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  • Lignans are polyphenols found in plants. (More Information)
  • Lignan precursors are found in a wide variety of plant-based foods, including seeds, whole grains, legumes, fruits, and vegetables. (More Information)
  • Flaxseeds are the richest dietary source of lignan precursors. (More Information)
  • When consumed, lignan precursors are converted to the enterolignans, enterodiol and enterolactone, by bacteria that normally colonize the human intestine. (More Information)
  • Enterodiol and enterolactone have weak estrogenic activity but may also exert biological effects through nonestrogenic mechanisms. (More Information)
  • Lignan-rich foods are part of a healthful dietary pattern, but the role of lignans in the prevention of hormone-associated cancers, osteoporosis, and cardiovascular diseases is not yet clear. (More Information)


The enterolignans, enterodiol and enterolactone (see chemical structures), are formed by the action of intestinal bacteria on lignan precursors found in plants (1). Because enterodiol and enterolactone can mimic some of the effects of estrogens, their plant-derived precursors are classified as phytoestrogens. Lignan precursors that have been identified in the human diet include pinoresinol, lariciresinol, secoisolariciresinol, matairesinol, and others (see chemical structures). Secoisolariciresinol and matairesinol were among the first lignan precursors identified in the human diet and are therefore the most extensively studied. Lignan precursors are found in a wide variety of foods, including flaxseeds, sesame seeds, legumes, whole grains, fruits, and vegetables. While most research on phytoestrogen-rich diets has focused on soy isoflavones, lignans are the principal source of dietary phytoestrogens in typical Western diets (2, 3).

Metabolism and Bioavailability

When plant lignans are ingested, they can be metabolized by intestinal bacteria to the enterolignans, enterodiol and enterolactone, in the intestinal lumen (4). Enterodiol can also be converted to enterolactone by intestinal bacteria. Not surprisingly, antibiotic use has been associated with lower serum enterolactone levels (5). Thus, enterolactone levels measured in serum and urine reflect the activity of intestinal bacteria in addition to dietary intake of plant lignans. Because data on the lignan content of foods are limited, serum and urinary enterolactone levels are sometimes used as markers of dietary lignan intake. 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 (6). Plasma enterodiol concentrations peaked at 73 nanomoles/liter (nmol/L) an average of 15 hours after ingestion of 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 among 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 (1). It is likely that individual differences in the metabolism of lignans, possibly due to gut microbes, influence the biological activities and health effects of these compounds.

Biological Activities

Estrogenic and Anti-Estrogenic Activities

Estrogens are signaling molecules (hormones) that exert their effects by binding to estrogen receptors within cells (see chemical structures). 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 (7). Although phytoestrogens can also bind to estrogen receptors, their estrogenic activity is much weaker than endogenous estrogens, and they may actually block or antagonize the effects of estrogen in some tissues (8). 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 enterolignans, enterodiol and enterolactone, are known to have weak estrogenic activity. At present, the extent to which enterolignans exert weak estrogenic and/or anti-estrogenic effects in humans is not well understood.

Estrogen Receptor-Independent Activities

Enterolignans also have biological activities that are unrelated to their interactions with estrogen receptors. By altering the activity of enzymes involved in estrogen metabolism, lignans may change the biological activity of endogenous estrogens (9). Lignans can act as antioxidants in the test tube, but the significance of such antioxidant activity in humans is not clear because lignans are rapidly and extensively metabolized (4). Although one cross-sectional study found that a biomarker of oxidative damage was inversely associated with serum enterolactone levels in men (10), it is not clear whether this effect was related to enterolactone or other antioxidants present in lignan-rich foods.

Disease Prevention

Cardiovascular Disease

Diets rich in foods containing plant lignans (whole grains, nuts and seeds, legumes, fruits, and vegetables) have been consistently associated with reductions in risk of cardiovascular disease. However, it is likely that numerous nutrients and phytochemicals found in these foods contribute to their cardioprotective effects. In a prospective cohort study of 1,889 Finnish men followed for an average of 12 years, those with the highest serum enterolactone levels (a marker of plant lignan intake) were significantly less likely to die from coronary heart disease (CHD) or cardiovascular disease than those with the lowest levels (11). However, a recent study in male smokers did not find strong support for an association between serum enterolactone levels and CHD (12). Flaxseeds are among the richest sources of plant lignans in the human diet, but they are also good sources of other nutrients and phytochemicals with cardioprotective effects, such as omega-3 fatty acids and fiber. Four small clinical trials found that adding 30-50 g/day of flaxseed to the usual diet for 4-12 weeks resulted in modest 8-14% decreases in LDL cholesterol levels (13-16), while four other trials did not observe significant reductions in LDL cholesterol after adding 30-40 g/day of flaxseed to the diet (17-20). More recently, a double-blind, randomized controlled trial in adults aged 44 to 75 found that supplementation with 40 g/day of flaxseed led to significant reductions in LDL cholesterol after five weeks, but cholesterol reductions were not statistically significant following ten weeks of supplementation (21). Additionally, a one-year clinical trial in menopausal women reported that supplementation with 40 g/day of flaxseed did not lower LDL cholesterol compared to a placebo containing wheat germ (22). Most of these trials used ground or crushed flaxseed, which much more bioavailable than whole flaxseed (23). Although the results of prospective cohort studies consistently indicate that diets rich in whole grains, nuts, fruits, and vegetables are associated with significant reductions in cardiovascular disease risk, it is not yet clear whether lignans themselves are cardioprotective.

Hormone-associated Cancers

Breast cancer

Overall, there is little evidence that dietary intake of plant lignans is significantly associated with breast cancer risk; studies to date have reported conflicting results. Two prospective cohort studies examining plant lignan intake and breast cancer found no association (24, 25). A more recent prospective study reported no association between total lignan intake and breast cancer in premenopausal women (26). In another prospective analysis, the same group of authors found postmenopausal women in the highest quartile of dietary lignan intake had a 17% lower risk of breast cancer compared to women in the lowest quartile, but this protective association was only observed in women with estrogen-positive and progesterone-positive tumors (27). A recent meta-analysis did not find an overall association between dietary lignan intake and breast cancer, but when the analysis was limited to postmenopausal women, the authors reported a 15% reduction in risk of breast cancer with high lignan intake (28). Several studies, mainly case-control studies, have examined the relationship between blood or urine levels of enterolactone and breast cancer; results of these studies are conflicting (29-31). Moreover, a recent meta-analysis did not find an association between blood levels of enterolactone and breast cancer (28). At present, it is not clear whether high intakes of plant lignans or high circulating levels of enterolignans offer significant protective effects against breast cancer.

Endometrial and Ovarian Cancer

In a case-control study of lignans and endometrial cancer, U.S. women with the highest intakes of plant lignans had the lowest risk of endometrial cancer, but the reduction in risk was statistically significant in postmenopausal women only (32). Yet, a recent prospective case-control study in three different countries (U.S., Sweden, and Italy) did not find an association between circulating enterolactone, a marker of lignan intake, and endometrial cancer in premenopausal or in postmenopausal women (33). In the only case-control study of lignans and ovarian cancer, U.S. women with the highest intakes of plant lignans had the lowest risk of ovarian cancer (34). However, high intakes of other phytochemicals associated with plant-based diets like fiber, carotenoids, and phytosterols were also associated with decreased ovarian cancer risk. Although these studies support the hypothesis that diets rich in plant foods may be helpful in decreasing the risk of hormone-associated cancers, they do not provide strong evidence that lignans are protective against endometrial or ovarian cancer.

Prostate Cancer

Although dietary lignans are the principal source of phytoestrogens in the typical Western diet, relationships between dietary lignan intake and prostate cancer risk have not been well-studied. Three prospective case-control studies examined the relationship between circulating enterolactone concentrations, a marker of lignan intake, and the subsequent development of prostate cancer in Scandinavian men (35-37). In all three studies, initial serum enterolactone concentrations in men who were diagnosed with prostate cancer five to 14 years later were not significantly different from serum enterolactone levels in matched control groups of men who did not develop prostate cancer. In a retrospective case-control study, recalled dietary lignan intake did not differ between U.S. men diagnosed with prostate cancer and a matched control group (38). More recently, serum enterolactone levels were not significantly associated with risk of prostate cancer in a case-control study in Swedish men (39). Additionally, two prospective, European case-control studies did not find an association between serum enterolactone and prostate cancer (40, 41). However, a case-control study conducted in Scotland found that higher serum enterolactone concentrations were associated with a lower risk of prostate cancer (42). At present, limited data from epidemiological studies do not support a relationship between dietary lignan intake and prostate cancer risk.


Research on the effects of dietary lignan intake on osteoporosis risk is very limited. In two small observational studies, urinary enterolactone excretion was used as a marker of dietary lignan intake. One study of 75 postmenopausal Korean women, who were classified as osteoporotic, osteopenic, or normal on the basis of bone mineral density (BMD) measurements, found that urinary enterolactone excretion was positively associated with BMD of the lumbar spine and hip (43). However, a study of 50 postmenopausal Dutch women found that higher levels of urinary enterolactone excretion were associated with higher rates of bone loss (44). In two separate placebo controlled trials, supplementation of postmenopausal women with 25-40 g/day of ground flaxseed for 3-4 months did not significantly alter biochemical markers of bone formation or bone resorption (loss) (19, 45). More research is necessary to determine whether high dietary intakes of plant lignans can decrease the risk or severity of osteoporosis.


Food Sources

Lignans are present in a wide variety of plant foods, including seeds (flax, pumpkin, sunflower, poppy, sesame), whole grains (rye, oats, barley), bran (wheat, oat, rye), beans, fruits (particularly berries), and vegetables (30, 46). Secoisolariciresinol and matairesinol were the first plant lignans identified in foods (47). Pinoresinol and laricresinol, two recently identified plant lignans, contribute substantially to total dietary lignan intakes. A survey of 4,660 Dutch men and women during 1997-1998 found that the median total lignan intake was 0.98 mg/day (48). Lariciresinol and pinoresinol contributed about 75% to the total lignan intake, while secoisolariciresinol and matairesinol contributed only about 25%. Plant lignans are the principal source of phytoestrogens in the diets of people who do not typically consume soy foods. The daily phytoestrogen intake of postmenopausal women in the U.S. was estimated to be less than 1 mg/day, with 80% from lignans and 20% from isoflavones (49).

Flaxseed is by far the richest dietary source of plant lignans (50), and lignan bioavailability can be improved by crushing or milling flaxseed (23). Lignans are not associated with the oil fraction of foods, so flaxseed oils do not typically provide lignans unless ground flaxseed has been added to the oil. A variety of factors may affect the lignan contents of plants, including geographic location, climate, maturity, and storage conditions. The table below provides the total lignan (secoisolariciresinol, matairesinol, pinoresinol, and lariciresinol) contents of selected lignan-rich foods (51).

Total Lignan Content of Selected Foods
Food Serving
Total Lignans (mg)
Flaxseeds 1 oz
Sesame seeds 1 oz
Curly kale ½ cup, chopped
Broccoli ½ cup, chopped
Apricots ½ cup, sliced
Cabbage ½ cup, chopped
Brussels sprouts ½ cup, chopped
Strawberries ½ cup
Tofu ¼ block (4 oz)
Dark rye bread 1 slice



Dietary supplements containing lignans derived from flaxseed are available in the U.S. without a prescription. One such supplement provides 50 mg of secoisolariciresinol diglycoside per capsule.


Adverse Effects

Lignan precursors in foods are not known to have any adverse effects. Flaxseeds, which are rich in lignan precursors as well as fiber, may increase stool frequency or cause diarrhea in doses of 45-50 g/day in adults (13, 52). The safety of lignan supplements in pregnant or lactating women has not been established. Therefore, lignan supplements should be avoided by women who are pregnant, breast-feeding, or trying to conceive.


Written in December 2005 by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University

Updated in January 2010 by:
Victoria J. Drake, Ph.D.
Linus Pauling Institute
Oregon State University

Reviewed in January 2010 by:
Johanna W. Lampe, Ph.D., R.D.
Full Member, Fred Hutchinson Cancer Research Center
Research Professor, Epidemiology
School of Public Health and Community Medicine, University of Washington
Seattle, WA

Copyright 2004-2015  Linus Pauling Institute


The Linus Pauling Institute Micronutrient Information Center provides scientific information on the health aspects of dietary factors and supplements, foods, and beverages for the general public. The information is made available with the understanding that the author and publisher are not providing medical, psychological, or nutritional counseling services on this site. The information should not be used in place of a consultation with a competent health care or nutrition professional.

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