Search

Background: Results of studies of the association between blood concentrations of homocysteine and depression in general populations and among psychiatric patients are inconsistent. Objective: The objective was to study the association between depression and serum concentrations of total homocysteine (tHcy). Design: A cross-sectional study of a sample of 924 men aged 46-64 y was conducted as a part of the Kuopio Ischaemic Heart Disease Risk Factor Study. Those who had a history of psychiatric disorder (6.0%) were excluded. Depressive symptoms were assessed with the 18-item Human Population Laboratory Depression Scale. Those who scored [greater than or equal to]5 at baseline or at the 4-y follow-up were considered to have a tendency toward depression. Results: The participants were ranked according to their blood tHcy concentration and divided into tertiles. Those in the upper tertile for serum tHcy had a more than twofold (odds ratio: 2.30: 95% CI: 1.35, 3.90; P = 0.002) higher risk of being depressed than did those in the lowest tertile for serum tHcy. The results remained significant after adjustment for the month of study, history of ischemic heart disease, smoking habits, alcohol consumption, marital status, education, and socioeconomic status in adulthood (odds ratio: 2.23; 95% CI: 1.30, 3.83: P = 0.004). Conclusion: High serum concentrations of tHcy may be associated with depression in middle-aged men. 1574-8. KEY WORDS Depression, homocysteine, folate, Kuopio Ischaemic Heart Disease Risk Factor Study

Background: Several, but not all, prospective studies have shown that low folate intakes, low circulating folate concentrations, or high plasma total homocysteine (tHcy) concentrations are associated with an increased risk of coronary artery disease (CAD). Objective: We examined the relations of both serum folate and serum tHcy concentrations with acute coronary events in middle-aged men from eastern Finland who had no CAD at baseline. Design: In a population-based prospective cohort study, 1027 men aged 46-64 y were examined in 1991-1993 as part of the Kuopio Ischaemic Heart Disease Risk Factor Study. During an average follow-up of 7.7 y (7900 person-years of follow-up), 114 acute coronary events were observed in 61 men who had no previous history of CAD (n = 810). Results: In a Cox model, compared with men whose serum folate concentrations were in the lowest tertile, those whose concentrations were in the highest tertile had a risk factor-adjusted relative risk of acute coronary events of 0.35 (95% CI: 0.17, 0.73; P = 0.005). Serum tHcy concentrations were not significantly associated with the risk of acute coronary events (for the highest tertile compared with the lowest, adjusted relative risk = 1.03; 95% CI: 0.57, 1.87; P = 0.932). Conclusions: The results of this prospective cohort study do not support the hypothesis that a high circulating tHcy concentration is a risk factor for acute coronary events in a male population free of prior heart disease. However, they do suggest that moderate-to-high serum folate concentrations are associated with a greatly reduced incidence of acute coronary events. KEY WORDS Serum folate, serum homocysteine, acute coronary events, Kuopio Ischaemic Heart Disease Risk Factor Study, men, Finland

Background: Interest in lycopene is growing rapidly following the recent publication of epidemiologic studies in which high circulating lycopene concentrations were associated with reductions in cardiovascular disease. Lycopene is one of the major carotenoids in the Western diet and is probably one of the protective factors in a vegetable-rich diet. Objective: We studied the hypothesis that the intima-media thickness of the common carotid artery (CCA-IMT) would be greater in men with low serum lycopene concentrations. Design: We investigated the relation between serum lycopene concentration and CCA-IMT in 1028 middle-aged men (aged 46-64 y) in eastern Finland who were participants in the Kuopio Ischaemic Heart Disease Risk Factor study and who were examined in 1991-1993. The subjects were classified into quarters according to serum lycopene concentration. Results: In a covariance analysis with adjustment for covariates, the men in the lowest quarter of serum lycopene concentration had a significantly higher mean CCA-IMT and maximal CCA-IMT (P = 0.005 and P = 0.001 for the difference, respectively) than did the other men. The mean and maximal CCA-IMT increased linearly across the quarters of serum lycopene concentration. Conclusions: A low serum lycopene concentration is associated with a higher CCA-IMT in middle-aged men from eastern Finland. This finding suggests that the serum lycopene concentration may play a role in the early stages of atherosclerosis. Increased thickness of the intima-media has been shown to predict coronary events; thus, lycopene intakes and serum concentrations may have clinical and public health relevance. KEY WORDS Lycopene, atherosclerosis, carotid arteries, intima-media thickness, carotenoids, Kuopio Ischaemic Heart Disease Risk Factor study, middle-aged men

Vitamin E is indispensible for reproduction in female rats. In humans, vitamin E deficiency primarily causes neurologic dysfunctions, but the underlying molecular mechanisms are unclear. Because of its antioxidative properties, vitamin E is believed to help prevent diseases associated with oxidative stress, such as cardiovascular disease, cancer, chronic inflammation, and neurologic disorders. However, recent clinical trials undertaken to prove this hypothesis failed to verify a consistent benefit. Given these findings, a group of European scientists met to analyze the most recent knowledge of vitamin E function and metabolism. An overview of their discussions is presented in this article, which includes considerations of the mechanisms of absorption, distribution, and metabolism of different forms of vitamin E, including the [alpha]-tocopherol transfer protein and [alpha]-tocopherol-associated proteins; the mechanism of tocopherol side-chain degradation and its putative interaction with drug metabolism; the usefulness of tocopherol metabolites as biomarkers; and the novel mechanisms of the antiatherosclerotic and anticarcinogenic properties of vitamin E, which involve modulation of cellular signaling, transcriptional regulation, and induction of apoptosis. Clinical trials were analyzed on the basis of the selection of subjects, the stage of disease, and the mode of intake, dosage, and chemical form of vitamin E. In addition, the scarce knowledge on the role of vitamin E in reproduction was summarized. In conclusion, the scientists agreed that the functions of vitamin E were underestimated if one considered only its antioxidative properties. Future research on this essential vitamin should focus on what makes it essential for humans, why the body apparently utilizes [alpha]-tocopherol preferentially, and what functions other forms of vitamin E have. KEY WORDS Vitamin E, metabolism, binding proteins, novel functions, chemical forms

Background: Evidence suggests that dietary supplementation of L-arginine, the precursor of nitric oxide, may protect arteries against atherosclerosis. Objective: We tested the hypothesis that dietary arginine intake is associated with a decreased risk of acute coronary events in Finnish men aged 42-60 y. Design: We investigated this association in a prospective cohort study of men who were free of prior coronary artery disease and who were examined in 1984-1989 in the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD). The dietary arginine intake of 1981 men was assessed by a 4-d food intake record during the baseline phase of the KIHD. Results: Men in the highest quintile of dietary arginine intake ([less than or equal to] 5691 mg/d) did not have a significantly lower risk of acute coronary events than did men in the 4 lower quintiles (relative risk after adjustment for potential coronary risk factors: 1.28; 95% CI: 0.85, 1.94). The covariates were age; examination years; body mass index; systolic blood pressure; serum total, HDL, and LDL cholesterol; serum triacylglycerols; urinary excretion of nicotine metabolites; maximal oxygen uptake in an exercise test: and alcohol intake. Splitting arginine intake into deciles or analyzing plant-and animal-derived arginine separately did not show any association between dietary arginine intake and the risk of acute coronary events. Arginine intake was also not consistently associated with blood pressure. Conclusion: Dietary arginine intake is not associated with the risk of acute coronary events in middle-aged men in eastern Finland. KEY WORDS Acute coronary events, arginine intake, nitric oxide, myocardial infarction, population studies, prospective studies, L-arginine, Kuopio Ischaemic Heart Disease Risk Factor Study, Finnish men

The protective effect of fruit and vegetables against cancer has been related to their high antioxidant content. However, results from intervention trials have not been conclusive on the protective effect of antioxidant supplementation. In a randomized placebo-controlled trial we investigated the effect of dietary supplementation with antioxidants on a biomarker of oxidative DNA damage with mechanistic relation to carcinogenesis. One hundred forty-two smoking men aged 35-65 y were randomly assigned to one of the following seven treatments for 2 mo: 100 mg D-[Alpha]-tocopheryl acetate plus 250 mg slow-release ascorbic acid twice a day (n = 20), 100 mg D-[Alpha]-tocopheryl acetate twice a day (n = 20), 250 mg ascorbic acid twice a day (n = 21), 250 mg slow-release ascorbic acid twice a day (n = 21), 30 mg coenzyme Q10 in oil three times a day (n = 20), 30 mg coenzyme Q10 as granulate three times a day (n = 20), or placebo twice a day (n = 20). The trial outcome was the urinary excretion rate of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG)--a repair product of oxidative DNA damage. Two months of supplementation did not result in significant changes in the urinary excretion rate of 8-ox-odG in any group. The lack of effect of antioxidant supplementation on the excretion rate of 8-oxodG, despite substantial increases in plasma antioxidant concentrations, agrees with the results from recent large intervention studies with cancer as an endpoint. The cancer-protective effect of fruit and vegetables seems to rely not on the effect of single antioxidants but rather on other anticarcinogenic compounds or on a concerted action of several micronutrients present in these foods.

Lipoprotein peroxidation is thought to play an important role in atherogenesis. In the Kuopio Atherosclerosis Prevention Study (KAPS) the intake of fat and fatty acids, the oxidation susceptibility of the plasma very-low-density + low-density lipoprotein (VLDL+LDL) fraction (by induction with copper or hemin and hydrogen peroxide), and concentrations of plasma antioxidants, serum lipids, and lipoproteins were measured in 393 men. In the multivariate-regression model dietary linoleic acid was the most important determinant of the maximal oxidation velocity for the hemin assay (standardized regression coefficient = 0.294, P < 0.0001). In the copper assay the association of dietary linoleic acid and maximal oxidation velocity was second in order of strength (standardized regression coefficient = 0.324, P < 0.0001). We conclude that high linoleic acid intake is associated with increased oxidation susceptibility of atherogenic lipoproteins in men.

Supplementation with high doses of [Alpha]-tocopherol has increased the oxidation resistance of LDL in many clinical trials. There have been only a few placebo-controlled trials in healthy persons of [Alpha]-tocopherol doses usually contained in dietary supplements. We carried out a single-blind, placebo-controlled, randomized trial to examine the effect of 200 mg RRR-[Alpha]-tocopheryl acetate/d on the oxidation resistance of atherogenic lipoproteins (VLDL+LDL including intermediate-density lipoproteins) in 40 smoking men. VLDL+LDL oxidation resistance was assessed as conjugated dienes after copper induction and hemin degradation after hydrogen peroxide induction. Also, the LDL total peroxyl-radical trapping antioxidant parameter (LDL TRAP) and plasma malondialdehyde were measured at baseline and alter 2 mo of supplementation. Plasma RRR-[Alpha]-tocopherol concentrations were measured at 2-h intervals for 12 h at baseline and after 2 mo of supplementation. Compared with placebo, 200-mg RRR-[Alpha]-tocopheryl acetate supplementation elevated plasma and VLDL+LDL [Alpha]-tocopherol concentrations, LDL TRAP, and oxidation resistance of VLDL+LDL. Plasma [Alpha]-tocopherol increased by 88% (P [is less than] 0.0001), VLDL+LDL [Alpha]-tocopherol increased by 90% (P [is less than] 0.0001), and LDL TRAP by 58% (P [is less than] 0.0001). The time to the start of oxidation (lag time) was prolonged by 34% when assessed with a copper-induced method and by 109% when assessed with a hemin + hydrogen peroxide-induced method; the time to maximal oxidation was prolonged by 21% (copper-induced method) in the vitamin E-supplemented group. Changes in plasma [Alpha]-tocopherol, lipid-standardized [Alpha]-tocopherol, and VLDL+LDL [Alpha]-tocopherol correlated significantly with changes in LDL TRAP, lag time, and time to maximal oxidation. Differences in changes between groups in the area under the curve for plasma [Alpha]-tocopherol were significant (P [is less than] 0.009). Our results suggest that 200 mg oral RRR-[Alpha]-tocopheryl acetate/d had a clear effect on the in vitro oxidation of VLDL+LDL in smoking men. Am J Clin Nutr 1998:68:1034-41. KEY WORDS Vitamin E, lipid peroxidation, low density lipoprotein, very-low-density lipoprotein