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Background: Current guidelines aim to limit the dietary glycemic index (GI) and intake of saturated fatty acids (SFA). Several studies have shown favorable effects of low-GI or low-SFA diets on intrahepatic lipid content (IHL), but these studies were performed under overfeeding conditions or extreme differences in GI or SFA to maximize the contrast between diets. By combining changes in GI and SFA, we can mimic how people can improve their diet in a realistic setting., Objectives: We investigated the effect on liver fat content and substrate metabolism of both reducing GI and replacing SFA with polyunsaturated fat in practically realistic amounts under isocaloric conditions., Design and Methods: In a randomized crossover study, thirteen overweight participants consumed two diets, one high in GI and SFA (high GI/SFA) and one low in GI and SFA (low GI/SFA) with identical macronutrient composition, for two weeks each. Diets were equal in caloric content, consisted of habitual food items, and had a macronutrient composition that can be easily achieved in daily life. At the end of each intervention, IHL content/composition and liver glycogen were measured by magnetic resonance spectroscopy. Additionally, fasted and postprandial hepatic de novo lipogenesis and glycemic and metabolic responses were investigated., Results: IHL was significantly lower (-28%) after the two-week low-GI/SFA diet (2.4 ± 0.5% 95% CI [1.4, 3.4]) than after the two-week high-GI/SFA diet (3.3 ± 0.6% 95% CI [1.9, 4.7], p < 0.05). Although hepatic glycogen content, hepatic de novo lipogenesis, hepatic lipid composition, and substrate oxidation during the night were similar between the two diets, the glycemic response to the low-GI/SFA diet was reduced ( p < 0.05)., Conclusions: Changes in macronutrient quality can already have drastic effects on liver fat content and postprandial glycemia after two weeks and even when energy content and the percentage of total fat and carbohydrate remains unchanged.

Introduction: Substantial response heterogeneity is commonly seen in dietary intervention trials. In larger datasets, this variability can be exploited to identify predictors, for example genetic and/or phenotypic baseline characteristics, associated with response in an outcome of interest., Objective: Using data from a placebo-controlled crossover study (the FINGEN study), supplementing with two doses of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs), the primary goal of this analysis was to develop models to predict change in concentrations of plasma triglycerides (TG), and in the plasma phosphatidylcholine (PC) LC n-3 PUFAs eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA), after fish oil (FO) supplementation. A secondary goal was to establish if clustering of data prior to FO supplementation would lead to identification of groups of participants who responded differentially., Methods: To generate models for the outcomes of interest, variable selection methods (forward and backward stepwise selection, LASSO and the Boruta algorithm) were applied to identify suitable predictors. The final model was chosen based on the lowest validation set root mean squared error (RMSE) after applying each method across multiple imputed datasets. Unsupervised clustering of data prior to FO supplementation was implemented using k-medoids and hierarchical clustering, with cluster membership compared with changes in plasma TG and plasma PC EPA + DHA., Results: Models for predicting response showed a greater TG-lowering after 1.8 g/day EPA + DHA with lower pre-intervention levels of plasma insulin, LDL cholesterol, C20:3 n -6 and saturated fat consumption, but higher pre-intervention levels of plasma TG, and serum IL-10 and VCAM-1. Models also showed greater increases in plasma PC EPA + DHA with age and female sex. There were no statistically significant differences in PC EPA + DHA and TG responses between baseline clusters., Conclusion: Our models established new predictors of response in TG (plasma insulin, LDL cholesterol, C20:3n-6, saturated fat consumption, TG, IL-10 and VCAM-1) and in PC EPA + DHA (age and sex) upon intervention with fish oil. We demonstrate how application of statistical methods can provide new insights for precision nutrition, by predicting participants who are most likely to respond beneficially to nutritional interventions., Competing Interests: Authors AW and EZ were employed by the Unilever Foods Innovation Centre Wageningen, which markets food products. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Potter, Horgan, Wanders, Zandstra, Zock, Fisk, Minihane, Calder, Mathers and de Roos.)

Background Habitual intake of long-chain omega-3 fatty acids, especially eicosapentaenoic and docosahexaenoic acid (EPA+DHA) from fish, has been associated with a lower risk of fatal coronary heart disease (CHD) in population-based studies. Whether that is also the case for patients with CHD is not yet clear. We studied the associations of dietary and circulating EPA+DHA and alpha-linolenic acid, a plant-derived omega-3 fatty acids, with long-term mortality risk after myocardial infarction. Methods and Results We analyzed data from 4067 Dutch patients with prior myocardial infarction aged 60 to 80 years (79% men, 86% on statins) enrolled in the Alpha Omega Cohort from 2002 to 2006 (baseline) and followed through 2018. Baseline intake of fish and omega-3 fatty acids were assessed through a validated 203-item food frequency questionnaire and circulating omega-3 fatty acids were assessed in plasma cholesteryl esters. Hazard ratios (HRs) with 95% CIs were obtained from Cox regression analyses. During a median follow-up period of 12 years, 1877 deaths occurred, of which 515 were from CHD and 834 from cardiovascular diseases. Dietary intake of EPA+DHA was significantly inversely associated with only CHD mortality (HR, 0.69 [0.52-0.90] for >200 versus ≤50 mg/d; HR, 0.92 [0.86-0.98] per 100 mg/d). Similar results were obtained for fish consumption (HR CHD , 0.74 [0.53-1.03] for >40 versus ≤5 g/d; P trend : 0.031). Circulating EPA+DHA was inversely associated with CHD mortality (HR, 0.71 [0.53-0.94] for >2.52% versus ≤1.29%; 0.85 [0.77-0.95] per 1-SD) and also with cardiovascular diseases and all-cause mortality. Dietary and circulating alpha-linolenic acid were not significantly associated with mortality end points. Conclusions In a cohort of Dutch patients with prior myocardial infarction, higher dietary and circulating EPA+DHA and fish intake were consistently associated with a lower CHD mortality risk. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03192410.

Context: Weight gain during adulthood increases cardiometabolic disease risk, possibly through adipocyte hypertrophy., Objective: We aimed to study the specific metabolomic profile of adult weight gain, and to examine its association with adipocyte volume., Methods: Nuclear magnetic resonance-based metabolomics were measured in the Netherlands Epidemiology of Obesity (NEO) study (n = 6347, discovery) and Oxford Biobank (n = 6317, replication). Adult weight gain was calculated as the absolute difference between body mass index (BMI) at middle age and recalled BMI at age 20 years. We performed linear regression analyses with both exposures BMI at age 20 years and weight gain, and separately with BMI at middle age in relation to 149 serum metabolomic measures, adjusted for age, sex, and multiple testing. Additionally, subcutaneous abdominal adipocyte biopsies were collected in a subset of the Oxford Biobank (n = 114) to estimate adipocyte volume., Results: Mean (SD) weight gain was 4.5 (3.7) kg/m2 in the NEO study and 3.6 (3.7) kg/m2 in the Oxford Biobank. Weight gain, and not BMI at age 20 nor middle age, was associated with concentrations of 7 metabolomic measures after successful replication, which included polyunsaturated fatty acids, small to medium low-density lipoproteins, and total intermediate-density lipoprotein. One SD weight gain was associated with 386 μm3 (95% CI, 143-629) higher median adipocyte volume. Adipocyte volume was associated with lipoprotein particles specific for adult weight gain., Conclusion: Adult weight gain is associated with specific metabolomic alterations of which the higher lipoprotein concentrations were likely contributed by larger adipocyte volumes, presumably linking weight gain to cardiometabolic disease., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Purpose: Palmitic and stearic acids have different effects on fasting serum lipoproteins. However, the effects on postprandial lipemia and glycemia are less clear. Also, the effects of a second meal may differ from those of the first meal. Therefore, we studied the effects of two consecutive mixed meals high in palmitic acid- or stearic acid-rich fat blends on postprandial lipemia and glycemia., Methods: In a randomized, crossover study, 32 participants followed 4-week diets rich in palmitic or stearic acids, At the end of each dietary period, participants consumed two consecutive meals each containing ± 50 g of the corresponding fat blend., Results: Postprandial concentrations of triacylglycerol (diet-effect: - 0.18 mmol/L; p = 0.001) and apolipoprotein B48 (diet-effect: - 0.68 mg/L; p = 0.002) were lower after stearic-acid than after palmitic-acid intake. Consequently, total (iAUC 0-8 h ) and first meal (iAUC 0-4 h ) responses were lower after stearic-acid intake (p ≤ 0.01). Second meal responses (iAUC 4-8 h ) were not different. Postprandial changes between the diets in non-esterified fatty acids (NEFA) and C-peptide differed significantly over time (p < 0.001 and p = 0.020 for diet*time effects, respectively), while those for glucose and insulin did not. The dAUC 0-8 h , dAUC 0-4 h , and dAUC 4-8 h for NEFA were larger after stearic-acid intake (p ≤ 0.05). No differences were observed in the iAUCs of C-peptide, glucose, and insulin. However, second meal responses for glucose and insulin (iAUC 4-8 h) tended to be lower after stearic-acid intake (p < 0.10)., Conclusion: Consumption of the stearic acid-rich meals lowered postprandial lipemia as compared with palmitic acid. After the second stearic acid-rich meal, concentrations of C-peptide peaked earlier and those of NEFA decreased more. Clinical trial registry This trial was registered at clinicaltrials.gov as NCT02835651 on July 18, 2016., (© 2021. The Author(s).)

Dietary macronutrient composition may affect hepatic liver content and its associated diseases, but the results from human intervention trials have been equivocal or underpowered. We aimed to assess the effects of dietary macronutrient composition on liver fat content by conducting a systematic review and meta-analysis of randomized controlled trials in adults. Four databases (PubMed, Embase, Web of Science, and COCHRANE Library) were systematically searched for trials with isocaloric diets evaluating the effect of dietary macronutrient composition (energy percentages of fat, carbohydrates, and protein, and their specific types) on liver fat content as assessed by magnetic resonance techniques, computed tomography or liver biopsy. Data on change in liver fat content were pooled by random or fixed-effects meta-analyses and expressed as standardized mean difference (SMD). We included 26 randomized controlled trials providing data for 32 comparisons on dietary macronutrient composition. Replacing dietary fat with carbohydrates did not result in changes in liver fat (12 comparisons, SMD 0.01 (95% CI -0.36; 0.37)). Unsaturated fat as compared with saturated fat reduced liver fat content (4 comparisons, SMD -0.80 (95% CI -1.09; -0.51)). Replacing carbohydrates with protein reduced liver fat content (5 comparisons, SMD -0.33 (95% CI -0.54; -0.12)). Our meta-analyses showed that replacing carbohydrates with total fat on liver fat content was not effective, while replacing carbohydrates with proteins and saturated fat with unsaturated fat was. More well-performed and well-described studies on the effect of types of carbohydrates and proteins on liver fat content are needed, especially studies comparing proteins with fats.

Background: The saturated fatty acid stearic acid (C18:0) lowers HDL cholesterol compared with palmitic acid (C16:0). However, the ability of HDL particles to promote cholesterol efflux from macrophages (cholesterol efflux capacity; CEC) may better predict coronary heart disease (CHD) risk than HDL cholesterol concentrations., Objective: We examined effects of exchanging dietary palmitic acid for stearic acid on ATP-binding cassette transporter A1 (ABCA1)-mediated CEC, and other conventional and emerging cardiometabolic risk makers., Design: In a double-blind, randomized, crossover study with two 4-week isocaloric intervention periods, 34 healthy men and postmenopausal women (61.5 ± 5.7 years, BMI: 25.4 ± 2.5 kg/m 2 ) followed diets rich in palmitic acids or stearic acids. Difference in intakes was 6% of daily energy. ABCA1-mediated CEC was measured from J774 macrophages to apolipoprotein (apo)B-depleted serum., Results: Compared with the palmitic-acid diet, the stearic-acid diet lowered serum LDL cholesterol (-0.14 mmol/L; p = 0.010), HDL cholesterol (-0.09 mmol/L; p=<0.001), and apoA1 (-0.05 g/L; p < 0.001). ABCA1-mediated CEC did not differ between diets (p = 0.280). Cholesteryl ester transfer protein (CETP) mass was higher on stearic acid (0.11 mg/L; p = 0.003), but CETP activity was comparable. ApoB100 did not differ, but triacylglycerol concentrations tended to be higher on stearic acid (p = 0.100). Glucose concentrations were comparable. Effects on insulin and C-peptide were sex-dependent. In women, the stearic-acid diet increased insulin concentrations (1.57 μU/mL; p = 0.002), while in men, C-peptide concentrations were lower (-0.15 ng/mL; p = 0.037). Interleukin 6 (0.15 pg/mL; p = 0.039) and tumor necrosis factor alpha (0.18 pg/mL; p = 0.005), but not high-sensitivity C-reactive protein, were higher on stearic acid. Soluble intracellular adhesion molecule (9 ng/mL; p = 0.033), but not soluble vascular cell adhesion molecule and endothelial-selectin concentrations decreased after stearic-acid consumption., Conclusions: As expected, stearic-acid intake lowered LDL cholesterol, HDL cholesterol, and apoA1. Insulin sensitivity in women and low-grade inflammation might be unfavorably affected by stearic-acid intake. However, palmitic-acid and stearic-acid intakes did not differently affect ABCA1-mediated CEC., Clinical Trial Registry: This trial was registered at clinicaltrials.gov as NCT02835651., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: The relation between dietary and circulating linoleic acid (18:2 n-6, LA), glucose metabolism and liver function is not yet clear. Associations of dietary and circulating LA with glucose metabolism and liver function markers were investigated., Methods: Cross-sectional analyses in 633 black South Africans (aged > 30 years, 62% female, 51% urban) without type 2 diabetes at baseline of the Prospective Urban Rural Epidemiology study. A cultural-sensitive 145-item food-frequency questionnaire was used to collect dietary data, including LA (percentage of energy; en%). Blood samples were collected to measure circulating LA (% total fatty acids (FA); plasma phospholipids), plasma glucose, glycosylated hemoglobin (HbA1c), serum gamma-glutamyl transferase (GGT), alanine (ALT) and aspartate aminotransferase (AST). Associations per 1 standard deviation (SD) and in tertiles were analyzed using multivariable regression., Results: Mean (±SD) dietary and circulating LA was 6.8 (±3.1) en% and 16.0 (±3.5) % total FA, respectively. Dietary and circulating LA were not associated with plasma glucose or HbA1c (β per 1 SD: - 0.005 to 0.010, P > 0.20). Higher dietary LA was generally associated with lower serum liver enzymes levels. One SD higher circulating LA was associated with 22% lower serum GGT (β (95% confidence interval): - 0.25 (- 0.31, - 0.18), P < 0.001), but only ≤9% lower for ALT and AST. Circulating LA and serum GGT associations differed by alcohol use and locality., Conclusion: Dietary and circulating LA were inversely associated with markers of impaired liver function, but not with glucose metabolism. Alcohol use may play a role in the association between LA and liver function., Trial Registration: PURE North-West Province South Africa study described in this manuscript is part of the PURE study. The PURE study is registered in ClinicalTrials.gov (Identifier: NCT03225586; URL).

Objective: To study plasma and dietary linoleic acid (LA) in relation to type 2 diabetes risk in post-myocardial infarction (MI) patients., Research Design and Methods: We included 3,257 patients aged 60-80 years (80% male) with a median time since MI of 3.5 years from the Alpha Omega Cohort and who were initially free of type 2 diabetes. At baseline (2002-2006), plasma LA was measured in cholesteryl esters, and dietary LA was estimated with a 203-item food-frequency questionnaire. Incident type 2 diabetes was ascertained through self-reported physician diagnosis and medication use. Hazard ratios (with 95% CIs) were calculated by Cox regressions, in which dietary LA isocalorically replaced the sum of saturated (SFA) and trans fatty acids (TFA)., Results: Mean ± SD circulating and dietary LA was 50.1 ± 4.9% and 5.9 ± 2.1% energy, respectively. Plasma and dietary LA were weakly correlated (Spearman r = 0.13, P < 0.001). During a median follow-up of 41 months, 171 patients developed type 2 diabetes. Plasma LA was inversely associated with type 2 diabetes risk (quintile [Q]5 vs. Q1: 0.44 [0.26, 0.75]; per 5%: 0.73 [0.62, 0.86]). Substitution of dietary LA for SFA+TFA showed no association with type 2 diabetes risk (Q5 vs. Q1: 0.78 [0.36, 1.72]; per 5% energy: 1.18 [0.59, 2.35]). Adjustment for markers of de novo lipogenesis attenuated plasma LA associations., Conclusions: In our cohort of post-MI patients, plasma LA was inversely related to type 2 diabetes risk, whereas dietary LA was not related. Further research is needed to assess whether plasma LA indicates metabolic state rather than dietary LA in these patients., (© 2019 by the American Diabetes Association.)

Background: Circulating odd-chain fatty acids pentadecanoic (15:0) and heptadecanoic acid (17:0) are considered to reflect dairy intake. In cohort studies, higher circulating 15:0 and 17:0 were associated with lower type 2 diabetes risk. A recent randomized controlled trial in humans suggested that fiber intake also increased circulating 15:0 and 17:0, potentially resulting from fermentation by gut microbes. We examined the associations of dairy and fiber intake with circulating 15:0 and 17:0 in patients with a history of myocardial infarction (MI)., Methods: We performed cross-sectional analyses in a subsample of 869 Dutch post-MI patients of the Alpha Omega Cohort who had data on dietary intake and circulating fatty acids. Dietary intakes (g/d) were assessed using a 203-item food frequency questionnaire. Circulating 15:0 and 17:0 (as % of total fatty acids) were measured in plasma phospholipids (PL) and cholesteryl esters (CE). Spearman correlations ( r s ) were computed between intakes of total dairy, dairy fat, fiber, and circulating 15:0 and 17:0., Results: Patients were on average 69 years old, 78% was male and 21% had diabetes. Total dairy intake comprised predominantly milk and yogurt (69%). Dairy fat was mainly derived from cheese (47%) and milk (15%), and fiber was mainly from grains (43%). Circulating 15:0 in PL was significantly correlated with total dairy and dairy fat intake (both r s  = 0.19, p  < 0.001), but not with dietary fiber intake ( r  = 0.11). Circulating 17:0 in PL was correlated both with dairy intake ( s  = 0.05, p  = 0.11). Circulating 17:0 in PL was correlated both with dairy intake ( r s  = 0.14 for total dairy and 0.11 for dairy fat, p  < 0.001), and fiber intake ( r s  = 0.19, p  < 0.001). Results in CE were roughly similar, except for a weaker correlation of CE 17:0 with fiber ( r s  = 0.11, p  = 0.001). Circulating 15:0 was highest in those with high dairy intake irrespective of fiber intake, while circulating 17:0 was highest in those with high dairy and fiber intake., Conclusions: In our cohort of post-MI patients, circulating 15:0 was associated with dairy intake but not fiber intake, whereas circulating 17:0 was associated with both dairy and fiber intake. These data suggest that cardiometabolic health benefits previously attributed to 17:0 as a biomarker of dairy intake may partly be explained by fiber intake., Competing Interests: Competing interestsAJW and PLZ are employed at Unilever R&D, The Netherlands; JMG received financial support from Unilever for epidemiological studies of dietary and circulating fatty acids; KP, LKK, JdG, no competing interest., (© The Author(s). 2019.)

Endothelial dysfunction is involved in the development of atherosclerosis, which precedes asymptomatic structural vascular alterations as well as clinical manifestations of cardiovascular disease (CVD). Endothelial function can be assessed non-invasively using the flow-mediated dilation (FMD) technique. Flow-mediated dilation represents an endothelium-dependent, largely nitric oxide (NO)-mediated dilatation of conduit arteries in response to an imposed increase in blood flow and shear stress. Flow-mediated dilation is affected by cardiovascular (CV) risk factors, relates to coronary artery endothelial function, and independently predicts CVD outcome. Accordingly, FMD is a tool for examining the pathophysiology of CVD and possibly identifying subjects at increased risk for future CV events. Moreover, it has merit in examining the acute and long-term impact of physiological and pharmacological interventions in humans. Despite concerns about its reproducibility, the available evidence shows that highly reliable FMD measurements can be achieved when specialized laboratories follow standardized protocols. For this purpose, updated expert consensus guidelines for the performance of FMD are presented, which are based on critical appraisal of novel technical approaches, development of analysis software, and studies exploring the physiological principles underlying the technique. Uniformity in FMD performance will (i) improve comparability between studies, (ii) contribute to construction of reference values, and (iii) offer an easy accessible and early marker of atherosclerosis that could complement clinical symptoms of structural arterial disease and facilitate early diagnosis and prediction of CVD outcomes., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Objective: To investigate the association between intakes of n-6 polyunsaturated fatty acids (PUFAs) and type 2 diabetes risk in three prospective cohort studies of U.S. men and women., Research Design and Methods: We followed 83,648 women from the Nurses' Health Study (NHS) (1980-2012), 88,610 women from NHSII (1991-2013), and 41,771 men from the Health Professionals Follow-Up Study (HPFS) (1986-2012). Dietary data were collected every 2-4 years by using validated food-frequency questionnaires. Self-reported incident diabetes, identified biennially, was confirmed by using a validated supplementary questionnaire., Results: During 4.93 million person-years of follow-up, 18,442 type 2 diabetes cases were documented. Dietary n-6 PUFAs accounted for 4.4-6.8% of total energy, on average, and consisted primarily of linoleic acid (LA) (≥98%). In multivariate-adjusted models, hazard ratios (95% CIs) of type 2 diabetes risk comparing extreme n-6 PUFA quintiles (highest vs. lowest) were 0.91 (0.85, 0.96) ( P trend = 0.002) for total n-6 PUFAs and 0.92 (0.87, 0.98) ( P trend = 0.01) for LA. In an isocaloric substitution model, diabetes risk was 14% (95% CI 5%, 21%) ( P = 0.002) lower when LA isocalorically replaced saturated fats (5% of energy), 17% (95% CI 9%, 24%) ( P < 0.001) lower for trans fats (2% of energy), or 9% (95% CI 17%, 0.1%) ( P = 0.047) lower for carbohydrates (5% of energy). Replacing n-3 PUFAs or monounsaturated fats with LA was not significantly associated with type 2 diabetes risk., Conclusions: Our study provides additional evidence that LA intake is inversely associated with risk of type 2 diabetes, especially when replacing saturated fatty acids, trans fats, or carbohydrates., (© 2019 by the American Diabetes Association.)

Rationale: Dietary monounsaturated fatty acids (MUFAs) can come from both plant and animal sources with divergent nutrient profiles that may potentially obscure the associations of total MUFAs with chronic diseases., Objective: To investigate the associations of cis-MUFA intake from plant (MUFA-P) and animal (MUFA-A) sources with total and cause-specific mortality., Methods and Results: We followed 63 412 women from the NHS (Nurses' Health Study; 1990-2012) and 29 966 men from the HPFS (Health Professionals Follow-Up Study; 1990-2012). MUFA-Ps and MUFA-As were calculated based on data collected through validated food frequency questionnaires administered every 4 years and updated food composition databases. During 1 896 864 person-years of follow-up, 20 672 deaths occurred. Total MUFAs and MUFA-Ps were inversely associated with total mortality after adjusting for potential confounders, whereas MUFA-As were associated with higher mortality. When MUFA-Ps were modeled to isocalorically replace other macronutrients, hazard ratios (HRs, 95% CIs) of total mortality were 0.84 (0.77-0.92; P<0.001) for replacing saturated fatty acids, 5% of energy); 0.86 (0.82-0.91; P<0.001) for replacing refined carbohydrates (5% energy); 0.91 (0.85-0.97; P<0.001) for replacing trans fats (2% energy), and 0.77 (0.71-0.82; P<0.001) for replacing MUFA-As (5% energy). For isocalorically replacing MUFA-As with MUFA-Ps, HRs (95% CIs) were 0.74 (0.64-0.86; P<0.001) for cardiovascular mortality; 0.73 (0.65-0.82; P<0.001) for cancer mortality, and 0.82 (0.73-0.91; P<0.001) for mortality because of other causes., Conclusions: Higher intake of MUFA-Ps was associated with lower total mortality, and MUFA-As intake was associated with higher mortality. Significantly lower mortality risk was observed when saturated fatty acids, refined carbohydrates, or trans fats were replaced by MUFA-Ps, but not MUFA-As. These data suggest that other constituents in animal foods, such as saturated fatty acids, may confound the associations for MUFAs when they are primarily derived from animal products. More evidence is needed to elucidate the differential associations of MUFA-Ps and MUFA-As with mortality.

Background and Aims: Population-based studies often use plasma fatty acids (FAs) as objective indicators of FA intake, especially for n-3 FA and linoleic acid (LA). The relation between dietary and circulating FA in cardiometabolic patients is largely unknown. We examined whether dietary n-3 FA and LA were reflected in plasma lipid pools in post-myocardial infarction (MI) patients., Methods and Results: Patients in Alpha Omega Cohort filled out a 203-item food-frequency questionnaire from which eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), and LA intake were calculated. Circulating individual FA (% total FA) were assessed in cholesteryl esters (CE; n = 4066), phospholipids (PL; n = 838), and additionally in total plasma for DHA and LA (n = 739). Spearman correlation coefficients (r s ) were calculated for dietary vs. circulating FA. Circulating FA were also compared across dietary FA quintiles, overall and in subgroups by sex, obesity, diabetes, statin use, and high alcohol intake. Patients were on average 69 years old and 79% was male. Moderate correlations between dietary and circulating levels were observed for EPA (r s ∼0.4 in CE and PL) and DHA (r s ∼0.5 in CE and PL, ∼0.4 in total plasma), but not for ALA (r s ∼0.0). Weak correlations were observed for LA (r s 0.1 to 0.2). Plasma LA was significantly lower in statin users and in patients with a high alcohol intake., Conclusions: In post-MI patients, dietary EPA and DHA were well reflected in circulating levels. This was not the case for LA, which may partly be influenced by alcohol use and statins., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

The objective of this meta-analysis was to investigate the effects of plant-derived polyunsaturated fatty acids (PUFAs) on glucose metabolism and insulin resistance. Scopus and PubMed databases were searched until January 2018. Eligible studies were randomized controlled feeding trials that investigated the effects of a diet high in plant-derived PUFA as compared with saturated fatty acids (SFA) or carbohydrates and measured markers of glucose metabolism and insulin resistance as outcomes. Data from 13 relevant studies (19 comparisons of plant-derived PUFA with control) were retrieved. Plant-derived PUFA did not significantly affect fasting glucose (-0.01 mmol/L (95 % CI - 0.06 to 0.03 mmol/L)), but lowered fasting insulin by 2.6 pmol/L (-4.9 to -0.2 pmol/L) and homeostatic model assessment-insulin resistance (HOMA-IR) by 0.12 units (-0.23 to - 0.01 units). In dose-response analyses, a 5% increase in energy (En%) from PUFA significantly reduced insulin by 5.8 pmol/L (95% CI -10.2 to -1.3 pmol/L), but not glucose (change -0.07, 95% CI -0.17 to 0.04 mmol/L) and HOMA-IR (change - 0.24, 95% CI -0.56 to 0.07 units). In subgroup analyses, studies with higher PUFA dose (upper tertiles) reduced insulin (-6.7, -10.5 to -2.9 pmol/L) and HOMA-IR (-0.28, -0.45 to -0.12 units), but not glucose (-0.09, 95% CI -0.18 to 0.01 mmol/L), as compared with an isocaloric control. Subgroup analyses showed no differences in effects between SFA and carbohydrates as replacement nutrients (p interaction ≥0.05). Evidence from randomized controlled trials indicated that plant-derived PUFA as an isocaloric replacement for SFA or carbohydrates probably reduces fasting insulin and HOMA-IR in populations without diabetes., Competing Interests: Competing interests: The authors of this manuscript have the following competing interests: AJW, WAMB, PLZ, MA are employed by Unilever, Vlaardingen, the Netherlands. Unilever markets food products made of vegetable oils such as dressings. Unilever has divested its spreads business, which is since July 2, 2018 operating under the name Upfield™. JMG received research funding from Unilever for studies on fatty acids and cardiovascular disease. IAB supervises a student whose project is partly funded by Unilever.

Results of intervention studies on the effects of α-linolenic acid (ALA; C18 : 3n-3) on blood pressure (BP) are conflicting. Discrepancies between studies may be due to differences in study population, as subjects with increased baseline BP levels may be more responsive. Therefore, we examined specifically the effects of ALA on 24-h ambulatory blood pressure (ABP) in (pre-)hypertensive subjects. In a double-blind, randomised, placebo-controlled parallel study, fifty-nine overweight and obese adults (forty males and nineteen females) with (pre-)hypertension (mean age of 60 (sd 8) years) received daily 10 g refined cold-pressed flaxseed oil, providing 4·7 g (approximately 2 % of energy) ALA (n 29) or 10 g of high-oleic sunflower oil as control (n 30) for 12 weeks. Compliance was excellent as indicated by vial count and plasma phospholipid fatty-acid composition. Compared with control, the changes of -1·4 mmHg in mean arterial pressure (MAP; 24 h ABP) after flaxseed oil intake (95 % CI -4·8, 2·0 mmHg, P=0·40) of -1·5 mmHg in systolic BP (95 % CI -6·0, 3·0 mmHg, P=0·51) and of -1·4 mmHg in diastolic BP (95 % CI -4·2, 1·4 mmHg, P=0·31) were not statistically significant. Also, no effects were found for office BP and for MAP, systolic BP, and diastolic BP when daytime and night-time BP were analysed separately and for night-time dipping. In conclusion, high intake of ALA, about 3-5 times recommended daily intakes, for 12 weeks does not significantly affect BP in subjects with (pre-)hypertension.

Background: Monounsaturated fatty acids (MUFAs) improve blood lipid profiles in intervention studies, but prospective evidence with regard to MUFA intake and coronary heart disease (CHD) risk is limited and controversial., Objective: We investigated the associations of cis MUFA intake from plant (MUFA-P) and animal (MUFA-A) sources with CHD risk separately among 63,442 women from the Nurses' Health Study (1990-2012) and 29,942 men from the Health Professionals Follow-Up Study (1990-2012)., Design: Intakes of MUFA-Ps and MUFA-As were calculated by using validated food-frequency questionnaires collected every 4 y. Incident nonfatal myocardial infarction and fatal CHD cases (n = 4419) were confirmed by medical record review., Results: During follow-up, MUFA-Ps and MUFA-As contributed 5.8-7.9% and 4.2-5.4% of energy on average, respectively. When MUFA-Ps were modeled to isocalorically replace other macronutrients, HRs (95% CIs) of CHD were 0.83 (0.68, 1.00) for saturated fatty acids (SFAs; 5% of energy), 0.86 (0.76, 0.97) for refined carbohydrates (5% of energy), and 0.80 (0.70, 0.91) for trans fats (2% of energy) (P = 0.05, 0.01, and 0.001, respectively). For MUFA-As, corresponding HRs (95% CIs) for the same isocaloric substitutions were 1.04 (0.79, 1.38) for SFAs, 1.11 (0.91, 1.35) for refined carbohydrates, and 0.88 (0.77, 1.01) for trans fats (P = 0.76, 0.31, and 0.08, respectively). Given the common food sources of SFAs and MUFA-As (Spearman correlation coefficients of 0.81-0.83 between these groups of fatty acids), we further estimated CHD risk when the sum of MUFA-As and SFAs (5% of energy) was replaced by MUFA-Ps, and found that the HR was 0.81 (95% CI: 0.73, 0.90; P < 0.001) for this replacement., Conclusions: The largely different associations of MUFA-Ps and MUFA-As with CHD risk suggest that plant-based foods are the preferable sources of MUFAs for CHD prevention. These findings are observational and warrant confirmation in intervention settings. This study was registered at clinicaltrials.gov as NCT00005152 and NCT00005182.

Aims/hypothesis: Glycaemic markers and fasting insulin are frequently measured outcomes of intervention studies. To extrapolate accurately the impact of interventions on the risk of diabetes incidence, we investigated the size and shape of the associations of fasting plasma glucose (FPG), 2 h post-load glucose (2hPG), HbA 1c , fasting insulin and HOMA-IR with incident type 2 diabetes mellitus., Methods: The study population included 1349 participants aged 50-75 years without diabetes at baseline (1989) from a population-based cohort in Hoorn, the Netherlands. Incident type 2 diabetes was defined by the WHO 2011 criteria or known diabetes at follow-up. Logistic regression models were used to determine the associations of the glycaemic markers, fasting insulin and HOMA-IR with incident type 2 diabetes. Restricted cubic spline logistic regressions were conducted to investigate the shape of the associations., Results: After a mean follow-up duration of 6.4 (SD 0.5) years, 152 participants developed diabetes (11.3%); the majority were screen detected by high FPG. In multivariate adjusted models, ORs (95% CI) for incident type 2 diabetes for the highest quintile in comparison with the lowest quintile were 9.0 (4.4, 18.5) for FPG, 6.1 (2.9, 12.7) for 2hPG, 3.8 (2.0, 7.2) for HbA 1c , 1.9 (0.9, 3.6) for fasting insulin and 2.8 (1.4, 5.6) for HOMA-IR. The associations of FPG and HbA 1c with incident diabetes were non-linear, rising more steeply at higher values., Conclusions/interpretation: FPG was most strongly associated with incident diabetes, followed by 2hPG, HbA 1c , HOMA-IR and fasting insulin. The strong association with FPG is probably because FPG is the most frequent marker for diabetes diagnosis. Non-linearity of associations between glycaemic markers and incident type 2 diabetes should be taken into account when estimating future risk of type 2 diabetes based on glycaemic markers.

Aims: To evaluate whether participant characteristics and way of expressing circulating fatty acids (FA) influence the strengths of associations between self-reported intake and circulating levels of linoleic acid (LA), alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA)., Methods: Cross-sectional analyses were performed in pooled data from the CODAM (n = 469) and Hoorn (n = 702) studies. Circulating FA were measured by gas liquid chromatography and expressed as proportions (% of total FA) and concentrations (µg/mL). Dietary intakes were calculated from a validated food frequency questionnaire. Effects of participant characteristics on associations between dietary and circulating FA were calculated using interaction analyses., Results: Standardized regression coefficients between dietary FA and proportions of circulating FA (% of total FA) were LA β = 0.28, ALA β = 0.13, EPA β = 0.34, and DHA β = 0.45. Body mass index (BMI), waist circumference, and presence of CVD influenced associations for LA; gender influenced LA, EPA, and DHA; alcohol intake influenced LA and DHA; and glucose tolerance status influenced ALA (p values interaction <0.05). Coefficients for circulating FA as concentrations were LA β = 0.19, ALA β = 0.10, EPA β = 0.31, and DHA β = 0.41., Conclusions: This study suggests that characteristics such as BMI, alcohol intake, and expressing circulating FA as proportions or concentrations, influence associations between dietary and circulating FA., (© 2018 S. Karger AG, Basel.)

Background: Replacement of saturated fatty acids (SFAs) with unsaturated fatty acids (UFAs), especially polyunsaturated fatty acids (PUFAs), has been associated with a lower risk of ischemic heart disease (IHD). Whether this replacement is beneficial for drug-treated patients with cardiac disease is not yet clear., Objective: In a prospective study of Dutch patients with cardiac disease (Alpha Omega Cohort), we examined the risk of cardiovascular disease (CVD) and IHD mortality when the sum of SFAs and trans fatty acids (TFAs) was theoretically replaced by total UFAs, PUFAs, or cis monounsaturated fatty acids (MUFAs)., Design: We included 4146 state-of-the-art drug-treated patients aged 60-80 y with a history of myocardial infarction (79% male patients) and reliable dietary data at baseline (2002-2006). Cause-specific mortality was monitored until 1 January 2013. HRs for CVD mortality and IHD mortality for theoretical, isocaloric replacement of dietary fatty acids (FAs) in quintiles (1-5) and continuously (per 5% of energy) were obtained from Cox regression models, adjusting for demographic factors, medication use, and lifestyle and dietary factors., Results: Patients consumed, on average, 17.5% of energy of total UFAs, 13.0% of energy of SFAs, and <1% of energy of TFAs. During ∼7 y of follow-up, 372 CVD deaths and 249 IHD deaths occurred. Substitution modeling yielded significantly lower risks of CVD mortality when replacing SFAs plus TFAs with total UFAs [HR in quintile 5 compared with quintile 1: 0.45 (95% CI: 0.28, 0.72)] or PUFAs [HR: 0.66 (95% CI: 0.44, 0.98)], whereas HRs in cis MUFA quintiles were nonsignificant. HRs were similar for IHD mortality. In continuous analyses, replacement of SFAs plus TFAs with total UFAs, PUFAs, or cis MUFAs (per 5% of energy) was associated with significantly lower risks of CVD mortality (HRs between 0.68 and 0.75) and IHD mortality (HRs between 0.55 and 0.70)., Conclusion: Shifting the FA composition of the diet toward a higher proportion of UFAs may lower CVD mortality risk in drug-treated patients with cardiac disease. This study was registered at clinicaltrials.gov as NCT03192410., (© 2017 American Society for Nutrition)

Purpose: Data on the relation between linoleic acid (LA) and alpha-linolenic acid (ALA) and type 2 diabetes mellitus (T2DM) risk are scarce and inconsistent. The aim of this study was to investigate the association of serum LA and ALA with fasting and 2 h post-load plasma glucose and glycated hemoglobin (HbA1c)., Method: This study included 667 participants from third examination (2000) of the population-based Hoorn study in which individuals with glucose intolerance were overrepresented. Fatty acid profiles in serum total lipids were measured at baseline, in 2000. Diabetes risk markers were measured at baseline and follow-up in 2008. Linear regression models were used in cross-sectional and prospective analyses., Results: In cross-sectional analyses (n = 667), serum LA was inversely associated with plasma glucose, both in fasting conditions (B = -0.024 [-0.045, -0.002]) and 2 h after glucose tolerance test (B = -0.099 [-0.158, -0.039]), but not with HbA1c (B = 0.000 [-0.014, 0.013]), after adjustment for relevant factors. In prospective analyses (n = 257), serum LA was not associated with fasting (B = 0.003 [-0.019, 0.025]) or post-load glucose (B = -0.026 [-0.100, 0.049]). Furthermore, no significant associations were found between serum ALA and glucose metabolism in cross-sectional or prospective analyses., Conclusions: In this study, serum LA was inversely associated with fasting and post-load glucose in cross-sectional, but not in prospective analyses. Further studies are needed to elucidate the exact role of serum LA and ALA levels and dietary polyunsaturated fatty acids in glucose metabolism.

After the discovery that trans fat increases the risk of coronary heart disease, trans fat content of foods have considerably changed. The aim of this study was to systematically review available data on intakes of trans fat and its dietary sources in general populations worldwide. Data from national dietary surveys and population studies published from 1995 onward were searched via Scopus and websites of national public health institutes. Relevant data from 29 countries were identified. The most up to date estimates of total trans fat intake ranged from 0.3 to 4.2 percent of total energy intake (En%) across countries. Seven countries had trans fat intakes higher than the World Health Organization recommendation of 1 En%. In 16 out of 21 countries with data on dietary sources, intakes of trans fat from animal sources were higher than that from industrial sources. Time trend data from 20 countries showed substantial declines in industrial trans fat intake since 1995. In conclusion, nowadays, in the majority of countries for which data are available, average trans fat intake is lower than the recommended maximum intake of 1 En%, with intakes from animal sources being higher than from industrial sources. In the past 20 years, substantial reductions in industrial trans fat have been achieved in many countries., Competing Interests: A.J.W. and P.L.Z. are employed by Unilever; Unilever markets food products made of vegetable oils, including margarines and dressings. I.A.B. supervises a student whose project is partly funded by Unilever R & D, The Netherlands.

Objective: The aim of this study was to examine the relations between intakes of total, saturated, mono-unsaturated, poly-unsaturated and trans fatty acids (SFA, MUFA, PUFA and TFA), and their dietary sources (dairy, meat and plant) with markers of type 2 diabetes risk., Subjects/methods: This was a cross-sectional analysis of baseline data of 5675 non-diabetic, middle-aged participants of the Netherlands Epidemiology of Obesity (NEO) study. Associations between habitual dietary intake and fasting and postprandial blood glucose and insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), HOMA of β-cell function (HOMA-B) and Disposition Index were assessed through multivariable linear regression models with adjustments for demographic, lifestyle and dietary factors., Results: Mean (s.d.) intakes in percent of energy (En%) were 34.4 (5.8) for total fatty acids, 12.4 (2.9) for SFA, 12.2 (2.4) for MUFA, 6.9 (1.9) for PUFA and 0.6 (0.2) for TFA. As compared with carbohydrates, only SFA was weakly inversely associated with fasting insulin, HOMA-IR and HOMA-B. When stratified by dietary source, all fatty acids from meat were positively associated with fasting insulin - total fatty acids meat (per 5 En%: 10.0%; 95% confidence interval: 4.0, 16.3), SFA meat (per 1 En%: 3.7%; 0.4, 7.2), MUFA meat (per 1 En%: 5.0%; 2.0, 8.1), PUFA meat (per 1 En%: 17.3%; 6.0, 29.7) and TFA meat (per 0.1 En%: 10.5%; 3.2, 18.3). Similarly, all fatty acids from meat were positively associated with HOMA-IR and HOMA-B and inversely with Disposition Index., Conclusions: Our study suggests that the relations between fatty acid intakes and markers of type 2 diabetes risk may depend on the dietary sources of the fatty acids. More epidemiological studies on diet and cardiometabolic disease are needed, addressing possible interactions between nutrients and their dietary sources.

Dietary fats have important effects on the risk of cardiovascular disease (CVD). Abundant evidence shows that partial replacement of saturated fatty acids (SAFA) with unsaturated fatty acids improves the blood lipid and lipoprotein profile and reduces the risk of coronary heart disease (CHD). Low-fat diets high in refined carbohydrates and sugar are not effective. Very long-chain polyunsaturated n-3 or omega-3 fatty acids (n-3 VLCPUFA) present in fish have multiple beneficial metabolic effects, and regular intake of fatty fish is associated with lower risks of fatal CHD and stroke. Food-based guidelines on dietary fats recommend limiting the consumption of animal fats high in SAFA, using vegetable oils high in monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA), and eating fatty fish. These recommendations are part of a healthy eating pattern that also includes ample intake of plant-based foods rich in fiber and limited sugar and salt., Competing Interests: Peter L. Zock and Wendy A.M. Blom are employed by Unilever Research & Development. Joyce A. Nettleton reports personal fees from Unilever Research & Development. Gerard Hornstra reports personal fees from MVO (Netherlands Oils and Fats Industry), EPOA (European Palm Oil Alliance), and Unilever/IUNS (International Union of Nutritional Sciences). Human and Animal Rights and Informed Consent This article does not contain any new data from studies with human or animal subjects performed by any of the authors.

Objectives: Brachial artery flow-mediated dilation (FMD) is a popular technique to examine endothelial function in humans. Identifying volunteer and methodological factors related to variation in FMD is important to improve measurement accuracy and applicability., Methods: Volunteer-related and methodology-related parameters were collected in 672 volunteers from eight affiliated centres worldwide who underwent repeated measures of FMD. All centres adopted contemporary expert-consensus guidelines for FMD assessment. After calculating the coefficient of variation (%) of the FMD for each individual, we constructed quartiles (n = 168 per quartile). Based on two regression models (volunteer-related factors and methodology-related factors), statistically significant components of these two models were added to a final regression model (calculated as β-coefficient and R). This allowed us to identify factors that independently contributed to the variation in FMD%., Results: Median coefficient of variation was 17.5%, with healthy volunteers demonstrating a coefficient of variation 9.3%. Regression models revealed age (β = 0.248, P < 0.001), hypertension (β = 0.104, P < 0.001), dyslipidemia (β = 0.331, P < 0.001), time between measurements (β = 0.318, P < 0.001), lab experience (β = -0.133, P < 0.001) and baseline FMD% (β = 0.082, P < 0.05) as contributors to the coefficient of variation. After including all significant factors in the final model, we found that time between measurements, hypertension, baseline FMD% and lab experience with FMD independently predicted brachial artery variability (total R = 0.202)., Conclusion: Although FMD% showed good reproducibility, larger variation was observed in conditions with longer time between measurements, hypertension, less experience and lower baseline FMD%. Accounting for these factors may improve FMD% variability.

Worldwide, the fat composition of spreads and margarines ("spreads") has significantly changed over the past decades. Data on fat composition of US spreads are limited and outdated. This paper compares the fat composition of spreads sold in 2013 to that sold in 2002 in the USA. The fat composition of 37 spreads representing >80% of the US market sales volume was determined by standard analytical methods. Sales volume weighted averages were calculated. In 2013, a 14 g serving of spread contained on average 7.1 g fat and 0.2 g trans-fatty acids and provided 22% and 15% of the daily amounts recommended for male adults in North America of omega-3 α-linolenic acid and omega-6 linoleic acid, respectively. Our analysis of the ingredient list on the food label showed that 86% of spreads did not contain partially hydrogenated vegetable oils (PHVO) in 2013. From 2002 to 2013, based on a 14 g serving, total fat and trans-fatty acid content of spreads decreased on average by 2.2 g and 1.5 g, respectively. In the same period, the overall fat composition improved as reflected by a decrease of solid fat (from 39% to 30% of total-fatty acids), and an increase of unsaturated fat (from 61% to 70% of total-fatty acids). The majority of US spreads no longer contains PHVO and can contribute to meeting dietary recommendations by providing unsaturated fat.

Brachial artery Flow Mediated Dilation (FMD) is widely used as a non-invasive measure of endothelial function. Adherence to expert consensus guidelines on FMD measurement has been found to be of vital importance to obtain reproducible data. This article lists the literature data which was considered in the development of a tool to aid in the objective judgement of the extent to which published studies adhered to expert guidelines for FMD measurement. Application of this tool in a systematic review of FMD studies (http://dx.doi.org/10.1016/j.atherosclerosis.2016.03.011) (Greyling et al., 2016 [1]) indicated that adherence to expert consensus guidelines is strongly correlated to the reproducibility of FMD data.

Background: Brachial artery FMD is widely used as a non-invasive measure of endothelial function. Adherence to expert guidelines is believed to be of vital importance to obtain reproducible measurements. We conducted a systematic review of studies reporting on the reproducibility of the FMD in order to determine the relation between adherence to current expert guidelines for FMD measurement and its reproducibility., Methods: Medline-database was searched through July 2015 and 458 records were screened for FMD reproducibility studies reporting the mean difference and variance of repeated FMD measurements. An adherence score was assigned to each of the included studies based on reported adherence to published guidelines on the assessment of brachial artery FMD. A Typical Error Estimate (TEE) of the FMD was calculated for each included study. The relation between the FMD TEE and the adherence score was investigated by means of Pearson correlation coefficients and multiple linear regression analysis., Results: Twenty-seven studies involving 48 study groups and 1537 subjects were included in the analyses. The adherence score ranged from 2.4 to 9.2 (out of a maximum of 10) and was strongly and inversely correlated with FMD TEE (adjusted R(2) = 0.36, P < 0.01). Use of automated edge-detection software, continuous diameter measurement, true peak diameter for %FMD calculation, a stereostatic probe holder, and higher age emerged as factors associated with a lower FMD TEE., Conclusions: These data demonstrate that adherence to current expert consensus guidelines and applying contemporary techniques for measuring brachial artery FMD decreases its measurement error., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Essential fatty acids (EFA) such as α-linolenic acid (ALA) and linoleic acid (LA) are needed for healthy growth and development of children. Worldwide, reliable intake data of EFA are often lacking. The objective of this study was to investigate dietary intake of EFA in Indonesian children. Dietary intake data of 4-12-year-old children (n 45,821) from a nationally representative Indonesian survey were used to estimate median intake and distribution of population fatty acid intake. Missing data on individual fatty acids in the Indonesian food composition table were complemented through chemical analyses of national representative food samples and imputation of data from the US nutrient database. Nutrient adequacy ratios were calculated as a percentage of FAO/WHO intake recommendations. The medians of total fat intake of the children was 26·7 (10th-90th percentile 11·2-40·0) percentage of total daily energy (%E). Intakes of fatty acids were 4·05 (10th-90th percentile 1·83-7·22) %E for total PUFA, 3·36 (10th-90th percentile 1·14-6·29) %E for LA and 0·20 (10th-90th percentile 0·07-0·66) %E for ALA. Median intake of PUFA was 67 % and that of ALA 40 % of the minimum amounts recommended by FAO/WHO. These data indicate that a majority of Indonesian children has intakes of PUFA and specifically ALA that are lower than recommended intake levels. Total fat and LA intakes may be suboptimal for a smaller yet considerable proportion of children. Public health initiatives should provide practical guidelines to promote consumption of PUFA-rich foods.

Background: The association between saturated fatty acid (SFA) intake and ischemic heart disease (IHD) risk is debated., Objective: We sought to investigate whether dietary SFAs were associated with IHD risk and whether associations depended on 1) the substituting macronutrient, 2) the carbon chain length of SFAs, and 3) the SFA food source., Design: Baseline (1993-1997) SFA intake was measured with a food-frequency questionnaire among 35,597 participants from the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort. IHD risks were estimated with multivariable Cox regression for the substitution of SFAs with other macronutrients and for higher intakes of total SFAs, individual SFAs, and SFAs from different food sources., Results: During 12 y of follow-up, 1807 IHD events occurred. Total SFA intake was associated with a lower IHD risk (HR per 5% of energy: 0.83; 95% CI: 0.74, 0.93). Substituting SFAs with animal protein, cis monounsaturated fatty acids, polyunsaturated fatty acids (PUFAs), or carbohydrates was significantly associated with higher IHD risks (HR per 5% of energy: 1.27-1.37). Slightly lower IHD risks were observed for higher intakes of the sum of butyric (4:0) through capric (10:0) acid (HRSD: 0.93; 95% CI: 0.89, 0.99), myristic acid (14:0) (HRSD: 0.90; 95% CI: 0.83, 0.97), the sum of pentadecylic (15:0) and margaric (17:0) acid (HRSD: 0.91: 95% CI: 0.83, 0.99), and for SFAs from dairy sources, including butter (HRSD: 0.94; 95% CI: 0.90, 0.99), cheese (HRSD: 0.91; 95% CI: 0.86, 0.97), and milk and milk products (HRSD: 0.92; 95% CI: 0.86, 0.97)., Conclusions: In this Dutch population, higher SFA intake was not associated with higher IHD risks. The lower IHD risk observed did not depend on the substituting macronutrient but appeared to be driven mainly by the sums of butyric through capric acid, the sum of pentadecylic and margaric acid, myristic acid, and SFAs from dairy sources. Residual confounding by cholesterol-lowering therapy and trans fat or limited variation in SFA and PUFA intake may explain our findings. Analyses need to be repeated in populations with larger differences in SFA intake and different SFA food sources., (© 2016 American Society for Nutrition.)

Objective: The study aimed to determine the potential of compliance with Food-Based Dietary Guidelines (FBDG) and increased vitamin D fortification to meet the recommended intake level of vitamin D at 10 µg/day based on minimal exposure to sunlight., Methods: The main dietary sources of vitamin D were derived from national dietary surveys in adults from United Kingdom (UK) (n = 911), Netherlands (NL) (n = 1,526), and Sweden (SE) (n = 974). The theoretical increase in population vitamin D intake was simulated for the following: (1) compliance with FBDG, (2) increased level of vitamin D in commonly fortified foods, and (3) combination of both., Results: Median usual vitamin D intake was 2.4 (interquartile range 1.7-3.4) µg/day in UK, 3.4 (2.7-4.2) µg/day in NL, and 5.3 (3.9-7.3) µg/day in SE. The top 3 dietary sources of vitamin D were fish, fat-based spreads (margarines), and meat. Together, these delivered up to two-thirds of total vitamin D intake on average. Compliance with FBDG for fish, margarine, and meat increased vitamin D intake to 4.6 (4.1-5.1) µg/day in UK, 5.2 (4.9-5.5) µg/day in NL, and 7.7 (7.0-8.5) µg/day in SE. Doubling the vitamin D levels in margarines and milk would increase vitamin D intake to 4.9 (3.6-6.5) µg/day in UK, 6.6 (4.8-8.6) µg/day in NL, and 7.2 (5.2-9.8) µg/day in SE. Combining both scenarios would increase vitamin D intake to 7.9 (6.8-9.2) µg/day in UK, 8.8 (7.4-10.4) µg/day in NL, and 8.9 (6.9-11.8) µg/day in SE., Conclusion: This study highlights the potential of dietary measures to double the current vitamin D intake in adults., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

1The development of food-based dietary guidelines for prevention of cardiovascular diseases requires knowledge of the contribution of common foods to SFA and PUFA intake. We systematically reviewed available data from European countries on population intakes and dietary sources of total fat, SFA, and PUFA. Data from national dietary surveys or population studies published >1995 were searched through Medline, Web of Science, and websites of national public health institutes. Mean population intakes were compared with FAO/WHO dietary recommendations, and contributions of major food groups to overall intakes of fat and fatty acids were calculated. Fatty acid intake data from 24 European countries were included. Reported mean intakes ranged from 28.5 to 46.2% of total energy (%E) for total fat, from 8.9 to 15.5%E for SFA, from 3.9 to 11.3%E for PUFA. The mean intakes met the recommendation for total fat (20-35%E) in 15 countries, and for SFA (<10%E) in two countries, and for PUFA (6-11%E) in 15 of the 24 countries. The main three dietary sources of total fat and SFA were dairy, added fats and oils, and meat and meat products. The majority of PUFA in the diet was provided by added fats and oils, followed by cereals and cereal products, and meat and meat products. Practical applications: While many European countries meet the recommended intake levels for total fat and PUFA, a large majority of European population exceeds the widely recommended maximum 10%E for SFA. In particular animal based products, such as dairy, animal fats, and fatty meat contribute to SFA intake. Adhering to food-based dietary guidelines for prevention of CHD and other chronic diseases in Europe, including eating less fatty meats, low-fat instead of full-fat dairy, and more vegetable fats and oils will help to reduce SFA intake and at the same time increase PUFA intake. In European countries, SFA intakes are generally higher than the recommended <10%E and PUFA intakes lower than the recommended 6-11%E. Adhering to food-based dietary guidelines for prevention of CHD and other chronic diseases including eating leaner variants of meat and dairy, and more vegetable fats and oils will help to decrease SFA intake and increase PUFA intake.

Background: Phytosterols (PSs) are known to lower low-density lipoprotein cholesterol (LDL-C), an established risk factor for cardiovascular disease (CVD). Whether a high intake of PS reduces CVD risk is unknown. This observational study aimed to investigate the associations between intake of naturally occurring PSs, blood lipids and CVD risk., Methods: The study included 35,597 Dutch men and women, participating in the European Prospective Investigation into Cancer and Nutrition-the Netherlands (EPIC-NL) study. At baseline, intakes of naturally occurring PSs were estimated with a validated food frequency questionnaire and non-fasting blood lipids were measured. Occurrence of CVD, coronary heart disease (CHD) and myocardial infarction (MI) was determined through linkage with registries., Results: The average energy-adjusted PS intake at baseline was 296 mg/d (range: 83-966 mg/d). During 12.2 years of follow-up, 3047 CVD cases (8.6%) were documented. After adjustment for confounders, PS intake was not associated with risk of CVD, CHD or MI (p-value trend > 0.05); hazard ratios ranged from 0.90-0.99 for CVD, from 0.83-0.90 for CHD and from 0.80-0.95 for MI risk across quintiles of PS intake and were almost all non-significant. Higher PS intake was associated with lower total cholesterol (-0.06 mmol/l per 50 mg/d; p-value = 0.038) and lower LDL-C (-0.07 mmol/l; p-value = 0.007), particularly among men. In mediation analysis, LDL-C did not materially affect the association between PS intake and CVD risk., Conclusions: In this population with a relatively narrow range of low naturally occurring PS intakes, intake of PS was not associated with reduced CVD risk despite lower LDL-C concentrations in men., (© The European Society of Cardiology 2014.)

Background: Prospective cohort studies showed inverse associations between the intake of flavonoid-rich foods (cocoa and tea) and cardiovascular disease (CVD). Intervention studies showed protective effects on intermediate markers of CVD. This may be due to the protective effects of the flavonoids epicatechin (in cocoa and tea) and quercetin (in tea)., Objective: We investigated the effects of supplementation of pure epicatechin and quercetin on vascular function and cardiometabolic health., Design: Thirty-seven apparently healthy men and women aged 40-80 y with a systolic blood pressure (BP) between 125 and 160 mm Hg at screening were enrolled in a randomized, double-blind, placebo-controlled, crossover trial. CVD risk factors were measured before and after 4 wk of daily flavonoid supplementation. Participants received (-)-epicatechin (100 mg/d), quercetin-3-glucoside (160 mg/d), or placebo capsules for 4 wk in random order. The primary outcome was the change in flow-mediated dilation from pre- to postintervention. Secondary outcomes included other markers of CVD risk and vascular function., Results: Epicatechin supplementation did not change flow-mediated dilation significantly (1.1% absolute; 95% CI: -0.1%, 2.3%; P = 0.07). Epicatechin supplementation improved fasting plasma insulin (Δ insulin: -1.46 mU/L; 95% CI: -2.74, -0.18 mU/L; P = 0.03) and insulin resistance (Δ homeostasis model assessment of insulin resistance: -0.38; 95% CI: -0.74, -0.01; P = 0.04) and had no effect on fasting plasma glucose. Epicatechin did not change BP (office BP and 24-h ambulatory BP), arterial stiffness, nitric oxide, endothelin 1, or blood lipid profile. Quercetin-3-glucoside supplementation had no effect on flow-mediated dilation, insulin resistance, or other CVD risk factors., Conclusions: Our results suggest that epicatechin may in part contribute to the cardioprotective effects of cocoa and tea by improving insulin resistance. It is unlikely that quercetin plays an important role in the cardioprotective effects of tea. This study was registered at clinicaltrials.gov as NCT01691404., (© 2015 American Society for Nutrition.)

Background: Previous experimental models suggest that vitamin E may ameliorate periodontitis. However, epidemiologic studies show inconsistent evidence in supporting this plausible association., Objective: We investigated the association between serum α-tocopherol (αT) and γ-tocopherol (γT) and periodontitis in a large cross-sectional US population., Methods: This study included 4708 participants in the 1999-2001 NHANES. Serum tocopherols were measured by HPLC and values were adjusted by total cholesterol (TC). Periodontal status was assessed by mean clinical attachment loss (CAL) and probing pocket depth (PPD). Total periodontitis (TPD) was defined as the sum of mild, moderate, and severe periodontitis. All measurements were performed by NHANES., Results: Means ± SDs of serum αT:TC ratio from low to high quartiles were 4.0 ± 0.4, 4.8 ± 0.2, 5.7 ± 0.4, and 9.1 ± 2.7 μmol/mmol. In multivariate regression models, αT:TC quartiles were inversely associated with mean CAL (P-trend = 0.06), mean PPD (P-trend < 0.001), and TPD (P-trend < 0.001) overall. Adjusted mean differences (95% CIs) between the first and fourth quartile of αT:TC were 0.12 mm (0.03, 0.20; P-difference = 0.005) for mean CAL and 0.12 mm (0.06, 0.17; P-difference < 0.001) for mean PPD, whereas the corresponding OR for TPD was 1.65 (95% CI: 1.26, 2.16; P-difference = 0.001). In a dose-response analysis, a clear inverse association between αT:TC and mean CAL, mean PPD, and TPD was observed among participants with relatively low αT:TC. No differences were seen in participants with higher αT:TC ratios. Participants with γT:TC ratio in the interquartile range showed a significantly lower mean PPD than those in the highest quartile., Conclusions: A nonlinear inverse association was observed between serum αT and severity of periodontitis, which was restricted to adults with normal but relatively low αT status. These findings warrant further confirmation in longitudinal or intervention studies., (© 2015 American Society for Nutrition.)

Objective: Epidemiological evidence has linked consumption of black tea, produced from Camellia sinensis, with a reduced risk of cardiovascular diseases. However, intervention studies on the effects of tea consumption on blood pressure (BP) have reported inconsistent results. Our objective was to conduct a systematic literature review with meta-analysis of controlled human intervention studies examining the effect of tea consumption on BP., Methods: We systematically searched Medline, Biosis, Chemical Abstracts and EMBASE databases through July 2013. For inclusion, studies had to meet the following pre-defined criteria: 1) placebo controlled design in human adults, 2) minimum of 1 week black tea consumption as the sole intervention, 3) reported effects on systolic BP (SBP) or diastolic BP (DBP) or both. A random effects model was used to calculate the pooled overall effect of black tea on BP., Results: Eleven studies (12 intervention arms, 378 subjects, dose of 4-5 cups of tea) met our inclusion criteria. The pooled mean effect of regular tea ingestion was -1.8 mmHg (95% CI: -2.8, -0.7; P = 0.0013) for SBP and -1.3 mmHg (95% CI: -1.8, -0.8; P<0.0001) for DBP. In covariate analyses, we found that the method of tea preparation (tea extract powders versus leaf tea), baseline SBP and DBP, and the quality score of the study affected the effect size of the tea intervention (all P<0.05). No evidence of publication bias could be detected., Conclusions: Our meta-analysis indicates that regular consumption of black tea can reduce BP. Although the effect is small, such effects could be important for cardiovascular health at population level.

Dietary polyphenols, such as those from grape products, may exert beneficial effects on cardiovascular health, including anti-hypertensive effects. We investigated the effect of a specific grape seed extract (GSE) rich in low-molecular-weight polyphenolic compounds on ambulatory blood pressure (ABP) in untreated subjects with pre- and stage I hypertension. In addition, potential mechanisms that could underlie the hypothesised effect of GSE on blood pressure (BP), and platelet aggregation, were explored. The study was designed as a double-blind, placebo-controlled, randomised, parallel-group intervention study including seventy healthy subjects with systolic BP between 120 and 159 mmHg. A 1-week run-in period was followed by an 8-week intervention period, during which subjects consumed capsules containing either 300 mg/d of GSE or a placebo (microcrystalline cellulose). Before and after the intervention, daytime ABP readings, 24 h urine samples and fasting and non-fasting blood samples were taken. The mean baseline systolic BP was 135.8 (SE 1.3) mmHg and diastolic BP was 81.5 (SE 0.9) mmHg. BP values were modestly, but not significantly, affected by the polyphenol-rich GSE treatment v. placebo with an effect of - 3.0 mmHg for systolic BP (95% CI - 6.5, 0.5) and - 1.4 mmHg for diastolic BP (95% CI - 3.5, 0.6). Vasoactive markers including endothelin-1, NO metabolites and asymmetric dimethylarginine, plasma renin activity and platelet aggregation were not affected by the GSE intervention. Our findings show that consumption of polyphenol-rich GSE does not significantly lower ABP in untreated subjects with pre- and stage I hypertension.

Background: Flow-mediated dilation (FMD) is an accepted technique to quantify endothelial function and has shown to have prognostic value for future cardiovascular disease (CVD). The predictive strength of FMD in CVD patients compared to populations not diagnosed for CVD warrants further investigation. We systematically reviewed prospective studies that investigated the association between brachial FMD and future cardiovascular events, with particular focus on the role of underlying health status., Methods: To obtain eligible studies, several literature databases were systematically searched through March 2011. Pooled overall risk estimates were calculated separately for continuous risk estimates for CVD (per 1% higher FMD) and for categorical risk estimates for CVD (having high vs. low FMD), based on random-effects models., Results: A total of 23 studies including 14,753 subjects were eligible for inclusion in the meta-analysis. For studies reporting continuous risk estimates, the pooled overall CVD risk was 0.92 (95%CI: 0.88; 0.95) per 1% higher FMD. The observed association seemed stronger (P-value<0.01) in diseased populations than in asymptomatic populations (0.87 (95%CI: 0.83; 0.92) and 0.96 (95%CI: 0.92; 1.00) per 1% higher FMD, respectively). For studies reporting categorical risk estimates, the pooled overall CVD risk for high vs. low FMD was similar in both types of populations, on average 0.49 (95%CI: 0.39; 0.62)., Conclusions: Our findings show that brachial FMD is inversely associated with future CVD events, with some indications for a stronger relation in diseased populations. Endothelial dysfunction may be considered relevant for classifying subjects in terms of CVD risk., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Plant sterols (PS) are well known for their low-density lipoprotein cholesterol-lowering effect. Until recently, they were believed to have little or no impact on blood triglycerides (TG). However, studies taken individually were possibly lacking statistical power to detect modest TG decreases. This study was performed to quantify the TG-lowering effect of PS by pooling individual subject data from 12 randomised controlled trials that investigated the effects of PS on blood lipids., Methods: The main outcome variable was the control-adjusted PS effect on relative (%) and absolute (mmol/L) changes in TG. The relative and absolute changes in high-density lipoprotein cholesterol (HDL-C) were also assessed. Differences in changes of serum lipid concentrations between PS and control treatments were estimated by an ANCOVA using a random effect model which included PS intake (active or control), study and predefined subject characteristics., Results: The twelve randomised controlled trials included in total 935 hypercholesterolaemic subjects not preselected based on their baseline TG concentrations. In most studies, the PS dose ranged between 1.6 and 2.5 g/day. PS intake significantly lowered serum TG by 6.0% (95% CI: -10.7, -1.2) or 0.12 mmol/L (95% CI: -0.20, -0.04). No significant interaction was observed between PS intake and baseline TG concentrations on relative changes, but, on absolute changes, interaction was significant with larger TG decreases observed with higher TG concentrations at baseline. No effects were observed on HDL-C concentrations., Conclusions: These results show that PS exert a modest TG-lowering effect which is dependent on baseline concentrations.

Aim: To systematically review data from different countries on population intakes of total fat, saturated fatty acids (SFA) and polyunsaturated fatty acids (PUFA), and to compare these to recommendations from the Food and Agriculture Organization of the United Nations/the World Health Organization (FAO/WHO)., Methods: Data from national dietary surveys or population studies published from 1995 were searched via MEDLINE, Web of Science and websites of national public health institutes., Results: Fatty acid intake data from 40 countries were included. Total fat intake ranged from 11.1 to 46.2 percent of energy intake (% E), SFA from 2.9 to 20.9% E and PUFA from 2.8 to 11.3% E. The mean intakes met the recommendation for total fat (20-35% E), SFA (<10% E) and PUFA (6-11% E) in 25, 11 and 20 countries, respectively. SFA intake correlated with total fat intake (r = 0.76, p < 0.01) but not with PUFA intake (r = 0.03, p = 0.84). Twenty-seven countries provided data on the distribution of fatty acids intake. In 18 of 27 countries, more than 50% of the population had SFA intakes >10% E and in 13 of 27 countries, the majority of the population had PUFA intakes <6% E., Conclusions: In many countries, the fatty acids intake of adults does not meet the levels that are recommended to prevent chronic diseases. The relation between SFA and PUFA intakes shows that lower intakes of SFA in the populations are not accompanied by higher intakes of PUFA, as is recommended for preventing coronary heart disease.

Background: Epidemiological data suggest that modest red wine consumption may reduce cardiovascular disease risk. Red wine polyphenols improved human endothelial vascular function and reduced blood pressure (BP) in animal studies, but the results of human intervention studies investigating the effect of red wine polyphenols on BP are inconsistent. The objective was to investigate whether polyphenols extracted from red wine reduce peripheral and central BP in subjects with high-normal BP or grade 1 hypertension., Methods: In a double-blind, placebo-controlled three-period crossover trial, we assigned 61 subjects (mean age 61.4 ± 8.4 years) with office systolic BP 135 ± 9 mm Hg and diastolic BP 82 ± 8 mm Hg to dairy drinks containing either placebo, 280 mg red wine polyphenols, or 560 mg red wine polyphenols. After each 4-week intervention period, office and 24-h ambulatory BP measurements, and central hemodynamic measurements derived from continuous finger BP recordings were assessed., Results: Polyphenol treatment did not significantly affect 24-h BP: systolic/diastolic BP was 143 ± 2/84 ± 1 mm Hg after placebo, 143 ± 2/84 ± 1 mm Hg after 280 mg/day of red wine polyphenols, and 142 ± 2/83 ± 1 mm Hg after 560 mg/day. Neither dose of polyphenol treatment changed office or central BP, aortic augmentation index (AIx) or pulse wave reflection index., Conclusions: Intake of red wine polyphenols in two different dosages for 4 weeks did not decrease peripheral or central BP in subjects with a high normal or grade 1 hypertension. Our findings do not support the hypothesis that polyphenols account for the suggested cardiovascular benefits of red wine consumption by lowering BP.

BACKGROUND: It is important to gain insight into opportunities for secondary prevention of cardiovascular disease. Our aim was to investigate levels and trends in cardiovascular risk factors and drug treatment in Dutch post-myocardial infarction (MI) patients between 2002 and 2006 and to make comparisons with the EUROASPIRE surveys (1999-2007). METHODS: We analysed data from 4837 post-MI patients (aged 69 years, 78% men) from 32 Dutch hospitals, using baseline cross-sectional data from the Alpha Omega Trial. RESULTS: Between 2002 and 2006, significant declines were found in the prevalence of smoking (23% to 16%, p < 0.001), hypercholesterolaemia (≥5 mmol/l; 54% to 27%, p < 0.0001) and hypertension (≥140/90 mmHg; 58% to 48%, p < 0.001). The prevalence of antithrombotic drugs was high (97%). The prevalence of lipid-modifying drugs and antihypertensives was high, and increased (74% to 90%, p < 0.0001 and 82% to 93%, p < 0.001, respectively). The prevalence of obesity (27%) was high in 2002 and decreased to 24% in 2006, albeit not significantly. Diabetes prevalence was high and increased between 2002 and 2006 (18% to 22%, p = 0.02). In comparison with EUROASPIRE patients, who were on average 8-10 years younger, our study in 2006 included patients with lower levels of obesity, hypertension, hypercholesterolaemia, diabetes and lower use of antiplatelets and β-blockers, but similar levels of lipid-modifying drugs. CONCLUSIONS: This study showed that older Dutch post-MI patients were adequately treated with drugs, and that risk factors reached lower levels than in the younger EUROASPIRE patients. However, there is room for improvement in diet and lifestyle, given the high prevalence of smoking, obesity, and diabetes.

Objective: We carried out a secondary analysis in high-risk patients with a previous myocardial infarction (MI) and diabetes in the Alpha Omega Trial. We tested the hypothesis that in these patients an increased intake of the n-3 fatty acids eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and α-linolenic acid (ALA) will reduce the incidence of ventricular arrhythmias and fatal MI., Research Design and Methods: A subgroup of 1,014 post-MI patients with diabetes aged 60-80 years was randomly allocated to receive one of four trial margarines, three with an additional amount of n-3 fatty acids and one placebo for 40 months. The end points were ventricular arrhythmia-related events and fatal MI. The data were analyzed according to the intention-to-treat principle, using multivariable Cox proportional hazards models., Results: The patients consumed on average 18.6 g of margarine per day, which resulted in an additional intake of 223 mg EPA plus 149 mg DHA and/or 1.9 g ALA in the active treatment groups. During follow-up, 29 patients developed a ventricular arrhythmia-related events and 27 had a fatal MI. Compared with placebo patients, the EPA-DHA plus ALA group experienced less ventricular arrhythmia-related events (hazard ratio 0.16; 95% CI 0.04-0.69). These n-3 fatty acids also reduced the combined end-point ventricular arrhythmia-related events and fatal MI (0.28; 0.11-0.71)., Conclusions: Our results suggest that low-dose supplementation of n-3 fatty acids exerts a protective effect against ventricular arrhythmia-related events in post-MI patients with diabetes.

Fatty acid composition of the diet may influence cardiovascular risk from early childhood onwards. The objective of the present study was to perform a systematic review of dietary fat and fatty acid intakes in children and adolescents from different countries around the world and compare these with the population nutrient intake goals for prevention of chronic diseases as defined by the WHO (2003). Data on fat and fatty acid intake were mainly collected from national dietary surveys and from population studies all published during or after 1995. These were identified by searching PubMed, and through nutritionists at local Unilever offices in different countries. Fatty acid intake data from thirty countries mainly from developed countries were included. In twenty-eight of the thirty countries, mean SFA intakes were higher than the recommended maximum of 10 % energy, whereas in twenty-one out of thirty countries mean PUFA intakes were below recommended (6-10 % energy). More and better intake data are needed, in particular for developing regions of the world, and future research should determine the extent to which improvement of dietary fatty acid intake in childhood translates into lower CHD risk in later life. Despite these limitations, the available data clearly indicate that in the majority of the countries providing data on fatty acid intake, less than half of the children and adolescents meet the SFA and PUFA intake goals that are recommended for the prevention of chronic diseases.

Background: Tea consumption is associated with a lower risk of cardiovascular disease including stroke. Direct effects of tea components on the vasculature, particularly the endothelium, may partly explain this association., Objective: We performed a meta-analysis of controlled human intervention studies on the effect of tea on flow-mediated dilation (FMD) of the brachial artery, a measurement of endothelial function, which is suggested to be associated with cardiovascular risk., Methods: Human intervention studies were identified by systematic search of the databases Medline, Embase, Chemical Abstracts and Biosis through March 2009 and by hand-searching related articles. Studies were selected based on predefined criteria: intervention with tea as the sole experimental variable, placebo-controlled design, and no missing data on FMD outcome or its variability. A random effects model was used to calculate the pooled overall effect on FMD due to the intake of tea. The impact of various subject and treatment characteristics was investigated in the presence of heterogeneity., Results: In total, 9 studies from different research groups were included with 15 relevant study arms. The overall absolute increase in FMD of tea vs. placebo was 2.6% of the arterial diameter (95% CI: 1.8-3.3%; P-value <0.001) for a median daily dose of 500 mL of tea (2-3 cups). This is a relative increase of approximately 40% compared to the average FMD of 6.3% measured under placebo or baseline conditions. There was significant heterogeneity between studies (P-value <0.001) that might partly be explained by the cuff position either distal or proximal to the area of FMD measurement. No indication for publication bias was found., Conclusion: Moderate consumption of tea substantially enhances endothelial-dependent vasodilation. This may provide a mechanistic explanation for the reduced risk of cardiovascular events and stroke observed among tea drinkers.

Data suggest that polyphenol-rich products may improve endothelial function and other cardiovascular health risk factors. Grape and wine contain high amounts of polyphenols, but effects of these polyphenols have hardly been investigated in isolation in randomized controlled studies. Our objective in this study was to test the chronic effect of polyphenol-rich solids derived from either a wine grape mix or grape seed on flow-mediated dilation (FMD). Blood pressure and other vascular function measures, platelet function, and blood lipids were secondary outcomes. Thirty-five healthy males were randomized in a double-blind, placebo-controlled crossover study consisting of three 2-wk intervention periods separated by 1-wk washout periods. The test products, containing 800 mg of polyphenols, were consumed as capsules. At the end of each intervention period, effects were measured after consumption of a low-fat breakfast (~751 kJ, 25% fat) and a high-fat lunch (~3136 kJ, 78% fat). After the low-fat breakfast, the treatments did not significantly affect FMD. The absolute difference after the wine grape solid treatment was -0.4% (95% CI = -1.8 to 0.9; P = 0.77) and after grape seed solids, 0.2% (95% CI = -1.2 to 1.5; P = 0.94) compared with after the placebo treatment. FMD effects after the high-fat lunch and effects on secondary outcomes also showed no consistent differences between both of the grape solids and placebo treatment. In conclusion, consumption of grape polyphenols has no major impact on FMD in healthy men. Future studies should address whether grape polyphenols can improve FMD and other cardiovascular health risk factors in populations with increased cardiovascular risk.

Aims: To determine the effects of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) from fish on the incidence of recurrent ventricular arrhythmia in implantable cardioverter defibrillator (ICD) patients by combining results from published trials., Methods and Results: We searched in the Medline, EMBASE, and Cochrane databases and performed a meta-analysis on all three available trials on fish oil and ventricular arrhythmia. Furthermore, we pooled individual data of two of these randomized, double-blind, placebo-controlled trials (Raitt et al. Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial. JAMA 2005;293:2884-2891 and Brouwer et al. Effect of fish oil on ventricular tachyarrhythmia and death in patients with implantable cardioverter defibrillators: the Study on Omega-3 Fatty Acids and Ventricular Arrhythmia (SOFA) randomized trial. JAMA 2006;295:2613-2619). The main outcome was time to first confirmed ventricular fibrillation (VF) or ventricular tachycardia (VT) combined with death for the meta-analysis, and time to first spontaneous confirmed VF or VT for the pooled analysis. The meta-analysis (n = 1148) showed no convincing protective effect of fish oil (RR 0.90; 95% CI 0.67-1.22). The hazard ratio for the subgroup of patients with coronary artery disease at baseline (0.79; 0.60-1.06) tended towards a protective effect. The pooled analysis (n = 722) showed that time to appropriate ICD intervention was similar for fish oil and placebo treatment (log-rank P = 0.79)., Conclusion: These findings do not support a protective effect of omega-3 PUFAs from fish oil on cardiac arrhythmia in all patients with an ICD. Current data neither prove nor disprove a beneficial or a detrimental effect for subgroups of patients with specific underlying pathologies.