Publications by authors named "Jari Kaikkonen"

34 Publications

Associations of Serum Fatty Acid Proportions with Obesity, Insulin Resistance, Blood Pressure, and Fatty Liver: The Cardiovascular Risk in Young Finns Study.

J Nutr 2021 04;151(4):970-978

Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.

Background: The links between fatty acids (FAs) and cardiometabolic outcomes are topics of debate.

Objective: Our aim was to investigate the associations between serum standardized FA percentages and cardiometabolic outcomes.

Methods: We used cross-sectional (n = 2187-2200 subjects, age 24-39 y, women 54%) and 10-year prospective data (n = 975-1414 subjects) from the Young Finns Study. Outcomes included prevalent and incident obesity, insulin resistance (HOMA-IR index in the upper quintile), elevated blood pressure (BP; taking medication, or diastolic or systolic BP in the upper quintile), and incident nonalcoholic fatty liver. Logistic regression models were used to calculate ORs per SD increase in fatty acids (FAs). The models were adjusted for age and sex, and additionally for other potential confounders.

Results: Several cross-sectional findings were also statistically significant in prospective models (Bonferroni corrected P < 0.003). In fully-adjusted models for obesity, these consisted of SFAs (OR: 1.28) and MUFAs (OR: 1.38), including palmitoleic (OR: 1.39) and oleic acids (OR: 1.37). Furthermore, PUFAs (OR: 0.70), including linoleic (OR: 0.67) and docosahexaenoic acids (OR: 0.75), were inversely related with obesity, whereas γ-linolenic acid (OR: 1.32) was positively associated with obesity. In age- and sex-adjusted models for insulin resistance, MUFAs (OR: 1.26) and oleic acid (OR: 1.25) were positively, and PUFAs (OR: 0.81), particularly linoleic acid (OR: 0.78), were inversely associated with HOMA-IR. Similarly with elevated BP, palmitic acid (OR: 1.22), MUFAs (OR: 1.28), and oleic acid (OR: 1.28) were positively associated with elevated BP, whereas PUFAs (OR: 0.77), n-6 (omega-6) PUFAs (OR: 0.79), and linoleic acid (OR: 0.77) were inversely associated. In fully-adjusted models for incident fatty liver, the most consistent predictors were high palmitic (OR: 1.61) and low linoleic acid (OR: 0.63) percentages. The n-6/n-3 (omega-3) PUFA ratio was not linked with any adverse outcomes.

Conclusions: High serum percentages of total SFAs and MUFAs and low PUFAs, but also several specific FAs, predict future unfavorable cardiometabolic outcomes in Finnish adults.
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http://dx.doi.org/10.1093/jn/nxaa409DOI Listing
April 2021

The associations of oxidized lipoprotein lipids with lipoprotein subclass particle concentrations and their lipid compositions. The Cardiovascular Risk in Young Finns Study.

Free Radic Biol Med 2021 01 21;162:225-232. Epub 2020 Oct 21.

From Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Finland; Centre for Population Health Research, University of Turku and Turku University Hospital, Finland; Departments of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Finland.

Objective: Oxidation of low-density lipoprotein (LDL) may promote atherosclerosis, whereas the reverse transport of oxidized lipids by high-density lipoprotein (HDL) may contribute to atheroprotection. To provide insights into the associations of lipoprotein lipid oxidation markers with lipoprotein subclasses at the population level, we investigated the associations of oxidized HDL lipids (oxHDL) and oxidized LDL lipids (oxLDL) with lipoprotein subclasses in a population-based cross-sectional study of 1395 Finnish adults ages 24-39 years.

Methods: The analysis of oxidized lipids was based on the determination of the baseline level of conjugated dienes in lipoprotein lipids. A high-throughput nuclear magnetic resonance (NMR) platform was used to quantify circulating lipoprotein subclass concentrations and analyze their lipid compositions.

Results: OxHDL were mainly not associated with lipoprotein subclass lipid concentrations and lipid composition after adjustment for Apolipoprotein-A1 (Apo-A1), waist circumference and age. OxLDL were associated with several markers of lipoprotein subclass lipid concentrations and composition after adjustment for Apolipoprotein-B (Apo-B), age and waist circumference. Several measures of HDL and LDL subclasses, including phospholipid and triglyceride composition, associated directly with oxLDL Cholesterol ester and free cholesterol composition in HDL and LDL associated inversely with oxLDL.

Conclusion: We conclude that these results do not support the idea that HDL's particle size or composition would reflect its functional capacity in the reverse transport of oxidized lipids. On the contrary, oxLDL were associated with the entire lipoprotein subclass profile, including numerous associations with the compositional descriptors of the particles. This is in line with the suggested role of LDL oxidation in atherogenesis.
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.10.020DOI Listing
January 2021

Metabolic profiling of fatty liver in young and middle-aged adults: Cross-sectional and prospective analyses of the Young Finns Study.

Hepatology 2017 02 24;65(2):491-500. Epub 2016 Dec 24.

Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.

Nonalcoholic fatty liver is associated with obesity-related metabolic disturbances, but little is known about the metabolic perturbations preceding fatty liver disease. We performed comprehensive metabolic profiling to assess how circulating metabolites, such as lipoprotein lipids, fatty acids, amino acids, and glycolysis-related metabolites, reflect the presence of and future risk for fatty liver in young adults. Sixty-eight lipids and metabolites were quantified by nuclear magnetic resonance metabolomics in the population-based Young Finns Study from serum collected in 2001 (n = 1,575), 2007 (n = 1,509), and 2011 (n = 2,002). Fatty liver was diagnosed by ultrasound in 2011 when participants were aged 34-49 years (19% prevalence). Cross-sectional associations as well as 4-year and 10-year risks for fatty liver were assessed by logistic regression. Metabolites across multiple pathways were strongly associated with the presence of fatty liver (P < 0.0007 for 60 measures in age-adjusted and sex-adjusted cross-sectional analyses). The strongest direct associations were observed for extremely large very-low-density lipoprotein triglycerides (odds ratio [OR] = 4.86 per 1 standard deviation, 95% confidence interval 3.48-6.78), other very-low-density lipoprotein measures, and branched-chain amino acids (e.g., leucine OR = 2.94, 2.51-3.44). Strong inverse associations were observed for high-density lipoprotein measures, e.g., high-density lipoprotein size (OR = 0.36, 0.30-0.42) and several fatty acids including omega-6 (OR = 0.37, 0.32-0.42). The metabolic associations were attenuated but remained significant after adjusting for waist, physical activity, alcohol consumption, and smoking (P < 0.0007). Similar aberrations in the metabolic profile were observed already 10 years before fatty liver diagnosis.

Conclusion: Circulating lipids, fatty acids, and amino acids reflect fatty liver independently of routine metabolic risk factors; these metabolic aberrations appear to precede the development of fatty liver in young adults. (Hepatology 2017;65:491-500).
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http://dx.doi.org/10.1002/hep.28899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5299457PMC
February 2017

Longitudinal study of circulating oxidized LDL and HDL and fatty liver: the Cardiovascular Risk in Young Finns Study.

Free Radic Res 2016 28;50(4):396-404. Epub 2016 Jan 28.

a Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku , Turku , Finland ;

Oxidative reactions are thought to play a role in the inflammatory condition called fatty liver. It is unclear whether oxidized lipoprotein lipids or proteins are associated with future fatty liver. In the Cardiovascular Risk in Young Finns Study, we determined the circulating levels of LDL and HDL oxidized lipids and studied their associations with fatty liver assessed by ultrasonography. There were 1286 middle-aged subjects with normal liver and 288 subjects with fatty liver. Analysis of oxidized lipids consisted of conjugated dienes in isolated HDL (oxHDLlipids) and LDL (oxLDLlipids). Oxidized LDL was also measured with a method based on antibodies against oxidized apolipoprotein B (oxLDLprot). After adjustment for age, sex, leisure-time physical activity, body mass index, alcohol intake, smoking, serum LDL and HDL cholesterol as well as particle concentrations, participants with elevated oxLDLlipids (odds ratio for 1-SD change in oxLDLlipids = 1.27, p =0.011) had an increased risk for fatty liver. Similarly, a high oxidation score (oxLDLlipids + oxLDLprot) was directly associated with fatty liver (odds ratio=1.34, p = 0.012). The strongest direct association was seen with a high oxLDLlipids/oxHDLlipids ratio (odds ratio=1.49, p = 0.001). These data suggest that oxidized lipoprotein lipids are linked with the risk of fatty liver in middle-aged adults.
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http://dx.doi.org/10.3109/10715762.2015.1133906DOI Listing
December 2016

Paraoxonase-1 and oxidized lipoprotein lipids. The Cardiovascular Risk in Young Finns Study.

Atherosclerosis 2015 Aug 6;241(2):502-6. Epub 2015 Jun 6.

Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Finland; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Finland.

Objective: Paraoxonase-1 (PON1) is suggested to have a role in the antioxidant activity of high-density lipoprotein (HDL). PON1 activity levels are strongly genetically determined by the rs662 polymorphism (PON1 Q192R). To clarify the role of PON1 in lipoprotein oxidation at the population level, we examined the relations between PON1 activity, the rs662 polymorphism and oxidized lipoprotein lipids in young adults.

Methods: A population-based cross-sectional study of 1895 Finnish adults ages 24-39 years (872 males and 1023 females). PON1 activity was determined with paraoxon as the substrate. Analysis of oxidized lipids in isolated HDL (oxHDLlipids) and low-density lipoprotein (oxLDLlipids) was based on the determination of conjugated dienes. Oxidized LDL was also measured with a method based on antibodies against oxidized Apo-B (oxLDLprot). Serum lipids and apolipoproteins were measured. Genotyping was performed with the Illumina Bead Chip (Human 670 K).

Results: In multivariable models, PON1 activity associated inversely with oxLDLlipids (p = 0.0001, semi-partial R(2) = 0.09%), but it was not associated with oxHDLlipids (p = 0.93). There was a borderline significant association between PON1 activity and oxLDLprot (p = 0.08). PON1 rs662 polymorphism was strongly associated with PON1 activity (P-value<0.0001), but not with oxidized lipoprotein lipids and oxLDLprot.

Conclusion: Higher PON1 activity is associated with decreased oxLDLlipids levels, but not with oxHDLlipids in a population of young Finnish adults. These findings support the suggestion that PON1 activity may have a role in the oxidation of LDL lipids. There is a strong association between PON1 rs662 polymorphism and PON1 activity, but PON1 rs662 polymorphism is not associated with oxidized lipoprotein lipids and oxLDLprot.
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http://dx.doi.org/10.1016/j.atherosclerosis.2015.06.004DOI Listing
August 2015

Factors associated with six-year weight change in young and middle-aged adults in the Young Finns Study.

Scand J Clin Lab Invest 2015 Apr 20;75(2):133-44. Epub 2015 Jan 20.

Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku , Turku , Finland.

Objective: To examine factors associated with weight change and obesity risk in young and middle-aged adults.

Subjects/methods: The Young Finns Study with its 923 women and 792 men aged 24-39 years at baseline were followed for six years. Variables associated with the weight change were investigated with regression models.

Results: The average weight change was 0.45 kg/year in women and 0.58 kg/year in men. In women, weight change was steady across all ages. In men, weight changes were more pronounced in younger age groups. In women (weight gain > 2 kg, n = 490), medication for anxiety, low occupational status, high baseline BMI (body mass index), high intake of sweet beverages, high childhood BMI, high salt (NaCl and/or KCl) use, low number of children, low childhood family income, high stature and low level of dependence (a temperament subscale) were associated with increased weight gain (in the order of importance). In men (weight gain > 2 kg, n = 455), high stature, high intake of french fries, low intake of sweet cookies, young age, recent divorce, low intake of cereals, high intake of milk, depressive symptoms, rural childhood origin, high baseline BMI and unemployment were associated with more pronounced weight gain. Sedentarity (screen-time) was associated with weight gain only in young men. Physical activity and genetic risk for high BMI (score of 31 known variants) were not consistently associated with weight change.

Conclusions: Socio-economic factors, temperamental and physical characteristics, and some dietary factors are related with weight change in young/middle-aged adults. The weight change occurring in adulthood is also determined by childhood factors, such as high BMI and low family income.
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http://dx.doi.org/10.3109/00365513.2014.992945DOI Listing
April 2015

Metabolite profiling and cardiovascular event risk: a prospective study of 3 population-based cohorts.

Circulation 2015 Mar 8;131(9):774-85. Epub 2015 Jan 8.

From Computational Medicine, Institute of Health Sciences, University of Oulu, Finland (P.W., P.S., T. Tynkkynen, Q.W., M.T., A.J.K., J. Kettunen, M.A.-K.); Department of Chronic Disease Prevention, National Institute for Health and Welfare, Finland (P.W., A.S.H., J. Kettunen, A.J., M.P., V.S.); Institute for Molecular Medicine Finland, University of Helsinki (P.W., A.S.H., M.P., S.P.); NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio (P.S., T. Tynkkynen, Q.W., M.T., M.A.-K.); Faculty of Epidemiology and Public Health, London School of Hygiene and Tropical Medicine, United Kingdom (D.P.-M., J.-P.C.); Institute of Cardiovascular Science, University College London, United Kingdom (T. Tillin, A.D.H., J.-P.C., N.C.); Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Framingham, MA (A.G., R.S.V.); Genome Analysis Center, Institute of Experimental Genetics, Helmholtz Zentrum München, Neuherberg, Germany (A.A., J.A.); Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Finland (J. Kaikkonen, V.M., O.T.R.); Department of Food and Environmental Sciences, University of Helsinki, Finland (V.M.,); Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Finland (M.K.); Department of Clinical Chemistry, Fimlab Laboratories, and School of Medicine, University of Tampere, Finland (T.L.); Medical Research Council Integrative Epidemiology Unit at the University of Bristol, United Kingdom (D.A.L., T.R.G., M.A.-K.); School of Social and Community Medicine, University of Bristol, United Kingdom (D.A.L., T.R.G., M.A.-K.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (N.S.); Hannover Medical School, Hannover Unified Biobank, Germany (T.I.); Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

Background: High-throughput profiling of circulating metabolites may improve cardiovascular risk prediction over established risk factors.

Methods And Results: We applied quantitative nuclear magnetic resonance metabolomics to identify the biomarkers for incident cardiovascular disease during long-term follow-up. Biomarker discovery was conducted in the National Finnish FINRISK study (n=7256; 800 events). Replication and incremental risk prediction was assessed in the Southall and Brent Revisited (SABRE) study (n=2622; 573 events) and British Women's Health and Heart Study (n=3563; 368 events). In targeted analyses of 68 lipids and metabolites, 33 measures were associated with incident cardiovascular events at P<0.0007 after adjusting for age, sex, blood pressure, smoking, diabetes mellitus, and medication. When further adjusting for routine lipids, 4 metabolites were associated with future cardiovascular events in meta-analyses: higher serum phenylalanine (hazard ratio per standard deviation, 1.18; 95% confidence interval, 1.12-1.24; P=4×10(-10)) and monounsaturated fatty acid levels (1.17; 1.11-1.24; P=1×10(-8)) were associated with increased cardiovascular risk, while higher omega-6 fatty acids (0.89; 0.84-0.94; P=6×10(-5)) and docosahexaenoic acid levels (0.90; 0.86-0.95; P=5×10(-5)) were associated with lower risk. A risk score incorporating these 4 biomarkers was derived in FINRISK. Risk prediction estimates were more accurate in the 2 validation cohorts (relative integrated discrimination improvement, 8.8% and 4.3%), albeit discrimination was not enhanced. Risk classification was particularly improved for persons in the 5% to 10% risk range (net reclassification, 27.1% and 15.5%). Biomarker associations were further corroborated with mass spectrometry in FINRISK (n=671) and the Framingham Offspring Study (n=2289).

Conclusions: Metabolite profiling in large prospective cohorts identified phenylalanine, monounsaturated fatty acids, and polyunsaturated fatty acids as biomarkers for cardiovascular risk. This study substantiates the value of high-throughput metabolomics for biomarker discovery and improved risk assessment.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.114.013116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351161PMC
March 2015

Role of childhood food patterns on adult cardiovascular disease risk.

Curr Atheroscler Rep 2014 Oct;16(10):443

Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Kiinamyllynkatu 10, 20520, Turku, Finland,

Accumulating evidence indicates that childhood nutrition plays a role in the adulthood cardiovascular health. A lifelong tracking of dietary habits, following a long-term exposure to unhealthy dietary patterns or independent effects, is a potential effect-mediating mechanism. Dietary patterns have been studied by data-driven and hypothesis-based approaches. Typically, either data-driven healthy or prudent childhood dietary patterns have been characterized and found to be associated with lower adulthood cardiovascular disease (CVD) risk in the published cohort studies. With regard to the individual food groups or food quality indices, intakes particularly of vegetables and fruits (or fiber indicating plant food intake) and polyunsaturated fatty acids have shown protective effects. The evidence which could confirm the long-term healthiness of a hypothesis-based Mediterranean diet is limited, requiring further investigation. Overall, the recent literature strengthens the view that a healthy childhood diet is associated with lowered adulthood CVD risk.
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http://dx.doi.org/10.1007/s11883-014-0443-zDOI Listing
October 2014

Low density lipoprotein-containing circulating immune complexes: role in atherosclerosis and diagnostic value.

Biomed Res Int 2014 18;2014:205697. Epub 2014 Jun 18.

Institute of General Pathology and Pathophysiology, Moscow, Russia ; Institute for Atherosclerosis Research, Skolkovo Innovation Center, Moscow, Russia.

It has been suggested that low density lipoprotein-containing circulating immune complexes (LDL-CIC) play a role in atherogenesis and are involved in the formation of early atherosclerotic lesion. These complexes, as well as anti-LDL autoantibodies, have been found in the blood and in the atherosclerotic lesions of patients with different cardiovascular diseases, as well as in the blood of animals with experimental atherosclerosis. It can be suggested that the presence of anti-LDL antibodies in the blood is a result of immune response induced by lipoprotein modification. LDL-CIC differs from native LDL in many aspects. It has much lower sialic acid content, smaller diameter, and higher density and is more electronegative than native LDL. Fraction of LDL-CICs is fundamental to the serum atherogenicity manifested at the cellular level. LDL-CIC, unlike native LDL, is able to induce intracellular accumulation of neutral lipids, especially esterified cholesterol, in cells cultured from uninvolved human aortic intima and in macrophage cultures. After removal of LDL-CIC, the CHD patient's sera lose their atherogenic properties. Titer of LDL-CIC in blood serum significantly correlates with progression of atherosclerosis in human in vivo and has the highest diagnostic value among other measured serum lipid parameters. Elevated CIC-cholesterol might well be a possible risk factor of coronary atherosclerosis.
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http://dx.doi.org/10.1155/2014/205697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4087281PMC
October 2015

The associations of oxidized high-density lipoprotein lipids with risk factors for atherosclerosis: the Cardiovascular Risk in Young Finns Study.

Free Radic Biol Med 2013 Dec 3;65:1284-1290. Epub 2013 Oct 3.

Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, FI-20520 Turku, Finland; Department of Clinical Physiology and Department of Nuclear Medicine, Turku University Hospital, Turku, Finland.

Scavenging and reverse transport of atherogenic oxidized lipids by high-density lipoprotein (HDL) was recently suggested to contribute to atheroprotection. We investigated the associations of oxidized HDL lipids (oxHDLlipids) with known risk factors for atherosclerosis in a population-based cross-sectional study of 1395 Finnish adults ages 24-39 years (54.9% women). Analysis of oxidized lipids in isolated HDL and LDL (oxLDLlipids) was based on the determination of conjugated dienes. Oxidized LDL was measured also with a method based on antibodies against oxidized Apo-B (oxLDLprot). Serum lipids and risk factors were measured. In multivariable models, oxHDLlipids were associated inversely with age (partial R(2)=2.9% in men, 0.8% in women) and directly with oxLDLlipids (partial R(2)=3.4% in men, 4.2% in women) after adjustment for Apo-A1 (partial R(2)=9.6% in men, 25.2% in women). In men, oxHDLlipids were also associated inversely with insulin (partial R(2)=1.1%). In women, oxHDLlipids were additionally inversely associated with waist circumference (partial R(2)=1.8%) and daily smoking (partial R(2)=0.7%) and directly with C-reactive protein (CRP; partial R(2)=0.5%) and alcohol use (partial R(2)=0.5%). We conclude that an elevated risk profile characterized primarily by advanced age is associated with lower oxHDLlipid levels in a population of young Finnish men and women. Higher levels of oxHDLlipids are additionally associated with higher oxLDLlipid levels. In men, higher insulin levels are also associated with lower oxHDLlipid levels. In women, increased waist circumference and daily smoking are also associated with lower oxHDLlipid levels, and higher CRP levels and alcohol use are associated with higher oxHDLlipid levels.
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http://dx.doi.org/10.1016/j.freeradbiomed.2013.09.023DOI Listing
December 2013

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

Ann Med 2013 Sep 3;45(5-6):455-64. Epub 2013 Jul 3.

The Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Finland.

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 β-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.
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http://dx.doi.org/10.3109/07853890.2013.809915DOI Listing
September 2013

Childhood serum fatty acid quality is associated with adult carotid artery intima media thickness in women but not in men.

J Nutr 2013 May 13;143(5):682-9. Epub 2013 Mar 13.

Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.

Childhood nutrition may play a role in the development of cardiovascular disease risk in adulthood. We examined the links between childhood dietary fatty acid quality and adult subclinical atherosclerosis in a cohort of 374 males and 449 females, aged 3-18 y at baseline in 1980, followed for 27 y. Serum cholesterol ester fatty acid (CEFA) percentages were analyzed as markers of dietary fatty acid intake. Adulthood carotid artery intima media thickness (cIMT, μm), adjusted for childhood and adulthood lipid and nonlipid risk markers, was used as the outcome. In women, after adjustment for age and childhood nonlipid risk markers, the childhood saturated CEFA (B = 11.3; P = 0.011), monounsaturated CEFA (B = 2.5; P = 0.025), and n3 (ω3) polyunsaturated CEFA (B = 16.2; P = 0.035) percentages were directly associated with adult cIMT. In contrast, the n6 (ω6) polyunsaturated CEFA percentage was negatively associated with cIMT (B = -2.3; P = 0.008). Similar relationships were observed between childhood dietary intake data and adult cIMT. In men, these associations were generally weak and nonsignificant (P > 0.05) after controlling for confounders. These longitudinal data suggest that fat quality as reflected in the serum cholesterol ester fraction in childhood is associated with adult cIMT in women.
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http://dx.doi.org/10.3945/jn.112.172866DOI Listing
May 2013

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

Am J Clin Nutr 2012 Jun 9;95(6):1422-31. Epub 2012 May 9.

Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.

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.
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http://dx.doi.org/10.3945/ajcn.111.030387DOI Listing
June 2012

Does childhood nutrition influence adult cardiovascular disease risk?--insights from the Young Finns Study.

Ann Med 2013 Mar 12;45(2):120-8. Epub 2012 Apr 12.

Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.

There is a paucity of detailed information about the role of childhood food patterns or on the impact of individual nutrients on adulthood cardiovascular disease (CVD). We review here the reports that have investigated these questions in the Young Finns Study with its 3596 subjects at baseline, aged 3 to 18 years. All the participants filled in a food habit questionnaire, and half of them provided a 48-hour dietary recall interview. In adulthood, cardiovascular risk factors as well as structural and functional markers of subclinical atherosclerosis were measured, i.e. carotid artery intima media thickness (IMT), and measurements of arterial elasticity and brachial artery endothelial function. Our data demonstrate that dietary patterns can already be identified in childhood. These patterns remain relatively stable over the life-course and associate with cardiovascular risk factors and vascular markers of subclinical atherosclerosis. For example, a traditional dietary pattern characterized by low intakes of fruits and vegetables was associated with elevated increased adulthood IMT especially in men, whereas a diet with a high intake of vegetables was independently associated with increased arterial elasticity in both genders. Our findings and the current literature suggest that childhood nutrition has a significant role in the progression of CVD.
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http://dx.doi.org/10.3109/07853890.2012.671537DOI Listing
March 2013

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

J Nutr 2010 Mar 20;140(3):501-8. Epub 2010 Jan 20.

Department of Nutrition and Food Science, Reference Center in Food Technology, Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain.

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.
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http://dx.doi.org/10.3945/jn.109.112912DOI Listing
March 2010

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

J Am Coll Nutr 2008 Apr;27(2):314-20

GC Descovich Atherosclerosis and Metabolic Disease Research Unit, Internal Medicine, Aging and Kidney Diseases Dept., University of Bologna, Via Massarenti, 9, 40138 Bologna, Italy.

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.
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http://dx.doi.org/10.1080/07315724.2008.10719705DOI Listing
April 2008

Effects of astaxanthin supplementation on lipid peroxidation.

Int J Vitam Nutr Res 2007 Jan;77(1):3-11

Research Institute of Public Health, University of Kuopio, P.O. Box 1627, FI-70211 Kuopio, Finland.

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.
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http://dx.doi.org/10.1024/0300-9831.77.1.3DOI Listing
January 2007

Type 2 diabetes whole-genome association study in four populations: the DiaGen consortium.

Am J Hum Genet 2007 Aug 26;81(2):338-45. Epub 2007 Jun 26.

Oy Jurilab, and Research Institute of Public Health, University of Kuopio, Kuopio, Finland, and Hope Hospital, Salford, UK.

Type 2 diabetes (T2D) is a common, polygenic chronic disease with high heritability. The purpose of this whole-genome association study was to discover novel T2D-associated genes. We genotyped 500 familial cases and 497 controls with >300,000 HapMap-derived tagging single-nucleotide-polymorphism (SNP) markers. When a stringent statistical correction for multiple testing was used, the only significant SNP was at TCF7L2, which has already been discovered and confirmed as a T2D-susceptibility gene. For a replication study, we selected 10 SNPs in six chromosomal regions with the strongest association (singly or as part of a haplotype) for retesting in an independent case-control set including 2,573 T2D cases and 2,776 controls. The most significant replicated result was found at the AHI1-LOC441171 gene region.
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http://dx.doi.org/10.1086/520599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1950819PMC
August 2007

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

J Nutr 2007 Jan;137(1):84-7

Department of Nutrition and Food Science, Centre of Reference in Technology of Food, Faculty of Pharmacy, University of Barcelona, s/n E-08028 Barcelona, Spain.

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.
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http://dx.doi.org/10.1093/jn/137.1.84DOI Listing
January 2007

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

FASEB J 2007 Jan 16;21(1):45-52. Epub 2006 Nov 16.

German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.

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.
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http://dx.doi.org/10.1096/fj.06-6328comDOI Listing
January 2007

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

Ann Intern Med 2006 Sep;145(5):333-41

Municipal Institute for Medical Research, Barcelona, Spain.

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.
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http://dx.doi.org/10.7326/0003-4819-145-5-200609050-00006DOI Listing
September 2006

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.

J Agric Food Chem 2006 Aug;54(16):5790-6

Division of Pharmaceutical Biology, Faculty of Pharmacy, University of Helsinki, Finland.

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.
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http://dx.doi.org/10.1021/jf0608928DOI Listing
August 2006

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

Free Radic Biol Med 2006 Feb 18;40(4):608-16. Epub 2005 Oct 18.

Lipids and Cardiovascular Epidemiology Unit, Institut Municipal d'Investigació Mèdica (IMIM), 08003 Barcelona, Spain.

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.
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http://dx.doi.org/10.1016/j.freeradbiomed.2005.09.027DOI Listing
February 2006

Serum homocysteine, folate and risk of stroke: Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study.

Eur J Cardiovasc Prev Rehabil 2005 Aug;12(4):369-75

Research Institute of Public Health, University of Kuopio, Kuopio, Finland.

Background: Homocysteine and folate have been suggested to have opposite effects on the risk of stroke, although the results are controversial.

Design And Methods: The purpose of this study was to assess the effects of serum total homocysteine (tHcy) and serum folate levels on the risk of stroke in a prospective cohort study. The subjects were 1015 men aged 46-64 years and free of prior stroke, examined in 1991-1993 in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study.

Results: At baseline the mean serum tHcy concentration was 10.9 micromol/l (SD 3.4). During an average follow-up time of 9.6 years, 49 men experienced a stroke, of which 34 were ischaemic. In Cox proportional hazards models, men in the highest tHcy third had a risk factor-adjusted hazard rate ratio (RR) of 2.77 [95% confidence interval (CI): 1.23-6.24] for any stroke and 2.61 (95% CI: 1.02-6.71) for ischaemic stroke, compared with men in the lowest third. The mean baseline serum folate concentration was 10.4 nmol/l (SD 4.1). Men in the highest third of serum folate (>11.2 nmol/l) had an adjusted RR for any stroke of 0.35 (95% CI: 0.14-0.87) and for ischaemic stroke of 0.40 (95% CI: 0.15-1.09), compared with men in the lowest third.

Conclusion: Elevated serum tHcy is associated with increased risk of all strokes and ischaemic strokes in middle-aged eastern Finnish men free of prior stroke. On the other hand, high serum folate concentration may protect against stroke.
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http://dx.doi.org/10.1097/01.hjr.0000160834.75466.b0DOI Listing
August 2005

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

J Agric Food Chem 2005 Apr;53(8):3017-22

Research Institute of Public Health, University of Kuopio, Kuopio, Finland.

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.
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http://dx.doi.org/10.1021/jf048448xDOI Listing
April 2005

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

Free Radic Biol Med 2005 Feb;38(4):527-34

Research Institute of Public Health, University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland.

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.
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http://dx.doi.org/10.1016/j.freeradbiomed.2004.11.025DOI Listing
February 2005

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

Free Radic Biol Med 2004 Nov;37(9):1351-9

Research Institute of Public Health, University of Kuopio, Kuopio, Finland.

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.
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http://dx.doi.org/10.1016/j.freeradbiomed.2004.06.002DOI Listing
November 2004

Serum ferritin concentration is associated with plasma levels of cholesterol oxidation products in man.

Free Radic Biol Med 2003 Oct;35(8):922-8

Research Institute of Public Health, University of Kuopio, Kuopio, Finland.

Cholesterol oxidation products, oxysterols, are thought to play a part in the initiation and development of human atherosclerotic lesions. Excessive body iron has been suggested to promote atherosclerosis and coronary heart disease through its pro-oxidative properties. In the present study, the associations between serum ferritin and plasma oxysterol concentrations were examined in 669 eastern Finnish men. Serum ferritin concentration had statistically significant (p <.05) direct correlations with most of the measured oxysterols. In multivariate adjusted regression models, serum ferritin concentration predicted significantly the levels of 27-hydroxycholesterol (beta = 0.13, p <.001), 7alpha-hydroxycholesterol (beta = 0.11, p =.005), 25-hydroxycholesterol (beta = 0.10, p =.007), 7-ketocholesterol (beta = 0.10, p =.009), and 7beta-hydroxycholesterol (beta = 0.10, p =.02). In conclusion, excess body iron, as assessed by serum ferritin, is associated with increased levels of circulating oxysterols, both of enzymatic and nonenzymatic origin, in man.
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http://dx.doi.org/10.1016/s0891-5849(03)00433-7DOI Listing
October 2003

New paraoxonase 1 polymorphism I102V and the risk of prostate cancer in Finnish men.

J Natl Cancer Inst 2003 Jun;95(11):812-8

Oy Jurilab Ltd., Kuopio, Finland.

Background: Human serum paraoxonase eliminates carcinogenic lipid-soluble radicals. Because expression of the main human paraoxonase gene PON1 varies widely in humans, certain PON1 polymorphisms might be associated with increased risks of cancer. We sought new functional mutations in PON1 and determined whether known or new PON1 mutations were associated with the risk for prostate cancer in a prospective, random, population-based sample of Finnish men and in a case-control study.

Methods: Serum paraoxonase activity was measured in 835 healthy men in the Kuopio Ischaemic Heart Disease Risk Factor Study. PON1 mutations were identified by hierarchical phenotype-targeted sequencing in DNAs from the 100 men with the lowest paraoxonase activity in this cohort, and 1595 men in the cohort were genotyped for PON1 mutations by restriction fragment length polymorphism. Multivariable analysis was used to investigate the association of known and new PON1 mutations with incident prostate cancer in 1569 cancer-free men in the cohort followed for 9-14 years. In a case-control study of Finnish men, the association of prostate cancer with the PON1 mutation identified in the cohort study was investigated in 69 case patients with familial prostate cancer and 69 unmatched healthy control subjects.

Results: We identified a new single-nucleotide PON1 polymorphism associated with decreased serum paraoxonase activity that caused an isoleucine-->valine change at codon 102 in exon 4 (I102V). Of the 1569 men cancer-free at baseline, 56 (3.6%) were carriers of the I102V mutation. After adjusting for age and cholesterol-lowering medications, the relative risk for developing prostate cancer during follow-up was 6.3 (95% confidence interval [CI] = 2.1 to 19.2) among 102V allele carriers compared with noncarriers. Other PON1 alleles were not statistically significantly associated with prostate cancer. In the case-control study, patients with familial prostate cancer were more likely to be carriers of the PON1 I102V mutation than control subjects (odds ratio = 4.3, 95% CI = 0.9 to 21.5).

Conclusion: The PON1 102V allele appears to be associated with an increased risk for prostate cancer.
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http://dx.doi.org/10.1093/jnci/95.11.812DOI Listing
June 2003

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

J Nutr 2003 Apr;133(4):1170-3

Department of Infectious Diseases, H:S, Rigshospitalet, University of Copenhagen, Denmark.

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.
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http://dx.doi.org/10.1093/jn/133.4.1170DOI Listing
April 2003
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