Effect of Dietary Linoleic Acid on Markers of Inflammation in Healthy Persons: A Systematic Review of Randomized Controlled Trials

Johnson, Guy H.; Fritsche, Kevin

doi:10.1016/j.jand.2012.03.029

Cited by 269Fatty Acid Research and HealthInflammatory mediators and NSAID effectsNutritional Studies and Diet

Effect of Dietary Linoleic Acid on Markers of Inflammation in Healthy Persons: A Systematic Review of Randomized Controlled Trials

Johnson, Guy H., Fritsche, Kevin·2012·Journal of the Academy of Nutrition and Dietetics

DOI 10.1016/j.jand.2012.03.029

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Abstract

The majority of evidence suggests that n-6 polyunsaturated fatty acids, including linoleic acid (LA), reduce the risk of cardiovascular disease as reflected by current dietary recommendations. However, concern has been expressed that a high intake of dietary n-6 polyunsaturated fatty acid contributes to excess chronic inflammation, primarily by prompting the synthesis of proinflammatory eicosanoids derived from arachidonic acid and/or inhibiting the synthesis of anti-inflammatory eicosanoids from eicosapentaenoic and/or docosahexaenoic acids. A systematic review of randomized controlled trials that permitted the assessment of dietary LA on biologic markers of chronic inflammation among healthy noninfant populations was conducted to examine this concern. A search of the English- and non-English-language literature using MEDLINE, the Cochrane Controlled Trials Register, and EMBASE was conducted to identify relevant articles. Fifteen studies (eight parallel and seven crossover) met inclusion criteria. None of the studies reported significant findings for a wide variety of inflammatory markers, including C-reactive protein, fibrinogen, plasminogen activator inhibitor type 1, cytokines, soluble vascular adhesion molecules, or tumor necrosis factor-α. The only significant outcome measures reported for higher LA intakes were greater excretion of prostaglandin E2 and lower excretion of 2,3-dinor-thromboxane B(2) in one study and higher excretion of tetranorprostanedioic acid in another. However, the authors of those studies both observed that these effects were not an indication of increased inflammation. We conclude that virtually no evidence is available from randomized, controlled intervention studies among healthy, noninfant human beings to show that addition of LA to the diet increases the concentration of inflammatory markers.

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Pro-inflammatory effects of LA have been theorized and popularized, but such inference is based largely on rodent experiments, with little supportive evidence in humans.
“While pro-inflammatory effects of LA have been theorized358 and popularized, such inference is based largely on rodent experiments; with little supportive evidence in humans.359-362”
From Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review (2016) · cites this paper as [362]

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Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review
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Dietary Linoleic Acid and Risk of Coronary Heart Disease: A Systematic Review and Meta-Analysis of Prospective Cohort Studies
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Dietary linoleic acid and human health: Focus on cardiovascular and cardiometabolic effects
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Linoleic Acid
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Omega−3 Polyunsaturated Fatty Acids (PUFAs): Emerging Plant and Microbial Sources, Oxidative Stability, Bioavailability, and Health Benefits—A Review
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Overeating Saturated Fat Promotes Fatty Liver and Ceramides Compared With Polyunsaturated Fat: A Randomized Trial
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A review of recent evidence in human studies of n-3 and n-6 PUFA intake on cardiovascular disease, cancer, and depressive disorders: does the ratio really matter?
Marventano, S., Kolacz, P., Castellano, S., Galvano, F., Buscemi, S., Mistretta, A., & Grosso, G. (2015) · International Journal of Food Sciences and Nutrition · doi:10.3109/09637486.2015.1077790 · Cited by 220 · see citing works
The Short Overview on the Relevance of Fatty Acids for Human Cardiovascular Disorders
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Circulating Omega-6 Polyunsaturated Fatty Acids and Total and Cause-Specific Mortality
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Current Evidence Supporting the Link Between Dietary Fatty Acids and Cardiovascular Disease
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Intake and metabolism of omega-3 and omega-6 polyunsaturated fatty acids: nutritional implications for cardiometabolic diseases
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Review of Eukaryote Cellular Membrane Lipid Composition, with Special Attention to the Fatty Acids
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Linoleic acid: Between doubts and certainties
Choque, B., Catheline, D., Rioux, V., & Legrand, P. (2013) · Biochimie · doi:10.1016/j.biochi.2013.07.012 · Cited by 194 · see citing works
Replacement of saturated with unsaturated fats had no impact on vascular function but beneficial effects on lipid biomarkers, E-selectin, and blood pressure: results from the randomized, controlled Dietary Intervention and VAScular function (DIVAS) study
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Dietary Polyunsaturated Fatty Acids and Inflammation: The Role of Phospholipid Biosynthesis
Raphael, W., & Sordillo, L. M. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms141021167 · Cited by 173 · see citing works
Dietary fats and cardiometabolic disease: mechanisms and effects on risk factors and outcomes
Wu, J. H. Y., Micha, R., & Mozaffarian, D. (2019) · Nature Reviews Cardiology · doi:10.1038/s41569-019-0206-1 · Cited by 167 · see citing works
Impact of Nonoptimal Intakes of Saturated, Polyunsaturated, and Trans Fat on Global Burdens of Coronary Heart Disease
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A Novel Anti-Inflammatory Role of Omega-3 PUFAs in Prevention and Treatment of Atherosclerosis and Vascular Cognitive Impairment and Dementia
Simonetto, M., Infante, M., Sacco, R. L., Rundek, T., & Della‐Morte, D. (2019) · Nutrients · doi:10.3390/nu11102279 · Cited by 156 · see citing works
Olive oil and prevention of chronic diseases: Summary of an International conference
Visioli, F., Franco, M., Toledo, E., Luchsinger, J. A., Willett, W. C., Hu, F. B., & Martínez‐González, M. Á. (2018) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2018.04.004 · Cited by 151 · see citing works
Diet-Gene Interactions and PUFA Metabolism: A Potential Contributor to Health Disparities and Human Diseases
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The Omega-6:Omega-3 ratio: A critical appraisal and possible successor
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Linoleic acid and the pathogenesis of obesity
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Modulation of obesity-induced inflammation by dietary fats: mechanisms and clinical evidence
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Dietary intake and biomarkers of linoleic acid and mortality: systematic review and meta-analysis of prospective cohort studies
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ω-6 Polyunsaturated Fatty Acids and Cardiometabolic Health: Current Evidence, Controversies, and Research Gaps
Maki, K. C., Eren, F., Cassens, M. E., Dicklin, M. R., & Davidson, M. H. (2018) · Advances in Nutrition · doi:10.1093/advances/nmy038 · Cited by 128 · see citing works
Fatty acids as modulators of neutrophil recruitment, function and survival
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Environmental Risk Factors in Psoriasis: The Point of View of the Nutritionist
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Dietary Fatty Acids and Their Potential for Controlling Metabolic Diseases Through Activation of FFA4/GPR120
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The Effects of Linoleic Acid Consumption on Lipid Risk Markers for Cardiovascular Disease in Healthy Individuals: A Review of Human Intervention Trials
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Clinical Advances in Immunonutrition and Atherosclerosis: A Review
Ruiz-León, A. M., Lapuente, M., Estruch, R., & Casas, R. M. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00837 · Cited by 101 · see citing works
The Impact of Seasonality in Pasture-Based Production Systems on Milk Composition and Functionality
Timlin, M., Tobin, J. T., Brodkorb, A., Murphy, E. G., Dillon, P., Hennessy, D., O’Donovan, M., Pierce, K. M., & O’Callaghan, T. F. (2021) · Foods · doi:10.3390/foods10030607 · Cited by 101 · see citing works
Is Grassfed Meat and Dairy Better for Human and Environmental Health?
Provenza, F. D., Kronberg, S. L., & Gregorini, P. (2019) · Frontiers in Nutrition · doi:10.3389/fnut.2019.00026 · Cited by 102 · see citing works
Fatty Acids and Cardiovascular Risk. Evidence, Lack of Evidence, and Diligence
Visioli, F., & Poli, A. (2020) · Nutrients · doi:10.3390/nu12123782 · Cited by 96 · see citing works
Important roles of linoleic acid and α-linolenic acid in regulating cognitive impairment and neuropsychiatric issues in metabolic-related dementia
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Beneficial effects of linoleic acid on cardiometabolic health: an update
Jackson, K. H., Harris, W. S., Belury, M. A., Kris‐Etherton, P. M., & Calder, P. C. (2024) · Lipids in Health and Disease · doi:10.1186/s12944-024-02246-2 · Cited by 91 · see citing works
Dietary Fatty Acids and Risk of Coronary Heart Disease in Men
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Genetic Variants in the FADS Gene: Implications for Dietary Recommendations for Fatty Acid Intake
Mathias, R. A., Pani, V., & Chilton, F. H. (2014) · Current Nutrition Reports · doi:10.1007/s13668-014-0079-1 · Cited by 89 · see citing works
Promising Sources of Plant-Derived Polyunsaturated Fatty Acids: A Narrative Review
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Dietary Fatty Acids and Inflammation: Focus on the n-6 Series
Poli, A., Agostoni, C. V., & Visioli, F. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054567 · Cited by 85 · see citing works
The role of n − 6 and n − 3 polyunsaturated fatty acids in the manifestation of the metabolic syndrome in cardiovascular disease and non-alcoholic fatty liver disease
Monteiro, J., Leslie, M. A., Moghadasian, M. H., Arendt, B. M., Allard, J. P., & David, W. L. (2014) · Food & Function · doi:10.1039/c3fo60551e · Cited by 82 · see citing works
Dietary Intake of Linoleic Acid, Its Concentrations, and the Risk of Type 2 Diabetes: A Systematic Review and Dose-Response Meta-analysis of Prospective Cohort Studies
Mousavi, S. M., Jalilpiran‬, Y., Karimi, E., Aune, D., Larijani, B. A., Mozaffarian, D., Willett, W. C., & Esmaillzadeh, A. (2021) · Diabetes Care · doi:10.2337/dc21-0438 · Cited by 83 · see citing works
Perspective on the health effects of unsaturated fatty acids and commonly consumed plant oils high in unsaturated fat
Petersen, K. S., Maki, K. C., Calder, P. C., Belury, M. A., Messina, M. J., Kirkpatrick, C. F., & Harris, W. S. (2024) · British Journal Of Nutrition · doi:10.1017/s0007114524002459 · Cited by 82 · see citing works
The health effects of soy: A reference guide for health professionals
Messina, M. J., Duncan, A. M., Messina, V., Lynch, H. M., Kiel, J., & Erdman, J. W. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.970364 · Cited by 73 · see citing works
Plasma Levels of 14:0, 16:0, 16:1n‐7, and 20:3n‐6 are Positively Associated, but 18:0 and 18:2n‐6 are Inversely Associated with Markers of Inflammation in Young Healthy Adults
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Soybean oil lowers circulating cholesterol levels and coronary heart disease risk, and has no effect on markers of inflammation and oxidation
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High‐Fat Diet Alters Serum Fatty Acid Profiles in Obesity Prone Rats: Implications for InVitro Studies
Cross, T.-W., Heden, T. D., Morris, E. M., Fritsche, K. L., Vieira‐Potter, V. J., & Thyfault, J. P. (2015) · Lipids · doi:10.1007/s11745-015-4061-5 · Cited by 69 · see citing works
Self-citation
Our landscapes, our livestock, ourselves: Restoring broken linkages among plants, herbivores, and humans with diets that nourish and satiate
Provenza, F. D., Meuret, M., & Gregorini, P. (2015) · Appetite · doi:10.1016/j.appet.2015.08.004 · Cited by 68 · see citing works
Omega-6 Fatty Acids and Cardiovascular Disease
Harris, W. S., & Shearer, G. C. (2014) · Circulation · doi:10.1161/circulationaha.114.012534 · Cited by 63 · see citing works
Sexually dimorphic brain fatty acid composition in low and high fat diet-fed mice
Rodríguez‐Navas, C., Morselli, E., & Clegg, D. J. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.06.014 · Cited by 61 · see citing works
Effects of supplemental long-chain omega-3 fatty acids and erythrocyte membrane fatty acid content on circulating inflammatory markers in a randomized controlled trial of healthy adults
Flock, M. R., Skulas‐Ray, A. C., Harris, W. S., Gaugler, T. L., Fleming, J. A., & Kris‐Etherton, P. M. (2014) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2014.07.006 · Cited by 59 · see citing works
Dietary LA and sex effects on oxylipin profiles in rat kidney, liver, and serum differ from their effects on PUFAs
Leng, S., Winter, T., & Aukema, H. M. (2017) · Journal of Lipid Research · doi:10.1194/jlr.m078097 · Cited by 58 · see citing works
Polyunsaturated fatty acid biosynthesis pathway and genetics. implications for interindividual variability in prothrombotic, inflammatory conditions such as COVID-19✰,✰✰,★,★★
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Corn Oil Lowers Plasma Cholesterol Compared with Coconut Oil in Adults with Above-Desirable Levels of Cholesterol in a Randomized Crossover Trial
Maki, K. C., Hasse, W., Dicklin, M. R., Bell, M., Buggia, M., Cassens, M. E., & Eren, F. (2018) · Journal of Nutrition · doi:10.1093/jn/nxy156 · Cited by 57 · see citing works
Metabolic indices of polyunsaturated fatty acids: current evidence, research controversies, and clinical utility
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Impact of physical exercise on visceral adipose tissue fatty acid profile and inflammation in response to a high-fat diet regimen
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Dietary linoleic acid intake and blood inflammatory markers: a systematic review and meta-analysis of randomized controlled trials
Su, H., Liu, R., Chang, M., Huang, J., & Wang, X. (2017) · Food & Function · doi:10.1039/c7fo00433h · Cited by 52 · see citing works
Influence of dietary fat intake on the endocannabinoid system in lean and obese subjects
Engeli, S., Lehmann, A., Kaminski, J., Haas, V. K., Janke, J., Zoerner, A. A., Luft, F. C., Tsikas, D., & Jordan, J. (2014) · Obesity · doi:10.1002/oby.20728 · Cited by 51 · see citing works
Impact of methods used to express levels of circulating fatty acids on the degree and direction of associations with blood lipids in humans
Sergeant, S., Ruczinski, I., Ivester, P., Lee, T. C., Morgan, T. M., Nicklas, B. J., Mathias, R. A., & Chilton, F. H. (2015) · British Journal Of Nutrition · doi:10.1017/s0007114515004341 · Cited by 51 · see citing works
Exchanging a few commercial, regularly consumed food items with improved fat quality reduces total cholesterol and LDL-cholesterol: a double-blind, randomised controlled trial
Ulven, S. M., Leder, L., Elind, E., Ottestad, I. O., Christensen, J. J., Telle‐Hansen, V. H., Skjetne, A. J., Raael, E., Sheikh, N. A., Holck, M., et al. (2016) · British Journal Of Nutrition · doi:10.1017/s0007114516003445 · Cited by 51 · see citing works
Polyunsaturated Fatty Acids and Serum C-Reactive Protein: The Rotterdam Study
Muka, T., Jong, J. C. K., Albert Hofman, D., Dehghan, A., Rivadeneira, F., & Franco, O. H. (2015) · American Journal of Epidemiology · doi:10.1093/aje/kwv021 · Cited by 50 · see citing works
Association of Adipose Tissue Fatty Acids With Cardiovascular and All-Cause Mortality in Elderly Men
Iggman, D., Ärnlöv, J., Cederholm, T., & Risérus, U. (2016) · JAMA Cardiology · doi:10.1001/jamacardio.2016.2259 · Cited by 50 · see citing works
High Dietary Intake of Vegetable or Polyunsaturated Fats Is Associated With Reduced Risk of Hepatocellular Carcinoma
Yang, W., Sui, J., Ma, Y., Simon, T. G., Petrick, J. L., Lai, M., McGlynn, K. A., Campbell, P. T., Giovannucci, E. L., Chan, A. T., et al. (2020) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2020.01.003 · Cited by 50 · see citing works
The pro-/anti-inflammatory effects of different fatty acids on visceral adipocytes are partially mediated by GPR120
Rodríguez‐Pacheco, F., Gutiérrez‐Repiso, C., García‐Serrano, S., Alaminos-Castillo, M. A., Ho‐Plagaro, A., Valdés, S., García-Arnés, J. A., Gonzalo, M., Andrade, R. J., Moreno‐Ruiz, F. J., et al. (2016) · European Journal of Nutrition · doi:10.1007/s00394-016-1222-0 · Cited by 49 · see citing works
The Novel Omega-6 Fatty Acid Docosapentaenoic Acid Positively Modulates Brain Innate Immune Response for Resolving Neuroinflammation at Early and Late Stages of Humanized APOE-Based Alzheimer's Disease Models
Ma, Q., Zhu, C., Morselli, M., Su, T., Pelligrini, M., Lu, Z., Jones, M. R., Denver, P., Castro, D., Gu, X., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.558036 · Cited by 48 · see citing works
Associations of serum n–3 and n–6 polyunsaturated fatty acids with prevalence and incidence of nonalcoholic fatty liver disease
Mäkelä, T. N., Tuomainen, T., Hantunen, S., & Virtanen, J. K. (2022) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqac150 · Cited by 48 · see citing works
Excessive dietary linoleic acid induces proinflammatory markers in rats
Marchix, J., Choque, B., Kouba, M., Fautrel, A., Catheline, D., & Legrand, P. (2015) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2015.07.010 · Cited by 48 · see citing works
Both linoleic and α-linolenic acid prevent insulin resistance but have divergent impacts on skeletal muscle mitochondrial bioenergetics in obese Zucker rats
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Chemical composition and biological activity of extracts from fruiting bodies and mycelial cultures of Fomitopsis betulina
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Comparative study of the nutritional composition of wild versus farmed yellowtail (Seriola lalandi)
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Key roles for GRB2-associated-binding protein 1, phosphatidylinositol-3-kinase, cyclooxygenase 2, prostaglandin E2 and transforming growth factor alpha in linoleic acid-induced upregulation of lung and breast cancer cell growth
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Nutritional Needs of the Older Adult
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The Effects of Cannabidiol Oil on Noninvasive Measures of Muscle Damage in Men
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Variation in the FADS1/2 gene cluster alters plasma n−6 PUFA and is weakly associated with hsCRP levels in healthy young adults
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The associations of serum n-6 polyunsaturated fatty acids with serum C-reactive protein in men: the Kuopio Ischaemic Heart Disease Risk Factor Study
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Authors: Johnson, G. H., & Fritsche, K.
Affiliations: University of Illinois Urbana-Champaign (US)
Corresponding author: Johnson, Guy H.
ORCID: Johnson, Guy H.
Fritsche, Kevin
Venue: Journal of the Academy of Nutrition and Dietetics
Publisher: Elsevier BV
Published: 2012-07
Volume: 112
Issue: 7
Pages: 1029-1041.e15
ISSN: 2212-2672 (ISSN-L)
DOI: 10.1016/j.jand.2012.03.029
OpenAlex: W2116488160
Cited by: 268
References: 85
Citations by year: 2026: 28 · 2025: 15 · 2024: 17 · 2023: 15 · 2022: 12 · 2021: 16 · 2020: 22 · 2019: 15 · 2018: 15 · 2017: 20 · 2016: 23 · 2015: 26 · 2014: 24 · 2013: 18 · 2012: 1
FWCI: 2.73
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Journal of the Academy of Nutrition and Dietetics (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
Keywords: linoleic acid, omega-6 fatty acids, chronic inflammation, inflammatory markers, eicosanoids, prostaglandin E2, thromboxane B2, C-reactive protein, fibrinogen, plasminogen activator inhibitor-1, cytokines, TNF-α, dietary fatty acid supplementation, cardiovascular risk
MeSH terms: C-Reactive Protein, Dietary Fats, Unsaturated, Fibrinogen, Humans, Inflammation, Tumor Necrosis Factor-alpha, Biomarkers, Randomized Controlled Trials as Topic, Cytokines, Plasminogen Activator Inhibitor 1, Linoleic Acid

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Effect of Dietary Linoleic Acid on Markers of Inflammation in Healthy Persons: A Systematic Review of Randomized Controlled Trials

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