Planta Med 2023; 89(06): 608-615
DOI: 10.1055/a-2013-2966
Biological and Pharmacological Activity
Reviews

Influence of Flaxseed (Linum usitatissimum) on Female Reproduction

Constantine the Philosopher University in Nitra, Nitra, Slovak Republic
› Author Affiliations
Supported by: Vedecká Grantová Agentúra MŠVVaŠ SR a SAV VEGA 1/0392/17
Supported by: Agentúra na Podporu Výskumu a Vývoja APVV-15-0296

Abstract

This review describes the chemical composition of flaxseed (Linum usitatissimum) and its general health effects, as well as the currently available knowledge concerning its action on the female reproductive state, functions on the ovary and ovarian cells and reproductive hormones, as well as possible constituents and extra- and intracellular mediators mediating its effects on female reproductive processes. Flaxseed contains a number of biologically active molecules, which, acting through multiple signalling pathways, can determine numerous physiological, protective and therapeutic effects of flaxseed. The available publications demonstrate the action of flaxseed and its constituents on the female reproductive system – ovarian growth, follicle development, the resulting puberty and reproductive cycles, ovarian cell proliferation and apoptosis, oo- and embryogenesis, hormonal regulators of reproductive processes and their dysfunctions. These effects can be determined by flaxseed lignans, alpha-linolenic acid and their products. Their actions can be mediated by changes in general metabolism, metabolic and reproductive hormones, their binding proteins, receptors and several intracellular signalling pathways, including protein kinases, transcription factors regulating cell proliferation, apoptosis, angiogenesis and malignant transformation. Flaxseed and its active molecules are found potentially useful for improving farm animal reproductive efficiency and treatment of polycystic ovarian syndrome and ovarian cancer.



Publication History

Received: 17 August 2022

Accepted after revision: 06 January 2023

Article published online:
20 February 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Singh KK, Mridula D, Rehal J, Barnwal P. Flaxseed: a potential source of food, feed and fiber. Crit Rev Food Sci Nutr 2011; 5: 210-222
  • 2 Martinchik AN, Baturin AK, Zubtsov VV, lu Molofeev V. [Nutritional value and functional properties of flaxseed]. Vopr Pitan 2012; 81: 4-10
  • 3 Parikh M, Netticadan T, Pierce GN. Flaxseed: Its bioactive components and their cardiovascular benefits. Am J Physiol Heart Circ Physiol 2018; 314: H146-H159
  • 4 Shayan M, Kamalian S, Sahebkar A, Tayarani-Najaran Z. Flaxseed for health and disease: Review of clinical trials. Comb Chem High Throughput Screen 2020; 23: 699-722 DOI: 10.2174/1386207323666200521121708.
  • 5 Tricco AC, Lillie E, Zarin W, OʼBrien KK, Colquhoun H, Levac D, Moher D, Peters MDJ, Horsley T, Weeks L, Hempel S, Akl EA, Chang C, McGowan J, Stewart L, Hartling L, Aldcroft A, Wilson MG, Garritty C, Lewin S, Godfrey CM, Macdonald MT, Langlois EV, Soares-Weiser K, Moriarty J, Clifford T, Tunçalp Ö, Straus SE. PRISMA extension for scoping reviews (PRISMA-ScR): Checklist and explanation. Ann Intern Med 2018; 169: 467-473 DOI: 10.7326/M18-0850.
  • 6 Saleem MH, Ali S, Hussain S, Kamran M, Chattha MS, Ahmad S, Aqeel M, Rizwan M, Aljarba NH, Alkahtani S, Abdel-Daim MM. Flax (Linum usitatissimum L.): A potential candidate for phytoremediation? Biological and economical points of view. Plants (Basel) 2020; 9: 496 DOI: 10.3390/plants9040496.
  • 7 Brito AF, Zang Y. A review of lignan metabolism, milk enterolactone concentration, and antioxidant status of dairy cows fed flaxseed. Molecules 2018; 24: 41 DOI: 10.3390/molecules2401004.
  • 8 Lane KE, Wilson M, Hellon TG, Davies IG. Bioavailability and conversion of plant based sources of omega-3 fatty acids – a scoping review to update supplementation options for vegetarians and vegans. Crit Rev Food Sci Nutr 2021; 1-16 DOI: 10.1080/10408398.2021.1880364.
  • 9 Zachut M. Short communication: Concentrations of the mammalian lignan enterolactone in preovulatory follicles and the correlation with intrafollicular estradiol in dairy cows fed extruded flaxseed. J Dairy Sci 2015; 98: 8814-8817 DOI: 10.3168/jds.2015-9699.
  • 10 Jahani-Moghadam M, Mahjoubi E, Dirandeh E. Effect of linseed feeding on blood metabolites, incidence of cystic follicles, and productive and reproductive performance in fresh Holstein dairy cows. J Dairy Sci 2015; 98: 1828-1835 DOI: 10.3168/jds.2014-8789.
  • 11 Komal F, Khan MK, Imran M, Ahmad MH, Anwar H, Ashfaq UA, Ahmad N, Masroor A, Ahmad RS, Nadeem M, Nisa MU. Impact of different omega-3 fatty acid sources on lipid, hormonal, blood glucose, weight gain and histopathological damages profile in PCOS rat model. J Transl Med 2020; 18: 349 DOI: 10.1186/s12967-020-02519-1.
  • 12 Vlčková R, Andrejčáková Z, Sopková D, Hertelyová Z, Kozioł K, Koziorowski M, Gancarčíková S. Supplemental flaxseed modulates ovarian functions of weanling gilts via the action of selected fatty acids. Anim Reprod Sci 2018; 193: 171-181 DOI: 10.1016/j.anireprosci.2018.04.066.
  • 13 Petit HV, Germiquet C, Lebel D. Effect of feeding whole, unprocessed sunflower seeds and flaxseed on milk production, milk composition, and prostaglandin secretion in dairy cows. J Dairy Sci 2004; 87: 3889-3898 DOI: 10.3168/jds.S0022-0302(04)73528-6.
  • 14 Zachut M, Dekel I, Lehrer H, Arieli A, Arav A, Livshitz L, Yakoby S, Moallem U. Effects of dietary fats differing in n-6:n-3 ratio fed to high-yielding dairy cows on fatty acid composition of ovarian compartments, follicular status, and oocyte quality. J Dairy Sci 2010; 93: 529-545 DOI: 10.3168/jds.2009-2167.
  • 15 Moallem U, Shafran A, Zachut M, Dekel I, Portnick Y, Arieli A. Dietary α-linolenic acid from flaxseed oil improved folliculogenesis and IVF performance in dairy cows, similar to eicosapentaenoic and docosahexaenoic acids from fish oil. Reproduction 2013; 146: 603-614 DOI: 10.1530/REP-13-0244.
  • 16 Rhee Y, Brunt A. Flaxseed supplementation improved insulin resistance in obese glucose intolerant people: a randomized crossover design. Nutr J 2011; 10: 44 DOI: 10.1186/1475-2891-10-44.
  • 17 Akhtar S, Ismail T, Riaz M. Flaxseed – a miraculous defense against some critical maladies. Pak J Pharm Sci 2013; 26: 199-208
  • 18 Piermartiri T, Pan H, Figueiredo TH, Marini AM. α-linolenic acid, a nutraceutical with pleiotropic properties that targets endogenous neuroprotective pathways to protect against organophosphate nerve agent-induced neuropathology. Molecules 2015; 20: 20355-20380 DOI: 10.3390/molecules201119698.
  • 19 Ren GY, Chen CY, Chen GC, Chen WG, Pan A, Pan CW, Zhang YH, Qin LQ, Chen LH. Effect of flaxseed intervention on inflammatory marker C-reactive protein: A systematic review and meta-analysis of randomized controlled trials. Nutrients 2016; 8: 136
  • 20 Mali AV, Padhye SB, Anant S, Hegde MV, Kadam SS. Anticancer and antimetastatic potential of enterolactone: Clinical, preclinical and mechanistic perspectives. Eur J Pharmacol 2019; 852: 107-124 DOI: 10.1016/j.ejphar.2019.02.022.
  • 21 Ribeiro DC, Pereira AD, da Silva PC, dos Santos Ade S, de Santana FC, Boueri BF, Pessanha CR, de Abreu MD, Mancini-Filho J, da Silva EM, do Nascimento-Saba CC, da Costa CA, Boaventura GT. Flaxseed flour (Linum usitatissinum) consumption improves bone quality and decreases the adipocyte area of lactating rats in the post-weaning period. Int J Food Sci Nutr 2016; 67: 29-34
  • 22 Kristensen M, Damgaard TW, Sørensen AD, Raben A, Lindeløv TS, Thomsen AD, Bjergegaard C, Sørensen H, Astrup A, Tetens I. Whole flaxseeds but not sunflower seeds in rye bread reduce apparent digestibility of fat in healthy volunteers. Eur J Clin Nutr 2008; 62: 961-967
  • 23 Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006. Accessed August 17, 2022 at: http://www.ncbi.nlm.nih.gov/books/NBK501895/
  • 24 Pal P, Hales K, Petrik J, Hales DB. Pro-apoptotic and anti-angiogenic actions of 2-methoxyestradiol and docosahexaenoic acid, the biologically derived active compounds from flaxseed diet, in preventing ovarian cancer. J Ovarian Res 2019; 12: 49 DOI: 10.1186/s13048-019-0523-3.
  • 25 McGrowder DA, Miller FG, Nwokocha CR, Anderson MS, Wilson-Clarke C, Vaz K, Anderson-Jackson L, Brown J. Medicinal herbs used in traditional management of breast cancer: Mechanisms of action. Medicines (Basel) 2020; 7: 47 DOI: 10.3390/medicines7080047.
  • 26 Teodor ED, Moroeanu V, Radu GL. Lignans from medicinal plants and their anticancer effect. Mini Rev Med Chem 2020; 20: 1083-1090 DOI: 10.2174/1389557520666200212110513.
  • 27 Dikshit A, Gao C, Small C, Hales K, Hales DB. Flaxseed and its components differentially affect estrogen targets in pre-neoplastic hen ovaries. J Steroid Biochem Mol Biol 2016; 159: 73-85 DOI: 10.1016/j.jsbmb.2016.02.028.
  • 28 Domínguez-López I, Yago-Aragón M, Salas-Huetos A, Tresserra-Rimbau A, Hurtado-Barroso S. Effects of dietary phytoestrogens on hormones throughout a human lifespan: A review. Nutrients 2020; 12: 2456 DOI: 10.3390/nu12082456.
  • 29 Tou JC, Chen J, Thompson LU. Dose, timing, and duration of flaxseed exposure affect reproductive indices and sex hormone levels in rats. J Toxicol Environ Health A 1999; 56: 555-570 DOI: 10.1080/00984109909350177.
  • 30 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 DOI: 10.22038/IJBMS.2018.25778.6349.
  • 31 Mehraban M, Jelodar G, Rahmanifar F. A combination of spearmint and flaxseed extract improved endocrine and histomorphology of ovary in experimental PCOS. J Ovarian Res 2020; 13: 32 DOI: 10.1186/s13048-020-00633-8.
  • 32 Pourjafari F, Haghpanah T, Sharififar F, Nematollahi-Mahani SN, Afgar A, Ezzatabadipour M. Evaluation of expression and serum concentration of anti-Mullerian hormone as a follicle growth marker following consumption of fennel and flaxseed extract in first-generation mice pups. BMC Complement Med Ther 2021; 21: 90 DOI: 10.1186/s12906-021-03267-5.
  • 33 Pourjafari F, Haghpanah T, Sharififar F, Nematollahi-Mahani SN, Afgar A, Asadi Karam G, Ezzatabadipour M. Protective effects of hydro-alcoholic extract of foeniculum vulgare and linum usitatissimum on ovarian follicle reserve in the first-generation mouse pups. Heliyon 2019; 5: e02540 DOI: 10.1016/j.heliyon.2019.e02540.
  • 34 Pourjafari F, Haghpanah T, Grazia Palmerini M, Ezzatabadipour M. Serum scavenging capacity and folliculogenesis impact following flaxseed consumption in the first-generation mice pups. J Toxicol 2022; 2022: 5342131 DOI: 10.1155/2022/5342131.
  • 35 Vlčková R, Sopková D, Andrejčáková Z, Lecová M, Fabian D, Šefčíková Z, Seidavi A, Sirotkin AV. Dietary supplementation of flaxseed (Linum usitatissimum L.) alters ovarian functions of xylene-exposed mice. Life (Basel) 2022; 12: 1152 DOI: 10.3390/life12081152.
  • 36 Vlčková R, Andrejčáková Z, Sopková D, Kozioł K, Hertelyová Z, Koziorowska A, Gancarčíková S. Effects of supplemental flaxseed on the ovarian and uterine functions of adult cycling mice. Gen Physiol Biophys 2022; 41: 205-219 DOI: 10.4149/gpb_2022003.
  • 37 Cadenas J, Sá NAR, Ferreira ACA, Paes VM, Aguiar FLN, Fernandes CCL, Rossetto R, Alves BG, Apgar GA, Magalhães-Padilha DM, Rondina D, Figueiredo JR. In vitro embryo production from early antral follicles of goats fed with a whole full-fat linseed based diet. Zygote 2022; 30: 194-199 DOI: 10.1017/S0967199421000472.
  • 38 Ulfina GG, Kimothi SP, Oberoi PS, Baithalu RK, Kumaresan A, Mohanty TK, Imtiwati P, Dang AK. Modulation of post-partum reproductive performance in dairy cows through supplementation of long- or short-chain fatty acids during transition period. J Anim Physiol Anim Nutr (Berl) 2015; 99: 1056-1064 DOI: 10.1111/jpn.12304.
  • 39 Ambrose DJ, Kastelic JP, Corbett R, Pitney PA, Petit HV, Small JA, Zalkovic P. Lower pregnancy losses in lactating dairy cows fed a diet enriched in alpha-linolenic acid. J Dairy Sci 2006; 89: 3066-3074 DOI: 10.3168/jds.S0022-0302(06)72581-4.
  • 40 Hutchinson IA, Hennessy AA, Waters SM, Dewhurst RJ, Evans AC, Lonergan P, Butler ST. Effect of supplementation with different fat sources on the mechanisms involved in reproductive performance in lactating dairy cattle. Theriogenology 2012; 78: 12-27 DOI: 10.1016/j.theriogenology.2011.12.031.
  • 41 Zachut M, Arieli A, Moallem U. Incorporation of dietary n-3 fatty acids into ovarian compartments in dairy cows and the effects on hormonal and behavioral patterns around estrus. Reproduction 2011; 141: 833-840 DOI: 10.1530/REP-10-0518.
  • 42 Eilati E, Bahr JM, Hales DB. Long term consumption of flaxseed enriched diet decreased ovarian cancer incidence and prostaglandin E2 in hens. Gynecol Oncol 2013; 130: 620-628 DOI: 10.1016/j.ygyno.2013.05.018.
  • 43 Dikshit A, Gomes Filho MA, Eilati E, McGee S, Small C, Gao C, Klug T, Hales DB. Flaxseed reduces the pro-carcinogenic micro-environment in the ovaries of normal hens by altering the PG and oestrogen pathways in a dose-dependent manner. Br J Nutr 2015; 113: 1384-1395 DOI: 10.1017/S000711451500029X.
  • 44 Dikshit A, Hales K, Hales DB. Whole flaxseed diet alters estrogen metabolism to promote 2-methoxtestradiol-induced apoptosis in hen ovarian cancer. J Nutr Biochem 2017; 42: 117-125 DOI: 10.1016/j.jnutbio.2017.01.002.
  • 45 Pal P, Hales K, Hales DB. The pro-apoptotic actions of 2-methoxyestradiol against ovarian cancer involve catalytic activation of PKCδ signaling. Oncotarget 2020; 11: 3646-3659 DOI: 10.18632/oncotarget.27760.
  • 46 Sacco SM, Jiang JM, Thompson LU, Ward WE. Flaxseed does not enhance the estrogenic effect of low-dose estrogen therapy on markers of uterine health in ovariectomized rats. J Med Food 2012; 15: 846-850 DOI: 10.1089/jmf.2011.0314.
  • 47 Dutra PA, Pinto LFB, Cardoso Neto BM, Gobikrushanth M, Barbosa AM, Barbosa LP. Flaxseed improves embryo production in Boer goats. Theriogenology 2019; 127: 26-31 DOI: 10.1016/j.theriogenology.2018.12.038.
  • 48 Chang VC, Cotterchio M, Boucher BA, Jenkins DJA, Mirea L, McCann SE, Thompson LU. Effect of dietary flaxseed intake on circulating sex hormone levels among postmenopausal women: a randomized controlled intervention trial. Nutr Cancer 2019; 71: 385-398 DOI: 10.1080/01635581.2018.1516789.
  • 49 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
  • 50 Ebrahimi FA, Samimi M, Foroozanfard F, Jamilian M, Akbari H, Rahmani E, Ahmadi S, Taghizadeh M, Memarzadeh MR, Asemi Z. The effects of omega-3 fatty acids and vitamin E co-supplementation on indices of insulin resistance and hormonal parameters in patients with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial. Exp Clin Endocrinol Diabetes 2017; 125: 353-359 DOI: 10.1055/s-0042-117773.
  • 51 Mirmasoumi G, Fazilati M, Foroozanfard F, Vahedpoor Z, Mahmoodi S, Taghizadeh M, Esfeh NK, Mohseni M, Karbassizadeh H, Asemi Z. The effects of flaxseed oil omega-3 fatty acids supplementation on metabolic status of patients with polycystic ovary syndrome: A randomized, double-blind, placebo-controlled trial. Exp Clin Endocrinol Diabetes 2018; 126: 222-228 DOI: 10.1055/s-0043-119751.
  • 52 Haidari F, Banaei-Jahromi N, Zakerkish M, Ahmadi K. The effects of flaxseed supplementation on metabolic status in women with polycystic ovary syndrome: a randomized open-labeled controlled clinical trial. Nutr J 2020; 19: 8 DOI: 10.1186/s12937-020-0524-5.
  • 53 Štochmalʼová A, Harrath AH, Alwasel S, Sirotkin AV. Direct inhibitory effect of flaxseed on porcine ovarian granulosa cell functions. Appl Physiol Nutr Metab 2019; 44: 507-511 DOI: 10.1139/apnm-2018-0547.
  • 54 Sirotkin AV. Regulators of Ovarian Functions. New York, USA: Nova Publishers, Inc.; 2014: 194
  • 55 Roa J, Tena-Sempere M. Connecting metabolism and reproduction: roles of central energy sensors and key molecular mediators. Mol Cell Endocrinol 2014; 397: 4-14 DOI: 10.1016/j.mce.2014.09.027.
  • 56 Evans MC, Anderson GM. Neuroendocrine integration of nutritional signals on reproduction. J Mol Endocrinol 2017; 58: R107-R128 DOI: 10.1530/JME-16-0212.
  • 57 Romualdi D, Immediata V, De Cicco S, Tagliaferri V, Lanzone A. Neuroendocrine regulation of food intake in polycystic ovary syndrome. Reprod Sci 2018; 25: 644-653 DOI: 10.1177/1933719117728803.
  • 58 Blaustein JD, Ismail N, Holder MK. Review: puberty as a time of remodeling the adult response to ovarian hormones. J Steroid Biochem Mol Biol 2016; 160: 2-8 DOI: 10.1016/j.jsbmb.2015.05.007.
  • 59 Lew R. Natural history of ovarian function including assessment of ovarian reserve and premature ovarian failure. Best Pract Res Clin Obstet Gynaecol 2019; 55: 2-13 DOI: 10.1016/j.bpobgyn.2018.05.005.
  • 60 Minkin MJ. Menopause: hormones, lifestyle, and optimizing aging. Obstet Gynecol Clin North Am 2019; 46: 501-514 DOI: 10.1016/j.ogc.2019.04.008.
  • 61 Paciuc J. Hormone therapy in menopause. Adv Exp Med Biol 2020; 1242: 89-120 DOI: 10.1007/978-3-030-38474-6_6.
  • 62 Tou JC, Chen J, Thompson LU. Flaxseed and its lignan precursor, secoisolariciresinol diglycoside, affect pregnancy outcome and reproductive development in rats. J Nutr 1998; 128: 1861-1868 DOI: 10.1093/jn/128.11.1861.