Flax Seed Lignan Studies and Research

There has been a great deal of scientific and medical interest in lignans. Provided below are quotations selected from flaxseed lignan studies published in peer-reviewed medical journals reporting on these promising compounds.

1)         A recent French study conducted over 7 years with 58,049 female participants concluded: High dietary intakes of plant lignans were associated with reduced risks of breast cancer in a Western population that does not consume a diet rich in soy
-Published Journal National Cancer Institute 2007;99:475-86. Touilland, Thiebout, et al.

2)        “Cancers of the breast and prostate, in their early phase of development, are hormone dependent and could be influenced by endocrine changes induced by lignans
-Morton MS Wilcox G Wahlqvist ML Griffiths Determination of lignans and isoflavonoids in human female plasma following dietary supplementation

3)        Flaxseed lignan studies for Hot Flashes— “Lignans in flax offer a ‘natural’, less potent estrogen effect on hot flashes than synthetic hormone therapy
-Sandhya Pruthi, MD. Mayo Clinic in Rochester, MN. Published February 1, 2008

4)        Dietary estrogens, such as lignan-rich flaxseed, are similar in structure to endogenous sex steroid hormones and act in vivo to alter hormone metabolism and reduce subsequent cancer risk in postmenopausal women.
-Hutchins A, Cancer Epidemiol Biomarkers Prev, 9(10): 1113, 2000

5)        There is considerable evidence from epidemiological studies correlating high concentrations of lignans in the body fluids with a low incidence of hormone-dependent tumors, in particular breast cancer. Kulling SE Jacobs E Pfeiffer -Metzler MStudies on the genotoxicity of the mammalian lignans enterolactone and enterodiol and their metabolic precursors at various endpoints in vitro.
In: Mutat Res (1998 Aug 7) 416(1 2):115 24

6)        There is a substantial reduction in breast cancer risk among women with a high intake (as measured by excretion) of phyto-oestrogens – particularly the isoflavone phyto-oestrogens equol and the lignan enterolactone. Findings in flaxseed lignan studies like this one could be important in the prevention of breast cancer.
-Ingram D Sanders K Kolybaba M Lopez D Case control study of phyto oestrogens and breast cancer In: Lancet (1997 Oct 4) 350(9083):990 4

7)        Reactive oxygen species (ROS) have been implicated in the development of diabetes mellitus. SDG isolated from flaxseed is an antioxidant. An investigation was made of the effects of SDG on the development of diabetes in rats, to determine if SDG can prevent/reduce the development of diabetes and if this prevention/reduction is associated with reduction in oxidative stress. RESULTS: SDG prevented the development of diabetes by 75%.
-Prasad K, et a, Mol Cell Biochem, 206(1-2): 2000; Prasad K. Mol Cell Biochem, 209(1-2): 89.2000

8)        Research suggests that SDG reduces hypercholesterolemic atherosclerosis and that this effect is associated with a decrease in serum cholesterol, LDL-C, and lipid peroxidation product and an increase in HDL-C and antioxidant reserve.
-Prasad K. Circulation, 99(10): 1355, 1999

9)        Flaxseed SDG may have a therapeutic role in lupus nephritis. (Clark W. et al Lupus, 9(6): 429, 2000)Asian men have a much lower incidence of prostate cancer and possibly of benign prostatic hyperplasia (BPH) than Western counterparts. Vegetarian men have a lower incidence of prostate cancer than omnivorous males. Plant lignans give rise to the mammalian lignans, enterodiol and enterolactone; the richest source is linseed (flaxseed). In addition to their oestrogenic activity, these plant compounds can interfere with steroid metabolism and bioavailability, and also inhibit enzymes, such as tyrosine kinase and topoisomerase, which are crucial to cellular proliferation and hence may contribute to lower incidences of prostrate cancer.
-Eur Urol, 35(5-6): 377, 1999

10)         Phytoestrogens are diphenolic compounds that are present in several plants eaten by human beings. Flaxseed is a particularly abundant source of phytoestrogens. When ingested in relatively large amounts, phytoestrogens have been shown to have significant estrogen agonists/antagonists effects in animals and humans. There is epidemiological, laboratory and clinical evidence which indicates that phytoestrogens, like certain selective estrogen receptor modulators, have an antiproliferative effect on the breast, and positive effects on the lipoprotein profile and bone density. They might also improve some of the climacteric symptoms.
-Brzezinski A & Bebi A. Eur J Obstet Gynecol Reprod Biol. 85(1): 47, 1999

11)        Maximum combined concentrations of lignans, during the linseed supplemental period approached 500 ng/ml. This value although representing the total rather than the free fraction, is some 10,000 times the concentration of free oestradiol seen in postmenopausal women and similar to the levels of the anti-estrogen Tamoxifin observed with breast cancer treated with 20 mg/day of this drug.
-Morton MS Wilcox G Wahlqvist ML Griffiths K Determination of lignans and isoflavonoids in human female plasma following dietary supplementation.

12)        Flaxseed is high in secoisolariciresinol diglycoside (SDG), the precursor of mammalian lignans, which can affect mammary gland structure. Lifetime or gestation and lactation exposure to 5 or 10% flaxseed induce structural changes in the mammary gland that may potentially reduce mammary cancer risk.
-Tou J & Thompson L. Carcinogenesis, 20(9): 1831, 1999

13)        Flaxseed and SDG, regardless of dose, appeared to delay the progression of MNU-induced mammary tumorigenesis.
-Rickard S. et al, Nutr Cancer; 35(1): 50, 1999

14)        Because flaxseed and its lignans are colon cancer protective, it is concluded that, in contrast to other flaxseed lignan studies, beta-glucuronidase activity may play a beneficial role in their presence by increasing mammalian lignan absorption and enterohepatic
-Jenab M, et al, Nutr Cancer, 33(2): 154, 1999

15)        Dietary supplementation with secoisolariciresinol diglycoside (SDG), a lignan precursor isolated from flaxseed, significantly reduced pulmonary metastasis cells and inhibited the growth of metastatic tumors that formed in the lungs.
-Li D. et al, Cancer Lett, 142(1): 91, 1999

16)        Flaxseed the richest source of lignans reduces metastasis and inhibits the growth of the metastatic secondary tumors in animals. Flaxseed may be a useful nutritional adjuvant to prevent melanoma metastasis in cancer patients.
-Yan L, et al, Cancer Lett, 124(2): 181, 1998

17)        Flaxseed contains lignans that have antioxidant activities and inhibit platelet-activating factor (PAF). Pretreatment with flaxseed attenuated emdotoxin induced cardiac dysfunction and cellular damage. Flaxseed antioxidant and anti-PAF agents may be effective in the treatment of ET shock.
-Pattanaik U & Prasad K, J Cardiovasc Pharmacol Ther, 3(4): 305. 1998

18)        The mammalian lignans enterolactone (EL) and enterodiol (ED) derived from precursors in foods, particularly flaxseed, have been shown to reduce the mammary tumor growth due to their antiestrogenic properties. Lignans are growth inhibitors of colon tumor cells and they may act through mechanism(s) other than antiestrogenic activity.
-Sung M, et al, Anticancer Res 18(3A: 1405, 1998

19)        Flaxseed, the richest source of mammalian lignan precursors, such as secoisolariciresinol diglycoside (SD), has been shown over the short term to decrease some early markers of colon cancer risk. This study determined that flaxseed has a colon cancer protective effect, that it is due, in part to SD and that the protective effects of flaxseed is associated with increase beta-glucuronidase activity.
-Jenab M & Thompson L, Carcinogenesis, 17:1343, 1996

20)        Flaxseed, a rich source of mammalian lignan precursor secoisolariciresinol-diglycoside _SD) and alpha-linolenic acid (ALA), has been shown to be protective at the early promotion stage of carcinogensis. In conclusion, the SD lignans in flaxseed appears to be beneficial throughout the promotional phase of carcinogenesis whereas the oil components is more effective at the stage when tumors have already been established.
-Thompson L, et al, Carcinogenesis, 17:1373, 1996)

21)        Flaxseed lignans have antitumor, antimitotic, antioxidant and weak estrogenic activity, are potentially the richest source of phytoestrogens in the human diet and may be linked to a low incidence of breast and colon cancer. Secoisolariciresinol was discovered to be a very potent antioxidant similar to BHA. No toxicity was found in the lignans.
-Obermeyer W, et al (US Food and Drug Administration, center for Food Safety and Applied Nutrition, Div. Contaminants Chem., Natural Products Branch), Meeting Of The Federation Of American Societies For Experimental Biology On Experimental Biology March/April, 1993, Faseb J (Fed Am Soc Exp Biol), A863, 1993

22)        Vitamin E-deficient diets containing 5 to 20% ground flaxseed protected mice against the malarial parasite Plasmodium voelii as shown by decreased parasitemia and enhanced survival.
-Levander O, et al, (USDA/ARS Human Nutrition Research Center, Vitamin Mineral Nutrition Laboratory), Nutrition Research, 11, 1991

23)        Excretion of both equol and enterolactone was associated with a substantial reduction in breast-cancer risk, with significant trends.
-Ingram D Sanders K Kolybaba M Lopez D Case control study of phyto oestrogens and breast cancer In: Lancet (1997 Oct 4) 350(9083):990 4

24)        The lower excretion of enterolactone by breast cancer patients in our study accords with the findings of a previous small study (seven cases) in which enterolactone excretion was significantly lower in post-menopausal breast cancer patients than in omnivorous and vegetarian controls.
-Ingram D Sanders K Kolybaba M Lopez DCase control study of phyto oestrogens and breast cancer In: Lancet (1997 Oct 4) 350(9083):990 4

25)        Mammalian lignans inhibit the growth of human breast cancer cells and partially inhibit angiogenesis. Rickard SE Orcheson LJ -Seidl MM Luyengi L Fong HH Thompson LUDose dependent production of mammalian lignans in rats and in vitro from the purified precursor secoisolariciresinol diglycoside in flaxseed.
In: J Nutr (1996 Aug) 126(8):2012 9

26)         Epidemiological studies indicated that plasma levels and urinary excretion of the lignan and isoflavonoid phytoestrogens correlated negatively with rates of breast and prostate cancer.
-Ren S Lien EJ Natural products and their derivatives as cancer chemopreventive agents. In: Prog Drug Res (1997) 48:147 71

27)        Lignans have been extensively investigated for their potential anticancer activity, and several have been used as chemotherapeutic agents.
-Axelson M Sjovall J Gustafsson BE Setchell KDOrigin of lignans in mammals and identification of a precursor from plants.

28)        Dietary studies and urinary analysis of lignans in postmenopausal women have shown that lignan secretion is significantly lower in urine in women with breast cancer than in healthy omnivorous and vegetarian women.
-Tham DM Gardner CD Haskell WLClinical review 97: Potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological, and mechanistic evidence.

29)        The lignan enterolactone showed a three-fold reduction (reduction in risk for breast cancer) in risk for the highest compared with the lowest quartile of excretion.
-Ingram D Sanders K Kolybaba M Lopez DCase control study of phyto oestrogens and breast cancer In: Lancet (1997 Oct 4) 350(9083):990 4

30)        Many Lignans have antitumor, antimitotic, antioxidant, weak estrogenic and antiestrogenic activities and some have been shown to prevent the growth of many tumors studied in the chemotherapy program of the U.S. National Cancer Institute.
-Mammalian Lignan Production From Various Foods Nutrition and Cancer; Lawrence Erlbaum Associates, Inc. 1991

31)        Lignan excretion in women is usually high in areas with low risk of breast cancer like North Karelia in Finland and in vegetarians and low in women living in high-risk areas like Boston, U.S.A. In older women with breast cancer in Boston the excretion was very low and it was relatively low in Finnish young women with breast cancer.
-Adlercreutz H Mousavi Y Clark J Hockerstedt K Hamalainen E Wahala K Makela T Hase TDietary phytoestrogens and cancer: in vitro and in vivo studies. In: J Steroid Biochem Mol Biol (1992 Mar) 41(3 8):331 7

32)        This study has significance in light of the recent observations that a diet with high-lignan producing capability may reduce the risk for carcinogenesis.
-Mammalian Lignan Production From Various Foods Nutrition and Cancer; Lawrence Erlbaum Associates, Inc. 1991

33)        Flax is a potent source of lignans.... studies suggested that they may interfere with the development of breast, prostate, colon, and other tumors in humans.
-Journal of the National Cancer Institute. Vol. 86 No.23. December 7, 1994 pg. 1748

34)        They (lignans) have now been shown to influence not only sex-hormone metabolism and biological activity but also intracellular enzymes, protein synthesis, growth factor action, malignant cell proliferation, differentiation and angiogenesis, making them strong candidates as natural cancer chemo-preventative compounds.
-Ren S Lien EJNatural products and their derivatives as cancer chemopreventive agents. In: Prog Drug Res (1997) 48:147 71

35)        A great deal of evidence supports the hypothesis that adequate lignan and isoflavone intakes reduce cancer risk. Several papers have reviewed the potential roles of phytoestrogens in preventing breast, colon, and prostate cancer.
-Kurzer MS Xu X Dietary phytoestrogens. In: Annu Rev Nutr (1997) 17:353 81

36)         Epidemiological data and biological properties of mammalian lignans suggest that they may have some protective effect against breast and colon cancer. Flaxseed in the most abundant source of lignan precursors known to date and it may have a high potential to reduce the risk for these diseases.
-Effect of Flaxseed on Breast and Colon Cancer: A Short Term Study Lilian U. Thompson Department of Nutritional Sciences; University of Toronto - Toronto, Canada

37)        Our studies show that increased excretion of some phyto-oestrogens is associated with substantial reduction in breast-cancer risk. This finding supports previous observational studies that reporter higher phyto-estrogen excretion among populations with a low frequency of breast cancer.
-Ingram D Sanders K Kolybaba M Lopez DCase control study of phyto oestrogens and breast cancer In: Lancet (1997 Oct 4) 350(9083):990 4

38)        Feeding of SD (the major mammalian lignan precursor in flaxseed) at 1.5 mg/day resulted in a significant reduction in tumor burden and the number of tumors per number of rats in the group.
-Thompson LU Seidl MM Rickard SE Orcheson LJ Fong HH Antitumorigenic effect of a mammalian lignan precursor from flaxseed. In: Nutr Cancer (1996) 26(2):159 65

39)        Our findings have implications for the control of breast cancer. Early detections by screening mammography and adjuvant systemic therapy both reduce breast-cancer mortality, but these techniques do not prevent the occurrence of cancer in the first place. They do little therefore; to reduce the enormous emotional and physical suffering the disease causes-nor do they reduce the massive financial cost to the community. Prevention is the only way to reduce the suffering and cost.
-Ingram D Sanders K Kolybaba M Lopez D Case control study of phyto oestrogens and breast cancerIn: Lancet (1997 Oct 4) 350(9083):990 4

40)        In addition to their inhibition of malignant cell proliferation the lignans may be protective with regard to PC (prostate cancer) or benign prostatic hyperplasia (BPH) due to their moderate aromatase inhibiting activity or to an effect on free testosterone levels via inhibition of LH secretion stimulation of SHBG synthesis. Both group of phytoestrogens show antioxidant properties which may play a role in carcinogenesis.
-Aldercreutz H Makela S Pylkkanen L Santti R Kinzel J van Reijsen M Markkanen H Kamarainen EL Watanabe S Fotsis T et al Dietary phytoestrogens and Prostate Cancer (Meeting abstract).

41)        As humans evolved with a variety of leguminous plants as basic food, human physiology appears to have depended upon the anti-oestrogen property of ingested lignans and isoflavonoids to inactivate circulating estrogens.
-Stephens FOBreast cancer: aetiological factors and associations (a possible protective role of phytoestrogens).In: Aust N Z J Surg (1997 Nov) 67(11):755 60

42)        Flaxseed, a rich source of mammalian lignan precursor secoisolariciresinol-diglucoside (S.D.) And alpha-linolenic acid (ALA) has been shown to be protective at the early promotion stage of carcinogenesis.
-Thompson LU Rickard SE Orcheson LJ Seidl MM Flaxseed and its lignan and oil components reduce mammary tumor growth at a late stage of carcinogenesis. In: Carcinogenesis (1996 Jun) 17(6):1373 6

43)        Both the presence and relative concentrations of the endogenous estrogens control the balance between estrogenic and antiestrogenic activity of mammalian lignans. Dietary supplementation of flaxseed has resulted in plasma lignan levels as high as 500 ng/ml which is 10,000 times that of normal circulating levels of steroidal estrogens.
-Health Effects of Flaxseed Mucilage, Lignans Inform, Vol. 8, no. 8 (August 1997)

44)        Flaxseed lignans studies found that flaxseed supplementation at the 5% level to a high-fat basal diet significantly lowered early neoplastic indices in both the colon and mammary gland of rats. With the purification of SDG from flaxseed, it was shown that both flaxseed (5% by weight) and SDG (at levels equivalent to that in the 5% flaxseed diet) can significantly reduce mammary tumor size and/or number when fed at early and late stages of carcinogenesis. Significant reductions in colon cancer risk markers, such as the size and multiplicity of aberrant crypt foci in carcinogen treated rats, have also been observed with flaxseed and SDG.
-Health Effects of Flaxseed Mucilage, Lignans Inform, Vol. 8, no. 8 (August 1997)

45)        In conclusion, flaxseed oil and flaxseed (in a dose dependant manner) reduced the growth of established tumors at a late stage of carcinogenesis whereas the mammalian lignans precursor S.D. exerted the greatest inhibitory effect on the development of new tumors. In contrast to new tumors, the size of established tumors was inversely related to the level of urinary mammalian lignans indicating that the lignans produced by S.D. played a role in the reduction of established tumor growth.
-Thompson LU Rickard SE Orcheson LJ Seidl MM Flaxseed and its lignan and oil components reduce mammary tumor growth at a late stage of carcinogenesis. In: Carcinogenesis (1996 Jun) 17(6):1373 6

46)        Flaxseed ash received attention from the National Cancer Institute because it contains large amounts of a phytochemical Secoisolariciresinol and omega-3 fatty acids. Lignans, as a class, have a wide variety of biological activity. Flaxseed lignans in particular, are being actively studied as a dietary intervention in breast and colon cancer.
-The FASEB Journal, Vol 7, Number 3, Febraury 19, 1993

47)        These dietary estrogens may provide a natural form of intervention therapy.
-Morton MS Wilcox G Wahlqvist ML Griffiths K Determination of lignans and isoflavonoids in human female plasma following dietary supplementation.

48)        Higher urinary levels have been found in humans and animals at lower risk of developing cancer.
-Rickard SE Orcheson LJ Seidl MM Luyengi L Fong HH Thompson LU Dose dependent production of mammalian lignans in rats and in vitro