Biomedical features of flaxseed against different pathologic situations: A narrative review

Document Type : Review Article


1 Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

2 Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran

3 Department of Cardiology, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran

4 Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

5 Legal Medicine Research Center, Legal Medicine Organization, Mashhad, Iran

6 Department of Anatomical Sciences, School of Medicine, Babol University of Medical Sciences, Babol, Iran

7 Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran


Flaxseed is a plant that grows and is cultivated in more than 50 countries; the main flax producer countries are Canada, China, the United States, and India. The purpose of the present study was to overview the source, chemical compounds, and mechanisms of the therapeutic effects of this valuable plant. For writing this manuscript, we made a list of relevant keywords and phrases, and then we started searching for studies in PubMed, Scopus, and Web of Science databases. The main constituents of flaxseed include lipids, proteins, lignans, fibers, and minerals. Flaxseed is full of antioxidants such as tocopherols, betacarotene, cysteine, and methionine which result in a decrease in blood pressure, heart disease, hepatic and neurological disorders, and increased insulin sensitivity. Flaxseed is commonly used for its antidiabetic and anticancer activities and also it is beneficial for cardiovascular, gastrointestinal, hepatic, urological, and reproductive disorders, and because of these beneficial effects, it is recognized as a medical plant.


1. Goyal A, Sharma V, Upadhyay N, Gill S, Sihag M. Flax and flaxseed oil: an ancient medicine & modern functional food. J Food Sci Technol 2014;51:1633-1653.
2. Bagheri A, Talei S, Hassanzadeh N, Mokhtari T, Akbari M, Malek F, et al. The neuroprotective effects of flaxseed oil supplementation on functional motor recovery in a model of ischemic brain stroke: upregulation of BDNF and GDNF. Acta Med Iran 2017;55:785-792.
3.  Dzuvor CKO, Taylor JT, Acquah C, Pan S, Agyei D. Bioprocessing of functional ingredients from flaxseed. Molecules. 2018;23:2444.
4. Rubilar M, Gutiérrez C, Verdugo M, Shene C, Sineiro J. Flaxseed as a source of functional ingredients. J Soil Sci Plant Nutr 2010;10:373-377.
5. Ivanov S, Rashevskaya T, Makhonina M. Flaxseed additive application in dairy products production. Procedia Food Sci 2011;1:275-280.
6. Pellizzon MA, Billheimer JT, Bloedon LT, Szapary PO, Rader DJ. Flaxseed reduces plasma cholesterol levels in hypercholesterolemic mouse models. J Am Coll Nutr 2007;26:66-75.
7. Cunnane SC, Ganguli S, Menard C, Liede AC, Hamadeh MJ, Chen Z-Y, et al. High α-linolenic acid flaxseed (Linum usitatissimum): some nutritional properties in humans. Br J Nutr 1993;69:443-453.
8. Singh K, Jhamb S, Kumar R. Effect of pretreatments on performance of screw pressing for flaxseed. J Food Process Eng 2012;35:543-556.
9. Wu S, Wang X, Qi W, Guo Q. Bioactive protein/peptides of flaxseed: A review. Trends Food Sci Tech 2019;92:184-193.
10.    Tarpila A, Wennberg T, Tarpila S. Flaxseed as a functional food. Curr Top Nutraceutical Res. 2005;3:167-188.
11.    Di Y, Jones J, Mansell K, Whiting S, Fowler S, Thorpe L, et al. Influence of flaxseed lignan supplementation to older adults on biochemical and functional outcome measures of inflammation. J Am Coll Nutr 2017;36:646-653.
12.    Kajla P, Sharma A, Sood DR. Flaxseed—a potential functional food source. J Food Sci Technol 2015;52:1857-1871.
13.    Raghuwanshi V, Agrawal R, Mane K. Flaxseed as a functional food: a review. J Pharmacogn Phytochem 2019;8:352-354.
14.    Oomah DB, Mazza G, Kenaschuk EO. Dehulling characteristics of flaxseed. LWT-Food Sci Technol 1996;29:245-250.
15.    Park E-R, Hong J-H, Lee D-H, Han S-B, Lee K-B, Park J-S, et al. Analysis and decrease of cyanogenic glucosides in flaxseed. J Korean Soc Food Sci Nutr 2005;34:875-879.
16.    Ebrahimi B, Forouzanfar F, Azizi H, Khoshdel-Sarkarizi H, Sadeghnia H, Rajabzadeh A. Effect of electroacupuncture and glibenclamide on blood glucose level and oxidative stress parameters in streptozotocin-induced diabetic rats and possible human implications. Acupunct Electrother Res 2020;44:213-228.
17.    Schwarz K, Bertelsen G, Nissen LR, Gardner PT, Heinonen MI, Hopia A, et al. Investigation of plant extracts for the protection of processed foods against lipid oxidation. Comparison of anti-oxidant assays based on radical scavenging, lipid oxidation and analysis of the principal anti-oxidant compounds. Eur Food Res Technol 2001;212:319-328.
18.    Pham LB, Wang B, Zisu B, Adhikari B. Covalent modification of flaxseed protein isolate by phenolic compounds and the structure and functional properties of the adducts. Food Chem 2019;293:463-471.
19.    Gholaminejhad M, Arabzadeh S, Akbari M, Mohamadi Y, Hassanzadeh G. Anti-oxidative and neuroprotective effects of flaxseed on experimental unilateral spinal cord injury in rat. J Contemp Med Sci  2017;3:213-217.
20.    Navaie F, Hassanzadeh G, Mahakizadeh S, Mehrannia K, Alizamir T, Dashti N, et al. Anti-oxidative and neuroprotective effects of supplementary flaxseed on oxidative damage in the hippocampus area of a rat model of hypoxia. Arch Neuro Sci 2018;5:e60193.
21.    Rajesha J, Murthy KNC, Kumar MK, Madhusudhan B, Ravishankar GA. Anti-oxidant potentials of flaxseed by in vivo model. J Agric Food Chem 2006;54:3794-3799.
22.    Sheih I-C, Wu T-K, Fang TJ. Anti-oxidant properties of a new anti-oxidative peptide from algae protein waste hydrolysate in different oxidation systems. Bioresour Technol 2009;100:3419-3425.
23.    Ebrahimi B, Azizi H, Sarkarizi HK, Bahrami-Taghanaki H, Rajabzadeh A. Comparing the effect of electroacupuncture and glibenclamide on blood glucose level and histological markers of pancreas in streptozotocin-induced diabetic rats. Altern Ther Health Med 2020;26:12-19.
24.    Bafadam S, Beheshti F, Khodabakhshi T, Asghari A, Ebrahimi B, Sadeghnia HR, et al. Trigonella foenum-graceum seed (fenugreek) hydroalcoholic extract improved the oxidative stress status in a rat model of diabetes-induced memory impairment. Horm Mol Biol Clin Investig. 2019;39:1-13.
25.    Pham-Huy LA, He H, Pham-Huy C. Free radicals, anti-oxidants in disease and health. Int J Biomed Sci 2008;4:89-96.
26.    Ren T, Ma A, Zhuo R, Zhang H, Peng L, Jin X, et al. Oleoylethanolamide increases glycogen synthesis and inhibits hepatic gluconeogenesis via the LKB1/AMPK pathway in type 2 diabetic model. J Pharmacol Exp Ther 2020;373:81-91.
27.    Prasad K, Dhar A. Flaxseed and diabetes. Curr Pharm Des 2016;22:141-144.
28.    Prasad K. Oxidative stress as a mechanism of diabetes in diabetic BB prone rats: effect of secoisolariciresinol diglucoside (SDG). Mol Cell Biochem 2000;209:89-96.
29.    Kezimana P, Dmitriev AA, Kudryavtseva AV, Romanova EV, Melnikova NV. Secoisolariciresinol diglucoside of flaxseed and its metabolites: Biosynthesis and potential for nutraceuticals. Front Genet 2018;9:641-650.
30.    Hsia DS, Zhang DJ, Beyl RS, Greenway FL, Khoo C. Effect of daily consumption of cranberry beverage on insulin sensitivity and modification of cardiovascular risk factors in obese adults: a pilot randomized placebo-controlled study. Br J Nutr 2020;124:577-585.
31.    Saleem MH, Ali S, Hussain S, Kamran M, Chattha MS, Ahmad S, et al. Flax (Linum usitatissimum L.): a potential candidate for phytoremediation? biological and economical points of view. Plants (Basel) 2020;9:496-512.
32.    Rodriguez-Leyva D, Weighell W, Edel AL, LaVallee R, Dibrov E, Pinneker R, et al. Potent antihypertensive action of dietary flaxseed in hypertensive patients. Hypertension 2013;62:1081-1089.
33.    Lucas EA, Wild RD, Hammond LJ, Khalil DA, Juma S, Daggy BP, et al. Flaxseed improves lipid profile without altering biomarkers of bone metabolism in postmenopausal women. J Clin Endocrinol Metab 2002;87:1527-1532.
34.    Ghule AE, Kandhare AD, Jadhav SS, Zanwar AA, Bodhankar SL. Omega-3-fatty acid adds to the protective effect of flax lignan concentrate in pressure overload-induced myocardial hypertrophy in rats via modulation of oxidative stress and apoptosis. Int Immunopharmacol 2015;28:751-763.
35.    Parikh M, Netticadan T, Pierce GN. Flaxseed: its bioactive components and their cardiovascular benefits. Am J Physiol Heart Circ Physiol 2018;314:146-159.
36.    David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 2014;505:559-563.
37.    Laurino C, Palmieri B, Vadalà M. Gastrointestinal activity of dietary flaxseed lignans, omega-3 fatty acids and fibres.Nutrafoods 2017:1-9.
38.    Cockerell KM, Watkins AS, Reeves LB, Goddard L, Lomer MC. Effects of linseeds on the symptoms of irritable bowel syndrome: a pilot randomised controlled trial. J Hum Nutr Diet 2012;25:435-443.
39.    Palla AH, Khan NA, Bashir S, Iqbal J, Gilani A-H. Pharmacological basis for the medicinal use of Linum usitatissimum (Flaxseed) in infectious and non-infectious diarrhea. J Ethnopharmacol 2015;160:61-68.
40.    Anaya K, Cruz AC, Cunha DC, Monteiro SM, Dos Santos EA. Growth impairment caused by raw linseed consumption: can trypsin inhibitors be harmful for health? plant foods Hum Nutr 2015;70:338-343.
41.    Seifried HE, Anderson DE, Fisher EI, Milner JA. A review of the interaction among dietary anti-oxidants and reactive oxygen species. J Nutr Biochem 2007;18:567-579.
42.    Al-Jumaily E, Al-Azawi A. Hepatoprotective activity of lignan compound from flaxseed (linumusitatissimum l.) against acetaminopheninduced hepatotoxicity in rabbits. World J Pharma Pharmaceut Sci 2013;3:56-72.
43.    Imran M, Ahmad N, Anjum FM, Khan MK, Mushtaq Z, Nadeem M, et al. Potential protective properties of flax lignan secoisolariciresinol diglucoside. Nutr J. 2015;14:71-77.
44.    Xu J, Gao H, Song L, Yang W, Chen C, Deng Q, et al. Flaxseed oil and alpha-lipoic acid combination ameliorates hepatic oxidative stress and lipid accumulation in comparison to lard. Lipids Health Dis. 2013;12:58-64.
45.    DeLuca JA, Garcia-Villatoro EL, Allred CD. Flaxseed bioactive compounds and colorectal cancer prevention. Curr Oncol Rep 2018;20:59-66.
46.    Lin Z, Taibi A, Lepp D, Power K, Thompson L, Comelli E. Effect of continuous administration of flaxseed and flaxseed components on the gut microbiota in female mice. J Can Assoc Gastroenterol 2018;1:453.
47.    Li L, Chen X, Liu CC, Lee LS, Man C, Cheng SH. Phytoestrogen bakuchiol exhibits in vitro and in vivo anti-breast cancer effects by inducing S phase arrest and apoptosis. Front Pharmacol. 2016;7:128-141.
48.    Kumaresan Indrapriyadharshini M, Sekar B, Ambika Murugesan M, Thuckanickenpalayam Ragunathan Yoithapprabhunath M. Role of vascular endothelial growth factor (VEGF) in tumor progression among oral epithelial dysplasia (OEDs), verrucous carcinoma (VC) and oral squamous cell carcinoma (OSCC)–An Immunohistochemical Study. Int J Adv Sci Technol 2019;28:720-728.
49.    Jungeström MB, Thompson LU, Dabrosin C. Flaxseed and its lignans inhibit estradiol-induced growth, angiogenesis, and secretion of vascular endothelial growth factor in human breast cancer xenografts in vivo. Clin Cancer Res 2007;13:1061-1067.
50.    Zhang L-y, Wang X-l, Sun D-x, Liu X-x, Hu X-y, Kong F. Regulation of zinc transporters by dietary flaxseed lignan in human breast cancer xenografts. Mol Biol Rep 2008;35:595-600.
51.    Tariq N, Jenkins DJ, Vidgen E, Fleshner N, Kendall CW, Story JA, et al. Effect of soluble and insoluble fiber diets on serum prostate specific antigen in men. J Urol 2000;163:114-118.
52.    Morton M, Chan P, Cheng C, Blacklock N, Matos‐Ferreira A, Abranches‐Monteiro L, et al. Lignans and isoflavonoids in plasma and prostatic fluid in men: samples from Portugal, Hong Kong, and the United Kingdom. Prostate 1997;32:122-128.
53.    Nelson W, De Matzo A. lsaacs WB. Prostate cancer N Engl I Med 2003;349:366-381.
54.    Kim SY, Moon A. Drug-induced nephrotoxicity and its biomarkers. Biomol Ther 2012;20:268-272.
55.    Schieppati A, Remuzzi G. Chronic renal diseases as a public health problem: epidemiology, social, and economic implications. Kidney Int 2005;68:7-10.
56.    Mamun M, Billah M, Ashek M, Ahasan M, Hossain M, Sultana T. Evaluation of diuretic activity of Ipomoea aquatica (Kalmisak) in mice model study. J Med Sci 2003;3:395-400.
57.    Mokhtari T, Faghir Ghanesefat H, Hassanzadeh G, Moayeri A, Haeri SMJ, Rezaee Kanavee A, et al. Effects of Flaxseed oil supplementation on renal dysfunction due to ischemia/reperfusion in rat. J Basic Res Med Sci 2017;4:22-29.
58.    Velasquez MT, Bhathena S, Ranich T, Schwartz AM, Kardon DE, Ali A, et al. Dietary flaxseed meal reduces proteinuria and ameliorates nephropathy in an animal model of type II diabetes mellitus. Kidney Int 2003;64:2100-2107.
59.    Clark WF, Parbtani A, Huff MW, Spanner E, de Salis H, Chin-Yee I, et al. Flaxseed: a potential treatment for lupus nephritis. Kidney Int 1995;48:475-480.
60.    Omar AMS. The potential protective influence of flaxseed oil against renal toxicity induced by thioacetamide in rats. Saudi J Biol Sci 2018;25:1696-1702.
61.    Ogborn MR, Nitschmann E, Bankovic-Calic N, Weiler HA, Aukema H. Dietary flax oil reduces renal injury, oxidized LDL content, and tissue n− 6/n− 3 FA ratio in experimental polycystic kidney disease. Lipids 2002;37:1059-1065.
62.    Yamamoto S, Hagiwara S, Hidaka S, Shingu C, Goto K, Kashima K, et al. The anti-oxidant EPC-K1 attenuates renal ischemia-reperfusion injury in a rat model. Am J Nephrol 2011;33:485-490.
63.    Moghimian M, Abtahi-Eivary S-H, Jajarmy N, Shahri MK, Adabi J, Shokoohi M. Comparing the effect of flaxseed and fish oils on acute ischemia-reperfusion injury in the rat kidney. Crescent J Med Biol Sci 2019;6:6-12.
64.    Poorhassan M, Navae F, Mahakizadeh S, Bazrafkan M, Nikmehr B, Abolhassani F, et al. Flaxseed can reduce hypoxia-induced damages in rat testes. Int J Fertil Steril 2018;12:235-241.
65.    Legro RS, Arslanian SA, Ehrmann DA, Hoeger KM, Murad MH, Pasquali R, et al. Diagnosis and treatment of polycystic ovary syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2013;98:4565-4592.
66.    Nowak DA, Snyder DC, Brown AJ, Demark-Wahnefried W. The effect of flaxseed supplementation on hormonal levels associated with polycystic ovarian syndrome: a case study. Curr Top Nutraceutical Res 2007;5:177-181.
67.    Farzana F, Sulaiman A, Ruckmani A, Vijayalakshmi K, Karunya Lakshmi G, Shri R. Effects of flax seeds supplementation in polycystic ovarian syndrome. Int J Pharm Sci Rev Res 2015;31:113-119.
68.    Nesbitt PD, Thompson LU. Lignans in homemade and commercial products containing flaxseed. Nutr Cancer 1997;29:222-227.
69.    Uauy R, Solomons N. Diet, nutrition, and the life-course approach to cancer prevention. J Nutr. 2005;135:2934-2945.
70.    Martin RM, McCarthy A, Smith GD, Davies DP, Ben-Shlomo Y. Infant nutrition and blood pressure in early adulthood: the Barry Caerphilly Growth study. Am J Clin Nutr 2003;77:1489-1497.
71.    Prasad K. Flax lignan complex slows down the progression of atherosclerosis in hyperlipidemic rabbits. J Cardiovasc Pharmacol Ther 2009;14:38-48.
72.    Prasad K, Mantha S, Muir A, Westcott N. Protective effect of secoisolariciresinol diglucoside against streptozotocin-induced diabetes and its mechanism. Mol Cell Biochem 2000;206:141-150.
73.    Soltanian N, Janghorbani M. A randomized trial of the effects of flaxseed to manage constipation, weight, glycemia, and lipids in constipated patients with type 2 diabetes. Nutr Metab. 2018;15:36-44.
74.    Hu P, Mei Q-Y, Ma L, Cui W-G, Zhou W-H, Zhou D-S, et al. Secoisolariciresinol diglycoside, a flaxseed lignan, exerts analgesic effects in a mouse model of type 1 diabetes: engagement of anti-oxidant mechanism. Eur J Pharmacol 2015;767:183-192.
75.    Barre D, Mizier-Barre K, Stelmach E, Hobson J, Griscti O, Rudiuk A, et al. Flaxseed lignan complex administration in older human type 2 diabetics manages central obesity and prothrombosis—an invitation to further investigation into polypharmacy reduction. J Nutr Metab 2012;2012:585170.
76.    Gök M, Ulusu NN, Tarhan N, Tufan C, Ozansoy G, Arı N, et al. Flaxseed protects against diabetes-induced glucotoxicity by modulating pentose phosphate pathway and glutathione-dependent enzyme activities in rats. J Diet Suppl 2016;13:339-351.
77.    Hadjighassem M, Kamalidehghan B, Shekarriz N, Baseerat A, Molavi N, Mehrpour M, et al. Oral consumption of α-linolenic acid increases serum BDNF levels in healthy adult humans. Nutr J 2015;14:20.
78.    Saad CT, Précoma DB, Merlini AB, Ioshii SO, Champosk AF. Evaluation of flaxseed effects on non-alcoholic fatty liver disease (NAFLD) in rabbits submitted to a hypercholesterolemic diet. Funct Foods Health Dis 2014;4:442-450.
79.    Rodriguez-Leyva D, Weighell W, Edel AL, LaVallee R, Dibrov E, Pinneker R, et al. Potent antihypertensive action of dietary flaxseed in hypertensive patients. Hypertension 2013;62:1081-1089.
80.    Edel AL, Rodriguez-Leyva D, Maddaford TG, Caligiuri SP, Austria JA, Weighell W, et al. Dietary flaxseed independently lowers circulating cholesterol and lowers it beyond the effects of cholesterol-lowering medications alone in patients with peripheral artery disease. J Nutr 2015;145:749-757.
81.    Bloedon LT, Balikai S, Chittams J, Cunnane SC, Berlin JA, Rader DJ, et al. Flaxseed and cardiovascular risk factors: results from a double blind, randomized, controlled clinical trial. J Am Coll Nutr 2008;27:65-74.
82.    Hernández-Salazar M, Guevara-González RG, Cruz-Hernández A, Guevara-Olvera L, Bello-Pérez LA, Castaño-Tostado E, et al. Flaxseed (Linum usitatissimum L.) and its total non-digestible fraction influence the expression of genes involved in azoxymethane-induced colon cancer in rats. Plant Foods Hum Nutr 2013;68:259-267.
83.    Millman J, Okamoto S, Kimura A, Uema T, Higa M, Yonamine M, et al. Metabolically and immunologically beneficial impact of extra virgin olive and flaxseed oils on composition of gut microbiota in mice. Eur J Nutr 2020;59:2411-2425.
84.    Rizwan S, Naqshbandi A, Farooqui Z, Khan AA, Khan F. Protective effect of dietary flaxseed oil on arsenic-induced nephrotoxicity and oxidative damage in rat kidney. Food Chem Toxicol 2014;68:99-107.
85.    Sankaran D, Bankovic-Calic N, Cahill L, Peng CY-C, Ogborn MR, Aukema HM. Late dietary intervention limits benefits of soy protein or flax oil in experimental polycystic kidney disease. Nephron Exp Nephrol 2007;106:122-128.
86.    Jelodar G, Masoomi S, Rahmanifar F. Hydroalcoholic extract of flaxseed improves polycystic ovary syndrome in a rat model. Iran J Basic Med Sci 2018;21:645-650.