Which antioxidants or chelators have demonstrated clinical benefit against cadmium poisoning in human studies?
Executive summary
Two classes of interventions appear in the human cadmium literature: nutritional antioxidants (notably vitamin E and broad vitamin supplementation) with a small number of human studies suggesting modulation of biomarkers, and chelating agents—most prominently EDTA and succimer/DMSA/DMPS-family drugs—used clinically for acute exposures though with limited proof of long‑term benefit for chronic accumulation (vitamin E: human studies; EDTA: clinical use in acute poisoning) [1] [2] [3].
1. Antioxidants with direct human data: narrow but real signals
Systematic reviews and narrative reviews report that vitamin E has been evaluated in vivo and in two human studies for its potential to reduce cadmium‑induced effects, and broader vitamin supplementation (vitamins C and E among others) has been associated with reduced markers of oxidative stress and inflammation in population studies, suggesting some clinical or biomarker benefit in humans exposed to cadmium [1] [4] [5]. Reviews of oxidative‑stress mechanisms summarize trials and interventions that used N‑acetylcysteine (NAC), selenium, vitamin C and vitamin E to boost antioxidant defenses and report decreased cadmium‑induced oxidative stress in kidney, liver and testes in many in vitro and animal studies, with a smaller footprint of human data [6] [7]. Large population‑level analyses from NHANES data found that a composite antioxidant/anti‑inflammatory diet score attenuated the association between cadmium exposure and systemic inflammation markers (CRP, ALP), indicating dietary antioxidant intake may modify cadmium effects in people [5].
2. Chelators used in clinical practice: EDTA first‑line for acute cases, mixed evidence for others
EDTA (ethylenediaminetetraacetic acid) is repeatedly identified as a priority therapy for acute cadmium poisoning in clinical reviews and recent clinical summaries, with the caveat that EDTA‑cadmium complexes are renally excreted and renal function must be monitored; chelation shows limited effect for chronic cadmium accumulation [3] [2]. Other classical chelators—dimercaprol (BAL), DMSA (succimer), and DMPS—are discussed: BAL is more toxic and now rarely used, while DMSA/DMPS are regarded as less toxic derivatives with clinical use in heavy‑metal cases, though robust human efficacy data for cadmium specifically are sparse and much of the stronger evidence comes from animal models [8] [3] [2]. Clinical resources and reviews also mention succimer in treatment discussions, but randomized controlled evidence demonstrating improved long‑term outcomes in cadmium poisoning in humans is limited [9] [2].
3. Where the evidence is strongest — and where it falls short
The strongest human‑facing evidence in the provided reporting is for vitamin E (two human studies summarized in reviews) and for dietary antioxidant patterns modifying biomarker associations in population studies, implying some protective or mitigating effect on cadmium‑related oxidative stress and inflammation [1] [5]. By contrast, many specific antioxidants and phytochemicals (curcumin, alpha‑lipoic acid, N‑acetylcysteine, selenium, zinc, magnesium, and various plant extracts) have compelling animal and in vitro data but lack confirmatory clinical trials in humans for cadmium poisoning per the cited literature [10] [11] [12] [7]. Chelation with EDTA and related agents is practiced in acute settings, but reviews emphasize renal risk, limited impact on chronic tissue burden, and a need for more documented human trials—an implicit admission that clinical benefit beyond acute toxin removal remains incompletely characterized [3] [2].
4. Practical takeaways, alternative viewpoints and research gaps
Clinically, acute severe cadmium toxicity is managed with chelation (EDTA prioritized) while antioxidants and dietary measures are positioned as adjuncts or population‑level mitigants rather than proven standalone cures [2] [3] [4]. Some experts and reviews propose combining chelators with antioxidants to improve efficacy and reduce toxicity, but this strategy is supported mainly by animal and mechanistic studies and deserves targeted human trials [11] [12]. Hidden agendas to watch for include extrapolation of abundant animal data into human treatment claims and commercial promotion of supplements without trial evidence; the literature repeatedly warns that many promising agents have not been validated in controlled human studies [7] [3]. The clear research need is randomized clinical trials of antioxidants (e.g., vitamin E, NAC, selenium) and chelator±antioxidant combinations in documented human cadmium poisoning, together with careful renal monitoring and objective clinical endpoints rather than surrogate biomarkers [1] [2] [5].