Copper-2 Hypothesis for Causation of the Current Alzheimer's

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The Copper-2 Hypothesis for Causation of the Current Alzheimer's Disease Epidemic George J. Brewer Chem. Res. Toxicol., Just Accepted Manuscript • DOI: 10.1021/acs.chemrestox.6b00373 • Publication Date (Web): 06 Feb 2017 Downloaded from http://pubs.acs.org on February 12, 2017

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Chemical Research in Toxicology

The Copper-2 Hypothesis for Causation of the Current Alzheimer’s Disease Epidemic Together with Dietary Changes that Enhance the Epidemic

George J. Brewer University of Michigan Medical School, University of Michigan, Ann Arbor, MI 48103, USA

Email: [email protected]; mailing address: 3820 Gensley Road, Ann Arbor, MI 48103, USA; phone: 734-761-7970

ACS Paragon Plus Environment


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Table of Contents 1. Introduction 2. History and Demographics of Alzheimer’s Disease (AD) 3. The Search for Environmental Factors Causing the AD Epidemic 4. The Hypothesis that Copper-2 Ingestion is the Major Cause of the AD Epidemic 5. Evidence Indicating that Increased Body Copper Load, Irrespective of Valence, Could Also Be Partially Causal of the AD Epidemic 6. Summary


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Abstract Alzheimer’s disease, the most common cause of dementia, is at epidemic proportions (15 to 44% depending on age, of those age 65 to 84) in the U.S. and other developed countries, but remains relatively rare in undeveloped countries. Surprisingly, solid historical data reveals the epidemic is a creature of the last century. That is, the disease was also rare in developed countries, until the 20

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century. It is disappointing that these historical and demographic facts have been ignored by the Alzheimer’s disease scientific community. Disappointing because these facts clearly point at an th

environmental change in the 20 century in developed countries as a major factor in causing the th

epidemic. Some scientists have discarded the claimed rarity of the disease in the 19 century as incorrect, saying that Alzheimer’s disease is a disease of aging, and the increasing lifespan of people accounts for the current high prevalence of the disease. But this cavalier attitude ignores historical data th

indicating there were many elderly people in the 19 century that weren’t getting Alzheimer’s disease with any significant frequency. In this review, after documenting that the observed assertions about historical and demographic facts are correct, evidence is amassed that the main environmental culprit causing the Alzheimer’s epidemic is ingestion of divalent copper, or copper-2. The two sources of copper-2 ingestion are drinking water and multimineral supplement pills containing copper. The increase in copper plumbing use in developed countries parallels the increasing prevalence of Alzheimer’s disease. It has been shown that enough copper is leached from copper plumbing in most households to cause Alzheimer’s disease, using the Alzheimer’s disease animal model studies as a guide to toxic levels. It is relatively easy to avoid or greatly diminish copper-2 ingestion by not using copper containing supplement pills, and testing drinking water for copper levels. If the copper in water is too high, a simple device can be put on the tap to remove copper. In addition to the copper-2 hypothesis, this review covers dietary changes that enhance the epidemic.



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1. Introduction Alzheimer’s disease (AD) is the most common cause of dementia in the U.S and other developed 1

countries. It is the sixth leading cause of death and is the only disease in the top 10 causes of death without effective treatment. One in three seniors dies with AD. In 2015 expenditures attributed to AD were 1

$22 billion in the U.S. These are impressive facts and underscore the important public health problem that AD has become. But these impressive facts don’t do justice to the really disheartening disease AD is to the AD patient and family. It strikes those nearing their retirement years when they and their family should be looking forward to the “golden years” of reward for a lifetime of hard work. Instead the patient steadily becomes dependent on others, eventually losing memory of even their loved ones, deteriorating to the point of needing around-the-clock care. The loss of cognition, especially the loss of memory, robs them of their humanity. An advanced AD patient is in many ways reminiscent of a pet animal. Meanwhile the family loses the companionship of this loved one, and often has to assume the crushing burden of care and financial costs. It is truly a disastrous disease. Other common killers, like heart disease, strokes or cancer, usually kill faster, and without loss of cognition, and therefore without loss of the patient’s humanity. All of this should lead to strong motivation for the health community to find answers to the underlying causes of AD and to find methods to prevent and/or treat the disease. Therefore, it is shocking that a major clue to AD causation is being ignored by the AD scientific community. This clue comes from a simple examination of the history and demographics of AD. Such an examination reveals that in the 19

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century AD was relatively rare in developed countries, while in the 20 century it blossomed into an 1

epidemic, involving 15% of those age 65 to 74, and 44% of those 75 to 84. This epidemic hasn’t involved undeveloped countries, where prevalence remains at around 1%. Some scientists discard these data, simply saying that since AD is a disease of aging, the increasingly aging population explains the AD th

epidemic. That is, there were simply not enough old people around in the 19 century to exhibit the disease. This is a rather cavalier explanation because it ignores historical data, including the U.S. census,


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which show that there were plenty of elderly people in the 19 century, such that at today’s rate, AD would have been seen frequently in clinics and at the autopsy table, and it was not. What clue to AD causation does this examination of historical and demographic data reveal? It practically shouts out, something in the environment of developed countries not shared by undeveloped th

countries has changed in the 20 century, and is causing the AD epidemic. This important clue should have marshaled huge efforts to identify this environmental culprit or culprits but it has not. Instead, rather desultory and unsuccessful efforts have been made to try to find a drug treatment. In this review, the new environmental culprit is shown to be ingestion of divalent copper, or copper-2. Most important, there are relatively simple methods to eliminate or minimize the ingestion of copper-2, and thus mitigate the epidemic of this disastrous disease.

2. History and Demographics of Alzheimer’s Disease (AD) The first demographic fact is that there is currently a major epidemic of AD in developed countries. For example in the U.S., as pointed out earlier, 15% of those age 65 to 74 and 44% of those age 75 to 84 1

have AD. The fact of a high prevalence of AD in the U.S. and other developed countries is widely accepted. The historical fact is that the disease was rare in developed countries prior to 1900. The 2

disease was first named in 1907 after its discoverer, Alois Alzheimer. But esteemed clinicians who wrote th

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extensively in the latter part of the 19 century did not describe an AD-like disease. Osler, who gathered all medical knowledge into a series of volumes including one volume on the brain, did not describe an 4

AD-like disease. Gowers who wrote a textbook of neurology, also did not describe an AD-like disease. 5

Freud, who wrote extensively on abnormal manifestations of the brain, also did not describe AD-like 6

disease. Most important, Boyd wrote a textbook of pathology during this period, and did not describe amyloid plaques or neurofibrillary tangles, hallmarks of AD pathology, in brains at autopsy. As said earlier, most scientists working in AD casually explain the difference in AD prevalence in th

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developed countries between the 19 and 20 century to longer life spans in the later periods, because AD is a disease of aging. But in 1911 in France there were 255,000 people age 65 to 75, and 115,000 7

people age 75 to 85, which at today/s rates, would have generated 100,000 patients, far more than enough to have been frequently observed at clinics and on the autopsy table. Further, the 1900 U.S.



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census shows there were 3.6 million people aged 60 and over, generating over 300,000 patients at today’s rate, again, plenty of patients to be seen in clinics and at the autopsy table. th

Other scientists explain the claim that an AD-like disease was rare in the 19 century to people just ascribing the dementia to normal aging, not realizing it was actually a disease process distinct from aging. In other words, the claim is that people didn’t notice the disease. While this could possibly explain the 3

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clinicians, Osler, Gowers, and Freud, not describing an AD-like disease, although it seems unlikely given their thoroughness and attention to detail, it does not explain brains not showing up at autopsy with 6

amyloid plaques and neurofibrillary tangles to be seen by Boyd and other pathologists. The second demographic fact is that AD prevalence is low in undeveloped countries. This is well documented and is not due to a lack of elderly people in these countries. In India, AD prevalence is 8

1.07% in those aged 65 and over. In Nigeria, Africa, the prevalence of AD in people aged 65 to 74 is 0.52%, and in those aged 75 to 84 it is 1.69%.

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Summarizing, the history and demographics of AD reveal that the disease was rare prior to 1900, th

then exploded into an epidemic in developed countries, particularly in the last half of the 20 century. Undeveloped countries have not shared in the AD epidemic, prevalence remaining low, around the 1% level. What are the possible explanations for the recent AD epidemic in developed countries? 7

Epidemics can be caused by infectious agents, and Waldman and Lamb who wrote a nice book laying out the history and demographics of AD similar to that described above, postulated that AD was a prion disease, and that the AD epidemic in developed countries was due to increased eating of infected beef. However, AD clearly does not behave like a prion disease, and there is no evidence that this is the cause. Likewise, no evidence has ever been found for any other causal infection in AD patients. A major change in an important risk factor for AD could be an explanation, so next these possibilities will be examined. Age is an important risk factor for AD, and certainly the aging of populations increases the case load. But th

as shown earlier, there were enough elderly people in developed countries in the latter 19 century to have revealed numerous cases of AD at today’s rate. Alleles of certain genes, particularly the E-4 allele of


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the apolipoprotein E gene, can cause significantly increased risk of AD. But alleles of genes would not th

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expect to change that fast from the 19 to the 20 centuries. Other risk factors are more minor. Since there is no new causal infectious agent, and no change in risk factors including genetic risk factors that can explain this new AD epidemic, all that seems to be left for an explanation is a change in th

the environment in developed countries in the 20 century. In the next section, the search for the causative environmental agents will be described.

3. The Search for Environmental Factors Causing the AD Epidemic In a book the author is currently writing on the environmental cause of AD and prevention measures, the evidence for all the putative AD causing environmental factors, to rule them in or out, as causative of the AD epidemic has been carefully reviewed. Space does not permit covering all of this information in detail here, but the search methodology and the results of the search are briefly summarized in this section. To be considered as causative of the AD epidemic, a putative agent had to pass two tests. The first was that the agent had to be tied in to AD pathogenesis in some manner. The second was that the th

presence of the agent had to be markedly different in the 20 century, when the epidemic was occurring, th

compared to the 19 century, when it was not occurring. Six metals were considered – aluminum, mercury, lead, iron, zinc and copper. The first three of these are known to cause brain toxicity. All six pass th

the second test, of much greater exposure in the 20 century. But only copper passed the first test, of being involved in AD pathogenesis. Only copper caused AD brain-type pathology in animals, and in human studies, the size of the blood free copper pool is intimately tied to AD pathogenesis, all of which will be reviewed in the next section. Copper-2 exposure was in particular called out, because copper-2 caused AD worsening in animal models and was toxic to human cognition, and exposure to copper-2 th

ingestion was much increased in the 20 century. Diet and lifestyle changes were considered in detail because quite a bit is being written about these factors, mitigating AD by Bredeson,

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or even reducing the risk of AD, by Barnard et al. Regarding th

dietary changes, only increased meat eating in the 20 century in developed countries passed both tests,



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because it increased copper absorption and caused a lifetime of mild increase in body copper load. Other lifestyle factors, such as exercise and mental stimulation, while known to mitigate the disease a little, and possibly reduce risk of AD a little, are not major enough factors to have caused the epidemic. For one th

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thing, there is not convincing evidence that these factors changed greatly from the 19 to the 20 century. Second, if one or more of them does reduce risk of AD a little, it is in the background of the huge number of cases currently occurring because of the major effect of exposure to copper-2 and body copper overload. In summary, copper-2 exposure and increased copper absorption from increased meat eating are identified as the new environmental agents causing the AD epidemic.

4. The Hypothesis that Copper-2 Ingestion is the Major Cause of the AD epidemic The first clue that there was something special about copper and AD causation came from 13

studies by Sparks and Schreurs published in 2003. They found that tiny amounts of copper (0.12 ppm) added to the drinking water of rabbits in an animal model of AD, greatly enhanced amyloid plaque formation and memory loss in the animals. This observation was somewhat fortuitous, but represents good scientific problem solving. The investigators were having problems replicating their AD animal model studies when they moved from W. Virginia to Arizona. Then they realized they were using distilled water for drinking water in Arizona, but had used tap water in W. Virginia. They carefully investigated what was the key agent that produced the disease when tap water was used, and it turned out to be trace 13

amounts (0.12 ppm) of copper. Twenty-five times this amount of copper could be added to rabbit food, and it would not cause this type of toxicity. For reference, the U.S. Environmental Protection Agency 14

(EPA) allows 1.3 ppm copper in human drinking water, ten times the amount found toxic in the animal 15

model. Later Sparks et al replicated these studies in other animal models, including the mouse model, and showed that the finding was specific for copper, it was not reproduced by adding zinc or aluminum to drinking water. These findings were also reproduced in another laboratory.


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Soon thereafter, Morris and colleagues published a paper involving a large Chicago population. They studied nutrient intake and cognition over a period of time. They found that those in the highest quintile of copper intake, who were there because they took a copper containing supplement pill, if they also ate a high fat diet, lost cognition at six times the rate of other groups. This rapid loss of cognition from copper supplement ingestion is shocking, since all multimineral and all multimineral/multivitamin pills contain copper, and a large number of people take these pills every day. 13

Since both the drinking water copper in the Sparks and Schreurs AD animal model studies, and 17

the copper in the supplements in the Morris et al studies are inorganic copper, as opposed to the organic copper of food, Brewer

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hypothesized that inorganic copper was causal of AD. His group had

earlier shown that a portion of ingested inorganic copper was absorbed differently than the organic 24

copper of food. They found that when they administered a radiolabeled inorganic copper orally as part of Wilson’s disease studies, up to 25% of the administered dose appears in the blood in 1-2 hours, much too soon to be processed by the liver. If organic food copper is radiolabeled, none of the label would appear in the blood for 1-2 days, and then it would be incorporated into proteins, such as ceruoplasmin secreted by the liver into the blood. In other words, food organic copper is all processed by the liver, but a significant portion of inorganic copper bypasses the liver and is absorbed directly into the blood, where it appears to be toxic to cognition. 25

The studies of Ceko et al have helped clarify the picture. They studied the speciation (that is, the valence) of copper in foods and drinking water. The copper of water was, as expected, divalent copper, or copper-2. Surprisingly, they found that almost all food copper was monovalent copper, or copper-1. This was surprising because in living tissue, copper-1 and copper-2 form a redox doublet, needed for the catalysis of many enzyme reactions critical to life. Apparently at death or harvest, in the absence of oxygen transport, most copper-2 is reduced to copper-1. That food contains mostly copper-1 and little copper-2 becomes important from the evolutionary standpoint. Copper is a toxic element, and it must be kept in safe channels. Human ancestors evolved 26

ingesting only food copper, primarily copper-1. So there is a receptor in the intestinal cell, called Ctr1,

which binds copper-1 and hands it off to a system that transports it to the liver. Ctr1 can’t bind copper-2.



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Copper-2 can be transported by the divalent cation transporter and by direct diffusion. Some copper-2 enters the blood directly,

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enters the blood free copper pool, and is cumulatively toxic to cognition.

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Thus, in the 19 century and before, humans ingested very little copper-2. But in the 20 century, the widespread use of copper plumbing and habit of ingesting multimineral pills containing copper-2 in developed countries has resulted in widespread ingestion of copper-2, without a safe way to absorb it, and consequently the epidemic of AD. As understanding has developed, the inorganic copper hypothesis has morphed into the copper-2 hypothesis

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for causation of the AD epidemic.

Copper plumbing is incriminated in the AD epidemic first, because the AD epidemic mirrors closely the use of copper plumbing in developed countries, and second, because enough copper is leached into drinking water in most homes to cause AD if the animal model studies are an adequate th

guide. Regarding the first point, copper plumbing began to be used at the start of the 20 century, was greatly slowed by two world wars, and then took off after 1950, such that now, 80-90% of U.S. homes 27

have copper plumbing. A similar pattern has occurred in other developed countries, but copper plumbing isn’t used in undeveloped countries because of the expense. The AD epidemic has followed this pattern th

closely, with a slow increase in cases in the first half of the 20 century, and then exploding into a high prevalence after 1950. With respect to the second point, whether enough copper is leached into the drinking water from copper plumbing, a study of copper content from 280 samples of drinking water from households all 20

across N. America has been conducted. It was found that about one third of them had copper content over 0.1 ppm, the amount causing AD in animal models, one third were below 0.01 ppm and deemed safe, and one third were between these values, and of unknown safety. Thus, one third to two thirds of N. American drinking water samples have enough copper-2 to cause AD, if the animal model studies are a reasonable guide. An interesting aspect of this is that Japan is a developed country, with a low prevalence of AD.

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But Japan has shunned the use of copper plumbing! Apparently, Japan has done this for fear of toxicity, which in retrospect, was a move of unusual foresight. Interestingly, when Japanese migrate to Hawaii, where copper plumbing is used, the prevalence of AD increases to that of other developed countries.


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Of

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course, the diet may have changed some also, but it seems unlikely that meat eating, the only known dietary factor causative of AD, would have changed very much. These Japanese demographics are very supportive of the copper-2 hypothesis. So, in this section the web of evidence indicting copper-2 ingestion as the cause of the current AD epidemic in developed countries has been presented, with the copper-2 coming from drinking water and copper-2 containing supplement pills. When a causal agent for a disease is hypothesized, as copper2 is here, ideally it is good to fulfill the last of Koch’s postulates, which is to give the agent and produce the disease. It is unethical to do such an experiment on humans, although in the Morris et al studies,

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humans have voluntarily ingested copper-2 supplement pills and shown loss of cognition. The studies of 13

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Sparks and Schruers and Sparks et al come as close as possible with animals to test the copper-2 causal hypothesis. Actually, these studies are a randomly controlled trial (an RCT), in animals which is the highest level of evidence in human trials. As in an RCT, animals were given the test substance (copper) in distilled drinking water, control animals were given only distilled water, and other control 15

animals were given aluminum or zinc in distilled drinking water. Only the animals receiving copper had enhanced amyloid plaque development and enhanced memory loss. So, it appears that the evidence is in and there isn’t going to be any more for a long time. Conceivably a human study could be done where a large group of people have copper-2 ingestion eliminated, while another group continues copper-2 ingestion at their normal rate, and after a certain number of years, an examination to see if AD is greatly curtailed in the copper-2 free group. But such a study might take a decade and be expensive. And there is no pharmaceutical company interest because there is no product involved. The major point of this review is that copper-2 ingestion is a major factor causing the AD epidemic. But there is also evidence indicating an increased body copper load irrespective of valence could be a factor in the AD epidemic. That evidence will be discussed in the next section.

5. Evidence Indicating that Increased Body Copper Load, Irrespective of Valence, Could Also Be Partially Causal of the AD Epidemic



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The Squitti group in Italy have done a series of nice studies in which they show that copper toxicity is playing an important role in AD pathogenesis. Their studies involve the blood free copper pool. By way of explanation, blood copper can be viewed as in two pools. The larger, comprising about 85-90% of the blood copper, is covalently bound to ceruloplasmin. The other 10-15% of blood copper is loosely bound to albumin and other molecules, and is the freely available copper used to fill the body’s needs for 30

copper. But if this pool becomes expanded, as it is greatly in untreated Wilson’s disease, the copper in it becomes toxic. The Squitti group has shown first, that the mean blood free copper level is increased in AD.

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Second, they have shown that the free copper level correlates with cognition scores in AD patients, that is 32

the higher the free copper level, the lower the cognition scores. Third, they have shown that the free copper predicts the rate of decrease of cognition scores aver time in AD patients, that is the higher the 33

free copper level, the greater the rate of cognition loss. Finally, they have shown that the higher the blood free copper level, the greater the risk of mild cognitively impaired (MCI) patients, the precursor state 34

to AD, to convert to full AD. These data tie the blood free copper elevations intimately to AD pathogenesis, and indicate strongly that at least in some patients, AD is a disease of copper toxicity. Of course, the valence of the copper isn’t studied in this work, so all it reveals is that copper toxicity in general is playing a role in AD pathogenesis. The Squitti group has also done another kind of copper-related study. They have found that there is a significantly increased prevalence of ATP7B mutant alleles in the AD patient population compared to 35

controls. This means that possessing an ATP7B allele increases risk of AD. ATP7B is the Wilson’s disease gene, and when both copies of this gene are disabled, Wilson’s disease, a disease of severe copper toxicity,

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develops. Carriers of one copy of a disabled ATP7B allele have a mild increase in body

copper loading, manifested by elevated liver and 24 hour urine copper levels. Assuming the ATP7B alleles the Squitti group find increased in prevalence in AD populations cause a mild increase in body copper loading, this indicates that a mild increase in body copper loading from any source, such as a dietary source, would also increase the risk of AD.


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Given that both AD and Wilson’s disease are copper toxicity diseases, the question arises, why do they have such different pathological and clinical effects on the brain? AD causes cognition loss clinically and amyloid plaques and neurofibrillary tangles pathologically, in parts of the brain affecting cognition, and no effect on movement control. Wilson’s disease causes a movement control disease clinically, and no effect on cognition, and no plaques or tangles pathologically. The answer may relate to the intensity and duration of copper toxicity. In the acute neurological presentation of Wilson’s disease, the basal ganglia and other parts of the brain that control movement may be most vulnerable to the very high levels of copper and intense copper toxicity. These patients either die young, or are treated while young, and the copper burden removed. Aging, a major risk factor in AD, doesn’t have time to play a role. In carriers of ATP7B mutant alleles, copper toxicity isn’t intense enough to damage the basal ganglia, but the small extra copper load, causing a mild copper toxicity over a lifetime, works with aging to produce AD. The increased prevalence of ATP7B mutant alleles in the AD population, and the increased AD risk they indicate, wouldn’t be a major factor in the AD epidemic, because the alleles would not change in prevalence enough during the relevant time period, to greatly increase AD cases. But they are a marker that a mild increased body copper loading from any source, including dietary sources, increases risk of AD. So the question can be asked – have there been dietary changes in developed countries in the 20

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century that would increase body loading of copper, and thus contribute to the AD epidemic? And the answer is yes, increased meat eating would do that. It is estimated that there is 50% greater absorption of copper from a normal meat containing diet 36

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compared to a vegetarian diet. Because of improving meat animal feed-lot technology in the 20

century, it has become possible in developed countries to raise enormous numbers of meat animals in a 37

short time. Poultry consumption has also increased. It is estimated, in the U.S. for example, that meat th

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eating has increased by 35% in the 20 century. Thus, it seems likely that the increase in meat eating in th

developed countries in the 20 century, resulting in increased copper absorption, has also contributed to the AD epidemic.

6. Summary



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In this review it was first shown that the history of AD in developed countries reveals that the th

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disease was rare in the 19 century but exploded into an epidemic in the last half of the 20 century. The current demographics reveal that undeveloped countries have not shared in the epidemic, AD prevalence remaining low. Although age is a risk factor for AD, the increasing lifespan of the population in developed countries is not an explanation for the AD epidemic, because there were enough elderly people in the 19

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century to have brought the disease to attention. In the absence of any other explanation, exposure to an th

environmental agent or agents arising in developed countries in the 20 century becomes a very likely cause of the AD epidemic. This likelihood seems to have escaped the attention of the AD scientific community. The major point of this review is to put forth the evidence supporting ingestion of copper-2 as an important cause of the AD epidemic. AD animal model studies

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were reviewed which showed that

tiny amounts of copper-2 in drinking water greatly enhanced AD disease. Human studies revealed that 17

ingestion of copper-2 in supplement pills caused rapid deterioration in cognition. It was shown that food 25

copper is almost all copper-1 and that ingested copper-1 has a safe path from intestinal track to liver,

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where it is put into safe channels. Copper-2 can’t be absorbed by this same pathway. Since copper-2 th

wasn’t ingested in any quantity until the 20 century evolution hasn’t provided a safe path for its absorption. Some of it appears immediately in the blood,

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bypassing the liver and appears to be toxic

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to cognition. In the 20 century humans are ingesting copper-2 from drinking water after it is leached from copper plumbing, and from copper-2 containing supplement pills. The AD epidemic parallels closely the th

explosive use of copper plumbing in the 20 century.

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A secondary point of this review is to also present the evidence that a mild increase in body copper load, irrespective of copper valence, for a lifetime is a risk for AD development. The major evidence for this is that ATP7B alleles which probably cause a mild increase in body copper load are a 35

risk factor for AD.

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The major cause of a mild increase in body copper load in the 20 century in

developed countries is increased meat eating.

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This would increase body copper load because copper

is much better absorbed from meat than from vegetable foods.

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Strong abatement of the AD epidemic should be relatively easy by halting ingestion of copper-2 by throwing away, or not buying, copper containing supplement pills, and by testing drinking water for copper levels. If copper levels are 0.01 ppm or lower they are probably safe. If over that, a reverse osmosis or similar device should be put on the drinking water tap to remove copper. While the copper-2 hypothesis isn’t finally proven, it is supported by very strong evidence. It can be pointed out that those who stopped cigarette smoking when its disease causing character was still an hypothesis, benefitted greatly during the many years until it became accepted as proven. Reducing meat eating is more problematic, because it involves a life style change, always rather difficult. The amount to reduce meat eating is also unknown, although a good estimate would be an average of 50% reduction, since absorption of copper from a typical meat containing diet is about 50% greater than from a vegetarian diet.

(36)

Another estimate would be a 35% reduction in meat eating since it th

th

is estimated meat eating increased about 35% from the 19 to the 20 centuries. According to Sinha et 39

al, reduction in meat eating would be an overall healthy move, since a 50% reduction would reduce overall mortality by 42%. Of the two, stopping copper-2 ingestion, or reducing meat eating, it is the opinion of the author that eliminating copper-2 ingestion is by far the most important. This opinion is based on the Japanese 28

29

data, where moving to Hawaii from Japan, changed AD prevalence from low to the high levels seen in other developed countries. The big difference appears to be the exposure to copper plumbing in Hawaii. The diet may have changed some, but it seems unlikely that meat ingestion would be very different. Abbreviations: AD: Alzheimer’s disease US: United States Ppm: Parts per million RCT: Randomly controlled trial MCI: Mild cognitively impaired



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Funding Sources: No funding was obtained for this review and the author has no competing financial interests.

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Author Biography Dr. George Brewer received his MD from the University of Chicago. He is currently Sellner Emeritus Professor of Human Genetics and Emeritus Professor of Internal Medicine at the University of Michigan. He obtained FDA approval of zinc as a Wilson's disease therapy in 1997, based solely on his data. He is a recognized expert on copper and zinc metabolism. He has shown that divalent copper (copper-2) is absorbed differently than copper-1. Food copper is primarily copper-1, and evolution has provided a safe passage only for copper-1. He has related the 20th century epidemic of Alzheimer's disease to 20th century exposure to copper-2, due to 20th century use of copper plumbing, and to ingestion of copper-2 containing supplement pills. This latter work is the subject of this review.


Copper-2 Hypothesis for Causation of the Current Alzheimer's

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