Clinical Pharmacist and Master’s student in Clinical Pharmacy with research interests in pharmacovigilance, behavioral interventions in mental health, and AI applications in clinical decision support. Experience includes digital health research with Bloomsbury Health (London) and pharmacovigilance practice in patient support programs. Published work covers drug awareness among healthcare providers, postpartum depression management, and patient safety reporting. 
Clinical Pharmacist and Master’s student in Clinical Pharmacy with research interests in pharmacovigilance, behavioral interventions in mental health, and AI applications in clinical decision support. Experience includes digital health research with Bloomsbury Health (London) and pharmacovigilance practice in patient support programs. Published work covers drug awareness among healthcare providers, postpartum depression management, and patient safety reporting. What was reviewed?
This narrative review examined clinical, epidemiological, and experimental research on nickel’s cardio-metabolic effects. PubMed studies published in English from the 1960s to January 2025 were included, focusing on cardiovascular diseases, metabolic syndrome, diabetes, obesity, lipid disorders, and fatty liver. The review covered epidemiological and cross-sectional studies (notably NHANES), human surveys, and animal experiments across exposure levels. It highlighted dose-response relationships, variable study endpoints, methodological differences, and population characteristics. Recent meta-analyses and mechanistic insights from animal studies on oxidative stress and organ-specific toxicity were also summarized.
Who was reviewed?
The review encompassed a diverse array of human populations and animal models. Human studies included both occupationally exposed workers and the general population from the United States and China, analyzed in large-scale epidemiological surveys such as NHANES and Chinese national cohorts. These studies spanned a wide age range, included both sexes, and examined subpopulations such as pregnant women, individuals with nickel allergies, and groups stratified by age, sex, education, and smoking status. Animal research reviewed included controlled experiments in mice, rats, and Japanese quails, which were exposed to varying dietary or environmental levels of nickel. The review also integrated data from meta-analyses involving tens of thousands of human participants, providing a broad perspective on the cardio-metabolic impacts of nickel across demographic, geographic, and exposure contexts.
Most Important Findings
| Key Findings | Details / Implications |
|---|---|
| Epidemiology | NHANES studies link urinary nickel (UNi) to CVD, diabetes, and MetS; risk rises up to ~0.2 µg/L, then plateaus. |
| Occupational exposure | Zinc, vanadium, and copper can modulate nickel effects. |
| Low-level exposure | Some studies report null or negative associations at low nickel levels. |
| Animal studies | Nickel causes cardiovascular/metabolic toxicity via oxidative stress, mitochondrial dysfunction, and antioxidant depletion. |
| Metal interactions | Zinc, vanadium, copper can modulate nickel effects. |
| Meta-analyses | Urinary nickel shows dose-dependent diabetes risk; blood nickel does not. |
| Methodology | Variations in MetS definitions, endpoints, and stats lead to inconsistent findings. |
| Certification relevance | Supports urinary nickel as a biomarker; nonlinear risk curves and oxidative stress highlight vulnerable populations. |
Key Implications
For industry and regulators, this review emphasizes the need to monitor and control nickel exposure in occupational and general settings. Even low-level chronic exposure may raise risks of metabolic and cardiovascular disease, especially in vulnerable populations. Nonlinear dose-response relationships suggest thresholds vary by population and endpoint. Inconsistencies at low exposure highlight the need for standardized study designs, harmonized outcomes, and longitudinal research. For heavy metal certification, urinary nickel testing is recommended in consumer products, food, water, and workplaces, with criteria updated as new data emerge. Co-exposures and individual susceptibility should be considered in risk assessment and regulatory decisions.
Citation
Liu, Y., Luo, X., Peng, Y., & Cai, L. (2025). Cardio-metabolic effects of nickel: A narrative review. Cardiovascular Toxicology, 25(7), 944-954. https://doi.org/10.1007/s12012-025-10014-6
Nickel is a widely used transition metal found in alloys, batteries, and consumer products that also contaminates food and water. High exposure is linked to allergic contact dermatitis, organ toxicity, and developmental effects, with children often exceeding EFSA’s tolerable daily intake of 3 μg/kg bw. Emerging evidence shows nickel crosses the placenta, elevating risks of preterm birth and congenital heart defects, underscoring HMTC’s stricter limits to safeguard vulnerable populations.
