Biomarker of anticancer effects of flaxseed in humans

Project Description

Flaxseed has been shown to reduce the mammary tumor incidence, number and/or size when provided at either the initiation, early or late promotion stages of carcinogenesis in carcinogen-treated rats. These are thought to be due to its exceptionally high concentrations of the mammalian lignan precursor, secoisolariciresinol diglycoside (SDG), which is metabolized to the mammalian lignans enterodiol (ED) and enterolactone (EL). The chemical structural similarity of these compounds to estradiol (E2) has led to the classification of these compounds as phytoestrogens.

Estradiol is a major proliferative stimulus to breast cancer cells and tumors. It is metabolized in the liver to the major urinary metabolites, 2-hydroxyestrone (2-OHEI) and 16a-hydroxyestrone (16a-OHE1). These compounds exhibit distinct biological activities. 16a-OHE1 is regarded as an estrogen agonist, while 2OHE1 is generally seen as having minimal biological activity. It has been suggested that a low ratio of 2/16a-OHE 1 may be an endocrine risk factor for breast cancer development. Therefore, by increasing this ratio the risk of breast cancer would be reduced.

Four studies have been conducted in our laborato1y to explore the health benefits of flaxseed in pre- and post-menopausal women. Urine samples from sub-samples of these subjects were collected and analyzed for the urinary estrogen metabolites, to explore the potential of flaxseed to influence estrogen metabolism. In the first study in postmenopausal women, daily diet supplementation with 25 g flaxseed for 16 weeks increased the urinary 2-OHEl and the 2/16aOHE1 ratio when compared to supplementation with 25 g soy or placebo muffins. Supplementation with soy did not cause significant changes in urinary estrogen metabolites when compared to supplementation with placebo muffin. In the second study in postmenopausal women, supplementation with 1, 2 or 3 tablespoons (10, 20 or 30 g) flaxseed for 3 months tended to increase the urinaiy 2/16a-OHE 1 ratio but the changes did not reach significance. In the third study in premenopausal women with dense manunogram, daily supplementation with 25 g flaxseed for 12 months resulted in significantly higher urinary 2/16a-OHE1 ratio compared with the control. Similar increase in urinary 2/16a-OHE1 ratio was observed in premenopausal women with cyclical mastalgia who supplemented their diet with 25 g FS daily for 3 months. Although flaxseed supplementation increased the urinary lignan excretion in all the studies, significant relationship between urinary lignans and the chai1ges in 2/l 6a-OHE1 ratios was observed only in the first study.

In conclusion, flaxseed supplementation significantly altered estrogen metabolism in a manner that suggested an overall antiestrogenic, and therefore cancer protective effect. This effect occurred in both postmenopausal and premenopausal women.