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1.
Two groups of five wethers each (40-50 kg body weight) were used. All were dosed intramuscularly (gluteus) with D-alpha-tocopherol. Five randomly selected sheep received a dose of 900 IU while the other five received 1800 IU. Doses were administered at 0, 6 and 14 days and at 7 day intervals for an additional 6 weeks. Plasma and liver samples were taken at various times. Single exponential equations provided good characterization of the multiple dose trough D-alpha-tocopherol concentrations in plasma and liver. There was a significant dose-response relationship for maximum concentration, area under the plasma curve and levels of hepatic alpha-tocopherol. These levels were proportional to the D-alpha-tocopherol dose given.  相似文献   

2.
1. Increases in plasma tocopherol concentrations were compared in sheep after a single oral administration of (per kg body-weight): 67 mg D- and 91 mg DL-epimers of alpha-tocopherol, and 74 mg D- and 100 mg DL-epimers of alpha-tocopheryl acetate, or intravenous administration of DL-alpha-tocopherol and DL-epimers of DL-alpha-tocopheryl acetate. 2. The results showed that biological availability was higher after D-alpha-tocopherol dosing than after the other forms. Intravenous administration of D-alpha-tocopherol acetate was a more effective way of dosing in sheep than equivalent intravenous amounts of DL-alpha-tocopheryl acetate or DL-alpha-tocopherol.  相似文献   

3.
A total of 24 sheep were used to study two routes of vitamin E administration: intraruminal (IR) and intraduodenal (ID). For each route of administration, 12 sheep were divided into 3 groups of 4, and each group received one of the following vitamin E treatments (mg/kg body weight): treatment 1, D-alpha-tocopherol (60 mg); treatment 2, D-alpha-tocopherol acetate (70 mg); treatment 3, DL-alpha-tocopherol (90 mg). The results showed that two major indices of bioavailability, i.e. concentration maximum and the area under the plasma concentration time-curve, were higher following IR administration than ID administration for all three vitamin E compounds used in this experiment. In sheep dosed intraruminally no difference was observed between the three vitamin E preparations in their plasma vitamin E response. For the ID administration the peak of plasma vitamin E concentration was lower after D-alpha-tocopherol acetate dosing than with the other two preparations. The results indicated a beneficial effect of rumen environment on the availability of vitamin E supplements.  相似文献   

4.
We administered high-dose vitamin E to healthy adult male volunteers and assessed the safety of such supplementation. Fourteen volunteers received daily 1,200 IU of vitamin E (800 mg of D-alpha-tocopherol) for 28 d and eight controls were also enrolled. The volunteers treated with vitamin E showed no abnormalities during the study period. The alpha-tocopherol concentrations of plasma and platelets were markedly elevated by vitamin E treatment, but there were no significant differences in platelet aggregation, coagulation, and the clinical parameters between the two groups. In conclusion, a high dose of vitamin E for 28 d had no adverse effects in healthy men.  相似文献   

5.
Five groups, each of 5 sheep of 40-45 kg body weight were used. One group acted as control (killed at 0 time, no vitamin E dose) while the other four groups were given a single oral dose of d-alpha-tocopherol acetate (100 mg/kg body weight) and killed 24, 48, 72 and 240 h after dosing. Samples of adrenal, adipose, heart, liver, kidney, lung, muscle, pancreas and spleen were taken from all 25 sheep and were analyzed for their vitamin E content. In the control sheep the tocopherol concentration in some tissues such as pancreas and adrenal were substantially higher than in the other tissues. Muscle and adipose tissue contained the lowest tocopherol concentrations among the various tissues. Tissues responded differently to the vitamin E dosing. Liver was characterized by a rapid accumulation of alpha-tocopherol at 24 h followed by a progressive loss. In the adrenal and lung the peak occurred 48 h after vitamin E loading. The variable pattern in tocopherol concentrations in the various sheep tissues following vitamin E dosing was considered a reflection of their different metabolic activities.  相似文献   

6.
The bioavailability of two vitamin E preparations (d-alpha-tocopherol and dl-alpha-tocopherol) suspended in sesame oil solution and administered intramuscularly was evaluated in sheep. In sheep administered d-alpha-tocopherol and killed after 360 hr (Group 2), there was a higher (P less than 0.01) bioavailability than for sheep injected with d-alpha-tocopherol (Group 3) or dl-alpha-tocopherol (Group 1) and killed 240 hr after dosing. In the 3 groups (5 sheep each) the highest blood plasma alpha-tocopherol increment occurred in the d-alpha-tocopherol injected sheep. For sheep injected with d-alpha-tocopherol and slaughtered at 360 hr (Group 2) the pancreatic, hepatic, lung, spleen and muscle tocopherol concentrations were higher (P less than 0.05) than in the control group. Also in group 2 there was a tendency for higher tissue tocopherol concentrations than in the other vitamin E treated sheep (Group 1 and 3).  相似文献   

7.
The fate of radiotocopherol was studied in plasma and tissues of sheep at various intervals after injection of single intravenous doses of 3H-labelled D-alpha-tocopherol. Plasma samples were taken at regular intervals after dosing and selected tissues were taken from all sheep after slaughter and assayed for radioactivity and D-alpha-tocopherol. Sheep were killed in groups of five at 24, 72, 96, 272 and 432 h post-dosing. Plasma profiles were characterized as a sum of three exponential terms. A principal component analysis of tissue concentrations was carried out to identify tissues with parallel profiles of log (disintegrations/min per microgram) over time. Five groups of tissues with distinct uptake and elimination processes were identified. The D-alpha-tocopherol in the liver and heart appeared to be consistent with the post-distributive kinetics of a highly perfused shallow compartment, while lung kinetics appeared to reflect a non-linear kinetic process. The third group, which included the spleen, neck brachiocephalicus muscle and pancreas, had depletion rates parallel to those of plasma for 24-272 h, but slower decreases than plasma over 272-432 h. Hip gluteus muscle and kidney comprised a fourth group, with depletion parallel to plasma rates for 24-96 h but progressively slower than plasma decreases over 96-272 h. Adrenal kinetics resembled the fourth group, but had a more rapid decrease in specific activities over 24-72 h.  相似文献   

8.
BACKGROUND: Little is known about factors that modulate dietary alpha-tocopherol bioavailability. OBJECTIVES: The study aimed to assess the efficacy of vitamin E-fortified apples as a low-fat vitamin E delivery system, the influence of fat on vitamin E absorption, and human vitamin E requirements by using plasma alpha-tocopherol kinetics at a dosage of alpha-tocopherol found in food. DESIGN: Apples fortified with deuterium-labeled alpha-tocopheryl acetate were consumed by 5 participants at a breakfast containing 0%, 6%, or 21% kcal from fat in 3 sequential trials. The trials were separated by a 2-wk washout period. Blood samples were obtained up to 72 h, and plasma was analyzed for labeled and unlabeled alpha-tocopherol. RESULTS: Compared with observations in the 0% fat trial, the maximum observed plasma d6-alpha-tocopherol concentrations (Cmax) and the areas under the curve increased 2- and 3-fold during the 6% and 21% fat trials, respectively. The mean (+/-SD) estimated percentage d6-alpha-tocopherol absorbed increased from 10 +/- 4% during the 0% fat trial to 20 +/- 3% and 33 +/- 5% during the 6% and 21% fat trials, respectively. The mean time to Cmax (9 +/- 2 h), fractional disappearance rates (0.022 +/- 0.003 pools/d), and half-lives (32 +/- 4 h) did not differ significantly between the trials. With the use of fractional disappearance rates and baseline plasma alpha-tocopherol concentrations, the estimated daily plasma alpha-tocopherol efflux was 13-14 mg. The estimated rate of alpha-tocopherol delivery to tissues was 5 mg/d. CONCLUSIONS: Given an estimated 33% absorption, the amount of dietary vitamin E needed daily to replace irreversible losses is 相似文献   

9.
Experiments were conducted to determine the basis of the reduction in tissue alpha-tocopherol concentrations by excess dietary zinc (Zn) in chicks fed purified diets. These reductions were preceded by elevations in the Zn concentrations of plasma and pancreas, and in the amylase activity of plasma and by reductions of exportable enzymes of the pancreas. Chicks fed similar levels of Zn as supplements to a non-purified diet showed no such impairments in either exocrine pancreatic function or tissue alpha-tocopherol concentrations. Depression of feed intake and subsequent changes of concentrations of tissue lipid components by excess dietary Zn accounted for only a minor portion of the reduction of tissue alpha-tocopherol concentrations. Tissue alpha-tocopherol concentrations were moderately correlated with tissue lipid concentrations. The rate of appearance of radioactivity from an oral dose of all-rac-alpha-tocopherol-[3,4-3H]2 in plasma was reduced by 64% by addition of 500 mg Zn/kg to the purified diet for 2 wk. These results indicate that impaired enteric absorption and/or transport of vitamin E as a consequence of Zn-induced pancreatic insufficiency is a major cause of reduced tissue concentrations of alpha-tocopherol produced by excess dietary Zn.  相似文献   

10.
The concentration of tocopherols in blood serum, liver and adipose tissue of growing pigs with different vitamin E supply was estimated gas-chromatographically. The animals were fed with a practical diet, supplemented with 0, 5, 15, 25 and 95 ppm dl-alpha-tocopheryl acetate (groups I-V). Based on a naturally vitamin E content of 7.4 and 8.6 mg per kg of the diet the control animals (group I) showed very low tocopherol concentrations of 0.5 mug per ml serum and about 1 mug per g tissue. No clinical vitamin E-deficiency symptoms were observed. The increasing alpha-tocopherol supplements raised the vitamin E contents in a proportional rate, and with high vitamin E supplies the highest quantities of tocopherols were stored in the adipose tissue. When the alpha-tocopherol content in the diet was raised by 1 mg, the concentration in the serum increased by 0.033 mug per ml, in the liver by 0.094 and in the adipose tissue by 0.129 mug per g, respectively (gamma = 0.99). This increase in the concentrations was strongly linear and can be interpreted by constant rates of absorption and retention of alpha-tocopherol in the present investigation. The growth of the pigs was no influenced by the different alpha-tocopherol supplements.  相似文献   

11.
Epidemiologic studies have repeatedly associated a high intake of lycopene and vitamin E with reduced prostate cancer risk. The present study examined the ability of the 2 compounds to reduce tumor growth and prostate-specific antigen (PSA) plasma levels in the PC-346C orthotopic mouse model of human prostate cancer. Three days after intraprostatic tumor injection, NMRI nu/nu mice were administered a daily oral dose of synthetic lycopene [5 or 50 mg/kg body weight (BW)], vitamin E in the form of alpha-tocopheryl acetate (5 or 50 mg/kg BW), a mixture of lycopene and vitamin E (5 mg/kg BW each), or vehicle. Intraprostatic tumor volume and plasma PSA concentrations were measured at regular intervals. Mice were killed when the tumor load exceeded 1000 mm(3) or on d 95 when the study was terminated. Prostate and liver were analyzed by HPLC for lycopene isomers and alpha- and gamma, delta-tocopherol concentrations. None of the single treatments significantly reduced tumor volume. In contrast, combined treatment with lycopene and vitamin E, at 5 mg/kg BW each, suppressed orthotopic growth of PC-346C prostate tumors by 73% at d 42 (P < 0.05) and increased median survival time by 40% from 47 to 66 d (P = 0.02). The PSA index (PSA:tumor volume ratio) did not differ between experimental groups, indicating that PSA levels were not selectively affected. Lycopene was detected only in mice supplemented with lycopene. As in humans, most tissue lycopene was in the cis-isomer conformation, whereas 77% trans-lycopene was used in the dosing material. Liver alpha-tocopherol concentrations were increased in mice supplemented with both 50 mg/kg (226%, P < 0.05) and 5 mg/kg vitamin E (41%, P < 0.05), whereas prostate alpha-tocopherol concentrations were increased only by the higher dose (83%, P < 0.05). Our data provide evidence that lycopene combined with vitamin E may inhibit the growth of prostate cancer and that PSA can serve as a biomarker of tumor response for this treatment regimen.  相似文献   

12.
Polyunsaturated fatty acids of biomembranes are a major target of lipid peroxidation. In vitamin E deficiency an efficient delivery of a high oral loading dose of all-rac-alpha-tocopheryl acetate to erythrocyte membranes could provide an early onset antioxidative effect. We investigated short-term changes in erythrocyte alpha-tocopherol after a single oral dose of 100 mg all-rac-alpha-tocopheryl acetate/kg in 10 vitamin E-deficient cystic fibrosis (CF) patients. Over 24 h, erythrocyte alpha-tocopherol increased 68% to 420% of preloading concentrations. With two exceptions, peak values were achieved 12 or 24 h after administration, which was 3-18 h later than peak plasma concentrations. Separate median-based curve estimates for the changes in erythrocyte alpha-tocopherol for five patients with and five without associated cholestatic liver disease were obtained. Cross-sectional test results revealed significantly lower erythrocyte alpha-tocopherol for the 9- and 24-h observations for patients with cholestatic liver disease compared with those without. Oral all-rac-alpha-tocopheryl acetate can be rapidly incorporated into erythrocyte membranes in vitamin E-deficient CF patients.  相似文献   

13.
BACKGROUND: The detection of tocotrienols in human plasma has proven elusive, and it is hypothesized that they are rapidly assimilated and redistributed in various mammalian tissues. OBJECTIVE: The primary study objective was to evaluate the postprandial fate of tocotrienols and alpha-tocopherol in human plasma and lipoproteins. DESIGN: Seven healthy volunteers (4 males, 3 females) were administered a single dose of vitamin E [1011 mg palm tocotrienol-rich fraction (TRF) or 1074 mg alpha-tocopherol] after a 7-d conditioning period with a tocotrienol-free diet. Blood was sampled at baseline (fasted) and 2, 4, 5, 6, 8, and 24 h after supplementation. Concentrations of tocopherol and tocotrienol isomers in plasma, triacylglycerol-rich particles (TRPs), LDLs, and HDLs were measured at each interval. RESULTS: After intervention with TRF, plasma tocotrienols peaked at 4 h (4.79 +/- 1.2 microg/mL), whereas alpha-tocopherol peaked at 6 h (13.46 +/- 1.68 microg/mL). Although tocotrienols were similarly detected in TRPs, LDLs, and HDLs, tocotrienol concentrations were significantly lower than alpha-tocopherol concentrations. In comparison, plasma alpha-tocopherol peaked at 8 h (24.3 +/- 5.22 microg/mL) during the alpha-tocopherol treatment and emerged as the major vitamin E isomer detected in plasma and lipoproteins during both the TRF and the alpha-tocopherol treatments. CONCLUSIONS: Tocotrienols are detected in postprandial plasma, albeit in significantly lower concentrations than is alpha-tocopherol. This finding confirms previous observations that, in the fasted state, tocotrienols are not detected in plasma. Tocotrienol transport in lipoproteins appears to follow complex biochemically mediated pathways within the lipoprotein cascade.  相似文献   

14.
OBJECTIVE: The purpose of this study was to investigate the dose-dependent effects of RRR-alpha-tocopherol supplementation in coronary heart disease (CHD) patients and healthy subjects on plasma alpha-tocopherol levels, plasma lipoprotein distribution, LDL oxidation, and inflammatory plasma markers. METHODS: 12 patients with coronary heart disease and 12 healthy subjects were supplemented with increasing dosages of RRR-alpha-tocopherol at 100, 200 and 400 mg/day for a period of 3 weeks per dose. Lipoproteins were separated by FPLC and ultracentrifugation. Alpha-tocopherol was measured by HPLC. Resistance of LDL to oxidation was determined by reading the absorption at 234 nm after CuCl2-induced oxidation. Clinical chemistry and inflammatory markers were measured on automated analysis systems. RESULTS: Plasma alpha-tocopherol concentrations at baseline were comparable between CHD-patients and healthy subjects (21.7 +/- 4.7 micromol/L and 25.8 +/- 7.6 micromol/L, respectively). CHD-patients showed a significant increase (59%) of plasma alpha-tocopherol concentrations to 34.6 +/- 9.8 micromol/L at a dosage of 100 mg/day RRR-alpha-tocopherol, whereas healthy subjects showed a significant (54%) increase to 39.7 +/- 6.1 micromol/L only with 400 mg/day RRR-alpha-tocopherol. In addition, CHD-patients showed a significantly increased enrichment of alpha-tocopherol in VLDL. Supplementation (200 mg/day) caused a significant decrease of the acute phase plasma proteins C-reactive protein (CRP) (-65%) and fibrinogen (-24%). CONCLUSION: Our data demonstrate that CHD-patients require lower dosages of alpha-tocopherol supplementation than healthy subjects to exert biological effects on plasma lipoproteins and acute phase response.  相似文献   

15.
To investigate the effect of a dietary oxidized fat on the concentrations of cholesterol in liver, plasma, and lipoproteins and the susceptibility of low-density lipoproteins (LDL) to lipid peroxidation, and to explore the effects of vitamins E and C, male guinea pigs were divided into five groups. Four groups were fed diets with an oxidized fat supplemented with 35 or 175 mg alpha-tocopherol equivalents/kg and 300 or 1000 mg of vitamin C/kg for 29 days. One group, used as a control, was fed the same basal diet with fresh fat with 35 mg alpha-tocopherol equivalents/kg and 300 mg of vitamin C/kg. Guinea pigs fed the oxidized-fat diets, irrespective of dietary vitamin E and C concentrations, had significantly lower concentrations of total cholesterol in the liver and a lower concentration of cholesterol in LDL than the control animals fed the fresh fat. According to the lag time before onset of lipid peroxidation, LDL of guinea pigs fed the oxidized-fat diet with 35 mg alpha-tocopherol equivalents and 300 mg vitamin C/kg were significantly more susceptible to copper-induced lipid peroxidation than those of guinea pigs fed the fresh fat diet. Within the groups fed the oxidized fat diets, increasing the dietary vitamin E concentration from 35 to 175 mg/kg significantly (p < 0.05) and increasing the dietary vitamin C concentration from 300 to 1000 mg/kg in tendency (p < 0.10) reduced the susceptibility of LDL to oxidation. LDL of guinea pigs fed the oxidized fat diets with 175 mg alpha-tocopherol equivalents/kg were even more resistant to oxidation than LDL of guinea pigs fed the fresh diet. In conclusion, the study shows that dietary oxidized fat influences the cholesterol metabolism and the susceptibility of LDL to lipid peroxidation; the latter can be modified by dietary vitamins E and C.  相似文献   

16.
A low vitamin-E-status was found in premature infants with birth weight less than or equal to 1,500 g. In this study the plasma vitamin-E-concentration of premature infants was analysed 2-3 h postpartal. During a total parenteral nutrition including fat emulsions the children received 4.5 mg all-rac-alpha-tocopherol acetate/kg/d (approximately 3 mg rrr alpha-tocopherol equivalents/kg/d) intravenously for 5 days. On the same days control-infants received the same fat emulsions without supplemented vitamin E. Serum alpha-tocopherol-levels were analysed on day 1, 3, 7 and 14 by HPLC. Initially the serum vitamin E level was 0.33 mg alpha-tocopherol/dl. Following the intravenous administration there was a significant increase in serum free alpha-tocopherol level. 7 days after end of supplementation the alpha-tocopherol concentration in serum reached 1,000 mg/dl serum. The highest level analysed after tocopheryl acetate supplementation was 2.45 mg alpha-tocopherol/dl. The choosen dose of 4.5 mg all-rac-alpha-tocopheryl acetate/kg body weight/day and this form of application were suitable to achieve normal serum alpha-tocopherol concentrations in premature infants without any complications.  相似文献   

17.
Biochemical assessment of vitamin A and vitamin E status of Taiwanese elderly persons was conducted by quantitative analysis of the concentration of retinol and alpha-tocopherol in plasma samples collected in the Elderly Nutrition and Health Survey in Taiwan (1999-2000). Plasma samples were analyzed by a reverse phase HPLC that can detect retinol and alpha-tocopherol simultaneously. The mean (SE) plasma retinol and alpha-tocopherol values in the 2373 valid samples were 2.73 (0.03) and 27.12 (0.47) microM, respectively, after weighting to the whole population using the SUDDAN program. Among the elderly persons studied, 99.52% of the population demonstrated normal plasma vitamin A status (plasma retinol equal to or greater than 0.7 microM or 0.2 microg/mL). The prevalence of deficient (less than 11.63 microM or 5 microg/mL) and marginal (greater than or equal to 11.63, but less than 16.28 microM or 7 g/mL) plasma alpha-tocopherol concentrations in the elderly population in Taiwan were 2.91% and 10.61%, respectively. However, the prevalence of low or inadequate vitamin E status decreased to 4.20% when the plasma alpha-tocopherol/cholesterol ratio was used as the indicator (less than 2.8 microg/mg). Results of the multiple linear regression analysis revealed that serum lipids had a strong influence on plasma alpha-tocopherol concentration. The results also showed that elderly men, those living in two Central Taiwan regions, and subjects with plasma cholesterol levels higher than 200 or lower than 174 mg/dL all had higher risk of low or inadequate alpha-tocopherol status than their counterparts. In conclusion, the plasma vitamin A and vitamin E status in the Taiwanese elderly are comparable to those reported for adults of developed Western societies.  相似文献   

18.
BACKGROUND: High doses of vitamin E have been shown to decrease lipid peroxidation in persons under oxidative stress. At present, the data are insufficient to predict whether lower doses offer the same benefit in healthy persons. OBJECTIVE: We studied the effect of moderate doses of a combination of vitamin E and carotenoids, incorporated into a food product, on markers of antioxidant status and lipid peroxidation in healthy persons. DESIGN: One hundred five healthy adults were randomly, evenly assigned in this double-blind, placebo-controlled, parallel, 11-wk intervention study. After a 2-wk stabilization period during which the subjects consumed a commercial unfortified spread, the subjects consumed 25 g/d of spread containing 43 mg alpha-tocopherol equivalents (alpha-TE; 2-3 fold the US dietary reference intake) and 0.45 mg carotenoids (spread A), 111 mg alpha-TE and 1.24 mg carotenoids (spread B), or 1.3 mg RRR-alpha-tocopherol without carotenoids (spread C). RESULTS: In subjects consuming spread A, plasma alpha-tocopherol concentrations increased 31% to 32 micromol/L, with small but significant increases in concentrations of alpha-carotene and lutein. This resulted in LDL with significantly higher total antioxidant capacity (17%) and an increased resistance to oxidation, as determined by lag time (18%). These improvements were dose dependent: larger increases in these variables were observed in subjects consuming spread B. Furthermore, consumption of spread B significantly reduced concentrations of the plasma lipid peroxidation biomarker F(2 alpha)-isoprostane (15%). CONCLUSION: The consumption of food products containing moderate amounts of vitamin E and carotenoids can lead to measurable and significant improvements in antioxidant status and biomarkers of oxidative stress in healthy persons.  相似文献   

19.
Dietary phosphatidylcholine (PC) increases the lymphatic absorption of triglyceride (TG). This result suggests that dietary PC might also enhance the absorption of other fat-soluble nutrients. We examined the effects of PC on lycopene and alpha-tocopherol absorption in male rats fitted with a thoracic lymph cannula. The lymphatic output was collected after administration of 1 mL of emulsified test oils containing lycopene and/or alpha-tocopherol in 3 separate experiments. The sodium taurocholate-emulsified test oils contained soybean oil (SO; 113 micromol triglyceride), SO containing soybean PC (SPC; 82.5 micromol SO plus 30.5 micromol purified soybean PC) or SO containing egg PC (EPC; 82.5 micromol SO plus 30.5 micromol purified egg PC) with both lycopene and alpha-tocopherol (Expt. 1) or SO, SPC, or EPC with lycopene (Expt. 2) or alpha-tocopherol alone (Expt. 3). In rats administered SPC or EPC, the lymphatic outputs of TG and lycopene were higher, and that of alpha-tocopherol was lower compared with rats administered SO (Expt. 1). The absorption rate for lycopene increased from 0.59% (SO group) to 2.16 and 1.28% in the SPC and EPC groups (P < 0.05), respectively, whereas the corresponding rates for tocopherol were 21.5% for the SO, 14.8% for the SPC, and 12.9% for the EPC groups. The increase in lycopene, but not in triglyceride absorption, was higher in the SPC than in the EPC groups. The promotive effects of SPC and EPC were decreased when lycopene alone was added to the test lipids (Expt. 2), and the inhibitory effects of PC were reduced when alpha-tocopherol alone was added to the test lipids (Expt. 3). Dietary PC increased the lymphatic output of lycopene and TG and decreased that of alpha-tocopherol, suggesting that differences exist between lycopene and alpha-tocopherol in the absorptive mechanisms. The present results also show that the promotive effects of PC on lycopene absorption are influenced by the type of fatty acids in PC.  相似文献   

20.
The pharmacokinetics of vitamin C following a 500 mg oral tablet dose were compared in a group of fourteen healthy young women whose age was 26.0 +/- 2.8 years (mean +/- s.d.), and in a group of fourteen healthy elderly women aged 68.1 +/- 2.6 years. The body composition of each subject was assessed using several anthropometric measurements in order to help explain any observed differences in the pharmacokinetic behavior of vitamin C. The vitamin C doses were characterized with the subjects in two states of vitamin C nutriture: a 'depleted' state which was achieved by 4-5 weeks on a vitamin C-restricted diet of less than 10 mg/d and a 'supplemented' state in which the subjects were given daily doses of 500 mg of vitamin C for 3 weeks. Plasma and urine samples were collected for 72 h following the dose of vitamin C from subjects in a 'depleted' state and for 24 h from subjects in a 'supplemented' state and analysed for their vitamin C content. None of the pharmacokinetic parameters measured differed significantly between the two age groups. In contrast, the vast majority of these parameters were significantly different in depleted and supplemented subjects. The peak times (tmax) were greater in the depleted state in both young and elderly groups whereas the peak concentrations (Cmax) were greater in the supplemented state. The absorption rate constant (Ka) was significantly larger in the supplemented state compared to the depleted state in the young group and the absorption half-life (t 1/2, Ka) was significantly greater in the depleted state in the young group only. The absorption lag time (tlag) did not differ with respect to age or nutritional status. The elimination half-life (t 1/2, Ke) was significantly longer in supplemented subjects. Although the apparent high volume of distribution (Vd) was not significantly different within each age group the Vd was significantly greater in the depleted state when the two age groups were combined. The clearance (CL), and the nonrenal clearance (CLNR) were significantly greater in the depleted state. The renal clearance (CLR) and the amounts of vitamin C excreted in the 0- to 12- and 12- to 24-h intervals were significantly larger in the supplemented state. The urinary excretion data also indicate that, in supplemented subjects, an average of about 40 percent of the administered dose is excreted as unchanged vitamin C in the first 12 h after dosing, with very little being excreted thereafter.  相似文献   

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