Flaxseed for Health and Disease: Review of Clinical Trials

Author(s): Mersedeh Shayan, Safa Kamalian, Amirhossein Sahebkar, Zahra Tayarani-Najaran*

Journal Name: Combinatorial Chemistry & High Throughput Screening
Accelerated Technologies for Biotechnology, Bioassays, Medicinal Chemistry and Natural Products Research

Volume 23 , Issue 8 , 2020


Become EABM
Become Reviewer
Call for Editor

Abstract:

Background: Flaxseed (Linum usitatissimum) is an oil-based seed that contains high amounts of alpha-linolenic acid, linoleic acid, lignans, fiber and many other bioactive components which is suggested for a healthier life. Nowadays, flaxseed is known as a remarkable functional food with different health benefits for humans and protects against cardiovascular disease, diabetes, dyslipidemia, obesity and altogether metabolic syndrome.

Methods: To review the bioactive components of flaxseed and their potential health effects, PubMed and Scopus were searched from commencement to July 2019. Keywords including: "flaxseed", "Linum usitatissimum", "metabolic syndrome", "obesity", "inflammation", "insulin resistance", "diabetes", "hyperlipidemia" and "menopause" were searched in the databases with varying combinations.

Conclusion: Consumption of flaxseed in different forms has valuable effects and protects against cardiovascular disease, hypertension, diabetes, dyslipidemia, inflammation and some other complications. Flaxseed can serve as a promising candidate for the management of metabolic syndrome to control blood lipid levels, fasting blood sugar, insulin resistance, body weight, waist circumference, body mass and blood pressure.

Keywords: Flaxseed, Linum usitatissimum, metabolic syndrome, inflammation, cardiovascular disease, menopause.

[1]
Gutte, K.B.; Sahoo, A.K.; Ranveer, R.C. Bioactive components of flaxseed and its health benefits. Int. J. Pharm. Sci. Rev. Res., 2015, 9, 42-51.
[2]
Youn Young, S.; Bo, G.; Paul, G.A.; Yong, W.; Martin, J.T.R. Flaxseed (Linum usitatissimum L.) bioactive compounds and peptide nomenclature: A review. Trends Food Sci. Technol., 2014, 38(1), 5-20.
[http://dx.doi.org/10.1016/j.tifs.2014.03.011]
[3]
Soni, R.P.; Katoch, M.; Kumar, A.; Verma, P. Flaxseed – composition and its benefits. Res. Environ. Life Sci., 2016, 9(3), 310-316.
[4]
Harper, C.R.; Edwards, M.J.; DeFilippis, A.P.; Jacobson, T.A. Flaxseed oil increases the plasma concentrations of cardioprotective (n-3) fatty acids in humans. J. Nutr., 2006, 136(1), 83-87. Erratum in: J. Nutr., 2007, 137(12), 2816. DeFilipis, A.P.
[http://dx.doi.org/10.1093/jn/136.1.83 ] [PMID: 16365063]
[5]
Hallund, J.; Tetens, I.; Bügel, S.; Tholstrup, T.; Bruun, J.M. The effect of a lignan complex isolated from flaxseed on inflammation markers in healthy postmenopausal women. Nutr. Metab. Cardiovasc. Dis., 2008, 18(7), 497-502.
[http://dx.doi.org/10.1016/j.numecd.2007.05.007 ] [PMID: 18502107]
[6]
Ren, G.Y.; Chen, C.Y.; Chen, G.C.; Chen, W.G.; Pan, A.; Pan, C.W.; Zhang, Y.H.; Qin, L.Q.; Chen, L.H. Effect of flaxseed intervention on inflammatory marker c-reactive protein: a systematic review and meta-analysis of randomized controlled trials. Nutrients, 2016, 8(3), 136.
[http://dx.doi.org/10.3390/nu8030136 ] [PMID: 26959052]
[7]
Cassani, R.S.; Fassini, P.G.; Silvah, J.H.; Lima, C.M.; Marchini, J.S. Impact of weight loss diet associated with flaxseed on inflammatory markers in men with cardiovascular risk factors: a clinical study. Nutr. J., 2015, 10, 14, 5. Retraction in; Cassani, R.S.; Fassini, P.G.; Silvah, J.H.; Lima, C.M.; Marchini. J.S. Nutr. J., 2016, 15, 59.
[8]
Spence, J.D.; Thornton, T.; Muir, A.D.; Westcott, N.D. The effect of flax seed cultivars with differing content of alpha-linolenic acid and lignans on responses to mental stress. J. Am. Coll. Nutr., 2003, 22(6), 494-501.
[http://dx.doi.org/10.1080/07315724.2003.10719327 ] [PMID: 14684754]
[9]
Caligiuri, S.P.B.; Parikh, M.; Stamenkovic, A.; Pierce, G.N.; Aukema, H.M. Dietary modulation of oxylipins in cardiovascular disease and aging. Am. J. Physiol. Heart Circ. Physiol., 2017, 313(5), H903-H918.
[http://dx.doi.org/10.1152/ajpheart.00201.2017 ] [PMID: 28801523]
[10]
Jones, P.J.; Senanayake, V.K.; Pu, S.; Jenkins, D.J.; Connelly, P.W.; Lamarche, B.; Couture, P.; Charest, A.; Baril-Gravel, L.; West, S.G.; Liu, X.; Fleming, J.A.; McCrea, C.E.; Kris-Etherton, P.M. DHA-enriched high-oleic acid canola oil improves lipid profile and lowers predicted cardiovascular disease risk in the canola oil multicenter randomized controlled trial. Am. J. Clin. Nutr., 2014, 100(1), 88-97.
[http://dx.doi.org/10.3945/ajcn.113.081133 ] [PMID: 24829493]
[11]
Ipatova, O.M.; Prozorovskaia, N.N.; Baranova, V.S.; Guseva, D.A. Biological activity of linseed oil as the source of omega-3 alpha-linolenic acid. Biomed. Khim., 2004, 50(1), 25-43.
[PMID: 15108624]
[12]
Covington, M.B. Omega-3 fatty acids. Am. Fam. Physician, 2004, 70(1), 133-140.
[PMID: 15259529]
[13]
Gillingham, L.G.; Harding, S.V.; Rideout, T.C.; Yurkova, N.; Cunnane, S.C.; Eck, P.K.; Jones, P.J. Dietary oils and FADS1-FADS2 genetic variants modulate [13C]α-linolenic acid metabolism and plasma fatty acid composition. Am. J. Clin. Nutr., 2013, 97(1), 195-207.
[http://dx.doi.org/10.3945/ajcn.112.043117 ] [PMID: 23221573]
[14]
Allman, M.A.; Pena, M.M.; Pang, D. Supplementation with flaxseed oil versus sunflowerseed oil in healthy young men consuming a low fat diet: effects on platelet composition and function. Eur. J. Clin. Nutr., 1995, 49(3), 169-178.
[PMID: 7774533]
[15]
Mirfatahi, M.; Tabibi, H.; Nasrollahi, A.; Hedayati, M. Effects of flaxseed oil on serum lipids and lipoproteins in hemodialysis patients: a randomized controlled trial. Iran. J. Kidney Dis., 2016, 10(6), 405-412.
[PMID: 27904000]
[16]
Lemos, J.R.; Alencastro, M.G.; Konrath, A.V.; Cargnin, M.; Manfro, R.C. Flaxseed oil supplementation decreases C-reactive protein levels in chronic hemodialysis patients. Nutr. Res., 2012, 32(12), 921-927.
[http://dx.doi.org/10.1016/j.nutres.2012.08.007 ] [PMID: 23244537]
[17]
Saxena, S.; Katare, C. Evaluation of flaxseed formulation as a potential therapeutic agent in mitigation of dyslipidemia. Biomed. J., 2014, 37(6), 386-390.
[http://dx.doi.org/10.4103/2319-4170.126447 ] [PMID: 25163498]
[18]
West, S.G.; Krick, A.L.; Klein, L.C.; Zhao, G.; Wojtowicz, T.F.; McGuiness, M.; Bagshaw, D.M.; Wagner, P.; Ceballos, R.M.; Holub, B.J.; Kris-Etherton, P.M. Effects of diets high in walnuts and flax oil on hemodynamic responses to stress and vascular endothelial function. J. Am. Coll. Nutr., 2010, 29(6), 595-603.
[http://dx.doi.org/10.1080/07315724.2010.10719898 ] [PMID: 21677123]
[19]
Machado, A.M.; de Paula, H.; Cardoso, L.D.; Costa, N.M. Effects of brown and golden flaxseed on the lipid profile, glycemia, inflammatory biomarkers, blood pressure and body composition in overweight adolescents. Nutrition, 2015, 31(1), 90-96.
[http://dx.doi.org/10.1016/j.nut.2014.05.002 ] [PMID: 25441591]
[20]
Caligiuri, S.P.B.; Aukema, H.M.; Ravandi, A.; Guzman, R.; Dibrov, E.; Pierce, G.N. Flaxseed consumption reduces blood pressure in patients with hypertension by altering circulating oxylipins via an α-linolenic acid-induced inhibition of soluble epoxide hydrolase. Hypertension, 2014, 64(1), 53-59.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.114.03179 ] [PMID: 24777981]
[21]
Paschos, G.K.; Magkos, F.; Panagiotakos, D.B.; Votteas, V.; Zampelas, A. Dietary supplementation with flaxseed oil lowers blood pressure in dyslipidaemic patients. Eur. J. Clin. Nutr., 2007, 61(10), 1201-1206.
[http://dx.doi.org/10.1038/sj.ejcn.1602631 ] [PMID: 17268413]
[22]
Prasad, K. Flaxseed and cardiovascular health. J. Cardiovasc. Pharmacol., 2009, 54(5), 369-377.
[http://dx.doi.org/10.1097/FJC.0b013e3181af04e5 ] [PMID: 19568181]
[23]
Caligiuri, S.P.B.; Rodriguez-Leyva, D.; Aukema, H.M.; Ravandi, A.; Weighell, W.; Guzman, R.; Pierce, G.N. Dietary flaxseed reduces central aortic blood pressure without cardiac involvement but through changes in plasma oxylipins. Hypertension, 2016, 68(4), 1031-1038.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.116.07834 ] [PMID: 27528063]
[24]
Yari, Z.; Rahimlou, M.; Eslamparast, T.; Ebrahimi-Daryani, N.; Poustchi, H.; Hekmatdoost, A. Flaxseed supplementation in non-alcoholic fatty liver disease: a pilot randomized, open labeled, controlled study. Int. J. Food Sci. Nutr., 2016, 67(4), 461-469.
[http://dx.doi.org/10.3109/09637486.2016.1161011 ] [PMID: 26983396]
[25]
Patenaude, A.; Rodriguez-Leyva, D.; Edel, A.L.; Dibrov, E.; Dupasquier, C.M.; Austria, J.A.; Richard, M.N.; Chahine, M.N.; Malcolmson, L.J.; Pierce, G.N. Bioavailability of alpha-linolenic acid from flaxseed diets as a function of the age of the subject. Eur. J. Clin. Nutr., 2009, 63(9), 1123-1129.
[http://dx.doi.org/10.1038/ejcn.2009.41 ] [PMID: 19584895]
[26]
Khalatbari Soltani, S.; Jamaluddin, R.; Tabibi, H.; Mohd Yusof, B.N.; Atabak, S.; Loh, S.P.; Rahmani, L. Effects of flaxseed consumption on systemic inflammation and serum lipid profile in hemodialysis patients with lipid abnormalities. Hemodial. Int., 2013, 17(2), 275-281.
[http://dx.doi.org/10.1111/j.1542-4758.2012.00754.x ] [PMID: 22998533]
[27]
Zhang, W.; Wang, X.; Liu, Y.; Tian, H.; Flickinger, B.; Empie, M.W.; Sun, S.Z. Dietary flaxseed lignan extract lowers plasma cholesterol and glucose concentrations in hypercholesterolaemic subjects. Br. J. Nutr., 2008, 99(6), 1301-1309.
[http://dx.doi.org/10.1017/S0007114507871649 ] [PMID: 18053310]
[28]
Patade, A.; Devareddy, L.; Lucas, E.A.; Korlagunta, K.; Daggy, B.P.; Arjmandi, B.H. Flaxseed reduces total and LDL cholesterol concentrations in Native American postmenopausal women. J. Womens Health (Larchmt.), 2008, 17(3), 355-366.
[http://dx.doi.org/10.1089/jwh.2007.0359 ] [PMID: 18328014]
[29]
Fukumitsu, S.; Aida, K.; Shimizu, H.; Toyoda, K. Flaxseed lignan lowers blood cholesterol and decreases liver disease risk factors in moderately hypercholesterolemic men. Nutr. Res., 2010, 30(7), 441-446.
[http://dx.doi.org/10.1016/j.nutres.2010.06.004 ] [PMID: 20797475]
[30]
Jenkins, D.J.; Kendall, C.W.; Vidgen, E.; Agarwal, S.; Rao, A.V.; Rosenberg, R.S.; Diamandis, E.P.; Novokmet, R.; Mehling, C.C.; Perera, T.; Griffin, L.C.; Cunnane, S.C. Health aspects of partially defatted flaxseed, including effects on serum lipids, oxidative measures, and ex vivo androgen and progestin activity: a controlled crossover trial. Am. J. Clin. Nutr., 1999, 69(3), 395-402.
[http://dx.doi.org/10.1093/ajcn/69.3.395 ] [PMID: 10075322]
[31]
Bloedon, L.T.; Balikai, S.; Chittams, J.; Cunnane, S.C.; Berlin, J.A.; Rader, D.J.; Szapary, P.O. Flaxseed and cardiovascular risk factors: results from a double blind, randomized, controlled clinical trial. J. Am. Coll. Nutr., 2008, 27(1), 65-74.
[http://dx.doi.org/10.1080/07315724.2008.10719676 ] [PMID: 18460483]
[32]
Kawakami, Y.; Yamanaka-Okumura, H.; Naniwa-Kuroki, Y.; Sakuma, M.; Taketani, Y.; Takeda, E. Flaxseed oil intake reduces serum small dense low-density lipoprotein concentrations in Japanese men: a randomized, double blind, crossover study. Nutr. J., 2015, 14, 39.
[http://dx.doi.org/10.1186/s12937-015-0023-2 ] [PMID: 25896182]
[33]
Kristensen, M.; Savorani, F.; Christensen, S.; Engelsen, S.B.; Bügel, S.; Toubro, S.; Tetens, I.; Astrup, A. Flaxseed dietary fibers suppress postprandial lipemia and appetite sensation in young men. Nutr. Metab. Cardiovasc. Dis., 2013, 23(2), 136-143.
[http://dx.doi.org/10.1016/j.numecd.2011.03.004 ] [PMID: 21802266]
[34]
Pu, S.; Eck, P.; Jenkins, D.J.; Connelly, P.W.; Lamarche, B.; Kris-Etherton, P.M.; West, S.G.; Liu, X.; Jones, P.J. Interactions between dietary oil treatments and genetic variants modulate fatty acid ethanolamides in plasma and body weight composition. Br. J. Nutr., 2016, 115(6), 1012-1023.
[http://dx.doi.org/10.1017/S0007114515005425 ] [PMID: 26806592]
[36]
Rhee, Y.; Brunt, A. Flaxseed supplementation improved insulin resistance in obese glucose intolerant people: a randomized crossover design. Nutr. J., 2011, 10, 44.
[http://dx.doi.org/10.1186/1475-2891-10-44 ] [PMID: 21554710]
[37]
Hutchins, A.M.; Brown, B.D.; Cunnane, S.C.; Domitrovich, S.G.; Adams, E.R.; Bobowiec, C.E. Daily flaxseed consumption improves glycemic control in obese men and women with pre-diabetes: a randomized study. Nutr. Res., 2013, 33(5), 367-375.
[http://dx.doi.org/10.1016/j.nutres.2013.02.012 ] [PMID: 23684438]
[38]
Brahe, L.K.; Le Chatelier, E.; Prifti, E.; Pons, N.; Kennedy, S.; Blædel, T.; Håkansson, J.; Dalsgaard, T.K.; Hansen, T.; Pedersen, O.; Astrup, A.; Ehrlich, S.D.; Larsen, L.H. Dietary modulation of the gut microbiota--a randomised controlled trial in obese postmenopausal women. Br. J. Nutr., 2015, 114(3), 406-417.
[http://dx.doi.org/10.1017/S0007114515001786 ] [PMID: 26134388]
[39]
Pan, A.; Sun, J.; Chen, Y.; Ye, X.; Li, H.; Yu, Z.; Wang, Y.; Gu, W.; Zhang, X.; Chen, X.; Demark-Wahnefried, W.; Liu, Y.; Lin, X. Effects of a flaxseed-derived lignan supplement in type 2 diabetic patients: a randomized, double-blind, cross-over trial. PLoS One, 2007, 2(11), e1148.
[http://dx.doi.org/10.1371/journal.pone.0001148 ] [PMID: 17987126]
[40]
Pan, A.; Demark-Wahnefried, W.; Ye, X.; Yu, Z.; Li, H.; Qi, Q.; Sun, J.; Chen, Y.; Chen, X.; Liu, Y.; Lin, X. Effects of a flaxseed-derived lignan supplement on C-reactive protein, IL-6 and retinol-binding protein 4 in type 2 diabetic patients. Br. J. Nutr., 2009, 101(8), 1145-1149.
[http://dx.doi.org/10.1017/S0007114508061527 ] [PMID: 18775100]
[41]
Zheng, J.S.; Lin, M.; Fang, L.; Yu, Y.; Yuan, L.; Jin, Y.; Feng, J.; Wang, L.; Yang, H.; Chen, W.; Li, D.; Tang, J.; Cai, W.; Shi, M.; Li, Z.; Wang, F.; Li, D. Effects of n-3 fatty acid supplements on glycemic traits in Chinese type 2 diabetic patients: A double-blind randomized controlled trial. Mol. Nutr. Food Res., 2016, 60(10), 2176-2184.
[http://dx.doi.org/10.1002/mnfr.201600230 ] [PMID: 27279274]
[42]
Taghizadeh, M.; Jamilian, M.; Mazloomi, M.; Sanami, M.; Asemi, Z. A randomized-controlled clinical trial investigating the effect of omega-3 fatty acids and vitamin E co-supplementation on markers of insulin metabolism and lipid profiles in gestational diabetes. J. Clin. Lipidol., 2016, 10(2), 386-393.
[http://dx.doi.org/10.1016/j.jacl.2015.12.017 ] [PMID: 27055970]
[43]
Jamilian, M.; Hashemi Dizaji, S.; Bahmani, F.; Taghizadeh, M.; Memarzadeh, M.R.; Karamali, M.; Akbari, M.; Asemi, Z. A randomized controlled clinical trial investigating the effects of omega-3 fatty acids and vitamin E co-supplementation on biomarkers of oxidative stress, inflammation and pregnancy outcomes in gestational diabetes. Can. J. Diabetes, 2017, 41(2), 143-149.
[http://dx.doi.org/10.1016/j.jcjd.2016.09.004 ] [PMID: 27881297]
[44]
Prasad, K.; Dhar, A. Flaxseed and diabetes. Curr. Pharm. Des., 2016, 22(2), 141-144.
[http://dx.doi.org/10.2174/1381612822666151112151230 ] [PMID: 26561065]
[45]
Repin, N.; Kay, B.A.; Cui, S.W.; Wright, A.J.; Duncan, A.M.; Douglas Goff, H. Investigation of mechanisms involved in postprandial glycemia and insulinemia attenuation with dietary fibre consumption. Food Funct., 2017, 8(6), 2142-2154.
[http://dx.doi.org/10.1039/C7FO00331E ] [PMID: 28581555]
[46]
Dahl, W.J.; Lockert, E.A.; Cammer, A.L.; Whiting, S.J. Effects of flax fiber on laxation and glycemic response in healthy volunteers. J. Med. Food, 2005, 8(4), 508-511.
[http://dx.doi.org/10.1089/jmf.2005.8.508 ] [PMID: 16379563]
[47]
Lafond, D.W.; Greaves, K.A.; Maki, K.C.; Leidy, H.J.; Romsos, D.R. Effects of two dietary fibers as part of ready-to-eat cereal (RTEC) breakfasts on perceived appetite and gut hormones in overweight women. Nutrients, 2015, 7(2), 1245-1266.
[http://dx.doi.org/10.3390/nu7021245 ] [PMID: 25689743]
[48]
Demmers, A.; Korthout, H.; van Etten-Jamaludin, F.S.; Kortekaas, F.; Maaskant, J.M. Effects of medicinal food plants on impaired glucose tolerance: A systematic review of randomized controlled trials. Diabetes Res. Clin. Pract., 2017, 131, 91-106.
[http://dx.doi.org/10.1016/j.diabres.2017.05.024 ] [PMID: 28750220]
[49]
Mani, U.V.; Mani, I.; Biswas, M.; Kumar, S.N. An open-label study on the effect of flax seed powder (Linum usitatissimum) supplementation in the management of diabetes mellitus. J. Diet. Suppl., 2011, 8(3), 257-265.
[http://dx.doi.org/10.3109/19390211.2011.593615 ] [PMID: 22432725]
[50]
Thakur, G.; Mitra, A.; Pal, K.; Rousseau, D. Effect of flaxseed gum on reduction of blood glucose and cholesterol in type 2 diabetic patients. Int. J. Food Sci. Nutr., 2009, 60(Suppl. 6), 126-136.
[http://dx.doi.org/10.1080/09637480903022735 ] [PMID: 19548163]
[51]
Almario, R.U.; Karakas, S.E. Lignan content of the flaxseed influences its biological effects in healthy men and women. J. Am. Coll. Nutr., 2013, 32(3), 194-199.
[http://dx.doi.org/10.1080/07315724.2013.791147 ] [PMID: 23885993]
[52]
Harper, C.R.; Edwards, M.C.; Jacobson, T.A. Flaxseed oil supplementation does not affect plasma lipoprotein concentration or particle size in human subjects. J. Nutr., 2006, 136(11), 2844-2848.
[http://dx.doi.org/10.1093/jn/136.11.2844 ] [PMID: 17056811]
[53]
Lohner, S.; Marosvölgyi, T.; Burus, I.; Schmidt, J.; Molnár, D.; Decsi, T. Dietary supplementation of obese children with 1000 mg alpha-linolenic acid per day: a placebo-controlled double blind study. Orv. Hetil., 2007, 148(32), 1499-1503.
[http://dx.doi.org/10.1556/OH.2007.28015 ] [PMID: 17675277]
[54]
Gillingham, L.G.; Gustafson, J.A.; Han, S.Y.; Jassal, D.S.; Jones, P.J. High-oleic rapeseed (canola) and flaxseed oils modulate serum lipids and inflammatory biomarkers in hypercholesterolaemic subjects. Br. J. Nutr., 2011, 105(3), 417-427.
[http://dx.doi.org/10.1017/S0007114510003697 ] [PMID: 20875216]
[55]
Zheng, J.S.; Chen, J.; Wang, L.; Yang, H.; Fang, L.; Yu, Y.; Yuan, L.; Feng, J.; Li, K.; Tang, J.; Lin, M.; Lai, C.Q.; Li, D. Replication of a gene-diet interaction at CD36, NOS3 and PPARG in response to omega-3 fatty acid supplements on blood lipids: a double-blind randomized controlled trial. EBioMedicine, 2018, 31, 150-156.
[http://dx.doi.org/10.1016/j.ebiom.2018.04.012 ] [PMID: 29703528]
[56]
Cândido, F.G.; de Oliveira, F.C.E.; Lima, M.F.C.; Pinto, C.A.; da Silva, L.L.; Martino, H.S.D.; Dos Santos, M.H.; Alfenas, R.C.G. Addition of pooled pumpkin seed to mixed meals reduced postprandial glycemia: a randomized placebo-controlled clinical trial. Nutr. Res., 2018, 56, 90-97.
[http://dx.doi.org/10.1016/j.nutres.2018.04.015 ] [PMID: 30055778]
[57]
Mirhashemi, S.M.; Rahimi, F.; Soleimani, A.; Asemi, Z. Effects of omega-3 fatty acid supplementation on inflammatory cytokines and advanced glycation end products in patients with diabetic nephropathy: a randomized controlled trial. Iran. J. Kidney Dis., 2016, 10(4), 197-204.
[PMID: 27514766]
[58]
Cornish, S.M.; Chilibeck, P.D. Alpha-linolenic acid supplementation and resistance training in older adults. Appl. Physiol. Nutr. Metab., 2009, 34(1), 49-59.
[http://dx.doi.org/10.1139/H08-136 ] [PMID: 19234585]
[59]
Turowski, J.B.; Pietrofesa, R.A.; Lawson, J.A.; Christofidou-Solomidou, M.; Hadjiliadis, D. Flaxseed modulates inflammatory and oxidative stress biomarkers in cystic fibrosis: a pilot study. BMC Complement. Altern. Med., 2015, 15, 148.
[http://dx.doi.org/10.1186/s12906-015-0651-2 ] [PMID: 25963404]
[60]
Faintuch, J.; Horie, L.M.; Barbeiro, H.V.; Barbeiro, D.F.; Soriano, F.G.; Ishida, R.K.; Cecconello, I. Systemic inflammation in morbidly obese subjects: response to oral supplementation with alpha-linolenic acid. Obes. Surg., 2007, 17(3), 341-347.
[http://dx.doi.org/10.1007/s11695-007-9062-x ] [PMID: 17546842]
[61]
Faintuch, J.; Bortolotto, L.A.; Marques, P.C.; Faintuch, J.J.; França, J.I.; Cecconello, I. Systemic inflammation and carotid diameter in obese patients: pilot comparative study with flaxseed powder and cassava powder. Nutr. Hosp., 2011, 26(1), 208-213.
[PMID: 21519749]
[62]
Heymach, J.V.; Shackleford, T.J.; Tran, H.T.; Yoo, S.Y.; Do, K.A.; Wergin, M.; Saintigny, P.; Vollmer, R.T.; Polascik, T.J.; Snyder, D.C.; Ruffin, M.T., IV; Yan, S.; Dewhirst, M.; Kunnumakkara, A.B.; Aggarwal, B.B.; Demark-Wahnefried, W. Effect of low-fat diets on plasma levels of NF-κB-regulated inflammatory cytokines and angiogenic factors in men with prostate cancer. Cancer Prev. Res. (Phila.), 2011, 4(10), 1590-1598.
[http://dx.doi.org/10.1158/1940-6207.CAPR-10-0136 ] [PMID: 21764858]
[63]
Babajafari, S.; Hojhabrimanesh, A.; Sohrabi, Z.; Ayaz, M.; Noorafshan, A.; Akrami, A. Comparing isolated soy protein with flaxseed oil vs isolated soy protein with corn oil and wheat flour with corn oil consumption on muscle catabolism, liver function, blood lipid, and sugar in burn patients: a randomized clinical trial. Trials, 2018, 19(1), 308.
[http://dx.doi.org/10.1186/s13063-018-2693-5 ] [PMID: 29866187]
[64]
Thompson, L.U.; Chen, J.M.; Li, T.; Strasser-Weippl, K.; Goss, P.E. Dietary flaxseed alters tumor biological markers in postmenopausal breast cancer. Clin. Cancer Res., 2005, 11(10), 3828-3835.
[http://dx.doi.org/10.1158/1078-0432.CCR-04-2326 ] [PMID: 15897583]
[65]
Esiyok, D.; Otles, S.; Akcicek, E. Herbs as a food source in Turkey. Asian Pac. J. Cancer Prev., 2004, 5(3), 334-339.
[PMID: 15373716]
[66]
Demark-Wahnefried, W.; Polascik, T.J.; George, S.L.; Switzer, B.R.; Madden, J.F.; Ruffin, M.T., IV; 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.; Vollmer, R.T. Flaxseed supplementation (not dietary fat restriction) reduces prostate cancer proliferation rates in men presurgery. Cancer Epidemiol. Biomarkers Prev., 2008, 17(12), 3577-3587.
[http://dx.doi.org/10.1158/1055-9965.EPI-08-0008 ] [PMID: 19064574]
[67]
Simons, R.; Sonawane, N.; Verbruggen, M.; Chaudhary, J. Efficacy and safety of a flaxseed hull extract in the symptomatic management of benign prostatic hyperplasia: a parallel, randomized, double-blind, placebo-controlled, pilot study. J. Med. Food, 2015, 18(2), 233-240.
[http://dx.doi.org/10.1089/jmf.2013.3129 ] [PMID: 25546379]
[68]
Zhang, W.; Wang, X.; Liu, Y.; Tian, H.; Flickinger, B.; Empie, M.W.; Sun, S.Z. Effects of dietary flaxseed lignan extract on symptoms of benign prostatic hyperplasia. J. Med. Food, 2008, 11(2), 207-214.
[http://dx.doi.org/10.1089/jmf.2007.602 ] [PMID: 18358071]
[69]
Francois, C.A.; Connor, S.L.; Bolewicz, L.C.; Connor, W.E. Supplementing lactating women with flaxseed oil does not increase docosahexaenoic acid in their milk. Am. J. Clin. Nutr., 2003, 77(1), 226-233.
[http://dx.doi.org/10.1093/ajcn/77.1.226 ] [PMID: 12499346]
[70]
Mirghafourvand, M.; Mohammad-Alizadeh-Charandabi, S.; Ahmadpour, P.; Javadzadeh, Y. Effects of Vitex agnus and Flaxseed on cyclic mastalgia: A randomized controlled trial. Complement. Ther. Med., 2016, 24, 90-95.
[http://dx.doi.org/10.1016/j.ctim.2015.12.009 ] [PMID: 26860808]
[71]
Pruthi, S.; Qin, R.; Terstreip, S.A.; Liu, H.; Loprinzi, C.L.; Shah, T.R.; Tucker, K.F.; Dakhil, S.R.; Bury, M.J.; Carolla, R.L.; Steen, P.D.; Vuky, J.; Barton, D.L. A phase III, randomized, placebo-controlled, double-blind trial of flaxseed for the treatment of hot flashes: North Central Cancer Treatment Group N08C7. Menopause, 2012, 19(1), 48-53.
[http://dx.doi.org/10.1097/gme.0b013e318223b021 ] [PMID: 21900849]
[72]
Hallund, J.; Tetens, I.; Bügel, S.; Tholstrup, T.; Ferrari, M.; Teerlink, T.; Kjaer, A.; Wiinberg, N. Daily consumption for six weeks of a lignan complex isolated from flaxseed does not affect endothelial function in healthy postmenopausal women. J. Nutr., 2006, 136(9), 2314-2318.
[http://dx.doi.org/10.1093/jn/136.9.2314 ] [PMID: 16920847]
[73]
Ghazanfarpour, M.; Sadeghi, R.; Abdolahian, S.; Latifnejad Roudsari, R. The efficacy of Iranian herbal medicines in alleviating hot flashes: A systematic review. Int. J. Reprod. Biomed. (Yazd), 2016, 14(3), 155-166.
[http://dx.doi.org/10.29252/ijrm.14.3.155 ] [PMID: 27294213]
[74]
Haggans, C.J.; Travelli, E.J.; Thomas, W.; Martini, M.C.; Slavin, J.L. The effect of flaxseed and wheat bran consumption on urinary estrogen metabolites in premenopausal women. Cancer Epidemiol. Biomarkers Prev., 2000, 9(7), 719-725.
[PMID: 10919743]
[75]
Pruthi, S.; Thompson, S.L.; Novotny, P.J.; Barton, D.L.; Kottschade, L.A.; Tan, A.D.; Sloan, J.A.; Loprinzi, C.L. Pilot evaluation of flaxseed for the management of hot flashes. J. Soc. Integr. Oncol., 2007, 5(3), 106-112.
[http://dx.doi.org/10.2310/7200.2007.007 ] [PMID: 17761129]
[76]
Dietz, B.M.; Hajirahimkhan, A.; Dunlap, T.L.; Bolton, J.L. Botanicals and their bioactive phytochemicals for women’s health. Pharmacol. Rev., 2016, 68(4), 1026-1073.
[http://dx.doi.org/10.1124/pr.115.010843 ] [PMID: 27677719]
[77]
Hutchins, A.M.; Martini, M.C.; Olson, B.A.; Thomas, W.; Slavin, J.L. Flaxseed influences urinary lignan excretion in a dose-dependent manner in postmenopausal women. Cancer Epidemiol. Biomarkers Prev., 2000, 9(10), 1113-1118.
[PMID: 11045796]
[78]
Cetisli, N.E.; Saruhan, A.; Kivcak, B. The effects of flaxseed on menopausal symptoms and quality of life. Holist. Nurs. Pract., 2015, 29(3), 151-157.
[PMID: 25882265]
[79]
Lewis, J.E.; Nickell, L.A.; Thompson, L.U.; Szalai, J.P.; Kiss, A.; Hilditch, J.R. A randomized controlled trial of the effect of dietary soy and flaxseed muffins on quality of life and hot flashes during menopause. Menopause, 2006, 13(4), 631-642.
[http://dx.doi.org/10.1097/01.gme.0000191882.59799.67 ] [PMID: 16837885]
[80]
Simbalista, R.L.; Sauerbronn, A.V.; Aldrighi, J.M.; Arêas, J.A. Consumption of a flaxseed-rich food is not more effective than a placebo in alleviating the climacteric symptoms of postmenopausal women. J. Nutr., 2010, 140(2), 293-297.
[http://dx.doi.org/10.3945/jn.109.113886 ] [PMID: 20007337]
[81]
Lucas, E.A.; Wild, R.D.; Hammond, L.J.; Khalil, D.A.; Juma, S.; Daggy, B.P.; Stoecker, B.J.; Arjmandi, B.H. Flaxseed improves lipid profile without altering biomarkers of bone metabolism in postmenopausal women. J. Clin. Endocrinol. Metab., 2002, 87(4), 1527-1532.
[http://dx.doi.org/10.1210/jcem.87.4.8374 ] [PMID: 11932276]
[82]
Lemay, A.; Dodin, S.; Kadri, N.; Jacques, H.; Forest, J.C. Flaxseed dietary supplement versus hormone replacement therapy in hypercholesterolemic menopausal women. Obstet. Gynecol., 2002, 100(3), 495-504.
[PMID: 12220769]
[83]
Dodin, S.; Cunnane, S.C.; Mâsse, B.; Lemay, A.; Jacques, H.; Asselin, G.; Tremblay-Mercier, J.; Marc, I.; Lamarche, B.; Légaré, F.; Forest, J.C. Flaxseed on cardiovascular disease markers in healthy menopausal women: a randomized, double-blind, placebo-controlled trial. Nutrition, 2008, 24(1), 23-30.
[http://dx.doi.org/10.1016/j.nut.2007.09.003 ] [PMID: 17981439]
[84]
Colli, M.C.; Bracht, A.; Soares, A.A.; de Oliveira, A.L.; Bôer, C.G.; de Souza, C.G.; Peralta, R.M. Evaluation of the efficacy of flaxseed meal and flaxseed extract in reducing menopausal symptoms. J. Med. Food, 2012, 15(9), 840-845.
[http://dx.doi.org/10.1089/jmf.2011.0228 ] [PMID: 22925074]
[85]
Mirmasoumi, G.; Fazilati, M.; Foroozanfard, F.; Vahedpoor, Z.; Mahmoodi, S.; Taghizadeh, M.; Esfeh, N.K.; 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(4), 222-228.
[http://dx.doi.org/10.1055/s-0043-119751 ] [PMID: 29117618]
[86]
Hashempur, M.H.; Homayouni, K.; Ashraf, A.; Salehi, A.; Taghizadeh, M.; Heydari, M. Effect of Linum usitatissimum L. (linseed) oil on mild and moderate carpal tunnel syndrome: a randomized, double-blind, placebo-controlled clinical trial. Daru, 2014, 22, 43.
[http://dx.doi.org/10.1186/2008-2231-22-43 ] [PMID: 24887185]
[87]
Thies, F.; Miles, E.A.; Nebe-von-Caron, G.; Powell, J.R.; Hurst, T.L.; Newsholme, E.A.; Calder, P.C. Influence of dietary supplementation with long-chain n-3 or n-6 polyunsaturated fatty acids on blood inflammatory cell populations and functions and on plasma soluble adhesion molecules in healthy adults. Lipids, 2001, 36(11), 1183-1193.
[http://dx.doi.org/10.1007/s11745-001-0831-4 ] [PMID: 11795850]
[88]
Barden, A.E.; Croft, K.D.; Durand, T.; Guy, A.; Mueller, M.J.; Mori, T.A. Flaxseed oil supplementation increases plasma F1-phytoprostanes in healthy men. J. Nutr., 2009, 139(10), 1890-1895.
[http://dx.doi.org/10.3945/jn.109.108316 ] [PMID: 19675101]
[89]
Nordström, D.C.; Honkanen, V.E.; Nasu, Y.; Antila, E.; Friman, C.; Konttinen, Y.T. Alpha-linolenic acid in the treatment of rheumatoid arthritis. A double-blind, placebo-controlled and randomized study: flaxseed vs. safflower seed. Rheumatol. Int., 1995, 14(6), 231-234.
[http://dx.doi.org/10.1007/BF00262088 ] [PMID: 7597378]
[90]
Kristensen, M.; Damgaard, T.W.; Sørensen, A.D.; Raben, A.; Lindeløv, T.S.; Thomsen, A.D.; 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(8), 961-967.
[http://dx.doi.org/10.1038/sj.ejcn.1602813 ] [PMID: 17522599]
[91]
Barceló-Coblijn, G.; Murphy, E.J.; Othman, R.; Moghadasian, M.H.; Kashour, T.; Friel, J.K. Flaxseed oil and fish-oil capsule consumption alters human red blood cell n-3 fatty acid composition: a multiple-dosing trial comparing 2 sources of n-3 fatty acid. Am. J. Clin. Nutr., 2008, 88(3), 801-809.
[http://dx.doi.org/10.1093/ajcn/88.3.801 ] [PMID: 18779299]
[92]
Vargas, M.L.; Almario, R.U.; Buchan, W.; Kim, K.; Karakas, S.E. Metabolic and endocrine effects of long-chain versus essential omega-3 polyunsaturated fatty acids in polycystic ovary syndrome. Metabolism, 2011, 60(12), 1711-1718.
[http://dx.doi.org/10.1016/j.metabol.2011.04.007 ] [PMID: 21640360]
[93]
Joshi, K.; Lad, S.; Kale, M.; Patwardhan, B.; Mahadik, S.P.; Patni, B.; Chaudhary, A.; Bhave, S.; Pandit, A. Supplementation with flax oil and vitamin C improves the outcome of Attention Deficit Hyperactivity Disorder (ADHD). Prostaglandins Leukot. Essent. Fatty Acids, 2006, 74(1), 17-21.
[http://dx.doi.org/10.1016/j.plefa.2005.10.001 ] [PMID: 16314082]
[94]
Flax, V.L.; Siega-Riz, A.M.; Reinhart, G.A.; Bentley, M.E. Provision of lipid-based nutrient supplements to Honduran children increases their dietary macro- and micronutrient intake without displacing other foods. Matern. Child Nutr., 2015, 11(Suppl. 4), 203-213.
[http://dx.doi.org/10.1111/mcn.12182 ] [PMID: 25819697]
[95]
Lagkouvardos, I.; Kläring, K.; Heinzmann, S.S.; Platz, S.; Scholz, B.; Engel, K.H.; Schmitt-Kopplin, P.; Haller, D.; Rohn, S.; Skurk, T.; Clavel, T. Gut metabolites and bacterial community networks during a pilot intervention study with flaxseeds in healthy adult men. Mol. Nutr. Food Res., 2015, 59(8), 1614-1628.
[http://dx.doi.org/10.1002/mnfr.201500125 ] [PMID: 25988339]
[96]
Edel, A.L.; Patenaude, A.F.; Richard, M.N.; Dibrov, E.; Austria, J.A.; Aukema, H.M.; Pierce, G.N.; Aliani, M. The effect of flaxseed dose on circulating concentrations of alpha-linolenic acid and secoisolariciresinol diglucoside derived enterolignans in young, healthy adults. Eur. J. Nutr., 2016, 55(2), 651-663.
[http://dx.doi.org/10.1007/s00394-015-0885-2 ] [PMID: 25808116]
[97]
De Spirt, S.; Stahl, W.; Tronnier, H.; Sies, H.; Bejot, M.; Maurette, J.M.; Heinrich, U. Intervention with flaxseed and borage oil supplements modulates skin condition in women. Br. J. Nutr., 2009, 101(3), 440-445.
[http://dx.doi.org/10.1017/S0007114508020321 ] [PMID: 18761778]
[98]
Wojtowicz, J.C.; Butovich, I.; Uchiyama, E.; Aronowicz, J.; Agee, S.; McCulley, J.P. Pilot, prospective, randomized, double-masked, placebo-controlled clinical trial of an omega-3 supplement for dry eye. Cornea, 2011, 30(3), 308-314.
[http://dx.doi.org/10.1097/ICO.0b013e3181f22e03 ] [PMID: 21045648]
[99]
Cohen, L.; Meira, J.; Cosendey, G.M.; de Souza, A.F.; Mattos, F.; Carneiro, J.R.; Rosado, E.L. Evaluation of the influence of whole and defatted flaxseed on satiety, glucose, and leptin levels of women in the late postoperative stage of bariatric surgery. Obes. Surg., 2013, 23(2), 157-166.
[http://dx.doi.org/10.1007/s11695-012-0733-x ] [PMID: 22930072]
[100]
Rusak, A.; Rybak, Z. New directions of research related to chronic wound healing. Polim. Med., 2013, 43(3), 199-204.
[PMID: 24377187]
[101]
McCarty, M.F.; DiNicolantonio, J. Suppression of NADPH oxidase activity may slow the expansion of osteolytic bone metastases. Healthcare (Basel), 2016, 4(3), E60.
[http://dx.doi.org/10.3390/healthcare4030060 ] [PMID: 27571113]
[102]
Gracious, B.L.; Chirieac, M.C.; Costescu, S.; Finucane, T.L.; Youngstrom, E.A.; Hibbeln, J.R. Randomized, placebo-controlled trial of flax oil in pediatric bipolar disorder. Bipolar Disord., 2010, 12(2), 142-154.
[http://dx.doi.org/10.1111/j.1399-5618.2010.00799.x ] [PMID: 20402707]
[103]
Griel, A.E.; Kris-Etherton, P.M.; Hilpert, K.F.; Zhao, G.; West, S.G.; Corwin, R.L. An increase in dietary n-3 fatty acids decreases a marker of bone resorption in humans. Nutr. J., 2007, 6, 2.
[http://dx.doi.org/10.1186/1475-2891-6-2 ] [PMID: 17227589]
[104]
Azrad, M.; Vollmer, R.T.; Madden, J.; Dewhirst, M.; Polascik, T.J.; Snyder, D.C.; Ruffin, M.T.; Moul, J.W.; Brenner, D.E.; Demark-Wahnefried, W. Flaxseed-derived enterolactone is inversely associated with tumor cell proliferation in men with localized prostate cancer. J. Med. Food, 2013, 16(4), 357-360.
[http://dx.doi.org/10.1089/jmf.2012.0159 ] [PMID: 23566060]
[105]
Widen, E.M.; Bentley, M.E.; Chasela, C.S.; Kayira, D.; Flax, V.L.; Kourtis, A.P.; Ellington, S.R.; Kacheche, Z.; Tegha, G.; Jamieson, D.J.; van der Horst, C.M.; Allen, L.H.; Shahab-Ferdows, S.; Adair, L.S. BAN Study Team. Antiretroviral treatment is associated with iron deficiency in hiv-infected malawian women that is mitigated with supplementation, but is not associated with infant iron deficiency during 24 weeks of exclusive breastfeeding. J. Acquir. Immune Defic. Syndr., 2015, 69(3), 319-328.
[http://dx.doi.org/10.1097/QAI.0000000000000588 ] [PMID: 25723140]
[106]
Neukam, K.; De Spirt, S.; Stahl, W.; Bejot, M.; Maurette, J.M.; Tronnier, H.; Heinrich, U. Supplementation of flaxseed oil diminishes skin sensitivity and improves skin barrier function and condition. Skin Pharmacol. Physiol., 2011, 24(2), 67-74.
[http://dx.doi.org/10.1159/000321442 ] [PMID: 21088453]
[107]
Ramos, C.I.; Andrade de Lima, A.F.; Grilli, D.G.; Cuppari, L. The short-term effects of olive oil and flaxseed oil for the treatment of constipation in hemodialysis patients. J. Ren. Nutr., 2015, 25(1), 50-56.
[http://dx.doi.org/10.1053/j.jrn.2014.07.009 ] [PMID: 25238699]
[108]
Pinheiro, M.N., Jr; dos Santos, P.M.; dos Santos, R.C. Barros, Jde.N.; Passos, L.F.; Cardoso Neto, J. [Oral flaxseed oil (Linum usitatissimum) in the treatment for dry-eye Sjögren’s syndrome patients. Arq. Bras. Oftalmol., 2007, 70(4), 649-655.
[PMID: 17906762]
[109]
Clark, W.F.; Kortas, C.; Heidenheim, A.P.; Garland, J.; Spanner, E.; Parbtani, A. Flaxseed in lupus nephritis: a two-year nonplacebo-controlled crossover study. J. Am. Coll. Nutr., 2001, 20(Suppl. 2), 143-148.
[http://dx.doi.org/10.1080/07315724.2001.10719026 ] [PMID: 11349937]
[110]
Downie, L.E.; Gad, A.; Wong, C.Y.; Gray, J.H.V.; Zeng, W.; Jackson, D.C.; Vingrys, A.J. Modulating contact lens discomfort with anti-inflammatory approaches: a randomized controlled trial. Invest. Ophthalmol. Vis. Sci., 2018, 59(8), 3755-3766.
[http://dx.doi.org/10.1167/iovs.18-24758 ] [PMID: 30046817]
[111]
Babajafari, S.; Akhlaghi, M.; Mazloomi, S.M.; Ayaz, M.; Noorafshan, A.; Jafari, P.; Hojhabrimanesh, A. The effect of isolated soy protein adjunctive with flaxseed oil on markers of inflammation, oxidative stress, acute phase proteins, and wound healing of burn patients; a randomized clinical trial. Burns, 2018, 44(1), 140-149.
[http://dx.doi.org/10.1016/j.burns.2017.05.014 ] [PMID: 28619236]
[112]
Marck, C.H.; De Livera, A.M.; Brown, C.R.; Neate, S.L.; Taylor, K.L.; Weiland, T.J.; Hadgkiss, E.J.; Jelinek, G.A. Health outcomes and adherence to a healthy lifestyle after a multimodal intervention in people with multiple sclerosis: Three year follow-up. PLoS One, 2018, 13(5), e0197759.
[http://dx.doi.org/10.1371/journal.pone.0197759 ] [PMID: 29791509]
[113]
Mirfatahi, M.; Imani, H.; Tabibi, H.; Nasrollahi, A.; Hedayati, M. Effects of flaxseed oil on serum bone turnover markers in hemodialysis patients: a randomized controlled trial. Iran. J. Kidney Dis., 2018, 12(4), 215-222.
[PMID: 30087216]
[114]
Basch, E.; Bent, S.; Collins, J.; Dacey, C.; Hammerness, P.; Harrison, M.; Smith, M.; Szapary, P.; Ulbricht, C.; Vora, M.; Weissner, W. Natural Standard Resource Collaboration. Flax and flaxseed oil (Linum usitatissimum): a review by the natural standard research collaboration. J. Soc. Integr. Oncol., 2007, 5(3), 92-105.
[http://dx.doi.org/10.2310/7200.2007.005 ] [PMID: 17761128]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 23
ISSUE: 8
Year: 2020
Published on: 02 November, 2020
Page: [699 - 722]
Pages: 24
DOI: 10.2174/1386207323666200521121708
Price: $65

Article Metrics

PDF: 26
HTML: 5