Life Extension Magazine®

Issue: Apr 2010

Lignans

Lignans are powerful agents that help prevent cancer, heart disease, and osteoporosis. New research illuminates the many ways these largely unheralded dietary components help maintain optimal health.

The Rhythm of Healing

Lignans contain powerful agents that assist in cancer1-23 and heart disease prevention,24-36 and help maintain bone strength.

New research illuminates the many ways these largely unheralded dietary components help maintain optimal health. Some of these include: reduction of chronic inflammation,37-39 thwarting viral infection,40,41 improving glycemic control among diabetics, and decreasing insulin resistance.26,42 The data regarding cancer protection are particularly compelling. As one researcher noted, “Experi-mental evidence in animals has shown clear anticarcinogenic effects of flaxseed or pure lignans in many types of cancer.”43

Join us as we explore the often overlooked benefits of these important nutrients.

More than 500 lignans are known to exist in the plant kingdom.

The Lowdown on Lignans

Lignans represent one of the four major classes of chemical compounds referred to collectively as phytoestrogens. Phytoestrogens are plant-based compounds structurally similar to estradiol, which is the primary estrogen hormone in humans. Phytoestrogens weakly engage estrogen receptors, figuratively flipping certain cellular “switches” on or off. These switches, or receptors, stud tissues located throughout the body, in both men and women. They affect everything from arterial health, to brain function, sexual maturation and reproduction. Under certain conditions, they play a direct role in promoting, or defusing, aggressive cancer growth. It is hypothesized that the interplay between natural estradiol and other estrogens, and plant-derived phytoestrogens, is a prerequisite for optimal health.44 Although much remains to be investigated, a preponderance of evidence indicates that dietary phytoestrogens exert positive, protective effects in humans.

Isoflavones, for instance, are another major class of phytoestrogens. Together, isoflavones and lignans are the most common phytoestrogens in the diet.45 Numerous studies have documented the link between a high intake of soy isoflavones and a reduced incidence of heart disease, osteo-porosis and certain cancers.46-53 Soy phytoestrogens have been shown to significantly reduce total cholesterol, low-density lipoprotein (LDL), and triglyceride levels. And a high intake of phytoestrogens—particularly lignans—has recently been associated with a reduced risk of breast cancer among premenopausal women.16 Another recent study found that Scottish men with the highest intake of lignans have the lowest incidence of prostate cancer.7 Animal studies have generally echoed these findings. While there is still some controversy regarding the overall role of phytoestrogens in health, scientists generally acknowledge that a higher intake of phyto-estrogens appears to be associated with a reduced risk of various diseases.7, 16, 48, 54-59

Lignan Lineage

Lignan Lineage

Significant quantities of lignans are present in foods ranging from whole grains (rye, wheat, oat, and barley) to berries, vegetables, legumes, and other fruits.60 Sesame is a rich source of the lignan, sesamin. And new research indicates that a “novel synergistic effect” of newly discovered lignans interacting with vitamin E accounts for “the anti-aging effect of sesame.” The lignans evidently help prevent the decomposition of sesame tocopherols (vitamin E compounds), preserving the antioxidant potency of the vitamin E. According to a Japanese review of sesame research, “Sesame lignans also showed other useful functions, such as acceleration of alcohol decomposition in the liver, antihypertensive activity, immunoregulatory activities, anticarcinogenic activity, and others.”61

The primary lignan in flaxseed is secoisolariciresinol. Other lignans bear equally tongue-twisting names, but only two lignans are of ultimate significance to human health: enterodiol and enterolactone. These biologically active lignans are known as enterolignans, or “mammalian lignans.” They are formed in the human digestive tract through the interaction of gut-dwelling bacteria with dietary lignans. Plant-based lignans are considered precursors, then, to the bioactive mammalian lignans.

Anti-Cancer Activity

While extra virgin olive oil is widely recognized as a heart-healthy oil, it also contains lignans, which further contribute to the beneficial nutritional profile of this functional food. Recently published research indicates that olive oil lignans, among other olive oil chemicals, may play an active role in protecting against breast cancer. This was demonstrated recently by Spanish researchers working with breast cancer cells that overexpress a protein known as Human Epidermal growth factor Receptor 2 (commonly abbreviated as HER2/neu).62,63 HER2 is a protein associated with highly aggressive growth by certain breast cancers, so thwarting this protein is especially desirable. In fact, Spanish researchers wrote recently, “…Humans have safely been ingesting…lignans as long as they have been consuming olives and olive oil, [supporting] the notion that…these phytochemicals might provide an excellent and safe platform for the design of new HER2-targeting agents.”63

Diets including plenty of whole grains, nuts, seeds, legumes, fruits, and vegetables are loaded with lignans, and such diets have been consistently associated with a reduced risk of cardiovascular disease.

One well-studied lignan, podophyllotoxin, is so effective at targeting cancer cells for destruction it has been modified for use in chemotherapy. Its semi-synthetic derivatives, etoposide, teniposide, and etoposide phosphate, are routinely used to combat deadly lung cancer, among other malignancies.5,64 Korean researchers showed recently that a lignan derived from an Asian medicinal plant, Daphne genkwa, arrested growth and induced apoptosis of promyelocytic leukemia cells in the laboratory. The lignan, researchers concluded, “may be a potential chemotherapeutic agent for the treatment of cancer.”13

In animal models of human breast cancer, dietary lignans, which are converted to entero-lactone, have been shown to inhibit or delay the growth of breast cancer.2 This effect is believed to be due to enterolactone’s ability to modulate estrogen signaling. This protective effect evidently extends well beyond breast cancer, however. Experimental evidence suggests that dietary lignans also offer significant protection against tumors of the liver, prostate, skin, colon and other organs.1,5,6,8,11,19-22,64

Anti-Cancer Activity

A Dutch case-control study found a clear association between a high intake of lignans and a reduced risk of colorectal adenomas, which are considered to be precursors to colon cancer. “We observed a substantial reduction in colorectal adenoma risk among subjects with high plasma concentrations of enterolignans,” investigators concluded.14

Of course, animal models are one thing, while actual effects in humans are another. But a variety of studies on human subjects support the conclusion that dietary lignans protect us against numerous cancers. For instance, French researchers conducted a prospective study of more than 58,000 postmenopausal women, who were followed for an average of 7.7 years. Statistical analysis revealed that a greater intake of dietary lignans was clearly associated with a reduced risk of breast cancer. “High dietary intakes of plant lignans and high exposure to enterolignans were associated with reduced risks of estrogen receptor- and progesterone receptor-positive postmenopausal breast cancer…” researchers concluded.23 A Swedish study reached a similar conclusion. After studying nearly 52,000 women, researchers concluded: “A significant 17% risk reduction for breast cancer overall in the high lignan quartile was observed…”11

Cardiovascular Protection

Cardiovascular Protection

Diets including plenty of whole grains, nuts, seeds, legumes, fruits, and vegetables are loaded with lignans, and such diets have been consistently associated with a reduced risk of cardiovascular disease. Of course, such diets also contain a host of other phytonutrients, so this cardioprotective effect would not necessarily be owed solely to the high lignan content. But studies that have investigated this question appear to confirm an important role for lignans in cardiovascular protection.32,34-37,65

In 1998, for example, Canadian researchers addressed the issue by examining the effects of two different types of flaxseed on markers of atherosclerosis in rabbits. One group received flaxseed high in both lignans and the omega-3 fatty acid, alpha-linolenic acid (ALA). A second group received a type of flaxseed, called Type II, which is high in lignans but virtually devoid of fatty acids. Both types of flaxseed reduced atherosclerosis. Type II flaxseed reduced the development of atherosclerosis by 69%. Researchers concluded that the reduction in atherosclerosis by the low-omega-3 flaxseed was due to a decrease in serum total cholesterol and LDL. “In conclusion,” they wrote, “[the atherosclerosis-reducing] activity of Type II flaxseed is not due to alpha-linolenic acid.”36

Several clinical trials have reported a link between flaxseed consumption and modest, but significant, reductions in LDL levels. Subjects experienced from 8 to 14% reductions in levels of this “bad” lipid.34,35,65 Of course, the importance of lowering LDL for optimal heart health is widely documented. More recently, US scientists conducted a randomized, placebo-controlled, double-blind study of the relationship between flaxseed consumption and cardiovascular disease risk factors in adults with high cholesterol.

Subjects consumed 40 grams ground flaxseed per day, or placebo, for 10 weeks. Compared to placebo (wheat), flax significantly reduced LDL levels at five weeks. Average reductions were 13%. By 10 weeks, reductions were approximately 7%. “Ground flaxseed has a modest but short lived LDL-cholesterol lowering effect,” researchers concluded. Additionally, levels of lipoprotein (a) were significantly reduced, by about 14%, and insulin sensitivity was significantly increased.30 High levels of lipoprotein (a) are associated with an increased risk of atherosclerosis, which is a root cause of most heart disease.66

Bolstering Bone Health

Osteoporosis threatens the health of both aging men and women, but it is especially troublesome for elderly women. In the United States, approximately 10 million Americans are affected by osteoporosis, and the financial impact of the disease is estimated to be at least $17.9 billion per year.52 Characterized by a progressive loss of bone mass through a process known as demineralization, osteoporosis increases bone fragility, thus increasing the risk of fracture.10 Among women, estrogen deficiency following menopause plays an enormous role in the development of bone fragility.67 Observational studies have shown that populations with a high intake of soy isoflavones experience a lower incidence of osteoporosis-related fractures compared to Western populations.49

Bolstering Bone Health

Researchers examined data from more than 70 studies for a 2003 review of the evidence regarding phytoestrogens (including lignans) and bone health. These included studies involving bone cells grown in the laboratory, investigations using animal models of human postmenopausal osteoporosis, and human observational/epidemiologic and human dietary intervention studies. “On balance,” wrote the authors of the review, “the collective data suggest that diets rich in phytoestrogens have bone-sparing effects in the long term…”50 More recently, Chinese researchers conducted a meta-analysis, in which data from numerous clinical trials is combined and statistically analyzed. After examining data from ten trials, involving more than 600 subjects, they wrote: “The spine bone mineral density in subjects who consumed isoflavones increased significantly…in comparison to that in subjects who did not consume isoflavones.”51

These investigators concluded: “Isoflavone intervention significantly attenuates bone loss of the spine in menopausal women. These favorable effects become more significant when more than 90 mg/day of isoflavones are consumed.” Furthermore, wrote the Beijing-based scientists, “…Soy isoflavone consumption for six months can be enough to exert beneficial effects on bone in menopausal women.”51 Thus it is possible to protect bone health even later in life, by increasing phytoestrogen intake.

While many of these studies have considered the bone-sparing effects of isoflavone phytoestrogens, rather than lignans in particular, there is strong evidence that lignans are equally effective at protecting against osteoporosis. For example, Japanese researchers conducted an experiment on female rats, removing their ovaries to simulate the effects of menopause on women. The bones of test animals that received the lignan, isotaxiresinol, for six weeks were compared to the bones of rats that did not receive the lignan. Both bone mineral content and bone mineral density were increased in test animals as compared to control rats, and decreases of three bone strength indexes, induced by the removal of the animals’ ovaries, were prevented. “Biochemical markers for bone remodeling revealed that isotaxiresinol slightly increased bone formation and significantly inhibited bone resorption [bone loss] without side effect on uterine tissue,” wrote the scientists.53

Summary

Lignans may not often make headlines, but chances are they’ve been protecting you from a variety of degenerative conditions for as long as you have been consuming whole grains, legumes, vegetables, soy and/or flaxseed. Life Extension® members consume potent lignan concentrates in the supplements they use every day. A plethora of evidence shows that these important phytochemicals work in a variety of ways to prevent cancer, protect the cardiovascular system, ward off viral infection, and maintain bone health.

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.

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