Effects of Supplemented Mediterranean Diets on Plasma-Phospholipid Fatty Acid Profiles and Risk of Cardiovascular Disease after 1 Year of Intervention in the PREDIMED Trial.

BACKGROUND: Plasma fatty acids (FAs) have been associated with cardiovascular disease (CVD) risk. Diet and endogenous metabolism influence the FA profile of the plasma phospholipid (PL) fraction. In the PREDIMED trial, we examined 1-year changes in the FA profile of plasma PL according to a nutritional intervention with Mediterranean diets, either supplemented with extra-virgin olive oil (MedDiet + EVOO) or mixed nuts (MedDiet + nuts), in a high cardiovascular risk population. We also analyzed if 1-year changes in PL FAs were associated with subsequent cardiovascular risk. METHODS: We included 779 participants in our case-cohort study: 185 incident cases and 594 participants in the subcohort (including 31 overlapping cases). The end point was the incidence of CVD. We measured the FAs of plasma PL at baseline and after 1 year of intervention. RESULTS: MedDiet + EVOO increased C17:0 and C20:3n9 in linear regression models [ß coefficientperSD : 0.215 (95% CI, 0.032-0.399) and 0.271 (0.107-0.434), respectively] and decreased 16:1n7 and C22:4n6 [ßperSD: -0.239 (95% CI, -0.416 to -0.061) and -0.287 (95% CI, -0.460 to -0.113), respectively] vs the control group. MedDiet + nuts increased C18:3n3 [ßperSD: 0.382 (95% CI, 0.225 - 0.539)], C18:2n6 [ßper SD: 0.250 (95% CI, 0.073 - 0.428)], C18:0 [ßperSD: 0.268 (95% CI, 0.085-0.452)], and C22:0 [ßper SD: 0.216 (95% CI, 0.031-0.402)]; and decreased the sum of six n6 FAs [ßper SD: -0.147 (95% CI, -0.268 to -0.027)] vs the control group. The 1-year increase in C18:2n6 was inversely associated with the subsequent CVD risk (HRperSD: 0.64 (95% CI, 0.44-0.92)). CONCLUSIONS: MedDiet interventions changed n6 FAs and C16:1n7c; other changes were specific for each group: MedDiet + EVOO increased C17:0 and C20:3n9, and MedDiet + Nuts C18:3n3, C18:2n6, C18:0, and C22:0 FAs.

Plasma acylcarnitines and risk of incident heart failure and atrial fibrillation: the Prevención con dieta mediterránea study.

INTRODUCTION AND OBJECTIVES: Fatty acid metabolic dysregulation in mitochondria is a common mechanism involved in the development of heart failure (HF) and atrial fibrillation (AF). We evaluated the association between plasma acylcarnitine levels and the incidence of HF or AF, and whether the mediterranean diet (MedDiet) may attenuate the association between acylcarnitines and HF or AF risk. METHODS: Two case-control studies nested within the Prevención con dieta mediterránea (PREDIMED) trial. High cardiovascular risk participants were recruited in Spain: 326 incident HF and 509 AF cases individually matched to 1 to 3 controls. Plasma acylcarnitines were measured with high-throughput liquid chromatography-tandem mass spectrometry. Conditional logistic regression models were fitted to estimate multivariable OR and 95%CI. Additive and multiplicative interactions were assessed by intervention group, obesity (body mass index ≥ 30 kg/m2), and type 2 diabetes. RESULTS: Elevated levels of medium- and long-chain acylcarnitines were associated with increased HF risk (adjusted ORperDE, 1.28; 95%CI, 1.09-1.51 and adjusted ORperDE, 1.21; 95%CI, 1.04-1.42, respectively). A significant association was observed for AF risk with long-chain acylcarnitines: 1.20 (1.06-1.36). Additive interaction of the association between long-chain acylcarnitines and AF by the MediDiet supplemented with extra virgin olive oil (P for additive interaction=.036) and by obesity (P=.022) was observed in an inverse and direct manner, respectively. CONCLUSIONS: Among individuals at high cardiovascular risk, elevated long-chain acylcarnitines were associated with a higher risk of incident HF and AF. An intervention with MedDiet+extra-virgin olive oil may reduce AF risk associated with long-chain acylcarnitines. This trial was registered at controlled-trials.com (Identifier: ISRCTN35739639).

Dietary vitamin D intake and colorectal cancer risk: a longitudinal approach within the PREDIMED study.

PURPOSE: We evaluated whether the intake of dietary vitamin D is associated with the incidence of both colorectal cancer (CRC) and colon cancer in the framework of the PREDIMED cohort of older adults at high cardiovascular risk. METHODS: We analyzed data from 7216 men and women (55-80 years) without CRC at baseline from the PREvención con DIeta MEDiterránea study. Baseline consumption of vitamin D was assessed using a validated 137-item food frequency questionnaire. Cox proportional hazards ratios (HRs) of CRC and colon cancer incidence were estimated for quartiles and per 1-SD of baseline vitamin D intake. RESULTS: During a median follow-up of 6 years, we documented 97 incident CRC cases after the exclusion of subjects with no baseline dietary data and/or outliers of energy intake. A non-significant HRs and 95% confidence intervals (CIs) of CRC for the comparison of extreme quartiles (4th vs 1st) of vitamin D intake were observed [0.55 (0.30-1.00), P for trend = 0.072], whereas it was significant for colon cancer incidence alone [0.44 (0.22-0.90), P for trend = 0.032]. However, this association became significant in CRC and colon cancer incidence, after excluding 391 subjects consuming baseline vitamin D and/or calcium medication or prescribed supplements [0.52 (0.28-0.96) and 0.41 (0.12-0.85), respectively]. CONCLUSION: A higher dietary intake of vitamin D was significantly associated with a reduced CRC risk in individuals at high cardiovascular risk.

Fibromyalgia and Nutrition: An Updated Review.

Due to the lack of specific and standardized treatments for the management of fibromyalgia (FM), available evidence suggests a multidisciplinary approach, and nutrition represents an important therapeutic strategy. This work aims to update the relationship between FM and nutrition, through a review of more recent scientific evidence based on a systematic research on PubMed. Of 66 records initially identified, 26 studies were selected and included in the present work. Although there is not sufficient evidence for the efficacy of specific nutritional protocols, the examined papers indicate a potential role of selected nutrients, micronutrients and food components in managing FM symptoms. However, several concerns persist as nutritional status and/or nutritional integration can improve FM symptoms, without expecting to lead to a remission of the disease. The use of targeted nutritional supplements may be of some relevance for the management of FM, but the up to date evidence remains weak. It is advisable, thus, to perform further studies of higher quality.KEY TEACHING POINTSFibromyalgia (FM) is characterized by chronic and diffuse musculoskeletal pain, often associated with a large set of symptoms.The therapeutic approach of FM include pharmacological and non-pharmacological interventions. Among them, an important role is played by nutrition.Of 66 record screened, 12 studies were included in the present review and five of them were randomized controlled trials. Nevertheless, the overall quality of those trials was scarce.Literature concerning FM and nutritions is growing. However, little evidence suggests that nutrition and/or nutritional intervention play a significant role on FM severity.The results of this review underline the need to carry out clinical studies of higher quality and rigor, possibly RCTs, focused on the role of nutrition in the symptoms and/or severity of FM.

Zinc Intake and Status and Risk of Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Zinc could have a protective role against type 2 diabetes mellitus (T2DM). This systematic review and meta-analysis aimed to evaluate the association between dietary, supplementary, and total zinc intake, as well as serum/plasma and whole blood zinc concentration, and risk of T2DM. Observational studies, conducted on cases of incident diabetes or T2DM patients and healthy subjects that reported a measure of association between zinc exposure and T2DM, were selected. Random effects meta-analyses were applied to obtain combined results. Stratified meta-analyses and meta-regressions were executed to assess sources of heterogeneity, as well as the impact of covariates on the findings. From 12,136 publications, 16 studies were selected. The odds ratio (OR) for T2DM comparing the highest versus lowest zinc intake from diet was 0.87 (95% CI: 0.78-0.98). Nevertheless, no association between supplementary or total zinc intake from both diet and supplementation, and T2DM was observed. A direct relationship was found between serum/plasma zinc levels and T2DM (OR = 1.64, 95% CI: 1.25-2.14). A moderately high dietary zinc intake, in relation to the Dietary Reference Intake, could reduce by 13% the risk of T2DM, and up to 41% in rural areas. Conversely, elevated serum/plasma zinc concentration was associated with an increased risk of T2DM by 64%, suggesting disturbances in zinc homeostasis.

Added Sugars and Low- and No-Calorie Sweeteners in a Representative Sample of Food Products Consumed by the Spanish ANIBES Study Population.

Low- and no-calorie sweeteners (LNCS), intensely sweet compounds that virtually contain no calories, are used to replace added sugars in food and drinks. Knowledge about different LNCS data in Spanish foods and added sugar sources in Spain is limited, therefore our aim was to identify and compare their presence across main food groups consumed. Food and beverage products (n = 434) were obtained from the ANIBES Study (anthropometric data, macronutrients and micronutrients intake, practice of physical activity, socioeconomic data and lifestyles), a cross-sectional study of a representative sample of the Spanish population (9⁻75 years old; n = 2009) carried out in 2013. Food records were obtained from a three-day dietary record using a tablet device. Label data from 1,164 products of different brands were collected and reviewed for content of added sugars and LNCS. LNCS were present in diet soft drinks (100%), "other sweets" (89%), soya drinks (45%), and yogurt and fermented milks (18%). Added sugars were present mainly in sugar soft drinks (100%), energy drinks (96%), sports drinks (96%), bakery and pastry (100%), chocolates (100%), ice cream (100%), breakfast cereals/bars (96%) and jams (89%). Main LNCS were acesulfame K, aspartame, cyclamate and sucralose. Sucrose, dextrose, glucose-fructose syrup, caramel and honey were the main added sugars. Our results show the diversity of foods groups including these ingredients. These data are not compiled in food composition databases, which should be periodically updated to include LNCS and added sugars to facilitate their assessment and monitoring in nutritional surveys.

The PlantLIBRA consumer survey: Findings on the use of plant food supplements in Italy.

BACKGROUND: Food supplements, and in particular those containing botanicals (plant food supplements, PFS), have in recent decades been of great interest both to consumers and to food/pharmaceutical industries. OBJECTIVES: The aim of this paper is to examine replies by Italian consumers to the PlantLIBRA consumers' survey in order to: 1) assess the behaviour of an Italian population with respect to the use of PFS, and to compare it with that of other 5 countries involved in the whole survey; 2) identify different habits in the 4 Italian cities selected according to their geographical distribution; 3) collect independent information on the actual intake of PFS and consumers' behaviour. SUBJECTS/SETTING: 397 Italian consumers enrolled, 187 males (49.5%) and 191 female (50.5%). The distribution of subjects among the 4 cities included was: Milan 99; Venice 90; Rome 96 and Catania 96. RESULTS: The interest in PFS in Italy is high, the prevalence of "regular" consumers being 22.7%. Some differences were observed between the 4 cities involved: the pattern of use during the year was specific to each city; consumers in Milan reported reasons to use PFS significantly different from those in the whole Italian sample and did not indicate supermarkets as an important place of purchase; respondents from Rome and Catania more frequently used family doctors and pharmacists as a source of recommendation. Some significant difference among cities, sex and age groups were observed when the most frequently used botanicals were ranked. CONCLUSIONS: The results provide new insights on the socio-economic characteristics and lifestyle of Italian PFS consumers, on their reasons for and pattern of use, and on their behaviour and expectations. The value of this information is not restricted to the specific country (Italy) but allows for a more general evaluation of the pattern of use, according to habits and geographical area.

Dietary sources and intakes of folates and vitamin B12 in the Spanish population: Findings from the ANIBES study.

BACKGROUND: Folates and vitamin B12 are key nutrients in one-carbon metabolism and related diseases. Updated and plausible information on population intakes and their major dietary sources is scarce and urgently needed in Spain in order to increase the knowledge that can lead as previous step to prevention by fortification and supplementation policies. AIMS: The present study aims to evaluate main dietary folate and vitamin B12 sources and intakes in the Spanish population. MATERIALS AND METHODS: Results were derived from the ANIBES cross-sectional study using a nationally representative sample of the Spanish population (9-75 years, n = 2,009). RESULTS: Food groups with the highest mean proportional contribution to total folate intakes in both males and females were vegetables (21.7-24.9%) and cereals (10.7-11.2%), while meat and meat products (26.4%) and milk and dairy products (27.3%) were for B12. Total median folate and B12 intakes amongst women were 156.3 µg/d and 4.0 µg/d while for men were 163.6 µg/d and 4.5 µg/d, respectively. In all age groups, vitamin intakes were significantly higher in plausible than in non-plausible energy reporters. CONCLUSION: A limited number of participants had adequate folate intakes, whereas vitamin B12 intakes were adequate for practically the entire population. There is a clear need for improving folates intake in the Spanish population.

Potato Consumption Does Not Increase Blood Pressure or Incident Hypertension in 2 Cohorts of Spanish Adults.

Background: Potatoes have a high glycemic load but also antioxidants, vitamins, and minerals. It is unclear what mechanisms are involved in relation to their effect on blood pressure (BP) and hypertension.Objectives: This study aimed to assess the association between potato consumption, BP changes, and the risk of hypertension in 2 Spanish populations.Methods: Separate analyses were performed in PREDIMED (PREvención con DIeta MEDiterránea), a multicenter nutrition intervention trial of adults aged 55-80 y, and the SUN (Seguimiento Universidad de Navarra) project, a prospective cohort made up of university graduates and educated adults with ages (means ± SDs) of 42.7 ± 13.3 y for men and 35.1 ± 10.7 y for women. In PREDIMED, generalized estimating equations adjusted for lifestyle and dietary characteristics were used to assess changes in BP across quintiles of total potato consumption during a 4-y follow-up. Controlled BP values (systolic BP <140 mm Hg and diastolic BP <90 mm Hg) during follow-up were also assessed. For SUN, multivariate-adjusted HRs for incident hypertension during a mean 6.7-y follow-up were calculated.Results: In PREDIMED, the total potato intake was 81.9 ± 40.6 g/d. No overall differences in systolic or diastolic BP changes were detected based on consumption of potatoes. For total potatoes, the mean difference in change between quintile 5 (highest intake) and quintile 1 (lowest intake) in systolic BP after multivariate adjustment was -0.90 mm Hg (95% CI: -2.56, 0.76 mm Hg; P-trend = 0.1) and for diastolic BP was -0.02 mm Hg (95% CI: -0.93, 0.89 mm Hg; P-trend = 0.8). In SUN, the total potato consumption was 52.7 ± 33.6 g/d, and no significant association between potato consumption and hypertension incidence was observed in the fully adjusted HR for total potato consumption (quintile 5 compared with quintile 1: 0.98; 95% CI: 0.80, 1.19; P-trend = 0.8).Conclusions: Potato consumption is not associated with changes over 4 y in blood pressure among older adults in Spain or with the risk of hypertension among Spanish adults. This trial was registered at www.controlled-trials.com as ISRCTN35739639.

Evidence-based practice within nutrition: what are the barriers for improving the evidence and how can they be dealt with?

BACKGROUND: Evidence-based clinical research poses special barriers in the field of nutrition. The present review summarises the main barriers to research in the field of nutrition that are not common to all randomised clinical trials or trials on rare diseases and highlights opportunities for improvements. METHODS: Systematic academic literature searches and internal European Clinical Research Infrastructure Network (ECRIN) communications during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project. RESULTS: Many nutrients occur in multiple forms that differ in biological activity, and several factors can alter their bioavailability which raises barriers to their assessment. These include specific difficulties with blinding procedures, with assessments of dietary intake, and with selecting appropriate outcomes as patient-centred outcomes may occur decennia into the future. The methodologies and regulations for drug trials are, however, applicable to nutrition trials. CONCLUSIONS: Research on clinical nutrition should start by collecting clinical data systematically in databases and registries. Measurable patient-centred outcomes and appropriate study designs are needed. International cooperation and multistakeholder engagement are key for success.

Reported Dietary Intake and Food Sources of Zinc, Selenium, and Vitamins A, E and C in the Spanish Population: Findings from the ANIBES Study.

Zinc, selenium, and the vitamins A, E and C, all have specific biological functions that are involved mainly in the antioxidant defence system, which has important implications for the development of chronic diseases. We aimed to assess the reported intake of those six nutrients, as well as the food that contributes to their sources of intakes. Data were obtained from the Spanish ANIBES ("Anthropometry, Intake and Energy Balance in Spain") study, n = 2009 (9-75 years old). The analyses were performed in the whole population and in the plausible energy reporters after a misreporting analysis according to the European Food and Safety Authority (EFSA) protocol. A validated, photo-based three-day food record was used to collect the data. Mean (max-min) reported intake for the whole population of zinc was 8.1 ± 0.1 mg/day, (2.3-27.3 mg/day), selenium 75 ± 1 µg/day, (14-265 µg/day), vitamin A 668 µg RE/day (2-11,017 µg RE/day), retinol 364 ± 18 µg/day (0-10,881 µg/day), carotenes 1735 ± 35 µg/day (13-13,962 µg/day), vitamin E 7.0 ± 0.1 mg α-TE/day (0.7-55.2 mg α-TE/day) and vitamin C 84.4 ± 1.4 mg/day (5.0-802.7 mg/day). The main source intakes for zinc were meat and meat products, for selenium cereals and grains, for vitamin E oils and fat, and for vitamin A and C vegetables. There is an elevated percentage of the Spanish ANIBES population not meeting the EFSA recommended intakes for all analysed micronutrients: zinc (83%), vitamin A (60%), vitamin E (80%), vitamin C (36%) and selenium (25%).

Association of Dietary Vitamin K1 Intake With the Incidence of Cataract Surgery in an Adult Mediterranean Population: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Cataract, one of the most frequent causes of blindness in developed countries, is strongly associated with aging. The exact mechanisms underlying cataract formation are still unclear, but growing evidence suggests a potential role of inflammatory and oxidative processes. Therefore, antioxidant and anti-inflammatory factors of the diet, such as vitamin K1, could play a protective role. Objective: To examine the association between dietary vitamin K1 intake and the risk of incident cataracts in an elderly Mediterranean population. Design, Setting, and Participants: A prospective analysis was conducted in 5860 participants from the Prevención con Dieta Mediterránea Study, a randomized clinical trial executed between 2003 and 2011. Participants were community-dwelling men (44.2%) and women (55.8%), and the mean (SD) age was 66.3 (6.1) years. Main Outcomes and Measures: Dietary vitamin K1 intake was evaluated using a validated food frequency questionnaire. The time to the cataract event was calculated as the time between recruitment and the date of the occurrence to cataract surgery, the time to the last visit of the follow-up, date of death, or the end of the study. Hazard ratios and 95% CIs for cataract incidence were estimated with a multivariable Cox proportional hazards model. Results: Participants were community-dwelling men (44.2%; n = 868) and women (55.8%; n = 1086), and the mean (SD) age was 66.3 (6.1) years. After a median of 5.6 years follow-up, we documented a total of 768 new cataracts. Participants in the highest tertile of dietary vitamin K1 intake had a lower risk of cataracts than those in the lowest tertile (hazard ratio, 0.71; 95% CI, 0.58-0.88; P = .002), after adjusting for potential confounders. Conclusions and Relevance: High intake of dietary vitamin K1 was associated with a reduced risk of cataracts in an elderly Mediterranean population even after adjusting by other potential confounders. Trial Registration: isrctn.org: ISRCTN35739639.

Reported Dietary Intake, Disparity between the Reported Consumption and the Level Needed for Adequacy and Food Sources of Calcium, Phosphorus, Magnesium and Vitamin D in the Spanish Population: Findings from the ANIBES Study.

Calcium, phosphorus, magnesium and vitamin D have important biological roles in the body, especially in bone metabolism. We aimed to study the reported intake, the disparity between the reported consumption and the level needed for adequacy and food sources of these four nutrients in the Spanish population. We assessed the reported intake for both, general population and plausible reporters. Results were extracted from the ANIBES survey, n = 2009. Three-day dietary reported intake data were obtained and misreporting was assessed according to the European Food Safety Authority (EFSA). Mean ± SEM (range) total reported consumption of calcium, phosphorus, magnesium, and vitamin D for the whole population were 698 ± 7 mg/day (71-2551 mg/day), 1176 ± 8 mg/day, (331-4429 mg/day), 222 ± 2 mg/day (73-782 mg/day), and 4.4 ± 0.1 µg/day (0.0-74.2 µg/day), respectively. In the whole group, 76% and 66%; 79% and 72%; and 94% and 93% of the population had reported intakes below 80% of the national and European recommended daily intakes for calcium, magnesium and vitamin D, respectively; these percentages were over 40% when the plausible reporters were analysed separately. The main food sources were milk and dairy products for calcium and phosphorus, cereals and grains for magnesium and fish for vitamin D. In conclusion, there is an important percentage of the Spanish ANIBES population not meeting the recommended intakes for calcium, magnesium and vitamin D.

Mediterranean diet and risk of heart failure: results from the PREDIMED randomized controlled trial.

AIMS: The aim of this study was to evaluate the effect of the Mediterranean diet (MedDiet) on the incidence of heart failure (HF), a pre-specified secondary outcome in the PREDIMED (PREvención con DIeta MEDiterránea) primary nutrition-intervention prevention trial. METHODS AND RESULTS: Participants at high risk of cardiovascular disease were randomly assigned to one of three diets: MedDiet supplemented with extra-virgin olive oil (EVOO), MedDiet supplemented with nuts, or a low-fat control diet. Incident HF was ascertained by a Committee for Adjudication of events blinded to group allocation. Among 7403 participants without prevalent HF followed for a median of 4.8 years, we observed 29 new HF cases in the MedDiet with EVOO group, 33 in the MedDiet with nuts group, and 32 in the control group. No significant association with HF incidence was found for the MedDiet with EVOO and MedDiet with nuts, compared with the control group [hazard ratio (HR) 0.68; 95% confidence interval (CI) 0.41-1.13, and HR 0.92; 95% CI 0.56-1.49, respectively]. CONCLUSION: In this sample of adults at high cardiovascular risk, the MedDiet did not result in lower HF incidence. However, this pre-specified secondary analysis may have been underpowered to provide valid conclusions. Further randomized controlled trials with HF as a primary outcome are needed to better assess the effect of the MedDiet on HF risk. TRIAL REGISTRATION: ISRCTN35739639.

Usage of Plant Food Supplements (PFS) for weight control in six European countries: results from the PlantLIBRA PFS Consumer Survey 2011-2012.

BACKGROUND: Obesity is increasing worldwide and weight-control strategies, including the consumption of plant food supplements (PFS), are proliferating. This article identifies the herbal ingredients in PFS consumed for weight control and by overweight/obese dieters in six European countries, and explores the relationship between their consumption and their self-reported BMI. METHODS: Data used were a subset from the PlantLIBRA PFS Consumer Survey 2011-2012, a retrospective survey of 2359 PFS consumers. The survey used a bespoke frequency-of-PFS-usage questionnaire. Analyses were performed in two consumer subsamples of 1) respondents taking the products for "body weight reasons", and 2) "dieters for overweight/obesity", to identify the herbal ingredients consumed for these reasons. The relationship between the 5 most consumed herbal ingredients and self-reported BMI in groups 1 and 2 is explored by comparing BMI proportions of consumers vs. non-consumers (using Chi-squared test). RESULTS: 252 PFS (8.8 %) were consumed for "body weight reasons" (by 240 PFS consumers); 112 PFS consumers (4.8 %) were "dieting for overweight/obesity". Spain is the country where consuming herbal ingredients for body weight control and dieting were most popular. Artichoke was the most consumed herbal ingredient. Considering only the 5 top products consumed by those who responded "body weight", when using the total survey sample, a greater proportion of BMI ≥ 25 was observed among consumers of PFS containing artichoke and green tea as compared to non-consumers (58.4 % vs. 49.1 % and 63.2 % vs. 49.7 % respectively). Considering only the 5 top products consumed by "dieters" and using only the "dieters" sample, a lower proportion of BMI ≥ 25 was observed among pineapple-containing PFS consumers (38.5 % vs. 81.5 %); however, when using the entire survey sample, a greater proportion of BMI ≥ 25 was observed among artichoke-containing PFS consumers (58.4 % vs. 49.1 %). CONCLUSIONS: A comparison of results among the scarce publications evaluating the use of weight-loss supplements at the population level is limited. Nevertheless every hint is important in finding out which are the self-treatment strategies used by overweight/obese individuals in European countries. Although limited by a small sample size, our study represents a first attempt at analysing such data in six EU countries. Our findings should encourage the conduction of further studies on this topic, long-term and large sample-sized studies, ideally conducted in the general population.

Adverse Effects of Plant Food Supplements Self-Reported by Consumers in the PlantLIBRA Survey Involving Six European Countries.

BACKGROUND: The use of food supplements containing botanicals is increasing in European markets. Although intended to maintain the health status, several cases of adverse effects to Plant Food Supplements (PFS) have been described. OBJECTIVES: To describe the self-reported adverse effects collected during the European PlantLIBRA PFS Consumer Survey 2011-2012, with a critical evaluation of the plausibility of the symptomatology reported using data from the literature and from the PlantLIBRA Poisons Centers' survey. SUBJECTS/SETTING: From the total sample of 2359 consumers involved in the consumers' survey, 82 subjects reported adverse effects due to a total of 87 PFS. RESULTS: Cases were self-reported, therefore causality was not classified on the basis of clinical evidence, but by using the frequency/strength of adverse effects described in scientific papers: 52 out of 87 cases were defined as possible (59.8%) and 4 as probable (4.6%). Considering the most frequently cited botanicals, eight cases were due to Valeriana officinalis (garden valerian); seven to Camellia sinensis (tea); six to Ginkgo biloba (Maidenhair tree) and Paullinia cupana (guarana). Most adverse events related to the gastrointestinal tract, nervous and cardiovascular systems. CONCLUSIONS: Comparing the data from this study with those published in scientific papers and obtained by the PlantLIBRA Poisons Centers' survey, some important conclusions can be drawn: severe adverse effects to PFS are quite rare, although mild or moderate adverse symptoms can be present. Data reported in this paper can help health professionals (and in particular family doctors) to become aware of possible new problems associated with the increasing use of food supplements containing botanicals.

Intake of selected bioactive compounds from plant food supplements containing fennel (Foeniculum vulgare) among Finnish consumers.

The purpose of this study was to estimate the intake of selected bioactive compounds from fennel-containing plant food supplements (PFS) among Finnish consumers. The estimated average intake of estragole was 0.20mg/d, of trans-anethole 1.15mg/d, of rosmarinic acid 0.09mg/d, of p-coumaric acid 0.0068mg/d, of kaempferol 0.0034mg/d, of luteolin 0.0525µg/d, of quercetin 0.0246mg/d, of matairesinol 0.0066µg/d and of lignans 0.0412µg/d. The intakes of kaempferol, quercetin, luteolin, matairesinol and lignans from PFS were low in comparison with their dietary supply. The intake of estragole was usually moderate, but a heavy consumption of PFS may lead to a high intake of estragole. The intake of trans-anethole did not exceed the acceptable daily intake, but PFS should be taken into account when assessing the total exposure. To our knowledge, this study provided the first intake estimates of trans-anethole, p-coumaric acid and rosmarinic acid in human populations.

Nutritional adequacy according to carbohydrates and fat quality.

PURPOSE: To investigate the association between carbohydrate quality, fat quality or adherence to the Mediterranean diet and intake adequacy of 19 micronutrients in the PREDIMED (PREvención con DIeta MEDiterránea) trial, a multicenter, randomized, controlled, parallel group and primary prevention trial conducted in Spain. METHODS: We assessed baseline dietary intake of 6,542 elderly subjects at high cardiovascular risk through a validated food frequency questionnaire (FFQ) and a validated 14-item Mediterranean diet (Med-diet) score. We used a multidimensional carbohydrate quality index (CQI) using four criteria and a fat quality index (FQI) according to the ratio (MUFA + PUFA)/(SFA + TFA). The probability of intake adequacy was calculated comparing the intakes to DRI, and also using the probabilistic approach. Absolute and adjusted probability of having inadequate intake for either ≥6 DRI or ≥8 DRI were estimated to assess nutritional adequacy according to quintiles of each index. RESULTS: The lowest prevalence of inadequate micronutrient intake (≥8 DRI) was found in the highest quintile of CQI or Med-diet score, and in the lowest quintile of FQI (adjusted fold risk: 1.4, 3.4 and 10.2 respectively in comparison with the lowest quintile). P for trend <0.001 in three multivariable models. A higher CQI or Med-Diet score and a lower FQI were significantly associated with a lower fold risk of unmet EAR values. CONCLUSIONS: A multidimensional assessment of CQI can be a useful tool to evaluate the quality of carbohydrates. This score and a 14-item Med-diet score were positively related to overall micronutrient adequacy in elderly participants.

Dietary fat intake and risk of cardiovascular disease and all-cause mortality in a population at high risk of cardiovascular disease.

BACKGROUND: Dietary fat quality and fat replacement are more important for cardiovascular disease (CVD) prevention than is total dietary fat intake. OBJECTIVE: The aim was to evaluate the association between total fat intake and fat subtypes with the risk of CVD (myocardial infarction, stroke, or death from cardiovascular causes) and cardiovascular and all-cause death. We also examined the hypothetical effect of the isocaloric substitution of one macronutrient for another. DESIGN: We prospectively studied 7038 participants at high CVD risk from the PREvención con DIeta MEDiterránea (PREDIMED) study. The trial was conducted from 2003 to 2010, but the present analysis was based on an expanded follow-up until 2012. At baseline and yearly thereafter, total and specific fat subtypes were repeatedly measured by using validated food-frequency questionnaires. Time-dependent Cox proportional hazards models were used. RESULTS: After 6 y of follow-up, we documented 336 CVD cases and 414 total deaths. HRs (95% CIs) for CVD for those in the highest quintile of total fat, monounsaturated fatty acid (MUFA), and polyunsaturated fatty acid (PUFA) intake compared with those in the lowest quintile were 0.58 (0.39, 0.86), 0.50 (0.31, 0.81), and 0.68 (0.48, 0.96), respectively. In the comparison between extreme quintiles, higher saturated fatty acid (SFA) and trans-fat intakes were associated with 81% (HR: 1.81; 95% CI: 1.05, 3.13) and 67% (HR: 1.67; 95% CI: 1.09, 2.57) higher risk of CVD. Inverse associations with all-cause death were also observed for PUFA and MUFA intakes. Isocaloric replacements of SFAs with MUFAs and PUFAs or trans fat with MUFAs were associated with a lower risk of CVD. SFAs from pastries and processed foods were associated with a higher risk of CVD. CONCLUSIONS: Intakes of MUFAs and PUFAs were associated with a lower risk of CVD and death, whereas SFA and trans-fat intakes were associated with a higher risk of CVD. The replacement of SFAs with MUFAs and PUFAs or of trans fat with MUFAs was inversely associated with CVD. This trial was registered at www.controlled-trials.com as ISRCTN 35739639.

Increased serum calcium levels and risk of type 2 diabetes in individuals at high cardiovascular risk.

OBJECTIVE: Insulin resistance and secretion depend on calcium homeostasis. Cross-sectional studies have associated elevated serum calcium levels with markers of impaired glucose metabolism. However, only one prospective cohort study has demonstrated an increased risk of diabetes in individuals with increased serum calcium concentrations. The aim of the current study was to prospectively investigate the association between albumin-adjusted serum calcium concentrations and type 2 diabetes in subjects at high cardiovascular risk. RESEARCH DESIGN AND METHODS: Prospective assessment of participants from two Spanish PREDIMED study centers where serum calcium levels were measured at baseline and yearly during follow-up. Multivariate-adjusted Cox regression models were fitted to assess associations between baseline and changes during follow-up in serum calcium levels and relative risk of diabetes incidence. RESULTS: After a median follow-up of 4.78 years, 77 new cases of type 2 diabetes occurred. An increase in serum calcium levels during follow-up was related to an increased risk of diabetes. In comparison with individuals in the lowest tertile (-0.78 ± 0.29 mg/dL), the hazard ratio (HR) and 95% CI for diabetes incidence in individuals in the higher tertile of change (0.52 ± 0.13 mg/dL) during follow-up was 3.48 (95% CI 1.48-8.17; P for trend = 0.01). When albumin-adjusted serum calcium was analyzed as a continuous variable, per 1 mg/dL increase, the HR of diabetes incidence was 2.87 (95% CI 1.18-6.96; P value = 0.02). These associations remained significant after individuals taking calcium supplements or having calcium levels out of normal range had been excluded. CONCLUSIONS: An increase in serum calcium concentrations is associated with an increased risk of type 2 diabetes in individuals at high cardiovascular risk.