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Plant Profiler

Flaxseed (Linum usitatissimum)


Synonyms / Common Names / Related Terms
Alashi, alpha-linolenic acid, Barlean's Flax Oil, Barlean's Vita-Flax, brazen, common flax, eicosapentaenoic acid, flachssamen, flax, gamma-linolenic acid, Graine de Lin, hu-ma-esze, keten, leinsamen, Linaceae, linen flax, lini semen, lino, lino usuale, linseed, linseed oil, lint bells, linum, Linum catharticum, Linum humile seeds, omega-3 fatty acid, phytoestrogen, prebiotic bread, sufulsi, tesi-mosina, Type I Flaxseed/Flaxseed (51-55% alpha-linolenic acid), Type II Flaxseed/CDC-flaxseed (2-3% alpha-linolenic acid), winterlien.





Mechanism of Action
Pharmacology:
  • Components of flaxseed: Alpha-linolenic acid (ALA), cyanogenic glycosides (linamarin, linustatin, neolinustin), unsaturated fatty acids (linolenic acid, linoleic acid, oleic acid), soluble flaxseed fiber mucilage (d-Xylose, L-Galactose, L-Rhamnose, d-galacturonic acid), lignans (secoisolariciresinol diglycoside (SDG)), monoglycerides, triglycerides, free sterols, sterol esters, hydrocarbons (protein), balast, phenylpropane derivatives. Components of flaxseed oil: Alpha-linolenic acid (ALA), unsaturated fatty acids (linolenic acid, linoleic acid, and oleic acid). Components of flax root: The roots of L. usitatissimum contain measurable concentrations of lignans and isoflavones.55
  • Overview: Flaxseed is composed of multiple chemical constituents, the mechanisms of which have not been fully elucidated. Studies have attributed different properties to the plant, seed, oil, and individual plant components. The biological activity of flax lignans is often attributed to their conversion to the mammalian lignans enterolactone and enterodiol.56 However, intermediate compounds generated during the digestion and metabolism of flax lignans, such as secoisolariciresinol diglycoside (SDG) and its aglycones and secoisolariciresinol (Seco), may also be the principal bioactive molecule. The plant, seed, and oil contain polyunsaturated fatty acids (PUFA), including alpha-linolenic acid (ALA) and linoleic acid. ALA is poorly converted by the human body to eicosapentaenoic acid (EPA) and decosahexaenoic acid (DHA) in certain populations that lack the enzymatic capacity to do this conversion.57 Flaxseed also contains monounsaturated fatty acids (MUFAs), such as oleic acid. ALA and linoleic acid are both essential fatty acids (EFA), meaning they cannot be synthesized by the human body and must be derived from the diet.58,59,60 ALA is a precursor to EPA61,62, and ingestion of flaxseed has been shown to increase cellular EPA levels in a linear manner62,63. However, the linoleic component of flaxseed (an omega-6 fatty acid) is reportedly capable of antagonizing the conversion of ALA to EPA.62 Flaxseed is a concentrated food source of the lignan SDG. Flaxseed also contains small quantities of the lignan matairesinol.27 SDG and matairesinol can be converted into mammalian lignans such as enterodiol and enterolactone by colonic bacteria.27,64
  • Antiarrhythmic effects: Limited human study and scientific reviews suggest a possible antiarrhythmic effect of ALA and omega-3 fatty acids.49,50,51,51. However, another study found that antiarrhythmic effects were concentration-dependently enhanced by DHA and EPA, but not by ALA.65 Higher intake of dietary linolenic acid might be associated with a reduced risk of abnormally prolonged repolarization in men and women.66
  • Anticoagulant and antiplatelet effects: Available data specific to flaxseed (which is unique from fish oil in that it contains up to 20% omega-6 fatty acids and its omega-3 fatty acids must be converted into eicosapentaenoic acid (EPA) and decosahexaenoic acid (DHA)) are conflicting regarding its effects on platelet function. Two studies comparing flaxseed oil to a linoleic acid control (one study in healthy volunteers (N=11) and one study in patients with rheumatoid arthritis (N=22)) reported that flaxseed oil decreased collagen-stimulated platelet aggregation and bleeding time.1,2 Use of a flaxseed supplement also decreased thrombin-stimulated platelet aggregation.3 Conversely, a crossover study in which 10 healthy volunteers consumed both a standardized diet with no supplementation and one supplemented with flaxseed oil found that flaxseed oil had no effect on bleeding time, prothrombin time, or partial thromboplastin time.15 There are case reports of possible interactions between fish oil and warfarin/aspirin67,68, though a recent review concludes that available clinical data do not support the existence of any such clinically relevant interaction 69.
  • Antidiabetic effects: Flax has been studied for its effects on blood sugar, but reports are inconclusive. In a case series, postprandial glucose was reduced by 27% following meals with flaxseed.14 In a case series including 15 obese patients, Nestel et al. reported that a four-week diet high in alpha-linolenic acid (ALA) (20g from margarine products based on flax oil) diminished insulin sensitivity.29 In men with type 2 diabetes, ingestion of omega-3 fatty acids (not specific to flax) showed increases in fasting glucose levels and a 22% increase in mixed meal glucose levels.13
  • Antihypertensive effects: Preliminary evidence suggests that higher levels of linolenic acid in human adipose tissues may correlate with lower blood pressures; for every 1% increase in linolenic acid, there was a 5mmHg drop in mean arterial blood pressure.12 However, it is not clear if these measured adipose levels of linolenic acid are causative, benign markers of disease, or adaptive. Flaxseed supplemented diets have had mixed effects on blood pressure in rats.21,22
  • Antilipemic effects: Proposed lipid-lowering effects of flaxseed (not flaxseed oil) have been attributed to the fiber component consisting of d-xylose, l-galactose, l-rhamnose, d-galacturonic acid, and galactose.7 It has been reported that defatted flaxseed (equivalent to the fiber component of flaxseed) can significantly reduce levels of total cholesterol and low-density lipoproteins (LDL)7, and triglycerides70. The fiber portion of flaxseed has been proposed to exert lipid-lowering effects by enhancing gastric emptying time, altering transit time, interfering with bulk-phase diffusion of fat and increasing excretion of bile acids. It is thought that flaxseed may exert a beneficial effect on atherosclerotic plaque formation due to the antioxidant properties of lignans.28 The results of a mouse study suggest that the lipid lowering effect of flax is not hepatic mediated and may be at the level of cholesterol absorption and/or bile acid reabsorption.71
  • Antineoplastic effects: In 2005, flaxseed was one of the most commonly used products for treating breast cancer.72 Flaxseed contains the highest amount of plant lignans and flaxseed and its defatted meal are the highest producers of mammalian lignans enterolactone and enterodiol (mean 60,110 ± 7,431) compared to other oilseeds, legume hulls, seaweeds and cereal brans.73The amount of lignan production in processed foods is generally linearly dependent on the percent of flaxseed in the product.74 Furthermore, several researchers noted that the breast cancer-modulating effects of phytoestrogens are dependent both on the background diet, genetic makeup, and on the timing of exposure in the life cycle.75,76 The lignan components of flaxseed are often attributed as the protection against hormone-sensitive cancers via antagonizing estrogen receptors or inhibiting enzymes involved with the synthesis of sex hormones27,23, or via effects on epidermal growth factor receptors24,25. However, it is unclear if flaxseed possesses estrogen receptor agonist or antagonist properties. Numerous epidemiologic, animal, in vitro, and in vivo studies support the hypothesis that mammalian lignans have cancer protective effects.30,31,32,33,34,35,36,37,38,39,40,9,41,42,43,44,45,46,47 Several mechanisms of action have been proposed for these effects including apoptosis20, inhibition of cancer cell growth due to enterolactone77, and reductions in plasma insulin-like growth factor 1 due to secoisolariciresinol diglycoside (SDG)78. Rat studies have reported that a 2% alpha linolenic acid (ALA) preparation reduces tumor size in nude mice over higher concentration (8%, 12%) preparations.79,80 Flaxseed (administered in a Western-style diet) did not protect against the development of intestinal neoplasia in ApcMin mice any more than a Western-style diet, adjusted for fiber and/or phytate content.81 This could be related to the fact that mammalian lignans are produced from plant lignans (in flaxseed) in the colon and cancers in the APCMin mice occur primarily in the small intestines. Feeding flaxseed, purified flaxseed lignan or oil to carcinogen treated rats have been shown to be protective against colon cancer.82,83,8,9,46
  • Antioxidant effects: Lignans can act as platelet-activating factor-receptor antagonists, and inhibit the production of oxygen free radicals by neutrophils.4,5 Secoisolariciresinol diglycoside (SDG), a plant lignan found in flaxseed, has been found to possess antioxidant properties.5 Pattanaik et al. demonstrated that cardiac cellular damage was attenuated when dogs were given an endotoxin with flaxseed vs. endotoxin alone.6 Theoretically, flaxseed (not flaxseed oil) may increase lipid peroxidation and thus may increase oxidative injury.7 Diets supplemented with defatted flaxseed have been associated with a decrease in protein thiol groups, suggesting an increase in oxidative stress.7
  • Arterial compliance: In a case series including 15 obese patients, it was found that a four-week diet high in alpha linolenic acid (ALA) (20g from margarine products based on flax oil) improves arterial compliance.29
  • Cognitive effects: Preliminary evidence supports the idea that deficiencies or imbalances in certain highly unsaturated fatty acids may contribute to attention deficit hyperactivity disorder (ADHD). Supplementation with flax in these populations resulted in an increase in alpha-LNA and a slight decrease in the ratio of arachidonic acid to eicosapentaenoic acid (EPA).52
  • Hormonal effects: Flaxseed (not flaxseed oil) is a rich source of plant lignans.4,5 Lignans are often referred to as phytoestrogens, and may possess estrogen receptor agonist or antagonist properties, with unclear effects on hormone-sensitive cancers such as breast, uterine, and prostate cancer.23 It has been proposed that flaxseed and its lignans have potent antiestrogenic effects on estrogen receptor-positive breast cancer.30 Flaxseed is a concentrated food source of the lignan secoisolariciresinol diglycoside (SDG).27 Enterlactone and enterodiol (metabolized from flaxseed in the bowel) may decrease cell proliferation and inhibit aromatase, 5-alpha-reductase, and 17-beta-hydroxysterioid dehydrogenase activity, which may offer a reduction in the risk of breast, prostate and other hormone sensitive cancers.27 It has also been shown that lignans increase sex-hormone-binding globulin synthesis.27 In humans, flaxseed has been reported to significantly reduce serum levels of 17-beta-estradiol and estrone sulfate and increase prolactin levels27, increase the urinary ratio of the two estrogen metabolites 2-hydroxyestrogen and 16 alpha-hydroxyestrone26,16, increase urinary excretion levels of enterodiol and enterolactone84, and increase fecal excretion of enterodiol, enterolactone, and matairesinol.17 It has been suggested that flaxseed has more potent effects on estrogen metabolism than soy.85
  • Inflammation/immune function: Flaxseed and flaxseed oil may possess anti-inflammatory properties due to the presence of ALA which when converted to EPA and DHA, inhibit neutrophil inflammatory responses in humans.10 These abilities may also result from the inactivation of LTA (leukotriene) epoxide hydrolase which decreases leukotriene B4 formation, and from the inhibition of leukotriene B4 and platelet-activating factor-stimulated chemotaxis via attenuation of the formation of [3H] inositol tris-phosphate by the phosphatidylinositol-selective phospholipase C. It has also been found that ALA decreases the production of arachidonic acid, thereby causing a reduction in inflammation.11 ALA may suppress cell-mediated immunity/T-cell function without affecting humoral immunity/B-cell function (shown in immunocompromised patients).86
  • Laxative effects: Flaxseed (not flaxseed oil) may produce laxative effects by increasing fecal volume and fecal weight18 and stimulating peristalsis due to stretch reflexes. Flaxseed does not appear to be affected by gastric acid or intestinal alkaline conditions. It has also been suggested that flaxseed may coat and protect intestinal mucosa.
  • Renoprotective effects: Flaxseed fed to rats with polycystic kidneys increases citrate excretion and reduces histological damage.87 A diet supplemented with 15% flaxseed for 14 weeks delays the onset of proteinuria and significantly reduces mortality in a mouse model of lupus nephritis.88
  • Weight loss effects: There is limited research on the effects of flaxseed flour in obese patients. Early study has not shown evidence of benefit in weight loss or reduction of BMI, although there may be a role of flax in treating inflammation associated with obesity.19 In one study, ingestion of alpha-linolenic acid (derived from flax) in combination with arginine and yeast RNA was associated with weight gain in HIV patients.48

Pharmacodynamics/Kinetics:
  • There are limited pharmacokinetic data available for flaxseed. Urinary excretion of lignan metabolites has been reported as a dose-dependent biomarker of flaxseed intake.89,89,90,91,20 Diets consisting of 5-10g of ground flaxseed per day significantly increased the urinary excretion of enterodiol, enterolactone, and total lignans vs. a diet without flaxseed. There is substantial inter-individual variation in plasma concentrations and urinary excretion of enterolignans.54,90
  • Bioavailability: In a randomized, crossover study, healthy subjects supplemented their diet with 0.3g whole, crushed, or ground flaxseed per kilogram of body weight per day).92 The mean relative bioavailability of enterolignans from whole flaxseed compared with ground flaxseed was 28% (p≤0.01), whereas that of crushed flaxseed compared with ground flaxseed was 43% (p≤0.01). Crushing and milling of flaxseed substantially improve the bioavailability of the enterolignans.
  • Metabolism: Alpha-linolenic acid (ALA) is a major dietary (n-3) fatty acid. ALA is converted to longer-chain (n-3) PUFA, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Precursors from unground whole flaxseed are converted by the bacterial flora in the colon to mammalian lignans.93
  • AUC: Peak blood glucose values and AUC were improved by ingestion of flax fiber in healthy subjects.18
  • Storage: Processing and cooking may alter the lipid content and stability of alpha-linolenic acid in spaghetti containing ground flaxseed.53 In a functional flaxseed mousse dessert, the amount of flaxseed was enough to satisfy 30% of recommended dietary allowance of linolenic acid. Shelf life data showed a good stability for this product as well as good consumer acceptability.94

References
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  2. Nordstrom, D. C., Honkanen, V. E., Nasu, Y., Antila, E., Friman, C., and Konttinen, Y. T. Alpha-linolenic acid in the treatment of rheumatoid arthritis. A double- blind, placebo-controlled and randomized study: flaxseed vs. safflower seed. Rheumatol Int 1995;14(6):231-234. 7597378
  3. Bierenbaum ML, Reichstein R, Watkins TR, and et al. Reducing atherogenic risk in hyperlipemic humans with flax seed supplementation: a preliminary report. J Am Coll Nutr 1993;12:501-504.
  4. Prasad, K., Mantha, S. V., Muir, A. D., and Westcott, N. D. Reduction of hypercholesterolemic atherosclerosis by CDC-flaxseed with very low alpha-linolenic acid. Atherosclerosis 1998;136(2):367-375. 9543108
  5. Prasad, K. Reduction of serum cholesterol and hypercholesterolemic atherosclerosis in rabbits by secoisolariciresinol diglucoside isolated from flaxseed. Circulation 3-16-1999;99(10):1355-1362. 10077521
  6. Pattanaik, U. and Prasad, K. Oxygen Free Radicals and Endotoxic Shock: Effect of Flaxseed. J Cardiovasc Pharmacol Ther 1998;3(4):305-318. 10684513
  7. Jenkins, D. J., Kendall, C. W., Vidgen, E., Agarwal, S., Rao, A. V., Rosenberg, R. S., Diamandis, E. P., Novokmet, R., Mehling, C. C., Perera, T., Griffin, L. C., and Cunnane, S. C. Health aspects of partially defatted flaxseed, including effects on serum lipids, oxidative measures, and ex vivo androgen and progestin activity: a controlled crossover trial. Am J Clin Nutr 1999;69(3):395-402. 10075322
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  10. Sperling, R. I., Benincaso, A. I., Knoell, C. T., Larkin, J. K., Austen, K. F., and Robinson, D. R. Dietary omega-3 polyunsaturated fatty acids inhibit phosphoinositide formation and chemotaxis in neutrophils. J Clin Invest 1993;91(2):651-660. 8381824
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  15. Kelley, D. S., Nelson, G. J., Love, J. E., Branch, L. B., Taylor, P. C., Schmidt, P. C., Mackey, B. E., and Iacono, J. M. Dietary alpha-linolenic acid alters tissue fatty acid composition, but not blood lipids, lipoproteins or coagulation status in humans. Lipids 1993;28(6):533-537. 8102770
  16. Haggans, C. J., Hutchins, A. M., Olson, B. A., Thomas, W., Martini, M. C., and Slavin, J. L. Effect of flaxseed consumption on urinary estrogen metabolites in postmenopausal women. Nutr Cancer 1999;33(2):188-195. 10368815
  17. Kurzer, M. S., Lampe, J. W., Martini, M. C., and Adlercreutz, H. Fecal lignan and isoflavonoid excretion in premenopausal women consuming flaxseed powder. Cancer Epidemiol Biomarkers Prev 1995;4(4):353-358. 7655330
  18. Dahl, W. J., Lockert, E. A., Cammer, A. L., and Whiting, S. J. Effects of flax fiber on laxation and glycemic response in healthy volunteers. J Med Food 2005;8(4):508-511. 16379563
  19. Faintuch, J., Horie, L. M., Barbeiro, H. V., Barbeiro, D. F., Soriano, F. G., Ishida, R. K., and Cecconello, I. Systemic inflammation in morbidly obese subjects: response to oral supplementation with alpha-linolenic acid. Obes Surg 2007;17(3):341-347. 17546842
  20. Thompson, L. U., Chen, J. M., Li, T., Strasser-Weippl, K., and Goss, P. E. Dietary flaxseed alters tumor biological markers in postmenopausal breast cancer. Clin Cancer Res 5-15-2005;11(10):3828-3835. 15897583
  21. Brandle M, Al Makdessi S, Weber RK, and et al. Prolongation of life span in hypertensive rats by dietary interventions. Effects of garlic and linseed oil. Basic Res Cardiol 1997;92:223-232.
  22. Talom, R. T., Judd, S. A., McIntosh, D. D., and McNeill, J. R. High flaxseed (linseed) diet restores endothelial function in the mesenteric arterial bed of spontaneously hypertensive rats. Life Sci 1999;64(16):1415-1425. 10321721
  23. Adlercreutz, H. Epidemiology of phytoestrogens. Baillieres Clin Endocrinol Metab 1998;12(4):605-623. 10384816
  24. Chen, J., Stavro, P. M., and Thompson, L. U. Dietary flaxseed inhibits human breast cancer growth and metastasis and downregulates expression of insulin-like growth factor and epidermal growth factor receptor. Nutr Cancer 2002;43(2):187-192. 12588699
  25. Dabrosin, C., Chen, J., Wang, L., and Thompson, L. U. Flaxseed inhibits metastasis and decreases extracellular vascular endothelial growth factor in human breast cancer xenografts. Cancer Lett 11-8-2002;185(1):31-37. 12142076
  26. Haggans, C. J., Travelli, E. J., Thomas, W., Martini, M. C., and Slavin, J. L. The effect of flaxseed and wheat bran consumption on urinary estrogen metabolites in premenopausal women. Cancer Epidemiol Biomarkers Prev 2000;9(7):719-725. 10919743
  27. Hutchins, A. M., Martini, M. C., Olson, B. A., Thomas, W., and Slavin, J. L. Flaxseed consumption influences endogenous hormone concentrations in postmenopausal women. Nutr Cancer 2001;39(1):58-65. 11588903
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