Papers by Begoña Olmedilla-alonso
Evaluación del efecto funcional: biomarcadores. En: "La carne y productos cárnicos como alimentos funcionales
ABSTRACT

Carcinogenesis, 1998
Carotenoids are thought to act as antioxidants in vivo, decreasing oxidative damage to biomolecul... more Carotenoids are thought to act as antioxidants in vivo, decreasing oxidative damage to biomolecules and thus protecting against coronary heart disease and cancer. However, human intervention studies with β-carotene have given equivocal results in terms of cancer incidence. In an alternative molecular epidemiological approach, we have employed the 'comet assay' (single cell alkaline gel electrophoresis) to measure strand breaks, oxidized pyrimidines and altered purines in the DNA of lymphocytes from volunteers supplemented with α/β-carotene, lutein, lycopene or placebo. In addition, we measured concentrations of the main serum carotenoids, and vitamins E and C, by HPLC. We report a significant negative correlation between basal concentrations of total serum carotenoids and oxidized pyrimidines. A similar correlation was seen between individual carotenoids (notably lutein and β-carotene) and oxidized pyrimidines. However, carotenoid supplementation did not have a significant effect on endogenous oxidative damage. This suggests that there are some factors in the basal diet, probably found in fruit and vegetables, that decrease oxidative damage to DNA. In this case, basal serum carotenoids may simply be markers of consumption of fruit and vegetables, they themselves having little or no protective value.

Clinical Chemistry, 1997
To establish reference ranges for use in clinical and epidemiological studies, we determined conc... more To establish reference ranges for use in clinical and epidemiological studies, we determined concentrations of retinol, α-tocopherol, β-carotene, α-carotene, β-cryptoxanthin, lutein, zeaxanthin, and lycopene in 450 Spanish control subjects and 123 Spanish patients with insulin-dependent diabetes mellitus (IDDM). Results were grouped according to sex, and samples were collected throughout the year. Concentrations of retinol were significantly lower and β-carotene and α-carotene were higher in women than in men, both in controls and IDDM subjects, whereas β-cryptoxanthin concentrations were higher only in control women. Conditional logistic regression analysis showed that retinol, β-carotene, and lycopene were the variables associated with diabetes. In comparison with other populations, our controls showed, in general, ordinary concentrations of retinol, comparatively low β-carotene and high β-cryptoxanthin concentrations, and a relatively high α-tocopherol/cholesterol ratio.

British Journal of Nutrition, 1998
Lutein, one of the major carotenoids present in serum, is also widely consumed by most population... more Lutein, one of the major carotenoids present in serum, is also widely consumed by most populations. For the purpose of testing the potential health benefits of several carotenoids, lutein was supplied as part of an intervention trial to test whether the consumption of these food constituents reduces oxidative damage to human tissue components. Lutein from a natural source (15 mg/d as mixed ester forms) was supplied for 4 months to eighteen non-smoking, apparently healthy volunteers (nine men, nine women) aged 25–45 years. The serum carotenoid profile was analysed at baseline and monthly thereafter. On average, lutein concentrations increased 5-fold after the first month of supplementation (mean 1·34 (range 0·6–3·34) μmol/l). On reviewing the results, in those volunteers whose lutein levels surpassed 1·05 μmol/l (fourteeen of seventeen), we tentatively identified lutein monopalmitate along with another unidentified ester (possibly from a monoketocarotenoid) in serum. Lutein levels re...

Seasonal and sex-related variations in six serum carotenoids, retinol, and α-tocopherol
The American Journal of Clinical Nutrition, 1994
We report the results of a study on the influence of season and sex on serum concentrations of si... more We report the results of a study on the influence of season and sex on serum concentrations of six carotenoids, retinol, and alpha-tocopherol, as determined by reversed-phase HPLC. The subjects were 111 healthy individuals (54 females, 57 males); 18 additional subjects (10 females, 8 males) were assessed for within-subject longitudinal seasonal variations. Men presented significantly higher retinol concentrations (P = 0.002) and lower concentrations of provitamin A carotenoids--alpha carotene (P = 0.006), beta-carotene (P < 0.001), and beta-cryptoxanthin (P < 0.001)--than women. There were no significant differences between the sexes with respect to nonprovitamin A carotenoids (lutein, zeaxanthin, and lycopene) or alpha-tocopherol. Significant seasonal increments (P < 0.05) in serum concentrations of alpha-carotene and beta-carotene (in summer) and of beta-cryptoxanthin (in winter) were detected in both sexes; in males, lutein was higher in summer whereas in females it rose in spring. No sex-related or seasonal variations were observed in alpha-tocopherol, zeaxanthin, or lycopene. Serum concentrations of provitamin A carotenoids vary according to the individual's sex and season of the year.

The FASEB Journal, 1998
The 'antioxidant hypothesis' proposes that vitamin C, vitamin E, carotenoids, and other antioxida... more The 'antioxidant hypothesis' proposes that vitamin C, vitamin E, carotenoids, and other antioxidants occurring in fruit and vegetables afford protection against heart disease and cancer by preventing oxidative damage to lipids and to DNA, respectively. To test elements of this hypothesis, we have measured blood levels of dietary antioxidants, and 8-oxodeoxyguanosine (8-oxo-dG) concentrations in lymphocyte DNA, in healthy men and women from five European countries: France, Ireland, The Netherlands, Spain, and the U.K. Volunteers, aged 25-45, all nonsmokers, gave blood samples before and after a 12-wk carotenoid supplementation regime. Vitamin C was measured in plasma and vitamin E and carotenoids were measured in serum by high-performance liquid chromatography (HPLC). 8-oxo-dG was assayed by HPLC (with coulometric detection) in DNA isolated from lymphocytes from the same blood samples. Mean values were calculated for groups of volunteers at each sampling time according to country, sex, and supplementation (between 9 and 24 individual samples contributing to each mean). We found that 8-oxo-dG levels in lymphocyte DNA vary significantly according to sex and country. A low mean 8oxo-dG concentration is seen in DNA of women from all five countries, and of men from France and Spain. 8-oxo-dG is significantly higher (up to about threefold) in lymphocyte DNA from men in Ireland and the U.K. Oxidative DNA damage is not significantly affected by carotenoid supplementation; nor is there any association with mean baseline levels of antioxidants, which are generally similar in the five countries. The five countries sampled lie on an axis from northern to southern Europe with a steep gradient in terms of premature heart disease. There is a strong association between premature coronary heart disease mortality in men and the mean levels of 8-oxo-dG for the five countries (r Å 0.95, P õ 0.01). Women have low coronary heart disease mortality rates, which do not correlate with 8-oxo-dG. In terms of cancer deaths, only colorectal cancer in men shows a significant positive correlation (r Å 0.91, P õ 0.05), and stomach cancer in women is negatively correlated with DNA oxidation (r Å 00.92, P Å 0.01).-Collins, A. R., Gedik, C. M., Olmedilla, B., Southon, S., Bellizzi, M. Oxidative DNA damage measured in human lymphocytes: large differences between sexes and between countries, and correlations with heart disease mortality rates.
Retinol and α-tocopherol in serum of type 1 diabetic patients with intensive insulin therapy
Nutrition, 2003
ObjectiveWe evaluated the effect of intensive insulin therapy and glycemic control in patients wi... more ObjectiveWe evaluated the effect of intensive insulin therapy and glycemic control in patients with type 1 diabetes on biochemical markers of vitamin A and E.
Vitamins A, C and E, folate and most carotenoids do not influence bladder cancer risk
Evidence-based Oncology, 2002

Revista Española de Cardiología (English Edition), 2005
Introducción y objetivos. El objetivo de este trabajo fue analizar el daño por isquemia-reperfusi... more Introducción y objetivos. El objetivo de este trabajo fue analizar el daño por isquemia-reperfusión mediado por radicales libres que se produce durante el trasplante cardíaco y evaluar el posible efecto citoprotector de la trimetazidina (TMZ). Material y método. Se realizaron 21 trasplantes cardíacos ortotópicos en cerdos. Dividimos los experimentos en 2 grupos: A (n = 11), en el que se realizó una protección miocárdica estándar, y B (n = 10), en el que se administró TMZ en la cardioplejía empleada para parar el corazón donante (TMZ, 10 -5 mol/l), como pretratamiento intravenoso del receptor (TMZ, 2,5 mg/kg) y como parte de la cardioplejía infundida en el receptor antes de despinzar la aorta (TMZ, 10 -5 mol/l). Se tomaron muestras de sangre del seno coronario del receptor en 3 momentos: basal, isquemia y reperfusión. Se determinó la concentración de malonildialdehído como marcador de peroxidación lipídica y de varios antioxidantes: glutatión peroxidasa, glutatión reductasa, superóxido dismutasa, α-tocoferol, retinol y estado de antioxidantes totales. Resultados. Durante la isquemia-reperfusión aumentó la producción de malonildialdehído y la actividad de los antioxidantes enzimáticos, mientras que el retinol disminuyó. El incremento de malonildialdehído y de la actividad de la glutatión peroxidasa entre el momento basal y la reperfusión fue significativamente mayor en el grupo A. Conclusiones. Durante el trasplante se incrementó progresivamente el nivel de peroxidación lipídica y se activaron los sistemas antioxidantes intracelulares. La TMZ ejerció un efecto citoprotector y limitó el daño por isquemia-reperfusión generado por los radicales libres, además de modificar el patrón de reacción de parte de los sistemas de defensa.

Revista Española de Cardiología, 2005
Introducción y objetivos. El objetivo de este trabajo fue analizar el daño por isquemia-reperfusi... more Introducción y objetivos. El objetivo de este trabajo fue analizar el daño por isquemia-reperfusión mediado por radicales libres que se produce durante el trasplante cardíaco y evaluar el posible efecto citoprotector de la trimetazidina (TMZ). Material y método. Se realizaron 21 trasplantes cardíacos ortotópicos en cerdos. Dividimos los experimentos en 2 grupos: A (n = 11), en el que se realizó una protección miocárdica estándar, y B (n = 10), en el que se administró TMZ en la cardioplejía empleada para parar el corazón donante (TMZ, 10 -5 mol/l), como pretratamiento intravenoso del receptor (TMZ, 2,5 mg/kg) y como parte de la cardioplejía infundida en el receptor antes de despinzar la aorta (TMZ, 10 -5 mol/l). Se tomaron muestras de sangre del seno coronario del receptor en 3 momentos: basal, isquemia y reperfusión. Se determinó la concentración de malonildialdehído como marcador de peroxidación lipídica y de varios antioxidantes: glutatión peroxidasa, glutatión reductasa, superóxido dismutasa, α-tocoferol, retinol y estado de antioxidantes totales. Resultados. Durante la isquemia-reperfusión aumentó la producción de malonildialdehído y la actividad de los antioxidantes enzimáticos, mientras que el retinol disminuyó. El incremento de malonildialdehído y de la actividad de la glutatión peroxidasa entre el momento basal y la reperfusión fue significativamente mayor en el grupo A. Conclusiones. Durante el trasplante se incrementó progresivamente el nivel de peroxidación lipídica y se activaron los sistemas antioxidantes intracelulares. La TMZ ejerció un efecto citoprotector y limitó el daño por isquemia-reperfusión generado por los radicales libres, además de modificar el patrón de reacción de parte de los sistemas de defensa.

Antioxidant effect of gamma-tocopherol supplied by propofol preparations (Diprivan) during ischemia-reperfusion in experimental lung transplantation
Transplant International, 2004
Free radicals are involved in ischemia-reperfusion injury and inflammatory processes. The commerc... more Free radicals are involved in ischemia-reperfusion injury and inflammatory processes. The commercial formulation of the anesthetic propofol contains gamma-tocopherol and delta-tocopherol, which may exert antioxidant effects during transplantation. Animals were randomly assigned to a control group or experimental groups for lung transplantation after 3 and 24 h of ischemia. Individual tocopherols, malondialdehyde, biochemical indices, and hemodynamic, blood gas, and ventilatory parameters were determined during reperfusion. Results showed that administration of commercially available propofol provoked a time- and dose-dependent increment in serum gamma-tocopherol and delta-tocopherol in control animals and in the group receiving lungs subjected to 3 h of ischemia, but not in the group with 24 h of ischemia. Malondialdehyde levels increased during reperfusion and did not differ significantly between the two experimental groups, which did not differ with respect to lung function either. gamma-Tocopherol, supplied by the anesthetic, may act as an antioxidant that is consumed during reperfusion. This potential effect could be relevant to the choice of anesthetic agents in situations where free radical damage to tissues is expected.

British Journal of Nutrition, 2001
A food frequency questionnaire (FFQ) and carotenoid database with information onα- and β-carotene... more A food frequency questionnaire (FFQ) and carotenoid database with information onα- and β-carotene, lutein, lycopene and β-cryptoxanthin was prepared and used to compare the carotenoid intakes in five European countries: UK, Republic of Ireland, Spain, France and The Netherlands. Eighty, age- (25–45 years) and sex-matched volunteers were recruited in each of the five countries. A FFQ and carotenoid database was prepared of the most commonly consumed carotenoid rich foods in the participating countries and the information was used to calculate frequency and intake of carotenoid-rich foods. The median total carotenoid intake based on the sum of the five carotenoids, was significantly higher (P<0.05) in France (16.1 mg/day) and lower in Spain (9.5 mg/day,) than the other countries, where the average intake was approximately 14 mg/day. Comparison of dietary source of carotenoids showed that carrots were the major source of β-carotene in all countries except Spain where spinach was mos...

British Journal of Nutrition, 2001
High intakes of fruits and vegetables, or high circulating levels of their biomarkers (carotenoid... more High intakes of fruits and vegetables, or high circulating levels of their biomarkers (carotenoids, vitamins C and E), have been associated with a relatively low incidence of cardiovascular disease, cataract and cancer. Exposure to a high fruit and vegetable diet increases antioxidant concentrations in blood and body tissues, and potentially protects against oxidative damage to cells and tissues. This paper describes blood concentrations of carotenoids, tocopherols, ascorbic acid and retinol in well-defined groups of healthy, non-smokers, aged 25–45 years, 175 men and 174 women from five European countries (France, UK (Northern Ireland), Republic of Ireland, The Netherlands and Spain). Analysis was centralised and performed within 18 months. Within-gender, vitamin C showed no significant differences between centres. Females in France, Republic of Ireland and Spain had significantly higher plasma vitamin C concentrations than their male counterparts. Serum retinol and α-tocopherol le...

British Journal of Nutrition, 2002
Within Europe there are differences in cardiovascular disease (CVD) risk between countries and th... more Within Europe there are differences in cardiovascular disease (CVD) risk between countries and this might be related to dietary habits. Oxidative modification of LDL is suggested to increase the risk of CVD and both the fatty acid and antioxidant content of LDL can affect its oxidation. In the present study, concentration of LDL fatty acid and antioxidant micronutrients (tocopherols and carotenoids) andex vivooxidative resistance of LDL (lag phase) was compared in volunteers from five countries with different fruit and vegetable intakes and reported rates of CVD. Eighty volunteers (forty males, forty females per centre), age range 25–45 years, were recruited from France, Northern Ireland, UK, Republic of Ireland, The Netherlands, and Spain, and their LDL composition and lag phase were measured. There were some differences in LDL carotenoid and α-tocopherol concentrations between countries. α-Tocopherol was low and β- + γ-tocopherol were high (P<0·001) in the Dutch subjects. β-Car...

British Journal of Nutrition, 2003
Lutein is one of the most widely found carotenoids distributed in fruits and vegetables frequentl... more Lutein is one of the most widely found carotenoids distributed in fruits and vegetables frequently consumed. Its presence in human tissues is entirely of dietary origin. Distribution of lutein among tissues is similar to other carotenoids but, along with zeaxanthin, they are found selectively at the centre of the retina, being usually referred to as macular pigments. Lutein has no provitamin A activity in man but it displays biological activities that have attracted great attention in relation to human health. Epidemiological studies have shown inconsistent associations between high intake or serum levels of lutein and lower risk for developing cardiovascular disease, several types of cancer, cataracts and age-related maculopathy. Also, lutein supplementation has provided both null and positive results on different biomarkers of oxidative stress although it is effective in increasing macular pigment concentration and in improving visual function in some, but not all, subjects with d...
Nutrition, 2003
We investigated the effect of long-term antioxidant supplementation (lutein andtocopherol) on ser... more We investigated the effect of long-term antioxidant supplementation (lutein andtocopherol) on serum levels and visual performance in patients with cataracts. Visual function in patients with age-related cataracts who received the lutein supplements improved, suggesting that a higher intake of lutein, through lutein-rich fruit and vegetables or supplements, may have beneficial effects on the visual performance of people with age-related cataracts.

Nutrition, 2002
OBJECTIVE: Epidemiologic studies have suggested that dietary intake and plasma concentrations of ... more OBJECTIVE: Epidemiologic studies have suggested that dietary intake and plasma concentrations of antioxidants have an inverse relation with coronary heart disease. To test whether fat-soluble antioxidants can play a role against the occurrence of myocardial infarction (MI), we measured plasma levels of retinol, tocopherols, and individual carotenoids in MI patients. METHODS: A case-control and follow-up study of patients in the Mo ´stoles area (Madrid, Spain). One hundred six patients (62 after 1 y) and 104 control subjects participated in the study. Blood samples were collected after overnight fast or during the first 24 h of MI onset for biochemical profiles of retinol, ␣and ␥-tocopherols, and carotenoid by means of a quality-controlled high-performance liquid chromatography. RESULTS: During the acute phase after MI onset, plasma levels of retinol, ␥-tocopherol, and xanthophylls (lutein/zeaxanthin and -cryptoxanthin) decreased, whereas ␣-tocopherol, ␣-carotene, -carotene, and lycopene showed levels similar to those of control subjects. Logistic regression analysis showed low concentrations of ␥-tocopherol (and retinol) in plasma as the only statistically significant factor associated with MI, after adjusting for traditional risk factors. However, 1 y later, the MI patients showed a general improvement in plasma lipids and fat-soluble antioxidant status, and none of the analytes was associated with MI. The decreased plasma status of retinol, ␥-tocopherol, and xanthophylls during the acute phase of MI normalized the year after the MI event, suggesting that most subjects had followed an overall healthier lifestyle and dietary pattern. The results also raise concerns on the usefulness of these plasma compounds as specific, relevant, and predictive markers in relation to coronary heart disease.
Evaluation of Retinol, α-Tocopherol, and Carotenoids in Serum of Men With Cancer of the Larynx Before and After Commercial Enteral Formula Feeding
Journal of Parenteral and Enteral Nutrition, 1996
Background: Both epidemiologic and in vitro studies have indicated the inverse correlation betwee... more Background: Both epidemiologic and in vitro studies have indicated the inverse correlation between intake and/or blood concentrations of different carotenoids, retinol, and tocoferol with different chronic and degenerative disturbances (cancer, cardiovascular diseases, ...

Pulsed electric fields–processed orange juice consumption increases plasma vitamin C and decreases F2-isoprostanes in healthy humans
The Journal of Nutritional Biochemistry, 2004
Orange juice, a rich source of vitamin C, accounts for 60% of all fruit juices and juice-based dr... more Orange juice, a rich source of vitamin C, accounts for 60% of all fruit juices and juice-based drinks consumed in western Europe. Orange juice preservation is currently accomplished by traditional pasteurization. Pulsed electric fields (PEF) have been studied as a nonthermal food preservation method. Food technology needs in the area of processing are driven by nutrition. Therefore, the objectives of this study were to assess the bioavailability of vitamin C from pulsed electric fields-treated orange juice in comparison with freshly squeezed orange juice and its impact on 8-epiPGF(2alpha) concentrations (biomarker of lipid peroxidation) in a healthy human population. Six subjects consumed 500 mL/day of pulsed electric fields-treated orange juice and six subjects consumed 500 mL/day of freshly squeezed orange juice for 14 days, corresponding to an intake of about 185 mg/day of ascorbic acid. On the first day of the study, subjects drank the juice in one dose, and on days 2-14 they consumed 250 mL in the morning and 250 mL in the afternoon. Blood was collected every hour for 6 hours on the first day and again on days 7 and 14. In the dose-response study, the maximum increase in plasma vitamin C occurred 4 hours postdose. Vitamin C remained significantly higher on days 7 and 14 in both orange juice groups. Plasma 8-epiPGF(2alpha) concentrations was lower at the end of the study (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) in both groups. Plasma levels of vitamin C and 8-epiPGF(2alpha) were inversely correlated. Pulsed electric fields-preservation of orange juice retains the vitamin C bioavailability and antioxidant properties of fresh juice with a longer shelf-life.
European Journal of Nutrition, 2002
Background Lutein, a non-provitamin A carotenoid, is frequently consumed in the human diet. It is... more Background Lutein, a non-provitamin A carotenoid, is frequently consumed in the human diet. It is distributed preferentially in certain human tissues (i. e., retina) and shows a high antioxidant activity. Type 1 diabetic patients have been considered to be at risk of increased oxidative stress that may contribute to accelerated
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Papers by Begoña Olmedilla-alonso