Toenail zinc as a biomarker: Relationship with sources of environmental exposure and with genetic variability in MCC-Spain study.

BACKGROUND: Toenails are commonly used as biomarkers of exposure to zinc (Zn), but there is scarce information about their relationship with sources of exposure to Zn. OBJECTIVES: To investigate the main determinants of toenail Zn, including selected sources of environmental exposure to Zn and individual genetic variability in Zn metabolism. METHODS: We determined toenail Zn by inductively coupled plasma mass spectrometry in 3,448 general population controls from the MultiCase-Control study MCC-Spain. We assessed dietary and supplement Zn intake using food frequency questionnaires, residential proximity to Zn-emitting industries and residential topsoil Zn levels through interpolation methods. We constructed a polygenic score of genetic variability based on 81 single nucleotide polymorphisms in genes involved in Zn metabolism. Geometric mean ratios of toenail Zn across categories of each determinant were estimated from multivariate linear regression models on log-transformed toenail Zn. RESULTS: Geometric mean toenail Zn was 104.1 µg/g in men and 100.3 µg/g in women. Geometric mean toenail Zn levels were 7 % lower (95 % confidence interval 1-13 %) in men older than 69 years and those in the upper tertile of fibre intake, and 9 % higher (3-16 %) in smoking men. Women residing within 3 km from Zn-emitting industries had 4 % higher geometric mean toenail Zn levels (0-9 %). Dietary Zn intake and polygenic score were unrelated to toenail Zn. Overall, the available determinants only explained 9.3 % of toenail Zn variability in men and 4.8 % in women. DISCUSSION: Sociodemographic factors, lifestyle, diet, and environmental exposure explained little of the individual variability of toenail Zn in the study population. The available genetic variants related to Zn metabolism were not associated with toenail Zn.

Trace elements concentration in adipose tissue and the risk of incident type 2 diabetes in a prospective adult cohort.

The aim of this work was to study the associations of adipose tissue trace element concentrations with type 2 diabetes (T2DM) incidence over a 16-year follow-up period in an adult cohort from Southern Spain. 16-year T2DM incidence was gathered from hospital records. Chemical analyses of Cr, V, Zn, Fe, Cu and Se in adipose tissue were performed using inductively coupled plasma mass spectrometry. Multivariable Cox-regression models were used. Complementary cross-sectional analyses with markers of glucose homeostasis at recruitment were performed by multivariable linear regression. Out of 214 participants, 39 developed T2DM during the follow-up. Adipose tissue concentrations of Fe (HR = 1.97, 95% CI: 0.99 to 2.58, p = 0.057), Cr (HR = 1.58, 95% CI: 1.07-2.33, p = 0.022) and Cu (HR = 1.61, 95% CI: 1.01-2.58, p = 0.046) were individually associated with T2DM incidence. When Fe, Cr and Cu were simultaneously entered in a model, only Cr was significantly associated with T2DM incidence (HR = 1.68, 95% CI: 1.02-2.76, p = 0.041). Furthermore, adipose tissue V (ß = 0.283, p = 0.004) and Zn (ß = 0.217, p = 0.028) concentrations were positively associated with ß-pancreatic cell function (HOMA-ß), while Se showed an inverse association (ß = -0.049, p = 0.027). Although further research is warranted on the potential mechanisms of action, our results suggest that adipose tissue concentrations of certain trace elements (particularly Fe, Cr and Cu) are associated with the risk of incident T2DM, while V and Zn might have a protective effect. These biomarkers might complement prediction algorithms and contribute to identify patients with an increased risk of T2DM.

Toenails as biomarker of exposure to essential trace metals: A review.

Health problems associated with essential trace metals can result from both inadequate (i.e., low intake) and excessive exposures (i.e., from environmental and/or occupational source). Thus, measuring the exposure level is a real challenge for epidemiologists. Among non-invasive biomarkers that intend to measure long-term exposure to essential trace metals, the toenail is probably the biological matrix with the greatest potential. This systematic review collects the current evidence regarding the validity of toenail clippings as exposure biomarker for trace metals such as boron, cobalt, copper, iron, manganese, molybdenum, selenium, silicon, vanadium and zinc. Special attention was paid to the time-window of exposure reflected by the toenail, the intraindividual variability in exposure levels over time in this matrix, and the relationship of toenail with other biomarkers, personal characteristics and environmental sources. Our search identified 139 papers, with selenium and zinc being the most studied elements. The variability among studies suggests that toenail levels may reflect different degrees of exposure and probably correspond to exposures occurred 3-12 months before sampling (i.e., for manganese/selenium). Few studies assessed the reproducibility of results over time and, for samples obtained 1-6 years apart, the correlation coefficient were between 0.26 and 0.66. Trace metal levels in toenails did not correlate well with those in the blood and urine and showed low-moderate correlation with those in the hair and fingernails. Available data suggests that for some elements (Se, Mn, Zn) toenail concentrations reflect long-term external exposures in fairly reproducible levels, while for other metals, this association has not yet been assessed. Among dietary factors, only toenail selenium showed clear associations with the intake of supplements or specific foods. The toenail levels could also represent occupational exposure, for instance, Mn exposure in welders. The scarcity of information on other essential trace elements, together with the great heterogeneity among studies makes the validation of the usage of toenails as biomarkers of exposure to these elements difficult. Standardization of sample collection, quality control, analytical techniques and reporting procedures might facilitate further research focused on the clear understanding of the significance of essential levels in this promising matrix and would enhance its utility in epidemiological research.

Maternal iron intake during pregnancy and the risk of small for gestational age.

Studies of iron and its association with the risk of small for gestational age (SGA) show inconsistent results. Consuming iron supplements during pregnancy is controversial because of possible risks. This study assessed the association between iron intake and the risk of having an SGA newborn and whether iron intake is associated with gestational diabetes. A case-control study of 518 pairs of Spanish women who were pregnant and attending five hospitals was conducted. Groups were matched 1:1 for age (±2 years) and hospital. Cases were women with an SGA newborn at delivery. Controls were women with normal-sized newborns at delivery. Data were gathered on demographic characteristics, socio-economic status, adverse habits (like smoking), and diet. A 137-item food frequency questionnaire was completed. Iron intakes were categorized in quintiles (Q1-Q5). Crude odds ratios (ORs) and adjusted ORs (aORs) with 95% confidence intervals (CIs) were estimated by conditional logistic regression. No significant relationship was found between dietary iron intake and SGA. A protective association was found for women receiving iron supplementation >40 mg/day and SGA versus women not taking supplements (aOR = 0.64, 95% CI [0.42, 0.99]). This association was identified in mothers both with (aOR = 0.57, 95% CI [0.40, 0.81]) and without (aOR = 0.64, 95% CI [0.64, 0.97]) anaemia. In women in the control group without anaemia, iron supplementation >40 mg/day was positively associated with gestational diabetes (aOR = 6.32, 95% CI [1.97, 20.23]). Iron supplementation in pregnancy may prevent SGA independently of existing anaemia but may also increase the risk of gestational diabetes.

Maternal dietary consumption of legumes, vegetables and fruit during pregnancy, does it protect against small for gestational age?

BACKGROUND: Different diets during pregnancy might have an impact on the health, reflected in the birthweight of newborns. The consumption of fruits and vegetables during pregnancy and the relationship with newborn health status have been studied by several authors. However, these studies have shown inconsistent results. PURPOSE: We assessed whether certain foods were related to the risk of small for gestational age (SGA). METHODS: A matched by age (± 2 years) and hospital 1:1 case-control study of 518 pairs of pregnant Spanish women in five hospitals was conducted. The cases were women with an SGA newborn at delivery (neonates weighting less than the 10th percentile, adjusted for gestational age at delivery and sex, were diagnosed as SGA). The control group comprised women giving birth to babies adequate for gestational age (AGA). Mothers who gave birth to babies large for gestational age (LGA) were excluded. Data were gathered concerning demographic characteristics, socioeconomic status, toxic habits and diet. A food frequency questionnaire (FFQ) comprising 137 items was completed by all participants. The intake of vegetables, legumes and fruits was categorized in quintiles (Q1-Q5). Crude values and and adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. The variables for adjustment were as follows: preeclampsia, education, smoking, weight gain per week during pregnancy, fish intake and previous preterm/low birthweight newborns. RESULTS: Total pulse intake showed an inverse association with the risk of SGA (trend p = 0.02). Women with an intake of fruits above 420 g/day (Q5), compared with women in Q1 (≤ 121 g/day) showed a decreased risk of SGA (AOR = 0.63, 95% CI = 0.40-0.98). The total consumption of vegetables was not associated with the risk of SGA. The intake of selenium was assessed: a protective association was observed for Q3-5; a daily intake above 60 µg was associated with a lower risk of SGA (AOR = 0.39, 95% CI: 0.22-0.69). CONCLUSIONS: Fruits, pulses and selenium reduce the risk of SGA in Spanish women.

Association between Vitamin Intake during Pregnancy and Risk of Small for Gestational Age.

Pregnancy increases the requirements of certain nutrients, such as vitamins, to provide nutrition for the newborn. The aim was to analyze the association between dietary intake of vitamins during pregnancy and risk of having a small for gestational age (SGA) newborn. A matched case-control study was conducted (518 cases and 518 controls of pregnant women) in Spain. Dietary vitamin intake during pregnancy was assessed using a validated food frequency questionnaire, categorized into quintiles. Odds ratios (ORs) and their 95% confidence intervals (CI) were estimated with conditional regression logistic models. A protective association was observed between maternal dietary intake of vitamins A and D and SGA. For vitamin B3 and B6, the observed protective effect was maintained after adjusting for potential confounding factors. For vitamin B9, we found only an effect in quintiles 3 and 4 (OR = 0.64; 95% CI, 0.41-1.00; OR = 0.58; 95% CI, 0.37-0.91). Protective effect for vitamin B12 was observed in 4th and 5th quintiles (OR = 0.61; 95% CI, 0.39-0.95; OR = 0.68; 95% CI, 0.43-1.04). No associations were detected between dietary intake of vitamins B2, E and C intake and SGA. Our results suggest a positive association between dietary vitamin intake during pregnancy and the weight of the newborn, although more studies are necessary and there could be a ceiling effect for higher intakes of some vitamins cannot be discarded.