CAPÍTULO III: MARCO METODOLÓGICO
3.4. Análisis de resultado
Some concerns have been discussed about the risks associated with PE, such as increased plasma concentration of isoflavones in babies that ingest soymilk, the ability of non-hormonal secondary plant metabolites to modify sex steroid metabolism, and the effects of PE on the thyroid (Ibarreta et al., 2001). In addition, the genetic toxicity potential of PE has been reviewed (Kulling et al., 2002). It has been reported that sheep consuming large amounts of clover which has with high amounts of PE showed infertility and reproductive disorders (Adams, 1995). Cheetahs in captivity also had reduced fertility rates when consuming a feline diet composed of a soybean product,
which was reversed when it was removed from the diet (Setchell et al., 1987). Toxicities associated with herbal medicines that include PE have also been presented in the literature (Sheehan, 1998).
As potential endocrine disrupters, PE may act as anti-oestrogens and harm the repro-ductive health of males (Santti et al., 1998).
Reduced sperm quality, undescended testes and urogenital tract abnormalities were increased in the sons of mothers taking diethyl-stilbestrol (DES) compared with those who did not take the miscarriage preventa-tive drug (Sheehan, 1998). Studies in cultured human lymphoblastoid cells reported that coumestrol was mutagenic and clastogenic (Domon et al., 2001). Other concerns related to PE are their effect on thyroxine, insulin and glucagon (Ohno et al., 1993). Hypothyroid cases were associated with infants fed soybean diets (Fort et al., 1990). In the USA, regulation is limited on standardization, preparation and extraction methods of the PE products being sold and marketed as nutritional supplements. As nutritional sup-plements these products are not supported by clinical trials and, therefore, should be
administered and taken with this in mind (This et al., 2001).
10.6 Conclusions
Diets rich in plant-derived products may supply a variety of phytoestrogens capable of producing a range of pharmacological effects in the human body. As people live longer, women are spending more of their lives in menopause, affected by a variety of oestrogen-related conditions such as osteoporosis, cog-nitive and cardiovascular disease, increased risk of breast cancer and other symptoms that decrease the overall quality of life. Epidemio-logical evidence and experimental data from animal studies are highly suggestive of the beneficial effects of PE on human health, but the clinical data supportive of such effects are either not available, or are awaiting design and execution of appropriate prospective large-scale clinical studies. Due to the func-tional and structural differences of PE, their biological activities are also highly variable and there may be other effects that have not yet been studied.
References
Adams, N.R. (1995) Detection of the effects of phytoestrogens on sheep and cattle. Journal of Animal Science 73, 1509–1515.
Adlercreutz, H. (1998) Evolution, nutrition, intestinal microflora, and prevention of cancer: a hypothesis.
Proceedings of the Society for Experimental Biology and Medicine 217, 241–246.
Adlercreutz, H. (2002) Phytoestrogens and cancer. Lancet Oncology 3, 364–373.
Adlercreutz, H. (2003) Phytoestrogens and breast cancer. Journal of Steroid Biochemistry and Molecular Biology 1803, 1–6.
Adlercreutz, H., Mazur, W., Bartels, P.V., Elomaa, V., Watanabe, S., Wahala, K., Landstrom, M., Lundin, E., Bergh, A., Damber, J.E., Aman, P., Widmark, A., Johansson, A., Zhang, J.X. and Hallmans, G. (2000a) Phytoestrogens and prostate disease. Journal of Nutrition 130, 658S–659S.
Adlercreutz, H., Mazur, W., Stumpf, K., Kikkinen, P., Hulten, K. and Hallmans, G. (2000b) Food containing phytoestrogens and breast cancer. BioFactors 12, 89–93.
Albertazzi, P. and Purdie, D.W. (2008) The nature and utility of the phytoestrogens: a review of the evidence.
Maturitas 61, 214–226.
Alves, R.C., Almeida, I.M.C., Casal, S. and Oliveira, M.B.P.P. (2010) Isoflavones in coffee: influence of species, roast degree, and brewing method. Journal of Agricultural and Food Chemistry 58, 3002–3007.
Amato, P., Christophe, S. and Mellon, P.L. (2002) Estrogenic activity of herbs commonly used as remedies for menopausal symptoms. Menopause 9, 145–150.
Anderson, J.J.B., Anthony, M., Messina, M. and Garner, S.C. (1999) Effects of phyto-oestrogens on tissues.
Nutrition Research Reviews 12, 75–116.
Anstead, G.M., Carlson, K.E. and Katzenellenbogen, J.A. (1997) The estradiol pharmacophore: ligand structure-estrogen receptor binding affinity relationships and a model for the receptor binding site. Steroids 62, 268–303.
Apers, S., Vlietinck, A. and Pieters, L. (2003) Lignans and neolignans as lead compounds. Photochemistry Reviews 2, 201–217.
Attoumbre, J., Bienaime, C., Dubois, F., Fliniaux, M.A., Chabbert, B. and Baltora-Rosset, S. (2010) Development of antibodies against secoisolanciresinol – Application to the immunolocalization of lignans in Linum usitatissimum seeds. Phytochemistry 71, 1979–1987.
Bambagiotti-Alberti, M., Coran, S.A., Ghiara, C., Giannelini, V. and Raffaelli, A. (1994a) Revealing the mam-malian lignan precursor secoisolariciresinol diglucoside in flax seed by ionspray mass spectrometry, Rapid Communications in Mass Spectrometry 8, 595–598.
Bambagiotti-Alberti, M., Coran, S.A., Ghiara, C., Moneti, G. and Raffaelli, A. (1994b) Investigation of mamma-lian lignan precursors in flax seed: first evidence of secoisolariciresinol diglucoside in two isomeric forms by liquid chromatography/mass spectrometry. Rapid Communications in Mass Spectrometry 8, 929–932.
Bartkiene, E., Juodeikiene, G., Basinskiene, L., Liukkonen, K.-H., Adlercreutz, H. and Kluge, H. (2011) Enterolignans enterolactone and enterodiol formation from their precursors by the action of intestinal microflora and their relationship with non-starch polysaccharides in various berries and vegetables.
Food Science and Technology 44, 48–53.
Beck, V., Rohr, U. and Jungbauer, A. (2005) Phytoestrogens derived from red clover: an alternative to estrogen replacement therapy? Journal of Steroid Biochemistry and Molecular Biology 94, 499–518.
Beejmohun, V., Fliniaux, O., Hano, C., Pilard, S., Grand, E., Lesur, D., Cailleu, D., Lamblin, F., Laine, E., Kovensky, J., Fliniaux, M.A. and Mesnard, F. (2007) Coniferin dimerisation in lignan biosynthesis in flax cells. Phytochemistry 68, 2744–2752.
Benassayag, C., Perrot-Applanat, M. and Ferre, F. (2002) Phytoestrogens as modulators of steroid action in target cells. Journal of Chromatography B – Analytical, Technological and Biomedical Life Science 777, 233–248.
Bergman, J.M., Thompson, 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 xeno-grafts in vivo. Clinical Cancer Research 13, 1061–1067.
Bhat, K.P.L., Kosmeder, J.W. II and Pezzuto, J.M. (2001) Biological effects of resveratrol. Antioxidants and Redox Signaling 3, 1041–1064.
Birt, D.F., Walker, B., Tibbels, M.G. and Bresnick, E. (1986) Anti-mutagenesis and antipromotion by apigenin, robinetin and indole-3-carbinol. Carcinogenesis 7, 959–963.
Blumenthal, M. (2004) The use of black cohosh to treat symptoms of menopause. Sexuality, Reproduction and Menopause 2, 27–34.
Boccardo, F., Puntoni, M., Guglielmini, P. and Rubagotti, A. (2006) Enterolactone as a risk factor for breast cancer: a review of the published evidence. Clinica Chimica Acta 365, 58–67.
Bonzanini, F., Bruni, R., Palla, G., Serlataite, N. and Caligiani, A. (2009) Identification and distribution of lignans in Punica granatum L. fruit endocarp, pulp, seeds, wood knots and commercial juices by GC-MS.
Food Chemistry 117, 745–749.
Bouker, K.B. and Hilakivi-Clarke, L. (2000) Genistein: does it prevent or promote breast cancer? Environmental Health Perspectives 108, 701–708.
Brusselmans, K., Vrolix, R., Verhoeven, G. and Swinnen, J.V. (2005) Induction of cancer cell apoptosis by flavonoids is associated with their ability to inhibit fatty acid synthase activity. Journal of Biological Chemistry 280, 5636–5645.
Brzezinski, A. and Debi, A. (1999) Phytoestrogens: the ‘natural’ selective estrogen receptor modulators?
European Journal of Obstetrics, Gynecology and Reproductive Biology 85, 47–51.
Brzezinski, A., Adlercreutz, H., Shaoul, R., Rosier, A., Shmueli, A., Tanos, V. and Schenker, J.G. (1997) Short-term effects of phytoestrogen-rich diet on postmenopausal women. Menopause 4, 89–94.
Brzozowski, A.M., Pike, A.C., Dauter, Z., Hubbard, R.E., Bonn, T., Engstrom, O., Ohman, L., Greene, G.L., Gustafsson, J.A. and Carlquist, M. (1997) Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 389, 753–758.
Burdette, J.E., Liu, J., Lantvit, D., Lim, E., Booth, N., Bhat, K.P.L., Hedayat, S., van Breemen, R.B., Constantinou, A.I., Pezzuto, J.M., Farnsworth, N.R. and Bolton, J.L. (2002) Trifolium pratense (red clover) exhibits estrogenic effects in vivo in ovariectomized Sprague-Dawley rats. Journal of Nutrition 132, 27–30.
Busquets, S., Ametller, E., Fuster, G., Olivan, M., Raab, V., Argilés, J.M. and López-Soriano, F.J. (2007) Resveratrol, a natural diphenol, reduces metastatic growth in an experimental cancer model. Cancer Letters 245, 144–148.
Cai, Y.Z., Mei, S., Jie, X., Luo, Q. and Corke, H. (2006) Structure-radical scavenging activity relationships of phenolic compounds from traditional Chinese medicinal plants. Life Science 78, 2872–2888.
Caltagirone, S., Rossi, C., Poggi, A., Ranelletti, F.O., Natali, P.G., Brunetti, M., Aiello, F.B. and Piantelli, M.
(2000) Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential.
International Journal of Cancer 87, 595–600.
Castello, L. and Tessitore, L. (2005) Resveratrol inhibits cell cycle progression in U937 cells. Oncology Reports 13, 133–137.
Chan, R.Y., Chen, W.F., Dong, A., Guo, D. and Wong, M.S. (2002) Estrogen like activity of ginsenoside Rg1 derived from Panax notoginseng. Journal of Clinical Endocrinology and Metabolism 87, 3691–3695.
Chen, J., Power, K.A., Mann, J., Cheng, A. and Thompson, L.U. (2007) Dietary flaxseed interaction with tamox-ifen induced tumor regression in athymic mice with MCF-7 xenografts by down regulating the expression of estrogen related gene products and signal transduction pathways. Nutrition and Cancer 58, 162–170.
Cherdshewasart, W., Sutjit, W., Pulcharoen, K. and Chulasiri, M. (2009) The mutagenic and antimutagenic effects of the traditional phytoestrogen-rich herbs, Pueraria mirifica and Pueraria lobata. Brazilian Journal of Medical and Biological Research 42, 816–823.
Clarkson, T.B. and Anthony, M.S. (1998) Phytoestrogens and coronary heart disease. Baillieres Clinical Endocrinology and Metabolism 12, 589–604.
Coldham, N.G. and Sauer, M.J. (2001) Identification, quantitation and biological activity of phytoestrogens in a dietary supplement for breast enhancement. Food and Chemical Toxicology 39, 1211–1224.
Constant, J. (1997) Alcohol, ischemic heart disease, and the French paradox. Coronary Artery Disease 8, 645–649.
Culpitt, S.V., Rogers, D.F., Fenwick, P.S., Shah, P., Matos, C.D., Russell, R.E.K., Barnes, P.J. and Donnelly, L.E.
(2003) Inhibition by red wine extract, resveratrol, of cytokine release by alveolar macrophages in COPD.
Thorax 58, 942–946.
Cunnane, S.C., Hamadeh, M.J., Liede, A.C., Thompson, L.U., Wolever, T.M. and Jenkins, D.J. (1995) Nutritional attributes of traditional flaxseed in healthy young adults. American Journal of Clinical Nutrition 61, 62–68.
Daly, D.C., Cameron, K.M. and Stevenson, D.W. (2001) Plant systematic in the age of genomics. Plant Physiology 127, 1328–1333.
de la Taille, A., Hayek, O.R., Burchardt, M., Burchardt, T. and Katz, A.E. (2000) Role of herbal compounds (PC-SPES) in hormone refractory prostate cancer: two case reports. Journal of Alternative and Complementary Medicine 6, 449–451.
de Ruvo, C., Amodio, R., Algeri, S., Martelli, N., Intilangelo, A., D’Ancona, G.M. and Esposito, E. (2000) Nutritional antioxidants as anti-degenerative agents. International Journal of Developmental Neuroscience 18, 359–366.
Dewick, P.M. (1993) Isoflavonoids. In: Harborne, J.B. (ed.) The Flavonoids: Advances in Research Since 1986.
Chapman and Hall, London, pp. 117–238.
Diel, P., Thomae, R.B., Caldarelli, A., Zierau, O., Kolba, S., Schmidt, S., Schwab, P., Metz, P. and Vollmer, G.
(2004) Regulation of gene expression by 8-prenylnaringenin in uterus and liver of Wistar rats. Planta Medica 70, 39–44.
Ding, X.Z. and Adrian, T.E. (2002) Resveratrol inhibits proliferation and induces apoptosis in human pancre-atic cancer cells. Pancreas 25, 71–76.
Dixon-Shanies, D. and Shaikh, N. (1999) Growth inhibition of human breast cancer cells by herbs and phy-toestrogens. Oncology Reports 6, 1383–1387.
Domon, O.E., McGarrity, L.J., Bishop, M., Yoshioka, M., Chen, J.J. and Morris, S.M. (2001) Evaluation of the genotoxicity of the phytoestrogen, coumestrol, in AHH-1 TK+/− human lymphoblastoid cells. Mutation Research 474, 129–137.
Duncan, A.M., Phipps, W.R. and Kurzer, M.S. (2003) Phyto-oestrogens. Best Practice and Research: Clinical Endocrinology and Metabolism 17, 253–271.
Effenberger, K.E., Johnsen, S.A., Monroe, D.G., Spelsberg, T.C. and Westendorf, J.J. (2005) Regulation of osteo-blastic phenotype and gene expression by hop-derived phytoestrogens. Journal of Steroid Biochemistry and Molecular Biology 96, 387–399.
Ehsanpour, S., Salehi, K., Zolfaghari, B. and Bakhtiari, S. (2012) the effect of red clover on quality of life in post-menopausal women. Iranian Journal of Nursing and Midwifery Research 17, 34–40.
Fang, J., Xia, C., Cao, Z., Zheng, J.Z., Reed, E. and Jiang, B.H. (2005) Apigenin inhibits VEGF and HIF-1 expression via PI3K/AKT/p70S6K1 and HDM2/p53 pathways. The Federation of American Societies for Experimental Biology Journal 19, 342–353.
File, S.E., Hartley, D.E., Alom, N. and Rattray, M. (2003) Soya phytoestrogens change cortical and hippocampal expression of BDNF mRNA in male rats. Neuroscience Letters 338, 135–138.
Ford, J.D., Huang, K.S., Wang, H.B., Davin, L.B. and Lewis, N.G. (2001) Biosynthetic pathway to the cancer chemopreventive secoisolariciresinol diglucoside-hydroxymethyl glutaryl ester-linked lignan oligomers in flax (Linum usitatissimum) seed. Journal of Natural Products 64, 1388–1397.
Fort, P., Moses, N., Fasano, M., Goldberg, T. and Lifshitz, F. (1990) Breast and soy-formula feedings in early infancy and the prevalence of autoimmune thyroid disease in children. Journal of the American College of Nutrition 9, 164–167.
Foster, S. and Tyler, V.E. (1999) Tyler’s Honest Herbal (ed.) A Sensible Guide to the Use of Herbs and Related Remedies. Haworth Herbal Press, New York.
Franke, A.A., Custer, L.J., Cerna, C.M. and Narala, K. (1995) Rapid HPLC analysis of dietary phytoestrogens from legumes and from human urine. Proceedings of Society for Experimental Biology and Medicine 208, 18–26.
Glazier, M.G. and Bowman, M.A. (2001) A review of the evidence for the use of phytoestrogens as a replace-ment for traditional estrogen replacereplace-ment therapy. Archives of Internal Medicine 161, 1161–1172.
Gruber, C.J., Tschugguel, W., Schneeberger, C. and Huber, J.C. (2002) Production and actions of estrogens.
New England Journal of Medicine 346, 340–352.
Gusman, J., Malonne, H. and Atassi, G. (2001) A reappraisal of the potential preventive and chemo-therapeutic properties of resveratrol. Carcinogenesis 22, 1111–1117.
Hardy, M.L. (2000) Herbs of special interest to women. Journal of American Pharmacists Association 40, 234–242.
Heber, D., Berdanier, C.D., Dwyer, J.T. and Feldman, E.B. (eds) (2008) Plant Foods and Phytochemicals in Human Health. CRC Press, Boca Raton, Florida, pp. 176–181.
Hosseinian, F.S. and Mazza, G. (2009) Triticale bran and straw: potential new sources of phenolic acids, proanthocyanidins, and lignans. Journal of Functional Foods 1, 57–64.
Hsieh, C.Y., Santell, R.C., Haslam, S.Z. and Helferich, W.G. (1998) Estrogenic effects of genistein on the growth of estrogen receptor positive human breast cancer (MCF-7) cells in vitro and in vivo. Cancer Research 58, 3833–3838.
Hu, C., Yuan, Y.V. and Kitts, D.D. (2007) Antioxidant activities of the flaxseed lignan secoisolariciresinol diglu-coside, its aglycone secoisolariciresinol and the mammalian lignans enterodiol and enterolactone in vitro. Food and Chemical Toxicology 45, 2219–2227.
Hu, J.Y. and Aizawa, T. (2003) Quantitative structure–activity relationships for estrogen receptor binding affin-ity of phenolic chemicals. Water Research 37, 1213–1222.
Humpel, M., Isaksson, P., Schaefer, O., Kaufmanna, U., Ciana, P., Maggic, A. and Schleuning, W.D. (2005) Tissue specificity of 8-prenylnaringenin: protection from ovariectomy induced bone loss with mini-mal trophic effects on the uterus. Journal of Steroid Biochemistry and Molecular Biology 97, 299–305.
Hwang, J., Hodis, H.N. and Sevanian, A. (2001) Soy and alfalfa phytoestrogen extracts become potent low-density lipoprotein antioxidants in the presence of acerola cherry extract. Journal of Agricultural and Food Chemistry 49, 308–314.
Ibarreta, D., Daxenberger, A. and Meyer, H.H. (2001) Possible health impact of phytoestrogens and xenoes-trogens in food. Acta Pathologica, Microbiologica et Immunologica 109, 161–184.
Ikeda, K., Arao, Y., Otsuka, H., Nomoto, S., Horiguchi, H., Kato, S. and Kayama, F. (2000) Terpenoids found in the Umbelliferae family act as agonists/antagonists for ER(alpha) and ER(beta): differential transcrip-tion activity between ferutinine-liganded ER(alpha) and ER(beta). Biochemical and Biophysical Research Communications 291, 354–360.
Jacobsen, B.K., Knutsen, S.F. and Fraser, G.E. (1998) Does high soy milk intake reduce prostate cancer inci-dence? The Adventist Health Study (United States). Cancer Causes and Control 9, 553–557.
Jang, M., Cai, L., Udeani, G.O., Slowing, K.V., Thomas, C.F., Beecher, C.W.W., Fong, H.H.S., Farnsworth, N.R., Kinghorn, A.D., Mehta, R.G., Moon, R.C. and Pezzuto, J.M. (1997) Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 275, 218–220.
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. and Cunnane, S.C. (1999) Health aspects of partially defatted flaxseed, including effects on serum lipids, oxidative measures, and ex vivo androgen and progestin activity: a controlled crossover trial. American Journal of Clinical Nutrition 69, 395–402.
Jenkins, D.J., Kendall, C.W., D’Costa, M.A., Jackson, C.J., Vidgen, E., Singer, W., Silverman, J.A., Koumbridis, G., Honey, J., Rao, A.V., Fleshner, N. and Klotz, L. (2003) Soy consumption and phytoestrogens: effect on serum prostate specific antigen when blood lipids and oxidized low density lipoprotein are reduced in hyperlipidemic men. Journal of Urology 169, 507–511.
Kaldas, M.I., Walle, U.K. and Walle, T. (2003) Resveratrol transport and metabolism by human intestinal CaCo-2 cells. Journal of Pharmacy and Pharmacology 55, 307–312.
Kaufman, P.B., Duke, J.A., Brielmann, H., Boik, J. and Hoyt, J.E. (1997) A comparative survey of leguminous plants as sources of the isoflavones, genistein and daidzein: implications for human nutrition and health.
Journal of Alternative and Complementary Medicine 3, 7–12.
Kelly, G.E., Joannou, G.E., Reeder, A.Y., Nelson, C. and Waring, M.A. (1995) The variable metabolic response to dietary isoflavones in humans. Proceedings of Society for Experimental Biology and Medicine 208, 40–43.
Kim, Y.M., Yun, J., Lee, C.K., Lee, H., Min, K.R. and Kim, Y. (2002) Oxyresveratrol and hydroxystilbene com-pounds. Inhibitory effect on tyrosinase and mechanism of action. Journal of Biological Chemistry 277, 16340–16344.
King, A. and Young, G. (1999) Characteristics and occurrence of phenolic phytochemicals. Journal of the American Dietetic Association 99, 213–218.
King, R.E., Kent, K.D. and Bomser, J.A. (2005) Resveratrol reduces oxidation and proliferation of human retinal pigment epithelial cells via extracellular signal-regulated kinase inhibition. Chemico Biological Interactions 151, 143–149.
Kitaoka, M., Kadokawa, H., Sugano, M., Ichikawa, K., Taki, M., Takaishi, S., Iijima, Y., Tsutsumi, S., Boriboon, M.
and Akiyama, T. (1998) Prenylflavonoids: a new class of non-steroidal phytoestrogen (Part 1). Isolation of 8-isopentenylnaringenin and an initial study on its structure–activity relationship. Planta Medica 64, 511–515.
Kitts, D.D. (1987) Studies on the estrogenic activity of a coffee extract. Journal of Toxicology and Environmental Health Sciences 20, 37–49.
Knight, D.C. and Eden, J.A. (1996) A review of the clinical effects of phytoestrogens. Obstetrics and Gynecology 87, 897–904.
Knowles, L.M., Zigrossi, D.A., Tauber, R.A., Hightower, C. and Milner, J.A. (2000) Flavonoids suppress androgen-independent human prostate tumor proliferation. Nutrition and Cancer 38, 116–122.
Kronenberg, F. and Fugh-Berman, A. (2002) Complementary and alternative medicine for menopausal symp-toms: a review of randomized, controlled trials. Annals of Internal Medicine 137, 805–813.
Kronenberg, F. and Hughes, C. (1999) Exogenous and endogenous estrogens: an appreciation of biological complexity. Menopause 6, 4–6.
Kuiper, G.G., Enmark, E., Pelto-Huikko, M., Nilsson, S. and Gustafsson, J.A. (1996) Cloning of a novel estro-gen receptor expressed in rat prostate and ovary. Proceedings of National Academy of Sciences USA 93, 5925–5930.
Kuiper, G.G., Lemmen, J.G., Carlsson, B., Corton, J.C., Safe, S.H., van der Saag, P.T., van der Burg, B. and Gustafsson, J.A. (1998) Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 139, 4252–4263.
Kulling, S.E., Lehmann, L. and Metzler, M. (2002) Oxidative metabolism and genotoxic potential of major isoflavone phytoestrogens. Journal of Chromatography B – Analytical Technology and Biomedical Life Sciences 777, 211–218.
Kurzer, M.S. and Xu, X. (1997) Dietary phytoestrogens. Annual Review of Nutrition 17, 353–381.
Kutuk, O., Adli, M., Poli, G. and Basaga, H. (2004) Resveratrol protects against 4-HNE induced oxidative stress and apoptosis in Swiss 3T3 fibroblasts. BioFactors 20, 1–10.
Landstrom, M., Zhang, J.X., Hallmans, G., Aman, P., Bergh, A., Damber, J.E., Mazur, W., Wahala, K. and Adlercreutz, H. (1998) Inhibitory effects of soy and rye diets on the development of Dunning R3327 prostate adenocarcinoma in rats. Prostate 36, 151–161.
Larrosa, M., Tomas-Barberan, F.A. and Espín, J.C. (2004) The grape and wine polyphenol piceatannol is a potent inducer of apoptosis in human SK-Mel-28 melanoma cells. European Journal of Nutrition 43, 275–284.
Lei, B., Roncaglia, V., Vigano, R., Cremonini, C., de Maria, N., del Buono, M.G., Manenti, F. and Villa, E.
(2002) Phytoestrogens and liver disease. Molecular and Cellular Endocrinology 193, 81–84.
Liang, Y.C., Huang, Y.T., Tsai, S.H., Lin-Shiau, S.Y., Chen, C.F. and Lin, J.K. (1999) Suppression of inducible cyclooxygenase and inducible nitric oxide synthase by apigenin and related flavonoids in mouse mac-rophages. Carcinogenesis 20, 1945–1952.
Liske, E., Hanggi, W., Henneicke-von, Z.H.H., Boblitz, N., Wustenberg, P. and Rahlfs, V.W. (2002) Journal of Women’s Health & Gender-Based Medicine 11, 163–174.
Liu, J., Burdette, J.E., Xu, H., Gu, C., van Breemen, R.B., Bhat, K.P., Booth, N., Constantinou, A.I., Pezzuto, J.M., Fong, H.H., Farnsworth, N.R. and Bolton, J.L. (2001) Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms. Journal of Agricultural and Food Chemistry 49, 2472–2479.
Liu, L.Z., Fang, J., Zhou, Q., Hu, X., Shi, X. and Jiang, B.H. (2005) Apigenin inhibits expression of vascular endothelial growth factor and angiogenesis in human lung cancer cells: implication of chemoprevention of lung cancer. Molecular Pharmacology 68, 635–643.
Llorens, F., Miro, F.A., Casanas, A., Roher, N., Garcia, L., Plana, M., Gomez, N. and Itarte, E. (2004) Unbalanced activation of ERK1/2 and MEK1/2 in apigenin-induced HeLa cell death. Experimental Cell Research 299, 15–26.
Matsuda, H., Shimoda, H., Morikawa, T. and Yoshikawa, M. (2001) Phytoestrogens from the roots of Polygonum cuspidatum (Polygonaceae): structure-requirement of hydroxyanthraquinones for estrogenic activity.
Bioorganic and Medicinal Chemistry Letters 11, 1839–1842.
Mazur, W. and Adlercreutz, H. (1998) Natural and anthropogenic environmental estrogens: the scientific basis for risk assessment. Naturally occurring oestrogens in food. Pure and Applied Chemistry 9, 1759–1776.
Mazur, W. and Adlercreutz, H. (2000) Overview of naturally occurring endocrine-active substances in the human diet in relation to human health. Nutrition, 16, 654–687.
Mazur, W., Fotsis, T., Wahala, K., Ojala, S., Salakka, A. and Adlercreutz, H. (1996) Isotope dilution gas chromatographic-mass spectrometric method for the determination of isoflavonoids, coumestrol, and lignans in food samples. Analytical Biochemistry 233, 169–180.
McCann, S.E., Wactawski-Wende, J., Kufel, K., Olson, J., Ovando, B., Kadlubar, S.N., Davis, W., Carter, L., Muti, P., Shields, P.G. and Freudenheim, J.L. (2007) Changes in 2-hydroxyestrone and 16alpha-hydroxyestrone metabolism with flaxseed consumption: modification by COMT and CYP1B1 genotype.
Cancer Epidemiology, Biomarkers and Prevention 16, 256–262.
McCoy, J. and Kelly, W. (1996) Survey of Cimicifuga racemosa for phytoestrogenic flavonoids. In: 212th American Chemical Society National Meeting, Orlando, Florida.
Meagher, L.P., Beecher, G.R., Flanagan, V.P. and Li, B.W. (1999) Isolation and characterization of the lignans, isolariciresinol and pinoresinol, in flaxseed meal. Journal of Agricultural and Food Chemistry 47, 3173–3180.
Merritt, J.C. (2001) Therapeutic options: hormone replacement therapy – soy therapy. Journal of National Medical Association 93, 288–292.
Messina, M., McCaskill-Stevens, W. and Lampe, J.W. (2006). Addressing the soy and breast cancer relationship:
review, commentary, and workshop proceedings. Journal of National Cancer Institute 98, 1275–1284.
Messina, M.J. and Loprinzi, C.L. (2001) Soy for breast cancer survivors: a critical review of the literature.
Journal of Nutrition 131, 3095S–3108S.
Miksicek, R.J. (1994) Interaction of naturally occurring nonsteroidal estrogens with expressed recombinant human estrogen receptor. Journal of Steroid Biochemistry and Molecular Biology 49, 153–160.
Milder, I.E.J., Arts, I.C.W., van de Putte, B., Venema, D.P. and Hollman, P.C.H. (2005) Lignan contents of Dutch plant foods: a database including lariciresinol, pinoresinol, secoisolariciresinol and matairesinol.
British Journal of Nutrition 93, 393–402.
Milligan, S.R., Kalita, J.C., Heyerick, A., Rong, H., de Cooman, L. and de Keukeleire, D. (1999) Identification of a potent phytoestrogens in hops (Humulus lupulus L.) and beer. Journal of Clinical Endocrinology and Metabolism 84, 2249–2252.
Moyad, M.A. (2002) Complementary/alternative therapies for reducing hot flashes in prostate cancer patients:
reevaluating the existing indirect data from studies of breast cancer and postmenopausal women.
Urology 59, 20S–33S.
Muir, A.D. and Westcott, N.D. (2000) Quantitation of the lignin secoisolariciresinol diglucoside in baked goods containing flax seed or flax meal. Journal of Agricultural Food Chemistry 48, 4048–4052.
Murkies, A.L., Wilcox, G. and Davis, S.R. (1998) Phytoestrogens. Journal of Clinical Endocrinology and Metabolism 83, 297–303.
Naftolin, F. and Stanbury, M.G. (2002) Phytoestrogens: are they really estrogen mimics? Fertility and Sterility 77, 15–17.
Nestel, P.J., Pomeroy, S.E., Sasahara, T., Yamashita, T., Liang, Y.L., Dart, A.M., Jennings, G.L., Abbey, M. and Cameron, J.D. (1997) Arterial compliance in obese subjects is improved with dietary plant n-3 fatty acid from flaxseed oil despite increased LDL oxidizability. Arteriosclerosis, Thrombosis and Vascular Biology 17, 1163–1170.
Ohno, T., Kato, N., Ishii, C., Shimizu, M., Ito, Y., Tomono, S. and Kawazu, S. (1993) Genistein augments cyclic
Ohno, T., Kato, N., Ishii, C., Shimizu, M., Ito, Y., Tomono, S. and Kawazu, S. (1993) Genistein augments cyclic