Lycopene bioavailability and metabolism in humans: an accelerator mass spectrometry study.

BACKGROUND: To our knowledge, there is no direct information on lycopene metabolism in humans. OBJECTIVE: The objective of this study was to quantify the long-term human bioavailability of lycopene in plasma and skin after a single dose of (14)C-lycopene and to profile the metabolites formed. DESIGN: We preselected 2 male subjects as lycopene absorbers and gave them an oral dose of 10 mg synthetic lycopene combined with ≈6 µg [6,6',7,7'-(14)C]lycopene (≈30,000 Bq; 92% trans lycopene). The appearance of (14)C in plasma, plasma triacylglycerol-rich lipoprotein (TRL) fraction, urine, expired breath carbon dioxide, and skin biopsies was measured over 42 d. The (14)C in lycopene-isomer fractions from plasma and TRL fraction was measured to assess the isomerization of lycopene in vivo. RESULTS: We quantified (14)C from (14)C-lycopene in plasma, the plasma TRL fraction, expired carbon dioxide, urine, and skin. The time to maximum concentration (t(max)) of total (14)C-lycopene in plasma was 6 h, and the elimination half-life (t(1/2)) was 5 d, which were different from the t(max) and t(1/2) of unlabeled lycopene (0.5 and 48 d, respectively). (14)C-Lycopene was extensively isomerized after dosing as a 92% all-trans isomer at dosing but changed to 50% trans, 38% 5 cis, 1% 9 cis, and 11% other cis isomers after 24 h. A similar pattern of isomerization was seen in plasma TRL fractions. CONCLUSIONS: Lycopene was extensively isomerized after dosing and rapidly metabolized into polar metabolites excreted into urine with the rapid peak of (14)CO(2) after dosing, which implies that ß-oxidation was involved in the lycopene metabolism. Lycopene or its metabolites were detected in skin for up to 42 d.

Absorption, conjugation and excretion of the flavanones, naringenin and hesperetin from alpha-rhamnosidase-treated orange juice in human subjects.

We have determined the absorption, conjugation and excretion of naringenin-7-O-rutinoside (narirutin) compared to the corresponding glucoside in an orange juice matrix in human subjects. Healthy volunteers (eight men and eight women), in a double blind, randomised, crossover study, consumed orange juice with (1) natural content of naringenin-7-O-rutinoside; (2) alpha-rhamnosidase-treated to yield naringenin-7-O-glucoside. Blood was sampled at twelve time points and three fractions of urine were collected over 24 h. The area under the plasma-time curve of naringenin from (2) alpha-rhamnosidase-treated orange juice was increased about 4-fold (P < 0.0001), peak plasma concentration (Cmax) was 5.4-fold higher (P < 0.0001) and Tmax was decreased from 311 to 92 min (P = 0.002) compared to untreated orange juice (1), indicating a change in absorption site from the colon to the small intestine. Furthermore, the amount in urine was increased from 7 to 47 % (P < 0.0001) of the dose after consumption of the alpha-rhamnosidase-treated orange juice (2). All urine samples contained both naringenin-7- and -4'-O-glucuronides. In addition, to examine the effect of dose and alpha-rhamnosidase treatment on hesperetin conjugate profiles, a further treatment where (3) orange juice fortified with three times the original content of hesperetin-7-O-rutinoside was used. Five hesperetin metabolites (3'-O-glucuronide; 7-O-glucuronide; 5,7-O-diglucuronide; 3',7-O-diglucuronide; 3'-O-sulphate) were present after all treatments (1-3), with the same profile of the conjugates. The present data show that bioavailability of naringenin is increased by conversion from rutinoside to glucoside, but the profile of the conjugates of flavanones formed and excreted in urine is neither affected by the absorption site nor by a 3-fold change in dose.

Increased bioavailability of hesperetin-7-glucoside compared with hesperidin results in more efficient prevention of bone loss in adult ovariectomised rats.

Hesperidin (Hp), a citrus flavonoid predominantly found in oranges, shows bone-sparing effects in ovariectomised (OVX) animals. In human subjects, the bioavailability of Hp can be improved by the removal of the rhamnose group to yield hesperetin-7-glucoside (H-7-glc). The aim of the present work was to test whether H-7-glc was more bioavailable and therefore more effective than Hp in the prevention of bone loss in the OVX rat. Adult 6-month-old female Wistar rats were sham operated or OVX, then pair fed for 90 d a casein-based diet supplemented or not with freeze-dried orange juice enriched with Hp or H-7-glc at two dose equivalents of the hesperetin aglycone (0.25 and 0.5 %). In the rats fed 0.5 %, a reduction in OVX-induced bone loss was observed regarding total bone mineral density (BMD):+7.0 % in OVX rats treated with Hp (HpOVX) and +6.6 % in OVX rats treated with H-7-glc (H-7-glcOVX) v. OVX controls (P < 0.05). In the rats fed 0.25 % hesperetin equivalents, the H-7-glcOVX group showed a 6.6 % improvement in total femoral BMD v. the OVX controls (P < 0.05), whereas the Hp diet had no effect at this dose. The BMD of rats fed 0.25 % H-7-glc was equal to that of those given 0.5 % Hp, but was not further increased at 0.5 % H-7-glc. Plasma hesperetin levels and relative urinary excretion were significantly enhanced in the H-7-glc v. Hp groups, and the metabolite profile showed the absence of eriodictyol metabolites and increased levels of hesperetin sulphates. Taken together, improved bioavailability of H-7-glc may explain the more efficient bone protection of this compound.

Review of the factors affecting bioavailability of soy isoflavones in humans.

Soy isoflavones have anticarcinogenic, antioxidant, and antiatherosclerotic activities. They also interact with the estrogen receptor, which makes them weak or moderate phytoestrogens. Because of their bioactivity, isoflavone bioavailability has been extensively studied in humans. This review summarizes data from intervention studies in humans, focusing on the factors that affect bioavailability. Summarizing data from 16 studies shows that the maximum concentration in plasma normalized to a constant dose of genistin is approximately 1.6 times that of genistein, and daidzin is approximately 1.8-fold higher than daidzein, whereas the half-life is not significantly different for aglycone and glucoside. There is a wide variation in the reported percentage urinary excretion that is not dependent on dose. Bioavailability is increased by a rapid gut transit time and by low fecal digestion rates and is decreased by a fiber-rich diet. There is no difference in bioavailability between pre- and postmenopausal women. The daily ingestion of soymilk for 1 wk does not affect bioavailability, but daily ingestion for a month increases excretion of equol in women. The factors or habitual diet characteristics that influence equol production are not clear, but equol production is limited with an immature flora. There is no consensus on which source of isoflavones results in the highest isoflavone bioavailability, and published studies present different results, although bioavailability is affected by whether the dose is given as food or drink. In conclusion, it is important to consider the factors affecting bioavailability of isoflavones when designing intervention studies.

Bioavailability is improved by enzymatic modification of the citrus flavonoid hesperidin in humans: a randomized, double-blind, crossover trial.

Hesperidin is the predominant polyphenol consumed from citrus fruits and juices. However, hesperidin is proposed to have limited bioavailability due to the rutinoside moiety attached to the flavonoid. The aim of this study was to demonstrate in human subjects that the removal of the rhamnose group to yield the corresponding flavonoid glucoside (i.e., hesperetin-7-glucoside) will improve the bioavailability of the aglycone hesperetin. Healthy volunteers (n=16) completed the double-blind, randomized, crossover study. Subjects randomly consumed hesperetin equivalents supplied as orange juice with natural hesperidin ("low dose"), orange juice treated with hesperidinase enzyme to yield hesperetin-7-glucoside, and orange juice fortified to obtain 3 times more hesperidin than naturally present ("high dose"). The area under the curve (AUC) for total plasma hesperetin of subjects consuming hesperetin-7-glucoside juice was 2-fold higher than that of subjects consuming the "low" dose hesperidin juice [3.45+/-1.27 vs. 1.16+/-0.52 mmol/(L.h), respectively, P>0.0001]. The AUC for hesperetin after consuming the hesperetin-7-glucoside juice was improved to the level of the "high" dose hesperidin juice [4.16+/-1.50 mmol/(L.h)]. The peak plasma concentrations (C(max)) of hesperetin were 4-fold higher (2.60+/-1.07 mmol/L, P<0.0001) after subjects consumed hesperetin-7-glucoside juice compared with those consuming "low" dose hesperidin juice (0.48 +/- 0.27 mmol/L), and 1.5-fold higher than those consuming "high" dose hesperidin juice (1.05+/-0.25 mmol/L). The corresponding T(max) was much faster (0.6+/-0.1 h, P<0.0001) after subjects consumed hesperetin-7-glucoside juice compared with "low" dose (7.0+/-3.0 h) and "high" dose (7.4+/-2.0 h) hesperidin juices. The results of this study demonstrated that the bioavailability of hesperidin was modulated by enzymatic conversion to hesperetin-7-glucoside, thus changing the absorption site from the colon to the small intestine. This may affect future interventions concerning the health benefits of citrus flavonoids.

Quantification of anthocyanins in commercial black currant juices by simple high-performance liquid chromatography. Investigation of their pH stability and antioxidative potency.

Quantitative determinations of the four black currant anthocyanins, cyanidin 3-O-beta-glucoside, cyanidin 3-O-beta-rutinoside, delphinidin 3-O-beta-glucoside, and delphinidin 3-O-beta-rutinoside, were achieved in black currant juices by a rapid and sensitive high-performance liquid chromatographic (HPLC) method. The method was validated, and quantification of anthocyanins in 13 commercially available black currant beverages was demonstrated. To optimize the handling of anthocyanin-containing samples, the pH-dependent stability of the anthocyanins was investigated. Four anthocyanins were incubated for 24 h in aqueous solutions at 13 different pH levels between 0.6 and 5.2, after which the samples were analyzed by HPLC. More than 90% of each anthocyanin remained intact up to pH 3.3. At pH 3.8 a local minimum in stability was detected, and at pH >4.5 the stability rapidly decreased. The antioxidant capacity of all 13 black currant juices was investigated by TEAC and FRAP, and the antioxidant potential of both the anthocyanin and the vitamin C contents in the juices was evaluated. This indicated that <70% of the antioxidant capacity of the juices could be attributed to the anthocyanin content or to vitamin C, signifying that other very potent antioxidants are present in commercial black currant juices.

Absorption and excretion of black currant anthocyanins in humans and watanabe heritable hyperlipidemic rabbits.

Anthocyanins are thought to protect against cardiovascular diseases. Watanabe heritable hyperlipidemic (WHHL) rabbits are hypercholesterolemic and used as a model of the development of atherosclerosis. To compare the uptake and excretion of anthocyanins in humans and WHHL rabbits, single-dose black currant anthocyanin studies were performed. Procedures for workup and analyses of urine and plasma samples containing anthocyanins were developed with high recoveries (99 and 81%, respectively) and low limits of quantification (> or =6.6 and > or =1.1 nM, respectively). The excretion and absorption of anthocyanins from black currant juice were found to be within the same order of magnitude in the two species regarding urinary excretion within the first 4 h (rabbits, 0.035%; humans, 0.072%) and t(max) (rabbits, approximately 30 min; humans, approximately 45 min). A food matrix effect was detected in rabbits, resulting in the absorption of a higher proportion of the anthocyanins from black currant juice than from an aqueous citric acid matrix. In humans the absorption and urinary excretion of anthocyanins from black currant juice were found to be proportional with dose and not influenced by the ingestion of a rice cake. In both species a larger proportion of the anthocyanin rutinosides than of the glucosides was absorbed, whereas the structure of the aglycon had no influence on the absorption and excretion. The anthocyanins had no effect in rabbits on the antioxidant capacity of plasma measured as Trolox equivalent antioxidant capacity and ferruc reducing ability of plasma.