Paediatric Brain Health and Cognitive Support

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young brainThe Evidence Backing Nutritional Tools That Support Pediatric Brain Health and a Healthy Attention Span

Because of the pandemic, many parents have had substantially more one-on-one time with their children. And it has not been limited to the typical activities of being Mum and Dad, suddenly, there is the job of teaching as well. Getting kids to do their homework and stay on task seemed like a struggle back in 2019 but took on a whole new meaning in 2020.

Herein, we look at key nutrients that support paediatric brain health and, with this, a healthy attention span.

Paediatric Nutritional Deficiencies

Nutrient deficiencies are prevalent in children worldwide, with iron, vitamin B6, vitamin D, folate, iodine, and zinc deficiencies being among the most common in developed regions.[1],[2],[3] A 2017 review of nutritional deficiencies in U.S. children reported that, in addition to these deficiencies, vitamins A, C, and E; calcium; and magnesium are also under consumed.[4] Though all children are at risk, the incidence of nutritional deficiency is especially high in children from low-income backgrounds and regions.

These nutritional deficiencies can lead to a host of health problems, including anaemia, poor wound healing,[5] developmental delays,[6] increased susceptibility to infectious diseases,[7] compromised bone growth,[8] and overall poorer health outcomes in adulthood.[9] Suboptimal nutrition also predisposes children to neurocognitive deficits like attention-deficit/hyperactivity disorder (ADHD).[10],[11]

Iron deficiency is particularly common in children with ADHD. In one study, done in Paris, France, serum ferritin levels were shown to be abnormally low in 84% of children with ADHD compared to only 18% of controls.[12] Additionally, low ferritin levels were correlated with more severe ADHD symptoms and greater cognitive deficits. A 2017 meta-analysis further demonstrated an association between low ferritin levels and ADHD.[13] Low levels of iron in certain regions of the brain is also associated with poor cognitive performance in otherwise healthy youths.[14]

Iodine is another nutrient that is important for normal cognitive development. With many individuals opting for more natural salts (rather than iodized table salt) or reducing the intake of salt altogether, iodine deficiency is resurging in developed countries. Unfortunately, many of the problems related to iodine deficiency in utero and infancy affect brain development.[15] Thus, when cognitive or behavioural issues show up later in life, studies suggest they will not be fully remediated with iodine supplementation. Because of this, it is very important to ensure maternal iodine adequacy during pregnancy and breastfeeding.[16]

Inadequate iodine intake in childhood and adolescence can also lead to impaired cognitive function.[17] A 2016 study found 71.9% of 89 children with ADHD to be iodine deficient, and further revealed a significant association between low iodine levels and hyperactivity.[18] An increased incidence of ADHD and lower intelligence quotient scores also has been shown in the offspring of mothers at a risk of iodine deficiency during pregnancy.[19]

Lower levels of vitamin D have been shown in children with ADHD as well.[20] Again, a recent (2018) meta-analysis also points toward this association, finding that a lower vitamin D status is associated with an increased likelihood of ADHD.[21]

Magnesium and zinc deficiencies have also been shown in children with ADHD, and are correlated with hyperactivity, inattention, and impulsivity.[22],[23],[24] Multiple meta-analyses show a relationship between low levels of these minerals and ADHD as well.[25],[26],[27]

In addition to these many vitamins and minerals, numerous studies have shown lower blood levels of omega-3 fatty acids and a heightened amount of oxidative stress in individuals with ADHD.[28],[29] Healthy children who have low levels of docosahexaenoic acid (DHA) have been shown to have below-average reading ability, diminished working memory performance, and increased oppositional behavior and emotional lability.[30]

Nutrients with Therapeutic Evidence

Although a nutritional deficiency state should be remedied for a multitude of reasons, correcting it does not necessarily mean it will resolve the characteristic behaviors of ADHD or improve cognitive function in general. Additionally, depending on the deficiency’s duration and the developmental stage during which it occurred, certain changes may not be reversible. Thus, we must also consider what research supports each of these as a therapeutic.

Iron

In children, the Recommended Dietary Allowance (RDA) of iron varies by age, ranging from 7 to 11 mg per day. Higher doses are often used to resolve iron deficiency, but before this course of therapy is embarked upon, testing must be done to assess for deficiency. In children with ADHD and low ferritin levels (25.9 +/- 9.2 ng/mL), supplementation with 5 mg/kg/day of an iron preparation for 30 days improved ferritin status to 44.6 +/- 18 ng/mL and significantly improved Conners’ Rating Scale (CRS) scores given by parents; however, scores given by the teacher were not improved.[31] In another study, non-anaemic children with ADHD and serum ferritin levels lower than 30 ng/mL were treated with 80 mg/day of ferrous sulfate (20% elemental iron) or placebo for 12 weeks.[32] Although there were improvements in both the parent and teacher CRS scores, improvements were not significant (P = 0.055 and 0.076, respectively). The small size of this study (N = 23) likely was a factor in the lack of significant findings.

In non-anaemic adolescent girls with iron deficiency, supplementation of 650 mg of ferrous sulfate twice weekly for eight weeks significantly improved test scores related to verbal learning and memory.[33] Other studies also point to some improvements in cognitive function or psychomotor development with iron supplementation.[34],[35],[36]

Iodine

The majority of studies investigating the impact of iodine supplementation on pediatric cognitive function look at iodine-repletion programs in iodine-deficient areas as opposed to routine, daily intake of a specifically prescribed amount of iodine.[37] That said, there are some studies looking at iodine as a monotherapy or in combination with other nutrients that are commonly associated with deficiencies.

In one such study of iodine-deficient youth, repletion of iodine and increased urinary iodine levels contributed to a significant improvement in mental performance after roughly a one-year period.[38] In moderately iodine-deficient children between 10 and 12 years of age, a single 400 mg bolus of oral iodine significantly improved performance scores at 24 weeks (versus placebo) related to information processing, fine motor skills, and visual problem solving.[39] In another, similar setting, moderately iodine-deficient children (six to eight years in age) given a single 490 mg dose of oral iodized oil were observed to have improvements one year later in fluid intelligence, perceptual skills, and hand-eye coordination.[40] Finally, in a study where children’s school lunches were supplemented with a seasoning powder containing 5 mg iron, 5 mg zinc, 50 μg iodine, and 270 μg vitamin A, there was an improvement in visual recall, along with a reduction in symptoms of upper respiratory tract infection and diarrhea, at 31 weeks.[41]

Vitamin D

Multiple studies have shown a positive impact of regular vitamin D supplementation on behavioural symptoms and cognitive function in children with ADHD. Although four of every 10 toddlers and children are deficient in vitamin D,[42] a deficiency state should be documented prior to supplementation of vitamin D that exceeds the RDA, which is 600 IU/day for children ranging from one to 17 years of age.[43]

In vitamin D–deficient children with ADHD, supplementation of 3000 IU of vitamin D3 daily for 12 weeks (in addition to methylphenidate (Ritalin) treatment) significantly improved cognitive function scores in the domains of conceptual level, inattention, hyperactivity, and impulsivity compared to baseline, while scores in these categories did not significantly improve in children receiving methylphenidate with placebo.[44] In a similar study, children with ADHD on a stable dose of methylphenidate were assigned to placebo or 50,000 IU of vitamin D3 orally each week for six weeks.[45] Demonstration of vitamin D deficiency was not required for inclusion in this study and of the participants, and 37, 42.7, and 19.8% were, respectively, shown to be vitamin D sufficient, insufficient, or deficient. In children with vitamin D insufficiency, parent CRS total and subscale scores were significantly improved compared to children in the placebo group. Compared to baseline, all CRS scores were significantly improved in the group receiving vitamin D while they were not in the placebo group. For the vitamin D group as a whole, CRS inattention subscores were also significantly improved compared to placebo.

Additional studies have shown improvements with vitamin D supplementation as an adjunctive to methylphenidate and in combination with daily supplemental magnesium.[46],[47]

Magnesium and Zinc

Magnesium and zinc are often underconsumed by children—particularly picky eaters or those on a restricted diet. Magnesium is probably the mineral we look to most often for “turning the circuits down”; e.g., it has therapeutic usefulness in adults for reducing anxiety, blood pressure, headaches, and muscle twitches, and it promotes relaxation and healthy sleep.[48],[49] We see similar effects in children: multiple studies have shown including 200 mg of magnesium daily in the therapeutic regime for children with ADHD improves outcomes, decreasing hyperactivity and impulsivity and improving cognitive function.[50],[51] The combination of magnesium with vitamin B6 (6 mg/kg/d and 0.6 mg/kg/d, respectively) has also been shown to be effective, improving hyperactivity, aggressiveness, and attention at school.[52]

Zinc deficiency also can be a factor in mood disorders such as anxiety and depression.[53] One consideration with zinc as a therapy is that if higher doses are taken for a prolonged period, it should be balanced at roughly a 10:1 ratio with copper.[54]

In one study, unmedicated children with ADHD were randomised to receive 150 mg of zinc sulfate (providing 40 mg of elemental zinc) or placebo for a period of 12 weeks.[55] At the end of the study period, children receiving zinc had significant improvements in hyperactive, impulsive, and impaired socialisation symptoms compared to the placebo group. Improvements were greatest in children that were older, had a higher body mass index, and/or lower pretreatment zinc or free fatty acid levels. A shorter, six-week study considered a lower, 15 mg daily dose of elemental zinc (55 mg of zinc sulfate) or placebo as an adjunctive to methylphenidate.[56] Although both groups saw improvements, as they were initially treatment naïve, significantly greater improvements in both parent and teacher scores of ADHD severity were reported in the children receiving zinc compared to placebo.

Omega-3 Fatty Acids

In addition to these essential vitamins and minerals that have systemic implications when there is deficiency, the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are essentially important to the health of every cell in the body. They have importance for the fatty tissues of the brain where they are found at high levels and impact not only inflammation and cellular membrane function but also neurotransmission.[57],[58],[59]

By far, the greatest amount of clinical studies on nutritional interventions in children with ADHD consider the use of omega-3 fatty acids. Omega-3 supplements, typically sourced from fish such as salmon, sardines, anchovies, or mackerel, have a high safety profile in individuals of all ages.[60],[61]

Numerous systemic reviews and meta-analyses have looked at the impact of omega-3s on the cognitive and behavioral performance of children with ADHD. A 2018 publication reviewing randomised, controlled trials found that omega-3 supplementation significantly improved clinical symptom scores and cognitive measures associated with attention in youths with ADHD.[62] A larger, 2015 review that also included healthy, typically developing youth found that omega-3 supplementation improved short-term memory in those with low omega-3 status.[63] An additional review found improved literacy, attention, and parent-rated behavior to be associated with increased blood levels of DHA + EPA.[64] Doses of the essential fatty acids in these studies were typically 250 to 500 mg/day for several weeks to months, although some were as high as 1,300 mg/day.

Although not all studies have shown better outcomes with omega-3s as an adjunctive to methylphenidate (Ritalin), some have. Additionally, when omega-3s were used in combination with methylphenidate, a lower dose of the medication was needed to achieve the same level of clinical improvement as those using the medication alone.[65] Despite these mixed findings, given omega-3 fatty acids’ high level of tolerability and greater safety, they are important to consider, particularly in children and adolescents with low levels of dietary intake.

Antioxidants

Numerous studies have shown an increased level of oxidative stress in children, adolescents, and adults with ADHD.[66],[67],[68],[69] Neurotransmitter imbalance,[70] lower levels of antioxidant-related enzymes,68,[71] lifestyle choices, and dietary deficiencies of substances such as zinc, vitamin D, and the omega-3 fatty acids (which also act as antioxidants and anti-inflammatories) may predispose one for higher levels of oxidative stress.[72] In addition to the antioxidants that have already been discussed, two botanical products with high antioxidant potential that have been studied in ADHD are French maritime pine bark (Pinus pinaster) extract and saffron (Crocus sativus).

A source of antioxidant compounds including phenolic acids and procyanidins,[73] French maritime pine bark (FMPB) extract has been investigated in multiple clinical studies for its impact on individuals with ADHD. In children, the typical dose of FMPB extract is 1 mg/kg/day. At this dose, after supplementation for a period of one month, treatment with FMPB was shown to normalise antioxidant status and urinary catecholamine concentration,[74],[75] reduce DNA damage,[76] and improve scores related to hyperactivity, attention, concentration, and visual-motor coordination in children with ADHD.[77] A study evaluating the compound against the standard pharmaceutical treatment for ADHD is ongoing.[78]

Saffron also is a source of many antioxidant compounds including the carotenoids crocin, crocetin, safranal, and picrocrocin,[79],[80] and has multiple clinical studies in pediatric populations. The active constituents found in saffron have been shown to interact with the GABAergic system and modulate levels of serotonin, dopamine, and norepinephrine.[81],[82],[83] In addition to positively impacting anxiety and depression in adolescent youth,[84] benefits have been seen with saffron in paediatrics with ADHD.[85]

Compared to methylphenidate, treatment with saffron (dosed at 20 mg/day for children <30 kg and 30 mg/day for those >30 kg) had comparable effects. By week three and at the end of the six-week study, in both groups parental and teacher symptom scores were significantly improved from baseline, and with no significant difference between groups. Marked improvement (defined as a decrease of more than 50% from baseline) was seen in more than 80% of study participants in both groups, as assessed by Parent ADHD Rating Scale scores. Side effects associated with treatment were mild and tolerable, with no significant difference between groups, although they were seen more frequently in those taking methylphenidate.

A Comprehensive Approach

Typically, the best way to ensure that nutritional needs are being met in children, especially picky eaters, is with a quality multivitamin and mineral supplement. A 2017 meta-analysis supports this, concluding, “Eight of ten trials assessing fluid intelligence reported significant positive effects of micronutrient supplementation among micronutrient-deficient children, especially those who were iron-deficient or iodine-deficient at baseline.”[86] In times of additional life challenges, it is also important to note that increased intake of many of these nutrients has a positive effect on mental health, improving depression, anxiety, and related behaviors.[87],[88],[89],[90] Beyond this, the additional nutrients with clinical research should be considered, often starting with omega-3 fatty acids due to the high level of evidence of their therapeutic value.

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