Source Of Isoflavones Research Articles

Evaluation of biological activities of a groundnut (Apios americana Medik) extract containing a novel isoflavone

Groundnut (Apios americana Medik) contains a novel isoflavone, genistein-7-O-gentiobioside. In the present study, we examined the biological activities of an alcohol extract of groundnut containing genistein-7-O-gentiobioside as the main component. Although the groundnut extract by itself did not show antioxidative activity, it drove the antioxidative system in cells. Pretreatment of human breast carcinoma MCF-7 cells for 24h with the groundnut extract and soybean isoflavone increased gene expression of heme oxygenase-1 (HO-1), a major antioxidative stress enzyme. These groundnut extract-treated cells showed antioxidative activity against free radicals derived from a radical initiator. Pretreatment of cells with 100μg/mL groundnut extract prevented the depletion of glutathione by the radical initiator; however, treatment with 100μg/mL of soybean isoflavone injured the cell membrane, indicating that glutathione might be released to the extracellular environment. These results suggest that the groundnut extract had isoflavone-like activity. Like soybean, groundnuts are a good source of isoflavones.

Ethanolic extract of seabuckthorn (Hippophae rhamnoides L) prevents high-fat diet–induced obesity in mice through down-regulation of adipogenic and lipogenic gene expression

Phenolic compounds and flavonoids ameliorate bodyweight, blood glucose, and serum lipid profile. Since seabuckthorn (Hippophae rhamnoides L.) is known as a rich source of isoflavones and flavonoids, we hypothesized that ethanolic extract of seabuckthorn leaves (SL) may have anti-obesity and hypoglycemic effects. To investigate the effect of ethanolic extract of SL, 32 C57BL/6J mice were randomly divided into 4 dietary groups, containing 8 mice in each group: normal diet group; high-fat diet (HD) control group; high-fat diet with SL extract, 500 mg/kg body weight (BW) (SL1) group; and high-fat diet with SL extract, 1000 mg/kg BW (SL2) group. After 13 weeks, it was observed that oral administration of SL extract significantly reduced the energy intake; BW gain; epididymal fat pad weight; hepatic triglyceride, hepatic, and serum total cholesterol levels; and serum leptin levels in the SL groups compared to the HD group. However, differences in serum triglyceride and insulin levels in the SL groups were not significant in comparison to the HD group. The hepatic mRNA expression of peroxisome proliferator-activated receptor (PPAR) α and carnitine palmitoyltransferase 1 along with PPAR-γ were significantly increased in SL groups, whereas the level of acetyl-CoA carboxylase was significantly reduced in SL groups compared to HD group. Our results indicated that SL is effective in preventing BW gain and fat accumulation in the liver; it also reduced adipose tissue mass, hepatic lipid profile, and serum leptin level in the mouse. Together, these observations suggest that SL is a potential agent to study in the management of obesity and related disorders.

Intakes and sources of isoflavones, lignans, enterolignans, coumestrol and soya-containing foods in the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk), from 7 d food diaries, using a newly updated database.

A diet rich in phyto-oestrogens has been suggested to protect against a variety of common diseases but UK intake data on phyto-oestrogens or their food sources are sparse. The present study estimates the average intakes of isoflavones, lignans, enterolignans and coumestrol from 7 d food diaries and provides data on total isoflavone, lignan and phyto-oestrogen consumption by food group. Development of a food composition database for twelve phyto-oestrogens and analysis of soya food and phyto-oestrogen consumption in a populationbased study. Men and women, aged 40–79 years, from the general population participating in the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) between 1993 and 1997, with nutrient and food data from 7 d food diaries. A subset of 20 437 participants. The median daily phyto-oestrogen intake for all men was 1199 mg (interquartile range 934–1537mg; mean 1504mg, SD 1502mg) and 888mg for all women (interquartile range 710–1135 mg; mean 1205 mg, SD 1701mg). In soya consumers, median daily intakes were higher: 2861 mg in men (interquartile range 1304–7269mg; mean 5051mg, SD 5031mg) and 3142 mg in women (interquartile range 1089–7327mg; mean 5396 mg, SD 6092 mg). In both men and women, bread made the greatest contribution to phyto-oestrogen intake – 40?8% and 35?6%, respectively. In soya consumers, vegetable dishes and soya/goat’s/sheep’s milks were the main contributors – 45?7% and 21?3% in men and 38?4% and 33?7% in women, respectively. The ability to estimate phyto-oestrogen intake in Western populations more accurately will aid investigations into their suggested effects on health.

Distribution of isoflavones and coumestrol in neglected tropical and subtropical legumes

Isoflavones and coumestrol from dietary legumes are plant constituents showing multiple beneficial effects on humans. Owing to their ability to bind with mammalian estrogenic receptors and thereby intervention in several kinds of hormone-related cancers, they have received much attention. Soybean (Glycine max) is currently the major source of isoflavonoids in human diet. However, dozens of tropical and subtropical leguminous species remain unexplored for their isoflavonoids content. We have analyzed 55 extracts from 41 tropical and subtropical legume species used either in human or animal diet by high-performance liquid chromatography for the content of soy isoflavones, biochanin A, daidzein, daidzin, formononetin, genistein, genistin, sissotrin, ononin and the coumestan coumestrol. Genistein and biochanin A were the most abundant compounds. The highest content of genistein was found in aerial parts of Andira macrothyrsa, seeds of Pachyrhizus tuberosus and aerial parts of Calopogonium mucunoides (598, 250 and 184 µg g(-1), respectively) and biochanin A in aerial parts of Cratylia argentea, C. mucunoides and flowers of A. macrothyrsa (76, 53 and 40 µg g(-1), respectively). None of the samples tested was richer overall source of soy isoflavones and coumestrol than soybean; nevertheless several species (C. mucunoides or A. macrothyrsa) may serve as a promising source of individual compounds.

Soy Isoflavones and Cardiovascular Disease Epidemiological, Clinical and -Omics Perspectives

Cardiovascular disease (CVD) mortality rates are lower in Asian countries where dietary patterns are very different from Western diet. A number of studies have linked these lower rates to the inclusion of soy products as a staple food in those countries. Soy is the richest dietary source of isoflavones, a type of phytoestrogen associated with many potentially beneficial effects. Isoflavone-containing soy protein consumption has been linked to reduced levels of LDL cholesterol in hypercholesterolemic patients. This effect is increased with the concomitant administration of isoflavones, and seems to be also complemented by the isoflavone capacity to restore the endothelial function in patients with weak and moderated endothelial dysfunction. The effects are variable depending on individuals� � � metabolism and in particular to their ability to convert daidzein to equol that seems to be restricted to approximately 1/3 of the population. Equol production has been indeed linked to a decreased arterial stiffness and antiatherosclerotic effects via NO production. Because the relevance of isoflavones consumption on the modulation of cardiovascular risk still remains unclear, this paper aims to review the existing knowledge on the biological activity of the isoflavones on the human cardiovascular system from an epidemiological, clinical and -omics point of view.

Isoflavone determination in spontaneous legumes identified by DNA barcodes

Isoflavones have been associated with several health protective effects. In this work spontaneous legume plants were screened as putative sources of dietary isoflavones. A molecular identification of the collected species was performed throughout DNA barcoding using ITS, rbcL, rpoC1 and matK sequences. The use of a multi-locus barcoding system complemented with basic morphological information allowed the unequivocal identification at the species level of 90% of the samples. The determination of isoflavone content was performed by high-performance liquid chromatography with diode-array detection. Total average contents in the studied species were significantly different, Ononis natrix and Cytisus scoparius possessing the highest total isoflavones content (396 and 273 mg kg(-1), respectively) and Lotus creticus, the lowest (20 mg kg(-1)). The correlation of total isoflavone content with the phylogeny of this set of plants as determined by the rpoC1 sequences was evaluated for the first time.

Positive Effects of Soy Isoflavone Food on Survival of Breast Cancer Patients in China

Soy foods are the major source of isoflavones, which are believed to play important roles in genesis of breast cancer and its progression. We here conducted a prospective study to evaluate the association of soy isoflavone food consumption with breast cancer prognosis. A prospective study was performed from January 2004 and January 2006 in China. Trained interviewers conducted face-to-face interviews using a structured questionnaire to collect information on dietary habits and potential confounding factors. The relative risk [hazard ratio (HR)] and 95% CI were calculated from the Cox regression model for all significant predictors from cancer diagnosis to the endpoint of the study (event). After a median follow up of 52.1 months (range, 9-60 months), a total of 79 breast cancer related deaths were recorded in our study, risk being inversely associated with a high intake of soy isoflavone. With an average intake of soy isoflavone above 17.3 mg/day, the mortality of breast cancer can be reduced by about 38-36%. We also found the decreased breast cancer death with high soy protein intake, with a HR (95% CI) of 0.71 (0.52-0.98). Stratified analysis with reference to the ER status, further demonstrated a better prognosis of ER positive breast cancer with a high intake of soy isoflavone (HR 0.59, 0.40-0.93). Our study shows the soy food intake is associated with longer survival and low recurrence among breast cancer patients. A cohort study with a larger sample size and long term follow-up is now needed.

Effects of Extracts fromTrifolium mediumL. andTrifolium pratenseL. on Development of Estrogen Deficiency-Induced Osteoporosis in Rats

Some plant species belonging to Trifolium L. genus are a source of isoflavones considered to exert phytoestrogenic activities. The aim of the present study was to examine the effects of standardized extract obtained from aerial parts of Trifolium medium L., in comparison with the extract of Trifolium pratense L., on the development of estrogen deficiency-induced osteoporosis in rats. Both Trifolium extracts, at doses corresponding to 10 and 20 mg/kg of isoflavone aglycones daily, or estradiol (0.2 mg/kg daily), were administered orally to ovariectomized (OVX) rats for 4 weeks. Serum bone turnover markers, bone mass, mineralization, and mechanical properties were studied. In OVX control rats, mechanical properties of the tibial metaphysis and femoral neck were strongly worsened in comparison with sham-operated control rats, and those of femoral diaphysis were unaffected. Estradiol counteracted the worsening of the tibial strength and increases in bone turnover markers. Both extracts significantly increased the strength of the femoral diaphysis and calcium and phosphorus content in the bone mineral, but only T. pratense extract increased the strength of the tibial metaphysis. In conclusion, effects of both Trifolium extracts differed from those of estradiol. It is possible that other than isoflavone extract constituents contributed to their skeletal effects.

Polyclonal antibodies against isoflavones: fast screening method for Forage legume species

Isoflavones are phytoestrogens widely used by industry for its beneficial effects as estrogens mimicked. The isolation of isoflavones are done from soybean and research one or more sources of isoflavones means biodiversity and sustainability, leaving soybean as a protein source for animal and human feeding. This study aimed to develop polyclonal antibodies to identify isoflavones in different leguminosae species, from a Tropical Forage Genebank, optimizing an immunoenzymatic assay. Our results indicate antibodies produced are highly sensitive and specific to isoflavones and can be used to screen plants with isoflavones in fast and easy method .

Determination of conjugated and free isoflavones in some legumes by LC–MS/MS

Some widely consumed legumes could potentially be used as alternatives to soy as a source of dietary isoflavones. In this study, 6 legumes (chickpea, red kidney bean, haricot bean, yellow lentil, red lentil and green lentil) were analysed to determine their contents for 10 different isoflavones (both free and conjugated). Methanolic extracts obtained by ultrasound-assisted extraction were analysed by triple quadrupole LC–MS/MS. Chickpeas were the best source of isoflavones (3078±372μg/kg total content), with a significant amount of biochanin A and its conjugated form, sissotrin. Kidney beans had the second highest concentration of isoflavones (1076μg/kg) and were particularly rich in genistin (946.4±228.5μg/kg). The total isoflavone concentrations of yellow split lentils, green lentils, red lentils and haricot beans were each below 200.0μg/kg. It was determined that the legumes commonly consumed in Western diets (those analysed in this study) are not good alternatives to soy and soy products as sources of isoflavones.

Novel major quantitative trait loci regulating the content of isoflavone in soybean seeds

Despite their medicinal, pharmaceutical, and nutritional importance of isoflavones, the genetic basis controlling the amounts of isoflavones in soybean seeds is still not well understood. The main obstacle is the great variability in the content of isoflavone in seeds harvested from different environments. In this study, quantitative trait loci (QTL) for the content of different isoflavones including daidzein, genistein, and glycitein were investigated in a population of recombinant inbred lines derived from the cross of “Hwangkeum” (Glycine max) by “IT182932” (Glycine soja). Seeds analyzed were harvested in three different experimental environments. QTL analyses for isoflavone content were conducted by composite interval mapping across a genomewide genetic map. Two major QTL were mapped to soybean chromosomes 5 and 8, which were designated QDZGT1 and QDZGT2, respectively. Both loci have not been previously reported in other isoflavone sources. The results from this study will be useful in cloning genes that can control the contents of isoflavones in soybean and for the development of soybean lines containing a high or low isoflavone content.

Early Life Exposure to Isoflavones Adversely Affects Reproductive Health in First but Not Second Generation Female CD-1 Mice

AbstractSoy-based infant formula (SBIF) can be a substantial source of soy isoflavones during early life. Because soy isoflavones have the capacity to mimic endogenous estrogen and thereby exert hormone-like effects, there is concern regarding reproductive health. The objectives were to determine if neonatal exposure to soy isoflavones altered reproductive health in females and, if so, whether such effects are transferred to subsequent generations. CD-1 mice were bred and F1 mouse offspring were cross-fostered at birth and randomized to 1 of 4 treatments: 7 mg soy isoflavoneskg body weight–1 d–1or corn oil from postnatal d (PND) 1 to 10 or from PND 1 to 21 (n= 8–13 females/group). Mice were subsequently bred to control males on PND 56 to obtain F2 females (n= 10–15/group). F1 mice that received isoflavones had ~15% greater body weight during wk 48 and markedly reduced fertility with a 55–60% success rate. Reduced fertility was associated with abnormal estrus cycles, fewer corpora lutea in ovaries, and increased incidence of hyperplasia and atypia in the uteri. Offspring (F2 mice) of isoflavone-treated F1 mice had ~15% higher body weight by wk 8 through 16 of age than controls and fertility was normal. In summary, early exposure to soy isoflavones resulting in serum isoflavone concentrations similar to human infants fed SBIF reduced fertility in F1 but not F2 mice and increased body weight in both generations of female offspring. Extrapolation of these findings to the human scenario are complex but can provide guidance for more fully understanding the implications for infants consuming SBIF.

Isoflavone profiles in different plant parts of red clover

Red clover (Trifolium pratense L., Fabaceae) is important source of isoflavones, among which the most present are: daidzein, genistein, formononetin and biochanin A [1]. These substances are considered to be beneficial for reduction of menopausal symptoms, prevention of osteoporosis, cancer and cardiovascular diseases. Since red clover extracts are used for production of dietary supplements, it is important to evaluate profile of these active compounds in plant parts. The aim of this study was to determine content of daidzein, genistein, formononetin and biochanin A in different plant parts of red clover, and to investigate which isoflavone is present in highest concentration.

Soybean isoflavones regulate dendritic cell function and suppress allergic sensitization to peanut

Although peanut and soybean proteins share extensive amino acid sequence homology, the incidence and severity of allergic reactions to soy are much less than those to peanut. Soybeans are rich in anti-inflammatory isoflavones and are the most common source of isoflavones in the human food supply. We hypothesized that the active isoflavones in the gut milieu are capable of modulating immune responses to dietary antigens by regulating dendritic cell (DC) function. We tested this hypothesis in a murine model of peanut allergy and in human monocyte-derived dendritic cells (MDDCs). C3H/HeJ mice were fed a diet containing genistein and daidzein. The mice were sensitized and challenged with peanut, and the anaphylactic symptoms were compared with those of mice fed a soy-free diet. Human MDDCs were activated with cholera toxin in the presence of isoflavones. The surface expression of DC activation markers and DC-mediated effector functions were analyzed by means of flow cytometry. Dietary isoflavones significantly reduced the anaphylactic symptoms and mast cell degranulation invivo after peanut challenge. Serum peanut-specific antibodies were markedly reduced in mice fed the isoflavone diet. Isoflavones inhibited cholera toxin-induced DC maturation in the mesenteric lymph nodes and human MDDCs and subsequent DC-mediated CD4(+) T-cell function invitro. These data suggest that dietary isoflavones suppress allergic sensitization and protect against peanut allergy invivo. Dietary supplementation of soybean isoflavones could be a novel strategy to prevent the development of allergic reactions to food.

Engineering of Soybean Extract Powder: Identification, Characterisation and Stability Evaluation

Soybeans and soy products are the main source of isoflavones. Soy isoflavones are phytochemicals of intense interest due to their association with a variety of health protective effects. The objective of this study was to identify, characterise, and to evaluate the soybean extracted powder . The extraction of soybean was prepared in dry powder by using spray drying technique. The powder was then investigated for their stability for 1 year. The studied parameters were identification of isoflavone by TLC and HPLC and some physicochemical properties such as moisture content, wettability and thermogram. The result showed that both genistein and daidzein were stable for 1 year of study whereas the extract form was not stable.

Soybean Isoflavones Regulate Dendritic Cell-mediated Effector Functions

RATIONALE: Soybeans are the most common source of isoflavones in the human diet. Isoflavones have been shown to possess anti-inflammatory and anti-oxidant properties. We hypothesized that active isoflavones in the gut milieu modulate immune responses to dietary antigens by regulating dendritic cell (DC) function. We have addressed this hypothesis in an in vitro DC activation model.

A genomic approach to isoflavone biosynthesis in kudzu (Pueraria lobata)

Roots of kudzu (Pueraria lobata) are a rich source of isoflavone O- and C-glycosides. Although O-glycosylation of (iso)flavonoids has been well characterized at the molecular level, no plant isoflavonoid C-glycosyltransferase genes have yet been isolated. To address the biosynthesis of kudzu isoflavonoids, we generated 6,365 high-quality expressed sequence tags (ESTs) from a subtraction cDNA library constructed using RNA from roots that differentially accumulate puerarin. The ESTs were clustered into 722 TCs and 3,913 singletons, from which 15 family I glycosyltransferases (UGTs) were identified. Hierarchical clustering analysis of the expression patterns of these UGTs with isoflavone synthase (IFS) in a range of tissues identified UGTs with potential functions in isoflavone glycosylation. The open reading frames of these UGTs were expressed in E. coli for functional analysis, and one was shown to preferentially glycosylate isoflavones at the 7-O-position. In addition, ESTs corresponding to chalcone synthase, chalcone reductase, chalcone isomerase (CHI) and 2-hydroxyisoflavanone dehydratase were identified. Recombinant CHI proteins had high activities with both 6'-deoxy- and 6'-hydroxy chalcones, typical of Type II CHIs. Establishment of this EST database and identification of genes associated with kudzu isoflavone biosynthesis and glycosylation provide a new resource for metabolic engineering of bioactive kudzu isoflavones.

Chemopreventive Potential of Synergy1 and Soybean in Reducing Azoxymethane-Induced Aberrant Crypt Foci in Fisher 344 Male Rats

Synergy1, a prebiotic composed of Inulin and Oligofructose (1 : 1). Soybean meal is a natural source of isoflavones. The objective was to investigate the effects of feeding Synergy1 and SM on the incidence of azoxymethane- (AOM-) induced aberrant crypt foci (ACF) in Fisher 344 male rats. Rats (54) were randomly assigned to 9 groups (n = 6). Control group (C) was fed AIN-93G and treatment groups Syn1 and SM at 5% and 10% singly and in combinations. Rats were injected with two s/c injections of AOM at 7 and 8 weeks of age at 16 mg/kg body weight and killed at 17 weeks by CO2 asphyxiation. Colonic ACF enumeration and hepatic enzyme activities were measured. Reductions (%) in total ACF among treatment groups fed combinations were higher (67–77) compared to groups fed singly (52–64). Synergistic mechanisms among phytochemicals may be responsible suggesting protective role in colon carcinogenesis with implications in food product development.

Estrogenic and Antiestrogenic Activities of Phytoalexins from Red Kidney Bean (Phaseolus vulgaris L.)

Legumes are the predominant source of isoflavones considered to be phytoestrogens that mimic the hormone 17β-estradiol (E2). Due to the risks associated with hormone replacement therapy, there is a growing need for alternative sources of estrogenic formulations for the treatment of menopausal symptoms. Legume phytoalexins (induced isoflavones) are produced under conditions of stress that include insect damage, wounding, or application of elicitors. The estrogenic and antiestrogenic activities of methanolic extracts obtained from red kidney bean treated with the fungus Aspergillus sojae were compared with those of untreated controls using an estrogen responsive element-based (ERE) luciferase reporter assay. A. sojae-treated red kidney bean extracts displayed both estrogenic and antiestrogenic activities. Analysis of elicitor-treated red kidney bean extracts showed that A. sojae treatments achieved maximal levels of kievitone at 1199 ± 101 μg/g and phaseollin at 227.8 ± 44 μg/g. The phytoalexins kievitone and phaseollin were isolated from A. sojae-treated red kidney bean extracts and analyzed for estrogenic activity using ERα and ERβ binding, ERE luciferase assays in MCF-7 and HEK 293 cells, and MCF-7 cell proliferation. Kievitone showed the highest relative binding affinity to ERα with kievitone (0.48%) > phaseollin (0.21%), and phaseollin showed the highest relative binding affinity to ERβ with phaseollin (0.53%) > kievitone (0.42%). In an ERE luciferase assay in MCF-7 cells, kievitone displayed high ER transactivation at 10 μM; phaseollin displayed low ER transactivation. Both kievitone and phaseollin stimulated MCF-7 cell proliferation, with kievitone displaying agonist activity between 0.1 and 10 μM. Cotransfection reporter assays performed in HEK 293 demonstrated that phaseollin selectively increased ERE transcriptional activity of ERβ and kievitone selectively increased ERE transcriptional activity of ERα. Although phaseollin displayed attenuation of ER transactivation in the ERE luciferase assay in MCF-7 cells, both phytoalexins attenuated the effects of E2 in an MCF-7 cell colonial survival assay. This work provides evidence that the red kidney bean phytoalexins kievitone and phaseollin possess both estrogenic and antiestrogenic activities.

Abstract CN06-04: Vegetable constituents and biotransformation enzymes: The effect of genetic variation on response

Abstract Essential nutrients, other dietary constituents, and various foods have been shown to be associated with cancer risk in epidemiologic studies and in animal models of carcinogenesis. Modulation of phase I and phase II biotransformation enzymes is one mechanism by which diet is hypothesized to influence cancer risk. These enzymes are involved in the metabolism of exogenous compounds, including drugs, carcinogens, and dietary constituents, and endogenous compounds, such as steroid hormones. Many phytochemicals in plant foods are metabolized by biotransformation enzymes, and they also influence expression and activities of these enzymes. Particular botanical families of plant foods are often unique, rich sources of specific classes of phytochemicals. For example the allium or onion family contains high amounts of allyl sulfides; apiaceous or carrot-family vegetables are sources of furanocoumarins; certain legumes are major sources of isoflavones; and cruciferous or broccoli-family vegetables are the primary dietary sources of precursors of isothiocyanates and indoles. This presentation will focus on epidemiologic and intervention studies that have investigated associations between plant food, particularly cruciferous vegetable, intakes and cancer risk or biotransformation enzyme activity and will examine the impact of genetic variation on these responses. Many of the genes that encode for biotransformation enzymes are highly polymorphic and variants in both phase I and phase II enzymes have been shown to modify response to dietary exposures. Phase I metabolic activation of carcinogens is typically catalyzed by the cytochrome P450 (CYP) family of oxidation enzymes and other classes of enzymes, such as peroxidases (e.g., cyclooxygenases), and transferases (e.g., N-acetyltransferase). CYP1A2 activates several procarcinogens, including heterocyclic amines, and is also the main enzyme involved in caffeine metabolism. In a study of BRCA1 mutation carriers, a polymorphism in CYP1A2 had no overall effect on breast cancer risk; however, among women with at least one variant C allele (AC or CC), those who consumed caffeinated coffee had a 64% reduction in breast cancer risk, compared with women who never consumed coffee (OR, 0.36; 95% CI, 0.18-0.73) (1). In controlled feeding studies, cruciferous vegetable consumption increases CYP1A2 activity in humans in a dose-dependent manner, whereas apiaceous vegetables decreases activity of this enzyme (2,3), due to the inhibitory effects of the furanocoumarins (4). When participants were stratified by CYP1A2 genotype, induction of CYP1A2 activity by cruciferous vegetables was most pronounced in the CC genotype (3). Interestingly, when cruciferous vegetables are fed concurrently with apiaceous vegetables, the effect is similar to when eating a fruit- and vegetable-free diet. Polymorphisms in the GSTM1 and GSTT1 genes result in complete lack of GSTM1-1 and GSTT1-1 proteins, respectively. Studies show effect modification of GSTM1 and GSTT1 genotypes on the association between cruciferous vegetable intake (or isothiocyanate exposure) and the risk of several cancers, including lung, gastric, prostate, bladder, and colon. Investigators have hypothesized that GSTM1-null or GSTT1-null individuals have reduced metabolism of isothiocyanates and therefore greater and longer exposure to these compounds. Interestingly, two studies show that GSTM1-null individuals tend to have more rapid and higher percentages of sulforaphane excretion than individuals who have at least one intact allele (i.e., GSTM1-positive) (5,6) and another shows no differences in isothiocyanate excretion (7). Despite this apparent lack of a metabolic difference, several short-term interventions with cruciferous vegetables suggest that GSTM1-null individuals have a greater intermediate biomarker response to isothiocyanates. For example, two levels of cruciferous vegetables supplementation significantly increased serum GST-alpha, primarily in GSTM1-null/GSTT1-null men (8). Broccoli supplementation also conferred increased protection against hydrogen peroxide-induced DNA strand breaks and lower levels of oxidized DNA bases in peripheral blood mononuclear cells from smokers (9). We have observed similar genotype differences in relation to changes in biomarkers of inflammation with cruciferous vegetable feeding. In conclusion, results of observational and intervention studies point to the complex interactions among types of foods consumed, genetic variation, and modulation of xenobiotic metabolism. Effects of genotype must be considered within the context of diet and other exposures in order to understand the impact of genetic variation on cancer risk and opportunity for prevention.