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      A Study of the Effects of Latent Iron Deficiency on Measures of Cognition: A Pilot Randomised Controlled Trial of Iron Supplementation in Young Women

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          Abstract

          Rates of iron deficiency are high amongst healthy young women. Cognitive impairment occurs secondary to iron deficiency in infants and children, but evaluation of the impact on cognition among young women is inconsistent. The aim was to determine the suitability of the IntegNeuro test battery for assessing cognitive function in iron-deficient and iron-sufficient young women. A pilot double-blinded, placebo-controlled intervention trial was conducted in iron-deficient (serum ferritin ≤ 20 μg/L and haemoglobin > 120 g/L) and iron-sufficient young women (18–35 years). Cognitive function and haematological markers of iron status were measured at baseline and follow-up. Iron-deficient participants ( n = 24) were randomised to receive placebo, 60 mg or 80 mg elemental iron daily supplements for 16 weeks. A control group of iron-sufficient participants ( n = 8) was allocated to placebo. Change scores for Impulsivity and Attention were significantly greater in plasma ferritin improvers than in non-improvers ( p = 0.004, p = 0.026). IntegNeuro was easy to administer and acceptable to young women. Based on the differences in Memory and Attention scores between iron-deficient participants on iron treatment and those on placebo, it was decided that between 26 and 84 participants would be required in each iron treatment group for an adequately powered extension of this pilot RCT.

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          Most cited references38

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          Randomised study of cognitive effects of iron supplementation in non-anaemic iron-deficient adolescent girls.

          Up to 25% of adolescent girls in the USA are iron deficient. This double-blind, placebo-controlled clinical trial assessed the effects of iron supplementation on cognitive function in adolescent girls with non-anaemic iron deficiency. 716 girls who enrolled at four Baltimore high schools were screened for non-anaemic iron deficiency (serum ferritin < or = 12 micrograms/L with normal haemoglobin). 98 (13.7%) girls had non-anaemic iron deficiency of whom 81 were enrolled in the trial. Participants were randomly assigned oral ferrous sulphate (650 mg twice daily) or placebo for 8 weeks. The effect of iron treatment was assessed by questionnaires and haematological and cognitive tests, which were done before treatment started and repeated after the intervention. We used four tests of attention and memory to measure cognitive functioning. Intention-to-treat and per-protocol analyses were done. Of the 81 enrolled girls with non-anaemic iron deficiency, 78 (96%) completed the study (39 in each group). Five girls (three control, two treatment) developed anaemia during the intervention and were excluded from the analyses. Thus, 73 girls were included in the per-protocol analysis. Ethnic distribution, mean age, serum ferritin concentrations, haemoglobin concentrations, and cognitive test scores of the groups did not differ significantly at baseline. Postintervention haematological measures of iron status were significantly improved in the treatment group (serum ferritin 27.3 vs 12.1 micrograms/L, p < 0.001). Regression analysis showed that girls who received iron performed better on a test of verbal learning and memory than girls in the control group (p < 0.02). In this urban population of non-anaemic iron-deficient adolescent girls, iron supplementation improved verbal learning and memory.
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            Iron deficiency alters brain development and functioning.

            John Beard (2003)
            Iron deficiency anemia in early life is related to altered behavioral and neural development. Studies in human infants suggest that this is an irreversible effect that may be related to changes in chemistry of neurotransmitters, organization and morphology of neuronal networks, and neurobiology of myelination. The acquisition of iron by the brain is an age-related and brain-region-dependent process with tightly controlled rates of movement of iron across the blood-brain barrier. Dopamine receptors and transporters are altered as are behaviors related to this neurotransmitter. The growing body of evidence suggests that brain iron deficiency in early life has multiple consequences in neurochemistry and neurobiology.
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              Long-lasting neural and behavioral effects of iron deficiency in infancy.

              Infants are at high risk for iron deficiency and iron-deficiency anemia. This review summarizes evidence of long-term effects of iron deficiency in infancy. Follow-up studies from preschool age to adolescence report poorer cognitive, motor, and social-emotional function, as well as persisting neurophysiologic differences. Research in animal models points to mechanisms for such long-lasting effects. Potential mechanisms relate to effects of iron deficiency during brain development on neurometabolism, myelination, and neurotransmitter function.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                23 June 2014
                June 2014
                : 6
                : 6
                : 2419-2435
                Affiliations
                [1 ]Priority Research Centre in Physical Activity and Nutrition and School of Health Sciences, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia; E-Mails: Alecia.Leonard@ 123456uon.ed.au (A.J.L.); Clare.Collins@ 123456newcastle.edu.au (C.E.C.); Amanda.Patterson@ 123456newcastle.edu.au (A.J.P.)
                [2 ]School of Psychology, Faculty of Science and IT, University of Newcastle, Callaghan, NSW 2308, Australia
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: Kerry.Chalmers@ 123456newcastle.edu.au ; Tel.: +61-2-4921-5757; Fax: +61-2-4921-6906.
                Article
                nutrients-06-02419
                10.3390/nu6062419
                4073160
                24959952
                ad1ca0d9-4ab4-4ecd-a425-bf289a1cb56a
                © 2014 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 17 April 2014
                : 06 June 2014
                : 16 June 2014
                Categories
                Article

                Nutrition & Dietetics
                iron,women,cognition,memory,attention,supplementation
                Nutrition & Dietetics
                iron, women, cognition, memory, attention, supplementation

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