Fatty acids as determinants of in-vivo lipid peroxidation: the EFFGE study in Eastern Finnish hypertensive and non-hypertensive subjects.

BACKGROUND: The degree of fatty acid (FA) unsaturation as a determinant of lipid peroxidation has been inadequately studied. METHODS: We examined associations of plasma free F2α-isoprostanes (F2-IsoPs), an indicator of in-vivo lipid peroxidation, with the levels/intake of FAs, adjusted for the risk factors of cardiovascular disease (CVD) in 1211 Finnish men and women, of whom 50% were hypertensive, aged 59.3 ± 8.3 years, mean ± SD. RESULTS: Elevated age- and sex-adjusted plasma free levels of omega-6 and omega-3 polyunsaturated Fas (PUFAs), saturated FAs (SFAs), and the PUFA/SFA and the omega-6/omega-3 PUFA ratios were all associated with decreased F2-IsoPs. High dietary SFA intake was associated with elevated F2-IsoP concentrations. In a multivariable regression (with clinical, nutritional, and behavioral CVD risk factors), female gender, body mass index (BMI), serum apolipoprotein A1, and NT-proBNP (natriuretic peptide) were positively associated with the F2-IsoPs, whereas the dietary PUFA/SFA ratio, plasma ß-carotene, the omega-6/omega-3 PUFA ratio, and protein intake showed inverse associations. CONCLUSIONS: We propose that elevated lipid peroxidation is associated with several risk factors of CVD, such as a low PUFA/SFA ratio, whereas the FA precursors of lipid peroxidation, i.e. omega-3 and omega-6 PUFAs are associated with attenuated F2-IsoP levels. These findings provide mechanistic support for earlier observations linking PUFA to improved cardiovascular health.

Childhood serum cholesterol ester fatty acids are associated with blood pressure 27 y later in the Cardiovascular Risk in Young Finns Study.

BACKGROUND: In adults, dietary fatty acids (FAs) modify blood pressure (BP), but it is not known whether childhood FA quality is associated with adulthood BP. OBJECTIVE: The purpose of the study was to investigate links between childhood serum cholesterol ester fatty acid (CEFA) proportions and adulthood systolic blood pressure (SBP) and diastolic blood pressure (DBP). DESIGN: We examined a cohort of 803 boys and girls (aged 3-18 y at baseline in 1980 and followed for 27 y) by using regression models adjusted for the known risk factors of BP. CEFAs were analyzed as markers of dietary FA intake. RESULTS: In men, serum SFA (B = 2.97, P < 0.001 for SBP; B = 1.48, P = 0.015 for DBP), MUFA (B = 0.61, P = 0.001 for SBP; B = 0.27, P = 0.078 for DBP), and omega-3 (n-3) PUFA (B = 5.50, P < 0.001 for SBP; B = 2.47, P = 0.015 for DBP) proportions, which were derived mainly from animal fats in this population, were positively associated with BP, whereas the omega-6 (n-6) PUFA proportion, which was derived mainly from vegetable oils and margarines, was negatively associated with BP (B = -0.56, P < 0.001 for SBP; B = -0.27, P < 0.018 for DBP). Serum cholesterol ester SFA and PUFA associations were supported by dietary intake data. In women, the associations between CEFA proportions and BP were weaker [for SBP: B = 0.36, P = 0.638 (NS) for SFA; B = 0.44, P = 0.019 for MUFA; B = 1.18, P = 0.376 (NS) for n-3 PUFA; and B = -0.33, P = 0.023 for n-6 PUFA]. CONCLUSION: Our findings suggest that fat quality as reflected in the serum cholesterol ester fraction in childhood is independently associated with adulthood BP particularly in men but also, to some extent, in women.

Elevated circulating LDL phenol levels in men who consumed virgin rather than refined olive oil are associated with less oxidation of plasma LDL.

In human LDL, the bioactivity of olive oil phenols is determined by the in vivo disposition of the biological metabolites of these compounds. Here, we examined how the ingestion of 2 similar olive oils affected the content of the metabolic forms of olive oil phenols in LDL in men. The oils differed in phenol concentrations as follows: high (629 mg/L) for virgin olive oil (VOO) and null (0 mg/L) for refined olive oil (ROO). The study population consisted of a subsample from the EUROLIVE study and a randomized controlled, crossover design was used. Intervention periods lasted 3 wk and were preceded by a 2-wk washout period. The levels of LDL hydroxytyrosol monosulfate and homovanillic acid sulfate, but not of tyrosol sulfate, increased after VOO ingestion (P < 0.05), whereas the concentrations of circulating oxidation markers, including oxidized LDL (oxLDL), conjugated dienes, and hydroxy fatty acids, decreased (P < 0.05). The levels of LDL phenols and oxidation markers were not affected by ROO consumption. The relative increase in the 3 LDL phenols was greater when men consumed VOO than when they consumed ROO (P < 0.05), as was the relative decrease in plasma oxLDL (P = 0.001) and hydroxy fatty acids (P < 0.001). Plasma oxLDL concentrations were negatively correlated with the LDL phenol levels (r = -0.296; P = 0.013). Phenols in LDL were not associated with other oxidation markers. In summary, the phenol concentration of olive oil modulates the phenolic metabolite content in LDL after sustained, daily consumption. The inverse relationship of these metabolites with the degree of LDL oxidation supports the in vivo antioxidant role of olive oil phenolics compounds.

Changes in LDL fatty acid composition as a response to olive oil treatment are inversely related to lipid oxidative damage: The EUROLIVE study.

OBJECTIVE: The aim of our study was to assess the changes in the fatty acid composition of low density lipoproteins (LDL) after sustained consumption of olive oil at real-life doses (25 mL/day) and their relationship with lipid oxidative damage. METHODS: A multi-center randomized, cross-over, clinical trial with 3 similar types of olive oils, but with differences in the phenolic content, was conducted on 200 healthy European subjects. Intervention periods were of 3 weeks separated by 2-week washout periods. The LDL fatty acid content was measured in samples drawn at baseline and after the last intervention period. RESULTS: After olive oil ingestion oleic acid concentration in LDL increased (1.9%; p < 0.001) and those of linoleic (1.1%; p < 0.002) and arachidonic acid (0.5%; p < 0.001) decreased. Monounsaturated/polyunsaturated fatty acid and oleic/linoleic acid ratios in LDL increased after olive oil consumption. An inverse relationship between the oleic/linoleic acid ratio and biomarkers of oxidative stress was observed. One unit increase in the oleic/linoleic acid ratio was associated with a decrease of 4.2 microg/L in plasma isoprostanes. CONCLUSION: Consumption of olive oil at real-life doses improved the fatty acid profile in LDL, the changes being associated with a reduction of the oxidative damage to lipids.

Effects of astaxanthin supplementation on lipid peroxidation.

Astaxanthin, the main carotenoid pigment in aquatic animals, has greater antioxidant activity in vitro (protecting against lipid peroxidation) and a more polar configuration than other carotenoids. We investigated the effect of three-month astaxanthin supplementation on lipid peroxidation in healthy non-smoking Finnish men, aged 19-33 years by using a randomized double-blind study design. Also absorption of astaxanthin from capsules into bloodstream and its safety were evaluated. The intervention group received two 4-mg astaxanthin (Astaxin) capsules daily, and the control group two identical-looking placebo capsules. Astaxanthin supplementation elevated plasma astaxanthin levels to 0.032 pmol/L (p < 0.001 for the change compared with the placebo group). We observed that levels of plasma 12- and 15-hydroxy fatty acids were reduced statistically significantly in the astaxanthin group (p = 0.048 and p = 0.047 respectively) during supplementation, but not in the placebo group and the change of 15-hydroxy fatty acid was almost significantly greater (p = 0.056) in the astaxanthin group, as compared with the placebo group. The present study suggests that intestinal absorption of astaxanthin delivered as capsules is adequate, and well tolerated. Supplementation with astaxanthin may decrease in vivo oxidation of fatty acids in healthy men.

Effect of olive oils on biomarkers of oxidative DNA stress in Northern and Southern Europeans.

High consumption of olive oil in the Mediterranean diet has been suggested to protect DNA against oxidative damage and to reduce cancer incidence. We investigated the impact of the phenolic compounds in olive oil, and the oil proper, on DNA and RNA oxidation in North, Central, and South European populations. In a multicenter, double-blind, randomized, controlled crossover intervention trial, the effect of olive oil phenolic content on urinary oxidation products of guanine (8-oxo-guanine, 8-oxo-guanosine and 8-oxo-deoxyguanosine) was investigated. Twenty-five milliliters of three olive oils with low, medium, and high phenolic content were administered to healthy males (n=182) daily for 3 wk. At study baseline the urinary excretion of 8-oxo-guanosine (RNA oxidation) and 8-oxo-deoxyguanosine (DNA oxidation) was higher in the Northern regions of Europe compared with Central and Southern European regions (P=0.035). Urinary excretion of the 8 hydroxylated forms of guanine, guanosine, deoxyguanosine and their nonoxidized forms were not different when comparing olive oils with low, medium, and high phenolic content given for 2 wk. Testing the effect of oil from urinary 8-oxo-deoxyguanosine changes from baseline to post-treatment showed a reduction of DNA oxidation by 13% (P=0.008). These findings support the idea that ingestion of olive oil is beneficial and can reduce the rate of oxidation of DNA. This effect is not due to the phenolic content in the olive oil. The higher DNA and RNA oxidation in Northern European regions compared with that in Central and Southern regions supports the contention that olive oil consumption may explain some of the North-South differences in cancer incidences in Europe.

Moderate consumption of olive oil by healthy European men reduces systolic blood pressure in non-Mediterranean participants.

We evaluated the effects of a moderate consumption of olive oil on lipid profile, BMI, and blood pressure (BP) in a group of 160 healthy men from non-Mediterranean regions [Northern Europe (n = 50; Finland and Denmark) and Central Europe (n = 60; Germany)] and Mediterranean regions [Southern Europe (n = 45; Italy and Spain)]. The study was a randomized, cross-over trial with 3 intervention periods of 3 wk and 2 wash-out periods of 2 wk. At the intervention periods, 3 similar olive oils (25 mL/d), differing only in their phenolic concentration, were administered to the healthy volunteers. Plasma oleic acid levels increased 2-3% (P < 0.05) in men from populations with lower habitual olive oil intakes (Northern and Central Europe). General linear models showed that the administration of the sequence of the 3 olive oils was responsible for a 3% decrease in systolic BP (SBP) (P < 0.05), but not in diastolic BP, in the non-Mediterranean subjects. Multivariate analysis indicated that the lipid profile did not change in either Mediterranean or non-Mediterranean men due to the olive oil intervention. The results of this study suggest that a moderate consumption of olive oil may be used as an effective tool to reduce SBP of healthy men who do not typically consume a Mediterranean diet. However, additional longer trials are necessary for confirmation.

The effect of polyphenols in olive oil on heart disease risk factors: a randomized trial.

BACKGROUND: Virgin olive oils are richer in phenolic content than refined olive oil. Small, randomized, crossover, controlled trials on the antioxidant effect of phenolic compounds from real-life daily doses of olive oil in humans have yielded conflicting results. Little information is available on the effect of the phenolic compounds of olive oil on plasma lipid levels. No international study with a large sample size has been done. OBJECTIVE: To evaluate whether the phenolic content of olive oil further benefits plasma lipid levels and lipid oxidative damage compared with monounsaturated acid content. DESIGN: Randomized, crossover, controlled trial. SETTING: 6 research centers from 5 European countries. PARTICIPANTS: 200 healthy male volunteers. MEASUREMENTS: Glucose levels, plasma lipid levels, oxidative damage to lipid levels, and endogenous and exogenous antioxidants at baseline and before and after each intervention. INTERVENTION: In a crossover study, participants were randomly assigned to 3 sequences of daily administration of 25 mL of 3 olive oils. Olive oils had low (2.7 mg/kg of olive oil), medium (164 mg/kg), or high (366 mg/kg) phenolic content but were otherwise similar. Intervention periods were 3 weeks preceded by 2-week washout periods. RESULTS: A linear increase in high-density lipoprotein (HDL) cholesterol levels was observed for low-, medium-, and high-polyphenol olive oil: mean change, 0.025 mmol/L (95% CI, 0.003 to 0.05 mmol/L), 0.032 mmol/L (CI, 0.005 to 0.05 mmol/L), and 0.045 mmol/L (CI, 0.02 to 0.06 mmol/L), respectively. Total cholesterol-HDL cholesterol ratio decreased linearly with the phenolic content of the olive oil. Triglyceride levels decreased by an average of 0.05 mmol/L for all olive oils. Oxidative stress markers decreased linearly with increasing phenolic content. Mean changes for oxidized low-density lipoprotein levels were 1.21 U/L (CI, -0.8 to 3.6 U/L), -1.48 U/L (-3.6 to 0.6 U/L), and -3.21 U/L (-5.1 to -0.8 U/L) for the low-, medium-, and high-polyphenol olive oil, respectively. LIMITATIONS: The olive oil may have interacted with other dietary components, participants' dietary intake was self-reported, and the intervention periods were short. CONCLUSIONS: Olive oil is more than a monounsaturated fat. Its phenolic content can also provide benefits for plasma lipid levels and oxidative damage. International Standard Randomised Controlled Trial number: ISRCTN09220811.

Consumption of juice fortified with oregano extract markedly increases excretion of phenolic acids but lacks short- and long-term effects on lipid peroxidation in healthy nonsmoking men.

Oregano has been shown to possess antioxidant capacity in various in vitro models and has thus been suggested to be potentially beneficial to human health, but studies in humans are lacking. The aim of this study was to investigate the bioavailability and the effects of Origanum vulgare extract supplementation on serum lipids and lipid peroxidation in healthy nonsmoking men. A four-week double-blinded supplementation trial was concluded in which volunteers (n = 45) were randomized to consume daily mango-orange juice (placebo), mango-orange juice enriched with 300 mg/d total phenolic compounds from oregano extract, or mango-orange juice enriched with 600 mg/d total phenolic compounds from oregano extract. The excretion of phenolic compounds was markedly increased in the higher phenolic group as compared to the placebo group, but no significant changes were observed in the safety parameters, serum lipids, or biomarkers of lipid peroxidation.

Postprandial LDL phenolic content and LDL oxidation are modulated by olive oil phenolic compounds in humans.

Olive oil phenolic compounds are potent antioxidants in vitro, but evidence for antioxidant action in vivo is controversial. We examined the role of the phenolic compounds from olive oil on postprandial oxidative stress and LDL antioxidant content. Oral fat loads of 40 mL of similar olive oils, but with high (366 mg/kg), moderate (164 mg/kg), and low (2.7 mg/kg) phenolic content, were administered to 12 healthy male volunteers in a cross-over study design after a washout period in which a strict antioxidant diet was followed. Tyrosol and hydroxytyrosol, phenolic compounds of olive oil, were dose-dependently absorbed (p<0.001). Total phenolic compounds in LDL increased at postprandial state in a direct relationship with the phenolic compounds content of the olive oil ingested (p<0.05). Plasma concentrations of tyrosol, hydroxytyrosol, and 3-O-methyl-hydroxytyrosol directly correlated with changes in the total phenolic compounds content of the LDL after the high phenolic compounds content olive oil ingestion. A 40 mL dose of olive oil promoted a postprandial oxidative stress, the degree of LDL oxidation being lower as the phenolic content of the olive oil administered increases. In conclusion, olive oil phenolic content seems to modulate the LDL phenolic content and the postprandial oxidative stress promoted by 40 mL olive oil ingestion in humans.

Polyphenol-rich phloem enhances the resistance of total serum lipids to oxidation in men.

In humans, polyphenol supplementation studies have resulted in inconsistent findings in lipid peroxidation. Our aim was to investigate the effects of a 4-week consumption of polyphenol-rich phloem on serum lipids and lipid peroxidation in the hydrophilic fraction of serum and on isolated lipoproteins. We conducted a randomized double-blind supplementation study consisting of 75 nonsmoking hypercholesterolemic men. Participants consumed 70 g daily of either rye bread (placebo) or phloem-fortified rye bread containing 31 mg (low polyphenol, LP) or 62 mg (high polyphenol, HP) of catechins. The ex vivo susceptibility of total serum lipids and VLDL and LDL to oxidation after copper induction was measured as a lag time to the maximal oxidation rate at the baseline and after the supplementation. In the HP group, an increase in the oxidation resistance of total serum lipids was observed (11.4%), while no effect was seen in the LP group (-0.8%) or in the placebo group (-1.0%) (p = 0.007). No differences were observed in the oxidation resistance of VLDL and LDL between the study groups. The phloem also increased in vitro oxidation resistance of serum lipids and radical scavenging activity (DPPH.) in a dose-dependent manner. Our results suggest that polyphenols may inhibit lipid peroxidation in the hydrophilic fraction of serum.

The effects of coffee consumption on lipid peroxidation and plasma total homocysteine concentrations: a clinical trial.

Despite extensive research, the cardiovascular effects of coffee consumption in humans remain controversial. Our aim was to investigate the excretion of coffee phenols and the effects of filtered coffee consumption on oxidative stress and plasma homocysteine (tHcy) concentration in humans. The study consisted of a multiple-dose clinical supplementation trial and a single-dose study. In the long-term trial, 43 healthy nonsmoking men optionally consumed daily either no coffee, 3 cups (450 mL), or 6 cups (900 mL) of filtered coffee for 3 weeks, while in the short-term study 35 subjects consumed a single dose of 0, 1 (150 mL), or 2 cups (300 mL) of coffee. Long-term consumption of coffee increased the urinary excretion of caffeic and ferulic acid. The change in the total excretion of phenolic acids in 3 and 6 cups groups represented 3.8 and 2.5% of the amount ingested daily. Plasma tHcy concentrations increased nonsignificantly, but the consumption of coffee had neither short-nor long-term effects on lipid peroxidation or the activity of measured antioxidant enzymes. In conclusion, the consumption of filtered coffee does not have any detectable effects on lipid peroxidation in healthy nonsmoking men. The effect of coffee consumption on tHcy concentrations needs further investigation.

Dark chocolate consumption increases HDL cholesterol concentration and chocolate fatty acids may inhibit lipid peroxidation in healthy humans.

Cocoa powder is rich in polyphenols and, thus, may contribute to the reduction of lipid peroxidation. Our aim was to study the effects of long-term ingestion of chocolate, with differing amounts of polyphenols, on serum lipids and lipid peroxidation ex vivo and in vivo. We conducted a 3 week clinical supplementation trial of 45 nonsmoking, healthy volunteers. Participants consumed 75 g daily of either white chocolate (white chocolate, WC group), dark chocolate (dark chocolate, DC group), or dark chocolate enriched with cocoa polyphenols (high-polyphenol chocolate, HPC group). In the DC and HPC groups, an increase in serum HDL cholesterol was observed (11.4% and 13.7%, respectively), whereas in the WC group there was a small decrease (-2.9%, p < 0.001). The concentration of serum LDL diene conjugates, a marker of lipid peroxidation in vivo, decreased 11.9% in all three study groups. No changes were seen in the total antioxidant capacity of plasma, in the oxidation susceptibility of serum lipids or VLDL + LDL, or in the concentration of plasma F2-isoprostanes or hydroxy fatty acids. Cocoa polyphenols may increase the concentration of HDL cholesterol, whereas chocolate fatty acids may modify the fatty acid composition of LDL and make it more resistant to oxidative damage.

Long-term combined supplementations with alpha-tocopherol and vitamin C have no detectable anti-inflammatory effects in healthy men.

Inflammatory and oxidative stresses play a pivotal role in atherogenesis. Vitamin E and vitamin C are the two most important dietary antioxidants; moreover, vitamin E has anti-inflammatory effects. Combined supplementations with vitamin E and vitamin C twice daily for 3 y reduced lipid peroxidation and retarded the progression of common carotid atherosclerosis in healthy men in the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study. To further elucidate the underlying mechanisms that retarded the progression of atherosclerosis in the ASAP study, we investigated the effect of a combined intake of vitamin E and vitamin C on inflammatory markers in vivo. Circulating levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and C reactive protein (CRP) were measured in 45- to 69-y-old men from the ASAP study with cholesterol >5.0 mmol/L before and after treatment with either placebo (n = 52) or a combined supplementation with 91 mg (136 IU) alpha-tocopherol and 250 mg of slow-release vitamin C twice a day (n = 55) for 3 y. Antioxidant treatment for 36 mo had no effect on circulating levels of TNF-alpha, IL-6 or CRP. In conclusion, long-term combined supplementations with alpha-tocopherol and vitamin C in reasonable doses have no detectable systemic anti-inflammatory effects in a healthy population of men with slight hypercholesterolemia and no overt signs of inflammation.

Six-year effect of combined vitamin C and E supplementation on atherosclerotic progression: the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) Study.

BACKGROUND: Self-selected supplementation of vitamin E has been associated with reduced coronary events and atherosclerotic progression, but the evidence from clinical trials is controversial. In the first 3 years of the ASAP trial, the supplementation with 136 IU of vitamin E plus 250 mg of slow-release vitamin C twice daily slowed down the progression of carotid atherosclerosis in men but not women. This article examines the 6-year effect of supplementation on common carotid artery (CCA) intima-media thickness (IMT). METHODS AND RESULTS: The subjects were 520 smoking and nonsmoking men and postmenopausal women aged 45 to 69 years with serum cholesterol > or =5.0 mmol/L (193 mg/dL), 440 (84.6%) of whom completed the study. Atherosclerotic progression was assessed ultrasonographically. In covariance analysis in both sexes, supplementation reduced the main study outcome, the slope of mean CCA-IMT, by 26% (95% CI, 5 to 46, P=0.014), in men by 33% (95% CI, 4 to 62, P=0.024) and in women by 14% (not significant). In both sexes combined, the average annual increase of the mean CCA-IMT was 0.014 mm in the unsupplemented and 0.010 mm in the supplemented group (25% treatment effect, 95% CI, 2 to 49, P=0.034). In men, this treatment effect was 37% (95 CI, 4 to 69, P=0.028). The effect was larger in subjects with either low baseline plasma vitamin C levels or CCA plaques. Vitamin E had no effect on HDL cholesterol. CONCLUSIONS: These data replicate our 3-year findings confirming that the supplementation with combination of vitamin E and slow-release vitamin C slows down atherosclerotic progression in hypercholesterolemic persons.

Coenzyme Q10: absorption, antioxidative properties, determinants, and plasma levels.

The purpose of this article is to summarise our studies, in which the main determinants and absorption of plasma coenzyme Q10 (Q10, ubiquinone) have been assessed, and the effects of moderate dose oral Q10 supplementation on plasma antioxidative capacity, lipoprotein oxidation resistance and on plasma lipid peroxidation investigated. All the supplementation trials carried out have been blinded and placebo-controlled clinical studies. Of the determinants of Q10, serum cholesterol, serum triglycerides, male gender, alcohol consumption and age were found to be associated positively with plasma Q10 concentration. A single dose of 30 mg of Q10, which is the maximum daily dose recommended by Q10 producers, had only a marginal elevating effect on plasma Q10 levels in non-Q10-deficient subjects. Following supplementation, a dose-dependent increase in plasma Q10 levels was observed up to a daily dose of 200 mg, which resulted in a 6.1-fold increase in plasma Q10 levels. However, simultaneous supplementation with vitamin E resulted in lower plasma Q10 levels. Of the lipid peroxidation measurements, Q10 supplementation did not increase LDL TRAP, plasma TRAP, VLDL+LDL oxidation resistance nor did it decrease LDL oxidation susceptibility ex vivo. Q10 with minor vitamin E dose neither decreased exercise-induced lipid peroxidation ex vivo nor muscular damage. Q10 supplementation might, however, decrease plasma lipid peroxidation in vivo, as assessed by the increased proportion of plasma ubiquinol (reduced form, Q10H2) of total Q10. High dose vitamin E supplementation decreased this proportion, which suggests in vivo regeneration of tocopheryl radicals by ubiquinol.

Association between low serum enterolactone and increased plasma F2-isoprostanes, a measure of lipid peroxidation.

Evidence suggests that low serum enterolactone concentration might be an independent risk factor for acute coronary events. Enterolactone is a lignan, which is formed by intestinal bacteria from precursors in plant foods. Due to the biphenolic structure of enterolactone, it could act as an antioxidant and through this contribute to cardiovascular health. The aim of this study was to test the hypothesis that a low serum enterolactone concentration is associated with increased in vivo lipid peroxidation, assessed by plasma F2-isoprostane concentrations. We investigated this association in a subset of participants in 'The Antioxidant Supplementation in Atherosclerosis Prevention' (ASAP) study. Out of 256 male participants a subsample of 100 consecutive men from baseline was selected for F2-isoprostane assays. The mean serum enterolactone concentration was 16.6 nmol/l and that of F2-isoprostanes 29.6 ng/l. The correlation coefficient for association between serum enterolactone and F2-isoprostane concentrations was -0.30 (P<0.003). Plasma F2-isoprostane levels decreased linearly across quintiles of serum enterolactone concentration (P=0.008 for a linear trend). In a multivariate model, enterolactone persisted as a significant predictor after adjustment for vitamins and other variables, with the strongest associations with F2-isoprostanes. Our present data suggest that low serum enterolactone concentration is associated with enhanced in vivo lipid peroxidation in men.