M. Pilar Vaquero

Effect of Vitamin D Supplementation on Blood Pressure: A Systematic Review and Meta-analysis Incorporating Individual Patient Data

IMPORTANCE Low levels of vitamin D are associated with elevated blood pressure (BP) and future cardiovascular events. Whether vitamin D supplementation reduces BP and which patient characteristics predict a response remain unclear. OBJECTIVE To systematically review whether supplementation with vitamin D or its analogues reduce BP. DATA SOURCES We searched MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.com augmented by a hand search of references from the included articles and previous reviews. Google was searched for gray literature (ie, material not published in recognized scientific journals). No language restrictions were applied. The search period spanned January 1, 1966, through March 31, 2014. STUDY SELECTION We included randomized placebo-controlled clinical trials that used vitamin D supplementation for a minimum of 4 weeks for any indication and reported BP data. Studies were included if they used active or inactive forms of vitamin D or vitamin D analogues. Cointerventions were permitted if identical in all treatment arms. DATA EXTRACTION AND SYNTHESIS We extracted data on baseline demographics, 25-hydroxyvitamin D levels, systolic and diastolic BP (SBP and DBP), and change in BP from baseline to the final follow-up. Individual patient data on age, sex, medication use, diabetes mellitus, baseline and follow-up BP, and 25-hydroxyvitamin D levels were requested from the authors of the included studies. For trial-level data, between-group differences in BP change were combined in a random-effects model. For individual patient data, between-group differences in BP at the final follow up, adjusted for baseline BP, were calculated before combining in a random-effects model. MAIN OUTCOMES AND MEASURES Difference in SBP and DBP measured in an office setting. RESULTS We included 46 trials (4541 participants) in the trial-level meta-analysis. Individual patient data were obtained for 27 trials (3092 participants). At the trial level, no effect of vitamin D supplementation was seen on SBP (effect size, 0.0 [95% CI, -0.8 to 0.8] mm Hg; P=.97; I2=21%) or DBP (effect size, -0.1 [95% CI, -0.6 to 0.5] mm Hg; P=.84; I2=20%). Similar results were found analyzing individual patient data for SBP (effect size, -0.5 [95% CI, -1.3 to 0.4] mm Hg; P=.27; I2=0%) and DBP (effect size, 0.2 [95% CI, -0.3 to 0.7] mm Hg; P=.38; I2=0%). Subgroup analysis did not reveal any baseline factor predictive of a better response to therapy. CONCLUSIONS AND RELEVANCE Vitamin D supplementation is ineffective as an agent for lowering BP and thus should not be used as an antihypertensive agent.

An oily fish diet increases insulin sensitivity compared to a red meat diet in young iron-deficient women

Beneficial effects of n-3 fatty acids on a variety of physiological functions have been reported, but information related to the effects of oily fish consumed within a varied diet on glucose metabolism and diabetes risk is scarce. The objective of the study was to compare the effects of a diet rich in oily fish to those of a diet rich in red meat on lipid profile, oxidative status, glucose metabolism and insulin sensitivity in young, iron-deficient women. The study was designed attending the CONSORT statement guidelines. It was a randomised crossover dietary intervention study with two 8-week periods. Two diets were designed differing only in their oily fish or red meat content (four portions per week). Twenty-five young iron-deficient women with normal lipid, glucose and insulin levels participated in the assay. Lipid profile (total, LDL- and HDL-cholesterol, TAG), fasting glucose, fasting insulin, and oxidation (lipoperoxides) and inflammation (soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1) biomarkers were analysed. Insulin sensitivity was assessed by the Homeostasis Model Assessment (HOMA) and Quantitative Insulin Sensitivity Check Index (QUICKI). Insulin levels significantly decreased and insulin sensitivity significantly increased with the oily fish diet. HDL-cholesterol significantly increased with the oily fish diet. Other parameters did not significantly differ between diets. An increase in oily fish consumption increases insulin sensitivity in young iron-deficient women. This outcome should be considered when giving dietary advice to this population.

Reduction in cardiovascular risk by sodium-bicarbonated mineral water in moderately hypercholesterolemic young adults

The effects of drinking sodium-bicarbonated mineral water on cardiovascular risk in young men and women with moderate cardiovascular risk were studied. Eighteen young volunteers (total cholesterol levels >5.2 mmol/L) without any disease participated. The study consisted of two 8-week intervention periods. Subjects consumed, as supplement to their usual diet, 1 L/day control low mineral water, followed by 1 L/day bicarbonated mineral water (48 mmol/L sodium, 35 mmol/L bicarbonate and 17 mmol/L chloride). Determinations were performed at the end of the control water period and on Weeks 4 and 8 of the bicarbonated water period. Body weight, body mass index (BMI), blood pressure, dietary intake, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, apolipoprotein (Apo) A-I, Apo B, triacylgycerols, glucose, insulin, adiponectin, high-sensitivity C-reactive protein (hs-CRP), soluble adhesion molecules [soluble intercellular adhesion molecule (sICAM) and soluble vascular adhesion molecule (sVCAM)], sodium and chloride urinary excretion, and urine pH were measured. Dietary intake, body weight and BMI showed no significant variations. Systolic blood pressure decreased significantly after 4 weeks of bicarbonated water consumption, without significant differences between Weeks 4 and 8. After bicarbonated water consumption, significant reductions in total cholesterol (by 6.3%; P=.012), LDL cholesterol (by 10%; P=.001), total/HDL cholesterol (P=.004), LDL/HDL cholesterol (P=.001) and Apo B (P=.017) were observed. Serum triacylglycerol, Apo A-I, sICAM-1, sVCAM-1 and hs-CRP levels did not change. Serum glucose values tended to decrease during the bicarbonated water intervention (P=.056), but insulin levels did not vary. This sodium-bicarbonated mineral water improves lipid profile in moderately hypercholesterolemic young men and women and could therefore be applied in dietary interventions to reduce cardiovascular risk.

Design and evaluation of a treatment programme for Spanish adolescents with overweight and obesity. The EVASYON Study

BackgroundThe prevalence of overweight and obesity (OW/OB) among adolescents worldwide has increased since the 60 s. Spain has reached one of the highest OW/OB prevalence rates among adolescents from European countries. The aim of this methodological paper is to describe the design and evaluation in the EVASYON study (Development, implementation and evaluation of the efficacy of a therapeutic programme for adolescents with OW/OB: integral education on nutrition and physical activity).Methods/DesignThe EVASYON was planned by a multidisciplinary team to treat OW/OB in Spanish adolescents. The EVASYON is a multi-centre study conducted in 5 hospitals in 5 Spanish cities (Granada, Madrid, Pamplona, Santander and Zaragoza) and two hundred and four OW/OB Spanish adolescents were recruited for this intervention. The treatment was implemented for approximately one-year follow-up. The adolescents were treated in groups of a maximum of 10 subjects; each group had 20 visits during the treatment period in two phases: intensive during the first 2 months (1st to 9th visits), and extensive during the last 11 months (10th to 20th visits). In order to assess the efficacy of the treatment, 8 dimensions were measured: diet; physical activity and fitness; eating behaviour; body composition; haematological profile; metabolic profile; minerals and vitamins; immuno-inflammatory markers. Moreover, genetic polymorphisms were also determined.DiscussionThe treatment programme developed in the EVASYON study was designed as a national pilot study to be implemented as an effective treatment for adolescents with OW/OB into the Spanish Health Care Service.

Oily Fish Increases Iron Bioavailability of a Phytate Rich Meal in Young Iron Deficient Women

Background: Iron deficiency is a major health problem worldwide, and is associated with diets of low iron bioavailability. Non-heme iron absorption is modulated by dietary constituents, one of which is the so-called “meat factor”, present in meat, fish (oily and lean) and poultry, which is an important enhancer of iron absorption in humans. Food processing also affects iron bioavailability. Objective: To evaluate the effect of consuming sous vide cooked salmon fish on non-heme iron bioavailability from a bean meal, rich in phytate, in iron-deficient women. Design: Randomized crossover trial in 21 young women with low iron stores (ferritin < 30 μg/L). Two test meals were extrinsically labelled with stable isotopes of iron (Fe-57 or Fe-58). Iron bioavailability was measured as the incorporation of stable isotopes into erythrocytes 14 d after meals consumption. Results: The addition of fish to the bean meal significantly increased (p < 0.001) iron absorption. Serum ferritin concentration and iron absorption were inversely correlated for both the bean meal (R2 = 0.294, p = 0.011) and the fish and bean meal (R2 = 0.401, p = 0.002). Conclusion: Sous vide cooked salmon fish increases iron absorption from a high phytate bean meal in humans.

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.

Iron absorption from meat pate fortified with ferric pyrophosphate in iron-deficient women

OBJECTIVE Preventing iron deficiency has been a main target of the World Health Organization since 1992. Difficulties to reach dietary recommended iron intakes and to enhance iron absorption should be overcome. We compared in iron-deficient women the bioavailability of iron of three meat pate products enriched with ferrous sulfate, ferric pyrophosphate encapsulated in liposomes, or ferric pyrophosphate encapsulated in liposomes plus a hemoglobin-based meat pigment. METHODS Seventeen women with low iron stores (ferritin <30 microg/L) took part in a three-way, randomized, crossover, double-blind postprandial intervention. Test meals consisted of 80 g of the three different enriched meat pate products, which were spread on two slices of white bread. The pate composition was 13.5 g of protein/100 g, 30 g of fat/100 g (49% monounsaturated fatty acids, 35% saturated fatty acids, 16% polyunsaturated fatty acids), 1 g of carbohydrates/100 g, and 19 mg of total iron (including 15 mg of iron from the test fortificants). Blood samples were taken at baseline and each hour for 6 h after eating the meal and serum iron was determined. RESULTS Serum iron concentration evolution during the postprandial study was similar with the three meals, and maximum concentrations were obtained between hours 2 and 4. The effect of type of fortificant was not significant. CONCLUSION Consumption of meat pate fortified with ferric pyrophosphate encapsulated in liposomes can be part of a dietary strategy for preventing iron deficiency in humans. The addition of larger amounts of a meat pigment rich in heme iron should be further studied.

Sodium bicarbonated mineral water decreases postprandial lipaemia in postmenopausal women compared to a low mineral water

The role of bicarbonated mineral waters on lipid metabolism and lipoprotein concentrations in man has scarcely been investigated. The present study aimed to investigate whether drinking sodium bicarbonated mineral water affects postprandial cholesterol and triacylglycerol metabolism in postmenopausal women. In a three-way, randomised, crossover study, eighteen healthy postmenopausal women consumed two sodium bicarbonated mineral waters (bicarbonated mineral water 1 and bicarbonated mineral water 2) and a low mineral water (500 ml of each) with a standard fat-rich meal (4552 kJ; 75.3 g fat). The bicarbonated waters were rich in sodium and bicarbonate and bicarbonated mineral water 1 contained 5.7 times more fluoride than bicarbonated mineral water 2. Fasting blood samples and postprandial blood samples were taken at 30, 60, 120, 240, 360 and 420 min after the end of the meal consumption. Cholesterol and triacylglycerols were determined in serum and chylomicrons. A significant water consumption effect was observed in the total area under the curve (TAUC) of serum and chylomicron triacylglycerols (ANOVA, P=0.008 and P=0.027, respectively). TAUC of serum triacylglycerols for bicarbonated mineral water 2 was significantly lower compared to low mineral water (Bonferroni, P=0.039). Peak concentration of serum triacylglycerols showed a significant water effect (P=0.025). Changes in chylomicron cholesterol were not significantly affected by the type of water. Bicarbonated mineral waters 1 and 2 did not show any significant differences. Drinking sodium bicarbonate-rich mineral waters reduces postprandial lipaemia in healthy postmenopausal women compared to drinking a low mineral water.

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.

Zinc and iron bioavailability in a powder or in-bottle-sterilized infant formula estimated by in vitro and in suckling rats

Maillard reaction and lactose isomerization may be induced during the processing involved in the manufacture of infant formulas. The effects of dehydratation and sterilization in an infant formula on iron and zinc bioavailability were studied. A powder (PIF), previously reconstituted, and an in-bottle-sterilized liquid infant formula (LIF), from the same manufacturer, were evaluated using an in vitro method and in suckling rats. After in vitro digestion the dialyzed and non-dialyzed soluble, and insoluble fractions of iron and zinc were separated. Two-week-old rat pups were fed PIF or LIF in a drinking bottle for 7 days. Infant formula intake (I), body weight and the fecal and urinary excretions were monitored and the following parameters calculated: apparent absorption (A), retention (R), and the coefficients %A/I, %R/A and %R/I. Soluble iron (dialyzed) and zinc (non-dialyzed) were higher (p < 0.001) in LIF than PIF after in vitro digestion. Insoluble iron was similar in both infant formulas but insoluble zinc was lower (p < 0.05) in LIF than PIF. Food intake (p = 0.045) and body weight on day 4 (p < 0.05) and on day 7 (p < 0.001) were lower in LIF compared to PIF. A, R (p < 0.05 for both minerals), %A/I, and %R/I (p < 0.001 and p < 0.05 for iron and zinc, respectively) were significantly lower in rats fed LIF. Similarly, the %R/A of iron was lower (p < 0.001) in this group. Hematocrit and hemoglobin did not show significant differences. Iron and zinc levels in liver, spleen and erythrocytes were similar in both groups, but skin iron concentration was higher in LIF. Therefore, in contrast with the in vitro results, consumption of the in-bottle-sterilized formula determines lower iron and zinc bioavailability compared to the reconstituted powder infant formula.