Flaxseed Lignans and Cancer Reduction

An estimated two out of five Canadians will be diagnosed with cancer during their lifetime and one out of four people are predicted to die from the disease (1). Lung, colorectal, breast and prostate cancers account for half of all cancers diagnosed in Canada. In the United States, over 1.7 million new cancer cases were detected in 2015 (2). The role of flaxseed consumption in cancer reduction and prevention are active areas of research and show much promise.

Flaxseed contains three components that may help to lower cancer risk: the plant lignan secoisolariciresinol diglucoside (SDG), representing 1% of dry weight, the omega-3 polyunsaturated fatty acid alpha-linolenic acid (ALA), accounting for 20% of flaxseed dry weight, and soluble fibre representing 6% of dry weight. Flaxseed and its components have been shown to possess numerous anti-cancer properties (3).

Lignans are phytoestrogens that are found in many plants, but flaxseed is the richest source (4). The predominant lignan in flaxseed is SDG, though small amounts of other lignans are also present, including pinoresinol, lariciresinol, and matairesinol. After ingestion, SDG is converted to mammalian lignans by bacteria in the colon. The first step in the conversion produces secoisolariciresinol (SECO), which is then converted to enterodiol and enterolactone (5). These lignans are structurally similar to estradiol, the major form of estrogen in the body, which permits their binding to estrogen receptors (5).

Prostate and breast cancers are the leading types of cancer diagnosed in men and women, respectively (2). Sex hormones (estrogen and testosterone) play key roles in the development and progression of these cancers by increasing cell proliferation (production of new cells), metastasis (spread of cancer to other organs), and angiogenesis (growth of new blood vessels that support the spread of cancer) (5). Lignans compete with estrogen and testosterone for binding to their respective receptors (6). When phytoestrogens bind to estrogen or testosterone receptors their estrogenic activity is weaker than that of endogenous hormones. Lignans also inhibit the enzyme aromatase which converts androgens into estrogen (6).

SECO, enterodiol and enterolactone (EL) possess antioxidant activity (5). Oxidative stress occurs when there is an imbalance between reactive oxygen species and antioxidants in the body which results in cellular damage. Oxidative stress and inflammation are closely linked (7). Plasma EL concentration has been shown to be inversely correlated with plasma F2-isoprostane levels, a biomarker of oxidative stress (8).

In animal models, flaxseed lignans have been shown to reduce tumour size, number, and degree of invasiveness of cancer cells as well as to induce physiological changes in the mammary gland and colon which are known to lower the risk of cancer development (5). Benefits of flaxseed lignans also include protecting healthy tissue while not hindering the effectiveness of the radiation in destroying tumours during cancer radiation therapy (9).

Several recent studies confirm the anti-carcinogenic effects of lignans. Anti-metastatic, anti-proliferative, anti-migratory and anti-clonogenic cellular mechanisms of EL were found in breast cancer cells (10). In addition, flaxseed lignans enhanced the cytotoxic effect of chemotherapeutic drugs in metastatic breast cancer cell lines (11).  In concert with previous research, these new investigations suggest a powerful anti-carcinogenic role for flaxseed lignans in several types of cancers.

References

  1. Canadian Cancer Society. Canadian Cancer Statistics 2017.
  2. American Cancer Society. Cancer Facts & Figures. American Cancer Society, 2018.
  3. Mason JK, et al. Appl Physiol Nutr Metab 2014;39:663-678.
  4. Lowcock EC, et al. Cancer Causes Control 2013;24:813-816.
  5. Adolphe JL, et al. Br J Nutr 2010;103:929-938.
  6. Saarinen N, et al. Mechanism of anticancer effects of lignans with a special emphasis on breast cancer In: Flaxseed in Human Nutrition. Thompson LU, Cunnane SC, eds.2nd ed: AOCS Press, 2003;223-231.
  7. Aggarwal BB, et al. Oncology (Williston Park) 2011;25:414-418.
  8. Vanharanta M, et al. Atherosclerosis 2002;160:465-469.
  9. Christofidou-Solomidou M, et al. Radiat Res 2012;178:568-580.
  10. Mali AV, Joshi AA, Hegde MV, Kadam ShS. Asian Pac J Cancer Prev. 2017 Apr 1;18(4):905-915.
  11. Di Y, De Silva F, Krol ES, Alcorn J. Nutr Cancer. 2018 Jan 5:1-10. doi: 10.1080/01635581.2018.1421677.