Maternal non-compliance with recommended folic acid supplement use alters global DNA methylation in cord blood of newborns: A cohort study.

BACKGROUND & AIMS: Prenatal folate exposure may alter epigenetic marks in the offspring. We aimed to evaluate associations between prenatal exposure to folic acid (FA) in preconception and in utero with cord blood DNA methylation in long interspersed nuclear element 1 (LINE-1) and Alu short interspersed nuclear elements (SINEs) as markers of global DNA methylation levels. METHODS: Data come from 325 mother-child pairs participating in the Nutrition in Early Life and Asthma (NELA) birth cohort (2015-2018). Pregnant women were asked about supplement use, including brand name and dose, one month before pregnancy (preconception) and through the trimesters of pregnancy. Maternal dietary folate intake was assessed using a validated food frequency questionnaire with additional questions for FA supplement use. Folate serum levels were measured in mothers at 24 weeks of gestation and in cord blood of newborns. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 5 LINE-1 and 3 Alu different elements. Associations were estimated using multivariable linear regression models. RESULTS: A reduction in methylation levels of LINE-1 in newborns was associated with the use of FA supplements below the recommended doses (<400 ug/day) during preconception (-0.50; 95% CI: -0.91, -0.09; P = 0.016), and from preconception up to 12 weeks of gestation (-0.48; 95% CI: -0.88, -0.08; P = 0.018). Maternal use of FA supplements above the tolerable upper intake level of 1000 ug/day from preconception until 12 weeks of gestation was also related to lower methylation in LINE-1 at birth (-0.77; 95% CI: -1.52, -0.02; P = 0.044). Neither FA supplement use after 12 weeks of gestation nor maternal total folate intake (diet plus supplements) were associated with global DNA methylation levels at birth. CONCLUSIONS: Maternal non-compliance with the use of FA supplement recommendations from preconception up to 12 weeks of gestation reduces offspring global DNA methylation levels at birth.

Folic Acid Supplementation during Pregnancy and Its Association with Telomere Length in Children at Four Years: Results from the INMA Birth Cohort Study.

This study examined the association between folic acid supplements (FAs) during different periods of pregnancy and offspring telomere length (TL) at age four in 666 children from the INMA study. FAs were self-reported using food-structured questionnaires during three periods of pregnancy (the first three months of pregnancy, from month fourth onward, and the whole pregnancy). For each period, the average daily dosage of FAs was categorised into (i) <400 µg/d, (ii) ≥400 to 999 µg/d, (iii) ≥1000 to 4999 µg/d, and (iv) ≥5000 µg/d. Leucocyte TL at age four was measured using quantitative PCR methods. Multiple robust linear log-level regression models were used to report the % difference among FA categories. During the first period, and compared with children whose mothers were classified in the reference group (<400 µg/d), children whose mothers took higher dosages of FAs showed shorter TL at age four (≥5000 µg/d). When the first and the second periods were mutually adjusted, children whose mothers self-reported ≥5000 µg/d during the first period of pregnancy had a statistically significant shorter TL than their counterparts (% difference: -7.28% [95% CI: -14.42 to -0.13]). Similar trends were observed for the whole period of pregnancy. When the analysis was stratified by sex, the association was more evident in boys (% difference: -13.5% [95% CI: -23.0 to -4.04]), whereas no association was observed in girls. This study suggests that high dosages of FAs in the first pregnancy period may be associated with a shorter TL in children at age four, particularly among boys. Further studies should confirm these results.

Caffeine and the Risk of Diabetic Retinopathy in Type 2 Diabetes Mellitus: Findings from Clinical and Experimental Studies.

The aim of this study was to assess the potential benefits of caffeine intake in protecting against the development of diabetic retinopathy (DR) in subjects with type 2 diabetes (T2D). Furthermore, we tested the effect of topical administration of caffeine on the early stages of DR in an experimental model of DR. In the cross-sectional study, a total of 144 subjects with DR and 147 individuals without DR were assessed. DR was assessed by an experienced ophthalmologist. A validated food frequency questionnaire (FFQ) was administered. In the experimental model, a total of 20 mice were included. One drop (5 µL) of caffeine (5 mg/mL) (n = 10) or vehicle (5 µL PBS, pH 7.4) (n = 10) was randomly administered directly onto the superior corneal surface twice daily for two weeks in each eye. Glial activation and retinal vascular permeability were assessed using standard methods. In the cross-sectional study in humans, the adjusted-multivariable model showed that a moderate and high (Q2 and Q4) caffeine intake had a protective effect of DR (odds ratio (95% confidence interval) = 0.35 (0.16-0.78); p = 0.011 and 0.35 (0.16-0.77); p = 0.010, respectively). In the experimental model, the administration of caffeine did not improve either reactive gliosis or retinal vascular permeability. Our results suggest a dose-dependent protective effect of caffeine in the development of DR, while the potential benefits of antioxidants in coffee and tea should also be considered. Further research is needed to establish the benefits and mechanisms of caffeinated beverages in the development of DR.

Increase from low to moderate, but not high, caffeinated coffee consumption is associated with favorable changes in body fat.

BACKGROUND & AIMS: Higher consumption of coffee and caffeine has been linked to less weight gain and lower body mass index in prospective cohort studies. The aim of the study was to longitudinally assess the association of changes in coffee and caffeine intake with changes in fat tissue, in particular, visceral adipose tissue (VAT) using dual x-ray absorptiometry (DXA). METHODS: In the setting of a large, randomized trial of Mediterranean diet and physical activity intervention, we evaluated 1483 participants with metabolic syndrome (MetS). Repeated measurements of coffee consumption from validated food frequency questionnaires (FFQ) and DXA measurements of adipose tissue were collected at baseline, 6 months, 12 months and 3 years of follow-up. DXA-derived measurements of total and regional adipose tissue expressed as % of total body weight were transformed into sex-specific z-scores. Linear multilevel mixed-effect models were used to investigate the relationship between changes in coffee consumption and corresponding concurrent changes in fat tissue during a 3-year follow-up. RESULTS: After adjustment for intervention group, and other potential confounders, an increase in caffeinated coffee consumption from no or infrequent consumption (≤3 cups/month) to moderate consumption (1-7 cups/week) was associated with reductions in total body fat (Δ z-score: -0.06; 95% CI: -0.11 to -0.02), trunk fat (Δ z-score: -0.07; 95% CI: -0.12 to -0.02), and VAT (Δ z-score: -0.07; 95% CI: -0.13 to -0.01). Neither changes from no or infrequent consumption to high levels of caffeinated coffee consumption (>1 cup/day) nor any changes in decaffeinated coffee consumption showed significant associations with changes in DXA measures. CONCLUSIONS: Moderate changes in the consumption of caffeinated coffee, but not changes to high consumption, were associated with reductions in total body fat, trunk fat and VAT in a Mediterranean cohort with MetS. Decaffeinated coffee was not linked to adiposity indicators. Moderate consumption of caffeinated coffee may be part of a weight management strategy. TRIAL REGISTRATION: The trial was registered at the International Standard Randomized Controlled Trial (ISRCTN: http://www.isrctn.com/ISRCTN89898870) with number 89898870 and registration date of 24 July 2014, retrospectively registered.

Association between the Use of Folic Acid Supplements during Pregnancy and Children's Cognitive Function at 7-9 Years of Age in the INMA Cohort Study.

This study investigated the association between maternal low (<400 µg/day) or high (≥1000 µg/day) folic acid supplements (FAs) use during pregnancy and the attentional function and working memory in boys and girls at age 7-9. A longitudinal analysis based on 1609 mother-child pairs from the Spanish Infancia y Medio Ambiente Project was carried out. Multivariable regression analyses revealed that, compared to the recommended FAs use, a low FAs use during the second period of pregnancy was associated with a lower alertness in all children (ß = 18.70 ms; 95% CI: 7.51; 29.89) and in girls (ß = 30.01 ms; 95% CI: 12.96; 47.01), and with a lower N-back Task performance in boys (d' number 2-back (ß = -0.25; 95% CI: -0.49; 0.01)). A high FAs use throughout the two periods of pregnancy was associated with a better N-back Task performance only in girls (d' number 2-back (ß = 0.28; 95% CI: 0.01; 0.56) and d' number 3-back (ß = 0.32; 95% CI: 0.08; 0.56)). The maternal use of FAs beyond the periconceptional period may affect children's attentional function and working memory at age 7-9 differently for boys and girls.

Tea consumption and gastric cancer: a pooled analysis from the Stomach cancer Pooling (StoP) Project consortium.

BACKGROUND: Evidence from epidemiological studies on the role of tea drinking in gastric cancer risk remains inconsistent. We aimed to investigate and quantify the relationship between tea consumption and gastric cancer in the Stomach cancer Pooling (StoP) Project consortium. METHODS: A total of 9438 cases and 20,451 controls from 22 studies worldwide were included. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of gastric cancer for regular versus non-regular tea drinkers were estimated by one and two-stage modelling analyses, including terms for sex, age and the main recognised risk factors for gastric cancer. RESULTS: Compared to non-regular drinkers, the estimated adjusted pooled OR for regular tea drinkers was 0.91 (95% CI: 0.85-0.97). When the amount of tea consumed was considered, the OR for consumption of 1-2 cups/day was 1.01 (95% CI: 0.94-1.09) and for >3 cups/day was 0.91 (95% CI: 0.80-1.03). Stronger inverse associations emerged among regular drinkers in China and Japan (OR: 0.67, 95% CI: 0.49-0.91) where green tea is consumed, in subjects with H. pylori infection (OR: 0.68, 95% CI: 0.58-0.80), and for gastric cardia cancer (OR: 0.64, 95% CI: 0.49-0.84). CONCLUSION: Our results indicate a weak inverse association between tea consumption and gastric cancer.

Omega-3 Fatty Acid Intake during Pregnancy and Child Neuropsychological Development: A Multi-Centre Population-Based Birth Cohort Study in Spain.

Background: There are few studies that look at the intake of all types of omega-3 polyunsaturated fatty acids (n-3 PUFAs) during the different stages of pregnancy along with a long-term neuropsychological follow-up of the child. This study aims to explore the association between maternal n-3 PUFA intake during two periods of pregnancy and the child's neuropsychological scores at different ages. Methods: Prospective data were obtained for 2644 pregnant women recruited between 2004 and 2008 in population-based birth cohorts in Spain. Maternal n-3 PUFA intake during the first and third trimester of pregnancy was estimated using validated food frequency questionnaires. Child neuropsychological functions were assessed using Bayley Scales of Infant Development version one (BSID) at 1 year old, the McCarthy Scale of Children's Abilities (MSCA) at 4 years old, and the Attention Network Test (ANT) at 7 years old. Data were analysed using multivariate linear regression models and adjusted for potential covariates, such as maternal social class, education, cohort location, alcohol consumption, smoking, breastfeeding duration, and energy intake. Results: Compared to participants in the lowest quartile (<1.262 g/day) of n-3 PUFA consumption during the first trimester, those in the highest quartile (>1.657 g/day) had a 2.26 points (95% confidence interval (CI): 0.41, 4.11) higher MSCA general cognitive score, a 2.48 points (95% CI: 0.53, 4.43) higher MSCA verbal score, and a 2.06 points (95% CI: 0.166, 3.95) higher MSCA executive function score, and a 11.52 milliseconds (95% CI: −22.95, −0.09) lower ANT hit reaction time standard error. In the third pregnancy trimester, the associations were weaker. Conclusions: Positive associations between n-3 PUFA intake during early pregnancy and child neuropsychological functions at 4 and 7 years of age were found, and further clinical research is needed to confirm these findings.

Allium vegetables intake and the risk of gastric cancer in the Stomach cancer Pooling (StoP) Project.

BACKGROUND: The role of allium vegetables on gastric cancer (GC) risk remains unclear. METHODS: We evaluated whether higher intakes of allium vegetables reduce GC risk using individual participant data from 17 studies participating in the "Stomach cancer Pooling (StoP) Project", including 6097 GC cases and 13,017 controls. Study-specific odds ratios (ORs) were pooled using a two-stage modelling approach. RESULTS: Total allium vegetables intake was inversely associated with GC risk. The pooled OR for the highest versus the lowest study-specific tertile of consumption was 0.71 (95% confidence interval, CI, 0.56-0.90), with substantial heterogeneity across studies (I2 > 50%). Pooled ORs for high versus low consumption were 0.69 (95% CI, 0.55-0.86) for onions and 0.83 (95% CI, 0.75-0.93) for garlic. The inverse association with allium vegetables was evident in Asian (OR 0.50, 95% CI, 0.29-0.86) but not European (OR 0.96, 95% CI, 0.81-1.13) and American (OR 0.66, 95% CI, 0.39-1.11) studies. Results were consistent across all other strata. CONCLUSIONS: In a worldwide consortium of epidemiological studies, we found an inverse association between allium vegetables and GC, with a stronger association seen in Asian studies. The heterogeneity of results across geographic regions and possible residual confounding suggest caution in results interpretation.

Coffee consumption and gastric cancer: a pooled analysis from the Stomach cancer Pooling Project consortium.

OBJECTIVE: This study aimed to evaluate and quantify the relationship between coffee and gastric cancer using a uniquely large dataset from an international consortium of observational studies on gastric cancer, including data from 18 studies, for a total of 8198 cases and 21 419 controls. METHODS: A two-stage approach was used to obtain the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for coffee drinkers versus never or rare drinkers. A one-stage logistic mixed-effects model with a random intercept for each study was used to estimate the dose-response relationship. Estimates were adjusted for sex, age and the main recognized risk factors for gastric cancer. RESULTS: Compared to never or rare coffee drinkers, the estimated pooled OR for coffee drinkers was 1.03 (95% CI, 0.94-1.13). When the amount of coffee intake was considered, the pooled ORs were 0.91 (95% CI, 0.81-1.03) for drinkers of 1-2 cups per day, 0.95 (95% CI, 0.82-1.10) for 3-4 cups, and 0.95 (95% CI, 0.79-1.15) for five or more cups. An OR of 1.20 (95% CI, 0.91-1.58) was found for heavy coffee drinkers (seven or more cups of caffeinated coffee per day). A positive association emerged for high coffee intake (five or more cups per day) for gastric cardia cancer only. CONCLUSIONS: These findings better quantify the previously available evidence of the absence of a relevant association between coffee consumption and gastric cancer.

Physical activity and metabolic syndrome severity among older adults at cardiovascular risk: 1-Year trends.

BACKGROUND AND AIMS: Modifiable lifestyle factors, such as physical activity (PA) and Mediterranean diet (MD), decrease metabolic syndrome (MetS). The aim was to assess 1-year changes of leisure-time physical activity (LTPA), sedentary behavior, and diet quality according to MetS severity in older population at high cardiovascular risk. METHODS AND RESULTS: Prospective analysis of 55-75-year-old 4359 overweight/obese participants with MetS (PREDIMED-Plus trial) categorized in tertiles according to 1-year changes of a validated MetS severity score (MetSSS). Anthropometrics, visceral adiposity index, triglycerides and glucose index, dietary nutrient intake, biochemical marker levels, dietary inflammatory index, and depression symptoms were measured. Diet quality was assessed by 17-item MD questionnaire. PAs were self-reported using the Minnesota-REGICOR Short Physical Activity Questionnaire and 30-s chair stand test. Sedentary behaviors were measured using the Spanish version of the Nurses' Health Study questionnaire. After 1-year follow-up, decreasing MetSSS was associated with an anti-inflammatory dietary pattern, high intake of vegetables, fruits, legumes, nuts, whole grain cereals, white fish, and bluefish and low intake of refined cereals, red and processed meat, cookies/sweets, and snacks/ready-to-eat-meals. It resulted in high intake of polyunsaturated fatty acids, omega-3 fatty acids, protein, fiber, vitamins B1, B6, B9, C, D, potassium, magnesium, and phosphorus and low glycemic index and saturated fatty acid, trans fatty acid, and carbohydrates intake. Regarding PA and sedentary behavior, decreasing MetSSS was associated with increased moderate-to-vigorous LTPA, chair stand test, and decreased sedentary and TV-viewing time. CONCLUSION: Decreasing MetSSS was associated with an anti-inflammatory dietary pattern, high LTPA, high MD adherence, low sedentary time, and low depression risk.

Coffee Consumption and All-Cause, Cardiovascular, and Cancer Mortality in an Adult Mediterranean Population.

We assessed the association between usual coffee consumption and all-cause, cardiovascular (CV), and cancer mortality in an adult population in Spain, taking into account both the amount and type of coffee consumed. We used baseline data on coffee consumption and other personal variables, and the number of deaths during an 18-year follow-up period, for 1567 participants aged 20 years and older from the Valencia Nutrition Study in Spain. Total, caffeinated, and decaffeinated coffee consumption was assessed using a validated food frequency questionnaire. Cox regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). During the 18-year follow-up period, 317 died; 115 due to CV disease and 82 due to cancer. Compared with no-consumption, the consumption of ≤1 cup per day and >1 cup per day of coffee was associated with a lower risk of all-cause mortality, HR = 0.73 (95% CI: 0.56-0.97) and HR 0.56 (95% CI: 0.41-0.77), respectively. A lower cancer mortality was observed among drinkers of more than 1 cup per day compared with nondrinkers, HR 0.41 (95% CI 0.20-0.86). Regarding the type of coffee, only the overall consumption of caffeinated coffee was associated with lower all-cause mortality at 12 and 18 years of follow-up, HR = 0.66 (95% CI:0.46-0.94) and HR = 0.59 (95% CI: 0.44-0.79), respectively. In conclusion, this study suggests that the moderate consumption of coffee, particularly caffeinated coffee (range 1-6.5 cups per day), is associated with a lower all-cause and cancer mortality after a long follow-up period. No significant association was found between coffee consumption and CVD mortality.

Self-Reported DHA Supplementation during Pregnancy and Its Association with Obesity or Gestational Diabetes in Relation to DHA Concentration in Cord and Maternal Plasma: Results from NELA, a Prospective Mother-Offspring Cohort.

Maternal supplementation of docosahexaenoic acid (DHA) during pregnancy has been recommended due to its role in infant development, but its effect on materno-fetal DHA status is not well established. We evaluated the associations between DHA supplementation in pregnant women with obesity or gestational diabetes mellitus (GDM) and maternal and neonatal DHA status. Serum fatty acids (FA) were analyzed in 641 pregnant women (24 weeks of gestation) and in 345 venous and 166 arterial cord blood samples of participants of the NELA cohort. Obese women (n = 47) presented lower DHA in serum than those lean (n = 397) or overweight (n = 116) before pregnancy. Linoleic acid in arterial cord was elevated in obese women, which indicates lower fetal retention. Maternal DHA supplementation (200 mg/d) during pregnancy was associated with enhanced maternal and fetal DHA levels regardless of pre-pregnancy body mass index (BMI), although higher arterial DHA in overweight women indicated an attenuated response. Maternal DHA supplementation was not associated with cord venous DHA in neonates of mothers with GDM. The cord arteriovenous difference was similar for DHA between GDM and controls. In conclusion, maternal DHA supplementation during pregnancy enhanced fetal DHA status regardless of the pre-pregnancy BMI while GDM may reduce the effect of DHA supplementation in newborns.

Consumption of caffeinated beverages and kidney function decline in an elderly Mediterranean population with metabolic syndrome.

It remains unclear whether caffeinated beverages could have deleterious renal effects in elderly population with underlying comorbid conditions. We investigated the associations between coffee, tea, or caffeine intake and 1-year changes in glomerular filtration rate (eGFR) in a large Spanish cohort of overweight/obese elderly with metabolic syndrome (MetS). This prospective analysis includes 5851 overweight/obese adults (55-75 years) with MetS from the PREDIMED-Plus study. We assessed coffee, tea, and caffeine consumption from a validated food-frequency questionnaire and creatinine-based eGFR using the Chronic Kidney Disease Epidemiology Collaboration equation. Multivariate-adjusted regression models were applied to test associations between baseline coffee, tea, or caffeine intake and 1-year eGFR changes. Caffeinated coffee (> 2 cups/day) and tea (at least 1 cup/day) drinkers had 0.88 and 0.93 mL/min/1.73 m2 greater eGFR decrease respectively, compared to those with less than 1 cup/day of coffee consumption or non-tea drinkers. Furthermore, caffeinated coffee consumption of > 2 cups/day was associated with 1.19-fold increased risk of rapid eGFR decline > 3 mL/min/1.73 m2 (95% CI 1.01-1.41). Similarly, individuals in the highest (median, 51.2 mg/day) tertile of caffeine intake had a 0.87 mL/min/1.73 m2 greater eGFR decrease. Decaffeinated coffee was not associated with eGFR changes. In conclusion, higher consumption of caffeinated coffee, tea, and caffeine was associated with a greater 1-year eGFR decline in overweight/obese adults with MetS.

The Use of Lower or Higher Than Recommended Doses of Folic Acid Supplements during Pregnancy Is Associated with Child Attentional Dysfunction at 4-5 Years of Age in the INMA Project.

We assessed the association between the use of lower- and higher-than-recommended doses of folic acid supplements (FAs) during pregnancy and attentional function in boys and girls at age of 4-5. We analyzed data from 1329 mother-child pairs from the mother-child cohort INfancia y Medio Ambiente Project (INMA) study. Information on FAs use during pregnancy was collected in personal interviews at weeks 12 and 30, and categorized in <400, 400-999 (recommended dose), and ≥1000 µg/day. Child attentional function was assessed by Conners' Kiddie Continuous Performance Test. Multivariable regression analyses were used to estimate incidence rate ratios (IRR) and beta coefficients with 95% confidence intervals (CI). Compared to recommended FAs doses, the periconceptional use of <400 and ≥1000 µg/day was associated with higher risk of omission errors-IRR = 1.14 (95% CI: 1.01; 1.29) and IRR = 1.16 (95% CI: 1.02; 1.33), respectively. The use of FAs < 400 µg/day and ≥1000 µg/day was significantly associated with deficits of attentional function only in boys. FAs use < 400 µg/day was associated with higher omission errors with IRR = 1.22 and increased hit reaction time (HRT) ß = 34.36, and FAs use ≥ 1000 µg/day was associated with increased HRT ß = 33.18 and HRT standard error ß = 3.31. The periconceptional use of FAs below or above the recommended doses is associated with deficits of attentional function in children at age of 4-5, particularly in boys.

Association between coffee consumption and total dietary caffeine intake with cognitive functioning: cross-sectional assessment in an elderly Mediterranean population.

PURPOSE: Coffee is rich in compounds such as polyphenols, caffeine, diterpenes, melanoidins and trigonelline, which can stimulate brain activity. Therefore, the possible association of coffee consumption with cognition is of considerable research interest. In this paper, we assess the association of coffee consumption and total dietary caffeine intake with the risk of poor cognitive functioning in a population of elderly overweight/obese adults with metabolic syndrome (MetS). METHODS: PREDIMED-plus study participants who completed the Mini-Mental State Examination test (MMSE) (n = 6427; mean age = 65 ± 5 years) or a battery of neuropsychological tests were included in this cross-sectional analysis. Coffee consumption and total dietary caffeine intake were assessed at baseline using a food frequency questionnaire. Logistic regression models were fitted to evaluate the association between total, caffeinated and decaffeinated coffee consumption or total dietary caffeine intake and cognitive impairment. RESULTS: Total coffee consumers and caffeinated coffee consumers had better cognitive functioning than non-consumers when measured by the MMSE and after adjusting for potential confounders (OR 0.63; 95% CI 0.44-0.90 and OR 0.56; 95% CI 0.38-0.83, respectively). Results were similar when cognitive performance was measured using the Clock Drawing Test (CDT) and Trail Making Test B (TMT-B). These associations were not observed for decaffeinated coffee consumption. Participants in the highest tertile of total dietary caffeine intake had lower odds of poor cognitive functioning than those in the reference tertile when screened by the MMSE (OR 0.64; 95% CI 0.47-0.87) or other neurophysiological tests evaluating a variety of cognitive domains (i.e., CDT and TMT-A). CONCLUSIONS: Coffee consumption and total dietary caffeine intake were associated with better cognitive functioning as measured by various neuropsychological tests in a Mediterranean cohort of elderly individuals with MetS. TRIAL REGISTRATION: ISRCTN89898870. Registration date: July 24, 2014.

Relationship between olive oil consumption and ankle-brachial pressure index in a population at high cardiovascular risk.

BACKGROUND AND AIMS: The aim of this study was to ascertain the association between the consumption of different categories of edible olive oils (virgin olive oils and olive oil) and olive pomace oil and ankle-brachial pressure index (ABI) in participants in the PREDIMED-Plus study, a trial of lifestyle modification for weight and cardiovascular event reduction in individuals with overweight/obesity harboring the metabolic syndrome. METHODS: We performed a cross-sectional analysis of the PREDIMED-Plus trial. Consumption of any category of olive oil and olive pomace oil was assessed through a validated food-frequency questionnaire. Multivariable linear regression models were fitted to assess associations between olive oil consumption and ABI. Additionally, ABI ≤1 was considered as the outcome in logistic models with different categories of olive oil and olive pomace oil as exposure. RESULTS: Among 4330 participants, the highest quintile of total olive oil consumption (sum of all categories of olive oil and olive pomace oil) was associated with higher mean values of ABI (beta coefficient: 0.014, 95% confidence interval [CI]: 0.002, 0.027) (p for trend = 0.010). Logistic models comparing the consumption of different categories of olive oils, olive pomace oil and ABI ≤1 values revealed an inverse association between virgin olive oils consumption and the likelihood of a low ABI (odds ratio [OR] 0.73, 95% CI [0.56, 0.97]), while consumption of olive pomace oil was positively associated with a low ABI (OR 1.22 95% CI [1.00, 1.48]). CONCLUSIONS: In a Mediterranean population at high cardiovascular risk, total olive oil consumption was associated with a higher mean ABI. These results suggest that olive oil consumption may be beneficial for peripheral artery disease prevention, but longitudinal studies are needed.

Dietary Polyphenol Intake is Associated with HDL-Cholesterol and A Better Profile of other Components of the Metabolic Syndrome: A PREDIMED-Plus Sub-Study.

Dietary polyphenol intake is associated with improvement of metabolic disturbances. The aims of the present study are to describe dietary polyphenol intake in a population with metabolic syndrome (MetS) and to examine the association between polyphenol intake and the components of MetS. This cross-sectional analysis involved 6633 men and women included in the PREDIMED (PREvención con DIeta MEDiterranea-Plus) study. The polyphenol content of foods was estimated from the Phenol-Explorer 3.6 database. The mean of total polyphenol intake was 846 ± 318 mg/day. Except for stilbenes, women had higher polyphenol intake than men. Total polyphenol intake was higher in older participants (>70 years of age) compared to their younger counterparts. Participants with body mass index (BMI) >35 kg/m2 reported lower total polyphenol, flavonoid, and stilbene intake than those with lower BMI. Total polyphenol intake was not associated with a better profile concerning MetS components, except for high-density lipoprotein cholesterol (HDL-c), although stilbenes, lignans, and other polyphenols showed an inverse association with blood pressure, fasting plasma glucose, and triglycerides. A direct association with HDL-c was found for all subclasses except lignans and phenolic acids. To conclude, in participants with MetS, higher intake of several polyphenol subclasses was associated with a better profile of MetS components, especially HDL-c.

High doses of folic acid in the periconceptional period and risk of low weight for gestational age at birth in a population based cohort study.

PURPOSE: We investigated the association between maternal use of folic acid (FA) during pregnancy and child anthropometric measures at birth. METHODS: We included 2302 mother-child pairs from a population-based birth cohort in Spain (INMA Project). FA dosages at first and third trimester of pregnancy were assessed using a specific battery questionnaire and were categorized in non-user, < 1000, 1000-4999, and ≥ 5000 µg/day. Anthropometric measures at birth (weight in grams, length and head circumference in centimetres) were obtained from medical records. Small for gestational age according to weight (SGA-w), length (SGA-l) and head circumference (SGA-hc) were defined using the 10th percentile based on Spanish standardized growth reference charts. Multiple linear and logistic regression analyses were used to explore the association between FA dosages in different stages of pregnancy and child anthropometric measures at birth. RESULTS: In the multiple linear regression analysis, we found a tendency for a negative association between the use of high dosages of FA (≥ 5000 µg/day) in the periconceptional period of pregnancy and weight at birth compared to mothers who were non-users of FA (ß = - 73.83; 95% CI - 151.71, 4.06). In the multiple logistic regression, a greater risk of SGA-w was also evident among children whose mothers took FA dosages of 1000-4999 (OR = 2.21; 95% CI 1.17, 4.19) and of ≥ 5000 µg/day (OR = 2.32; 95% CI 1.06, 5.08) compared to mothers non-users of FA in the periconceptional period of pregnancy. CONCLUSION: Our findings suggest that a high dosage of FA (≥ 1000 µg/day) may be associated with an increased risk of SGA-w at birth.

Factors associated with serum 25-hydroxyvitamin D concentrations in older people in Europe: the EUREYE study.

BACKGROUND/OBJECTIVES: We aimed to describe serum 25-hydroxyvitamin D (25OHD) concentrations in older Europeans and to investigate associations between 25OHD and lifestyle factors, including dietary intake and supplement use. SUBJECTS/METHODS: Men and women aged ≥ 65 years were recruited from seven centres across north to south Europe. Serum 25OHD2 and 25OHD3 concentrations were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) in 4495 samples and total 25OHD (25OHD2 + 25OHD3) was adjusted for season of blood collection. RESULTS: The mean (25th, 75th quartile) of seasonally adjusted 25OHD was 46 (34, 65) nmol/L, with the highest concentration of 25OHD in Bergen [61 (49, 79) nmol/L], and the lowest in Paris [36 (24, 57) nmol/L)]. Vitamin D deficiency (25-50 nmol/L) and vitamin D insufficiency (50-75 nmol/L) were found in 41 and 33% of the population, respectively. In multivariable analysis controlled for confounders, seasonally adjusted 25OHD concentrations were significantly (p < 0.05) lower in smokers and participants with self-reported diabetes and higher with increasing dietary vitamin D, and supplement use with fish liver oil, omega-3, and vitamin D. Additionally, in further analysis excluding Bergen, 25OHD was associated with higher intakes of oily fish and increasing UVB exposure. We observed low concentrations of 25OHD in older people in Europe. CONCLUSIONS: Our findings of the higher 25OHD concentrations in supplement users (omega-3 fish oil, fish liver oil, vitamin D) add to current recommendations to reduce vitamin D deficiency. We were unable to fully assess the role of dietary vitamin D as we lacked information on vitamin D-fortified foods.

Coffee consumption and mortality from all causes of death, cardiovascular disease and cancer in an elderly Spanish population.

PURPOSE: The effect of coffee consumption on mortality has been scarcely investigated in the elderly. We assessed the association between coffee consumption and mortality from all-cause, cardiovascular disease (CVD) and cancer, in an elderly population of Spain. METHODS: We studied 903 individuals (511 women) aged 65 years and older from two population-based studies, the EUREYE-Spain study and the Valencia Nutritional Survey. Coffee consumption and diet were assessed using a validated food frequency questionnaire. Information on education, anthropometry, sleeping time, smoking, alcohol intake, physical activity and pre-existing disease was collected at baseline. Deaths were ascertained during a 12-year follow-up period, and Cox proportional hazards regression models were used to estimate adjusted hazard ratios (HR). RESULTS: There were 403 deaths during the 12-year period (40% from CVD), 174 of which occurred during the first 6 years. We observed evidence of a lower CVD mortality among coffee drinkers in the first 6 years of follow-up. Drinkers of ≤1 cup of coffee/day and > 1 cup/day showed lower CVD mortality than non-drinkers of coffee, HR 0.82 (95% CI 0.46-1.44) and HR 0.38 (0.15-0.96), respectively (p trend = 0.04). This association of coffee with CVD mortality attenuated after 12 years of follow-up. No significant association was observed with all-cause or cancer mortality, neither for caffeinated and decaffeinated coffee. CONCLUSIONS: In this study, coffee consumption was associated with lower CVD mortality in elderly. Although this association should be further investigated, coffee consumption appears to be safe for the elderly since no increased mortality was observed in coffee drinkers.