Dr. Pink Posted May 3, 2009 Share Posted May 3, 2009 http://www.soymilkquick.com/tofualzheimersdisease.php ??? I don't know what exactly to believe. but if tofu really does cause Alzheimers, well that would just plain suck. Link to comment Share on other sites More sharing options...
beforewisdom Posted May 3, 2009 Share Posted May 3, 2009 I would explain to you how there is nothing to worry about, but I....................................Dam, I had soy for dinner! Link to comment Share on other sites More sharing options...
Nathan Nearing Posted May 3, 2009 Share Posted May 3, 2009 http://www.soymilkquick.com/tofualzheimersdisease.php ??? I don't know what exactly to believe. but if tofu really does cause Alzheimers, well that would just plain suck. Did you read the article? If not, I would suggest it. Link to comment Share on other sites More sharing options...
MollyMormon Posted May 3, 2009 Share Posted May 3, 2009 Tofu causes alzheimers because after you eat enough of it you forget what actual food tastes like. Link to comment Share on other sites More sharing options...
Vegan Joe Posted May 3, 2009 Share Posted May 3, 2009 Coreect me if I'm wrong, but those same isoflavonoids can be found other legumes and sweet potatoes ?Anyway. To much of a good thing is bad.Not to mention.There is no such thing as a fountain of youth. Link to comment Share on other sites More sharing options...
vivalasvegans Posted May 3, 2009 Share Posted May 3, 2009 LOL there's a ton of spurious variables in there, that thing doesn't show that tofu causes alzheimers. Um wut was i saying? Link to comment Share on other sites More sharing options...
Vegan Joe Posted May 3, 2009 Share Posted May 3, 2009 PotentialThough the gonadal hormone estrogen is found only in animals, certain plants contain other very similar chemicals. These are called phytoestrogens. Phytoestrogens are further divided into isoflavonoids, flavonoids and lignins. In the human body, the phytoestrogens behave very much the same way as human estrogen. TypesSome foods that are high in phytoestrogens are soy foods, flax seeds and sesame seeds. Garlic, dried apricots, sweet potatoes, pomegranates, hummus, olive oil and peanuts contain some phytoestrogens, but much less than flax seeds or soy. Herbal supplements that contain phytoestrogens are saw palmetto, dong quai, red clover and wild yam. ......................................... Isoflavonoid - 2 reference results Benefits of QuercetinFRS Healthy Energy Free Trial All day energy with no crash!http://www.FRS.com/FreeTrialThe Original Wu-Long TeaOfficial home of Okuma's WuLong Tea Don't be fooled by cheap imitationshttp://www.WuLongForLife.comAntioxidantsTop 4 Antioxidants Rated & Reviewed Find Which Antioxidant Work BestSponsored Resultswww.AntioxidantsExposed.comFlavonoidThe term flavonoid (or bioflavonoid) refers to a class of plant secondary metabolites. According to the IUPAC nomenclature, they can be classified into: flavonoids, derived from 2-phenylchromen-4-one (2-phenyl-1,4-benzopyrone) structure isoflavonoids, derived from 3-phenylchromen-4-one (3-phenyl-1,4-benzopyrone) structure neoflavonoids, derived from 4-phenylcoumarine (4-phenyl-1,2-benzopyrone) structure.Flavonoids are most commonly known for their antioxidant activity. However, it is now known that the health benefits they provide against cancer and heart disease are the result of other mechanisms. Flavonoids are also commonly referred to as bioflavonoids in the media – the terms are largely equivalent and interchangeable, for most flavonoids are biological in origin. BiosynthesisFlavonoids are synthesized by the phenylpropanoid metabolic pathway in which the amino acid phenylalanine is used to produce 4-coumaroyl-CoA. This can be combined with malonyl-CoA to yield the true backbone of flavonoids, a group of compounds called chalcones, which contain two phenyl rings (see polyphenols). Conjugate ring-closure of chalcones results in the familiar form of flavonoids, the three-ringed structure of a flavone. The metabolic pathway continues through a series of enzymatic modifications to yield flavanones → dihydroflavonols → anthocyanins. Along this pathway, many products can be formed, including the flavonols, flavan-3-ols, proanthocyanidins (tannins) and a host of other polyphenolics. Biological effectsFlavonoids are widely distributed in plants fulfilling many functions including producing yellow or red/blue pigmentation in flowers and protection from attack by microbes and insects. The widespread distribution of flavonoids, their variety and their relatively low toxicity compared to other active plant compounds (for instance alkaloids) mean that many animals, including humans, ingest significant quantities in their diet. Flavonoids have been referred to as "nature's biological response modifiers" because of strong experimental evidence of their inherent ability to modify the body's reaction to allergens, viruses, and carcinogens. They show anti-allergic, anti-inflammatory , anti-microbial and anti-cancer activity.Consumers and food manufacturers have become interested in flavonoids for their medicinal properties, especially their potential role in the prevention of cancers and cardiovascular disease. The beneficial effects of fruit, vegetables, and tea or even red wine have been attributed to flavonoid compounds rather than to known nutrients and vitamins. Health benefits aside from antioxidant valuesIn 2007, research conducted at the Linus Pauling Institute and published in Free Radical Biology and Medicine indicates that inside the human body, flavonoids themselves are of little or no direct antioxidant value. Unlike in the controlled conditions of a test tube, flavonoids are poorly absorbed by the human body (less than 5%), and most of what is absorbed is quickly metabolized and excreted from the body. The huge increase in antioxidant capacity of blood seen after the consumption of flavonoid-rich foods is not caused directly by the flavonoids themselves, but most likely is due to increased uric acid levels that result from expelling flavonoids from the body. According to Frei, "we can now follow the activity of flavonoids in the body, and one thing that is clear is that the body sees them as foreign compounds and is trying to get rid of them. But this process of gearing up to get rid of unwanted compounds is inducing so-called Phase II enzymes that also help eliminate mutagens and carcinogens, and therefore may be of value in cancer prevention... Flavonoids could also induce mechanisms that help kill cancer cells and inhibit tumor invasion." Their research also indicated that only small amounts of flavonoids are necessary to see these medical benefits. Taking large dietary supplements provides no extra benefit and may pose some risks. Diarrhea A study done at Children's Hospital & Research Center Oakland, in collaboration with scientists at Heinrich Heine University in Germany, has shown that epicatechin, quercetin and luteolin can inhibit the development of fluids that result in diarrhea by targeting the intestinal cystic fibrosis transmembrane conductance regulator Cl– transport inhibiting cAMP-stimulated Cl– secretion in the intestine. Important flavonoidsQuercetinQuercetin is a flavonoid and, to be more specific, a flavonol (see below), that constitutes the aglycone of the glycosides rutin and quercitrin. In studies, quercetin is found to be the most active of the flavonoids, and many medicinal plants owe much of their activity to their high quercetin content. Quercetin has demonstrated significant anti-inflammatory activity because of direct inhibition of several initial processes of inflammation. For example, quercetin inhibits both the production and release of histamine and other allergic/inflammatory mediators. In addition, it exerts potent antioxidant activity and vitamin C-sparing action. It may also help to prevent some types of cancer. Quercetin can be found in the herbal products based on Hawthorn, which are used for acute symptoms of congestive heart failure. One study that people who ate quercetin-rich foods at least four times a week, on average, were 51% less likely to have lung cancer than those who ate none. Please note the above comments on the article appear inaccurate. I have tried to locate the study that shows "people who ate quercetin-rich foods at least four times a week, on average, were 51% less likely to have lung cancer than those who ate none" but as far as I can tell, no such study exists. There are other articles on the internet claiming the same fact, but none link to ANY study or scientific journal I can find. As far as the american cancer society is concerned, there are no conclusive studies done on the topic. I quote "While some early lab results appear promising, as of yet there is no reliable clinical evidence that quercetin can prevent or treat cancer in humans." - you can read the full article here : http://www.cancer.org/docroot/ETO/content/ETO_5_3x_Quercetin.asp . As far as I can tell, the only sites that appear to brashly claim the magical healing properties of quercetin are sites such as "alternativehealing.org" hardly a proven reliable source of medical claims. Please be aware that this article may have been modified by people within the nutrician industry ie. people without doctorates and an interest in promoting alternative medicine. Remember that anyone can call themselves a nutritionalist without any form of qualification. I would suggest that either the sources for the studies above are found and placed in the "citation needed" section or this section is removed altogether. EpicatechinEpicatechin improves blood flow and thus seems good for cardiac health. Cocoa, the major ingredient of dark chocolate, contains relatively high amounts of epicatechin and has been found to have nearly twice the antioxidant content of red wine and up to three times that of green tea in in-vitro tests. But in the test outlined above it now appears the beneficial antioxidant effects are minimal as the antioxidants are rapidly excreted from the body. Oligomeric proanthocyanidinsProanthocyanidins extracts demonstrate a wide range of pharmacological activity. Their effects include increasing intracellular vitamin C levels, decreasing capillary permeability and fragility, scavenging oxidants and free radicals, and inhibiting destruction of collagen, the most abundant protein in the body. Important dietary sourcesGood sources of flavonoids include all citrus fruits, berries, ginkgo biloba, onions, parsley, pulses, tea (especially white and green tea), red wine, seabuckthorn, and dark chocolate (with a cocoa content of seventy percent or greater). CitrusThe citrus bioflavonoids include hesperidin (a glycoside of the flavanone hesperetin), quercitrin, rutin (two glycosides of the flavonol quercetin), and the flavone tangeritin. In addition to possessing antioxidant activity and an ability to increase intracellular levels of vitamin C, rutin and hesperidin exert beneficial effects on capillary permeability and blood flow. They also exhibit some of the anti-allergy and anti-inflammatory benefits of quercetin. Quercetin can also inhibit reverse transcriptase, part of the replication process of retroviruses. The therapeutical relevance of this inhibition has not been established. Hydroxyethylrutosides (HER) have been used in the treatment of capillary permeability, easy bruising, hemorrhoids, and varicose veins. GinkgoLeaf extract from the Ginkgo tree is widely marketed as an herbal supplement. The active ingredients are flavoglycosides. TeaGreen tea flavonoids are potent antioxidant compounds, thought to reduce incidence of cancer and heart disease. The major flavonoids in green tea are the kaempferol and catechins (catechin, epicatechin, epicatechin gallate, and epigallocatechin gallate (EGCG)). In producing teas such as oolong tea and black tea, the leaves are allowed to oxidize, during which enzymes present in the tea convert some or all of the catechins to larger molecules. However, green tea is produced by steaming the fresh-cut leaf, which inactivates these enzymes, and oxidation does not significantly occur. White tea is the least processed of teas and is shown to present the highest amount of catechins known to occur in camellia sinensis. WineGrape skins contain significant amounts of flavonoids as well as other polyphenols. Both red and white wine contain flavonoids; however, since red wine is produced by fermentation in the presence of the grape skins, red wine has been observed to contain higher levels of flavonoids, and other polyphenolics such as resveratrol. Dark chocolateFlavanoids exist naturally in cacao, but because they can be bitter, they are often removed from chocolate, even the dark variety. SubgroupsOver 5000 naturally occurring flavonoids have been characterized from various plants. They have been classified according to their chemical structure, and are usually subdivided into the following subgroups (for further reading see ): FlavonesFlavones are divided into four groups:Group Skeleton Examples Description Functional groups Structural formula 3-hydroxyl 2,3-dihydro - Luteolin, Apigenin, Tangeritin or -- Quercetin, Kaempferol, Myricetin, Fisetin, Isorhamnetin, Pachypodol, Rhamnazin -- Hesperetin, Naringenin, Eriodictyol, Homoeriodictyol or or --- Taxifolin (or Dihydroquercetin), Dihydrokaempferol Isoflavones Isoflavones :Isoflavones use the 3-phenylchromen-4-one skeleton (with no hydroxyl group substitution on carbon at position 2). :Examples: Genistein, Daidzein, Glycitein Flavan-3-ols and Anthocyanidins Flavan-3-ols (also known as Flavanols) :Flavan-3-ols use the 2-phenyl-3,4-dihydro-2H-chromen-3-ol skeleton. :Examples: Catechins (Catechin ©, Gallocatechin (GC), Catechin 3-gallate (Cg), Gallocatechin 3-gallate (GCg)), Epicatechins (Epicatechin (EC), Epigallocatechin (EGC), Epicatechin 3-gallate (ECg), Epigallocatechin 3-gallate (EGCg)) Anthocyanidins :Anthocyanidins are the aglycones of anthocyanins. Anthocyanidins use the flavylium (2-phenylchromenylium) ion skeleton :Examples: Cyanidin, Delphinidin, Malvidin, Pelargonidin, Peonidin, Petunidin Availability through microorganismsA number of recent research articles have demonstrated the efficient production of flavonoid molecules from genetically-engineered microorganisms. See also Phytochemistry Phytoalexin ReferencesExternal links USDA Database of Flavonoid content of food (pdf) Flavonoids (chemistry) Flavonoids (chemistry) Cornell news on Cocoa A Dark Chocolate a Day Keeps the Doctor Away Antioxidant in Green Tea may fight Alzheimer's-EGCG Therapeutic potential of the NF-kB pathway in the treatment of inflammatory disorders http://www.reference.com/search?q=Isoflavonoid http://www.ehow.com/about_4687198_help-woman-gain-breast-tissue.html Link to comment Share on other sites More sharing options...
Vegan Joe Posted May 3, 2009 Share Posted May 3, 2009 Isoflavones are found primarily in members of the Leguminosae family and occur in varying amounts in legumes consumed by humans. Foods such as soy, lentils, beans and chickpeas are sources of isoflavones, however, soybeans are one of the few foods that contain appreciable amounts of isoflavones (17). Lignans aremore ubiquitous. They are diphenolic precursors of the polymeric lignins, occur typically in vascular plants and are found in roots and rhizomes and the woody parts, stems, leaves, seeds and fruits. The oilseeds (flax, soy, rapeseed), whole-grain cereals (wheat, oats, rye), legumes and various vegetables and fruit (particularly berries) are rich sources of lignans (18,19). The isoflavones and lignans are associated with the protein and nonstarch polysaccharide fractions, respectively; the oils of phytoestrogen-containing plant foods are not significant sources of these compounds. Isoflavones and lignans are biologically active plant-food constituents that have potential chemopreventive properties. Quantitation of isoflavones and lignans in humans is necessary to establish the benefits and risks of exposure to these compounds in populations and to determine which components of a mixed diet contribute to the exposure. Isoflavones and lignans are metabolized by colonic bacteria to more biologically active metabolites; thus both the parent compounds and the metabolites are measured routinely. Isoflavonoids (genistein, daidzein, dihydrodaidzein, O-desmethylangolensin and equol) and lignans (enterolactone, enterodiol, matairesinol and secoisolariciresinol) can be quantified in various body fluids. Typically, high concentrations of isoflavonoids in urine and serum are associated with soy consumption, and high concentrations of lignans are associated primarily with intake of whole grains and other fiber-containing plant foods. Controlled feeding studies and nutritional epidemiologic studies demonstrate a linear dose response between dietary intake and urinary excretion of isoflavones. Lignan excretion is associated positively with dietary fiber intake as well as with diets that are on average higher in fiber and carbohydrate and lower in fat; thus lignans have also been proposed as a marker of healthier dietary patterns. The complex interactions between the colonic environment and the external and internal factors that modulate it contribute to significant variation in serum and urinary phytoestrogen levels among individuals. Understanding these sources of variation is important to be able to use these measures effectively as dietary biomarkers. -------------------------------------------------------------------------------- KEY WORDS: • biomarkers • diet assessment • epidemiology • isoflavonoids • lignans • nutrition • phytoestrogens Phytoestrogens are plant-derived compounds that have estrogenic properties. The term "phytoestrogens" includes primarily two groups of compounds, isoflavones and lignans, that are present in significant amounts in the human diet. Although identified originally for their weak estrogenic activity, many of these compounds have a variety of other biologic activities that may influence disease risk (1,2). Thus monitoring dietary exposure to these compounds is desirable for reasons beyond just their hormonelike effects. Additional compounds and other classes of phytochemicals (e.g., coumestrol, resveratrol and phytosterols) also have been identified as nonsteroidal estrogens (3–5). However, their use as dietary biomarkers has not been investigated, thus this review focuses on the isoflavones and lignans. To date much of the emphasis of phytoestrogen research has centered on the potential cancer-preventive effects of isoflavones and lignans. However, animal studies and in vitro work support the potential for these phytoestrogens to influence risk factors for the major chronic diseases through a variety of mechanisms (2). These include but are not limited to antiviral and antibacterial, antioxidant, antiproliferative and antiangiogenic activities and inhibition of effects of cytokines and growth factors [reviewed in (2) and (1)]. Intervention studies in humans demonstrate the capacity of isoflavones to modulate risk factors for cardiovascular disease (6– and maintain bone mass (7) and of lignans and isoflavones to alter estrogen metabolism (9–11). Despite the great enthusiasm for the beneficial effects of these compounds, some research suggests that potential risks have not been examined sufficiently (12–16). The eagerness with which the public has embraced soyfoods and phytoestrogen supplements is resulting in a major population-based experiment, which could have wide-ranging health consequences, possibly both positive and negative. The ability to monitor objectively exposure to these compounds may be very important in understanding the health effects of these dietary constituents. During the past decade, analysis of foods for lignans and isoflavones (2,19–23) has led to the compilation of several databases (24–26) and the development and modification of food-intake questionnaires to estimate intake of these various compounds (27–29). As is the general case for measurement of nutrient intakes, accurate determination of dietary phytoestrogen intake is limited not only by the constraints of intake-measurement methodologies but also by the problems associated with establishing the phytoestrogen content of foods. The lignan or isoflavone concentration can vary substantially within a food according to variety, crop season, location and processing methods (30,31). Furthermore, given the ever-growing list of preprepared foods, functional foods and dietary supplements that are available to consumers, a food-intake instrument may be hard pressed to capture fully the intake of these classes of compounds. Measuring lignans and isoflavones in biologic samples provides another approach to estimating human exposure to these compounds, however, this presents its own set of issues and challenges. Measurement in biologic samples Isoflavones and lignans have been quantified in many types of biologic specimens including urine (32,33), feces (34,35), serum and plasma (36,37), nipple aspirate fluid (38) and prostatic fluid (39). They have also been measured in breast milk (40), umbilical cord plasma (41), amniotic fluid (41) and in several tissues in humans (38) and animals (42,43). Isoflavone concentrations in human breast tissue (obtained at surgery) have been shown in one study to be comparable to those found in serum with supplemental soy increasing both breast tissue and serum daidzein concentrations (38). Given that the collecting of tissue samples from humans can be difficult, requires invasive procedures and often deters individuals from participating in studies, it would be helpful to establish as soon as possible whether measuring concentrations in tissue is necessary or whether serum concentrations are a sufficient surrogate for tissue exposure. Phytoestrogen concentrations are higher in fluid collected from breast (38) and prostatic (39) ducts compared with serum or plasma, which is suggestive of accumulation of these compounds within the ducts. In a cross-sectional observational study, prostatic duct fluid concentrations of daidzein correlated positively with plasma concentrations among men in Hong Kong, but plasma and duct fluid concentrations of enterolactone were not correlated (39). In women, nipple aspirate fluid concentrations of isoflavones and lignans did not correlate well with circulating levels and did not respond to 2-wk soy supplementation. Therefore, nipple aspirate fluid concentrations are probably not accurate indicators of recent exposure (38). Ductal fluid concentrations may prove useful for monitoring long-term cumulative exposure, however to date, this has not been investigated. Isoflavones and lignans in urine and serum or plasma are probably most pertinent to the application of their measurement as dietary biomarkers in human population-based studies. Several reviews have summarized the accumulated data on the physiologic ranges of isoflavones and lignans in urine and plasma that have been observed in various populations worldwide and in relation to disease risk (1,44–46). In the U.S.A. alone, wide ranges in urinary isoflavonoid excretion, which are dependent in part on dietary behaviors, have been reported: daily daidzein excretion [µmol/d; geometric mean (range)] values were 0.28 (0 to 14) in women from a multiethnic population in California (47); 0.56 (0.04–29.48) in a predominantly Caucasian population in Minnesota (48); and 0.37, 3.64 and 1.42 in premenopausal women who consumed omnivorous, macrobiotic or lacto-ovovegetarian diets, respectively (44). By comparison, a daidzein level of 2.58 µmol/d (range, 1.60–5.25) was reported for men and women who consume a traditional Japanese diet (49). Urinary enterodiol and enterolactone excretion values [µmol/d; geometric mean (range)] were 0.69 (0 to 5.5) and 4.31 (0–22.7) among the California women of Caucasian origin (47), 0.45 (0.02–29.31) and 2.12 (0.14–32.75) in the Minnesota group (48) and 0.24 and 1.92, 7.10 and 19.9, and 1.03 and 4.97 in premenopausal women who consumed omnivorous, macrobiotic and lacto-ovovegetarian diets, respectively (44). Lignan excretion among the Japanese appears to be lower: urinary enterodiol and enterolactone levels were 0.27 (0.09–3.39) and 0.50 (0.04–3.25) µmol/d, respectively (49). Populations that consume a Western diet typically have very low circulating levels of isoflavones. Reported plasma concentrations (nmol/L; geometric mean) of daidzein and genistein were 4.2 and 4.9 in Finland and 2.1 and 5.7 in the U.S.A. (50,51), whereas among six men who consume a traditional Japanese diet, mean daidzein and genistein concentrations [geometric mean (range)] were 163 (58–924) and 248 (90–1204) nmol/L, respectively (50). Mean plasma lignan concentrations (enterodiol plus enterolactone) appear to be in the range of 10–270 nmol/L in studies where plasma was collected from individuals that consumed their usual diets (46). However, as with urinary levels, wide ranges in plasma enterolactone concentrations—from below the detectable limit to 1,078 nmol/L—have been reported (36). Generally under habitual dietary conditions, enterolactone is the lignan in highest concentration in plasma (37,50,52), however, this varies among groups studied in that enterodiol concentrations higher than enterolactone have also been reported (38,53). Little work has been done to assess the long-term reliability of phytoestrogen measurements in biologic samples. One study of 60 women (both pre- and postmenopausal) in New York measured phytoestrogens in serum samples collected from women at three different time points over a 3-y time period (51). The median enterodiol concentration was 1.5 nmol/L, and over one-third of the serum samples had concentrations < 1.00 nmol/L, which was the sensitivity level of the assay. Enterolactone concentrations were higher, with only 2% of the assays < 1.00 nmol/L. On average, 28% of the daidzein and 8% of the genistein concentrations were < 1.00 nmol/L. Concentrations of equol and O-desmethylangolensin (ODMA)4 were very low, with approximately two-thirds of the samples being < 1.0 nmol/L. Overall, the reliability coefficients were low (< 0.4) for all compounds except for enterolactone (0.55). The higher reliability coefficient for enterolactone likely reflects regular intake of the appropriate precursors. These data point to potential problems in using plasma phytoestrogen concentrations, particularly isoflavones, as dietary biomarkers in populations that consume Western diets. Phytoestrogen metabolism. Phytoestrogen metabolism in humans involves the action of intestinal microflora as well as enzymatic modification by the conjugating enzymes, UDP-glucuronosyltransferases (UGT) and sulfotransferases and possibly the cytochromes P450. Lignans and isoflavones are present in plants predominantly as glycosides, although plant foods that include a fermentation step in the processing or preparation have an increased proportion of aglycones (1). In soy, the major isoflavone glycosides are genistin, daidzin and glycetin (20). Some legumes also contain biochanin A and formononetin, which are precursors of genistein and daidzein, respectively (22). The two dietary lignans, secoisolariciresinol and matairesinol, are derived from coniferyl alcohol (54) and are immediate precursors of the mammalian lignans enterodiol and enterolactone, respectively (55). Studies suggest that there are probably additional mammalian lignan precursors (2,56). Upon ingestion, the sugar moities of isoflavone and lignan glycosides are hydrolyzed by gastric hydrochloric acid, ß-glucosidases in foods and human gut bacterial ß-glucosidases, thereby releasing the aglycones (57). These are absorbed or can be metabolized further in the gut to additional metabolites (Table 1). The importance of the microflora in the metabolism of lignans and isoflavones has been well demonstrated by the observations that antibiotic administration prevents production of the metabolites (58), individuals without an intact colon have low plasma and urinary lignan levels (59) and infants fed soy formulas during the first 4 mo of life when gut microflora are underdeveloped do not excrete appreciable amounts of equol, a metabolite of daidzein (60). View this table:[in this window][in a new window] TABLE 1 Common dietary isoflavones and lignans and metabolites1 Absorbed lignans and isoflavones and their metabolites are conjugated by sulfotransferases and UDP-glucuronosyltransferases in intestinal epithelium and liver (61). They are excreted in urine and bile. The conjugated forms that are reexcreted through the bile duct can undergo enterohepatic recycling: deconjugation by bacterial ß-glucuronidases and sulfatases may promote reabsorption, further metabolism or degradation in the colon (62). Although intestinal microbes play a primary role in the metabolism of plant lignans, there is evidence that additional metabolism beyond glucuronidation and sulfation occurs in the mammalian host. Hepatic microsomes from humans as well as rats are able to hydroxylate enterolactone and enterodiol at both the aliphatic and aromatic positions (63). To date, products of aromatic monohydroxylation at the para and ortho positions have been identified in human urine, whereas products of aliphatic hydroxylation have not been detected (64). It remains to be determined whether the lack of these aliphatically hydroxylated compounds is because they are not produced in vivo, are metabolized further or are lost during the extraction process. Although these metabolites have not been quantitated accurately, it is estimated that they account for < 5% of the total urinary lignans at least with high intakes of lignan precursors (64). Thus the amount of and the interindividual variation in production of these hydroxylated compounds may not contribute significantly to the wide ranges in urinary and plasma enterodiol and enterolactone levels that are observed in the various flaxseed supplementation studies. Urinary recovery of daidzein and genistein has been reported in the ranges of 42–62 and 7–18%, respectively (65–70). Conversion of genistein to p-ethylphenol, a compound that is a major metabolite of genistein in sheep but is not routinely measured in humans (1,71), may account for the low urinary recovery of genistein in the form of the parent compound and metabolites. Given the relatively low recovery of daidzein and genistein in feces (68,69), it seems likely that there are other isoflavone metabolites that need to be identified and measured to characterize fully the pharmacokinetics of these compounds. Equol, a bacterial metabolite of daidzein, is only produced by 30–40% of individuals in response to a soy challenge (72,73). Although the capacity to produce equol appears to be a relatively stable phenotype (57), there is at least one report of individuals who converted from being equol nonexcreters to excreters with chronic soy ingestion (74). This may be the result of a microfloral change or may reflect an inadequate assessment of equol-excretion status at baseline. Several studies have shown that equol does not appear in the urine until 72 h post-daidzein ingestion, and typically at least 3 d of soy intake are needed to distinguish between excreters and nonexcreters in a population that regularly does not consume soy (72,73). Phytoestrogen pharmacokinetics. Measured from their plasma appearance and disappearance curves, the plasma half-life for daidzein and genistein has been estimated to be 7.9 h in adults with peak plasma concentrations occurring 6–8 h after ingestion of the pure compounds (1) and soy powder (68). Similarly, excretion half-lives for genistein, daidzein and equol with soy supplementation are 7, 4 and 9 h, respectively (70,74). Typically all of the urinary recovery of genistein and daidzein from a single time-point intake is complete within 24–36 h, whereas postchallenge urinary recovery of equol and ODMA remains measurable for at least 3 d (75). This has significant implications for monitoring urine or serum to determine isoflavone exposure in populations that may only consume soy once or twice per week. Isoflavones are present in urine predominantly as conjugates: 75–85% are present as glucuronides, 15–25% as sulfates and < 1% as free aglycones (76). A more detailed analysis by Adlercreutz et al. (77) suggests that conjugation patterns differ for the various isoflavonoids: ODMA occurred predominantly as a monoglucuronide (97%); equol was found as the monoglucuronide (32–93%), sulfoglucuronide (0–43%), monosulfate (0–15%) and disulfate (0–10%); daidzein was present as the monoglucuronide (79–82%), sulfoglucuronide (6–17%) and free form (1–5%); and genistein was excreted as monoglucuronide (53–76%), diglucuronide (12–26%), sulfoglucuronide (2–15%) and disulfate (1–4%) conjugates. Few studies have examined lignan pharmacokinetics in humans. These studies are small and of short duration—blood samples are not collected beyond 24 h—and there are no data on lignan disappearance from circulation. Feeding men a baked product that contained 15 g of soybean flour and 15 g of cracked linseed (flaxseed), Morton et al. (78) reported that plasma enterolactone concentrations did not increase measurably until 8.5 h after the men ate the flaxseed. The next blood sample taken was at 24 h. This had the highest enterolactone concentration, but it was also the last blood sample collected. The mean plasma lignan concentration at 24 h was 102 nmol/L (range, 36–146 nmol/L). In a similar study, supplementation of 500 g of strawberries (which contained 11.7 mg of secoisolariciresinol and 0.6 mg of matairesinol) also resulted in significantly elevated plasma enterolactone concentrations 24 h postingestion (20.6 vs. 10.3 nmol/L); however blood samples were not collected between 8 and 24 h or beyond 24 h (79). In women, significant increases in plasma lignan concentrations (enterolactone plus enterodiol) also were reported by 9 h after consumption of 25 g of flaxseed. These concentrations did not change significantly at 12 or 24 h (53). The mean lignan concentration 24 h postflaxseed dose was 66 nmol/L. In these same women, 7 d of flaxseed supplementation resulted in the total plasma area under the curve being significantly higher on day 8 than on day 1: 1,840 and 1,027 nmol·L-1·h-1, respectively. These studies suggest that because enterodiol and enterolactone are products of microfloral metabolism, appearance of the compounds in plasma is delayed, however, there is substantial variation in this time frame among participants. Similar to the isoflavones, the major proportion of lignans in urine are conjugated. Enterolactone and enterodiol are excreted primarily as monoglucuronides (95 and 85%, respectively) with small percentages being excreted as monosulfates (2–10%) and free aglycones (0.3–1%) (77). Measurement of phytoestrogens. Several types of analytic methods have been described in the literature to measure phytoestrogens and their metabolites in body fluids. All have some limitations, including a reduced capacity to measure certain active metabolites, a need for large volumes of urine or plasma, laborious cleanup and derivitization steps, expensive equipment or antibodies and standards that are not commercially available. Choice of method will depend on the type of study, the level of sensitivity required, the amount of biologic sample available, etc. (Table 2). View this table:[in this window][in a new window] TABLE 2 Detection limits for daidzein and enterolactone using different analytic methods Chromatographic separation coupled with various detection systems is most commonly used for measuring phytoestrogens in urine and plasma. Methods have been published using gas chromatography/mass spectrometry in selected-ion monitoring mode (GC/MS-SIM) (33,50,80), GC with flame-ionization detection (FID) (81), high performance liquid chromatography (HPLC) with ultraviolet (82), diode array (83) or coulometric electrode array detection (42,84), and LC with MS (76) or electrospray (ES)/MS (85) or MS/MS detection (86). GC/MS-SIM methods, which are adapted from the highly specific and sensitive approaches used for measuring steroid hormones and using deuterated internal standards of the phytoestrogens and their metabolites, have been used effectively for analysis of urine and serum. Rapid and sensitive LC/MS (76) and LC/MS/MS (86) systems allow for isoflavone measurement in small volumes of urine (0.5–1 mL) and plasma (1 mL); however the detection limit for equol using negative single-ion monitoring is 40 times higher than for the other isoflavonoids (76). Other methods such as HPLC with diode array detection (83) and GC/FID (81) require a large starting volume of urine (20 mL), which is then concentrated 10–20-fold before analysis. These methods are best suited to studies in which high phytoestrogen concentrations are expected (e.g., interventions using phytoestrogen-containing foods, high-dose pharmacokinetic studies, etc.). Coulometric electrode array detection improves sensitivity and can be used to monitor plasma phytoestrogen profiles in samples (0.5–1 mL) from individuals that consume their habitual diets not supplemented with phytoestrogens (84,87). Immunoassays using radiolabeled, enzyme-linked or fluorescently tagged monoclonal antibodies have been developed to measure genistein (88,89), daidzein (90,91) and enterolactone (92) in serum, plasma or urine. These provide an attractive alternative for the analysis of large numbers of samples, however at present, only the enterolactone fluoroimmunoassay is available commercially. The majority of the methods involve initial enzymatic hydrolysis of the sulfate and glucuronide conjugates in samples thus providing a measure of "total" amounts of the phytoestrogens and their metabolites. A comprehensive analysis of sulfate and glucuronide conjugates of isoflavones and lignans and their metabolites can be obtained using a series of enzymatic hydrolysis steps and subsequent GC/MS or LC/MS to separate and quantitate these compounds in urine (76,77) and plasma (50). These methods are labor intensive and require pure enzyme preparations (e.g., a sulfatase enzyme that is relatively free of glucuronidase activity). Although they may be useful for understanding the pharmacokinetics and mechanisms of action of phytoestrogens, this approach is probably overkill for studies using isoflavones and lignans as biomarkers of dietary exposure. The variation among individuals as a result of conjugation patterns is probably minor compared to the variation due to habitual diet, etc., although this has not been tested under controlled conditions. Utility of isoflavonoid and lignan phytoestrogens as dietary biomarkers TOPABSTRACTMeasurement in biologic samplesUtility of isoflavonoid and...Factors affecting measurement of...LITERATURE CITED Although estimated dietary phytoestrogen intakes (5,27) and urinary and circulating concentrations of lignans and isoflavonoids are being used in epidemiologic studies (93,94), few studies have compared concurrently phytoestrogen levels in biologic specimens against dietary phytoestrogen estimates. To date the majority of observational studies that have used isoflavones and lignans as biomarkers have relied on urine collections of varying length and completeness that ranged from spot urines to 3-d collections. Several studies of populations that typically consume soyfoods have established a strong positive association between soy intake and isoflavone excretion. Soy product intake (estimated from food records) and urinary isoflavones (from a 3-d urine collection) were significantly correlated in a group of 19 men and women that consumed a typical Japanese diet (49). Among Singapore Chinese, urinary daidzein and the sum of urinary daidzein, genistein and glycitein measured in spot urine collections were also associated in a dose-dependent manner with intake of traditional Chinese soyfoods (95). Similarly, among Chinese women in Shanghai, isoflavones in overnight urine collections were also associated with soy intake (r = 0.5; P < 0.001) (96). Maskarinec et al. (29), studying a multiethnic population of women in Hawaii (n = 102), showed an association between isoflavones measured in overnight urine samples and soy protein intake, both in the previous 24 h (rs = 0.61; P < 0.0001) and in the past year (rs = 0.32; P < 0.0012). Franke and Custer (97), also in Hawaii, reported the ability to discriminate, using overnight-urine isoflavone levels, between seven women who consumed tofu more frequently than once a week and 16 women who ate tofu less than once a week. By comparison, even in a predominantly Caucasian population of which < 30% reported on a food-frequency questionnaire (FFQ) that they consumed soy more than once a month, daily isoflavone excretion (from a 3-d collection) was significantly associated with immediate soy intake estimated from a 5-d food record (r = 0.4) and over the past year estimated by FFQ (r = 0.25) (48). On average, urinary isoflavones were also higher in the group of individuals that consumed soy more than once a month compared with those that consumed soy less than once a month or never. High isoflavone excretion among some individuals with no reported soy intake (48) suggests that on a typical American (U.S.) diet, other food sources contribute substantially to isoflavone intake. The most likely candidates are processed foods that contain soy flour or soy protein but not soybean oil (30); isoflavones from these sources are difficult to detect by the usual self-report methods of monitoring soyfood intake. Other non-soy-based foods are also sources of isoflavones. Daidzein and genistein have been identified in legume sprouts such as clover and alfalfa (22) and in some alcoholic beverages (98). Equol is present in low amounts in cow's milk (99), and milk-product consumption appears to contribute in part to small differences in equol excretion (100). Thus measuring isoflavones in biologic samples may be useful to monitor more completely overall exposure to isoflavones. The efficacy of serum isoflavone concentrations as markers of soy exposure has not yet been established in observational studies. Two cross-sectional studies (48,49) have reported that equol excretion is associated with meat intake. Because only one-third of individuals have colonic bacteria that are capable of producing equol from daidzein (73), equol would not be expected to be associated with intake of a particular dietary constituent except maybe soy. We cannot determine from these data whether the relationship between urinary equol excretion and meat intake reflects a diet-induced isoflavone-metabolizing profile with improved production of equol from daidzein or instead is due to equol in the meat itself. Adlercreutz et al. (49) hypothesized that consuming more fat and meat creates a colonic environment that is capable of sustaining equol-producing bacteria. However, in a study designed to identify equol excreters using a prescribed soy dose, there was no relationship between fat or animal protein intake and equol-excreter status (73). Another possible explanation for the association between high-fat meat intake and equol excretion is that equol is present in the meat of animals that receive soy-, alfalfa- or clover-supplemented feed (48). At present, regular intake of discrete soyfoods is still relatively low and uncommon in the continental U.S.A. At the same time, soy protein and other soybean derivatives are added frequently to foods. Thus although monitoring exposure to isoflavones using biologic measures offers certain advantages, it also poses a number of challenges. First, unless a person is a regular soy consumer, within-person variability in intake may exceed between-person variability. Second, the half-lives of the isoflavones genistein and daidzein are short (68), therefore, if isoflavone exposure is monitored using urinary or plasma markers, intermittent soy consumption may be severely under- or overestimated. Intake of total dietary fiber and fiber from grains (estimated by food records) has been most strongly associated with lignan excretion (48,101,102). Adlercreutz et al. (49) also reported that in Japanese men and women, lignan excretion was correlated significantly with intakes of green and yellow vegetables, pulses and beans and boiled soybeans. Lampe et al. (48) reported a significant association between intake of vegetables and fruit and urinary lignan excretion, but this relationship was due exclusively to an association between fruit intake and lignan excretion; there was no association with vegetable intake. This was surprising, given that Kirkman et al. (103) demonstrated previously that vegetable supplementation, as part of a low-fiber low-phytochemical diet, significantly increased lignan excretion. These data suggest that additional factors need to be considered when examining the relationships between intake of particular nutrients or food groups and lignan excretion. Apart from these few relatively small studies (48,49,101,104), the association between diet and levels of lignans in biologic samples in observational studies has not been investigated. Significantly more work is needed in this area. There were no significant relationships between lignan excretion and intake of dietary fiber or vegetables and fruit when intake over the past year was measured using an FFQ (48). This reflects in part 1) the measurement error inherent in assessing diet by FFQ (105); 2) the variation in lignan content of high-fiber foods; 3) the seasonal and varietal variation in lignan content within a food (31); and 4) the effects of food processing on lignan precursor availability. Given the ubiquitous nature and more regular intake of lignans, one might expect a stronger relationship between dietary constituents and lignans than between soy intake and isoflavones. Results of several studies also suggest that among individuals consuming a Western diet, plasma and urinary phytoestrogen levels may reflect differences in dietary patterns and possibly more healthy dietary patterns. Adlercreutz et al. (102) showed that there are differences in lignan and isoflavone excretion among groups that consume very different diets (e.g., macrobiotic, vegetarian and omnivorous diets). Compared with omnivores, vegetarians excreted significantly higher amounts of lignans in urine and feces (34,104). Similarly plasma lignan concentrations tend to be higher in vegetarians compared with omnivores (50). Furthermore urinary lignan and phytoestrogen excretion values (lignans and isoflavonoids combined) were greater in individuals who self-reported higher versus lower intakes of vegetables and fruit and on average had higher intakes of dietary fiber and soy foods and lower percent of total energy from fat (48). Urinary and plasma or serum isoflavone and lignan measures have been used as markers of compliance for dietary intervention trials in which participants consumed their normal diets supplemented with a phytoestrogen source (9,38,66,106) or controlled diets provided by the investigators (11). Urine collections assayed ranged from 72-h (9) to 24-h (66,106) collections. On average, phytoestrogen concentrations in serum and levels in urine reflect intake of the precursor compounds in a dose-dependent manner (9,82,107,108). For example, daily daidzein excretion values were 0.44, 3.65, 5.29 and 9.86 µmol/d with daily soy protein powder intakes of 0, 5, 10 and 20 g (0, 3.25, 6.5 and 13 mg of daidzein), respectively (108). However in these studies, even under controlled dietary conditions, investigators have reported substantial interindividual variation in urinary excretion of lignans and isoflavones. This poses potential problems if these measures are going to be used to gauge dietary compliance at the level of the individual. Factors affecting measurement of isoflavones and lignans TOPABSTRACTMeasurement in biologic samplesUtility of isoflavonoid and...Factors affecting measurement of...LITERATURE CITED In theory several factors can affect the measurement of isoflavones and lignans and more specifically can influence the interpretation of phytoestrogen measures as dietary biomarkers. One factor is the effect of dietary constituents and the form of phytoestrogen-containing foods on isoflavone and lignan availability, which has received attention in a few small studies. In short-term trials (e.g., 1-d and single feedings), background diet and the form of the soyfood (69) as well as the addition of wheat fiber (109) appear to have little effect on isoflavone bioavailability. Similarly, a 9-d feeding study that compared isoflavone administration as tempeh and soy pieces showed modest differences in urinary recovery of daidzein and genistein (110). At the same time, no studies have addressed the influence of chronic dietary patterns on phytoestrogen availability. For lignans, ingestion of ground flaxseed as cooked versus raw did not affect total urinary lignan excretion (53). Because the lignans are closely associated with the fiber matrix of grains and seeds, it is possible that particle size (e.g., coarseness of grind) might influence lignan availability; however there are no data available in this area. Furthermore the bioavailability of lignans from various food sources has not been explored. If the substantial variation in bioavailability of other phytonutrients in relation to vegetable matrices is any indication (111), this also warrants investigation in the case of lignans. Another factor that needs to be considered is colonic environment. Production of the lignans enterolactone and enterodiol and isoflavone metabolites such as equol and ODMA is dependent on metabolism of parent compounds by gastrointestinal bacteria (62). Several of the flaxseed-feeding trials have noted significant interindividual variation in enterodiol-to-enterolactone ratios (53,112): some individuals convert most of the enterodiol to enterolactone, whereas others produce little enterolactone. The specific microbes responsible for the conversion of enterodiol to enterolactone have not been identified. Based on early work in this area, they appear to be facultative anaerobic bacteria present in concentrations of between 103 and 104 bacteria/g of stool (113). In the case of metabolism of daidzein to equol, the species and/or strains that are involved in this metabolic pathway have not been elucidated either, and to date little work has been done to establish what factors contribute to the capacity to produce equol. Among equol producers, urinary equol can account for 25–30% of the daidzein excreted (108). Thus measurement of the related metabolites (e.g., enterodiol and enterolactone or daidzein plus its metabolites) rather than reliance on a single metabolite presumably would help to minimize the measurement error. Antibiotic use would be expected to contribute to variation in urinary and plasma phytoestrogen concentrations among individuals. Horn-Ross et al. (47) found no difference in urinary phytoestrogen levels between women who had used (43%) or not used (57%) antibiotics within the year before interview and sample collection. However, antibiotic treatment has been shown clearly to reduce isoflavone and lignan excretion (72,104). To date, the large range and significant variation in phytoestrogen levels in observational studies with relatively small sample sizes probably precludes detecting the effects of antibiotic use. There are some data to suggest that chronic exposure to isoflavones may change usual plasma concentrations or urinary excretion. In a sample of four individuals, Barnes et al. (61) observed a decrease in plasma concentrations of daidzein and genistein over a 2-wk period. Similarly, Lu et al. (74) reported a decrease in urinary isoflavone excretion in women that consumed soy milk for 30 d, and Xu et al. (9) reported greater excretion of ODMA than daidzein in women that consumed soy protein for 100 d. In an observational study, Chinese and Native Hawaiian compared to Japanese women also excreted lower amounts of isoflavones in an overnight urine collection despite soy protein intakes being similar in the three ethnic groups (29). Hypothetically, these effects could be the result of altered biotransformation enzyme (e.g., UDP-glucuronosyltransferase and sulfotransferase) expression and/or activity or colonic microfloral metabolism, however, to date this has not been investigated in humans. The effect of endogenous and exogenous hormones on isoflavone and lignan metabolism and excretion has not been fully established. Enterolactone was originally identified in the urine of premenopausal women as a compound that was found to fluctuate during the menstrual cycle and to increase significantly during the midluteal phase (32). However, lignan differences between follicular and luteal phases were not detectable in 3-d pooled urine collections (112). Oral contraceptive use was also not shown to influence urinary phytoestrogen excretion in observational studies (47,48); however the number of women in these studies was very small and probably inadequate to provide conclusive data. Additional studies that are in progress should be able to provide useful data in this area. Sex differences in isoflavone and lignan metabolism and excretion were also reported. Under controlled dietary conditions, isoflavonoid excretion half-lives were longer in women than in men with an initial exposure to soy milk but were shortened in women and lengthened in men with chronic ingestion (114). In this group, women also had higher urinary isoflavonoid recoveries initially and had lower recoveries by the end of the study period. Less controlled conditions and shorter interventions showed no differences in 24-h isoflavonoid excretion (73,103). Higher enterodiol-to-enterolactone ratios in men compared with women were observed in a randomized crossover trial of vegetable feeding (103). Interpretation of these sex-difference results is limited: all the studies were small and provided phytoestrogens as fixed doses and not according to body weight. Because body weight and sex are frequently confounded, it is not clear whether observed excretion differences between men and women are due to physiologic differences in intestinal function or are merely dose effects. The last decade saw the development of several new methodologies for measuring lignans and isoflavones. Improved levels of assay detection coupled with minimal sample extraction and the capacity to use small amounts of urine, serum or tissue will further the use of lignans and isoflavones as biomarkers in large population-based studies. Additional research efforts are needed to establish more clearly the relationship between phytoestrogen levels and habitual diet in larger population-based studies and to determine in greater detail what contributes to the significant interindividual variation in plasma and urinary levels of lignans and isoflavones. Much of the variation in these measures is attributed primarily to differences in colonic microfloral populations; however the factors that potentially influence these populations and their metabolism have not been studied and seldom are monitored in population-based studies. Factors that may influence endogenous metabolism of phytoestrogens (e.g., conjugating enzymes) also warrant characterization. ACKNOWLEDGMENTS The author thanks Margaret T. Grate and Heather E. Skor for their assistance with the preparation of this manuscript. FOOTNOTES 1 Published as part of The Journal of Nutrition supplement publication "Biomarkers of Nutritional Exposure and Nutritional Status." This series of articles was commissioned and financially supported by International Life Sciences Institute, North America's Technical Committee on Food Components for Health Promotion. For more information about the committee or ILSI N.A., call 202-659-0074 or E-mail [email protected]. The opinions expressed herein are those of the authors and do not necessarily represent the views of ILSI N.A. The guest editor for this supplement publication was Jo Freudenheim, University at Buffalo, State University of New York, Buffalo, NY 14214. 2 Supported by National Institutes of Health Grants U01 CA-72035 and R03 CA-80648 and the Fred Hutchinson Cancer Research Center. 4 Abbreviations used: FID, flame-ionization detection; GC/MS-SIM, gas chromatography/mass spectrometry in selected-ion monitoring mode; HPLC, high performance liquid chromatography; ODMA, O-desmethylangolensin LITERATURE CITED http://jn.nutrition.org/cgi/content/full/133/3/956S Link to comment Share on other sites More sharing options...
Marcina Posted May 3, 2009 Share Posted May 3, 2009 Holy crap, Joe. Did you actually read all of that? Cuz I'm sure not gonna!! Lol Btw I don't think tofu causes alzheimer's. I read up on it and it was another study that wasn't done properly.. Kinda like the sperm one. Link to comment Share on other sites More sharing options...
Vegan Joe Posted May 3, 2009 Share Posted May 3, 2009 Holy crap, Joe. Did you actually read all of that?Yes, but it's how much I remembered or understood that has me worried.Somebody pass the eggplant with bean curd please. Link to comment Share on other sites More sharing options...
Jason Posted May 4, 2009 Share Posted May 4, 2009 My scroll finger got tired just scrolling over that I didn't need to read it because I don't eat tofu, so I can't get Alzheimer's Link to comment Share on other sites More sharing options...
Jason Posted May 4, 2009 Share Posted May 4, 2009 Btw I don't think tofu causes alzheimer's. I read up on it and it was another study that wasn't done properly.. Kinda like the sperm one.Sperm causes Alzheimer's? Link to comment Share on other sites More sharing options...
Marcina Posted May 4, 2009 Share Posted May 4, 2009 Btw I don't think tofu causes alzheimer's. I read up on it and it was another study that wasn't done properly.. Kinda like the sperm one.Sperm causes Alzheimer's? Lulz no. But people were going around saying that soy lowered sperm count.. Which it doesn't. Link to comment Share on other sites More sharing options...
cubby2112 Posted May 4, 2009 Share Posted May 4, 2009 I know a lot of the scare about tofu causing alzheimers stems from the fact that men in Hawaii who were found to consume tofu were more prone to alzheimers. This caused quite an uproar until people found out that tofu produced in Hawaii contains high levels of aluminum for some reason. Link to comment Share on other sites More sharing options...
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