Pharmacokinetics of metal excretion following different doses of sodium EDTA infusion

Abstract

Chelation therapy is a promising approach to mitigating health risks associated with toxic metal exposure, which contributes to cardiovascular disease, neurotoxicity, and other chronic conditions. disodium ethylene diamine tetraacetic acid (EDTA) is widely used, but its optimal dosing strategy remains unclear. This study evaluates the dose-dependent efficacy of EDTA in mobilizing toxic metals, including lead (Pb), cadmium (Cd), and gadolinium (Gd), while minimizing the loss of essential metals like copper (Cu) and manganese (Mn) to optimize therapeutic safety and efficacy. Ten volunteers (≥50 years) received 3 infusions at doses of 0.5, 1, and 3 g of EDTA over 30 min, 1 h, and 3 h, respectively. Urine and blood samples were analyzed pre- and post-infusion to assess pharmacokinetics of metal chelation. Urinary Pb excretion increased by 2200% at 0.5 g, with only a marginal gain at higher doses (3300%), supporting low-dose EDTA efficacy. Urinary Cd clearance required 3 g EDTA due to its strong tissue binding. Notably, Gd excretion increased by up to 78 000% even at 0.5 g EDTA, highlighting EDTA's potential to reduce long-term Gd burden post-MRI. Urinary excretion of essential metals varied, with Mn and Zn loss increasing at higher EDTA doses, underscoring the need for dose optimization while Cu and Ca only showed a clear increase urinary excretion at 3 g EDTA. Overall, a 0.5 g EDTA dose effectively mobilized Pb and Gd while minimizing essential metal depletion, reducing infusion time to 30 min, and improving patient compliance. These findings align with TACT and TACT 2 studies, reinforcing EDTA's long-term benefits in Pb reduction and supporting low-dose EDTA as a safe, efficient, and well-tolerated detoxification strategy.

Graphical Abstract

Figure 1.

Timeline of chelation study design. Each participant received three infusions: 0.5, 1, and 3 g. Blood and urine samples were collected preinfusion and urine postinfusion after 6, 24, 48, and 72 h.

Figure 2.

Urinary excretion of toxic metals (A) lead (Pb), (B) gadolinium (Gd), and (C) cadmium (Cd) over time (0, 6, 24, 48, and 72 h) following EDTA infusion at three doses (0.5, 1, and 3 g). Urinary metal concentrations were normalized for hydration status using urine specific gravity.

Figure 3.

Total urinary excretion of toxic metals—(A) lead (Pb), (B) gadolinium (Gd), and (C) cadmium (Cd)—summed across collection time points (6, 24, 48, and 72 h) for three EDTA infusion doses (0.5, 1, and 3 g) in 10 participants. The black line represents the average excretion of these metals across all participants.

Figure 4.

Change in blood levels of (A) lead (Pb) and (C) cadmium (Cd) for 10 participants prior receiving the EDTA infusion of 0.5, 1, and 3 g of EDTA. Association between blood levels of (B) Pb and (D) Cd prior to infusion and urinary clearance after 6 h of infusion for three different EDTA doses.

Figure 5.

Urinary excretion of essential metals (A) copper (Cu), (B) manganese (Mn), (C) iron (Fe), (D) zinc (Zn), and (E) calcium (Ca) over time (0, 6, 24, 48, and 72 h) following EDTA infusion at three doses (0.5, 1, and 3 g). Urinary metal concentrations were normalized for hydration status using urine specific gravity.

Figure 5.

Urinary excretion of essential metals (A) copper (Cu), (B) manganese (Mn), (C) iron (Fe), (D) zinc (Zn), and (E) calcium (Ca) over time (0, 6, 24, 48, and 72 h) following EDTA infusion at three doses (0.5, 1, and 3 g). Urinary metal concentrations were normalized for hydration status using urine specific gravity.

Figure 6.

Total urinary excretion of essential metals—(A) copper (Cu), (B) manganese (Mn), (C) iron (Fe), (D) zinc (Zn), and (E) calcium (Ca)—summed across collection time points (6, 24, 48, and 72 h) for three EDTA doses (0.5, 1, and 3 g) in 10 participants. The black line represents the average excretion of these metals across all participants.

Figure 7.

Blood levels of essential metals (A) Cu, (B) Mn, (C) Fe, and (D) Zn for the 10 participants prior receiving the EDTA infusion of 0.5, 1, and 3 g of EDTA. Red line shows the mean blood metal levels for all particpants preinfusion.