Life Extension Magazine

Life Extension Magazine April 2010

Nutraceutical Update

Lignans 

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