Reported in the prestigious medical journal, The Lancet, high urinary excretion of lignan is associated with a substantial reduction in breast-cancer risk.

According to the prestigious medical journal, The Lancet, high urinary excretion of lignan is associated with a substantial reduction in breast-cancer risk.

"There is a substantial reduction in breast cancer risk among women with high intake of phytoestrogens - particularly the isoflavonic phytoestrogens equol and the lignan enterolactone," note investigators in the October 4, 1997 issue of The Lancet. "These findings could be important in the prevention of breast cancer."

In this landmark study published in 1997, 144 women aged 30 to 84 who had been just diagnosed with early breast cancer were interviewed and 72 hour urine collection and blood samples were taken before any treatment started.

An additional 144 women volunteers (totaling 288 participants) without breast cancer were matched by age and identical postal area code with each breast cancer patient.

The non-breast cancer controls were informed only of participation in a "dietary study" with no mention of breast cancer as the study topic. The volunteers' participation involved completing an identical questionnaire and providing the researchers with the same type urine and blood samples required of the breast cancer cases.

The purpose of the study was to measure the urinary excretion of lignans and other phytoestrogens in the urine of breast cancer cases, and make comparisons with women without breast cancer. The essential question was whether a high urinary output of lignans (indicative of high physiologic levels) could be correlated with reduced breast cancer risk.

The results of the study indicate a resounding yes. A dramatic 300% reduction in breast cancer risk was determined for the women consuming the highest intake of lignan (as indicated by urinary excretion) compared with women whose consumption of lignan was relatively low. This high degree of risk reduction remained valid after adjustment for all other known or suspected risk factors for breast cancer. In the words of the researchers:

"Our findings have implications for the control of breast cancer. Early detection 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 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 this suffering and cost. We are aware of no previously investigated preventative factor that has shown the degree of risk reduction similar to that found for some phytoestrogens in this study; and none had equal potential as a simple intervention as phytoestrogens. A cultural movement towards increasing consumption of phytoestrogen-containing food is taking place, encouraged by magazines and other lay media. Our findings go some way towards providing a rationale for these changes."

References:
1. Case control study of phytoestrogens and breast cancer
In: Lancet (1997 Oct 4) 350(9083):990 4

Study Quotations

There is a great deal of scientific and medical interest in the potential health applications of lignans. Provided herein are quotations selected from studies published in peer-reviewed medical journals reporting on these promising compounds.

Brevail contains the plant lignan secoisolariciresinol, (SDG) for short. Once ingested, colonic bacteria convert SDG to the mammalian lignans enterolactone and enterodiol. There has been a great deal of scientific and medical interest in these three lignans. Provided below are quotations selected from studies published in peer-reviewed medical journals reporting on these promising compounds.

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 E Metzler M

Studies 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

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

There is a substantial reduction in breast cancer risk among women with a high intake (as measured by excretion) of phyto-oestrogens - particularly the isoflavonic phyto-oestrogens equol and the lignan enterolactone. These findings 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

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 D
Case control study of phyto oestrogens and breast cancer
In: Lancet (1997 Oct 4) 350(9083):990 4

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 LU
Dose 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

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

Cancers of the breast and prostate, in their early phase of development, are hormone dependant and could be influenced by endocrine changes induced by lignans and isoflavones.

Morton MS Wilcox G Wahlqvist ML Griffiths K
Determination of lignans and isoflavonoids in human female plasma following dietary supplementation.

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 KD
Origin of lignans in mammals and identification of a precursor from plants.

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 WL
Clinical review 97: Potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological, and mechanistic evidence.

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 D
Case control study of phyto oestrogens and breast cancer In: Lancet (1997 Oct 4) 350(9083):990 4

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

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 T
Dietary phytoestrogens and cancer: in vitro and in vivo studies.
In: J Steroid Biochem Mol Biol (1992 Mar) 41(3 8):331 7

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

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

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 EJ
Natural products and their derivatives as cancer chemopreventive agents.
In: Prog Drug Res (1997) 48:147 71

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

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

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 D
Case control study of phyto oestrogens and breast cancer
In: Lancet (1997 Oct 4) 350(9083):990 4

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

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 cancer
In: Lancet (1997 Oct 4) 350(9083):990 4

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).

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 oestrogens.

Stephens FO
Breast cancer: aetiological factors and associations (a possible protective role of phytoestrogens).
In: Aust N Z J Surg (1997 Nov) 67(11):755 60

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

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)

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)

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

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

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.

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 from the purified precursor secoisolariciresinol diglycoside in flaxseed.
In: J Nutr (1996 Aug) 126(8):2012 9

American adherents of macrobiotics had the greatest urinary lignan excretion 15,228-35,363 nmol/day, while Finnish breast cancer patients showed a low urinary lignan excretion pf 1302 - 2835 nmol/day.

Kurzer MS Xu X
Dietary phytoestrogens.
In: Annu Rev Nutr (1997) 17:353 81

Antiestrogenic effects of phytoestrogens have also been observed. At concentrations 100-1000 times of estradiol (the probable levels in human plasma after regular phytoestrogen consumption), it has been proposed that phytoestrogens may be able to compete effectively with endogenous mammalian estrogens, bind the ER, and prevent estrogen-stimulating growth in mammals.

Kurzer MS Xu X
Dietary phytoestrogens. In: Annu Rev Nutr (1997) 17:353-81

Development and growth of breast cancer is related to female sex hormone levels, the most obvious changes being with early menarche, years of menstrual cycling, pregnancy and late menopause. Long term estrogen deficiency is associated with a reduced risk of breast cancer.

Stephens FO
Breast cancer: aetiological factors and associations (a possible protective role of phytoestrogens).
In: Aust N Z J Surg (1997 Nov) 67(11):755 60

In another study conducted by scientists from the University of Minnesota and the University of Helsinki, lignans and other phytoestrogens known as flavonoids inhibited enzyme activity necessary for estrogen production from fatty tissue, the main source of estrogen in postmenopausal women. This form of estrogen is thought to contribute to estrogen-dependant tumors.

Journal of the National Cancer Institute. Vol. 86 No.23. December 7, 1994 pg. 1748

It would seem very reasonable to propose that these weakly oestrogenic compounds act as the natural tamoxifin in Asian and Mediterranean people.

Morton MS Wilcox G Wahlqvist ML Griffiths K

Determination of lignans and isoflavonoids in human female plasma following dietary supplementation.
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.
Serraino & Thompson reported that supplementation of a high-fat diet with lignan-rich flaxseed flour or deffated flaxseed meal (5% or 10%) reduced epithelial cell proliferation by 38.8-55.4% and nuclear aberrations by 58.8 - 65.9% in the female rat mammary gland, with optimum effects seen at 5% flaxseed flour.

Kurzer MS Xu X
Dietary phytoestrogens.
In: Annu Rev Nutr (1997) 17:353 81

Dietary phytoestrogens may attenuate the adverse consequences of obesity on development of post menopausal breast cancer which may explain the low breast cancer rates of post menopausal Hispanic women despite their greater adiposity.

Stephens FO
Breast cancer: aetiological factors and associations (a possible protective role of phytoestrogens).
In: Aust N Z J Surg (1997 Nov) 67(11):755 60

It has been concluded that lignans and isoflavonoids may influence sex hormone metabolism and cancer by influencing plasma SHBG levels resulting in lower uptake and less biological activity of these steroids and by inhibiting growth and proliferation of hormone-dependant cancer cells.

Adlercreutz H Mousavi Y Clark J Hockerstedt K Hamalainen E Wahala K Makela T Hase T
Dietary phytoestrogens and cancer: in vitro and in vivo studies.
In: J Steroid Biochem Mol Biol (1992 Mar) 41(3 8):331 7

A major problem of Western diets may not be the presence of meat or dairy products in the diet but the absence of desirable ingredients of vegetarian diets, namely dietary fiber and certain plant lignans and isoflavonoids.

Stephens FO
Breast cancer: aetiological factors and associations (a possible protective role of phytoestrogens).
In: Aust N Z J Surg (1997 Nov) 67(11):755 60

In Summery: high concentrations of lignans and isoflavonoids are attained in plasma by supplementing the normal diet with small amounts of the linseed, soya or clover products. These compounds may play a significant role in the molecular processes concerned with the patho-genesis of hormone-dependant cancer, with a real possibility that they exercise a restraining influence on the development of hormone-promoted clinical disease.

Morton MS Wilcox G Wahlqvist ML Griffiths K
Determination of lignans and isoflavonoids in human female plasma following dietary supplementation.
In: J Endocrinol (1994 Aug) 142(2):251 9

The data presented in this study provide consistent evidence that lignans ENL, END, MAT and SEC are devoid of genotoxicity under the experimental conditions used in this study.

Kulling SE Jacobs E Pfeiffer E Metzler M
Studies 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

In premenopausal women, flaxseed consumption over three menstrual cycles lengthened the luteal phase indicating an antiestrogenic effect.

Health Effects of Flaxseed Mucilage, Lignans Inform, Vol. 8, no. 8 (August 1997)

Nevertheless, we are aware of no previously investigated preventative factor that has shown a degree of risk reduction similar to that found for some phyto-oestrogens in this study; and none has equal potential as a simple intervention as phyto-oestrogens. A cultural movement towards increased consumption of phyto-oestrogen-containing foods is taking place, encouraged by magazines and other lay media. Our findings go some way towards providing a rationale for these changes.

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

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