Nutrition for Brain Health and Cognition in early years
From the period that the foetus develops in the womb, the brain is vulnerable to be affected by nutrition. While the fact that a direct link between early nutrition and the cognitive function at a later date has been difficult to establish, there is a crying need for a randomized trial of nutritional intervention and outcomes in humans. Studies depriving nutrition are blatantly unethical so most of the studies carried out have been by nutritional supplementation in a poor and undernourished population. This may confound the relationship, making the effect of undernutrition difficult to understand. Given the wide range of nutritional deficiencies that could occur, the million-dollar question would be whether general or specific nutritional failings can influence cognitive e function.
Having necessary amounts of the required vitamins, minerals and energy producing macronutrients begins preconceptually. The foetus depends entirely what the mother provides for its nutrition. They say,”the foetus is the perfect parasite” suggesting that the foetus grows at the cost of the mother. After birth, by lactation the mother continues proving the necessary nutrition facilitating a proper development of the brain and other organs in the neonate. The nutritional wellbeing – the quality and quantity- of nutrition to the developing zygote, then foetus, then neonate and then, finally, adult is one of the factors that manifest in adulthood. This is called the foetal origins of disease or developmental origins of disease (Gueant et al, 2013, Monk et al, 2013).
Many women enter into motherhood with less than adequate nutritional values in their bodies. Obesity, low intakes of long chain polyunsaturated fatty acids, proteins, zinc, iron, choline and a host of other nutrients put the foetus at a heightened risk for low birth weight babies or preterm births ( Ramakrishnan et al, 2012). Thus, during gestation, a multivitamin, multimineral supplement may confer more benefit than a single supplement.
For the development of the brain and the cognitive functions, adequate quantities of iodine, iron, folate are extremely important and there is evidence to suggest that zinc, Vitamin B12 and Omega-3 polyunsaturated fatty acids too have an important role to play in cerebral development. What remains to be studied is the interaction between the micronutrients and
the macronutrients with emphasis on executing higher functions in children with nutritional deficiencies or in those suffering from attention deficit hyperactivity disorder and dyslexia.
We are lacking in studies which examine the relationship between dietary patterns and cognitive development. There is evidence to show that malnutrition can impair cognitive development while breast feeding could be beneficial for cognition. Also, while there is little evidence to establish a relationship between cognition and obesity, eating breakfast has been proven to be beneficial for the development of the brain.
Brain development has a genetic pattern which is influenced by environmental factors including nutrition ( Bryan et al 2004, Toga et al 2006, Giedd et al 2010). Without altering the gene sequence, environmental influences may modify gene expression. These factors can cause long lasting or heritable changes in biological programs ( Levi and Sanderson, 2004 ; Lillycrop and Burdge, 2011; Jimenz-Chillaron et al,2012). The Dutch Hunger Winter of the 1940s was one of the first and the best known studies of Nutritional Epigenomics. It revealed that the offspring of mothers exposed to famine during pregnancy had an increased risk of cardiovascular, kidney, lung and metabolic disroders and reduced cognitive functions (Roseboom et al 2006; De Rooij et al, 2010). There is evidence to prove that the timing of nutritional deficiencies can significantly affect brain development. It is well known that folic acid deficiency between 21 and 28 days after conception (when the neural tube closes) predisposes the foetus to a congenital malformation, called a neural tube defect. This time frame where a critical irreversible damage could occur is called a critical period. A sensitive period tends to reflect a broader timeframe; during such a developmental period the brain is more sensitive to specific interventions. They could develop skills and proficiencies outside this time frame, though with less proficiency. A typical example is a deaf child who receives cochlear implants within a sensitive period for brain development (i.e., before the age of 3–5 years) shows better language development than those who receive a cochlear implant after this period (Penhune, 2011).
Since rapid brain growth occurs during the first 2 years of life (and by the age of 2 the brain reaches 80% of its adult weight), this period of life may be particularly sensitive to deficiencies in diet (Bryan et al., 2004; Lenroot and Giedd, 2006). Adolescence is also a significant and sensitive developmental period, with research indicating that structural reorganization, brain and cognitive maturation and—in particular—major developments in the prefrontal cortex take place during puberty.
MICRONUTRIENTS AND COGNITIVE DEVELOPMENT
Omega 3 Fatty Acids
The two core fatty acids in the brain - docosahexaenoic acid and arachidonic acid form 20% of the lipids which, in turn, is responsible for 60% of the dry weight of the human brain. These are frequently found insufficient in the diet of children and adults.
They are not only the basic components of neuronal membranes, but they modulate membrane fluidity and volume and thereby influence receptor and enzyme activities in addition to affecting ion channels. Essential fatty acids are also precursors for active mediators that play a key role in inflammation and immune reaction. They promote neuronal and dendritic spine growth and synaptic membrane synthesis, and hence influence signal processing, and neural transmission. In addition, essential fatty acids regulate gene expression in the brain.
Therefore, the existing literature strongly suggests that essential fatty acids are critical for brain development and function.
Vitamin B12, Folic Acid and Choline
It is more readily found in the developing countries and in the older age group and in vegetarians and patients with absorption problems. A lot of studies are being done on them and many countries have made it mandatory to supplement certain foods with folic acid. Folate affects neural stem cell proliferation and differentiation, decreases apoptosis, alters DNA biosynthesis, and has an important role in homocysteine and S-adenosylmethionine biosynthesis.
It is believed that choline has similar roles in brain development as folate. choline and folate deficiency may result in DNA hypomethylation, thereby altering gene transcription (Zeisel, 2009). In addition, choline is a component of phospholipids in cell membranes and a precursor for the neurotransmitter acetylcholine (Zeisel, 2006b).
Vitamin B12 has a role in axon myelination that is important for impulse conduction from cell to cell, and it also protects neurons from degeneration. Vitamin B12 may also alter the synthesis of different cytokines, growth factors and oxidative energy metabolites such as lactic acid. In children, the association between vitamin B12 and cognitive development has been mainly observed in infants born of vegetarian/vegan mothers or mothers on a
macrobiotic diet. These diets can result in vitamin B12 deficiency, as vitamin B12 is largely found in animal products.
The association between maternal blood folate status and cognitive development has been investigated in several studies (Tamura et al., 2005; Veena et al., 2010). Tamura et al. (2005) did not find any relationship between maternal blood folate status (“low” vs. “normal”) during the second half of the pregnancy and cognitive development of their children at the age of 5–6 years on different cognitive tests including Differential Ability Scales, Visual and Auditory Sequential Memory, Knox Cube, the Gross Motor Scale and the Grooved Pegboard.
It is possible that vitamin B12 affects some cognitive functions only if the person is severely deficient, as can be seen in vegetarian mothers and their children.
Although there is no sufficient data about the requirements of choline in humans, choline does not seem to be deficient in the general population, with the exception of experimental conditions. Also, There is only one study to date that has evaluated the impact of maternal blood choline (represented across a wide range of concentrations) on intelligence (measured on the Wechsler Preschool and Primary Scale of Intelligence-Revised) in 5 year old children. However, the authors did not find a significant correlation between the two (Signore et al., 2008).
In summary, the impact of vitamin B12, folate and choline on children's cognitive development has not been adequately researched to date in humans.
Zinc
Zinc deficiency is a major problem worldwide, affecting 40% of the global population (Maret and Sandstead, 2006). Zinc supplementation has a positive effect on the immune status of infants and may prevent congenital malformations (Shah and Sachdev, 2006). However, the relationship between maternal zinc status and the child's cognitive development has not been fully investigated. In an observational study, low maternal zinc intake in Egyptian mothers was associated with lower levels of focused attention in newborns, measured with the Brazelton Neonatal Behavior Assessment Scale (Kirksey et al., 1994). More recent randomized control trials from India (Taneja et al., 2005) and Bangladesh (Black et al., 2004), where malnutrition is common among children, did not find that zinc supplementation alone affects infants' cognitive development on the Bayley Scales of Infant Development test.
Taken together with other studies, the findings do not consistently show a positive relationship between maternal zinc status and cognitive development of children. Additional studies are therefore needed to examine the long term benefit of zinc on brain development.
Iron
One of the most common nutritional deficiencies in both developing and developed countries is iron deficiency. In some parts of the world, South-East Asia, the prevalence is more than 40%.
It is believed that iron is involved with different enzyme systems in the brain, including: the cytochrome c oxidase enzyme system in energy production, tyrosine hydroxylase for dopamine receptor synthesis, delta-9- desaturase for myelination, and fatty acid synthesis, and ribonucleotide reductase for brain growth regulation (Deungria, 2000; Lozoff and Georgieff, 2006; Georgieff, 2007; Rioux et al., 2011). In addition, iron appears to modify developmental processes in hippocampal neurons by altering dendritic growth (Jorgenson et al., 2003; Lozoff and Georgieff, 2006).
Tamura et al. (2002) found significantly inferior performance in language skills, fine motor skills and attention (and lower but not significant scores in every other test) in 5 years old children whose cord ferritin levels lay in the lowest quartile. Grantham-McGregor and Ani (2001) reviewed a range of longitudinal studies and reported that anaemic infants had poorer cognitive and school performance in the long term, and that short-term iron treatment trials in anaemic children did not show benefits in cognitive development. A Cochrane review based on seven randomized controlled trials reached a similar conclusion, i.e., that short term iron treatment for anaemia in children less than 3 years old did not improve cognitive development.
In summary, there is a lack of epidemiological evidence or data from well-designed intervention trials demonstrating the impact of maternal iron supplementation on the cognitive development of healthy children. There is evidence that older anaemic children benefit from iron treatments. However, cognitive performance tests including the Bayley Scales of Infant Development and the Denver Developmental Screening Test may not be sensitive enough to detect small changes in short-term supplementation or treatment in young children (Armstrong, 2002). Furthermore, if iron deficiency occurs in very early life, the
damage may be irreversible, and it may not be possible to reverse this damage with iron treatment (Beard, 2008).
Iodine
Iodine deficiency is a significant worldwide public health issue, especially in children and during pregnancy (World Health Organization, 2004). Iodine deficiency in the soils in many countries has led to food fortification, most commonly the use of iodized salt (World Health Organization, 2004). The relationship between iodine and cognitive development is extensively researched. It is well known today that severe iodine deficiency during pregnancy may cause “cretinism” in children (Forrest, 2004; Zimmermann, 2007, 2009, 2011; Melse-Boonstra and Jaiswal, 2010). The clinical manifestation of cretinism depends on the severity of iodine deficiency; the features may include mental retardation, speech and hearing impairment, upper motor neuron and extrapyramidal lesions (Delong et al., 1985).
Iodine is necessary for the production of thyroid hormones in the body. Thyroid hormones play an important role in neurodevelopment and numerous neurological processes including neuronal cell differentiation, maturation and migration, myelination, neurotransmission, and synaptic plasticity. Qian et al. (Qian, 2005) conducted a meta-analysis on studies from different locations in China where the soil is severely iodine deficient, and found a 12.3 point decrease in the IQ of those children whose mothers lived in iodine deficient areas compared to those living in iodine sufficient locations. The association between mild-moderate maternal iodine deficiency and cognitive development is not yet very clear as compared to severe iodine deficiency.
In conclusion, the above literature suggests that iodine is important for the cognitive development of older children. Furthermore, although iodine supplementation is critical for severely iodine deficient pregnant women, there is no general consensus about the effectiveness of iodine supplementation during pregnancy in countries with mild iodine deficiency.
Multivitamin and Mineral Supplementation
Although it is important to investigate nutrients individually, deficiencies of nutrients rarely occur in isolation, and an inadequate diet typically causes multiple micronutrient deficiencies. In addition, nutrients interact with each other and do not work separately.
A recent systematic review of prenatal maternal micronutrient supplementation and children's cognitive and psychomotor development considered 18 studies, including six multiple-micronutrient supplementation trials. This review found some evidence that multivitamin and mineral supplementation might positively influence certain aspects of brain development in children (Leung et al., 2011). It is currently unknown whether the cognitive development of children of well-nourished mothers from higher income countries would benefit from multiple-micronutrient supplementation.
Breast Feeding
Many of these studies demonstrate significantly positive associations between the two; however, the associations typically diminish or are no longer significant after controlling for confounders including maternal IQ, which is believed to be the strongest predictor of children's intelligence (Rey, 2003; McCann and Ames, 2005; Michaelsen et al., 2009). Furthermore, it remains unclear whether the remaining, diminished associations between breastfeeding and child cognitive development are further confounded by factors that have not been controlled for (Michaelsen et al., 2009).
The debate concerning whether breastfeeding and cognitive development have a positive association appears to continue, but with more advanced neuroimaging technologies now
available, future research may offer greater insights. Nevertheless, as Gökçay (2010) pointed out, breast milk provides the best nutritional intake for infants, regardless of its putative association with cognitive development.
Maternal Malnutrition : MICRONUTRIENTS AND COGNITIVE DEVELOPMENT
Maternal Malnutrition during Pregnancy can cause:
Maternal hemorrhage
Pre term birth
Maternal anemia
Preeclampsia and eclampsia
Postpartum complications
Long term adverse effects on mother and offspring health
fetal and neonatal complication
Cognition and behavior
IUGR
Birth defects
Cretinism
Maternal insulin resistance
Impairment of offspring growth and development
Breakfast
The level of glucose metabolism in children's brains increases from birth until 4 years of age, reaching twice that of the adults' metabolic rate. This rate of glucose metabolism in children remains elevated until 9–10 years of age, before it declines to the adult level by late adolescence (Chugani, 1998). Therefore, regular meals and continuous glucose supply (to
provide the brain with the required glucose for its high metabolism) is more important in children than in adults (Bellisle, 2004). Accordingly, children are more prone to the adverse effect of overnight fasting, and breakfast is a very important meal to provide fuel to the brain in the morning (Bellisle, 2004). A systematic review concluded that having breakfast is beneficial for cognitive function and development, especially in malnourished children.
Conclusions & Future Research
The majority of studies, which have investigated the association between nutrition and cognitive development, have focused on individual micronutrients, including omega-3 fatty acids, vitamin B12, folic acid, zinc, iron, and iodine. The evidence is more consistent from observational studies, which suggest these micronutrients play an important role in the cognitive development of children. However, the results from intervention trials of single nutrients are inconsistent and inconclusive, prompting the need for better controlled and more adequately powered studies in the future. It is plausible that children living in poor countries may encounter more multiple micronutrient deficiencies, as opposed to children living in rich countries who are reasonably well nourished (and where a small deficiency in one nutrient may not result in measurable, long-term change in cognitive outcomes, due to compensation over time). These are important considerations, because nutrients do not act alone; rather, they have in some contexts synergistic and in other contexts antagonistic effects with each other.
Individuals consume combinations of food and poor overall diet can cause multiple macro-and micronutrient deficiencies and imbalances. If an overall healthy diet synergistically enhances cognitive development in children, then public health interventions should focus on the promotion of overall diet quality rather than isolated micronutrients or dietary components consumed by children and adolescents.