Jeannine Baumgartner

Urinary Iodine Concentrations Indicate Iodine Deficiency in Pregnant Thai Women but Iodine Sufficiency in Their School-Aged Children

The median urinary iodine concentration (UI) in school-aged children is recommended for assessment of iodine nutrition in populations. If the median UI is adequate in school-aged children, it is usually assumed iodine intakes are also adequate in the remaining population, including pregnant women. But iodine requirements sharply increase during pregnancy. In this study, our aim was to measure UI in pairs of pregnant women and their school-aged children from the same family, who were sharing meals, to directly assess whether a household food basket that supplies adequate iodine to school-aged children also meets the needs of pregnant women. UI was measured in spot urine samples from pairs (n = 302) of healthy pregnant mothers and their school-aged children in metropolitan Bangkok, Thailand. A dietary questionnaire was completed. The UI [median (range)] in the pregnant women {108 (11-558) microg/L [0.85 (0.086-4.41) micromol/L]} were lower than those of their school-aged children {200 (25-835) microg/L [1.58 (0.20-6.52) micromol/L]} (P < 0.001), indicating optimal iodine status in the children but mild-to-moderate iodine deficiency in their pregnant mothers. The estimated iodine intakes in the 2 groups were in the range of 130-170 microg/d. There was a modest positive correlation between UI in the pairs (r = 0.253; P < 0.01). A higher frequency of seafood meals was a significant predictor of UI in both groups, but household use of iodized salt was not. These data suggest the median UI in school-aged children should not be used as a surrogate for monitoring iodine status in pregnancy in central Thailand; pregnant women should be directly monitored.

A Micronutrient Powder with Low Doses of Highly Absorbable Iron and Zinc Reduces Iron and Zinc Deficiency and Improves Weight-For-Age Z-Scores in South African Children

Micronutrient powders (MNP) are often added to complementary foods high in inhibitors of iron and zinc absorption. Most MNP therefore include high amounts of iron and zinc, but it is no longer recommended in malarial areas to use untargeted MNP that contain the Reference Nutrient Intake for iron in a single serving. The aim was to test the efficacy of a low-iron and -zinc (each 2.5 mg) MNP containing iron as NaFeEDTA, ascorbic acid (AA), and an exogenous phytase active at gut pH. In a double-blind controlled trial, South African school children with low iron status (n = 200) were randomized to receive either the MNP or the unfortified carrier added just before consumption to a high-phytate maize porridge 5 d/wk for 23 wk; primary outcomes were iron and zinc status and a secondary outcome was somatic growth. Compared with the control, the MNP increased serum ferritin (P < 0.05), body iron stores (P < 0.01) and weight-for-age Z-scores (P < 0.05) and decreased transferrin receptor (P < 0.05). The prevalence of iron deficiency fell by 30.6% (P < 0.01) and the prevalence of zinc deficiency decreased by 11.8% (P < 0.05). Absorption of iron from the MNP was estimated to be 7-8%. Inclusion of an exogenous phytase combined with NaFeEDTA and AA may allow a substantial reduction in the iron dose from existing MNP while still delivering adequate iron and zinc. In addition, the MNP is likely to enhance absorption of the high native iron content of complementary foods based on cereals and/or legumes.

Effects of iron and n−3 fatty acid supplementation, alone and in combination, on cognition in school children: a randomized, double-blind, placebo-controlled intervention in South Africa

BACKGROUND Little is known about the combined effects of iron and n-3 (omega-3) fatty acid (FA) supplementation on cognitive performance. The provision of either DHA/EPA or iron alone in rats with combined iron and n-3 FA deficiency has been reported to exacerbate cognitive deficits associated with deficiency. OBJECTIVE We investigated the effects of iron and DHA/EPA supplementation, alone and in combination, in children with poor iron and n-3 FA status. DESIGN In a 2-by-2 factorial trial, children with iron deficiency (ID) (n = 321; aged 6-11 y) were allocated to receive 1) iron (50 mg) plus DHA/EPA (420/80 mg), 2) iron plus placebo, 3) placebo plus a mixture of DHA and EPA (DHA/EPA), or 4) placebo plus placebo as oral supplements (4/wk) for 8.5 mo. Cognition was assessed at baseline and endpoint by using the Hopkins Verbal Learning Test (HVLT) and subscales of the Kaufman Assessment Battery for Children. RESULTS Both iron and DHA/EPA significantly increased weight-for-age z scores. Iron increased the number of words recalled at HVLT recall 2 (intervention effect: 0.90; 95% CI: 0.18, 1.62), and in anemic children, iron increased scores in the Atlantis Delayed test (1.51; 95% CI: 0.03, 2.99) and HVLT recall 2 (2.02; 95% CI: 0.55, 3.49). DHA/EPA showed no benefit in any of the cognitive tests but decreased Atlantis test scores (-2.48; 95% CI: -3.99, -0.96) in children who were anemic at baseline and decreased Atlantis delayed scores (-0.9; 95% CI: -1.45, -0.36) in girls with ID, whereas boys tended to perform better. CONCLUSIONS In children with poor iron and n-3 FA status, iron supplementation improved verbal and nonverbal learning and memory, particularly in children with anemia. In contrast, DHA/EPA supplementation had no benefits on cognition and impaired working memory in anemic children and long-term memory and retrieval in girls with ID.

Overweight impairs efficacy of iron supplementation in iron-deficient South African children: a randomized controlled intervention

Background:Many countries in the nutrition transition have high rates of iron deficiency (ID) and overweight (OW). ID is more common in OW children; this may be due to adiposity-related inflammation reducing iron absorption.Objective:We investigated whether weight status predicts response to oral iron supplementation in ID South African children.Design:A placebo-controlled trial of oral iron supplementation (50 mg, 4 × weeks for 8.5 months) was done in ID 6- to 11-year-old children (n=321); 28% were OW or obese. BMI-for-age z-scores (BAZ), hepcidin (in a sub-sample), hemoglobin, serum ferritin (SF), transferrin receptor (TfR), zinc protoporphyrin (ZnPP) and C-reactive protein (CRP) were measured; body iron was calculated from the SF to TfR ratio.Results:At baseline, BAZ correlated with CRP (r=0.201, P<0.001) and CRP correlated with hepcidin (r=0.384, P<0.001). Normal weight children supplemented with iron had significantly lower TfR concentrations at endpoint than the OW children supplemented with iron and the children receiving placebo. Higher BAZ predicted higher TfR (β=0.232, P<0.001) and lower body iron (β=−0.090, P=0.016) at endpoint, and increased the odds ratio (OR) for remaining ID at endpoint in both the iron and placebo groups (iron: OR 2.31, 95% CI: 1.13, 4.73; placebo: OR 1.78, 95% CI: 1.09, 2.91). In the children supplemented with iron, baseline hepcidin and BAZ were significant predictors of endpoint TfR, with a trend towards a hepcidin × BAZ interaction (P=0.058).Conclusion:South African children with high BAZ have a two-fold higher risk of remaining ID after iron supplementation. This may be due to their higher hepcidin concentrations reducing iron absorption. Thus, the current surge in OW in rapidly developing countries may undercut efforts to control anemia in vulnerable groups. The trial is registered at clinicaltrials.gov as NCT01092377.

Effects of iron supplementation on dominant bacterial groups in the gut, faecal SCFA and gut inflammation: a randomised, placebo-controlled intervention trial in South African children.

Fe supplementation is a common strategy to correct Fe-deficiency anaemia in children; however, it may modify the gut microbiota and increase the risk for enteropathogenic infection. In the present study, we studied the impact of Fe supplementation on the abundance of dominant bacterial groups in the gut, faecal SCFA concentration and gut inflammation in children living in rural South Africa. In a randomised, placebo-controlled intervention trial of 38 weeks, 6- to 11-year-old children with Fe deficiency received orally either tablets containing 50 mg Fe as FeSO₄ (n 22) for 4 d/week or identical placebo (n 27). In addition, Fe-sufficient children (n 24) were included as a non-treated reference group. Faecal samples were analysed at baseline and at 2, 12 and 38 weeks to determine the effects of Fe supplementation on ten bacterial groups in the gut (quantitative PCR), faecal SCFA concentration (HPLC) and gut inflammation (faecal calprotectin concentration). At baseline, concentrations of bacterial groups in the gut, faecal SCFA and faecal calprotectin did not differ between Fe-deficient and Fe-sufficient children. Fe supplementation significantly improved Fe status in Fe-deficient children and did not significantly increase faecal calprotectin concentration. Moreover, no significant effect of Fe treatment or time × treatment interaction on the concentrations of bacterial groups in the gut or faecal SCFA was observed compared with the placebo treatment. Also, there were no significant differences observed in the concentrations of any of the bacterial target groups or faecal SCFA at 2, 12 or 38 weeks between the three groups of children when correcting for baseline values. The present study suggests that in African children with a low enteropathogen burden, Fe status and dietary Fe supplementation did not significantly affect the dominant bacterial groups in the gut, faecal SCFA concentration or gut inflammation.

Amyloid fibril systems reduce, stabilize and deliver bioavailable nanosized iron

Iron-deficiency anaemia (IDA) is a major global public health problem. A sustainable and cost-effective strategy to reduce IDA is iron fortification of foods, but the most bioavailable fortificants cause adverse organoleptic changes in foods. Iron nanoparticles are a promising solution in food matrices, although their tendency to oxidize and rapidly aggregate in solution severely limits their use in fortification. Amyloid fibrils are protein aggregates initially known for their association with neurodegenerative disorders, but recently described in the context of biological functions in living organisms and emerging as unique biomaterial building blocks. Here, we show an original application for these protein fibrils as efficient carriers for iron fortification. We use biodegradable amyloid fibrils from β-lactoglobulin, an inexpensive milk protein with natural reducing effects, as anti-oxidizing nanocarriers and colloidal stabilizers for iron nanoparticles. The resulting hybrid material forms a stable protein-iron colloidal dispersion that undergoes rapid dissolution and releases iron ions during acidic and enzymatic in vitro digestion. Importantly, this hybrid shows high in vivo iron bioavailability, equivalent to ferrous sulfate in haemoglobin-repletion and stable-isotope studies in rats, but with reduced organoleptic changes in foods. Feeding the rats with these hybrid materials did not result in abnormal iron accumulation in any organs, or changes in whole blood glutathione concentrations, inferring their primary safety. Therefore, these iron-amyloid fibril hybrids emerge as novel, highly effective delivery systems for iron in both solid and liquid matrices.

Optimization of a New Mass Spectrometry Method for Measurement of Breast Milk Iodine Concentrations and an Assessment of the Effect of Analytic Method and Timing of Within-Feed Sample Collection on Breast Milk Iodine Concentrations.

BACKGROUND Breast milk iodine concentration (BMIC) may be an indicator of iodine status during lactation, but there are few data comparing different analytical methods or timing of sampling. The aims of this study were: (i) to optimize a new inductively coupled plasma mass spectrometry (ICP-MS) method; and (ii) to evaluate the effect of analytical method and timing of within-feed sample collection on BMIC. METHODS The colorimetric Sandell-Kolthoff method was evaluated with (a) or without (b) alkaline ashing, and ICP-MS was evaluated using a new (129)I isotope ratio approach including Tellurium (Te) for mass bias correction (c) or external standard curve (d). From iodine-sufficient lactating women (n = 97), three samples were collected within one breast-feeding session (fore-, mid-, and hind-feed samples) and BMIC was analyzed using (c) and (d). RESULTS Iodine recovery from NIST SRM1549a whole milk powder for methods (a)-(d) was 67%, 24%, 105%, and 102%, respectively. Intra- and inter-assay coefficients of variation for ICP-MS comparing (c) and (d) were 1.3% versus 5.6% (p = 0.04) and 1.1% versus 2.4% (p = 0.33). The limit of detection (LOD) was lower for (c) (0.26 μg/kg) than it was for (d) (2.54 μg/kg; p = 0.02). Using (c), the median [95% confidence interval (CI) obtained by bootstrap] BMIC (μg/kg) in foremilk (179 [CI 161-206]) and in mid-feed milk (184 [CI 160-220]) were not significantly different (p = 0.017), but were higher than in hindmilk (175 [CI 153-216]; p < 0.001). In foremilk using (d), BMIC was 199 ([CI 182-257]; p < 0.001 vs. (c)). The variation in BMIC comparing (c) and (d) (13%) was greater than variation within feeding (5%; p < 0.001). CONCLUSIONS Because of poor recoveries, (a) and (b) should not be used to measure BMIC. Compared with (d), (c) has the advantages of higher precision and a lower LOD. In iodine-sufficient women, BMIC shows low variation within a breast-feeding session, so timing of sampling is not a major determinant of BMIC.

Effects of a multi-micronutrient-fortified beverage, with and without sugar, on growth and cognition in South African schoolchildren: a randomised, double-blind, controlled intervention

Little is known about the effects of combined micronutrient and sugar consumption on growth and cognition. In the present study, we investigated the effects of micronutrients and sugar, alone and in combination, in a beverage on growth and cognition in schoolchildren. In a 2 × 2 factorial design, children (n 414, 6-11 years) were randomly allocated to consume beverages containing (1) micronutrients with sugar, (2) micronutrients with a non-nutritive sweetener, (3) no micronutrients with sugar or (4) no micronutrients with a non-nutritive sweetener for 8.5 months. Growth was assessed and cognition was tested using the Kaufman Assessment Battery for Children version II (KABC-II) subtests and the Hopkins Verbal Learning Test (HVLT). Micronutrients decreased the OR for Fe deficiency at the endpoint (OR 0.19; 95% CI 0.07, 0.53). Micronutrients increased KABC Atlantis (intervention effect: 0.76; 95% CI 0.10, 1.42) and HVLT Discrimination Index (1.00; 95% CI 0.01, 2.00) scores. Sugar increased KABC Atlantis (0.71; 95% CI 0.05, 1.37) and Rover (0.72; 95% CI 0.08, 1.35) scores and HVLT Recall 3 (0.94; 95% CI 0.15, 1.72). Significant micronutrient × sugar interaction effects on the Atlantis, Number recall, Rover and Discrimination Index scores indicated that micronutrients and sugar in combination attenuated the beneficial effects of micronutrients or sugar alone. Micronutrients or sugar alone had a lowering effect on weight-for-age z-scores relative to controls (micronutrients - 0.08; 95% CI - 0.15, - 0.01; sugar - 0.07; 95% CI - 0.14, - 0.002), but in combination, this effect was attenuated. The beverages with micronutrients or added sugar alone had a beneficial effect on cognition, which was attenuated when provided in combination.

Combined Deficiency of Iron and (n-3) Fatty Acids in Male Rats Disrupts Brain Monoamine Metabolism and Produces Greater Memory Deficits Than Iron Deficiency or (n-3) Fatty Acid Deficiency Alone

Deficiencies of iron (Fe) (ID) and (n-3) fatty acids (FA) [(n-3)FAD] may impair brain development and function through shared mechanisms. However, little is known about the potential interactions between these 2 common deficiencies. We studied the effects of ID and (n-3)FAD, alone and in combination, on brain monoamine pathways (by measuring monoamines and related gene expression) and spatial working and reference memory (by Morris water maze testing). Using a 2 × 2 design, male rats were fed an ID, (n-3)FAD, ID+(n-3)FAD, or control diet for 5 wk postweaning (postnatal d 21-56) after (n-3)FAD had been induced over 2 generations. The (n-3)FAD and ID diets decreased brain (n-3) FA by 70-76% and Fe by 20-32%, respectively. ID and (n-3)FAD significantly increased dopamine (DA) concentrations in the olfactory bulb (OB) and striatum, with an additive 1- to 2-fold increase in ID+(n-3)FAD rats compared with controls (P < 0.05). ID decreased serotonin (5-HT) levels in OB, with a significant decrease in ID+(n-3)FAD rats. Furthermore, norepinephrine concentrations were increased 2-fold in the frontal cortex (FC) of (n-3)FAD rats (P < 0.05). Dopa decarboxylase was downregulated in the hippocampus of ID and ID+(n-3)FAD rats (fold-change = -1.33; P < 0.05). ID and (n-3)FAD significantly impaired working memory performance and the impairment positively correlated with DA concentrations in FC (r = 0.39; P = 0.026). Reference memory was impaired in the ID+(n-3)FAD rats (P < 0.05) and was negatively associated with 5-HT in FC (r = -0.42; P = 0.018). These results suggest that the combined deficiencies of Fe and (n-3) FA disrupt brain monoamine metabolism and produce greater deficits in reference memory than ID or (n-3)FAD alone.

In Male Rats with Concurrent Iron and (n-3) Fatty Acid Deficiency, Provision of Either Iron or (n-3) Fatty Acids Alone Alters Monoamine Metabolism and Exacerbates the Cognitive Deficits Associated with Combined Deficiency

Concurrent deficiencies of iron (Fe) (ID) and (n-3) fatty acids [(n-3)FAD)] in rats can alter brain monoamine pathways and impair learning and memory. We examined whether repletion with Fe and DHA/EPA, alone and in combination, corrects the deficits in brain monoamine activity (by measuring monoamines and related gene expression) and spatial working and reference memory [by Morris water maze (MWM) testing] associated with deficiency. Using a 2 × 2 design, male rats with concurrent ID and (n-3)FAD [ID+(n-3)FAD] were fed an Fe+DHA/EPA, Fe+(n-3)FAD, ID+DHA/EPA, or ID+(n-3)FAD diet for 5 wk [postnatal d 56-91]. Biochemical measures and MWM performance after repletion were compared to age-matched control rats. The provision of Fe in combination with DHA/EPA synergistically increased Fe concentrations in the olfactory bulb (OB) (Fe x DHA/EPA interaction). Similarly, provision of DHA/EPA in combination with Fe resulted in higher brain DHA concentrations than provision of DHA alone in the frontal cortex (FC) and OB (P < 0.05). Dopamine (DA) receptor D1 was upregulated in the hippocampus of Fe+DHA/EPA rats (fold-change = 1.25; P < 0.05) and there were significant Fe x DHA/EPA interactions on serotonin (5-HT) in the OB and on the DA metabolite dihydroxyphenylacetic acid in the FC and striatum. Working memory performance was impaired in ID+DHA/EPA rats compared with controls (P < 0.05). In the reference memory task, Fe+DHA/EPA improved learning behavior, but Fe or DHA/EPA alone did not. These findings suggest that feeding either Fe or DHA/EPA alone to adult rats with both ID and (n-3)FAD affects the DA and 5-HT pathways differently than combined repletion and exacerbates the cognitive deficits associated with combined deficiency.