Review assesses how trace mineral optimisation can mitigate anxiety disorder

Anxiety disorder is characterised by excessive fear or avoidance of perceived threats that can be persistent and debilitating. According to the World Health Organization​, 301 million people were living with an anxiety disorder in 2019, including 58 million children and adolescents. 

Nutritional psychiatry is an emerging discipline​ that involves the practice of using food and nutritional supplements to improve mood disorders in conjunction with conventional treatments, showing promise for enhanced methods to treat anxiety.

There is growing evidence​ that diet interventions show potential for the prevention or treatment of various mental health disorders. Specific nutrients play important roles in maintaining brain health and central nervous system homeostasis. For example, polyunsaturated omega-3 fatty acids, such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have known beneficial effects on brain structure and function.

Monounsaturated fatty acids have been shown to modulate brain activity. Quality proteins provide amino acids such as tryptophan and tyrosine for the synthesis of key neurotransmitters, including serotonin, melatonin, and dopamine. High fiber carbohydrates provide prebiotics for a healthy microbiome by stimulating the synthesis of short chain fatty acids for immune system protection and anti-inflammatory effects with a downstream effect on mood.

Vitamins, minerals, and bioactive compounds have also been shown​ to improve brain health through improved cognition, increased antioxidant activity, and protection against neurodegeneration.

Key micronutrients regulate stress responses through their role in the production and metabolism of neurotransmitters​ and are involved in the synthesis of omega-3 fatty acids that are associated with a lower risk of anxiety. Additionally, certain dietary nutrients have an impact on neuronal membrane structure and neurotransmitter release. 

Hypothesised biological mechanisms​ by which food, specific nutrients, and nutraceuticals impact mental health include inflammation, oxidative stress, brain plasticity effects, mitochondrial dysfunction, and neurotransmitter metabolism.

Broad spectrum micronutrient interventions have shown promise for reducing symptoms associated with stress and anxiety​. Specific mineral treatments for the relief of anxiety have also been investigated​.

Narrative review

The current literature review, published in 'Dietetics', focused on the influence of essential trace minerals zinc, copper, iron, and selenium on anxiety treatment and prevention based on the latest peer-reviewed scientific evidence.

Studies were chosen by searching PubMed for articles published between 1990–2022, as well as Google Scholar, ProQuest, and JSTOR.

The authors conclude that there is evidence to suggest an inverse association between anxiety and dietary trace minerals zinc, iron, and selenium.

Although there is some evidence that a deficiency in copper may be correlated with anxiety, there is more evidence to suggest that copper overload has a greater influence on the development of anxiety, they say.

Ultimately, they state that more research is needed to understand the specific neurobiological mechanisms involved but there are promising findings regarding the importance of optimising trace mineral homeostasis for the mitigation of anxiety disorders and preservation of mental health.

Selenium

The report concludes that there appears to be a positive correlation between dietary selenium intake or selenium-based treatments and reduced anxiety.

"To the best of our knowledge, there was only one study that found no association, and no evidence to suggest that dietary selenium or high selenium serum levels can lead to increased anxiety."

The authors postulate that it is possible that the beneficial influence of selenium on anxiety symptoms results from a combination of reduced oxidative stress, improved regulation of thyroid function, and optimized function of selenoproteins.

Several clinical and preclinical studies found increased antioxidant capacity after selenium supplementation, suggesting that the anxiolytic effect of selenium is mainly attributed to its protective function against oxidative stress.

However they note that one limitation when drawing conclusions regarding selenium status and anxiety is the lack of research in humans that have anxiety disorder as their primary health concern. Several of the studies reviewed were conducted in patients with comorbidities, such as chronic renal failure, polycystic ovary syndrome, and euthyroid nodular goiter.

Th authors therefore state that further investigation of the impact of dietary selenium on patients with anxiety disorder alone would help clarify the relationship between this trace element and mental health.

Another limitation is that animal studies have mainly involved selenium derivatives such as 4-PSQ and 6-((4-fluorophenyl) selanyl)-9H-purine rather than dietary selenium. The team suggest future research in animals could include selenium-enriched or selenium-deficient diets compared to a control diet to provide a more translatable evaluation of the impact of dietary selenium on anxiety-like behaviour.

Iron

Likewise, the review concludes that the current evidence demonstrates that iron status has an impact on anxiety as revealed through both human and animal models.

However, they note that although many studies have been published on the topic of IDA and anxiety or iron supplementation for the attenuation of anxiety, there are limited studies focused on the relationship between dietary iron and anxiety disorder.

"Future investigations could include iron-fortified diet interventions for iron-deficient individuals for the potential improvement of anxiety symptoms," they suggest, adding: "Investigating gender differences in effectiveness of iron supplementation or iron-fortified diets for the mitigation of anxiety would be valuable.

"These gaps in the scientific literature present an opportunity for future research to better understand the relationship between dietary or supplemental iron and anxiety disorder, providing an opportunity for safe, alternative treatment options or adjunctive diet-based treatments for the improvement of mental health."

Zinc

The authors also conclude there is a potential relationship between zinc and anxiety.

"Most of the evidence shows that there is an association between zinc deficiency and anxiety, and that zinc repletion may alleviate the symptoms," the report states.

"However, other studies show that there is no connection... Due to variations in genetics, age, sex, and study design, it is not surprising that there are conflicting results."

They say more research is needed to determine the cause and effect relationship and to determine the proper dose and form of zinc for clinical supplementation.

"More investigation is needed to understand how zinc dysregulation impacts different brain regions, such as the amygdala and hippocampus, how zinc supplementation influences HGF levels and other neurotrophic factors, and how zinc-dependent antioxidants may play a role in the development of anxiety disorders," the report adds.

Copper

Regarding copper's impact on anxiety, the authors say current evidence suggests that copper overload is a more substantial concern than copper deficiency as it relates to anxiety disorders.

They state: "There is limited research that specifically quantifies dietary copper intake and the subsequent impact on anxiety, thus providing an opportunity for continued research to understand if there is a significant relationship between this trace element and anxiety disorders."

Source: Dietetics​

https://doi.org/10.3390/dietetics2010008​

"Trace Minerals and Anxiety: A Review of Zinc, Copper, Iron, and Selenium"​

Authors: Totten, M.S.; Davenport, T.S.; Edwards, L.F.; Howell, J.M.