Poisoning
of Mankind: Blood Types, Copper
Deficiency,
Evolution Theory, Shroud of Turin & Illuminati
Copper: The Maligned Mineral
This
article first appeared in the
April-July/August, 1994
issues of VRP's Newsletter
by A.S. Gissen
Few dietary components are more
misunderstood than copper. Although copper is the third most abundant essential
trace mineral in the body, after iron and zinc, most people consider it
unimportant. Even worse, many people have actually taken steps to exclude it
from their diets and dietary supplements, believing it to be nothing more than
a cause of free radical reactions. This is surprising, because copper has been
recognized as an essential nutrient since the 1920's.1 In the past
seventy years, much has been learned about the important biological roles of
copper and the copper-dependent enzymes. In fact, copper is emerging as one of
the most important minerals in our diet. While unbound, free copper does
generate free radicals in vitro, the relevance of this in the body has been
called more imaginary than real.2 In fact,
copper has an entirely different role in the body, being a component of two of
our most important antioxidant enzymes, copper-zinc superoxide dismutase and
ceruloplasmin.3
Copper Biochemistry
Unbound, free copper is not found in large quantities in the human body.
Instead, almost all of the copper in our bodies is bound to either
transport proteins (ceruloplasmin and copper-albumin), storage proteins
(metallothioneins), or copper containing enzymes.4 A
substantial number of copper metalloenzymes have been found in the human body.
Copper is essential for the proper functioning of these copper-dependent
enzymes, including cytochrome C oxidase (energy production), superoxide
dismutase (antioxidant protection), tyrosinase (pigmentation), dopamine
hydroxylase (catecholamine production), lysyl oxidase (collagen and elastin
formation), clotting factor V (blood clotting), and ceruloplasmin (antioxidant
protection, iron metabolism, and copper transport).5 Most
features of severe copper deficiency can be explained by a failure of one or
more of these copper-dependent enzymes. For instance, depigmentation can be
explained by a tyrosinase deficiency, and the defects of collagen and elastin
causing abnormalities in the connective tissue and vascular system can be
explained by a lysyl oxidase deficiency.
Unfortunately, most research into copper
deficiency has focused on acute, severe deficiency. This is relatively rare in
humans and animals on typical, varied diets. Marginal, chronic deficiency,
however, is much more common. The determination of copper needs and marginal
deficiency is complicated by the fact that while copper deficiency doesn't
necessarily lower the level of copper-dependent enzymes, it does significantly
lower their activity.6 As an example lets look at
lysyl oxidase, one of the most important and best understood roles of copper in
the body. This is the main enzyme involved in the necessary cross-linking of
connective tissue. Optimal functioning of lysyl oxidase ensures the proper
cross-linking of collagen and elastin, vital for the strength and flexibility
of our connective tissue. A reduction in lysyl oxidase activity affects the
integrity of numerous tissues, including our skin, bones, and blood vessels. In
copper deficiency the level of lysyl oxidase isn't altered, but the activity of
the enzyme can be reduced by more than fifty percent.7 Not
surprisingly, some of the hallmarks of copper deficiency are connective tissue
disorders, osteoporosis, and blood vessel damage.
Copper Metabolism
The adult human body contains between 80 and 150 milligrams of copper.8 The liver
is the major location of stored copper, containing about 10 percent of the
total-body content.9 Maintaining
a steady level of copper in the body depends upon a
balance between intestinal absorption and biliary excretion. Biliary excretion
of copper is capable of substantially increasing when excess copper is
ingested.10
The exception to this is in persons with the genetic defect causing Wilson's Disease (hepatolenticular degeneration). This genetic
disease, affecting approximately 1500 Americans, is characterized by a lack of
circulating ceruloplasmin, low serum copper levels, and copper accumulation in
the liver.11
This disease is characterized by an inability of the liver to normally
transport copper, leading to copper overload. In most animals and humans,
however, copper is essentially non -toxic.
Dietary copper is distributed in many
foods. Dried beans and nuts are exceptional sources, while milk and dairy
products are poor sources.12 Studies
have found a wide range of intake among different population groups. In the
Copper is rapidly absorbed from the
stomach and small intestine, and this is influenced little by the form of
copper ingested.15 Although
the absorption of copper may not sound like an exciting subject, if you take
vitamin/mineral supplements containing vitamin C or zinc you should pay close
attention. This is because convincing evidence has accumulated suggesting that
zinc and vitamin C supplements are strong antagonists of copper status and
absorption. In the case of zinc, numerous studies have shown that relatively small increases in dietary zinc significantly lowers
copper absorption.16 This
antagonism has been utilized as a treatment of Wilson's Disease,
with 50 milligrams of zinc taken with each meal being effective in lowering the
abnormal accumulation of copper in people afflicted with this genetic disease
of copper metabolism. Much lower levels of zinc supplementation, as little as
50 milligrams a day, has also been shown to antagonize
copper status in healthy adults.17 Numerous
cases of zinc-induced copper deficiency have been reported in scientific
journals, usually resulting in anemia and blood lipid abnormalities.18 The use
of supplemental vitamin C to lower copper absorption, and hasten copper
deficiency, has been well documented in laboratory animals.19 It has
subsequently been shown in several human studies that vitamin C supplements of
as little as 1500 milligrams can adversely affect markers of copper status,
including copper-zinc superoxide dismutase and ceruloplasmin activity.20 While
the evidence for benefits from taking megadoses of zinc (>50 milligrams
daily) and vitamin C (>1000 milligrams daily) are tentative at best, the
negative consequences of poor copper status are well documented and certain.
There seems little doubt that these interactions will receive increasing
attention in the coming years, due to the documented importance of adequate
copper intake and the common practice of consuming supplemental vitamin C and
zinc without concern or copper supplements.
The long term effects of marginal,
subclinical copper deficiency are not well defined. It has been hypothesized
that low copper status is not only common, but plays a substantial role in
numerous, common degenerative diseases and conditions. If all this has come as
a shock to you, that lowly copper could be so vitally important to your health,
don't be. Over the years the importance of copper in nutrition has even escaped
many of the "so called" experts in the field of nutrition. In the
words of one author who reviewed copper's role in human nutrition, "
...but copper has languished as an orphan among human nutritionists because of
the obscurity of clinical copper-deficiency states in man. As medical
investigators we may have gone down the long road, missing the forest for the
trees...But, the influence of subtle differences in dietary intakes of copper
on human health may be more important than frank copper depletion."21 Indeed,
in next month's newsletter we will continue our review of copper and nutrition,
including copper's role in cardiovascular disease, diabetes, arthritis,
osteoporosis, free radical damage, cancer, inflammatory diseases, immune
function, blood lipids, and thyroid function. In addition, we will examine the remarkable
properties of copper complexes like copper salicylate. These copper complexes
have been extensively studied for their anti-inflammatory and antioxidant
activity, as well as their ability to mimic the superoxide-radical scavenging
activity of superoxide dismutase.
PART 2
Copper and Cardiovascular
Disease
Although the relationship between nutrition
and cardiovascular disease is generally accepted by most people, rarely will
you hear copper mentioned as a contributing factor in this relationship. Based
on the scientific evidence, this is surprising. Almost twenty years ago, it was
postulated that there is a direct relationship between the level of copper in
the human diet and the incidence of cardiovascular disease.22 Copper
has been known to be associated with lipid metabolism since 1973,23 and
research in numerous animal models, including humans, has shown that copper
deficiency can significantly increase the plasma cholesterol concentration.24
Additionally, this increase in cholesterol results in an increase in
It is well documented that animals with
copper deficiency often have abnormal electrocardiograms, and die suddenly.26 In one study that looked at
this relationship, it was found that copper deficiency reduced the life -span
of rats by almost 75%. People with ischaemic heart disease usually die
suddenly, often within one hour of the onset of symptoms. The hearts of people
who die of ischaemic heart disease are hypertrophied and fibrotic, with edema,
loss of cellular outline, and heart rupture often being found.27
Interestingly, all of these pathological changes are found in animals deficient
in copper. In one human study that compared heart copper levels in heart attack
victims and controls that died of other causes, it was found that the hearts of
people that died of myocardial infarction were low in copper.28
Atherosclerotic arteries in humans have degenerative changes similar to those
found in the arteries of copper deficient animals.29 It has
also been demonstrated that copper deficiency significantly increases the susceptibility
of lipoproteins and cardiovascular tissues to lipid peroxidation, thus
increasing the risk of cardiovascular disease.30
While the role of adequate copper levels
in maintaining cardiovascular health is well established, it is not entirely
surprising that copper's importance has been overlooked. One of the laboratory
findings often found in cardiovascular disease is increased serum levels of
copper. While this may sound confusing, recent research has helped to explain
this paradox. It has been suggested, for instance, that an elevated serum
copper level is an independent risk factor for heart disease.29 Many
researchers have considered this elevation of serum copper to play a role in
the pathogenesis of cardiovascular disease, although other researchers have
strongly disagreed with this hypothesis. A recent animal study, however, seems
to have explained this relationship between copper levels and cardiovascular
disease. This study examined the effects of diet-induced atherosclerosis on the
copper levels and status of numerous tissues.30 It was
found that serum copper levels increase significantly, while aorta and liver
copper levels decrease significantly, in rats with experimental
atherosclerosis. Instead of assuming that these elevated copper levels
contribute to the formation of atherosclerosis, these researchers examined the
effects of increasing the dietary copper levels in these animals.
Administration of additional copper resulted in a further increase in serum
copper, a significant decrease in serum cholesterol, and an increase and
normalization in aorta and liver copper levels. However, instead of increasing
the incidence of atherosclerosis, additional copper significantly decreased the
incidence of atherosclerosis in the aorta and coronary arteries. Further, it
has been shown that excess dietary cholesterol causes cardiovascular disease by
lowering the absorption of copper, an effect that is preventable by increasing
the copper level in the diet.31
Taken as a whole, the role of copper in
maintaining cardiovascular health is well established. Copper is essential both
for its role in antioxidant enzymes, like Cu-Zn Superoxide Dismutase and
Ceruloplasmin, as well as its role in Lysyl Oxidase, essential for the strength
and integrity of the heart and blood vessels. With such a central role in
cardiovascular health, it is disappointing that copper has been generally
overlooked in the debate over improving our cardiovascular health. Copper deficiency
has produced many of the same abnormalities present in cardiovascular disease.
It seems almost certain that copper plays a large role in the development of
this killer disease, not because of its excess in the diet, but rather its
deficiency.
PART 3
Copper and Free Radicals
The function of copper as an integral
component of Cu-Zn Superoxide Dismutase (SOD) and Ceruloplasmin is well
established. Cu-Zn SOD, for example, performs antioxidant functions in varied
tissues and fluids, and is indispensable to oxygen-metabolizing organisms.32 In
addition, it has been demonstrated that most copper containing enzymes,
including CuZn-SOD, are produced at a similar rate regardless of copper status,
although their function is significantly impaired by copper deficiency.33 Thus,
the activity of these enzymes are significantly lessened in spite of no
decrease in their production.
Copper deficiency has been shown to
result in a 2-fold increase in the level of lipid hydroperoxides in liver
mitochondria.34
However, an interesting finding was that while the specific activity of Cu-Zn
SOD decreased significantly, so did the activity of catalase and glutathione
peroxidase, two other important antioxidant enzymes that don't require copper
for their activity. Other research has shown that copper deficiency induces an
increase in intracellular and extracellular glutathione levels, which the
authors ascribed to a compensatory adaptive response to the negative effect of
copper deficiency on glutathione peroxidase and Cu-Zn SOD activity.35 It
appears clear that the decrease in antioxidant protection caused by copper
deficiency goes beyond a decrease in the activity of copper-dependent antioxidant
enzymes by inducing a wide range of disturbances in other antioxidant enzyme
systems. Additionally, copper deficiency depresses Cu-Zn SOD activity and
prostacyclin synthesis in the aorta,36 as well
as increases the susceptibility of lipoproteins and heart tissue to
peroxidation, providing strong evidence that copper plays a vital role in the
protection of the cardiovascular system from free -radical mediated damage and
disease.37
Thus, it appears clear that adequate copper is vital for optimal functioning of
many antioxidant enzymes, both copper dependent and otherwise, in varied organs
and tissues.
Copper and Osteoporosis
Almost two hundred years ago, the German physician Rademacher empirically
established that broken bones healed faster when the patient was given copper
supplements.38
In the years that have followed, compelling evidence has established a vital
role for copper in the biosynthesis of bone and connective tissues and their
maintenance.
Lysyl Oxidase, which is involved in the
synthesis of the collagen that constitutes much of bone and connective tissue,
is a copper dependent enzyme. Like other copper dependent enzymes, synthesis of
Lysyl Oxidase is unaffected by copper deficiency, although its activity is
significantly impaired.39
Copper-deficiency induced osteoporosis has been documented in numerous animal
species, including humans.40 While
this condition has most often been documented in young, growing animals and
children, it has been found in young adults and the elderly.41 Copper
deficiency has even been implicated in the etiology of idiopathic scoliosis.42 Skeletal
abnormalities have often been found concurrently with low copper status, and
these have usually been associated with osteoporitic changes and increased
susceptibility to fractures.43
Insufficient copper intake has also been shown to lower bone calcium levels
during long-term deficiency.44
With the essential role that copper plays
in maintaining bone health, it is surprising how little attention has been
given to copper's role in bone diseases. Interestingly, estrogens, which have a
beneficial effect on preventing post-menopausal bone loss, have been shown to
raise the level of ceruloplasmin (the main copper transport protein) two to
three fold, providing a possible explanation for how estrogen positively
influences bone health, as well as cardiovascular health.45
Prolonged cortisone treatment, well known for promoting the development and
accelerating the progression of osteoporosis, has been shown to increase the
body's excretion of copper and lower copper status, providing more evidence of
a correlation between copper status and osteoporosis.46
PART 4
Copper and Immune Function
It has been well documented that adequate copper status is essential for
normal functioning of the immune system in laboratory and domestic animals.47 For
instance, not only has it been shown that the functioning of macrophages were decreased in severely copper deficient rats, but even
marginally copper-deficient rats had impaired immune functioning.48 Interestingly,
immune function was significantly impaired at dietary copper levels that didn't
seem to decrease tissue copper or the activity of red blood cell Cu,Zn-superoxide dismutase (SOD).49 However,
neutrophil SOD-activity and neutrophil function was significantly diminished,
suggesting that immune function may be more sensitive to diets low in copper
than standard measures of copper status. It was also found that immune impairment
could be detected as soon as one week after the initiation of a diet low or
marginal in copper, and the addition of adequate copper reversed the immune
suppression within one week of supplementation. The authors concluded that,
"...the adverse effects of inadequate copper intake on neutrophil activity
occur rapidly and are readily reversed by dietary copper repletion."
Additionally, it has been demonstrated that copper deficiency reversibly
impairs
Copper, Cancer, and
Carcinogenesis
The role of copper in the development of cancer is somewhat similar to
copper's role in cardiovascular disease. This is because the serum level of
copper is often elevated in animals and humans with cancer.52 Like the
elevation of serum copper in cardiovascular disease, it seems that the
elevation of serum copper that occurs in conjunction with cancer is part of the
bodies biological response to the cancer, rather than its cause. Numerous
studies examining varied types of tumors have demonstrated that with remission
usually comes a decrease in serum copper levels to normal.53 Patients
who responded to therapy or surgery usually had a return to normal serum copper
levels, while nonresponders had a persistently elevated serum copper level.
Interestingly, most tumor cells have decreased Cu-Zn SOD activity compared to
normal cells,54 and it
has been suggested that the elevation in serum copper is a physiological
response designed to activate SOD or other copper enzymes in cancer cells to inhibit
their growth. Indeed, numerous copper complexes that demonstrate SOD-mimetic
properties, including copper salicylate, have been shown to possess anticancer,
anticarcinogenic, and antimutagenic effects both in vitro and in vivo.55 In fact,
there is some experimental evidence that copper complexes can cause established
tumor cells to redifferentiate into normal cells,56 and
because of this it has been suggested that, "..the
future use of copper complexes to treat neoplastic diseases has some exciting
possibilities."57
Because copper is an essential component
of several endogenous antioxidant enzymes, and free radicals have been proposed
to play a role in the process of carcinogenesis, the effects of dietary copper
levels on the development of cancer has been investigated. Rats fed low copper
diets show a higher incidence of carcinogen -induced colon tumors when compared
with rats fed a high copper diet.58 Another study
in rats found similar results, but with the additional finding of a decrease in
aortic integrity possibly leading to eventual aneurysm.59 These
findings are especially interesting for two reasons. To begin with, dietary
copper has often been incorrectly suggested to be a cause or promoter of
cancer. If this was true increased dietary copper would enhance, rather than
inhibit, carcinogen-induced gastrointestinal malignancy. Lastly, it has been
shown that there is a relationship between aortic aneurysmal disease and
malignancy in humans, and this is likely the result of decreased copper status
as demonstrated in the animal study mentioned above.60
Copper, Inflammation, and
Arthritis
As long ago as 1000 B.C., foods high in copper and copper bracelets were
thought to be beneficial in treating arthritic conditions.61 In 1945, patients with
rheumatoid arthritis were shown to exhibit higher than normal serum copper
levels.62
Indeed, the copper content of serum is known to be elevated above normal values
in various inflammatory diseases in man and laboratory animals.63 Despite
this seeming contradiction, copper complexes were successfully used from the
1940's to 1970's in the treatment of numerous conditions characterized by
arthritic changes and inflammation.64 Even the
time-tested copper bracelet was eventually shown to be an effective
anti-inflammatory, due to the absorption of copper through the skin.65 However,
the development of anti-inflammatory steroids and aspirin-like nonsteroidal
anti-inflammatory drugs quickly replaced copper compounds in the treatment of
these conditions. Numerous researchers have examined the paradoxical role of
copper in the process of inflammation, and they have determined that the
increase in serum copper is a physiological response to inflammation, rather
than a promoter of it.66 In fact,
the main copper containing enzyme, ceruloplasmin, is significantly elevated in
inflammatory conditions and has anti -inflammatory activity.67
Additionally, it has been shown that copper deficiency increases the severity
of experimentally-induced inflammation,68 and that
dietary copper must be increased to maintain adequate copper status of animals
in an inflammatory state.69
With the knowledge that many copper
complexes possess anti-inflammatory activity, and the finding that these copper
complexes almost always have significantly stronger activity than their parent
compounds, it has been hypothesized that the active form of many popular
anti-inflammatory drugs are their copper chelates. Interest in copper complexes
as anti-inflammatory drugs and antiarthritics is evidenced by the large number
of reviews and symposia proceedings published in recent years.70 The sum
of this research has shown that copper chelates of most anti-inflammatory
compounds, as well as many other compounds, have strong anti-inflammatory
activity in numerous models of inflammation. Also, these copper chelates have
lower toxicity and stronger anti -inflammatory activity than their parent
compounds.
Copper Complexes
Although most research utilizing copper
complexes has been to determine anti-inflammatory activity, copper complexes
have shown potential as a physiological approach to the treatment of numerous
chronic diseases. This potential has been expanded to include, in addition to
inflammatory diseases, gastrointestinal ulcers, cancers, carcinogenesis, and
diabetes. In these conditions much of the research interest has centered on the
finding that many copper complexes demonstrate superoxide dismutase (SOD)
activity. Because of this, many of these compounds have been designated as
SOD-mimetics. One of the better recent reviews on this topic of copper
complexes is a good example of the breadth of research that has been published
on this topic. This review, published in the journal Progress in Medicinal
Chemistry, is 110 pages long and contains a bibliography of 736 references.71
Unfortunately, despite the tremendous promise that copper complexes have in
many varied diseases and conditions, clinical interest in these compounds has been
almost nonexistent. While copper is slowly becoming less misunderstood, one can
only hope that it will eventually be properly utilized in its potential for
maintaining health and treating disease.
Copper Supplementation
The importance that adequate copper nutriture plays in ensuring health,
coupled with the fact that few of us obtain the recommended 2-3 milligrams
daily of copper in a normal diet, makes copper supplementation essential if we
are to prevent an inadequate copper intake. Most human supplements of copper
contain either copper sulfate or copper gluconate, two well utilized forms of
copper. However, because copper outside of biological systems can catalyze
oxidation, the preferred type for multivitamin/mineral supplements is a coated
form of copper, such as coated copper gluconate. This allows for all the
important benefits of copper, without having the copper lower the
vitamin/mineral supplements shelf-life. For most of us on average diets that
contain 1-2 milligrams of copper, and not consuming large amounts of the copper
antagonists vitamin C (>1000 milligrams) and zinc (>30 milligrams) daily,
a daily supplement of 1-3 milligrams of copper should be adequate. Consumers of
larger amount of vitamin C and zinc would be well advised to supplement with 3
milligrams of copper daily. Additionally, some people may wish to supplement
with special forms of copper such as copper salicylate. Total copper
supplementation should not exceed 5 milligrams daily, except under a
physician's supervision.
No information in this article should be
taken as a recommendation. If you have any questions about the relationship
between copper and your health, seek the advice of a qualified physician.
Back
To Main Page – Poisoning of Mankind – Copper Deficiency
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Poisoning
of Mankind: Blood Types, Copper
Deficiency,
Evolution Theory, Shroud of Turin & Illuminati