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The structure of [(tBu)2Al(3,5-Me2py)]2(μ-O) has been determined as a consequence of the preferential hydrolytic cleavage of an Al–O versus an Al–C bond from the hydrolysis of the quinone bridged compound, [(tBu)2Al(3,5-Me2py)]2(μ-OC6H4O). The Al–O distance is 1.710(1) A and the Al–O–Al angle is 180° because of crystallographic symmetry. Crystal data: triclinic, P\(\overline 1\), a = 9.334(2) A, b = 10.639(2) A, c = 10.661(2) A, α = 112.65(3)°, β = 93.84(3)°, γ = 115.84(3)°, V = 843.4(3) A3, Z = 1, R = 0.0581, Rw = 0.1674.

To evaluate the effect of fruit and vegetables consumption on markers of risk for cardiovascular disease.Randomised, diet controlled, parallel study.Forty-eight apparently healthy (40--60 y) volunteers with a low usual consumption of fruit and vegetables. Forty-seven of them completed the study.During 4 weeks 24 volunteers consumed a standardised meal, consisting of 500 g/day fruit and vegetables and 200 ml/day fruit juice ('high' group) and 23 volunteers consumed 100 g/day fruit and vegetables ('low' group) with an energy and fat controlled diet.Final total cholesterol was 0.2 (95% CI -0.5--0.03) mmol/l lower in the high group than in the low group (P0.05). Final fibrinogen and systolic blood pressure were 0.1 (-0.1--0.4) g/l and 2.8 (-2.6--8.1) mmHg higher in the high group than in the low group (P0.05), respectively. Also, other final serum lipid concentrations, diastolic blood pressure and other haemostatic factors did not differ between both groups.This was a small randomised well-controlled dietary intervention trial of short duration with a considerable contrast in fruit and vegetable consumption. No effects on serum lipids, blood pressure and haemostatic variables were observed.

Objective: The purpose was to study the association between vegetable and fruit consumption and lung cancer incidence using 1074 cases after 6.3 years of follow-up in the Netherlands Cohort Study. Methods: Dietary intake was assessed using a 150-item food-frequency questionnaire. Multivariate models were used including age, sex, family history of lung cancer, highest educational level attained, and smoking history. Results: Statistically significant inverse associations were found with total vegetables and most vegetable groups. Rate ratios (RRs) based on consumption frequency showed the strongest effect of vegetables from the Brassica group (RR 0.5, 95% confidence interval (95% CI) 0.3-0.9, for consumption ≥ 3 times per week versus ≤ once a month). RR of highest versus lowest quintile of total vegetable consumption was 0.7 (95% CI 0.5-1.0, p-trend 0.001). Statistically significant inverse associations were found for all fruits listed in the questionnaire. RRs for quintiles of total fruit intake were 1.0, 0.7, 0.6, 0.6 and 0.8 respectively (p-trend < 0.0001). Protective effects of fruits and vegetables were stronger in current than in former smokers, and weaker for adenocarcinomas than for other types of tumors. Conclusions: Inverse associations with lung cancer are found for both vegetable and fruit intake, but no specific type of vegetable or fruit seems to be particularly responsible.

The relation between vegetable and fruit consumption and colorectal cancer risk was comprehensively assessed in the Netherlands Cohort Study on Diet and Cancer using a validated 150-item food frequency questionnaire. After 6.3 years of follow-up (1986-1992), over 1,000 incident cases of colorectal cancer were registered. Using case-cohort analysis, the authors calculated rate ratios and 95% confidence intervals adjusted for age, alcohol intake, and family history of colorectal cancer. For colon cancer, no statistically significant associations with total vegetable intake or total fruit intake were found. However, among women, an inverse association was observed with vegetables and fruits combined (for the highest quintile vs. the lowest, the rate ratio was 0.66 (95% confidence interval: 0.44, 1.01)). Brassica vegetables and cooked leafy vegetables showed inverse associations for both men and women. Among women and, to a lesser extent, among men, inverse associations were stronger for distal colonic tumors than for proximal colonic tumors. For rectal cancer, no statistically significant associations were found for vegetable consumption or fruit consumption or for specific groups of vegetables and fruits; only Brassica vegetables showed a positive association in women. As in other cohort studies, the observed inverse relation between vegetable and fruit consumption and occurrence of colorectal cancer was less strong than relations reported in case-control studies.

The fatty acid composition of dietary fats and oils from 14 European countries was analyzed with particular emphasis on isomerictransfatty acids. The proportion oftransfatty acids in typical soft margarines and low-fat spreads ranged between 0.1 and 17% of total fatty acids and that ofcis-unsaturated fatty acids between 55 and 81%. Hard household margarines and industrial fats for cooking and baking (shortenings) had slightly higher proportions oftransfatty acids and highest amounts, up to 50%, were found in fats for deep frying. Vegetable oils contained only small amounts oftransfatty acids, usually less than 1%. Isomers of C18:1 comprised up to 94% of thetransfatty acids in hardened vegetable oils and 52-68% in butter, whereas hardened fish oils showed a more even distribution oftransmonoenoic fatty acids between C16:1 and C22:1, and C18:1 isomers contributed by 28-42% to totaltransfatty acids. Fat spreads with very low content (

In the TRANSFAIR study, foods contributing to 95% of total fat intake were collected in 14 European countries. In addition to edible fats, dairy, meat, and bakery products some specific food items with relatively high amounts oftransfatty acids were found. French fried potatoes, both those from fast-food restaurants and those from the supermarkets (including potato chips), contained mostly between 12 and 35%transfatty acid, but some products fried in animal fat or vegetable oil contained lower proportions between 0.5 and 7% total fatty acids. Deep-fried croquettes were also rich intransfatty acids. Microwave popcorn samples contained 27-34%transfatty acids. Ready-made popcorn was low intransfatty acids but generally contained even more saturated fatty acids. Dry soup and sauce mixes and cubes and high-fat, frosted breakfast cereals were other examples of foods that often contained >10%transfatty acids. It is concluded that any deep-fried product such as French fried potatoes may contain high proportions of isomerictransfatty acids. Processed foods with a long shelf life such as dry soup powders and cubes, savory snacks, and popcorn often contained relatively high proportions oftransfatty acids, although the contributions of these products to total fat intake are probably small. The foods and snacks with a high proportion oftransfatty acids usually contained less saturated fatty acids and morecis-unsaturated fatty acids than respective foods prepared with low-transsaturated vegetable fats or animal fats. © 1998 Academic Press.

The fatty acid composition of dairy products and meat from 14 European countries was analyzed with particular emphasis ontransfatty acids. In cow's milk, butter, and cheese the proportions oftransfatty acids ranged between 3.2 and 6.2% of fatty acids. C18:1 isomers comprised about 60% and C16:1 and C18:2 isomers about 15% each of totaltransfatty acids. Goat's and sheep's milk and cheese contained between 2.7 and 7.1%transfatty acids. Summer milk contained up to 57% moretransfatty acids, both C18:1 and C18:2 isomers, morecis-unsaturated and less saturated fatty acids than winter milk. Ice-cream with partially hydrogenated vegetable oils contained between 21 and 31%transfatty acids and low-transmodified-fat ice-cream between 0.2 and 0.9%. The high-transice-cream samples contained morecis-unsaturated and less saturated fatty acids than most dairy-fat and low-transproducts. Beef contained 2.8-9.5% and lamb meat 4.3-9.2%transfatty acids whereas pork (0.2-2.2%) and chicken (0.2-1.7%) and meat from other nonruminants were lower intransfatty acids. With very few exceptions, sausages contained pork and showed lowtransfatty acid levels. In conclusion, ruminant fats contained moderate amounts oftransfatty acids, mainly C18:1 isomers. There were considerable differences both between and within the countries, probably due to seasonal factors and differences in feeding practices and the age of the animals. © 1998 Academic Press.

One of the aims of the TRANSFAIR study is to provide reliable and comparable data ontransfatty acid (TFA) content of foods in Europe. We performed a market basket study in 14 European countries. In each country, a maximum of 100 food samples representative of the total fat intake were sampled according to a standardized stepwise approach. Samples were analyzed for fat content and fatty acid composition in one central laboratory. This paper describes the design of the market basket study and the analytical methods. Detailed results of separate food groups are presented in the following four separate papers. The current health concern on TFA seems to have resulted in a number of consumer products like soft margarines that are low in TFA. On the other hand, shortenings, frying fats, and convenience foods are frequently high in TFA. There may not be a health benefit if a reduction in TFA is achieved by a similar increase in saturated fatty acid. Moreover, health implications are dependent on overall consumption patterns and these will be studied in the second part of the TRANSFAIR study. © 1998 Academic Press.

The fatty acid composition of bakery products from 14 European countries was analyzed with particular emphasis ontransfatty acids. The proportion oftransfatty acids in cookies and biscuits ranged from

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.

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.

The mechanisms by which brassica vegetables might decrease the risk of cancer are reviewed in this paper. Brassicas, including all types of cabbages, broccoli, cauliflower and Brussels sprouts, may be protective against cancer due to their relatively high glucosinolate content. Glucosinolates are usually broken down through hydrolysis catalyzed by myrosinase, an enzyme that is released from damaged plant cells. Some of the hydrolysis products, viz. indoles and isothiocyanates, are able to influence phase 1 and phase 2 biotransformation enzyme activities, thereby possibly influencing several processes related to chemical carcinogenesis, e.g. the metabolism, DNA-binding and mutagenic activity of promutagens. A reducing effect on tumor formation has been shown in rats and mice. The anticarcinogenic action of isothiocyanates and indoles depends upon many factors, such as the test system, the target tissue, the type of carcinogen challenge and the anticarcinogenic compound, their dosage, as well as the timing of the treatment. Most evidence concerning anticarcinogenic effects of glucosinolate hydrolysis products and brassica vegetables has come from studies in animals. Animal studies are invaluable in identifying and testing potential anticarcinogens. In addition, studies carried out in humans using high but still realistic human consumption levels of indoles and brassica vegetables have shown putative positive effects on health.

Several in vitro and in vivo experiments have implicated oxysterols in the aetiology and progression of atherosclerosis. Oxysterols may be formed endogenously by oxidation of cholesterol and thus may form a marker of LDL oxidation. They may also be obtained exogenously through dietary intake. We investigated the association of oxysterols with the degree of coronary stenosis in patients undergoing coronary angiography. Cases with severe coronary atherosclerosis 80 stenosis in one of the major coronary vessels, n =80 were compared with controls with no or minor stenosis 50 stenosis in all three major coronary vessels, n =79 . Cases and controls were prestratified on age, gender and smoking habits. Evaluated were plasma levels of unesterified 7 hydroxycholesterol, 7 hydroxycholesterol, 25 hydroxycholesterol, 7 ketocholesterol, cholestane triol and 5,6 epoxycholestanol. 7 Hydroxycholesterol made up 67 of the total amount of plasma oxysterol concentration and was the only one significantly higher in cases 1.53 mu g per 100 ml vs 1.27 mu g per 100 ml, p 0.05 . Further, cases had somewhat higher LDL cholesterol levels and significantly lower HDL cholesterol levels than controls. After multivariate adjustment to account for this difference in lipid levels and for the prestratification factors the mean difference between cases and controls for 7 hydroxycholesterol 0.14 mu g per 100 ml was no longer significant. Also the other oxysterols showed no significant association with the degree of coronary stenosis. Multiple logistic regression analyses showed an adjusted odds ratio of 1.07 95 CI, 0.45-2.59 in the highest tertile of total plasma oxysterol level. We conclude, that this study does not support the hypothesis that plasma oxysterols form an additional risk factor for coronary atherosclerosis.

A high intake of glucosinolate-containing cruciferous vegetables, such as Brussels sprouts (Brassica oleraceae), has been linked to a decreased cancer risk, but the underlying mechanism is still unclear. The aim of this study was to reveal possible modulating effects of consumption of Brussels sprouts on duodenal, rectal and lymphocytic (i) glutathione S-transferase (GST) enzyme activity, (ii) GST isozyme levels and (iii) glutathione (GSH) content. Ten healthy non-smoking volunteers were randomly assigned to two groups in a cross-over design. Five persons started on a glucosinolate-free diet (control period), while the other five consumed 300 g/day cooked Brussels sprouts, at the expense of 300 g glucosinolate-free vegetables (sprouts period). After 7 days the regimen was changed for a further week. At the end of both periods blood samples and duodenal and rectal biopsies were taken. Mean GST activity showed marked differences between duodenal, rectal and lymphocytic cytosols (737 +/- 54, 321 +/- 29 and 154 +/- 14 nmol/min/mg protein respectively), but was uninfluenced by the dietary regimen. Isozyme distribution varied greatly between the tissues. In duodenum GST-alpha, -pi, and -mu isozymes were expressed in considerable amounts (8441 +/- 1365, 3002 +/- 223 and 536 +/- 248 ng/mg protein respectively). Rectal biopsies also contained above three GST classes, but here GST-pi was the most pronounced expressed isozyme (2849 +/- 246) followed by GST-mu (495 +/- 242), while GST-alpha was only present in minor quantities (149 +/- 31). In lymphocytes only GST-pi (755 +/- 96) and GST-mu (83 +/- 54) could be detected. As a result of the dietary regimen rectal GST-alpha and -pi levels were slightly increased at the end of the sprouts period, by 30 and 15% respectively. GSH contents were uninfluenced by the dietary regimen. In conclusion, consumption of glucosinolate-containing Brussels sprouts for 1 week results in increased rectal GST-alpha and -pi isozyme levels. We hypothesize that these enhanced detoxification enzyme levels may partly explain the epidemiological association between a high intake of glucosinolates (cruciferous vegetables) and a decreased risk of colorectal cancer.

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.

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.

Epidemiologic studies have demonstrated an inverse relation between vitamin A intake and lung cancer rate. There is strong evidence that the provitamin A, β-carotene, plays a more important role in the protective effect than vitamin A itself. The anticarcinogenic properties of β-carotene have so far been attributed to its scavenger properties in deactivating or trapping reactive chemical species such as singlet oxygen and certain organic free radicals. Smoking results in increased excretion of detoxification products of electrophilic agents (mercapturic acids) in urine. Since reactive electrophilic intermediates are involved in carcinogenesis, we performed a double-blind, placebo-controlled intervention trial to investigate whether the intake of β-carotene by smokers would affect urinary thioether excretion. Before the intervention the β-carotene group (n = 62) and the placebo group (n = 61) had similar thioether excretion levels in urine (4.2 vs 4.3mmolSH/molcreatinine). During the intervention (20 mg β-carotene daily for 14 weeks) the placebo group showed a 12% increase, whereas the β-carotene group showed a 5% decrease (P=0.004). After the intervention the β-carotene group had a 15% lower thioether excretion level than the placebo group (4.1 vs 4.7 mmol SH/mol creatinine; P=0.0017). Our study shows that urinary thioether excretion varies considerably over time, and that smokers have a decreased excretion of thioethers in urine after the use of β-carotene. This latter observation suggests a role of β-carotene in the detoxification of tobacco smoke constituents. Our observations warrant further studies on the involvement of β-carotene in the generation and detoxification of electrophilic intermediates.

The putative cancer-preventive potential of beta-carotene may be explained by its anti-oxidant capacity to prevent free-radical-induced DNA damage. To evaluate this hypothesis, we studied the effect of 14 weeks of beta-carotene supplementation on the frequency of sister chromatid exchanges (SCE) in lymphocytes in 143 heavy smokers in a randomized, double-blind, placebo-controlled intervention trial. Age, smoking habits and pretreatment blood levels of cotinine, beta-carotene, retinol and vitamins C and E were similar in the placebo group (n = 73) and the treatment group (n = 70). Plasma beta-carotene levels increased 13-fold in the treatment group during intervention, whereas the other parameters remained stable in both groups. Initial SCE levels were similar in the treatment and placebo groups (5.10 +/- 0.98 vs. 5.00 +/- 0.99 SCE/lymphocyte). During the intervention, both groups showed an almost identical decrease, and at the end of the intervention period there was no difference in SCE levels between the treatment and the placebo groups (4.37 +/- 0.38 vs. 4.24 +/- 0.37 SCE/lymphocyte). This study shows no protective effect of beta-carotene on DNA damage as reflected by sister chromatid exchanges in lymphocytes. Our results thus do not yield support for a cancer-preventive mechanism of beta-carotene involving this form of DNA damage. It cannot be excluded, however, that beta-carotene prevents other forms of smoking-induced DNA damage, affects other tissues, or is preventive in later stages of carcinogenesis.

Several lines of evidence suggest that oxidatively modified low density lipoprotein (LDL) is atherogenic and that antioxidants may protect LDL against oxidation. In addition, cigarette smoking is known to induce oxidant stress. We have examined the effect of ingestion of the antioxidants D,L-alpha-tocopherol (vitamin E) and beta-carotene and of smoking on the resistance of LDL against copper-mediated oxidation. Six healthy nonsmoking volunteers ingested 1,000 IU/day D,L-alpha-tocopherol acetate for 7 days. After vitamin E ingestion concentrations of alpha-tocopherol in plasma and LDL increased 3.0- and 2.4-fold, respectively. Simultaneously, the oxidation resistance of LDL was elevated significantly (+41%), and the rate of oxidation was decreased significantly (-19%). The increase in alpha-tocopherol content of LDL and the increase in resistance time were highly correlated (rs = 0.89, p = 0.014). Eight weeks after termination of the vitamin E intake, alpha-tocopherol concentrations in plasma and LDL and oxidation resistance of LDL had returned to baseline values. In smokers (n = 46), plasma levels of vitamin C (-26%) and concentrations of beta-carotene (-44%, -43%) and total carotenoids (-23%, -29%) in plasma and LDL, respectively, were significantly lower compared with nonsmokers (n = 23). No differences were found in alpha-tocopherol content of LDL and the susceptibility of LDL to lipid peroxidation in both groups. Supplementation of a group of smokers in a 14-week randomized, double-blind, placebo-controlled intervention trial with beta-carotene resulted in a 16.6- and 5.0-fold increase of LDL beta-carotene and total carotenoid content, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

To obtain more insight into the effect of moderate alcohol intake on vitamin B-6 status indicators, we studied the associations of alcohol intake (unadjusted and adjusted for intake of vitamin B-6 and protein) with the erythrocyte aspartate aminotransferase activation coefficient (EAST-AC) and plasma pyridoxal 5'-phosphate (PLP) level. Data obtained from men (n = 224) and women (n = 217) aged 65-79 (nationwide sample in the Netherlands) were used for this purpose. Although alcohol intake (a maximum of 21% of the energy came from alcohol) tended to be positively associated with PLP, this association never reached statistical significance (p greater than or equal to 0.05). EAST-AC was inversely associated with alcohol intake, whether or not it was adjusted for vitamin B-6 and protein intake. Similar results were found for the total EAST activity (after adding PLP) or apoenzyme activity; the basal EAST activity (before adding PLP) or holoenzyme activity was not associated with the alcohol intake. These results indicate that caution is needed in the interpretation of the specificity of EAST-AC (i.e., the degree to which EAST-AC is unaffected by other factors) as an indicator of vitamin B-6 intake.

The effects of consumption of glucosinolate-containing Brussels sprouts on plasma and urinary glutathione S-transferase (GST) class-alpha and -pi were investigated. Five male and five female non-smoking volunteers were randomly assigned to two groups in a crossover design. Five persons started on a glucosinolate-free diet (control period), while the other five consumed 300 g of cooked Brussels sprouts per day, at the expense of 300 g of glucosinolate-free vegetables (sprouts period). Dietary regimes were reversed after 1 week. GST levels were measured by enzyme-linked immunoabsorbent assay. At the end of the sprouts period, a significant increase (1.5-fold) in plasma class-alpha GST levels was observed in males but not in females (control versus sprouts, paired t-test; P-values 0.031 and 0.317 respectively), while plasma GST class-pi levels as well as secretion of urinary GST class-alpha and -pi levels remained unchanged. We conclude that (i) increased plasma GST class-alpha levels in males originate probably solely from the liver and not from stomach, intestine or kidney; (ii) males are more susceptible for induction of hepatic GSTs than females; and (iii) urinary GST concentration seems less useful as a biomarker for hepatic GST induction.

Background: Acute effects of UV irradiation include UV-induced erythema. Sunlight plays an important role in the development of skin cancer. Several predictive factors of UV-induced erythema could also be predictive for skin cancer. Objective: Our objective was to quantitatively assess phenotypical and nutritional determinants of sensitivity to UV irradiation, as assessed by the minimal erythema dose (MED). Design: We conducted a cross-sectional study among 335 volunteers. Sensitivity to UV irradiation was established through assessment of the MED. Phenotypical determinants, including skin melanin content, hair color and iris color were determined by skin reflectance spectrometry, a subjective questionnaire and an objective classification system, respectively. Furthermore, dietary exposure was measured by carotenoids, vitamin C, retinol and alpha-tocopherol in serum. Results: Male subjects were found to be more sensitive to UV irradiation; that is, the MED was significantly lower compared to female subjects. Skin melanin content, which was positively associated with iris color in both sexes and with hair color in men, was the main phenotypical determinant of sensitivity to UV irradiation. No associations were found between serum carotenoids and MED in the total study group. Vitamin C was inversely associated with MED. However, associations between carotenoids concentrations and MED showed a positive trend in subjects with melanin values above and a negative trend in subjects below the median after adjustment for gender and total cholesterol. Conclusions: Skin melanin content and gender are important determinants of sensitivity to UV irradiation. No relation was found between serum carotenoids and MED in the total study group. The inverse association between vitamin C and MED was against our hypothesis. For the modifying effect of melanin on the association between carotenoids and MED, we do not have a clear biological explanation.

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 μg/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 μg/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. © 2003 Elsevier Ireland Ltd. All rights reserved.

The effect of consumption of glucosinolate-containing Brussels sprouts on alpha-class glutathione S-transferase levels in human blood plasma was investigated in 10 healthy, male, non-smoking volunteers. Following a 3-week run-in period, five volunteers continued on a glucosinolate-free diet during a subsequent 3-week intervention period (control group), while the other five (sprouts group) consumed 300 g of cooked Brussels sprouts per day, at the expense of 300 g of a glucosinolate-free vegetable. alpha-Class glutathione S-transferases were measured by radioimmunoassay. In the control group, similar alpha-class glutathione S-transferase levels were observed in both periods (P = 0.814), while in the sprouts group the alpha-class glutathione S-transferase levels were elevated by a factor of 1.4 (P = 0.002). We hypothesize that the elevated alpha-class GST levels in plasma reflect GST-alpha induction in tissues such as liver and small intestine under non-toxic conditions. The present findings indicate that alpha-class GST levels in plasma may be used as a biomarker for alpha-class GST levels in tissues. In addition, they support the results of epidemiologic studies that consumption of cruciferous vegetables may result in a decreased cancer risk.

This paper first gives an overview of the epidemiological data concerning the cancer-preventive effect of brassica vegetables, including cabbages, kale, broccoli, Brussels sprouts, and cauliflower. A protective effect of brassicas against cancer may be plausible due to their relatively high content of glucosinolates. Certain hydrolysis products of glucosinolates have shown anticarcinogenic properties. The results of six cohort studies and 74 case-control studies on the association between brassica consumption and cancer risk are summarized. The cohort studies showed inverse associations between the consumption of brassica's and risk of lung cancer, stomach cancer, all cancers taken together. Of the case-control studies 64% showed an inverse association between consumption of one or more brassica vegetables and risk of cancer at various sites. 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. The mechanisms by which brassica vegetables might decrease the risk of cancer are reviewed in the second part of this paper. Brassicas, including all types of cabbages, broccoli, cauliflower, and Brussels sprouts, may be protective against cancer due to their glucosinolate content. Glucosinolates are usually broken down through hydrolysis catalysed by myrosinase, an enzyme that is released from damaged plant cells. Some of the hydrolysis products, viz. indoles, and isothiocyanates, are able to influence phase 1 and phase 2 biotransformation enzyme activities, thereby possibly influencing several processes related to chemical carcinogenesis, e.g. the metabolism, DNA-binding, and mutagenic activity of promutagens. Most evidence concerning anticarcinogenic effects of glucosinolate hydrolysis products and brassica vegetables has come from studies in animals. In addition, studies carried out in humans using high but still realistic human consumption levels of indoles and brassica vegetables have shown putative positive effects on health. The combination of epidemiological and experimental data provide suggestive evidence for a cancer preventive effect of a high intake of brassica vegetables.

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 μmol/l for cases and controls, respectively. The CoQ10/LDL-cholesterol ratio (μmol/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 μmol/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. Chemicals/CAS: ubidecarenone, 303-98-0; Antioxidants; Cholesterol, LDL; coenzyme Q10, 303-98-0; Ubiquinone, 1339-63-5

Observational epidemiologic studies have shown that a high consumption of fruits and vegetables is associated with a decreased risk of chronic diseases. Little is known about the bioavailability of constituents from vegetables and fruits and the effect of these constituents on markers for disease risk. Currently, the recommendation is to increase intake of a mix of fruits and vegetables ("five a day"). We investigated the effect of this recommendation on plasma carotenoids, vitamins and homocysteine concentrations in a 4-wk dietary controlled, parallel intervention study. Male and female volunteers (n = 47) were allocated randomly to either a daily 500-g fruit and vegetable ("high") diet or a 100-g fruit and vegetable ("low") diet. Analyzed total carotenoid, vitamin C and folate concentrations of the daily high diet were 13.3 mg, 173 mg and 228.1 microg, respectively. The daily low diet contained 2.9 mg carotenoids, 65 mg vitamin C and 131.1 microg folate. Differences in final plasma levels between the high and low group were as follows: lutein, 46% [95% confidence interval (CI) 28-64]; beta-cryptoxanthin, 128% (98-159); lycopene, 22% (8-37); alpha-carotene, 121% (94-149); beta-carotene, 45% (28-62); and vitamin C, 64% (51-77) (P0.05). The high group had an 11% (-18 to -4) lower final plasma homocysteine and a 15% (0.8-30) higher plasma folate concentration compared with the low group (P0.05). This is the first trial to show that a mix of fruits and vegetables, with a moderate folate content, decreases plasma homocysteine concentrations in humans.

This paper first gives an overview of the epidemiological data concerning the cancer-preventive effect of brassica vegetables, including cabbages, kale, broccoli, Brussels sprouts, and cauliflower. A protective effect of brassicas against cancer may be plausible due to their relatively high content of glucosinolates. Certain hydrolysis products of glucosinolates have shown anticarcinogenic properties. The results of six cohort studies and 74 case-control studies on the association between brassica consumption and cancer risk are summarized. The cohort studies showed inverse associations between the consumption of brassica's and risk of lung cancer, stomach cancer, all cancers taken together. Of the case-control studies 64% showed an inverse association between consumption of one or more brassica vegetables and risk of cancer at various sites. 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. The mechanisms by which brassica vegetables might decrease the risk of cancer are reviewed in the second part of this paper. Brassicas, including all types of cabbages, broccoli, cauliflower, and Brussels sprouts, may be protective against cancer due to their glucosinolate content. Glucosinolates are usually broken down through hydrolysis catalysed by myrosinase, an enzyme that is released from damaged plant cells. Some of the hydrolysis products, viz, indoles, and isothiocyanates, are able to influence phase 1 and phase 2 biotransformation enzyme activities, thereby possibly influencing several processes related to chemical carcinogenesis, e.g. the metabolism, DNA-binding, and mutagenic activity of promutagens. Most evidence concerning anticarcinogenic effects of glucosinolate hydrolysis products and brassica vegetables has come from studies in animals. In addition, studies carried out in humans using high but still realistic human consumption levels of indoles and brassica vegetables have shown putative positive effects on health. The combination of epidemiological and experimental data provide suggestive evidence for a cancer preventive effect of a high intake of brassica vegetables. Chemicals/CAS: Anticarcinogenic Agents

Objective: To assess the intake of trans fatty acids (TFA) and other fatty acids in 14 Western European countries. Design and subjects: A maximum of 100 foods per country were sampled and centrally analysed. Each country calculated the intake of individual trans and other fatty acids, clusters of fatty acids and total fat in adults and/or the total population using the best available national food consumption data set. Results: A wide variation was observed in the intake of total fat and (clusters) of fatty acids in absolute amounts. The variation in proportion of energy derived from total fat and from clusters of fatty acids was less. Only in Finland, Italy, Norway and Portugal total fat did provide on average less than 35% of energy intake. Saturated fatty acids (SFA) provided on average between 10% and 19% of total energy intake, with the lowest contribution in most Mediterranean countries. TFA intake ranged from 0.5% (Greece, Italy) to 2.1% (Iceland) of energy intake among men and from 0.8% (Greece) to 1.9% among women (Iceland) (1.2-6.7 g/d and 1.7-4.1 g/d, respectively). The TFA intake was lowest in Mediterranean countries (0.5 -0.8 en%) but was also below 1% of energy in Finland and Germany. Moderate intakes were seen in Belgium, The Netherlands, Norway and UK and highest intake in Iceland. Trans isomers of C(18:1) were the most TFA in the diet. Monounsaturated fatty acids contributed 9-12% of mean daily energy intake (except for Greece, nearly 18%) and polyunsaturated fatty acids 3-7%. Conclusion: The current intake of TFA in most Western European countries does not appear to be a reason for major concern. In several countries a considerable proportion of energy was derived from SFA. It would therefore be prudent to reduce intake of all cholesterol-raising fatty acids, TFA included. Sponsorship: Commission of the European Communities (AIR 2421); National Funds; European Industries supported the chemical analyses.

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 index1.00 (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.

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 K(i) 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. Copyright (C) 1999 Elsevier Science Inc.

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.

Toxicological risk assessment has long been based on animal experiments and in vitro studies. Apart from the question of whether or to what extent these data can be extrapolated to humans, many of these (animal) models are not suitable for studying the effects of the low doses to which humans are frequently exposed (Henderson et al., 1989). Moreover, these models do not account for the large individual variation in sensitivity among human beings. Because of the limitations inherent in both animal experiments and in vitro studies, as well as ethical issues connected with animal experiments, interest arose many years ago in exploring exposure, early health effects and variation in sensitivity in humans based on parameters that act as indicators of effects of various xenobiotic substances in the human body (‘biomarkers’) (Jenderson et al., 1989; Harris, 1989; Shields and Harris, 1991; Hulka et al., 1990). The term biomarker is used in a broad sense to describe parameters reflecting an interaction between a biological system and a potential hazard of a chemical, biological and physical nature. The measured response may be functional, physiological, and biochemical at a cellular or molecular level. Biomarkers are used to assess exposure and the risk of possible health-related outcomes of exposure in environmental epidemiology. The concept of ‘biomarker’ covers, as such, the continuum between external exposure and the clinical manifestation of a disease, such as cancer.

Nutrition is essential to support life, but at the same time it can paradoxically be considered the main cause of cancer. As concerns the latter, Doll and Peto (1981) estimated that in the USA the proportion of cancer deaths due to the diet was approximately 30%. Indeed, on the one hand, food contains a wide variety of mutagens and/or carcinogens, some of which occur naturally, and others that might be introduced during the preparation of food (Pariza et al., 1990; Wakabayashi et al., 1991), whereas, on the other hand, the human diet also contains a number of compounds that protect against cancer (Birt and Bresnick, 1991; Stich, 1991; Dragsted et al., 1993; Verhagen et al., 1993). This is in close agreement with epidemiological findings of negative associations between cancer and consumption of fibre-containing foods, fresh fruits, vegetables, vitamins and minerals (Archer, 1988; Birt and Bresnick, 1991; Steinmetz and Potter, 1991a,b). Many a compound of dietary origin has been claimed to have chemopreventive potential. Therefore chemoprevention of cancer is an area of great scientific, public and economic interest.

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.

Trans unsaturated fatty acids in plasma phospholipids and coronary heart disease: a case-control study.van de Vijver LP, van Poppel G, van Houwelingen A, Kruyssen DA, Hornstra G.Department of Epidemiology, TNO Nutrition and Food Research, Zeist, Netherlands. vandeVijver@Voeding.TNO.NLA 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.

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.

OBJECTIVE AND CONCLUSIONS: This article gives an overview of observational and experimental epidemiological studies relating beta-carotene to risk of cancer and cardiovascular disease. Observational epidemiological studies have consistently shown that a diet rich in beta-carotene-rich fruits and vegetables or high blood levels of beta-carotene are associated with a reduced risk of cancer at a number of common sites, such as lung and stomach. For other cancer sites, such as prostate and breast, the observational evidence is not very consistent or absent altogether. For cardiovascular disease, observational studies are less numerous but do point to a protective effect of high beta-carotene intake. The associations from observational epidemiology may indeed be ascribed to beta-carotene, since a number of plausible preventive mechanisms have been demonstrated for cancer as well as cardiovascular disease. However, observational epidemiology cannot resolve the question whether other constituents from fruits and vegetables or other factors may explain the findings from the case-control and cohort studies. The results of intervention studies undertaken so far are disappointing and do not indicate a preventive potential for beta-carotene. Further intervention trials with longer follow-up may be needed to elucidate whether beta-carotene is protective against certain forms of cancer and against cardiovascular disease.

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.

Consumption of black tea and cancer risk: a prospective cohort study.Goldbohm RA, Hertog MG, Brants HA, van Poppel G, van den Brandt PA.Department of Epidemiology, Netherlands Organization for Applied Scientific Research [TNO] Nutrition and Food Research Institute, Zeist, The Netherlands.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.

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.

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.

A high intake of beta-carotene has been associated with a decreased risk for cardiovascular disease. To evaluate whether beta-carotene may exert a protective effect through an impact on haemostasis a randomized, placebo-controlled trial was conducted in male smokers (n = 149) using 20 mg/day beta-carotene for 14 weeks. For comparisons, haemostatic indicators were also evaluated in a group of non-smokers (n = 54). Smokers compared with non-smokers had higher fibrinogen (3.5 vs. 3.1 mg/ml, P0.01), higher tissue-type plasminogen activator antigen (t-PA; 8.03 vs. 6.60 ng/ml, P0.05), lower levels of soluble fibrin (3.40 vs. 5.16 micrograms/ml, P0.01) and slightly higher plasma levels of total degradation products of fibrin and fibrinogen (TDP; 47.0 vs. 41.3 ng/ml, P = 0.21). Within the group of smokers, there were no initial differences in the four haemostatic indicators between the placebo (n = 77) and beta-carotene (n = 72) groups, and in both groups there was virtually no change in the indicators during the 14 weeks treatment. It is concluded that the different haemostatic profile in smokers may partly explain their increased risk for cardiovascular disease. beta-Carotene has no influence on the measured haemostatic indicators, and cardiovascular protection for beta-carotene via a beneficial effect on haemostasis seems improbable.