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Thirty women participated in human oral dosing clinical
studies with Brevail. Lignan levels were raised
and maintained in urine and blood comparable to women with an extraordinary
history of breast and hormonal health.
One hundred women participated in a subsequent trial usage
program with Brevail and reported improvement in
mood, sense of well-being and peace of mind, as well as relief from symptoms
related to PMS, peri, pre, menopausal and post menopausal discomforts.
Scientific Validation - Case Control Study:
Phytoestrogens and Breast Cancer
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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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