Low dose oral iodized oil for control of iodine deficiency in children

In areas where iodized salt is not available, oral iodized oil is often used to correct I deficiency despite a lack of consensus on the optimal dose or duration of effect, particularly in children, a main target group. Annual doses ranging from 400 to 1000 mg have been advocated for school-age children. Because lower doses of iodized oil have been shown to be effective in treating I deficiency in adults, the aim of this study was to evaluate the efficacy and safety of a low dose of oral iodized oil in goitrous I-deficient children. Goitrous children (n 104, mean age 8·4 years, range 6-12 years, 47 % female) received 0·4 ml oral iodized poppyseed-oil containing 200 mg I. Baseline measurements included I in spot urines (UI), serum thyroxine (T4), whole blood thyroid-stimulating hormone (TSH), and thyroid-gland volume using ultrasound. At 1, 5, 10, 15, 30 and 50 weeks post-intervention, UI, TSH and T4 were measured. At 10, 15, 30 and 50 weeks, thyroid-gland volume was remeasured. At 30 and 50 weeks the mean percentage change in thyroid volume from baseline was -35 % and -41 % respectively. The goitre rate fell to 38 % at 30 weeks and 17 % at 50 weeks. No child showed signs of I-induced hypo- or hyperthyroidism. UI remained significantly increased above baseline for the entire year (P < 0·001); the median UI at 50 weeks was 97 μg/l, at the World Health Organization cut-off value (100 μg/l) for I-deficiency disorders risk. In this group of goitrous children, an oral dose of 200 mg I as Lipiodol (Guerbert, Roissy CdG Cedex, France) was safe and effective for treating goitre and maintaining normal I status for at least 1 yea

The effect of retinyl palmitate added to iron-fortified maize porridge on erythrocyte incorporation of iron in African children with vitamin A deficiency

Retinyl palmitate added to Fe-fortified maize bread has been reported to enhance Fe absorption in adult Venezuelan subjects but not in Western Europeans. It is not known to what extent these results were influenced by differences in vitamin A status of the study subjects. The objective of the present study was to evaluate the influence of retinyl palmitate added to Fe-fortified maize porridge on erythrocyte incorporation of Fe in children with vitamin A deficiency, before and after vitamin A supplementation. Erythrocyte incorporation of Fe-stable isotopes was measured 14 d after intake of maize porridge (2·0 mg Fe added as ferrous sulfate) with and without added retinyl palmitate (3·5 μmol; 3300 IU). The study was repeated 3 weeks after vitamin A supplementation (intake of a single dose of 210 μmol retinyl palmitate; ‘vitamin A capsule'). Vitamin A status was evaluated by the modified relative dose-response (MRDR) technique. Retinyl palmitate added to the test meal reduced the geometric mean erythrocyte incorporation of Fe at baseline from 4·0 to 2·6 % (P=0·008, n 13; paired t test). At 3 weeks after vitamin A supplementation, geometric mean erythrocyte incorporation was 1·9 and 2·3 % respectively from the test meal with and without added retinyl palmitate (P=0·283). Mean dehydroretinol:retinol molar ratios were 0·156 and 0·125 before and after intake of the single dose of 210 μmol retinyl palmitate; ‘vitamin A capsule' (P=0·15). In conclusion, retinyl palmitate added to the labelled test meals significantly decreased erythrocyte incorporation of Fe in children with vitamin A deficiency at baseline but had no statistically significant effect 3 weeks after vitamin A supplementation. The difference in response to retinyl palmitate added to Fe-fortified maize porridge on erythrocyte incorporation of Fe before and after intake of the vitamin A capsule indicates, indirectly, changes in vitamin A status not measurable by the MRDR technique. The lack of conclusive data on the effect of retinyl palmitate on Fe absorption indicates the complexity of the interactions between vitamin A status, dietary vitamin A and Fe metabolis

Sodium iron EDTA and ascorbic acid, but not polyphenol oxidase treatment, counteract the strong inhibitory effect of polyphenols from brown sorghum on the absorption of fortification iron in young women

In addition to phytate, polyphenols (PP) might contribute to low Fe bioavailability from sorghum-based foods. To investigate the inhibitory effects of sorghum PP on Fe absorption and the potential enhancing effects of ascorbic acid (AA), NaFeEDTA and the PP oxidase enzyme laccase, we carried out three Fe absorption studies in fifty young women consuming dephytinised Fe-fortified test meals based on white and brown sorghum varieties with different PP concentrations. Fe absorption was measured as the incorporation of stable Fe isotopes into erythrocytes. In study 1, Fe absorption from meals with 17mg PP (8·5%) was higher than that from meals with 73mg PP (3·2%) and 167mg PP (2·7%; P<0·001). Fe absorption from meals containing 73 and 167mg PP did not differ (P=0·9). In study 2, Fe absorption from NaFeEDTA-fortified meals (167mg PP) was higher than that from the same meals fortified with FeSO4 (4·6 v. 2·7%; P<0·001), but still it was lower than that from FeSO4-fortified meals with 17mg PP (10·7%; P<0·001). In study 3, laccase treatment decreased the levels of PP from 167 to 42mg, but it did not improve absorption compared with that from meals with 167mg PP (4·8 v. 4·6%; P=0·4), whereas adding AA increased absorption to 13·6% (P<0·001). These findings suggest that PP from brown sorghum contribute to low Fe bioavailability from sorghum foods and that AA and, to a lesser extent, NaFeEDTA, but not laccase, have the potential to overcome the inhibitory effect of PP and improve Fe absorption from sorghum food

Iron deficiency up-regulates iron absorption from ferrous sulphate but not ferric pyrophosphate and consequently food fortification with ferrous sulphate has relatively greater efficacy in iron-deficient individuals

Fe absorption from water-soluble forms of Fe is inversely proportional to Fe status in humans. Whether this is true for poorly soluble Fe compounds is uncertain. Our objectives were therefore (1) to compare the up-regulation of Fe absorption at low Fe status from ferrous sulphate (FS) and ferric pyrophosphate (FPP) and (2) to compare the efficacy of FS with FPP in a fortification trial to increase body Fe stores in Fe-deficient children v. Fe-sufficient children. Using stable isotopes in test meals in young women (n 49) selected for low and high Fe status, we compared the absorption of FPP with FS. We analysed data from previous efficacy trials in children (n 258) to determine whether Fe status at baseline predicted response to FS v. FPP as salt fortificants. Plasma ferritin was a strong negative predictor of Fe bioavailability from FS (P<0·0001) but not from FPP. In the efficacy trials, body Fe at baseline was a negative predictor of the change in body Fe for both FPP and FS, but the effect was significantly greater with FS (P<0·01). Because Fe deficiency up-regulates Fe absorption from FS but not from FPP, food fortification with FS may have relatively greater impact in Fe-deficient children. Thus, more soluble Fe compounds not only demonstrate better overall absorption and can be used at lower fortification levels, but they also have the added advantage that, because their absorption is up-regulated in Fe deficiency, they innately ‘target' Fe-deficient individuals in a populatio

Iron absorption from ferrous fumarate in adult women is influenced by ascorbic acid but not by Na2EDTA

Ascorbic acid and Na2EDTA enhance Fe absorption from the water-soluble Fe compound FeSO4 but their effect on poorly water-soluble Fe compounds such as ferrous fumarate is less well established. In the present study, the effects of ascorbic acid and Na2EDTA on Fe absorption from ferrous fumarate were evaluated in adult women (ten women/study) from the erythrocyte incorporation of Fe stable isotopes (57Fe or 58Fe) 14 d after administration. Two separate studies were made with test meals of Fe-fortified infant cereal (5 mg Fe/meal). Data were evaluated by paired t tests and the results are presented as geometric means. In study 1a, the comparison between Fe absorption from ferrous fumarate- and FeSO4-fortified cereal showed that adult women absorb Fe as well from ferrous fumarate as from FeSO4 (3·0 and 3·1 % respectively, P=0·85). After addition of Na2EDTA (Na2EDTA:fortification Fe molar ratio of 1:1), Fe absorption from FeSO4 was significantly higher than from ferrous fumarate (5·3 v. 3·3 % respectively, P<0·01; study 1b). In study 2, Fe absorption was compared from ferrous fumarate-fortified meals with and without ascorbic acid added at a 4:1 molar ratio (relative to fortification Fe) and the results showed that ascorbic acid increased Fe absorption from ferrous fumarate significantly (6·3 v. 10·4 %, P=0·02). The results of the present studies show that Fe absorption from ferrous fumarate is enhanced by ascorbic acid but not by Na2EDTA, thus emphasising that not all findings from Fe absorption studies made with FeSO4 can be extrapolated to Fe compounds with different solubility propertie

A micronised, dispersible ferric pyrophosphate with high relative bioavailability in man

Ferric pyrophosphate is a water-insoluble Fe compound used to fortify infant cereals and chocolate-drink powders as it causes no organoleptic changes to the food vehicle. However, it is only of low absorption in man. Recently, an innovative ferric pyrophosphate has been developed (Sunactive Fe™) based on small-particle-size ferric pyrophosphate (average size 0·3 μm) mixed with emulsifiers, so that it remains in suspension in liquid products. The aim of the present studies was to compare Fe absorption of micronised, dispersible ferric pyrophosphate (Sunactive Fe™) with that of ferrous sulfate in an infant cereal and a yoghurt drink. Two separate Fe absorption studies were made in adult women (ten women/study). Fe absorption was based on the erythrocyte incorporation of stable isotopes (57Fe and 58Fe) 14 d after the intake of labelled test meals of infant cereal (study 1) or yoghurt drink (study 2). Each test meal was fortified with 5 mg Fe as ferrous sulfate or micronised, dispersible ferric pyrophosphate. Results are presented as geometric means. There was no statistically significant difference between Fe absorption from micronised, dispersible ferric pyrophosphate- and ferrous sulfate-fortified infant cereal (3·4 and 4·1 % respectively; P=0·24) and yoghurt drink (3·9 and 4·2 % respectively; P=0·72). The results of the present studies show that micronised, dispersible ferric pyrophosphate is as well absorbed as ferrous sulfate in adults. The high relative Fe bioavailability of micronised, dispersible ferric pyrophosphate indicates the potential usefulness of this compound for food fortificatio

Short communication Low dose oral iodized oil for control of iodine de®ciency in children

In areas where iodized salt is not available, oral iodized oil is often used to correct I de®ciency despite a lack of consensus on the optimal dose or duration of effect, particularly in children, a main target group. Annual doses ranging from 400 to 1000 mg have been advocated for schoolage children. Because lower doses of iodized oil have been shown to be effective in treating I de®ciency in adults, the aim of this study was to evaluate the ef®cacy and safety of a low dose of oral iodized oil in goitrous I-de®cient children. Goitrous children (n 104, mean age 8×4 years, range 6±12 years, 47 % female) received 0×4 ml oral iodized poppyseed-oil containing 200 mg I. Baseline measurements included I in spot urines (UI), serum thyroxine (T 4 ), whole blood thyroidstimulating hormone (TSH), and thyroid-gland volume using ultrasound. At 1, 5, 10, 15, 30 and 50 weeks post-intervention, UI, TSH and T 4 were measured. At 10, 15, 30 and 50 weeks, thyroidgland volume was remeasured. At 30 and 50 weeks the mean percentage change in thyroid volume from baseline was -35 % and -41 % respectively. The goitre rate fell to 38 % at 30 weeks and 17 % at 50 weeks. No child showed signs of I-induced hypo-or hyperthyroidism. UI remained signi®cantly increased above baseline for the entire year (P , 0×001); the median UI at 50 weeks was 97 mg/l, at the World Health Organization cut-off value (100 mg/l) for I-de®ciency disorders risk. In this group of goitrous children, an oral dose of 200 mg I as Lipiodol (Guerbert, Roissy CdG Cedex, France) was safe and effective for treating goitre and maintaining normal I status for at least 1 year

Iron homeostasis during anemia of inflammation: a prospective study in patients with tuberculosis.

Anemia of inflammation is a hallmark of tuberculosis. Factors controlling iron metabolism during anemia of inflammation and its resolution are uncertain. Whether iron supplements should be given during anti-tuberculosis treatment to support Hb recovery is unclear. Before and during treatment of tuberculosis, we assessed iron kinetics, and changes in inflammation and iron metabolism indices. In a 26-wk prospective study, Tanzanian adults with tuberculosis (n=18) were studied before treatment and then every two weeks during treatment; oral and intravenous iron tracers were administered before treatment, after intensive phase (8/12 wk) and complete treatment (24 wk); no iron supplements were given. Before treatment, hepcidin and erythroferrone (ERFE) were greatly elevated, erythrocyte iron utilization was high (~80%) and iron absorption was negligible (<1%). During treatment, hepcidin and IL-6 decreased ~70% after only 2 wk (p<0.001); in contrast, ERFE did not significantly decrease until 8 wk (p<0.01). ERFE and IL-6 were the main opposing determinants of hepcidin (p<0.05) and greater ERFE was associated with reticulocytosis and hemoglobin (Hb) repletion (p<0.01). Dilution of baseline tracer concentration was 2.6-fold higher during intensive phase treatment (p<0.01) indicating enhanced erythropoiesis. After treatment completion, iron absorption increased ~20-fold (p<0.001); Hb increased ~25% (p<0.001). In tuberculosis-associated anemia of inflammation, our findings suggest elevated ERFE is unable to suppress hepcidin and iron absorption is negligible. During treatment, as inflammation resolves, ERFE may remain elevated, contributing to hepcidin suppression and Hb repletion. Iron is well-absorbed only after tuberculosis treatment and supplementation should be reserved for patients remaining anemic after treatment. (ClinicalTrials.gov Identifier:NCT02176772)

Arthritogenic Monoclonal Antibodies from K/BxN Mice

Arthritis in the K/BxN mouse model is provoked by pathogenic antibodies (Abs) directed against a ubiquitously expressed protein, glucose-6-phosphate isomerase (GPI). To begin dissecting the repertoire of arthritogenic immunoglobulins (Igs) in the K/BxN model, and to provide a basis for comparison with RA patientswe have generated anti-GPI monoclonal Abs (mAbs) from spontaneously activated B cells in the lymphoid organs of arthritic mice. B cell clones with anti-GPI specificities were present at extraordinarily high frequencies in the spleen, and less frequently in other lymphoid organs and in the synovial fluid. None of the anti-GPI mAbs induced arthritis when injected individually into healthy recipients, but most were effective when combined in pairs or larger pools. Arthritogenic combinations depended on mAbs of the IgG1 isotype, which bound to GPI with Kd in the 10−9 M range, with no indication of cooperative binding between complementing pairs. Pathogenicity was not associated with recognition of a particular epitope, but the ability to form mAb/GPI multimers by simultaneous recognition of different epitopes was clearly required, consistent with the known role of complement and FcRs in this model. Sequence analysis revealed structural similarities amongst the mAbs, indicating that a particular subset of B cells may evade tolerance in K/BxN mice, and that affinity maturation by somatic mutation likely takes place. These results confirm that GPI itself, rather than a cross-reactive molecule, is the target of pathogenic Igs