Abstract
Low red blood cell (RBC) membrane content of EPA and DHA, i.e., the omega-3 index
(O3I), and elevated RBC distribution width (RDW) are risk factors for all-cause mortality.
O3I and RDW are related with membrane fluidity and deformability. Our objective was
to determine if there is a relationship between O3I and RDW in healthy adults. Subjects
without inflammation or anemia, and with values for O3I, RDW, high-sensitivity C-reactive
protein (CRP), body mass index (BMI), age and sex were identified (n = 25,485) from a clinical laboratory dataset of > 45,000 individuals. RDW was inversely
associated with O3I in both sexes before and after (both p < 0.00001) adjusting models for sex, age, BMI and CRP. Stratification by sex revealed
a sex-O3I interaction with the RDW-O3I slope (p < 0.00066) being especially steep in females with O3I ≤ 5.6%. In healthy adults of
both sexes, the data suggested that an O3I of > 5.6% may help maintain normal RBC
structural and functional integrity.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Prostaglandins, Leukotrienes and Essential Fatty AcidsAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Improved classification of anemias by MCV and RDW.Am. J. Clin. Pathol. 1983; 80: 322-326https://doi.org/10.1093/ajcp/80.3.322
- Association of the Red Cell Distribution Width with Red Blood Cell Deformability.in: Welch W.J. Palm F. Bruley D.F. Harrison D.K. Oxygen Transport to Tissue XXXIV. Springer New York, New York, NY2013: 211-216https://doi.org/10.1007/978-1-4614-4989-8_29
- Red cell distribution width in sickle cell anemia.Am. J. Med. Technol. 1981; 47: 231-233
- Laboratory evaluation of anemia.West J. Med. 1987; 146: 443-451
- Red cell distribution width, mean corpuscular volume, and transferrin saturation in the diagnosis of iron deficiency.JAMA Intern. Med. 1988; 148: 2128-2130
- Relation between red blood cell distribution width and cardiovascular event rate in people with coronary disease.Circulation. 2008; 117: 163-168https://doi.org/10.1161/CIRCULATIONAHA.107.727545
- Gender and ethnic differences in red cell distribution width and its association with mortality among low risk healthy united state adults.Am. J. Cardiol. 2012; 109: 1664-1670https://doi.org/10.1016/j.amjcard.2012.01.396
- Relation between changes in red cell distribution width and clinical outcomes in acute decompensated heart failure.Int. J. Cardiol. 2013; 167: 1412-1416https://doi.org/10.1016/j.ijcard.2012.04.065
- Red blood cell distribution width: a novel predictive indicator for cardiovascular and cerebrovascular diseases.Dis. Markers. 2017; 2017: 1-23https://doi.org/10.1155/2017/7089493
- Red cell distribution width and risk of cardiovascular mortality: insights from National Health and Nutrition Examination Survey (NHANES)-III.Int. J. Cardiol. 2017; 232: 105-110https://doi.org/10.1016/j.ijcard.2017.01.045
- Association between red blood cell distribution width and in-hospital mortality in acute myocardial infarction.Medicine (Baltimore). 2021; 100: e25404https://doi.org/10.1097/MD.0000000000025404
- Red blood cell distribution width as a novel prognostic marker after myocardial revascularization or cardiac valve surgery.Sci. Rep. 2021; 11: 7889https://doi.org/10.1038/s41598-021-87075-4
- Association of red blood cell distribution width with mortality risk in hospitalized adults with SARS-CoV-2 infection.JAMA Network Open. 2020; 3e2022058https://doi.org/10.1001/jamanetworkopen.2020.22058
- Red cell distribution width is associated with mortality in non-anemic patients with COVID-19.J. Med. Virol. 2021; (jmv.27011)https://doi.org/10.1002/jmv.27011
- Predictive value of prognostic nutritional index on COVID-19 severity.Front. Nutr. 2021; 7582736https://doi.org/10.3389/fnut.2020.582736
- Are average platelet volume, red cell distribution width and platelet distribution width guiding markers for acute appendicitis treatment options?.Int. J. Clin. Pract. 2021; https://doi.org/10.1111/ijcp.14232
- Association between red cell distribution width and hospital mortality in patients with sepsis.J. Int. Med. Res. 2021; 49030006052110042https://doi.org/10.1177/03000605211004221
- Red cell distribution width as a predictor for bronchopulmonary dysplasia in premature infants.Sci. Rep. 2021; 11: 7221https://doi.org/10.1038/s41598-021-86752-8
- Increased red blood cell distribution width associates with cancer stage and prognosis in patients with lung cancer.PLoS ONE. 2013; 8: e80240https://doi.org/10.1371/journal.pone.0080240
- Nomograms incorporating preoperative RDW level for the prediction of postoperative complications and survival in colorectal liver metastases after resection.Ann. Palliat. Med. 2021; 10: 4143-4158https://doi.org/10.21037/apm-20-2418
- The fine-tuning of cell membrane lipid bilayers accentuates their compositional complexity.BioEssays. 2021; : 1-15https://doi.org/10.1002/bies.202100021
- The Omega-3 Index: a new risk factor for death from coronary heart disease?.Prev. Med. 2004; 39: 212-220https://doi.org/10.1016/j.ypmed.2004.02.030
- Incorporation of n-3 fatty acids into plasma lipid fractions, and erythrocyte membranes and platelets during dietary supplementation with fish, fish oil, and docosahexaenoic acid-rich oil among healthy young men.Lipids. 1997; 32: 697-705
- Determinants of erythrocyte omega-3 fatty acid content in response to fish oil supplementation: a dose–response randomized controlled trial.J. Am. Heart Assoc. 2013; 2e000513https://doi.org/10.1161/JAHA.113.000513
- Effect of oral administration of highly purified eicosapentaenoic acid on platelet function, blood viscosity and red cell deformability in healthy human subjects.Atherosclerosis. 1983; 46: 321-331
- The effects of dietary omega-3 polyunsaturated fatty acids on erythrocyte membrane phospholipids, erythrocyte deformabilit and blood viscosity in healthy volunteers.Atherosclerosis. 1985; 55: 267-281
- Effects of fish oil capsules in two dosages on blood pressure, platelet functions, haemorheological and clinical chemistry parameters in apparently healthy subjects.Ann. Nutr. Metab. 1989; 33: 359-367https://doi.org/10.1159/000177559
- Freshwater fish diet affects lipid composition, deformability and aggregation properties of erythrocytes.Atherosclerosis. 1990; 82: 37-42
- Predicting the effects of supplemental EPA and DHA on the omega-3 index.Am. J. Clin. Nutr. 2019; 110: 1034-1040https://doi.org/10.1093/ajcn/nqz161
- F. The Fatty acids and outcomes research consortium, blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies.Nat. Commun. 2021; 12: 1-9https://doi.org/10.1038/s41467-021-22370-2
- The role of red blood cell distribution width (RDW) in cardiovascular risk assessment: useful or hype?.Ann. Transl. Med. 2019; 7 (581–581)https://doi.org/10.21037/atm.2019.09.58
- Relation of red blood cell distribution width to risk of major adverse cardiovascular events, death, and effect of alirocumab after acute coronary syndrome.American Heart Association. American Heart Association, Phildadelphia, PA2019: 1
- Impact of Chronic Inflammation, Assessed by hs-CRP, on the Association between Red Cell Distribution Width and Arterial Cardiovascular Disease: the Tromsø Study.TH Open. 2018; 02: e182-e189https://doi.org/10.1055/s-0038-1651523
- Diagnostic implications of C-reactive protein.Arch. Surg. 2003; 138: 220https://doi.org/10.1001/archsurg.138.2.220
- Postdiagnosis C-reactive protein and breast cancer survivorship: findings from the WHEL study.Cancer Epidemiol Biomarkers Prev. 2014; 23: 189-199https://doi.org/10.1158/1055-9965.EPI-13-0852
- C-reactive Protein Concentrations As a Marker of Inflammation Or Infection For Interpreting Biomarkers of Micronutrient Status.World Health Organization, Geneva, Switzerland2014
- The application of high-sensitivity C-reactive protein in clinical practice: a 2015 update.US Pharmacist. 2015; 40: 50-53
S. Jafarnejad, V. Boccardi, B. Hosseini, M. Taghizadeh, Z. Hamedifard, A meta-analysis of randomized control trials: the impact of vitamin C Supplementation on serum CRP and serum hs-CRP concentrations, (2018). https://doi.org/10.2174/1381612824666181017101810.
- The red blood cell distribution width.J. Emerg. Med. 1991; 9: 71-74https://doi.org/10.1016/0736-4679(91)90592-4
- Anemia in clinical practice—definition and classification: does hemoglobin change with aging?.Sem. Hematol. 2015; 52: 261-269https://doi.org/10.1053/j.seminhematol.2015.07.006
- Biomarkers of cholesterol homeostasis in a clinical laboratory database sample comprising 667,718 patients.J. Clin. Lipidol. 2015; 9: 807-816https://doi.org/10.1016/j.jacl.2015.08.003
- Changes in erythrocyte membrane trans and marine fatty acids between 1999 and 2006 in older Americans.J. Nutr. 2012; 142: 1297-1303https://doi.org/10.3945/jn.112.158295
- Red blood cells as an organ? How deep omics characterization of the most abundant cell in the human body highlights other systemic metabolic functions beyond oxygen transport.Expert Rev. Proteomics. 2018; 15: 855-864https://doi.org/10.1080/14789450.2018.1531710
- Squeezing for life – properties of red blood cell deformability.Front. Physiol. 2018; 9: 656https://doi.org/10.3389/fphys.2018.00656
- Membranes as metabolic pacemakers.Clin. Exp. Pharmacol. Physiol. 2003; 30: 559-564https://doi.org/10.1046/j.1440-1681.2003.03883.x
- RBC and WBC fatty acid composition following consumption of an omega 3 supplement: lessons for future clinical trials.Lipids Health Dis. 2010; 9: 31https://doi.org/10.1186/1476-511X-9-31
- The influence of dietary fatty acids on immune responses.Nutrients. 2019; 11: 2990https://doi.org/10.3390/nu11122990
- Dietary Sardine Oil Increases Erythrocyte Membrane Fluidity in Diabetic Patients.Diabetes. 1986; 35: 604-611
- Membrane lipid raft organization is uniquely modified by n-3 polyunsaturated fatty acids.PLEFA. 2013; 88: 43-47
- The structure of DHA in phospholipid membranes.Lipids. 2003; 38: 445-452
- Effects of purified eicosapentaenoic acid on red blood cell distribution width and vascular endothelial function in patients with coronary artery disease.Vasc Fail. 2017; 1: 15-21https://doi.org/10.30548/vascfail.1.1_15
- Advances in the measurement of red blood cell deformability: a brief review.J. Cell Biotechnol. 2015; 1: 63-79https://doi.org/10.3233/JCB-15007
- Red blood cell distribution width: a simple parameter with multiple clinical applications.Crit. Rev. Clin. Lab. Sci. 2015; 52: 86-105https://doi.org/10.3109/10408363.2014.992064
- Oxidative stress, aging, and diseases.Clin. Intervent. Aging. Volume. 2018; 13: 757-772https://doi.org/10.2147/CIA.S158513
- The microenvironment can shift erythrocytes from a friendly to a harmful behavior: pathogenetic implications for vascular diseases.Cardiovasc. Res. 2007; 75: 21-28https://doi.org/10.1016/j.cardiores.2007.03.007
- Omega-3 fatty acids supplementation and oxidative stress parameters: a systematic review and meta-analysis of clinical trials.Pharmacol. Res. 2019; 149104462https://doi.org/10.1016/j.phrs.2019.104462
- Association between red cell distribution width and cardiovascular outcomes – systematic review and meta-analysis.MRAJ. 2021; 9https://doi.org/10.18103/mra.v9i7.2468
- Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance.Bioch. Biophys. Acta: Mol Cell Biol Lipids. 2015; 1851: 469-484https://doi.org/10.1016/j.bbalip.2014.08.010
- Eicosapentaenoic and docosahexaenoic acid derived specialised pro-resolving mediators: concentrations in humans and the effects of age, sex, disease and increased omega-3 fatty acid intake.Biochimie. 2020; 178: 105-123https://doi.org/10.1016/j.biochi.2020.08.015
- Red blood cell fatty acids and biomarkers of inflammation: a cross-sectional study in a community-based cohort.Atherosclerosis. 2015; 240: 431-436https://doi.org/10.1016/j.atherosclerosis.2015.03.043
- Effect of marine-derived n-3 polyunsaturated fatty acids on C-Reactive Protein, interleukin 6 and tumor necrosis factor α: a meta-analysis.PLoS ONE. 2014; 9: e88103https://doi.org/10.1371/journal.pone.0088103
US Dept Health & Human Services, Nutrient Assessment for DRI Review, Nutient Assessment for DRI Review. (2014). https://health.gov/our-work/food-nutrition/dietary-reference-intakes-dris/nutrient-assessment-dri-review (accessed October 20, 2020).
- Beyond Nutrient Deficiency—Opportunities to Improve Nutritional Status and Promote Health Modernizing DRIs and Supplementation Recommendations.Nutrients. 2021; 13: 1-25https://doi.org/10.3390/nu13061844
- Dietary reference intakes for DHA and EPA.PLEFA. 2009; 81: 99-104https://doi.org/10.1016/j.plefa.2009.05.011
- Towards establishing dietary reference intakes for eicosapentaenoic and docosahexaenoic acids.J. Nutr. 2009; 139: 804S-819Shttps://doi.org/10.3945/jn.108.101329
- Omega-3 fatty acids are a potential therapy for patients with sickle cell disease.Nat. Rev. Dis. Primers. 2018; 4: 15https://doi.org/10.1038/s41572-018-0012-9
- Biochemical and therapeutic effects of Omega-3 fatty acids in sickle cell disease.Complement. Therap. Med. 2020; 52102482https://doi.org/10.1016/j.ctim.2020.102482
- Effect of purified eicosapentaenoic acid on red cell distribution width in patients with ischemic heart disease.Heart Vessels. 2015; 30: 587-594https://doi.org/10.1007/s00380-014-0526-3
- n-3 PUFAs improve erythrocyte fatty acid profile in patients with small AAA: a randomized controlled trial.J. Lipid Res. 2019; 60: 1154-1163https://doi.org/10.1194/jlr.P093013
- Comparison of cardiometabolic risk biomarkers from a national clinical laboratory with the US adult population.J. Clin. Lipid. 2015; 9: 817-823https://doi.org/10.1016/j.jacl.2015.07.014
- Long-chain omega-3 fatty acid serum concentrations across life stages in the USA: an analysis of NHANES 2011–2012.BMJ Open. 2021; 11e043301https://doi.org/10.1136/bmjopen-2020-043301
- Comparative analysis of red cell distribution width and high sensitivity C-reactive protein for coronary heart disease mortality prediction in multi-ethnic population: findings from the 1999–2004 NHANES.Int. J. Cardiol. 2013; 168: 5156-5161https://doi.org/10.1016/j.ijcard.2013.07.109
- Red cell distribution width and risk of cardiovascular mortality: insights from National Health and Nutrition Examination Survey (NHANES)-III.Int. J. Cardiol. 2017; 232: 105-110https://doi.org/10.1016/j.ijcard.2017.01.045
- The Omega-3 Index: clinical Utility for Therapeutic Intervention.Curr. Cardiol. Rep. 2010; 12: 503-508https://doi.org/10.1007/s11886-010-0141-6
Article info
Publication history
Published online: November 22, 2021
Accepted:
November 18,
2021
Received in revised form:
November 15,
2021
Received:
October 6,
2021
Identification
Copyright
© 2021 Elsevier Ltd. All rights reserved.
