The role of fatty acids (FA) in prostate carcinogenesis is unclear. Interest in the inter-relationship among different types of FA has resulted in new analytic approaches to FA and their role in cancer development. We evaluated the association between erythrocyte FA and prostate cancer in 127 prostate cancer patients and 183 screen negative controls. We present three approaches to the analyses of the FA and prostate cancer association;(1) individual or common groups of FA,(2) biologically meaningful FA ratios and (3) principal components analysis. Monounsaturated FA and the alpha-linolenic:eicosapentaenoic ratio were associated with reduced risk of prostate cancer. However, Factor 1, which was strongly correlated with some long chain saturated FA, was associated with an increased risk of prostate cancer. We provide an example of modeling FA and their inter-relationships on the risk of prostate cancer. Comparing three approaches suggests the importance of considering the impact of the entire fatty acid profile in disease prevention.

AIM In the Insulin Resistance and Atherosclerosis Study (IRAS), we have previously shown a protective effect of plasma alpha-tocopherol concentration against diabetes incidence among persons not taking vitamin E supplements. The biologic mechanism for such a protective effect could involve improvement in either insulin sensitivity (S(I)), insulin secretion or both. Thus, we examined vitamin E in relation to insulin secretion and S(I) among persons not taking vitamin E supplements. METHODS This analysis included 457 adults aged 40-69 years without a previous diabetes diagnosis or vitamin E supplement use at baseline and seen at the 5-year follow-up examination. Baseline nutrient intake was estimated from a validated 1-year food frequency questionnaire; plasma levels of alpha-tocopherol were also assessed. At follow up, a frequently sampled intravenous glucose tolerance test determined S(I), acute insulin response to glucose (AIR), and the disposition index (DI) was calculated as the sum of the log-transformed AIR and S(I) to reflect pancreatic compensation for insulin resistance. RESULTS In multivariable regression analyses, no relationship was observed for vitamin E intake and either S(I), AIR or DI. However, plasma alpha-tocopherol concentration was positively associated with log-transformed S(I)(beta= 0.27 +/- 0.09, p < 0.01) and DI (beta= 0.41 +/- 0.14, p < 0.01), but not with log-transformed AIR. CONCLUSIONS Plasma concentration of alpha-tocopherol may improve S(I) and pancreatic compensation for insulin resistance, although it does not seem to be related to acute insulin response.

Induction or inhibition of biotransformation enzymes, enzymes that activate or detoxify numerous xenobiotics, is one mechanism by which vegetables may alter cancer risk. Using a randomized crossover design, we examined the effect of various vegetable diets on cytochrome P450 (CYP) 1A2, N-acetyltransferase 2 (NAT2) and xanthine oxidase activity in humans. Men and women, non-smokers, on no medication and 20-40 years of age ate four 6-day controlled diets: basal (vegetable-free) and basal with three botanically defined vegetable groups. Enzyme activities were determined by measuring urinary caffeine metabolite ratios after a 200 mg caffeine dose on the last day of each feeding period. Mean CYP1A2 activity for 19 men and 17 women (least squares means adjusted for sex, GSTM1 genotype, urine volume and feeding period) with basal, brassica, allium and apiaceous vegetable diets differed significantly (P </=ISOdia</= 0. 0005) by diet, irrespective of the caffeine metabolite molar ratio used to describe CYP1A2 activity; brassica vegetables increased (P <0.04) and apiaceous vegetables decreased (P </=ISOdia</= 0.02) activity compared with the basal and allium diets. There was no effect of diet on NAT2 and xanthine oxidase activities and none of the subjects differed by GSTM1 genotype. These results demonstrate that while one vegetable subgroup induces human CYP1A2 activity, another subgroup inhibits it. This points to a complex association between consumption of a typical diet of various vegetables and biotransformation enzyme activities in humans, an association that may be difficult to interpret in observational studies.

Preeclampsia is characterized by diffuse vascular endothelial dysfunction. Tumor necrosis factor-alpha (TNF-alpha), which plays a key role in the cytokine network responsible for immunoregulation, is also known to contribute to endothelial dysfunction and other metabolic disturbances noted in preeclampsia. Results from cross-sectional studies and one longitudinal study indicate that TNF-alpha (or its soluble receptor, sTNFp55) is increased in the peripheral circulation and amniotic fluid of women with preeclampsia as compared with normotensive women. Between December 1993 and August 1994, prediagnostic sTNFp55 concentrations (a marker of excessive TNF-alpha release) were measured in 35 women with preeclampsia and 222 normotensive women to determine whether elevations precede the clinical manifestation of the disorder. Logistic regression procedures were used to calculate maximum likelihood estimates of odds ratios and 95% confidence intervals. Mean second trimester (15-22 weeks' gestation) serum sTNFp55 concentrations, measured by enzyme-linked immunosorbent assay, were 14.4% higher in preeclamptic women than in normotensive controls (716.6 pg/ml (standard deviation 193.6) vs. 626.4 pg/ml (standard deviation 158.0); p = 0.003). The relative risk of preeclampsia increased across successively higher quintiles of sTNFp55 (odds ratios were 1.0, 1.3, 2.1, and 3.7, with the lowest quintile used as the referent; p for trend = 0.007). After adjustment for maternal age, adiposity, and parity, the relative risk between extreme quintiles was 3.3 (95% confidence interval 0.8-13.4). These findings indicate that the level of TNF-alpha in maternal circulation is increased prior to the clinical manifestation of the disorder, and they are consistent with the hypothesized role of cytokines in mediating endothelial dysfunction and the pathogenesis of preeclampsia. Further work is needed to identify modifiable risk factors for the excessive synthesis and release of TNF-alpha in pregnancy, and to assess whether lowering of TNF-alpha concentrations in pregnancy alters the incidence and severity of preeclampsia.

BACKGROUND Animal studies indicate that omega-6 fatty acids promote and omega-3 fatty acids inhibit tumor development. This pilot study was designed to evaluate whether these fatty acids are associated with human prostate cancer. METHODS Levels of erythrocyte membrane omega-3 and omega-6 fatty acids were determined for 67 incident prostate cancer cases and 156 population-based controls. RESULTS Prostate cancer risk was increased in the highest compared to the lowest quartile of alpha-linolenic acid (OR = 2.6, 95% CI = 1.1-5.8, trend P = 0.01). Positive associations were also observed with higher levels of linoleic acid (OR = 2.1, 95% CI = 0.9-4.8) and total omega-6 fatty acids (OR = 2.3, 95% CI = 1.0-5.4). CONCLUSIONS Results are consistent with other studies showing that linoleic and total omega-6 fatty acids increase risk of prostate cancer. Contrary to animal studies, alpha-linolenic acid was also positively associated with risk. Further research will be required to clarify the role of these fatty acids in human prostate cancer.

OBJECTIVE: Elevated plasma homocyst(e)ine is a risk factor for endothelial dysfunction and vascular disease. In late gestation, levels of homocyst(e)ine are higher in preeclamptics, as compared with normotensive pregnant women. Our objective was to determine whether homocyst(e)ine elevations precede the development of preeclampsia. STUDY DESIGN: We used a prospective nested case-control study design to compare second trimester maternal serum homocyst(e)ine concentrations in 52 patients who developed preeclampsia (pregnancy-induced hypertension with proteinuria) compared with 56 women who remained normotensive throughout pregnancy. Study subjects were selected from a base population of 3, 042 women who provided blood samples at an average gestational age of 16 weeks and later delivered at our center. Serum homocyst(e)ine was measured by high-performance liquid chromatography and electrochemical detection. RESULTS: Approximately 29% of preeclamptics, as compared to 13% of controls had homocyst(e)ine levels >/=5.5 micromol/l (upper decile of distribution of control values). Adjusted for maternal age, parity, and body mass-index, a second trimester elevation of homocyst(e)ine was associated with a 3. 2-fold increased risk of preeclampsia (adjusted OR = 3.2; 95% CI 1. 1-9.2; p = 0.030). There was evidence of a interaction between maternal adiposity (as indicated by her prepregnancy body mass index) and parity with second trimester elevations in serum homocyst(e)ine. Nulliparous women with elevated homocyst(e)ine levels experienced a 9.7-fold increased risk of preeclampsia as compared with multiparous women without homocyst(e)ine elevations (95% CI 2.1-14.1; p = 0.003). Women with a higher prepregnancy body mass index (>/=21.4 kg/m(2), or upper 50th percentile) and who also had elevated homocyst(e)ine levels, as compared with leaner women without homocyst(e)ine elevations were 6.9 times more likely to later develop preeclampsia (95% CI 1.4-32.1; p = 0.016). CONCLUSION: Our findings are consistent with other indications of vascular endothelial dysfunction predating clinical preeclampsia. Studies designed to examine the effect of dietary and/or pharmacological mediators of homocyst(e)ine metabolism in preeclampsia are warranted.

Past studies of the association of trans-fatty acid intake with coronary heart disease have been hindered by the lack of a database on the trans-fatty acid content of various foods. The authors used new data from the US Department of Agriculture to estimate trans-fatty acid intake using a self-administered food frequency questionnaire (FFQ), and they assessed the validity of the FFQ by comparing the dietary estimates with trans-fatty acid concentrations in adipose tissue. The 1996 study included 27 women and 24 men aged 51-78 years. The mean consumption of total trans-fatty acids estimated from the FFQ was 2.24 g per day and 5% of total dietary fat. The mean concentration of total trans-fatty acids in buttock adipose tissue was 4.7% of total fatty acids. Pearson correlations between total dietary intake of trans-fatty acids and total trans-fatty acid levels in adipose tissue were 0.67 (95% confidence interval (CI) 0.36-0.84) among men and 0.58 (95% CI 0.26-0.79) among women. After adjustment for energy intake, age, and body mass index, the correlation coefficients were 0.76 (95% CI 0.51-0.89) among men and 0.52 (95% CI 0.17-0.75) among women. The FFQ validated in this study is an important new tool for assessing usual intake of trans-fatty acids.

This case-control study was conducted in Lima, Peru, from June 1997 through January 1998 to assess whether plasma concentrations of carotenoids (alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin, beta-cryptoxanthin), retinol, and tocopherols (alpha-tocopherol and gamma-tocopherol) are decreased in women with preeclampsia. A total of 125 pregnant women with preeclampsia and 179 normotensive pregnant women were included. Plasma concentrations of antioxidants were determined using high performance liquid chromatography. After adjusting for maternal demographic, behavioral, and reproductive characteristics and total plasma lipid concentrations, the authors found a linear increase in risk of preeclampsia with increasing concentrations of alpha-tocopherol (odds ratio of the highest quartile = 3.13; 95% confidence interval: 1.06, 9.23, with the lowest quartile as the reference group; p value of the test of linear trend = 0.040). The risk of preeclampsia decreased across increasing quartiles of concentrations for retinol (odds ratio of the highest quartile = 0.32; 95% confidence interval: 0.15, 0.69, with the lowest quartile as the reference group; p value of the test of linear trend = 0.001). Some of these results are inconsistent with the prevailing hypothesis that preeclampsia is an antioxidant-deficient state. Preliminary findings confirm an earlier observation of increased plasma concentrations of alpha-tocopherol among women with preeclampsia as compared with normotensive pregnant women.

Preeclampsia is a systemic disease characterized by diffuse endothelial dysfunction, increased peripheral vascular resistance, coagulation abnormalities, antioxidant deficiency, persistent elevations of maternal leukocyte-derived cytokines, and hyperlipidemia. Fish oil, rich in omega-3 polyunsaturated fatty acids, is known to reduce fasting and postprandial triglycerides and to decrease platelet and leukocyte reactivity; it may also decrease blood pressure. Additionally, omega-3 fatty acids may beneficially influence vessel wall characteristics and blood rheology. In light of the potential beneficial effects of dietary omega-3 fatty acids, we conducted a cross-sectional case-control study to examine the hypothesized exposure-effect relation between maternal dietary intake of marine omega-3 fatty acids and risk of preeclampsia. We measured polyunsaturated fatty acids in erythrocytes obtained from 22 preeclamptic women and 40 normotensive women; we measured polyunsaturated fatty acids as the percentage of total fatty acids from gas chromatography. We employed logistic regression procedures to estimate odds ratios (ORs) and 95% confidence intervals (CIs). After adjusting for confounders, women with the lowest levels of omega-3 fatty acids were 7.6 times more likely to have had their pregnancies complicated by preeclampsia as compared with those women with the highest levels of omega-3 fatty acids (95% CI = 1.4-40.6). A 15% increase in the ratio of omega-3 to omega-6 fatty acids was associated with a 46% reduction in risk of preeclampsia (OR = 0.54; 95% CI = 0.41-0.72). Low erythrocyte levels of omega-3 fatty acids and high levels of some omega-6 fatty acids, particularly arachidonic acid, appear to be associated with an increased risk of preeclampsia.

OBJECTIVES Dyslipidemia is thought to be of etiological importance in pre-eclampsia. We studied the relationship between maternal plasma lipid concentrations and risk of pre-eclampsia. METHODS A total of 125 pre-eclampsia cases and 179 normotensive control subjects were included in this case-control study conducted in Lima, Peru, between August 1997 and January 1998. Postdiagnosis, antepartum plasma lipid profiles were determined by standard enzymatic methods. Logistic regression procedures were used to calculate odds ratios (OR) adjusted for potential confounders. RESULTS Mean plasma total cholesterol and triglyceride concentrations were, on average, 6% and 21% higher in pre-eclamptics than controls, respectively. High-density lipoprotein (HDL) cholesterol concentrations were, on average, 9% lower in cases than controls. After adjusting for maternal age, prepregnancy body mass index, education, parity and other potential confounders, the risk of pre-eclampsia increased with successively higher quartiles of plasma triglyceride (adjusted OR: 1.00, 1.62, 2.21, 5.00, with the lowest quartile as referent; P-value for trend < 0.001). The association between pre-eclampsia risk and plasma total cholesterol was much less pronounced. In general, there was an inverse association between pre-eclampsia risk and HDL cholesterol concentration (adjusted OR: 1.00, 0.41, 0.50, 0.38, with the first quartile as the referent group; P-value for trend = 0.02). CONCLUSIONS These findings suggest that high triglyceride and low HDL cholesterol concentrations are important risk factors for pre-eclampsia among Peruvian women.

We sought to examine the relationship between excessive tumor necrosis factor-alpha (TNF-alpha) release (as measured by sTNFp55 plasma concentrations) and risk of eclampsia and preeclampsia, respectively, among sub-Saharan African women delivering at Harare Maternity Hospital, Zimbabwe. In total, 33 pregnant women with eclampsia, 138 women with preeclampsia and 185 normotensive women were included in a case-control study conducted during the period, June 1995 through April 1996. Postpartum plasma sTNFp55 was measured by enzyme linked immunosorbent assay. Women with eclampsia had significantly higher sTNFp55 than normotensive controls (1.87 vs 1.35 ng/ml, P<0.001). Similarly, women with preeclampsia had sTNFp55 concentrations higher than normotensive controls (1.69 vs 1.35 ng/ml, P < 0.001). The odds ratio for eclampsia was 5.00 (adjusted odds ratio (OR) 5.00, 95% confidence interval (CI) 1.20-20.92) among women in the highest quartile of the control sTNFp55 distribution compared with women in the lowest quartile. The corresponding odds ratio and 95% CI for preeclampsia was 2.37 (1.11-5.06). Postpartum plasma sTNFp55 concentrations are increased among Zimbabwean women with eclampsia and preeclampsia as compared with their normotensive counterparts. These findings are consistent with the hypothesized role of cytokines in mediating endothelial dysfunction and the pathogenesis of preeclampsia/eclampsia. Additional work is needed to identify modifiable risk factors for the excessive synthesis and release of TNF-alpha in pregnancy; and to assess whether measurements of sTNFp55 early in pregnancy may be used to identify women likely to benefit from anti-inflammatory therapy.

OBJECTIVE Trans fatty acids, formed by the partial hydrogenation of vegetable oils, are associated with increases in plasma concentrations of cholesterol, triglyceride, lipoprotein (a), and coronary heart disease risk. Trans fatty acids may also increase platelet aggregation and alter eicosanoid biosynthesis. We studied the relation between maternal dietary intake of trans fatty acids and risk of preeclampsia. METHODS Maternal intake of elaidic acid, one of the most abundant dietary trans fatty acids and other fatty acids were estimated using gas-liquid chromatography on erythrocytes from 22 women with preeclampsia and 40 normotensive controls. Fatty acids were expressed as the percentage of total fatty acids in erythrocytes. Logistic regression procedures were used to estimate odds ratios and 95% confidence intervals. RESULTS Mean levels of elaidic acid were 28% higher among preeclamptics (0.43 +/- 0.12) as compared with controls (0.31 +/- 0.12; p < 0.001). After adjusting for confounding factors, women with the highest levels of elaidic acid (median = 0.47) were 7.4 times (odds ratio = 7.4; 95% confidence interval 1.4-39.7) more likely to have had their pregnancy complicated by preeclampsia as compared with those women with the lowest levels (median 0.24). Risk of preeclampsia appeared to increase with increasing levels of elaidic acid (p value for linear trend = 0.05). CONCLUSION These cross-sectional data suggest that diets high in elaidic acid may be associated with an increased risk of preeclampsia. This hypothesis should be examined in larger longitudinal studies.