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NTP-CERHR Expert Panel Report on the Reproductive andDevelopmental Toxicity of Soy FormulaKarl K. Rozman1, Jatinder Bhatia2, Antonia M. Calafat3, Christina Chambers4, MartineCulty5, Ruth A. Etzel6, Jodi A. Flaws7, Deborah K. Hansen8, Patricia B. Hoyer9, Elizabeth H.Jeffery10, James S. Kesner11,‡, Sue Marty12, John A. Thomas13, and David Umbach141Department of Pharmacology and Toxicology, University of Kansas Medical Center, Kansas City, KS2Division of Neonatology, Department of Pediatrics, Medical College of Georgia, Augusta, GA3National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA4Departments of Pediatrics and Family and Preventive Medicine, University of California San Diego MedicalCenter, San Diego, CA5Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, Washington,DC6George Washington University School of Public Health and Health Services, Washington, DC7Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine,Baltimore, MD8Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, Jefferson,AR9Department of Physiology, University of Arizona, Tucson, AZ10Department of Food Science and Human Nutrition, University of Illinois, Urbana, IL11National Institute for Occupational Safety and Health, Cincinnati, OH12Toxicology Research Laboratory, The Dow Chemical Company, Midland, MI13Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN14National Institute of Environmental Health Sciences, Research Triangle Park, NCPREFACEThe National Toxicology Program (NTP) and the National Institute of Environmental HealthSciences (NIEHS) established the NTP Center for the Evaluation of Risks to HumanReproduction (CERHR) in June 1998. The purpose of the Center is to provide timely, unbiased,scientifically sound evaluations of human and experimental evidence for adverse effects onreproduction and development caused by agents to which humans may be exposed.Soy formula was selected for expert panel evaluation because of public concern for the possiblehealth effects. Soy formula contains soy protein isolates and is fed to infants as a supplementCorrespondence to: Michael D. Shelby, PhD, NIEHS EC-32, PO Box 12233, Research Triangle Park, NC 27709. E-mail:firstname.lastname@example.com.‡Dr. Kesner was unable to participate in the Expert Panel meeting but participated in the drafting and review of the report before andafter the meeting.†This article is a U.S. Government work and, as such, is in the public domain in the United States of America.NIH Public AccessAuthor ManuscriptBirth Defects Res B Dev Reprod Toxicol. Author manuscript; available in PMC 2008 March 11.Published in final edited form as:Birth Defects Res B Dev Reprod Toxicol. 2006 August ; 77(4): 280–397.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscript
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to or replacement for human milk or cow milk. Soy protein isolates contain phytoestrogensthat occur naturally in some legumes, especially soybeans. Phytoestrogens are non-steroidal,estrogenic compounds. In plants, nearly all phytoestrogens are bound to sugar molecules andthese phytoestrogen-sugar complexes are not hormonally active. Phytoestrogens are found inmany food products in addition to soy formula, especially soy-based foods such as tofu, soymilk, and in some over-the-counter dietary supplements.To obtain information about soy formula for the CERHR evaluation, the PubMed (Medline)and Toxline databases were searched through February 2006 with genistein and its CAS RN(446-72-0), soy, soya, and relevant keywords. References were also identified from databasessuch as REPROTOX®, HSDB, IRIS, and DART and from the bibliographies of reports beingreviewed.This evaluation results from the effort of a 14-member panel of government and non-government scientists that culminated in a public expert panel meeting held March 15–17,2006. This report is a product of the expert panel and is intended to (1) interpret the strengthof scientific evidence that soy formula is a reproductive or developmental toxicant based ondata from in vitro, animal, or human studies, (2) assess the extent of human exposures to includethe general public, occupational groups, and other sub-populations, (3) provide objective andscientifically thorough assessments of the scientific evidence that adverse reproductive/developmental health effects may be associated with such exposures, and (4) identifyknowledge gaps to help establish research and testing priorities to reduce uncertainties andincrease confidence in future evaluations. This report has been reviewed by members of theexpert panel and by CERHR staff scientists. Copies have been provided to the CERHR CoreCommittee that is made up of representatives of NTP-participating agencies.This Expert Panel Report will be included in the subsequent NTP-CERHR Monograph on thePotential Human Reproductive and Developmental Effects of Soy Formula. This monographwill include the NTP-CERHR Brief, the Expert Panel Report, and all public comments on theExpert Panel Report. The NTP-CERHR Monograph will be made publicly available andtransmitted to appropriate health and regulatory agencies.The NTP-CERHR is headquartered at NIEHS, Research Triangle Park, NC and is staffed andadministered by scientists and support personnel at NIEHS and at Sciences International, Inc.,Alexandria, Virginia.1.0 CHEMISTRY, USE, AND HUMAN EXPOSURE1.1 ChemistrySoy infant formula refers to infant food made using soy protein isolate and other components.The term, "soy formula" is used as a synonym for "soy infant formula" in this report. The terms"soy" and "soybean" are used commonly for the leguminous Asian plant Glycine max. Soybeanis also used to designate the edible seed of this plant. In this report, the term "soy" is used asan adjective to denote products derived from the edible seed (e.g., soy milk, soy formula, soymeal) and "soybean" is used to refer to the edible seed itself. In the U.S., the nutrientcomposition of soy and other infant formulas is regulated by the Food and Drug Administration(FDA, 2000). Table 1 lists the primary ingredients in some common brands of powdered soyinfant formulas. Those ingredients include corn syrup, soy protein isolate, vegetable oils, andsugar (Drugstore.com, 2004). In addition, the formulas are fortified with nutrients such as iron,calcium, phosphorous, magnesium, zinc, manganese, copper, iodine, selenium sodium,potassium, chloride, choline, inositol, and vitamins A, C, D, E, K, and B (B1, B2, B6, B12,niacin, folic acid, pantothenic acid, biotin). Before feeding, 8.7–9.3 g powdered formula isRozman et al.Page 2Birth Defects Res B Dev Reprod Toxicol. Author manuscript; available in PMC 2008 March 11.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscript
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added to 2 fluid ounces of water (Drugstore.com, 2004). Soy formulas are also available asconcentrated liquids and as ready-to-feed formulations (USDA, 2002b).Contaminants of soy protein include phytates (1.5%), which bind minerals, and proteaseinhibitors, which have antitrypsin, antichymotrypsin, and anti elastin properties (AAP, 1998).As discussed further in Section 1.2.1, formulas are fortified with minerals to compensate forphytate binding and heated to inactivate protease inhibitors. Aluminum is found in soy formulasat concentrations of 600–1300 ng/mL, levels that exceed aluminum concentrations in humanmilk, 4–65 ng/mL (AAP, 1998). Mineral salts added to soy formulas are the source ofaluminum.Soy products contain phytoestrogens of the isoflavone class (MAFF, 1998b; Setchell et al.,1998; UK Committee on Toxicity, 2003). Isoflavones can be conjugated to glucose or othercarbohydrate moieties. Carbohydrate conjugates are generically called glycosides, and glucoseconjugates are called glucosides. Small amounts of isoflavones are present in soy products intheir unconjugated (aglycone) forms. The three main aglycones found in soy formula aregenistein, daidzein, and to a smaller extent, glycitein. The genistein content of soy formula hasbeen the subject of commentary because of concern about exposure of infants to estrogeniccompounds; however, soy formula and other soy-based foods contain many components ofwhich genistein is only one. In this report, attention will be focused on the effects of feedingsoy formulas and other soy-based products to humans or experimental animals. A separateCERHR Expert Panel Report on Genistein (Rozman et al., in press) will focus on the effectsof administering genistein itself, isolated from other plant components. When studies havebeen carried out using administration of isoflavone mixtures, the Expert Panel will judgewhether the isoflavone mixture is expected to be informative on possible effects of feeding soyproducts or the mixture is more appropriately discussed as estimating possible effects ofgenistein. The Expert Panel recognizes that it is not entirely satisfactory to discuss isoflavonemixtures as either representing soy foods or purified genistein.Chen and Rogan (2004) reported that only 3.2–5.8% of total isoflavone in soy formula consistsof unconjugated genistein and daidzein, and that amounts can vary by batch. The majority(<65%) of isoflavones detected in soy formula are conjugated to sugar molecules to formglycosides (Setchell et al., 1998). Glucose groups on glycoside compounds can be esterifiedwith acetyl or malonyl groups to form acetyl- or malonylglycosides (UK Committee onToxicity, 2003). Isoflavones detected in soy infant formula by Setchell et al. (Setchell et al.,1998) or the U.K. Ministry of Agriculture, Fisheries, and Food (MAFF, 1998b) are listed inFigure 1, along with their structures.Conjugation with glucose groups increases water solubility of isoflavones, which are lowmolecular-weight hydrophobic compounds (UK Committee on Toxicity, 2003). Glucosidecompounds can be deconjugated to form the biologically active aglycone compound by gutmicroflora (MAFF, 1998b), under acidic conditions (UK Committee on Toxicity, 2003), or bymetabolic enzymes (Setchell et al., 1998). Therefore, exposure to a particular isoflavone (e.g.,genistein) is theoretically the sum of the aglycone and respective glycoside compoundconcentrations converted on the basis of molecular weight. However, the aglycone isreconjugated in the gut wall leaving approximately 1–2% free aglycone to enter the portalcirculation. Chen and Rogan (2004) report that isoflavones are glucuronidated and circulatedprimarily in conjugated form. Estimated infant exposures to particular isoflavones through soyformula are discussed in Section 1.2.3.Setchell et al. (1998) stated that isoflavone levels in soybeans can vary as a result of geographiclocation, climate, and growing conditions. They noted that high temperatures during processingof formula could affect the profile of conjugated isoflavones but are not expected to affect totalRozman et al.Page 3Birth Defects Res B Dev Reprod Toxicol. Author manuscript; available in PMC 2008 March 11.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscript
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isoflavone levels. For example, malonyl groups are especially heat labile and decompose toform their respective acetylglycoside compounds.1.2 Use and Human Exposure1.2.1 Production information—In the manufacture of soy infant formula, the hull of thesoybean is removed and the pulp is processed into oil and flake (AAP, 1998). Soy proteinisolate is extracted from the flake using a slightly alkaline solution and is precipitated at theisoelectric point of 4.5. The resulting isolate has a purity of ≥90% soy protein. The soy proteinisolate is fortified with L-methionine, L-carnitine, and taurine. L-methionine improves thebiological quality of the protein. Carnitine is needed for oxidation of long-chain fatty acids.Taurine is an antioxidant that is a major conjugate of bile acids in infants. Both carnitine andtaurine are added at concentrations found in human milk. Vegetable oils such as soy, palm,sunflower, olein, safflower, and coconut are added to provide fats. Corn starch, tapioca starch,and sucrose are used as carbohydrate sources. Phytates, which bind minerals, are present insoy proteins at 1.5%. Therefore, total phosphorus and calcium are added at concentrations thatare 20% higher than in cow-milk formulas, and the formulas are supplemented with iron andzinc. Heat applied during the processing of soy protein removes 80–90% of protease inhibitoractivity.Manufacturers of soy formula and some brand names of soy formula sold in the U.S. are listedin Table 184.108.40.206 Use—Soy formulas are used generally to feed infants who are allergic to dairy productsor are intolerant of lactose, galactose, or cow-milk protein (Essex, 1996; Tuohy, 2003). Infantsare often changed from cow-milk to soy formula when they have symptoms such as colic,crying, diarrhea, and vomiting (Forsyth et al., 1985). Some parents feed their infants soyformula to maintain a vegetarian lifestyle or because of perceived health benefits of soy foodconsumption (Badger et al., 2002). Soy formula is not recommended currently for preterminfants.Essex (1996) reported that soy formulas represented 7% of infant formula sales in the U.K.,13% in New Zealand, and 10–20% in the U.S. A 1998 infant-feeding survey conducted byRoss Products Division indicated that 18% of infants are fed soy formula during the first yearof life (Strom et al., 2001). Based on the 2000 U.S. Census estimate of 4 million Americaninfants younger than 1 year of age, Strom et al. (2001) estimated that 750,000 U.S. infants peryear are fed soy formula. According to marketing data and hospital discharge records, it hasbeen estimated that 25% of newborns in the U.S. are fed soy formula (Badger et al., 2002). Astudy conducted at Yale University examined formula changes in 189 breast-fed infants and184 formula-fed infants and reported that a total of 87 infants [23%] received soy formulasometime during the first 4 months of life (Forsyth et al., 1985). A telephone survey in Israelidentified soy formula feeding in 31.5% of 1803 infants at some time during the first year oflife (Berger-Achituv et al., 2005). Of the children on soy formula, 65% used it for 12 monthsor more. The decision to use soy formula as opposed to cow-milk formula was made by themother rather than a health care provider in the majority of instances in the Israeli survey. Themother's decision was most often based on her personal preference rather than concerns forcow milk allergies or for symptoms.1.2.3 Occurrence and infant exposure—Levels of isoflavones and their glycosides ininfant soy formula were reported in a survey of soy foods conducted by the U.S. Departmentof Agriculture (USDA) and Iowa State University (USDA, 2002b). The survey included resultspublished by Murphy et al. (1997), Nguyenle et al. (1995), and Setchell et al. (1997).Unpublished data and analyses conducted at Iowa State University were also included in theRozman et al.Page 4Birth Defects Res B Dev Reprod Toxicol. Author manuscript; available in PMC 2008 March 11.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscript
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survey. Results were presented for the most common isoflavones, genistein, daidzein, andglycitein, and their glycosides, although some studies did not include glycitein values.Glycoside values were converted to free-form (aglycone) values. Total isoflavones werecalculated if values were available for daidzein and genistein equivalents, but it was noted thatreported total isoflavone values may not equal values obtained by adding individual isoflavoneequivalents. The survey included results for formula powders, liquid concentrates, andreconstituted or ready-to-eat formulas. Results of the infant soy formula survey are reportedin Table 3. Reconstituted or ready-to-feed soy formulas contained genistein equivalents 1.58–2.26 mg/100 g formula [15.8–22.6 µg/g formula], daidzein equivalents 0.75–1.91 mg/100 gformula [7.5–19.1 µg/g formula], glycitein equivalents 0.28–0.35 mg/100 g formula [2.8–3.5µg/g formula], and total isoflavone equivalents 2.63–4.17 mg/100 g formula [26.3–41.7 µ/gformula]. As expected, levels of isoflavone equivalents were higher in soy formula powdersand liquid concentrates. Percentages for individual isoflavones were genistein equivalents36.8–70.1%, daidzein equivalents 18.2–45.8%, and glycitein equivalents 7.9–13.0%.In studies supported by Wyeth Laboratories, Protein Technologies International, and theNational Institutes of Health (NIH), Setchell et al. (1997) measured isoflavone levels in infantsoy formula and in the blood of infants (n=7) consuming soy formula. Results of the study, aswell as additional details about methodology, were published in a later report by Setchell et al.(1998). After extraction with methanol, isoflavone levels in five U.S. infant formulas weremeasured by high performance liquid chromatography (HPLC). Genistein and daidzeinconjugates, mainly glycosides, were the most abundant isoflavone-related compoundsidentified. Mean percentages of isoflavones and their respective conjugates were reported at67.1% genistein equivalents, 28.7% daidzein equivalents, and ~ 5% glycitein equivalents insoy infant formula. Levels of individual isoflavones, based on conversion to aglyconeconcentrations, are included in Table 3, which summarizes the USDA survey of soy formulas.Total average isoflavone equivalents concentrations were reported at 32–47 mg/L in preparedformulas. Table 4 lists estimated intakes of isoflavones and the assumptions used to estimateexposure. Depending on infant age, isoflavone equivalents intake was estimated at 6–12 mg/kg bw/day. A comparison of estimated isoflavone equivalents intake from soy formulasavailable in different countries is included in Table 5, which also includes estimates ofindividual isoflavone equivalents levels based on mean levels detected in formula.Franke et al. (1998) measured isoflavone+conjugate levels in four U.S. brands of soy formulausing methanol extraction and HPLC with diode-array ultraviolet detection. Isoflavoneconjugation patterns were similar to those found in soy foods and included malonates (32–43%), glucosides (37–52%), acetates (6–7%), and aglycones (9–13%). Total isoflavones weremeasured at 155.1–281.4 µg/g. Percentages of each type of isoflavone included 55.3–57.7%genistein equivalents, 34–36.1% daidzein equivalents, and 7.4–8.5% glycitein equivalents.Based on an intake of 1 L formula, a body weight of 4.5 kg, and instructions for preparingformula, the authors estimated infant isoflavone equivalents exposure at ~ 7 mg/kg bw/day.The authors stated that isoflavone+conjugate exposure in infants fed soy formula is 4–6 timeshigher than in adults eating a soy-rich diet (~ 30 g/day).Irvine et al. (1998a) used an HPLC technique to measure isoflavone equivalents levels in infantsoy formulas and foods such as cereals and pureed meats or vegetables purchased in NewZealand. In both soy formula and infant foods, the majority of genistein and daidzein werepresent as their respective glucosides. In soy formula, total concentrations of isoflavones (mean±SEM) were 87±3 µg/g genistein and 49±2 µg/g daidzein. [If it is assumed that genisteinand daidzein are the only isoflavones in the formulas, the percentages of total isoflavonerepresented by each compound are 64% genistein equivalents and 36% daidzeinequivalents.] Estimated infant exposures resulting from soy formula intake are summarizedin Table 6. In three different infant cereals [composition not indicated] and two differentRozman et al. Page 5Birth Defects Res B Dev Reprod Toxicol. Author manuscript; available in PMC 2008 March 11.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscript
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infant dinners [composition not indicated], genistein+conjugate levels were measured at 3–287 mg aglycone equivalents/kg food and daidzein levels at 2–276 mg aglycone equivalents/kg food. The study authors noted that a single serving of one of the cereals could result inisoflavone exposures ranging from 0.01–0.8 mg aglycone equivalents/kg bw/day in a 4-month-old infant, thus increasing isoflavone intake by >25%.Murphy et al. (1997) analyzed six brands of soy formula sold in the U.S. and reported that totalisoflavone levels were similar across brands and were comprised of 59% genistein equivalents,29% daidzein equivalents, and 12% glycitein equivalents. Levels of isoflavones and theirconjugates are reported in the USDA survey (Table 3), and estimates of infant exposure arereported in Table 6.Hoey et al. (2004) used a liquid chromatography-mass spectrometry (LC-MS) method tomeasure isoflavone+conjugate levels in three soy-based infant formulas from the U.K. Thetotal isoflavone content of soy formulas consisted of ~ 58–67% genistein equivalents, 27–29%daidzein equivalents, and 6–16% glycitein equivalents. The study authors estimated that 4–6-month-old infants consumed between 17.5 and 33.0 mg/day isoflavone equivalents or 1.7–4.4mg aglycone equivalents/kg bw/ day. Infants fed the cow-milk formula with the highestisoflavone content (2.1 mg/kg formula) were estimated to consume 0.16–0.27 mg/dayisoflavone equivalents, or 0.02–0.03 mg aglycone equivalents/kg bw/day.The U.K. Ministry of Agriculture, Fisheries, and Food (MAFF, 1998a,b) conducted a surveyof isoflavone levels in 6 brands of infant soy formulas. The formulas were analyzed for 14different isoflavones and their conjugates and one coumestan compound using methanolextraction followed by HPLC and LC-MS. Isoflavone levels were normalized to aglyconeconcentrations. Isoflavones were detected in all soy formulas at concentrations of 18–41 mg/L made-up formula. The majority of iso-flavones were present as glycosides, but smalleramounts of acetyl and malonyl forms and aglycones were also present. The most abundantisoflavones, genistein-, daidzein-, and glycitein-related compounds, represented an average of58, 36, and 6% of formulations on a molar basis, respectively. The isoflavones/conjugatesglycitein, 6′-O-acetylglycitin, formononetin, and biochanin A and the coumestan coumestrolwere not detected. Eight batches of one soy formula, SMA Wysoy, purchased at different timesand locations were analyzed to determine variation between batches. Isoflavone concentrationswere 18–33 mg aglycone equivalents/L formula as made up. The U.K. Ministry of Agriculture,Fisheries, and Food concluded that isoflavone levels did not vary enough to significantly impactexposure. Statistical analyses by analysis of variance (ANOVA) and F-test did not find asignificant difference at the 5% level in isoflavone levels between batches of the same brandand between different brands.The U.K. Ministry of Agriculture, Fisheries, and Food summarized and compared levels ofisoflavones and their conjugates measured in soy formula from other countries, and thosevalues are outlined in Table 5. The Ministry of Agriculture, Fisheries, and Food concluded thatisoflavone levels in soy formula from the U.K. were similar to concentrations reported in othercountries; differences most likely resulted from batch variations in soy isolate isoflavone levels,slight variations in formulas, and minor differences in analytic methodology.The U.K. Ministry of Agriculture, Fisheries, and Food estimated isoflavone+conjugate intakein 1–2-month-old and 4–6-month-old infants based on survey results, average body weight,and intake data. Isoflavone+conjugate intake was estimated at 5 mg aglycone equivalents/kgbw/day in 1–2-month-old infants and 4.5 mg aglycone equivalents/kg bw/day in 4–6-month-old infants. A comparison of the U.K. values with values obtained from other countries isincluded in Table 6.Rozman et al.Page 6Birth Defects Res B Dev Reprod Toxicol. Author manuscript; available in PMC 2008 March 11.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscript
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Setchell et al. (1997, 1998) used a gas chromatography (GC)-MS method to compare isoflavonelevels in soy formula and human milk and to measure isoflavone levels in human milk aftersoy food ingestion. In comparison to soy formula, levels of isoflavones (measured by GC/MS)were substantially lower in cow-milk formula (below detection limit, which was not reported)and in milk collected from nine healthy, omnivorous, lactating women (mean±SD = 5.6 ± 4.4µg/L) (Setchell et al., 1998). Equol was detected in seven of nine human-milk samples. A >10-fold increase in milk isoflavone levels was observed after ingestion of 30 mg isoflavones +conjugates in the form of 10 g toasted soy nuts. [Figure 2 in the study report suggests thatmilk daidzein levels increased >40-fold and genistein levels increased >10-fold 1 day afterthe ingestion of soy nuts.] The study authors noted that isoflavones occur predominantly asglucuronide conjugates in human milk. The U.K. Ministry of Agriculture, Fisheries, and Food(MAFF, 1998a) analyzed three cow-milk formulas for isoflavones using HPLC and LC-MSmethods, and reported that isoflavone levels were below the detection limit of 0.25–0.5 mg/L.Irvine et al. (1998a) used an HPLC method to measure isoflavone levels in dairy-based formulaand in human milk. Levels of genistein and daidzein were below the detection limit (0.1 µg/g) in human milk samples from 11 mothers and in the dairy-based formulas. Hoey et al.(2004) used an LC-MS method to measure isoflavone levels in cow milk-based infant formulasfrom the UK. Isoflavones were not detected in the majority of the cow-milk infant formulas(0.5 mg/kg detection limit). King et al. (1998) conducted HPLC analyses on Australian cowmilk and reported mean isoflavone levels of <5 ng / mL daidzein, 4–29 ng/mL genistein, and45–293 ng/mL equol.After hydrolyzing samples to convert conjugated isoflavones to aglycones, Setchell et al.(1997, 1998) used a GC-MS method to measure total plasma isoflavone levels in seven 4-month-old male infants fed Isomil soy formula. Mean±SD levels of genistein and daidzeinwere reported at 683±442.6 and 295.3±59.9 µg/L, respectively, and total isoflavones werereported at 552–1775 µg/L (mean 980 µg/L). [Plasma glycitein levels were not measured.]The study authors noted that they did not attempt to measure the extent of isoflavoneconjugation in infant plasma. These total plasma isoflavone levels were 50–100-fold higher ininfants fed soy formula compared to 4-month-old male infants fed human milk (mean±SD 4.7±1.3 µg/L, n = 7) and cow-milk formula (mean±SD 9.3±1.2 µg/L, n = 7). Plasma isoflavonelevels in infants fed soy formula were also higher compared to adults (50–200 µg/L) andJapanese adults (40–240 µg/L) ingesting similar levels of isoflavones+conjugates from soy-based foods.The CERHR Expert Panel Report on Genistein provides estimates of adult exposures toisoflavones + conjugates and allows for a comparison of isoflavone exposures in infants fedsoy formula (Rozman et al., in press). Most estimates of adult exposure were based on dietarysurveys, whereas infant exposures were based on isoflavone levels measured in soy formulaand assumed body weight and formula intake. Based on limited information provided in theGenistein report, mean or median genistein + conjugate exposures are estimated at ≤1 mgaglycone equivalents/day (0.01 mg aglycone equivalents/kg bw/day assuming a 70 kg bw) inU.S. adults with no specified dietary preferences, 10–15 mg aglycone equivalents/day (0.1–0.2 mg aglycone equivalents/kg bw/day) in semi-vegetarian or vegetarians in one U.S. survey,and 5–50 mg aglycone equivalents/day (0.1–1 mg aglycone equivalents/kg bw/day) in Asianadults. Based on mean mg/kg bw/day intake estimates, infants fed soy formula can be exposedto isoflavone+conjugate levels that are two to three orders of magnitude higher than U.S. adultswith low isoflavone exposure, one to two orders of magnitude higher than vegetarians inWestern countries, and within the same order of magnitude to one order of magnitude higherthan Asians. Comparisons of isoflavone+conjugate intake in infants and adults based on foodor formula intake were fairly consistent with comparisons based on blood isoflavone levelspresented in Section 2.Rozman et al.Page 7Birth Defects Res B Dev Reprod Toxicol. Author manuscript; available in PMC 2008 March 11.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscript
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Differences in soy food exposure patterns throughout life were noted for Americans comparedto Asians (Badger et al., 2002). In the U.S., typical diets are low in soy food intake, and thefetus is thus exposed to low levels of genistein. Significant exposure to genistein and itsconjugates occurs in the approximately 25% of infants who are fed soy formula. After thoseinfants are weaned, soy food intake and genistein exposure drops and typically remain lowover the lifetime. In Asian cultures consuming soy products, the fetus is exposed to genisteinand its conjugates as a result of maternal soy food intake. At birth, most infants are either breastfed or fed cow-milk formula, so exposure to genistein is very low during infancy. On weaning,the infants begin receiving soy foods and exposure to soy products and genistein+conjugatesremain high over their lifetime.1.3 Utility of DataThe human exposure data consist of a database reporting isoflavone+conjugate levels in soyformulas in the U.S. and other countries. Exposures of infants to isoflavones and theirconjugates through consumption of soy formulas have been estimated based on levels ofisoflavones+conjugates measured in formulas, formula intakes, and infant body weights. Onestudy reported blood levels of isoflavones in infants fed soy formulas and compared the valuesto infants fed cow milk or human milk and to adults who ingested soy products. The availabledata provide a good foundation for estimating approximate exposure and dose within broadpopulations or within individuals when the soy formula and the infants' weight and age areknown.1.4 Summary of Human Exposure DataSoy formula refers to infant food made using soy protein isolate and other components suchas corn syrup, vegetable oils, and sugar (Drugstore.com, 2004). The soy protein isolate isfortified with L-methionine, L-carnitine, and taurine (AAP, 1998). The formulas are fortifiedwith nutrients (Drugstore.com, 2004). Contaminants of soy protein include phytates (1.5%),which bind minerals, and protease inhibitors, which have antitrypsin, antichymotrypsin, andanti elastin properties (AAP, 1998). Phosphorus, calcium, iron, and zinc are added to soyformula to compensate for phytate binding of minerals. Heat applied during the processing ofsoy protein removes 80–90% of protease inhibitor activity. Aluminum is present in soyformulas because of the addition of mineral salts.Soy products contain phytoestrogens of the isoflavone class (MAFF, 1998b; Setchell et al.,1998; UK Committee on Toxicity, 2003). The primary isoflavones detected in soybeans arederived from genistein, daidzein, and to a smaller extent, glycitein. The majority (>65%) ofisoflavones in soy formula are conjugated to sugar molecules to form glycosides (Setchell etal., 1998). Glucose groups in glycoside compounds can be esterified with acetyl or malonylgroups to form acetyl- or malonyl glycosides (UK Committee on Toxicity, 2003). Smallamounts of genistein and daidzein (3.2–5.8%) are present in soy products in their unconjugated(aglycone) forms (Chen and Rogan, 2004). Isoflavones detected in soy infant formula bySetchell et al. (1998) or the U.K. Ministry of Agriculture, Fisheries, and Food (MAFF,1998b) are listed in Figure 1 with their structures. Because glycosidic compounds can bedeconjugated in the body to form the biologically active aglycone compound, exposure to aparticular isoflavone (e.g., genistein) is theoretically the sum of the aglycone and respectiveglycoside compound concentrations converted on the basis of molecular weight (MAFF,1998b; Setchell et al., 1998; UK Committee on Toxicity, 2003). Isoflavone levels in soybeansare reported to vary as a result of geographic location, climate, and growing conditions (Setchellet al., 1998).It is estimated that 10–20% of infants in the U.S. are fed soy formula some time during thefirst year of life (Essex, 1996; Strom et al., 2001). Soy formulas are generally used to feedRozman et al.Page 8Birth Defects Res B Dev Reprod Toxicol. Author manuscript; available in PMC 2008 March 11.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscript
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infants who are allergic to dairy products or are intolerant of lactose, galactose, or cow-milkprotein (Essex, 1996; Tuohy, 2003). Infants are sometimes given soy formula when they havesymptoms such as colic, crying, diarrhea, or vomiting (Forsyth et al., 1985) or to maintain avegetarian or perceived healthy lifestyle (Badger et al., 2002).A number of studies measured total isoflavone (aglycone + glycoside) levels in infant formulas,determined percentages of individual isoflavones, or estimated infant exposures. In a USDAsurvey of infant formulas, total isoflavone levels reported in reconstituted formulas or ready-to-feed formulas were reported at 15.8–22.6 µg genistein equivalents/g formula, 7.5–19.1 µgdaidzein equivalents/g formula, 2.8–3.5 µg glycitein equivalents/g formula, and 26.3–41.7 µgtotal isoflavone equivalents/g formula (USDA, 2002b). On a mg isoflavone equivalents/Lready-to-feed formula basis, total isoflavone levels were reported at 25–47 mg/L in U.S. soyformulas (Murphy et al., 1997; Setchell et al., 1998) except for one study reporting a totalisoflavone level of 155–281 mg/L (Franke et al., 1998) and at 18–41 mg/L in formulas obtainedfrom the U.K. and Australia (Knight et al., 1998; MAFF, 1998a,b). Percentages of individualisoflavones representing total isoflavone levels in U.S. soy formulas were estimated at 36.8–70.1% genistein equivalents, 18.2–45.8% daidzein equivalents, and 5–13.0% glyciteinequivalents (Murphy et al., 1997; Setchell et al., 1997, 1998; Franke et al., 1998; USDA,2002b). Percentages of individual isoflavones in formulas from the U.K. were reported at 58–67% genistein equivalents, 27–36% daidzein equivalents, and 6–16% glycitein equivalents(MAFF, 1998a,b; Hoey et al., 2004).Isoflavone exposure through soy formula intake has been estimated in the U.S. and othercountries based on total isoflavone levels measured in soy formulas and assumptions of formulaintakes and infant body weights. In the U.S., total isoflavone intake by infants was estimatedat 1–12 mg/kg bw/day (Murphy et al., 1997; Setchell et al., 1997, 1998; Franke et al., 1998).In the U.K. and New Zealand, isoflavone intake by infants was estimated at 1.7–5 mg/kg bw/day (Irvine et al., 1998a; MAFF, 1998a,b; Hoey et al., 2004).Mean ± SD plasma levels of total isoflavones in infants fed soy formula were reported at 683±442.6 µg/L for genistein equivalents, 295.3±59.9 µg/L for daidzein equivalents, and 552–1775 µg/L (mean 980 µg/L) for total isoflavones (Setchell et al., 1997, 1998). Mean plasmatotal isoflavone levels were ~ 2 orders of magnitude higher than in infants fed cow-milk formulaor human milk. Mean plasma levels of infants fed soy formulas were ~ 5–20 times higher thanJapanese adults or adults ingesting similar levels of total isoflavones from soy-based foods, ~50 times higher than vegetarian adults in Western populations, and ~ 500 times higher thanomnivorous adults in Western populations (Setchell et al., 1997, 1998) (Table 7). Dietaryexposure estimates comparing total isoflavone intake in infants ingesting soy formula versusadults are fairly consistent to comparisons based on plasma total isoflavone levels [see(Rozman et al., in press)].2.0 GENERAL TOXICOLOGY AND BIOLOGICAL EFFECTS2.1 Toxicokinetics and MetabolismThis section focuses on toxicokinetics and metabolism of 2 of the isoflavones, genistein anddaidzein, found in soy formula and other soy foods. There are few studies available ontoxicokinetics in infants. Therefore, a large part of this section is based on studies conductedin adults. Studies that focus on toxicokinetics after exposure to pure genistein are discussed inthe CERHR Expert Panel Report on Genistein (Rozman et al., in press).2.1.1 Human22.214.171.124 Absorption: Genistein and daidzein exist mainly as glycosides in unfermented soyfoods. Due to their high water solubility and molecular weight, isoflavone glycosides are notRozman et al.Page 9Birth Defects Res B Dev Reprod Toxicol. Author manuscript; available in PMC 2008 March 11.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscript
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readily absorbed across the gastrointestinal tract, as shown in a study of adults by Setchell etal. (1998) (reviewed in UK Committee on Toxicity, 2003). For absorption to occur, isoflavonesmust first be hydrolyzed to their aglycones, which have some hydrophobicity and lowermolecular weights. Absorption occurs primarily in the small and large intestine. Table 7 reportsblood levels in infants and adults resulting from typical dietary exposures, and Table 8 reportsblood levels in studies where humans were fed soy-based foods or supplements.Infants are able to absorb isoflavones, and infants fed soy formula were shown to have plasmatotal isoflavone blood levels exceeding those of Japanese adults several-fold (Table 7) (Setchellet al., 1998). Higher concentrations in infants are postulated to result from lower body weight,frequent feedings, and reduced metabolism.Studies examining the bioavailability [appearance of aglycone in plasma] of isoflavonesingested as glycosides versus aglycones have reported conflicting findings (UK Committee onToxicity, 2003). Although some studies reported that bioavailability is increased whenisoflavones are ingested as aglycones compared to glycosides, other studies found nodifferences in bioavailability. One study reported that genistein levels peaked a mean of 6.6 hrafter ingestion of the aglycone compared to 9 hr when ingested as glycosides (Setchell et al.,2001). Bioavailability, as determined by area under the time-concentration curve (AUC), wasreported to be greater for the glycosides than the aglycones. In a second study, Xu et al.(2000) observed that bioavailability of isoflavones did not vary when they were administeredto women as foods containing a high percentage of aglycones (e.g., tempeh) compared to ahigh percentage of glycosides (e.g., soybeans) but noted that a study by Hutchins et al.(1995) found increased bioavailability for the aglycones. [The Expert Panel notes thatbioavailability in pharmacology and toxicology refers to the ratio of AUC after oralingestion to the AUC after intravenous (i.v.) injection. The term bioavailability is oftenused in different ways by different authors.]A study by Xu et al. (2000) found that increases in dietary fat, protein, and cholesterol had noeffect on bioavailability of isoflavones administered three times daily to eight women throughpowdered soy milk. Nevertheless, it has been postulated that bioavailability may be affectedby food matrix, inter-individual variations, and intestinal microflora. Indeed, some studiesreported that dietary fiber may lower isoflavone absorption (ILSI, 1999; UK Committee onToxicity, 2003). A detailed evaluation of genistein and daidzein kinetics after ingestion ofdifferent soy foods was published by Cassidy et al. (2006). Men aged 18–55 years (n = 21),premenopausal regularly-cycling women aged 18–53 (n = 21), and postmenopausal womenaged 48–69 (n = 17) were evaluated [only the men and premenopausal women will beconsidered here]. Subjects were given each of three soy foods separated by at least 2 weeksafter which blood samples were drawn periodically over 72 hr for measurement of total daidzeinand genistein after hydrolysis. The foods were soy milk containing 15.2–19.6 µg daidzeinaglycone equivalents and 22.3–28.3 µg genistein aglycone equivalents, bread rolls made withtextured vegetable protein containing 163.2 µg daidzein aglycone equivalents and 312.9 µggenistein aglycone equivalents, and tempeh burgers containing 72.4–137.1 µg daidzeinaglycone equivalents and 140.3–186.4 µg genistein aglycone equivalents. As noted above,tempeh isoflavones are present largely as aglycones. The kinetic parameters were normalizedby the isoflavone content of the food (Table 9). The authors of this study noted that isoflavoneswere absorbed more rapidly from liquid than from solid matrices and that absorption and AUCare higher when foods contain predominantly aglycones (tempeh burgers) as opposed toglycuronides (textured vegetable protein rolls).Blood levels of genistein and daidzein (see Table 8) did not suggest saturated absorption in 12women administered isoflavones at 0.7, 1.3, or 2.0 mg/kg bw through soy milk powder (44%genistein and 56% daidzein) (Xu et al., 1994).Rozman et al.Page 10Birth Defects Res B Dev Reprod Toxicol. Author manuscript; available in PMC 2008 March 11.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscript
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Absorption half-lives for both daidzin and genistein, presumably as glucuronides and sulfatesof daidzein and genistein, were reported at ~ 1–3 hr after intake of foods containing ≤210 mgof each isoflavone or providing doses of ≤2 mg/kg bw/day of each isoflavone (Lu et al.,1995; Lu and Anderson, 1998; Whitten and Patisaul, 2001). Genistein and daidzein equivalentswere reported to peak at ~ 6–8 hr after ingestion of soy foods (Whitten and Patisaul, 2001;Pumford et al., 2002; UK Committee on Toxicity, 2003).184.108.40.206 Distribution: One study reported volume of distribution for genistein and daidzeinafter intake of 50 mg of the compounds as aglycones and glycosides (Setchell et al., 2001).After intake of each compound in its glycosidic form, the mean volume of distribution for thebioavailable fraction was reported at ~ 161 L [2.7 L/kg bw assuming a 60 kg bw] for genisteinand ~ 236 L [3.9 L/kg bw] for daidzein. Ingestion of the glycosidic compounds resulted involumes of distribution for the bioavailable fraction of ~ 112 L [1.9 L/kg bw] for genisteinand 77 L [1.3 L/kg bw] for daidzein. Similar mean volumes of distribution were reported fortotal genistein and daidzein in male and female volunteers who consumed 1–16 mg/kg bwformulations containing 70–100% unconjugated isoflavones; the volumes of distribution were~ 1–6 L/kg bw for genistein and ~ 1–3 L/kg bw for daidzein (Bloedon et al., 2002; Busby etal., 2002). In the same studies, volumes of distribution were higher for free isoflavones, ~ 16–877 L/kg for genistein and 15–245 L/kg bw/day daidzein. The study authors noted that thehigher volumes of distribution for the free versus total isoflavones suggest that free genisteinand daidzein are more likely to enter or be sequestered within tissues. [There are problemsin the reporting of volumes of distribution for the aglycones in these studies. The ExpertPanel finds ranges of 16–877 and 15–245 L/kg bw/day to be implausible in this variability.In addition, volumes of distribution in the range of <10 L/kg bw in some reports are notconsistent with volumes of distribution in the hundreds of L/kg bw in other reports. It ispossible that the lower values were obtained from a mixture of aglycones andglucuronides with glucuronides predominating. The higher number may not take intoconsideration the bias toward the conjugated compounds in equilibrium.]Adlercreutz et al. (1999) used a GC-MS method to measure maternal plasma, cord plasma, andamniotic fluid phytoestrogen levels in seven healthy omnivorous Japanese women (20–30years old) who had just given birth. Results for isoflavones and two metabolites are listed inTable 10, with total levels of isoflavone levels reported for maternal blood and unconjugatedand conjugated levels reported for cord plasma and amniotic fluid. Conjugated andunconjugated values were not reported for maternal plasma because the authors stated thatpatterns in plasma are well established. Isoflavone and metabolite levels were variable betweensubjects, and three subjects had very low levels of equol. Levels of isoflavones and metabolitesin cord blood and amniotic fluid were similar to maternal cord blood levels. Pearsoncorrelations are shown in Table 11. Levels of O-demethylangolensin and equol in maternalplasma correlated significantly with levels in cord plasma and amniotic fluid. Significantcorrelations between cord plasma and amniotic fluid were found for all the isoflavones andmetabolites. Lignans were also detected in maternal and fetal compartments but at much lowerlevels. The authors concluded that phytoestrogens cross the placenta. Levels in fetuses weresimilar to maternal levels, and conjugation patterns were reportedly similar to those observedin Japanese individuals.Foster et al. (2002b) measured phytoestrogens in 57 human amniotic fluid samples collectedbetween 15 and 23 weeks of gestation. Samples were collected in Los Angeles [ethniccomposition and dietary factors not discussed]. Measurements were made by GC/MS afterglucuronidase treatment to hydrolyze the conjugates. Genistein equivalents were measurablein 42 of the samples with a mean±SD concentration of 1.08±0.91 ng/mL [4.0±3.4 nM] (range0.4–4.86 ng/mL [1.5–17.9 nM]). In a different study (Foster et al., 2002a), these authorsreported genistein concentrations in 59 amniotic fluid samples obtained from 53 pregnantRozman et al.Page 11Birth Defects Res B Dev Reprod Toxicol. Author manuscript; available in PMC 2008 March 11.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscript
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women at 15–23 weeks of gestation (four sets of twins and one woman who was sampled threetimes). There were 42 women with measurable amniotic fluid genistein concentrations. Themean±SD genistein equivalents concentration was 1.69±1.48 ng/mL [6.25±5.48 nM](maximum 6.54 ng/mL [24.2 nM]). [In a table, the mean±SD is reported as 1.37±1.00 ng/mL (5.07±3.7 nM) with a median of 0.99 ng/mL (3.7 nM). It is not known whether thereare any samples represented in both articles.] Engel et al. (2006) measured genistein anddaidzein in amniotic fluid samples obtained before 20 weeks. The samples were collected forthe sole indication of "advanced maternal age" (>35 years). The median (range) genisteinconcentration was 1.38 (0.20–7.88) µg/L and the median (range) daidzein concentration was9.52 (3.84–17.4) µg/L.Franke et al. (1998) and Franke and Custer (1996) measured isoflavone and metabolite levelsin the milk and urine of two women who consumed 5, 10, and 20 g roasted soybeans at 0, 24,and 72 hr of the study, respectively. Plasma levels were also examined in one study (Frankeet al., 1998). In the first study (Franke and Custer, 1996), isoflavone levels were measured insoybeans and found to be (in aglycone equivalents): daidzein 830 mg/kg soybean, genistein913 mg/kg soy-bean, and glycitein 174 mg/kg soybean. Authors estimated the three daidzeindoses at 0.08, 0.15, and 0.30 mg/kg bw and the three genistein doses at 0.08, 0.17, and 0.33mg/kg bw. In the second study (Franke et al., 1998), the soybeans reportedly contained daidzein0.85 mg/kg soybean and genistein 1.1 mg/kg soybean, and the authors stated that consumptionof 20 g soybeans would result in intake of 37 mg isoflavones. [Based on the authors' valuefor isoflavone intake, it seems that the units of isoflavones in soybeans should have beenmg/g soybean instead of mg/kg soybean, consistent with data reported for maturesoybeans in the USDA (2002b) survey. Assuming that the correct unit for the isoflavonesis mg/g soybean, 20 g soybeans would contain ~ 17 mg total daidzein and 22 mg totalgenistein.] Milk samples were collected each time the infant was nursed, and blood sampleswere drawn in one study after an overnight fast. Isoflavones and metabolites were hydrolyzedenzymatically, extracted from samples using methanol or ethyl acetate, and analyzed by HPLC.In both studies, isoflavone levels in milk were below the detection limit (1–3 pM) beforehydrolysis, suggesting that isoflavones occur in milk as glucuronide and sulfate conjugates.Soybean intake resulted in a rapid and dose-dependent increase in genistein and daidzeinderivatives in milk. Concentrations peaked 10–14 hr after consumption of soybeans andreturned to baseline levels 2–4 days later. A biphasic pattern of isoflavone detection wasobserved in milk after consumption of 20 g soybeans. Milk samples did not contain glyciteinor the metabolites equol and O-demethylangolensin at detectable levels. Milk contained higherconcentrations of genistein than daidzein conjugates. Levels of genistein conjugates were alsohigher in plasma [data were not shown]. In urine, the ratio of isoflavones to metabolitessuggested preferential excretion of metabolites [data were not shown]. In contrast to resultsfor milk and plasma, urinary conjugates of daidzein were higher than conjugates of genistein.Glycitein and the isoflavone metabolites equol and O-demethylangolensin were also detectedin urine.In the Franke and Custer (1996) study, intake of 5, 10, and 20 g soybeans by a single subjectresulted in maximum milk total genistein levels of 32, 46, and 71 nM and total daidzein levelsof 16, 34, and 62 nM, respectively. The respective maximum urinary excretion rates for totalgenistein were 60, 300, and 300 nmol/hr and for total daidzein, 150, 500, and 600 nmol/hr.Milk and urine levels were compared to those of a Chinese woman who ate her usual diet,which included one serving/day of tofu soup. The woman's milk contained total genistein at30–50 nM and total daidzein at 80–110 nM; urinary excretion rates ranged from 8–33 nmol/hr for total genistein and from 80–150 nmol/hr for total daidzein. In the Franke et al. (1998)study, mean total isoflavone concentrations after consumption of 20 g soybeans were 0.2 µMRozman et al.Page 12Birth Defects Res B Dev Reprod Toxicol. Author manuscript; available in PMC 2008 March 11.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscript
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in milk and 2 µM in plasma; urinary excretion rate for isoflavone was 3.0 µmol/hr. [The datafor "total isoflavones" were presented in the study abstract.]A mean±SD isoflavone level of 5.6±4.4 µg/L was reported in milk samples from nine healthylactating women (Setchell et al., 1998). Equol was detected in seven of nine milk samples. A≤10-fold increase in milk isoflavone levels was observed in a woman who ate 30 mg isoflavonesin the form of 10 g toasted soy nuts. [Figure 2 in the study report suggests that milk totaldaidzein levels increased >15-fold and total genistein levels increased <10-fold 1 day afterthe ingestion of the soy nuts.] The study authors noted that isoflavones occur predominantlyas glucuronide conjugates in human milk. A second study reported that levels of total genisteinand total daidzein were below the detection limit (0.1 µg/g) in milk samples from 11 mothersin New Zealand (Irvine et al., 1998a).Isoflavone levels were measured in breast tissue from four women eating bread rollssupplemented with isoflavones 45 mg for 14 days before undergoing breast biopsy (Pumfordet al., 2002). Results were compared to those from four women who did not receive soysupplementation before biopsy. In women receiving soy supplementation, breast tissuecontained total genistein 0.655 (range = 0.571–0.723) nmol/g wet tissue and total daidzein0.145 (range = 0.083–0.128) nmol/g wet tissue. Breast tissue from women not undergoingsupplementation contained total genistein 0.120 (range = 0.103–0.142) nmol/g wet tissue andtotal daidzein 0.021 (range = 0.017–0.028) nmol/g wet tissue.Studies in humans reported that daidzein concentrations in prostate fluid were ~ 2–4 timeshigher than plasma levels and equol concentrations in prostate fluid were 44 times higher thanin plasma (Whitten and Patisaul, 2001).126.96.36.199 Metabolism: The complete metabolic fates of genistein and daidzein are not known,but some information is available (Fig. 2, Fig. 3). Most of the information was obtained fromreviews describing metabolism of iso-flavones after soy intake. However, some informationobtained in studies with daidzein aglycone is also briefly discussed.Metabolism of isoflavone glycosides begins with hydrolysis of the compounds to theirrespective aglycones, a step that must occur before the compounds can enter the systemiccirculation. According to the UK Committee on Toxicity (2003), there is disagreement aboutwhether hydrolysis occurs in the stomach. Intestinal bacteria such as Lactobacilli,Bifidobacteria, and Bacteroides contain β-glycosidase activity that may facilitate thehydrolysis of isoflavone glycosides, but the specific types of bacteria involved have not beenidentified. Bacterial flora is scarce in the small intestine but abundant in the large intestine.One study suggested that enzymes in saliva can hydrolyze isoflavone glycosides. β-Glucosidases in foods can also contribute to hydrolysis of glycosides (Kurzer and Xu, 1997),but their contribution to overall hydrolysis of the glycosides is minor.Before entering the systemic circulation, the majority of genistein and daidzein are furthermetabolized to their conjugates, as noted in Figure 2 and Figure 3 (Joannou et al., 1995;Kurzerand Xu, 1997;UK Committee on Toxicity, 2003). It is thought that additional metabolites canbe generated both by intestinal and liver enzymes and by intestinal microflora. The metabolicprofile has been reported to vary among individuals. Some individuals produce little or noequol or O-demethylangolensin.Genistein and daidzein are conjugated with glucuronic acid by uridine diphosphate-glucuronosyltransferase (UDPGT) or to a much lesser extent, with sulfate by sulfotransferases.In a study described in greater detail in the CERHR Expert Panel Report on Genistein (Rozmanet al., in press), the study authors concluded that the intestine plays a major role in theglucuronidation of genistein (Doerge et al., 2000). In studies conducted with daidzein, theRozman et al.Page 13Birth Defects Res B Dev Reprod Toxicol. Author manuscript; available in PMC 2008 March 11.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscript
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ability to glucuronidate daidzein was the same for microsomes from kidney and liver, whereasmicrosomes from colon had no measurable activity (Doerge et al., 2000). The 1A10 isoformof UDPGT, which is present in the gut but not in liver, lacked activity toward daidzein, whereasthe 1A1 and 1A9 isoforms, found in gut and liver, had the greatest activity. Thus, study authorsconcluded that most daidzein glucuronidation occurs in liver (Doerge et al., 2000).The glucuronide and sulfate conjugates enter the systemic circulation, and it has been reportedthat most isoflavones in the circulation are present in conjugated form. In individuals whoingested a soy supplement consisting of isoflavone glycosides, glucuronides represented 69–98% of circulating genistein and 40–62% of circulating daidzein (Doerge et al., 2000). In thesame study, sulfate conjugates represented 4% of circulating daidzein compounds in one malebut were not detected in a female subject. Genistein sulfates were not detected in the male orfemale. A second study reported mean steady-state circulating unconjugated isoflavones at2.7% for daidzein and 1.6% for genistein when the compounds were taken as aglycones orglycosides (Setchell et al., 2001). The conjugated isoflavones undergo enterohepaticcirculation, and on return to the intestine, they are deconjugated by bacteria with β-glucuronidase or aryl-sulfatase activity. The metabolites may be reabsorbed or furthermetabolized by gut microflora.Limited ability of infants to produce equol was shown by Setchell et al. (1997, 1998), whodetected equol in plasma of four of seven infants fed soy milk formulas but with a peak areaone to two orders of magnitude lower than in infants fed cow-milk formula. Equol was detectedin cow-milk samples from Australia (King et al., 1998). The finding was consistent withprevious studies that found no equol in urine of infants fed soy formula and others that reportedage-related increases in β-glucosidase activity (Setchell et al., 1998).The ability of infants to absorb and metabolize isoflavones was shown by Hoey et al. (2004).The study examined 60 infants and children, aged 4 months to 6 years, who were assigned toeither a soy-formula or control group (N = 30 in each) depending on whether they had consumedsoy or cow-milk formula during infancy. Subjects were also divided into four groups accordingto age (4–6 months, 7–12 months, 1–3 years, and 3–7 years). Genistein, daidzein, and glyciteinwere present in the urine of all soy-fed infants in the 4–6-month age group, whereas O-demethylangolensin and equol were detected in 75% and 25% of soy-fed infants, respectively.In contrast, isoflavonoids were very low or not detected in the 4–6-month control group. Insubjects aged 7 months to 7 years who were given a soy challenge, O-demethylangolensin waspresent in the urine of 75% of soy subjects and 50% of control subjects, whereas equol waspresent in the urine of 19% of soy subjects and 5% of control subjects. These percentages weresimilar between groups in the 3–7-year age group. Analysis of fecal samples showed that thetotal bacterial count was significantly higher in cow milk-fed infants than in the soy formula-fed infants. More specifically, the bacterial counts for Bifidobacteria, Bacteroides, andClostridia were significantly higher in the cow milk-fed group, whereas the combined countfor Lactobacillus + Enterococcus was not significantly different between groups. There wereno significant differences between the soy-formula and control groups in fecal enzymeactivities, pH, or short-chain fatty acid concentrations. The researchers concluded from the 4–6-month age group data that the isoflavones genistein, daidzin, and glycitein were wellabsorbed after hydrolysis in the gut because significant concentrations of their glucuronideswere found in urine samples. They also deduced that the ability to hydrolyze glycosides toaglycones developed by the age of 4–6 months because such hydrolysis is required forabsorption. Although a higher percentage of soy formula-fed infants than cow milk-fed infantsof the younger age groups were able to convert daidzein to equol, the percentages were similaramong the older children. Thus, the authors concluded that isoflavone exposure early in lifehas no lasting effect on isoflavone metabolism. They also noted the influence of formula typeon the composition of the microflora present in the gut of infants.Rozman et al.Page 14Birth Defects Res B Dev Reprod Toxicol. Author manuscript; available in PMC 2008 March 11.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscript
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Setchell et al. (2001) reported that no adult females administered daidzein produced equol butthat two of four women given daidzin produced equol; the study authors speculated that daidzinmay have traveled further down the intestinal tract, where it was metabolized by bacteria. Half-lives for equol formation were reported at 2–4 hr in adults eating soy foods (Lu et al., 1995;Lu and Anderson, 1998). A review by Price and Fenwick (1985) reported that most equol wasexcreted as glucuronide, with smaller amounts excreted as the sulfate conjugate in somehumans.Setchell (1998) reported that recent studies conducting detailed qualitative analysis of humanurine identified numerous diphenolic metabolites generated in intermediates steps of genisteinand daidzein biotransformation. At the time the Setchell review was published, the intermediatemetabolites had not yet been identified by MS.Mean recoveries of genistein and daidzein within 24–48 hr are well below 100%, as outlinedin Table 12. Incomplete recoveries suggest the formation of additional metabolites such as p-ethylphenol or 2,4,6-tri-hydroxybenzoic acid (Steer et al., 2003). In some reviews such as theone conducted by Whitten and Patisaul (2001), recoveries were considered to representbioavailability. Because recovery of daidzein and its metabolites usually exceeds that ofgenistein and its metabolites, it has been concluded that daidzein is more bioavailable thangenistein; however, this conclusion is not supported by blood data that sometimes indicatehigher levels of total genistein than total daidzein (Table 7,Table 8). Two studies by Setchellet al. (2001,2003) reported greater bioavailability of genistein and derivatives than of daidzeinand its metabolites based on blood levels measured over time; the authors noted that somestudies reporting greater bioavailability of daidzein measured only two time points in theelimination period and could have reached erroneous conclusions. Setchell et al. (2003) alsonoted that urinary daidzein concentrations are consistently higher than genistein glucuronideconcentrations when the two compounds are administered at equimolar concentrations, whichis expected because of the greater plasma clearance rate of daidzein. In two trials of a studywhere 0.4 mg/kg bw of the 13C-labeled compounds were administered as aglycones to twodifferent groups of eight women, the mean±SEM plasma clearance rates were reported at 26.73±4.29 L/hr for daidzein and 20.17±3.50 L/hr for genistein.There is some evidence that cytochrome P450 (CYP) may be involved in the metabolism ofisoflavones. Unidentified metabolites considered to be hydrolysis products have been detectedafter in vitro incubation of genistein with human recombinant CYP1A1, 1A2, 1B1, 2E1, or3A4 isoforms (UK Committee on Toxicity, 2003).The role of gut microflora in the metabolism of isoflavones has been clearly established (UKCommittee on Toxicity, 2003). Experiments conducted with cultured human fecal bacteriashowed the formation of equol from textured vegetable protein and the conversion of daidzeinto dihydrodaidzein, benzopyran-4,7-diol, 3,-(4-hydroxyphenol), and equol. Information ongenistein metabolites is provided in the CERHR Expert Panel Report on Genistein (Rozmanet al., in press).In a review, Munro et al. (2003) reported that variations in metabolic pathways of isoflavonescan occur as a result of differences in microflora, intestinal transit time, pH, or redox potential,factors that can be affected by diet, drugs, intestinal disease, surgery, and immunity.188.8.131.52 Excretion: Reviews that primarily addressed isoflavone exposure through soy productintake reported that most ingested genistein is excreted in urine, with very little excreted infeces (reviewed in ILSI, 1999; UK Committee on Toxicity, 2003). In studies in whichvolunteers ate soy-based foods, isoflavone excretion was reported at ~ 30% in urine and 1–4%in feces (Xu et al., 2000). An additional study in which volunteers drank soy milk reportedRozman et al.Page 15Birth Defects Res B Dev Reprod Toxicol. Author manuscript; available in PMC 2008 March 11.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscript
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We turn to the One whose words never fail.
Please click to read the full text of Psalm 91.
We turn to the One whose words never fail.
Please click to read the full text of Psalm 91.
I mustache you to enjoy this emoticon moment on Twitter with blogger Jenny Dewey and her fiancé Mark.
Twitter does have some redeeming qualities.
A cheerful heart is good medicine,
but a broken spirit saps a person's strength. Proverbs 17:22 NLT
And now it's time for a silly song with Larry… Love me some VeggieTales.
What's your favorite emoticon?
Please demonstrate in the comments.
Filed under humor
This past Monday, I'd had it with Twitter. Rather than give up, I took the bull by the horns. Because that's what we do here.
I deactivated my Twitter account @everydayepistle. Please follow me now @AimeeWhetstine if you like.
Inquiring minds want to know. Why this change? Why now? Here's the skinny:
1. Forgive me for being undiplomatic, but I hate Twitter.
Maybe I just don't get it. People have explained Twitter to me as a cocktail party where you can chat with absolutely anyone. How cool is that?!
Eh. There's something to be said for hanging out at a barbecue with people I already know. Dear Mr. Zuckerberg's endless string of arbitrary changes is tiresome, but Facebook is more my speed. There's context to Facebook—mutual friends, profiles, photos, a virtual paper trail of posts, comments, likes. Yes, some people present falsely, but only the hopelessly diabolical can keep up a Facebook farce for long. True colors shine through.
Meanwhile, Twitter is context-free. Commitment-free. A breeding ground for trolls and propaganda. It's easy to hide behind 140 characters. Olé!
Unless you have a gazillion tweeting friends or followers, Twitter is also like an echo chamber. It's you, standing alone in the arena, waiting for the bull to rush you. Your tweets disappear into the chaos of the crowd. Who knows where they've gone or who'll read them? Who knows if anyone will read them at all or if you've just wasted two precious minutes of your life distilling a profound thought into an acceptable tweet. There isn't enough time in the day, folks.
And yet, if I want to write, if I want to participate in social media, if I want to connect with people in the 21st century, Twitter is a necessary evil.
2. If I write it, my byline needs to be on it.
Ross Douthat has more than 21,000 followers on Twitter and follows 110. Peggy Noonan has nearly 75,000 followers and follows 85. Beth Moore has more than 300,000 followers and follows 50. Seth Godin has more than 260,000 followers and follows no one.
These are a few of my favorite writers. They don't follow. They tweet and leave the following to others. They invest their time doing what they're obviously good at and what I suspect they enjoy most. Notice it's not Twitter.
They tweet with their own names—except for Seth who uses @ThisIsSethsBlog. It's rather spiffy to use a cool Twitter handle, brand name, or blog title. It's just that for me, for now, I want ownership and accountability. I'm no Peggy or Beth, but I want you to know who's speaking and who you're speaking to.
3. It's time to clean house.
The terrorist attack in Boston was less than two hours old this past Monday afternoon when a writer I was following tweeted something beyond irresponsible. I've told you here before that if you so much as breathe the wrong way on my child, Momma Bear will make an appearance. Well, kicking my country when it's down isn't a good idea either.
Liberal news outlets have carelessly, callously promoted inappropriate ideas since the bombing, but this writer was first to do it on my feed. I'd mistaken her for someone she isn't. I'd been gored.
And you know what? It's my bad. I'd assumed without knowing. I'd trusted without verifying. Her response to my calling her on the insensitive tweet showed she clearly couldn't care less who I am or what I think or even how her tweet insulted citizens who still love America and emboldened those who hate us. (By the way, if you live in America and hate America, please consider moving. Abroad. Think of how much happier
we'd all you'd be.)
That was the last straw. Within 24 hours, I'd closed my old Twitter account and started over, determined to make a fresh start. Ah, catharsis.
Between you, me, and the fencepost, I'd like to continue writing about things that are important to me, but life isn't a popularity contest and Twitter doesn't have to be a blood sport. Read and follow if you like. Block me if you don't. I've got work to do. As myself. As Aimee Whetstine.
God bless America.
"Forget the former things;
do not dwell on the past.
See, I am doing a new thing!
Now it springs up; do you not perceive it?
I am making a way in the wilderness
and streams in the wasteland." Isaiah 43:18-19 NIV
Pasodobles Españoles by Pepe El Trumpeta.
I cannot be the only person out there with Twitter malaise. Can you relate? Or if you love Twitter, won't you kindly share a tip or two?
photo credit: Contando Estrelas via photopin cc
Hi. How you been?
My spring blogging break lasted longer than expected. Lots to tell you. Where to start?
Amy at Using Our Words writes a regular column of 10 things she's learned each week. She's the boss of this format, which I am not—and she's funny, which I am occasionally. In homage to Amy, here's my list of 10 things I learned while I wasn't blogging.
Carry on.
Love never gives up, never loses faith, is always hopeful, and endures through every circumstance. 1 Corinthians 13:7 NLT
Something good this way comes.
Guess what? (No spoilers if you know what.)
Somehow, someway, we made it to spring break. Hallelujah!
Change is fast approaching. We got some things going on here. I hope to tell you more soon. For now, I'm taking some time off with my guys to regroup.
I'll still be around, so it's not like I'm going cold turkey.
It's more like I'm going shrimp cocktail.
Yes, chilled shrimp cocktail with just enough fresh horseradish in the red sauce to stir the heart.
Now that hits the spot.
See you on the other side of delicious.
Truly my soul finds rest in God; my salvation comes from Him. Psalm 62:1 NIV
Not for a Moment by Meredith Andrews. Beautiful, beautiful song.
Thank you for blessing me with your readership. Happy Spring Break!
Comments Off on Going Shrimp Cocktail
Filed under life
Women and guns. Guns and women.
Will she ever stop writing about this?
Yes, I have other things to say. Come back tomorrow.
Today I need a favor.
BlogHer published a new story I wrote. No matter what side you're on, please go, read, comment, share. Our country deserves to hear many voices in the debate about Second Amendment rights. Post haste. Go now.
I can lose my hard earned freedom if my fear defines my world.
One Girl Revolution by Superchick!
Filed under America, women's studies
My research to write about women and guns has connected me with many thoughtful, intelligent, brave women gun owners and enthusiasts. It's been an honor to hear their stories.
They're a beautiful bunch.
Take a look at a dozen of the photos they sent me. They communicate a simple, yet profound message: the entire United States Constitution applies to all American citizens, male and female.
Now hear this: One Woman Army by Kate Earl. A brilliant, new favorite. There's a sweet twist at the end of the video, so watch the whole thing.
If you liked this post, you'll love Lindsay McCrum's stunning book of photography, Chicks with Guns. Real women with the real guns they own.
You'll also love The Debutante Hunters, a documentary short by Maria White. The film, featuring Lowcountry women who hunt, won the Audience Award in the 2012 Sundance Film Festival. The Debutante Hunters will be released on iTunes this spring.
Disclosure: I am not being compensated to promote Chicks with Guns, The Debutante Hunters, or the U.S. Constitution.
If you're a woman who owns a gun and would like to share your story, please email aimee (at) everyday epistle (dot) com.
Filed under America, women's studies
This past weekend, I read an article in The New York Times that crushed me: The Holocaust Just Got More Shocking.
That story, coupled with Modern American Poetry's photo essay of the Holocaust, reminded me of a quote from Martin Niemöller, a Protestant pastor who spoke out against the Nazis and spent seven years in concentration camps.
How could so many people know what was happening right under their noses and not speak out? What do you know about that's happening right under your nose?
Will you speak out?
Speak out for those who cannot speak… from Proverbs 31:8 NRSV
Filed under America, words to remember
Today my first story about American women gun owners was published on The Broad Side, an online women's opinion magazine.
I'm grateful to the women gun owners and others who generously shared their personal stories for this post. Their impassioned narratives inspire me.
You know that Titanic feeling you get the moment you realize you may have hit the tip of an iceberg?
I'm astounded that my informal request to hear from women who own guns is still yielding heartfelt responses. It's as if women gun owners haven't been asked to comment on our country's current gun debate. Or, if they have been asked, their perspectives have largely been ignored.
I don't own a gun, but the research I've done so far about gun rights gives me pause. What if I want or need a gun in the future and can't get one because the government says so?
What if, by not exercising my Second Amendment right to bear arms, I inadvertently jeopardize that right for my fellow citizens like the law-abiding women in my article, not to mention for myself, my son, and generations of Americans yet to come?
Our Founding Fathers (and Mothers) must be rolling over in their graves right about now.
My head is spinning with story ideas to follow (including plans for a photo essay of all the wonderful pictures the women gun owners sent me). But for today, I ask you to click over to The Broad Side to read Women Gun Owners Shoot Straight About Firearms, Violence, Second Amendment. Whether you are pro-guns or pro-gun control, I'd appreciate your thoughtful and respectful comments, and I'd covet your shares of the post.
The Broad Side admittedly skews left. Publishing an article like this is a big step for them, and I admire their courage to do so. I hope you'll join me in demonstrating how listening to different perspectives on controversial topics is one of the best ways to ensure the health of our republic.
Please read:
Filed under America, women's studies
"SHOPPING IS NOT A HOBBY," read the pretentious bumper sticker.
That's true. Shopping is not a hobby. It's a sport.
Like the Olympics, there are many categories and events. Shoppers with higher incomes excel in Brands, Early Adoption (buy it before it hits the racks), Boutique, Custom, and Couture. Creative divas and penny pinchers make out like bandits in events like I-Got-This-At-Walmart-But-You-Can't-Tell-Can-You?, DIY, Consignment, Thrift, and Yard Sale.
Me? I specialize in Bargain Hunting New Merchandise, with major wins in the Women's and Children's Clothing divisions.
Once I bought a floor-length Ralph Lauren evening gown for $9. Set a personal record. Wore it to my brother's wedding. Alas, the victory was bittersweet since I got it at Lord & Taylor's closing sale.
Then there was the time I paid $5 for a wool pea coat for my son. A darling post-season triumph he wore with panache the next winter.
Before the big snow fell this year in Wichitawesome, I snagged a pair of leather and calf-hair, zebra-print gloves at Ann Taylor for $12.
Anything animal print counts as Big Game and earns extra points.
My aptitude is genetic, geographic, and circumstantial. My mother was a Bargainista before Bargainista was cool. I grew up in a textile manufacturing town. We didn't have a lot of money to spend on clothes. Trained by example, opportunity, and necessity, I have the makings of one of Gladwell's Outliers.
Mom was a pro. At true factory outlets—the kind located in tiny, dimly-lit rooms inside actually factories—she fished out overstocked nightgowns from big cardboard boxes for pennies per pound. She bought me a pair of pants with a small tear at the ankle for $2. Roll up those preppy chinos and no one knows the difference. She waded through piles of Esprit and Liz Claiborne 80 percent off at Dillard's Clearance.
Full-court bargain shopping may be beneath some women, but that's where champions are made. Take the Smith & Hawken store in Chicago. Had to reach for it. Bottom of the box. Linen sundress. $16. Nothing but net.
I've made plenty of mistakes along the way. Impulse buys that were just not right. Like the time I bought a candy pink sweatshirt with "PRINCESS" emblazoned in large, white letters across the front. It cost me less than $10, but I was 34.
"My daughter would love your shirt!" said a neighbor as I pushed my son past her in the stroller on our way to the park. That Sunday I promptly wrapped the sweatshirt in a nondescript, brown paper bag and slipped it to a man at church between praise songs.
"It's for your 15-year-old," I whispered. "I hope she enjoys it."
The older I get, the more likely I am to pay full-price for a basic wardrobe piece of superior quality, fit, style, and color. Do the math. A bargain is only a bargain if you wear it. A $100 dress worn 20 times costs less per wear than a $10 dress worn once.
My husband reminds me the cost of my time also needs to figure into the equation. Shopping for sport, especially Bargain Hunting, burns a lot of hours.
But it's like I tell him, practice makes perfect.
She is clothed with strength and dignity, and she laughs without fear of the future. Proverbs 31:25 NLT
"Madame Onassis got nothing on you." You Wear It Well by Rod Stewart.
What's your shopping story?
Filed under humor, women's studies
When Aimee invited me to share a post about my family, I struggled with what I wanted to say. Any family is more than one story.
We are each a million stories. Which one do I tell? Even narrowing it down to writing about my experience being in a multiracial family and what that has meant for me leaves so many possibilities to choose from. This is just one part of our experience.
I am a white woman married to a black man and the mother of two biracial children (two beautiful, amazing, radiant children, if I may say so). Being so intimately connected to two different cultures through my family and sorting through what that means for us is a blessing. It challenges me to look more deeply at my own attitudes. It pushes me to try my best to figure out what race means and what it doesn't. And because of the implications for my children, I'm attuned to subtleties of racism that I may have remained oblivious to otherwise.
By virtue of my family, race has moved from a somewhat intellectual issue to a very personal and emotional one. I can't speak for other mixed race families, but I have talked to many other white mommas of brown children and I believe that my experience—the eye-opening transition and becoming more sensitized to all the ways that racism manifests—is one that many of them share.
Over the past decade, I've wrestled with the knowledge that what others think and believe about me and about my family may be based more on skin color than on fact or fairness. People passing by may not think to themselves, "There's a couple with graduate degrees and good jobs, who have been together for a rock-solid 14 years. Look at those sweet boys they're working so hard to raise right." Filtered through stereotypes and preconceived notions, their judgments may be, well, less flattering.
As someone who has always cared a little too much what others think and taken pride in her smart-girl, good-girl image, the idea of someone thinking poorly of me or my family was something I struggled with and sometimes still do. (Feel free to read more about that here.) But that struggle has pushed me to really think about how we all deserve to be treated with the utmost compassion and respect as we move through life, regardless of our back stories. It's easy to pay lip service to that belief, but it's another thing entirely to fully grasp and practice it.
In the four walls of our home, we don't think much about race. We think about what we're having for dinner and whether our kindergartener has done his homework. We wonder if we're being too strict and then we wonder if we're being too lenient. We snuggle up and read stories at bedtime. We give baths and we say "I love you" and we play trains on the living room floor. In short, we do what families do.
But there are concerns I have that, if my kids were white, wouldn't even be on my radar screen. There are things I do because I am always trying to make sure my boys have a strong, healthy sense of self, one that will fortify them against the racism they will inevitably experience.
I make sure they feel positive about being black and about their appearance as black children—their curly hair, their brown skin. Somewhere along the way society will tell them these features are less than desirable, and I want them to know that is a lie. If you've ever gone to your local store to look for a black action figure for your child, you know that they're not easy to find. I worry about what message this sends my children. With limited success, I look for children's television shows and movies with African-American boys in lead roles because I know that "you can't be what you can't see."
I worry about the impact of stereotypes they'll be exposed to once they move beyond children's programming. Research shows that media does affect how African-American children feel about themselves. I point out positive black role models everywhere I can—their father, the President, in a story on the news—hoping those examples prove to be a more powerful influence than limiting stereotypes.
I go out of my way to make sure my children's teachers know that my husband and I are involved and invested in their education, because I worry that if the teachers don't know us, they'll expect less of my children than they do of their white peers. It's a reasonable fear, because research has shown that teachers often expect less of black students, even if they don't realize it.
I dread the day that my children are insulted or rejected on account of race because I know that they are loving, curious, imaginative, and downright amazing souls and the idea that anyone would not see that based simply on the color of their skin just breaks my heart. And I dread the day that another parent doesn't want their child to date mine. And, chances are, that day will come. We've come a long way with the rise in interracial relationships in this country, but we still have a long way to go, especially with respect to feelings about black-white marriage. (Check out this 2012 Pew Research article summarizing U.S. Census statistics and attitudes toward interracial marriage.)
When I hear about someone not wanting their child to date a black person or be friends with a black classmate, I just want to grab them by the shoulders, look them in the eye and say, "What do you mean? Are you telling me that this boy I have loved and nurtured, just as you have loved and nurtured your child, is somehow not good enough? That my beautiful child is less than your beautiful child?" I wonder what they would say. Imagine someone telling you that your child is not good enough for theirs, not because of anything he or she has done, but simply because of the color of their skin.
I worry about racial profiling and how it will affect my boys. I consider that if my little one continues to be off-the-charts in height, he won't just grow up to be a black man but he'll grow up to be a big black man—and it scares me what that could mean for his safety as he moves out into the world. The death of Trayvon Martin shook me to my core, as it did so many parents of black children, because I realized that could be my child someday. I worry about what happens when they must step out of this bubble we've built around them and into the real world.
These are things I probably wouldn't worry about if my children were white. This is how I know race still matters and in unfair ways. We have come a long way, but we still have a long ways to go before racial and cultural differences are pervasively seen as something to be celebrated and appreciated, rather than the basis for division and discrimination.
The beauty of raising young children is that they are a living example that race is a social construct, not a biological truth. I see how accepting my children are of people from different backgrounds, because no one has taught them otherwise and because my husband and I are doing all we can to ensure they hold onto that belief. They notice skin color, but without judgment or assumption.
We can't change problems if we don't recognize them. My family experience has pushed me to examine my own biases and being more aware means I can make more conscious choices over what I believe and what I feel.
If things are going to change, we have to open our hearts and be willing to learn. We need to seek out different perspectives and really try to understand the impact of our history on the present. For those of us who are white, we must be willing to examine our own biases and acknowledge where our skin color has afforded us privileges we may not deserve, and we have to be willing to do something about it.
Read more at Musing Momma about Ellie's experiences from how her interracial relationship has shaped her identity to debating whether to change school districts to conversations with her sons about race. She also features other multiracial families who are gracious enough to share their experiences. Ellie highly recommend the online magazine Multicultural Familia and their list of favorite sites on race and culture as good places to learn more.
photo credit: Lubs Mary. via photopin cc
photo credit: werthmedia via photopin cc
Filed under America, family & friends, women's studies

subset: commoncrawl


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Tag Results: josh griffith
June 8, 2015 DAYS Mary Beth Evans On November Airdate Scripts: "I Laugh, I Cry, You Will All Go As Crazy As I Am … I Can't Even Begin To Tell You!!!!! Stay Tuned!!! WOW!"
May 30, 2015 DAYS Peter Reckell Shares: "These New Writers Are Really Inspired For The 50th Anniversary. They Will Have You Laughing, Crying, Jumping For Joy!"
February 9, 2015 DAYS Head Writing Shake-Up: Dena Higley and Josh Griffith IN! Gary Tomlin and Chris Whitesell OUT!
December 29, 2013 On-Air On-Soaps Names The Best and Worst of 2013!
October 16, 2013 The Shelly Altman Interview – The Young and the Restless
October 13, 2013 Y&R's Michael Muhney Previews Adam's Huge Emotional Story & Josh Griffith's Genoa City Swan Song!
September 5, 2013 The Eric Braeden Interview – The Young and the Restless
August 26, 2013 The Melody Thomas Scott Interview – The Young and the Restless
August 22, 2013 Eric Braeden On Who Should Be New Y&R Headwriter: "I don't give a goddamn where they come from, as long as you hire people who understand the characters & know the history of Y&R!"


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Jim Callis is an MLB.com Draft and prospect expert. He has been covering the Draft and prospects since 1988.
|Baseball's annual preview of coming attractions, better known as the Arizona Fall League, is set to raise the curtain on its 24th season on Tuesday, highlighted by 11 players who are ranked on MLB Pipeline.com's Top 100 Prospects list.
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|Phil Bickford, the 18th overall pick in the 2015 Draft, is one of several pitchers at Giants instructional league. Sam Coonrod, who was drafted in 2014, and Ray Black, who can throw as fast 103 MPH join Bickford in Arizona.
More» Phil Bickford, RHP, Giants
|The Greenville Drive may not have made the low Class A South Atlantic League playoffs, but they were absolutely loaded with infielders Yoan Moncada, Rafael Devers, Javier Guerra and Michael Chavis, outfielder Andrew Benintendi and right-hander Anderson Espinoza. Several of those players have spent the early offseason honing their skills in the Red Sox' instructional league program in Fort Myers, Fla., which began Sept. 18 and will conclude Tuesday.
More» Yoan Moncada, INF, Red Sox
|There's no easy formula for assembling a winner. Just look at the World Series champions from this decade so far. From trades to free agency, Jim Callis breaks down how the 2015 postseason teams built their rosters.
More»MLB.com looks at the makeup of the 2015 Postseason
|Here's a look at how the Houston Astros used the Draft, trades, free agency and international signings to build its postseason team.
More»MLB.com looks at the makeup of the 2015 Astros
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Jan Brewer's Reminder After Defying Conserva-nuts: I Signed SB 1070, Remember?
Governor Jan Brewer recently pissed off her far-right-wing-nut base by vetoing three bills it desperately wanted, and today she's trying to make amends by bringing up the issue that got her elected: Arizona Senate Bill1070.
The bills Brewer vetoed include the ridiculous "Birther Bill," which could have required presidential candidates to provide documentation describing what their penises look like to get on the ballot in Arizona.
As we mentioned at the time, it seemed the governor caught a brief case of common sense -- very brief.
In what appears to be an attempt to say hey, Conserva-nuts, look at me, look at me -- I'm still one of you, Brewer issued a press release today reiterating her support for SB 1070, Arizona's controversial immigration law.
Tomorrow marks the one-year anniversary of Brewer's signing the bill, and the politically savvy gov isn't gonna let that opportunity pass by without screeching to anyone who'll listen that she signed the bill.
See Jan's entire statement below.
"One year ago Saturday, I signed into law the Support our Law Enforcement and Safe Neighborhoods Act, better known as SB 1070. I said at the time -- and it bears repeating now -- that my signature on SB 1070 represents my steadfast support for enforcing the law, both against illegal immigration and racial profiling.
"So, where are we one year later? Federal courts have blocked some of the most critical portions of the law. But they let stand its prohibition on 'sanctuary city' policies, meaning local authorities can no longer turn a blind eye to illegal immigration. Just as important, the courts couldn't sap SB 1070's strength as a rallying point for those of us sick and tired of hearing that our nation's border can't be secured, illegal immigration is just too big a problem to be solved or that we all must simply accept drug smugglers on our soil and drop houses in our neighborhoods. With the signing of SB 1070, Arizona said loudly and clearly: 'Enough.
"Despite SB 1070 being misunderstood and erroneously portrayed by numerous initial media reports, support for the legislation spread across the entire nation. That support remains strong, whether measured by public polling or the nearly $4 million in private donations given freely by those who have contributed to the legal defense fund established last year: KeepAZSafe.com.
"The outpouring of support from all over the country has had a significant impact. Remember, it wasn't until a month after SB 1070 was signed that President Obama agreed to send National Guard troops to the border. Arizona's actions and the subsequent national attention that resulted has helped pressure the White House to act on border security in ways it never would have otherwise. Now, we must keep up the pressure.
"Arizona has been more than patient in waiting for Washington to take concrete steps to stem the flow of illegal immigration. After decades of federal inaction and misguided policy, I and the Legislature had no choice but to stand up for the rule of law and the citizens of this great country. Arizona is willing to do the job that the federal government won't do.
"One year after the signing of SB1070, I'm determined to fight for this legislation - all the way to the Supreme Court, if necessary. But it is equally clear that the mission ahead of us is not merely to defend SB 1070. As Governor, I will continue to defend and protect the safety, health and welfare of Arizona citizens.
"Let no one doubt that, one year later, Arizona is stronger and more united than ever before in its resolve."
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[467] Biodiversity Hotspots for Conservation Priorities." Nature 403, no. 6772 (2000): 853-858. Abstract"
[439] Projected Climate Change Effects on Rocky Mountain and Great Plains Birds: Generalities of Biodiversity Consequences." Global Change Biology 9, no. 5 (2003): 647-655. Abstract"
[441] Shorebird Breeding Biology in Wetlands of the Playa Lakes, Texas, USA." Waterbirds 28, no. 2 (2005): 129-138. Abstract"
[69] Human-modified Temperatures Induce Species Changes: Joint Attribution." Proceedings of the National Academy of Sciences of the United States of America 102, no. 21 (2005): 7465-7469. Abstract"