hydroxynonenal, potentially inducing oxidative stress and lipid peroxidation in cellular membranes. Furthermore, excess LA might elevate pro-inflammatory eicosanoid levels (e.g., prostaglandin E2) and disrupt gut microbiota, fostering dysbiosis and immune dysregulation. Evidence, however, derives primarily from preclinical studies, with limited human data but epidemiological signals are strongest for breast (age-standardized incidence, approximately 130/100000 women), colorectal (approximately 39/100000), prostate (approximately 112/100000 men) and cutaneous melanoma (approximately 26/100000) cancers, where higher LA biomarkers or intakes have been repeatedly observed. Ketogenic diets, historically prioritized for metabolic benefits, reduce blood glucose, an effect possibly beneficial in cancer contexts, but may impair gut health by restricting fermentable fiber, potentially decreasing short-chain fatty acid production. This review explores LA’s hypothetical role in cancer-related pathways and the trade-offs of carbohydrate restriction. A proposed “terrain restoration” protocol, emphasizing reduced LA intake, gradual carbohydrate reintroduction to support microbiota, and nutrients like pentadecanoic acid (C15:0) for mitochondrial function, lacks clinical validation. While optimizing diet to bolster metabolic and immune resilience holds promise for cancer prevention, rigorous research is essential.
Core Tip: Industrial seed-oil boom has tripled linoleic acid (LA) intake since 1900, tracking the surge in cancer. This review synthesizes cutting-edge data showing how excess LA seeds oxidative lipid peroxidation, succinate-driven pseudohypoxia, mitochondrial dysfunction, hormonal-inflammatory amplification and gut dysbiosis that together create a “pro-cancer terrain”. It also challenges blanket ketogenic prescriptions, warning that carb exclusion can worsen LA-induced dysbiosis, and outlines a phased “terrain-restoration” plan: Slash dietary LA, reintroduce selective fibers, add odd-chain pentadecanoic acid and metabolic supports to revive mitophagy, microbiota and immune surveillance. The article spotlights urgent research gaps and testable clinical strategies.
