Zinc intake-status-health relationships and the impact of multiple micronutrient supplementation on cognitive function in Peruvian pre-school children.

Background: Dietary zinc recommendations vary widely across Europe. The EURRECA (European Micronutrient Recommendations Aligned) Network of Excellence was brought together to harmonise the approach to setting micronutrient recommendations. The overall aim was to produce a set of guidelines and an extensive database that may be of use to expert panels in underpinning future micronutrient recommendations, based on a series of systematic reviews and meta-analysis of published data. A secondary aim was to identify gaps in knowledge regarding micronutrient status, intake and health outcomes for future research. A third aim, coming from the result of the secondary aim, was to investigate the long term effect of supplementation on cognition. Objectives: The objectives of this thesis were: (1) To adapt the methodology for undertaking a systematic review and meta-analysis developed by EURRECA for zinc in all population groups (infants, children, adolescents, pregnant and lactating women and adults and elderly). (2) To identify knowledge gaps in the research through the assessment of the interrelationships between zinc intake, status and health outcomes. (3) To design and implement a study to explore the intake-status-health relationships between micronutrient supplementation and cognitive function in Peruvian children. Methods: Phase 1: The EURRECA systematic review. Database searches were conducted in MEDLINE, Embase and the Cochrane library, from inception to March 2014. For the assessment of the intake-status relationship, an intake-status regression coefficient (^) was estimated for each individual study and the overall pooled ^ and SE ^ was calculated using random effect meta-analysis on a double log scale. The systematic review included randomized controlled trials, cohort studies, cross sectional studies and nested case-control studies in healthy children and adult populations that measured zinc intake (diet and supplements) and zinc status (serum/plasma zinc) in association health outcomes that included cognitive function and psychomotor development. Phase 2: Empirical study. This included the assessment of multiple micronutrients (MMN) supplementation and cognitive development in Peruvian children when compared with giving iron supplements alone. These tests were considered to reflect theoretical dimensions of working memory (Nine boxes), and inhibitory control (Day/Night stroop task). Intelligence Quotient (IQ) was measured using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI); social-emotional behaviour was assessed via the Brief Infant–Toddler Social and Emotional Assessment (BITSEA) and reasoning through the theory of mind test. Results: Meta-analysis of data reporting zinc intake and status revealed that doubling intake increased plasma zinc concentration by 9% in children, by 3% during pregnancy, by 1% during lactation and by 6% in adults and elderly. The systematic review of zinc and health outcomes highlighted the need for further research on the relationship between micronutrients and cognitive function. The empirical study was therefore designed and undertaken. The results revealed that there were no significant differences between the iron and the MMN supplemented groups for all cognitive tests, with the exception of the vocabulary WPPSI subtest in girls (mean±SD), (MMN, 6.83±2.05; iron 5.78±1.59, p = 0.028) and no significant differences were found for plasma zinc and haemoglobin concentrations between the two groups. Conclusions: The systematic reviews provided novel dose-response estimates between zinc intake-status that could be used either qualitatively or quantitatively with balance studies when setting future zinc recommendations. Following an assessment of the impact of micronutrient supplementation on cognitive and social-emotional development in Peruvian preschool children, it can be concluded that MMN supplements had no long term additional effects on cognitive function compared with iron alone, however the timing of the supplement for maximal potential benefit needs to be explored further.