Vitamin A supplementation in children with poor vitamin A and iron status increases erythropoietin and hemoglobin concentrations without changing total body iron.

BACKGROUND: Vitamin A deficiency impairs iron metabolism; vitamin A supplementation of vitamin A-deficient populations may reduce anemia. The mechanism of these effects is unclear. In vitro and in animal models, vitamin A treatment increases the production of erythropoietin (EPO), a stimulant of erythropoiesis. OBJECTIVE: We measured the effect of vitamin A supplementation on hemoglobin, iron status, and circulating EPO concentrations in children with poor iron and vitamin A status. DESIGN: In a double-blind, randomized trial, Moroccan schoolchildren (n = 81) were given either vitamin A (200,000 IU) or placebo at baseline and at 5 mo. At baseline, 5 mo, and 10 mo, hemoglobin, indicators of iron and vitamin A status, and EPO were measured. RESULTS: At baseline, 54% of children were anemic; 77% had low vitamin A status. In the vitamin A group at 10 mo, serum retinol improved significantly compared with the control group (P < 0.02). Vitamin A treatment increased mean hemoglobin by 7 g/L (P < 0.02) and reduced the prevalence of anemia from 54% to 38% (P < 0.01). Vitamin A treatment increased mean corpuscular volume (P < 0.001) and decreased serum transferrin receptor (P < 0.001), indicating improved iron-deficient erythropoiesis. Vitamin A decreased serum ferritin (P < 0.02), suggesting mobilization of hepatic iron stores. Calculated from the ratio of transferrin receptor to serum ferritin, overall body iron stores remained unchanged. In the vitamin A group at 10 mo, we observed an increase in EPO (P < 0.05) and a decrease in the slope of the regression line of log10(EPO) on hemoglobin (P < 0.01). CONCLUSION: In children deficient in vitamin A and iron, vitamin A supplementation mobilizes iron from existing stores to support increased erythropoiesis, an effect likely mediated by increases in circulating EPO.

Iron deficiency due to consumption of a habitual diet low in bioavailable iron: a longitudinal cohort study in Moroccan children.

BACKGROUND: In many developing countries, cereal and legume-based diets contain low amounts of bioavailable iron, which may increase the risk of iron deficiency. OBJECTIVE: The objective was to measure change in iron status in Moroccan children who consumed their habitual diet containing low amounts of bioavailable iron. DESIGN: The design was a prospective, longitudinal, free-living cohort study in iron-replete, nonanemic 6-10-y-old children (n = 126). Hemoglobin, serum ferritin, and transferrin receptor were measured at baseline. The children then consumed their habitual cereal and legume-based diet for 15 mo, when their iron status was retested. We used weighed food records and direct food analysis to calculate dietary iron intake and iron bioavailability. On the basis of the change in hemoglobin and body iron stores calculated from the serum transferrin receptor-to-ferritin ratio, iron balance and iron absorption were estimated over the 15-mo period. RESULTS: Mean daily iron intake was 10.8 mg/d, 97% of which was nonheme iron. Estimated nonheme-iron bioavailability from algorithms was 1.0-4.3% adjusted for low body iron stores. Over 15 mo, the mean change in total body iron was -142 mg, and mean iron absorption was estimated to be 0.22 mg/d, or 2% of dietary iron. Mean hemoglobin concentration decreased 12 g/L. At 15 mo, 75% of the cohort had deficits in tissue iron, and one-third had mild iron deficiency anemia. CONCLUSION: Low iron bioavailability from legume and cereal-based diets is a cause of iron deficiency anemia in children in rural Africa.

The effects of vitamin A deficiency and vitamin A supplementation on thyroid function in goitrous children.

In developing countries, children are at high risk for both the iodine deficiency disorders (IDD) and vitamin A deficiency (VAD). The study aim was to determine the effects of VAD and vitamin A (VA) supplementation on thyroid function in an area of endemic goiter. In a double-blind, randomized, 10-month trial, Moroccan children with IDD and VAD (n = 138) were given iodized salt and either VA (200,000 IU) or placebo at 0 and 5 months. At 0, 5, and 10 months, measurements of VA status and thyroid function were made. At baseline, increasing VAD severity was a predictor of greater thyroid volume and higher concentrations of TSH and thyroglobulin (P < 0.001). In children with VAD, the odds ratio for goiter was 6.51 (95% confidence interval, 2.94, 14.41). VAD severity was also a strong predictor of higher concentrations of total T(4) (P < 0.001); the odds ratio for hypothyroidism in VAD was 0.06 (95% confidence interval, 0.03, 0.14). During the intervention, mean thyroglobulin, median TSH, and the goiter rate significantly decreased in the VA-treated group compared with those in the placebo group (P < 0.01). The findings indicate that VAD in severely IDD-affected children increases TSH stimulation and thyroid size and reduces the risk for hypothyroidism. This effect could be due to decreased VA-mediated suppression of the pituitary TSHbeta gene. In IDD- and VAD-affected children receiving iodized salt, concurrent VA supplementation improves iodine efficacy.

Triple fortification of salt with microcapsules of iodine, iron, and vitamin A.

BACKGROUND: In many developing countries, children are at high risk of goiter, vitamin A deficiency, and iron deficiency anemia. OBJECTIVE: We aimed to develop a stable, efficacious salt fortified with iodine, iron, and vitamin A. DESIGN: A novel spray-cooling technique was used with hydrogenated palm oil to package potassium iodate, micronized ferric pyrophosphate, and retinyl palmitate into microcapsules (mean particle size: 100 mum). We used the microcapsules to create triple-fortified salt (TFS) with 30 mug I, 2 mg Fe, and 60 mug vitamin A/g salt. After storage trials, we compared the efficacy of TFS with that of iodized salt in a 10-mo, randomized, double-blind trial in goitrous schoolchildren (n = 157) who had a high prevalence of vitamin A deficiency and iron deficiency anemia. RESULTS: After storage for 6 mo, losses of iodine and vitamin A from the TFS were approximately 12-15%, and color was stable. In the TFS group, mean hemoglobin increased by 15 g/L at 10 mo (P < 0.01), iron status indexes and body iron stores improved significantly (P < 0.05), and mean serum retinol, retinol-binding protein, and the ratio of retinol-binding protein to prealbumin increased significantly (P < 0.01). At 10 mo, prevalences of vitamin A deficiency and iron deficiency anemia were significantly lower in the TFS group than in the iodized salt group (P < 0.001). CONCLUSION: Newly developed microcapsules containing iodine, iron, and vitamin A are highly stable when added to local African salt. TFS was efficacious in reducing the prevalence of iron, iodine, and vitamin A deficiencies in school-age children.

Dual fortification of salt with iodine and micronized ferric pyrophosphate: a randomized, double-blind, controlled trial.

BACKGROUND: In many developing countries, children are at high risk for both goiter and anemia. In areas of subsistence farming in rural Africa, salt is one of the few regularly purchased food items and could be a good fortification vehicle for iodine and iron, provided that a stable yet bioavailable iron fortificant is used. OBJECTIVE: We tested the efficacy of salt dual-fortified with iodine and micronized ferric pyrophosphate for reducing the prevalence of iodine and iron deficiencies in children. DESIGN: In rural northern Morocco, we fortified local salt with 25 microg I (as potassium iodate)/g salt and 2 mg Fe (as micronized ferric pyrophosphate; mean particle size = 2.5 microm)/g salt. After storage and acceptability trials, we compared the efficacy of the dual-fortified salt (DFS) with that of iodized salt in a 10-mo, randomized, double-blind trial in iodine-deficient 6-15-y-old children (n = 158) with a high prevalence of anemia. RESULTS: After storage for 6 mo, there were no significant differences in iodine content or color lightness between the DFS and iodized salt. During the efficacy trial, the DFS provided approximately 18 mg Fe/d; iron absorption was estimated to be approximately 2%. After 10 mo of treatment in the DFS group, mean hemoglobin increased by 16 g/L (P < 0.01), iron status and body iron stores increased significantly (P < 0.01), and the prevalence of iron deficiency anemia decreased from 30% at baseline to 5% (P < 0.001). In both groups, urinary iodine (P < 0.001) and thyroid volume (P < 0.01) improved significantly from baseline. CONCLUSION: A DFS containing iodine and micronized ferric pyrophosphate can be an effective fortification strategy in rural Africa.

Addition of microencapsulated iron to iodized salt improves the efficacy of iodine in goitrous, iron-deficient children: a randomized, double-blind, controlled trial.

OBJECTIVE: In many developing countries, children are at high risk for both goiter and anemia. Iron (Fe) deficiency adversely effects thyroid metabolism and reduces efficacy of iodine prophylaxis in areas of endemic goiter. The study aim was to determine if co-fortification of iodized salt with Fe would improve efficacy of the iodine in goitrous children with a high prevalence of anemia. DESIGN AND METHODS: In a 9-month, randomized, double-blind trial, 6-15 year-old children (n=377) were given iodized salt (25 microg iodine/g salt) or dual-fortified salt with iodine (25 microg iodine/g salt) and Fe (1 mg Fe/g salt, as ferrous sulfate microencapsulated with partially hydrogenated vegetable oil). RESULTS: In the dual-fortified salt group, hemoglobin and Fe status improved significantly compared with the iodized salt group (P<0.05). At 40 weeks, the mean decrease in thyroid volume measured by ultrasound in the dual-fortified salt group (-38%) was twice that of the iodized salt group (-18%) (P<0.01). Compared with the iodized salt group, serum thyroxine was significantly increased (P<0.05) and the prevalence of hypothyroidism and goiter decreased (P<0.01) in the dual-fortified salt group. CONCLUSION: Addition of encapsulated Fe to iodized salt improves the efficacy of iodine in goitrous children with a high prevalence of anemia.