Ans Eilander

Multiple micronutrient supplementation for improving cognitive performance in children: systematic review of randomized controlled trials

BACKGROUND Although multiple micronutrient interventions have been shown to benefit childrens intellectual development, a thorough evaluation of the totality of evidence is currently lacking to direct public health policy. OBJECTIVE This study aimed to systematically review the present literature and to quantify the effect of multiple micronutrients on cognitive performance in schoolchildren. METHODS The Institute for Scientific Information Web of Knowledge and local medical databases were searched for trials published from 1970 to 2008. Randomized controlled trials that investigated the effect of > or =3 micronutrients compared with placebo on cognition in healthy children aged 0-18 y were included following protocol. Data were extracted by 2 independent researchers. The cognitive tests used in the trials were grouped into several cognitive domains (eg, fluid and crystallized intelligence), and pooled effect size estimates were calculated per domain. Heterogeneity was explored through sensitivity and meta-regression techniques. RESULTS Three trials were retrieved in children aged <5 y, and 17 trials were retrieved in children aged 5-16 y. For the older children, pooled random-effect estimates for intervention were 0.14 SD (95% CI: -0.02, 0.29; P = 0.083) for fluid intelligence and -0.03 SD (95% CI: -0.21, 0.15; P = 0.74) for crystallized intelligence, both of which were based on 12 trials. Four trials yielded an overall effect of 0.30 SD (95% CI: 0.01, 0.58; P = 0.044) for academic performance. For other cognitive domains, no significant effects were found. CONCLUSIONS Multiple micronutrient supplementation may be associated with a marginal increase in fluid intelligence and academic performance in healthy schoolchildren but not with crystallized intelligence. More research is required, however, before public health recommendations can be given.

Essential fats: how do they affect growth and development of infants and young children in developing countries? A literature review.

Omega-3 and omega-6 fatty acids, particularly docosahexaenoic acid (DHA), are known to play an essential role in the development of the brain and retina. Intakes in pregnancy and early life affect growth and cognitive performance later in childhood. However, total fat intake, alpha-linolenic acid (ALA) and DHA intakes are often low among pregnant and lactating women, infants and young children in developing countries. As breast milk is one of the best sources of ALA and DHA, breastfed infants are less likely to be at risk of insufficient intakes than those not breastfed. Enhancing intake of ALA through plant food products (soy beans and oil, canola oil, and foods containing these products such as lipid-based nutrient supplements) has been shown to be feasible. However, because of the low conversion rates of ALA to DHA, it may be more efficient to increase DHA status through increasing fish consumption or DHA fortification, but these approaches may be more costly. In addition, breastfeeding up to 2 years and beyond is recommended to ensure an adequate essential fat intake in early life. Data from developing countries have shown that a higher omega-3 fatty acid intake or supplementation during pregnancy may result in small improvements in birthweight, length and gestational age based on two randomized controlled trials and one cross-sectional study. More rigorous randomized controlled trials are needed to confirm this effect. Limited data from developing countries suggest that ALA or DHA supplementation during lactation and in infants may be beneficial for growth and development of young children 6-24 months of age in these settings. These benefits are more pronounced in undernourished children. However, there is no evidence for improvements in growth following omega-3 fatty acid supplementation in children >2 years of age.

Effect of fortification with multiple micronutrients and n−3 fatty acids on growth and cognitive performance in Indian schoolchildren: the CHAMPION (Children's Health and Mental Performance Influenced by Optimal Nutrition) Study

BACKGROUND Fortification with multiple micronutrients has been shown to improve growth and cognitive performance among children in developing countries, but it is unknown whether higher concentrations are more effective than lower concentrations. OBJECTIVE We compared the effect of 2 different concentrations of a combination of micronutrients and n-3 (omega-3) fatty acids on indicators of growth and cognitive performance in low-income, marginally nourished schoolchildren in Bangalore, India. DESIGN In a 2-by-2 factorial, double-blind, randomized controlled trial, 598 children aged 6-10 y were individually allocated to 1 of 4 intervention groups to receive foods fortified with either 100% or 15% of the Recommended Dietary Allowance of micronutrients in combination with either 900 mg alpha-linolenic acid plus 100 mg docosahexaenoic acid or 140 mg alpha-linolenic acid for 12 mo. Anthropometric and biochemical assessments were performed at baseline and 12 mo. Cognitive performance was measured at baseline and at 6 and 12 mo. RESULTS The high micronutrient treatment significantly improved linear growth at 12 mo (0.19 cm; 0.01, 0.36) and short-term memory at 6 mo (0.11 SD; 0.01, 0.20) and was less beneficial on fluid reasoning at 6 (-0.10 SD; -0.17, -0.03) and 12 (-0.12 SD; -0.20, -0.04) mo than was the low micronutrient treatment, whereas no differences were observed on weight, retrieval ability, cognitive speediness, and overall cognitive performance. No significant differences were found between the n-3 treatments. CONCLUSIONS The high micronutrient treatment was more beneficial for linear growth than was the low micronutrient treatment. However, with some small differential effects, higher micronutrient concentrations were as effective as lower concentrations on cognitive performance. This trial was registered at clinicaltrials.gov as NCT00467909.

Essential fats for future health. Proceedings of the 9 th Unilever Nutrition Symposium, 26-27 May 2010

The 9th Unilever Nutrition Symposium entitled ‘Essential fats for future health’, held on 26–27 May 2010, aimed to review the dietary recommendations for essential fatty acids (EFA); discuss the scientific evidence for the roles of EFA in cognition, immune function and cardiovascular health; and to identify opportunities for joint efforts by industry, academia, governmental and non-governmental organizations to effectively improve health behaviour. This paper summarizes the main conclusions of the presentations given at the symposium. Linoleic acid (LA) and α-linolenic acid (ALA) are EFA that cannot by synthesized by the human body. Docosahexaenoic acid (DHA) is considered as conditionally essential because of its limited formation from ALA in the human body and its critical role in early normal retinal and brain development and, jointly with eicosapentaenoic acid (EPA), in prevention of cardiovascular disease (CVD). Some evidence for possible beneficial roles of n-3 fatty acids for immune function and adult cognitive function is emerging. A higher consumption of polyunsaturated fatty acids (PUFA; >10%E), including LA, ALA and at least 250–500 mg per day of EPA+DHA, is recommended for prevention of coronary heart disease (CHD). Two dietary interventions suggest that EFA may affect CVD risk factors in children similarly as in adults. To ensure an adequate EFA intake of the population, including children, public health authorities should develop clear messages based on current science; ensure availability of healthy, palatable foods; and collaborate with scientists, the food industry, schools, hospitals, health-care providers and communities to encourage consumers to make healthy choices.

Intake of fatty acids in general populations worldwide does not meet dietary recommendations to prevent coronary heart disease: a systematic review of data from 40 countries.

Aim: To systematically review data from different countries on population intakes of total fat, saturated fatty acids (SFA) and polyunsaturated fatty acids (PUFA), and to compare these to recommendations from the Food and Agriculture Organization of the United Nations/the World Health Organization (FAO/WHO). Methods: Data from national dietary surveys or population studies published from 1995 were searched via MEDLINE, Web of Science and websites of national public health institutes. Results: Fatty acid intake data from 40 countries were included. Total fat intake ranged from 11.1 to 46.2 percent of energy intake (% E), SFA from 2.9 to 20.9% E and PUFA from 2.8 to 11.3% E. The mean intakes met the recommendation for total fat (20-35% E), SFA (<10% E) and PUFA (6-11% E) in 25, 11 and 20 countries, respectively. SFA intake correlated with total fat intake (r = 0.76, p < 0.01) but not with PUFA intake (r = 0.03, p = 0.84). Twenty-seven countries provided data on the distribution of fatty acids intake. In 18 of 27 countries, more than 50% of the population had SFA intakes >10% E and in 13 of 27 countries, the majority of the population had PUFA intakes <6% E. Conclusions: In many countries, the fatty acids intake of adults does not meet the levels that are recommended to prevent chronic diseases. The relation between SFA and PUFA intakes shows that lower intakes of SFA in the populations are not accompanied by higher intakes of PUFA, as is recommended for preventing coronary heart disease.

B Vitamins and n–3 Fatty Acids for Brain Development and Function: Review of Human Studies

Background: Nutrition is one of many factors that affect brain development and functioning, and in recent years the role of certain nutrients has been investigated. B vitamins and n–3 polyunsaturated fatty acids (PUFA) are two of the most promising and widely studied nutritional factors. Methods: In this review, we provide an overview of human studies published before August 2011 on how vitamin B6, folate, vitamin B12 and n–3 PUFA may affect the brain, their nutrient status and the existing evidence for an association between these nutrients and brain development, brain functioning and depression during different stages of the life cycle. Results: No recommendation can be given regarding a role of B vitamins, either because the number of studies on B vitamins is too limited (pregnant and lactating women and children) or the studies are not consistent (adults and elderly). For n–3 PUFA, observational evidence may be suggestive of a beneficial effect; however, this has not yet been sufficiently replicated in randomized controlled trials (RCTs). Conclusions: We found that the existing evidence from observational studies as well as RCTs is generally too limited and contradictory to draw firm conclusions. More research is needed, particularly a combination of good-quality long-term prospective studies and well-designed RCTs.

The Impact of Polyunsaturated Fatty Acids in Reducing Child Attention Deficit and Hyperactivity Disorders

Objectives: To review the impact of polyunsaturated fatty acids (PUFA) in reducing ADHD symptoms in children. Methods: Peer-reviewed experimental literature published from 1980 to Mai 2009 is consulted (Psychinfo, Medline, and resulting reference lists). Results: Placebo-controlled studies with ADHD or hyperactive children show no effects on behaviors or cognition when only n-6 (omega-6) PUFA, only docosahexaenoic acid (DHA), or n-6 and n-3 (omega-3) short-chain PUFA are supplemented. Yet three out of four studies suggest that a combination of long-chain n-3 and n-6 fatty acids (DHA, eicosapentaenoic acid [EPA], and gamma-linolenic acid [GLA]) supplemented daily for 3 to 4 months could lead to a reduction in ADHD symptomatology. Results on cognitive outcomes are inconsistent. Conclusions: Evidence is too limited to reach definitive conclusions but suggests that research on the impact of long-chain PUFA (n-3 and n-6) should continue with special focus on individual differences (genetic and fatty acid markers), mechanisms (brain imaging), and new enhanced methods of systematic observations of behaviors.

Reduced Symptoms of Inattention after Dietary Omega-3 Fatty Acid Supplementation in Boys with and without Attention Deficit/Hyperactivity Disorder

Attention deficit/hyperactivity disorder (ADHD) is one of the most common child psychiatric disorders, and is often treated with stimulant medication. Nonpharmacological treatments include dietary supplementation with omega-3 fatty acids, although their effectiveness remains to be shown conclusively. In this study, we investigated the effects of dietary omega-3 fatty acid supplementation on ADHD symptoms and cognitive control in young boys with and without ADHD. A total of 40 boys with ADHD, aged 8–14 years, and 39 matched, typically developing controls participated in a 16-week double-blind randomized placebo-controlled trial. Participants consumed 10 g of margarine daily, enriched with either 650 mg of eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) each or placebo. Baseline and follow-up assessments addressed ADHD symptoms, fMRI of cognitive control, urine homovanillic acid, and cheek cell phospholipid sampling. EPA/DHA supplementation improved parent-rated attention in both children with ADHD and typically developing children. Phospholipid DHA level at follow-up was higher for children receiving EPA/DHA supplements than placebo. There was no effect of EPA/DHA supplementation on cognitive control or on fMRI measures of brain activity. This study shows that dietary supplementation with omega-3 fatty acids reduces symptoms of ADHD, both for individuals with ADHD and typically developing children. This effect does not appear to be mediated by cognitive control systems in the brain, as no effect of supplementation was found here. Nonetheless, this study offers support that omega-3 supplementation may be an effective augmentation for pharmacological treatments of ADHD (NCT01554462: The Effects of EPA/DHA Supplementation on Cognitive Control in Children with ADHD; http://clinicaltrials.gov/show/NCT01554462).

Undernutrition, fatty acid and micronutrient status in relation to cognitive performance in Indian school children: a cross-sectional study

While undernutrition and anaemia have previously been linked to poor development of children, relatively little is known about the role of B-vitamins and fatty acids on cognition. The present study aims to explore the associations between indicators of body size, fatty acid and micronutrient status on cognitive performance in 598 Indian school children aged 6-10 years. Baseline data of a clinical study were used to assess these associations by analyses of variance adjusting for age, sex, school, maternal education and cognitive tester. The Kaufman Assessment Battery for Children II was used to measure four cognitive domains, including fluid reasoning, short-term memory, retrieval ability and cognitive speediness. Scores were combined into an overall measure, named mental processing index (MPI). Body size indicators and Hb concentrations were significantly positively related to cognitive domains and MPI, such that increases of 1 sd in height-for-age and weight-for-age z-scores would each translate into a 0.09 sd increase in MPI, P = 0.0006 and 0.002, respectively. A 10 g/l increase in Hb concentrations would translate into a 0.08 sd increase in MPI, P = 0.0008. Log-transformed vitamin B12 concentrations were significantly inversely associated with short-term memory, retrieval ability and MPI (beta (95 % CI) = - 0.124 (- 0.224, - 0.023), P = 0.02). Other indicators of Fe, iodine, folate and fatty acid status were not significantly related to cognition. Our findings for body size, fatty acids and micronutrients were in agreement with previous observational studies. The inverse association of vitamin B12 with mental development was unexpected and needed further study.

Dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in children - a workshop report.

There is controversy whether children should have a dietary supply of preformed long-chain polyunsaturated n-3 fatty acids EPA and DHA. The aims of the workshop were to review evidence for a possible benefit of a preformed EPA and/or DHA supply, of data required to set desirable intakes for children aged 2-12 years, and of research priorities. The authors concluded that EPA and DHA intakes per kg body weight may often be low in 2- to 12-year-old children, relative to intakes per kg body weight of breast-fed infants and adult intakes, but reliable data are scarce. Little information is available that increasing dietary intakes of EPA or DHA in children has benefits to physical or mental function or other health endpoints. Studies addressing EPA and DHA intakes and tissue status among groups of children with different dietary habits, and measures of relevant development and health endpoints, are needed for developing potential advice on desirable intakes of EPA and/or DHA in children. At this time it appears prudent to advise that dietary intakes in childhood are consistent with future eating patterns supporting adult health, such as prevention of metabolic disorders and CVD, supporting immune function, and reproductive health. In conclusion, the available information relating dietary EPA and DHA intakes in children aged 2-12 years to growth, development and health is insufficient to derive dietary intake recommendations for EPA and DHA. Adequately designed studies addressing dietary intakes, measures of status and relevant functional or health effects across this age group are needed.