Nutrigenomics approach elucidates health-promoting effects of high vegetable intake in lean and obese men.

We aimed to explore whether vegetable consumption according to guidelines has beneficial health effects determined with classical biomarkers and nutrigenomics technologies. Fifteen lean (age 36 ± 7 years; BMI 23.4 ± 1.7 kg m(-2)) and 17 obese (age 40 ± 6 years; BMI 30.3 ± 2.4 kg m(-2)) men consumed 50- or 200-g vegetables for 4 weeks in a randomized, crossover trial. Afterward, all subjects underwent 4 weeks of energy restriction (60 % of normal energy intake). Despite the limited weight loss of 1.7 ± 2.4 kg for the lean and 2.1 ± 1.9 kg for the obese due to energy restriction, beneficial health effects were found, including lower total cholesterol, LDL cholesterol and HbA1c concentrations. The high vegetable intake resulted in increased levels of plasma amino acid metabolites, decreased levels of 9-HODE and prostaglandin D3 and decreased levels of ASAT and ALP compared to low vegetable intake. Adipose tissue gene expression changes in response to vegetable intake were identified, and sets of selected genes were submitted to network analysis. The network of inflammation genes illustrated a central role for NFkB in (adipose tissue) modulation of inflammation by increased vegetable intake, in lean as well as obese subjects. In obese subjects, high vegetable intake also resulted in changes related to energy metabolism, adhesion and inflammation. By inclusion of sensitive omics technologies and comparing the changes induced by high vegetable intake with changes induced by energy restriction, it has been shown that part of vegetables' health benefits are mediated by changes in energy metabolism, inflammatory processes and oxidative stress.

Short-term digestive tolerance of different doses of NUTRIOSE FB, a food dextrin, in adult men.

OBJECTIVE: To determine the tolerance of increasing dosages of an incompletely hydrolysed and/or incompletely absorbed food dextrin coming from wheat starch, NUTRIOSE FB, at daily levels of 10 and 15 g up to 60 and 80 g, respectively. DESIGN: A randomized, double-blind, multiple dose, placebo-controlled, combined crossover and parallel trial. SETTING: The metabolic ward of TNO Nutrition and Food Research. SUBJECTS: A total of 20 healthy men (age 31.7 +/- 9.1 y; BMI 24.5 +/- 2.9 kg/m2). INTERVENTION: One group of 10 subjects consumed on top of their diet 10, 30 and 60 g of NUTRIOSE FB or maltodextrin (placebo) daily. The other group of 10 subjects consumed 15, 45 and 80 g daily. Each dose was consumed for 7 days. RESULTS: Compared with placebo, flatulence occurred more frequently over the last 6 days on 30, 60 or 80 g/day of NUTRIOSE FB (P < 0.05). During the last 24 h, that is, days 6-7, of 60 and 80 g/day of NUTRIOSE FB, the frequency of flatulence was even higher (P < 0.05). During the last 24 h on a daily dose of 60 g NUTRIOSE FB, the frequency of defecation decreased (P < 0.05). Bloating occurred more often during the last 24 h on 80 g/day of NUTRIOSE FB (P < 0.05). None of the doses of NUTRIOSE FB resulted in diarrhoea. Compared to baseline levels, breath H2 excretion, which was only measured after a week with 10 and 15 g of NUTRIOSE FB daily, increased (P < 0.05). However, no difference in area under the curve was found. CONCLUSIONS: NUTRIOSE FB is a fermentable carbohydrate and is well tolerated up to a dose of 45 g daily. Higher daily dosages (60 and 80 g) may result in flatulence, but does not result in diarrhoea. SPONSORSHIP: TNO Nutrition and Food Research was assigned by Roquette Frères to perform the study.

Determinants of skin sensitivity to solar irradiation.

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.

Soluble intercellular adhesion molecule 1 and flow-mediated dilatation are related to the estimated risk of coronary heart disease independently from each other.

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.

Effects of sugar intake on body weight: a review.

Weight reduction programmes are mainly focused on reducing intake of fat and sugar. In this review we have evaluated whether the replacement of dietary (added) sugar by low-energy sweeteners or complex carbohydrates contributes to weight reduction. In two experimental studies, no short-term differences in weight loss were observed after use of aspartame as compared to sugar in obese subjects following a controlled energy-restricted diet. However, consumption of aspartame was associated with improved weight maintenance after a year. In two short-term studies in which energy intake was not restricted, substitution of sucrose by artificial sweeteners, investigated mostly in beverages, resulted in lower energy intake and lower body weight. Similarly, two short-term studies, comparing the effect of sucrose and starch on weight loss in obese subjects did not find differences when the total energy intake was equal and reduced. An ad libitum diet with complex carbohydrates resulted in lower energy intake compared to high-sugar diets. In two out of three studies, this was reflected in lower body weight in subjects consuming the complex carbohydrate diet. In conclusion, a limited number of relatively short-term studies suggest that replacing (added) sugar by low-energy sweeteners or by complex carbohydrates in an ad libitum diet might result in lower energy intake and reduced body weight. In the long term, this might be beneficial for weight maintenance. However, the number of studies is small and overall conclusions, in particular for the long term, cannot be drawn.

Association between trans fatty acid intake and cardiovascular risk factors in Europe: the TRANSFAIR study.

BACKGROUND: High intakes of trans fatty acids (TFA) have been found to exert an undesirable effect on serum lipid profiles, and thus may increase the risk for cardiovascular disease. OBJECTIVES: Investigation of the association between TFA intake and serum lipids. DESIGN: Cross-sectional study in eight European countries (Finland, France, Greece, Iceland, The Netherlands, Portugal, Spain, Sweden) among 327 men and 299 women (50-65 y). Using a dietary history method, food consumption was assessed and TFA intake was calculated with recent figures on TFA levels of foods, collected in the TRANSFAIR study. RESULTS: Mean (+/-s.d.) TFA intake was 2.40+/-1.53 g/day for men and 1.98+/-1.49 g/day for women (0.87+/-0.48% and 0. 95+/-0.55% of energy, respectively), with the highest consumption in Iceland and the lowest in the Mediterranean countries. No associations were found between total TFA intake and LDL, HDL or LDL/HDL ratio after adjustment for cardiovascular risk factors. Additional adjustment for other fatty acid clusters resulted in a significant inverse trend between total TFA intake and total cholesterol (Ptrend<0.03). The most abundantly occurring TFA isomer, C18:1 t, contributed substantially to this inverse association. The TFA isomers C14:1 t9, C16:1 t9 and C22:1 t were not associated or were positively associated with LDL or total cholesterol. CONCLUSIONS: From this study we conclude that at the current European intake levels of trans fatty acids they are not associated with an unfavourable serum lipid profile. SPONSORSHIP: Unilever Research Laboratorium, the Dutch Dairy Foundation on Nutrition and Health, Cargill BV, the Institute of Food Research Norwich Laboratory, the Nutrition Branch of the Ministry of Agriculture, Fisheries and Food, the International Fishmeal and Oil Manufacturers' Association, Kraft Foods, NV Vandemoortele Coordination Center, Danone Group, McDonalds Deutschland Inc, Danish Veterinary and Food Administration, Valio Ltd, Raisio Group. European Journal of Clinical Nutrition (2000) 54, 126-135

Determinants of bone mass and bone geometry in adolescent and young adult women.

Bone mass and bone geometry are considered to have independent effects on bone strength. The purpose of this study was to obtain data on bone mass and geometry in young female populations and how they are influenced by body size and lifestyle factors. In a cross-sectional, observational study in six European countries, 1116 healthy Caucasian girls aged 11-15 and 526 women aged 20-23 participated. Their radius was scanned at the ultradistal site and at a site approximately 30% of the radius length from the distal end with dual energy X-ray absorptiometry (DXA). The following parameters were assessed from the scans: bone mineral content (BMC), bone mineral density (BMD), cortical wall thickness (CWT), middistal diameter (D), cortical index (CI = 2CWT/D), and the Breaking Bending Resistance Index (BBRI = (D4 - [D-CWT]4)/D). Calcium intake was assessed by 3-day food records and physical activity by questionnaire. Body size parameters were measured by anthropometry. All parameters showed an increasing trend with pubertal stage and age, except for physical activity and calcium intake. BMC and BMD were relatively more dependent on body weight and age at menarche, whereas variation in D and the mechanical index BBRI was better explained by differences in height and grip strength. CI and CWT were relatively independent of variation in body size, whereas BMC and BBRI especially were explained for a substantial proportion (25-33% in the young adults) by body size parameters. Dietary intake of calcium and level of physical activity seem to contribute little to variation in bone parameters.

Oxidation of LDL and extent of peripheral atherosclerosis.

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.

Determinants of p,p-dichlorodiphenyldichloroethane (DDE) concentration in adipose tissue in women from five European cities.

To identify the determinants of p,p'-dichlorodiphenyldichloroethane (p,p'-DDE) in adipose tissue in subjects who participated in a cross-sectional study, we analyzed fatty acids, antioxidants, and p,p'-DDE in aspirates of adipose tissue of 328 postmenopausal women from 5 European countries. The overall mean of p,p'-DDE concentration was 1.66 microg/g of fatty acids (95% confidence interval = 1.46, 1.88). In a multiple-regression analysis, the main predictors of log10(p,p'DDE) were center of recruitment (p < .0001), adipose arachidic acid (p = .001), and adipose retinol (p = .04). These factors explained 14.9% of the overall variability of log10(p,p'-DDE). In our subjects, adipose tissue p,p'DDE concentrations were only weakly related with biomarkers reflecting intake of fish and other foods. This result is consistent with the notion that p,p'-DDE exists in different foods and, given the widespread contamination of the food chain, is relatively evenly distributed among foods.

Calcium intake is weakly but consistently negatively associated with iron status in girls and women in six European countries.

Several studies indicate that intake of calcium can inhibit iron absorption especially when taken simultaneously. In the CALEUR study, a cross-sectional study among girls (mean 13.5 y) and young women (mean 22.0 y) in six European countries, the association between calcium intake and iron status was studied. In 1,080 girls and 524 women, detailed information on calcium intake was collected by means of a 3-d food record, and serum ferritin, serum iron, serum transferrin and transferrin saturation were measured as indicators of iron status. The mean levels of serum iron, ferritin and transferrin were 15.8 +/- 6.1 mmol/L, 34.5 +/- 19.1 microg/L and 3. 47 +/- 0.47 g/L, respectively, in girls and 16.9 +/- 7.5 mmol/L, 40. 2 +/- 30.5 and microg/L, 3.59 +/- 0.60 g/L, respectively, in women. A consistent inverse association between calcium intake and serum ferritin was found, after adjusting the linear regression model for iron intake, age, menarche, protein, tea and vitamin C intake and country, irrespective of whether calcium was ingested simultaneously with iron. The adjusted overall regression coefficients for girls and women were -0.57 +/- 0.20 and -1.36 +/- 0.46 per 100 mg/d increase in calcium intake, respectively. Only in girls, transferrin saturation as a measure for short-term iron status was inversely associated with calcium intake (adjusted overall coefficient -0.18 +/- 0.08). However, analysis per country separately showed no consistency. We conclude that dietary calcium intake is weakly inversely associated with blood iron status, irrespective of whether calcium was ingested simultaneously with iron.

Dietary calcium and bone density in adolescent girls and young women in Europe.

The objective of this study was to investigate the association between dietary calcium intake and radial bone density among young women, over the whole range of intake and at different levels of calcium intake. The study design was a cross-sectional, observational multicenter investigation in six European countries. One thousand one hundred and sixteen healthy Caucasian girls aged 11-15 years and 526 women aged 20-23 years participated, after having been selected from larger population samples to represent a large range in calcium intake. Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry at the ultradistal and middistal radius. Calcium intake was assessed with 3-day food records. Other potential determinants of BMD were measured by anthropometry or questionnaires. Mean calcium intake among the girls varied between 609 mg/day in Italy and 1267 mg/day in Finland; intakes for women were in a similar range. After adjustment for height, weight, and age at menarche for the women, and adjustment for age, height, weight, Tanner stage, and bone area for the girls, radial BMD at both sites did not significantly vary among quartiles of calcium intakes for both age groups. In multivariate linear regression, calcium was weakly positively associated with BMD at both sites in the girls (per 100 mg of calcium: beta = 0.57 mg/cm2, p = 0.03 for middistal BMD and beta = 0.56 mg/cm2, p = 0.01 for ultradistal BMD). For middistal BMD, the association was observed predominantly in pre-menarcheal girls. The associations were no longer statistically significant after full adjustment for all determinants of BMD, except again in pre-menarcheal girls. Radial BMD in the women was not associated with calcium intake, except after full adjustment for determinants of BMD, when ultradistal BMD became inversely associated with calcium intake (per 100 mg beta = -1.02, p = 0.03); this finding was due to results in one of the countries and not found in other countries. There was no evidence for a different relation between calcium and BMD at different levels of intake; although there was a positive association at calcium intake levels < 600 mg/day, the interaction was not significant and there was no consistent trend over intake categories. These results do not support the hypothesis that dietary calcium is a determinant of peak BMD in European women, for a wide range of intake. This study does not provide evidence that Recommended Dietary Allowances for calcium should be increased.

Omega-3 fatty acids in adipose tissue and risk of myocardial infarction: the EURAMIC study.

Omega-3 fatty acids have potential antiatherogenic, antithrombotic, and antiarrhythmic properties, but their role in coronary heart disease remains controversial. To evaluate the association of omega-3 fatty acids in adipose tissue with the risk of myocardial infarction in men, a case-control study was conducted in eight European countries and Israel. Cases (n=639) included patients with a first myocardial infarction admitted to coronary care units within 24 hours from the onset of symptoms. Controls (n=700) were selected to represent the populations originating the cases. Adipose tissue levels of fatty acids were determined by capillary gas chromatography. The mean (+/-SD) proportion of alpha-linolenic acid was 0.77% (+/-0.19) of fatty acids in cases and 0.80% (+/-0.19) of fatty acids in controls (P=0.01). The relative risk for the highest quintile of alpha-linolenic acid compared with the lowest was 0.42 (95% confidence interval [CI] 0.22 to 0.81, P-trend=0.02). After adjusting for classical risk factors, the relative risk for the highest quintile was 0.68 (95% CI 0.31 to 1.49, P-trend=0.38). The mean proportion of docosahexaenoic acid was 0.24% (+/-0.13) of fatty acids in cases and 0.25% (+/-0.13) of fatty acids in controls (P=0. 14), with no evidence of association with risk of myocardial infarction. In this large case-control study we could not detect a protective effect of docosahexaenoic acid on the risk of myocardial infarction. The protective effect of alpha-linolenic acid was attenuated after adjusting for classical risk factors (mainly smoking), but it deserves further research.

Plasma coenzyme Q10 concentrations are not decreased in male patients with coronary atherosclerosis.

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.

Phyto-oestrogen excretion and rate of bone loss in postmenopausal women.

OBJECTIVE: The hypothesis was tested that the rate of postmenopausal bone loss is inversely associated with long-term urinary excretion of phyto-oestrogens, as a marker of habitual dietary intake. DESIGN: Secondary analysis of a 10-year follow-up study (1979 1989) among postmenopausal women in the Netherlands. SUBJECTS: From the original population of 154 women, 32 women were selected with an annual rate of radial bone loss of < or = 0.5% over the first 5 years of the study and 35 women with a rate of > or = 2.5% per year. METHODS: The isoflavonoids genistein, daidzein and equol, and the lignan enterolactone were determined by gas chromatography mass spectrometry in aggregate samples from annually collected urine samples. Cortical bone density of the radius had previously been measured annually by single-photon absorptiometry. RESULTS: Excretion of isoflavonoids did not differ between both groups, although in multivariate analysis equol excretion was weakly positively associated with rate of bone loss in the 5 years after the menopause. Enterolactone excretion was significantly higher in the group with high rate of bone loss. This positive association remained in multivariate linear regression analysis after adjustment for age, years since menopause, body mass index and intake of calcium, vegetable protein and dietary fibre. CONCLUSIONS: Enterolactone excretion is likely to be an indicator of consumption of grains and legumes; it is not clear whether the observed positive association with rate of bone loss is a causal one. Our results do not support a preventive effect of low, unsupplemented dietary intake of phyto-oestrogens on postmenopausal cortical bone loss. However, no conclusions can be drawn about effects of higher doses of phyto-oestrogens.

Tissue stores of individual monounsaturated fatty acids and breast cancer: the EURAMIC study. European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Breast Cancer.

The strongest evidence that monunsaturated fat may influence breast cancer risk comes from studies of southern European populations, in whom intake of oleic acid sources, particularly olive oil, appears protective. No previous study has examined the relation of adipose tissue fatty acid content to breast cancer in such a population. We used adipose biopsies with diverse fat intake patterns gathered in 5 European centers, including southern Europe (Malaga, Spain), to test the hypothesis that stores of oleic acid or other monounsaturates are inversely associated with breast cancer. Gluteal fat aspirates were obtained from 291 postmenopausal incident breast cancer patients and 351 control subjects, frequency-matched for age and catchment area. Logistic regression was used to model breast cancer by monounsaturates, with established risk factors controlled for. Oleic acid showed a strong inverse association with breast cancer in the Spanish center. The odds ratio for the difference between 75th and 25th percentiles was 0.40 (95% CI: 0.28, 0.58) in Malaga and 1.27 (0.88, 1.85) in all other centers pooled, with a peak at 2.36 (1.01, 5.50) for Zeist. Palmitoleic and myristoleic acids showed evidence of an inverse association outside Spain, and cis-vaccenic acid showed a positive association in 3 centers. These data do not support the hypothesis that increasing tissue stores of oleic acid are protective against breast cancer in non-Spanish populations. This finding implies that the strong protective associations reported for olive oil intake in dietary studies may be due to some other protective components of the oil and not to the direct effect of oleic acid uptake. Alternatively, high olive oil intake may indicate some other protective aspect of the lifestyle of these women.

LDL oxidation and extent of coronary atherosclerosis.

Accumulated evidence indicates that oxidative modification of LDL plays an important role in the atherogenic process. Therefore, we investigated the relation between coronary atherosclerosis and susceptibility of LDL to oxidation in a case-control study in men between 45 and 80 years of age. Case subjects and hospital control subjects were selected from subjects undergoing a first coronary angiography. Subjects with severe coronary stenosis (> or = 85% stenosis in one and > or = 50% stenosis in a second major coronary vessel) were classified as case subjects (n=91). Hospital control subjects with no or minor stenosis (< or = 50% stenosis in no more than two of the three major coronary vessels, n=94) and population control subjects free of plaques in the carotid artery (n=85) were pooled for the statistical analysis into one control category. Enrollment procedures allowed for similar distributions in age and smoking habits. Case subjects had higher levels of total and LDL cholesterol and triglycerides and lower levels of HDL cholesterol. Resistance time, maximum rate of oxidation, and maximum diene production were measured ex vivo using copper-induced LDL oxidation. A borderline significant inverse trend was observed for coronary atherosclerosis risk at increasing resistance time. Odds ratios (95% confidence interval) for the successive quartiles were 1.0 (reference), 0.77 (0.39 to 1.53), 0.67 (0.33 to 1.34), and 0.55 (0.27 to 1.15) (ptrend=0.07). No relation with maximum rate of oxidation was found, and higher maximum diene levels were found in control subjects (P<.01). The main determinant of oxidation was the fatty acid composition of LDL. No effect of smoking or use of medication was observed. We conclude that although LDL resistance to oxidation may be a factor in atherogenesis, the ex vivo measure is not a strong predictor of severity of coronary atherosclerosis.

Adipose tissue omega-3 and omega-6 fatty acid content and breast cancer in the EURAMIC study. European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Breast Cancer.

The fatty acid content of adipose tissue in postmenopausal breast cancer cases and controls from five European countries in the European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Cancer (EURAMIC) breast cancer study (1991-1992) was used to explore the hypothesis that fatty acids of the omega-3 family inhibit breast cancer and that the degree of inhibition depends on background levels of omega-6 polyunsaturates. Considered in isolation, the level of omega-3 or omega-6 fat in adipose tissue displayed little consistent association with breast cancer across study centers. The ratio of long-chain omega-3 fatty acids to total omega-6 fat showed an inverse association with breast cancer in four of five centers. In Malaga, Spain, the odds ratio for the highest tertile relative to the lowest reached 0.32 (95% confidence interval 0.13-0.82). In this center, total omega-6 fatty acid was strongly associated with breast cancer. With all centers pooled, the odds ratio for long-chain omega-3 to total omega-6 reached 0.80 for the second tertile and 0.65 for the third tertile, a downward trend bordering on statistical significance (p for trend = 0.055). While not definitive, these results provide evidence for the hypothesis that the balance between omega-3 and omega-6 fat may play a role in breast cancer.

Lycopene and myocardial infarction risk in the EURAMIC Study.

A multicenter case-control study was conducted to evaluate the relations between antioxidant status assessed by biomarkers and acute myocardial infarction. Incidence cases and frequency matched controls were recruited from 10 European countries to maximize the variance in exposure within the study. Adipose tissue needle aspiration biopsies were taken shortly after the infarction and analyzed for levels of carotenoids and tocopherols. An examination of colinearity including all covariates and the three carotenoids, alpha-carotene, beta-carotene, and lycopene, showed that the variables were sufficiently independent to model simultaneously. When examined singularly, each of the carotenoids appeared to be protective. Upon simultaneous analyses of the carotenoids, however, using conditional logistic regression models that controlled for age, body mass index, socioeconomic status, smoking, hypertension, and maternal and paternal history of disease, lycopene remained independently protective, with an odds ratio of 0.52 for the contrast of the 10th and 90th percentiles (95% confidence interval 0.33-0.82, p = 0.005). The associations for alpha- and beta-carotene were largely eliminated. We conclude that lycopene, or some substance highly correlated which is in a common food source, may contribute to the protective effect of vegetable consumption on myocardial infarction risk.

Adipose tissue trans fatty acids and breast cancer in the European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Breast Cancer.

To investigate the relationship between trans fatty acids and postmenopausal breast cancer in European populations differing greatly in their dietary fat intakes, a case control study using adipose tissue stores of trans fatty acids as a biomarker of exposure was conducted. Subjects included 698 postmenopausal incident cases of primary breast cancer and controls randomly drawn from local population and patient registries, ages 50-74 Concentrations of individual trans fatty acids in gluteal fat biopsies were measured in these women. The adipose concentration of trans fatty acids showed a positive association with breast cancer. The covariate-adjusted association with breast cancer. The covariate-adjusted OR was 1.40 (95% confidence interval: 1.02, 1.93) for the difference between the 75th and 25th percentiles of total adipose trans. The adjusted OR for trans in the lowest tertile of polyunsaturated fatty acid reached 3.6 (2.2, 6.1). These associations were not attributable to differences in age, body mass index, exogenous hormone use, or socioeconomic status. These findings suggest an association of adipose stores of trans fatty acids with postmenopausal breast cancer in European women. They require confirmation in other populations, with concomitant consideration of the potential roles of dietary saturated and monounsaturated fats.

Seasonal variation in low density lipoprotein oxidation and antioxidant status.

Accumulating evidence indicates that oxidative modification of low-density lipoproteins is atherogenic and that antioxidants may play a role in protection of LDL against oxidation. Several studies have reported a seasonal fluctuation in antioxidant levels, but to date nothing is known about seasonal fluctuations in parameters of oxidizability. We collected blood from 10 volunteers at four different periods over one year (February, May, September and December), and measured the amount of plasma lipids, plasma antioxidants, lipid and fatty acid composition of the LDL particle, LDL antioxidant content, LDL particle size and oxidation parameters (lag time and propagation rate). No seasonal fluctuation for lag time and propagation rate of copper ion-induced LDL oxidation was found. Small seasonal fluctuations were observed for some determinants of LDL oxidation, e.g. plasma and LDL vitamin E and LDL particle size, and for plasma lipids, plasma and LDL lutein and LDL beta-carotene. Fatty acid composition of LDL did not change during the year. The main determinant of oxidation susceptibility was the fatty acid composition of LDL. We conclude that LDL oxidation parameters do not change over the year.