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Single-dose pharmacokinetic study of lycopene delivered in a well-defined food-based lycopene delivery system (tomato paste-oil mixture) in healthy adult male subjects.
Gustin DM, Rodvold KA, Sosman JA, Diwadkar-Navsariwala V, Stacewicz-Sapuntzakis M, Viana M, Crowell JA, Murray J, Tiller P, Bowen PE
(2004) Cancer Epidemiol Biomarkers Prev 13: 850-60
MeSH Terms: Administration, Oral, Adolescent, Adult, Analysis of Variance, Antioxidants, Biological Availability, Carotenoids, Chromatography, High Pressure Liquid, Chylomicrons, Dose-Response Relationship, Drug, Drug Carriers, Drug Delivery Systems, Humans, Lycopene, Male, Maximum Tolerated Dose, Middle Aged, Probability
Show Abstract · Added March 5, 2014
This report details the findings of a single-dose Phase I pharmacokinetic and toxicity study of a food-based formulation of lycopene in healthy adult male subjects. Five dosing groups (n = 5 per group) were sequentially treated with increasing doses of lycopene ranging from 10 to 120 mg. Blood samples were collected for a total of 28 days (672 h) after administration of single doses of lycopene. The mean time (t(max)) to reach maximum total lycopene concentration (C(max)) ranged from 15.6 to 32.6 h. The C(max) for total lycopene ranged between 4.03 and 11.27 microg/dl (0.075-0.210 microm). Mean AUC(0-96) and elimination half-life for total lycopene ranged from 214 to 655 microg h/dl (3.986-12.201 micromol h/l) and 28.1 and 61.6 h, respectively. The changes observed in lycopene exposure parameters (e.g., C(max) and AUC(0-96)) were not proportional to increments in dose, with larger increases observed at the lowest end of the dosing range (10-30 mg). Chylomicron lycopene was measured during the first 12 h with the differences observed among the dosing groups not reaching statistical significance. These findings may reflect a process of absorption that is saturable at very low dosing levels or may be explained by the large interindividual variability in attained lycopene concentrations that were observed within each dosing group. Pharmacokinetic parameters for trans- and cis-lycopene isomers were calculated and are reported here. The formulation was well tolerated with minimal side effects, which were mainly of gastrointestinal nature and of very low grade.
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18 MeSH Terms
A NUTRITION SURVEY OF THREE RURAL PUERTO RICAN COMMUNITIES.
PLOUGH IC, FERNANDEZLOPEZ NA, ANGEL CR, ROBERTS LJ
(1963) Bol Asoc Med P R 55: SUPPL:1-51
MeSH Terms: Adolescent, Alkaline Phosphatase, Biometry, Blood Chemical Analysis, Blood Proteins, Carotenoids, Child, Cholesterol, Deficiency Diseases, Economics, Geriatrics, Health Surveys, Hemoglobinometry, Hispanic Americans, Humans, Infant, Nutrition Surveys, Parasitic Diseases, Puerto Rico, Social Conditions, Vitamin A, Vitamins
Added December 10, 2013
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22 MeSH Terms
A physiological pharmacokinetic model describing the disposition of lycopene in healthy men.
Diwadkar-Navsariwala V, Novotny JA, Gustin DM, Sosman JA, Rodvold KA, Crowell JA, Stacewicz-Sapuntzakis M, Bowen PE
(2003) J Lipid Res 44: 1927-39
MeSH Terms: Adult, Anticarcinogenic Agents, Antioxidants, Beverages, Carotenoids, Chromatography, High Pressure Liquid, Diet, Dose-Response Relationship, Drug, Humans, Lipids, Liver, Lycopene, Lycopersicon esculentum, Male, Middle Aged, Olive Oil, Plant Oils, Tissue Distribution, Vitamins
Show Abstract · Added March 5, 2014
A physiological pharmacokinetic model was developed to describe the disposition of lycopene, delivered as a tomato beverage formulation in five graded doses (10, 30, 60, 90, or 120 mg), for a phase I study in healthy male subjects (five per dose). Blood was collected before dose administration (0 h) and at scheduled intervals until 672 h. Serum concentrations of carotenoids and vitamins were measured by high performance liquid chromatography analysis. The model was comprised of seven compartments: gastrointestinal tract, enterocytes, chylomicrons, plasma lipoproteins, fast-turnover liver, slow-turnover tissues, and a delay compartment before the enterocytes. As predicted, the percent absorption at the 10 mg dose (33.9 +/- 8.1%) was significantly greater than at the higher doses; however, the amount of lycopene absorbed (mg) was not statistically different (mean: 4.69 +/- 0.55 mg) between doses, suggesting a possible saturation of absorptive mechanisms. The slow-turnover tissue compartment served as a slow-depleting reservoir for lycopene, and the liver represented the fast-turnover pool. Independent of dose, 80% of the subjects absorbed less than 6 mg of lycopene. This may have important implications for planning clinical trials with pharmacological doses of lycopene in cancer control and prevention if absorption saturation occurs at levels that are already being consumed in the population.
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19 MeSH Terms
Individual carotenoid concentrations in adipose tissue and plasma as biomarkers of dietary intake.
El-Sohemy A, Baylin A, Kabagambe E, Ascherio A, Spiegelman D, Campos H
(2002) Am J Clin Nutr 76: 172-9
MeSH Terms: Adipose Tissue, Aged, Biomarkers, Carotenoids, Case-Control Studies, Cholesterol, HDL, Cholesterol, LDL, Cholesterol, VLDL, Costa Rica, Cryptoxanthins, Diet, Energy Intake, Female, Humans, Lutein, Male, Middle Aged, Sex Characteristics, Surveys and Questionnaires, Xanthophylls, Zeaxanthins, beta Carotene
Show Abstract · Added April 24, 2015
BACKGROUND - Plasma and adipose tissue concentrations of carotenoids are thought to reflect short- and long-term intakes of carotenoids, respectively. The ability of adipose tissue carotenoid concentrations to reflect dietary intake in population studies is unknown.
OBJECTIVE - We examined the relation between intakes of the major dietary carotenoids and their concentrations in plasma and adipose tissue.
DESIGN - A blood sample and an adipose tissue biopsy sample were collected from 115 women and 344 men in Costa Rica after they had fasted overnight, and a dietary interview based on a 135-item food-frequency questionnaire was administered. After carotenoid intake was adjusted for total energy intake and plasma concentrations were adjusted for HDL-, LDL-, and VLDL-cholesterol concentrations, we calculated partial Spearman correlation coefficients that were adjusted for age, sex, smoking, and body mass index.
RESULTS - In women, the correlations (r) between intakes and concentrations of alpha-carotene, beta-carotene, beta-cryptoxanthin, and lutein+zeaxanthin were 0.25, 0.29, 0.44, and 0.17, respectively (P < 0.05 for r > or = 0.19), in adipose tissue and 0.26, 0.13, 0.55, and 0.22 in plasma. In men, these values were 0.04, 0.07, 0.23, and 0.06 in adipose tissue and 0.24, 0.22, 0.44, and 0.20 in plasma. In women and men, correlations for lycopene were higher in plasma (r = 0.19 and 0.35, respectively) than in adipose tissue (r = 0.14 and 0.26). The relative abundance of each carotenoid in the diet was similar to its distribution in plasma but not in adipose tissue.
CONCLUSION - The usefulness of adipose tissue and plasma carotenoids as biomarkers of intake is similar, although correlations for individual carotenoids vary substantially.
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22 MeSH Terms
Application of the method of triads to evaluate the performance of food frequency questionnaires and biomarkers as indicators of long-term dietary intake.
Kabagambe EK, Baylin A, Allan DA, Siles X, Spiegelman D, Campos H
(2001) Am J Epidemiol 154: 1126-35
MeSH Terms: Adipose Tissue, Biomarkers, Carotenoids, Costa Rica, Epidemiologic Research Design, Factor Analysis, Statistical, Fatty Acids, Fatty Acids, Unsaturated, Female, Humans, Lycopene, Male, Mental Recall, Middle Aged, Minority Groups, Nutrition Surveys, Reproducibility of Results, Sensitivity and Specificity, Surveys and Questionnaires, Time Factors, Tocopherols
Show Abstract · Added April 24, 2015
Little is documented about the performance of the food frequency questionnaire (FFQ) in US minority groups and in populations in developing countries. The authors applied a novel technique, the method of triads, to assess the validity and reproducibility of the FFQ among Hispanics. The subjects were men (n = 78) and women (n = 42) living in Costa Rica. Seven 24-hour dietary recalls and two FFQ interviews (12 months apart) were conducted between 1995 and 1998 to estimate dietary intake during the past year. Plasma and adipose tissue samples were collected from all subjects. Validity coefficients, which measure the correlation between observed and "true" dietary intake, were also estimated. The median validity coefficients for tocopherols and carotenoids estimated by dietary recall, the average of the two FFQs, and plasma were 0.71, 0.60, and 0.52, respectively. Compared with adipose tissue, plasma was a superior biomarker for carotenoids and tocopherols. Adipose tissue was a poor biomarker for saturated and monounsaturated fatty acids but performed well for polyunsaturated fatty acids (validity coefficients, 0.45-1.01) and lycopene (validity coefficient, 0.51). This study also showed that biomarkers did not perform better than the FFQ and that they should be used to complement the FFQ rather than substitute for it.
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21 MeSH Terms
Decreased plasma beta-carotene levels in women with uterine cervical dysplasias and cancer.
Palan PR, Romney SL, Mikhail M, Basu J, Vermund SH
(1988) J Natl Cancer Inst 80: 454-5
MeSH Terms: Carotenoids, Female, Humans, Uterine Cervical Dysplasia, Uterine Cervical Neoplasms, beta Carotene
Added March 5, 2014
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6 MeSH Terms
Effects of smoking and oral contraception on plasma beta-carotene levels in healthy women.
Palan PR, Romney SL, Vermund SH, Mikhail MG, Basu J
(1989) Am J Obstet Gynecol 161: 881-5
MeSH Terms: Adolescent, Adult, Carotenoids, Chromatography, High Pressure Liquid, Contraceptives, Oral, Female, Humans, Reference Values, Smoking, Vitamin A, beta Carotene
Show Abstract · Added March 5, 2014
Oral contraceptive use and smoking have been known to affect plasma vitamin levels. Total carotenoids have been studied with spectrophotometry, a relatively insensitive technique. In this study plasma concentrations of beta-carotene and retinol were measured in coded samples by sensitive high-pressure liquid chromatography in a cross-sectional study of 149 normal healthy women attending a family planning clinic. At the time of recruitment in the morning, a general health questionnaire was administered for patient age, methods of contraception, smoking habits, and food intake at breakfast. Of the 149 enrolled volunteers, 88 were oral contraceptive users and 61 were not users. Among users, 21 smoked cigarettes, and there were 18 smokers among nonusers. Oral contraceptive users had significantly lower plasma concentrations of beta-carotene (p less than 0.001) and higher retinol levels (p less than 0.0001). Plasma beta-carotene or retinol levels did not differ among users of intrauterine contraceptive devices or barrier methods of contraception. No association was noted between the plasma levels of these two micronutrients and age greater than or less than 30 years. Cigarette smoking alone was associated with significantly reduced plasma beta-carotene levels in nonusers (p less than 0.001). Combined cigarette smoking and oral contraceptive usage were associated with low plasma beta-carotene levels; the results appear to be additive. These findings suggest a possible synergistic effect on plasma beta-carotene levels from the use of both cigarette smoking and oral contraception.
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11 MeSH Terms
Plasma ascorbic acid and beta-carotene levels in women evaluated for HPV infection, smoking, and cervix dysplasia.
Basu J, Palan PR, Vermund SH, Goldberg GL, Burk RD, Romney SL
(1991) Cancer Detect Prev 15: 165-70
MeSH Terms: Adult, Ascorbic Acid, Carotenoids, Chromatography, High Pressure Liquid, DNA, Viral, Female, Humans, Papanicolaou Test, Papillomaviridae, Smoking, Tumor Virus Infections, Uterine Cervical Dysplasia, Vaginal Smears, Vitamin A
Show Abstract · Added March 5, 2014
The association of the plasma levels of the essential micronutrients, ascorbic acid and beta-carotene, with smoking and human papillomaviruses (HPV) infection has been studied in 75 women referred to a colposcopy clinic for an abnormal Pap smear. Each patient had a repeat Pap smear and a colposcopically directed biopsy of a visually perceived cervix abnormality. Cervicovaginal lavage specimen and peripheral venous blood sample were obtained for HPV DNA hybridization studies and nutrient analyses, respectively. Samples were obtained and analyzed without knowledge of each woman's clinical status. A group of 45 subjects had histopathologically diagnosed dysplasias of varying grades of severity. Among women with dysplasias, 53.3% were smokers. Of subjects with and of subjects without dysplasias, 66 and 34%, respectively, were positive for HPV infection. The mean plasma reduced ascorbic acid, retinol, and beta-carotene levels between the dysplastic groups were comparable. A strong association with smoking history and plasma reduced ascorbic acid level was note independent of cervical dysplasias or HPV status. The findings underscore the importance of smoking, ascorbic acid, and beta-carotene as nutritional variables, and HPV infection in the pathogenesis of cervical dysplasias.
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14 MeSH Terms