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Lignans

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Principal Proposed Uses

None

Other Proposed Uses

Cancer Prevention; Elevated Cholesterol; Kidney Disease; Menopausal Symptoms

Lignans are naturally occurring chemicals widespread within the plant and animal kingdoms. Several lignans—with intimidating names such as secoisolariciresinol—are considered to be phytoestrogens, plant chemicals that mimic the hormone estrogen. These are especially abundant in flaxseeds and sesame seeds. Bacteria in our intestines convert the naturally occurring phytoestrogens from flaxseed into two other lignans, enterolactone and enterodiol, which also have estrogen-like effects. In this article, the term lignans refers to these two specific lignans as well as the phytoestrogen kind, but not to the wide variety of other lignans.

Lignans are being studied for possible use in cancer prevention, particularly breast cancer. Like other phytoestrogens (such as soy isoflavones), they hook onto the same spots on cells where estrogen attaches. If there is little estrogen in the body (after menopause, for example), 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 cells. This displacement of the hormone may help prevent those cancers, such as breast cancer, that depend on estrogen to start and develop. In addition, at least one test tube study suggests that lignans may help prevent cancer in ways that are unrelated to estrogen.1

Requirements/Sources

The richest source of lignans is flaxseed (sometimes called linseed), containing more than 100 times the amount found in other foods! 11Flaxseed oil, however, does not contain appreciable amounts of lignans.12 Sesame seed is an equally rich source.44 Other food sources are pumpkin seeds, whole grains, cranberries, and black or green tea.13

Therapeutic Dosages

Effective dosages of purified lignans have not been determined. In studies of flaxseed as a source of lignans, flaxseed has been taken at a dose of 5 to 38 g daily.

Cooking flaxseed apparently does not decrease the amount of lignans absorbed by the body.

Therapeutic Uses

A number of preliminary human and animal studies suggest that lignans may be helpful for cancer prevention, particularly of the colon and breast.47,48

Despite positive preliminary results in animal studies,14,15 studies in humans have yielded mixed results for improving cholesterol levels.45,46

There is also mixed evidence as to whether or not flaxseeds or lignans decrease menopausal symptoms.49,50

Lignans may improve kidney function in various types of kidney disease (specifically, lupus nephritis and polycystic kidney disease).17,18Warning: Flaxseed or other treatments for kidney disease should be taken only under a doctor's supervision, due to the serious nature of these disorders.

Metabolic syndrome consists of a constellation of conditions increasing the risk of cardiovascular disease, including obesity, unhealthy cholesterol and triglyceride levels, high blood pressure, and pre-diabetes. In one study, 100 people with metabolic syndrome were randomized to receive flaxseed lignans (4 g/per day) or placebo during a 6-month exercise program.51 A number of tests were done, including body composition, cholesterol levels, blood pressure, and bone mineral density. But, no significant differences turned up between the two groups.

Benign prostatic hyperplasia (BPH) causes a range of urinary problems in men. A 4-month randomized, controlled trial involving 78 men with BPH found that those treated with lignans experienced an improvement in their symptoms compared to the placebo group.52

Researchers have also explored whether the lignan enterolactone can reduce the risk of heart disease. But, there is only weak evidence to support this.53

What Is the Scientific Evidence for Lignans?

The most promising use for lignans is in cancer prevention. According to observational studies, people who eat more lignan-containing foods have a lower incidence of breast and perhaps colon cancer.19 For example, in 2 systematic reviews of up to 23 studies, researchers found an association between a high intake of lignans and a reduced risk of breast cancer in postmenopausal women.47,48

This, however, does not prove that lignans are the cause of the benefit, for other factors in these foods, or in the characteristics of the people who consume these foods, may have been responsible. Double-blind, placebo-controlled studies are necessary to prove that a medical treatment provides benefits, and none have yet been reported for lignans. (For information on why this type of study is so important, see Why Does This Database Rely on Double-blind Studies?)

Nonetheless, animal studies offer additional support for a potential cancer-preventive or even cancer-treatment effect. Several studies showed that lignan-rich foods or lignans found in flax inhibited breast and colon cancer in animals 20,21,22 and reduced metastases from melanoma (a type of skin cancer) in mice.23Test tube studies have found that flaxseed or one of its lignans inhibited the growth of human breast cancer cells 24 and that the lignans enterolactone and enterodiol inhibited the growth of human colon tumor cells.25

In many of these studies, it isn't clear whether lignans are responsible for the benefit seen, as flaxseeds contain many other substances. Animal and human studies have begun to examine specific lignans, and results seem to confirm that at least some of the positive effects probably come from the lignans themselves.26,27,28 Still, until more and better designed trials are done, we will not know lignans' precise effects on the human body, or the precise dose needed to prevent cancer.

In one study, 38 postmenopausal women were randomized to eat 2 slices of bread with 46 mg of lignans or 2 slices of bread with less than 1 mg of lignans (placebo).49 At the end of the 12-week study, the women in the high-lignan group did not experience a reduction in hot flashes or other menopausal symptoms.

Another study, though, offers more positive news. Eighty postmenopausal women were randomized to receive a combination treatment (lignans plus isoflavones and black cohosh ) or calcium only.50 After 3 months, the women receiving the combination product had an improvement in their menopausal symptoms, though it is unclear which component(s) of the combined treatment produced the beneficial effect.

Safety Issues

Women who are pregnant or breastfeeding should avoid high intake of flaxseed or purified lignans. One study found that pregnant rats who ate large amounts of flaxseed (5% or 10% of their diet), or a purified lignan present in flaxseed, gave birth to offspring with altered reproductive organs and functions, and that lignans were also transferred to the baby rats during nursing.36 In humans, eating 25 g of flaxseed per day amounts to about 5% of the diet.37

High intake of lignans may not be safe for women with a history of estrogen-sensitive cancer, such as breast cancer or uterine cancer. A few test tube studies suggest that certain cancer cells can be stimulated by lignans such as those present in flaxseed.38 Other studies found that lignans inhibit cancer cell growth.39 As with estrogen, lignans' positive or negative effects on cancer cells may depend on dose, type of cancer cell, and levels of hormones in the body. If you have a history of cancer, particularly breast cancer, talk with your doctor before consuming large amounts of flaxseeds.

Other potential concerns are discussed in the safety section of the Flaxseed article.

References

Sung MK, Lautens M, Thompson LU. Mammalian lignans inhibit the growth of estrogen-independent human colon tumor cells. Anticancer Res. 1998;18:1405-1408.

Prasad K. Hydroxyl radical-scavenging property of secoisolariciresinol diglucoside (SDG) isolated from flax-seed. Mol Cell Biochem. 1997;168:117-123.

Yuan YV, et al. Short-term feeding of flaxseed or its lignan has minor influence on in vivo hepatic antioxidant status in young rats. Nutr Res. 1999;19:1233-1243.

Jenkins DJ, Kendall CW, Vidgen E, et al. Health aspects of partially defatted flaxseed, including effects on serum lipids, oxidative measures, and ex vivo androgen and progestin activity: a controlled crossover trial. Am J Clin Nutr. 1999;69:395-402.

Arjmandi BH, Khan DA, Juma S, et al. Whole flaxseed consumption lowers serum LDL-cholesterol and lipoprotein(a) concentrations in postmenopausal women. Nutr Res. 1998;18:1203-1214.

Prasad K. Dietary flax seed in prevention of hypercholesterolemic atherosclerosis. Atherosclerosis. 1997;132:69-76.

Prasad K. Reduction of serum cholesterol and hypercholesterolemic atherosclerosis in rabbits by secoisolariciresinol diglucoside isolated from flaxseed. Circulation. 1999;99:1355-1362.

Adlercreutz H, Mazur W. Phyto-oestrogens and Western diseases. Ann Med. 1997;29:95-120.

Clark WF, Parbtani A, Huff MW, et al. Flaxseed: a potential treatment for lupus nephritis. Kidney Int. 1995;48:475-480.

Ogborn MR, Nitschmann E, Bankovic-Calic N, et al. The effect of dietary flaxseed supplementation on organic anion and osmolyte content and excretion in rat polycystic kidney disease. Biochem Cell Biol. 1998;76;553-559.

Thompson LU. Experimental studies on lignans and cancer. Baillieres Clin Endocrinol Metab. 1998;12:691-705.

Thompson LU. Experimental studies on lignans and cancer. Baillieres Clin Endocrinol Metab. 1998;12:691-705.

Adlercreutz H, Mazur W. Phyto-oestrogens and Western diseases. Ann Med. 1997;29:95-120.

Prasad K. Dietary flax seed in prevention of hypercholesterolemic atherosclerosis. Atherosclerosis. 1997;132:69-76.

Prasad K. Reduction of serum cholesterol and hypercholesterolemic atherosclerosis in rabbits by secoisolariciresinol diglucoside isolated from flaxseed. Circulation. 1999;99:1355-1362.

Adlercreutz H, Mazur W. Phyto-oestrogens and Western diseases. Ann Med. 1997;29:95-120.

Clark WF, Parbtani A, Huff MW, et al. Flaxseed: a potential treatment for lupus nephritis. Kidney Int. 1995;48:475-480.

Ogborn MR, Nitschmann E, Bankovic-Calic N, et al. The effect of dietary flaxseed supplementation on organic anion and osmolyte content and excretion in rat polycystic kidney disease. Biochem Cell Biol. 1998;76;553-559.

Adlercreutz H, Mazur W. Phyto-oestrogens and Western diseases. Ann Med. 1997;29:95-120.

Thompson LU. Experimental studies on lignans and cancer. Baillieres Clin Endocrinol Metab. 1998;12:691-705.

Thompson LU, Rickard SE, Orcheson LJ, et al. Flaxseed and its lignan and oil components reduce mammary tumor growth at a late stage of carcinogenesis. Carcinogenesis. 1996;17:1373-1376.

Serraino M, Thompson LU. The effect of flaxseed supplementation on the initiation and promotional stages of mammary tumorigenesis. Nutr Cancer. 1992;17:153-159.

Yan L, Yee JA, Li D, et al. Dietary flaxseed supplementation and experimental metastasis of melanoma cells in mice. Cancer Lett. 1998;124:181-186.

Adlercreutz H, Mazur W. Phyto-oestrogens and Western diseases. Ann Med. 1997;29:95-120.

Sung MK, Lautens M, Thompson LU. Mammalian lignans inhibit the growth of estrogen-independent human colon tumor cells. Anticancer Res. 1998;18:1405-1408.

Sung MK, Lautens M, Thompson LU. Mammalian lignans inhibit the growth of estrogen-independent human colon tumor cells. Anticancer Res. 1998;18:1405-1408.

Thompson LU. Experimental studies on lignans and cancer. Baillieres Clin Endocrinol Metab. 1998;12:691-705.

Thompson LU, Rickard SE, Orcheson LJ, et al. Flaxseed and its lignan and oil components reduce mammary tumor growth at a late stage of carcinogenesis. Carcinogenesis. 1996;17:1373-1376.

Prasad K. Dietary flax seed in prevention of hypercholesterolemic atherosclerosis. Atherosclerosis. 1997;132:69-76.

Prasad K. Reduction of serum cholesterol and hypercholesterolemic atherosclerosis in rabbits by secoisolariciresinol diglucoside isolated from flaxseed. Circulation. 1999;99:1355-1362.

Arjmandi BH, Khan DA, Juma S, et al. Whole flaxseed consumption lowers serum LDL-cholesterol and lipoprotein(a) concentrations in postmenopausal women. Nutr Res. 1998;18:1203-1214.

Jenkins DJ, Kendall CW, Vidgen E, et al. Health aspects of partially defatted flaxseed, including effects on serum lipids, oxidative measures, and ex vivo androgen and progestin activity: a controlled crossover trial. Am J Clin Nutr. 1999;69:395-402.

Tarpila S, Kivinen A. Ground flaxseed is an effective hypolipidemic bulk laxative [abstract]. Gastroenterology. 1997;112:A836.

Jenkins DJ, Kendall CW, Vidgen E, et al. Health aspects of partially defatted flaxseed, including effects on serum lipids, oxidative measures, and ex vivo androgen and progestin activity: a controlled crossover trial. Am J Clin Nutr. 1999;69:395-402.

Arjmandi BH, Khan DA, Juma S, et al. Whole flaxseed consumption lowers serum LDL-cholesterol and lipoprotein(a) concentrations in postmenopausal women. Nutr Res. 1998;18:1203-1214.

Tou JC, Chen J, Thompson LU. Flaxseed and its lignan precursor, secoisolariciresinol diglycoside, affect pregnancy outcome and reproductive development in rats. J Nutr. 1998;128:1861-1868.

Thompson LU. Experimental studies on lignans and cancer. Baillieres Clin Endocrinol Metab. 1998;12:691-705.

Adlercreutz H, Mazur W. Phyto-oestrogens and Western diseases. Ann Med. 1997;29:95-120.

Adlercreutz H, Mazur W. Phyto-oestrogens and Western diseases. Ann Med. 1997;29:95-120.

Wanasundara PK, Shahidi F. Process-induced compositional changes of flaxseed. Adv Exp Med Biol. 1998;434:307-325.

Wanasundara PK, Shahidi F. Process-induced compositional changes of flaxseed. Adv Exp Med Biol. 1998;434:307-325.

Facsicule 1. Lini semen, linseed. In: European Scientific Cooperative on Phytotherapy. Monographs on the medicinal uses of plant drugs. Dusseldorf, Germany:IDW-Verlag. 1997:1-5.

Hutchins AM, Martini MC, Olson BA, et al. Flaxseed consumption influences endogenous hormone concentrations in postmenopausal women. Nutr Cancer. 2001;39:58-65.

Coulman KD, Liu Z, Hum WQ, et al. Whole sesame seed is as rich a source of Mammalian lignan precursors as whole flaxseed. Nutr Cancer. 2005;52:156-65.

Hallund J, Ravn-Haren G, Bugel S, et al. A lignan complex isolated from flaxseed does not affect plasma lipid concentrations or antioxidant capacity in healthy postmenopausal women. J Nutr. 2005;136:112-6.

Zhang W, Wang X, Liu Y, et al. Dietary flaxseed lignan extract lowers plasma cholesterol and glucose concentrations in hypercholesterolaemic subjects. Br J Nutr. 2007 Dec 6.

Buck K, Zaineddin AK, Vrieling A, Linseisen J, Chang-Claude J. Meta-analyses of lignans and enterolignans in relation to breast cancer risk. Am J Clin Nutr. 2010;92(1):141-153.

Velentzis LS, Cantwell MM, Cardwell C, Keshtgar MR, Leathem AJ, Woodside JV. Lignans and breast cancer risk in pre- and post-menopausal women: meta-analyses of observational studies. Br J Cancer. 2009 May 5;100(9):1492-1498. Epub 2009 Mar 31.

Simbalista RL, Sauerbronn AV, Aldrighi JM, Arêas JA. Consumption of a flaxseed-rich food is not more effective than a placebo in alleviating the climacteric symptoms of postmenopausal women. J Nutr. 2010;140(2):293-297.

Sammartino A, Tommaselli GA, Gargano V, di Carlo C, Attianese W, Nappi C. Short-term effects of a combination of isoflavones, lignans and Cimicifuga racemosa on climacteric-related symptoms in postmenopausal women: a double-blind, randomized, placebo-controlled trial. Gynecol Endocrinol. 2006;22(11):646-650.

Cornish SM, Chilibeck PD, Paus-Jennsen L, et al. A randomized controlled trial of the effects of flaxseed lignan complex on metabolic syndrome composite score and bone mineral in older adults. Appl Physiol Nutr Metab. 2009;34(2):89-98.

Zhang W, Wang X, Liu Y, Tian H, Flickinger B, Empie MW, Sun SZ. Effects of dietary flaxseed lignan extract on symptoms of benign prostatic hyperplasia. J Med Food. 2008;11(2):207-14.

Kilkkinen A, Erlund I, Virtanen MJ, Alfthan G, Ariniemi K, Virtamo J. Serum enterolactone concentration and the risk of coronary heart disease in a case-cohort study of Finnish male smokers. Am J Epidemiol. 2006;163(8):687-693.

Last reviewed July 2012 by EBSCO CAM Review Board

Please be aware that this information is provided to supplement the care provided by your physician. It is neither intended nor implied to be a substitute for professional medical advice. CALL YOUR HEALTHCARE PROVIDER IMMEDIATELY IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with any questions you may have regarding a medical condition.

Copyright © EBSCO Publishing. All rights reserved.

 
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