Molecular evaluation of vitamin D responsiveness of healthy young adults.

Vitamin D3 has via its metabolites 25-hydroxyvitamin D3 (25(OH)D3) and 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) direct effects on the transcriptome and the epigenome of most human cells. In the VitDbol study we exposed 35 healthy young adults to an oral vitamin D3 dose (2000µg) or placebo and took blood samples directly before the supplementation as well as at days 1, 2 and 30. Within 24h the vitamin D3 intake raised the average serum levels of both 25(OH)D3 and 1,25(OH)2D3 by approximately 20%. However, we observed large inter-individual differences in these serum levels, reflected by the average ratios between 25(OH)D3 and 1,25(OH)2D3 concentrations ranging from 277 to 1365. Interestingly, average serum parathyroid hormone (PTH) levels increased at day 1 by some 10% but then decreased within the following four weeks to levels 5% below baseline. In peripheral blood mononuclear cells (PBMCs) that were isolated at the same time points we determined vitamin D-modulated chromatin accessibility by FAIRE-qPCR at selected genomic loci. This method is well suited to evaluate both short-term and long-term in vivo effects of vitamin D on the epigenome of human subjects. The differential vitamin D responsiveness of the VitDbol study participants was determined via individual changes in their PTH levels or chromatin accessibility in relation to alterations in 25(OH)D3 concentrations. This led to the segregation of the subjects into 14 high, 11 mid and 10 low responders. In summary, the vitamin D responsiveness classification provides additional information compared to a vitamin D status assessment based on single 25(OH)D3 serum measurements. The study was registered at Clinicaltrials.gov (NCT02063334).

ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies.

IMPORTANCE: The role of ω-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. OBJECTIVE: To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5ω-3), docosapentaenoic acid (DPA; 22:5ω-3), and docosahexaenoic acid (DHA; 22:6ω-3) and plant-derived α-linolenic acid (ALA; 18:3ω-3) for incident CHD. DATA SOURCES: A global consortium of 19 studies identified by November 2014. STUDY SELECTION: Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue ω-3 biomarkers and ascertained CHD. DATA EXTRACTION AND SYNTHESIS: Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, ω-6 levels, and FADS desaturase genes. MAIN OUTCOMES AND MEASURES: Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI). RESULTS: The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with ω-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the ω-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses. CONCLUSIONS AND RELEVANCE: On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived ω-3 fatty acids are associated with a modestly lower incidence of fatal CHD.

Serum long-chain omega-3 polyunsaturated fatty acids and risk of orthostatic hypotension.

Long-chain omega-3 polyunsaturated fatty acids (PUFAs) from fish have been shown to lower blood pressure. However, there is little information about the association with orthostatic hypotension, for which hypertension is a risk factor. We investigated the associations between serum long-chain omega-3 PUFAs and orthostatic hypotension in 1666 middle-aged or older men and women free of cardiovascular disease (CVD), diabetes or hypertension in 1998-2001 in the Kuopio Ischemic Heart Disease Risk Factor Study (KIHD) in eastern Finland. We also investigated the associations with mercury exposure, a major source of which is fish, and which has been associated with higher CVD risk in KIHD. Orthostatic hypotension was defined as decrease in systolic blood pressure of at least 20 mm Hg or diastolic blood pressure of at least 10 mm Hg within 1 min of standing. Orthostatic hypotension was found in 146 participants (8.8%). The mean serum concentrations were 1.67% (s.d. 0.92) for eicosapentaenoic acid, 0.79% (s.d. 0.16) for docosapentaenoic acid (DPA) and 2.78 (s.d. 0.92) for docosahexaenoic acid of all serum fatty acids. The mean pubic hair mercury concentration was 1.5 µg g(-1) (s.d. 1.6). We did not find statistically significant associations between the serum long-chain omega-3 PUFAs or pubic hair mercury and risk of orthostatic hypotension, except for DPA. Those in the highest vs. the lowest serum DPA tertile had multivariate-adjusted 41% lower odds for orthostatic hypotension (95% confidence interval 7-63%, P-trend=0.02). Serum long-chain omega-3 PUFAs or mercury exposure were not associated with the risk of orthostatic hypotension, except for the inverse association with DPA.

Food and Nutrient Intake and Nutritional Status of Finnish Vegans and Non-Vegetarians.

BACKGROUND: Vegetarian and vegan diets have become more popular among adolescents and young adults. However, few studies have investigated the nutritional status of vegans, who may be at risk of nutritional deficiencies. OBJECTIVE: To compare dietary intake and nutritional status of Finnish long-term vegans and non-vegetarians. METHODS: Dietary intake and supplement use were estimated using three-day dietary records. Nutritional status was assessed by measuring biomarkers in plasma, serum, and urine samples. Vegans' (n = 22) data was compared with those of sex- and age-matched non-vegetarians (n = 19). RESULTS: All vegans adhered strictly to their diet; however, individual variability was marked in food consumption and supplementation habits. Dietary intakes of key nutrients, vitamins B12 and D, were lower (P < 0.001) in vegans than in non-vegetarians. Nutritional biomarker measurements showed lower concentrations of serum 25-hydroxyvitamin D3 (25(OH)D3), iodine and selenium (corrected for multiple comparisons, P < 0.001), Vegans showed more favorable fatty acid profiles (P < 0.001) as well as much higher concentrations of polyphenols such as genistein and daidzein (P < 0.001). Eicosapentaenoic acid proportions in vegans were higher than expected. The median concentration of iodine in urine was below the recommended levels in both groups. CONCLUSIONS: Long-term consumption of a vegan diet was associated with some favorable laboratory measures but also with lowered concentrations of key nutrients compared to reference values. This study highlights the need for nutritional guidance to vegans.

Glucose Metabolism Effects of Vitamin D in Prediabetes: The VitDmet Randomized Placebo-Controlled Supplementation Study.

Epidemiological evidence suggests a role for vitamin D in type 2 diabetes prevention. We investigated the effects of vitamin D3 supplementation on glucose metabolism and inflammation in subjects with prediabetes. A 5-month randomized, double-blind, placebo-controlled intervention with three arms (placebo, 40 µg/d, or 80 µg/d vitamin D3) was carried out among sixty-eight overweight (BMI 25-35) and aging (≥60 years) subjects from Finland, with serum 25-hydroxyvitamin D3 [25(OH)D3] < 75 nmol/L and either impaired fasting glucose or impaired glucose tolerance. Analyses included 66 subjects who completed the trial. Glucose metabolism was evaluated by fasting and 2-hour oral glucose tolerance test-derived indices and glycated hemoglobin. Inflammation was evaluated by high-sensitive C-reactive protein and five cytokines. Although a dose-dependent increase in serum 25(OH)D3 over the supplementation period was observed (P trend < 0.001), there were no other statistically significant differences in changes in the 13 glucose homeostasis indicators between the study groups other than increase in the 120 min glucose concentration (P trend = 0.021) and a decreasing trend both in 30 min plasma insulin (P trend = 0.030) and glycated hemoglobin (P trend = 0.024) concentrations. A borderline statistically significant decreasing trend in interleukin-1 receptor antagonist concentration was observed (P = 0.070). Vitamin D3 supplementation does not improve glucose metabolism in ageing subjects with prediabetes but may have modest anti-inflammatory effects.

Dissecting high from low responders in a vitamin D3 intervention study.

Vitamin D3 is a pleiotropic signaling molecule that has via activation of the transcription factor vitamin D receptor (VDR) a direct effect on the expression of more than 100 genes. The aim of this study was to find transcriptomic and clinical biomarkers that are most suited to identify vitamin D3 responders within 71 pre-diabetic subjects during a 5-month intervention study (VitDmet). In hematopoietic cells, the genes ASAP2, CAMP, CD14, CD97, DUSP10, G0S2, IL8, LRRC8A, NINJ1, NRIP1, SLC37A2 and THBD are known as primary vitamin D targets. We demonstrate that each of these 12 genes carries a conserved VDR binding site within its genomic region and is expressed in human peripheral blood mononuclear cells (PBMCs). The changes in the expression of these genes in human PBMCs at the start and the end of the vitamin D-intervention were systematically correlated with the alteration in the circulating form of vitamin D3, 25-hydroxyvitamin D3 (25(OH)D3). Only 39-44 (55-62%) of the study subjects showed a highly significant response to vitamin D3, i.e., we considered them as "responders". In comparison, we found for 37-53 (52-75%) of the participants that only 12 biochemical and clinical parameters, such as concentrations of parathyroid hormone (PTH) and insulin, or computed values, such as homeostatic model assessment and insulin sensitivity index, show a correlation with serum 25(OH)D3 levels that is as high as that of the selected VDR target genes. All 24 parameters together described the pleiotropic vitamin D response of the VitDmet study subjects. Interestingly, they demonstrated a number of additional correlations that define a network, in which PTH plays the central role. In conclusion, vitamin D3-induced changes in human PBMCs can be described by transcriptomic and serum biomarkers and allow a segregation into high and low responders. This article is part of a Special Issue entitled '17th Vitamin D Workshop' .

Dietary fatty acids and risk of coronary heart disease in men: the Kuopio Ischemic Heart Disease Risk Factor Study.

OBJECTIVE: The epidemiological evidence of the role of dietary saturated fatty acids (SFA) in the development of coronary heart disease (CHD) is inconsistent. We investigated the associations of dietary fatty acids with the risk of CHD and carotid atherosclerosis in men with high SFA intake and high rates of CHD. APPROACH AND RESULTS: In total, 1981 men from the population-based Kuopio Ischemic Heart Disease Risk Factor Study (KIHD), aged 42 to 60 years and free of CHD at baseline in 1984 to 1989, were investigated. Food consumption was assessed with 4-day food recording. Multivariate nutrient-density models were used to analyze isocaloric replacement of nutrients. CHD events were ascertained from national registries. Carotid atherosclerosis was assessed by ultrasonography of the common carotid artery intima-media thickness in 1015 men. During the average follow-up of 21.4 years, 183 fatal and 382 nonfatal CHD events occurred. SFA or trans fat intakes were not associated with CHD risk. In contrast, monounsaturated fat intake was associated with increased risk and polyunsaturated fat intake with decreased risk of fatal CHD, whether replacing SFA, trans fat, or carbohydrates. The associations with carotid atherosclerosis were broadly similar, whereas the associations with nonfatal CHD were weaker. CONCLUSIONS: Our results suggest that SFA intake is not an independent risk factor for CHD, even in a population with higher ranges of SFA intake. In contrast, polyunsaturated fat intake was associated with lower risk of fatal CHD, whether replacing SFA, trans fat, or carbohydrates. Further investigation on the effect of monounsaturated fat on the CHD risk is warranted.

Changes in vitamin D target gene expression in adipose tissue monitor the vitamin D response of human individuals.

SCOPE: Vitamin D3, its biologically most active metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), and the vitamin D receptor (VDR) are important for adipose tissue biology. METHODS AND RESULTS: We extrapolated genomic VDR association loci in adipocytes from 55 conserved genome-wide VDR-binding sites in nonfat tissues. Taking the genes DUSP10, TRAK1, NRIP1, and THBD as examples, we confirmed the predicted VDR binding sites upstream of their transcription start sites and showed rapid mRNA up-regulation of all four genes in SGBS human pre-adipocytes. Using adipose tissue biopsy samples from 47 participants of a 5-month vitamin D3 intervention study, we demonstrated that all four primary VDR target genes can serve as biomarkers for the vitamin D3 responsiveness of human individuals. Changes in DUSP10 gene expression appear to be the most comprehensive marker, while THBD mRNA changes characterized a rather different group of study participants. CONCLUSION: We present a new approach to predict vitamin D target genes based on conserved genomic VDR-binding sites. Using human adipocytes as examples, we show that such ubiquitous VDR target genes can be used as markers for the individual's response to a supplementation with vitamin D3.

Primary vitamin D receptor target genes as biomarkers for the vitamin D3 status in the hematopoietic system.

Vitamin D(3) belongs to the few nutritional compounds that has, via the binding of its metabolite 1α,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) to the transcription factor vitamin D receptor (VDR), a direct effect on gene regulation. The relation of thousands of genomic VDR-binding sites to a few hundred primary 1,25(OH)(2)D(3) target genes is still largely unresolved. We studied chromatin domains containing genes for the adhesion molecules CD97 and LRRC8A, the glucose transporter SLC37A2 and the coactivator NRIP1. These domains vary significantly in size (7.3 to 956 kb) but contain each one major VDR-binding site. In monocytic cells these four sites are associated with open chromatin and occupied by VDR, while in macrophage-like cells only the sites of LRRC8A, SLC37A2 and NRIP1 are accessible and receptor bound. The VDR site of CD97 does, in contrast to the three other loci, not carry any DR3-type binding sequence. CD97, LRRC8A, SLC37A2 and NRIP1 are early responding 1,25(OH)(2)D(3) target genes in monocytic cells, while in macrophage-like cells they respond less and, in part, delayed. In primary human peripheral blood mononuclear cells from 71 prediabetic subjects of a vitamin D(3) intervention study (VitDmet) CD97, LRRC8A, SLC37A2 and NRIP1 can be used as transcriptomic biomarkers for classifying human individuals for their possible benefit from vitamin D(3) supplementation. In particular, NRIP1 exceeds the potential of the previously identified marker CD14 by more than 40% and seems to be a well-suited molecular marker for the vitamin D(3) status in the hematopoietic system.

Serum omega-3 polyunsaturated fatty acids and risk of incident type 2 diabetes in men: the Kuopio Ischemic Heart Disease Risk Factor study.

OBJECTIVE The relationship between fish or omega-3 polyunsaturated fatty acids (PUFAs) and type 2 diabetes is inconclusive. Even contaminants in fish, such as mercury, may modify the effects. We investigated the associations between serum omega-3 PUFAs eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), α-linolenic acid (ALA), hair mercury, and risk of incident type 2 diabetes in middle-aged and older Finnish men. RESEARCH DESIGN AND METHODS A total of 2,212 men from the prospective, population-based Kuopio Ischemic Heart Disease Risk Factor study, aged 42-60 years and free of type 2 diabetes at baseline in 1984-1989, were investigated. Serum PUFA and hair mercury were used as biomarkers for exposure. Dietary intakes were assessed with 4-day food recording. Type 2 diabetes was assessed by self-administered questionnaires and fasting and 2-h oral glucose tolerance test blood glucose measurement at re-examination rounds 4, 11, and 20 years after the baseline and by record linkage to hospital discharge registry and reimbursement register on diabetes medication expenses. Cox proportional hazards models were used to analyze associations. RESULTS During the average follow-up of 19.3 years, 422 men developed type 2 diabetes. Men in the highest versus the lowest serum EPA + DPA + DHA quartile had 33% lower multivariate-adjusted risk for type 2 diabetes (95% CI 13-49; P trend 0.01). No statistically significant associations were observed with serum or dietary ALA, dietary fish or EPA + DHA, or hair mercury. CONCLUSIONS Serum long-chain omega-3 PUFA concentration, an objective biomarker for fish intake, was associated with long-term lower risk of type 2 diabetes.

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.

Primary vitamin D target genes allow a categorization of possible benefits of vitamin D3 supplementation.

Vitamin D deficiency has been associated with an increased risk of developing a number of diseases. Here we investigated samples from 71 pre-diabetic individuals of the VitDmet study, a 5-month high dose vitamin D3 intervention trial during Finnish winter, for their changes in serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations and the expression of primary vitamin D target genes in peripheral blood mononuclear cells and adipose tissue. A negative correlation between serum concentrations of parathyroid hormone and 25(OH)D3 suggested an overall normal physiological vitamin D response among the participants. The genes CD14 and thrombomodulin (THBD) are up-regulated primary vitamin D targets and showed to be suitable gene expression markers for vitamin D signaling in both primary tissues. However, in a ranking of the samples concerning their expected response to vitamin D only the top half showed a positive correlation between the changes of CD14 or THBD mRNA and serum 25(OH)D3 concentrations. Interestingly, this categorization allows unmasking a negative correlation between changes in serum concentrations of 25(OH)D3 and the inflammation marker interleukin 6. We propose the genes CD14 and THBD as transcriptomic biomarkers, from which the effects of a vitamin D3 supplementation can be evaluated. These biomarkers allow the classification of subjects into those, who might benefit from a vitamin D3 supplementation, and others who do not.

Dietary zinc intake and the risk of depression in middle-aged men: a 20-year prospective follow-up study.

BACKGROUND: Zinc is an immunomodulatory trace element suggested to be beneficial in the augmentation of antidepressant therapy. Cross-sectional studies have also suggested an association between low dietary zinc and depression. This study examined the association between dietary zinc intake and depression in a prospective setting in initially depression-free men during a 20-year follow-up. METHODS: The study formed a part of the population-based Kuopio Ischemic Heart Disease Risk Factor (KIHD) Study, and comprised 2317 Finnish men aged 42-61 years. Zinc intake was assessed at baseline by a 4-d food record. Baseline depression severity was recorded with the Human Population Laboratory Depression Scale. In the prospective setting, depression was defined as having received a hospital discharge diagnosis of unipolar depressive disorder. Individuals who at baseline had elevated depressive symptoms were excluded (n=283). RESULTS: Altogether, 60 (2.7%) individuals received a hospital discharge diagnosis of depression during the 20-year follow-up. In Cox regression analysis adjusted for age, baseline depression severity, smoking, alcohol use, physical exercise and the use of dietary supplements, belonging to the lowest tertile of energy-adjusted zinc intake was not associated with an increased depression risk (RR 1.06, 95% CI 0.59-1.90). LIMITATIONS: These observations may not be generalizable to women, or to individuals with a depression level not warranting hospitalization. CONCLUSIONS: Our findings suggest that a low dietary zinc intake may not longitudinally precede depression in men. Dietary zinc intake may not have relevance for the prevention of depression in middle-aged men with a sufficient dietary zinc intake.

Association of serum 25-hydroxyvitamin D with the risk of death in a general older population in Finland.

PURPOSE: To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] concentration, a marker of vitamin D status, and risk of all-cause and cardiovascular mortality in a general older population with relatively low average serum 25(OH)D concentrations. METHODS: The study population included 552 men and 584 women aged 53-73 years who were free of CVD and cancer at baseline in 1998-2001 from the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. Deaths were ascertained by a computer linkage to the national cause of death register. All deaths that occurred from the study entry to December 31, 2008, were included. Cox proportional hazards regression models were used to analyze the association between serum 25(OH)D and risk of death. RESULTS: The mean serum 25(OH)D concentration was 43.7 nmol/L (SD 17.8), with a strong seasonal variation. During the average follow-up of 9.1 years, 87 participants died, 35 from cardiovascular disease (CVD). After multivariable-adjustments, the hazard ratios (HR) for all cause death in the tertiles of serum 25(OH)D were 1, 1.68 (95% CI: 0.92, 3.07) and 2.06 (95% CI: 1.12, 3.80), p for trend = 0.02. CONCLUSIONS: Our study supports the accumulating evidence from epidemiological studies that vitamin D deficiency is associated with increased risk of death. Large-scale primary prevention trials with vitamin D supplementation are warranted.

Coffee, tea and caffeine intake and the risk of severe depression in middle-aged Finnish men: the Kuopio Ischaemic Heart Disease Risk Factor Study.

OBJECTIVE: Only a few cross-sectional studies have assessed the association between coffee, tea and caffeine and the risk of depression. Our aim was to determine the association in a population-based cohort study. DESIGN: The population-based Kuopio Ischaemic Heart Disease Risk Factor Study cohort was recruited between 1984 and 1989 and followed until the end of 2006. We investigated the association between the intake of coffee, tea and caffeine and depression. SETTING: Eastern Finland. SUBJECTS: Middle-aged men (n 2232). RESULTS: Altogether, forty-nine men received a discharge diagnosis of depression. We classified subjects into quartiles according to their mean daily coffee intake: non-drinkers (n 82), light drinkers (<375 ml/d, n 517), moderate drinkers (375-813 ml/d, n 1243) and heavy drinkers (>813 ml/d, n 390). Heavy drinkers had a decreased risk (RR = 0.28, 95 % CI 0.08, 0.98) for depression when compared with non-drinkers, after adjustment for age and examination years. Further adjustment for socio-economic status, alcohol consumption, smoking, maximal oxygen uptake, BMI and the energy-adjusted daily intakes of folate and PUFA did not attenuate this association (relative risk (RR) = 0.23, 95 % CI 0.06, 0.83). No associations were observed between depression and intake of tea (drinkers v. non-drinkers; RR = 1.19, 95 % CI 0.54, 2.23) or caffeine (highest quartile v. lowest quartile; RR = 0.99, 95 % CI 0.40, 2.45). CONCLUSIONS: Coffee consumption may decrease the risk of depression, whereas no association was found for tea and caffeine intake.

Dietary intake and urinary excretion of lignans in Finnish men.

Intake of lignans has been assessed in different study populations, but so far none of the studies has compared the daily intake of lignans and the urinary excretion of plant and enterolignans. We assessed the intake of lariciresinol, pinoresinol, secoisolariciresinol and matairesinol in 100 Finnish men consuming their habitual omnivorous diet, and measured the 24 h urinary excretion of plant and enterolignans to compare the intake and metabolism. Dietary determinants of lignan intake and their urinary excretion were also determined. The mean intake of lignans was 1224 (sd 539) mug/d, of which lariciresinol and pinoresinol covered 78 %. Almost half (47 %) of the intake of lignans was explained by the intake of rye products, berries, coffee, tea and roots. The urinary excretion of plant lignans corresponded to 17 % and enterolignans to 92 % of the intake of lignans. The urinary excretion of plant lignans was explained 14 % by the intake of rye products and intake of coffee, and consequently 3-7 % by the intake of water-insoluble fibre. The urinary excretion of enterolactone was explained 11 % by the intake of vegetables and rye products, 14 % by the intake of water-soluble fibre and only 4 % by the intake of lariciresinol. Although the assessed intake of lignans corresponded well with the urinary excretion of lignans, the enterolactone production in the human body depended more on the dietary sources of lignans than the absolute intake of lignans.

Serum long-chain n-3 polyunsaturated fatty acids and risk of hospital diagnosis of atrial fibrillation in men.

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia. Regular fish consumption has been shown to reduce the risk of AF in some but not all studies. Long-chain n-3 polyunsaturated fatty acids (PUFAs) from fish have been suggested to account for these beneficial effects. We tested this hypothesis by studying the association between the serum long-chain n-3 PUFAs eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid and risk of AF in men. METHODS AND RESULTS: A total of 2174 men from the prospective population-based Kuopio Ischemic Heart Disease Risk Factor Study, 42 to 60 years old and free of AF at baseline in 1984 to 1989, were studied. During the average follow-up time of 17.7 years, 240 AF events occurred. In the Cox proportional hazards model, the multivariable-adjusted hazard ratio in the highest (>5.33%) versus the lowest (<3.61%) quartile of eicosapentaenoic acid plus docosapentaenoic acid plus docosahexaenoic acid was 0.65 (95% confidence interval 0.44 to 0.96, P for trend=0.07). Evaluated individually, only serum docosahexaenoic acid was associated with the risk of AF (hazard ratio in the highest versus the lowest quartile 0.62, 95% confidence interval 0.42 to 0.92, P for trend=0.02). Exclusion of subjects (n=233) with myocardial infarction or congestive heart failure either at baseline or that preceded the AF event during follow-up slightly strengthened the associations. Serum intermediate chain-length n-3 PUFA, alpha-linolenic acid, or hair methylmercury concentration were not associated with the risk. CONCLUSIONS: An increased concentration of long-chain n-3 PUFAs in serum, a marker of fish or fish oil consumption, may protect against AF. Serum docosahexaenoic acid concentration had the greatest impact.