Excretion Of Flavonoids Research Articles

Flavonoid Metabolites in Serum and Urine after the Ingestion of Selected Tropical Fruits.

The serum concentration and urinary excretion of flavonoids after the ingestion of guava, pineapple, and pomelo were determined using liquid chromatography-mass spectroscopy (LC-MS/MS). Each group of healthy volunteers was given 200 g of fresh fruit after overnight fasting and a 24-h flavonoid-free diet. The results demonstrate that only the glucuronic-conjugated metabolites of luteolin, quercetin, kaempferol, and myricetin were detected after fruit ingestion. The metabolites were first detected after 2 h, with the time to maximum concentration (Tmax) at 6 h. The most abundant metabolites for guava, pineapple, and pomelo were the glucuronide metabolites of quercetin (AUC0-8 5.4 ± 1.3 μg·h/mL), kaempferol (AUC0-8 9.9 ± 2.3 μg·h/mL), and luteolin (AUC0-8 6.4 ± 1.1 μg·h/mL), respectively. The flavonoids found in the 24-h urinary excretions were glucuronic- and mainly sulfate-conjugated metabolites. Quercetin metabolites were the most abundant after guava and pineapple ingestion, accounting for 900 and 700 μg, respectively. Luteolin metabolites were the most abundant after pomelo ingestion, accounting for 450 μg. The serum and urinary metabolite profiles suggested that guava and pineapple are good sources of quercetin, pineapple is a good source of kaempferol, and pomelo is a good source of luteolin. The study of flavonoid profiles may provide information for the selection of fruits as functional foods for their health benefits to help with various health conditions.

Associations Between a Targeted Metabolomics Panel of Urinary Flavonoids and Flavonoid Intakes from Fruits and Vegetables Across Dietary Assessment Periods

Abstract Objectives Aligning dietary intake and food composition data with biomarkers of exposure is critical for advancing assessment methodology. Flavonoids present in fruits and vegetables (FV) are rapidly metabolized and excreted in urine; therefore they may serve as acute intake biomarkers. Yet, the optimal dietary assessment period has not been determined. The objective of this study was to evaluate associations between a targeted metabolomics panel of six urinary flavonoids and dietary intakes of these flavonoids from FV across varying dietary assessment periods. Methods In this cross-sectional study, three-day diet records from 17 individuals were analyzed via Nutrition Data System for Research to determine FV intakes over one-day, two-day, and three-day assessment periods. Dietary flavonoids from FV were estimated via the Phenol-Explorer database; total intakes of targeted flavonoids (quercetin, kaempferol, isorhamnetin, phloretin, naringenin, hesperetin) were calculated by summing aglycone and glycosylated forms. Twenty-four-hour (24-h) urine was collected on the final day of diet records. Urinary flavonoid aglycones were quantified using HPLC; total urinary flavonoids were calculated by summing targeted flavonoids. Spearman correlations between flavonoid intakes and urinary flavonoids were analyzed by dietary assessment period. Results Mean targeted flavonoid intake from FV was 53.6 mg/day. Ten specific FV provided >95% of dietary flavonoids, with greatest contributions from citrus (orange juice, grapefruit, orange) and onion. Mean urinary flavonoid excretion was 9.5 μmol/24-h. Urinary flavonoids were moderately associated with flavonoid intakes from the one-day assessment period on the day prior to urine collection (rs = 0.485, P = 0.048) and summed intakes from the two-day assessment period (rs = 0.598, P = 0.011), but not from intakes over the three-day assessment period. Conclusions Urinary flavonoids are most strongly associated with dietary flavonoids consumed within two days of 24-h urine collection, indicating two-day diet records aligned with 24-h urine collection is optimal for assessing (poly)phenol exposure from FV in future research. Funding Sources OSU CCTS, Rosita Schiller Award, OSU Comprehensive Cancer Center MCC Program, and OSU CAFFRE.

Flavonoids and phenolic acids from cranberry juice are bioavailable and bioactive in healthy older adults

Cranberries (Vaccinium macrocarpon) are a rich source of phenolic phytochemicals, which likely contribute to their putative health benefits. A single-dose pharmacokinetic trial was conducted in 10 healthy adults ⩾50y to evaluate the acute (24-h) absorption and excretion of flavonoids, phenolic acids and proanthocyanidins (PACs) from a low-calorie cranberry juice cocktail (54% juice). Inter-individual variability was observed in the Cmax and Tmax of many of these compounds in both plasma and urine. The sum total concentration of phenolics detected in plasma reached a peak of 34.2μg/ml between 8 and 10h, while in urine this peak was 269.8μg/mg creatinine, and appeared 2–4h earlier. The presence of PAC-A2 dimers in human urine has not previously been reported. After cranberry juice consumption, plasma total antioxidant capacity assessed using ORAC and TAP assays correlated with individual metabolites. Our results show phenolic compounds in cranberry juice are bioavailable and exert antioxidant actions in healthy older adults.

Urinary flavonoid excretion and risk of acute coronary syndrome in a nested case-control study

Epidemiologic studies have suggested that a higher intake of flavonoids may be associated with lower risk of ischemic heart disease. However, the traditional estimation of flavonoid intake by using dietary assessment methods is affected by subjective measures. We examined whether the objective measurement of dietary flavonoids excreted in urine is associated with lower risk of acute coronary syndrome (ACS). A case-control study was nested in the Danish Diet, Cancer and Health cohort study. Cases were identified in participants who had received a first-time ACS diagnosis in the Danish National Patient Registry after the time of enrollment into the Diet, Cancer and Health study. The excretion of 10 flavonoids, which represent 5 subclasses, was measured in spot urine samples by using liquid chromatography-mass spectrometry. A total of 393 eligible cases with ACS were identified and matched to 393 noncases by using incidence density sampling. For kaempferol, most of the individual ORs were statistically significant and from 42% to 61% lower when the higher 4 quintiles were compared with the lowest quintile. The P-trend was not significant. For daidzein, individual ORs were 5-38% lower. None of the individual ORs were significant, but the P-trend was 0.041. For the remaining flavonoids, there were no significant relations between urinary excretion and risk of ACS. Except for kaempferol and daidzein, there were no significant associations between the urinary excretion of flavonoids and risk of ACS. A lack of relations may be a result of the use of short-term exposure measures.

Free fruit at workplace intervention increases total fruit intake: a validation study using 24 h dietary recall and urinary flavonoid excretion

To validate 24 h dietary recall of fruit intake by measuring the total 24 h excretion of 10 different flavonoids in 24 h urine during an intervention with free fruit at workplaces. Employees at workplaces offering a free-fruit program, consisting of daily free and easy access to fresh fruit, and controls employees at workplaces with no free-fruit program were enrolled in this validation study (n=103). Dietary intake was assessed by using a 24 h dietary recall questionnaire at baseline and approximately 5 months later. Ten flavonoids, quercetin, isorhamnetin, tamarixetin, kaempferol, hesperetin, naringenin, eriodictyol, daidzein, genistein, and phloretin, were measured using HPLC-electrospray ionization-MS. The 24 h urinary excretion of total flavonoids and the estimated intake of fruits were significantly correlated (r (s)=0.31, P<0.01). The dietary intake of citrus fruits and citrus juices was significantly correlated with total excretion of citrus specific flavonoids (r (s)=0.28, P<0.01), and orange was positively correlated with naringenin (r (s)=0.24, P<0.01) and hesperetin (r (s)=0.24, P<0.01). Phloretin in urine was correlated with apple intake (r (s)=0.22, P<0.01) and also with overall estimated intake of fruit (r (s)=0.22, P<0.01). This study shows that a 24 h dietary recall can be used as a valid estimate of the intake of fruits in agreement with an objective biomarker of fruit intake in free fruit at workplace interventions.

Urine flavonoids and plasma carotenoids in the validation of fruit, vegetable and tea intake during pregnancy in the Norwegian Mother and Child Cohort Study (MoBa)

To validate a new food-frequency questionnaire (FFQ) for measuring the intake of fruit, vegetables and tea reported by women participating in the Norwegian Mother and Child Cohort Study (MoBa). Intake of fruits, vegetables and tea estimated by the FFQ was compared with urinary flavonoid excretion, plasma carotenoid concentration and intake measured by a 4-day weighed food diary (FD). The triangular method was applied to calculate FFQ validity coefficients using two independent biomarkers. One hundred and nineteen women participating in MoBa. The FFQ estimate of fruit intake was significantly correlated with urine phloretin (r = 0.33), citrus fruit/juice with urine hesperetin (r = 0.44), cooked vegetables with plasma alpha-carotene (r = 0.37), and tea with urine kaempferol (r = 0.41) (P < 0.01 for all). On average, 60% of the participants fell into the same or adjacent quintiles when classified by FFQ and biomarkers. Significant correlations between the FFQ and FD were found for fruit (r = 0.39), vegetables (r = 0.34), juices (r = 0.50) and tea (r = 0.53). The FFQ validity coefficient was 0.65 for citrus fruit/juice and 0.59 for cooked vegetables as calculated by the triangular method. The validation study shows that the MoBa FFQ can be used to estimate fruit, juice, vegetable and tea intake in pregnant Norwegian women, and to rank individuals within the distribution.

Self-Reported Dietary Supplement Use Is Confirmed by Biological Markers in the Norwegian Mother and Child Cohort Study (MoBa)

Background/Aims: A food frequency questionnaire (FFQ) and a database for dietary supplements were developed for use in the Norwegian Mother and Child Cohort Study (MoBa). The aim of the present study was to investigate the relation between reported use and biomarkers in supplement and nonsupplement users and to validate self-reported intake of dietary supplements in mid pregnancy. Method: 120 women were recruited from MoBa, and 119 subjects completed the MoBa FFQ and a 4-day weighed food diary. Information on supplement use was collected by both methods. Venous blood specimens and 24-hour urine samples were obtained for measurement of dietary biomarkers. Results: Biomarker concentration/excretion and intake differed significantly between supplement and nonsupplement users for vitamin D, carotenoids, folate, the n–6/n–3 fatty acid ratio and iodine (p < 0.05 for all variables). Flavonoid excretion was higher in flavonoid-supplement users (p < 0.05). Significant correlations between total dietary intake (food and supplements) and biomarker concentration/excretion were found for vitamin D (r = 0.45, p < 0.001), folate (r = 0.26, p = 0.005), the n–6/n–3 fatty acid ratio (r = 0.36, p < 0.001) and iodine (r = 0.42, p < 0.001). Conclusion: The biochemical indicators examined in this study confirmed differences in self-reported micronutrient intake between supplement and nonsupplement users for vitamin D, beta-carotene, folate, n–3 fatty acids, flavonoids and iodine.

Urinary Excretion of Flavonoids Reflects Even Small Changes in the Dietary Intake of Fruits and Vegetables

Abstract Background: Due to the random and systematic measurement errors associated with current dietary assessment instruments, there is a need to develop more objective methods of measuring the intake of foods of importance to human health. Objective: The purpose of this study was to test whether urinary excretion of flavonoids could be used to identify subjects who are meeting Norwegian recommendations for fruit and vegetable intake (5 servings per day) from individuals who are consuming the national average amount of fruits and vegetables (2 servings per day). Design: Twenty-four-hour urine samples were collected in a strict crossover controlled feeding study. Forty healthy subjects (19–34 years) were included in the study. After a 1-week run-in period, one group was given a controlled diet that included 2 servings (300 g) of fruits and vegetables daily for 14 days, while the other group was given a diet containing 5 servings (750 g) per day. Following a 2-week washout and a 1 week run-in period, the regimens were switched between the groups. Results: An increased intake of mixed fruits and vegetables from 2 to 5 servings per day significantly enhanced urinary excretion of eriodictyol, naringenin, hesperetin, quercetin, kaempferol, isorhamnetin, and tamarixetin. The citrus flavonoids naringenin and hesperetin showed a steep dose-response relationship to dietary intake of fruits and vegetables, whereas the association to eriodictyol, quercetin, kaempferol, isorhamnetin, and tamarixetin was more moderate. Conclusion: The present study indicates that urinary excretion of dietary flavonoids may be used to assess changes of mixed fruit and vegetable intake corresponding to an increase from the present national intake in Norway to the recommended amount of 5 servings of fruits and vegetables daily.

Urinary Total Flavonoid Excretion but Not 4-Pyridoxic Acid or Potassium Can Be Used as a Biomarker for the Intake of Fruits and Vegetables

To gain better insight into the potential health effects of fruits and vegetables, reliable biomarkers of intake are needed. The main purpose of this study was to investigate the ability of flavonoid excretion in both 24-h and morning urine samples to reflect a low intake and moderate changes in fruit and vegetable consumption. Furthermore, the urinary excretions of 4-pyridoxic acid (4-PA) and potassium were investigated as other potential biomarkers of fruit and vegetable intake. The study was designed as a 5-d randomized, controlled crossover study. On d 1-3, the men (n = 12) consumed a self-restricted flavonoid-free diet. On d 4, they were provided a strictly controlled diet containing no fruits or vegetables (basic diet). On d 5, they consumed the basic diet supplemented with 300 or 600 g of fruits and vegetables. The total excretion of flavonoids in 24-h urine samples increased linearly with increasing fruit and vegetable intakes (r(s) = 0.86, P < 1 x 10(-6)). The total excretion of flavonoids in morning urine also increased, but the association was weaker (r(s) = 0.59, P < 0.0001). Urinary 4-PA in 24-h and morning urine samples increased significantly only with the 600-g increase in fruit and vegetable intake, whereas the excretion of potassium in urine did not reflect the changes in fruit and vegetable intake. We conclude that the total excretion of flavonoids in 24-h urine may be used as a new biomarker for fruit and vegetable intake.

Non-nutritive bioactive food constituents of plants: bioavailability of flavonoids.

Flavonoids are polyphenols widely distributed in the plant kingdom, and are present in fruits and vegetables regularly consumed by humans. In vitro metabolic studies of flavonoids in rat liver microsomes identified the 3',4'-dihydroxylated derivatives as the major metabolic endpoint. However, in vivo in rats almost none of this metabolite and only minor amounts of the 4'-monohydroxylated derivative was produced. Flavonoids with the 4'-monohydroxylated structure were generally not metabolised and were excreted unchanged in urine in higher amounts than other flavonoids investigated. It has for long been a controversy, whether flavonoids are absorbed as the intact glycoside or whether they have to be hydrolysed to the free aglycon prior to absorption. Recent data suggest that beta-glucosidases and maybe also lactase phlorizin hydrolase (LPH) in the small intestine are capable of hydrolysing flavonoid glucosides and these compounds are thus taken up as the free aglycon and not as the intact glycosides. LC-MS analyses of 12 dietary flavonoids in human urine showed that no flavonoid glycosides were excreted, and that the citrus flavanones and phloretin are excreted in higher amounts than the flavonols. Furthermore, total flavonoid excretion may be a useful biomarker for habitual fruit and vegetable consumption.

Rhizobium Inoculation Induces Condition-Dependent Changes in the Flavonoid Composition of Root Exudates From Trifolium subterraneum

Rapid induction of chalcone synthase (predominantly CHSS) gene expression occurs within 6 h following the inoculation of Rhizobium leguminosarum bv. trifolii strain ANU843 on Trifolium subterraneum or wounding of plants (C. G. R. Lawson, M. A. Djordjevic, J. J. Weinman and B. G. Rolfe. 1994. Molecular Plant-Microbe Interactions 7, 498-507). Experiments were conducted under the same conditions to examine the time of onset of synthesis and excretion of flavonoids that might result from this early CHS expression. Flavonoids in root tissues and root exudates were examined by HPLC analysis and the ability of fractionated and unfractionated material to induce nodulation gene expression in Rhizobium measured. There were no detectable changes in nod-gene-inducing activity of individual HPLC fractions of root exudates of 1 day dark-grown roots after Rhizobium inoculation. In contrast, after 3 days exposure to Rhizobium, analysis of specific HPLC fractions showed the presence of an additional nod-gene-inducing compound which the data indicate was 4′,7-dihydroxyflavone. A different and additional nod gene inducer was found in inoculated 5 day samples of root exudate of light-grown plants indicating that light exposure changes the HPLC profiles as well as the nod-gene-inducing compound(s). Exudates collected from wounded plants were considerably different from those from Rhizobium-inoculated and uninoculated plants and contained no detectable nod gene inducers. The late detection (at day 3) of Rhizobium-induced flavonoid excretion may occur too late to be directly correlated with the observed expression of CHS 6 h after inoculation. In addition, the data suggest that although the CHS5 promotor responds to both wounding and Rhizobium inoculation, the biochemical consequences of CHS5 induction resulting from these treatments are different.

Verification of Sideritis incana X S. angustifolia hybrids by flavonoid analysis

The occurrence of interspecific hybrids of Sideritis angustifolia and S. incana has been biochemically verified by TLC and HPLC analyses of external and internal flavonoids. A correlation between the excretion of flavonoids and the presence of glands in the taxa studied has been observed. The hybrids produce flavonoid patterns which contain the substances typical of both parents.