1229 replies to this topic

[mag1]

OK, let's see if we can think up some more analogies.

 

Insuring your megamansion for $350 is a good one, though that is only your house (if a fire took out the main house, then you could always relocate to the

$25 million guest cottages). With dementia there are no guest cottages to relocate to: you only have one brain. Once it has neurodegenerated there are

no easy answers.

 

I think a fairly good analogy of where we are now is when I decided to wait till the night before the Quantum Mechanics final to crack open the text. How tough can it be?

After reading the first sentence starting "Obviously,....", well it took a few years to get out of the fetal position.

 

Denying reality can be an adaptive psychological response (to a point). If you have made no meaningful attempt to address the crisis of this century this late in the game,

then you need to prepare for some very rough sledding ahead.

 

Governments all over the world have pretended that an overwhelming wave of dementia would not arrive. This has been obviously not true for decades. Now this truly

devastating catastrophe is within sight and for whatever reason the response is still fairly mute.

 

One of the more obvious consequences would likely be an opening up of the clinical trial process. CRISPR technology could probably profoundly alter the course of the dementia

epidemic. Many patients would be willing to try it, probably even now. And why not? Right to Try is the law of the land. When is the government going to be required to obey its own laws?

 

A useful research strategy would be to first define the genetics of dementia to an exacting standard and then go in with CRISPR. We simply might not have much more

time to do unfocused basic research. It will likely become politically impossible to continue with the endless regulatory delays when the dementia epidemic truly hits the shoreline.

The ante in America is already $200 billion per year. What happens when it hits $1 trillion as expected in the decades to come?

   

 

 

Edited by mag1, 23 December 2015 - 05:33 PM.

[mag1]

There was a peace dividend: Why not a dementia dividend?

 

America spends over $500 billion per year on the military.

The real threat to national security is the dementia epidemic.

 

If those who threaten us truly understood how the dementia epidemic is shaping our lives,

they might just move onto another lifestyle.

It is surprising how much dementia reconfigures your state of consciousness and changes your perception of what is important in life.

Perhaps if some of those who have become so preoccupied with violence could become more familiar with dementia, then their

consciousness might change as well.

 

Getting your macho out there is the way of undirected youth,

caring for your loved ones with dementia is the path of enlightened maturity.

 

 

Edited by mag1, 23 December 2015 - 06:15 PM.

[resveratrol_guy]

The problem is that dementia, like influenza, isn't a battle of civilizations which grabs the headlines. It's a depressing and extremely difficult challenge which is so hard to solve that many have simply given up. People think emotionally, not statistically. (This is kind of incredible, considering the group survival advantage of the latter. But if you have any doubts, just look at Donald Trump's poll numbers.)

 

I'm sorry to say that I disagree with your optimism about government. Yes, the improvement in investment is a good use of tax money, but in absolute terms, it's too little to do anything much, considering the cost of getting the FDA to lift a finger these days. The "solution" is becoming clear: confiscate the assets of dementia patients, then imprison them in "care" facilities and feed them cheap junk food until they die. This is the way it happens in the US, for the most part. These medicare hellholes are so depressing, frankly, that being homeless and demented seems like a better experience in some regards. At least, the air is clean and one can enjoy the parks and beaches.

 

The real answer is to raise to awareness for companies like BioViva, who won't stand for this travesty and are looking overseas in order to sidestep the dementia death camps and FDA stalling. Right to Try won't help much, unfortunately: in most states' implementations, it's reserved for terminally ill patients, for whom even the best experimental technology is probably inadequate.

 

As you've suggested, the cure for dementia is to avoid getting it in the first place, for example, using TERT therapy to prevent plaque formation in the hippocampus. There are probably 100 separate strategies required. I say, start with the cheap ones which carry little risk, and escalate from there as needed. Thanks to you, I've already told many people about the hazards of copper-2, for example. My wife's vitamin pills went into the garbage last week, and with them, a good slice of susceptibility to this terrible disease. I would not be surprised if your post here did more for her future health than any doctor's advice she ever received.

Edited by resveratrol_guy, 24 December 2015 - 12:18 AM.

[mag1]

Yes, this is quite true that dementia does not have the high drama of other top line news stories, though it is becoming and is expected to become the main driver of 21st Century reality.
We are all so blessed that there are forums such as Longecity to break free from a journalistic narrative that simply does not truthfully reflect the life experience of the wider public.

Dementing illness is a rapidly emerging truth for millions of people. {Many of whom might never have had a strong family history of the disease. Dementia is essentially an illness
that results from success. Many developing nations might have only a vague familiarity with it.}

The copper-2 angle makes me wonder how truly difficult dementia would be to solve. Breaking almost anything requires nearly no skill, though trying to piece everything back together
surely requires considerable skill. If this pandemic could be stopped by simply moving away from copper plumbing, then at some point there might be no alternative but to
implement such a change. Trying to reverse neurodegeneration after it has already started might be too difficult a challenge. It is possible that decades more of basic research
might be required to definitively prove this conjecture: We do not have decades anymore to monkey around with this! If copper plumbing is the problem, then we should actually translate
research to action. Perhaps, given the severity of the threat already posed by dementia, we should implement a trial project for non-copper plumbing now based on the precautionary principle.

I suppose one of the problems is that a fair few people actually do confuse feeling emotion with rationally thinking statistically.
I just wish that all these weak minded people who think with their emotions are good swimmers when the boat we are on keels over.

I do find the recent increase in funding encouraging. It feels like a conversion moment: something like a repentance from Ebenezer.
Now that the inertia point has changed, government can recalibrate future increases based on what has now already been done.
Changing course is couragous and takes some wisdom, future leaders can now simply go steady on the growth curve that has already been charted.

I have a fairly good idea what you mean by such medical facilities. A few years ago we needed to bring our loved one to hospital for a simple
procedure related to dementia progression. It was extraordinary how many medical problems arose during the stay ( none have arisen
in the several years afterwards while our loved one has lived in a home environment). In fact I wound up coughing up blood for over a week
as a result of my visits to the hospital. This is all the more surprising to me as I can honestly not remember a single day before this incident
in the last 25 years in which I needed to take bedrest for a medical problem.

I will be very interested to see what other nations will be able to offer for AD patients in the years to come. It does not seem reasonable to imagine
that CRISPR could be held back eternally in less regulated contexts given the intensifying magnitude of the dementia crisis.

Copper-2 does seem to be an especially worrisome chemical. The logic presented in the recent article does seem as startlingly clear as was suggested.
The body does not have a copper-2 handling system, so it can travel directly to the brain without binding to proteins. There does not appear to be
any justification for this inorganic copper to be consumed. Even trace amounts of inorganic copper in the water of rabbits fed a high fat diet led to amyloid
neuropathology. This was known 10 years ago! The recent article has presented a compelling explanation. I wonder when the FDA will step in.

Would they really encourage pregnant women to take a copper-2 supplement to provide copper to their newborns given this information?

When you look into almost any of these topics simple minded suggestions often turn out to be misinformed.
For example, on further reading I discovered that Alzheimer patients actually often have a significant deficiency of copper. etc. etc.

Life is complicated; it is typically not wise to try to find simple solutions to complex problems.

However, copper-2 appears to be a truly irredeemable villain.
Like so many of these man made forms of metals that exhibit neurotoxic properties, people have no defense against them.
Perhaps if we wait a few million years a copper-2 converting protein will emerge in our genome, though we can't wait.
If we can't CRISPR a new gene, then we can always have the good sense not to ingest it in a multivitamin.
Wonder if there are any copper-1 supplements?

Oh, and thank you for your zinc suggestion. I have taken 50 mg of zinc citrate once or twice a week now and I feel zincerficous!

Edited by mag1, 25 December 2015 - 02:28 AM.

[resveratrol_guy]

You're certainly correct that AD is not a simple disease. Even its set of causes is much more complicated than merely copper-2. But I think the importance of this research is to show that copper-2 may be its earliest, and in some countries, most prevalent cause. So while eating burgers all day will still result in AD, it probably won't do so as rapidly as in the case of high copper-2 exposure.

 

I think gene tweaks are something that we should investigate as methods by which to bias the odds in our favor, but as you pointed out, the more direct approach of copper-2 abandonment is cheap and immediately effective by way of prevention. I suspect that even existing AD sufferers would not progress as rapidly if their exposure were halted.

 

But I don't think that copper-2 is a magical cause of AD. It seems, from many studies, that's it's simply the most common plaque nucleation agent in the West. There is no reason to believe, in my view, that the "wrong" form of iron or titanium could not accomplish the same pathology, given sufficient exposure. For this reason, I've made a conscious effort to get my hemoglobin level down to what is barely sufficient for good health. I'm also leaning toward removing my titanium plates once my bones heal from jaw surgery.

 

That in mind, I suspect that the next shoe to drop will be titanium alloy implants. It has been proven extensively that these devices leach titanium and other elements into the blood, likely as aqueous salts as opposed to metal-bound proteins. At some point, there will be a study examining the connection between metal implants and dementia. I think I know what they'll find. We should probably migrate from titanium alloys to carbon fiber, which is lighter, stronger, and more resistant to deterioration. But that will take a century. In the meantime, people with incompetent hips and knees will need to weigh the risk of dementia against the probability of severe injury due to falls.

 

The only certainty is that we should take the low-risk high-benefit steps first, such as eliminating copper-2 exposure and avoiding hemochromatosis from red meat.

 

Zinc is great for competing with copper, but in theory, it, too, could serve as a nucleation agent. I don't know what to advise in this regard, other than caution and careful research.

[mag1]

It is just amazing how many things seem to act as metal chelators.

 

The news seemed pretty clear that coffee helped reduce AD risk.

Some of the reports that have been published are impressive.

 

Now it turns out that coffee can bring down magnesium levels.

http://www.ncbi.nlm....pubmed/11425281

 

Probably not a good thing.

http://content.iospr...sease/jad150538

 

Would like to see a clinical trial that combined coffee with magnesium supplements in AD prevention.

[chrisp2]

As someone stated, copper is essential, right?  It's just how much copper II is in the copper that's in your multi?

 

LEF uses copper bisglycinate chelate...  1mg I think.

[resveratrol_guy]

As someone stated, copper is essential, right?  It's just how much copper II is in the copper that's in your multi?

 

LEF uses copper bisglycinate chelate...  1mg I think.

 

I tried to find out if copper bisglycinate uses copper-1 or copper-2. I'm unable to find the answer, so by default I assume copper-2.

 

However, LEF 2 Per Day does not contain copper at all. They have a variety of different multivitamins so evidently yours contains it.

 

Copper is indeed essential. I recommend getting it from a variety of vegetables.

 

Most multivitamins also contain inorganic iron, molybdenum, and manganese, none of which are desirable from an Alzheimer's prevention standpoint. From this perspective, 2 Per Day isn't perfect, either. But at least it lacks the copper-2.

[chrisp2]

Of course Life Extension does make a copper free version of their flagship multi...

[mag1]

The real breakthrough in thought here is that copper-2 is not essential.

Multivitamins typically provide copper as the inorganic copper-2 form.

 

The body has no mechanism to safely bind copper-2 into protein form, so it just floats into the bloodstream without such

processing and then has free access to enter the brain.

 

I think that is absurdly dangerous.

Several on the thread have indicated likewise.

 

Research that looked at the intake of copper-2 versus Alzheimer's risk would be useful.

It seems quite possible that some populations might have very minimal intakes of copper-2. 

  

The definitive study of this might be published in 50 years, though I see no reason to wait.

We have been experiencing an escalating Alzheimer's pandemic for over a century and it is only expected to intensify yet more

in the approaching decades.  

 

The article was accurate when it suggested that a moment of clarity has been reached.

So, often the research literature becomes so ridiculously complicated that one can no longer make

any statement without there being a contrary study.

 

This is clearly true with copper and Alzheimer's as well.  

For example, in severe Alzheimer's there is a significant copper deficiency, copper becomes bound in amyloid . etc. etc.

Research has been trying to determine how copper could be placed at the right place in the brain.

This research has been ongoing now for decades. The recent clinical trial from Prana testing this idea was not successful.

 

However, there is an absence of such ambiguity in the discussion of copper-2 and Alzheimer's .

Copper-2 does not appear to have any known biological purpose.

Inorganic copper has only been part of the human experience over the last century or two.

Thus, the body has evolved no system to cope with it, whereas such a system has evolved for normal organic copper.

 

As noted there are a whole bunch more inorganic metals also added to multivitamin supplements.

It is possible that some of these metals might actually have been present in the human environment in an inorganic form for

a long period of time and thus, it would be expected that some sort of genetically controlled system evolved to process such metals.

However, this is likely an overly optimistic assumption. For example, it is known that aluminium plays no biological role in humans

and that that even the amount in tap water has caused dementia in children undergoing dialysis. In fact, most metals are known

neurotoxins (e.g. mercury, arsenic, lead, iron etc.) Why would we expect otherwise?  Metals by their very nature are redox agents.

This is a known pathological process in Alzheimer's.  

 

 

The idea that copper-2 is non-essential is somewhat of a conjecture.

However, this form of copper is mostly an invention of the modern industrial age as noted in the article.

We have been conducting this uncontrolled experiment on the human population over the last century or so to see what happens 

to the human nervous system when we introduce all sorts of unresearched species of metals into the food supply.

 

I am guessing here, though I would think that if we could travel back in time even 200 years we would find that people had greatly lower levels of 

metals in their bodies (and brains). I am not sure whether exhuming people from that era might help answer that question. However, it is almost

certainly true without needing any confirmation. We could simply trace back the industrial history of the metal industry. 

 

 

 

 

Edited by mag1, 27 December 2015 - 05:33 PM.

[resveratrol_guy]

The real breakthrough in thought here is that copper-2 is not essential.

Multivitamins typically provide copper as the inorganic copper-2 form.

 

The body has no mechanism to safely bind copper-2 into protein form, so it just floats into the bloodstream without such

processing and then has free access to enter the brain.

 

I think that is absurdly dangerous.

Several on the thread have indicated likewise.

 

Research that looked at the intake of copper-2 versus Alzheimer's risk would be useful.

It seems quite possible that some populations might have very minimal intakes of copper-2. 

  

The definitive study of this might be published in 50 years, though I see no reason to wait.

We have been experiencing an escalating Alzheimer's pandemic for over a century and it is only expected to intensify yet more

in the approaching decades.  

 

The article was accurate when it suggested that a moment of clarity has been reached.

So, often the research literature becomes so ridiculously complicated that one can no longer make

any statement without there being a contrary study.

 

This is clearly true with copper and Alzheimer's as well.  

For example, in severe Alzheimer's there is a significant copper deficiency, copper becomes bound in amyloid . etc. etc.

Research has been trying to determine how copper could be placed at the right place in the brain.

This research has been ongoing now for decades. The recent clinical trial from Prana testing this idea was not successful.

 

However, there is an absence of such ambiguity in the discussion of copper-2 and Alzheimer's .

Copper-2 does not appear to have any known biological purpose.

Inorganic copper has only been part of the human experience over the last century or two.

Thus, the body has evolved no system to cope with it, whereas such a system has evolved for normal organic copper.

 

As noted there are a whole bunch more inorganic metals also added to multivitamin supplements.

It is possible that some of these metals might actually have been present in the human environment in an inorganic form for

a long period of time and thus, it would be expected that some sort of genetically controlled system evolved to process such metals.

However, this is likely an overly optimistic assumption. For example, it is known that aluminium plays no biological role in humans

and that that even the amount in tap water has caused dementia in children undergoing dialysis. In fact, most metals are known

neurotoxins (e.g. mercury, arsenic, lead, iron etc.) Why would we expect otherwise?  Metals by their very nature are redox agents.

This is a known pathological process in Alzheimer's.  

 

 

The idea that copper-2 is non-essential is somewhat of a conjecture.

However, this form of copper is mostly an invention of the modern industrial age as noted in the article.

We have been conducting this uncontrolled experiment on the human population over the last century or so to see what happens 

to the human nervous system when we introduce all sorts of unresearched species of metals into the food supply.

 

I am guessing here, though I would think that if we could travel back in time even 200 years we would find that people had greatly lower levels of 

metals in their bodies (and brains). I am not sure whether exhuming people from that era might help answer that question. However, it is almost

certainly true without needing any confirmation. We could simply trace back the industrial history of the metal industry. 

 

I see no point at all to experiment with inorganic metals in the diet. In my view, we should push back on whatever vitamin vendors will listen, in order to formulate an oganic-only supply of metals, by which I mean that the redox states are equivalent to what we would find in vegetables. Worst case, perhaps it's time to give up on multivitamins altogether, other than zinc gluconate or zinc citrate, as zinc is difficult to obtain other than via oysters. Get your selenium from organic eggs.

 

I see the copper-2 revelations as the tip of the iceberg. Plenty of other metals should be on trial for crimes against humanity at this point, aluminum not the least of which. (Aluminum wasn't even isolated in its pure form until the 1800s.)

 

I don't see Prana's failed drug as disproof of this theory. After all, we're talking about inorganic metal ions as mere initiators of AD. That doesn't mean that we can easily remove those ions once they nucleate plaque, or even if that's possible, that it will make much difference, any more than putting out a cigarette lighter would be expected to cause the cigarette itself to stop burning.

 

It seems virtually guaranteed that testing exhumed bodies from centuries ago would reveal lower concentrations of these metals, right up until the beginning of the industrial age.

 

Apart from halting exposure immediately, those of us without evident cognitive deficits should consider various dietary changes and supplements which might reverse nucleation while they still can. The last line of defense is basically hippocampal TERT therapy in an attempt to preclude tau aggregation...

[mag1]

Yeah, I really couldn`t in good faith argue to my last breath that many of these presumed neurotoxic metals had any specific

redeeming qualities.

 

I just wanted to hedge a bit on whether the inorganic metal (copper-2) insight would apply broadly to other

metals with different ionic forms. There is a long list of metals that are neurotoxic: Arsenic, lead, methylmercury, etc. .

I was just not as clear about for example iron. Is iron-2 in any neurotoxically way worse than iron-3?

 

It is interesting to look at the oxidation states of the metals in a periodic table and consider the potential

neurotoxicity. 

http://www.vertex42....table_color.pdf

 

Notably the well behaved metals typically only have a single oxidation state.

Consider sodium, magnesium, potassium, calcium and zinc.

At the same time, aluminum with only one oxidation state still has been shown to have

neurotoxic potential.

 

Also of interest is the allowable intakes of the non-transtition metals versus the transition metals.

For example, allowable calcium intake is over 10,000 times higher than that of molybdenum.

 

I am not sure whether the neurotoxicity of different metals could be guessed by simply eyeballing

the periodic table, though it does appear to offer some insights. There are a range of other metals 

that could be investigated for potential toxicities including gold, silver platinum, palladium, tungsten,

etc. . Fortunately many of these other metals would likely not be present in the human tissues in 

significant quantities. 

 

On this one I think it would be very sensible to go with the paleodieters. The levels and species of

metals in our pre-modern ancestors would be a much better guide than trying to work through all of the

potentially dangerous new age metals that are completely removed from any relevant genetic selection time frame.

 

When i look at the world map for metals imports, I get this sickening feeling that one could simply overlay global 

dementia rates and have a fair amount of correlation.

https://en.wikipedia.org/wiki/Metal

 

This has a personal meaning for us as our loved one is now coping with dementia.

There might be a metals connection for their dementia as a homozygous TCGA haplotype

in the ATP7B gene is present as well as the HFE (hemochromatosis {iron gene}) C282Y mutation.

http://www.ncbi.nlm....82274/table/T3/

 

Other families members have various combinations also including the TF (Transferrin {iron gene}) C2 mutation.

By themselves these mutations have not been shown to substantially increase Alzheimer's risk.

However, one does begin to wonder whether enough of these mutants were present in a specific

environment enriched with formally exotic metal species dementia might develop. 

 

The million plus person data set at 23andme might be a great place to start to try and answer some of

these questions. Searching for those with rare combinations (say 1 in 10,000) enriched with metals

variants might shed light on the risk of metals for some of the more vulnerable people in the

community. They could be the canaries in the coal mine for the rest of the population. 

 

Due to our loved ones dementia it has been necessary to use enteral feeding. After reading some of the literature

it was found that it has been known for some time that iron levels in some enteral feeds are not at safe levels for

those with neurodegenerative illnesses. The research was done specifically in ALS. We contacted our medical

team about this and it turned out that there is no available alternative for the feed that we use. 

 

Here are the amounts of metals in our loved one's enteral feeding solution bottle:

sodium 112

potassium 180

magnesium 27

calcium 100

 

chromium 0.012

molybdenum 0.008

manganese 0.2

iron 1.2

copper 0.13

zinc 1.7

selenium 0.007

iodine 0.016

 

The story of metals and neurodegeneration is one I would be very interesting in reading.

The entire narrative would probably be a cautionary tale in the startling recklessness and uneducatable

essence of humanity. It would be sort of a Jackass on the truly epic scale of all humanity.

 

Possibly the Roman empire experience with mental illness caused by metals would be the logical starting point.

It is possible though that there would even be references of metals' neurodegeneration predated that debacle.

Perhaps at the start of the copper age itself? 

Yet, there would also be so many examples that could be included from the modern day.

 

It is astonishing!

It is not that long ago that cars actually had lead added to the fuel to prevent knocking.

It was the equivalent of putting a lead smelter on every major intersection.

The current standard is to strive for a zero lead level in the population.

 

Apparently when aluminium was first produced it was more expensive than gold and was considered a

luxury item.

 

This would surely be a good read. Perhaps we could start a Kickstarter campaign to fund an author to write that book!

In the meanwhile, i would be happy if a researcher could explain how the other essential metals listed above from the

enteral feed container might also be interpreted under the organic-inorganic distinction (analogously to copper). 

 

Edited by mag1, 28 December 2015 - 10:04 PM.

[mag1]

Can anyone chime in on whether the below metals are in the "good" form.

For example, is ferrous sulphate preferred over ferric sulphate?  

 

Here is the list from the enteral feeding container of the forms of metals present:

 

potassium citrate, tricalcium phosphate, dimagnesium phosphate, sodium chloride, potassium chloride

magnesium chloride, potassium iodide, ferrous sulphate, manganese sulphate, zinc sulphate, sodium selenate,

chromium chloride, sodium moybdate, copper gluconate

 

https://en.wikipedia...opper_gluconate

Wiki calls copper gluconate as copper(II) gluconate.

 

This would seem to be jackassing at a rarefied level.

Someone with known neurodegeneration is being fed a 100% copper(II) diet?

This might be fairly standard across all neurodegenerative illnesses fed enterally.

 

 

Edited by mag1, 28 December 2015 - 10:49 PM.

[mag1]

Copper(II) gluconate and cupric sulphate are used for medical treatment.

 

"Used to treat acne vulgaris, common cold, hypertension, premature labor, Leishmaniasis, visceral postoperative complications"

https://en.wikipedia...opper_gluconate

 

I think I would prefer to live with acne or the common cold than have an injection of copper(II).

 

This treatment angle might be the logical point of weakness that could be exploited.

The FDA has a standard of care to protect people from medically dangerous treatments.

FDA filings can stretch to over 100,000 pages.

What is the expert opinion on giving these copper(II) treatments?

 

 

"In addition, premature infants may need additional copper  ...

Injectable copper is given by or under the supervision of a health care professional. Another form of copper is available without a prescription. "

 

http://www.drugs.com...-gluconate.html

 

 

Wow!!!!

This is like looking directly into total insanity.

There appear to be numerous industries where copper toxicities might have arisen in the past and possibly present.

 

"As a herbicide, fungicide and pesticide

Mixed with lime it is called Bordeaux mixture and used to control fungus on grapes, melons, and other berries.

{Do they have organic berries?}

 

 It is used in swimming pools as an algicide.

Copper ions are highly toxic to fish, so care must be taken with the dosage.

{Not even the fish can tolerate the toxicity of copper?}

 

For most of the twentieth century, chromated copper arsenate (CCA) was the dominant type of wood preservation for uses other than deep driven piles, utility poles, and railroad ties.

In printing it is an additive to book binding pastes and glues to protect paper from insect bites;

Copper sulfate is commonly included in children's chemistry sets.

Copper sulfate was also used in the past as an emetic.^[26] It is now considered too toxic for this use."

 

And for the cherry on the cake:

 

"An artist filled an abandoned waterproofed council flat in London with 75,000 liters of copper sulfate solution. The solution was left to crystallize for several weeks before the flat was drained, leaving crystal-covered walls, floors and ceilings. The work is titled Seizure.^[32]Since 2011, it has been on exhibition at the Yorkshire Sculpture Park."

 

Does anyone know the number to call in an emergency response Hasmet team to Yorkshire?

The work should be retitled  Insanity.

 

 

https://en.wikipedia...per(II)_sulfate

 

Edited by mag1, 29 December 2015 - 12:03 AM.

[mag1]

"... it has become clear that Aβ is a metalloprotein,21,22 and that the brain’s intrinsic supply of Cu2+ and Zn2+ (and possibly Fe3+) mediates the peptide’s toxicity (through radical and hydrogen peroxide production) and aggregation. We first observed that Aβ is rapidly precipitated by Zn2+.19,20,23 Cu2+ and Fe3+ also induce marked Aβ aggregation but only under mildly acidic conditions (e.g., pH 6.8--7.0),19,20,23 such as those in the brains of AD patients."

 

Might have caught a break with ferrous (iron(II)) sulphate.

 

http://www.ncbi.nlm....les/PMC2518205/

[mag1]

I would agree that the miss on the Prana trial really cannot be considered a definitive rebuttal to the metals hypothesis.

It is so easy to mess everything up by adding inorganic copper to the human diet. It does not follow that solving this

problem will be equally as straightforward. Almost always piecing things back together is much more difficult than not breaking

them in the first place.

 

Going through the copper pathway.

http://www.kegg.jp/k...&keyword=copper

http://www.ncbi.nlm....les/PMC1785011/

 

Our loved one's exome scan had some scary variants in the STEAP family of genes.

A homozygous variant with an MAF of 5% and in another of these genes a string of missense variants.

By themselves none of these might show up on GWAS studies, though perhaps combined with variants in

the ATP7B, the HFE etc. substantially increased risk of dementia could result.

 

Would be interesting to trace through the entire genetic pathway of copper metabolism

 

Appears as though the reduced form of iron and copper ( i.e. lower charges, Fe2+, Cu1+)  are the good ones.  

"Reduction of both metals, which exist primarily in the oxidized form in the environment, is an obligate step for efficient transport across the plasma membrane by high-affinity transporters." 

Edited by mag1, 29 December 2015 - 03:10 AM.

[mag1]

There seems to be a whole range of neurodegenerative illnesses associated with abnormal iron/copper metabolism

aside from the ATP7B mutations leading to Wilson's copper neurodegeneration there are also mutations in the CP gene

(Ceruloplasmin) that can lead to dementing symptoms.

 

https://en.wikipedia...ruloplasminemia

[resveratrol_guy]

Can anyone chime in on whether the below metals are in the "good" form.

For example, is ferrous sulphate preferred over ferric sulphate?  

 

Here is the list from the enteral feeding container of the forms of metals present:

 

potassium citrate, tricalcium phosphate, dimagnesium phosphate, sodium chloride, potassium chloride

magnesium chloride, potassium iodide, ferrous sulphate, manganese sulphate, zinc sulphate, sodium selenate,

chromium chloride, sodium moybdate, copper gluconate

 

https://en.wikipedia...opper_gluconate

Wiki calls copper gluconate as copper(II) gluconate.

 

This would seem to be jackassing at a rarefied level.

Someone with known neurodegeneration is being fed a 100% copper(II) diet?

This might be fairly standard across all neurodegenerative illnesses fed enterally.

 

I think there's a straightforward reason why oxidation state matters so much. Basically, the more electrons you strip off of a neutral metal atom, the more positively charged (cationic) it becomes. In turn, these higher oxidation states are better able to form the glue that holds plaque fibers together in the brain and other organs.

 

I think the reason that we lack the biological machinery to deal with these cations is that biomolecules tend to be much larger than metal salts. So they never develop a strong electric polarization; instead, their electron clouds are quite evenly smeared all over the place. As a result, they generally lack the ability to rip lots of electrons off of metal atoms, which are strongly attracted to the protons in the metal nucleus. So we end up with lots of +1 states and not much else.

 

The "jackass" aspect of all this is that it's relatively obvious that inorganic metal salts are not food, and this could have been determined a century ago merely by realizing that our traditional human diet did not involve any of the ingredients in your idiotic dietary supplement. But we went on to use them in vast quantities, for everything from baking additives to preservatives to vitamin pills, on top of industrial uses such as antiknock fuel treatments and plumbing. Then, to maximize the effect, we all decided to lose weight by going on a low fat diet of margarine and high fructose corn syrup. And now we act as if the AD epidemic is a mystery!

Edited by resveratrol_guy, 29 December 2015 - 01:18 PM.

[ceridwen]

Does this mean that all minerals are toxic? Is it safe to take them at all? I want to take zinc.

[resveratrol_guy]

I must say, I'm not really fazed by the family of evil genes involving metal toxicity. The reason is that, if you look at statistics available on 23andMe, it's rare that any particular gene increases the chances of anything by more than a factor of 2. When averaged across several genes, the impact is almost always much smaller still. That's why it's called "genetic predisposition" and not "genetic condemnation". You still can't start a fire without an ignition source. So I'd rather have all these bad genes in the absence of inorganic metals exposure, than none of them while living in China and eating vitamin pills.

 

For years, I've been using copper sulphate and on off. Not for creating toxic art work, but for killing snail infestations in my aquariums. It's quite effective and widely used in the hobby for that purpose. But I never asked the obvious question: why is snail pesticide present in my multivitamin? Is something as basic as inorganic metal processing actually different between them and me? It should have rung the alarm bells that snails have truly extensive exposure to biomolecules. These guys ride on a layer of mucus in order to eat all manner of biofilm, loaded with every protein, bacteria, and virus conceivable. Seriously, they eat raw sewage for a living! They exist almost everywhere except in deserts and at the poles. So if inorganic copper kills them, that ought to make it plainly clear: this stuff is not a nutrient.

[resveratrol_guy]

Does this mean that all minerals are toxic? Is it safe to take them at all? I want to take zinc.

 

See mag1's note above about Zn(2+) dissolving amyloid plaque. I would think that zinc gluconate or zinc citrate is safe for adults up to the tolerable upper intake. Personally, I'm planning to stick very close to that limit for at least several months, while reducing my intake of all nondietary copper and iron to zero.

 

Metal salts involving metals other than Group 1 and 2 might, in fact, all be toxic. But biological sources of metals, such as those bound to enzymes or other proteins, are probably fine in paleolithic dietary quantities.
 

Edited by resveratrol_guy, 29 December 2015 - 01:49 PM.

[mag1]

That dietary supplement that I listed above is actually a medically prescribed food.

This would be something that might be administered to extremely ill people with a range of neurodegenerative or

other serious health issues in a hospital setting.

 

As I mentioned this could be the perfect entry point for an examination of copper-2 and other metals by the FDA.

People are allowed to do all sorts of crazy stuff like take copper-2 supplements by their own free will.

However, when something is a medically administered treatment there is an entirely different burden of responsibility by regulators.

 

The graph in wiki showing the time series for global copper production also gave me the chills.

There was virtually no copper production before the 20th century.

There has been a greater than eight fold increase in copper production since the 1950s. 

https://en.wikipedia.org/wiki/Copper

 

Somewhat more disturbing is comparing the copper production time series to the aluminum production time series.

https://en.wikipedia.../wiki/Aluminium

 

Before the 1950s aluminum essentially did not exist as a consumer metal.

I suppose we can just wait and see how much dementia eventually presents in the community: sort of like a natural

experiment in which everyone can injest a whole range of neurotoxic metals and we can just see what happens. 

In such a scenario it might not be possible to hermetically insulate oneself against all these metals. 

 

There was just no room for the snail reference. The copper-2 sulphate wiki page has as an overflowing abundance of absurdities that I needed to edit down. That art exhibit with 75,000 liters of copper(II) sulphate is almost beyond comprehension.

I wouldn't want to even breath the air at such an exhibit.

 

Another fairly startling thing is that wiki actually has two articles on copper sulphate.

Any idea which one is more elaborate?

In fact, one of them could be described as truly minimalist.

 

https://en.wikipedia...pper(I)_sulfate

https://en.wikipedia...per(II)_sulfate

 

Anyone want to put some money on the table and starting the bidding for a copper(I) sulphate supplement?  

 

This has also got me thinking of the very beginnings of the age of metals. In particular, I remembered how the Otzi mummy is thought to have

a high level of arsenic due to being involved in the copper industry of that time. Interestingly, it is also thought that he was involved in a violent

at the time of his demise.  

https://en.wikipedia...a.org/wiki/Ötzi

 

Has the use of metals been at the center of humanity's violent streak, even from the dawn of history?

Edited by mag1, 29 December 2015 - 03:23 PM.

[ceridwen]

I am going to start taking something called HMD which claims to flush the toxins out. People here will probably disapprove of that as it's partially homeopathic but I don't think there would be any harm trying it.

[ceridwen]

Otzi had Lyme and copper toxicity. Interesting. He had a lot of things wrong with him didn't he. More so than most people of his time?

[ceridwen]

I guess the question relating to all the above must be is the government trying to kill us?

[ceridwen]

I have zinc picolinate

[mag1]

This has me thinking: Perhaps all this could be solved by switching to copper-1.

I would be OK with copper-1 plumbing, copper(1) gluconate enteral feeding solution, copper-1 sulphate.

 

The 75,000 liters of copper sulphate art exhibit would still be too crazy for me even if it were copper-1.

 

I wonder whether any of this makes sense.

 

It would sure be a great way to head off the angry townspeople.

A Kickstarter campaign for copper(1) sulphate might be a good idea.

 

[resveratrol_guy]

The connection between metals exposure and violence surely exists. After all, violent outbursts are just another symptom of dementia. The bottom line is that we need to avoid nondietary metals to the extent possible. Speaking of which, it's interesting that Otzi had so much arsenic in him, presumably from drinking well water. A recent study showed that US well water is, in places, heavily tainted with arsenic. It just goes to show how hard it is to avoid all this stuff, especially for people living in heavily polluted industrial areas.

 

I've started to look seriously at the idea of taking narrow supplements just for what I know is defficient in my diet, e.g. zinc, but otherwise giving up on multivitamins.

 

What would your Kickstarter campaign attempt to accomplish, and how?

[mag1]

The connection between violence and metals immediately made me wonder how there might be a relationship with the extreme level of violence in conflicts that began starting near the time of the American Civil War and carried on through the 20th Century. Perhaps a level of cognitive impairment developed in the metal magnets who acquired power in the political structure in part by supplying government with the metals that were needed as weapon systems modernized.There might have been a vicious cycle of more destructive weapons controlled by leaders with some degree of subtle dementing symptoms resulting in yet more wanton destruction. Notably the conflicts that occurred before the mid-19th century were almost civilized in comparison with what came afterwards (e.g. The War of 1812, American Revolutionary War etc. ).

 

Yes, I was trying to get the terminology tied down. "Organic" metals should denote those metals that have appeared relatively recently and are outside of humans evolutionary context or are now consumed in quantities far outside of the paleolithic RDAs. So, it is not entirely true that copper-2 has no evolutionary history in humans. In fact, the STEAP family of genes are designed to convert dietary copper-2 to copper-1. However, what we are likely seeing is a greatly elevated level of consumption of copper-2 that has never been seen before. This is where the unbound copper-2 going straight into the brain enters the picture.

 

It seems unlikely to me that before the 20th century anyone had ever existed exclusively on a copper-2 diet as our loved now does. This has also made me wonder whether our loved one might actually have less metals exposure than the typical person. The enteral feed that has been prescribed likely contains close to zero of the other metals that have neurotoxic properties (e.g. arsenic, mercury, lead etc. ). For those not a scientific diet the government always needs to determine how much mercury is safe in  the food supply. Given the extensive level of metals in the envirornement a level of zero neurotoxic metals in the food supply is probably not a reasonable regulatory limit. With a scientific diet zero non-essential neurotoxic metals is a highly achievable target. Maybe others should consider going on an exclusively Ensure type diet to avoid metals contamination and to have a much better idea of what they are actually putting into their bodies. Making a shift to such a scientific diet would have overwhelming benefits for the health of the nation.

 

The Otzi story as reported on wiki is quite interesting. The description of Otzi gives one the impression that he was quite a prosperous and accomplished fellow. His shoes were finely constructed as were his other clothes. He had all the gear for a camping trip: flint stone, copper axe, kindling fungus, etc.. There he was out for a nice hike in the Alps about 5000 years ago having a great time. It was also noted that he appeared to have the DNA of someone else on his clothes. This was thought to be the result of possibly carrying a wounded friend. The man was a humanitarian!

 

It also appears that the DNA of two people were on his arrow heads. It is thought that this might have resulted from shooting them and removing the arrow. Hmm, so he was something of a homicidal maniac. The comrade he was carrying on his back simply could have been one of his gang. On further examination they found that he had high levels of arsenic. This was attributed to his possible employment in the Copper Age's copper industry.

 

Otzi might be the first instance in the record of humanity of copper dementia. He appeared to be a rageholic. They found evidence for no fewer than 

3 serious injuries in the 6 months before his final fateful stroll.

 

 

His genome has been sequenced. It would be extremely interesting to know what a brain pathology scan might find. While he was only about 45 years of age, what if they found that he had Alzheimer's or at least some early amyloid pathology? In the modern context, copper levels have probably been established so that cognitive impairment/ dementia would not manifest until around 70. It is likely in his day that the workplace health and safety standards regarding arsenic copper-2 exposure were greatly laxer than today's regulations. With his genome sequence it could be determined whether he might have any early onset genes for AD, if not how might a middle aged man who enjoyed invigorating walks in the Alps have developed AD?  

 

For the Kickstarter campaign I was thinking of finding some sort of copper-1 compound that could be used as a supplement. I have the feeling that there are quite a few people who have read our thread and agree that taking a copper-2 is nuts. It would be mostly a consciousness raising type exercise. Moving such a product through FDA approval would likely be almost impossible. GRAS status would be helpful.  If we could attract the attention of the major supplement makers then perhaps they would be interested in scooping up the market that we could build for them.

 

The problem is that it does not appear that easy to find a copper-1 compound. I thought copper-1 chloride sounded very promising, as almost every

other metal chloride is quite safe, though copper-1 chloride is not one of them. Most of the copper-1 compounds that I came across seemed fairly toxic.

{Above I made an erroneous suggestion for a chemical to be used in a copper supplement that should be ignored.}     

 

Edited by mag1, 31 December 2015 - 01:50 AM.

[laurence]

In this paper, we have shown that resveratrol catalyzes the reduction of Cu(II) to Cu(I), which is accompanied by the formation of ‘oxidized product(s)’ of resveratrol, which in turn also appear to catalyze the reduction of Cu(II).
http://www.sciencedi...304383500003517

 

 
I don't have access to the full paper but it would be interesting to find out the concentrations used.

Edited by laurence, 31 December 2015 - 02:27 AM.