Daniel López de Romaña

Risks and benefits of copper in light of new insights of copper homeostasis.

Copper is an essential micronutrient involved in a variety of biological processes indispensable to sustain life. At the same time, it can be toxic when present in excess, the most noticeable chronic effect being liver damage. Potent, efficient regulatory mechanisms control copper absorption in the digestive tract and copper biliary excretion; absorption ranges between 12 and 60% in humans, depending on Cu intake, presence of other factors in the diet that may promote or inhibit its absorption and on the copper status of the individual. Current evidence suggests that copper deficiency may be more prevalent than previously thought, while copper toxicity is uncommon under customary daily life conditions. Menkes syndrome and Wilson disease are genetic conditions associated with severe copper deficiency and severe copper toxicity, respectively. Effects of milder degrees of copper deficiency and excess copper exposure are not well described, mainly due to lack of sensitive and specific indicators; serum copper concentration and ceruloplasmin are the most frequently used indicators, but they only detect rather intense changes of copper status. Of the many proteins assessed as potential markers of copper status the chaperone of Zn-Cu superoxide dismutase (CCS1) has yielded promising results; data on its performance under different conditions are needed to confirm its use as an indicator of early copper deficiency. Defining copper requirements and upper safe limits of consumption (UL) is a complex process since there are adverse health consequences from both copper deficiency and copper excess (U shape curve). The regulatory framework for risk assessment of essential trace elements introduced by the International Programme on Chemical Safety (IPCS) has proposed a homeostatic model to determine the Adequate Range of Oral Intake (AROI) of essential trace elements; the nadir of the resulting U shape curve serves to define the AROI. At this range of intake physiological mechanisms allow for normal homeostasis and basically, there are no detectable adverse effects. At present, Recommended Dietary Intakes (DRIs) and Adequate Intakes (AIs) are used to recommend copper intakes at different ages and life situations. Evidence obtained in humans and non-human primates presented here suggest that current copper UL should be re evaluated. Developing the scientific basis for a copper UL and evaluating the relevance of copper deficiency globally are future key challenges for copper researchers.

Calcium Does Not Inhibit the Absorption of 5 Milligrams of Nonheme or Heme Iron at Doses Less Than 800 Milligrams in Nonpregnant Women

Calcium is the only known component in the diet that may affect absorption of both nonheme and heme iron. However, the evidence for a calcium effect on iron absorption mainly comes from studies that did not isolate the effect of calcium from that of other dietary components, because it was detected in single-meal studies. Our objective was to establish potential effects of calcium on absorption of nonheme and heme iron and the dose response for this effect in the absence of a meal. Fifty-four healthy, nonpregnant women were selected to participate in 4 iron absorption studies using iron radioactive tracers. We evaluated the effects of calcium doses between 200 and 1500 mg on absorption of 5 mg nonheme iron (as ferrous sulfate). We also evaluated the effects of calcium doses between 200 and 800 mg on absorption of 5 mg heme iron [as concentrated RBC (CRBC)]. Calcium was administered as calcium chloride in all studies and minerals were ingested on an empty stomach. Calcium doses ≥1000 mg diminished nonheme iron absorption by an average of 49.6%. A calcium dose of 800 mg diminished absorption of 5 mg heme iron by 37.7%. In conclusion, we demonstrated an isolated effect of calcium (as chloride) on absorption of 5 mg of iron provided as nonheme (as sulfate) and heme (as CRBC) iron. This effect was observed at doses higher than previously reported from single-meal studies, starting at ~800 mg of calcium.

Less than adequate vitamin D status and intake in Latin America and the Caribbean:a problem of unknown magnitude.

Background The prevalence of vitamin D deficiency in Latin America and the Caribbean is unknown. Objective To examine the prevalence data available on vitamin D deficiency in Latin America and the Caribbean. Methods A systematic review was conducted in 2011. Studies using biochemical biomarkers and dietary intake estimation were included. Studies conducted in apparently healthy individuals, independently of age, latitude, skin pigmentation, and season of the year at the time of blood collection, were included. Results A total of 243 studies were identified. The final number of selected studies was 28, including two National Health Surveys (Mexico and Argentina). There are studies that report the vitamin D status of specific subgroups conducted in Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, and Mexico. However, the small sample sizes in these studies and thus the low national representativeness of the reported data do not allow for an accurate assessment of vitamin D status at the regional level. In the majority of the countries with available data, we observed that vitamin D insufficiency was classified as a mild, moderate, or severe public health problem. The only country with a nationally representative sample was Mexico, which found 24%, 10%, 8%, and 10% prevalence rates of vitamin D insufficiency (25-hydroxyvitamin D < 50 nmol/L) in preschoolers, schoolchildren, adolescents, and adults, respectively. The prevalence of vitamin D deficiency (25-hydroxyvitamin D < 20 nmol/L) was less than 1% for all groups. Conclusions There is some indication that vitamin D insufficiency may be a public health problem in Latin America and the Caribbean, but the exact magnitude is currently unknown.

Body mass index, iron absorption and iron status in childbearing age women.

BACKGROUND The prevalence of obesity has increased at an alarming rate worldwide. Some studies have observed an association between iron (Fe) deficiency (ID) and obesity, however more research is needed. OBJECTIVE To assess whether body mass index (BMI) is associated with both Fe absorption and Fe status. METHODS A cross sectional sample of 318 Chilean childbearing age women was studied. The women received either a single dose of 0.5mg of Fe (n=137, group 1) or 3mg of Fe plus ascorbic acid (1:2 molar ratio) (n=181, group 2), both as FeSO4 with labeled radioisotopes. Fe absorption was assessed through radio Fe erythrocyte incorporation. Fe status was determined by hemoglobin (Hb), mean corpuscular volume, serum Fe, total iron binding capacity, transferrin saturation, erythrocyte Zn protoporphyrin and serum ferritin (SF). RESULTS 29%, 47% and 24% of the women were classified as normal, overweight or obese, respectively. Fe absorption was significantly lower in obese women (p<0.05). In group 1, the geometric mean and range ±1 SD of the percentage of Fe absorption for normal-weight women was 32.9% vs. 19.7% in obese. For group 2, this percentage was 36% vs. 30%, respectively (2-way ANOVA: BMI classification and Fe dose p<0.05; interaction p=0.34). Although Fe absorption was lower in obese women, they had higher SF (p<0.01) and Hb (p<0.05) concentrations. CONCLUSION Although we did not observe a relationship between BMI and Fe status, obese women displayed lower Fe absorption compared with overweight and normal weight women, possibly due to subclinical inflammation associated with obesity.

Effect of dietary protein on heme iron uptake by Caco-2 cells

ObjectiveTo study heme iron bioavailability and the role of dietary protein (animal and vegetable) on iron uptake using an in vitro model (Caco-2 cell line).MethodsCaco-2 cells were seeded in bicameral chambers with different animal (beef, chicken or fish) or vegetable (peas, lentils, and soybeans) proteins or with pure animal (collagen and casein) or vegetable (gliadin, zein, and glutein) protein extracts. The effect of each protein over heme iron absorption was assessed.ResultsIntact heme uptake was higher than either heme plus albumin or digested heme plus albumin, but lower than digested heme. White meal exerted the highest inhibitory effect on hemin uptake. Heme iron uptake decreased in the presence of all legume extracts, but was not significantly different among them (one-way ANOVA, NS). Pure animal (collagen and casein) and vegetable (zein and glutelin) proteins increased heme iron uptake, except for gliadin.ConclusionAnimal and vegetable protein in general decreased heme iron uptake. However, purified animal and vegetable protein induce an increase in heme iron uptake.

Baseline evaluation of nutritional status and government feeding programs in Chiclayo, Peru.

Background Because of the rapid growth of the urban population in Peru, food and nutrition insecurity will occur increasingly in this population. For appropriate policy setting and programming, the food and nutrition situation of the urban poor requires better understanding. Objective To gain information about the nature, magnitude, severity, and causes of the nutritional problems of the population in low-income areas of the city of Chiclayo, Peru. Methods A cross-sectional nutrition survey was conducted in 1,604 households, covering children under 5 years of age and their parents. Results The prevalence rates of stunting, wasting, overweight. and anemia in children were 15.4%, 1.3%, 4.6%, and 65.7%, respectively; one third of adults were overweight, and one tenth were obese; 2.1% of the mothers were underweight; and 34.3% of mothers and 12.2% of fathers had anemia. Governmental feeding programs did not address these problems adequately. Conclusions Interventions must have adequate targeting; address appropriate responses at the household, community, and national levels; and reduce stunting, obesity, and iron-deficiency anemia.

Prepubertal Adiposity, Vitamin D Status, and Insulin Resistance.

OBJECTIVE: To evaluate the following from prepuberty to the puberty-onset: (1) changes in serum 25-hydroxyvitamin-D (25[OH]D), adiposity, and insulin resistance (IR); (2) the effect of prepubertal adiposity on serum 25(OH)D changes; and (3) the combined effect of prepubertal obesity and suboptimal-25(OH)D on IR at puberty-onset. METHODS: A total of 426 prepubertal children (∼54% girls) were followed during pubertal-onset assessing before and after puberty-onset serum 25(OH)D, adiposity (BMI and waist circumference) and IR indicators (homeostasis-model-assessment of IR [HOMA-IR]). Associations were tested using multiple and logistic regression models adjusted by age, gender, and seasonality. RESULTS: At puberty-onset, mean serum 25(OH)D decreased (32.2 ± 8.9 Tanner I vs 25.2 ± 8.3 ng/mL Tanner II) and total and central obesity increased (BMI-for-age-z-score ≥2 SD [%]: 16.4 vs 22.1; waist-circumference ≥75th percentile [%]: 27.2 vs 37.1, all P < .05). Children with higher adiposity before puberty onset had higher risk of suboptimal-25(OH)D (<30 ng/mL) in Tanner II (ie, odds ratio = 2.7 [1.1–6.7] for obesity and 2.7 [1.4–5.5] for central-obesity) after adjusting for relevant covariates. Children with higher adiposity and suboptimal-25(OH)D before puberty-onset had higher HOMA-IR compared with their counterparts in Tanner II (HOMA-IR: 2.8 [2.5–3.1] if central-obese and suboptimal-25[OH]D vs 2.1 [1.9–2.3] no central-obesity and optimal-25[OH]D). CONCLUSIONS: We found that serum 25(OH)D declined with puberty-onset, likely because of adiposity increase. Moreover, children with the combined condition of central-obesity and suboptimal-25(OH)D before puberty-onset had higher pubertal IR. These results highlight the need of ensuring adequate-25(OH)D status before pubertal-onset, particularly in obese children.

EL ZINC EN LA SALUD HUMANA - II

El zinc es un cation divalente con multiples funciones en el cuerpo humano. La absorcion de zinc ocurre en el intestino delgado y es junto con la excrecion de zinc por las heces, uno de los dos puntos de control de la homeostasis de zinc. El zinc es un nutriente esencial con un rol especifico en mas de 300 enzimas, las cuales participan en todas las reacciones bioquimicas importantes del cuerpo humano. Por ende, el estado de la nutricion de zinc tiene un efecto directo en el crecimiento, el desarrollo neurologico y de comportamiento y en el sistema inmune. El diagnostico de deficiencia de zinc en seres humanos no es posible pues aun no existe un marcador lo suficientemente sensible. Sin embargo, el zinc serico es aceptable para evaluar poblaciones. Finalmente, se pueden usar las estrategias de suplementacion, fortificacion y/o modificacion alimentaria para controlar y/o prevenir la deficiencia de este elemento

One-month of calcium supplementation does not affect iron bioavailability: A randomized controlled trial

OBJECTIVES Calcium (Ca) and iron (Fe) are essential minerals for normal growth and development. Although previous studies have shown that Ca inhibits acute Fe absorption, there is no evidence of the possible long- or medium-term effects of Ca supplementation on Fe bioavailability. The aim of this study was to determine the effect of 34 d of Ca supplementation on heme Fe and non-heme Fe bioavailability in non-pregnant women of ages 33 to 47 y. METHODS This was a prospective, randomized, double-blind, placebo-controlled trial. Twenty-six healthy women (40 ± 5 y) were randomly assigned to receive either 600 mg of elemental Ca/d as CaCO3 (Ca group, n = 13) or a placebo (P group, n = 13) for 34 d. Heme Fe and non-heme Fe bioavailability were determined before and after treatment using (55)Fe and (59)Fe radioisotopes. A two-factor, repeated-measures analysis of variance was used to assess differences by treatment and timing. RESULTS The geometric mean (range ± 1 SD) of heme Fe bioavailability before and after treatment was 16.5% (8.3-32.8) and 26% (15.5-43.6) for the Ca group and 21.8% (13.0-36.6) and 25.1% (16.5-38.3) for the P group. Non-heme Fe bioavailability before and after treatment was 39.5% (19.9-78.7) and 34.1% (19.1-60.6) for the Ca group, and 44.6% (24.9-79.7) and 39.3% (24.3-63.4) for the P group. There were no differences in either heme Fe or non-heme Fe bioavailability either at baseline or after treatment. CONCLUSION The administration of calcium supplements for 34 d does not affect iron bioavailability. This trial is registered with Controlled-trials.gov, number ISRCTN 89888123.

Supplementation with zinc between meals has no effect on subsequent iron absorption or on iron status of Chilean women.

OBJECTIVE Studies on the effect of zinc (Zn) supplementation on iron absorption and iron status have shown mixed results. We investigated the effect of daily supplementation with 20 mg of Zn for a period of 2 mo on iron absorption and iron status of Chilean women. METHODS Forty-four non-anemic, clinically healthy women 35 to 45 y of age were randomly selected to receive daily 20 mg of Zn, as Zn sulfate, or a placebo between meals for a period of 2 mo. Iron and zinc biochemical indicators and iron absorption studies were assessed at baseline and at the end of the study. Iron absorption was measured using the double radioisotopic technique. RESULTS The geometric mean (range +/- 1 standard deviation) absorption of iron before supplementation between the Zn-supplemented and placebo groups was similar (31.2, 11.2 +/- 86.3, versus 27.4, 14.4 +/- 52.2, respectively, P = 0.97). Absorption increased significantly after the 2-mo supplementation period (P = 0.049), but there were no group-wise differences at the end of the trial (34.4, 17.5 +/- 67.3, versus 39.8, 20.9 +/- 75.8, respectively, P = 0.97). The geometric mean plasma Zn concentrations did not change significantly in either group during the course of the study (P = 0.47). There was no significant effect of Zn supplementation on any of the iron indicators studied. CONCLUSION Supplementation of 20 mg of Zn between meals for a period of 2 mo had no effect on subsequent iron absorption or iron status of Chilean women.