Plasma linoleic acid levels and cardiovascular risk factors: results from the norwegian ace 1950 study

ABSTRACT BACKGROUND A high intake of linoleic acid (LA), the major dietary polyunsaturated fatty acid (PUFA), has previously been associated with reduced cardiovascular (CV) morbidity and

mortality in observational studies. However, recent secondary analyses from clinical trials of LA-rich diet suggest harmful effects of LA on CV health. METHODS A total of 3706 participants,

all born in 1950, were included in this cross-sectional study. We investigated associations between plasma phospholipid levels of LA and CV risk factors in a Norwegian general population,

characterized by a relative low LA and high marine n-3 PUFA intake. The main statistical approach was multivariable linear regression. RESULTS Plasma phospholipid LA levels ranged from 11.4

to 32.0 wt%, with a median level of 20.8 wt% (interquartile range 16.8–24.8 wt%). High plasma LA levels were associated with lower serum low-density lipoprotein cholesterol levels

(standardized regression coefficient [Std. β-coeff.] −0.04, _p_ = 0.02), serum triglycerides (Std. β-coeff. −0.10, _p_ < 0.001), fasting plasma glucose (Std. β-coeff. −0.10, _p_ < 

0.001), body mass index (Std. β-coeff. −0.13, _p_ < 0.001), systolic and diastolic blood pressure (Std. β-coeff. −0.04, _p_ = 0.03 and Std. β-coeff. −0.02, _p_ = 0.02, respectively) and

estimated glomerular filtration rate (Std. β-coeff. −0.09, _p_ < 0.001). We found no association between plasma LA levels and high-density lipoprotein cholesterol levels, glycated

hemoglobin, carotid intima-media thickness, or C-reactive protein. CONCLUSION High plasma LA levels were favorably associated with several CV risk factors in this study of a Norwegian

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Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS ASSOCIATIONS OF PLASMA OMEGA-3 AND OMEGA-6 PUFA LEVELS WITH ARTERIAL ELASTICITY: THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS

Article 09 June 2022 BLOOD N-3 FATTY ACID LEVELS AND TOTAL AND CAUSE-SPECIFIC MORTALITY FROM 17 PROSPECTIVE STUDIES Article Open access 22 April 2021 ASSOCIATIONS OF PLASMA PHOSPHOLIPID

CIS-VACCENIC ACID WITH INSULIN RESISTANCE MARKERS IN NON-DIABETIC MEN WITH HYPERLIPIDEMIA Article Open access 11 September 2024 REFERENCES * Whelan J, Fritsche K. Linoleic acid. Adv Nutr.

2013;4:311–2. PubMed  PubMed Central  Google Scholar  * Farvid MS, Ding M, Pan A, Sun Q, Chiuve SE, Steffen LM, et al. Dietary linoleic acid and risk of coronary heart disease: a systematic

review and meta-analysis of prospective cohort studies. Circulation. 2014;130:1568–78. CAS  PubMed  PubMed Central  Google Scholar  * Wu JH, Lemaitre RN, King IB, Song X, Psaty BM, Siscovick

DS, et al. Circulating omega-6 polyunsaturated fatty acids and total and cause-specific mortality: the Cardiovascular Health Study. Circulation. 2014;130:1245–53. CAS  PubMed  PubMed

Central  Google Scholar  * Marklund M, Wu JHY, Imamura F, Del Gobbo LC, Fretts A, de Goede J, et al. Biomarkers of dietary omega-6 fatty acids and incident cardiovascular disease and

mortality. Circulation. 2019;139:2422–36. CAS  PubMed  PubMed Central  Google Scholar  * Ramsden CE, Zamora D, Leelarthaepin B, Majchrzak-Hong SF, Faurot KR, Suchindran CM, et al. Use of

dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis. BMJ.

2013;346:e8707. PubMed  PubMed Central  Google Scholar  * Ramsden CE, Zamora D, Majchrzak-Hong S, Faurot KR, Broste SK, Frantz RP, et al. Re-evaluation of the traditional diet-heart

hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73). BMJ. 2016;353:i1246. PubMed  PubMed Central  Google Scholar  * Fritsche KL. The science of fatty acids

and inflammation. Adv Nutr. 2015;6:293S–301S. CAS  PubMed  PubMed Central  Google Scholar  * Harris WS, Mozaffarian D, Rimm E, Kris-Etherton P, Rudel LL, Appel LJ, et al. Omega-6 fatty acids

and risk for cardiovascular disease: a science advisory from the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on

Cardiovascular Nursing; and Council on Epidemiology and Prevention. Circulation. 2009;119:902–7. PubMed  Google Scholar  * Legrand P, Morise A, Kalonji E. Update of French nutritional

recommendations for fatty acids. World Rev Nutr Diet. 2011;102:137–43. CAS  PubMed  Google Scholar  * EFSA. Labelling reference intake values for n-3 and n-6 polyunsaturated fatty acids.

EFSA J. 2009;1176:1–11. Google Scholar  * Sioen I, van Lieshout L, Eilander A, Fleith M, Lohner S, Szommer A, et al. Systematic review on n-3 and n-6 polyunsaturated fatty acid intake in

european countries in light of the current recommendations—focus on specific population groups. Ann Nutr Metab. 2017;70:39–50. CAS  PubMed  PubMed Central  Google Scholar  * Engeset D,

Alsaker E, Ciampi A, Lund E. Dietary patterns and lifestyle factors in the Norwegian EPIC cohort: the Norwegian Women and Cancer (NOWAC) study. Eur J Clin Nutr. 2005;59:675–84. CAS  PubMed 

Google Scholar  * Nordic Council of Ministers. Nordic nutrition recommendations 2012. 2014;5:1. https://doi.org/10.6027/Nord2014-002. * Hodson L, Skeaff CM, Fielding BA. Fatty acid

composition of adipose tissue and blood in humans and its use as a biomarker of dietary intake. Prog Lipid Res. 2008;47:348–80. CAS  PubMed  Google Scholar  * Hodge AM, Simpson JA, Gibson

RA, Sinclair AJ, Makrides M, O’Dea K, et al. Plasma phospholipid fatty acid composition as a biomarker of habitual dietary fat intake in an ethnically diverse cohort. Nutr Metab Cardiovasc

Dis. 2007;17:415–26. CAS  PubMed  Google Scholar  * Berge T, Vigen T, Pervez MO, Ihle-Hansen H, Lyngbakken MN, Omland T, et al. Heart and brain interactions—the Akershus Cardiac Examination

(ACE) 1950 Study Design. Scand Cardiovasc J. 2015;49:308–15. PubMed  Google Scholar  * Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ

Tech Rep Ser. 2000;894:1–253. Google Scholar  * Expert Panel on Detection Evaluation, Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of The National

Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486–97. Google

Scholar  * Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–12. PubMed  PubMed

Central  Google Scholar  * Ihle-Hansen H, Vigen T, Ihle-Hansen H, Ronning OM, Berge T, Thommessen B, et al. Prevalence of carotid plaque in a 63- to 65-year-old Norwegian cohort from the

general population: the ACE (Akershus Cardiac Examination) 1950 Study. J Am Heart Assoc. 2018;7. * Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of

total lipides from animal tissues. J Biol Chem. 1957;226:497–509. CAS  PubMed  Google Scholar  * Burdge GC, Wright P, Jones AE, Wootton SA. A method for separation of phosphatidylcholine,

triacylglycerol, non-esterified fatty acids and cholesterol esters from plasma by solid-phase extraction. Br J Nutr. 2000;84:781–7. CAS  PubMed  Google Scholar  * Wu JHY, Marklund M, Imamura

F, Tintle N, Ardisson Korat AV, de Goede J, et al. Omega-6 fatty acid biomarkers and incident type 2 diabetes: pooled analysis of individual-level data for 39 740 adults from 20 prospective

cohort studies. Lancet Diabetes Endocrinol. 2017;5:965–74. CAS  PubMed  PubMed Central  Google Scholar  * Cabout M, Alssema M, Nijpels G, Stehouwer CDA, Zock PL, Brouwer IA, et al.

Circulating linoleic acid and alpha-linolenic acid and glucose metabolism: the Hoorn Study. Eur J Nutr. 2017;56:2171–80. CAS  PubMed  Google Scholar  * Imamura F, Micha R, Wu JH, de Oliveira

Otto MC, Otite FO, Abioye AI, et al. Effects of saturated fat, polyunsaturated fat, monounsaturated fat, and carbohydrate on glucose-insulin homeostasis: a systematic review and

meta-analysis of randomised controlled feeding trials. PLoS Med. 2016;13:e1002087. PubMed  PubMed Central  Google Scholar  * Knottnerus SJG, Bleeker JC, RCI Wust, Ferdinandusse SLIJ, Wijburg

FA, et al. Disorders of mitochondrial long-chain fatty acid oxidation and the carnitine shuttle. Rev Endocr Metab Disord. 2018;19:93–106. CAS  PubMed  PubMed Central  Google Scholar  * Liu

X, Li Y, Tobias DK, Wang DD, Manson JE, Willett WC, et al. Changes in types of dietary fats influence long-term weight change in US women and men. J Nutr. 2018;148:1821–9. PubMed  PubMed

Central  Google Scholar  * Nakamura MT, Nara TY. Structure, function, and dietary regulation of delta6, delta5, and delta9 desaturases. Annu Rev Nutr. 2004;24:345–76. CAS  PubMed  Google

Scholar  * Warensjö E, Risérus U, Vessby B. Fatty acid composition of serum lipids predicts the development of the metabolic syndrome in men. Diabetologia. 2005;48:1999–2005. * Vessby B,

Gustafsson IB, Tengblad S, Boberg M, Andersson A. Desaturation and elongation of Fatty acids and insulin action. Ann NY Acad Sci. 2002;967:183–95. CAS  PubMed  Google Scholar  * Hussein N,

Ah-Sing E, Wilkinson P, Leach C, Griffin BA, Millward DJ. Long-chain conversion of [13C]linoleic acid and alpha-linolenic acid in response to marked changes in their dietary intake in men. J

Lipid Res. 2005;46:269–80. CAS  PubMed  Google Scholar  * Rett BS, Whelan J. Increasing dietary linoleic acid does not increase tissue arachidonic acid content in adults consuming

Western-type diets: a systematic review. Nutr Metab. 2011;8:36. CAS  Google Scholar  * Johnson GH, Fritsche K. Effect of dietary linoleic acid on markers of inflammation in healthy persons:

a systematic review of randomized controlled trials. J Acad Nutr Diet. 2012;112:1029–41. 41 e1-15 CAS  PubMed  Google Scholar  * Kelley-Hedgepeth A, Lloyd-Jones DM, Colvin A, Matthews KA,

Johnston J, Sowers MR, et al. Ethnic differences in C-reactive protein concentrations. Clin Chem. 2008;54:1027–37. CAS  PubMed  Google Scholar  * Brenna JT. Efficiency of conversion of

alpha-linolenic acid to long chain n-3 fatty acids in man. Curr Opin Clin Nutr Metab Care. 2002;5:127–32. CAS  PubMed  Google Scholar  * Mensink RP, Zock PL, Kester AD, Katan MB. Effects of

dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Am J Clin Nutr.

2003;77:1146–55. CAS  PubMed  Google Scholar  * Drouin-Chartier JP, Tremblay AJ, Lepine MC, Lemelin V, Lamarche B, Couture P. Substitution of dietary omega-6 polyunsaturated fatty acids for

saturated fatty acids decreases LDL apolipoprotein B-100 production rate in men with dyslipidemia associated with insulin resistance: a randomized controlled trial. Am J Clin Nutr.

2018;107:26–34. PubMed  PubMed Central  Google Scholar  * van Schalkwijk DB, Pasman WJ, Hendriks HF, Verheij ER, Rubingh CM, van Bochove K, et al. Dietary medium chain fatty acid

supplementation leads to reduced VLDL lipolysis and uptake rates in comparison to linoleic acid supplementation. PLoS ONE. 2014;9:e100376. PubMed  PubMed Central  Google Scholar  *

Al-Khudairy L, Hartley L, Clar C, Flowers N, Hooper L, Rees K. Omega 6 fatty acids for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2015:CD011094. * Polak

JF, O’Leary DH. Carotid intima-media thickness as surrogate for and predictor of CVD. Glob. Heart. 2016;11:295–312 e3. Google Scholar  * Sala-Vila A, Cofan M, Perez-Heras A, Nunez I,

Gilabert R, Junyent M, et al. Fatty acids in serum phospholipids and carotid intima-media thickness in Spanish subjects with primary dyslipidemia. Am J Clin Nutr. 2010;92:186–93. CAS  PubMed

  Google Scholar  * Ren L, Cai J, Liang J, Li W, Sun Z. Impact of cardiovascular risk factors on carotid intima-media thickness and degree of severity: a cross-sectional study. PLoS ONE.

2015;10:e0144182. PubMed  PubMed Central  Google Scholar  * Touboul PJ, Labreuche J, Bruckert E, Schargrodsky H, Prati P, Tosetto A, et al. HDL-C, triglycerides and carotid IMT: a

meta-analysis of 21,000 patients with automated edge detection IMT measurement. Atherosclerosis. 2014;232:65–71. CAS  PubMed  Google Scholar  * Lauretani F, Semba RD, Bandinelli S, Miller ER

3rd, Ruggiero C, Cherubini A, et al. Plasma polyunsaturated fatty acids and the decline of renal function. Clin Chem. 2008;54:475–81. CAS  PubMed  PubMed Central  Google Scholar  * Pertiwi

K, Wanders AJ, Harbers MC, Küpers LK, Soedamah-Muthu SS, de Goede J, et al. Plasma and dietary linoleic acid and 3-year risk of type 2 diabetes after myocardial infarction: a prospective

analysis in the alpha omega cohort. Diabetes Care. 2020;43:358–65. CAS  PubMed  Google Scholar  * Pertiwi K, Kok DE, Wanders AJ, de Goede J, Zock PL, Geleijnse JM. Circulating n-3 fatty

acids and linoleic acid as indicators of dietary fatty acid intake in post-myocardial infarction patients. Nutr Metab Cardiovasc Dis. 2019;29:343–50. CAS  PubMed  PubMed Central  Google

Scholar  Download references ACKNOWLEDGEMENTS We acknowledge the skilled study staff at the Clinical Trial Unit, Division of Medicine, Akershus University Hospital, and the Department of

Medical Research, Bærum Hospital, Vestre Viken Hospital Trust. We also thank the staff at The Lipid Research Laboratory, Aalborg University Hospital, Denmark, who performed the fatty acid

analyses. Finally, we would like to thank the study participants. FUNDING The ACE (Akershus Cardiac Examination) 1950 Study is funded by two health trusts (Akershus University Hospital HF

and Vestre Viken HF), and the South-Eastern Norway Regional Health Authority, the University of Oslo, and the Norwegian Health Association. AC was supported by public funding grants from

Akershus University Hospital. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Renal Medicine, Division of Medicine, Akershus University Hospital, Lørenskog, Norway Anupam

Chandra, My Svensson & Ivar Anders Eide * Institute of Clinical Medicine, University of Oslo, Oslo, Norway Anupam Chandra, Helge Røsjø, My Svensson, Thea Vigen, Ole Morten Rønning, 

Magnus Nakrem Lyngbakken, Torbjørn Omland & Arnljot Tveit * Division of Research and Innovation, Akershus University Hospital, Lørenskog, Norway Helge Røsjø * Division of Medicine,

Akershus University Hospital, Lørenskog, Norway Thea Vigen, Eivind Bjørkan Orstad, Ole Morten Rønning, Magnus Nakrem Lyngbakken & Torbjørn Omland * Department of Medical Research, Bærum

Hospital, Vestre Viken Hospital Trust, Drammen, Norway Håkon Ihle-Hansen, Trygve Berge & Arnljot Tveit * Centre for Bioinformatics, Department of Informatics, University of Oslo, Oslo,

Norway Ståle Nygård * Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway Ståle Nygård * Department of Cardiology, Aalborg University Hospital, Aalborg,

Denmark Erik Berg Schmidt Authors * Anupam Chandra View author publications You can also search for this author inPubMed Google Scholar * Helge Røsjø View author publications You can also

search for this author inPubMed Google Scholar * My Svensson View author publications You can also search for this author inPubMed Google Scholar * Thea Vigen View author publications You

can also search for this author inPubMed Google Scholar * Håkon Ihle-Hansen View author publications You can also search for this author inPubMed Google Scholar * Eivind Bjørkan Orstad View

author publications You can also search for this author inPubMed Google Scholar * Ole Morten Rønning View author publications You can also search for this author inPubMed Google Scholar *

Magnus Nakrem Lyngbakken View author publications You can also search for this author inPubMed Google Scholar * Ståle Nygård View author publications You can also search for this author

inPubMed Google Scholar * Trygve Berge View author publications You can also search for this author inPubMed Google Scholar * Erik Berg Schmidt View author publications You can also search

for this author inPubMed Google Scholar * Torbjørn Omland View author publications You can also search for this author inPubMed Google Scholar * Arnljot Tveit View author publications You

can also search for this author inPubMed Google Scholar * Ivar Anders Eide View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS AC, IAE, and MS

designed the present study. HR, TO, MNL, TB, and AT designed and organized the ACE 1950 Study including baseline examinations and data collection. TV, HI-H, EBO, and OMR performed carotid

ultrasound and baseline examinations. EBS was responsible for the fatty acid analyses. AC, IAE, and SN analyzed the data. AC, IAE, and MS edited the paper, EBS, TO, HR, TV, HI-H, SN, EBO,

OMR, MNL, TB, and AT co-edited the paper. All the authors approved the final version of the paper. AC submitted the paper. CORRESPONDING AUTHOR Correspondence to Anupam Chandra. ETHICS

DECLARATIONS CONFLICT OF INTEREST The authors declare that they have no conflict of interest. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer Nature remains neutral with regard to

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CITE THIS ARTICLE Chandra, A., Røsjø, H., Svensson, M. _et al._ Plasma linoleic acid levels and cardiovascular risk factors: results from the Norwegian ACE 1950 Study. _Eur J Clin Nutr_ 74,

1707–1717 (2020). https://doi.org/10.1038/s41430-020-0641-4 Download citation * Received: 19 September 2019 * Revised: 08 April 2020 * Accepted: 08 April 2020 * Published: 27 April 2020 *

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