Influenced by our environment, we are constantly being exposed to elements, whether nutritional or toxic. They are a big contribution to the yin yang dualism of health and disease. 

With heavy metals, contamination is so extensive nowadays that it is no longer a question of whether exposure took place, but rather what the level of exposure was or continues to be.

Toxicity from low levels of exposure can lead to a wide array of neurological disturbances and can be much more insidious in presentation than acute toxicity, which is, in contrast, rather obvious in its presentation. While the effects of heavy metal exposure may be superficially innocuous at first, over time the body distributes and stores heavy metals (“bioaccumulation”), and neurotoxic effects become inevitable. 

One protein at a time, these minuscule toxic monsters hijack our brain proteins, displacing the elements that we really need for proper neuronal function, and replacing them with ones that permanently propagate oxidative stress—meanwhile stripping the body of important defensive mechanisms. Living with a haunting legacy of chronic exposure to arsenic, bromine, cadmium, and mercury from industrial pollution can have grave consequences, masked by seemingly unrelated symptoms of depression, anxiety, insomnia, headaches, memory problems, aggression, developmental issues, and many others. 

In other words, exposure to moderate contamination levels is implicated in cognitive and neurological deficits associated with poorer mental health quality, that can symptomatically be difficult to decipher.

On the flip side, diet is becoming increasingly recognized as a potentially modifiable factor that is inherently intertwined with human cognition, behavior and emotions.  Insufficient dietary intake of certain minerals has been associated with neurocognitive deficits, especially in vulnerable populations like children, whose nervous systems continue to develop for many years before reaching maturity [1].

Starting this month, ZRT will be offering an option to test elements together with neurotransmitters. This powerful combination offers an opportunity to confirm a clinical suspicion and glean a deeper understanding of how a patient's micronutrient or perhaps toxic element exposure is contributing to a shifting mood balance. Below is a brief synopsis of ZRT's elements test in dried urine, offering a literature-based rationale for their importance for the health of the nervous system.

Iodine

As an essential component of the active thyroid hormone triiodothyronine (T3), a deficiency of iodine impacts thyroid hormone synthesis and severely compromises thyroid function throughout the body. Adequate thyroid function is required for proper neurological development and iodine’s role in brain development and growth has long been recognized [2]. Children born to mothers residing in even moderately iodine-deficient areas develop behavioral, psychoneurological and intellectual difficulties [1] [3]. 

Bromine

In high amounts through exposure to environmental pollutants (e.g., brominated flame retardants), bromine can induce neurotoxicity by inappropriately modifying glycine, glutamate, and GABA signaling.  Additionally, excessive bromine levels can interfere with iodine uptake into the thyroid gland, thereby preventing thyroid hormone synthesis.  Neurological abnormalities from excessive bromine exposure can include detrimental changes in cognition and mood [4].

Selenium

Anti-inflammatory and neuroprotective in nature, selenium is an essential trace element that combats mercury and cadmium toxicity. Selenium is vital for proper functioning of several selenoproteins involved in antioxidant defenses in the brain and the rest of the body.  Selenoproteins play an essential role in the activation of thyroid hormone and in glutathione production [5], those biochemical systems, dysregulation of which is associated with neuropsychiatric manifestations.  

There appears to be an optimal selenium range in relation to depressive symptoms.  Studies show that both too low and too high selenium levels are linked with oxidative and inflammatory pathways, offering a potential mechanistic explanation for the link between selenium levels and depression [6]. 

Specifically with regard to neurotransmission, selenium displays selective inhibition of monoamine oxidase A (MAO A), an enzyme that breaks down serotonin (and dopamine to a certain extent) [7]. Selectively inhibiting MAO A would have a serotonin-elevating effect, and for patients afflicted with mood issues rooted in serotonin deficiency, increased serotonin may be key to feeling better. Furthermore, in dopaminergic neurons, which are particularly vulnerable to oxidative stress, selenium plays a protective role and prevents neurodegeneration [8].

Arsenic

Arsenic disrupts serotonin and dopamine metabolism, thus compromising neuronal health. Even at low-level exposure, arsenic predisposes to cognitive dysfunction and susceptibility to mood disorders. Additionally, arsenic can induce neuronal death by stimulating processes implicated in Alzheimer’s disease [9] [10] [11].

Cadmium

Cadmium upsets the delicate balance between glycine, glutamate, and GABA to negatively impact memory and cognition by being especially destructive to white matter in the brain. Cadmium exposure has detrimental effects on neurocognitive development in children, and is associated with learning disabilities, lower IQ, attention deficits, behavioral problems, and hearing loss [10] [12] [13] [14] [15].

Mercury

“Mad as a hatter” cases of mercury poisoning are historically-documented examples of gold and silver mining casualties [16]. Mercury is well-known as a potent neurotoxin, which increases oxidative stress by permanently inhibiting glutathione function, thereby stripping neurons of their defensive mechanisms. Mercury radically skews neurotransmission – it stimulates excitatory signaling (e.g., glutamate, dopamine) and decreases inhibitory signaling (e.g., GABA). Mercury exposure can cause a variety of neurological symptoms, including irritability, mood swings, headaches, concentration and memory difficulties, and sleep disturbances [5] [17] [18].

Lithium

Lithium, in trace amounts, has been shown to improve mood and slow the progression of dementia. Overall, lithium’s effects on the brain are neuroprotective, antioxidant and regenerative. Lithium can modulate monoamine oxidase activity to appropriately break down serotonin, dopamine, and phenethylamine [19] [20]. 

Laboratory testing in addition to exposure history, clinical signs, and symptoms must all be taken into account during diagnosis of heavy metal toxicity or mineral nutrient deficiency. The body is an intricate system of checks and balances shaped by nutritional elements or heavy metals engaging one another and other molecules in the body in a complex biochemical waltz to control many body processes. 

Monitoring exposure to heavy metals alerts to insidious exposure before too much bioaccumulation can occur, helping to prevent more severe damage. And testing for dietary deficiencies of the nutrients allows the opportunity to rectify these by supplementation or dietary changes, while preventing excessive intake that can also have undesired effects. Combining neurotransmitters and elements testing gives a clearer picture of how elements can be contributing to neurotransmitter imbalances or mood disorders.

Related Resources

• Blog: Finally Focused - Mineral Imbalances & ADHD 
• Blog: Mitochondria & Mental Health
• Blog: Neurotransmitters, Mood & the Perception of Stress

References 

[1] I. Velasco, S.C. Bath, M.P. Rayman, Iodine as Essential Nutrient during the First 1000 Days of Life, Nutrients 10(3) (2018).

[2] S. Henjum, I. Aakre, A.M. Lilleengen, L. Garnweidner-Holme, S. Borthne, Z. Pajalic, E. Blix, E.L.F. Gjengedal, A.L. Brantsaeter, Suboptimal Iodine Status among Pregnant Women in the Oslo Area, Norway, Nutrients 10(3) (2018).

[3] F. Vermiglio, V.P. Lo Presti, M. Moleti, M. Sidoti, G. Tortorella, G. Scaffidi, M.G. Castagna, F. Mattina, M.A. Violi, A. Crisa, A. Artemisia, F. Trimarchi, Attention deficit and hyperactivity disorders in the offspring of mothers exposed to mild-moderate iodine deficiency: a possible novel iodine deficiency disorder in developed countries, J Clin Endocrinol Metab 89(12) (2004) 6054-60.

[4] M.M. Dingemans, M. van den Berg, R.H. Westerink, Neurotoxicity of brominated flame retardants: (in)direct effects of parent and hydroxylated polybrominated diphenyl ethers on the (developing) nervous system, Environ Health Perspect 119(7) (2011) 900-7.

[5] H.A. Spiller, Rethinking mercury: the role of selenium in the pathophysiology of mercury toxicity, Clin Toxicol (Phila)  (2017) 1-14.

[6] J. Wang, P. Um, B.A. Dickerman, J. Liu, Zinc, Magnesium, Selenium and Depression: A Review of the Evidence, Potential Mechanisms and Implications, Nutrients 10(5) (2018).

[7] C.A. Bruning, M. Prigol, J.A. Roehrs, C.W. Nogueira, G. Zeni, Involvement of the serotonergic system in the anxiolytic-like effect caused by m-trifluoromethyl-diphenyl diselenide in mice, Behav Brain Res 205(2) (2009) 511-7.

[8] N.D. Solovyev, Importance of selenium and selenoprotein for brain function: From antioxidant protection to neuronal signalling, J Inorg Biochem 153 (2015) 1-12.

[9] Y.C. Lin, C.T. Su, H.S. Shiue, W.J. Chen, Y.H. Chen, C.S. Choy, H.Y. Chiou, B.C. Han, Y.M. Hsueh, The Methylation Capacity of Arsenic and Insulin Resistance are Associated with Psychological Characteristics in Children and Adolescents, Sci Rep 7(1) (2017) 3094.

[10] V. Karri, M. Schuhmacher, V. Kumar, Heavy metals (Pb, Cd, As and MeHg) as risk factors for cognitive dysfunction: A general review of metal mixture mechanism in brain, Environ Toxicol Pharmacol 48 (2016) 203-213.

[11] L.L. Wu, W. Gong, S.P. Shen, Z.H. Wang, J.X. Yao, J. Wang, J. Yu, R. Gao, G. Wu, Multiple metal exposures and their correlation with monoamine neurotransmitter metabolism in Chinese electroplating workers, Chemosphere 182 (2017) 745-752.

[12] C. Marchetti, Interaction of metal ions with neurotransmitter receptors and potential role in neurodiseases, Biometals 27(6) (2014) 1097-113.

[13] M. Mendez-Armenta, C. Rios, Cadmium neurotoxicity, Environ Toxicol Pharmacol 23(3) (2007) 350-8.

[14] K. Gustin, F. Tofail, M. Vahter, M. Kippler, Cadmium exposure and cognitive abilities and behavior at 10years of age: A prospective cohort study, Environ Int 113 (2018) 259-268.

[15] Y. Liu, X. Huo, L. Xu, X. Wei, W. Wu, X. Wu, X. Xu, Hearing loss in children with e-waste lead and cadmium exposure, Sci Total Environ 624 (2018) 621-627.

[16] K. Schofield, The Metal Neurotoxins: An Important Role in Current Human Neural Epidemics?, Int J Environ Res Public Health 14(12) (2017).

[17] S. Caito, M. Aschner, Neurotoxicity of metals, Handb Clin Neurol 131 (2015) 169-89.

[18] F. Woimant, J.M. Trocello, Disorders of heavy metals, Handb Clin Neurol 120 (2014) 851-64.

[19] M.A. Nunes, T.A. Viel, H.S. Buck, Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimer's disease, Curr Alzheimer Res 10(1) (2013) 104-7.

[20] G.N. Schrauzer, E. de Vroey, Effects of nutritional lithium supplementation on mood. A placebo-controlled study with former drug users, Biol Trace Elem Res 40(1) (1994) 89-101.