{"title":"Impact of linoleic acid on apolipoprotein B in individuals without previous diagnosis of cardiovascular disease: A Mendelian Randomization study","authors":"Gregory S. Nacarelli , Tracy Fasolino , Puya Yazdi , Vivian Haley-Zitlin , Stephanie Trammel","doi":"10.1016/j.clnesp.2025.06.008","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Apolipoprotein B is an essential causal marker of cardiovascular disease. Studies have attempted to understand the impact of fatty acids on cardiovascular disease risk by measuring changes in apolipoprotein B. Linoleic acid is an omega-6 polyunsaturated fatty acid that has demonstrated effects on cardiovascular disease outcomes.</div></div><div><h3>Objective</h3><div>This study attempts to investigate the causal association of plasma concentrations of linoleic acid with apolipoprotein B via Mendelian Randomization, in addition to confounders of this relationship.</div></div><div><h3>Methods</h3><div>The UK Biobank was used to obtain participant data for omega-6 polygenic risk scores, linoleic acid, and apolipoprotein B concentrations, in addition to confounding variable data. This study excluded individuals with a cardiovascular disease diagnosis or taking cholesterol-lowering medications. Multivariable regression was utilized to identify statistically significant impacts on apolipoprotein B, followed by Mendelian Randomization via two-stage least-squares analysis.</div></div><div><h3>Results</h3><div>Multivariable regression identified a statistically significant association of apolipoprotein B with linoleic acid, monounsaturated fatty acids, saturated fatty acids, age, sex, fasting, BMI, alcohol intake frequency, vigorous exercise, and smoking status. Two-stage least-squares analysis found a statistically significant causal association of genetically predicted linoleic acid on apolipoprotein B concentration (b = 0.23; 95 % CI: 0.207–0.243; p < 0.001), with the first stage of the analysis yielding an eigenvalue of 755.79 and F-statistic of 2796.93 and the second stage of the analysis yielding a statistically significant Wald χ <sup>2</sup> value of 27276.48 and R<sup>2</sup> of 0.62.</div></div><div><h3>Conclusions</h3><div>This study demonstrates a causal association of linoleic acid with apolipoprotein B concentrations. Future studies should evaluate this association and the confounders of this relationship.</div></div>","PeriodicalId":10352,"journal":{"name":"Clinical nutrition ESPEN","volume":"68 ","pages":"Pages 619-625"},"PeriodicalIF":2.9000,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical nutrition ESPEN","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2405457725003547","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Apolipoprotein B is an essential causal marker of cardiovascular disease. Studies have attempted to understand the impact of fatty acids on cardiovascular disease risk by measuring changes in apolipoprotein B. Linoleic acid is an omega-6 polyunsaturated fatty acid that has demonstrated effects on cardiovascular disease outcomes.
Objective
This study attempts to investigate the causal association of plasma concentrations of linoleic acid with apolipoprotein B via Mendelian Randomization, in addition to confounders of this relationship.
Methods
The UK Biobank was used to obtain participant data for omega-6 polygenic risk scores, linoleic acid, and apolipoprotein B concentrations, in addition to confounding variable data. This study excluded individuals with a cardiovascular disease diagnosis or taking cholesterol-lowering medications. Multivariable regression was utilized to identify statistically significant impacts on apolipoprotein B, followed by Mendelian Randomization via two-stage least-squares analysis.
Results
Multivariable regression identified a statistically significant association of apolipoprotein B with linoleic acid, monounsaturated fatty acids, saturated fatty acids, age, sex, fasting, BMI, alcohol intake frequency, vigorous exercise, and smoking status. Two-stage least-squares analysis found a statistically significant causal association of genetically predicted linoleic acid on apolipoprotein B concentration (b = 0.23; 95 % CI: 0.207–0.243; p < 0.001), with the first stage of the analysis yielding an eigenvalue of 755.79 and F-statistic of 2796.93 and the second stage of the analysis yielding a statistically significant Wald χ 2 value of 27276.48 and R2 of 0.62.
Conclusions
This study demonstrates a causal association of linoleic acid with apolipoprotein B concentrations. Future studies should evaluate this association and the confounders of this relationship.
期刊介绍:
Clinical Nutrition ESPEN is an electronic-only journal and is an official publication of the European Society for Clinical Nutrition and Metabolism (ESPEN). Nutrition and nutritional care have gained wide clinical and scientific interest during the past decades. The increasing knowledge of metabolic disturbances and nutritional assessment in chronic and acute diseases has stimulated rapid advances in design, development and clinical application of nutritional support. The aims of ESPEN are to encourage the rapid diffusion of knowledge and its application in the field of clinical nutrition and metabolism. Published bimonthly, Clinical Nutrition ESPEN focuses on publishing articles on the relationship between nutrition and disease in the setting of basic science and clinical practice. Clinical Nutrition ESPEN is available to all members of ESPEN and to all subscribers of Clinical Nutrition.