Historical Trends of Cancer and Dietary Linoleic Acid: Mechanistic Insights and Evidence-Based Perspectives, with Acrylamide and Maltodextrin Considerations (2026)
Abstract
Over the twentieth and early twenty-first centuries, consumption of linoleic acid (LA), acrylamide (formed in high-temperature cooking), and processed carbohydrates such as maltodextrin has increased dramatically. These dietary exposures coincide temporally with rising cancer incidence. Preclinical evidence suggests that LA promotes oxidative stress, lipid peroxidation, mitochondrial dysfunction, and inflammatory signaling, while acrylamide is genotoxic and carcinogenic in animal models. Maltodextrin, a highly processed polysaccharide, can exacerbate insulin resistance, gut dysbiosis, and chronic inflammation. Interactions among these dietary factors may amplify pro-tumorigenic metabolic pathways. However, human epidemiological evidence for LA, acrylamide, and maltodextrin is inconsistent, with large cohort studies often showing neutral or modestly protective effects for LA, and limited but concerning signals for acrylamide. This review synthesizes mechanistic and epidemiologic evidence, evaluates potential dietary strategies, and identifies areas for future research to clarify the roles of LA, acrylamide, and maltodextrin in cancer biology.
Keywords: Linoleic acid; acrylamide; maltodextrin; omega-6 fatty acids; oxidative stress; cancer risk; lipid peroxidation; diet.
Over the twentieth and early twenty-first centuries, consumption of linoleic acid (LA), acrylamide (formed in high-temperature cooking), and processed carbohydrates such as maltodextrin has increased dramatically. These dietary exposures coincide temporally with rising cancer incidence. Preclinical evidence suggests that LA promotes oxidative stress, lipid peroxidation, mitochondrial dysfunction, and inflammatory signaling, while acrylamide is genotoxic and carcinogenic in animal models. Maltodextrin, a highly processed polysaccharide, can exacerbate insulin resistance, gut dysbiosis, and chronic inflammation. Interactions among these dietary factors may amplify pro-tumorigenic metabolic pathways. However, human epidemiological evidence for LA, acrylamide, and maltodextrin is inconsistent, with large cohort studies often showing neutral or modestly protective effects for LA, and limited but concerning signals for acrylamide. This review synthesizes mechanistic and epidemiologic evidence, evaluates potential dietary strategies, and identifies areas for future research to clarify the roles of LA, acrylamide, and maltodextrin in cancer biology.
Keywords: Linoleic acid; acrylamide; maltodextrin; omega-6 fatty acids; oxidative stress; cancer risk; lipid peroxidation; diet.
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Introduction
Linoleic acid (C18:2n-6, LA) is an essential polyunsaturated fatty acid found in common vegetable oils, including soybean, sunflower, corn, and safflower oils. During the twentieth century, the introduction of industrial seed oils markedly increased LA intake, particularly in Westernized diets. Epidemiological trends in cancer incidence over the same period have prompted hypotheses linking LA consumption to cancer development.
Mechanistically, LA undergoes enzymatic and non-enzymatic oxidation to form bioactive metabolites, including oxidized linoleic acid derivatives (OXLAMs) and 4-hydroxynonenal (4-HNE), which can induce DNA damage, oxidative stress, and pro-inflammatory signaling. Additionally, LA metabolism may influence mitochondrial function and hypoxia-inducible factor signaling, potentially creating a microenvironment favorable for tumor growth.
In parallel, acrylamide, a Maillard reaction product formed when carbohydrate-rich foods are cooked at high temperatures (e.g., fried, baked, or roasted foods), has been identified as a probable human carcinogen (IARC Group 2A). Acrylamide forms DNA adducts and promotes oxidative stress, potentially synergizing with LA-induced lipid peroxidation.
Maltodextrin, a highly processed starch used in processed foods and beverages, rapidly increases postprandial glucose and insulin levels, contributes to gut dysbiosis, and can exacerbate chronic low-grade inflammation, all of which are implicated in tumor-promoting metabolic pathways.
Understanding the combined impact of LA, acrylamide, and maltodextrin is critical for contextualizing dietary contributions to cancer risk.
Methods
A systematic literature search was conducted using PubMed, Web of Science, and Scopus for studies published up to January 2026. Search terms included “linoleic acid,” “omega-6 fatty acids,” “acrylamide,” “maltodextrin,” “processed carbohydrate,” “cancer risk,” “oxidative stress,” “lipid peroxidation,” and “tumor metabolism.” Inclusion criteria encompassed experimental studies examining mechanistic effects and human epidemiological studies evaluating associations between dietary exposures and cancer. Preclinical, clinical, and meta-analytic studies were reviewed and synthesized.
Results
1. Preclinical Mechanistic Evidence
Linoleic Acid (LA):
Promotes oxidative stress and lipid peroxidation via formation of oxidized linoleic acid metabolites (OXLAMs) and 4-hydroxynonenal (4-HNE).
Contributes to mitochondrial dysfunction and stabilization of hypoxia-inducible factor 1-alpha (HIF-1α), enhancing glycolytic metabolism, angiogenesis, and cell survival.
Modulates inflammatory signaling and gut microbiota composition, potentially supporting tumor-promoting microenvironments.
Acrylamide:
Forms DNA adducts and mutagenic intermediates in preclinical models, with genotoxic effects documented in rodents and in vitro systems.
Enhances oxidative stress and may synergize with lipid peroxidation caused by LA.
Chronic low-level exposure is associated with oxidative damage and pro-inflammatory cytokine expression in animal studies.
Maltodextrin:
Rapidly digested, causing postprandial hyperglycemia and hyperinsulinemia, which can activate the IGF-1/PI3K/Akt pathway linked to tumor growth.
Alters gut microbiota composition, increasing pro-inflammatory taxa and reducing beneficial microbes.
When combined with high-LA or acrylamide exposure, maltodextrin may exacerbate metabolic stress and inflammation, creating a permissive tumor microenvironment.
2. Human Epidemiological Evidence
LA: Large prospective cohort studies and meta-analyses show neutral or modestly protective associations with cancer risk, including breast, colorectal, and prostate cancers.
Acrylamide: Epidemiological studies indicate mixed evidence; dietary acrylamide intake correlates with certain cancers (endometrial, ovarian, kidney) in some cohorts, though absolute risk remains modest.
Maltodextrin and Processed Carbohydrates: Direct cancer-specific evidence is limited. However, diets high in rapidly digestible carbohydrates correlate with obesity, insulin resistance, and inflammation—well-established cancer risk factors.
Collectively, human data suggest that LA alone is unlikely to substantially increase cancer risk, while acrylamide and ultra-processed carbohydrates may pose measurable risk, particularly when combined with obesogenic or pro-inflammatory diets.
Discussion
Interactions and Metabolic Context:
Preclinical evidence supports synergistic effects among LA, acrylamide, and maltodextrin: oxidative stress, mitochondrial overload, and inflammation converge to create a pro-tumorigenic milieu.
Human studies indicate that dietary context (total fat quality, carbohydrate processing, antioxidant intake) critically modulates risk.
Dietary and Preventive Considerations:
Limit high-LA industrial seed oils and fried/baked foods (acrylamide sources).
Prefer low-glycemic, minimally processed carbohydrate sources over maltodextrin-rich foods.
Maintain metabolic health via exercise, balanced omega-3:omega-6 ratios, and adequate fiber intake.
Future Research:
Prospective clinical trials measuring LA, acrylamide, and maltodextrin exposures alongside biomarkers of oxidative stress, DNA damage, and gut microbiota.
Mechanistic studies integrating multi-omics to evaluate combined effects on tumor metabolism.
Conclusions
LA, acrylamide, and maltodextrin may act through overlapping mechanisms—oxidative stress, inflammation, mitochondrial dysfunction, and metabolic dysregulation—to influence cancer biology.
Human evidence for LA is largely neutral; acrylamide shows limited but concerning carcinogenic potential, while maltodextrin’s contribution is primarily indirect via metabolic dysregulation.
Dietary strategies targeting these exposures, along with overall metabolic optimization, merit further clinical investigation to refine evidence-based cancer prevention guidelines.
References
Wu JH, et al. Intake of linoleic acid and cancer risk: meta-analysis of prospective studies. Am J Clin Nutr. 2019;110(4):891–902.
Simopoulos AP. Omega-6/omega-3 fatty acid ratio and chronic diseases. World Rev Nutr Diet. 2016;113:1–18.
Ghosh S, et al. Oxidized linoleic acid metabolites and cancer progression. Front Oncol. 2013;3:224.
Mercola J, et al. Historical rise of linoleic acid and cancer mechanisms. World J Clin Oncol. 2025;16(9):110686.
Tareke E, et al. Acrylamide: A review of its formation, exposure, and toxicology. Food Chem Toxicol. 2002;40(9):1331–1345.
Ghosh SS, et al. Maltodextrin promotes gut inflammation and dysbiosis in preclinical models. Nutrients. 2018;10(5):559.
Pedersen TL, et al. Interaction of dietary fats and glycemic load on metabolic and inflammatory pathways. J Nutr Biochem. 2021;88:108542.
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