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Nutrients Jul 2023The intake of linoleic acid (LA) has increased dramatically in the standard American diet. LA is generally promoted as supporting human health, but there exists... (Review)
Review
The intake of linoleic acid (LA) has increased dramatically in the standard American diet. LA is generally promoted as supporting human health, but there exists controversy regarding whether the amount of LA currently consumed in the standard American diet supports human health. The goal of this narrative review is to explore the mechanisms that underlie the hypothesis that excessive LA intake may harm human health. While LA is considered to be an essential fatty acid and support health when consumed in modest amounts, an excessive intake of LA leads to the formation of oxidized linoleic acid metabolites (OXLAMs), impairments in mitochondrial function through suboptimal cardiolipin composition, and likely contributes to many chronic diseases that became an epidemic in the 20th century, and whose prevalence continues to increase. The standard American diet comprises 14 to 25 times more omega-6 fatty acids than omega-3 fatty acids, with the majority of omega-6 intake coming from LA. As LA consumption increases, the potential for OXLAM formation also increases. OXLAMs have been associated with various illnesses, including cardiovascular disease, cancer, and Alzheimer's disease, among others. Lowering dietary LA intake can help reduce the production and accumulation of OXLAMs implicated in chronic diseases. While there are other problematic components in the standard American diet, the half-life of LA is approximately two years, which means the damage can be far more persistent than other dietary factors, and the impact of reducing excessive LA intake takes time. Therefore, additional research-evaluating approaches to reduce OXLAM formation and cardiolipin derangements following LA consumption are warranted.
Topics: Humans; Linoleic Acid; Cardiolipins; Chronic Disease; Diet
PubMed: 37513547
DOI: 10.3390/nu15143129 -
Linoleic acid binds to SARS-CoV-2 RdRp and represses replication of seasonal human coronavirus OC43.Scientific Reports Nov 2022Fatty acids belong to a group of compounds already acknowledged for their broad antiviral efficacy. However, little is yet known about their effect on replication of...
Fatty acids belong to a group of compounds already acknowledged for their broad antiviral efficacy. However, little is yet known about their effect on replication of human coronaviruses. To shed light on this subject, we first screened 15 fatty acids, three lipid-soluble vitamins, and cholesterol, on SARS-CoV-2 RdRp, and identified the four fatty acids with the highest RdRp inhibitory potential. Among them, linoleic acid was found to have the greatest interaction with SARS-CoV-2 RdRp, with its direct binding to the cavity formed by the RNA double helix and protein. Linoleic acid forms hydrophobic interactions with multiple residues, and at the same time forms electrostatic interactions including the hydrogen bond with Lys593 and Asp865. In line with these results, a dose-dependent inhibition of HCoV-OC43 replication in vitro was observed, additionally strengthened by data from in vivo study, which also confirmed anti-inflammatory potential of linoleic acid. Based on these results, we concluded that our study provides a new understanding of the antiviral properties of fatty acids against human coronaviruses including the SARS-CoV-2 strain. Particularly, they lays down a new prospect for linoleic acid's RdRp-inhibitory activity, as a candidate for further studies, which are warranted to corroborate the results presented here.
Topics: Humans; SARS-CoV-2; Coronavirus OC43, Human; Linoleic Acid; Seasons; Antiviral Agents; RNA-Dependent RNA Polymerase; COVID-19 Drug Treatment
PubMed: 36352079
DOI: 10.1038/s41598-022-23880-9 -
International Journal of Molecular... Mar 2021While approximately 2000 mutations have been discovered in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR), only a small amount (about... (Review)
Review
While approximately 2000 mutations have been discovered in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR), only a small amount (about 10%) is associated with clinical cystic fibrosis (CF) disease. The discovery of the association between CFTR and the hyperactive epithelial sodium channel (ENaC) has raised the question of the influence of ENaC on the clinical CF phenotype. ENaC disturbance contributes to the pathological secretion, and overexpression of one ENaC subunit, the β-unit, can give a CF-like phenotype in mice with normal acting CFTR. The development of ENaC channel modulators is now in progress. Both CFTR and ENaC are located in the cell membrane and are influenced by its lipid configuration. Recent studies have emphasized the importance of the interaction of lipids and these proteins in the membranes. Linoleic acid deficiency is the most prevailing lipid abnormality in CF, and linoleic acid is an important constituent of membranes. The influence on sodium excretion by linoleic acid supplementation indicates that lipid-protein interaction is of importance for the clinical pathophysiology in CF. Further studies of this association can imply a simple clinical adjuvant in CF therapy.
Topics: Animals; Cell Membrane; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Epithelial Sodium Channels; Humans; Linoleic Acid; Mice
PubMed: 33800499
DOI: 10.3390/ijms22052739 -
Nutrients Aug 2017Zinc (Zn) deficiency is a common aliment predicted to affect 17% of the world's population. Zinc is a vital micronutrient used for over 300 enzymatic reactions and... (Review)
Review
Zinc (Zn) deficiency is a common aliment predicted to affect 17% of the world's population. Zinc is a vital micronutrient used for over 300 enzymatic reactions and multiple biochemical and structural processes in the body. Although whole blood, plasma, and urine zinc decrease in severe zinc deficiency, accurate assessment of zinc status, especially in mild to moderate deficiency, is difficult as studies with these biomarkers are often contradictory and inconsistent. Hence, as suggested by the World Health Organization, sensitive and specific biological markers of zinc status are still needed. In this review, we provide evidence to demonstrate that the LA:DGLA ratio (linoleic acid:dihomo-γ-linolenic acid ratio) may be a useful additional indicator for assessing Zn status more precisely. However, this biomarker needs to be tested further in order to determine its full potential.
Topics: 8,11,14-Eicosatrienoic Acid; Biomarkers; Humans; Linoleic Acid; Nutritional Status; Zinc
PubMed: 28763004
DOI: 10.3390/nu9080825 -
Cancer Metastasis Reviews Sep 2020
Review
Topics: Animals; Carcinogenesis; Cytochrome P-450 Enzyme System; Humans; Linoleic Acid; Neoplasms; Oxylipins
PubMed: 32623533
DOI: 10.1007/s10555-020-09904-8 -
International Journal of Molecular... Mar 2021Linoleic acid (LA), an n-6 polyunsaturated fatty acid (PUFA), is essential for fetal growth and development. We aimed to investigate the effect of maternal and postnatal...
Linoleic acid (LA), an n-6 polyunsaturated fatty acid (PUFA), is essential for fetal growth and development. We aimed to investigate the effect of maternal and postnatal high LA (HLA) diet on plasma FA composition, plasma and hepatic lipids and genes involved in lipid metabolism in the liver of adult offspring. Female rats were fed with low LA (LLA; 1.44% LA) or HLA (6.21% LA) diets for 10 weeks before pregnancy, and during gestation/lactation. Offspring were weaned at postnatal day 25 (PN25), fed either LLA or HLA diets and sacrificed at PN180. Postnatal HLA diet decreased circulating total n-3 PUFA and alpha-linolenic acid (ALA), while increased total n-6 PUFA, LA and arachidonic acid (AA) in both male and female offspring. Maternal HLA diet increased circulating leptin in female offspring, but not in males. Maternal HLA diet decreased circulating adiponectin in males. Postnatal HLA diet significantly decreased aspartate transaminase (AST) in females and downregulated total cholesterol, HDL-cholesterol and triglycerides in the plasma of males. Maternal HLA diet downregulated the hepatic mRNA expression of in both male and female offspring and decreased the hepatic mRNA expression of and in females. Both maternal and postnatal HLA diet decreased hepatic mRNA expression of in females. Postnatal diet significantly altered circulating fatty acid concentrations, with sex-specific differences in genes that control lipid metabolism in the adult offspring following exposure to high LA diet in utero.
Topics: Animals; Diet, High-Fat; Fatty Acids, Omega-6; Female; Humans; Lactation; Leptin; Linoleic Acid; Lipid Metabolism; Liver; Male; Maternal Nutritional Physiological Phenomena; Pregnancy; Rats; Sex Characteristics; Triglycerides
PubMed: 33799409
DOI: 10.3390/ijms22062946 -
Missouri Medicine 2014Should we listen to warnings that linoleic acid (LA) promotes inflammation and that Americans would be healthier if they restricted their intake of LA (i.e., vegetable... (Review)
Review
Should we listen to warnings that linoleic acid (LA) promotes inflammation and that Americans would be healthier if they restricted their intake of LA (i.e., vegetable oils)? A recently published systematic review of 15 clinical trials failed to find any support for the "diet LA causes inflammation hypothesis." These findings support current recommendations that a diet with 5 to 10 energy percentage from polyunsaturated fatty acids, such as LA, is healthful and appropriate for most Americans.
Topics: Biomarkers; Cardiovascular Diseases; Dietary Fats; Energy Intake; Feeding Behavior; Humans; Inflammation; Linoleic Acid
PubMed: 24645297
DOI: No ID Found -
The American Journal of Clinical... Jul 2020Current evidence on associations between intakes of linoleic acid (LA), the predominant n-6 (ω-6) fatty acid, and mortality is inconsistent and has not been summarized... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Current evidence on associations between intakes of linoleic acid (LA), the predominant n-6 (ω-6) fatty acid, and mortality is inconsistent and has not been summarized by a systematic review and meta-analysis.
OBJECTIVE
The aim was to perform a systematic review and meta-analysis of prospective cohort studies to examine associations between LA intake and mortality.
METHODS
We conducted a comprehensive search of MEDLINE and EMBASE databases through 31 July 2019 for prospective cohort studies reporting associations of LA (assessed by dietary surveys and/or LA concentrations in adipose tissue or blood compartments) with mortality from all causes, cardiovascular disease (CVD), and cancer. Multivariable-adjusted RRs were pooled using random-effects meta-analysis.
RESULTS
Thirty-eight studies reporting 44 prospective cohorts were identified; these included 811,069 participants with dietary intake assessment (170,076 all-cause, 50,786 CVD, and 59,684 cancer deaths) and 65,411 participants with biomarker measurements (9758 all-cause, 6492 CVD, and 1719 cancer deaths). Pooled RRs comparing extreme categories of dietary LA intake (high vs low) were 0.87 (95% CI: 0.81, 0.94; I2 = 67.9%) for total mortality, 0.87 (95% CI: 0.82, 0.92; I2 = 3.7%) for CVD mortality, and 0.89 (95% CI: 0.85, 0.93; I2 = 0%) for cancer mortality. Pooled RRs for each SD increment in LA concentrations in adipose tissue/blood compartments were 0.91 (95% CI: 0.87, 0.95; I2 = 64.1%) for total mortality, 0.89 (95% CI: 0.85, 0.94; I2 = 28.9%) for CVD mortality, and 0.91 (95% CI: 0.84, 0.98; I2 = 26.3%) for cancer mortality. Meta-regressions suggested baseline age and dietary assessment methods as potential sources of heterogeneity for the association between LA and total mortality.
CONCLUSIONS
In prospective cohort studies, higher LA intake, assessed by dietary surveys or biomarkers, was associated with a modestly lower risk of mortality from all causes, CVD, and cancer. These data support the potential long-term benefits of PUFA intake in lowering the risk of CVD and premature death.
Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Fatty Acids, Omega-6; Female; Humans; Linoleic Acid; Male; Middle Aged; Neoplasms; Prospective Studies; Randomized Controlled Trials as Topic; Young Adult
PubMed: 32020162
DOI: 10.1093/ajcn/nqz349 -
Prostaglandins, Leukotrienes, and... Sep 2020Cystic fibrosis (CF) is a recessively inherited fatal disease that is the subject of extensive research and ongoing development of therapeutics targeting the defective... (Review)
Review
Cystic fibrosis (CF) is a recessively inherited fatal disease that is the subject of extensive research and ongoing development of therapeutics targeting the defective protein, cystic fibrosis transmembrane conductance regulator (CFTR). Despite progress, the link between CFTR and clinical symptoms is incomplete. The severe CF phenotypes are associated with a deficiency of linoleic acid, which is the precursor of arachidonic acid. The release of arachidonic acid from membranes via phospholipase A is the rate-limiting step for eicosanoid synthesis and is increased in CF, which contributes to the observed inflammation. A potential deficiency of docosahexaenoic acid may lead to decreased levels of specialized pro-resolving mediators. This pathophysiology may contribute to an early and sterile inflammation, mucus production, and to bacterial colonization, which further increases inflammation and potentiates the clinical symptoms. Advances in lipid technology will assist in elucidating the role of lipid metabolism in CF, and stimulate therapeutic modulations of inflammation.
Topics: Arachidonic Acid; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Docosahexaenoic Acids; Humans; Inflammation; Linoleic Acid; Lipid Metabolism; Lung; Mucus
PubMed: 32750662
DOI: 10.1016/j.plefa.2020.102156 -
Neurochemistry International Mar 2023Linoleic acid (LA, 18:2n-6) is an essential nutrient for optimal infant growth and brain development. The effects of LA in the brain are thought to be mediated by...
Linoleic acid (LA, 18:2n-6) is an essential nutrient for optimal infant growth and brain development. The effects of LA in the brain are thought to be mediated by oxygenated metabolites of LA known as oxidized LA metabolites (OXLAMs), but evidence is lacking to directly support this hypothesis. This study investigated whether OXLAMs modulate key neurodevelopmental processes including axon outgrowth, dendritic arborization, cell viability and synaptic connectivity. Primary cortical neuron-glia co-cultures from postnatal day 0-1 male and female rats were exposed for 48h to the following OXLAMs: 1) 13-hydroxyoctadecadienoic acid (13-HODE); 2) 9-hydroxyoctadecadienoic acid (9-HODE); 3) 9,10-dihydroxyoctadecenoic acid (9,10-DiHOME); 4) 12(13)-epoxyoctadecenoic acid (12(13)-EpOME); 5) 9,10,13-trihydroxyoctadecenoic acid (9,10,13-TriHOME); 6) 9-oxo-octadecadienoic acid (9-OxoODE); and 7) 12,13-dihydroxyoctadecenoic acid (12,13-DiHOME). Axonal outgrowth, evaluated by Tau-1 immunostaining, was increased by 9-HODE, but decreased by 12,13-DiHOME in male but not female neurons. Dendrite arborization, evaluated by MAP2B-eGFP expression, was affected by 9-HODE, 9-OxoODE, and 12(13)-EpOME in male neurons and, by 12(13)-EpOME in female neurons. Neither cell viability nor synaptic connectivity were significantly altered by OXLAMs. Overall, this study shows select OXLAMs modulate neuron morphology in a sex-dependent manner, with male neurons being more susceptible.
Topics: Male; Rats; Animals; Linoleic Acid; Neurons; Neuroglia
PubMed: 36758902
DOI: 10.1016/j.neuint.2023.105506