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PURPOSE: Coffee is widely consumed and implicated in numerous health outcomes but the mechanisms by which coffee contributes to health is unclear. The purpose of this study was to test the effect of coffee drinking on candidate proteins involved in cardiovascular, immuno-oncological and neurological pathways.METHODS: We examined fasting serum samples collected from a previously reported single blinded, three-stage clinical trial. Forty-seven habitual coffee consumers refrained from drinking coffee for 1 month, consumed 4 cups of coffee/day in the second month and 8 cups/day in the third month. Samples collected after each coffee stage were analyzed using three multiplex proximity extension assays that, after quality control, measured a total of 247 proteins implicated in cardiovascular, immuno-oncological and neurological pathways and of which 59 were previously linked to coffee exposure. Repeated measures ANOVA was used to test the relationship between coffee treatment and each protein.RESULTS: Two neurology-related proteins including carboxypeptidase M (CPM) and neutral ceramidase (N-CDase or ASAH2), significantly increased after coffee intake (P Q P Q > 0.05); 9, 8 and 29 of these proteins related to cardiovascular, immuno-oncological and neurological pathways, respectively, and the levels of 41 increased with coffee intake.CONCLUSIONS: CPM and N-CDase levels increased in response to coffee intake. These proteins have not previously been linked to coffee and are thus novel markers of coffee response worthy of further study.

Adequate iron supply in pregnancy is important for both the woman and the fetus, but iron status is often assessed late in first trimester, if assessed at all. Therefore, identification of factors associated with iron status is important to target vulnerable groups with increased risk of deficiency. Our objectives were to (1) describe iron status in mid-pregnancy and (2) identify sociodemographic and lifestyle predictors of pregnancy iron status. This cross-sectional study uses data from The Norwegian Mother, Father and Child Cohort Study (collected 2002–2008) and The Medical Birth Registry of Norway. Iron status was measured as non-fasting plasma ferritin (P-Fe) and transferrin in gestational week (GW) 18 (n 2990), and by lowest reported Hb in GW 0–30 (n 39 322). We explored predictors of iron status with elastic net, linear and log-binomial regression models. Median P-Fe was 33 μg/l, and 14 % had depleted iron stores (P-Fe

Background Few randomized clinical trials have explored the health effects of bilberries in humans. The aim was to test the effect of bilberry and red grape-juice consumption on visual memory, motor speed and dexterity as well as inflammatory and tissue damage biomarkers of plasma in aged men with subjective memory impairment. Methods Nine-week double-blind, placebo-controlled, dietary intervention study of aged men (n = 60, age ≥ 67 years) with subjective memory impairment randomized to consume a 50/50 mix of bilberry/red grape-juice or an iso-caloric placebo juice. A selection of Cambridge Cognition Test Battery (CANTAB), Grooved Pegboard tests and blood-sampling for biomarker analysis were performed before and after the intervention. Results Compared to placebo the selected memory and motor test scores were un-affected by the bilberry/red grape intervention. However, the plasma levels of tissue damage biomarkers decreased significantly more in the bilberry/red grape group. In particular lactate dehydrogenase (LDH) decreased from 362 U/L (median, baseline) to 346 U/L (median, post intervention) in the bilberry/red grape group. Also, several biomarkers of inflammation (EGF, IL6, IL9, IL10 and TNFα) decreased significantly more in the bilberry/red grape group. Furthermore, several plasma polyphenols; p-coumaric acid, hippuric acid, protocatechuic acid, 3HPAA and vanillic acid, increased significantly more in the bilberry/red grape group compared to placebo with the largest increase in p-coumaric acid with 116%; from 2.2 [1.0,5.5] to 4.7 [2.8,8.1] μM/L (median [95% CL]). Conclusions The results indicate that a nine-week bilberry/red grape juice intervention has no measurable effects on the selected memory scores in aged men experiencing memory problems but decreases the level of biomarkers of inflammation and tissue damage. Whether the dampening effects on inflammation and tissue damage biomarkers have relevance for neuroinflammatory brain pathology remains to be established. Trial registration Registration number (ClinicalTrials.gov: NCT00972972), September 9, 2009.

Children’s plasma metabolome, especially lipidome, reflects gene regulation and dietary exposures, heralding the development of islet autoantibodies (IA) and type 1 diabetes (T1D). The Environmental Determinants of Diabetes in the Young (TEDDY) study enrolled 8,676 newborns by screening of HLA-DR-DQ genotypes at six clinical centers in four countries, profiled metabolome, and measured concentrations of ascorbic acid, 25-hydroxyvitamin D [25(OH)D], and erythrocyte membrane fatty acids following birth until IA seroconversion under a nested case-control design. We grouped children having an initial autoantibody only against insulin (IAA-first) or GAD (GADA-first) by unsupervised clustering of temporal lipidome, identifying a subgroup of children having early onset of each initial autoantibody, i.e., IAA-first by 12 months and GADA-first by 21 months, consistent with population-wide early seroconversion age. Differential analysis showed that infants having reduced plasma ascorbic acid and cholesterol experienced IAA-first earlier, while early onset of GADA-first was preceded by reduced sphingomyelins at infancy. Plasma 25(OH)D prior to either autoantibody was lower in T1D progressors compared with nonprogressors, with simultaneous lower diglycerides, lysophosphatidylcholines, triglycerides, and alanine before GADA-first. Plasma ascorbic acid and 25(OH)D at infancy were lower in HLA-DR3/DR4 children among IA case subjects but not in matched control subjects, implying gene expression dysregulation of circulating vitamins as latent signals for IA or T1D progression.

Background: Prevention and treatment of iodine deficiency-related diseases remain an important public health challenge. Iodine deficiency can have severe health consequences, such as cretinism, goi...

Publisher's version (útgefin grein), Iodine is an essential nutrient for growth and development during infancy. Data on iodine status of exclusively (EBF) and partially breastfed (PBF) infants as well as breast milk iodine concentration (BMIC) are scarce. We aimed to assess (a) infant iodine nutrition at the age of 5.5 months by measuring urinary iodine concentration (UIC) in EBF (n = 32) and PBF (n = 28) infants and (b) mothers' breast milk iodine concentration (n = 57). Sixty mother–infant pairs from three primary health care centres in Reykjavik and vicinities provided urine and breast milk samples for iodine analysis and information on mothers' habitual diet. The mother–infant pairs were participants of the IceAge2 study, which focuses on factors contributing to infant growth and development, including body composition and breast-milk energy content. The median (25th–75th percentiles) UIC was 152 (79–239) μg/L, with no significant difference between EBF and PBF infants. The estimated median iodine intake ranged from 52 to 86 μg/day, based on urinary data (assuming an average urine volume of 300–500 ml/day and UIC from the present study). The median (25th–75th percentiles) BMIC was 84 (48–114) μg/L. It is difficult to conclude whether iodine status is adequate in the present study, as no ranges for median UIC reflecting optimal iodine nutrition exist for infants. However, the results add important information to the relatively sparse literature on UIC, BMIC, and iodine intake of breastfed infants., We would like to thank all the infants and their mothers for participat-ing in the study. Furthermore, we are grateful to the primary healthcare centres for their part in the recruitment process. The Iceage2study (Growth and Body Composition in Breastfed Infants: Study onAge of Introduction of Complementary Foods in Iceland, clinicaltrials.gov identifier NCT02586571) was funded by the University of Iceland Research fund. Analysis of UIC and BMIC was funded by NordicWorking Group for Diet, Food & Toxicology (NKMT), and EUthyroidproject (funded by the Horizon 2020 Framework Programme forResearch and Innovation) with Grant agreement 634453.

Background: Knowledge about the population's iodine status is important, because it allows adjustment of iodine supply and prevention of iodine deficiency. The validity and comparability of iodine-related population studies can be improved by standardization, which was one of the goals of the EUthyroid project. The aim of this study was to establish the first standardized map of iodine status in Europe by using standardized urinary iodine concentration (UIC) data. Materials and Methods: We established a gold-standard laboratory in Helsinki measuring UIC by inductively coupled plasma mass spectrometry. A total of 40 studies from 23 European countries provided 75 urine samples covering the whole range of concentrations. Conversion formulas for UIC derived from the gold-standard values were established by linear regression models and were used to postharmonize the studies by standardizing the UIC data of the individual studies. Results: In comparison with the EUthyroid gold-standard, mean UIC measurements were higher in 11 laboratories and lower in 10 laboratories. The mean differences ranged from −36.6% to 49.5%. Of the 40 postharmonized studies providing data for the standardization, 16 were conducted in schoolchildren, 13 in adults, and 11 in pregnant women. Median standardized UIC was

Historically, Iceland has been an iodine sufficient nation due to notably high fish and dairy consumption. Due to this fact the country does not have a strategy related to iodine status, such as fortification of salt. Iodine status of pregnant women has only been assessed once before in Iceland (in 2009). The median UIC was found to be 180 μg/L, which was in line with the recommended range of 150–249 μg/L defined by the World Health Organization (WHO). Intake of fish and dairy has decreased considerably in the past 10 years. The aim of the present study was to re-evaluate the iodine status of pregnant women in Iceland using data from the PREWICE study (PREgnant Women in ICEland). Subjects were women (n = 983; 73% of the eligible sample) attending their first ultrasound appointment in gestational weeks 11–14 in the period October 2017-March 2018. Spot urine samples were collected for assessment of urinary iodine concentration (UIC) and creatinine. The ratio of iodine to creatinine (I/Cr) was calculated. Diet was assessed using a semi-quantitative food frequency questionnaire (FFQ), which provided information on main dietary sources of iodine in the population studied (dairy and fish). The median UIC (95% CI) and I/Cr of the study population was 89 μg/L (42, 141) and 100 (94, 108) μg/g, respectively. UIC increased with higher frequency of dairy intake, ranging from median UIC of 55 (35, 79) μg/L for women consuming dairy products < 1 time per week to 124 (98, 151) μg/L in the group consuming dairy > 2 times per day (p for trend < 0.001). A small group of women reporting complete avoidance of fish (n = 18) had UIC of 50 (21, 123) μg/L and significantly lower I/Cr compared with those who did not report avoidance of fish (58 (34,134) μg/g vs. 100 (94, 108) μg/g, p = 0.041). Women taking supplements containing iodine (n = 34, 3.5%) had higher UIC compared with those who did not take supplements (141 (77, 263) vs. 87 (82, 94) μg/L, p = 0.037. For the first time, insufficient iodine status is being observed in an Icelandic population. There is an urgent need for a public health action aiming at improving iodine status of women of childbearing age in Iceland.

Background: Studies indicate that mild to moderate iodine deficiency in pregnancy may have a long-term negative impact on child neurodevelopment. These effects are likely mediated via changes in maternal thyroid function, since iodine is essential for the production of thyroid hormones. However, the impact of iodine availability on thyroid function during pregnancy and on thyroid function reference ranges are understudied. The aim of this study was to investigate the association between iodine intake and thyroid function during pregnancy. Design: In a population-based pregnancy cohort including 2910 pregnant women participating in The Norwegian Mother and Child Cohort Study, we explored cross sectional associations of maternal iodine intake measured (1) by a food frequency questionnaire and (2) as iodine concentration in a spot urine sample, with plasma thyroid hormones and antibodies. Results: Biological samples were collected in mean gestational week 18.5 (standard deviation 1.3) and diet was assessed in gestational week 22. Median iodine intake from food was 121lg/day (interquartile range 90, 160), and 40% reported use of iodine-containing supplements in pregnancy. Median urinary iodine concentration (UIC) was 59lg/L among those who did not use supplements and 98lg/L in the women reporting current use at the time of sampling, indicating mild to moderate iodine deficiency in both groups. Iodine intake as measured by the food frequency questionnaire was not associated with the outcome measures, while UIC was inversely associated with FT3 (p=0.002) and FT4 (p

BackgroundCoffee is widely consumed and contains many bioactive compounds, any of which may impact pathways related to disease development. ObjectiveTo identify individual metabolite changes in response to coffee. MethodsWe profiled the metabolome of fasting serum samples collected from a previously reported single‐blinded, three‐stage clinical trial. Forty‐seven habitual coffee consumers refrained from drinking coffee for 1 month, consumed four cups of coffee/day in the second month and eight cups/day in the third month. Samples collected after each coffee stage were subject to nontargeted metabolomic profiling using UPLC‐ESI‐MS/MS. A total of 733 metabolites were included for univariate and multivariate analyses. ResultsA total of 115 metabolites were significantly associated with coffee intake (P < 0.05 and Q < 0.05). Eighty‐two were of known identity and mapped to one of 33 predefined biological pathways. We observed a significant enrichment of metabolite members of five pathways (P < 0.05): (i) xanthine metabolism: includes caffeine metabolites, (ii) benzoate metabolism: reflects polyphenol metabolite products of gut microbiota metabolism, (iii) steroid: novel but may reflect phytosterol content of coffee, (iv) fatty acid metabolism (acylcholine): novel link to coffee and (v) endocannabinoid: novel link to coffee. ConclusionsThe novel metabolites and candidate pathways we have identified may provide new insight into the mechanisms by which coffee may be exerting its health effects.

Aims/hypothesis We investigated the association of early serum fatty acid composition with the risk of type 1 diabetes-associated autoimmunity. Our hypothesis was that fatty acid status during infancy is related to type 1 diabetes-associated autoimmunity and that long-chain n-3 fatty acids, in particular, are associated with decreased risk. Methods We performed a nested case-control analysis within the Finnish Type 1 Diabetes Prediction and Prevention Study birth cohort, carrying HLA-conferred susceptibility to type 1 diabetes (n = 7782). Serum total fatty acid composition was analysed by gas chromatography in 240 infants with islet autoimmunity and 480 control infants at the age of 3 and 6 months. Islet autoimmunity was defined as repeated positivity for islet cell autoantibodies in combination with at least one of three selected autoantibodies. In addition, a subset of 43 infants with primary insulin autoimmunity (i.e. those with insulin autoantibodies as the first autoantibody with no concomitant other autoantibodies) and a control group (n = 86) were analysed. A third endpoint was primary GAD autoimmunity defined as GAD autoantibody appearing as the first antibody without other concomitant autoantibodies (22 infants with GAD autoimmunity; 42 infants in control group). Conditional logistic regression was applied, considering multiple comparisons by false discovery rate

Background: Inadequate stores or intakes of essential minerals in pregnancy, or too high exposure to both toxic and essential elements, can have adverse effects on mother and child. The main aims of this study were to 1) describe the concentrations and patterns of essential and toxic elements measured in maternal whole blood during pregnancy; 2) identify dietary, lifestyle and sociodemographic determinants of element status; and 3) explore the impact of iron deficiency on blood element concentrations. Methods: This study is based on blood samples collected from 2982 women in gestational week 18 in The Norwegian Mother and Child Cohort study (MoBa) which were analyzed as part of the Norwegian Environmental Biobank. We derived blood element patterns by exploratory factor analysis, and associations between blood element patterns and diet were explored using sparse partial least squares (sPLS) regression. Results: Blood concentrations were determined for the essential elements (in the order of most abundant) Zn > Cu > Se > Mn > Mo > Co, and the toxic metals Pb > As > Hg > Cd > Tl. The concentrations were in ranges that were similar to or sometimes more favorable than in other pregnant and non-pregnant European women. We identified two blood element patterns; one including Zn, Se and Mn and another including Hg and As. For the Zn-Se-Mn pattern, use of multimineral supplements was the most important dietary determinant, while a high score in the Hg-As pattern was mainly determined by seafood consumption. Concentrations of Mn, Cd and Co were significantly higher in women with iron deficiency (plasma ferritin < 12 μg/L) than in women with plasma ferritin ≥ 12 μg/L. Conclusion: Our study illustrates complex relationships and coexistence of essential and toxic elements. Their potential interplay adds to the challenges of studies investigating health effects related to either diet or toxicants.

Summary Background Maternal diet during pregnancy may contribute to the risk of offspring adiposity. Objectives The objective of the study is to explore the associations between maternal antenatal dietary fatty acid intake and the risk of offspring overweight and obesity at the ages of 2 to 7 years. Methods In a prospective Finnish birth cohort with 3807 mother–child pairs, maternal diet in late pregnancy was assessed with a food frequency questionnaire. Intakes of total fatty acids and individual saturated, monounsaturated and polyunsaturated fatty acids (PUFAs) were calculated. Generalized estimating equation models were used to study the associations of maternal dietary variables with repeatedly measured offspring overweight and obesity. Results In girls, maternal intake ratio of n-6:n-3 PUFAs had a U-shaped association with obesity (adjusted OR for the lowest 2.0 [95% CI 1.27–3.20] and the highest 1.7 [1.03–2.73] vs. the two middle quartiles of n-6:n-3 PUFAs, p = 0.01). In boys, arachidonic acid (20:4n-6): docosahexaenoic acid + eicosapentaenoic acid ratio was associated with obesity (adjusted OR for the lowest 1.0 [0.60–1.57] and the highest 0.5 [0.26–0.88] vs. the two middle quartiles, p = 0.02). Saturated fatty acids and monounsaturated fatty acids were not associated with overweight or obesity in either sex. Conclusions Maternal intakes of PUFAs in late pregnancy were associated with risk of later obesity differently in girls and boys.

Fruit and vegetable intake has been associated with a reduced risk of many chronic diseases. These foods are the main dietary source of carotenoids. The aim of the present study was to evaluate the associations between dietary intake and serum concentrations of &alpha, and &beta, carotene in a sample of young Finnish children from the population-based birth cohort of the Type 1 Diabetes Prediction and Prevention (DIPP) Study. The current analysis comprised 3-day food records and serum samples from 207 children aged 1, 2 and 3 years. Spearman and partial correlations, as well as a cross-classification analyses, were used to assess the relationship between dietary intake and the corresponding biomarkers. Serum concentrations of &alpha, carotene were significantly higher among the 1-year-old compared to the 3-year-old children. Dietary intakes of &alpha, carotene correlated significantly with their respective serum concentrations in all age groups, the association being highest at the age of 1 year (&alpha, carotene r = 0.48, p &lt, 0.001 and &beta, carotene r = 0.47, 0.001), and lowest at the age of 3 years (&alpha, carotene r = 0.44, carotene r = 0.30, 0.001). A cross-classification showed that 72&ndash, 81% of the participants were correctly classified to the same or adjacent quartile, when comparing the reported dietary intakes and the concentrations of the corresponding carotenoid in serum. The 3-day food record seems to be reasonably valid in the assessment of root vegetable consumption among young Finnish children. Root vegetables were the main dietary source of both carotenoids in all age groups. The high consumption of commercial baby foods among the 1-year-old children was reflected in the relatively high dietary intake and serum concentration of both carotenoids.

Inadequate iodine intake has been identified in populations considered iodine replete for decades. The objective of the current study is to evaluate urinary iodine concentration (UIC) and the probability of adequate iodine intake in subgroups of the Norwegian population defined by age, life stage and vegetarian dietary practice. In a cross-sectional survey, we assessed the probability of adequate iodine intake by two 24-h food diaries and UIC from two fasting morning spot urine samples in 276 participants. The participants included children (n = 47), adolescents (n = 46), adults (n = 71), the elderly (n = 23), pregnant women (n = 45), ovo-lacto vegetarians (n = 25), and vegans (n = 19). In all participants combined, the median (95% CI) UIC was 101 (90, 110) µg/L, median (25th, 75th percentile) calculated iodine intake was 112 (77, 175) µg/day and median (25th, 75th percentile) estimated usual iodine intake was 101 (75, 150) µg/day. According to WHOs criteria for evaluation of median UIC, iodine intake was inadequate in the elderly, pregnant women, vegans and non-pregnant women of childbearing age. Children had the highest (82%) and vegans the lowest (14%) probability of adequate iodine intake according to reported food and supplement intakes. This study confirms the need for monitoring iodine intake and status in nationally representative study samples in Norway.

Coffee is widely consumed and contains many bioactive compounds, any of which may impact pathways related to disease development. Our objective was to identify individual lipid changes in response to coffee drinking. We profiled the lipidome of fasting serum samples collected from a previously reported single blinded, three-stage clinical trial. Forty-seven habitual coffee consumers refrained from drinking coffee for 1 month, consumed 4 cups of coffee/day in the second month and 8 cups/day in the third month. Samples collected after each coffee stage were subject to quantitative lipidomic profiling using ion-mobility spectrometry&ndash, mass spectrometry. A total of 853 lipid species mapping to 14 lipid classes were included for univariate analysis. Three lysophosphatidylcholine (LPC) species including LPC (20:4), LPC (22:1) and LPC (22:2), significantly decreased after coffee intake (p &lt, 0.05 and q &lt, 0.05). An additional 72 species mapping to the LPC, free fatty acid, phosphatidylcholine, cholesteryl ester and triacylglycerol classes of lipids were nominally associated with coffee intake (p &lt, 0.05 and q &gt, 0.05), 58 of these decreased after coffee intake. In conclusion, coffee intake leads to lower levels of specific LPC species with potential impacts on glycerophospholipid metabolism more generally.

Background Secreted frizzled-related protein 5 (Sfrp5) has been described as novel adipokine in mice with insulin-sensitising and anti-inflammatory properties similar to adiponectin. The aim of this study was to compare serum concentrations and determinants of Sfrp5, its pro-inflammatory antagonist wingless-type MMTV integration site family member (Wnt)5a and adiponectin in humans and their regulation by coffee. Material and methods Serum concentrations of Sfrp5, Wnt5a and adiponectin were measured in 47 individuals who participated in a coffee intervention study. Associations with demographic, metabolic and immunological variables and regulation of serum levels by different amounts of daily coffee intake were analysed. Results At baseline, fasting serum Sfrp5 levels ranged between 96 and 4056 ng/mL. Sfrp5 was directly correlated with a surrogate of insulin resistance (homeostasis model assessment of insulin resistance/HOMA-IR; r = 0·32, P

Background The antioxidant hypothesis regarding the risk of asthma in childhood has resulted in inconsistent findings. Some data indicate that the role of antioxidants in childhood asthma risk may have a critical time window of effect, but only a well-designed longitudinal cohort study can clarify this hypothesis. Objective To study the longitudinal associations between serum carotenoid and tocopherol concentrations during the first 4 years of life and asthma risk by the age of 5 years. Methods Based on a case-control design nested within a Finnish birth cohort, 146 asthma cases were matched to 270 controls on birth time, sex, genetic risk, and birth place. Non-fasting blood samples were collected at the ages of 1, 1.5, 2, 3, and 4 years and serum carotenoids and tocopherols were analysed. Parents reported the presence and age at start of persistent doctor-diagnosed asthma in the child at the age of 5 years. Data analyses were conducted using generalized estimating equations. Results We did not find strong associations between serum carotenoids and tocopherols and the risk of asthma based on age-specific and longitudinal analyses. Both lower and higher quarters of α-carotene and γ-tocopherol increased the risk of asthma. Conclusions The current findings do not support the suggestion that the increased prevalence of asthma may be a consequence of decreased intake of antioxidant nutrients. Moreover, we did not confirm any critical time window of impact of antioxidants on asthma risk. Replication of these findings in similar longitudinal settings will strengthen this evidence base.

Previous studies suggest that consumption of chokeberries may improve cardiovascular disease risk factor profiles. We hypothesized that chokeberries (Aronia mitschurinii) have beneficial effects on blood pressure, low-grade inflammation, serum lipids, serum glucose, and platelet aggregation in patients with untreated mild hypertension. A total of 38 participants were enrolled into a 16-week single blinded crossover trial. The participants were randomized to use cold-pressed 100% chokeberry juice (300 mL/d) and oven-dried chokeberry powder (3 g/d), or matched placebo products in random order for 8 weeks each with no washout period. The daily portion of chokeberry products was prepared from approximately 336 g of fresh chokeberries. Urinary excretion of various polyphenols and their metabolites increased during the chokeberry period, indicating good compliance. Chokeberries decreased daytime blood pressure and low-grade inflammation. The daytime ambulatory diastolic blood pressure decreased (-1.64 mm Hg, P = .02), and the true awake ambulatory systolic (-2.71 mm Hg, P = .077) and diastolic (-1.62 mm Hg, P = .057) blood pressure tended to decrease. The concentrations of interleukin (IL) 10 and tumor necrosis factor α decreased (-1.9 pg/mL [P = .008] and -0.67 pg/mL [P = .007], respectively) and tended to decrease for IL-4 and IL-5 (-4.5 pg/mL [P = .084] and -0.06 pg/mL [P = .059], respectively). No changes in serum lipids, lipoproteins, glucose, and in vitro platelet aggregation were noted with the chokeberry intervention. These findings suggest that inclusion of chokeberry products in the diet of participants with mildly elevated blood pressure has minor beneficial effects on cardiovascular health.

Article, 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., published version, http://purl.org/eprint/status/PeerReviewed

High intake of fruits and vegetables is associated with reduced cardiovascular risk. A number of fruits and vegetables are rich in anthocyanins, which constitute a subgroup of the flavonoids. Anthocyanins have demonstrated anti-inflammatory and anti-oxidative properties, and anthocyanin-rich interventions have indicated beneficial effects on blood pressure and other cardiovascular risk factors. We assessed whether a purified anthocyanin supplement improves cardiovascular metabolic risk factors and markers of inflammation and oxidative stress in prehypertensive participants, and whether plasma polyphenols are increased 1-3 h following intake. In all, 31 men between 35-51 years with screening blood pressure >140/90 mm Hg without anti-hypertensive or lipid-lowering medication, were randomized in a double-blinded crossover study to placebo versus 640 mg anthocyanins daily. Treatment durations were 4 weeks with a 4-week washout. High-density lipoprotein (HDL)-cholesterol and blood glucose were significantly higher after anthocyanin versus placebo treatment (P=0.043 and P=0.024, respectively). No effects were observed on inflammation or oxidative stress in vivo, except for von Willebrand factor, which was higher in the anthocyanin period (P=0.007). Several plasma polyphenols increased significantly 1-3 h following anthocyanin intake. The present study strengthens the evidence that anthocyanins may increase HDL-cholesterol levels, and this is demonstrated for the first time in prehypertensive and non-dyslipidemic men. However, no other beneficial effects in the short term were found on pathophysiological markers of cardiovascular disease.

Bilberries are abundant in polyphenols. Dietary polyphenols have been associated with strategies for prevention and treatment of chronic inflammatory diseases. We investigated the effect of bilberry juice on serum and plasma biomarkers of inflammation and antioxidant status in subjects with elevated levels of at least one risk factor for cardiovascular disease (CVD).In a randomized controlled trial, participants consumed either bilberry juice (n = 31) or water (n = 31) for 4 weeks.Supplementation with bilberry juice resulted in significant decreases in plasma concentrations of C-reactive protein (CRP), interleukin (IL)-6, IL-15, and monokine induced by INF-gamma (MIG). Unexpectedly, an increase in the plasma concentration of tumor nuclear factor-alpha (TNF-alpha) was observed in the bilberry group. CRP, IL-6, IL15, MIG, and TNF-alpha are all target genes of nuclear factor- kappa B (NF-kappaB), -a transcription factor that is crucial in orchestrating inflammatory responses. Plasma quercetin and p-coumaric acid increased in the bilberry group, otherwise no differences were observed for clinical parameters, oxidative stress or antioxidant status. Furthermore, we studied the effect of polyphenols from bilberries on lipopolysaccharide (LPS)-induced NF-kappaB activation in a monocytic cell line. We observed that quercetin, epicatechin, and resveratrol inhibited NF-kappaB activation.These findings suggest that supplementation with bilberry polyphenols may modulate the inflammation processes. Further testing of bilberry supplementation as a potential strategy in prevention and treatment of chronic inflammatory diseases is warranted.

Berries are a rich source of various polyphenols. The objective of this study was to investigate the bioavailability of polyphenols from berries. Middle-aged subjects (n = 72) consumed moderate amounts of berry or control products for 8 weeks in a randomized, placebo-controlled dietary intervention trial. Average intake of berries was 160 g/day (bilberries, lingonberries, black currants, and chokeberries). Plasma and urine polyphenols were analyzed by GC-MS and HPLC and berry polyphenols by HPLC. The total intake of polyphenols was 837 mg/day. Plasma quercetin, p-coumaric acid, 3-hydroxyphenylacetic acid, caffeic acid, protocatechuic acid, vanillic acid, homovanillic acid, and 3-(3-hydroxyphenyl)propionic acid increased significantly from the baseline in the berry group compared to the control group (p < 0.05). The urinary excretion of quercetin, p-coumaric acid, and 3-hydroxyphenylacetic acid increased significantly in the berry group compared to the control group (p < 0.05). In conclusion, a number of polyphenols are bioavailable from a diet containing moderate amounts of blue and red berries.

Background: The aetiology of colorectal cancer has strong dietary links, and there may be an association between coffee and colorectal cancer risk. Objective: To study the effects of filtered (low levels of kahweol/cafestol) and unfiltered (high levels of kahweol/cafestol) coffee on tumour formation in multiple intestinal neoplasia (ApcMin/+) mice. Design: ApcMin/+ mice (n=11 per group) were fed for 9 weeks with 10% w/w of these two types of coffee. Coffee was served as a dietary ingredient mixed with a semi-synthetic AIN-93G-based diet. Plasma levels of caffeine and paraxanthine were used as compliance markers. At the end of the feeding period intestinal tumour number and size were determined. The levels of β-catenin and cyclin D1, two cell-signalling proteins important to the progression of neoplasia, were also analysed in the tumour tissue. Results: Plasma caffeine and paraxanthine concentrations were 3.2±1.4 and 1.7±0.4 µmol l-1 in the filtered coffee group and 3.6±2.3 and 1.6±0.6 µmol l-1 in the unfiltered coffee group. The level of plasma xanthines was below detection in the control group. The total number of tumours was equal between the dietary groups: 29 for the control, 30 (p=0.767) for the filtered coffee and 29 (p=0.430) for the unfiltered coffee groups. The levels of β-catenin and cyclin D1 in the nuclear fraction of the tumour tissue were also the same between the groups. Conclusions: Filtered or unfiltered coffee (10% w/w) does not exert antitumorigenic activity in ApcMin/+ mice or change β-catenin and cyclin D1 signalling in the adenoma tissues. The results suggest that coffee does not change neoplasia progression in this animal model. Keywords: ApcMin/+ mice; caffeine; coffee; colon cancer; paraxanthine

Berries are a rich source of various polyphenols, including the flavonoid quercetin. In this article, the results of three intervention studies investigating the bioavailability of quercetin from berries are reviewed. In the first study, we investigated the short-term kinetics of quercetin after consumption of black currant juice and showed that quercetin is rapidly absorbed from it. In the second study, we showed that plasma quercetin levels increase up to 50% in subjects consuming 100 g/day of bilberries, black currants, and lingonberries as a part of their normal diets for 2 mo. In the third study, healthy subjects consumed a diet high or low in vegetables, berries, and other fruit for 6 wk. Quercetin concentrations nearly doubled in the high-vegetable, -berry, and -other fruit group and decreased by 30% in subjects consuming less of these foods than normally. The results showed that plasma quercetin is bioavailable from a diet containing berries and indicate that it may be a good biomarker of fruit and vegetable intake in general.

The bioactivities, dietary sources, bioavailability, metabolism, and epidemiology of 3 flavonoids, quercetin, hesperetin, and naringenin, are reviewed. The use of their plasma concentrations as biomarkers of dietary intake is also discussed. The compounds were chosen because of their significant dietary intakes and promising bioactivities, and in the case of quercetin, because epidemiological studies suggest protection against cardiovascular disease.

Background: Coffee consumption is associated with a decreased risk of type 2 diabetes. Suggested mechanisms underlying the association have included attenuation of subclinical inflammation and a reduction in oxidative stress. Objective: The aim was to investigate the effects of daily coffee consumption on biomarkers of coffee intake, subclinical inflammation, oxidative stress, glucose, and lipid metabolism. Design: Habitual coffee drinkers (n = 47) refrained for 1 mo from coffee drinking; in the second month they consumed 4 cups of filtered coffee/d and in the third month 8 cups of filtered coffee/d (150 mL/cup). Blood samples were analyzed by gas chromatography‐ mass spectrometry, bead-based multiplex technology, enzymelinked immunosorbent assay, or immunonephelometry. Results: Coffee consumption led to an increase in coffee-derived compounds, mainly serum caffeine, chlorogenic acid, and caffeic acid metabolites. Significant changes were also observed for serum concentrations of interleukin-18, 8-isoprostane, and adiponectin (medians: ‐8%, 216%, and 6%, respectively; consumption of 8 compared with 0 cups coffee/d). Serum concentrations of total cholesterol, HDL cholesterol, and apolipoprotein A-I increased significantly by 12%, 7%, and 4%, respectively, whereas the ratios of LDL to HDL cholesterol and of apolipoprotein B to apolipoprotein A-I decreased significantly by 8% and 9%, respectively (8 compared with 0 cups coffee/d). No changes were seen for markers of glucose metabolism in an oral-glucose-tolerance test. Conclusions: Coffee consumption appears to have beneficial effects on subclinical inflammation and HDL cholesterol, whereas no changes in glucose metabolism were found in our study. Furthermore, many coffee-derived methylxanthines and caffeic acid metabolites appear to be useful as biomarkers of coffee intake. Am J Clin Nutr 2010;91:950‐7.

Background The role of circulating levels of total homocysteine tHcy in the development of coronary heart disease (CHD) is still under debate. One reason for conflicting results between previous studies on homocysteine and heart diseases could be consequence of different interactions between homocysteine and genes in different study populations. Many genetic factors play a role in folate-homocysteine metabolism, like functional polymorphism (Val108Met) in the Catechol-O-methyltransferase (COMT) gene. Methodology and Findings Our aim was to examine the role of COMT Val158Met polymorphism and interaction of this polymorphism with serum tHcy and folate concentration on the risk of acute coronary and events in middle-aged men from eastern Finland. A population-based prospective cohort of 792 men aged 46–64 years was examined as part of the Kuopio Ischaemic Heart Disease Risk Factor Study. During an average follow-up of 9.3 years, there were 69 acute coronary events in men with no previous history of CHD. When comparing the COMT low activity genotype with the others, we found an age and examination year adjusted hazard rate ratio (HRR) of 1.73 (95% confidence interval (CI), 1.07–2.79), and an age, examination year, serum LDL and HDL cholesterol, and triglyceride concentration, systolic blood pressure and smoking adjusted HRR of 1.77 (95% CI, 1.05–2.77). Although serum tHcy concentration was not statistically significantly associated with acute coronary events (HRR for the highest third versus others 1.52, 95% CI, 0.93–2.49), subjects with both high serum tHcy and the COMT low activity genotype had an additionally increased adjusted risk of HRR 2.94 (95% CI 1.50–5.76) as compared with other men. Conclusions This prospective cohort study suggests that the functional COMT Val158Met polymorphism is associated with increased risk of acute coronary events and it may interact with high serum tHcy levels.

The flavanones naringenin and hesperetin exhibit estrogenic, anticarcinogenic and antioxidative properties. Orange juice and grapefruit juice contain high amounts of these compounds, and therefore their intake from the diet can be relatively high. No data are available regarding plasma concentrations or plasma kinetics of flavanones. The objectives of this study were to develop methods allowing the analysis of naringenin and hesperetin from plasma and urine and to study their plasma kinetics and urinary excretion. We also wanted to assess whether plasma or urine flavanone concentrations can be used as biomarkers of intake. Healthy volunteers ingested orange juice (five women and three men) or grapefruit juice (two women and three men) once (8 mL/kg). Eleven blood samples and urine were collected between 0 and 24 h after juice administration. Flavanones were analyzed by HPLC with electrochemical detection. Naringenin and hesperetin were bioavailable from the studied juices, but interindividual variation in bioavailability was remarkable. The resulting plasma concentrations were comparatively high, and the peak plasma concentrations (C(max)) were 0.6 +/- 0.4 micromol/L (means +/- SD) for naringenin from orange juice and 6.0 +/- 5.4 micromol/L for naringenin from grapefruit juice. The corresponding value for hesperetin from orange juice was 2.2 +/- 1.6 micromol/L. The elimination half-lives were between 1.3 and 2.2 h, and therefore plasma concentrations reflect short-term intake. The relative urinary excretion varied depending on the flavanone source and dose and was 30.2 +/- 25.5% and 1.1 +/- 0.8% for naringenin from grapefruit juice and orange juice, respectively, and 5.3 +/- 3.1% for hesperetin from orange juice. The considerable difference in the relative urinary excretion of naringenin from the two juices was most likely caused by dose-dependent renal clearance rather than differences in bioavailability (as indicated by the similar C(max)-to-dose ratios). The results indicate that urine flavanone concentrations are not good biomarkers of dietary intake. We conclude that because of the relatively high concentrations of flavanones in plasma after ingestion of orange juice or grapefruit juice, considerable health effects could ensue in individuals consuming them regularly.

A validated method for the quantitation of trace levels of quercetin from human plasma to be used in pharmacokinetic and biomarker studies is presented. Quercetin conjugates were hydrolysed enzymatically, plasma proteins were removed using a Bond Elut C18 extraction column and additional interferences were removed by extracting them into a toluene–dichloromethane mixture. The HPLC system consisted of an Inertsil ODS-3 column (250×4.0 mm) and a mobile phase with 59% methanol in phosphate buffer (pH 2.4). High selectivity and a low quantitation limit (0.63 μg/l) were achieved by using electrochemical detection at a low potential. The method has excellent reproducibility: R.S.D. values of peak-heights were 2% and 7.9%, respectively, for within-day and between-day precision. The method was applied to a small scale study of quercetin pharmacokinetics and quercetin was shown to be absorbed from a 20 mg dose. No free quercetin was detected in plasma and no evidence of significant amounts of quercetin glycosides in plasma was found.

Background Berries are a particularly rich source of polyphenols. They also contain other bioactive substances, such as vitamin C. Previous studies indicated that the consumption of polyphenol-rich foods (eg, cocoa, tea, and red wine) may induce beneficial changes in pathways related to cardiovascular health. Whether the consumption of berries has similar effects is unknown. Objective We aimed to investigate the effects of berry consumption on hemostatic function, serum lipids, and blood pressure (BP). Design Middle-aged unmedicated subjects (n = 72) with cardiovascular risk factors consumed moderate amounts of berry or control products for 8 wk in a single-blind, randomized, placebo-controlled intervention trial. Results Berry consumption inhibited platelet function as measured with a platelet function analyzer (using collagen and ADP as platelet activator) [changes: 11% and -1.4% in the berry and control groups, respectively; P = 0.018, analysis of covariance (ANCOVA)]. Plasma biomarkers of platelet activation, coagulation, and fibrinolysis did not change during the intervention. Serum HDL-cholesterol concentrations increased significantly more (P = 0.006, ANCOVA) in the berry than in the control group (5.2% and 0.6%, respectively), but total cholesterol and triacylglycerol remained unchanged. Systolic BP decreased significantly (P = 0.050, ANCOVA); the decrease mostly occurred in subjects with high baseline BP (7.3 mm Hg in highest tertile; P = 0.024, ANCOVA). Polyphenol and vitamin C concentrations in plasma increased, whereas other nutritional biomarkers (ie, folate, tocopherols, sodium, and potassium) were unaffected. Conclusion The consumption of moderate amounts of berries resulted in favorable changes in platelet function, HDL cholesterol, and BP. The results indicate that regular consumption of berries may play a role in the prevention of cardiovascular disease.