Flax Hull Lignans

Lignans are a chemical found in plants called phytoestrogens. There are several types of phytoestrogens and flaxseed has by far the most of any plant. This lignan, secoisolariciresinol diglucoside (SDG), plays a role in plant growth, but functions as an antioxidant in human metabolism. In addition, dietary phytoestrogens and human estrogens interact in many complex ways that are not well understood. Nonetheless, because phytoestrogens are biologically active, there is evidence that they may help maintain health and prevent chronic diseases.

+General Information

+What are Phytoestrogens?

What are Phytoestrogens?

Sometimes called "dietary estrogens," phytoestrogens are a diverse group of naturally occurring non steroidal plant compounds that because of their structural similarity with estradiol (17ß-estradiol), have the ability to cause estrogenic or/and antiestrogenic effects.

Their name comes from phyto = plant and estrogen = estrus (period of fertility for female mammals) + gen = to generate. The similarities, at molecular level, of estrogens and phytoestrogens, allows these to mildly mimic and sometimes act as antagonist to estrogen.

Phytoestrogens were first observed in 1926 but it was unknown if they could have any effect in human or animal metabolism. In the 1940s it was noticed by first time that red clover (a phytoestrogen-rich plant) pastures had effects on the fertility of grazing sheep. Researchers are still exploring the nutritional role of these substances in such diverse metabolic functions as the regulation of cholesterol, and the maintaining of proper bone density post-menopause.

Evidence is accruing that phytoestrogens may have protective action against diverse health disorders as prostate, breast, bowel, and other cancers, cardiovascular disease, brain function disorders, menopausal symptoms and osteoporosis.

+What are Lignans?

What are Lignans?

Lignans are one class of phytoestrogens, estrogen-like chemicals found in plants that also have antioxidant properties. Other classes of phytoestrogens include isoflavones, falvonoids and coumestans. The actions of phytoestrogens include binding to the estrogen receptor on cell membranes and exerting an estrogenic or anti-estrogenic effect on mammalian tissues.

There are many types of lignans inlcuding secoisolariciresinol diglucoside (SDG), matairesinol, pinoresinol, lariciresinol, isolariciresinol and secoisolariciresinol (Seco). All of these are found in flax, with SDG in the highest concentration.

Mammals gain lignans through ingestion. As part of the diet, most lignans are converted by intestinal bacteria in the colon into the mammalian lignans: enterodiol (ED) and enterolactone (EL).

+Dietary Sources of Lignans

Dietary Sources of Lignans

While most plants have lignans, flax is by far the highest known source of lignan. The principal lignan precursor found in flaxseed is secoisolariciresinol diglucoside (SDG). Other sources of lignans include pumpkin seeds, sesame seeds, rye, soybeans, broccoli, beans, and some berries (table 1, table 2).

Table 1: Lignan Content of Select Foods
Food	Serving size	Total Lignans
Flax seeds	1 oz.	85.5 mg.
Sesame seeds	1 oz.	11.2 mg.
Curly kale	½ cup, chopped	0.8 mg.
Broccoli	½ cup, chopped	0.6 mg.
Apricots	½ cup, sliced	0.4 mg.
Cabbage	½ cup, chopped	0.3 mg.
Brussel sprouts	½ cup, chopped	0.3 mg.
Strawberries	½ cup	0.2 mg.
Tofu	4 oz.	0.2 mg.
Dark rye bread	1 slice	0.1 mg.
Source: Milder IE, et al. Lignan contents of Dutch plant foods: a database including lariciresinol, pinoresinol, secoisolariciresinol and matairesinol. Br J Nutr. 2005:93(3):393-402.

Table 2: Lignan Content of Select Foods
Seed Oil	Per 100g dry weight
Flaxseed	370,000 mg.
Caraway seeds	221 mg.
Berries
Strawberry	1500 mg.
Cranberry	1054 mg.
Red raspberry	139 mg.
Grains & Cereals
Barley	58 mg.
Rye	47 mg.
Oats	13 mg.
Fruits
Banana	3040 mg.
Guava	700 mg.
Cantaloupe	184 mg.
Legumes
Soybean	273 mg.
Kidney bean	153 mg.
Peanuts	298 mg.
Vegetables
Broccoli	414 mg.
Garlic	379 mg.
Carrot	192 mg.
Source: Adapted from Mazur W. Bailliere’s Clin Endocrin Metab. (1998). Vol. 12; pp. 729-42.

Secoisolariciresinol and matairesinol were the first plant lignans identified in foods. Pinoresinol and laricresinol are more recently identified plant lignans that contribute substantially to total dietary lignan intakes. Typically, lariciresinol and pinoresinol contribute about 75% to the total lignan intake while secoisolariciresinol and matairesinol contribute only about 25%.

+How does the body convert phytoestrogens?

Metabolism and Bioavailability of Phytoestrogens in the Body

When plant lignans are ingested, they can be metabolized by intestinal bacteria to the mammalian lignans, enterodiol and enterolactone. Enterodiol can also be converted to enterolactone by intestinal bacteria. Enterodiol and enterolactone are called mammalian lignans (enterolignans) because they are produced only in the gut of mammals and cannot be found in plants.

The presence of certain bacteria in the gut is necessary for optimum biological activity of flax and other plant lignans. Some people may be lacking in the right type or sufficient numbers of the proper gut bacteria to convert SDG and other lignans to enterodiol and enterolactone. Taking antibiotics can essentially stop production of enterodiol and enterolactone for several weeks.

Recent antibiotic use affects the level of bacteria in the intestine and was associated with lower serum enterolactone levels. Thus, enterolactone levels measured in serum and urine reflect the activity of intestinal bacteria in addition to dietary intake of plant lignans. It is often recommended to supplement with probiotics to optimize the use of lignans (eat your flax with yogurt).

Because data on the lignan content of foods are limited, serum and urinary enterolactone levels are sometimes used as markers of dietary lignan intake in research. A pharmacokinetic study that measured plasma and urinary levels of enterodiol and enterolactone after a single dose (0.9 mg/kg of body weight) of secoisolariciresinol, the principal lignan in flaxseed, found that at least 40% was available to the body as enterodiol and enterolactone. Plasma enterodiol concentrations peaked at 73 nanomoles/liter (nmol/L) an average of 15 hours after ingesting secoisolariciresinol, and plasma enterolactone concentrations peaked at 56 nmol/L an average of 20 hours after ingestion. Thus, substantial amounts of ingested plant lignans are available to humans in the form of enterodiol and enterolactone.

Considerable variation between individuals in urinary and serum enterodiol:enterolactone ratios has been observed in flaxseed feeding studies, suggesting that some individuals convert most enterodiol to enterolactone, while others convert relatively little. It is likely that individual differences in the metabolism of lignans influence the biological activities and health effects of these compounds.

While most research on phytoestrogen-rich diets has focused on soy isoflavones, lignans are the principal source of dietary phytoestrogens in typical Western diets. Additiionally, lignan metabolism is far more complex than originally thought. Plant lignans are not metabolized completely to mammalian lignans and some plant lignans can be detected in plasma. Furthermore, lignan metabolism may not stop at enterodiol and enterolalctone. There are additional metabolites derived from these mammalian lignans. These new findings raise questions about which lignan is the most important and most biologically active.

References

· Morris, Diane H. 2007. Flax - A Health and Nutrition Primer, Fourth Edition, 2007, courtesy of Flax Council of Canada.
· Muir AD. 2006. Flax lignans – analytical methods and how they influence our understanding of biological activity. J. AOAC Int. 89: 1147-1157.
· Raffaelli B, Hoikkala A, Leppälä E, Wähälä K. 2002. Enterolignans. J. Chromatogr. B 777: 29-43.
· Clavel T, Borrmann D, Braune A, et al. 2006. Occurrence and activity of human intestinal bacteria involved in the conversion of dietary lignans. Anaerobe 12: 140-147.
· Lampe JW. 2006. Assessing exposure to lignans and their metabolites in humans. J. AOAC Int. 89: 1174-1181.

+How do phytoestrogens work in the body?

Lignans in the Body: Estrogenic and Anti-Estrogenic Activities

Estrogens are signaling molecules (hormones) that exert their effects by activating a family of proteins called estrogen receptors within cells. The estrogen-receptor complex interacts with DNA to change the expression of estrogen-responsive genes. Estrogen receptors are present in numerous tissues other than those associated with reproduction, including bone, liver, heart and brain.

The chemical structure of phytoestrogens is similar to estrogen and they can act as mimics of estrogen. Working in this manner, phytoestrogens can boost the estrogen effect in the body (estrogenic) or reduce the effect of the body’s natural (endogenous) estrogen (anti-estrogenic). The effect of phytoestrogens depends on the presence of endogenous estrogen such as estradiol, the amount of phytoestrogen as well as the state of bacteria in the intestine.

When the body is low in estrogen, such as during menopause, phytoestrogens can fill in the empty spaces in the estrogen receptors and provide a greater overall estrogenic effect. This makes lignans an effective alternative to Hormone Replacement Therapy.

When estrogen is too high in the body, phytoestrogens can compete for the spaces in the estrogen receptors. However, because the estrogenic effect of phytoestrogens is much weaker than endogenous estrogen, they may actually block or antagonize the effects of estrogen in some tissues.

Scientists are interested in the tissue-selective activities of phytoestrogens because anti-estrogenic effects in reproductive tissue could help reduce the risk of hormone-associated cancers (breast, uterine, ovarian and prostate), while estrogenic effects in bone could help maintain bone density. The mammalian lignans, enterodiol and enterolactone, are known to have weak estrogenic activity. At present, the extent to which mammalian lignans exert weak estrogenic and/or anti-estrogenic effects in humans is not well-understood.

+Effect of Baking on Lignans

Lignans in the Body: Estrogenic and Anti-Estrogenic Activities

Estrogens are signaling molecules (hormones) that exert their effects by activating a family of proteins called estrogen receptors within cells. The estrogen-receptor complex interacts with DNA to change the expression of estrogen-responsive genes. Estrogen receptors are present in numerous tissues other than those associated with reproduction, including bone, liver, heart and brain.

The chemical structure of phytoestrogens is similar to estrogen and they can act as mimics of estrogen. Working in this manner, phytoestrogens can boost the estrogen effect in the body (estrogenic) or reduce the effect of the body’s natural (endogenous) estrogen (anti-estrogenic). The effect of phytoestrogens depends on the presence of endogenous estrogen such as estradiol, the amount of phytoestrogen as well as the state of bacteria in the intestine.

When the body is low in estrogen, such as during menopause, phytoestrogens can fill in the empty spaces in the estrogen receptors and provide a greater overall estrogenic effect. This makes lignans an effective alternative to Hormone Replacement Therapy.

When estrogen is too high in the body, phytoestrogens can compete for the spaces in the estrogen receptors. However, because the estrogenic effect of phytoestrogens is much weaker than endogenous estrogen, they may actually block or antagonize the effects of estrogen in some tissues.

Scientists are interested in the tissue-selective activities of phytoestrogens because anti-estrogenic effects in reproductive tissue could help reduce the risk of hormone-associated cancers (breast, uterine, ovarian and prostate), while estrogenic effects in bone could help maintain bone density. The mammalian lignans, enterodiol and enterolactone, are known to have weak estrogenic activity. At present, the extent to which mammalian lignans exert weak estrogenic and/or anti-estrogenic effects in humans is not well-understood.

+Clinical Effects of SDG Lignans

+Women’s Health

+Hormone Regulation

SDG Lignans and Breast Cancer

The American Cancer Society reports that one in eight women will contract breast cancer. Unfortunately, breast cancer may be present for as long as 4 years before it can be detected by mammography or self-examination. According to Dr. Ross Pelton, author of Preventing Breast Cancer, the largest misconception among women is that if they do not have a history of breast cancer, they are at low risk. Dr. Pelton elaborates by stating that the majority of newly diagnosed cases of breast cancer are in women with no family history of the disease.

Standard medical treatment for breast cancer includes lumpectomy (partial removal of the breast), mastectomy (total removal of the breast), chemotherapy, and radiation. Each of these treatments is harmful and destructive, while more natural treatments, such as dietary modification with SDG are noninvasive, nondestructive and can be effective.

Lignans Exert Positive Effect on Breast Cancer Risk

Evidence of lignans in reducing breast cancer came from the University Department of Surgery, Queen Elizabeth II Medical Center, Perth, Western Australia. In this case-control study, published in Lancet, women with newly diagnosed breast cancer were interviewed by means of questionnaires, and a 72-hour urine collection and blood sample were taken. The urine samples were assayed for various plant constituents including the lignans enterodiol and enterolactone. Adjustments were made for age at menarche (onset of menstruation), parity (number of children a woman has given birth to), alcohol intake, and total fat intake. A high excretion of both equol (a plant estrogen) and enterolactone was associated with a "substantial reduction in breast-cancer risk," the researchers stated. They further concluded:

"There is a substantial reduction in breast-cancer risk among women with high intake (as measured by excretion) of phytoestrogens—particularly the isoflavonic phytoestrogen equol and the lignan enterolactone. These findings could be important in the prevention of breast cancer."

Lignans help prevent or reduce breast cancer partly due to the fact that the lignan constituents in plants such as SDG in flax seed resemble the female hormone estrogen. Lignans, like other phytoestrogens, attach to the same spots on the cell where estrogen attaches. When natural estrogen is abundant in the body, lignans reduce estrogen's effects by displacing it from cells. This displacement of the hormone can help prevent those cancers, such as breast cancer, that depend on estrogen to start and develop.

Lignans and Tumorigenesis

In a 1996 study, SDG was tested for effects on mammary tumorigenesis in rats. The consumption of SDG resulted in a 37% reduction in the number of tumors per tumor-bearing rat and a 46% reduction in the number of mammary tumors per number of rats in each group. This study showed, for the first time, that SDG has an anti-tumor effect when provided at the early promotion stage of tumorigenesis. However, it had no effect on the volume of established tumors. Thus, SDG may exert a stronger effect on new tumor development, whereas milled flax and flax oil appear to exert their effects at later stages of tumor development.

Another study was conducted to determine if SDG could reduce mammary tumor growth at the late stage of carcinogenesis. Flax SDG supplementation began 13 weeks after carcinogen administration to see if it would reduce the size of established mammary tumors (present at the start of treatment) and the appearance of new tumors in rats. After 7 weeks of SDG treatment established tumor volume was over 50% smaller in all treatment groups, while there was no change in the rats on the normal control diet. New tumor number and volume were also lower in the SDG group. The conclusions were that SDG is beneficial throughout the promotional phase of carcinogenesis and at the stage when tumors have already been established.

Yet another study found that SDG, regardless of dose, appeared to delay the progression of MNU-induced mammary tumorigenesis. There was a SDG dose-dependent effect on tumor multiplicity. Both the tumor's ability to invade new tissue and the grade were decreased in all treatment groups compared with the control group.

Mammary Gland Development during Lactation

During lactation, breast development occurs involving the terminal end bud (TEB) structures in the breast. A test was conducted to see if flaxseed lignans affected the development of the mammary gland in rats during lactation. This was important because mammary glands with more TEBs are more susceptible to carcinogens. The results were that lignans taken during early postnatal life induced structural change in the mammary gland that may reduce the risk of developing breast cancer. Thus lignans work in several different ways to fight breast cancer.

Tumor Growth

Lignan consumption may be particularly beneficial in hormone sensitive cancers such as those of the breast, endometrium and prostate. A recent clinical trial was conducted involving 50 women diagnosed with breast cancer. While waiting for surgery, half of the women received muffins containing 25g of milled flaxseed daily, while the other half received ordinary muffins. The women who received the flaxseed muffins had slower growing tumors compared to the other group.

Mastalgia

A further study was conducted with 116 women suffering from cyclical mastalgia (breast pain). Women were fed either a muffin containing 25g of flaxseed or a placebo for 4 menstrual cycles. The women who received the flax muffins had significant reductions in breast swelling and pain. Mastalgia has been linked to the development of certain forms of breast cancer.

In a mouse model of melanoma (a darkly pigmented cancerous growth), SDG decreased the number of tumors, the size of tumors, and the rate or extent of metastasis.

SDG inhibited metastasis in two studies of implanted ER- human breast cancer cells in nude mice. Feeding SDG decreased metastasis to lung, lymph nodes and other organs, but its effects were enhanced when it was combined with flax oil, where the combination significantly decreased total metastasis by ~43%. The researchers concluded that the inhibitory effects of milled flax were mediated by both the oil and lignan (SDG) components.

Regarding lignans and breast cancer, two reviews of epidemiologic studies published since 1997 determined that most case-control studies found a protective effect of plant and mammalian lignans, although their anticancer effects may be limited to premenopausal women and differ by the type of estrogen receptor in breast tissue. One recent prospective cohort study found that among 58,049 postmenopausal French women, those with the highest intake of lignans (>1395 µg/day) had a significantly reduced risk of breast cancer. When breast cancer risk was analyzed by receptor status, the inverse relationship between lignan intake and breast cancer risk was limited to breast cancers that were ER+ and progesterone-positive. These findings suggest that hormone receptors control the biologic effects of lignans.

The mammalian lignans inhibit the activity of aromatase, an enzyme involved in the production of estrogens. Decreased aromatase activity may be one way in which lignans protect against breast cancer.

References

· Touillaud MS, Thiébaut ACM, Fournier A, et al. 2007. Dietary lignan intake and postmenopausal breast cancer risk by estrogen and progesterone receptor status. J. Natl. Cancer Inst. 99: 475-486.
· Wang L-Q. 2002. Mammalian phytoestrogens: enterodiol and enterolactone. J. Chromatogr. B 777: 289-309.
· Brooks JD, Thompson LU. 2005. Mammalian lignans and genistein decrease the activities of aromatase and 17ß-hydroxysteroid dehydrogenase in MCF-7 cells. J. Steroid Biochem. Mol. Biol. 94: 461-467.
· Yan L, Yee JA, Li D, et al. 1998. Dietary flaxseed supplementation and experimental metastasis of melanoma cells in mice. Cancer Lett. 124: 181-186.
· Li D, Yee JA, Thompson LU, Yan L. 1999. Dietary supplementation with secoisolariciresinol diglycoside (SDG) reduces experimental metastasis of melanoma cells in mice. Cancer Lett. 142: 91-96.
· Thompson LU, Rickard SE, Orcheson LJ, Seidl MM. 1996. Flaxseed and its lignan and oil components reduce mammary tumor growth at a late stage of carcinogenesis. Carcinogenesis 17: 1373-1376.
· Wang L, Chen J, Thompson LU. 2005. The inhibitory effect of flaxseed on the growth and metastasis of estrogen receptor negative human breast cancer xenografts is attributed to both its lignan and oil components. Int. J. Cancer 116: 793-798.
· Chen J, Wang L, Thompson LU. 2006. Flaxseed and its components reduce metastasis after surgical excision of solid human breast tumor in nude mice. Cancer Lett. 234: 168-175.
· Thompson LU, Seidl MM, Rickard SE, et al. 1996. Antitumorigenic effect of a mammalian lignan precursor from flaxseed. Nutr. Cancer 26:159-165.
· Boccardo F, Puntoni M, Guglielmini P, Rubagotti A. 2006. Enterolactone as a risk factor for breast cancer: a review of the published evidence. Clin. Chim. Acta 365: 58-67.
· Lof M, Weiderpass E. 2006. Epidemiologic evidence suggests that dietary phytoestrogen intake is associated with reduced risk of breast, endometrial, and prostate cancers. Nutr. Res. 26: 609-619.
· Ingram, D., et al. "Case-control Study of Phyto-oestrogens and Cancer." Lancet, 1997; 350(9083):990-4.
· Thompson L.U., et al., "Antitumorigenic Effect of a Mammalian Lignan Precursor from Flaxseed." Nutr. Cancer, 1996: 26(2):159-65.
· Thompson, L.U. Richard, S.E., "Flaxseed and its Lignan and Oil Components Reduce Mammary Tumor Growth at a Late Stage of Carcinogenesis," Carcinogenesis, 17(6): 1373-6.
· Rickard S, et al, Nutr Cancer; 35(1): 50, 1999.
· Tou, J.C., "Exposure to Flaxseed or its Lignan Component during Different Development Stages Influences Rat Mammary Gland Structures," Carcinogenesis, Sep. 19.
· Thompson, L, Li. T., Chen, J. Goss, P.E. 2000. Biological Effects of Dietary Flaxseed in Patients with Breast Cancer. ABST 23rd ann Breast Cancer Symposium, San Antonio, TX December 6-9.
· Goss, P.E., Theriualt, M., Pinto, S., Thompson, L. 2000. Effects of Dietary Flaxseed in Women with Cyclical Mastalgia. ABST 23rd ann Breast Cancer Symposium, San Antonio, TX December 6-9

+Menstruation

SDG Lignans and Menstruation Regularity

Lignans in flaxseed have been shown to regulate the menstrual cycle. In one study, women consuming lignans in flaxseed did not miss a single cycle, compared to the control group who missed several cycles. In another study, women supplemented their diet with a dose of 10 g/day of flax, resulting in elevated progesterone:estradiol ratios in the luteal phase due to a decreased estradiol concentration. The concentration of lignans measured in the urine showed the level of lignans absorbed and the significant impact on controlling women's menstrual cycle.

In a study with rats, the effects of flax and its lignan SDG was compared with tamoxifen, an antiestrogen drug, by monitoring rat estrous cycling. After four weeks, 66% of the rats taking flax SDG had more regular cycling produced by a cessation or lengthening of estrous cycles. In the rats given tamoxifen, 83% of the animals had irregular cycles or were in persistent diestrus (the stage of the cycle in which the ovary is functional and the predominant ovarian hormone produced is progesterone). The conclusion was that flaxseed and SDG were effective in being antiestrogenic without gross tissue toxicity. The control that lignan has over the menstrual cycle has an influence on cancer growth because the less time a woman spends in the luteal phase, the lower the risk of breast cancer.

References

· Lampe JW et al. "Urinary lignan and isoflavonoid excretion in premenopausal women consuming flaxseed powder." Am. Jour. Clin. Nutr., 1994; 60:122-8.
· Phipps, W & Martini, M., Jour. Clin. Endocrinol Metah., 1993, 77:1215-1219. Lampe, J., Am. Jour. Clin. Nutr, 1994, 60:122-128.
· Orcheson, LJ., et al., "Flaxseed and its Mammalian Ugnan Precursor Cause a Lengthening or Cessation of Estrous Cycling in Rats."
· Henderson, B., et al.. Cancer, 1985, 56:1206-1208.

+Pregnant Women

SDG Lignans and Pregnant Women

Pregnant females and their young are especially sensitive to hormones. While high estrogen levels are needed by the mother to prepare the uterus for the growing fetus, too much estrogen in pregnant animals can reduce litter size and the birth weight of offspring.

Lignans and other phytoestrogens like those in soy, alfalfa and clover can affect the reproductive tract of animals. In rats, exposure to flax diets during pregnancy and lactation had an adverse effect on the weights of sex organs, serum levels of sex hormones, the onset of puberty and, in females, the length of the estrous cycle.

Characteristic for phytoestrogens, lignans can weakly bind to estrogen receptors. A sufficient level of these lignans can compete with natural estrogen for the estrogen receptors, resulting in blalanc3d estrogen levels in the blood.

This is not to say that pregnant women should not eat flax. However, it does suggest that large amounts, especially therapeutic amounts, should be avoided. It is suggested that pregnant women avoid lignan isolate, but they may consume a moderate amount (1 teaspoon) of ground flax daily. Flax is highly nutritious and contains the omega-3 essential fatty acid ALA (alpha-linolenic acid), which can be converted by the body to the omega-3 essential fatty acid DHA, essential for brain development in the fetus.

+Breast Cancer

SDG Lignans and Breast Cancer

The American Cancer Society reports that one in eight women will contract breast cancer. Unfortunately, breast cancer may be present for as long as 4 years before it can be detected by mammography or self-examination. According to Dr. Ross Pelton, author of Preventing Breast Cancer, the largest misconception among women is that if they do not have a history of breast cancer, they are at low risk. Dr. Pelton elaborates by stating that the majority of newly diagnosed cases of breast cancer are in women with no family history of the disease.

Standard medical treatment for breast cancer includes lumpectomy (partial removal of the breast), mastectomy (total removal of the breast), chemotherapy, and radiation. Each of these treatments is harmful and destructive, while more natural treatments, such as dietary modification with SDG are noninvasive, nondestructive and can be effective.

Lignans Exert Positive Effect on Breast Cancer Risk

Evidence of lignans in reducing breast cancer came from the University Department of Surgery, Queen Elizabeth II Medical Center, Perth, Western Australia. In this case-control study, published in Lancet, women with newly diagnosed breast cancer were interviewed by means of questionnaires, and a 72-hour urine collection and blood sample were taken. The urine samples were assayed for various plant constituents including the lignans enterodiol and enterolactone. Adjustments were made for age at menarche (onset of menstruation), parity (number of children a woman has given birth to), alcohol intake, and total fat intake. A high excretion of both equol (a plant estrogen) and enterolactone was associated with a "substantial reduction in breast-cancer risk," the researchers stated. They further concluded:

"There is a substantial reduction in breast-cancer risk among women with high intake (as measured by excretion) of phytoestrogens—particularly the isoflavonic phytoestrogen equol and the lignan enterolactone. These findings could be important in the prevention of breast cancer."

Lignans help prevent or reduce breast cancer partly due to the fact that the lignan constituents in plants such as SDG in flax seed resemble the female hormone estrogen. Lignans, like other phytoestrogens, attach to the same spots on the cell where estrogen attaches. When natural estrogen is abundant in the body, lignans reduce estrogen's effects by displacing it from cells. This displacement of the hormone can help prevent those cancers, such as breast cancer, that depend on estrogen to start and develop.

Lignans and Tumorigenesis

In a 1996 study, SDG was tested for effects on mammary tumorigenesis in rats. The consumption of SDG resulted in a 37% reduction in the number of tumors per tumor-bearing rat and a 46% reduction in the number of mammary tumors per number of rats in each group. This study showed, for the first time, that SDG has an anti-tumor effect when provided at the early promotion stage of tumorigenesis. However, it had no effect on the volume of established tumors. Thus, SDG may exert a stronger effect on new tumor development, whereas milled flax and flax oil appear to exert their effects at later stages of tumor development.

Another study was conducted to determine if SDG could reduce mammary tumor growth at the late stage of carcinogenesis. Flax SDG supplementation began 13 weeks after carcinogen administration to see if it would reduce the size of established mammary tumors (present at the start of treatment) and the appearance of new tumors in rats. After 7 weeks of SDG treatment established tumor volume was over 50% smaller in all treatment groups, while there was no change in the rats on the normal control diet. New tumor number and volume were also lower in the SDG group. The conclusions were that SDG is beneficial throughout the promotional phase of carcinogenesis and at the stage when tumors have already been established.

Yet another study found that SDG, regardless of dose, appeared to delay the progression of MNU-induced mammary tumorigenesis. There was a SDG dose-dependent effect on tumor multiplicity. Both the tumor's ability to invade new tissue and the grade were decreased in all treatment groups compared with the control group.

Mammary Gland Development during Lactation

During lactation, breast development occurs involving the terminal end bud (TEB) structures in the breast. A test was conducted to see if flaxseed lignans affected the development of the mammary gland in rats during lactation. This was important because mammary glands with more TEBs are more susceptible to carcinogens. The results were that lignans taken during early postnatal life induced structural change in the mammary gland that may reduce the risk of developing breast cancer. Thus lignans work in several different ways to fight breast cancer.

Tumor Growth

Lignan consumption may be particularly beneficial in hormone sensitive cancers such as those of the breast, endometrium and prostate. A recent clinical trial was conducted involving 50 women diagnosed with breast cancer. While waiting for surgery, half of the women received muffins containing 25g of milled flaxseed daily, while the other half received ordinary muffins. The women who received the flaxseed muffins had slower growing tumors compared to the other group.

Mastalgia

A further study was conducted with 116 women suffering from cyclical mastalgia (breast pain). Women were fed either a muffin containing 25g of flaxseed or a placebo for 4 menstrual cycles. The women who received the flax muffins had significant reductions in breast swelling and pain. Mastalgia has been linked to the development of certain forms of breast cancer.

In a mouse model of melanoma (a darkly pigmented cancerous growth), SDG decreased the number of tumors, the size of tumors, and the rate or extent of metastasis.

SDG inhibited metastasis in two studies of implanted ER- human breast cancer cells in nude mice. Feeding SDG decreased metastasis to lung, lymph nodes and other organs, but its effects were enhanced when it was combined with flax oil, where the combination significantly decreased total metastasis by ~43%. The researchers concluded that the inhibitory effects of milled flax were mediated by both the oil and lignan (SDG) components.

Regarding lignans and breast cancer, two reviews of epidemiologic studies published since 1997 determined that most case-control studies found a protective effect of plant and mammalian lignans, although their anticancer effects may be limited to premenopausal women and differ by the type of estrogen receptor in breast tissue. One recent prospective cohort study found that among 58,049 postmenopausal French women, those with the highest intake of lignans (>1395 µg/day) had a significantly reduced risk of breast cancer. When breast cancer risk was analyzed by receptor status, the inverse relationship between lignan intake and breast cancer risk was limited to breast cancers that were ER+ and progesterone-positive. These findings suggest that hormone receptors control the biologic effects of lignans.

The mammalian lignans inhibit the activity of aromatase, an enzyme involved in the production of estrogens. Decreased aromatase activity may be one way in which lignans protect against breast cancer.

References

· Touillaud MS, Thiébaut ACM, Fournier A, et al. 2007. Dietary lignan intake and postmenopausal breast cancer risk by estrogen and progesterone receptor status. J. Natl. Cancer Inst. 99: 475-486.
· Wang L-Q. 2002. Mammalian phytoestrogens: enterodiol and enterolactone. J. Chromatogr. B 777: 289-309.
· Brooks JD, Thompson LU. 2005. Mammalian lignans and genistein decrease the activities of aromatase and 17ß-hydroxysteroid dehydrogenase in MCF-7 cells. J. Steroid Biochem. Mol. Biol. 94: 461-467.
· Yan L, Yee JA, Li D, et al. 1998. Dietary flaxseed supplementation and experimental metastasis of melanoma cells in mice. Cancer Lett. 124: 181-186.
· Li D, Yee JA, Thompson LU, Yan L. 1999. Dietary supplementation with secoisolariciresinol diglycoside (SDG) reduces experimental metastasis of melanoma cells in mice. Cancer Lett. 142: 91-96.
· Thompson LU, Rickard SE, Orcheson LJ, Seidl MM. 1996. Flaxseed and its lignan and oil components reduce mammary tumor growth at a late stage of carcinogenesis. Carcinogenesis 17: 1373-1376.
· Wang L, Chen J, Thompson LU. 2005. The inhibitory effect of flaxseed on the growth and metastasis of estrogen receptor negative human breast cancer xenografts is attributed to both its lignan and oil components. Int. J. Cancer 116: 793-798.
· Chen J, Wang L, Thompson LU. 2006. Flaxseed and its components reduce metastasis after surgical excision of solid human breast tumor in nude mice. Cancer Lett. 234: 168-175.
· Thompson LU, Seidl MM, Rickard SE, et al. 1996. Antitumorigenic effect of a mammalian lignan precursor from flaxseed. Nutr. Cancer 26:159-165.
· Boccardo F, Puntoni M, Guglielmini P, Rubagotti A. 2006. Enterolactone as a risk factor for breast cancer: a review of the published evidence. Clin. Chim. Acta 365: 58-67.
· Lof M, Weiderpass E. 2006. Epidemiologic evidence suggests that dietary phytoestrogen intake is associated with reduced risk of breast, endometrial, and prostate cancers. Nutr. Res. 26: 609-619.
· Ingram, D., et al. "Case-control Study of Phyto-oestrogens and Cancer." Lancet, 1997; 350(9083):990-4.
· Thompson L.U., et al., "Antitumorigenic Effect of a Mammalian Lignan Precursor from Flaxseed." Nutr. Cancer, 1996: 26(2):159-65.
· Thompson, L.U. Richard, S.E., "Flaxseed and its Lignan and Oil Components Reduce Mammary Tumor Growth at a Late Stage of Carcinogenesis," Carcinogenesis, 17(6): 1373-6.
· Rickard S, et al, Nutr Cancer; 35(1): 50, 1999.
· Tou, J.C., "Exposure to Flaxseed or its Lignan Component during Different Development Stages Influences Rat Mammary Gland Structures," Carcinogenesis, Sep. 19.
· Thompson, L, Li. T., Chen, J. Goss, P.E. 2000. Biological Effects of Dietary Flaxseed in Patients with Breast Cancer. ABST 23rd ann Breast Cancer Symposium, San Antonio, TX December 6-9.
· Goss, P.E., Theriualt, M., Pinto, S., Thompson, L. 2000. Effects of Dietary Flaxseed in Women with Cyclical Mastalgia. ABST 23rd ann Breast Cancer Symposium, San Antonio, TX December 6-9

+Menopause

SDG Lignans and Menopause

A study of 28 postmenopausal women was conducted in which they consumed lignan-rich flaxseed. The supplementation significantly increased urinary excretion of the estrogen metabolites 2-hydroxyestrogen and 16 alpha-hydroxyestrone. These results suggest that lignan from flaxseed may have chemo-protective effects in postmenopausal women.

Dietary estrogens, such as lignans, 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.

In addition to having anticancer effects, a new study suggests that postmenopausal women who have a high intake of lignans perform better on tests of memory than women with low intakes. The intake of lignans, but not isoflavones (found in soy products, beans, peas, nuts), was related to better cognitive function in this study.

References

· Franco OH, et al. J Nutr. 2005;135:1190-1195.
· Haggans, C.J., "Effect of Flaxseed on Urinary Estrogen Metabolites in Postmenopausal Women," Nutr. Cancer, 1999, 33(2): 188-95.
· Hutchins A, Cancer Epidemiol Biomarkers Prev, 9(10): 1113,2000)

+Osteoporosis and Bone Loss

SDG Lignans and Hormone Regulation

As phytoestrogens, lignans are scientifically indicated to affect hormone levels in women resulting in relief of menopausal problems, improved bone health and healthy cholesterol levels. During menopause, decreasing and fluctuating estrogen levels lead t symptoms such as hot flashes and insomnia. Flax hull lignans can help balance these levels.

Lignans are effective in treating several health issues for women. If there is little estrogen in the body (for example, following menopause), lignans may act like weak estrogen; but when natural estrogen is abundant in the body, lignans may instead reduce estrogen's effects by displacing it from the cells. This hormone displacement can help prevent breast cancer.

A clinical study has shown that SDG phytoestrogen in particular, exhibits agonist properties to the estrogen receptor. This property is of specific value to post-menopausal women, who typically exhibit low estrogen levels. Women consuming lignan-rich flaxseed oil products generally report a reduction in breast tenderness, bloating, hot flashes, sweating, vaginal dryness, and other symptoms related to PMS and menopause.

References

· Brzezinski A., and Cebi A, t'ur. J. Obst. Gyn. Reprod. Bioi., 1999; 85:17-51.
· Knight D.C and Eden J.A., Obstet. Gynecol., 1987 (5 pt.2), 897-904.

+Heart Disease

SDG Lignans and Heart Disease

It is well known that flax oil fights heart disease by lowering dangerous LDL-cholesterol and triglycerides and by reducing the build up of atherosclerotic plaque on artery walls. But now evidence is revealing that SDG lignan in pure, concentrated form has an equal or greater effect in fighting heart disease.

Researchers produced a high concentration from flax meal consisting of 99% pure SDG. The 99% pure SDG was fed to rabbits on a high cholesterol diet for a period of 8 weeks. Another group was fed a diet high in cholesterol but received no SDG treatment. After 8 weeks the rabbits were sacrificed. It was discovered that the addition of SDG resulted in a 73% reduction in atherosclerotic plaques compared to the untreated rabbits. It was also noted that there was a 33% reduction in serum cholesterol in the SDG-fed rabbits. This shows that flaxseed SDG is effective in reducing hypercholesterolemic atherosclerosis.

The ability of SDG in reducing atherosclerosis is partly due to its antioxidant activity. Oxygen free radicals have been implicated in the development of the disease. Dr. Prasad states that oxygen free radicals damage the lining of the blood vessels and set the stage for development of atherosclerosis. SDG's antioxidant activity has the ability to remove toxic metabolites of oxygen or free radicals, thus retarding atherosclerosis.

Recent work from the University of Saskatchewan has demonstrated that the reduction of hypercholesterolemia atherosclerosis is greater with SDG than with the whole flaxseed. The decrease is associated with a reduction of serum cholesterol and LDL-cholesterol. These studies show the need for a purer and more concentrated form of lignan than what is in most "lignan flax oils" in order to obtain the greater benefits it offers against heart disease.

In one study several dogs were pretreated with lignan-rich flaxseed. The pretreatment attenuated endotoxin induced cardiac dysfunction and cellular damage. Thus the lignans antioxidant and anti-PAF agents may be effective in the treatment of endotoxic shock.

References

· Prasad, K., Atherosclerosis, 1997, 132(1):69.
· Prasad, K., J. Kalra, "Oxygen Free Radicals and Hypercholesterolemic Atherosclerosis," Am. Heart Jour., 1993, 125:958-973.
· McLennan, B., "Flaxseed-Lignan Research: the Potential for Inproved Health Care." College of Medicine & Alumni Review, University of Saskatchewan, 1996, 4(2): 7-8.
· Pattanaik, U., Jour. Cardiovasc. Pharmacol. Trier., 1995, 3(4):305

+Prostate Cancer

SDG Lignans and Prostate Cancer

Cancer of the prostrate gland is the second leading cause of death among men, primarily occurring in men over sixty years old. By the age of 80, 80% of all men have prostrate cancer to some extent. Fortunately, in most cases prostrate cancer is a slow-growing cancer, doubling in mass every six years. The rate of prostrate cancer is rising in the US, due in part to high-fat diets and exposure to chemicals. Current treatments are radical prostatectomy and radiation therapy.

Flax consumption does not appear to affect sex hormone metabolism in men, based on findings of the one study published in this area. Eating 13.5g milled flax daily for 6 weeks had no effect on plasma concentrations of testosterone, free testosterone or sex-hormone-binding globulin in six healthy men. It is not known whether sex hormone metabolism in men is affected by long-term flax consumption.

Flaxseed ingestion produces large amounts of mammalian lignans with weak estrogenic/anti-estrogenic properties. In tests these properties reduced adult relative prostrate weight and cell proliferation, suggesting potential protection against prostatic disease, without affecting hormone levels.

Researchers from the University of Wales, College of Medicine, Cardiff, United Kingdom, determined the concentration of lignans in prostrate fluid from Portuguese, Chinese and British men. The mean concentration of enterolactone and other plant estrogens were very high among Portuguese and Asian men, respectively. The research team concluded that the levels of lignans and related plant estrogens may be responsible, in part, for lower incidences of prostate cancer in men from Mediterranean countries.

A very recent study involved twenty-five patients with prostrate cancer, who were given a lignan-rich flaxseed supplementation. The results show a favorable affect on prostrate cancer biology and associated biomarkers.

By interacting with the complex mechanism of testosterone metabolism, lignans bring back the natural balance in hormone levels such as BPH, a common problem among aging men leading to painful and difficult urination. Other supplements currently sold for prostate bring relief based on anti-inflammatory actions. Flax lignans not only reduce the inconveniences related to urinary flow, frequency and volume, but can also decrease the size of an enlarged prostate.

Plant and mammalian lignans appear to have beneficial anticancer effects in test tube studies (in vitro). Only a handful of prostate cancer studies have been conducted in animals, but the general finding is that lignans decrease tumor mass and increase cell apoptosis. The findings of human studies are mixed, with three studies reporting beneficial results in men who consumed a lignan-rich diet, one study finding no effect of soy and flax taken together in bread on prostate cancer biomarkers, and two studies finding no link between serum enterolactone concentrations and prostate cancer risk. The latter studies suffer from the same limitation as those in which blood measurements of fatty acids like ALA are correlated with prostate cancer risk – serum enterolactone levels are not a valid measurement of long-term lignan intake and prostate cancer risk, especially as the prostate gland can achieve much higher concentrations of lignans than can blood.

A recent case-control study conducted among 1499 Swedish men with prostate cancer and 1130 controls found that a high intake of foods rich in phytoestrogens, including lignans, was associated with a decreased risk of prostate cancer. This may be the first large-scale population study in which the diet assessment instrument – a 261-item food frequency questionnaire (FFQ) – asked specifically about the consumption of phytoestrogen-rich foods like flax, berries, nuts, peanuts, beans, sunflower seeds and soy as part of a typical diet. The FFQ’s ability to estimate dietary phytoestrogen intake was validated against serum levels of enterolactone in this study.

Conclusions regarding diet and prostate cancer

Three conclusions can be drawn from studies related to diet and prostate cancer risk:

1)   The exact cause of prostate cancer is not known, but the most consistent risk factors for its development are advancing age, family history and race. Diet is believed to contribute to the pathology of prostate cancer, based on differences between its incidence in Eastern and Western populations whose diets differ in the intakes of fats, cereals, fruits and vegetables. Environmental factors such as infectious agents, chemicals and diet may contribute to prostate cancer by triggering inflammatory reactions. Roughly 20% of all human cancers are caused by chronic infection or inflammation.
2)   No consistent dietary effect has emerged from the human cohort and case-control studies. Two dietary factors are the most likely contributors to prostate cancer development – excess calories and total fat. The dietary ratio of omega-6 to omega-3 fatty acids may also be important. In the Physicians’ Health Study and the Health Professionals Follow-up Study, eating red meat emerged as a risk factor for prostate cancer. Even though meat contains only small amounts of ALA, it is a leading source of ALA in some people’s diets, making it a marker for a diet rich in animal fat and meat. Indeed, Australian men who ate a high-meat diet had significantly higher intakes of ALA than men who ate a moderate-meat diet or who were ovolactovegetarians or vegans. Thus, ALA may be guilty by association in some studies because it was linked with red meat, which is itself associated with increased prostate cancer risk. Otherwise, there are too many inconsistencies among the research findings to be confident that any one fatty acid contributes to cancer development in humans. These inconsistencies apply to most fatty acids, not just ALA. For instance, LA was associated with an increase in prostate cancer risk in 2 studies, had no association with prostate cancer in 7 studies and had an inverse relationship with prostate cancer in 5 studies.
3)   There is no conclusive evidence of a dose-response relationship between the dietary intake of ALA and prostate cancer risk. In other words, if ALA is associated with tumor development, then the risk of prostate cancer should increase steadily as ALA intake increases. The Uruguay study reported evidence of such a dose-response relationship. However, men in the PLCO study, which found no evidence of a link between ALA intake and prostate cancer risk, had higher ALA intakes than men in the Health Professionals Follow-up Study, which reported that ALA intake was associated with increased risk of prostate cancer. If a dose-response relationship exists, one would expect men in the PLCO study to exhibit a greater risk of prostate cancer due to their higher ALA intakes.

References

· Morris, Diane H. 2007. Flax - A Health and Nutrition Primer, Fourth Edition, 2007, courtesy of Flax Council of Canada.
Cunnane SC. 2003. Dietary sources and metabolism of á-linolenic acid. In: Flaxseed in Human Nutrition, eds Thompson LU and Cunnane SC, 2nd ed, AOCS Press, Champaign, IL, p 63-91.
Hedelin M, Klint Á, Chang ET, et al. 2006. Dietary phytoestrogen, serum enterolactone and risk of prostate cancer: the Cancer Prostate Sweden Study (Sweden). Cancer Causes Control 17: 169-180.
Shultz TD, Bonorden WR, Seaman WR. 1991. Effect of short-term flaxseed consumption on lignan and sex hormone metabolism in men. Nutr. Res. 11: 1089-1100.
Demark-Wahnefried W, Price DT, Polascik TJ, et al. 2001. Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal levels, prostate-specific antigen, and histopathologic features. Urology 58: 47-52.
Zhou J-R, Blackburn GL. 1997. Bridging animal and human studies: What are the missing segments in dietary fat and prostate cancer? Am. J. Clin. Nutr. 66: 1572S-1580S.
McCann MJ, Gill CIR, McGlynn H, Rowland IR. 2005. Role of mammalian lignans in the prevention and treatment of prostate cancer. Nutr. Cancer 52: 1-14.
Coffey DS. 2001. Similarities of prostate and breast cancer: evolution, diet, and estrogens. Urol. 57(suppl 4A): 31-38.
Demark-Wahnefried W, Robertson CN, Walther PJ, et al. 2004. Pilot study to explore effects of low-fat, flaxseed-supplemented diet on proliferation of benign prostatic epithelium and prostate-specific antigen. Urol. 63: 900-904.
Dalais FS, Meliala A, Wattanapenpaiboon N, et al. 2004. Effects of a diet rich in phytoestrogens on prostate-specific antigen and sex hormones in men diagnosed with prostate cancer. Urol. 64: 510-515.
De Marzo AM, Platz EA, Sutcliffe S, et al. 2007. Inflammation in prostate carcinogenesis. Nature Rev. 7: 256-269.
Harvei S, Bjerve KS, Tretli S, et al. 1997. Prediagnostic level of fatty acids in serum phospholipids: Ù-3 and Ù-6 fatty acids and the risk of prostate cancer. Int. J. Cancer 71: 545-551.
Newcomer LM, King IB, Wicklund KG, Stanford JL. 2001. The association of fatty acids with prostate cancer risk. Prostate 47: 262-268.
Yang YJ, Lee SH, Hong SJ, Chung BC. 1999. Comparison of fatty acid profiles in the serum of patients with prostate cancer and benign prostatic hyperplasia. Clin. Biochem. 32: 405-409.
Godley PA, Campbell MK, Gallagher P, et al. 1996. Biomarkers of essential fatty acid consumption and risk of prostatic carcinoma. Cancer Epidemiol. Biomarkers Prev. 5: 889-895.
Männistö S, Pietinen P, Virtanen MJ. 2003. Fatty acids and risk of prostate cancer in a nested case-control study in male smokers. Cancer Epidemiol. Biomarkers Prev. 12: 1422-1428.
Gann PH, Hennekens CH, Sacks FM, et al. 1994. Prospective study of plasma fatty acids and risk of prostate cancer. J. Natl. Cancer Inst. 86: 281-286.
Chavarro JE, Stampfer MJ, Li H, et al. 2007. A prospective study of polyunsaturated fatty acid levels in blood and prostate cancer risk. Cancer Epidemiol. Biomarkers Prev. 16: OF1-OF7.
Andersson S-O, Wolk A, Bergström R, et al 1996. Energy, nutrient intake and prostate cancer risk: a population-based case-control study in Sweden. Int. J. Cancer 68: 716-722.
Bairati I, Meyer F, Fradet Y, Moore L. 1998. Dietary fat and advanced prostate cancer. J. Urol. 159: 1271-1275.
Bidoli E, Talamini R, Bosetti C, et al. 2005. Macronutrients, fatty acids, cholesterol and prostate cancer risk. Ann. Oncol. 16: 152-157.
De Stefani E, Deneo-Pellegrini H, Boffetta P, et al. 2000. á-Linolenic acid and risk of prostate cancer: a case-control study in Uruguay. Cancer Epidemiol. Biomarkers Prev. 9: 335-338.
Koralek DO, Peters U, Andriole G, et al. 2006. A prospective study of dietary alpha-linolenic acid and the risk of prostate cancer (United States). Cancer Causes Control 17: 783-791.
Laaksonen DE, Laukkanen JA, Niskanen L, et al. 2004. Serum linoleic and total polyunsaturated fatty acids in relation to prostate and other cancers: a population-based cohort study. Int. J. Cancer 111: 444-450.
Schuurman AG, van den Brandt PA, Dorant E, et al. 1999. Association of energy and fat intake with prostate carcinoma risk: results from the Netherlands Cohort Study. Cancer 86: 1019-1027.
Giovannucci E, Rimm EB, Colditz GA, et al. 1993. A prospective study of dietary fat and risk of prostate cancer. J. Natl. Cancer Inst. 85: 1571-1579.
Giovannucci E, Liu Y, Platz EA, et al. 2007. Risk factors for prostate cancer incidence and progression in the Health Professionals Follow-up Study. Int. J. Cancer (published online 20 Apr 2007). DOI: 10.1002/ijc.22788.
Leitzmann MF, Stampfer MJ, Michaud DS, et al. 2004. Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer. Am. J. Clin. Nutr. 80: 204-216.
Bylund A, Lundin E, Zhang JX, et al. 2003. Randomised controlled short-term intervention pilot study on rye bran bread in prostate cancer. Eur. J Cancer Prev. 12: 407-415.
Kilkkinen A, Virtamo J, Virtanen MJ, et al. 2003. Serum enterolactone concentration is not associated with prostate cancer risk in a nested case-control study. Cancer Epidemiol. Biomarkers Prev. 12: 1209-1212.
Stattin P, Bylund A, Biessy C, et al. 2004. Prospective study of plasma enterolactone and prostate cancer risk (Sweden). Cancer Causes Control 15: 1095-1102.
Denis L, Morton MS, Griffiths K. 1999. Diet and its preventive role in prostatic disease. Eur. Urol. 35: 377-387.
Kolonel LN, Nomura AMY, Cooney RV. 1999. Dietary fat and prostate cancer: current status. J. Natl. Cancer Inst. 91: 414-428.
Bougnoux P, Chajès V. 2003. á-Linolenic acid and cancer. In: Flaxseed in Human Nutrition, eds Thompson LU and Cunnane SC, 2nd ed, AOCS Press, Champaign, IL, p 232-244.
Mann N, Pirotta Y, O’Connell S, et al. 2006. Fatty acid composition of habitual omnivore and vegetarian diets. Lipids 41: 637-646.
Dwyer JT. 1997. Human studies on the effects of fatty acids on cancer: summary, gaps, and future research. Am. J. Clin. Nutr. 66: 1581S-1586S.
Tou, J., et al Jour. Toxicol Environ. Health, 1999, 56(8):55.
Morton, M.S., et al. "Lignans and Isoflavonoids in Plasma and Prostatic fluid in men: samples from Portugal, Hong Kong, and the United Kingdom." Prostrate, 1997: 32(2):122-8.
Demark-Wahnefried, W., et al., Urology, Jul., 2001, 58(l):47-52.

+Immune System

SDG Lignans and the Immune System

Flaxseed may prove useful in the nutritional management of patients with autoimmune diseases. For example, systemic lupus erythematosus (SLE) is an inflammatory disease that occurs mainly in young women. It is characterized by a variety of clinical findings, including inflammation of the kidney (nephritis). Studies have shown that patients with SLE exhibit increased production of platelet-activating factor (PAF), a mediator of immune response and promoter of platelet aggregation. Dietary flaxseed has provided significant benefits in animal models of lupus nephritis and in patients with this condition. In one study of nine patients with lupus nephritis, PAF-induced platelet aggregation was inhibited and renal function improved when subjects consumed 15g to 45g flaxseed/day for four weeks. The lignan component of flaxseed is believed to be responsible for this effect.

Flaxseed favorably influences immune response. The flaxseed component, ALA, alters membrane phospholipids, inhibits arachidonic acid biosynthesis from linoleic acid, inhibits the production of proinflammatory eicosanoids from arachidonic acid, and suppresses lymphocyte proliferation and cytokine production. Flaxseed lignans are potent inhibitors of platelet-activating factor, a mediator of inflammation. Through these effects, flaxseed has the potential to be used for the treatment of disorders characterized in part by activated lymphocytes and a hyper-stimulated immune response. Such disorders include rheumatoid arthritis, psoriasis, multiple sclerosis and systemic lupus erythematosus.

A Non-Profit Group, AIDS Research & Assistance Institute, conducted an anecdotal study from 2003-2006 and reported the following:

This report is made on the anecdotal information obtained from the Flax Hull Lignan study conducted by AIDS Research & Assistance Institute. The study was originally started to test healthy individuals and others with health issues such as high blood pressure, diabetes, heart disease, hormone specific issues as breast lumps, perimenopausal and postmenopausal problems, prostate issues, high cholesterol and autoimmune diseases like arthritis and HIV/AIDS. The goal was to see if adding the lignan product to their daily diet would boost their immune systems to fight these various problems. The fact that people with HIV/AIDS and cancer have problems with nutrition and with vomiting and diarrhea, the goal was to control those problems to stabilize their nutritional needs and to help the body's own defenses to fight back. Since organizational funds were limited and lab studies on individuals not included, ARAI had to rely on the participants to share any lab work their primary physicians or specialists ordered for them. Some did share their information. All participants agreed that if we gave them the flax product free, they would furnish ARAI with a testimonial report. Some participants did not follow through with the full 90 day agreement, and therefore we did not include them in the official reporting.

The instructions for taking the flax began with 2 scoops per day. 15% of the participants experienced constipation with this amount of high fiber flax lignan. Therefore, the dosage was immediately dropped to 1 scoop per day for all participants; 2 weeks after the trial began. 25% experienced "flu-like" symptoms that lasted only a few days.

Of the cancer patients who responded to the study, 100% did report a decrease in size or a total disappearance of tumors. However, the one patient with non Hodgkins lymphoma also had times of increasing then decreasing in tumor size. One breast cancer patient experienced a total disappearance of tumors as long as she continual to take the flax. A few months after stopping the flax, tumors came back once again. She recently reported that after she resumed taking the flax, the tumors are once again shrinking.

Of the HIV/AIDS patients, 85% reported feeling a lot more energetic, increased appetites with almost total cessation of nausea, vomiting and diarrhea. Of those which we were able to measure with their blood tests, 71% had a drop in viral loads over the 90 day period. 28% of those with blood tests reported a decrease to total non-detectable viral load and increase in CD4 values. With one international patient (India) during phase 1 testing, we could not measure response, but only to say he felt better and several of his KS lesions disappeared. There was a 71% drop in viral loads of those we could measure.

There were four people who wanted to take the flax but did not want to join the study. Each reported significant drop in blood glucose levels. One lady on an insulin pump happily reported her doctor told her that she had normal glucose readings for the first time in five years. Her cholesterol dropped and lipids panels showed normal triglycerides, LDL’s and HDL’s. One lady is now off all oral hypoglycemic. Her diabetes is now controlled by diet and exercise. To say there was a 100% decrease in blood glucose needs to be understood that it required compliance with proper diet, exercise and pharmaceutical support. The same can be said for those with high cholesterol, hypertension, etc.

With these results and the reports ARAI is receiving from African studies, we see a definite correlation between using the flax lignans as a nutritional supplement and an increase in immune system response. Definite benefits for numerous other medical conditions are also noted.

The testimonials from the participants in America and the nurses in America and South Africa can be found at www.aidshivawareness.org

References

· Tetta C, et al. tnt Arch Allergy Appl fmmunol. 1990;91:244-256.
· Parbtani A and Clark WF. In: Flaxseed in Human Nutrition. Cunnane SC and Thompson LU, eds. Champaign, IL: A DCS Press, 1995, pp. 244-260.
· Clark, W.F., et al. Kidney Int. 1995;48:475-480.
· Ingram A.J., et al. Am. Jour. Kidney Dis. 1995;25:320-329.
· Leaf A and Weber PC. N Engl J Med. 1988;318:549-557.
· Nair SSD, et al. J Nutr. 1997;127:383-393.
· Parbtani A and Clark WF. In: Flaxseed in Human Nutrition. Cunnane SC and Thompson LU, eds. Champaign, IL: AOCS Press, 1995, pp. 244-260.
· Blok WL, et al. J Nutr. 1996;126:1515-1533.

+Lupus

SDG Lignans and Lupus

Lupus is a chronic inflammatory disease that can affect many of the body's organs and skin. On the skin, it is characterized by remissions and exacerbations of a scaling, red, macular rash. Late in the disease patients suffer significant morbidity from kidney failure and accelerated vascular disease with heart attacks, strokes and other atherogenic complications. There is no cure and complete remissions are rare.

Lupus research at the University of Western Ontario indicates that SDG has a therapeutic role in animal and human lupus nephritis. It is known that in patients with lupus nephritis (SLE) there is an increase in the production of platelet activating factors (PAF) and a decrease in their metabolism. Platelets are the fragments of megakaryocytes (large cells in the bone marrow) which get into the blood. Lignans act as PAF receptor antagonists, which means the lignans reduce the accumulation PAF's.

In one study, eight lupus patients were given 15, 30, and 45 grams of flaxseed per day for four weeks. PAF-induced platelet aggregation was inhibited by all doses. In conclusion, the flaxseed conferred significant benefits in reducing inflammatory and atherogenic mechanisms important in the pathogenesis of lupus nephritis. Tests so far indicate that very beneficial results are occurring from use of lignan-rich flaxseed (concentrated flax hull lignans).

References

· Karsh, J., et al. “Mortality in Lupus Nephritis,” Arthr. Rheum., 1979, 22:764-69.
· Clark, W.F., et al. “Flaxseed: A Potential Treatment for Lupus Nephritis,” Kidney Int., Aug. 1995, 48(2):475-80.

+Antioxidant Effects

Antioxidant Activity of SDG Lignans

It has become evident that many diseases, including cancer, can begin or be advanced by damage caused by free radicals in the body. The causes of free radicals can be linked to diets high in unhealthy fats, fried foods, alcohol, exposure to radiation, and environmental pollutants. Free radicals can damage tissues and have been implicated in the pathology of many diseases like atherosclerosis, cancer and Alzheimer disease.

These are more than the body’s normal antioxidants (vitamins A, C, E and phytochemicals) are able to keep up with. The imbalance in the body of antioxidants to free radicals could literally be matter life and death.

Previously the ability of flax seed to scavenge oxygen radicals (antioxidant properties) was not known. Recent research has proven the ability of the main flax lignan, SDG, to scavenge hydroxyl radicals. In a rat study, feeding flax at levels of 5% and 10% in the diet prior to administering a liver toxin protected against oxidative stress in liver tissue compared with a normal diet not containing flax. The mammalian lignans, enterodiol and enterolactone, also act as antioxidants. Indeed, the antioxidant action of SECO and enterodiol is greater than that of vitamin E.

In a study at the University of Saskatchewan, College of Medicine, tests were performed to determine the effectiveness and potency of SDG isolated from flaxseed as an antioxidant, along with its mammalian metabolites secoisolariciresinol (SECO), Enterodiol (ED) and enterolactone (EL). Vitamin E was also tested for a comparison. The results of the tests show that the metabolities of SDG have strong antioxidant activity. In comparison to vitamin E, SDG was 1.27 times more potent as an antioxidant. However, the lignan EL was 4.35 times, more potent, SECO was 4.86 times more potent, and ED was 5.02 times more potent than vitamin E.

At the University of British Columbia, SDG and its mammalian lignans enterodiol (ED) and enterolactone (EL) were evaluated in both lipid and aqueous in vitro model systems. All three lignans significantly inhibited the linoleic acid peroxidation and hydroxyl radicals, with ED and EL providing more scavenging activity than SDG. It was included that there is an efficacy of SDG and particularly the mammalian lignans ED and EL to act as antioxidants. This is evidence of a potential anticarcinogenic mechanism in the flaxseed lignan SDG and ED and EL.

The above studies showed that the higher the concentration of SDG, the greater the antioxidant effect. However, according to the Linus Pauling Institute, while lignans can act as antioxidants in the test tube, the significance of such antioxidant activity in humans is not clear because lignans are rapidly and extensively metabolized. Although one cross-sectional study found that a biomarker of oxidative damage was inversely associated with serum enterolactone levels in men, it is not clear whether this effect was related to enterolactone or other antioxidants present in lignan-rich foods.

References

· Morris, Diane H. 2007. Flax - A Health and Nutrition Primer, Fourth Edition, 2007, courtesy of Flax Council of Canada.
· Prasad K. 1997. Hydroxyl radical-scavenging property of secoisolariciresinol diglucoside (SDG) isolated from flax-seed. Mol. Cell. Biochem. 168: 117-123.
· Praticò D. 2001. In vivo measurement of the redox state. Lipids 36: S45-S47.
· Rajesha J, Murthy KNC, Kumar MK, et al. 2006. Antioxidant potentials of flaxseed by in vivo model. J. Agric. Food Chem. 54: 3794-3799.
· Kitts DD, Yuan YV, Wijewickreme AN, Thompson LU. 1999. Antioxidant activity of the flaxseed lignan secoisolariciresinol diglycoside and its mammalian lignan metabolites enterodiol and enterolactone. Mol. Cell. Biochem. 202: 91-100.
· Bhathena SJ, Velasquez MT. 2002. Beneficial role of dietary phytoestrogens in obesity and diabetes. Am. J. Clin. Nutr. 76: 1191-1201.

+Diabetes

SDG Lignans and Diabetes

Diabetes is currently the ninth leading cause of death in the United States of America. The most common form of diabetes, mellitus, is generally divided into two categories: type I, called insulin-dependent or juvenile diabetes, and type II, called adult-onset or non-insulin-dependent diabetes.

Several studies at the University of Saskatchewan indicate that the lignan SDG from flaxseed can help prevent or significantly delay the development of diabetes. In a study with rats published in 2001, Dr. Prasad of the College of Medicine, Physiology Department, found that SDG reduces development of adult-onset (type II) diabetes by 80% and delays the development of the disease significantly.

The findings of this study build on Prasad's previously published studies involving two animal models of type I (juvenile) diabetes. These two studies showed that SDG reduces the development of the type I diabetes by 71% and 75% respectively.

Prasad has shown that both type I and type II diabetes are associated with oxidative stress (increase in toxic metabolites of oxygen known as oxygen free radicals). But because of SDG's potent antioxidants activity, its ingestion is effective in preventing and reducing the development of diabetes by reducing this oxidative stress. As a complex-carbohydrate, lignans can help reduce blood sugar levels.

Prasad stresses that diabetic patients would have to consume very large amounts of whole flax seed to get enough SDG to provide the equivalent beneficial effect found in the animal studies. Drawbacks to doing this would also include high caloric intake (flaxseed is 35-40% oil) and a laxative effect. For that reason, SDG extracts derived from newly developed extraction methods would be needed.

Additionally, the mammalian lignans stimulate the synthesis of sex hormone-binding globulin (SHBG), which binds sex hormones and reduces their circulation in the bloodstream, thus decreasing their biologic activity. In a meta-analysis, higher blood levels of SHBG were associated with an 80% lower risk of type II diabetes in women and 52% lower risk in men. Low blood levels SHBG have been found in postmenopausal women with breast cancer.

References

· Morris, Diane H. 2007. Flax - A Health and Nutrition Primer, Fourth Edition, 2007, courtesy of Flax Council of Canada.
· Adlercreutz H. 1995. Phytoestrogens: epidemiology and a possible role in cancer protection. Environ. Health Perspect. 103(suppl 7): 103-112.
· Ding EL, Song Y, Malik VS, Liu S. 2006. Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA 295: 1288-1299.
· Adlercreutz H, Hämäläinen E, Gorbach SL, et al. 1989. Diet and plasma androgens in postmenopausal vegetarian and omnivorous women and postmenopausal women with breast cancer Am. J. Clin. Nutr. 49: 433-442.
· Prasad, K., Jour. of Lab. & Clinical Med., July, 2001, 138: 32-39.
· Prasad, K., et al., Mol. Cell Biochem., 2000, 206(1-2): 141. Prasad, K., Mol. Cell Biochem., 2000, 209(1-2):89.

+Kidney Disorder

SDG Lignans and Kidney Disorder

The kidneys are the major regulators of the water electrolyte and acid-base (pH) content of the blood and, indirectly, all body fluids. Kidney disease is often the result of damage done to kidneys by exposure to certain drugs or toxins, heavy metals, solvents, poisons or pesticides. Impaired kidney function can also accompany or result from other disorders, such as diabetes, lupus, hypertension, and liver disease.

There is growing evidence that dietary phytoestrogens, such as flax lignan, have a beneficial role in chronic renal (kidney) disease. Recent findings from dietary intervention studies performed in animals and human suggest that consumption of flaxseed rich in lignans (concentrated flax hull lignans) retards the development and progression of chronic renal disease.

In one study to test the effect of dietary supplement of concentrated flax hull lignans, it was noted that lignans produce specific reversible and completive inhibition of PAF. This PAF factor has been implicated with the onset of renal injury. Mortality was lower in the flaxseed-fed mice.

In a study at the University of Manitoba, it was discovered that lignans in flaxseed improve kidney function in certain types of kidney diseases. When rats with kidney dysfunctions were given flaxseed in their diet, it preserved renal function and reduced histological injury.

Flaxseed has been investigated in both immune and non-immune models of renal injury. It was concluded that in both models, flaxseed was beneficial in slowing the decline in renal function. Studies comparing defatted flaxseed meal with full meal indicate that components other than the oil, such as fiber or lignans, have desirable properties in some aspects of renal disease.

References

· Blach, J. Prescription for Nutritional Healing, 1997, p. 357.
· Velazquez, M.T., Am. J. Kidney Dis., May, 2001, 37(5):1056-68.br /> · Clark, W.T. & Parbtani, A. “Flaxseed in Experimental and Clinical Lupus Nephritis,” University of Western Ontario, 2000, p. 17-22. Hall, A.V., et al. Am. J. Kidney Dis., 1993, 22(2):326-32.br /> · Ogborn, M.R., et al., "The effect of dietary flaxseed supplementation on organic anion and osmolyte content and excretion in rat polycystic kidney disease," Biochem. Celt. Bio/., 1998, 76(2-3):553-9.br /> · Parbtani, A. & W.F. Clark, "Flaxseed and its Components in Renal Disease," Flaxseed in Human Nutrition, 1995, AOCS Press, 244-260.

+Colon Cancer

SDG Lignans and Colon Cancer

There are various factors that put people are risk for colon cancer: lack of dietary fiber and calcium, a build up of toxins in the colon, continued constipation and/or diarrhea, polyps, an unhealthy, high-fat diet. Because the plant lignan SDG is converted into the mammalian lignans enterolactone and enterodiol directly within the colon, SDG is particularly effective in combating cancer of the colon.

In a 1992 study, it was discovered that flaxseed ingestion produced anticarcinogenic lignans in the colon. This study determined that flaxseed decreases the risk for colon carcinogenesis. Following an injection of azoxymethane (to induce carcinogenesis) five groups of male rats were fed a high-fat diet with or without supplementation with flax meal for 4 weeks. In the colons of the supplemented groups, it was discovered that the total number of aberrant crypt and foci were significantly reduced by 41-53% and 48-57% respectively. This suggests that consumption of flaxseed and its lignans may reduce the risk for colon carcinogenesis.

The above study shows that SDG lignan over the short term decreases some early markers of colon cancer risks. Studies at the University of Toronto Department of Nutritional Medicine, were conducted which showed that over the long term flaxseed lignan still exerts a colon cancer protective effect. Six groups of rats were fed 100 days either a regular diet of one supplemented with 2.5% or 5% defatted flaxseed. All rats were injected with a single dose of azoxymethane one week prior to commencing the dietary treatments. This was done to induce colon cancer. The rats which were fed the defatted flax had significantly reduced number of aberrant crypts in the distal colon compared to the control group. It was concluded that flaxseed had colon cancer protective effect due, in part, to the lignan SDG and that the productive effect of flaxseed and SDG is associated with increased beta-glucuronidase activity.

Another research was performed which involved the mammalian lignans enterolactone(EL) and enterodiol (ED), which are derived from SDG. In this research, four human colon tumor cell lines were incubated with various levels of EL, ED, or 17 beta-estradiol for 8 to 10 days. At 100 microM concentration, both lignans significantly reduced cell proliferation of all cell lines. EL was more than twice as effective as ED at this concentration. The growth was not affective by the presence of 17 beta-estradiol, implying that these cells are not estrogen-sensitive. The conclusion was the lignans are growth inhibitors of colon tumor cells and may act through mechanisms other than anti-estrogenic activity.

+Skin Cancer

SDG Lignans and Skin Cancer and Melanoma

There are several different types of skin cancer, some of which are benign and others malignant. An estimated 600,000 Americans develop some type of skin cancer each year and over 10,000 die from the disease. A recent review suggests that both isoflavonoids and lignans are natural cancer protective compounds and useful against skin cancer.

Research from the Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, Nebraska, investigated the effect of dietary supplementation of flaxseed, the richest source of lignans, on experimental melanoma cells. Flax reduces tumor occurrence by up to 63%. The addition of flaxseed to the diet also caused a dose-dependant decrease in tumor area and volume, showing that it could be beneficial in both prevention and treatment. Further, the rich source of lignans reduced metastasis and inhibited the growth of the metastatic secondary tumors in the animals tested.

References

· Adlercreurz, H., "Phytoesrrogens: Epidemiology and a Possible Role in Cancer Protection," Environ. Health Perspectives, 1995, 103:103-112.
· Van, L, et al. "Dietary flaxseed supplement and experimental metastasis of melanoma cells in mice." Cancer Lett, 1998; 124(2):181-6

+Athletes

SDG Lignans and the Athlete

The biological properties of lignans have several beneficial effects for the athlete. Their potent anti-estrogenic effect has drawn the interest of bodybuilders who are always looking to increase their testosterone to estrogen ratio. The lignans provide an economical, natural way to alter the ratio without adverse effects either physically or legally.

Lignans may also offer a benefit to those who are athletic, do heavy lifting or strenuous work by preventing damage to muscles. It was demonstrated that rats that were pretreated with a lignan-enriched extract were protected against physical exercise-induced muscle damage.

References

· Ko, K.M., Duncan, H., Phytotherapy Research, vol.10, Issue 5, 1996, pp. 450-452.

+Other Clinical Conditions

Additional Physiological Effects of SDG Lignans

There is evidence that lignans are anti-parasitic. In one test, vitamin E deficient diets containing 5 to 20% ground flaxseed protected mice against the malarial parasite Plasmodium voelii as shown by decrease parasitemia and enhanced survival.

Dietary supplementation with SDG, the lignan from flaxseed, significantly reduced pulmonary metastasis of melanoma cells and inhibited the growth of metastasis tumors that formed in the lungs. This may aid in the fight against lung cancer.

Flax lignan is useful for pets and livestock. Flax has been used since antiquity to maintain healthy animals. In cattle its reported uses included the correction of digestive disturbances in calves, easier calving, and reduction of certain infectious diseases such as hoof-and-mouth. Horse owners have reported using it to produce glossy looking coats and to the diets of pets to improve their appearance and general health.

Flaxseed and its lignan have been shown to reduce inflammatory responses, but did not prevent macrophages (cells of the immune system) from killing bacteria. The research of Dr. W. Clark involving lupus revealed that lignans are beneficial for reducing inflammation.

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*These statements have not been evaluated by the FDA. The information provided is intended solely for informational and educational purposes. Our products are not intended to diagnose, treat, cure or prevent any disease. They are intended to be included as part of a healthy diet that includes regular exercise. Please consult a medical or health professional regarding questions about your health.