45 replies to this topic

[Blue]

Purpose of review: To review the toxicity and risks of free copper in Wilson's disease, Alzheimer's disease, other disease of neurodegeneration, and cognitive loss in the general population. We will also review the anticopper drugs and how lowering free copper levels with an anticopper drug inhibits fibrosis, inflammation, and autoimmunity.
Recent findings: Some exciting recent work indicates that free copper levels are increased in Alzheimer's disease, and copper may be involved in disease pathogenesis, opening the way to possible therapy of Alzheimer's disease with anticopper drugs. Copper may also be involved in other diseases of neurodegeneration. A very exciting recent study indicts high intake of copper, mostly from copper supplements, in conjunction with a high-fat diet in more rapid cognitive decline in the general population. Other data indicate that even low levels of copper in drinking water, perhaps similar to copper supplements, bypasses the liver, enters the circulation, increases the blood-brain penetration of copper, and may cause damage.
Summary: Some of the implications are that Alzheimer's disease and other diseases of neurodegeneration and fibrotic, inflammatory, and autoimmune diseases may be treatable by lowering the availability of free copper. People in the general population may wish to take steps to lower their free copper levels and, in particular, to abstain from taking copper supplements and ingesting significant amounts of copper in drinking water.
http://journals.lww...._and_the.9.aspx

Scientists say the association between copper and Alzheimer disease is based on no fewer than five animal models, a large epidemiologic study, numerous in vitro studies and, now, a compelling model for how it might function in the brain... ...the four researchers whose work has been quoted here: all four have given up drinking unfiltered tap water, which typically contains trace levels of copper.
http://www.neurotodayonline.com/pt/re/neur...#33;8091!-1

These highly statistically significant findings confirm previously reported scientific results implicating the involvement of elevated levels of "free" copper in the pathogenesis of Alzheimer’s disease. One possibility is that these patients present with increased ‘free’ copper is due to their dietary source of highly oxidative mineral. It is well known that many municipal tap water sources as well as dietary supplements, such as multi-vitamins which generally contain up to 2mg of free copper, can supply more copper than an elderly patients might need.
http://www.adeonapha...?...9&newsID=26

Among persons whose diets were high in saturated and trans fats, higher copper intake was associated with a faster rate of cognitive decline. In multiple-adjusted mixed models, the difference in rates for persons in the highest (median, 2.75 mg/d) vs lowest (median, 0.88 mg/d) quintiles of total copper intake was –6.14 standardized units per year (P<.001) or the equivalent of 19 more years of age. There was also a marginally statistically significant association (P = .07) with the highest quintile of food intake of copper (median, 1.51 mg/d) and a strong dose-response association with higher copper dose in vitamin supplements. Copper intake was not associated with cognitive change among persons whose diets were not high in these fats,
http://archneur.ama-...tract/63/8/1085

BACKGROUND: Serum copper not bound to ceruloplasmin ("free") appears slightly elevated in patients with Alzheimer disease (AD). We explored whether a deregulation of the free copper pool can predict AD clinical worsening. METHODS: We assessed levels of copper, iron, zinc, transferrin, ceruloplasmin, peroxides, total antioxidant capacity, free copper, and apolipoprotein E genotype in 81 patients with mild or moderate AD, mean age 74.4, SD = 7.4 years, clinically followed up after 1 year. The association among biologic variables under study and Mini-Mental State Examination (MMSE) (primary outcome), activities of daily living (ADL), and instrumental activities of daily living (IADL) (secondary outcomes) performed at study entry and after 1 year were analyzed by multiple regression. RESULTS: Free copper predicted the annual change in MMSE, adjusted for the baseline MMSE by means of a linear regression model: it raised the explained variance from 2.4% (with only sex, age, and education) to 8.5% (p = 0.026). When the annual change in MMSE was divided into < 3 or > or = 3 points, free copper was the only predictor of a more severe decline (predicted probability of MMSE worsening 23%: odds ratio = 1.23; 95% confidence interval = 1.03-1.47; p = 0.022). Hyperlipidemic patients with higher levels of free copper seemed more prone to worse cognitive impairment. Free copper at baseline correlated with the ADL and IADL clinical scales scores at 1 year. CONCLUSIONS: These results show an association between copper deregulation and unfavorable evolution of cognitive function in Alzheimer disease. Further research is needed to establish whether copper is an independent risk factor for cognitive decline.
http://www.ncbi.nlm....pubmed/19122030

Excess copper exposure is thought to be linked to the development of Alzheimer's disease (AD) neuropathology. However, the mechanism by which copper affects the CNS remains unclear. To investigate the effect of chronic copper exposure on both beta-amyloid and tau pathologies, we treated young triple transgenic (3×Tg-AD) mice with 250 ppm copper-containing water for a period of 3 or 9 months. Copper exposure resulted in altered amyloid precursor protein processing; increased accumulation of the amyloid precursor protein and its proteolytic product, C99 fragment, along with increased generation of amyloid-beta peptides and oligomers. These changes were found to be mediated via up-regulation of BACE1 as significant increases in BACE1 levels and deposits were detected around plaques in mice following copper exposure. Furthermore, tau pathology within hippocampal neurons was exacerbated in copper-exposed 3×Tg-AD group. Increased tau phosphorylation was closely correlated with aberrant cdk5/p25 activation, suggesting a role for this kinase in the development of copper-induced tau pathology. Taken together, our data suggest that chronic copper exposure accelerates not only amyloid pathology but also tau pathology in a mouse model of AD.
http://www3.intersci...l...=1&SRETRY=0

[Lufega]

Wilson's can be diagnosed by a quantitative copper liver test. I had one done just a few weeks ago and it was normal. What level of free copper is considered high to be included as a causative agent for Alzheimer's?

[Blue]

<br />Wilson's can be diagnosed by a quantitative copper liver test. I had one done just a few weeks ago and it was normal. What level of free copper is considered high to be included as a causative agent for Alzheimer's?<br /><br /><br />

The penultimate study above stated "Serum copper not bound to ceruloplasmin ("free") appears slightly elevated in patients with Alzheimer disease (AD).". I suspect very low elevations may be problematic since the second link states "a study in mice, half of whom were fed water with .12 mg of copper per liter (less than one-tenth the Environmental Protection Agency's limit for drinking water) and half fed distilled water without copper. Mice fed copper had about twice as much of the metal in their endothelial cells as the control mice, about one-third fewer LRP molecules and one-third more amyloid beta in their brains after 10 weeks."

[Blue]

Hopefully the problem regarding supplements can be avoided if a non-free form of copper is used (and it is not broken down to free copper before being absorbed).

[Blue]

Or maybe multis should not contain copper at all since copper defiency is rare. Yes, zinc is inversly related to copper but since zinc defiency is much more common so a multi with a small amout of zinc without copper may not cause problems.

Hm, high copper may be generally bad:
Data from the Paris Prospective Study 2, a cohort of 4035 men age 30-60 years at baseline, were used to assess the association between serum zinc, copper, and magnesium and all-cause, cancer, and cardiovascular disease mortality.... ....High copper values (4th quartile) were associated with a 50% increase in RRs for all-cause deaths (RR = 1.5; 95% confidence interval = 1.1-2.1), a 40% increase for cancer mortality (1.4; 0.9-2.2), and a 30% increase for cardiovascular mortality (1.3; 0.6-2.8) compared with low values (1st quartile).
http://journals.lww....p;type=abstract

[Blue]

Fascinating, high copper serum is actually worse than high iron levels in a prospective study:

Three hundred seven cancer deaths (ICD-9 140–195, 199–208) were identified during 83,664.4 person-years of follow-up. Cancer mortality per 1000 person-years was 3.7 (4.7 for men and 2.8 for women). For men and women combined, the adjusted RRs (95% confidence intervals, CI) for the four levels were 0.96 (0.57–1.61), 1.00 (reference), 1.12 (0.80–1.58), 1.86 (1.07–3.22) for iron; 0.97 (0.56–1.70), 1.00 (reference), 1.36 (0.99–1.87), 1.82 (1.10–3.02) for TS; 0.76 (0.44–1.31), 1.00 (reference), 1.10 (0.77–1.58), 1.89 (1.07–3.32) for copper; and 0.75 (0.50–1.13), 1.00 (reference), 0.64 (0.47–0.88), 0.84 (0.53–1.33) for zinc. When the exposures were analyzed as continuous variables, the adjusted RRs (CI) were 1.66 (1.03–2.68) for 100 μg/dl iron increase, 1.17 (1.01–1.36) for 10% TS increase, 1.98 (1.12–3.50) for 100 μg/dl copper increase, and 0.57 (0.16–1.96) for 100 μg/dl zinc increase. Sex differences in the adjusted RRs for iron, TS, and copper were suggestive.
http://linkinghub.el...047279703001194

Copper should probably be eliminated from multis like iron.

Edited by Blue, 03 July 2009 - 11:41 PM.

[nameless]

I'm not sure if serum copper is very accurate, or in fact even measures copper status. Same goes with many minerals, which are just rough estimates (like zinc and magnesium).

Via Linus Pauling Institute:
It is important to note that serum copper largely reflects serum ceruloplasmin and is not a sensitive indicator of copper nutritional status. Serum ceruloplasmin levels are known to increase by 50% or more under certain conditions of physical stress, such as trauma, inflammation, or disease. Because over 90% of serum copper is carried in ceruloplasmin, which is increased in many inflammatory conditions, elevated serum copper may simply be a marker of inflammation that accompanies atherosclerosis. In fact, serum copper was recently found to be elevated in patients with rheumatic heart disease (16). In contrast to the epidemiological findings linking serum copper to heart disease, two autopsy studies found copper levels in heart muscle were actually lower in patients who died of CHD than those who died of other causes (17)

[Blue]

<br />I'm not sure if serum copper is very accurate, or in fact even measures copper status. Same goes with many minerals, which are just rough estimates (like zinc and magnesium).<br /><br />Via Linus Pauling Institute:<br />It is important to note that serum copper largely reflects serum ceruloplasmin and is not a sensitive indicator of copper nutritional status. Serum ceruloplasmin levels are known to increase by 50% or more under certain conditions of physical stress, such as trauma, inflammation, or disease. Because over 90% of serum copper is carried in ceruloplasmin, which is increased in many inflammatory conditions, elevated serum copper may simply be a marker of inflammation that accompanies atherosclerosis. In fact, serum copper was recently found to be elevated in patients with rheumatic heart disease (16). In contrast to the epidemiological findings linking serum copper to heart disease, two autopsy studies found copper levels in heart muscle were actually lower in patients who died of CHD than those who died of other causes (17)<br />

<br /><br /><br />

True, but not that the two studies above were prospective with serum taken before clinical disease. Although of course subclinical disease may have increased the levels.

[Blue]

More bad news for copper:

In this review, we point out that natural selection does not act to lessen human diseases after the reproductive and caregiving period and that normal levels of iron and copper that may be healthy during the reproductive years appear to be contributing to diseases of aging and possibly the aging process itself. It is clear that oxidant damage contributes to many of the diseases of aging, such as atherosclerosis, Alzheimer’s disease, Parkinson’s diseases, diabetes, diseases of inflammation, diseases of fibrosis, diseases of autoimmunity, and so on. It is equally clear that both iron and copper can contribute to excess production of damaging reactive oxygen species through Fenton chemistry. Here, we examine the evidence that "normal" levels of iron and copper contribute to various diseases of aging.
http://www.ebmonline...tract/232/2/323

[synaesthetic]

Uh oh!

've been taking Jarrow Zinc Balance (with copper)

I should test my copper levels so I'm not just haphazardly taking copper.

[nameless]

Uh oh!

've been taking Jarrow Zinc Balance (with copper)

I should test my copper levels so I'm not just haphazardly taking copper.

How do you accurately test copper levels? Serum is no good. Hair is inaccurate. Barring a liver biopsy, how will you know your true copper status by some test? And I expect Lufega to tell you that isn't the most pleasant experience. I wouldn't worry about the 1 mg of copper in zinc balance, and even if a concern, a serum test won't be of much use anyway. Maybe measure your dietary intake?

[niner]

Uh oh!

've been taking Jarrow Zinc Balance (with copper)

I should test my copper levels so I'm not just haphazardly taking copper.

How do you accurately test copper levels? Serum is no good. Hair is inaccurate. Barring a liver biopsy, how will you know your true copper status by some test? And I expect Lufega to tell you that isn't the most pleasant experience. I wouldn't worry about the 1 mg of copper in zinc balance, and even if a concern, a serum test won't be of much use anyway. Maybe measure your dietary intake?

It might be difficult to get dietary values. You would need to know the level of the water that you drink and cook with. It's pretty easy to see 1ppm in drinking water as I recall, so drink a liter, get a mg.

[niner]

Blue, thanks for bringing this to our attention. What led to your interest in copper?

[markymark]

Uh oh!

've been taking Jarrow Zinc Balance (with copper)

I should test my copper levels so I'm not just haphazardly taking copper.

Copper in whole blood might be useful.
Calculation of free copper from coeruloplasmin and serum copper gives info about too much of the free copper fraction

I would like to remind us, that Copper is an essential metal.
What is the right dose and level of copper:
under excessive Zinc supplementation
under high-dose resveratrol ...?

There are some more of these neurologic papers on copper deficiency and neurological symptoms in Pubmed

1: J Neurol Neurosurg Psychiatry. 2009 May;80(5):524-7. Epub 2008 May 21.

Clinical and electrodiagnostic findings in copper deficiency myeloneuropathy.

Goodman BP, Bosch EP, Ross MA, Hoffman-Snyder C, Dodick DD, Smith BE.

Department of Neurology, Mayo Clinic, Scottsdale, AZ 85259, USA.
goodman.brent@mayo.edu

INTRODUCTION: Copper deficiency is an increasingly recognised cause of
neurological impairment. This retrospective review highlights clinical and
electrodiagnostic findings in patients diagnosed at our institution with copper
deficiency. METHODS: Clinical, radiographic and electrodiagnostic findings were
reviewed in patients with evidence of copper deficiency. Patients with other
potential causes of myelopathy or neuropathy were excluded. RESULTS: The
predominant clinical feature in all six patients was a sensory ataxia, resulting
in marked gait unsteadiness. Nerve conduction studies and needle EMG were
performed in all patients and revealed a mild to moderate distal, axonal,
sensorimotor peripheral neuropathy. Median and tibial somatosensory evoked
potentials were abnormal in all five patients in which it was performed, showing
impaired conduction in central or proximal peripheral somatosensory pathways.
CONCLUSIONS: This pattern of electrodiagnostic findings suggests that impairment
in somatosensory pathways demonstrated by somatosensory evoked potential testing
is the main cause of the sensory ataxia in patients with copper deficiency.

[Blue]

Blue, thanks for bringing this to our attention. What led to your interest in copper?

I was searching Google scholar for something else and happened to stumble upon this.

I would like to remind us, that Copper is an essential metal.
What is the right dose and level of copper:
under excessive Zinc supplementation
under high-dose resveratrol ...?

If it has prooxidant effects that are similar to iron, then as for iron one would ideally want just enough to build the substances that incorporate copper, but as little as possible beyond this. So its ideal daily intake range would be quite narrow with too little or too much causing adverse effects.

[Blue]

Here is an interesting patent (I am not in any way associated with it) that advocates that copper (and iron) supplementation should be in slow-release form (again, I think for multis with only a moderate amount of zinc the better option would be no copper since zinc deficiency is much more common than copper deficiency which is rare):


"Copper and iron are essential trace elements but are also the primary oxidants to people. Since copper and iron are necessary, their intake is recommended. Copper and iron enter the blood with the flux of water resulting in elevated free copper and iron in blood. In the elderly, copper and iron also may enter the brain due to the leaky blood brain barrier. It is a function of the liver to process excess copper and iron in the blood (and brain) and bring these toxins down. However, processing is not instantaneous, and elderly people who generally have impaired liver function, and younger people with impaired liver function, the levels of copper and iron oxidants often stay elevated much longer and may cross the blood/brain barrier.

Moreover, despite its essentiality, however, copper also is an extremely reactive oxidative species that has the potential to be very toxic to cells, proteins, and organ systems such as the liver, brain and vasculature. In order to deliver and utilize copper in the body on demand wherever it is needed, mammalian systems have developed an elaborate regulatory network of highly specific, homeostatic, copper-binding cuproproteins that serve to properly scavenge, store, transport, chaperone and excrete copper while minimizing the potential for copper to inadvertently oxidize or reduce proteins and lipids. Many different cuproproteins have been identified and their functions have been elucidated over the years. Examples of such cuproproteins include, but are not limited to, matrix metalloprotein, ceruloplasmin, copper/zinc superoxide dismutase, amyloid precursor protein, apolipoprotein E, tau, homocysteine, albumin and chaperone for copper zinc superoxide dismutase, to name a few.

One of the most problematic and potentially toxic sources of copper for humans is the abundance of toxic copper ions that exists in drinking water systems. Unlike the copper found in food, which is bound to proteins and the absorption of which is relatively easily regulated by the intestines and the slow dissolution from food during digestion, copper in drinking water occurs in the form of cupric ion (Cu ⁺² ) in either an unbound form or in a form complexed only loosely with organic ligands. Copper ions are generally more bioavailable in water than they are in food; there may be components in food that can influence the metabolism, absorption and mobilization of copper in human diets."


"Solubilized copper or copper loosely bound to small ligands, such as that commonly found in tap water, is highly bioavailable (up to 65%) and, due to water fluxes in the intestines, has the capacity to overwhelm the copper homeostasis mechanisms of the gastrointestinal enterocytes and liver, and enter the portal and systemic circulation in a potentially toxic form loosely bound to albumin and other low kinetic copper binding proteins."

"Most nutritional supplements that contain copper or iron contain the copper or iron as pure salts. However, when supplied is pure salts, the copper and iron may enter the blood too quickly, resulting in elevated free copper and iron in the blood, which in turn may result in problems as discussed above."


http://www.freepaten...2008112824.html

Edited by Blue, 04 July 2009 - 01:08 PM.

[david ellis]

http://journals.lww....p;type=abstract[/b]

Blue,
Your source came to the conclusion that copper was only bad when there was a shortage of magnesium or zinc.---The risk of copper was much smaller when there was sufficient zinc or magnesium. Maybe the problem is not too much copper, but not enough of something else.

From Your Link
"Conclusions: High serum copper, low serum magnesium, and concomitance of low serum zinc with high serum copper or low serum magnesium contribute to an increased mortality risk in middle-aged men."

A little more nuance from Relentless Improvement "Balanced Zinc-to-Copper ratios. Getting too much of either of these nutrients creates a functional deficiency in the other". The advice from them is to take your copper and zinc in balanced amounts and avoid trouble.

[Blue]

http://journals.lww....p;type=abstract[/b]

Blue,
Your source came to the conclusion that copper was only bad when there was a shortage of magnesium or zinc.---The risk of copper was much smaller when there was sufficient zinc or magnesium. Maybe the problem is not too much copper, but not enough of something else.

From Your Link
"Conclusions: High serum copper, low serum magnesium, and concomitance of low serum zinc with high serum copper or low serum magnesium contribute to an increased mortality risk in middle-aged men."

A little more nuance from Relentless Improvement "Balanced Zinc-to-Copper ratios. Getting too much of either of these nutrients creates a functional deficiency in the other". The advice from them is to take your copper and zinc in balanced amounts and avoid trouble.

Your interpretation is not what the study found (just one of the many I have linked to). High copper and low magnesium when looked at individually was generally very bad (RR of 1.5 for the highest serum quartile for copper alone). Also having low serum zinc increased the risk even more (an amazing increased RR of 2.6 for all-cause deaths).

Results: High copper values (4th quartile) were associated with a 50% increase in RRs for all-cause deaths (RR = 1.5; 95% confidence interval = 1.1-2.1), a 40% increase for cancer mortality (1.4; 0.9-2.2), and a 30% increase for cardiovascular mortality (1.3; 0.6-2.8) compared with low values (1st quartile). High magnesium values were negatively related to mortality with a 40% decrease in RR for all-cause (0.6; 0.4-0.8) and cardiovascular deaths (0.6; 0.2-1.2) and by 50% for cancer deaths (0.5; 0.3-0.8). Additionally, subjects with a combination of low zinc and high copper values had synergistically increased all-cause (2.6; 1.4-5.0) and cancer (2.7; 1.0-7.3) mortality risks. Similarly, combined low zinc and high magnesium values were associated with decreased all-cause (0.2; 0.1-0.5) and cancer (0.2; 0.1-0.8) mortality risks.

The opinion of a vitamin reseller is not of high significance compared to clinical studies.

Edited by Blue, 04 July 2009 - 02:10 PM.

[david ellis]

The opinion of a vitamin reseller is not of high significance compared to clinical studies.

Relentless Improvement's good reputation is based on respect for their reading of clinical studies.

[OneScrewLoose]

So, is this copper causing these illnesses or high copper being a result? I am inclined to believe the latter.

[Blue]

The opinion of a vitamin reseller is not of high significance compared to clinical studies.

Relentless Improvement's good reputation is based on respect for their reading of clinical studies.

Actually, they are just quoting AOR:
"Balanced Zinc-to-Copper ratios. Getting too much of either of these nutrients creates a functional deficiency in the other. It is therefore essential that supplementation provide a harmonious amount of each mineral. Unfortunately, many formulas contain potentially harmful Zinc-to-Copper ratios. Animal and human evidence suggests that an adequate Zinc-to-Copper ratio should be of about ten to one. Studies using a 23.5 to 1 ratio led to reductions in levels of copper-based antioxidants, increased total and LDL cholesterol and caused abnormalities in cardiac function."
http://www.aor.ca/ht...ucts.php?id=142

Unfortunately no links. I have tried to search for these studies but can only find adverse effects when giving high doses of zinc. 50 mg/day or more as compared to the RDA which is 11 mg/day for men and 8mg/day for women.

"The major consequence of long-term consumption of excessive zinc is copper deficiency. Total zinc intakes of 60 mg/day (50 mg supplemental and 10 mg dietary zinc) have been found to result in signs of copper deficiency. In order to prevent copper deficiency, the U.S. Food and Nutrition Board set the tolerable upper level of intake (UL) for adults at 40 mg/day, including dietary and supplemental zinc."
http://lpi.oregonsta.../minerals/zinc/

"Abstract Pharmacological doses of zinc can adversely affect body copper status. The resulting copper deficiency can impact directly upon cholesterol metabolism and a suboptimal copper status has been observed to influence markers of hemostasis (specifically fibrinogen and the copper-containing coagulation factors V and VIII). The aim of this investigation was to examine the effect of a low level of zinc supplementation, to include dietary intake, at the United States tolerable upper intake level of 40 mg/d upon indicators of lipid metabolism, hemostasis, and copper. Thirty-eight subjects were recruited onto a double-blind placebo-controlled intervention trial and randomly selected to one of two groups. Group 1 took zinc supplements (30 mg/d) for 14 wk followed by copper supplements (3 mg/d) for 8 wk (to counteract adverse effects, if any, of zinc supplementation). A second group took placebo supplements for the full duration of the trial. Estimated dietary zinc intake approximated 10 mg/d. The effect of supplement was analyzed by repeated-measures analysis of variance (anova). Results indicate that no effect of zinc supplementation on putative indices of copper status, lipoprotein metabolism, and markers of hemostasis. These results indicate that short-term low-level zinc supplementation (total intake 40 mg/d) is not detrimental to health."
http://www.springerl...8m30612tm25n26/

So a total of 40 mg/day of zinc appears to be safe regarding copper status. Please give a study if claiming otherwise. Now, if a a multi contains only the RDA of of 11 mg for men, which adds to average food intake of 13 mg zinc for men (slightly lower values for women), then there is no reason or evidence that it must also contain copper due to zinc causing copper malabsorption. The studies finding harmful effects from copper supplements, possible very harmful effects from the prooxidant effects of high copper levels in general, and the rarity of deficiency suggests that multis should not contain copper at all.

[nameless]

There are a couple of issues to consider:

First, are the studies measuring copper accurate? Meaning, are they measuring actual copper status, or inflammation instead (which appears as high serum copper)?

Are the negative results due to high levels of copper or deficiencies in zinc? High copper usually = low zinc. Would adequate zinc levels offset any negative effects from copper?

Is copper pro-oxidant at a certain level in the body, and what is this level? According to AOR, I think it's 7mg or higher.

[Blue]

So, is this copper causing these illnesses or high copper being a result? I am inclined to believe the latter.

Regarding free copper, for example this suggests that copper is a cause and not an effect. "a study in mice, half of whom were fed water with .12 mg of copper per liter (less than one-tenth the Environmental Protection Agency's limit for drinking water) and half fed distilled water without copper. Mice fed copper had about twice as much of the metal in their endothelial cells as the control mice, about one-third fewer LRP molecules and one-third more amyloid beta in their brains after 10 weeks."
http://www.neurotodayonline.com/pt/re/neur...#33;8091!-1

Regarding the two prospective studies looking at general mortality they were prospective with serum levels (not free copper) taken before outset of clinical disease. Yes, subclinical disease may have caused the copper-binding ceruloplasmin to increase due to inflammation and other factors. But for the first study they looked at mortality during an 18-year follow up and for the second it seems to be a 14-year follow-up. If there were a subclinical disease still sufficiently severe to affect the whole body and cause such a very large increase in ceruloplasmin I would expect the subclinical disease to become clinical relatively quickly and not ten years later.

[nameless]

Regarding the two prospective studies looking at general mortality they were prospective with serum levels (not free copper) taken before outset of clinical disease. Yes, subclinical disease may have caused the copper-binding ceruloplasmin to increase due to inflammation and other factors. But for the first study they looked at mortality during an 18-year follow up and for the second it seems to be a 14-year follow-up. If there were a subclinical disease still sufficiently severe to affect the whole body and cause such a very large increase in ceruloplasmin I would expect the subclinical disease to become clinical relatively quickly and not ten years later.

Heart disease could be one example of long term inflammation, resulting in increased mortality + high serum copper. Heart disease doesn't tend to just 'happen' and kill you right away, it takes years and years. Did those studies state what most participants with high copper died of?

Edited by nameless, 04 July 2009 - 05:51 PM.

[Blue]

Heart disease could be one example of long term inflammation, resulting in increased mortality + high serum copper. Heart disease doesn't tend to just 'happen' and kill you right away, it takes years and years. Did those studies state what most participants with high copper died of?

There are a couple of issues to consider:

First, are the studies measuring copper accurate? Meaning, are they measuring actual copper status, or inflammation instead (which appears as high serum copper)?

Are the negative results due to high levels of copper or deficiencies in zinc? High copper usually = low zinc. Would adequate zinc levels offset any negative effects from copper?

Is copper pro-oxidant at a certain level in the body, and what is this level? According to AOR, I think it's 7mg or higher.

Heart disease could be one example of long term inflammation, resulting in increased mortality + high serum copper. Heart disease doesn't tend to just 'happen' and kill you right away, it takes years and years. Did those studies state what most participants with high copper died of?

Please have a look at links to the two prospective studies I gave earlier. They may answer some of your questions.
http://journals.lww....p;type=abstract
http://linkinghub.el...047279703001194

I have not seen any particular level at which the prooxidant effect of copper appear although the severity of course increases. Seems similar to iron. Likely has a prooxident effect by itself at any level so its damage must be lessened by various antioxidant defense mechanisms. Also at those levels when it is essential and needed as building material for compounds. Copper can take the place of iron in the Fenton Reaction, see earlier study.
http://en.wikipedia.org/wiki/Fenton's_reagent

Both the prospective studies looked at cancer deaths. One only at those. When a cancer is so large that it cause a large increase in an inflammatory marker I suspect that that clinical presentation is not far away.

Regardless of the significance of the total serum copper prospective studies, the free copper caused by copper supplements looks likely to contribute to at least Alzheimer's, so at the very least it would be better if multis used a more slowly absorbed form.

Edited by Blue, 05 July 2009 - 12:04 AM.

[nameless]

Hmm... the cancer issue could be significant. Then again, they used serum levels. One could alternately say: bad lifestyle/diet = subclinical inflammation = increased risk of cancer = high serum copper.

As for pro-oxidant effects, according to AOR:

Aside from an overemphasis on the benefits of zinc and a mysterious tendency to ignore copper's benefits, much of the reason for unbalanced zinc supplementation has come from the myth that copper is a ‘pro-oxidant' mineral, which might accelerate free radical damage in the body. The reason for this concern is the so-called Fenton reaction, whereby "transition metals" (such as iron and copper), when present in their free, ionic form, can catalytically convert the mildly-dangerous hydrogen peroxide into the vicious hydroxyl radical.

But while copper ions can trigger the Fenton reaction in the artificial conditions of the test tube, it's a non-issue from a health perspective - because the body just doesn't contain enough free, ionic copper to be of concern. Test-tube studies showing that ionic copper can accelerate the oxidation of LDL (‘bad') cholesterol, for instance, have used copper ion concentrations that are literally millions of times as high as are found in the body. In fact, controlled human studies have shown that even at high intakes (up to 7 milligrams a day), copper supplements don't increase free radical damage in the body, but actually tend to decrease it, probably because of the nutrient's indispensable role in the body' antioxidant defenses.
------

Maybe email them for information or studies backing up their claims? They are usually pretty good with responding. Even though they are a supplement company, they tend to think out their formulas and use studies to back of their choices.

I'm not convinced that 1-1.5 mg of copper in their supplements (if taken at a full dose) is enough to have a pro-oxidant effect. Although that Alzheimer's data is worrisome... but what is the optimal amount (if any) of copper one should consume?

Edited by nameless, 05 July 2009 - 12:24 AM.

[Tim1023]

One study, and people are ready to throw out their copper containing supplements? Don't throw them out - I'll take them!


Tim

[Blue]

One study, and people are ready to throw out their copper containing supplements? Don't throw them out - I'll take them!


Tim

One study? Please reread.

Hmm... the cancer issue could be significant. Then again, they used serum levels. One could alternately say: bad lifestyle/diet = subclinical inflammation = increased risk of cancer = high serum copper.

As for pro-oxidant effects, according to AOR:

Aside from an overemphasis on the benefits of zinc and a mysterious tendency to ignore copper's benefits, much of the reason for unbalanced zinc supplementation has come from the myth that copper is a 'pro-oxidant' mineral, which might accelerate free radical damage in the body. The reason for this concern is the so-called Fenton reaction, whereby "transition metals" (such as iron and copper), when present in their free, ionic form, can catalytically convert the mildly-dangerous hydrogen peroxide into the vicious hydroxyl radical.

But while copper ions can trigger the Fenton reaction in the artificial conditions of the test tube, it's a non-issue from a health perspective - because the body just doesn't contain enough free, ionic copper to be of concern. Test-tube studies showing that ionic copper can accelerate the oxidation of LDL ('bad') cholesterol, for instance, have used copper ion concentrations that are literally millions of times as high as are found in the body. In fact, controlled human studies have shown that even at high intakes (up to 7 milligrams a day), copper supplements don't increase free radical damage in the body, but actually tend to decrease it, probably because of the nutrient's indispensable role in the body' antioxidant defenses.
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Maybe email them for information or studies backing up their claims? They are usually pretty good with responding. Even though they are a supplement company, they tend to think out their formulas and use studies to back of their choices.

I'm not convinced that 1-1.5 mg of copper in their supplements (if taken at a full dose) is enough to have a pro-oxidant effect. Although that Alzheimer's data is worrisome... but what is the optimal amount (if any) of copper one should consume?

I would be really helpful if AOR provided sources for their claims. Like for example lef does. Their claims seems to have been proven false regarding at least the free copper provided by supplements and tap water (in turn from copper tubing). Which seems to able overwhelm to the copper binding defense systems of the body by being quickly absorbed. Their unsourced claims regarding 7 mg per day may or may not be correct regarding copper slowly released from food.

I may email them when I have done some more research. Currently looking into chelated metals which may be able to solve the problem. For example Ferrochel, a chelated iron product, is a very impressive product and seems to solve a lot of the problems with iron supplementation.
http://www.rockwelln...s/ferrochel.pdf
http://www.bwiseonli...m/ferrochel.pdf

Something similar would probably be preferable for copper supplementation.

[nameless]

I would be really helpful if AOR provided sources for their claims. Like for example lef does. Their claims seems to have been proven false regarding at least the free copper provided by supplements and tap water (in turn from copper tubing).

I must have missed this reference in this thread. Where were they proven false exactly?

I may email them when I have done some more research. Currently looking into chelated metals which may be able to solve the problem. For example Ferrochel, a chelated iron product, is a very impressive product and seems to solve a lot of the problems with iron supplementation.
http://www.rockwelln...s/ferrochel.pdf
http://www.bwiseonli...m/ferrochel.pdf

Something similar would probably be preferable for copper supplementation.

Wouldn't a chelated mineral simply absorb better? How does that solve anything? All it should do is allow more copper to be absorbed by the body.

Right now, AOR uses copper citrates, which absorb somewhat decently (using magnesium citrate as a basis for saying that) but it is probably absorbed less by the body than a glycinate chelate would be.

Edited by nameless, 06 July 2009 - 06:41 PM.

[Blue]

I must have missed this reference in this thread. Where were they proven false exactly?

Wouldn't a chelated mineral simply absorb better? How does that solve anything? All it should do is allow more copper to be absorbed by the body.

Right now, AOR uses copper citrates, which absorb somewhat decently (using magnesium as a basis) but it is probably absorbed less by the body than a glycinate chelate would be.

Greatly accelerated dose-responsive cognitive decline was seen with copper supplementation. Se my first post. So obviously not safe up to 7 mg/day. From my first post where the link to the source is:

"Among persons whose diets were high in saturated and trans fats, higher copper intake was associated with a faster rate of cognitive decline. In multiple-adjusted mixed models, the difference in rates for persons in the highest (median, 2.75 mg/d) vs lowest (median, 0.88 mg/d) quintiles of total copper intake was –6.14 standardized units per year (P<.001) or the equivalent of 19 more years of age. There was also a marginally statistically significant association (P = .07) with the highest quintile of food intake of copper (median, 1.51 mg/d) and a strong dose-response association with higher copper dose in vitamin supplements. Copper intake was not associated with cognitive change among persons whose diets were not high in these fats"

Correct, chelated minerals have much higher bioavailability so more is aborbed. But this occurs more slowly which causes less free elemental metal not bound to proteins. A temporary effect after intake but can still be damaging. Chelated minerals are similar to minerals more slowly absorbed from food which we are adopted for. Unlike copper tubing and supplement pills which are new creations.

Also, if you read the links regarding Ferrochel it is claimed that the chelated iron is not absorbed if body iron stores are full. Unlike elemental iron.

Edited by Blue, 06 July 2009 - 07:05 PM.