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Sidorkiewicz M. The Cardioprotective Effects of Polyunsaturated Fatty Acids Depends on the Balance Between Their Anti- and Pro-Oxidative Properties. Nutrients 2024; 16:3937. [PMID: 39599723 PMCID: PMC11597422 DOI: 10.3390/nu16223937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 11/08/2024] [Accepted: 11/12/2024] [Indexed: 11/29/2024] Open
Abstract
Polyunsaturated fatty acids (PUFAs) are not only structural components of membrane phospholipids and energy storage molecules in cells. PUFAs are important factors that regulate various biological functions, including inflammation, oxidation, and immunity. Both n-3 and n-6 PUFAs from cell membranes can be metabolized into pro-inflammatory and anti-inflammatory metabolites that, in turn, influence cardiovascular health in humans. The role that PUFAs play in organisms depends primarily on their structure, quantity, and the availability of enzymes responsible for their metabolism. n-3 PUFAs, such as eicosapentaenoic (EPA) and docosahexaenoic (DHA), are generally known for anti-inflammatory and atheroprotective properties. On the other hand, n-6 FAs, such as arachidonic acid (AA), are precursors of lipid mediators that display mostly pro-inflammatory properties and may attenuate the efficacy of n-3 by competition for the same enzymes. However, a completely different light on the role of PUFAs was shed due to studies on the influence of PUFAs on new-onset atrial fibrillation. This review analyzes the role of PUFAs and PUFA derivatives in health-related effects, considering both confirmed benefits and newly arising controversies.
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Affiliation(s)
- Malgorzata Sidorkiewicz
- Department of Medical Biochemistry, Faculty of Health Sciences, Medical University of Lodz, 90-419 Lodz, Poland
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Garg PK, Guan W, Nomura S, Weir NL, Tintle N, Virtanen JK, Hirakawa Y, Qian F, Sun Q, Rimm E, Lemaitre RN, Jensen PN, Heckbert SR, Imamura F, Steur M, Leander K, Laguzzi F, Voortman T, Ninomiya T, Mozaffarian D, Harris WS, Siscovick DS, Tsai MY. n-6 fatty acid biomarkers and incident atrial fibrillation: an individual participant-level pooled analysis of 11 international prospective studies. Am J Clin Nutr 2023; 118:921-929. [PMID: 37769813 DOI: 10.1016/j.ajcnut.2023.09.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Revised: 09/02/2023] [Accepted: 09/18/2023] [Indexed: 10/03/2023] Open
Abstract
BACKGROUND The presence of atrial fibrillation (AF) is associated with an over 2-fold increased risk of stroke, heart failure, and cardiovascular mortality. Long chain n-6 PUFAs have been suggested to have a variety of beneficial biologic effects that may reduce AF development; however, prior studies evaluating this relationship are limited. OBJECTIVES We prospectively evaluated the association between circulating levels of linoleic acid (LA) and arachidonic acid (AA) with incident AF. METHODS We used participant-level data from a global consortium of 11 prospective cohort studies with measurements of LA and AA in adults (aged ≥18 y). Participating studies conducted de novo analyses using a prespecified analytical plan with harmonized definitions for exposures, outcomes, covariates, and subgroups. Associations were pooled using inverse-variance weighted meta-analysis. RESULTS Among 41,335 participants, 6173 incident cases of AF were ascertained, with median follow-up time of 14 y. In multivariable analysis, per interquintile range (difference between the 10th and 90th percentiles for each fatty acid), circulating n-6 levels were not associated with incident AF. For LA, the hazard ratio per interquintile range was 0.96 (95% confidence interval [CI]: 0.89, 1.04), and for AA, 1.02 (95% CI: 0.94, 1.10), with little evidence of heterogeneity between cohorts. Associations were similarly nonsignificant across subgroups of age, race, and biomarker fraction. CONCLUSIONS Biomarkers of n-6 fatty acids including LA and AA are not associated with incident AF. These findings suggest that overall effects of n-6 PUFAs on influencing AF development are neutral.
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Affiliation(s)
- Parveen K Garg
- Division of Cardiology, University of Southern California Keck School of Medicine, Los Angeles, CA, United States
| | - Weihua Guan
- Division of Biostatistics, University of Minnesota, Minneapolis, MN, United States
| | - Sarah Nomura
- Department of Lab Medicine and Pathology, University of Minnesota, Minneapolis, MN, United States
| | - Natalie L Weir
- Department of Lab Medicine and Pathology, University of Minnesota, Minneapolis, MN, United States
| | - Nathan Tintle
- Department of Population Health Sciences, College of Nursing, University of Illinois-Chicago, Chicago, IL, United States
| | - Jyrki K Virtanen
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - Yoichiro Hirakawa
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Frank Qian
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Qi Sun
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States
| | - Eric Rimm
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States
| | - Rozenn N Lemaitre
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, United States
| | - Paul N Jensen
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, United States
| | - Susan R Heckbert
- Department of Epidemiology, University of Washington, Seattle, WA, United States
| | - Fumiaki Imamura
- MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom
| | - Marinka Steur
- Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
| | - Karin Leander
- Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Federica Laguzzi
- Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Trudy Voortman
- Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
| | - Toshiharu Ninomiya
- Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Dariush Mozaffarian
- Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, United States; Division of Cardiology, Tufts Medical Center, Boston, MA, United States
| | - William S Harris
- Department of Internal Medicine, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, United States
| | | | - Michael Y Tsai
- Department of Lab Medicine and Pathology, University of Minnesota, Minneapolis, MN, United States.
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Plasma Oxylipin Profile Discriminates Ethnicities in Subjects with Non-Alcoholic Steatohepatitis: An Exploratory Analysis. Metabolites 2022; 12:metabo12020192. [PMID: 35208265 PMCID: PMC8875408 DOI: 10.3390/metabo12020192] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Revised: 02/14/2022] [Accepted: 02/17/2022] [Indexed: 02/04/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a common liver pathology that includes steatosis, or non-alcoholic fatty liver (NAFL), and non-alcoholic steatohepatitis (NASH). Without a clear pathophysiological mechanism, it affects Hispanics disproportionately compared to other ethnicities. Polyunsaturated fatty acids (PUFAs) and inflammatory lipid mediators including oxylipin (OXL) and endocannabinoid (eCB) are altered in NAFLD and thought to contribute to its pathogenesis. However, the existence of ethnicity-related differences is not clear. We employed targeted lipidomic profiling for plasma PUFAs, non-esterified OXLs and eCBs in White Hispanics (HIS, n = 10) and Caucasians (CAU, n = 8) with biopsy-confirmed NAFL, compared with healthy control subjects (HC; n = 14 HIS; n = 8 CAU). NAFLD was associated with diminished long chain PUFA in HIS, independent of histological severity. Differences in plasma OXLs and eCBs characterized ethnicities in NASH, with lower arachidonic acid derived OXLs observed in HIS. The secondary analysis comparing ethnicities within NASH (n = 12 HIS; n = 17 CAU), confirms these ethnicity-related differences and suggests lower lipoxygenase(s) and higher soluble epoxide hydrolase(s) activities in HIS compared to CAU. While causes are not clear, these lipidomic differences might be with implications for NAFLD severity and are worth further investigation. We provide preliminary data indicating ethnicity-specific lipidomic signature characterizes NASH which requires further validation.
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Serum n-6 polyunsaturated fatty acids and risk of atrial fibrillation: the Kuopio Ischaemic Heart Disease Risk Factor Study. Eur J Nutr 2021; 61:1981-1989. [PMID: 34961890 PMCID: PMC9106603 DOI: 10.1007/s00394-021-02780-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 12/09/2021] [Indexed: 12/14/2022]
Abstract
Purpose N-6 polyunsaturated fatty acids (PUFA), particularly linoleic acid (LA), have been associated with lower risk of coronary heart disease (CHD), but little is known about their antiarrhythmic properties. We investigated the association of the serum n-6 PUFAs with the risk of atrial fibrillation (AF), the most common type of cardiac arrhythmia. Methods The study included 2450 men from the Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42–60 years at baseline. The total n-6 PUFA includes linoleic acid (LA), arachidonic acid (AA), γ-linolenic acid (GLA) and dihomo-γ-linolenic acid (DGLA). Cox proportional hazards regression was used to estimate hazard ratio (HR) of incident events. Results During the mean follow-up of 22.4 years, 486 AF cases occurred. The multivariable-adjusted HR in the highest versus the lowest quartile of total serum n-6 PUFA concentration was 0.79 (95% CI 0.58–1.08, P trend = 0.04). When evaluated individually, only serum LA concentration was inversely associated with AF risk (multivariable-adjusted extreme-quartile HR 0.69, 95% CI 0.51–0.94, P trend = 0.02). These associations were stronger among the men without history of CHD or congestive heart failure at baseline, compared to men with such disease history (P for interaction = 0.05 for total n-6 PUFA and LA). Similar associations were observed with dietary LA and AA intakes. No significant associations were observed with serum AA, GLA or DGLA concentrations. Conclusions Higher circulating concentration and dietary intake of n-6 PUFA, mainly LA, are associated with lower risk of AF, especially among men without history of CHD or congestive heart failure. Supplementary Information The online version contains supplementary material available at 10.1007/s00394-021-02780-0.
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