Núria Aranda

Effects of iron deficiency on neonatal behavior at different stages of pregnancy.

Animal and human studies have shown that prenatal and postnatal iron deficiency is a risk factor for behavioral, emotional and cognitive development. The aim of this study was to determine the associations between iron status of pregnant women and the behavior of their newborn, taking into account the timing in which the deficit occurs. This study was conducted in Spain (developed country) where: the general population is well-nourished; during pregnancy routine obstetrical checks are carried out; and pregnant women are systematically iron supplemented. A total of 216 healthy and well-nourished pregnant women and their term, normal weight newborn participated in this study. The neonatal behavior was assessed by the Neonatal Behavior Assessment Scale (NBAS). The results showed that in the first and second trimesters of pregnancy, iron deficiency was a weak and significant predictor of the NBAS autonomous nervous system cluster score, and in the third trimester, this condition predicted the NBAS motor and state organization clusters score and the NBAS robustness and endurance supplementary item. In conclusion, iron deficiency during pregnancy is related to the neonates general autonomous response, motor performance and self regulation capabilities.

Hemochromatosis (HFE) gene mutations and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Hereditary hemochromatosis (HH) is a strong risk factor for hepatocellular cancer, and mutations in the HFE gene associated with HH and iron overload may be related to other tumors, but no studies have been reported for gastric cancer (GC). A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), including 365 incident gastric adenocarcinoma and 1284 controls matched by center, sex, age and date of blood collection. Genotype analysis was performed for two functional polymorphisms (C282Y/rs1800562 and H63D/rs1799945) and seven tagSNPs of the HFE genomic region. Association with all gastric adenocarcinoma, and according to anatomical localization and histological subtype, was assessed by means of the odds ratio (OR) and 95% confidence interval (CI) estimated by unconditional logistic regression adjusted for the matching variables. We observed a significant association for H63D with OR (per rare allele) of 1.32 (CI = 1.03-1.69). In subgroup analyses, the association was stronger for non-cardia anatomical subsite (OR = 1.60, CI = 1.16-2.21) and intestinal histological subtype (OR = 1.82, CI = 1.27-2.62). Among intestinal cases, two tagSNPs (rs1572982 and rs6918586) also showed a significant association that disappeared after adjustment for H63D. No association with tumors located in the cardia or with diffuse subtype was found for any of the nine SNPs analyzed. Our results suggest that H63D variant in HFE gene seems to be associated with GC risk of the non-cardia region and intestinal type, possibly due to its association with iron overload although a role for other mechanisms cannot be entirely ruled out.

Polyphenol-rich foods exhibit DNA antioxidative properties and protect the glutathione system in healthy subjects.

SCOPE Polyphenols (ingested via food items) can decrease DNA, and oxidative damage of proteins and lipids. However, polyphenol effects in healthy populations have not been well defined. The aim of this study was to assess the relationship between urinary total polyphenol excretion (TPE), a biomarker of total polyphenol intake (TPI), polyphenol-rich foods, and oxidative stress biomarkers in healthy adults of different ages participating in the cross-sectional PAScual MEDicina study. METHODS AND RESULTS Urinary TPE was determined by Folin-Ciocalteau method in spot urine samples of 81 participants (46 women), classified into three age groups: 18 to 39, 40 to 54, and 55 to 72 years of age. TPI was quantified from 3-day dietary records using the Phenol-Explorer database. Urinary TPE increased with age (p < 0.001). Urinary TPE was inversely associated with urinary 8-hydroxydeoxyguanosine (8-OHdG; p<0.001) and erythrocyte-oxidized glutathione concentrations (p < 0.05). A negative association between urinary 8-OHdG and daily intake of polyphenols from vegetables and fermented beverages such as red wine was observed. CONCLUSION Urinary TPE increased with age and may reflect attenuation of oxidative damage. These results could explain the beneficial effects in healthy individuals of a diet rich in vegetables and moderate red wine; food items typical of the Mediterranean diet.

BDNF Val66Met polymorphism, energy intake and BMI: a follow-up study in schoolchildren at risk of eating disorders

BackgroundEating disorders (ED) have a multifactorial aetiology in which genetics play an important role. Several studies have found an association between the Val66Met (G196A) polymorphism of the Brain-Derived Neurotrophic Factor (BDNF) and Eating disorders.The aim of this study was to determine the association of the Val66Met (G196A) polymorphism of the BDNF gene and its effect on eating disorders (ED), energy intake and BMI in schoolchildren.MethodsTwo-year cohort study (preadolescence to adolescence). From an initial sample of 1336 Caucasian children (mean age = 11.37 years), a group at risk of ED (n = 141) and a control group (n = 117) were selected using the Childrens Eating Attitudes Test. Two years later, they were re-classified into an at-risk group (n = 41) and a control group (n = 159) using the Eating Attitudes Test. The diagnosis of the individuals at risk of ED was confirmed by means of the Diagnostic Interview for Children and Adolescents. BMI, energy intake and the Val66Met (G196A) polymorphism of the BDNF gene were analysed in the at-risk and control groups.ResultsThe frequency of genotypes of the Val66Met (G196A) polymorphism of the BDNF gene is 28.6% (95% CI: 22.4-34.9) in the heterozygous form (Val/Met) and 5% (95% CI: 2.4-9) in the homozygous form (Met/Met). We detected no association between Val66Met genotypes and the severity of ED. Over time, the carriers of the Met66 allele with a persistent risk of ED significantly restricted energy intake (507 Kcal/day; p = 0.033).ConclusionWe have not found an association between Val66Met (G196A) polymorphism of the BDNF and ED in schoolchildren from general population. The relationship found between this polymorphism and energy intake restriction in adolescents with a persistent risk of ED should be replicated in a larger sample.

Diet, iron biomarkers and oxidative stress in a representative sample of Mediterranean population

BackgroundThe consumption pattern characterized by high consumption of vegetables, fruit, fish, olive oil and red wine has been associated with improvements in the total antioxidant capacity of individuals and reduced incidence of diseases related to oxidation. Also, high body iron levels may contribute to increase the oxidative stress by the generation of reactive oxygen species. The objective of this study is to analyze the relationship between antioxidant and pro-oxidant factors obtained from the diet and iron biomarkers on lipoprotein oxidation and total antioxidant capacity in a representative sample of the Mediterranean population.MethodsCross-sectional prospective study, carried out with 815 randomly selected subjects (425 women and 390 men). Dietary assessment (3-day food records), iron biomarkers (serum ferritin, serum iron and transferrin saturation), biochemical markers of lipoperoxidation (TBARS), antioxidant capacity (ORAC) and CRP (C-Reactive Protein) were determined. Multiple Linear Regression (MLR) models were applied to analyze the association between diet factors and iron biomarkers on TBARS and ORAC levels.ResultsWe observed that lipoperoxidation measured by TBARS increased by age but no differences were observed by sex. Antioxidant capacity measured by ORAC is independent of age and sex. In general, increasing age, tobacco, heme iron intake from meat and fish and transferrin saturation were independently and positively associated with TBARS, while non-heme iron was negatively associated. Vegetables, vitamin C intake and serum ferritin were positively associated with ORAC, whereas saturated fatty acids and meat intake were negatively associated.ConclusionsIn our general population, we observed that oxidative stress is related to aging, but antioxidant capacity is not. The highest intake of dietary non-heme iron, vegetables and vitamin C intake exerts a protective effect against oxidation while the highest intake of dietary heme iron from meat and fish and saturated fatty acids are associated with increased oxidative stress. High levels of circulating iron measured by transferrin saturation are associated with increased oxidative stress in women however its association with the higher levels of serum ferritin is controversial.

Paraoxonase-1 status in patients with hereditary hemochromatosis

Hereditary hemochromatosis (HH) is characterized by accumulation of iron, oxidative stress, inflammation, and fibrogenesis in liver tissue. In this setting, research on the protection afforded by intracellular antioxidants is of clinical relevance. Paraoxonase-1 (PON1) is an enzyme that degrades lipid peroxides. This study investigates the alterations in serum PON1 status, PON1 gene polymorphisms, and PON1 hepatic expression in patients with HH. We performed a case-control study in 77 patients with HH (80.5% men, 22–70 years of age) and 408 healthy individuals (43.1% men, 26–74 years of age). Serum PON1 activities against different substrates and PON1192 and PON155 polymorphisms were analyzed. PON1 protein expression was investigated in 20 liver biopsies. HH patients had significantly lower serum PON1 activity, which was inversely correlated with ferritin (marker of iron stores) and serum 8-isoprostane concentrations (index of oxidative stress). PON1 protein expression in liver tissue was higher in patients and showed stronger staining in hepatocytes surrounding the areas of inflammation. Our study provides preliminary evidence that PON1 may play a role in protecting against iron-induced oxidative stress in hereditary hemochromatosis.

Excess body iron and the risk of type 2 diabetes mellitus: a nested case–control in the PREDIMED (PREvention with MEDiterranean Diet) study

A prospective nested case-control study within the PREvention with MEDiterranean Diet (PREDIMED) was conducted to evaluate the relationship between excess body Fe (measured as serum ferritin (SF), soluble transferrin receptor (sTfR) and sTfR:ferritin ratio) and the risk of type 2 diabetes mellitus (T2DM) in a Mediterranean population at a high risk of CVD, without T2DM at the start of the study. The study contained 459 subjects, 153 with incident T2DM (cases) and 306 without incident T2DM (controls). The follow-up period was for 6.0 (interquartile range 3.9-6.5) years. For each incident diabetic subject, two subjects were selected as controls who were matched broadly for age as well as for sex, intervention group and BMI. We observed a relationship between SF values >257 μg/l in males and >139 μg/l in females and the risk of T2DM, following adjustment in the conditional logistic regression model for high-sensitivity C-reactive protein, fasting glucose and other components of the metabolic syndrome (OR 3.62, 95% CI 1.32, 19.95; P= 0.022). We also found an association between low sTfR:ferritin ratio levels and the incidence of T2DM (OR 3.02, 95% CI 1.09, 8.39; P= 0.042), but no association with sTfR (OR 1.29, 95% CI 0.51, 3.23; P= 0.722). Oxidative stress has been hypothesised to contribute to the development of insulin resistance and β-cell dysfunction, the two key events in the clinical development of T2DM. Following adjustment for other risk factors for T2DM, excess body Fe (measured as SF and sTfR:ferritin ratio) was associated with an increased risk of developing T2DM in a Mediterranean population at a high risk of CVD.

Prevalence of iron deficiency states and risk of haemoconcentration during pregnancy according to initial iron stores and iron supplementation

OBJECTIVE To describe the prevalence of iron depletion (ID), iron-deficiency anaemia (IDA) and risk of haemoconcentration during pregnancy and at delivery and to assess the influence of initial Fe stores and Fe supplementation on that prevalence. DESIGN Longitudinal study. SETTING Hospital Universitari Sant Joan de Reus (Catalonia, Spain). SUBJECTS Two hundred and eighty-five pregnant women. Serum ferritin and Hb were measured in the first, second and third trimesters and at delivery. Women were classified according to initial Fe stores as ID or no ID (serum ferritin

Increased iron levels and lipid peroxidation in a Mediterranean population of Spain

12mg/l) and according to Fe supplement use as supplemented or nonsupplemented. RESULTS Initial ID was 16.2%. At delivery, 45.7% had ID, 13.5% IDA and 13.3% had risk of haemoconcentration. Initial ID and non-supplemented groups had significantly higher prevalences of ID and IDA and lower risk of haemoconcentration at delivery than the other groups. In the multiple logistic models, no initial ID and Fe supplementation exerted a protective effect against ID at delivery (adjusted OR50.28; 95% CI 0.13, 0.58 and adjusted OR50.39; 95% CI 0.22, 0.69, respectively). Moderate Fe supplementation did not seem to clearly prevent IDA (adjusted OR50.91; 95% CI 0.42, 1.96) or to enhance the haemoconcentration (adjusted OR51.42; 95% CI 0.58, 3.50). CONCLUSIONS The prevalence of ID and IDA was high in late pregnancy in healthy pregnant women, particularly in those with initial ID and/or those not taking supplements. Starting pregnancy with no ID and/or taking moderate Fe supplementation decreased the likelihood of ID at delivery. The risk of haemoconcentration was high at delivery, but did not seem to be promoted by Fe supplementation. Further research is necessary to determine the most appropriate nutritional advice for pregnant women.

Body iron status and gastric cancer risk in the EURGAST study.

Many chronic diseases are adversely affected by elevated iron levels. It has been speculated that this relationship is mediated by increased oxidative stress, due to the ability of iron to generate reactive oxygen species. The aim of this study was to assess the relationship between elevated iron levels and lipid peroxidation in Caucasian adults residing in the north‐eastern Mediterranean region of Spain.