Flaxseed and Human Health: Reviewing Benefits and Adverse Effects

References

• Daar , A.S. , Singer , P.A. , Persad , D.L. , Pramming , S.K. , Matthews , D.R. , Beaglehole , R. , Bernstein , A. , Borysiewicz , L.K. , Colagiuri , S. , Ganguly , N. , Glass , R.I. , Finegood , D.T. , Koplan , J. , Nabel , E.G. , Sarna , G. , Sarrafzadegan , N. , Smith , R. , Yach , D. and Bell , J. 2007 . Grand challenges in chronic non-communicable diseases . Nature , 450 : 494 – 496 .
   PubMed Web of Science ®Google Scholar
• Oomah , B.D. 2001 . Flaxseed as a functional food source . J. Sci. Food Agric. , 81 : 889 – 894 .
   Web of Science ®Google Scholar
• Guseva , D.A. 2010 . [Natural source of omega-3-linseed-oil: Its particular qualities and metabolic changes in the organism] . Vopr. Pitan. , 79 ( 1 ) : 13 – 22 .
   PubMedGoogle Scholar
• Chung , M.W.Y. , Lei , B. and Li-Chan , E.C.Y. 2005 . Isolation and structural characterization of the major protein fraction from NorMan flaxseed (Linum usitatissimum L.) . Food Chem. , 90 : 271 – 279 .
   Web of Science ®Google Scholar
• Udenigwe , C.C. and Aluko , R.E. 2010 . Antioxidant and angiotensin converting enzyme-inhibitory properties of a flaxseed protein-derived high Fischer ratio peptide mixture . J. Agric. Food Chem. , 58 ( 8 ) : 4762 – 4768 .
   PubMed Web of Science ®Google Scholar
• Morris , D. 2001 . Essential nutrients and other functional compounds in flaxseed . Nutr. Today. , 36 : 159 – 162 .
   Google Scholar
• Papathanasopoulos , A. and Camilleri , M. 2010 . Dietary Fiber supplements: Effects in obesity and metabolic syndrome and relationship to gastrointestinal functions . Gastroenterology , 138 ( 1 ) : 65 – 72 .
   PubMed Web of Science ®Google Scholar
• Pellizzon , M.A. and et al . 2007 . Flaxseed reduces plasma cholesterol levels in hypercholesterolemic mouse models . J. Am. Coll. Nutr. , 26 ( 1 ) : 66 – 75 .
   PubMed Web of Science ®Google Scholar
• Hussein , N. , Ah-Sing , E. , Wilkinson , P. , Leach , C. , Griffin , B. and Millward , D. 2005 . Long-chain conversion of linoleic acid and alpha-linolenic acid in response to marked changes in their dietary intake in men . J. Lipid. Res. , 46 : 269 – 80 .
   PubMed Web of Science ®Google Scholar
• Simopoulos , A. 2008 . The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic disease . Exp. Biol. Med. , 233 : 674 – 688 .
   PubMed Web of Science ®Google Scholar
• Bozan , B and Temelli , F. 2008 . Chemical composition and oxidative stability of flax, safflower and poppy seed and seed oils. Bioresour . Technol. , 99 ( 14 ) : 6354 – 6359 .
   Google Scholar
• Morri, D.H. Linaza—una recopilación sobre sus efectos en la salud y nutriciónaccessed November 24, 2008 http://www.flaxcouncil.ca/spanish/index.php?p=primer_spanish (http://www.flaxcouncil.ca/spanish/index.php?p=primer_spanish)
   Google Scholar
• Handelman , G.J. , Li , M. , Fitch , K. , Weiter , J.J. and Dratz , E.A. 1985 . Oral aipha-tocopherol supplements decrease plasma gammatocopherol levels in humans . J. Nutr. , 1 ( 15 ) : 807 – 813 .
   Google Scholar
• Esterbauer , H. , Schmidt , R. and Hayn , M. 1997 . Relationship among oxidation of low-density lipoprotein, antioxidant protection, and atherosclerosis . Adv. Pharmacol. , 38 : 425 – 456 .
   PubMedGoogle Scholar
• Strandås , C. , Kamal-Eldin , A. , Andersson , R. and Åman , P. 2008 . Phenolic glucosides in bread containing flaxseed . Food Chem. , 110 : 997 – 999 .
   PubMed Web of Science ®Google Scholar
• Milder , I.E.J. and et al . 2005 . Lignan contents of Dutch plant foods: A database including lariciresinol, pinoresinol, secoisolariciresinol and matairesinol . Br. J. Nutr. , 93 ( 3 ) : 393 – 402 .
   PubMed Web of Science ®Google Scholar
• Wang , C.Z. , Ma , X.Q. , Yang , D.H. , Guo , Z.R. , Liu , G.R. , Zhao , G.X. , Tang , J. , Zhang , Y.N. , Ma , M. , Cai , S.Q. , Ku , B.S. and Liu , S.L. 2010 . Production of enterodiol from defatted flaxseeds through biotransformation by human intestinal bacteria . BMC Microbiol. , 16 ( 10 ) : 1 – 9 .
   Google Scholar
• Adlercreutz , H. 2007 . Lignans and human health . Crit. Rev. Clin. Lab. Sci. , 44 ( 5–6 ) : 483 – 525 .
   PubMed Web of Science ®Google Scholar
• Nesbitt , P.D. and et al . 1999 . Human metabolism of mammalian lignan precursors in raw and processed flaxseed . Am. J. Clin. Nutr. , 69 ( 3 ) : 549 – 555 .
   PubMed Web of Science ®Google Scholar
• Morisset , A.S. , Lemieux , S. , Veilleux , A. , Bergeron , J. , Weisnagel , S.J. and Tchernof , A. 2009 . Impact of a lignan-rich diet on adiposity and insulin sensitivity in post-menopausal women . Br. J. Nutr. , 102 : 195 – 200 .
   PubMed Web of Science ®Google Scholar
• Bell , A. , McSteen , P.M. , Cebrat , M. , Picur , B. and Siemion , I.Z. 2000 . Antimalarial activity of cyclolinopeptide A and its analogues . Acta Pol. Pharm. , 57 : 134 – 136 .
   PubMedGoogle Scholar
• Cintra , D.E.C. , Costa , A.G.V. , Peluzio , M.C.G. , Matta , S.L.P. , Silva , M.T.C. and Costa , N.M.B. 2006 . Lipid profile of rats fed high-fat diets based on flaxseed, peanut, trout, or chicken skin . Nutrition , 22 ( 2 ) : 197 – 205 .
   PubMed Web of Science ®Google Scholar
• Kristensen , M. , Damgaard , T.W. , Sorensen , A.D. , Raben , A. , Lindelov , T.S. , Thimsen , A.D. , Bjergegaard , C. , Sorensen , H. , Astrup , A. and Tetens , I. 2008 . Whole flaxseeds but not sunflower seeds in rye bread reduce apparent digestibility of fat in health volunteers . Eur. J. Clin. Nutr. , 62 ( 8 ) : 961 – 967 .
   PubMed Web of Science ®Google Scholar
• Du , H. , van der A , D.L. , Boshuizen , H.C. , Forouhi , N.G. , Wareham , N.J. , Halkjær , J. , Tjønneland , A. , Overvad , K. , Jakobsen , M.U. , Boeing , H , Buijsse , B , Masala , G. , Palli , D. , Sørensen , T.I. , Saris , W.H.M. and Feskens , E.J.M. 2010 . Dietary fiber and subsequent changes in body weight and waist circumference in European men and women . Am. J. Clin. Nutr. , 91 ( 2 ) : 329 – 336 .
   PubMed Web of Science ®Google Scholar
• Wu , H. , Pan , A. , Yu , Z. , Qi , Q. , Lu , L. , Zhang , G. , Yu , D. , Zong , G. , Zhou , Y. , Chen , X. , Tang , L. , Feng , Y. , Zhou , H. , Chen , X. , Li , H. , Demark-Wahnefried , W. , Hu , F.B. and Lin , X. 2010 . Lifestyle counseling and supplementation with flaxseed or walnuts influence the management of metabolic syndrome . J. Nutr. , 140 ( 11 ) : 1937 – 1942 .
   PubMed Web of Science ®Google Scholar
• Faintuch , J. and et al . 2006 . Propriedades antiinflamatórias da farinha de linhaça em pacientes obesos. Rev. Bras . Nutr. Clin. , 21 ( 4 ) : 273 – 277 .
   Google Scholar
• Bathena , S.J. , Ali , A. , Haudenschild , C. , Latham , P. , Ranich , T. , Mohamed , A.I. , Hansen , C. T. and Velasquez , M.T. 2003 . Dietary flaxseed meal is more protective than soy protein concentrate against hypertriglyceridemia and steatosis of the liver in an animal model of obesity . J. Am. Coll. Nutr. , 22 ( 2 ) : 157 – 164 .
   PubMed Web of Science ®Google Scholar
• Malaisse , W.J. , Bulur , N. , Ying , Z. , Hacquebard , M. , Portois , L. , Sener , A. and Carpentier , Y.A . 2009 . The metabolic syndrome of omega3-depleted rats . I. Liver data. Int. J. Mol. Med. , 24 ( 1 ) : 111 – 123 .
   PubMed Web of Science ®Google Scholar
• Sener , A. , Zhang , Y. , Bulur , N. , Louchami , K. , Malaisse , W.J. and Carpentier , Y.A. 2009 . The metabolic syndrome of omega3-depleted rats. II. Body weight, adipose tissue mass and glycemic homeostasis . Int. J. Mol. Med. , 24 ( 1 ) : 125 – 129 .
   PubMed Web of Science ®Google Scholar
• Lóránd , T. , Vigh , E. and Garai , J. 2010 . Hormonal action of plant derived and anthropogenic non-steroidal estrogenic compounds: Phytoestrogens and xenoestrogens . Curr. Med. Chem. , 17 ( 30 ) : 3542 – 3574 .
   PubMed Web of Science ®Google Scholar
• Fukumitsu , S. and et al . 2008 . Flaxseed lignan attenuates high-fat diet-induced fat accumulation and induces adiponectin expression in mice . Br. J. Nutr. , 100 ( 3 ) : 669 – 676 .
   PubMed Web of Science ®Google Scholar
• Tominaga , S. , Sugahara , T. , Nishimoto , S. , Yamawaki , M. , Nakashima , Y. , Kishida , T. , Akiyama , K. , Maruyama , M. and Yamauchi , S. 2010 . The effect of secoisolariciresinol on 3t3-L1 adipocytes and the relationship between molecular structure and the activity . Anim. Cell Technol. Basic Appl. Aspects , 16 : 345 – 351 .
   Google Scholar
• Taylor , C.G. , Noto , A.D. , Stringer , D.M. , Froese , S. and Malcolmson , L. 2010 . Dietary milled flaxseed and flaxseed oil improve N-3 fatty acid status and do not affect glycemic control in individuals with well-controlled type 2 diabetes . J. Am. Coll. Nutr. , 29 ( 1 ) : 72 – 80 .
   PubMed Web of Science ®Google Scholar
• Figueiredo , M.S. , Moura , E.G. , Lisboa , P.C. , Troina , A.A. , Trevenzoli , I.H. , Oliveira , E. , Boaventura , G.T. and Passos , M.G.F. 2009 . Flaxseed supplementation of rats during lactation changes the adiposity and glucose homeostasis of their offspring . Life Sci. , 85 ( 9–10 ) : 365 – 371 .
   PubMed Web of Science ®Google Scholar
• Liyana-Pathirana , C.M. and Shahidi , F. 2006 . Importance of insoluble-bound phenolics to antioxidant properties of wheat . J. Agric. Food Chem. , 54 : 1256 – 1264 .
   PubMed Web of Science ®Google Scholar
• Bassett , C. and et al . 2009 . Experimental and clinical research findings on the cardiovascular benefits of consuming flaxseed . Appl. Physiol. Nutr. Metab. , 34 ( 5 ) : 965 – 74 .
   PubMed Web of Science ®Google Scholar
• Bloedon , L.T. , Balikai , S. , Chittams , J. , Cunnane , S.C. , Berlin , J.A. , Rader , D.J. and Szapary , P.O. 2008 . Flaxseed and cardiovascular risk factors: Results from a double blind, randomized, controlled clinical trial . J. Am. Coll. Nutr. , 27 ( 1 ) : 65 – 74 .
   PubMed Web of Science ®Google Scholar
• Pan , A. , Sun , J. , Chen , Y. and et al . 2007 . Effects of a flaxseed-derived lignan supplement in type 2 diabetic patients: A randomized, double-blind, cross-over trial . PLoS ONE 2. , 2 ( 11 ) : e1148
   PubMed Web of Science ®Google Scholar
• Patade , A. and et al . 2008 . Flaxseed reduces total and LDL cholesterol concentrations in native american postmenopausal women . J. Womens Health , 17 ( 3 ) : 355 – 366 .
   Web of Science ®Google Scholar
• Jensen , J. , Nilas , L. and Christiansen , C. 1990 . Influence of menopause on serum lipids and lipoproteins . Maturitas , 12 : 321 – 331 .
   PubMed Web of Science ®Google Scholar
• Mandasescu , S. , Mocanu , V. , Dascalita , A.M. , Haliga , R. , Nestian , I. , Stitt , P.A. and Luca , V. 2005 . Flaxseed supplementation in hyperlipidemic patients . Rev. Med. Chir. Soc. Med. Nat. Iasi. , 109 ( 3 ) : 502 – 506 .
   PubMedGoogle Scholar
• Hallund , J. , Ravn-Haren , G. , Bügel , S. , Tholstrup , T. and Tetens , I. 2006 . A lignan complex isolated from flaxseed does not affect plasma lipid concentrations or antioxidant capacity in healthy postmenopausal women . J. Nutr. , 136 : 112 – 116 .
   PubMed Web of Science ®Google Scholar
• Adolphe , J.L. , Whiting , S.J. , Juurlink , B.H.J. , Thorpe , L.U. and Alcorn , J. 2010 . Health effects with consumption of the flax lignan Secoisolariciresinol diglucoside . Br. J. Nutr. , 103 : 929 – 938 .
   PubMed Web of Science ®Google Scholar
• Varga , Z. 2008 . [Omega-3 polyunsatured fatty acids in the prevention of atherosclerosis] . Orv. Hetil. , 149 ( 14 ) : 627 – 637 .
   PubMedGoogle Scholar
• Fuchs , D. , Piller , R. , Linseisen , J. , Daniel , H. and Wenzel , U . 2007 . The human peripheral blood mononuclear cell proteome responds to a dietary flaxseed-intervention and proteins indentified suggest a protective effect in atherosclerosis . Proteomics , 7 ( 18 ) : 3278 – 3288 .
   PubMed Web of Science ®Google Scholar
• Prasad , K. 2008 . Regression of hypercholesterolemic atherosclerosis in rabbits by secoisolariciresinol diglucoside isolated from flaxseed . Atherosclerosis , 197 ( 1 ) : 34 – 42 .
   PubMed Web of Science ®Google Scholar
• Penumathsa , S.V. , Koneru , S. , Thirunavukkarasu , M. , Zhan , L. , Prasad , K. and Maulik , N. 2007 . Secoisolariciresinol diglucoside: Relevance to angiogenesis and cardioprotection against ischemia-reperfusion injury . Pharmacol.Exp. Ther. , 320 ( 2 ) : 951 – 959 .
   PubMed Web of Science ®Google Scholar
• Pan , L. , Xia , X. , Feng , Y. , Jiang , C. , Cui , Y. and Huang , Y. 2008 . Exposure of juvenile rats to phytoestrogen daidzein impairs erectile function in a dose-related manner at adulthood . J. Androl. , 29 : 55 – 62 .
   PubMed Web of Science ®Google Scholar
• Duda , M. K. and et al . 2009 . Fish oil, but not flaxseed oil, decreases inflammation and prevents pressure overload-induced cardiac dysfunction . Cardiovasc. Res. , 81 ( 2 ) : 319 – 327 .
   PubMed Web of Science ®Google Scholar
• Nelson , T.L. , Stevens , J.R. and Hickey , M.S. 2010 . Adiponectin levels are reduced, independent of polymorphisms in the adiponectin gene, after supplementation with alpha-linolenic acid among healthy adults . Metabolism , 56 ( 9 ) : 1209 – 1215 .
   Google Scholar
• Prasad , K. 2009 . Flaxseed and cardiovascular health . J. Cardiovasc. Pharmacol. , 54 ( 5 ) : 369 – 377 .
   PubMed Web of Science ®Google Scholar
• Kaul , N. , Kreml , R. , Austria , J.A. , Richard , M.N. , Edel , A.L. , Dibrov , E. , Hirono , S. , Zettler , M.E. and Pierce , G.N. 2008 . A comparison of fish oil, flaxseed oil and hempseed oil supplementation on selected parameters of cardiovascular health in healthy volunteers . J. Am. Coll. Nutr. , 27 ( 1 ) : 51 – 58 .
   PubMed Web of Science ®Google Scholar
• Pan , A. , Yu , D. , Demark-Wahnefried , W. , Franco , O.H. and Lin , X. 2009; 90 . Meta-analysis of the effects of flaxseed interventions on blood lipids . Am. J. Clin. Nutr. , : 288 – 297 .
   PubMed Web of Science ®Google Scholar
• Thakur , G. , Mitra , A. , Pal , K. and Rosseau , D. 2009 . Effect of flaxseed gum on reduction of blood glucose and cholesterol in type 2 diabetic patients . Int. J. Food Sci. Nutr. , 22 : 1 – 11 .
   Google Scholar
• Barre , D. E. and et al . 2008 . High dose flaxseed oil supplementation may affect fasting blood serum glucose management in human type 2 diabetics . J. Oleo Sci. , 57 ( 5 ) : 269 – 273 .
   PubMed Web of Science ®Google Scholar
• Polonsky , K.S. 2006 . Retinol-binding protein 4, insulin resistance, and type 2 diabetes . N. Engl. J. Med. , 354 : 2596 – 2598 .
   PubMed Web of Science ®Google Scholar
• Qi , Q. , Yu , Z. , Ye , X. and et al . 2007 . Elevated retinol-binding protein 4 levels are associated with metabolic syndrome in Chinese people . J. Clin. Endocrinol. Metab. , 92 : 4827 – 4834 .
   PubMed Web of Science ®Google Scholar
• Haliga , R. , Mocanu , V. , Paduraru , I. , Stoica , B. , Oboroceanu , T. and Luca , V. 2009 . Effects of dietary flaxseed supplementation on renal oxidative stress in experimental diabetes . Rev. Med. Chir. Soc. Med. Nat. Iasi , 113 ( 4 ) : 1200 – 1204 .
   PubMedGoogle Scholar
• Makni , M. , Sefi , M. , Fetoui , H. , Garoui , E.M. , Gargouri , N.K. , Boudawara , T. and Zeghal , N. 2010 . Flax and Pumpkin seeds mixture ameliorates diabetic nephropaty in rats . Food Chem. Toxicol. , 48 ( 8–9 ) : 2407 – 2412 .
   PubMed Web of Science ®Google Scholar
• Haliga , R. , Mocanu , V. , Oboroceanu , T. , Stitt , P.A. and Luca , V.C. 2007 . The effects of dietary flaxseed supplementation in streptozicin-induced diabetic hamsters . Rev. Med. Chir. Soc. Med. Nat. Iasi. , 111 ( 2 ) : 472 – 476 .
   PubMedGoogle Scholar
• Bandera , E.V. , Williams , M.G. , Sima , C. , Bayuga , S. , Pulick , K. , Wilcox , H. , Soslow , R. , Zauber , A.G. and Olson , S.H. 2009 . Phytoestrogen consumption and endometrial cancer risk: A population-based case–control study in New Jersey . Cancer Causes Control , 20 ( 7 ) : 1117 – 1127 .
   PubMed Web of Science ®Google Scholar
• Lamblin , F. , Hano , C. , Fliniaux , O. , Mesnard , F. , Fliniaux , M.A. and Lainé , E. 2008 . [Interest of lignans in prevention and treatment of cancers] . Med. Sci. , 24 ( 5 ) : 511 – 519 .
   Google Scholar
• Lehraiki , A. , Attoumbré , J. , Bienaimé , C. , Matifat , F. , Bensaddek , L. , Nava-Saucedo , E. , Fliniaux , M.E. , Ouadid-Ahidouch , H. and Baltora-Rosset , S. 2010 . Extraction of lignans from flaxseed and evaluation of their biological effects on breast cancer MCF-7 and MDA-MB-231 cell lines . J. Med. Food. , 13 ( 4 ) : 834 – 841 .
   PubMed Web of Science ®Google Scholar
• Fabian , C.J. , Kimler , B.F. , Zalles , C.M. , Klemp , J.R. , Petroff , B.K. , Khan , Q.J. , Sharma , P. , Setchell , K.D.R. , Zhao , X. , Phillips , T.A. , Metheny , T. , Hughes , J.R. , Yeh , H.W. and Johnson , K.A. 2010 . Reduction in ki-67 in benign breast tissue of high risk women with the lignan secoisolariciresinol diglycoside (SDG) . Cancer Prev. Res. , 3 : 1342 – 1350 .
   PubMed Web of Science ®Google Scholar
• Power , K.A. , Chen , J.M. , Saarinen , N.M. and Thompson , L.U. 2008 . Changes in biomarkers of estrogen receptor and growth factor signaling pathways in MCF-7 tumors after short- and long-term treatment with soy and flaxseed . J. Steroid Biochem. Mol. Biol. , 112 ( 1–3 ) : 13 – 19 .
   PubMed Web of Science ®Google Scholar
• Saggar , J.K. , Chen , J. , Corey , P. and Thompson , L.U. 2010 . Dietary flaxseed lignan or oil combined with tamoxifen treatment affect MCF-7 tumor growth through estrogen receptor- and growth factor-signaling pathways . Mol. Nutr. Food Res. , 54 ( 3 ) : 415 – 425 .
   PubMed Web of Science ®Google Scholar
• Demark-Wahnefried , W. , Polascik , T.J. , George , S.L. , Switzer , B.R. , Madden , J.F. , Ruffin , M.T. , Snyder , D.C. , Owzar , K. , Hars , V. , Albala , D.M. , Walther , P.J. , Robertson , C.N. , Moul , J.W. , Dunn , B.K. , Brenner , D. , Minasian , L. , Stella , P. and Vollmer , R.T. 2008 . Flaxseed supplementation (not dietary fat restriction) reduces prostate cancer proliferation rates in men presurgery . Epidemiol Biomarkers Prev. , 17 ( 12 ) : 3577 – 3587 .
   PubMed Web of Science ®Google Scholar
• Freedlans , S.J. and Aronson , W.J. 2009 . Dietary intervention strategies to modulate prostate cancer risk and prognosis . Curr. Opin. Urol. , 19 ( 3 ) : 263 – 267 .
   PubMed Web of Science ®Google Scholar
• McCann , M.J. , Gill , C.I. , McGlynn , H. and Rowland , I.R. 2005 . Role of mammalian lignans in the prevention and treatment of prostate cancer . Nutr. Cancer , 52 : 1 – 14 .
   PubMed Web of Science ®Google Scholar
• Webb , A.L. and McCullough , M.L. 2005 . Dietary lignans: Potential role in cancer prevention . Nutr. Cancer. , 51 : 117 – 131 .
   PubMed Web of Science ®Google Scholar
• Kilkkinen , A. , Stumpf , K. , Pietinen , P. , Valsta , L.M. , Tapanainen , H. and Adlercreutz , H. 2001 . Determinants of serum enterolactone concentration . Am. J. Clin. Nutr. , 73 : 1094 – 1100 .
   PubMed Web of Science ®Google Scholar
• Qu , H. , Madl , R.L. , Takemoto , D.L. , Baybutt , R.C. and Wang , W. 2005 . Lignans are involved in the antitumor activity of wheat bran in colon cancer SW480 cells . J. Nutr. , 135 : 598 – 602 .
   PubMed Web of Science ®Google Scholar
• Rosa , D.D. , Sales , R.L , Moraes , L.F.S. , Cesário Lourenço , F.C. , Neves , C.A. , Sabarense , C.M. , Ribeiro , S.M.R. and Peluzio , M.C.G. 2010 . Flaxseed, olive and fish oil influence plasmatic lipids, lymphocyte migration and morphometry of the intestinal of Wistar rats . Acta Cir. Bras. , 25 ( 3 ) : 275 – 280 .
   PubMed Web of Science ®Google Scholar
• Rodríguez , R. , Jiménez , A. , Fernández-Bolaños , B , Guillén , R. and Heredia , A. 2006 . Dietary fibre from vegetable products as source of functional ingredients . Trends Food Technol. , 17 : 3 – 15 .
   Web of Science ®Google Scholar
• Theodoratou , E. , McNeill , G. , Cetnarsky , R. , Farrington , S.M. , Tenesa , A. , Barnetson , R. , Porteous , M. , Dunlop , M. and Campbell , H. 2007 . Dietary fatty acids and colorectal cancer: A case-control study . Am. J. Epidemiol. , 166 : 181 – 195 .
   PubMed Web of Science ®Google Scholar
• Mason , J.K. and Thompsom , L.U. 2010 . Flaxseed oil-trastuzumab interaction in breast cancer . Food Chem. Toxicol. , 48 ( 8–9 ) : 2223 – 2226 .
   PubMed Web of Science ®Google Scholar
• Saggar , J.K. , Chen , J. , Corey , P. and Thompson , L.U. 2010 . The effect of secoisolariciresinol diglucoside and flaxseed oil alone and in combination, on MCF-7 tumor grpwth and signaling pathways . Nutr. Cancer. , 62 ( 4 ) : 533 – 542 .
   PubMed Web of Science ®Google Scholar
• Saini , A. , Harjai , K. , Mohan , H. , Punia , R.P.S. and Chhibber , S. 2010 . Long-term flaxseed oil supplementation diet protects BALB/c mice against Streptococcus pneumoniae infection . Med. Microbiol. Immunol. , 199 : 27 – 34 .
   PubMed Web of Science ®Google Scholar
• Rajesha , J. , Murthy , K.N. , Ravishankar , G.A. , Kumar , M.K. and Madhusudhan , B. 2006 . Antibacterial potentials of flaxseed by in vivo model . J. Agric. Food Chem. , 54 : 3794 – 3799 .
   PubMed Web of Science ®Google Scholar
• Moujir , L. , Seca , A.M. , Silva , A.M. , López , M.R. , Padilla , N. , Cavaleiro , J.A. and Neto , C.P. 2007 . Cytotoxic activity of lignans from hibiscus cannabinus . Fitoterapia , 78 : 385 – 387 .
   PubMed Web of Science ®Google Scholar
• Rajesha , J. , Rao , A.R. , Madhusudhan , B. and Karunakumar , M. 2010 . Antibacterial Properties of secoisolariciresinol diglucoside isolated from Indian flaxseed cultivars . Curr. Trends Biotechnol. Pharm. , 4 ( 1 ) : 551 – 560 .
   Google Scholar
• Faintuch , J. and et al . 2007 . Obesity, inflammation, vascular reactivity, and cardiocirculatory events . Clinics , 62 : 357 – 358 .
   PubMed Web of Science ®Google Scholar
• Varma , S. , Eskin , M.N.A. , Bird , R. , Dolenko , B. , Raju , J. , Ijare , O.B. and Bezabeh , T. 2010 . Potential of magnetic resonance spectroscopy in assessing the effect of fatty acids on inflammatory bowel disease in an animal model . Lipids , 45 ( 9 ) : 843 – 854 .
   PubMed Web of Science ®Google Scholar
• Dugani , A. , Auzzi , A. , Naas , F. and Megwez , S. 2009 . Effects of the oil and mucilage from flaxseed (Linum usitatissimum) on gastric lesions induced by ethanol in rats . Libyan J. Med. , : 166 – 169 . AOP: 080612
   PubMed Web of Science ®Google Scholar
• Tarpila , S. , Tarpila , A. , Gröhn , P. , Silvennoinen , T. and Lindberg , L. 2004 . Efficacy of ground flaxseed on constipation in patients with irritable bowel syndrome . Curr. Top. Nutraceut. Res. , 2 : 119 – 125 .
   Google Scholar
• Pruthi , S. , Thompson , S.L. , Novotny , P.J. , Barton , D.L. , Kottschade , L.A. , Tan , A.D. , Sloan , J.A. and Loprinzi , C.L. 2007 . Pilot evaluation of flaxseed for the management of hot flashes . J. Soc. Integr. Oncol. , 5 : 106 – 112 .
   PubMedGoogle Scholar
• Bommareddy , A. , Arasada , B.L. , Mathees , D. P. and Dwivedi , C. 2007 . Determination of mammalian lignans in biological samples by modified gas chromatography/mass spectrometry . J AOAC Int. , 90 : 641 – 646 .
   PubMed Web of Science ®Google Scholar
• Simbalista , R.L. , Sauerbronn , A.V. , Aldrighi , J.M. and Arêas , J.A.G. 2010 . Consumption of a flaxseed-rich food is not more effective than a placebo in alleviating the climacteric symptoms of postmenopausal women . J. Nutr. , 140 : 293 – 297 .
   PubMed Web of Science ®Google Scholar
• Carmina , E. and Azziz , R. 2006 . Diagnosis, phenotype, and prevalence of polycystic ovary syndrome . Fertil. Steril. , 86 ( 1 ) : S7 – S8 .
   Google Scholar
• Nowak , D.A. , Snyder , D.C. , Brown , A.J. and Demark-Wahnefried , W. 2007 . The effect of flaxseed supplementation on hormonal levels associated with polycystic ovarian syndrome: A case study . Curr. Top. Nutraceut. Res. , 5 ( 4 ) : 177 – 181 .
   PubMed Web of Science ®Google Scholar
• Sturgeon , S.R. , Heersink , J.L. , Volpe , S.L. , Bertone-Johnson , E.R. , Puleo , E. , Stanczyk , F.Z. , Sabelawski , S. , Wähälä , K. , Kurzer , M.S. and Bigelow , C. 2008 . Effect of dietary flaxseed on serum levels of estrogens and androgens in postmenopausal women . Nutr. Cancer. , 60 ( 5 ) : 612 – 618 .
   PubMed Web of Science ®Google Scholar
• O'Neil , M.R. , Lardy , G.P. , Wilson , M.E. , Lemley , C.O. , Reynolds , L.P. , Caton , J.S. and Vonnahme , K.A. 2009 . Estradiol-17β and linseed meal interact to alter visceral organ mass and hormone concentrations from ovariectomized ewes . Domest. Anim. Endocrinol. , 37 ( 3 ) : 148 – 158 .
   PubMed Web of Science ®Google Scholar
• Saarinen , N.M. and Thompson , L.U. 2010 . Prolonged administration of secoisolariciresinol diglycoside increases lignin excretion and alters lignin tissue distribution in adult male and female rats . Br. J. Nutr. , 104 ( 6 ) : 833 – 841 .
   PubMed Web of Science ®Google Scholar
• Edwards , T.M. , Moore , B.C. and Guillette , L.J. Jr. 2006 . Reproductive dysgenesis in wild life . A comparative view. Int. J. Androl. , 29 : 109 – 121 .
   PubMed Web of Science ®Google Scholar
• Mitsunaga , K. , Araki , K. , Mizusaki , H. , Morohashi , K. , Haruna , K. , Nakagata , N. , Giguere , V. , Yamamura , K. and Abe , K. 2004 . Loss of PGC-specific expression of the orphan nuclear receptor ERR-beta results in reduction of germ cell number in mouse embryos . Mech. Dev. , 121 : 237 – 246 .
   PubMed Web of Science ®Google Scholar
• Goyal , H.O. , Robateau , A. , Braden , T.D. , Williams , C.S. , Srivastava , K.K. and Ali , K. 2003 . Neonatal estrogen exposure of male rats alters reproductive functions at adulthood . Biol. Reprod. , 68 : 2081 – 2091 .
   PubMed Web of Science ®Google Scholar
• Atanassova , N.N. , Walker , M. , McKinnell , C. , Fisher , J.S. and Sharpe , R.M. 2005 . Evidence that androgens and oestrogens, as well as folliclestimulating hormone, can alter Sertoli cell number in the neonatal rat . J. Endocrinol. , 184 : 107 – 117 .
   PubMed Web of Science ®Google Scholar
• Fisher , J.S. , Turner , K.J. , Brown , D. and Sharpe , R.M. 1999 . Effect of neonatal exposure to estrogenic compounds on development of the excurrent ducts of the rat testis through puberty to adulthood. Environ . Health Perspect. , 107 : 397 – 405 .
   Google Scholar
• Nonclerq , D. , Reverse , D. , Toubeau , G. , Beckers , J.F. , Sulon , J. , Laurent , G. , Zanen , J. and Heuson-Stiennon , J.A. 1996 . In situ demonstration of germinal cell apoptosis during diethylstilbestrol-induced testis regression in adult male Syrian hamsters . Biol. Reprod. , 55 : 1368 – 1376 .
   PubMed Web of Science ®Google Scholar
• Assinder , S. , Davis , R. , Fenwick , M. and Glover , A. 2007 . Adult-only exposure of male rats to a diet of high phytoestrogen content increases apoptosis of meiotic and post-meiotic germ cells . Reproduction , 133 : 11 – 19 .
   PubMed Web of Science ®Google Scholar
• Ruhlen , R. , Howdeshell , K.L. , Mao , J. , Taylor , J.A. , Bronson , F.H. , Newbold , R.R. , Welshons , V.W. and vom Saal , F.S. 2008 . Low phytoestrogen levels in feed increase fetal serum estradiol resulting in the “fetal estrogenization syndrome” and obesity in cd-1 mice. Environ . Health Perspect. , 116 ( 3 ) : 322 – 328 . S31–S38
   Google Scholar
• Mourvaki , E. , Cardinali , R. , Dal Bosco , A. , Corazzi , L. and Castellini , C. 2010 . Effects of flaxseed dietary supplementation on sperm quality and on lipid composition of sperm subfractions and prostatic granules in rabbit . Theriogenology , 73 ( 5 ) : 629 – 637 .
   PubMed Web of Science ®Google Scholar
• Stubbs , C.D. and Smith , A.D. 1984 . The modification of mammalian polyunsaturated fatty acid composition in relation to membrane fluidity and function, Biochem . Biophys. Acta , 779 : 89 – 137 .
   PubMed Web of Science ®Google Scholar
• Eskenazi , B. , Kidd , S.A. , Marks , A.R. , Sloter , E. , Block , G. and Wyrobek , A.J. 2005 . Antioxidant intake is associated with semen quality in healthy men. Hum . Reprod. , 20 ( 4 ) : 1006 – 1012 .
   Web of Science ®Google Scholar
• Wanasundara , P.K.J.P.D. and et al . 1999 . Changes in flax (Linum usitatissmum) seed nitrogenous compounds during germination . Food Chem. , 65 ( 3 ) : 289 – 295 .
   Web of Science ®Google Scholar
• Marques , A.Y.C. 2008 . Propriedades funcionais da linhaça (linum usitatissimum l.) em diferentes condições de preparo e de uso em alimentos . Centro de ciências rurais, Universidade Federal De Santa Maria, Santa Maria ,
   Google Scholar
• Lei , B. , Li-Chan , E.C.Y. , Oomah , B.D. and Mazza , G. 2003 . Distribution of cadmium-binding components in flax (Linum usitatissimum L.) Seed . J. Agric. Food Chem. , 51 ( 3 ) : 814 – 821 .
   PubMed Web of Science ®Google Scholar
• Haque , M.R. and Bradbury , J.H . 2002 . Total cyanide determination of plants and foods using the picrate and acid hydrolysis methods . Food Chem. , 77 ( 1 ) : 107 – 114 .
   Web of Science ®Google Scholar
• Lyman , R. L. and Lepkovsky , S. 1957 . The effect of raw soybean meal and trypsin inhibitor diets on pancreatic enzyme secretion in the rat . J. Nutr. , 62 : 269 – 284 .
   PubMed Web of Science ®Google Scholar
• Guerrero-Beltrán , J.A. , Estrada-Girón , Y. , Swanson , B. and Barbosa-Cánovas , G.V. 2009 . Pressure and temperature combination for inactivation of soymilk trypsin inhibitors . Food Chem. , 16 : 676 – 679 .
   Web of Science ®Google Scholar
• Larsson , M. , Rossander-Hulthen , L. , Sandstrom , B. and Sandberg , A.-S. 1996 . Improved zinc and iron absorption from breakfast meals containing malted oats with reduced phytate content . Br. J. Nutr. , 76 : 677 – 688 .
   PubMed Web of Science ®Google Scholar
• Tarpila , A. , Wennberg , T. , Tarpila , S. and et al . 2005 . Flaxseed as a functional food . Curr. Top. Nutraceut. Res. , 3 ( 3 ) : 167 – 188 .
   Google Scholar
• World Health Organization (WHO) . 2006 . “ Guideline for drinking-water quality ” . In Water Criteria and Other Supporting Information , Geneva, 2 : WHO .
   Google Scholar
• Oomah , B. D. and Mazza , G. 1998 . Compositional changes during commercial processing of flaxseed . Ind. Crops Prod. , 9 ( 1 ) : 29 – 37 .
   Web of Science ®Google Scholar
• Conn , E.E. 1969 . Cyanogenic glycosides . J. Agric. Food Chem. , 17 ( 3 ) : 519 – 526 .
   Web of Science ®Google Scholar
• Cunnane , S.C. and et al . 1993 . High-linolenic acid flaxseed (Linum usitatissimum):some nutritional properties in humans . Br. J. Nutr. , 69 ( 2 ) : 443 – 453 .
   PubMed Web of Science ®Google Scholar
• World Health Organization (WHO) . 2003 . Cyanogen Chloride in Drinking-Water. Background Document for Preparation of WHO Guidelines for Drinking-Water Quality , Geneva : World Health Organization .
   Google Scholar
• Austria , J.A. and et al . 2008 . Bioavailability of alpha-linolenic acid in subjects after ingestion of three different forms of flaxseed . J. Am. Coll. Nutr. , 27 ( 2 ) : 214 – 221 .
   PubMed Web of Science ®Google Scholar
• Hallund , J. , Tetens , I. , Bugel , S. , Tholstrup , T. and Bruun , J.M. 2008 . The effect of a lignan complex isolated from flaxseed on inflammation markers in healthy postmenopausal women . Nutr. Metab. Cardiovasc. Dis. , 18 : 497 – 502 .
   PubMed Web of Science ®Google Scholar
• Hallund , J. , Tetens , I. , Bugel , S. , Tholstrup , T. and Bruun , J.M. 2008 . The effect of a lignan complex isolated from flaxseed on inflammation markers in healthy postmenopausal women . Nutr. Metab. Cardiovasc. Dis. , 18 : 497 – 502 .
   PubMed Web of Science ®Google Scholar
• Dodin , S. , Cunnane , S.C. , Mâsse , B. , Lemay , A. , Jacques , H. , Asselin , G. , Tremblay-Mercier , J. , Marc , I. , Lamarche , B. , Légaré , F. and Forest , J.C. 2008 . Flaxseed on cardiovascular disease markers in healthy menopausal women: A randomized, double-bind, placebo-controlled trial . Nutrition. , 24 ( 1 ) : 23 – 30 .
   PubMed Web of Science ®Google Scholar
• Paschos , G.K. , Magkos , F. , Panagiotakos , D.B. , Votteas , V. and Zampelas , A. 2007 . Dietary supplementation with flaxseed oil lowers blood pressure in dyslipidemic patients . Eur. J. Clin. Nutr. , 61 ( 10 ) : 1201 – 1206 .
   PubMed Web of Science ®Google Scholar
• Makni , M. and et al . 2008 . Hypolipidemic and hepatoprotective effects of flax and pumpkin seed mixture rich in [omega]-3 and [omega]-6 fatty acids in hypercholesterolemic rats . Food Chem. Toxicol. , 46 ( 12 ) : 3714 – 3720 .
   PubMed Web of Science ®Google Scholar
• Dupasquier , C.M. , Dibrov , E. , Kneesh , A.L. , Cheung , P.K.M. , Lee , K.G.Y. , Alexander , H.K. , Yeganeh , B.K. , Moghadasian , M.H. and Pierce , G.N. 2007 . Dietary flaxseed inhibits atherosclerosis in the LDL receptor-deficient mouse in part through antiproliferative and anti-inflammatory actions . Am. J. Physiol. Heart Circ. Physiol. , 293 : 2394 – 2402 .
   PubMed Web of Science ®Google Scholar
• Vijaimohan , K. and et al . 2006 . Beneficial effects of alpha linolenic acid rich flaxseed oil on growth performance and hepatic cholesterol metabolism in high fat diet fed rats . Life Sci. , 79 ( 5 ) : 448 – 454 .
   PubMed Web of Science ®Google Scholar
• Prasad , K. and et al . 1998 . Reduction of hypercholesterolemic atherosclerosis by CDC-flaxseed with very low alpha-linolenic acid . Atherosclerosis , 136 ( 2 ) : 367 – 375 .
   PubMed Web of Science ®Google Scholar
• Prasad , K. 1997 . Dietary flax seed in prevention of hypercholesterolemic atherosclerosis . Atherosclerosis , 132 ( 1 ) : 69 – 76 .
   PubMed Web of Science ®Google Scholar
• Kelley , D.S. , Vemuri , Madhuri , Adkins , Yuriko , Sher Himmat , S. , Gill , Fedor , Dawn , Bruce , E. and Mackey . 2009 . Flaxseed oil prevents trans-10, cis-12-conjugated linoleic acid-induced insulin resistance in mice . Br. J. Nutr. , 101 : 701 – 708 .
   PubMed Web of Science ®Google Scholar
• Prasad , K. 2001 . Secoisolariciresinol diglucoside from flaxseed delays the development of type 2 diabetes in Zucker rat . J. Lab. Clin. Med. , 138 ( 1 ) : 32 – 39 .
   PubMedGoogle Scholar
• Thompson , L.U. , Chen , J.M. , Strasser-Weippl , K. and Goss , P.E. 2005 . Dietary flaxseed alters tumor biological markers in postmenopausal breast cancer . Clin. Cancer Res. , 11 : 3828 – 3835 .
   PubMed Web of Science ®Google Scholar
• Demark-Wahnefried , W. and et al . 2001 . Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: Exploring the effects on hormonal levels, prostate-specific antigen, and histopathologic features . Urology , 58 ( 1 ) : 47 – 52 .
   PubMed Web of Science ®Google Scholar
• Chen , J. , Saggar , J.K. , Corey , P. and Thompson , L.U. 2009 . Flaxseed and pure secoisolariciresinol diglucoside, but not flaxseed hull, reduce human breast tumor growth (MCF-7) in athymic mice . J. Nutr. , 139 ( 11 ) : 2061 – 2066 .
   PubMed Web of Science ®Google Scholar
• Chen , J. , Power , K.A. , Mann , J. , Cheng , A. and Thompson , L.U. 2007 . Flaxseed alone or in combination with tamoxifen inhibits MCF-7 breast tumor growth in ovariectomized athymic mice with high circulating levels of estrogen . Exp. Biol. Med. , 232 : 1071 – 1080 .
   PubMed Web of Science ®Google Scholar
• Williams , D. , Verghese , M. , Walker , L.T. , Boateng , J. , Shackelford , L. and Chawan , C.B. 2007 . Flax seed oil and flax seed meal reduce the formation of aberrant crypt foci (ACF) in azoxymethane-induced colon cancer in Fisher 344 male rats . Food Chem. Toxicol. , 45 ( 1 ) : 153 – 159 .
   PubMed Web of Science ®Google Scholar
• Jungeström , B. , Thompsom , L.U. and Dabrosin , C. 2007 . 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. , 13 ( 3 ) : 1061 – 1067 .
   PubMed Web of Science ®Google Scholar
• Cornish , S.M. , Chilibeck , P.D. , Paus-Jennsen , L. , Biem , H.J. , Khozani , T. , Senanayake , V. , Vatanparast , H. , Little , J.P. , Whiting , S.J. and Pahwa , P. 2009 . A randomized controlled trial of the effects of flaxseed lignin complex on metabolic syndrome composite score and bone mineral in older adults . Appl. Physiol. Nutr. Metabol. , 34 ( 2 ) : 89 – 98 .
   PubMed Web of Science ®Google Scholar
• Dodin , S. , Lemay , A. , Jacques , H. , Légaré , F. , Forest , J.C. and Mâsse , B. 2005 . The effects of flaxseed dietary supplement on lipid profile, bone mineral density, and symptoms in menopausal women: A randomized, double-blind, wheat germ placebo-controlled clinical trial . J. Clin. Endocrinol. Metabol. , 90 ( 3 ) : 1390 – 1397 .
   PubMed Web of Science ®Google Scholar
• Zhan , Z.P. , Huang , F.R. , Luo , J. , Dai , J.J. , Yan , X.H. and Peng , J. 2009 . Duration of feeding linseed diet influences expression of inflammation related genes and growth performance of growing-finishing barrows . J. Anim. Sci. , 87 ( 2 ) : 603 – 611 .
   PubMed Web of Science ®Google Scholar
• Ward , W.E. , Yuan , Y.V. , Cheung , A.M. and Thompson , L.U. 2001 . Exposure to purified lignan from flaxseed (Linum usitatissimum) alters bone development in female rats . Br. J. Nutr. , 86 : 499 – 505 .
   PubMed Web of Science ®Google Scholar