Dissecting the role of cadmium, lead, arsenic, and mercury in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

Tinkov, Alexey A.; Aschner, Michael; Santamaria, Abel; Bogdanov, Alfred R.; Tizabi, Yousef; Virgolini, Miriam B.; Zhou, Ji-Chang; Skalny, Anatoly V.

doi:10.1016/j.envres.2023.117134

Cited by 6 publications

(3 citation statements)

References 150 publications

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“…In the present study, cadmium, cobalt and tungsten emerged as the heavy metals exhibiting the most significant impact on frailty. Cadmium, regarded as one of the most toxic and widely distributed heavy metals, tends to accumulate in the liver [ 42 ], kidneys [ 43 ], and bones [ 44 ], which leads to a close association with renal tubular damage, urinary calcium loss, accelerated bone demineralization, and the development of osteoporosis [ 45 ]. Moreover, cadmium has been linked in the pathogenesis of diabetes, hypertension, and an elevated risk of cardiovascular disease, posing a serious threat to population health through various pathways [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

The association of urinary heavy metal exposure with frailty susceptibility and mortality in middle-aged and older adults: a population-based study

Zheng,

Luo,

Xue

2024

Arch Public Health

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Heavy metals’ presence as environmental pollutants has a close link to adverse health effects. Frailty, a clinical syndrome hallmarked by elevated vulnerability to stressors, presents a substantial challenge in healthcare. However, the association between exposure to heavy metals and frailty largely remains unexplored. Utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2003–2018 and correlated with the U.S. National Death Index (NDI) from 2019, we investigated mortality outcomes. Logistic regression, Cox regression, Kaplan-Meier survival curves, weighted quantile-sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were employed to assess the association between heavy metal exposure and frailty incidence and mortality in the frail population. Eight metals were measured in urine using inductively coupled plasma mass spectrometry with values adjusted for urinary creatinine, which was used to reflect heavy metal exposure. The cohort incorporated 5370 female participants aged 45 and above, with 1518 diagnosed with frailty. The findings indicated a substantial correlation between exposure to specific heavy metals, namely tungsten (odds ratio [OR]: 1.94, 95% confidence interval [CI]: 1.31–2.89), cobalt (OR: 1.64, 95% CI: 1.40–1.93), cadmium (OR: 1.93, 95% CI: 1.52–2.43), and uranium (OR: 7.36, 95% CI: 1.53–35.28), and an elevated risk of frailty. WQS and BKMR regression models identified cadmium, cobalt, and tungsten as main contributors to frailty. Cox regression analysis, after adjustment for covariates, suggested that the higher the exposure levels to cadmium and lead, the higher the risk of death in frail patients, with associated hazard ratios (HR) of 95% CI: 1.96 (1.53, 2.52) and 1.30 (1.13, 1.49), respectively. Our study revealed a significant positive correlation between exposure to heavy metal mixtures and frailty onset in middle-aged and older adults, along with increased mortality in frail patients. Cobalt, cadmium, and tungsten emerged as prominent contributors to frailty, with cobalt and cadmium directly impacting the long-term life expectancy of frail patients.

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Section: Discussionmentioning

confidence: 99%

The association of urinary heavy metal exposure with frailty susceptibility and mortality in middle-aged and older adults: a population-based study

Zheng,

Luo,

Xue

2024

Arch Public Health

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“…Animal experiments have demonstrated that Cd exposure exacerbates hepatic steatosis induced by a high-fat diet [36]. Cd exposure may promote lipid synthesis, inhibit fatty acid beta-oxidation, and suppress mitochondrial transfer, leading to intracellular triglyceride accumulation in liver cells [16,23,37]. Additionally, Cd can induce oxidative stress, trigger iron death, and activate apoptotic signaling, thus contributing to the progression of NAFLD [14,[38][39][40].…”

Section: Discussionmentioning

confidence: 99%

“…Some researchers have examined the relationship between blood Cd levels and NAFLD [20][21][22]. A recent review summarized existing epidemiological and laboratory research ndings, suggesting an association between cadmium exposure and an increased risk of NAFLD as well as changes in liver damage markers [23]. However, there is a lack of conclusive evidence regarding the effect of blood cadmium levels on the prognosis of patients with NAFLD.…”

Section: Introductionmentioning

confidence: 99%

Association of blood cadmium levels with all-cause and cause-specific mortality among adults with Non-Alcoholic Fatty Liver Disease: A prospective cohort study

Xu,

Li,

Hao

et al. 2024

Preprint

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Background Cadmium (Cd) accumulates in the body over time, damaging organs such as the liver, kidneys, and brain. Some researchers have suggested that elevated blood Cd levels may contribute to the onset and progression of nonalcoholic fatty liver disease (NAFLD). However, only a few studies have investigated the association between Cd exposure and long-term health outcomes in patients with NAFLD. This study aimed to evaluate the predictive value of blood cadmium levels for mortality risk in patients with NAFLD. Methods This study analyzed data from 13,790 patients with NAFLD in the National Health and Nutrition Examination Survey (NHANES) database, covering the years 1999 to 2018. Patients were categorized into three groups based on their blood Cd levels. The relationship between blood cadmium concentrations and all-cause, cardiovascular, and cancer mortality in NAFLD patients was assessed using Cox proportional hazards regression while accounting for potential confounders. Results were visualised using Kaplan-Meier and restricted cubic spline (RCS) curves. Stratified analyses were performed for validation of the robustness of the results. Results The study included 13,790 individuals. After adjusting for all covariates, blood Cd levels were positively associated with all-cause, cardiovascular, and cancer mortality in patients with NAFLD, showing a significant linear dose-response relationship. Specifically, for each unit increase in Log-transformed blood cadmium concentration, the risk of all-cause mortality increased by 195% (HR = 2.95, 95% CI: 2.43–3.58); cardiovascular mortality risk increased by 173% (HR = 2.73, 95% CI: 1.90–3.93); and cancer mortality risk increased by 277% (HR = 3.77, 95% CI: 2.54–5.59). Stratified analysis confirmed the robustness of these findings, indicating that female patients and those under 60 were more susceptible to the effects of blood cadmium on all-cause mortality. Additionally, patients with hypertension and those under 60 years of age were more vulnerable to cardiovascular mortality. Conclusions Our study suggests that high Blood Cd levels adversely affect the prognosis of patients with NAFLD. Individuals with NAFLD should be aware of Cd exposure and take preventive measures. Moreover, stricter environmental protection policies may be necessary to reduce Cd exposure.

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Mixture analysis of associations between environmental and workplace toxins and liver damage and telomere length, stratified by race/ethnicity

Ma,

Yip,

Woodward

et al. 2024

Journal of Environmental Sciences

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Dissecting the role of cadmium, lead, arsenic, and mercury in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

Cited by 6 publications

References 150 publications

The association of urinary heavy metal exposure with frailty susceptibility and mortality in middle-aged and older adults: a population-based study

The association of urinary heavy metal exposure with frailty susceptibility and mortality in middle-aged and older adults: a population-based study

Association of blood cadmium levels with all-cause and cause-specific mortality among adults with Non-Alcoholic Fatty Liver Disease: A prospective cohort study

Mixture analysis of associations between environmental and workplace toxins and liver damage and telomere length, stratified by race/ethnicity

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