RESUMO
BACKGROUND: Tea is one of the most frequently consumed beverages in the world. Antioxidant polyphenol compounds (such as catechins and flavonols) are abundantly present in both green and black teas and have been observed to have anticarcinogenic properties in cell and animal model studies. In black tea, however, most of the catechins have been oxidized to forms that may have reduced anticarcinogenic properties. Despite indications from experimental studies that tea may protect against cancer, epidemiologic evidence has been inconclusive. PURPOSE: The association between black tea consumption and the subsequent risk of stomach, colorectal, lung, and breast cancers was investigated in The Netherlands Cohort Study on Diet and Cancer among 58,279 men and 62,573 women aged 55-69 years. METHODS: Subjects in the cohort completed a self-administered questionnaire on dietary habits and other risk factors for cancer at base line in 1986. Follow-up for cancer was done by means of computerized record linkage with all nine regional cancer registries in The Netherlands and the national pathology database. During 4.3 years of follow-up, 200, 650, 764, and 650 cases of stomach, colorectal, lung, and breast cancers were diagnosed, respectively. The questionnaire data of case subjects and those of a random subcohort (n = 3500) were used to calculate rate ratios (RRs) of cancer in categories of consumers of black tea compared with nonconsumers. RESULTS: Tea was not used by 13% of the subjects in the cohort, whereas 37%, 34%, and 16% consumed one to two, three to four, and five or more cups of tea per day, respectively. No association was observed between tea consumption and risk of colorectal cancer: The risk among tea drinkers in each consumption category was similar to that among nondrinkers. The RR of breast cancer among consumers of five or more cups of tea per day was 1.3 (95% confidence interval = 0.9-2.0); no dose-response association was observed. In age- and sex-adjusted analyses, consumption of tea was inversely associated with stomach (two-sided P for trend = .147) and lung (two-sided P for trend < .001) cancers. However, tea drinkers appeared to smoke less and to eat more vegetables and fruits than nondrinkers. When smoking and dietary factors were taken into account, tea in itself did not appear to protect against stomach and lung cancers: The RRs in all consumption categories were close to unity. Analysis of the tea and cancer relationship in a subgroup that included subjects in the lowest two quintiles of consumption of vegetables and fruits also failed to reveal a protective effect of tea consumption on the risk of three cancer types studied (colorectal, lung, and breast cancers). CONCLUSIONS: This investigation does not support the hypothesis that consumption of black tea protects against four of the major cancers in humans; a cancer-enhancing effect was not evident, either.
Assuntos
Neoplasias/epidemiologia , Neoplasias/etiologia , Chá , Idoso , Neoplasias da Mama/etiologia , Neoplasias Colorretais/etiologia , Fatores de Confusão Epidemiológicos , Dieta , Feminino , Humanos , Neoplasias Pulmonares/etiologia , Masculino , Registro Médico Coordenado , Pessoa de Meia-Idade , Análise Multivariada , Países Baixos/epidemiologia , Razão de Chances , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Neoplasias Gástricas/etiologiaRESUMO
In 1981 it was hypothesized that a high dietary intake of beta-carotene might reduce human cancer rates. Since then, several observational epidemiologic studies have addressed this topic. The results of both case-control and cohort studies show a remarkable consistency for the association of increased lung cancer risk with low amounts of dietary beta-carotene or low plasma beta-carotene concentrations. For stomach cancer, the evidence is also consistent, although the number of studies is more modest. For breast and prostate cancer, the studies indicate no consistent association of plasma or dietary beta-carotene and reduced cancer risk. For colorectal cancer, the effect will be moderate, if existent. For several other cancer sites, the numbers of cases in prospective studies are often small, implying that only strong associations can be detected. For some of these sites, results from retrospective studies are promising. The epidemiologic studies should be carefully interpreted because dietary habits may be misclassified and smoking may reduce plasma beta-carotene concentrations. Observational epidemiology cannot definitively resolve whether associations are indeed due to beta-carotene, or to other components of fruit and vegetables that are rich in beta-carotene. However, overall results are promising and several plausible cancer preventive mechanisms have been reported for beta-carotene. The ongoing human intervention studies will provide more answers regarding cancer prevention by beta-carotene but may need long follow-ups to be conclusive.
Assuntos
Antioxidantes/administração & dosagem , Carotenoides/administração & dosagem , Neoplasias/prevenção & controle , Humanos , beta CarotenoRESUMO
To evaluate the immunomodulatory effects of beta-carotene we performed a randomized, double-blind trial in healthy male cigarette smokers. Lymphocyte subsets in peripheral blood were assessed by using double labeling with monoclonal antibodies before and after 14 wk beta-carotene (20 mg/d; n = 21) or placebo (n = 24) supplements. In addition we measured the ex vivo phytohemagglutinin and concanavalin A induced lymphocyte proliferation in a separate group (23 placebo, 24 beta-carotene). The beta-carotene and placebo groups were comparable on all initial characteristics. During the intervention plasma concentrations of beta-carotene increased 13-fold in the treatment group whereas retinol concentrations remained constant. Beta-carotene had no effect on lymphocyte subpopulations in peripheral blood. After treatment the beta-carotene group showed 12% higher PHA-induced lymphocyte proliferations than the placebo group (P = 0.02). For ConA induced proliferations no significant difference was observed. These results suggest that supplementary beta-carotene can moderately enhance certain aspects of immune response in healthy male cigarette smokers.
Assuntos
Carotenoides/farmacologia , Fumar/sangue , Adulto , Anticorpos Monoclonais , Carotenoides/sangue , Carotenoides/uso terapêutico , Concanavalina A/farmacologia , Método Duplo-Cego , Humanos , Contagem de Leucócitos , Ativação Linfocitária/efeitos dos fármacos , Subpopulações de Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Fito-Hemaglutininas/farmacologia , Vitamina A/sangue , beta CarotenoRESUMO
A high intake of beta-carotene has been associated with a decreased risk for cardiovascular disease. To evaluate whether beta-carotene intake may exert a protective effect through an impact on lipoprotein metabolism, we conducted a randomized, double-blind trial in healthy, male cigarette smokers. Total cholesterol, high-density-lipoprotein (HDL) cholesterol, apolipoprotein A-I (apo) A-I, apo B-100, and lipoprotein(a) were measured before and after 14 wk of treatment with beta-carotene (20 mg/d, n = 25) or placebo (n = 25). The beta-carotene and placebo groups were comparable with respect to all initial characteristics, but initial apo B-100 was significantly higher in the beta-carotene group (1.23 vs 1.44 g/L). During the intervention, plasma concentrations of beta-carotene increased 15-fold in the treatment group. Mean concentrations of total and HDL cholesterol, lipoprotein(a), apo A-I, and apo B-100 did not change significantly in either group. We conclude that a 20 mg beta-carotene supplement/d does not influence plasma lipoproteins in healthy male smokers.
Assuntos
Carotenoides/farmacologia , Alimentos Fortificados , Lipoproteínas/efeitos dos fármacos , Fumar , Adulto , Método Duplo-Cego , Humanos , Lipoproteínas/sangue , Masculino , beta CarotenoRESUMO
Low plasma concentrations of high-density lipoprotein (HDL) are associated with increased risk of coronary heart disease. Several drugs that induce the microsomal cytochrome P-450-dependent enzyme system in liver and intestine, the sites of HDL apolipoprotein (apo) A-I and A-II synthesis, raise plasma HDL concentrations in humans. To test the hypothesis that phytochemicals with cytochrome P-450-inducing activity may also increase plasma HDL concentrations, two controlled dietary trials were undertaken in healthy nonsmoking males aged 20-28 y. One study examined the effect of replacing 300 g glucosinolate-free vegetables with 300 g Brussels sprouts/d for 3 wk. The other study examined the effects of 150 mg eugenol/d in capsule form, using a double-blind, placebo-controlled crossover design. There were no significant increases in plasma apo A-I, apo A-II, HDL cholesterol, or HDL phospholipids. These results suggest that dietary phytochemicals that induce members of the cytochrome P-450 system do not necessarily raise plasma HDL concentrations in humans, but do not exclude the possibility that some phytochemicals may have such an effect.
Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Glucosinolatos/farmacologia , Lipoproteínas HDL/sangue , Adulto , Apolipoproteína A-II/biossíntese , Brassica , Estudos Transversais , Sistema Enzimático do Citocromo P-450/análise , Método Duplo-Cego , Eugenol/farmacologia , Humanos , Intestinos/enzimologia , Fígado/enzimologia , Masculino , VerdurasRESUMO
Biomarkers for increased cytogenetic damage in smokers include sister chromatid exchanges (SCE) in peripheral lymphocytes and micronuclei in sputum cells. These markers may reflect increased cancer risk. Increased cancer risk has also been associated with lower blood levels of the antioxidants beta-carotene and vitamin C and with genetic deficiency of the detoxification enzyme glutathione S-transferase mu (GST-mu). We therefore evaluated the associations of plasma antioxidants, GST-mu phenotype, and indices for tobacco exposure with SCEs and micronuclei in a group of 156 male cigarette smokers and 38 nonsmokers. As expected, smokers as compared with nonsmokers had higher SCE levels (5.08 versus 4.71 SCE/lymphocyte) and lower levels of plasma beta-carotene (0.31 versus 0.48 mumol/liter) and blood vitamin C (36.6 versus 33.8 mumol/liter). In smokers, SCEs were weakly correlated with plasma cotinine (r = 0.186) but not with plasma antioxidants (all r < 0.04). Micronuclei in smokers were not correlated with either cotinine or antioxidants (all r < 0.14). As reported previously, SCEs were higher (5.24 versus 4.97 SCE/lymphocyte) in GST-mu-deficient smokers than in nondeficient smokers. Micronuclei, however, were similar in both GST-mu phenotypes (4.3 versus 4.9 micronuclei/3000 cells). No correlation was observed between micronuclei and SCEs (r = -0.025). Large random variations in both SCEs and micronuclei make it difficult to interpret the absence of relations unambiguously. The results indicate that SCEs and micronuclei have only limited sensitivity to variations in cigarette smoke exposure. The association between GST-mu and cancer risk may be mediated through increases in certain forms of smoking-induced DNA damage in GST-mu deficiency.
Assuntos
Antioxidantes/análise , Biomarcadores/análise , Glutationa Transferase/genética , Micronúcleos com Defeito Cromossômico/ultraestrutura , Troca de Cromátide Irmã/genética , Fumar/genética , Adulto , Consumo de Bebidas Alcoólicas/sangue , Consumo de Bebidas Alcoólicas/genética , Consumo de Bebidas Alcoólicas/patologia , Ácido Ascórbico/sangue , Carotenoides/sangue , Cotinina/sangue , Estudos Transversais , Citogenética , Ácido Desidroascórbico/sangue , Glutationa Transferase/deficiência , Humanos , Linfócitos/ultraestrutura , Masculino , Fenótipo , Fumar/sangue , Fumar/metabolismo , Fumar/patologia , Escarro/citologia , Vitamina A/sangue , Vitamina E/sangue , beta CarotenoRESUMO
This paper gives an overview of the epidemiological data concerning the cancer-preventive effect of brassica vegetables, including cabbage, kale, broccoli, Brussels sprouts, and cauliflower. The protective effect of brassicas against cancer may be due to their relatively high content of glucosinolates. Certain hydrolysis products of glucosinolates have shown anticarcinogenic properties. The results of 7 cohort studies and 87 case-control studies on the association between brassica consumption and cancer risk are summarized. The cohort studies showed inverse associations between the consumption of cabbage, cauliflower, and broccoli and risk of lung cancer; between the consumption of brassicas and risk of stomach cancer; between broccoli consumption and risk of all cancers taken together; and between brassica consumption and the occurrence of second primary cancers. Of the case-control studies, 67% showed an inverse association between consumption of total brassica vegetables and risk of cancer at various sites. For cabbage, broccoli, cauliflower, and Brussels sprouts, these percentages were 70, 56, 67, and 29%, respectively. Although the measured effects might have been distorted by various types of bias, it is concluded that a high consumption of brassica vegetables is associated with a decreased risk of cancer. This association appears to be most consistent for lung, stomach, colon, and rectal cancer and least consistent for prostatic, endometrial, and ovarian cancer. It is not yet possible to resolve whether associations are to be attributed to brassica vegetables per se or to vegetables in general. Further epidemiological research should separate the anticarcinogenic effect of brassica vegetables from the effect of vegetables in general.
Assuntos
Brassica , Neoplasias/epidemiologia , Anticarcinógenos/análise , Viés , Brassica/química , Estudos de Casos e Controles , Estudos de Coortes , Neoplasias do Colo/epidemiologia , Dieta , Neoplasias do Endométrio/epidemiologia , Métodos Epidemiológicos , Feminino , Glucosinolatos/análise , Glucosinolatos/metabolismo , Humanos , Hidrólise , Neoplasias Pulmonares/epidemiologia , Masculino , Neoplasias/prevenção & controle , Segunda Neoplasia Primária/epidemiologia , Neoplasias Ovarianas/epidemiologia , Neoplasias da Próstata/epidemiologia , Neoplasias Retais/epidemiologia , Fatores de Risco , Neoplasias Gástricas/epidemiologiaRESUMO
Many studies have reported inverse associations between vegetable and fruit consumption and lung cancer risk. The aim of the present study was to elucidate the role of several antioxidants and folate in this relationship. In the Netherlands Cohort Study on Diet and Cancer, 58,279 men of ages 55-69 years at baseline in 1986 returned a questionnaire including a 150-item food frequency questionnaire. After 6.3 years of follow-up, 939 male lung cancer cases were registered. A new Dutch carotenoid database was used to estimate intake of alpha-carotene, beta-carotene, lutein + zeaxanthin, beta-cryptoxanthin, and lycopene, completed with the antioxidant vitamins C and E and folate. Using case-cohort analysis, rate ratios were calculated, adjusted for age, smoking, educational level, and family history of lung cancer. Protective effects on lung cancer incidence were found for lutein + zeaxanthin, beta-cryptoxanthin, folate, and vitamin C. Other carotenoids (alpha-carotene, beta-carotene, and lycopene) and vitamin E did not show significant associations. After adjustment for vitamin C, only folate remained inversely associated, and after adjustment for folate, only beta-cryptoxanthin and vitamin C remained significantly associated. Inverse associations were strongest among current smokers and weaker for former smokers at baseline. Inverse associations with carotenes, lutein + zeaxanthin, and beta-cryptoxanthin seemed to be limited to small cell and squamous cell carcinomas. Only folate and vitamin C intake appeared to be inversely related to small cell and squamous cell carcinomas and adenocarcinomas. Folate, vitamin C, and beta-cryptoxanthin might be better protective agents against lung cancer in smokers than alpha-carotene, beta-carotene, lutein + zeaxanthin, and lycopene.
Assuntos
Antioxidantes/farmacologia , Ácido Fólico/farmacologia , Neoplasias Pulmonares/prevenção & controle , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Dieta , Ácido Fólico/análogos & derivados , Humanos , Incidência , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fumar/efeitos adversosRESUMO
This article gives an overview of the current state of knowledge on the cancer preventive potential of carotenoids. Numerous retrospective and prospective epidemiological studies have shown that a high intake of carotenoid-rich fruits and vegetables is associated with a decreased risk of cancer at a number of common sites. For several other cancer sites, however, the epidemiological evidence is not very consistent. A number of mechanisms for the cancer preventive properties of carotenoids have been proposed. Conversion to retinol, possibly in posthepatic tissues, would allow an effect on cellular differentiation and proliferation, and on cell-to-cell communication. Antioxidant functions could prevent free radical-induced damage to cellular DNA and other macromolecules. Immunomodulatory effects could enhance immune surveillance in tumorigenesis. In addition, non-retinol-mediated effects of carotenoids on metabolism of carcinogens and cell-to-cell communication have been shown. Observational epidemiology cannot resolve whether associations are due to a specific carotenoid, or to an associated factor in fruits and vegetables, whereas interpretation of animal studies is hampered by uncertainties in extrapolation between species, more so because the metabolism of carotenoids in most animals differs notably from that in humans. Human intervention studies on biomarkers related to cancer risk and on cancer incidence are, therefore, necessary. Human intervention studies performed so far suggest that beta-carotene can affect carcinogenesis, though not at all stages and not at all cancer sites. Implications for future human intervention research are discussed.
Assuntos
Carotenoides/administração & dosagem , Dieta , Neoplasias/prevenção & controle , Transformação Celular Neoplásica , Feminino , Frutas , Humanos , Masculino , Estudos Prospectivos , Estudos Retrospectivos , VerdurasRESUMO
A high intake of trans fatty acids (TFAs) has been shown to have an undesirable effect on serum lipid profiles and lipoprotein(a) (Lpa)) levels and may thereby increase the risk for coronary heart disease (CHD). We performed a study in CHD patients, and measured the TFA concentration of the plasma phospholipid fraction. Comparison was made between a case group with angiographically documented severe CHD (> 80% stenosis in one coronary vessel, n = 83) and a control group of patients who had just minor stenosis on the coronary angiography (< 50% stenosis in all three major vessels, n = 78): All subjects were under 68 years of age and were prestratified on age, gender and smoking habits. The two groups were comparable according to the prestratification criteria, body mass index, blood pressure, number of cigarettes smoked and total fat intake. Controls had higher plasma HDL levels (P < 0.001) and lower, albeit not significantly lower, (P = 0.07) plasma LDL levels. No significant correlations were found between percentages of TFAs in plasma phospholipids and plasma LDL or HDL cholesterol levels. Of the major fatty acid classes, only the percentage of saturated fatty acids was significantly higher in cases (46.2 +/- 0.92%) than in controls (45.8 +/- 1.07% (means +/- S.D.)). The difference in total TFA content between cases and controls (0.32 +/- 0.02% versus 0.35 +/- 0.02%) was -0.03% (P = 0.2). For the specific TFAs C16:1n-7tr, C18:1n-9tr and C18: 2n-6tr, just minor differences were found. Adjusted odds ratios for tertiles of TFA percentages were 0.56 (0.25-1.23) and 0.76 (0.36-1.61) for the highest middle tertile compared to the lowest. These findings do not support an association between TFA intake and risk for coronary heart disease.
Assuntos
Doença das Coronárias/sangue , Ácidos Graxos Insaturados/sangue , Fosfolipídeos/química , Idoso , Estudos de Casos e Controles , Angiografia Coronária , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/epidemiologia , Gorduras na Dieta/efeitos adversos , Ácidos Graxos Insaturados/efeitos adversos , Comportamento Alimentar , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Análise Multivariada , Fosfolipídeos/sangue , Fatores de Risco , Fumar/epidemiologiaRESUMO
To evaluate the antioxidant hypothesis with regard to atherosclerosis, we compared plasma selenium, serum alpha-tocopherol, serum polyunsaturated fatty acids (PUFA), and the ratios of selenium and alpha-tocopherol to PUFAs in subjects with varying degrees of coronary atherosclerosis. Cases had more than 85% stenosis in at least one coronary vessel and controls had less than 50% stenosis in all three vessels. Plasma selenium was significantly lower in cases than controls (95.1 +/- 21.0 micrograms/l and 108.8 +/- 29.3 micrograms/l, respectively). Though alpha-tocopherol and PUFA levels were similar in both groups, the ratios Se/linoleic acid, Se/total PUFA and Se/total n-6 acids were significantly lower in cases. In particular, these differences were observed in subjects with low serum alpha-tocopherol level (below the median; 1452 micrograms/dl). Moreover, in this subgroup the ratio Se/PUFA was significantly lower in cases than in controls for all PUFAs except eicosapentaenoic and docosahexaenoic acid. Though definitive conclusions cannot be drawn from our data, it is hypothesized that high PUFA levels, when insufficiently protected by antioxidants against peroxidation, may indicate a higher risk of atherosclerosis.
Assuntos
Doença da Artéria Coronariana/sangue , Ácidos Graxos Insaturados/sangue , Oxigênio/metabolismo , Selênio/sangue , Vitamina E/sangue , Doença da Artéria Coronariana/metabolismo , Feminino , Sequestradores de Radicais Livres , Humanos , Peroxidação de Lipídeos , Masculino , Pessoa de Meia-IdadeRESUMO
Autoantibodies against oxidized low-density lipoprotein (LDL) have been reported to be associated with atherosclerosis. However, data are not consistent. We compared the titres of autoantibodies to malondialdehyde-modified LDL in three groups, a case group with angiographically documented severe coronary stenosis (> 80% stenosis in at least 1 vessel, n = 47), a hospital control group with minor stenosis on the coronary angiography (< 50% stenosis in all three major vessels, n = 47) and a healthy population control group with no history of coronary heart disease (n = 49). Age ranged from 26 to 68 years. Subjects were frequency-matched for gender distribution and storage time of the blood samples. No relevant differences in autoantibody titre between case and control groups were found. The mean autoantibody titres (+/- S.D.) were 1.44 +/- 1.82, 1.46 +/- 1.40 and 1.62 +/- 1.95 for cases, hospital controls and population controls, respectively. No correlations were found between autoantibody titre and age, number of cigarettes smoked and LDL or total cholesterol. Autoantibody titres were correlated with body mass index (r = 0.2) and high-density lipoprotein (HDL) (r = -0.2). Odds ratios (OR) were calculated by tertiles of autoantibody titres for the hospital control group and the population control group, respectively. Age-adjusted OR (95% confidence interval) for medium and high compared to low autoantibody titre were 0.76 (0.27-2.14) and 1.09 (0.39-2.95) for the comparison between cases and hospital controls and 1.09 (0.39-3.07) and 0.90 (0.32-2.56) for the comparison between cases and population controls. Adjustment for gender, body mass index, smoking habits and HDL yielded essentially the same results. This study does not support an association between autoantibody titres to oxidized LDL and the extent of coronary stenosis.
Assuntos
Autoanticorpos/análise , Doença da Artéria Coronariana/imunologia , Lipoproteínas LDL/imunologia , Malondialdeído/imunologia , Adulto , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Angiografia Coronária , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lipoproteínas LDL/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Oxirredução , Distribuição Aleatória , Análise de Regressão , Fatores de RiscoRESUMO
BACKGROUND: Flow mediated dilatation (FMD) of the brachial artery and soluble intercellular adhesion molecule 1 (sICAM-1) are measures of distinct functions of the endothelium, reflecting nitric oxide (NO)-mediated and pro-inflammatory status, respectively. The comparative value of the two measures in relation to cardiovascular risk is unknown. OBJECTIVE: To study and quantify the relation between these two measures, and their relative value in relation to the risk of coronary heart disease as estimated by the Framingham risk function. METHODS: We performed a single centre population-based study of 85 men and 81 women, aged 18-73 years. Endothelial function was assessed biochemically by sICAM-1 and functionally by FMD. In addition traditional cardiovascular risk factors, CRP, leukocyte count, homocysteine and fibrinogen were determined. Analyses were performed with multivariate linear regression, adjusted for age, gender, and CRP. RESULTS: Median sICAM-1 levels were 217.0 microg/l (interquartile range: 174.0-348.5). Mean FMD was 4.5% (S.D.: 3.9). The regression coefficient for the association between sICAM-1 and FMD was -3.3 microg/l (95% CI: -6.0;-0.6) per percentage rise in FMD, after adjustment for age, gender, smoking, oral contraceptives (OC) use, classical risk factors and CRP. After adjustment for CRP and sICAM-1, the estimated risk of coronary heart disease in the next 10 years varied from 1.55% (95%CI: 0.89; 2.70) in the highest quintile of FMD to 3.92% (95% CI: 2.23; 6.92) in the lowest quintile. For sICAM-1, estimated risk, adjusted for FMD and CRP varied from 1.50% (95%CI: 0.85; 2.64) in the lowest quintile of sICAM-1 to 4.15% (95%CI: 2.35; 7.34) in the highest quintile. P-values for trends were 0.02 and 0.01 for quintiles of FMD and quintiles of sICAM-1, respectively. CONCLUSION: These findings indicate that sICAM-1 and FMD are related in healthy individuals, independently of cardiovascular risk factors and CRP, and that they are both related to the estimated risk of coronary heart disease, independently of each other.
Assuntos
Circulação Coronária/fisiologia , Doença das Coronárias/sangue , Doença das Coronárias/fisiopatologia , Molécula 1 de Adesão Intercelular/sangue , Vasodilatação/fisiologia , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Pressão Sanguínea/fisiologia , Proteína C-Reativa/metabolismo , LDL-Colesterol/sangue , Doença das Coronárias/epidemiologia , Diástole/fisiologia , Dilatação Patológica/sangue , Dilatação Patológica/epidemiologia , Dilatação Patológica/fisiopatologia , Feminino , Fibrinogênio/metabolismo , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Fatores de Risco , Fatores Sexuais , Fumar/sangue , Fumar/epidemiologia , Fumar/fisiopatologia , Solubilidade , Estatística como Assunto , Sístole/fisiologia , Triglicerídeos/sangueRESUMO
The prospect that high intake of certain vitamins may confer protection against cancer has drawn substantial attention during the last decades. This paper gives a concise update of the role of a number of promising vitamins in prevention of cancer. Vitamin A and its analogues have an important role in cellular processes related to carcinogenesis. However, blood vitamin A levels are under strict control and a high intake of preformed vitamin A does not seem to be relevant for cancer prevention. The antioxidant vitamins C and E and beta-carotene may also have other biological activities than free radical trapping that relate to their cancer preventive properties. Mechanisms include immune stimulation, inhibition of nitrosamine formation, enhancement of cell communication and an influence on metabolic activation of carcinogens. Epidemiological data for the antioxidant vitamins are promising, but cannot rule out that another factor or combination of factors in fruits and vegetables might be responsible for a protective effect. The B vitamin folic acid is one of these potential factors that is currently thought to have an influence on DNA methylation and thus on proto-oncogene expression. Folic acid seems to be promising and deserves further study. Vitamin D might be relevant in colon cancer development due to its close links with calcium metabolism that might influence cell proliferation. Overall, results are promising, but the first human intervention trials on (antioxidant) vitamins and human cancer have yielded somewhat disappointing results. At this moment the data seem insufficient to make recommendations for vitamin supplementation to prevent cancer. The results are certainly in line with the advice that a diet rich in fruits and vegetables will help reduce cancer risk.
Assuntos
Neoplasias/epidemiologia , Neoplasias/prevenção & controle , Vitaminas/farmacologia , Vitaminas/uso terapêutico , Antioxidantes/uso terapêutico , Ácido Ascórbico/uso terapêutico , Feminino , Ácido Fólico/uso terapêutico , Humanos , Masculino , Proto-Oncogene Mas , Selênio/uso terapêutico , Vitamina A/uso terapêutico , Vitamina E/uso terapêutico , beta Caroteno/uso terapêuticoRESUMO
The effect of consumption of Brussels sprouts on the excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) into human urine was investigated. Ten non-smoking volunteers (five males and five females) were randomly assigned to two groups. Five volunteers started on a diet of 300 g of glucosinolate-free vegetables whereas the other five consumed 300 g of Brussels sprouts per day. After 1 week dietary regimes were reversed. Levels of 8-oxodG in 24-h urine samples were measured by high-performance liquid chromatography. In four of five males a reduction in 8-oxodG was found, whereas in the fifth male the 8-oxodG excretion was high in the control period and was even much higher in the sprouts period. In females no effect of consumption of Brussels sprouts on excretion of 8-oxodG was found. Our previous and present findings support the results of epidemiologic studies that consumption of brassica vegetables may diminish cancer risk.
Assuntos
Dano ao DNA , Desoxiguanosina/análogos & derivados , Dieta , Verduras , 8-Hidroxi-2'-Desoxiguanosina , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Desoxiguanosina/urina , Feminino , Humanos , Masculino , Oxirredução , Fatores SexuaisRESUMO
The effect of consumption of glucosinolate-containing Brussels sprouts on flavin-containing monooxygenase functional activity in humans was investigated in 10 healthy, male, non-smoking volunteers. After a 3-week run-in period, 5 volunteers continued on a glucosinolate-free diet for 3 weeks (control group), and 5 others consumed 300 g of cooked Brussels sprouts per day (sprouts group). Human flavin-containing monooxygenase activity was measured by determining the levels of urinary trimethylamine and trimethylamine N-oxide. In the control group similar trimethylamine to trimethylamine N-oxide ratios were observed, while in the sprouts group the trimethylamine to trimethylamine N-oxide ratios were increased 2.6- to 3.2-fold, and thus flavin-containing monooxygenase functional activity was decreased significantly. To investigate the molecular basis for the in vivo inhibition of functional human flavin-containing monooxygenase activity, in vitro studies were carried out examining the effect of acid condensation products of indole-3-carbinol, anticipated to be formed after transit of Brussels sprouts through the gastrointestinal system, on the prominent cDNA-expressed human flavin-containing monooxygenase form 3 enzymes. Two indole-containing materials were observed to be potent inhibitors of human flavin-containing monooxygenases, having Ki values in the low micromolar range. The results suggested that acid condensation products expected to be formed upon transit of Brussels sprouts materials through the gastrointestinal system were potent competitive inhibitors of human flavin-containing monooxygenase form 3 enzymes. The findings indicate that daily intake of Brussels sprouts may lead to a decrease in human flavin-containing monooxygenase activity, and this may have consequences for metabolism of other xenobiotics or dietary constituents.
Assuntos
Brassica/química , Indóis/farmacologia , Oxigenases/antagonistas & inibidores , Adulto , Antioxidantes/farmacologia , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/metabolismo , Estudos Cross-Over , Dieta , Humanos , Indóis/metabolismo , Masculino , Proteínas Ligantes de Maltose , Metilaminas/urina , Oxigenases/metabolismoRESUMO
This review summarizes the scientific evidence for a possible role of antioxidants in the prevention of coronary heart disease (CHD). Dietary antioxidants include vitamin E, vitamin C and beta-carotene, whereas selenium is an integral part of the antioxidant enzyme glutathione peroxidase. Experimental studies suggest that the oxidation of low-density lipoproteins (LDL) in the vessel wall plays an important role in the development of atherosclerotic lesions. The resistance of LDL to oxidation is increased by antioxidant supplementation, at least in vitro. Epidemiological studies have not demonstrated unequivocally that a high intake of antioxidants leads to a decreased risk of CHD. Studies on dietary intake and serum levels of antioxidants do point in the direction of a preventive effect of antioxidants, whereas the results of intervention studies are less conclusive. Beta-carotene supplementation is not associated with any decrease in CHD; high doses of vitamin E may be beneficial, but results from large trials are to be awaited. General preventive measures based on antioxidant supplementation are not yet justifiable.
Assuntos
Antioxidantes/farmacologia , Doença das Coronárias/prevenção & controle , Lipoproteínas LDL/química , Lipoproteínas LDL/metabolismo , Animais , Ácido Ascórbico/farmacologia , Doenças Cardiovasculares/dietoterapia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Doença das Coronárias/epidemiologia , Doença das Coronárias/mortalidade , Dieta , Feminino , Radicais Livres/química , Humanos , Lipoproteínas LDL/efeitos dos fármacos , Masculino , Oxirredução/efeitos dos fármacos , Estudos Prospectivos , Fatores de Risco , Selênio/farmacologia , Vitamina E/farmacologia , beta Caroteno/farmacologiaRESUMO
The use of biomarkers is a promising approach to the study of human cancer risk. Bronchial metaplasia in sputum cytology may be a marker for potential premalignancy that can be used for population studies. We recently performed a randomized, controlled trial in smokers on the effect of 14 weeks beta-carotene (20mg/day) on markers for DNA damage. We now have evaluated the application of sputum cytology in this study and performed a preliminary evaluation of the effect of beta-carotene. Of the 150 potential participants in this trial 75 were not eligible because they failed to produce sputum samples (n = 29), or because samples were unsatisfactory (n = 46). The eligible group was older (41 vs 37 years) and had smoked longer (23 vs 19 years), but had similar cigarette consumption (mean 21/day) and plasma cotinine levels. Metaplasia was graded in seven categories. Only 11 subjects (15%) showed minor or mild atypia on study entry. Agreement within and between observers was 95% within the same or an adjacent category. We observed no significant correlation between before and after treatment final metaplasia scores in either the beta-carotene (Spearman R = 0.18, P = 0.3) or placebo group (Spearman R = 0.17, P = 0.3). Initial metaplasia scores were somewhat higher in the beta-carotene group (n = 33) than in the placebo group (n = 42) (P = 0.06). Final metaplasia scores were similar in both groups (P = 0.69), and there was no decrease in metaplasia scores in the beta-carotene group (P = 0.75). This study indicates that sputum cytology may not yet be a readily applicable marker in studies of a healthy asymptomatic population, because many smokers do not spontaneously produce sputum, more severe lesions are rare, and variation over time in the minor lesions in large. Therefore, the preliminary evidence that beta-carotene has no influence should be interpreted with care.
Assuntos
Dano ao DNA , Neoplasias Pulmonares/patologia , Fumar/efeitos adversos , Escarro/citologia , beta Caroteno/farmacologia , Adulto , Biomarcadores/sangue , Método Duplo-Cego , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/prevenção & controle , Masculino , Metaplasia , Pessoa de Meia-Idade , Estatísticas não Paramétricas , beta Caroteno/uso terapêuticoRESUMO
Evidence has accumulated for oxidative modification of low-density lipoproteins (LDL) to play an important role in the atherogenic process. Therefore, we investigated the relation between susceptibility of LDL to oxidation and risk of peripheral atherosclerosis among 249 men between 45 and 80 years of age. The ankle-arm index was calculated for both legs as the ratio of systolic blood pressure in the leg divided by the arm systolic blood pressure. The lowest of both ankle-arm indices was used to categorize subjects. Thirty-nine men with an ankle-arm index < 1.00 (20% cut-off point of distribution) were classified as subjects with peripheral atherosclerosis. Subjects with peripheral atherosclerosis reported more often the use of a special diet and the use of antihypertensive medication, aspirin and coumarin derivatives. No significant differences in total, LDL and HDL cholesterol and triglycerides were present between groups. Resistance time and maximum rate of oxidation were measured ex vivo using copper-induced LDL oxidation. Subjects with peripheral atherosclerosis had a significantly lower resistance time, whereas the maximum rate of oxidation tended to be increased in subjects with peripheral atherosclerosis. Odds ratios (ORs, and 95% confidence interval) for the successive tertiles of resistance time were 1.00 (reference), 0.37 (0.15-0.89) and 0.37 (0.16-0.86) (p(trend) < 0.01). ORs for the successive tertiles of maximum rate of oxidation were 1.00 (reference), 1.34 (0.47-3.82) and 1.50 (0.55-4.15). This inverse association was borderline significant (p(trend) = 0.07). These results support an association between LDL oxidation and the development of peripheral atherosclerosis.
Assuntos
Arteriosclerose/sangue , Peroxidação de Lipídeos , Lipoproteínas LDL/metabolismo , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Arteriosclerose/terapia , Aspirina/uso terapêutico , Colesterol na Dieta/administração & dosagem , Cumarínicos/uso terapêutico , Dieta com Restrição de Gorduras , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de RiscoRESUMO
Coenzyme Q10 (CoQ10) is an important mitochondrial electron transfer component and has been postulated to function as a powerful antioxidant protecting LDL from oxidative damage. It could thus reduce the risk of cardiovascular disease. Thus far, beneficial effects of supplementation with CoQ10 have been reported. To study the relation between unsupplemented concentrations of plasma CoQ10 and coronary atherosclerosis, we performed a case-control study among 71 male cases with angiographically documented severe coronary atherosclerosis and 69 healthy male controls free from symptomatic cardiovascular disease and without atherosclerotic plaques in the carotid artery. Plasma CoQ10 concentrations (mean +/- SE) were 0.86+/-0.04 vs. 0.83+/-0.04 micromol/l for cases and controls, respectively. The CoQ10/LDL-cholesterol ratio (micromol/ mmol) was slightly lower in cases than in controls (0.22+/-0.01 vs. 0.26+/-0.03). Differences in CoQ10 concentrations and CoQ10/LDL-cholesterol ratio did not reach significance. The odds ratios (95% confidence interval) for the risk of coronary atherosclerosis calculated per micromol/l increase of CoQ10 was 1.12 (0.28-4.43) after adjustment for age, smoking habits, total cholesterol and diastolic blood pressure. We conclude that an unsupplemented plasma CoQ10 concentration is not related to risk of coronary atherosclerosis.