Reference values are provided by governmental agencies for some, but not all toxins. A reference value indicates the upper value as statistically established from the generally healthy population to a given environmental toxin. In simple terms, the upper reference range can vary depending on the overall environmental situation. People living in a clean environment, will have healthy people that are less exposed to environmental toxins and hence the statistical evaluation will provide an upper reference range for a given toxin that may be lower than that of a population living in a polluted area.
Reference ranges (RR) are established on so-called healthy people, and these RR are used to identify subjects with an increased level of exposure. However, levels exceeding these RR do not represent health related criteria i.e. a urine Arsenic level mildly exceeding the RR indicates a slightly greater exposure as has been determined for the average population. A higher than expected exposure may not indicate a signficant risk. Symptoms of intoxication may not (yet) be present or be diffuse.
To establish the risk factor, further diagnostics tests are warranted.
Since Reference Ranges (RR) for urine metals are statistically determined from unprovoked urine, these RR can only be used for unprovoked urine samples (morning urine, spot sample, 24hr collection etc).
Chelating agents force metal binding, and thus chelation treatment is expected to increase urinary metal concentration and excretion. To compare the metal concentration of a urine sample collected after the use of a chelating agent such as DMPS or EDTA to the RR that applies to unprovoked urine is misleading. It would be wrong to compare the metal excretion values of an EDTA or DMSA or DMPS provocation urine with reference ranges that apply to unprovoked urine. In fact, the metal binding ability of DMPS is different than the metal binding ability of DMSA, and significantly different than that of EDTA.
To have relevant comparisons, we developed ORIENTATION RANGES (OR) for the chelating agents DMPS, DMSA and EDTA.
To develop these ranges, we used the same principle that applies to the developement of reference ranges for normal urine or blood. We statistically evaluated urine samples from people who had received treatment with specific chelation agents (DMSA, DMPS, EDTA) and determined upper metal ranges.
For instance, for the DMPS OR, we statistically evaluated 330 adults who had received 1 ampule of DMPS i.v., using the same principle as is used for the development of reference ranges. We determined a 95th percentile of 18mcg/g creatinine for Hg, which is considerably higher than the officially recommended RR of 1mcg/g creatinine for 'normal' urine.
Rationale for the OR: If the metal concentration of a urine sample following chelation exceeds the OR, the exposure is considered higher than statistically expected. The risk for suffering symptoms of metal overexposure is greater.
We believe that our approach will help chelation therapists to properly evaluate urine metal results following chelation. We also hope to have added credibility to the diagnostics used in chelation therapy.