The Copper Toxicity Project
As previously mentionned, Copper toxicity is a serious and largely unrecognized epidemic occuring throughout Australia and other Western countries. Sheep farmers have long been aware of the seriousness of Copper toxicosis affecting their herds across the country. This results from sheep grazing on pastures that are deficient in the trace mineral molybdenum. But copper toxicosis occurs in humans as well, for a number of very different reasons!
Copper is essential for the normal functioning of many different enzymes.
-Superoxide dismutase (Cu-Zn SOD) - an important antioxidant enzyme
-Dopamine beta hydroxylase - converts dopamine to noradrenaline in both brain and adrenal medulla
-Lysyl oxidase - needed for stabilization (cross-linking) of newly formed collagen & elastin
-L-ascorbate oxidase - important in Vitamin C metabolism
-Tyrosinase - important in skin & hair coloration
-Cytochrome-c oxidase - important in cellular (mitochondrial) energy metabolism
Major sources of copper include:
Diet – beef & beef liver, fish, oysters & crab meat, mushrooms, nuts, chocolate, cocoa
Water supplies – old copper pipes
Industrial exposure from nearby industry
Occupational exposure – metalworkers
Copper overload may be asymptomatic, or may be suggested by the following characteristics:
Red or auburn hair or reddish tints to blonde or brown hair; commonly have freckles
Celtic / Scandinavian ancestry
Super active mind, but constantly anxious & exhausted; may become depressed as a result
Marked insomnia (sleeplessness)
Poor appetite and/or weight loss
Difficulty digesting and hence distaste for red and white meats
Cravings for chocolate or chocolate cake (or, strangely enough, other copper-rich foods)
Recurrent ear infections or behavioural problems in childhood
Impaired immunity incl. recurrent Candida / yeast infections
Oestrogen dominance in women
PMS, menorrhagia or Post-partum depression
High Ca, low K on HTMA
Typically Slow 1 metabolic types, (but not always)
Much research into the field of human Copper toxicity was conducted by the late Dr Paul Eck & Dr Lawrence Wilson at ARL laboratories in Arizona, who recognized that certain individuals accumulate excessive amounts of copper, over & above their body's basic metabolic needs. We now know that this is principally due to one of three distinct mechanisms:
1. Excessive dietary exposure, including that resulting from the breakdown of the lining of old copper pipes, particularly as a result of the passage of acidic water, leads to the up-regulation of intestinal CTR1 copper transporters.
2. Single Nucleotide Polymorphisms (SNPs) in the genes that code for these CTR1 transporters. This explains the prevalence of the condition in families of Celtic or Scandinavian ancestry. CTR1 transport proteins are present on virtually every cell type throughout the body. Normally, homeostatic mechanisms finely regulate the numbers of these proteins on the cell surface. Over 3,600 of these SNPs have been found by geneticists for the CTR1 gene; albeit only a relatively small proportion have been correlated with either increased or decreased transporter function at the present time.
3. Multiple copies of the CTR1 transporter gene. Just as with the salivary amylase gene on Chromosome 1, some individuals inherit additional copies of the CTR1 gene, leading to increased copper absorption throughout their lifetime(s).
As a general rule, Single Nucleotide Polymorphisms either result in a loss or reduction of the function of the protein for which they encode, or have seemingly no effect whatsoever. However, some SNPs increase the functioning of the respective protein, which in a sense, is like having additional copies of the transporter upon cell surfaces throughout the body. Both mechanisms would therefore account for the occurance of copper toxicity as an heritable trait in Celtic & Scandinavian famiies and wherever the Vikings of old may have interbred with native populations, e.g. in parts of Belgium, Normandy & some Mediterranean countries.
Where such changes code for increased copper absorption, or the homeostatic regulatory mechanisms are faulty (which may occur with concomitant mercury poisoning) then each and every cell throughout the body will accumulate more & more copper. This is okay, so long as the cell's copper storage & disposal mechanisms are working normally. Once the intracellular storage capacity is exceeded, then excess copper becomes stored in the extracellular tissues, attached to cell-surface Integrin molecules. Additionally, free, unbound copper begins to accumulate in the bloodstream, thereby affecting a whole range of biological processes.
Whilst working at the National Institute of Integrative Medicine in Melbourne, l examined the incidence of tissue copper excess in both hair samples and in 24hr urine samples before & after an intravenous DMPS Challenge test. The results were quite surprising, given that most patients either came from Melbourne or Country Victoria.
We found the overall mean for copper from 75 random hair samples was 4.97 mg %, compared with the International mean of 2.4 mg %. Furthermore, 12 patients (16 %) recorded values of between 3.9-6.9 mg %; eight patients (10.7 %) recorded values in excess of 6.9 mg % whilst only three patients recorded levels of 0.9 mg % or below. So, in effect, 20 patients (26.7 %) out of the total of 75 recorded hair tissue copper levels above the International Reference Range for this element, whilst only 4 % scored below this range.
When we next looked at the Challenge test results (from a subset of patients selected on specific HTMA criteria for further investigation of possible Heavy Metal toxicity), we uncovered the following:
1.You cannot predict 24hr urinary copper excretion based on hair testing alone. It simply gives one an indication of copper dynamics in respect of the transfer of free copper molecules into the matrix germinal epithelium of the hair root
2.The quantity of copper excreted in the first 24hr collection does not correlate with the quantity excreted following an I/V DMPS Challenge (see later)
3.In other words, some people bind a significant quantity of copper in their extracellular tissues (bio-unavailable copper), whilst other people do not. This reservoir is tapped during an I/V DMPS Challenge, because DMPS preferentially extracts copper from both intravascular and extracellular compartments. Only a small amount is removed from intracellular stores. (Dr Johann Ruprecht – Heyl, Germany)
The Copper Bioavailability Index.
This Index is a simple measure of the extent to which copper, (or mercury or any other metal) can become sequestered in extracellular tissues. It is calculated from pre & post-DMPS Challenge tests by the following formula:
BIx (copper) = [(Cu : post) – (Cu : pre)] ÷ [(Cu : pre)]
This index represents the amount of copper mobilized from vascular & extracellular compartments by the binding effects of the infusion of DMPS molecules, as compared with the unprovoked, urinary excretion of that element.
Now, the following data has been derived from 23 patients whom have all had HTMA testing through InterClinical Labs, and pre & post-DMPS urine testing by Genova Laboratories, North Carolina, USA.
What we see, when we calculate the Bioavailability Index, are two clearly defined patient populations, that l have labelled as Accumulators and Eliminators.
Note that when calculating the Bioavailability Index, scores less than 10 should be regarded as normal. Any score greater than 10 indicates a propensity to accumulate copper in extracellular tissues.
In the first group (Eliminators), we find a mean pre-DMPS copper of 26.66 μg/g creatinine, c/f the post-DMPS figure of 129.88 μg/g creatinine. That is an 4.87 x increase in urinary copper excretion.
By comparison, in the second group (Accumulators), urinary excretion increases from a mean of 7.71 to 182.18; i.e an 23.6 fold increase.
In this study, there were 11 patients in the Eliminator group and 12 in the Accumulator group. Whilst this distribution occurred purely by chance, it may reflect fundamental differences in the handling of copper by these two distinct populations. Interestingly, there was literally no-one who attained a Bioavailability Index in the intermediate range,
i.e. 8 - 16.
1. Hair copper is recorded in milligram percent (mg%)
2. Pre-DMPS refers to 24hr urinary copper excretion prior to the DMPS Challenge
3. Post-DMPS refers to 24hr urinary excretion following the intravenous DMPS Challenge (3mg/kg DMPS in Normal Saline up to a 250mg maximum administered over one hour).
4. Bioavailability Index - see above for definition
5. All results are mean values for their respective categories
6. Also of interest, is the observation that in the pre-DMPS collections in the Accumulator group, the mean 24hr copper excretion was almost 3.5x lower than in the Eliminator group, which perhaps suggests that copper that is filtered by the renal glomeruli is more readily absorbed (i.e. conserved) across the renal tubules in this population.
These data clearly demonstrate the presence of two separate populations in their handling of mineral copper.
It is postulated that those patients in the Accumulator group will benefit from Clinical Nutritional intervention to reduce their copper levels and quite possibly reduce their lifetime risks of either Cancer or Alzheimer's disease.