Reactive oxygen species (ROS) have been implicated in the development of diabetes mellitus.  SDG isolated from flaxseed is an antioxidant.  An investigation was made of the effects of SDG on the development of diabetes in rats, to determine if SDG can prevent/reduce the development of diabetes and if this prevention/reduction is associated with reduction in oxidative stress.  RESULTS:  SDG prevented the development of diabetes by 75%. (Prasad K, et a, Mol Cell Biochem, 206(1-2):  2000; Prasad K. Mol Cell Biochem, 209(1-2): 89.2000)

Flaxseed SDG may have a therapeutic role in lupus nephritis. (Clark W. et al Lupus, 9(6): 429, 2000)

Asian men have a much lower incidence of prostate cancer and possibly of benign prostatic hyperplasia (BPH) than Western counterparts.  Vegetarian men have a lower incidence of prostate cancer than omnivorous males. Plant lignans give rise to the mammalian lignans, enterodiol and enterolactone; the richest source is linseed (flaxseed).  In addition to their oestrogenic activity, these plant compounds can interfere with steroid metabolism and bioavailability, and also inhibit enzymes, such as tyrosine kinase and topoisomerase, which are crucial to cellular proliferation and hence may contribute to lower incidences of prostrate cancer.  (Eur Urol, 35(5-6): 377, 1999)

Dietary estrogens, such as lignan-rich flaxseed, are similar in structure to endogenous sex steroid hormones and act in vivo to alter hormone metabolism and reduce subsequent cancer risk in postmenopausal women. (Hutchins A, Cancer Epidemiol Biomarkers Prev, 9(10): 1113, 2000)

Research suggests that SDG reduces hypercholesterolemic atherosclerosis and that this effect is associated with a decrease in serum cholesterol, LDL-C, and lipid peroxidation product and an increase in HDL-C and antioxidant reserve.  (Prasad K. Circulation, 99(10): 1355, 1999)

Phytoestrogens are diphenolic compounds that are present in several plants eaten by human beings.  Flaxseed is a particularly abundant source of phytoestrogens.  When ingested in relatively large amounts, phytoestrogens have been shown to have significant estrogen agonists/antagonists effects in animals and humans.  There is epidemiological, laboratory and clinical evidence which indicates that phytoestrogens, like certain selective estrogen receptor modulators, have an antiproliferative effect on the breast, and positive effects on the lipoprotein profile and bone density.  They might also improve some of the climacteric symptoms.  (Brzezinski A & Bebi A. Eur J Obstet Gynecol Reprod Biol. 85(1): 47, 1999.

Flaxseed is high in secoisolariciresinol diglycoside (SDG), the precursor of mammalian lignans, which can affect mammary gland structure.  Lifetime or gestation and lactation exposure to 5 or 10% flaxseed induce structural changes in the mammary gland that may potentially reduce mammary cancer risk. (Tou J & Thompson L. Carcinogenesis, 20(9): 1831, 1999)

Flaxseed and SDG, regardless of dose, appeared to delay the progression of MNU-induced mammary tumorigenesis.  (Rickard S. et al, Nutr Cancer; 35(1): 50, 1999)

Because flaxseed and its lignans are colon cancer protective, it is concluded that, in contrast to other studies, beta-glucuronidase activity may play a beneficial role in their presence by increasing mammalian lignan absorption and enterohepatic, (Jenab M, et al, Nutr Cancer, 33(2): 154, 1999)

Dietary supplementation with secoisolariciresinol diglycoside (SDG), a lignan precursor isolated from flaxseed, significantly reduced pulmonary metastasis cells and inhibited the growth of metastatic tumors that formed in the lungs. (Li D. et al, Cancer Lett, 142(1): 91, 1999)

Flaxseed the richest source of lignans reduces metastasis and inhibits the growth of the metastatic secondary tumors in animals.  Flaxseed may be a useful nutritional adjuvant to prevent melanoma metastasis in cancer patients. (Yan L, et al, Cancer Lett, 124(2): 181, 1998)

Flaxseed contains lignans that have antioxidant activities and inhibit platelet-activating factor (PAF).  Pretreatment with flaxseed attenuated emdotoxin induced cardiac dysfunction and cellular damage.  Flaxseed antioxidant and anti-PAF agents may be effective in the treatment of ET shock. (Pattanaik U & Prasad K, J Cardiovasc Pharmacol Ther, 3(4): 305. 1998)

The mammalian lignans enterolactone (EL) and enterodiol (ED) derived from precursors in foods, particularly flaxseed, have been shown to reduce the mammary tumor growth due to their antiestrogenic properties. Lignans are growth inhibitors of colon tumor cells        and they may act through mechanism(s) other than antiestrogenic activity, (Sung M, et al, Anticancer Res 18(3A: 1405, 1998)

Flaxseed, the richest source of mammalian lignan precursors, such as secoisolariciresinol diglycoside (SD), has been shown over the short term to decrease some early markers of colon cancer risk.  This study determined that flaxseed has a colon cancer protective effect, that it is due, in part to SD and that the protective effects of flaxseed is associated with increase beta-glucuronidase activity. (Jenab M & Thompson L, Carcinogenesis, 17:1343, 1996)

Flaxseed, a rich source of mammalian lignan precursor secoisolariciresinol-diglycoside _SD) and alpha-linolenic acid (ALA), has been shown to be protective at the early promotion stage of carcinogensis. In conclusion, the SD lignans in flaxseed appears to be beneficial throughout the promotional phase of carcinogenesis whereas the oil components is more effective at the stage when tumors have already been established. (Thompson L, et al, Carcinogenesis, 17:1373, 1996)

Flaxseed lignans have antitumor, antimitotic, antioxidant and weak estrogenic activity, are potentially the richest source of phytoestrogens in the human diet and may be linked to a low incidence of breast and colon cancer.  Secoisolariciresinol was discovered to be a very potent antioxidant similar to BHA.  No toxicity was found in the lignans.  (Obermeyer W, et al (US Food and Drug Administration, center for Food Safety and Applied Nutrition, Div. Contaminants Chem., Natural Products Branch), Meeting Of The Federation Of American Societies For Experimental Biology On Experimental Biology March/April, 1993, Faseb J (Fed Am Soc Exp Biol), A863, 1993)

Vitamin E-deficient diets containing 5 to 20% ground flaxseed protected mice against the malarial parasite Plasmodium voelii as shown by decreased parasitemia and enhanced survival. (Levander O, et al, (USDA/ARS Human Nutrition Research Center, Vitamin Mineral Nutrition Laboratory), Nutrition Research, 11, 1991)

Cyanogenic Glycosides

Flaxseed is increasingly being used in many food products because of its high content of alpha-linolenic acid and dietary fiber.  However, flaxseed contains cyanogenic glycosides, which release toxic hydrogen cyanide in the presence of water (autohydrolysis).  (Chadha R, et al (Food Research Division, Bureau of Chemical Safety, Ottawa, Ontario, Canada), Food Addit Contam, 12: 527, 1995) Cyanogenic glycosides) linamarin, linustatin, neolinustatin) were highest in extracted flaxseed mucilage. We conclude that up to 50 g high-alpha-linolenic acid flaxseed is palatable, safe and may be nutritionally beneficial in humans by raising n-3 fatty acids in plasma and erythrocytes and by decreasing post-prandial glucose responses. Cunnane S, et al, (University of Toronto, Toronto, Canada) Br J Nutr, 69:443, 1993)

The presence of cyanogenic glycosides and diglucosides in flaxseed is a concern, as they may release cyanide upon hydrolysis. In addition, the polyunsaturated fatty acid may undergo thermal or auto-oxidation (rancidity) when exposed to air or high temperatures that are used in food preparation (& needed to detoxify the cyanogenic glycosided in the mucilage).  Cyanide levels produced as a result of autolysis, are below the harmful limits to humans (remember however that “the dose maketh the poison”) (Wanasundara P & Shahidi F, Adv Exp Med Biol, 434: 307, 1998)

Cyanogenic Glycosides in Flaxseed

The presence of cyanogenic glycosides in the diet is significant only in relation to dose and the nutritional status of the consumer.  Flax seed meal contains two cyanogenic glycosides, linustatin and neolinustatin. Many foods are slightly cyanogenid (e.g. wheat and barley!), probably as an evolutionary adaptation to discourage herbivory and our body has a limited capacity to detoxify low concentrations of cyanide through addition of sulpher (from amino acids) to form thiocyanate or reaction with cysteine directly to form beta-cyanoalanine.  Thus if the dietary levels of sulpher-containing amino acids are high the body can resist a low intake of cyanide, but if the diet is low in protein overall or due to imbalances in vegetable protein amino acid composition it is low in the sulphur containing amino acids, then we see toxicity.

The two most common symptoms of chronic cyanide intoxication are goiter, probably cause by high levels of thiocyanate formation where dietary protein levels are adequate and the detoxification mechanism is operation in high gear but the body can’t clear the thiocyanate product quickly enough, and fibrocalculous pancreatic diabetes associated with protein malnutrition, where toxicity is probably directly due to cyanide because of the lack of adequate detoxification.  Few of us are not likely to consume significant quantities of flaxseed, nor are those people consuming flax seed likely to have protein malnutrition.

Robin J Marles. Ph.D Associate Professor, Botany Department Brandon University, Brandon, MB R7A 6A9 CANADA