Nutrition Effects on Childhood Executive Control

Author(s):
Nathaniel Willis
Naiman A. Khan

Longitudinal studies suggest that greater abilities for cognitive control have long-term benefits for children’s academic and vocational success, as well as quality of life in adulthood. Therefore, lifestyle approaches with the potential to support cognitive control in childhood stand to have long-term implications not only for physical but also for cognitive health. Nutrition plays a fundamental role in brain structure and function and has the potential to influence cognitive abilities [1]. Emerging evidence provides preliminary support for the importance particular nutrients (e.g., water, dietary fibers, carotenoids, and choline) typically studied in the context of physical health but not cognitive function. Understanding the cognitive implications of such nutrients has become increasingly important as the nutrient priorities of individuals expand beyond avoiding deficiencies and increasingly focus on optimization of cognitive function.


This article represents a brief narrative review that aims to highlight knowledge on key nutrients (i.e., water, choline, lutein, and fiber) with the potential to promote childhood cognitive function. Literature on the cognitive influence of overall diet quality suggests that greater adherence to the recommended dietary guidelines of Americans and other composite indices is associated with superior cognitive control among school-age
children [2]. Recent work has even demonstrated this relationship in children as young as 4 years, suggesting that the influence of diet quality on cognitive abilities is evident in early childhood [3]. Similar relationships have been observed between cognitive control abilities and the habitual consumption of key nutrients known to characterize higher quality diets including water, choline, lutein, as well as dietary fiber [4]. It is likely that these nutrients could impact cognitive function via multiple mechanisms, including modulation of the gastrointestinal microbiota, reducing stress and risk for metabolic impairments, as well as providing neuroprotection to enhance sensory perception and/or cognitive processing. However, much of this work has only recently emerged in child populations, and several limitations are worth acknowledging such as the scarcity of randomized, controlled trials as well as the heterogeneity of cognitive tasks employed. Additionally, the specific mechanisms that directly or indirectly link the specific nutrients to cognitive control are unclear and should be a goal of future studies.

Nevertheless, emerging cross-sectional evidence, accompanied with limited data from clinical trials, points to the potential of these key nutrients in supporting cognitive control in children. Certainly, additional research is needed to continue developing the evidence base for dietary patterns and nutrients that preferentially support cognitive control during childhood. This is an important goal given that nutritional recommendations for children’s cognitive function are absent from the US dietary guidelines [5], making the endeavor to develop the evidence base for dietary patterns and nutrients that preferentially cognitive control during childhood all the more important.

References
1. Georgieff MK: Nutrition and the developing brain: nutrient priorities and measurement. Am J Clin Nutr 2007;85:614S–620S
2. Khan NA, Raine LB, Drollette ES, et al: Dietary fiber is positively associated with cognitive control among prepubertal children. J Nutr 2015;145:143–149.
3. Khan NA, Cannavale C, Iwinski S, et al: Visceral adiposity and diet quality are differentially associated with cognitive abilities and early academic skills among preschool age children. Front Pediatr 2020;7:548.
4. Khan NA, Raine LB, Donovan SM, Hillman CH: IV. The cognitive implications of obesity and nutrition in childhood. Monogr Soc Res Child Dev 2014;79:51–71.
5. DeSalvo KB, Olson R, Casavale KO: Dietary guidelines for Americans. JAMA 2016;315:457–458.
 

 

Abstract

Greater abilities for executive control in childhood have long-term benefits for academic and vocational success. Therefore, lifestyle approaches with the potential to support executive control in childhood stand to have long-term implications not only for physical but also for cognitive health. Nutrition plays a fundamental role in brain structure and function. While a considerable amount of literature demonstrates the detrimental effects of deficiencies in essential nutrients, comparatively little is known is about the role of overall diet quality in promoting executive control among children without diagnosed nutrient deficiencies. Emerging evidence provides preliminary support for the importance of key nutrients (e.g., water, dietary fiber, carotenoids, and choline) that contribute to diet quality. This article represents a brief narrative review that aims to highlight the importance of habitual diet quality for executive control in childhood. Additional research is needed to continue developing the evidence base for diet patterns and nutrients that preferentially support executive control during childhood. This is an important goal given that nutritional recommendations for children’s cognitive function are absent from the US dietary guidelines, making the endeavor to develop the evidence base for diet patterns and nutrients that preferentially support executive control during childhood all the more important. 

Introduction

Individuals with greater ability for executive control, also known as executive functions
(i.e., inhibitory control, working memory, and cognitive flexibility), are more likely to have a higher quality of life across several domains of personal and professional success [1]. Given that childhood is an important period for brain growth and development, lifestyle approaches with the potential to promote executive control could have a lasting impact on children’s long-term cognitive health. Specifically, improving diet quality may provide an efficacious target for interventions that aim to positively impact aspects of executive control. Preclinical studies have demonstrated that deficiencies in essential lipids, amino acids, minerals, and vitamins can lead to severe decrements in brain structure and poorer cognitive function [2]. However, while there has been a considerable accumulation of literature demonstrating the detrimental effects of deficiencies in essential nutrients, comparatively little is known is about the role of diet quality in promoting executive control among children without diagnosed nutrient deficiencies. Emerging literature has focused on key nutrients that may play an important role in neural development and physiological health. A comprehensive review of the numerous essential and nonessential nutrients that comprise brain structure and support the myriad of cognitive functions is beyond the scope of any one article. Therefore, this
article is focused on a brief narrative review that aims to highlight the importance of specific nutrients (e.g., water, dietary fiber, carotenoids, and choline), known to reflect habitual diet quality, for executive control in childhood.

Lutein

Carotenoids are a diverse class of orange, yellow, and red lipophilic pigments present in many fruits and vegetables, as well as some animal food sources such as eggs. Some carotenoids contribute to vitamin A formation, serving functions in vision, epithelial cell regeneration, and gene expression [3]. Carotenoids also reduce the risk of chronic diseases such as cancers, cardiovascular diseases, and age-related macular degeneration [4]. Lutein and its isomer zeaxanthin are both examples of non-provitamin A carotenoids known as xanthophylls. These xanthophylls and the lutein metabolite meso-zeaxanthin comprise the macular pigment, playing important roles as blue-light filters and in countering the exceedingly high oxidative stress in the retina [4]. Relative to other carotenoids, lutein disproportionately accumulates across different regions of the infant brain, including the prefrontal cortex and hippocampus, indicating a  particularly important role in the development and function of neural tissue [5]. At molecular level, lutein is uniquely positioned to ameliorate oxidative stress with the presence of terminal hydroxyl groups. The molecule is believed to embed in neural tissue membranes, allowing the terminal polar groups to protect against the oxidation of vulnerable lipids [4]. One of the earliest opportunities to augment lutein status in children is through mother’s milk or fortified infant formula. Preclinical work has shown lutein deposition in the brain of breastfed infant macaques to be up to 5 times higher (depending on the location) than in those fed a carotenoid-supplemented formula, demonstrating the importance of lutein for maternal nutrition [6]. Among human infants,
a double-blind trial revealed that the human milk group had a sixfold higher geometric mean serum lutein than the unfortified and fortified formula groups, further substantiating the higher bioavailability of lutein in human breast milk [7]. On the
other end of the age spectrum, increased macular pigment optical density (MPOD) has long been associated with improved visual performance and has been impactful in delaying the effects of age-related macular degeneration. The retinal mechanisms are multifaceted but widely believed to be twofold: (1) lutein and zeaxanthin absorb and filter short-wave light protecting the macula from damage and (2) improve neurophysiology by potentially reducing myelin oxidation and allowing for more efficient communication among neurons [4]. Further, MPOD is a strong correlate of brain lutein concentration and provides a noninvasive approach to studying lutein effects on brain and cognitive functions. Lutein and zeaxanthin supplementation studies in adults have consistently demonstrated benefits for MPOD and executive control processes in
young as well as older adults [8–10]. Pertinent to the literature in children, MPOD, assessed using a customized heterochromatic flicker photometry approach, can be measured with moderate reliability in preadolescent children as well as adults [11]. Among preadolescent children, MPOD has been positively correlated to subject-specific tests of reading, math, and written language, as well as overall academic achievement [12] and accuracy on a modified flanker task [13], and negatively correlated to task performance (error rate) in a relational memory task [14]. Although intervention trials are lacking in children, the emerging cross-sectional studies in children provide preliminary support for the importance of neural lutein status on executive control, making a compelling case for rigorous experimental approaches in future studies.

Choline

Choline is a nutrient, much like lutein, that exerts a neuroprotective and developmental
function through both structural and functional roles. Choline is required for endogenous synthesis of the neurotransmitter acetylcholine and the membrane components phosphatidylcholine and sphingomyelin [15]. Within
the myelin sheath, phosphatidylcholine is a primary membrane lipid, and choline-
deficient diets have been linked to a reduction in both circulating phosphatidylcholine
and neural processing speed [16]. Additionally, declining cholinergic
neurotransmission and membrane integrity are both processes that have been implicated in degenerative diseases such as Alz heimer disease [15]. While important for neurological health throughout the life cycle, choline may play a particularly important role in development. Myelination begins during the latter stages of gestation, accelerates through the first 2–3 postnatal years, and continues into early adulthood [16]. A recent double-blind, randomized, controlled study observed that third-trimester maternal choline supplementation (930 mg/day) improved infant’s performance on an attention task through the first 15 months of life [17]. This task was previously shown to be predictive of information processing speed and IQ in childhood [17]. Furthermore, there was evidence in the low-intake group indicating that even slight increases in
choline intake during pregnancy may have lasting effects on children [17]. Recent work from our laboratory suggests that the beneficial influence of dietary choline on executive control processes is evident even among young adults [18]. Specifically, dietary choline was associated with more efficient neural processing among a sample of overweight and obese adults, as indicated by a lower peak amplitude of the P300 waveform during incongruent trials of a modified Eriksen flanker task. While this is a cross-sectional finding, it is suggestive of the potential role that choline plays in cognitive health throughout life. Much of the research in dietary or supplement interventions with choline focus on the effects in gestational or geriatric periods – an approach supported by knowledge of the importance of choline in both the structural development of the myelin sheath during pregnancy and the role that abnormal methylation could play in neurodegeneration. However, additional experimental intervention studies are needed to investigate the effects of choline consumption throughout childhood and adolescence as it is unclear whether meeting daily needs for
choline in later childhood provides added benefits for cognitive function.

Water

The human body contains 55–75% water, comprising a significant proportion
of body composition at the tissue and cellular level. Adequate water intake is
crucial to sustaining vital physiological functions, including the transportation
of oxygen, nutrients, and waste products. However, evidence from across the
globe suggests that the majority of children are chronically dehydrated or insufficiently hydrated. In fact, a recent systematic review showed that on average
60 ± 24% of children failed to meet water intake guidelines of their respective
countries [19]. Similarly, recent work from our laboratory has shown that the
ad libitum urine concentration of children is quite low. Children in this study
exhibited a urine osmolality at baseline that was remarkably similar to their
urine osmolality during the water restriction condition (< 500 mL of plain water
per day) [20]. This is concerning and suggests that children may already be undergoing
physiological adaptations to chronic suboptimal hydration. Water restriction induces hypovolemia which affects peripheral blood flow. In mice, 24-h water deprivation disrupts cerebrovascular regulation and induces cognitive deficits [21]. Further, dehydration increases plasma osmolality, encouraging the osmotic transfer of water out of tissues. Studies have shown that dehydration could potentially reduce brain volume as water is extracted from brain cells into the blood with an inevitable compensatory enlargement of the ventricles [21, 22]. Kempton et al. [22] showed ventricular enlargement proportional to body weight loss following an exercise dehydration protocol in adolescents. Further, while the authors found no significant differences in the performance of a Tower of London task based on hydration status, functional MRI showed increased blood flow to the frontal lobe in the dehydrated state, which is indicative of an increased resource demand to reach the same level of performance.

Understanding the implications of insufficient hydration on cognitive function in children is particularly important since children have a higher surface/ mass ratio, which puts them at greater risk of increased loss of body water. Further, children are reliant on caretakers regarding opportunities for drinking water. Findings from our recent 3-condition crossover hydration intervention in children showed that higher water intake was selectively related to improvements in cognitive flexibility and working memory [3]. Specifically, higher working memory cost was observed during the low intake condition (< 500 mL/ day) when compared to the high intake condition (> 2,500 mL/day). These findings were broadly consistent with previous work indicating the benefits of water
consumption for cognitive function in school-age children. Overall, such finding suggest adequate hydration may benefit complex cognitive operations. Given that these aspects of cognitive function underlie academic achievement, it is promising that low-cost lifestyle interventions, such as increasing water intake, may benefit effective functioning throughout the school day. However, much of the literature has focused on the detrimental effects of dehydration for cognitive function. Therefore, additional water intervention studies are needed in children with insufficient habitual hydration to better elucidate the health benefits of improved hydration. 

Dietary Fibers

Dietary fibers are indigestible carbohydrate polymers, which are neither digested
nor absorbed [23]. Increasing dietary fiber has been linked to lowering of a myriad of disease risk factors, including blood pressure and serum cholesterol, while improving glycemia and insulin sensitivity [24] with similar benefits for children as well as adults. Additionally, dietary fibers are subjected to bacterial fermentation [23], impacting the composition of bacterial communities as well as microbial metabolic activities in the gastrointestinal tract. As the gut-microbiota- brain axis incorporates elements of the central, autonomic, and enteric nervous systems, the immune system, and the endocrine system, modulation of the gastrointestinal microbiota by dietary fiber could impact cognitive and brain health via several pathways. Indeed, the microbiome – the term used to refer to the microbial organisms in the gut and their collective genome – has been shown to be cross-sectionally related to human behavior, mental health,
body composition, and cognition [25]. The bacteria in the human gut exist in symbiosis, metabolizing indigestible fibers to produce products that can be further absorbed by the host. These endpoints include short- and branched-chain fatty acids, vitamins and minerals, neurotransmitters (serotonin, GABA, and histamine), and many others in smaller concentration [25, 26]. It is also important to note that the microbial communities in the human gut are directly influenced by diet and can be modulated in the short term by dietary interventions [25].

Modulation of gastrointestinal microbiota by indigestible carbohydrates is evident in early life [27]. Preclinical work has shown a positive impact of non digestible human milk oligosaccharides on hippocampal function and long-term potentiation in rodents [28]. For most mammals, the ingestion of mother’s milk is the first case of oral intake of food, and human milk oligosaccharides are important for fueling the newborn microbiome. There is, however, little evidence as to the impact of the human infant’s microbiome on cognitive development. This is especially challenging due to the fluctuations in gut microbe communities up until around 2 years of age when an infant generally transitions to solid foods [27].

In prepubertal children, total dietary fiber consumption from a 3-day diet record was shown to be positively associated with attentional inhibition assessed using a modified flanker task [29]. Further, insoluble fiber and pectin intakes (two types of dietary fiber that would be particularly available to gut microbiota) were positively correlated with the task condition placing greater demands on inhibitory control. These findings suggest that fiber intake may be influential in the upregulation of cognitive control in childhood. However, this was a cross sectional study that did not include assessment of the gastrointestinal microbiome. Therefore, the potential microbiome-dependent mechanisms by which dietary fiber impacts on cognitive function in preadolescent children warrant further examination.

At the latter end of the life cycle, it is thought that the gastrointestinal microbial
community decreases and interpersonal variability increases [26]. Intervention studies on fiber supplementation are few and have shown mixed results with some studies reporting positive effects on mood, memory, and executive control in adults while others have shown no effect [30]. Focusing specifically on the microbiome, observational studies in elderly patients have revealed correlations between the relative abundance of gut microbes and cognitive performance such that performance was negatively correlated with Enterobacteriaceae and positively correlated with Lactobacillales. Further, recent findings in patients with Alzheimer disease suggest a microbiome characterized by an over presence of gram-negative bacteria [26]. The potential mechanisms of interaction are widespread and include modulation of peripheral neural pathways, vagal nerve stimulation, inhibition of the HPA axis, direct effects on blood-brain barrier permeability, absorption of bacterial toxins, and epigenetic mechanisms [25]. Most relevant to diet and cognition: short-chain fatty acids, specifically butyrate, play a direct role in blood-brain barrier permeability, epigenetic modulation of gene transcription in the brain, and the promotion of neurotransmitter and hormone synthesis, as well as the absorption of bacterial toxin, which promotes the production
of proinflammatory cytokines resulting in neuroinflammation, apoptosis, and amyloid deposition [25, 26]. These pathways are thought to work in opposition such that a healthy diet may foster a healthier microbial ratio and encourage protective effects via butyrate production – serving to inhibit toxin absorption, reduce systemic and neural inflammation, and delay neurodegeneration. Gut microbiota is relatively transient given its susceptibility to dietary variations, illness, infections, and pharmacotherapies. We are still at the early stages of understanding exact mechanisms, but the work to elucidate the role of butyrate in ameliorating neurodegeneration is promising [26]. Furthermore, there is compelling evidence supporting the involvement of the gut-brain axis across the life cycle. Dietary modulation of the microbiome using dietary fiber may be involved in influencing the development of the immune system and metabolic
pathways in infancy, while also contributing to cognitive function in childhood and protecting against neurodegeneration in later life.

Conclusion
Children are in a period of development to establish habits that can be predictive of future health and are poised to optimize potential for growth. Nutritional intake at this stage is a potent moderator of health. Furthermore, some nutrients discussed here (i.e., carotenoids, choline, water, and dietary fiber) could play a major role in the proper development of neural tissue, the amelioration of cognitive decline, and efficient regulation of cognitive resources. Whereas there is potential of these nutrients to promote executive control, the literature has several limitations. First, a limited number of randomized, controlled trials and a large heterogeneity of cognitive tasks employed present challenges in terms of establishing causality and gaining insights into the specificity of the nutrient effects. Further, the potential mechanisms are largely untested, and future work should strive to elucidate these pathways. Finally, an evidence base needs to be established for specific dietary patterns and nutrients that affect childhood development. This is of special importance as nutritional recommendations for cognitive health of children are absent from the US dietary guidelines.

Conflict of Interest Statement
The authors declare no conflicts of interest.

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