Zinc (Zn) is the second most abundant metal in the human body and is essential for the function of 10% of all proteins. As metals cannot be synthesized or degraded, they must be assimilated from the diet by specialized transport proteins, which unfortunately also provide an entry route for the toxic metal pollutant cadmium (Cd). The intestinal absorption of Zn depends on the composition of food that is consumed, firstly the amount of Zn itself and then the quantity of other food constituents such as phytate, protein, and calcium (Ca). In cells, Zn is involved in the regulation of intermediary metabolism, gene expression, cell growth, differentiation, apoptosis, and antioxidant defense mechanisms. The cellular influx, efflux, subcellular compartmentalization, and trafficking of Zn are coordinated by transporter proteins, solute-linked carriers 30A and 39A (SLC30A and SLC39A), known as the ZnT and Zrt/Irt-like protein (ZIP). Because of its chemical similarity with Zn and Ca, Cd disrupts the physiological functions of both. The concurrent induction of a Zn efflux transporter ZnT1 (SLC30A1) and metallothionein by Cd disrupts the homeostasis and reduces the bioavailability of Zn. The present review highlights the increased mortality and the severity of various diseases among Cd-exposed persons and the roles of Zn and other transport proteins in the manifestation of Cd cytotoxicity. Special emphasis is given to Zn intake levels that may lower the risk of vision loss and bone fracture associated with Cd exposure. The difficult challenge of determining a permissible intake level of Cd is discussed in relation to the recommended dietary Zn intake levels.

The preventability of acute lymphocytic leukemia during childhood is currently receiving great attention, as it is one of the most common cancers in children. Among the known risk factors so far are those affecting the development of gut microbiota, such as a short duration or absence of breastfeeding, cesarean section, a diet lacking in short-chain fatty acids (SCFAs), the use of antibiotics, absence of infection during infancy, and lack of pets, among other factors. Namely, it has been shown that iron deficiency anemia (IDA) and lack of vitamin D may cause intestinal dysbiosis, while at the same time, both increase the risk of hematological malignancies. The presence of IDA and vitamin D deficiency have been shown to lead to a decreased proportion of Firmicutes in stool, which could, as a consequence, lead to a deficit of butyrate. Moreover, children with IDA have increased blood concentrations of cadmium, which induces systemic inflammation and is linked to the onset of an inflammatory microenvironment in the bone marrow. Finally, IDA and Cd exposure increase fibroblast growth factor 23 (FGF23) blood levels, which in turn suppresses vitamin D synthesis. A lack of vitamin D has been associated with a higher risk of ALL onset. In brief, as presented in this review, there are three independent ways in which IDA increases the risk of acute lymphocytic leukemia (ALL) appearance. These are: intestinal dysbiosis, disruption of vitamin D synthesis, and an increased Cd load, which has been linked to systemic inflammation. All of the aforementioned factors could generate the appearance of a second mutation, such as ETV6/RUNX1 (TEL-AML), leading to mutation homozygosity and the onset of disease. ALL has been observed in both IDA and thalassemia. However, as IDA is the most common type of anemia and the majority of published data pertains to it, we will focus on IDA in this review.

The pathophysiological basis of Parkinson’s disease (PD) remains incompletely understood. However, the influence of environmental factors, such as continuous cadmium exposure, requires further investigation. Notably, common comorbidities such as iron deficiency anemia (IDA), chronic obstructive pulmonary disease (COPD), and zinc deficiency are linked with increased cadmium bioavailability, and elevated blood cadmium levels have been reported in individuals with PD. Cd (II) deposits in the midbrain, causing the accumulation of inflammatory lipids, which promote neuronal destruction. Cd-treated animals develop Parkinson-like syndromes, and cadmium exposure is associated with neuronal loss and disruption of dopaminergic receptor expression. Neurofilament light chain (NfL), a biomarker of neurodegeneration, has been found to be elevated in patients with Parkinson’s disease and correlates with Cd blood concentrations. Iron deficiency promotes the secretion of FGF-23, which depletes vitamin D levels, further increasing the risk of PD. Moreover, COPD and IDA are two well-known examples of systemic hypoxia, which attracts metals bound to transferrin, such as cadmium and iron, leading to increased metal accumulation in various tissues, including the brain. Lead levels are also elevated in individuals with IDA, contributing to the risk of PD. Additionally, Cd exposure is associated with a reduced abundance of Lachnospiraceae in stool and decreased levels of butyrate, both of which are characteristic features of patients with Parkinson’s disease. Therefore, this review aims to explore how COPD, IDA, and zinc deficiency—known risk factors for Parkinson’s disease—lead to an increased cadmium burden and contribute to the onset and progression of the disease.