Magnesium: An Intervention for Attention Deficit Hyperactivity Disorder

Retraction Note: The article entitled “Magnesium: An Intervention for Attention Deficit Hyperactivity Disorder” has been accepted for publication in the Vitamins & Minerals considering the statements provided in the article as personal opinion of the author which was found not having any conflict or biasness towards anything. As the article was a perspective one, information provided by the author was considered as an opinion to be expressed through publication. Soon after the publication of the paper, we witnessed some serious concerns and many of them argued that the paper is a personal perspective and had not discussed any relevant ethical issue considered under the journal scope. Moreover, the paper is neither innovative nor thought provoking. Publisher took decision to make the article online solely based on the reviewers suggestion which considered the article not but a personal opinion of the author. However, it is found that the article has some unavoidable mistakes and issues, therefore, being retracted from the journal. Vitamins & Minerals Terrazas, Vitam Miner 2017, 6:2 DOI: 10.4172/2376-1318.1000160

Approximately 60% of the US population is deficient in magnesium and 68% do not consume the recommended daily allowance (RDA) for Magnesium see (Table 1) [21,22,29].This is due to low magnesium levels in soil, water filtration, increased amounts of consumed processed foods, foods that block absorption, decreased supplementation, disease states, profuse sweating, and stress [22,23,32].Refining and processing foods, result in the loss of 80-90% of magnesium and the promulgation of the Western Diet has increased the number of people who are deficient in magnesium worldwide [22,29,32].

Assessing magnesium in the body
Evaluating magnesium in the body is challenging and magnesium values are not part of routine blood panels.Normal plasma serum levels are 1.5-1.9mEq/L or 0.75-0.95mmol/L but may not accurately reflect total body stores [21,22,32].An equilibrium is maintained in the blood by resorbing magnesium from the bone stores.Approximately 0.3% of total body magnesium is present in serum with 50-60% in boney stores [22,33].Homeostasis is ensured with resorption from these stores and when serum levels are low [22,23,[33][34][35].When total body magnesium is significantly depleted it may take weeks or years to replenish [32,35].
As serum magnesium levels don't always reflect total body magnesium stores, an easy and accurate method that more closely measures total body magnesium is needed.Several studies have suggested a more appropriate way to measure red blood cell magnesium levels or perform magnesium load testing [22,23,32,33,36].A more recent comparison study looking at serum, red blood cell and hair magnesium measurements found that hair levels are a better surrogate for total body magnesium stores [37].In a further study by El Baza et al. it was shown that using Coupled Mass Spectroscopy (ICP-MS), to measure hair magnesium levels correlated most closely with total body stores.Unfortunately, this test is only offered in limited locations and is not cost effective [38].

Influence of magnesium on learning disabilities and mental health
Magnesium is a crucial mineral and appropriate levels in the body are essential for normal cognitive function and mental health [22,29,39].This is true for all people but may be more so for those who suffer from ADHD.Seventy-two to 96% of those diagnosed with ADHD have been found to be significantly deficient in magnesium [37,38].Studies have shown that in these patients, supplementation with magnesium improves attention and working memory and decreases anxiety, depression and emotional dysregulation [14,17,22,29,[38][39][40][41][42].El Baza et al. has suggested that magnesium deficiency may be at the root of the behavioural manifestations seen in patients with ADHD [38].This may be multifactorial and related to the fact that magnesium's inhibitory role neuromuscular junction [31,38].Magnesium deficiency may also lead to dysfunction of the amygdala, which may increase anxiety and depression and in turn lead to hypothalamic dysregulation and the ability to process information, further decreasing working memory.This is thought to be mediated by magnesium's effect at the level of the N-methyl-D-aspartate (NMDA) receptors [8,22,31,[38][39][40]43].
N-methyl-D-aspartate (NMDA) is a common receptor that has both inhibitory and excitatory function in different regions of the brain [22,39,43].It is also involved in controlling synaptic plasticity, mood, learning and memory.The interplay between different receptors in the brain is mediated by ion fluctuations and low magnesium levels play a role [8,22,42,43].When magnesium stores are low, γ-aminobutyric acid (GABA) receptor function is inhibited and may lead to the behavioural inability to calm one's self efficiently [22,43].This chain of events this thought to cause a decrease in neural plasticity, learning and memory, as well as depression and anxiety [22].Eby notes that 60% of clinical depression is considered treatment resistant and sites the imbalance of the NMDA receptor as a possible cause [29].In addition, NMDA may create an over-excitability in the synaptic transmission and lead to the formation of reactive oxygen species (ROS) to form which may cause neuronal death [22,29,43,44].Mechanisms which inhibit this over-excitability of NMDA receptors may induce neuroprotection [22,44].In traumatic brain injury (TBI), ROS formation is common and in rat studies magnesium supplementation is thought to be neuroprotective and has been shown to improve both cognitive and motor function but these results could not be reproduced in human studies [22,44].
In 1921, magnesium was first used to treat depression [22,41] Jorgensen et al. showed that magnesium restriction led to depression in as little as six weeks [30].Additionally, Ghafari et al. found altered NMDA receptor function not only cause depression but reduced the ability of the amygdala-hypothalamic receptors to receive information and impaired learning and spatial memory.They felt this was mediated by elevated glutamate levels [31].Pochwat et al. found magnesium supplementation alleviated generalized depression and depression from CMS [8].Those with ADHD are in a constant state of CMS which may lead to depression.Through these mechanisms magnesium therapy may be a solution to decrease depression and anxiety and increase learning ability, without the negative side effects of traditional medications and at significantly lower cost.

Implications for practice and research
While stimulant drugs do help reduce some of the symptoms of ADHD, though these drugs may not be targeting one of the main problems which is low magnesium.Stimulant medications excite the prefrontal cortex and increase working memory.This can decrease symptoms of ADHD.These drugs increase other disorders within the body though, some of which may be mediated by magnesium deficiency [7,20].No research had been found on this and therefore this is an area of need.
There are very few studies that assess both behavioural and cognitive function associated with magnesium treatment [38].A large, randomized, controlled study is required to investigate whether magnesium supplementation can decrease the symptoms of ADHD, mitigate the negative behaviours and increase learning.Additionally, investigation is required to determine an accurate, cost effective means to measure magnesium status in the body.Finally, clarification of the dosage and most bioavailable form of magnesium treatment is needed.With any future research, treatment compliance rates should also be measured especially for those with comorbid psychiatric disorders.Magnesium may be a better solution than stimulant drugs to decrease the symptoms of depression and anxiety and increase learning ability, without the negative clinical side effects at significantly lower cost.