Iron metabolism in heterozygotes for hemoglobin E (HbE), alpha-thalassemia 1, or beta-thalassemia and in compound heterozygotes for HbE/beta-thalassemia

BACKGROUND: Despite large populations carrying traits for thalassemia in countries implementing universal iron fortification, there are few data on the absorption and utilization of iron in these persons. OBJECTIVE: We aimed to determine whether iron absorption or utilization (or both) in women heterozygous for beta-thalassemia, alpha-thalassemia 1, or hemoglobin E (HbE) differed from that in control subjects and compound HbE/beta-thalassemia heterozygotes. DESIGN: In Thai women (n = 103), red blood cell indexes, iron status, non-transferrin-bound iron, and growth differentiation factor 15 were measured, and body iron was calculated. Fractional iron absorption was measured from meals fortified with isotopically labeled ((57)Fe) Fe sulfate, and iron utilization was measured by the infusion of ((58)Fe) Fe citrate. RESULTS: Iron utilization was approximately 15% lower in alpha-thalassemia 1 or beta-thalassemia heterozygotes than in controls. When corrected for differences in serum ferritin, absorption was significantly higher in the alpha- and beta-thalassemia groups, but not the HbE heterozygotes, than in controls. HbE/beta-thalassemia compound heterozygotes had lower iron utilization and higher iron absorption and body iron than did controls. Nontransferrin-bound iron and growth differentiation factor 15 were higher in the compound heterozygotes, but not in the other groups, than in the controls. CONCLUSIONS: In alpha-thalassemia 1 and beta-thalassemia heterozygotes with ineffective erythropoesis, dietary iron absorption is not adequately down-regulated, despite a modest increase in body iron stores. In populations with a high prevalence of these traits, a program of iron fortification could include monitoring for possible iron excess and for iron deficiency.     

Overweight increases risk of first trimester hypothyroxinaemia in iodine‐deficient pregnant women

Hypothyroxinaemia early in pregnancy may impair fetal brain development. Increased body weight has been associated with low thyroxine concentrations in non‐pregnant women. In pregnant women, morbid maternal obesity is a risk factor for thyroid dysfunction. But whether lesser degrees of overweight that are much more common could be a risk factor for hypothyroxinaemia in pregnancy is unclear. The objective of this study was to investigate if overweight increases risk for thyroid dysfunction, and specifically hypothyroxinaemia, in iodine‐deficient pregnant women. We performed a cross‐sectional study at first hospital visit among healthy Thai pregnant women. We measured weight and height, urinary iodine concentration (UIC), serum thyroid hormones and thyroglobulin. Pre‐pregnancy weight and relevant dietary factors were determined by questionnaire, and body mass index (BMI) was used to classify weight status. Among 514 women (mean gestational age, 11 weeks) with a median UIC of 111 μg dL^–1, indicating mild iodine deficiency, 12% had low free thyroxine (fT4) concentrations: 3% had overt hypothyroidism; 7% had subclinical hypothyroidism; and 8% had isolated hypothyroxinaemia. Based on pre‐pregnancy BMI, 26% of women were overweight or obese. In a multiple regression model, BMI was a negative predictor of fT4 (β = ?0.20, P < 0.001). Compared to normal weight women, the prevalence ratio (95% CI) of a low fT4 in overweight women was 3.64 (2.08–6.37) (P < 0.01). Iodine‐deficient pregnant Thai women who are overweight have a 3.6‐fold higher risk of hypothyroxinaemia in the first trimester compared to normal weight women. Targeted screening should consider overweight a potential risk factor for thyroid dysfunction in pregnant women in iodine‐deficient areas.     

A micronutrient-fortified seasoning powder reduces morbidity and improves short-term cognitive function, but has no effect on anthropometric measures in primary school children in northeast Thailand: a randomized controlled trial

BACKGROUND: Reductions in iodine and zinc deficiencies and improvements in hemoglobin were achieved from a micronutrient-fortified seasoning powder consumed in school lunches by children in northeast Thailand. OBJECTIVE: The objective was to determine whether fortification with 4 micronutrients in a school lunch results in changes in children's growth, morbidity, and cognitive function compared with no fortification. DESIGN: In a randomized controlled trial of 569 children aged 5.5-13.4 y from 10 schools, we compared the efficacy of a seasoning powder fortified with or without 5 mg Fe, 5 mg Zn, 50 mug I, and 270 mug vitamin A per serving consumed with a school lunch 5 d/wk. Here we report on results of the secondary functional outcomes. RESULTS: The groups were comparable concerning compliance and loss to follow-up. The intervention had no statistically significant effect on anthropometric measures over 31 wk, but reduced the incidence of respiratory-related illnesses [rate ratio (RR): 0.83; 95% CI: 0.73, 0.94], symptoms of runny nose (RR: 0.80; 95% CI: 0.70, 0.92), cough (RR: 0.80; 95% CI: 0.66, 0.96), and diarrhea (RR: 0.38; 95% CI: 0.16, 0.90). For the visual recall test, those in the fortified group recalled 0.5 more items (95% CI: 0.1, 0.9) than did the controls. There were no statistically significant differences between groups in the results of the digits forward and backward tests or in school grades at the conclusion of the 2 semesters. CONCLUSION: The beneficial effects on morbidity and visual recall over a short period, in addition to some biochemical improvements, highlight the potential of this micronutrient-fortified seasoning powder supplied in a school lunch. This trial was registered at clinical trials.gov as ACTRN12605000341628.     

Does zinc deficiency play a role in stunting among primary school children in NE Thailand?

Stunting in school-age years may result in a decrease in adult size, and thus reduced work capacity and adverse reproductive outcomes. We have compared the mean intakes of energy, protein and selected growth-limiting nutrients in fifty-eight stunted children and 172 non-stunted controls drawn from 567 children aged 6-13 years attending ten rural schools in NE Thailand. Control children were selected randomly after stratifying children by age in each school. Dietary data were calculated from 24-h recalls using nutrient values from Thai food composition data and chemical analysis. Inter-relationships between stunting and sociodemographic, anthropometric and biochemical variables were also examined. Biochemical variables investigated were serum albumin, zinc, ferritin, transferrin receptor and retinol, and iodine in casual urine samples. Significantly more males than females were stunted (males, n 38, 65.5% v. females, n 20. 34.5%: P=0.025). Stunted males had lower mean intakes of energy, protein, calcium, phosphorus and zinc, and a lower mean (95% CI) serum zinc (9.19 (8.53, 9.84) v. 9.70 (8.53, 9.29) micromol/1) than non-stunted males; no other biochemical differences were noted. Stunted males also had a lower mean arm muscle area (P= 0.015), after adjusting for age, than non-stunted males. In conclusion, the lower dietary intakes of the stunted males compared to their non-stunted counterparts may be associated with anorexia and hypogeusia induced by zinc deficiency. Hence, zinc deficiency may be a factor limiting linear growth, especially among boys in NE Thailand, but more research is needed to establish whether other factors also play a role.     

Risk of zinc, iodine and other micronutrient deficiencies among school children in North East Thailand

INTRODUCTION: Micronutrient deficiencies during childhood can contribute to impairments in growth, immune competence, and mental and physical development, and the coexistence of several such deficiencies can adversely affect the efficacy of single micronutrient interventions. OBJECTIVE: To assess the prevalence of zinc and iodine deficiency and their interrelationships with vitamin A deficiency and anemia and associations with socio-economic status, hemoglobin type, and anthropometry in a cross-sectional study. SETTING: A total of 10 primary schools in North East Thailand. METHODS: Non-fasting venipuncture blood samples and casual urine samples were collected from 567 children aged 6-13 years. Anthropometric measures and serum zinc, albumin, C-reactive protein and urinary iodine, are reported here and integrated with published data on vitamin A, anemia, and socio-economic status. RESULTS: Of the children, 57% had low serum zinc and 83% had urinary iodine levels below the 100 microg/l cutoff. Suboptimal serum zinc and urinary iodine concentrations may result from low intakes of zinc and iodized salt. Significant risk factors for low serum zinc were serum retinol <1.05 micromol/l and being male. Those for urinary iodine <100 microg/l were height-for-age score>median and being female. For serum retinol <1.05 micromol/l, risk factors were low hemoglobin, low serum zinc, and <9 years, and for low hemoglobin indicative of anemia risk factors were <9 years, AE hemoglobinopathy, and serum retinol <1.05 micromol/l. Of the children, 60% were at risk of two or more coexisting micronutrient deficiencies, most commonly suboptimal urinary iodine and low serum zinc. CONCLUSION: The findings emphasize the need for multimicronutrient interventions in North East Thailand.     

Comparison of the efficacy of wheat-based snacks fortified with ferrous sulfate, electrolytic iron, or hydrogen-reduced elemental iron: randomized, double-blind, controlled trial in Thai women

BACKGROUND: Although elemental iron powders are widely used to fortify cereal products, little data exist on their efficacy in humans. OBJECTIVE: We compared the efficacy of wheat-based snacks fortified with ferrous sulfate, electrolytic iron, or hydrogen-reduced iron in Thai women with low iron stores. DESIGN: A double-blind intervention was conducted in 18-50-y-old women (n = 330) randomly assigned into 4 groups to receive either no fortification iron or 12 mg Fe/d for 6 d/wk for 35 wk as ferrous sulfate, electrolytic iron, or hydrogen-reduced iron in a baked, wheat-flour-based snack. Snacks were not consumed with meals, and consumption was monitored. At baseline, 20 wk, and 35 wk, hemoglobin status and iron were measured and the groups were compared. RESULTS: Between baseline and 35 wk, geometric mean serum ferritin (SF) increased significantly in all 3 groups receiving iron (P < 0.01), and geometric mean serum transferrin receptor (TfR) decreased significantly in the groups receiving ferrous sulfate and electrolytic iron (P < 0.05). Calculated mean (+/-SD) body iron stores increased from 1.5 +/- 2.8 to 5.4 +/- 2.9 mg/kg in the ferrous sulfate group, from 1.5 +/- 3.5 to 4.4 +/- 3.6 mg/kg in the electrolytic iron group, and from 1.3 +/- 3.2 to 3.2 +/- 4.3 mg/kg in the hydrogen-reduced iron group (P < 0.01 for all 3 groups) but did not change significantly in the control group. CONCLUSIONS: Ferrous sulfate, electrolytic iron, and hydrogen-reduced iron, fortified into wheat-based snacks, significantly improved iron status. On the basis of the change in body iron stores during the 35-wk study, the relative efficacy of the electrolytic and hydrogen-reduced iron compared with ferrous sulfate was 77% and 49%, respectively.     

A multimicronutrient-fortified seasoning powder enhances the hemoglobin, zinc, and iodine status of primary school children in North East Thailand: a randomized controlled trial of efficacy

Anemia and co-existing deficiencies of zinc, iron, iodine, and vitamin A occur among children in many developing countries including NE Thailand, probably contributing to impairments in growth, immune competence, and cognition. Sustainable strategies are urgently required to combat these deficiencies. We assessed the efficacy of a micronutrient-fortified seasoning powder served with a school lunch on reducing anemia and improving the micronutrient status of rural NE Thai children. Children (n = 569) aged 5.5-13.4y from 10 schools were randomly assigned to receive a seasoning powder either unfortified or fortified with zinc (5 mg), iron (5 mg), vitamin A (270 microg), and iodine (50 microg) (per serving) and incorporated into a school lunch prepared centrally and delivered 5 d/wk for 31 wk. Teachers monitored school lunch consumption. Baseline and final micronutrient status, hemoglobinopathies, and infection or inflammation were assessed from blood and urine samples. For the primary outcome, anemia (based on hemoglobin), no intervention effect was apparent (odds ratio: 1.02 95% CI: 0.69, 1.51) after adjustment for design strata. The odds of zinc (based on serum zinc) and urinary iodine deficiency in the fortified group were 0.63 (0.42, 0.94) and 0.52 (0.38, 0.71) times those in the unfortified group, respectively. Fortification had no effect on serum retinol (0.61: 0.25,1.51), ferritin (1.12: 0.43, 2.96), or mean red cell volume (1.16: 0.82, 1.64). Therefore, a micronutrient-fortified seasoning powder is a promising vehicle for improving zinc, iodine, and hemoglobin status, and its potential for incorporation into lunch programs in day care centers and schools in NE Thailand warrants investigation.