The Casa Pia Children’s Amalgam Trial
The FDA’s Evidence that amalgam exposure does not affect long-term health outcomes
Woods, J.S. et al., “Biomarkers of Kidney Integrity in Children and Adolescents with Dental Amalgam Mercury Exposure: Findings from the Casa Pia Children’s Amalgam Trial,” Environmental Research, Vol. 108, pp. 393-399, 2008.
The FDA is STILL using the above-referenced study, and others, on their website (hyperlinked above) and in the Special Controls document[1] to tout the safety of Amalgam fillings, despite new data to refute or reduce the impact of the initial study findings.
The data for this, and prior and subsequent studies came from the Casa Pia trial in which urinary porphyrin data, sensitive indicators of mercury exposure, were acquired but not examined in initial reports.
In this trial, increases in urine mercury younger children were observed (8–9 years) during peak exposure at years 2–3*, suggesting potential subclinical renal impact[2]. Third, they identified strong sex differences in urinary mercury. The FDA chose to ignore these findings.
*In the trial urinary mercury (U-Hg) peaked at ~3.2 µg/L in year 2 and then declined to baseline by year 7 (despite acquiring more amalgam fillings) – likely reflecting excretory limitations rather than reduced exposure, potentially underestimating internal body burden.[3]
In a New England trial, microalbuminuria (a marker of subtle kidney dysfunction) was significantly more frequent in the amalgam group during years 3–5 (OR ~1.8), including persistent cases, calling into question the claim of “no organ-level effect.”[4]
Even large cohorts (n ≈ 500) may lack sensitivity to detect subtle neurocognitive or renal effects, especially when using broad clinical tests rather than specialized neurotoxicological endpoints.[5] Critics have suggested that continuous measures (e.g., nerve conduction, attention tasks) or genetically susceptible subpopulations (e.g., metallothionein polymorphisms) were not adequately examined.
These two points are crucial: Reviewers criticize the selective presentation of endpoints, notably porphyrin data, (which was collected but not presented), and the exclusion of genetically or clinically vulnerable children, which biases conclusions toward safety.
| Critique Area | Specific Concern |
| Biomarkers | Missing subtle renal/neurotoxic signals in urinary porphyrins |
| Exposure metrics | Declining U-Hg levels reflect excretion limits, not true exposure |
| Renal effects | Microalbuminuria suggests mild kidney stress/damage |
| Statistical sensitivity | Study may be underpowered for small effect sizes |
| Endpoint selection | Coarse tests may overlook nuanced neurotoxicity or susceptible subgroups |
The above-listed findings highlight that while Lauterbach et al. concluded no neurological harm, valid concerns remain regarding subtle renal effects, limitations in exposure measurement, and the potential for overlooked neurotoxic impacts in sensitive subgroups. Comprehensive follow-up studies with targeted biomarkers and sensitive testing are still warranted.[6] Additionally, the amount of exposure was not accounted for – regardless of exposure to amalgam, all amalgam-bearers were lumped together. This is another crucial point.
Additional Follow up Studies
Genetic Polymorphisms & Increased Vulnerability
Modification of neurobehavioral effects of mercury by genetic polymorphisms of metallothionein in children
Children (aged 8–12) from the original Casa Pia trial were genotyped for two metallothionein variants (MT1M rs2270837 and MT2A rs10636). Among boys, specific alleles of MT1M and MT2A showed significant interactions with urinary mercury exposure, correlating with worse performance across multiple neurobehavioral domains (memory, attention, etc.). No such effect was observed in girls indicating that genetically susceptible subgroups, particularly boys with certain MT variants, can and do experience adverse effects even when average results appear safe.[7]
Extended Neurological & Renal Follow-Up
Bellinger et al. (New England Children’s Amalgam Trial – NECAT)
Children were followed up for 5 years, assessing IQ, memory, visuomotor skills, attention, and executive function. No average group differences between amalgam vs composite groups; however, the study acknowledged the possibility of subtle or delayed effects not captured.[8] Further, all amalgam-bearers were placed in one group, regardless of exposure level – no correlational analyses were performed.
Reanalysis by Geier and Geier 2012 of the Casa Pia trial, found a significant dose-dependent relationship between mercury exposure from dental amalgams and urinary mercury levels.[9]
Continued Porphyrin & Mercury Biomarker Analysis
Another reanalysis of the Casa Pia dataset, conducted by Geier et al. (2012) examined urinary mercury and porphyrin profiles in detail. Porphyrins are molecules in the pathway that produce heme. Heme plays several roles in the human body, one of which is as a component of hemoglobin, the molecule that delivers oxygen to our cells. There are several stages in the pathway, and therefore several different porphyrins. Mercury, and only mercury, inhibits the production of the final 3 porphyrins. Mercury exposure was compared to all stages of the porphyrin pathway. A direct relationship was shown, such that exposure to mercury through amalgam fillings resulted in significant reductions in the last 3 porphyrins.
Thus, when the same data are analyzed appropriately, using dose-dependent measures, rather than grouping subjects as amalgam-bearers vs not, the data confirm that greater exposure to amalgam fillings (i.e., size, number and length of time of exposure) increase urinary mercury AND decrease the efficiency of heme production, a basic function of the human body. The FDA continue to deny this – but simple common sense and a reading of the literature, including the letter that must have been written in futility by the authors of the early Casa Pia Trial papers,[10] refuting the Geier and Geier science, clearly show that even a relatively short exposure (8 years) to mercury from amalgam fillings cause disruption of cell function and therefore, mercury amalgam fillings can only be classified as unsafe. One must wonder how DeRouen and Lauterbach sleep at night knowing that deeper dives into the data such as dose-response analyses are crucial to unveiling effects. Why do they insist on grouping all amalgam-bearers into one category, muddying the data? Any decent epidemiologist knows the flaws of conducting science in such a way.
| Focus | Findings |
| Genetic susceptibility | MT variants linked to adverse neurobehavioral outcomes in boys (pubmed.ncbi.nlm.nih.gov) |
| Sample stratification | Effects may be masked when genetic variability is not considered |
| Renal/biomarkers | Urinary mercury and porphyrin profiles reflect dose–response heterogeneity |
| Long-term exposure | Mercury excretion dynamics change over time, suggesting tissue effects need further study |
Broader Evidence of Genetic Interactions
An FDA white paper (2021) reviews several studies showing: Polymorphisms in BDNF, CPOX4, and MT genes can significantly affect neurobehavioral and psychomotor outcomes in dental professionals exposed to low-level mercury.[11]
Casa Pia and NECAT studies both showed urinary mercury peaked around 2–4 years post-amalgam placement, even when new amalgams were placed, and then declined, likely due to changing excretion dynamics, not reduced exposure.[12]
[1] Center for Devices and Radiological Health, “Dental Amalgam, Mercury, and Amalgam Alloy – Class II Special Controls Guidance for Industry and FDA Staff,” FDA, FDA, March 23, 2021, https://www.fda.gov/medical-devices/guidance-documents-medical-devices-and-radiation-emitting-products/dental-amalgam-mercury-and-amalgam-alloy-class-ii-special-controls-guidance-industry-and-fda-staff.
[2] Xibiao Ye et al., “Nephrotoxicity, Neurotoxicity, and Mercury Exposure among Children with and without Dental Amalgam Fillings,” International Journal of Hygiene and Environmental Health 212, no. 4 (2009): 10.1016/j.ijheh.2008.09.004, https://doi.org/10.1016/j.ijheh.2008.09.004.
[3] James S. Woods et al., “The Contribution of Dental Amalgam to Urinary Mercury Excretion in Children,” Environmental Health Perspectives 115, no. 10 (2007): 1527–31, https://doi.org/10.1289/ehp.10249.
[4] Lars Barregard et al., “Renal Effects of Dental Amalgam in Children: The New England Children’s Amalgam Trial,” Environmental Health Perspectives 116, no. 3 (2008): 394–99, https://doi.org/10.1289/ehp.10504.
[5] Gene E. Watson et al., “Neurodevelopmental Outcomes at 5 Years in Children Exposed Prenatally to Maternal Dental Amalgam: The Seychelles Child Development Nutrition Study,” Neurotoxicology and Teratology 39 (2013): 57–62, https://doi.org/10.1016/j.ntt.2013.07.003.
[6] Martin Lauterbach et al., “Neurological Outcomes in Children with and without Amalgam-Related Mercury Exposure: Seven Years of Longitudinal Observations in a Randomized Trial,” Journal of the American Dental Association (1939) 139, no. 2 (2008): 138–45, https://doi.org/10.14219/jada.archive.2008.0128.
[7] James S. Woods et al., “Modification of Neurobehavioral Effects of Mercury by Genetic Polymorphisms of Metallothionein in Children,” Neurotoxicology and Teratology 39 (2013): 36–44, https://doi.org/10.1016/j.ntt.2013.06.004.
[8] D. C. Bellinger et al., “A Dose-Effect Analysis of Children’s Exposure to Dental Amalgam and Neuropsychological Function: The New England Children’s Amalgam Trial,” J Am Dent Assoc 138 (September 2007): 1210–16.
[9] DA Geier et al., “A Dose-Dependent Relationship between Mercury Exposure from Dental Amalgams and Urinary Mercury Levels: A Further Assessment of the Casa Pia Children’s Dental Amalgam Trial,” Human & Experimental Toxicology 31, no. 1 (2012): 11–17, https://doi.org/10.1177/0960327111417264.
[10] TA DeRouen et al., “Critique of Reanalysis of Casa Pia Data on Associations of Porphyrins and Glutathione-S-Transferases with Dental Amalgam Exposure,” Human & Experimental Toxicology 34, no. 3 (2015): 330–32, https://doi.org/10.1177/0960327114542885.
[11] Food and Drug Administration, “White Paper: FDA Update/Review of Potential Adverse Health Risks Associated with Exposure to Mercury in Dental Amalgam,” FDA, FDA, January 30, 2025, https://www.fda.gov/medical-devices/dental-amalgam-fillings/white-paper-fda-updatereview-potential-adverse-health-risks-associated-exposure-mercury-dental.
[12] Woods et al., “The Contribution of Dental Amalgam to Urinary Mercury Excretion in Children.”
