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Effect of parsley (Petroselinum crispum) intake on urinary apigenin excretion, blood antioxidant enzymes and biomarkers for oxidative stress in human subjects.

Seven men and seven women participated in a randomized crossover trial to study the effect of intake of parsley (Petroselinum crispum), containing high levels of the flavone apigenin, on the urinary excretion of flavones and on biomarkers for oxidative stress. The subjects received a strictly controlled diet low in flavones and other naturally occurring antioxidants during the 2 weeks of intervention. This basic diet was supplemented with parsley providing 3.73-4.49 mg apigenin/MJ in one of the intervention weeks. Urinary excretion of apigenin was 1.59-409.09 micrograms/MJ per 24 h during intervention with parsley and 0-112.27 micrograms/MJ per 24 h on the basic diet (P < 0.05). The fraction of apigenin intake excreted in the urine was 0.58 (SE 0.16)% during parsley intervention. Erythrocyte glutathione reductase (EC 1.6.4.1; GR) and superoxide dismutase (EC 1.15.1.1; SOD) activities increased during intervention with parsley (P < 0.005) as compared with the levels on the basic diet, whereas erythrocyte catalase (EC 1.11.1.6) and glutathione peroxidase (EC 1.11.1.9) activities did not change. No significant changes were observed in plasma protein 2-adipic semialdehyde residues, a biomarker of plasma protein oxidation. In this short-term investigation, an overall decreasing trend in the activity of antioxidant enzymes was observed during the 2-week study. The decreased activity of SOD was strongly correlated at the individual level with an increased oxidative damage to plasma proteins. However, the intervention with parsley seemed, partly, to overcome this decrease and resulted in increased levels of GR and SOD.

Adult↗

Biological effects of epicuticular flavonoids from Primula denticulata on human leukemia cells.

The biological effects of epicuticular substances in farinose exudates accumulated on inflorescence shafts and calyces of Primula denticulata on human acute myeloid leukemia cells (HL-60) were analyzed. The crude material possessed little antioxidative capacity but strong cytostatic properties. Some of its known components (5-hydroxyflavone, 2'-hydroxyflavone, 5,2'-dihydroxyflavone, and 5,8-dihydroxyflavone) were further tested to identify the biologically active compounds. The effects of these flavones on cell cycle progression, mitochondrial membrane potential, and reactive oxygen species have been investigated by flow cytometry. The flavonol quercetin was included in the study as reference compound because of its known cytostatic properties and its activity as radical scavenger. Compared to quercetin the flavones induced little apoptosis (up to 40 microM), but despite their low toxicity, the Primula flavonoids possessed strong cytostatic properties even at low concentrations. The cell cycle distribution showed a characteristic time-dependent shift, giving evidence of a generally short-lived effect of the test compounds in the exposed cells. The antioxidative properties quantified according to two different methods correlated with the number of hydroxyl groups. Whereas quercetin strongly affected the mitochondrial membrane potential, none of the Primula flavones showed a comparable effect.

Antioxidants↗

Plant anticancer agents, XLVIII. New cytotoxic flavonoids from Muntingia calabura roots.

From a cytotoxic Et2O-soluble extract of Muntingia calabura roots, twelve new flavonoids were isolated, constituting seven flavans 1-7, three flavones 8, 10, and 12, and two biflavans 9 and 11. The structures of compounds 1-12 were established by the interpretation of spectral data, with the nmr assignments of these constituents being based on 1H-1H COSY, 1H-13C HETCOR, and selective INEPT experiments. This is the first report of the occurrence of 7,8-di-O-substituted flavans, biflavans, and flavones. Most of the isolates demonstrated cytotoxic activity when tested against cultured P-388 cells, with the flavans being more active than the flavones. Furthermore, certain of these structurally related flavonoids exhibited somewhat selective activities when evaluated with a number of human cancer cell lines.

Animals↗

Effect of flavonoids on feeding preference and development of the crucifer pest Mamestra configurata Walker.

Thirty-seven flavonoid compounds (9 flavones, 18 flavonols, 8 flavanones, and 2 flavanonols) were investigated for their effect on feeding choice with bertha armyworm (Mamestra configurata Walker; BAW). Feeding choice was dependent upon subtle differences in biochemical structure. Unsubstituted flavone and flavanone were the strongest feeding deterrents in the choice bioassay, while 7.4'-dihydroxyflavone and dihydroquercetin stimulated BAW to feed. The constitutive flavonoids of Brassica napus, isorhamnetin-3-sophoroside-7-glucoside and kaempferol-3,7-diglucoside, were effective deterrents when supplemented at concentrations higher than endogenous levels. In a no-choice bioassay, flavone reduced both larval weight as well as larval and pupal development time.

Animals↗

Arginine to lysine 108 substitution in recombinant CYP1A2 abolishes methoxyresorufin metabolism in lymphoblastoid cells.

1. Cytochrome P4501A2 (CYP1A2) activates a large number of procarcinogens to carcinogens. Phytochemicals such as flavones can inhibit CYP1A2 activity competitively, and hydroxylated derivatives of flavone (galangin) may be potent, selective inhibitors of CYP1A2 activity relative to CYP1A1 activity. Molecular modelling of the CYP1A2 interaction with hydroxylated derivatives of flavone suggests that a number of hydrophobic residues of the substrate-binding domain engage in hydrogen bonding with such inhibitors. 2. We have tested this model using site-directed mutagenesis of these residues in expression plasmids transfected into the human B-lymphoblastoid cell line, AHH-1 TK+/-. 3. Consistent with the molecular model's predicted placement in the active site, amino acid substitutions at the predicted residues abolished CYP1A2 enzymatic activity. 4. Transfected cell lines contained equal amounts of immunoreactive CYP1A2. 5. Our results support the molecular model's prediction of the critical amino acid residues present in the hydrophobic active site, residues that can hydrogen bond with CYP1A2 inhibitors and modify substrate binding and/or turnover.

Amino Acid Substitution↗

Quantitative trait loci and metabolic pathways.

The interpretation of quantitative trait locus (QTL) studies is limited by the lack of information on metabolic pathways leading to most economic traits. Inferences about the roles of the underlying genes with a pathway or the nature of their interaction with other loci are generally not possible. An exception is resistance to the corn earworm Helicoverpa zea (Boddie) in maize (Zea mays L.) because of maysin, a C-glycosyl flavone synthesized in silks via a branch of the well characterized flavonoid pathway. Our results using flavone synthesis as a model QTL system indicate: (i) the importance of regulatory loci as QTLs, (ii) the importance of interconnecting biochemical pathways on product levels, (iii) evidence for "channeling" of intermediates, allowing independent synthesis of related compounds, (iv) the utility of QTL analysis in clarifying the role of specific genes in a biochemical pathway, and (v) identification of a previously unknown locus on chromosome 9S affecting flavone level. A greater understanding of the genetic basis of maysin synthesis and associated corn earworm resistance should lead to improved breeding strategies. More broadly, the insights gained in relating a defined genetic and biochemical pathway affecting a quantitative trait should enhance interpretation of the biological basis of variation for other quantitative traits.

Journal Article↗

Flavopiridol inhibits NF-kappaB activation induced by various carcinogens and inflammatory agents through inhibition of IkappaBalpha kinase and p65 phosphorylation: abrogation of cyclin D1, cyclooxygenase-2, and matrix metalloprotease-9.

Flavopiridol, a synthetic flavone closely related to a compound originally isolated from the stem bark of the native Indian plant Dysoxylum binectariferum, has been found to inhibit cyclin-dependent kinases, induce apoptosis, suppress inflammation, and modulate the immune response. Because several genes in which expression is altered by flavopiridol are regulated by NF-kappaB, we propose that this flavone must affect the activation of NF-kappaB. For this report, we investigated the effect of flavopiridol on NF-kappaB activation by various carcinogens and inflammatory agents. Flavopiridol suppressed tumor necrosis factor (TNF)-activation of NF-kappaB in a dose- and time-dependent manner in several cell types, with optimum inhibition occurring upon treatment of cells with 100 nm flavopiridol for 6 h. This effect was mediated through inhibition of IkappaBalpha kinase, phosphorylation, ubiquitination, and degradation of IkappaBalpha (an inhibitor of NF-kappaB), and suppression of phosphorylation, acylation, and nuclear translocation of the p65 subunit of NF-kappaB. Besides TNF, flavopiridol also suppressed NF-kappaB activated by a carcinogen (cigarette smoke condensate), tumor promoters (phorbol myristate acetate and okadaic acid), and an inflammatory agent (H2O2). TNF-induced NF-kappaB-dependent reporter gene transcription was also suppressed by this flavone. NF-kappaB reporter activity induced by TNF receptor 1, TNF receptor-associated death domain, TNF receptor-associated factor-2, NF-kappaB-inducing kinase, and IkappaBalpha kinase, were all blocked by flavopiridol but not that activated by p65. Furthermore, flavopiridol suppressed TNF-induced activation of Akt. Flavopiridol also inhibited the expression of the TNF-induced NF-kappaB-regulated gene products cyclin D1, cyclooxygenase-2, and matrix metalloproteinase-9. Overall, our results indicated that flavopiridol inhibits activation of NF-kappaB and NF-kappaB-regulated gene expression, which may explain the ability of flavopiridol to suppress inflammation, modulate the immune response, and regulate cell growth.

Carcinogens↗

Inhibition of 7-ethoxycoumarin O-deethylase activity in rat liver microsomes by naturally occurring flavonoids: structure-activity relationships.

1. The inhibitory effects of several naturally occurring flavonoids and related compounds on cytochrome P450-dependent 7-ethoxycoumarin O-deethylase (ECOD) and the structure-activity relationships were studied in liver microsomes from rats treated with 3-methylcholanthrene (MC). 2. All the flavonoids (flavone, apigenin, chrysin, flavonol, fisetin, kaempferol, morin, myrisetin, quercetin, flavanone, hesperetin and naringenin) studied inhibited microsomal ECOD activity in the following order: flavones > flavonols > flavanones, were mixed type inhibitors and had Ki in the range of 0.17-4.5 microM. (+/-)-Catechin had no effect. 3. The double bond between C2 and C3 of the C ring, the keto group and hydroxyl group of this ring in the flavonoids seem to play major roles in inhibiting the ECOD activity. 4. The hydroxyl groups in the C5 and C7 positions of A ring in the flavone and the hydroxyl group in the C3 position of C ring in the flavonol classes, respectively, were important factors for the inhibition of the enzyme. 5. In a series of 3, 5, 7-trihydroxyflavones, the hydroxyl group at the C4 in the B ring was also an important factor for the inhibition of ECOD activity, but hydroxyl groups in other positions of the B ring had little effect on the inhibition. 6. We conclude that all the flavonoids studied inhibit ECOD activity by interfering with the binding of substrate to the active site and other site(s) of the enzyme and that their structural differences lead to different binding affinities at the active site and possibly to binding at other site(s) of the enzyme for the flavonoids.

7-Alkoxycoumarin O-Dealkylase↗

Inhibition of ethoxyresorufin deethylase activity by natural flavonoids in human and rat liver microsomes.

Several flavones and flavonols (chrysin, quercetin, luteolin, flavone and 7, 8-benzoflavone) were found to inhibit ethoxyresorufin deethylase (EROD) activity in human and rat liver microsomes. In man, molecules without hydroxyl groups are more powerful inhibitors than polyhydroxylated flavonoids (7, 8-benzoflavone greater than flavone greater than chrysin greater than luteolin greater than quercetin greater than morin). In rat, chrysin was the strongest inhibitor and the less effective were morin and 7,8-benzoflavone. For all molecules human microsomes were more sensitive than rat microsomes. The most important difference concerned 7,8-benzoflavone which was 10,000-fold more potent in man.

Animals↗

Interactions of flavonoids with iron and copper ions: a mechanism for their antioxidant activity.

The metal chelating properties of flavonoids suggest that they may play a role in metal-overload diseases and in all oxidative stress conditions involving a transition metal ion. A detailed study has been made of the ability of flavonoids to chelate iron (including Fe3+) and copper ions and its dependence of structure and pH. The acid medium may be important in some pathological conditions. In addition, the ability of flavonoids to reduce iron and copper ions and their activity-structure relationships were also investigated. To fulfill these objectives, flavones (apigenin, luteolin, kaempferol, quercetin, myricetin and rutin), isoflavones (daidzein and genistein), flavanones (taxifolin, naringenin and naringin) and a flavanol (catechin) were investigated. All flavonoids studied show higher reducing capacity for copper ions than for iron ions. The flavonoids with better Fe3+ reducing activity are those with a 2,3-double bond and possessing both the catechol group in the B-ring and the 3-hydroxyl group. The copper reducing activity seems to depend largely on the number of hydroxyl groups. The chelation studies were carried out by means of ultraviolet spectroscopy and electrospray ionisation mass spectrometry. Only flavones and the flavanol catechin interact with metal ions. At pH 7.4 and pH 5.5 all flavones studied appear to chelate Cu2+ at the same site, probably between the 5-hydroxyl and the 4-oxo groups. Myricetin and quercetin, however, at pH 7.4, appear to chelate Cu2+ additionally at the ortho-catechol group, the chelating site for catechin with Cu2+ at pH 7.4. Chelation studies of Fe3+ to flavonoids were investigated only at pH 5.5. Only myricetin and quercetin interact strongly with Fe3+, complexation probably occurring again between the 5-hydroxyl and the 4-oxo groups. Their behaviour can be explained by their ability to reduce Fe3+ at pH 5.5, suggesting that flavonoids reduce Fe3+ to Fe2+ before association.

Antioxidants↗

Health effects and bioavailability of dietary flavonols.

Flavonoids are polyphenolic compounds that are ubiquitously present in foods of plant origin. Flavonoids are categorised into flavonols, flavones, catechins, flavanones, anthocyanidins, and isoflavonoids. They may have beneficial health effects because of their antioxidant properties and their inhibitory role in various stages of tumour development in animal studies. It is estimated that the human intake of all flavonoids is a few hundreds of milligram per day. Flavonoids present in foods used to be considered non-absorbable because they are bound to sugars as beta-glycosides. However, we found that human absorption of the quercetin glycosides from onions (52%) is far better than that of the pure aglycone (24%). The sugar moiety is an important determinant of their absorption and bioavailability. Flavonol glycosides might contribute to the antioxidant defences of blood. The average intake of the flavonols quercetin, myricetin and kaempferol and the flavones luteolin and apigenin in the Netherlands was 23 mg/day. The intake of these flavonols and flavones was inversely associated with subsequent coronary heart disease in some but not all prospective epidemiological studies. A protective effect of flavonols on cancer was found in one prospective study; two others showed no association. Thus the epidemiological evidence does not yet allow a decision on the involvement of flavonols in the etiology of either cardiovascular diseases or cancer.

Animals↗

Effects of the flavonoids quercetin and apigenin on hemostasis in healthy volunteers: results from an in vitro and a dietary supplement study.

Intake of dietary flavonols and flavones was inversely associated with risk for cardiovascular disease in several epidemiologic studies. This may have been due to effects on hemostasis because flavonoids have been reported to inhibit platelet aggregation in vitro. We indeed found that 2500 micromol/L of the flavonol quercetin and the flavone apigenin significantly inhibited collagen- and ADP-induced aggregation in platelet-rich plasma and washed platelets by approximately 80-97%. However, lower concentrations, such as might occur in vivo, had no effect. To test this in vivo we fed 18 healthy volunteers 220 g onions/d providing 114 mg quercetin/d, 5 g dried parsley/d providing 84 mg apigenin/d, or a placebo for 7 d each in a randomized crossover experiment with each treatment period lasting 2 wk. Onion consumption raised mean plasma quercetin concentrations to 1.5 micromol/L; plasma apigenin could not be measured. No significant effects of onions or parsley were found on platelet aggregation, thromboxane B2 production, factor VII, or other hemostatic variables. We conclude that the antiaggregatory effects of flavonoids seen in vitro are due to concentrations that cannot be attained in vivo. Effects of dietary flavonols and flavones on cardiovascular risk are possibly not mediated by hemostatic variables.

Adult↗

Flavonoid intake and the risk of cardiovascular disease in women.

BACKGROUND: Despite emerging evidence of the role of flavonoids in cardiovascular disease (CVD) prevention, the association remains unclear. OBJECTIVE: We examined whether flavonoids and selected flavonols and flavones or their food sources are associated with CVD risk. DESIGN: Women (n = 38 445) free of CVD and cancer participated in a prospective study with a mean follow-up of 6.9 y. On the basis of a food-frequency questionnaire, total flavonoids and selected flavonols and flavones were categorized into quintiles, and food sources were categorized into 4 groups. Relative risks were computed for important vascular events (519 events; excluding revascularizations) and CVD (729 events), including myocardial infarction, stroke, revascularization, and CVD death. RESULTS: The mean flavonoid intake was 24.6 +/- 18.5 mg/d, primarily as quercetin (70.2%). For both CVD and important vascular events, no significant linear trend was observed across quintiles of flavonoid intake (P = 0.63 and 0.80, respectively). No individual flavonol or flavone was associated with CVD. Broccoli and apple consumption were associated with nonsignificant reductions in CVD risk: 25-30% and 13-22%, respectively. A small proportion of women (n = 1185) consuming > or =4 cups (946 mL) tea/d had a reduction in the risk of important vascular events but with a nonsignificant linear trend (P = 0.07). CONCLUSIONS: Flavonoid intake was not strongly associated with a reduced risk of CVD. The nonsignificant inverse associations for broccoli, apples, and tea with CVD were not mediated by flavonoids and warrant further study.

Brassica↗

Induction and inhibition of aromatase (CYP19) activity by natural and synthetic flavonoid compounds in H295R human adrenocortical carcinoma cells.

Flavonoids and related structures (e.g., flavones, isoflavones, flavanones, catechins) exert various biological effects, including anticarcinogenic, antioxidant and (anti-)estrogenic effects, and modulation of sex hormone homeostasis. A key enzyme in the synthesis of estrogens from androgens is aromatase (cytochrome P450 19; CYP19). We investigated the effects of various natural and synthetic flavonoids on the catalytic activity and promoter-specific expression of aromatase in H295R human adrenocortical carcinoma cells. Natural flavones were consistently more potent inhibitors than flavanones. IC(50) values for 7-hydroxyflavone, chrysin, and apigenin were 4, 7, and 20 microM, respectively; for the flavanones 7-hydroxyflavanone and naringenin the IC(50) values were 65 and 85 microM, respectively. The steroidal aromatase inhibitor (positive control) 4-hydroxyandrostenedione had an IC(50) of 20 nM. The inhibition by apigenin and naringenin coincided with some degree of cytotoxicity at 100 microM. The natural flavonoid derivative rotenone (IC(50) 0.3 microM) was the most potent aromatase inhibitor tested. Several synthetic flavonoid and structurally related quinolin-4-one analogs inhibited aromatase activity. The most potent inhibitor was 4'-tert-butyl-quinolin-4-one (IC(50) 2 microM), followed by two 2-pyridinyl-substituted alpha-naphthoflavones (IC(50)s 5 and >30 microM). The two 2-pyridinyl-substituted gamma-naphthoflavones consistently produced biphasic concentration-response curves, causing about 1.5-fold aromatase induction at concentrations below 1 microM and inhibition above that level (IC(50)s 7 and >30 microM). The natural flavone quercetin and isoflavone genistein induced aromatase activity 4- and 2.5-fold induction, respectively, at 10 microM. This coincided with increased intracellular cAMP concentrations and increased levels of the cAMP-dependent pII and to a lesser extent 1.3 promoter-specific aromatase transcripts. These results shed light on the structure-activity relationships for aromatase inhibition as well as mechanisms of induction in human H295R cells.

Adrenal Gland Neoplasms↗

Pathway engineering for healthy phytochemicals leading to the production of novel flavonoids in tomato fruit.

Flavonoids are a large family of plant polyphenolic secondary metabolites. Although they are widespread throughout the plant kingdom, some flavonoid classes are specific for only a few plant species. Due to their presumed health benefits there is growing interest in the development of food crops with tailor-made levels and composition of flavonoids, designed to exert an optimal biological effect. In order to explore the possibilities of flavonoid engineering in tomato fruits, we have targeted this pathway towards classes of potentially healthy flavonoids which are novel for tomato. Using structural flavonoid genes (encoding stilbene synthase, chalcone synthase, chalcone reductase, chalcone isomerase and flavone synthase) from different plant sources, we were able to produce transgenic tomatoes accumulating new phytochemicals. Biochemical analysis showed that the fruit peel contained high levels of stilbenes (resveratrol and piceid), deoxychalcones (butein and isoliquiritigenin), flavones (luteolin-7-glucoside and luteolin aglycon) and flavonols (quercetin glycosides and kaempferol glycosides). Using an online high-performance liquid chromatography (HPLC) antioxidant detection system, we demonstrated that, due to the presence of the novel flavonoids, the transgenic tomato fruits displayed altered antioxidant profiles. In addition, total antioxidant capacity of tomato fruit peel with high levels of flavones and flavonols increased more than threefold. These results on genetic engineering of flavonoids in tomato fruit demonstrate the possibilities to change the levels and composition of health-related polyphenols in a crop plant and provide more insight in the genetic and biochemical regulation of the flavonoid pathway within this worldwide important vegetable.

Antioxidants↗

New metabolic pathways for flavanones catalyzed by rat liver microsomes.

Flavonoids represent a diverse group of natural pigments widely distributed in the plant kingdom and are an important component of human diet due to their high content in fruits and vegetables. Since many flavonoids have been shown to be potent inhibitors, substrates, and even inducers of various cytochrome P450 isoforms, there is considerable interest in studying interactions of this class of molecules with the cytochrome P450 enzyme system. In this study, the metabolism of several simple flavanones by rat liver microsomes was investigated and compared. In addition to the expected aromatic hydroxylation products, several novel metabolic pathways were observed including C-ring desaturation to form the corresponding flavones, oxidation of the B-ring to generate an unusual quinol oxidation product, B-ring cleavage with the formation of chromone derivatives, and reduction of carbonyl group to form flavan-4-ol derivatives. The metabolites were characterized and identified primarily by using liquid chromatographytandem mass spectrometry with comparison to authentic standards. Formation of flavones from dietary flavanones might have biological significance since flavones often exhibit pharmacological activities that are different from those of flavanones. However, little is known about the pharmacological activities of the other types of flavonone metabolites.

Animals↗

Flavonoid structure-activity studies identify 6-prenylchrysin and tectochrysin as potent and specific inhibitors of breast cancer resistance protein ABCG2.

Overexpression of breast cancer resistance protein ABCG2 confers multidrug resistance in cancer cells. The GF120918-sensitive drug efflux activity of human wild-type (R482) ABCG2-transfected cells was used for rational screening of inhibitory flavonoids and establishment of structure-activity relationships. Flavones were found more efficient than flavonols, isoflavones, and flavanones. Differentially substituted flavone derivatives indicated positive OH effects at position 5, in contrast to positions 3 and 7. A methoxy at position 7 was slightly positive in tectochrysin, whereas a strong positive effect was produced by prenylation at position 6. The potency of 6-prenylchrysin was comparable with that of GF120918 (IC50 = 0.3 micromol/L). Both 6-prenylchrysin and tectochrysin seemed specific for ABCG2 because no interaction was detected with either P-glycoprotein or MRP1. The ABCG2 resistance profile in vitro is altered by mutation at amino acid 482. The R482T mutation limited the effect of prenylation on ABCG2 inhibition. Whereas GF120918 strongly inhibited the ATPase activity of wild-type ABCG2, neither 6-prenylchrysin nor tectochrysin altered the activity. In contrast, all three inhibitors stimulated the ATPase activity of mutant ABCG2. 6-Prenylchrysin at 0.5 micromol/L efficiently sensitized the growth of wild-type ABCG2-transfected cells to mitoxantrone, whereas higher concentrations were required for the mutant ones. In contrast, 1 micromol/L tectochrysin was sufficient to fully sensitize mutant ABCG2-transfected cells, whereas higher concentrations were required for the wild-type ones. Both flavones exhibited a lower intrinsic cytotoxicity than GF120918 and were apparently not transported by ABCG2. 6-Prenylchrysin and tectochrysin therefore constitute new and promising inhibitors for the reversal of ABCG2-mediated drug transport.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Flavonoids and breast cancer risk in Italy.

Few epidemiologic studies have investigated the potential relation between flavonoids and breast cancer risk. We have applied recently published data on the composition of foods and beverages in terms of six principal classes of flavonoids (i.e., flavanones, flavan-3-ols, flavonols, flavones, anthocyanidines, and isoflavones) on dietary information collected in a large-case control study of breast cancer conducted in Italy between 1991 and 1994. The study included 2,569 women with incident, histologically confirmed breast cancer, and 2,588 hospital controls. Odds ratios (OR) and 95% confidence intervals were estimated by multiple logistic regression models. After allowance for major confounding factors and energy intake, a reduced risk of breast cancer was found for increasing intake of flavones (OR, 0.81, for the highest versus the lowest quintile; P-trend, 0.02), and flavonols (OR, 0.80; P-trend, 0.06). No significant association was found for other flavonoids, including flavanones (OR, 0.95), flavan-3-ols (OR, 0.86), anthocyanidins (OR, 1.09), as well as for isoflavones (OR, 1.05). The findings of this large study of an inverse association between flavones and breast cancer risk confirm the results of a Greek study.

Adult↗