Ruth Blanco-Rojo

Efficacy of a microencapsulated iron pyrophosphate-fortified fruit juice: a randomised, double-blind, placebo-controlled study in Spanish iron-deficient women.

Fe-deficiency anaemia is a worldwide health problem. We studied the influence of consuming an Fe-fortified fruit juice on Fe status in menstruating women. A randomised, double-blind, placebo-controlled study of 16 weeks of duration was performed. Subjects were randomised into two groups: the P group (n 58) or the F group (n 64), and consumed, as a supplement to their usual diet, 500 ml/d of a placebo fruit juice or an Fe-fortified fruit juice, respectively. The Fe-fortified fruit juice, containing microencapsulated iron pyrophosphate, provided 18 mg Fe/d (100 % of the RDA). At baseline and monthly, dietary intake, body weight and Fe parameters were determined: total erythrocytes, haematocrit, mean corpuscular volume (MCV), red blood cell distribution width (RDW), Hb, serum Fe, serum ferritin, serum transferrin, transferrin saturation, soluble transferrin receptor (sTfR) and zinc protoporphyrin (ZnPP). The fruit juice consumption involved increased intake of carbohydrates and vitamin C, and increased BMI within normal limits. Ferritin was higher in the F group after week 4 (P < 0·05) and became 80 % higher than in the P group after week 16 (P < 0·001), and transferrin decreased in the F group compared with the P group after week 4 (P < 0·001). RDW was higher at weeks 4 and 8 in the F group compared with the P group (P < 0·05). Transferrin saturation increased after week 8, and haematocrit, MCV and Hb increased after week 12, in the F group compared with the P group. Serum Fe did not change. sTfR and ZnPP decreased in the F group at week 16 (P < 0·05). Iron pyrophosphate-fortified fruit juice improves Fe status and may be used to prevent Fe-deficiency anaemia.

Four variants in transferrin and HFE genes as potential markers of iron deficiency anaemia risk: an association study in menstruating women

BackgroundIron deficiency anaemia is a worldwide health problem in which environmental, physiologic and genetic factors play important roles. The associations between iron status biomarkers and single nucleotide polymorphisms (SNPs) known to be related to iron metabolism were studied in menstruating women.MethodsA group of 270 Caucasian menstruating women, a population group at risk of iron deficiency anaemia, participated in the study. Haematological and biochemical parameters were analysed and 10 selected SNPs were genotyped by minisequencing assay. The associations between genetic and biochemical data were analysed by Bayesian Model Averaging (BMA) test and decision trees. Dietary intake of a representative subgroup of these volunteers (n = 141) was assessed, and the relationship between nutrients and iron biomarkers was also determined by linear regression.ResultsFour variants, two in the transferrin gene (rs3811647, rs1799852) and two in the HFE gene (C282Y, H63D), explain 35% of the genetic variation or heritability of serum transferrin in menstruating women. The minor allele of rs3811647 was associated with higher serum transferrin levels and lower transferrin saturation, while the minor alleles of rs1799852 and the C282Y and H63D mutations of HFE were associated with lower serum transferrin levels. No association between nutrient intake and iron biomarkers was found.ConclusionsIn contrast to dietary intake, these four SNPs are strongly associated with serum transferrin. Carriers of the minor allele of rs3811647 present a reduction in iron transport to tissues, which might indicate higher iron deficiency anaemia risk, although the simultaneous presence of the minor allele of rs1799852 and HFE mutations appear to have compensatory effects. Therefore, it is suggested that these genetic variants might potentially be used as markers of iron deficiency anaemia risk.

Effects of an Iron or Iron and Vitamin D–Fortified Flavored Skim Milk on Iron Metabolism: A Randomized Controlled Double-Blind Trial in Iron-Deficient Women

Objectives: Iron deficiency anemia and vitamin D deficiency are considered global pandemics. The aim of this study was to determine whether the consumption of a dairy product fortified with iron and vitamin D, compared to the equivalent with only added iron, exerts an additional effect on iron metabolism in iron-deficient menstruating women. Methods: The design was a randomized, placebo-controlled, double-blind, parallel-group trial of 16 weeks’ duration. Subjects were randomized into 2 groups that consumed, as part of their usual diet, 500 mL/day of an iron (n = 54) or iron- and vitamin D–fortified (n = 55) flavored skim milk. At baseline and monthly, dietary intake, body weight, and hematological and iron metabolism biomarkers were determined. Serum 25-hydroxyvitamin D was analyzed at baseline and weeks 8 and 16. Data were analyzed by analysis of variance (ANOVA) of repeated measures for time and Time×Group interaction effects. Results: A total of 109 volunteers completed the study. Calcium and iron intakes increased during the intervention (p < 0.001 for both groups). Serum 25-hydroxyvitamin D significantly increased in Fe + D group during the assay (p < 0.001) and at week 16 it was higher compared to the Fe group (p < 0.05). Serum ferritin, serum transferrin, mean corpuscular volume, mean corpuscular hemoglobin, and red blood cell distribution width showed significant time effects but no Time×Group interaction. Higher values of erythrocytes (p = 0.01), hematocrit (p = 0.05), and hemoglobin (p = 0.03) at week 8 were observed in the Fe + D group compared to the Fe group. Conclusion: Iron-fortified flavored skim milk does not improve iron status in iron-deficient menstruating women. However, vitamin D fortification slightly enhances erythropoiesis and iron status.

Influence of Diet, Menstruation and Genetic Factors on Iron Status: A Cross-Sectional Study in Spanish Women of Childbearing Age

The aim of this study was to investigate the combined influence of diet, menstruation and genetic factors on iron status in Spanish menstruating women (n = 142). Dietary intake was assessed by a 72-h detailed dietary report and menstrual blood loss by a questionnaire, to determine a Menstrual Blood Loss Coefficient (MBLC). Five selected SNPs were genotyped: rs3811647, rs1799852 (Tf gene); rs1375515 (CACNA2D3 gene); and rs1800562 and rs1799945 (HFE gene, mutations C282Y and H63D, respectively). Iron biomarkers were determined and cluster analysis was performed. Differences among clusters in dietary intake, menstrual blood loss parameters and genotype frequencies distribution were studied. A categorical regression was performed to identify factors associated with cluster belonging. Three clusters were identified: women with poor iron status close to developing iron deficiency anemia (Cluster 1, n = 26); women with mild iron deficiency (Cluster 2, n = 59) and women with normal iron status (Cluster 3, n = 57). Three independent factors, red meat consumption, MBLC and mutation C282Y, were included in the model that better explained cluster belonging (R2 = 0.142, p < 0.001). In conclusion, the combination of high red meat consumption, low menstrual blood loss and the HFE C282Y mutation may protect from iron deficiency in women of childbearing age. These findings could be useful to implement adequate strategies to prevent iron deficiency anemia.

Changes in blood pressure and lipid levels in young women consuming a vitamin D-fortified skimmed milk: a randomised controlled trial.

Vitamin D exerts a variety of extra-skeletal functions. Aim: to know the effects of the consumption of a vitamin D-fortified skimmed milk on glucose, lipid profile, and blood pressure in young women. Methods: a randomised, placebo-controlled, double-blind parallel-group trial of 16 weeks duration was conducted in young women with low iron stores who consumed a skimmed milk fortified with iron and 200 IU/day (5 μg) of vitamin D (D-fortified group, n = 55), or a placebo without vitamin D (D-placebo group, n = 54). A reference group (n = 56) of iron-sufficient women was also recruited. Results: baseline serum 25-hydroxyvitamin D was inversely correlated with total-cholesterol (r = −0.176, p = 0.023) and low density lipoprotein-cholesterol (LDL-chol) (r = −0.176, p = 0.024). During the assay, LDL-cholesterol increased in the D-placebo group (p = 0.005) while it tended to decrease in the D-fortified group (p = 0.07). Neither group displayed changes in total-cholesterol, high density lipoprotein-cholesterol (HDL-chol), triglycerides or glucose levels. Systolic (p = 0.017) and diastolic (p = 0.010) blood pressure decreased during the assay in the D-fortified group without significant differences compared to the D-placebo. Conclusion: consumption of a dairy product fortified with vitamin D reduces systolic and diastolic blood pressure but does not change lipid levels in young women.

A Novel SNaPshot Assay to Detect Genetic Mutations Related to Iron Metabolism

The minisequencing method is a cost-effective tool to study single-nucleotide polymorphisms in human disease. For this reason, a novel polymerase chain reaction multiplex SNaPshot reaction has been developed that targets 10 autosomal mutations in genes, or regions near to them, reported to be involved in iron metabolism: TMPRSS6, TF, and HFE. To validate this multiplex, 284 samples from unrelated women from the Spanish population were tested at a fertile age. The novel polymerase chain reaction multiplex SNaPshot reaction developed is a very simple, sensitive, and low-cost approach, and therefore will be useful as a tool of clinic diagnosis in iron metabolism alterations and to replicate results obtained from genome-wide linkage analysis.

Bone remodelling is reduced by recovery from iron-deficiency anaemia in premenopausal women

Iron-deficiency anaemia (IDA), one of the most common and widespread health disorders worldwide, affects fundamental metabolic functions and has been associated with deleterious effects on bone. Our aim was to know whether there are differences in bone remodelling between a group of premenopausal IDA women and a healthy group, and whether recovery of iron status has an effect on bone turnover markers. Thirty-five IDA women and 38 healthy women (control group) were recruited throughout the year. IDA women received pharmacological iron treatment. Iron biomarkers, aminoterminal telopeptide of collagen I (NTx), procollagen type 1 N-terminal propeptide (P1NP), 25-hydroxyvitamin D, and parathormone (PTH) were determined at baseline for both groups and after treatment with pharmacological iron for the IDA group. IDA subjects were classified as recovered (R) or non-recovered (nR) from IDA after treatment. NTx levels were significantly higher (p <0.001), and P1NP levels tended to be lower in IDA women than controls after adjusting for age and body mass index (BMI), with no differences in 25-hydroxyvitamin D or PTH. After treatment, the R group had significantly lower NTx and P1NP levels compared to baseline (p <0.05 and p <0.001 respectively), whilst no significant changes were seen in the nR group. No changes were seen in 25-hydroxyvitamin D or PTH for either group. IDA is related to higher bone resorption independent of age and BMI. Recovery from IDA has a concomitant beneficial effect on bone remodelling in premenopausal women, decreasing both bone resorption and formation.

Vitamin B12 and folate levels increase during treatment of iron deficiency anaemia in young adult woman

The relationship between iron deficiency and vitamin B12 and folate was recognized several decades ago. Combined deficiency is important in clinical practice owing to its relationship with malabsorption syndromes. By contrast, iron deficiency and low levels of serum vitamin B12 with normal metabolic markers were often found mostly in young adults. In this work, vitamin B12/folate changes were investigated during treatment of iron deficiency anaemia (IDA) with pharmacological iron in young adult women.

Identification of a Novel Quantitative Trait Nucleotype Related to Iron Status in a Calcium Channel Gene

Several iron-related parameters have been reported to show significant heritability, and thus, seemed to be genetically regulated. A genome wide family-based study revealed two regions that showed a linkage signal with transferrin receptor levels. The aim of the study was to identify genetic markers associated with iron status biomarkers. Ten SNPs selected from the literature were tested, and parameters related to iron metabolism were analysed, in a group (n=284) of Spanish women. Data were analyzed using Bayesian Model Averaging (BMA) test and decision trees. The rs1375515, located in an intronic region of the calcium channel gene CACNA2D3, showed strong associations with levels of mean corpuscular volume according to BMA test, and with levels of haemoglobin and ferritin according to decision trees. The allele G was associated to low levels of these parameters which suggests higher iron deficiency anaemia risk. This SNP along with the C282Y mutation explained significant differences in the distribution of individuals in three iron-related clinical phenotypes (normal, iron deficient and iron deficiency anaemic). In conclusion, the rs1375515, or other genetic polymorphisms in linkage, may play important roles in iron status, probably by affecting the function of a calcium channel. These findings may be useful for further investigation in the etiology of iron diseases.

Genetic contribution to iron status: SNPs related to iron deficiency anaemia and fine mapping of CACNA2D3 calcium channel subunit

Numerous studies associate genetic markers with iron- and erythrocyte-related parameters, but few relate them to iron-clinical phenotypes. Novel SNP rs1375515, located in a subunit of the calcium channel gene CACNA2D3, is associated with a higher risk of anaemia. The aim of this study is to further investigate the association of this SNP with iron-related parameters and iron-clinical phenotypes, and to explore the potential role of calcium channel subunit region in iron regulation. Furthermore, we aim to replicate the association of other SNPs reported previously in our population. We tested 45 SNPs selected via systematic review and fine mapping of CACNA2D3 region, with haematological and biochemical traits in 358 women of reproductive age. Multivariate analyses include back-step logistic regression and decision trees. The results replicate the association of SNPs with iron-related traits, and also confirm the protective effect of both A allele of rs1800562 (HFE) and G allele of rs4895441 (HBS1L-MYB). The risk of developing anaemia is increased in reproductive age women carriers of A allele of rs1868505 (CACNA2D3) and/or T allele of rs13194491 (HIST1H2BJ). Association of SNPs from fine mapping with ferritin and serum iron suggests that calcium channels could be a potential pathway for iron uptake in physiological conditions.