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Heavy metals can cause health problems if low vitamin D (depression in this study) – Nov 2024

Vitamin D deficiency may exacerbate the role of metal exposure in depression: A cross-sectional analysis of NHANES data from 2007 to 2018

J. of Affective Disorders Vol. 365 , 15 Nov 2024, Pages 265-275 https://doi.org/10.1016/j.jad.2024.08.004

Highlights

  • The study evaluated the correlation between single metal and its mixture exposure and depression and vitamin D deficiency.
  • Multiple models were used to analyze the correlation between metal exposure and depression and vitamin D deficiency.
  • Vitamin D deficiency may aggravate depression caused by metal exposure.

People are paying more and more attention to the effects of environmental factors such as heavy metals on depression, and heavy metals may destroy the homeostasis of vitamin D in the body by affecting human metabolism, and the lack of vitamin D will increase the risk of depression. There are few studies on vitamin D deficiency in depression caused by heavy metals, and it is not deep enough. Therefore, this study used logistic regression, restricted cubic spline curve, weighted quantile and Quantile g-computation model to analyze the effects of heavy metal exposure alone and in combination on vitamin D and depression, as well as the potential role of vitamin D deficiency in the process of heavy metal-induced depression. The results showed that cadmium exposure alone or in combination increased the risk of depression (P < 0.05). When Cd increased by 1 unit, the risk of depressive symptoms increased by 1.178 units. Arsenic and its compounds and lead affected vitamin D levels in the body and contributed the second highest or highest weight in the mixture (P < 0.05). It is worth noting that after grouping according to vitamin D deficiency, compared with the normal group, the mixed exposure of heavy metals in the vitamin D deficiency group had more types of metals related to depression and contributed more weight (P < 0.05). This study found that single metal or multi-metal mixed exposure is associated with depression. Vitamin D deficiency may increase the risk of depression. Vitamin D may be a potential factor in the treatment of depression caused by metal, and the specific mechanism of action needs further study.

Introduction
According to the World Health Organization (WHO), approximately 5 % of adults worldwide experience depression (Indirli et al., 2023). Depression is a common psychiatric disorder that is characterized by prolonged low mood and diminished interest. Currently, it is a global health concern with profound impacts on individuals' physical and mental well-being (Moussavi et al., 2007). Studies have shown that depression is affected by various social, genetic, psychological, and environmental factors. However, the intricacy of its components has hindered the development of an efficient treatment for depression (Tian et al., 2022). Nevertheless, the prevalence of depression has been increasing in recent years, necessitating a thorough investigation into its etiology and pathogenesis (Jacobson et al., 2022).

Heavy metals are defined as metals with a density >5 g/cm3 (Järup, 2003). Heavy metals in the environment can enter the human body through a variety of routes, including food, water, inhalation of contaminated air, and contact with the skin, and they can accumulate in the body. Heavy metals have been shown to cross the blood-brain barrier and accumulate in the brain, which can lead to impaired nerve cell function and induce or aggravate mental disorders, such as depression and anxiety (Barbagallo et al., 2021).
Animal studies have shown that exposure to some common environmental toxins, such as

  • mercury (Hg),
  • lead (Pb),
  • manganese (Mn),
  • arsenic (As), and
  • cadmium (Cd),

affects autism spectrum disorders,
and exposure to

  • manganese and lead during pregnancy

is associated with poor fetal neurobehavioral development (Hill et al., 2015). Additionally, depression-like symptoms in mice that were exposed to heavy metals were particularly prominent 8 weeks after exposure. Heavy metal exposure induces DNA damage, apoptosis, and oxidative stress in the body (M et al., 2006). Firstly, metals disrupt calcium homeostasis in the neurons, leading to a breakdown in the mitochondrial membrane potential, a release of cytochrome C, and activation of the cysteine asparaginase cascade, ultimately leading to apoptosis (Zhou et al., 2015). Secondly, heavy metals induce the generation of free radicals, causing oxidative stress and damage to the neurons and their function, which in turn induces depression (Amity Institute of Biotechnology, Amity Institute of Biotechnology, and Department of Biochemistry, 2018). Heavy metals can also affect the metabolism and transportation of neurotransmitters, such as 5-hydroxytryptamine, dopamine, and norepinephrine, disrupting neurotransmitter homeostasis and inducing mental disorders, such as depression (Karri et al., 2016).

Vitamin D is a fat-soluble vitamin, and 7-dehydrocholesterol in the skin is irradiated with ultraviolet light, producing pro-vitamin D3, which then undergoes hydroxylation in the liver and kidneys and is converted to the active form of 1,25-dihydroxyvitamin D3 (Bikle, 2014). Vitamin D not only plays a key role in calcium and phosphorus metabolism and bone health but is also involved in a wide range of neuroprotective, neurodevelopmental, and neuromodulatory processes (Eyles, 2020). Studies have shown that vitamin D receptors are expressed in the hippocampus, prefrontal cortex, and other brain regions that are closely related to mood regulation. Vitamin D regulates the production of nerve growth factors, maintains neuronal integrity, and is involved in the metabolism of a variety of neurotransmitters (e.g., 5-hydroxytryptamine and dopamine) (Kaviani et al., 2020). Heavy metals, such as lead, mercury, and cadmium, can impede the process of vitamin D synthesis by disrupting the endocrine system and affecting the activity of hydroxylase in the liver and kidneys (Moon, 2013). Furthermore, heavy metals can directly affect key enzymes of the vitamin D metabolic pathway, such as 1α-hydroxylase and 24-hydroxylase (Rahman et al., 2018). Lead exposure can inhibit 1α-hydroxylase activity in the renal tubular epithelial cells and reduce the production of active vitamin D3, leading to vitamin D deficiency in the body (Rahman et al., 2018). Vitamin D deficiency due to chronic heavy metal exposure causes bone health problems, such as osteoporosis, rickets, and an increased risk of fractures (Rahman et al., 2018). However, recent studies have found that vitamin D deficiency due to heavy metal exposure is also associated with cardiovascular diseases, autoimmune diseases, neurological disorders, and certain types of cancer (Domenico et al., 2022; E et al., 2019; Éva et al., 2023). Thus, heavy metal pollution may exacerbate vitamin D metabolism disorders and be one of the risk factors for the aforementioned diseases.

Several studies have found that vitamin D deficiency is positively associated with the incidence and severity of depression, and it may influence depression through the modulation of the neurotransmitter system, oxidative stress states, and effects on neurodevelopment in the brain. In a population-based cohort study, adults aged 65 years and older with lower levels of 25(OH2)D3 had more severe depressive states (Corinna et al., 2020). Although the centrality of vitamin D in the treatment of depression has yet to be established, an increasing number of scholars have suggested that vitamin D supplementation may be useful as an adjunctive treatment, particularly for depressed individuals with vitamin D deficiency (Kaviani et al., 2020). Thus, future research is needed on the optimal dose of vitamin D supplementation, its duration, and the possibility of combining it with other antidepressant therapies.

Heavy metals can not only directly damage the nervous system and induce depression but also may cause vitamin D deficiency and aggravate depression by interfering with vitamin D metabolism. Therefore, an in-depth study of the association between heavy metals and vitamin D metabolism could provide a basis for minimizing the adverse health effects of heavy metals and provide a more precise strategy for the treatment and prevention of depression. Consequently, in this study, we analyzed the association between the effect of heavy metal exposure on depression and vitamin metabolism and investigated the potential role of metals in depression and vitamin D deficiency. This study focused on the population that participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018 to provide some insights into the reduction of adverse health effects caused by metals and for the prevention and treatment of depression.

Section snippets
Study design and participants
This study followed the reporting guidelines of STROBE (Reporting to Strengthen Epidemiological Observational Studies) and used data from NHANES for secondary analysis. The NHANES is a cross-sectional survey of the US population to assess its health and nutritional status. All participants in the survey provided informed consent and were recognized by the Research Ethics Review Committee of the National Center for Health Statistics. The survey used a complex multi-stage probability sampling …

Population characteristics
The mean age of the 5754 participants was 49.02 ± 17.81 years. Among them, 2915 (49.0 %) were males and 2839 (51.0 %) were females (Table 1). Most of the participants were non-Hispanic white (69.8 %) and married (54.2 %). There were 531 people with depressive symptoms in the study population. The weighted age of people with depressive symptoms was 48.37 ± 16.28, and the weighted age of people without depressive symptoms was 49.09 ± 17.96. The proportion of women, drinkers, smokers and people….

Discussion
Depression is a prevalent mental health problem globally, and with the increase in environmental pollution, people have begun to pay attention to the impact of environmental factors on human mental health. Heavy metals, such as lead, mercury, cadmium, and arsenic, pose a serious threat to human health because they are difficult to degrade in the environment and tend to accumulate through the food chain (Environmental, Occupational Health, Environmental, and Occupational Health, 2020). In….

Conclusion
In conclusion, the findings suggest that mono- or polymetallic mixed exposures may be associated with depression and that vitamin D deficiency could increases depressive symptoms. These results indicate that Vitamin D may be a simple, efficient, and achievable treatment and prevention method for metal-induced depression than traditional pharmacological treatments for depression. It may provide a proven measure for people at increased risk of depression due to exposure to heavy metals in their….

57 References include:
  • N.H. Duc et al.– Interactions between cadmium, lead, mercury, and arsenic and depression: a molecular mechanism involved – J. Affect. Disord. (2023)
  • R. Jin et al. Associations of renal function with urinary excretion of metals: evidence from NHANES 2003–2012 Environ. Int. (2018)
  • V. Karri et al 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. (2016)
  • A.P. Sanders et al. – Combined exposure to lead, cadmium, mercury, and arsenic and kidney health in adolescents age 12–19 in NHANES 2009–2014 Environ. Int. (2019)
  • D.S. Hill et al.– Autism-like Behavior and Epigenetic Changes Associated With Autism as Consequences of in Utero Exposure to Environmental Pollutants in a Mouse Model (2015)

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Heavy metals can cause health problems if low vitamin D (depression in this study) – Nov 2024        
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