{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T20:18:19Z","timestamp":1771273099909,"version":"3.50.1"},"reference-count":35,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,18]],"date-time":"2020-04-18T00:00:00Z","timestamp":1587168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Nutricia grant No RG-2 2015","award":["Nutricia grant No RG-2 2015"],"award-info":[{"award-number":["Nutricia grant No RG-2 2015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Being rich in polyunsaturated fatty acids, flaxseed (Linum usitatissimum L.) is thought to be able to decrease lipid levels and dampen inflammation. In this pilot study, we aimed to determine whether flaxseed supplementation could improve the profiles of lipids and inflammatory mediators in patients with severe hyperlipidemia resistant to conventional lipid-lowering pharmacotherapy and requiring lipoprotein apheresis. To this end, six patients received, blindly\u2014in addition to their normal lipoprotein apheresis regimen\u2014a 10-week dietary supplementation with flaxseed (28 g\/d) administered in biscuits. This was followed by a 10-week washed out-period and a 10-week supplementation phase with whole wheat placebo. Blood samples were collected at the end of each phase, before the lipoprotein apheresis session. The primary endpoint was the lipid profile and the secondary endpoints were the concentrations of inflammatory mediators and tolerability. Flaxseed supplementation was well-tolerated and resulted in a consistent and significant decrease in total cholesterol and low-density lipoprotein (LDL) levels. The median (and range) percentage decrease was 11.5% (0\u201318.8) and 7.3% (4.4\u201326.6), for cholesterol (p = 0.015) and LDL-C (p = 0.003), respectively. On the other hand, there was no significant effect of flaxseed on lipoprotein(a) (Lp(a)), C-reactive protein (CRP), and interleukin 6 (IL-6) concentrations. These observations indicate that flaxseed can produce a cholesterol- and LDL-lowering effect in patients treated with lipoprotein apheresis. Thus, flaxseed supplementation may help to control cholesterol in this patient population. The flaxseed supplementation protocol applied may be of use for further adequately-powered studies to validate and extend our findings.<\/jats:p>","DOI":"10.3390\/nu12041137","type":"journal-article","created":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T04:49:38Z","timestamp":1587444578000},"page":"1137","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Flaxseed (Linum Usitatissimum L.) Supplementation in Patients Undergoing Lipoprotein Apheresis for Severe Hyperlipidemia\u2014A Pilot Study"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8433-5745","authenticated-orcid":false,"given":"Dominika","family":"Kanikowska","sequence":"first","affiliation":[{"name":"Department of Pathophysiology, Poznan University of Medical Sciences, Rokietnicka 8, 60-806 Pozna\u0144, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6291-0814","authenticated-orcid":false,"given":"Katarzyna","family":"Korybalska","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Poznan University of Medical Sciences, Rokietnicka 8, 60-806 Pozna\u0144, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1707-3807","authenticated-orcid":false,"given":"Agnieszka","family":"Mickiewicz","sequence":"additional","affiliation":[{"name":"1st Department of Cardiology, Medical University of Gdansk, Marii Sk\u0142odowskiej-Curie 3a, 80-210 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafa\u0142","family":"Rutkowski","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Poznan University of Medical Sciences, Rokietnicka 8, 60-806 Pozna\u0144, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2264-1442","authenticated-orcid":false,"given":"Agnieszka","family":"Kuchta","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Medical University of Gdansk, Marii Sk\u0142odowskiej-Curie 3a, 80-210 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maki","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Institutional Research, Aichi Medical University, Nagakute, Aichi 480-1195, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewelina","family":"Kreft","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Medical University of Gdansk, Marii Sk\u0142odowskiej-Curie 3a, 80-210 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcin","family":"Fija\u0142kowski","sequence":"additional","affiliation":[{"name":"1st Department of Cardiology, Medical University of Gdansk, Marii Sk\u0142odowskiej-Curie 3a, 80-210 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcin","family":"Grucha\u0142a","sequence":"additional","affiliation":[{"name":"1st Department of Cardiology, Medical University of Gdansk, Marii Sk\u0142odowskiej-Curie 3a, 80-210 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4540-6955","authenticated-orcid":false,"given":"Maciej","family":"Jankowski","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Medical University of Gdansk, Marii Sk\u0142odowskiej-Curie 3a, 80-210 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrzej","family":"Br\u0119borowicz","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Poznan University of Medical Sciences, Rokietnicka 8, 60-806 Pozna\u0144, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janusz","family":"Witowski","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Poznan University of Medical Sciences, Rokietnicka 8, 60-806 Pozna\u0144, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1093\/aje\/kwh236","article-title":"Genetic causes of monogenic heterozygous familial hypercholesterolemia: A HuGE prevalence review","volume":"160","author":"Austin","year":"2004","journal-title":"Am. J. Epidemiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1152\/japplphysiol.00619.2013","article-title":"Familial hypercholesterolemia impairs exercise-induced systemic vasodilation due to reduced NO bioavailability","volume":"115","author":"Merkus","year":"2013","journal-title":"J. Appl. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.jacl.2015.02.003","article-title":"National lipid association recommendations for patient-centered management of dyslipidemia: Part 1-full report","volume":"9","author":"Jacobson","year":"2015","journal-title":"J. Clin. Lipidol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2844","DOI":"10.1093\/eurheartj\/ehq386","article-title":"Lipoprotein(a) as a cardiovascular risk factor: Current status","volume":"31","author":"Nordestgaard","year":"2010","journal-title":"Eur. Heart J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/joim.12981","article-title":"Familial hypercholesterolemia and elevated lipoprotein(a): Double heritable risk and new therapeutic opportunities","volume":"287","author":"Vuorio","year":"2020","journal-title":"J. Intern. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3616","DOI":"10.2174\/1381612824666181009095522","article-title":"Multimodal Treatment of Homozygous Familial Hypercholesterolemia","volume":"24","author":"Gossios","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1056\/NEJMoa1905239","article-title":"Lipoprotein(a) Reduction in Persons with Cardiovascular Disease","volume":"382","author":"Tsimikas","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.phymed.2015.10.018","article-title":"Polyphenol-based nutraceuticals for the prevention and treatment of cardiovascular disease: Review of human evidence","volume":"23","author":"Visioli","year":"2016","journal-title":"Phytomedicine"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1016\/j.immuni.2013.05.015","article-title":"Omega-3 fatty acids prevent inflammation and metabolic disorder through inhibition of NLRP3 inflammasome activation","volume":"38","author":"Yan","year":"2013","journal-title":"Immunity"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"H146","DOI":"10.1152\/ajpheart.00400.2017","article-title":"Flaxseed: Its bioactive components and their cardiovascular benefits","volume":"314","author":"Parikh","year":"2018","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1177\/0003319719842005","article-title":"The Role of n-3 Fatty Acids in Cardiovascular Disease: Back to the Future","volume":"71","author":"Katsiki","year":"2020","journal-title":"Angiology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"931","DOI":"10.17219\/acem\/31243","article-title":"PUFAs: Structures, Metabolism and Functions","volume":"24","author":"Nowak","year":"2015","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1526S","DOI":"10.1093\/ajcn\/83.6.1526S","article-title":"n-3 fatty acid dietary recommendations and food sources to achieve essentiality and cardiovascular benefits","volume":"83","author":"Gebauer","year":"2006","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1017\/S0007114514000750","article-title":"LDL-cholesterol-lowering effect of plant sterols and stanols across different dose ranges: A meta-analysis of randomised controlled studies","volume":"112","author":"Ras","year":"2014","journal-title":"Br. J. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.plipres.2018.04.001","article-title":"Phytosterols and their derivatives: Structural diversity, distribution, metabolism, analysis, and health-promoting uses","volume":"70","author":"Moreau","year":"2018","journal-title":"Prog. Lipid Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6724","DOI":"10.2174\/0929867325666180622151438","article-title":"Phytosterols and Inflammation","volume":"26","author":"Vilahur","year":"2019","journal-title":"Curr. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1136\/ewjm.173.1.43","article-title":"Plant sterol and stanol margarines and health","volume":"173","author":"Law","year":"2000","journal-title":"West J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.atherosclerosis.2016.03.025","article-title":"Efficacy of clinical diagnostic criteria for familial hypercholesterolemia genetic testing in Poland","volume":"249","author":"Mickiewicz","year":"2016","journal-title":"Atherosclerosis"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1007\/s00394-014-0764-2","article-title":"Benefits of foods supplemented with vegetable oils rich in \u03b1-linolenic, stearidonic or docosahexaenoic acid in hypertriglyceridemic subjects: A double-blind, randomized, controlled trail","volume":"54","author":"Dittrich","year":"2015","journal-title":"Eur. J. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"288","DOI":"10.3945\/ajcn.2009.27469","article-title":"Meta-analysis of the effects of flaxseed interventions on blood lipids","volume":"90","author":"Pan","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1001\/jamapediatrics.2013.1442","article-title":"Flaxseed in pediatric hyperlipidemia: A placebo-controlled, blinded, randomized clinical trial of dietary flaxseed supplementation for children and adolescents with hypercholesterolemia","volume":"167","author":"Wong","year":"2013","journal-title":"JAMA Pediatr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"104622","DOI":"10.1016\/j.phrs.2019.104622","article-title":"Effect of flaxseed supplementation on lipid profile: An updated systematic review and dose-response meta-analysis of sixty-two randomized controlled trials","volume":"152","author":"Hadi","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"451","DOI":"10.3109\/08820139.2015.1025960","article-title":"Partial Reversal of Obesity-Induced Insulin Resistance Owing to Anti-Inflammatory Immunomodulatory Potential of Flaxseed Oil","volume":"44","author":"Bashir","year":"2015","journal-title":"Immunol. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"H2394","DOI":"10.1152\/ajpheart.01104.2006","article-title":"Dietary flaxseed inhibits atherosclerosis in the LDL receptor-deficient mouse in part through antiproliferative and anti-inflammatory actions","volume":"293","author":"Dupasquier","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1139\/H09-087","article-title":"Experimental and clinical research findings on the cardiovascular benefits of consuming flaxseed","volume":"34","author":"Bassett","year":"2009","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1161\/01.RES.0000127122.22685.0A","article-title":"Peroxisome proliferator-activated receptors and atherogenesis: Regulators of gene expression in vascular cells","volume":"94","author":"Marx","year":"2004","journal-title":"Circ. Res."},{"key":"ref_27","unstructured":"Sahebkar, A., Katsiki, N., Ward, N., and Reiner, \u017d. (2019). Flaxseed Supplementation Reduces Plasma Lipoprotein(a) Levels: A Meta-Analysis. Altern. Ther. Health Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1080\/07315724.2003.10719336","article-title":"Dietary treatment of hypercholesterolemia: Can we predict long-term success?","volume":"22","author":"Henkin","year":"2003","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1093\/nutrit\/nuw059","article-title":"Interindividual variability in the cholesterol-lowering effect of supplementation with plant sterols or stanols","volume":"75","author":"Fumeron","year":"2017","journal-title":"Nutr. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"154922","DOI":"10.1016\/j.cyto.2019.154922","article-title":"Effect of flaxseed supplementation on markers of inflammation and endothelial function: A systematic review and meta-analysis","volume":"126","author":"Askarpour","year":"2020","journal-title":"Cytokine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.1007\/s11695-017-2704-8","article-title":"Unsaturated Fatty Acids Improve Atherosclerosis Markers in Obese and Overweight Non-diabetic Elderly Patients","volume":"27","author":"Kovacs","year":"2017","journal-title":"Obes. Surg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"243","DOI":"10.3945\/ajcn.110.003871","article-title":"Dose-response effects of omega-3 fatty acids on triglycerides, inflammation, and endothelial function in healthy persons with moderate hypertriglyceridemia","volume":"93","author":"Harris","year":"2011","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1093\/cvr\/cvy191","article-title":"Interleukin 6 trans-signalling and risk of future cardiovascular events","volume":"115","author":"Ziegler","year":"2019","journal-title":"Cardiovasc. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1038\/srep25550","article-title":"Cleavage Site Localization Differentially Controls Interleukin-6 Receptor Proteolysis by ADAM10 and ADAM17","volume":"6","author":"Riethmueller","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.3945\/jn.115.211375","article-title":"The Antiatherogenic Effect of Fish Oil in Male Mice Is Associated with a Diminished Release of Endothelial ADAM17 and ADAM10 Substrates","volume":"145","author":"Speck","year":"2015","journal-title":"J. Nutr."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/4\/1137\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:09:01Z","timestamp":1760364541000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/4\/1137"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,18]]},"references-count":35,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["nu12041137"],"URL":"https:\/\/doi.org\/10.3390\/nu12041137","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,18]]}}}