Heavy metal exposure and all health outcomes: An umbrella review of meta-analyses.

We aimed to systematically evaluate the strength and credibility of evidence linking exposure to five major heavy metals, including arsenic, cadmium, lead, mercury, and chromium, with health outcomes (PROSPERO, CRD420251169899). Literature searches of PubMed/Embase, CINAHL, and Google Scholar up to April 20, 2025, identified meta-analyses of observational studies assessing these associations. Effect sizes were recalculated using random-effects models and expressed as equivalent odds ratios (eOR) with 95 % confidence intervals (CIs). The methodological quality of the included reviews was assessed using the AMSTAR2, and the credibility of associations was graded according to predefined criteria: Class I (convincing), Class II (highly suggestive), Class III (suggestive), Class IV (weak), and non-significant (NS). A total of 35 meta-analyses encompassing 103 health outcomes were included. Arsenic exposure was associated with melanoma (eOR 1.50 [95 % CI, 1.0-2.24], CE=IV), digestive cancers (1.23 [1.07-1.41], CE=III), gestational diabetes mellitus (1.47 [1.11-1.95], CE=III), hypertension (1.15 [1.06-1.24], CE=III), and preterm birth (1.12 [1.04-1.21], CE=III). Lead exposure showed significant associations with autistic disorder in children (12.70 [3.93-41.10], CE=IV), hearing loss (7.55 [6.69-8.53], CE=III), age-related eye disease (9.80 [1.72-55.85], CE=IV), and amyotrophic lateral sclerosis (1.46 [1.16-1.83], CE=III). Mercury exposure was linked to increased risk in membranous nephropathy (5.75 [1.54-21.44], CE=IV) and thyroid cancer (1.90 [1.55-2.33], CE=IV). Cadmium exposure was associated with renal cancer (1.47 [1.26-1.71], CE=II), cardiovascular disease (1.33 [1.05-1.69], CE=IV), stroke (1.36 [1.10-1.68], CE=III), diabetes mellitus (1.27 [1.07-1.52], CE=III), fracture risk (1.30 [1.13-1.49], CE=III), and age-related eye disease (113.26 [16.86-760.68], CE=III). Chromium exposure was associated with stomach cancer (1.28 [1.16-1.41], CE=I), supporting convincing evidence. Overall, exposures to these metals were consistently associated with diverse diseases across organ systems and life stages, suggesting proactive implications against heavy metal exposures.