Guest guest Posted June 19, 2005 Report Share Posted June 19, 2005 Lignans: Beyond Flaxseed Oil JoAnn Guest Jun 19, 2005 13:08 PDT Dallas Clouatre, Ph.D. http://www.willner.com/article.aspx?artid=58 Flaxseed is one of the world's oldest foods. It was consumed by the ancient Babylonians more than 5,000 years ago and was prized by the Greeks and Romans for its health-promoting benefits. The seeds supply both essential fatty acids and fiber, much of it soluble like that found in fruit and oat bran. Recent research has brought to light yet more benefits from components contained within flaxseed fiber known as lignans. Many health-conscious shoppers are familiar with flax oil. Approximately 41 percent of flaxseed consists of fatty acids, of which about 70 percent is polyunsaturated. There is a high ratio of alpha-linolenic acid (an omega-3 fatty acid) to linoleic acid (an omega-6 fatty acid). More than half the fat in flaxseed is of the omega-3 fatty acid type. Both alpha-linolenic acid and linoleic acid are essential because the body cannot manufacture them from any other substances, yet they are the parent compounds for many physiologically active substances, such as eicosanoids. The average American's diet supplies a ratio of the two which is roughly 1:20 in favor of omega-6, whereas an ideal ratio of omega-3 to omega-6 fatty acids is between 1:1 and 1:3. Therefore, eating flaxseed or flaxseed oil can help to balance the ratio of these fatty acids found in the normal diet. Omega-3 fatty acids protect against coronary heart disease, stroke, hypertension, inflammation, autoimmune disorders and a number of cancers. What Are Flax Lignans? Several years ago, I first ran across lignans, another component found in flaxseed that helps to defend against sex-based cancers in both women and men. (See The Prostate Miracle, Kennsington Books, 2000.) Lignans are a group of sugar-like molecules that are found in plants, especially the seeds. Lignans should not be confused with lignin, which is an insoluble fiber that is structurally related. Indeed, in the plant world, lignans might be said to be the building blocks for lignin. Lignans are especially abundant in flaxseed, with some authorities estimating that flax contains from 75 to 800 times as much of these items as do other food sources. Flax lignans form fibrous chains that effectively bind toxins found in the gastrointestinal tract. However, flax lignans are far more than just fiber. Lignans are phytoestrogens, that is, plant compounds which weakly resemble estrogens, the female sex hormones produced in the human body in both women and men. Other such phytoestrogenic compounds included isoflavones, coumestans, flavonoids and phytosterols. Phytoestrogens can compete for receptor sites with the body's own estrogen when estrogen levels are high or supplement estrogenic activity when estrogen levels are low. Just as significantly, they complete with what are known as xenoestrogens. Xenoestrogens are harmful estrogen-like molecules from the environment, such as are found in pesticides, solvents, adhesives, soap emulsifiers, plastics, PCB's, etc. One reason that eating fruits, vegetables and legumes promotes health and reduces the risk of cancer is that phytoestrogens found in these foods help to protect us from toxins that we have added to the environment. Flax is particularly rich in the lignan secoisolariciresinol diglycoside (SDG), and it also contains small amounts of the lignans matairesinol, pinoresinol and isolariciresinol. Bacteria in the digestive tract act on some of these lignans and convert them into yet more potent substances. The lignans SDG, matairesinol and pinoresinol in flax are converted in the colon of humans and other animals to the mammalian lignans enterodiol and enterolactone. Enterodiol and enterolactone are called mammalian lignans because they are produced by bacteria in the mammalian colon, but are not found in plants. After a circuitous route through the body, these flax lignan metabolites are removed by the kidneys. The Benefits of Lignans Although flax lignans are not as powerful as the body's own estrogens, they still can exert important effects. In general, flax lignans are balancing to estrogen metabolism. If the level of estrogens in the blood is high, such as in some women who suffer from premenstrual syndrome, then lignans will tend to reduce the body's response. If the level of estrogens in the blood is low, such as in women after menopause, then lignans will tend to increase the body's response. Hence, lignans can act either as phytoestrogens (weak estrogens) or as antiestrogens, depending on the circumstances. The major benefits of flax lignans that have been researched thus far are in these areas: protection against breast, prostate and colon cancers; improvements in cardiovascular health; reduction in menopause symptoms; antioxidant protection; support for bone health. At this point in time, more than 100 research studies have been published on flax lignans. Many of these concern the role of lignans is preventing or ameliorating cancers. As already indicated, lignans can act either as weak estrogens or as antiestrogens. The impact on sex hormone sensitive cancers, such as breast and prostate cancers, may be significant. Flax lignans (after their transformation in the gut to mammalian lignans) stimulate the production by the liver of sex hormone- binding globulin (SHBG). This increases the clearance of sex hormones from the body and may have other effects. By displacing estrogen being carried by SHBG, lignans, moreover, can reduce the level of estrogen carried to the tissues. Lignans, furthermore, decrease the activity of an enzyme known as estrogen synthetase (aromatase), which can increase estrogen production undesirably from fat cells and other sources in men as well as women. Animal studies and human population studies support the protective role of lignans against hormone-sensitive cancers. As of yet, however, clinical trials testing only purified lignans remain rare and much information must be extrapolated from studies using flaxseed or reduced-oil flaxseed. In a group of postmenopausal women, consumption of 10 grams of ground flax daily for seven weeks significantly increased the urinary excretion of 2-hydroxyestrogen, a metabolite of estrogen that is considered to protect against breast cancer. In another preliminary study, this one involving 39 women with newly-diagnosed breast tumors, the subjects every day ate a muffin containing either no flax or 25 grams of flaxseed for just over a month. The women who ate the flaxseed muffins exhibited reductions in breast cell proliferation and in the rate of tumor growth. Men, too can benefit. At least one pilot clinical trial can be found in the medical literature regarding prostate cancer. The finding was a reduction in the markers for cancer activity. Interestingly, flax consumption does not appear to affect testosterone levels in men and, as noted already, flax lignans inhibit that activity of the aromatase enzyme that increases estrogen production. There may be other mechanisms at work than the antiestrogenic factor. Lignans seem to reduce the incidence of colon cancer, which is nonhormone-sensitive. Research with patients with prostate and other cancers has shown that there is a dramatic lowering of the lignan content in the body wastes compared with non-cancerous individuals. This suggests that lignan compounds may help boost immune response and the detoxification of the by-products of metabolic processes. Research also suggests that flax and its lignans may decrease angiogenesis (the growth of blood vessels that supply oxygen and nutrients to tumors for growth). Flaxseed as a source of fiber and omega-3 fatty acids already might be expected to influence cardiovascular health. Now we know that flax lignans by themselves offer additional benefits. They possess antioxidant properties and in animal trials have been found to lower cholesterol and to protect against induced atherosclerosis. Women may have the most to gain in terms of total health benefits. Because lignans are phytoestrogens, under conditions of low blood estrogen levels, such as menopause, lignans can weakly activate estrogen receptors. This action is similar to that found with isoflavones from various legumes. Flaxseed consumption (40 grams per day for four months) in one study was as effective as hormone replacement therapy in reducing menopause symptoms among 25 menopausal women. Conversely, an antiestrogenic effect (and perhaps an improved rate of estrogen clearance) would seem to have been demonstrated in a trials with premenopausal women taking flax seed who exhibited reduced breast pain and tenderness during the menstrual period. The fact that flax acts to return balance to sex hormone clearance and receptor responses rather than simply driving reactions in one or another direction indicates the inherent safety of flax and its constituent components. Other potential benefits include improvements in bone health and kidney function. There even is evidence that suggests that lignans may help to protect against hair loss and acne. Flaxseed and flaxseed lignans thus promise a remarkable range of benefits to both women and men. Finally, it should not be forgotten that flaxseed can be used to dramatically improve efforts at losing and maintaining proper weight while promoting good health. Ann Louise Gittleman gives a very nice program in The Fat Flush Plan (McGraw-Hill, 2002) and I provide detailed instructions in Chapter 3 of Anti-Fat Nutrients, 4th edition (Basic Health Publications, 2004). Differences In Sources of Flaxseed and Other Issues Flaxseed comes in both brown and golden forms. According to the Flax Council Of Canada website, there is no significant difference between brown flax seed and golden (yellow) flax seed in terms of nutrition. Some individuals prefer the taste of one to the other. Minor differences in oil content and other characteristics exist among flax varietals, of course. A couple of rounded tablespoonsful (12 - 15 grams) of ground flaxseed typically will supply about 200 milligrams of all lignan fractions. To put this in context of the studies discussed above, 10 grams of flax provides approximated 20 milligrams of secoisolariciresinol, the active fraction of the primary flax lignan secoisolariciresinol diglycoside (SDG). Studies with ground flaxseed at dosages from 5 to 50 grams per day thus supplied 10 to 350 milligrams of secoisolariciresinol. This indicates the inherent safety of flax and its lignans. The only group which perhaps should not supplement with large amounts of flaxseed or its lignans (flax oil is OK) is pregnant women or those looking to conceive. No harm has ever been found, but simple prudence suggests caution in taking any type of supplement during pregnancy. Flax lignans now are available not only from flaxseed itself, but also from enriched flax oils and from specially concentrated lignan extracts. Some authorities suggest that flaxseed is best utilized when the daily diet is supplemented with small amounts of vitamin B6 (perhaps 5 milligrams) and the mineral zinc (15 milligrams). A good intake of flaxseed is 5 to 30 grams per day. If supplementing with a concentrated source of secoisolariciresinol diglycoside (SDG), look to increase intake from up to 50 milligrams per day. Dallas Clouatre, Ph.D., is a Jarrow Formulas consultant based in Santa Monica, California. He is a prominent industry consultant in the US, Europe, and Asia, and is a sought-after speaker and spokesperson. He earned his A.B. from Stanford and his Ph.D. in European Intellectual History from the University of California at Berkeley. A member of the American College of Nutrition, he is a regular contributor to various industry publications. He is the author of numerous books, including FAQ: All About Grapeseed Extract, SAM-e: The Ultimate Methyl Donor, Anti-Fat Nutrients (3rd edition), and The Prostrate Cancer Miracle. SELECTED REFERENCES Adlercreutz, H., Fotsis, T., Heikkinen, R., et al. " Excretion of the lignans enterolactone and enterodiol and of equol in omnivorous and vegetarian postmenopausal women and in women with breast cancer. " Lancet (1982). Vol. 2 pp. 1295-9. Adlercreutz, H., Bannwart, C., Wahala ,K., et al. " Inhibition of human aromatase by mammalian lignans and isoflavonoid phytoestrogens. " J Steroid Biochem Mol Biol. (1993). Vol. 44 pp. 147- 53. Adlercreutz, H., Hockerstedt, K., Bannwart, C., et al. " Effect of dietary components, including lignans and phytoestrogens, on enterohepatic circulation and liver metabolism of estrogens and on sex hormone binding globulin (SHBG). " J Steroid Biochem. (1987). Vol. 27 pp. 1135-44. Arjmandi, B. H., Juma, S., Lucas, E. A., et al. " Flaxseed supplementation positively influence bone metabolism in postmenopausal women. " JANA (1998). Vol. 1 pp. 27-32. Dabrosin, C., Chen, J., Wang, L., Thompson, L. U. " Flaxseed inhibits metastasis and decreases extracellular vascular endothelial growth factor in human breast cancer xenografts. " Cancer Letters (2000). Vol. 185 pp. 31-7. Demark-Wahnefried, W., Price, D. T., Polascik, T. J., Robertson, C. N., et al. " Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal levels, prostate-specific antigen, and histopathologic features. " Urology (2001). Vol. 58 pp. 47-52. Denis, L., Morton, M. S., Griffiths, K. " Diet and its preventive role in prostatic disease, " Eur Urol. (1999). Vol. 35 pp. 377-87. Evans, B. A. J., Griffiths, K., Morton, M. S. " Inhibition of 5 alpha- reductase in genital skin fibroblasts and prostate tissue by dietary lignans and isoflavonoids. " Journal of Endocrinology (1995). Vol. 147 pp. 295-302. Haggans, C. J., Hutchins, A. M., Olson, B. A., et al. " Effect of flaxseed consumption on urinary estrogen metabolites in postmenopausal women. " Nutr Cancer (1999). Vol. 33 pp. 188-95. Hagans, C. J., Travelli, E. J., Thomas, W., et al. " The effect of flaxseed and wheat bran consumption on urinary estrogen metabolites in premenopausal women. " Cancer Epidemiol Biomarkers Prev. (2000). Vol. 9 pp. 719-25. Lemay, A., Dodin, S., Kadri, N., et al. " Flaxseed dietary supplement versus hormone replacement therapy in hypercholesterolemic menopausal women. " Obstet Gynecol. (2002). Vol. 100 pp. 495-504. Lin, X., Gingrich, J. R., Bao, W., et al. " Effect of flaxseed supplementation on prostatic carcinoma in transgenic mice. " Urology (2002). Vol. 60 pp. 919-24. Lin, X., Switzer, B. R., Demark-Wahnefried, W. " Effect of mammalian lignans on the growth of prostate cancer cell lines. " Anticancer Research (2001). Vol. 21 pp. 3995 -4000. Lucas, E. A., Wild, R. D., Hammond, L. J., et al. " Flaxseed improves lipid profile without alterine biomarkers of bone metabolism in postmenopausal women. " J Clin Endocrinol Metab. (2002). Vol. 87 pp. 1527-32. Morton, M. S., Matos-Ferreira, A., Abranches-Monteiro, L., et al. " Measurement and metabolism of isoflavonoids and lignans in the human male. " Cancer Letters (1997). Vol. 114 pp. 145-51. Pietinen, P., Stumpf, K., Mannisto, S., et al. " Serum enterolactone and risk of breast cancer: a case-control study in eastern Finland. " Cancer Epidemiol Biomarkers Prev. (2001). Vol. 10 pp. 339-44. Prasad, K. " Flaxseed and Atherosclerosis " In: Thompson, L. U. and Cunnane, S. C., ed. Flaxseed in Human Nutrition, 2nd ed. Champaign, IL: AOCS Press (2003). pp. 260-73. Prasad, K. " Antioxidant Activity of Secoisolariciresinol Diglycoside- derived Metabolites, Secoisolariciresinol, Enterodiol and Enterolactone, " International Journal of Angiology (2000). Vol. 9 pp. 220-5. Thompson, L. U., Li, T., Chen, J., Goss, P. E. " Biological effects of dietary flaxseed in patients with breast cancer " (abstract). Breast Cancer Res Treat. (2000). Vol. 64 p. 50. Thompson, L. U. " Experimental studies on lignans and cancer. " Bailliere's Clinical Endocrin Metab. (1998). Vol. 12 p. 691-705. A Matter of Perspective ... by Dr. Michael Murray It amazes me that adverse reactions to prescription drugs are estimated to kill over 106,000 Americans every year, yet all it seems that the media is interested in is inaccurately portraying the dietary supplement industry as dangerous and " unregulated. " I think a little perspective is in order. Consumer Reports " Dirty Dozen " Recently, Consumer Reports came up with what they referred to as the " Dirty Dozen. " Actually, this report is actually the stimulus of this editorial. While I agree that some of the compounds listed are potentially harmful, when you take a look at the list as a whole it is laughable compared to the dangers of even as something as simple as aspirin. What am I talking about? It is a well established fact that each year the use of aspirin and other NSAIDs (Non-Steroidal Anti- Inflammatory Drugs) accounts for an estimated 7,600 deaths and 76,000 hospitalizations in the United States. " NSAIDs include aspirin, ibuprofen, naproxen, diclofenac, ketoprofen, and tiaprofenic acid. While I agree that androstenedione (or andro, for short) is certainly not a dietary supplement and that aristolochic acid and pennyroyal oil are definitely hazardous, most of the health food stores that I have been in do not carry these products or others on the Consumer Reports list. For example, the natural product industry has been aware of the dangers of the pyrrolizidine alkaloids found in comfrey for almost 20 years. In fact, I haven't seen a comfrey product designed for oral use containing these compounds in a health food store in the last 15 years or so. Now, I could be wrong and there could be some loose comfrey being sold as a tea out there, but my point is that is comfrey really a public health hazard? My point here is if you really take a look at some of the other members of the 'dirty dozen, " you will see that they pose little risk simply because they are not widely available. The media keeps harping on the dangers of ephedra, but was ephedra really all that bad? My feeling is that it was the abuse of ephedra that was the primary issue. Used responsibly at appropriate dosages there is no question that ephedra is a safe and effective natural product. Granted, there was the tendency of abuse because of the typical American belief that if a little is good, a lot is even better. But, again let's try to keep things in perspective. In the worst case scenario, over the last 20 years ephedra was linked to approximately 150 deaths (virtually all of which were related to excessive dosage or abuse). In contrast, approximately 2,000,000 people in the United States died from adverse drug reactions including over 140,000 deaths caused by aspirin and other NSAIDs. Taking anything by mouth, whether it is a food, drug, or supplement requires some personal responsibility. But, the relative risk of danger from taking a nutritional supplement or herbal product is substantially less than that seen with prescription and over-the- counter drugs. That fact is very clear. Table - Consumer Reports Dirty Dozen Androstenedione (or andro, for short) Aristolochic acid Bitter orange Chaparral Comfrey Germander Kava (or kava kava) Lobelia Organ/glandular extracts Pennyroyal oil Skullcap Yohimbe Adverse Drug Reactions (ADRs) It has been difficult to get a true accounting of the scope of the problem with adverse drug reactions. Why? It is because fewer than 10% of all such effects are ever reported. Reporting ADRs to the FDA is a voluntary system even if the drug caused significant harm or even death. The data that does exist on the scope of the problem with ADRs is staggering. For example, based upon detailed analysis and projections presented in the most respected medical journals including the Journal of the American Medical Association it is estimated that 6.7% of hospitalized patients have a serious adverse drug reaction with a fatality rate of 0.32%. This translates to more than 2,216,000 serious ADRs in hospitalized patients, causing over 106,000 deaths annually.1 These sobering statistics do not include the number of ADRs that occur outside the hospital or the estimated 350,000 ADRs that occur in U.S. nursing homes each year.2 If we put these statistics into monetary figures it is estimated that the cost of drug-related illness and mortality is likely now over $200 billion annually.3 To put this dollar amount into perspective this amount is more than the total cost of treating diabetes or heart disease in the United States. The obvious question is " Why are there so many ADRs? " There are many reasons. Here are just a few. First, more people are being placed on drugs than ever before. For example, roughly 4 billion prescriptions were filled last year. That is about 12 prescriptions for every person in the United States. Second, more and more people are being placed on a combination of drugs - many times to deal with side effects caused by some of the other drugs. The rate of ADRs increases exponentially after a patient is on 4 or more medications.4 Third, many of the newer drugs are more dangerous than older drugs. The FDA has approved many of these drugs without complete safety data. Drug companies can now pay a fee to speed up approval. Of the 548 new drugs approved by the FDA from 1975-1999, 56 of these (10%) were given a new black box warning because of severe ADRs or were withdrawn from the market because of reports of deaths. Lastly, the majority of health complaints patients see doctors for owe their origin to dietary and lifestyle factors. Trying to treat the symptoms with a drug (a biochemical band-aid) fails to address the underlying cause and leads to side effects as a result. One of the big reasons why more people are relying on drugs more than ever before is direct to consumer advertising by drug companies. Prior to 1997 drug companies were prohibited from marketing their product directly to consumers. If you watch the evening news or soap operas, or read magazines like Time and Newsweek or read newspapers, it is clear that ads for prescription and over-the-counter drugs dominate advertising. In fact, the marketing budget alone of the drug companies is 50% greater than the total retail sales for every vitamin, mineral, or herbal product sold in the United States through any channel of trade. Direct to consumer advertising is estimated to have increased the number of prescriptions last year by nearly 30 million. As an example of the power of direct to consumer advertising, the sexual potency drug, Viagra, can probably serve as the poster child. Within a few months of its introduction, several million men began taking Viagra, and many serious side effects, including fatalities, suddenly appeared. The FDA has no idea on how deep the problem with ADRs runs relying on their current reporting system. For example, the FDA receives an average of 80 reports each year about adverse reactions caused by the drug digoxin. This relatively small number of reports seems to indicate that digoxin was not a big problem. However a systematic survey of Medicare records revealed 202,211 hospitalizations for adverse reactions to digoxin during a seven- year period. The Power of the Drug Companies Two years ago an entire issue of the Journal of the American Medical Association (JAMA 2002 vol. 287 #21) was devoted to looking at some major problems with the relationship between drug companies, physicians, the FDA, and medical journals. Here are just of few of the findings: More than half of the experts hired to advise the government on the safety and effectiveness of drugs have financial relationships with drug companies that will be helped or hurt by their decisions. Federal law generally prohibits the FDA from using experts with financial conflicts of interest, but the FDA has waived the restriction more than 800 times from January 1998 to June 2000. Approximately 85% of authors of " Clinical Practice Guidelines " are financially dependent upon drug companies. Of 359 studies from JAMA, NEJM, BMJ, AIM, & Lancet only 26 did not contain misleading statistics. Of new releases on studies receiving drug company financing only 22% reported the source of funding. Negative findings are suppressed. One of the conclusions of the editors was that the issues presented " underscore that the findings presented in the press and medical journals are not always facts. " I think these issues have far greater social significance than some of the " non-issues " that the media have tried to create over the last few years in regards to natural products. Wouldn't you agree? The Bottom Line It seems that the FDA seems intent on trying to create a shroud of doubt on the safety of natural products. The media feeds on this attempted frenzy and repeatedly states that the dietary supplement industry is " unregulated. " I don't understand how that statement can continually pop up in the media when there are well-established federal regulations governed and enforced by the FDA regarding the safety and manufacture of dietary supplements. I hope that the media is not being swayed into a bias against the supplement industry just because a major portion of its advertising revenue is coming from the drug companies. My suggestion to the FDA is that instead of focusing energy on trying to create issues with the supplement industry, it would serve us better by developing programs and procedures to better protect us all from a much more significant danger - adverse drug reactions. In addition, it seems that the FDA should attempt to do a better job of separating itself from the interests of drug companies and instead better serve the public's interest. If that were the case, I think there would be a dramatic move towards the promotion of the use of natural products to promote health. Key References: Pomeranz B, Corey PN. Incidence of adverse drug reactions in hospitalized patients: A meta-analysis of prospective studies. JAMA 1998;279:1200-1205. Avorn J, McCormick D, Jain S, Eckler M, et al. Incidence and preventability of adverse drug events in nursing homes. Am J Med 2000;109(2):87-94. Johnson JA, Bootman JL. Drug-related morbidity and mortality. A cost- of-illness model. Arch Intern Med 1995;155(18):1949-1956. Jacubeit T, Drisch D, Weber E. Risk factors as reflected by an intensive drug monitoring system. Agents Actions 1990;29: 117-125. print this page Disclaimer The information provided on this site, or linked sites, is provided for informational purposes only, and should not be used as a substitute for advice from your physician or other health care professional. Product information contained herein has not necessarily been evaluated or approved by the U.S. Food and Drug Administration, and is not intended to diagnose, treat, cure or prevent disease. AIM Barleygreen " Wisdom of the Past, Food of the Future " http://www.geocities.com/mrsjoguest/Diets.html Quote Link to comment Share on other sites More sharing options...
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