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Conclusions
The first half of the article, which deals with inorganic copper from drinking water and supplement pills as a causal factor in our epidemic of AD, has to be viewed as a hypothesis. What we have as a main observation is an association between introduction of copper plumbing and increasing prevalence of copper in multivitamins with the AD epidemic. As any statistician will tell you, association does not prove causation. There are, of course, other observations that support the hypothesis. The studies which show that trace amounts of copper added to drinking water greatly enhance AD-like disease in rabbits, mice, and beagles have tested this hypothesis in animals. But animals are not humans. One can't ethically test a potentially toxic substance by giving it to humans, but Morris et al. have come as close as one can get by studying what humans have done to themselves when ingesting a higher copper dose in vitamin supplements. It is a bit hard to visualize what study or studies would provide the definitive test that one seeks when evaluating this hypothesis. An epidemiologic study could be done, looking at whether a high proportion of those with AD, compared with age-matched controls, used copper plumbing or consumed copper supplements during their lives, but this would be very difficult.
It is not likely that a definitive test of this hypothesis will occur in the next few years, especially because there is no profit motive for a drug company to do so. In the meantime, we draw an analogy to the history of cigarette smoking. Those who took alarm three or four decades ago to the early association of cigarette smoking with lung cancer and heart attacks, and who stopped smoking, gained great benefit when it was later established that the association was causal. We liken the copper situation to the previous cigarette smoking situation. If you believe in a high likelihood that this hypothesis is correct, and therefore decrease ingestion of inorganic copper now, you will benefit greatly if it is correct.
If you wish to take action now, the following are our recommendations:
1. Discard all copper-containing nutritional supplements. Copper deficiency is rare, and most people don't require supplementary copper, and this type of inorganic copper is dangerous. Special groups of people who may require copper supplementation are those who have had surgery that removed a part of the small intestine, those with gastric bypass surgery, those using and swallowing large quantities of dental adhesives containing zinc, and those taking a daily dose of more than 50 mg/day of zinc. All these groups should have their copper levels checked before taking a copper supplement. Everyone else should look carefully at the label of any supplements they take. Nowadays, most multivitamin formulas contain copper, as do eye formulas.
The second half of this article, which deals with zinc deficiency in AD and the likely benefit of zinc administration's slowing or halting loss of cognition in AD, is fact based. It is a fact that, on average, AD patients are zinc deficient. It is a fact that zinc plays many roles, some of which protect against neuronal damage in the brain. It seems highly likely, but not is yet proved, that zinc therapy helps protect against cognition loss in AD. At this time, it is uncertain when a second, definitive study of zinc therapy in AD will be done.
AD patients and their families, and those who think they are at risk of developing AD, must decide for themselves whether to take zinc supplements. If they do, particularly if they take a high dose (more than 50 mg/day), it should be done under a physician's supervision. That physician should be aware of how to monitor for copper deficiency, the main risk from high-dose zinc therapy, then lower the zinc dose if that occurs. Also, zinc must be taken between meals, because food substances bind zinc and prevent its effect on blocking copper absorption. To be clear, AD patients taking zinc should not try to compensate the partial loss of copper absorption by taking supplementary copper, because one intent of zinc therapy is to lower copper.
Measuring the free copper level in your blood: If you want to evaluate the impact of reducing your copper intake, this can theoretically be done by monitoring your free copper level, which you calculate from your serum copper and serum ceruloplasmin measured in the same blood draw.
Typically, ceruloplasmin is given as mg/dl of serum with a normal range of 20 to 35. Serum copper is given as mcg/dl of serum with a normal range of 80 to 120. Free copper in your blood is calculated by multiplying the ceruloplasmin value by 3 (because there are 3 mcg of copper per mg of ceruloplasmin), then subtracting that number from the serum copper value. For example, if your ceruloplasmin is 30, multiplied by 3 equals 90. If your serum copper is 100, 100 minus 90 equals 10 mcg/dl, the free copper level in your blood.
When ceruloplasmin is measured by the immunologic method (the one most used clinically), the normal range of free copper is 5 to 15 mcg/dl, but it may be very low or even less than 0. This is acceptable. It simply means that the free copper value is low. When ceruloplasmin is measured by the more accurate oxidase method, a normal range of free copper is about 30 to 35 mcg/dl. There is some error in these measurements, so they are a somewhat rough approximation of free copper; but as long as the same method is used consistently, you can evaluate your free copper over time.
2. What about dietary changes – are they recommended? The most effective dietary strategy to reduce both copper and iron in the body is to reduce meat intake. Both copper and iron are much more effectively absorbed (more bioavailable) from meat than from vegetable foods. One shouldn't be confused by our suggestion here to reduce intake of meat copper, which is organic copper and which we have called "safe" copper. Our first prohibition is against ingestion of inorganic copper, because some of it contributes immediately to enlarging the serum free copper pool. But too much organic copper can also be bad, by slowly building up total body copper, which over time can gradually increase the serum free copper as well. In fact, recent studies have shown that overall health would be improved and mortality reduced if intake of meat by many in the population was lowered. A large study conducted by NIH and the American Association of Retired Persons found that people who ate about 5 ounces of red meat per day had a 30% higher mortality than those who averaged about 2/3 of an ounce. Processed meats, which include hot dogs, sausage, and bacon, also have an effect.61,62 People who ate about 60 grams (2 ounces) of processed meat per day had a 20% higher mortality than those who ate about 9 to 18 grams (about 1/3 to 2/3 ounces)/day. A similar study in Europe confirmed the effects of processed meat on mortality. The effect of higher meat eating on mortality may be due, in part, to the increased copper and iron absorption, which would increase oxidative damage, important to many disease processes besides AD, such as atherosclerosis.63
High levels of copper have been detected in US beef. Unlike other countries, the US has not established thresholds for many dangerous substances. A 2010 review by the USDA inspector general found that meat with harmful residues (dioxin, copper, arsenic, drugs, pesticides) is being distributed. In 2008, when Mexican authorities rejected a shipment of US beef because it contained copper in excess of Mexico's tolerances, the Food Safety and Inspection Service had no basis to stop distribution of this meat in the US.64
The US government also allows unregulated residues of copper sulfate on our food. Copper sulfate (pentahydrate) is exempt from the requirement of a tolerance when applied as a bactericide/fungicide on meat, fat, and meat byproducts of cattle and hogs. Copper sulfate is also exempt from the requirement of a tolerance when applied as a fungicide to growing crops or to raw agricultural commodities after harvest.65 (Copper sulfate is the form of copper used by Sparks and Schreurs in their animal experiments.)
The top crops for copper sulfate use in California in 2009 were (in descending order): rice, wild rice, cherries, oranges, wine grapes, peaches, nectarines, walnuts, almonds, lemons, apricots, and grapefruit. Even certified organic products are allowed to contain ingredients treated with copper sulfate, which is also commonly applied to cocoa for the treatment of black pod disease. This toxic copper remains in the soil for a long time, where it's a threat to workers as well as to water sources.
3. Test your water for copper. (Inexpensive copper test strips are available from SenSafe.com.) What copper level is safe? When rabbits consumed a concentration of 0.12 ppm (mg/L) copper in their drinking water, they had enhanced AD-type brain pathology and a decrease in cognition – their ability to carry out tasks. According to the study, these 2.2 kg rabbits consumed between 300 and 600 ml of water per day for a copper dosage of 0.016 to 0.033 mg/kg/day.22 For a 70 kg human, the equivalent dose would be 1.1 to 2.3 mg of copper per day. But extrapolations from the 10-week rabbit study are confounded by the fact that human water consumption lasts for many decades. What then is a safe concentration of copper in drinking water? We advise as close to 0 as possible, but never more than 0.05 ppm (0.05mg/L). That way, 1 liter of water would contain no more than 50 micrograms of copper.
If your water copper level is higher than that, you can filter it. A reverse osmosis system is about 99% effective at removing copper, while pitchers that use monthly disposable filters are 85% to 95% effective. Distilled water has no copper present. Bottled water is an unreliable source, because copper levels may be unknown or vary from lot to lot.
Copper corrosion in drinking water is a complex function of pipe age, water quality, stagnation time, and type of phosphate inhibitor. Disinfectant chemicals used to treat water – chlorine, ammonia, and chloramine – are all hostile to copper in that they induce copper stress cracking and/or can dissolve it. Chloramine will also react with fluosilicic acid, the most widely used water fluoridating agent, to produce ammonium fluosilicate, an established solvent for copper alloys.66
The Dartmouth Toxic Metals Superfund Research Program advises to use only water from the cold tap for drinking and for preparing food. Run the water until it gets very cold after it has been sitting in the pipes overnight. More copper leaches from hot water. Also, soft water is likely to contain more copper than hard water. Making sure that no electrical appliances are grounded to the plumbing can reduce corrosion of pipes.
Notes
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 Dr. George J. Brewer is Sellner Professor Emeritus of Human
Genetics and Emeritus Professor of Internal Medicine,
University of Michigan Medical School, Ann Arbor, Michigan.
John D. MacArthur is a neuroscience writer whose report,
"Overdosed: Fluoride, Copper, and Alzheimer's Disease,"
is published in this issue of the Townsend Letter (p. 63).
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