Valeria Galetti

Iodine intake as a risk factor for thyroid cancer: a comprehensive review of animal and human studies

Thyroid cancer (TC) is the most common endocrine malignancy and in most countries, incidence rates are increasing. Although differences in population iodine intake are a determinant of benign thyroid disorders, the role of iodine intake in TC remains uncertain. We review the evidence linking iodine intake and TC from animal studies, ecological studies of iodine intake and differentiated and undifferentiated TC, iodine intake and mortality from TC and occult TC at autopsy, as well as the case–control and cohort studies of TC and intake of seafood and milk products. We perform a new meta-analysis of pooled measures of effect from case–control studies of total iodine intake and TC. Finally, we examine the post-Chernobyl studies linking iodine status and risk of TC after radiation exposure. The available evidence suggests iodine deficiency is a risk factor for TC, particularly for follicular TC and possibly, for anaplastic TC. This conclusion is based on: a) consistent data showing an increase in TC (mainly follicular) in iodine deficient animals; b) a plausible mechanism (chronic TSH stimulation induced by iodine deficiency); c) consistent data from before and after studies of iodine prophylaxis showing a decrease in follicular TC and anaplastic TC; d) the indirect association between changes in iodine intake and TC mortality in the decade from 2000 to 2010; e) the autopsy studies of occult TC showing higher microcarcinoma rates with lower iodine intakes; and f) the case control studies suggesting lower risk of TC with higher total iodine intakes.

Effect of iodine supplementation in pregnant women on child neurodevelopment: a randomised, double-blind, placebo-controlled trial

BACKGROUND Iodine deficiency during pregnancy might be associated with reduced intelligence quotient (IQ) score in offspring. We assessed the effect of iodine supplementation in mildly iodine-deficient pregnant women on neurodevelopment of their offspring in areas where schoolchildren were iodine sufficient. METHODS In this randomised, placebo-controlled trial, pregnant women in Bangalore, India, and Bangkok, Thailand, were randomly assigned (1:1) to receive 200 μg iodine orally once a day or placebo until delivery. Randomisation was done with a computer-generated sequence and stratified by site. Co-primary outcomes were verbal and performance IQ scores on the Wechsler Preschool and Primary Scale of Intelligence Third Edition (WPPSI-III) and the global executive composite score from the Behaviour Rating Inventory of Executive Function-Preschool Version (BRIEF-P) in the children at age 5-6 years. The trial was double-blinded; some unmasking took place at age 2 years for an interim analysis, but participants and nearly all investigators remained masked to group assignment until age 5-6 years. Analysis was by intention to treat using mixed-effects models. This trial is registered with ClinicalTrials.gov, number NCT00791466. FINDINGS Between Nov 18, 2008, and March 12, 2011, 832 women entered the trial at a mean gestational age of 10·7 weeks (SD 2·7); median urinary iodine concentration was 131 μg/L (IQR 81-213). Mean compliance with supplementation was 87%, assessed by monthly tablet counts. 313 children (iodine group, n=159; placebo group, n=154) were analysed for verbal and performance IQ with WPPSI-III and 315 (iodine group, n=159; placebo group, n=156) for overall executive function with BRIEF-P. Mean WPPSI-III scores for verbal IQ were 89·5 (SD 9·8) in the iodine group and 90·2 (9·8) in the placebo group (difference -0·7, 95% CI -2·9 to 1·5; p=0·77), and for performance IQ were 97·5 (12·5) in the iodine group and 99·1 (13·4) in the placebo group (difference -1·6, -4·5 to 1·3; p=0·44). The mean BRIEF-P global executive composite score was 90·6 (26·2) in the iodine group and 91·5 (27·0) in the placebo group (difference -0·9, -6·8 to 5·0; p=0·74). The frequency of adverse events did not differ between groups during gestation or at delivery: 24 women in the iodine group and 28 in the placebo group reported adverse events (iodine group: abortion, n=20; blighted ovum, and n=2; intrauterine death, n=2; placebo group: abortion, n=22; blighted ovum, n=1; intrauterine death, n=2; early neonatal death, n=1; and neonatal death, n=2). INTERPRETATION Daily iodine supplementation in mildly iodine-deficient pregnant women had no effect on child neurodevelopment at age 5-6 years. FUNDING Swiss National Science Foundation, Nestlé Foundation, Wageningen University and Research, and ETH Zurich.

Rural Beninese Children Are at Risk of Zinc Deficiency According to Stunting Prevalence and Plasma Zinc Concentration but Not Dietary Zinc Intakes

BACKGROUND Three commonly recommended indicators for risk assessment of population zinc deficiency are stunting rates among children aged <5 y, prevalence of inadequate dietary zinc intake, and prevalence of low plasma zinc (PZn). Data on zinc status in Benin are mainly drawn from stunting rates and data on PZn and dietary zinc intake are lacking. OBJECTIVES The aims of this study were 1) to assess the risk of zinc deficiency in preschool and school-age children from rural communities in northern Benin by means of the 3 indicators for population assessment, 2) to evaluate their level of agreement, and 3) to identify predictors of PZn and height-for-age z scores (HAZ). METHODS We analyzed preintervention data collected during 2 efficacy trials and cross-sectionally assessed the risk of zinc deficiency in preschool (1-5 y, n = 326) and school-age children (5-10 y, n = 272) by 1) conducting a 3-d weighed food record survey, coupled with direct zinc and phytic acid analysis of consumed foodstuffs, and calculating usual dietary zinc intakes in a subsample of school-age children (n = 36); 2) analyzing PZn in all children (n = 598); and 3) measuring anthropometry indexes for assessment of stunting (HAZ <-2 SD) in all children (n = 594) and in <5-y-old children only (n = 273). We derived predictors of PZn and HAZ by using multivariate regression with mixed-effect models. RESULTS Prevalence of inadequate intakes of zinc ranged from 11% to 80% depending on whether the estimated average requirements (EARs) by the International Zinc Nutrition Consultative Group or the EARs derived from the WHOs recommended nutrient intakes were used. Prevalence of low PZn adjusted for acute-phase protein status was 45.7%, with higher rates among preschoolers than school-age children (P = 0.002). The stunting rate in <5-y-old children was 51.3%. PZn was predicted by age, methodologic factors, and socioeconomic status, whereas HAZ was predicted by age, sex, hemoglobin, and socioeconomic status. CONCLUSIONS The prevalence of <5-y stunting and the prevalence of low PZn indicate that the risk of zinc deficiency is elevated in this population. Risk estimates based on the prevalence of inadequacy of zinc intakes varied depending on the EARs used, and a consensus would facilitate nutrition survey evaluations. These trials were registered at clinicaltrials.gov as NCT01472211 and NCT01790321.

A dose-response crossover iodine balance study to determine iodine requirements in early infancy

BACKGROUND Optimal iodine intake during infancy is critical for brain development, but no estimated average requirement (EAR) is available for this age group. OBJECTIVE We measured daily iodine intake, excretion, and retention over a range of iodine intakes in early infancy to determine the minimum daily intake required to achieve iodine balance. DESIGN In a dose-response crossover study, we randomly assigned healthy infants (n = 11; mean ± SD age 13 ± 3 wk) to sequentially consume over 33 d 3 infant formula milks (IFMs) containing 10.5, 19.3, and 38.5 μg I/100 kcal, respectively. Each IFM was consumed for 11 d, consisting of a 6-d run-in period followed by a 4-d balance period and 1 run-out day. RESULTS Iodine intake (mean ± SD: 54.6 ± 8.1, 142.3 ± 23.1, and 268.4 ± 32.6 μg/d), excretion (55.9 ± 8.6, 121.9 ± 21.7, and 228.7 ± 39.3 μg/d), and retention (-1.6 ± 8.3, 20.6 ± 21.6, and 39.8 ± 34.3 μg/d) differed among the low, middle, and high iodine IFM groups (P < 0.001 for all). There was a linear relation between daily iodine intake and both daily iodine excretion and daily iodine retention. Zero balance (iodine intake = iodine excretion, iodine retention = 0 μg/d) was achieved at a daily iodine intake of 70 μg (95% CI: 60, 80 μg). CONCLUSION Our data indicate the iodine requirement in 2- to 5-mo-old infants is 70 μg/d. Adding an allowance for accumulation of thyroidal iodine stores would produce an EAR of 72 μg and a recommended dietary allowance of 80 μg. This trial was registered at clinicaltrials.gov as NCT02045784.

Efficacy of highly bioavailable zinc from fortified water: a randomized controlled trial in rural Beninese children

BACKGROUND Zinc deficiency and contaminated water are major contributors to diarrhea in developing countries. Food fortification with zinc has not shown clear benefits, possibly because of low zinc absorption from inhibitory food matrices. We used a novel point-of-use water ultrafiltration device configured with glass zinc plates to produce zinc-fortified, potable water. OBJECTIVE The objective was to determine zinc bioavailability from filtered water and the efficacy of zinc-fortified water in improving zinc status. DESIGN In a crossover balanced study, we measured fractional zinc absorption (FAZ) from the zinc-fortified water in 18 healthy Swiss adults using zinc stable isotopes and compared it with zinc-fortified maize porridge. We conducted a 20-wk double-blind randomized controlled trial (RCT) in 277 Beninese school children from rural settings who were randomly assigned to receive a daily portion of zinc-fortified filtered water delivering 2.8 mg Zn (Zn+filter), nonfortified filtered water (Filter), or nonfortified nonfiltered water (Pump) from the local improved supply, acting as the control group. The main outcome was plasma zinc concentration (PZn), and the 3 groups were compared by using mixed-effects models. Secondary outcomes were prevalence of zinc deficiency, diarrhea prevalence, and growth. RESULTS Geometric mean (-SD, +SD) FAZ was 7-fold higher from fortified water (65.9%; 42.2, 102.4) than from fortified maize (9.1%; 6.0, 13.7; P < 0.001). In the RCT, a significant time-by-treatment effect on PZn (P = 0.026) and on zinc deficiency (P = 0.032) was found; PZn in the Zn+filter group was significantly higher than in the Filter (P = 0.006) and Pump (P = 0.025) groups. We detected no effect on diarrhea or growth, but our study did not have the duration and power to detect such effects. CONCLUSIONS Consumption of filtered water fortified with a low dose of highly bioavailable zinc is an effective intervention in children from rural African settings. Large community-based trials are needed to assess the effectiveness of zinc-fortified filtered water on diarrhea and growth. These trials were registered at clinicaltrials.gov as NCT01636583 and NCT01790321.

Consumption of galacto-oligosaccharides increases iron absorption from a micronutrient powder containing ferrous fumarate and sodium iron EDTA: a stable-isotope study in Kenyan infants

Background: Whether consumption of prebiotics increases iron absorption in infants is unclear.Objective: We set out to determine whether prebiotic consumption affects iron absorption from a micronutrient powder (MNP) containing a mixture of ferrous fumarate and sodium iron EDTA (FeFum+NaFeEDTA) in Kenyan infants.Design: Infants (n = 50; aged 6-14 mo) consumed maize porridge that was fortified with an MNP containing FeFum+NaFeEDTA and 7.5 g galacto-oligosaccharides (GOSs) (Fe+GOS group, n = 22) or the same MNP without GOSs (Fe group, n = 28) each day for 3 wk. Then, on 2 consecutive days, we fed all infants isotopically labeled maize porridge and MNP test meals containing 5 mg Fe as 57FeFum+Na58FeEDTA or ferrous sulfate (54FeSO4). Iron absorption was measured as the erythrocyte incorporation of stable isotopes. Iron markers, fecal pH, and bacterial groups were assessed at baseline and 3 wk. Comparisons within and between groups were done with the use of mixed-effects models.Results: There was a significant group-by-compound interaction on iron absorption (P = 0.011). The median percentages of fractional iron absorption from FeFum+NaFeEDTA and from FeSO4 in the Fe group were 11.6% (IQR: 6.9-19.9%) and 20.3% (IQR: 14.2-25.7%), respectively, (P < 0.001) and, in the Fe+GOS group, were 18.8% (IQR: 8.3-37.5%) and 25.5% (IQR: 15.1-37.8%), respectively (P = 0.124). Between groups, iron absorption was greater from the FeFum+NaFeEDTA (P = 0.047) in the Fe+GOS group but not from the FeSO4 (P = 0.653). The relative iron bioavailability from FeFum+NaFeEDTA compared with FeSO4 was higher in the Fe+GOS group than in the Fe group (88% compared with 63%; P = 0.006). There was a significant time-by-group interaction on Bifidobacterium spp. (P = 0.008) and Lactobacillus/Pediococcus/Leuconostoc spp. (P = 0.018); Lactobacillus/Pediococcus/Leuconostoc spp. decreased in the Fe group (P = 0.013), and there was a nonsignificant trend toward higher Bifidobacterium spp. in the Fe+GOS group (P = 0.099). At 3 wk, iron absorption was negatively correlated with fecal pH (P < 0.001) and positively correlated with Lactobacillus/Pediococcus/Leuconostoc spp. (P = 0.001).Conclusion: GOS consumption by infants increased iron absorption by 62% from an MNP containing FeFum+NaFeEDTA, thereby possibly reflecting greater colonic iron absorption. This trial was registered at clinicaltrials.gov as NCT02666417.

Sensitivity of fatty acid desaturation and elongation to plasma zinc concentration: a randomised controlled trial in Beninese children

Zn status may affect fatty acid (FA) metabolism because it acts as a cofactor in FA desaturase and elongase enzymes. Zn supplementation affects the FA desaturases of Zn-deficient rats, but whether this occurs in humans is unclear. We evaluated the associations between baseline plasma Zn (PZn) concentration and plasma total phospholipid FA composition, as well as the effect of daily consumption of Zn-fortified water on FA status in Beninese children. A 20-week, double-blind randomised controlled trial was conducted in 186 school age children. The children were randomly assigned to receive a daily portion of Zn-fortified, filtered water delivering on average 2·8 mg Zn/d or non-fortified filtered water. Plasma total phospholipid FA composition was determined using capillary GLC and PZn concentrations by atomic absorption spectrometry. At baseline, PZn correlated positively with dihomo-γ-linolenic acid (DGLA, r 0·182; P=0·024) and the DGLA:linoleic acid (LA) ratio (r 0·293; P<0·000), and negatively with LA (r -0·211; P=0·009) and the arachidonic acid:DGLA ratio (r -0·170; P=0·036). With the intervention, Zn fortification increased nervonic acid (B: 0·109; 95 % CI 0·001, 0·218) in all children (n 186) and more so in children who were Zn-deficient (n 60) at baseline (B: 0·230; 95 % CI 0·023, 0·488). In conclusion, in this study, Zn-fortified filtered water prevented the reduction of nervonic acid composition in the plasma total phospholipids of children, and this effect was stronger in Zn-deficient children. Thus, Zn status may play an important role in FA desaturation and/or elongation.