Intracellular Copper Overload – the Western Metabolic Bomb

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  ” If we are going to discover nature’s form, it is probably imperative to drive as hard as possible at the critical  points  of mystery.” Henry P. STAPP ( 1989 )

” The EPSICO model  ( EPS = Excessive Prolonged Stress ) centered on the  ICO = Intracellular Copper Overload  =  the indisputable Generator of all chronic diseases; connecting the emotional and physiological realms, it could become the biochemical core of the  New American Medicine. “

Modern ( conventional ) medicine is very proficient at handling acute care, mainly due to the advanced technology and to the drastically simplified picture of most emergency ( crisis ) situations. However, in the field of chronic disorders, things are very different; despite some local successes, it became clearly that modern medicine experiences serious difficulties when approaching the etiology of chronic diseases. This chronic counter-performance could be explained by ignoring or superficially approaching the essential connection between stress, individual mineral status ( especially the intracellular copper overload – Cu↑) and, correlatively, copper interference toxicity – CIT, a chronic form of mineral toxicity that plays a unique role in the etiology of all chronic diseases – infectious, inflammatory and degenerative.
The main conclusion of this study ( EPSICO model ) is that the true generator of the epidemic of chronic diseases is not the genes, nor the germs, and nor the chronic / silent / hidden inflammation – all these are no more than some important modulators – but the intracellular copper overload – the master metabolic imbalance of the contemporary Western  society.

By reading carefully this  unusual paper ( refused shortly by a notorious  mainstream medical journal ) you’ll understand – as specialists or laymen -some of the  ” biggest mysteries ” of the contemporary medicine  ( I’ve stubbornly studied them for decades  in  Brasov and Evanston ). For instance :

–  the definitely lack of progress  in  understanding / preventing / treating of  cancer(s) :  Copper overload ( neglected  by the most cancer  experts )   incredibly increases the apoptotic resistance ( biological stability )  of  cancerous cells , concomitantly diminishing  the vitality of the  healthy cells; I think it’s  a very… promising starting point  for a decisive / generalized  application of …chemotherapy, don’t you  ?);

Cu ↑ constitutes the shortest way  towards  a …firm, inescapable  obesity ( via : Cu ↑ → Cr ↓, etc. ); what the numbers say: 66% of Americans are copper dominant / chromium defficient, while 65 % are overweight. A mere coincidence ?

– Dehydration problem can’t be solved simply by drinking  8 ( or more ) water cups / daily because,  due to the same copper overload ,the cells  are / remain  deficient in : choline, sodium, aldosterone ( all being  …reputed copper antagonists! );

– Frequent  accidents  of the first class sportsmen / women  are due  mainly to  a ligamentous laxity  , caused by the chronic deficiency of Manganese: Cu ↑ → Mn ↓, correlatively, their poor healing of ( chronic  ) wounds  being due to : Cu ↑ → Hyaluronic acid ↓ ;



Abbreviations: EPS = excessive, prolonged stress; CIT = copper interference toxicity;
EPS/ICO = excessive, prolonged stress / intracellular copper overload.
MT = metallothionein or stress protein; Cuf ↓= functional copper deficiency, produced by intracellular copper overload ( Cu↔ MT)↑, according to the scheme:
EPS→ Cortisol↑ → MT↑ →(Cu↔MT)↑ →  Cuf↓

Attention: All information on this site is for general education purposes only. Because  everybody is  different , you have to  contact your doctor to establish  the best treatment / protocol  for your specific condition.

1. The most important sources of chronicity

Chronicity is a multifactorial process, the three most important factors being:

1.1 Progressive demineralization of the soil – uncompensated exhaustion of some essential minerals and notorious copper antagonists, such as: chromium ( Cr ), zinc ( Zn ), manganese ( Mn )…

1.2 EPS → Cu↑ → Cr↓, Zn↓, Mn↓

2 out of 3 Americans are copper dominant. The tendency to absorb /retain too much copper is typical for Western societies, currently under a debilitating stress; in normal stress conditions, the copper absorption / retention is about 30 % from the daily intake, while EPS raises this parameter to 80 %.

1.3 Industrial refining of food ( grains / carbohydrates, oils, salt ); for instance, obtaining white flour from whole wheat leads to 92 % loss of the initial content ( already diminished, see 1.1 ) of Cr, Zn, Mn.

2. C I T ( copper interference toxicity ) – a metabolic downward spiral

EPS →(Cu ↔MT)↑ =  CIT → Downregulation of antagonists & upregulation of agonists → Hypoadrenalism / Hypothyroidism / Immune System Malfunction → CHRONIC DISEASES ( infectious: Cu↑↓; degenerative: Cu↔MT↑; inflammatory: Cuf↓ )

Intracellular copper overload determines the intracellular, stable depletion of copper antagonists, with serious implications in distortion of mineral and general metabolism:

(Cu↔MT)↑ → Cr↓, Zn↓, Mn↓, S↓( sulfur ), Se↓(selenium ),Vitamin C complex↓, vitamin A ↓, Complex B ↓

Copper overload causes also a stable over- retention ( excess) of its synergists, especially calcium: (Cu↔MT)↑ → Ca↑ ( calcium ), ( Mg↑↓ ). Magnesium , though a copper antagonist, has a special/ better place being a calcium, zinc and chromium agonist. The particular importance of this overlooked chronic toxicity ( CIT ) is that no management of chronic problems ( symptoms, syndromes, diseases ) could be optimal once the intracellular copper overload is present. Only by bringing and maintaining the copper level within the physiological range – accomplished by synergistic procedures – all chronic conditions could be efficiently controlled, from joint laxity and low back pain to diabetes complications, cancers and beyond.

3. Copper Overload = Inefficient Metabolic Regulation

Chromium depletion: ( Cu↔MT)↑ → Cr↓

Chromium depletion constitutes a basic factor of human overweight: 66 % of the Americans are copper dominant / chromium deficient, while 65 % are overweight. Why is the chromium deficiency so massive and so  difficult to control in our  Western societies ? Here is my answer:

Copper ( Cu )  ↑ → Cr ↓

Sugar  ↑  →  Cr ↓

Calcium ( Ca )  ↑ → Cr ↓

Potassium ( K )↑ → Cr ↓

Iron ( Fe ) ↑ → Cr ↓

Cr↓ is the major contributor to the so called “ mineral resonances “ which explain why the chronic diseases are sometimes closely related:

Insulin resistance, underactive  adrenals:  Cr↓

Diabetes: Cr↓, Zn↓, Mg↓, Mn↓

Obesity: Cr↓, Zn↓, Mg↓, Ca↑.

Any regular treatment of these conditions can’t provide optimal and lasting results  as long as the ratio Cr↓/ Cu↑ is not normalized.

Zinc depletion: (Cu↔MT)↑ → Zn↓

Sexual dysfunction of the Western population is centered on Zn deficiency. Zinc is still under-evaluated in all Western societies. For instance, people recognize that our soil is low in zinc, our diet is zinc deficient and our life is high in stress ( EPS →( Cu↔MT )↑ → Zn↓ ), however, the same people renovate their houses, replacing the galvanized (zinc) pipes with copper pipes ( leading to about  1.0 mg Cu ↑ /day / person ). It is metabolically counter-indicated to prescribe zinc ( Zn→ MT ↑ → (Cu↔MT)↑ ) to increase the sex drive if EPS / CIT is present since, this way, the estrogenization is amplified ( copper parallels estrogen: Cu↑→ Zn↓ → aromatase↑ → estrogen↑ ). Important to know :  taking Zn greatly  increases the induced  MT,  but because copper has a MT affinity much higher than Zinc, the  retention of  Zn will be drastically diminished and, correlatively , the  intracellular copper stores      ( and the ratio Cu / Zn  ) become  higher than  beforehand.

Statins or Superoxide dismutase ( SOD )?

Decreasing cholesterol is just a modulator ; more important is to strengthen the antioxidant protection, especially by correcting the usual deficient SOD enzyme , induced  according to the diagram:
(Cu↔MT)↑ → Cuf↓, Zn↓ →Cu,Zn SOD↓ → Superoxide Anion↑→ LDL C oxidation

Vitamin C deficiency : ( Cu↔MT)↑ → vitamin C↓ → Silent scurvy

Why are the Western populations prone to gum disease? Statistics show that most Americans reaching 60-65 years, being copper dominant , lost their teeth, despite intensively practicing mechanical procedures such as brushing and flossing. To correct this deficiency , vitamin C complex , meaning ascorbic acid ( as “pure” vitamin C – the old hexuronic acid ) associated with bioflavonoids ( such as rutin and hesperidin ) as metabolic enhancers, seems to be the best option. However, administering vitamin C  when CIT is present, doesn’t lead automatically to an increase of the vit.C content in the intra- or extracellular compartments, but , first of all, it contributes to a decrease of toxic deposits of copper (and calcium).This explains why many patients don’t have any normal antioxidant symptoms only after ingesting megadoses ( 5,000 mg vit.C / day or more). Note: under stress ( EPS ),   the metabolic requirements  of the body for some nutrients   ( especially the copper antagonists ) are greatly ( 10 – 100 times ) increased. This should  be a very good news for  some  mega – experts since we can establish as many  Pauling ( and,  correlatively , ortho- medicines ) as  copper antagonists, namely : vitamin C ( sorry, the job is done ), sulfur, chromium,  a.s.o.

Silent ( asymptomatic ) implications of the copper imbalance:

Silent acidosis : Cu↑ → Ca i ↓, Mg i ↓ ( Me i = mineral in soluble,ionic state );

Silent scurvy: Cu↑→vitamin C ↓;

silent infection: Cu↑↓;

silent inflammation: Cuf↓;

silent degeneration : Cu↑ → XIAP↓( lowering the normal cell apoptotic threshold);

Copper pipes Copper found in our drinking water and food may play a role in the onset of  Alzheimer’s disease and other ” silent ” implications  ( Courtesy: Medical News Today )

silent estrogenization: Cu↑→Zn↓→ aromatase↑;

silent overweight : Cu ↑ → Cr ↓ ; Cu ↑ → Ca ↑

silent dehydration: Cu↑→ choline↓, sodium↓;

silent hypertension: Cu↑→Cuf↓→Lox activity↓→ arterial fibrosis (collagen deposition)…

silent hypothyroidism : Cu ↑ → Zn ↓, Mn ↓, Se ↓,… ( T4–⁄→ T3 )

silent cancer : Cu ↑→ Zn ↓ → vitamin A ↓ ( abnormal cell differentiation / proliferation );

silent heart failure: Cu↑ → Cu f↓, Zn ↓, Mn ↓→ Cu, Zn SOD ↓; MnSOD ↓  → ( mitochondrial / intracellular hyperoxidative stress )

silent dementia :  due to impaired  adrenals & liver activity → copper / zinc imbalance  leading to over-stimulation of the emotional brain ( di – encephalon) 

silent Alzheimer’s : Cu↑ ( due to age, etc. ) → pseudo- chaperone effect  of the  beta- amyloid proteins → plaque formation



1. It is currently asserted that Alzheimer’s  ( and / or dementia ) is incurable. I strongly disagree . I consider that we are actually  dealing  with a  unique ( but very  complex! ) problem of copper toxicity  ( intra and extra- cellular ,having as modulators some other toxic metals like  Fe, Zn, Hg, Cd,…; complex means  not just direct  hyper-oxidative effect, not  just  sub/ under or over-methylation ,… but equally  – or more exactly  especially-  copper interference toxicity  = CIT , according  to our model . A main correlative, aggravating  aspect  is  the deficiency of  copper controlling proteins  such as MT ( metallothionein ) and CP ( ceruloplasmin ) involving some exhausted ( aged, etc.  ) adrenals  : EPS → weak adrenals → cortisol ↓ → MT ↓, mainly leading  to a lack of sequestration = the main   mechanism of  controlling   copper overload and, implicitly, to the   imbalance  of a crucial  ( emotional ) ratio: copper / zinc,  as well  as to a lack of  preventing  – by the drastic different affinities – of  the  toxic involving of  beta-amyloid proteins in  pseudo-chaperone effects leading  finally to the formation of ” plaque”. What we have to do, in my opinion, is to look for some  efficient , synergistic  strategies aiming to bring and maintain   the intra-cellular  copper level  and  the production  of MT / CP  within the normal  ( highly individualized ! ) physiological range.


Cateva precizari adresate  in mod special  colegilor din Romania ( ca si nespecialistilor  direct interesati ) privind implicarea copper overload  in formarea  beta – amyloid- plaque, in spatiul extracelular  ( vezi Fig. de mai sus ),  precum si  sugestii pt. preventia / tratamentul AD  cu ajutorul unor chelatori metalici specifici . Exista inca nu putini  cercetatori – autori care  considera contributia -cheie a copper la formarea placii  senile ca fiind inacceptabila  datorita  unor particularitati  functionale  cum ar fi  concentratia insuficienta a ionilor de cupru in compartimentul vizat, afinitatea  prea redusa a  subsistemelor  implicate ( beta  amyloid peptides ) fata de acesti ioni, etc. Cea mai concludenta  abordare / explicitare a  acestor  rezerve o ofera  articolul  publicat de un grup de cercetatori  britanici ( Univ. of London )  , condus de C.D.SYME  si intitulat “ Copper Binding to the Amyloid – Beta  Peptide Associated with Alzheimer ‘s Disease ” ( J.Biol. Chemistry, 2004, vol. 279 / 18, p. 18169 ). Citez un pasaj clarificator:
“There is now direct evidence that copper is bound  to Amyloid – Beta ( AB ) peptide in senile plaque of Alzheimer’s disease. Copper is also linked  with the neurotoxicity of AB and free radical damage, and Cu2+ chelators represent a possible therapy  for Alzheimer’s disease.” 

Studiul  colegilor londonezi face cateva trimiteri  semnificative  (inclusiv referitoare la dizolvarea placii  toxice de catre  chelatori bine alesi ) dintre care  eu recomand in special cele 3 references (  nr, 14;24; 25  )  semnate de  ATWOOD C.S., CHERNY  R.A. , DONG J. , and coll.  Un paper  mai recent  ( 2012 ) , scotand in evidenta , de asemenea rolul chelatorilor metalici  este semnat de  gruparea condusa de  GENG J.  ( J.Med. Chem, 55 / 21 , pp 9146-55 ).

In opinia mea – bazata atat pe cercetarile proprii  cat si pe  concluziile altor  specialisti, cel mai specific chelator pt. Cu2+ este resveratrol-ul , care poate fi utilizat  atat in preventie cat si in tratamentul AD. Intrucat  acest ” trifenol ” natural ( denumire sistematica : 3,5,4′-trihydroxystilbene ) este ” ridicol de ieftin “, el neputand fi ” imitat ”  ( sintetizat ) in laborator ( si daca totusi ar fi , pacientii naturisti au la dispozitie  o sursa  pe cat de accesibila pe atat de…delicioasa =the  red wine / vinul rosu ). Fraza anterioara explica  faptul  ca resveratrol-ul nu este promovat  de catre medicina si farmacologia conventionala al caror obiectiv major il constituie nu optimizarea  starii de sanatate  ( health / wellness ) a populatiei ci  realizarea   unui profit maxim, repet : MAXIM. Prezint in continuare cateva dintre performantele  general-protective ( in perspectiva deopotriva profilactica  si curativa ) ale resveratrol-ului, conform  jurnalului “Natural Health News Report”  issue # 120 :

                             ” Resveratrol protects you from Head to Toe”:

– Healthy heart, arteries ( promoting  normal cholesterol levels  and  healthy homocysteine  concentration );

– fortifies your immunity by fighting free radicals;

– prevents  oxidation of fatty foods ( for cardiovascular boost );

– protects brain  and memory ( brain = more than 90 % fat ! );

– maintains healthy veins , circulation and blood pressure ( red wine acting as a vasodilator );

– keeps skin looking young, tight , fresh…



 I like to underline that my optimistic conclusion is  based on   some  remarkable  accomplishments  due to a series of  dedicated researchers  such as: Anne Louise GITTLEMAN, Paul C. ECK, Lisa MILLER,  James L. WILSON, Carl PFEIFFER ( d. in 1988 ), William  J.WALSH, Emily MULLIN, Veronika A.SZALAI, Rashid DEANE, Yadong HUANG , Zhijian SU  and coll.  The  relevant  discovery of my conceptual friends from Northwestern University – Evanston ( Javeria HASMI and  A.V. APKARIAN’s team ) = the ” distant ” link between  chronic back pain associated with  marked changes  in  brain activity  is not at all  omitted / overlooked  by me , rather it is embedded in  general stress symbol “EPS”.

2. Don’t confuse the stress induced functional copper deficiency ( Cuf↓ ) – the major form of copper deficiency for the Western societies – and the copper nutritional deficiency, a rare, unlikely phenomenon.
Cuf↓ is defined as low availability of copper for intra –  and extracellular activity ( enzyme activation, etc.), despite of high copper stores in the body ( tissues, cells ).
For instance, lysyl oxidase inactivation due to copper deficiency, leads to diminished cross-linking collagen and elastin and, consequently, to connective tissue defects ( Steinmann et al, 1993 ). The two forms of copper deficiency (stress and malnutrition induced ) should be corrected by two radically different procedures: activation of intracellular copper overload versus normal copper supplementing.To prescribe copper supplements in the case of stress induced deficiency constitutes a “ toxic supplementation”, unfortunately frequently practiced with many Holocaust survivors.

Manganese depletion (connective tissue degeneration): (Cu↔MT)↑→ Mn↓

Human manganese deficiency is still underevaluated though it is involved in some major metabolic disorders such as: ligamentous laxity, poor healing of ( chronic ) wounds, improper thyroid function, etc. Before deciding for cortisone shots or for surgery ( knee, wrist, discectomy,..) – these interventions of last resort being able to amplify the local degeneration- the world class sportsmen / women need to assimilate a simple metabolic truth: it is high intracellular copper level ( that is the exceptional emotional overload, often unprofessionally compensated ) that contributes to a stable but reversible Mn deficiency and, correlatively, to inactivation of glycosyl transferase enzyme, that determine the most connective tissues defects. The same about CIT and poor healing of chronic wounds:

(Cu↔MT)↑ → Mn↓, ( Mg↓ ) → Hyaluronic acid↓.

4. Degeneration – a non-inflammatory issue. The Degenerator

Degeneration constitutes one of the most interesting problems of the contemporary, post-genomic medical science. Unfortunately, its specific approach is still slowed down because of the facile temptation to consider degeneration an annex of the inflammation ( Andre Weil, MD: ” Chronic inflammation just may be the root of all degenerative diseases “ ). Here are some of the most important methodological shortcomings that keep the degeneration category conceptually underdeveloped:

1. subevaluation of the stress role in starting and promoting degeneration – stress is often considered just a modulator, and with no genuine generator, an artificial and painful deterministic play follows between symptoms / effects: inflammation is the cause of degeneration ; infection is the cause of inflammation, etc …I called this comfortable swimming into the sea of effects / symptoms – the downstream syndrome of the contemporary medical research ( the idea of inactivating the caspase machinery to promote a regular apoptosis – while the upstream generator ( Cu↔MT)↑ remains untouched – is just one of the last, high tech examples).
2. the regular use of anti-inflammatory strategies / medications in situations that are totally or predominantly degenerative ( apoptotic degeneration );
3. the conceptual confusion between degeneration and degradation ( this way masking the fact that primary degenerative events take place not in ECM – extracellular matrix- but intracellularly ) : “ collagen and /or ECM degeneration” ( the correct term – degradation ) also, “ cartilage degradation “  ( the correct term – degeneration );

4. ignoring , confusing or underevaluating the MT’s ( metallothionein ) role in the normal and pathologic metabolism. Don’t confuse the acute copper toxicity ( due to mineral saturated MT ) and chronic copper toxicity ( CIT ) involving copper undersaturated MT.
Centered on cellular damage – the primary event in any degeneration – here is my  working definition of degeneration:

inefficient regulation of cell activity during post-injury healing and / or tissue turnover (development, disease state, aging ), resulting in a reduced tissue organization / cellularity ( excessive apoptosis ) and subsequently matrix degradation.
Special merits for differentiation between degenerative and inflammatory, go to some researchers from the tendinopathy field ( PUDDU G. et al.) who, since 1976, proposed to use the term ‘ tendinosis ” instead the incorrect term “ tendinitis “, every time the tendon degeneration is implied, without some clinical or histological signs of inflammation. Using our model, the two chronic conditions can be efficiently distinguished as follows:

tendinosis ( degeneration ) : (Cu↔MT)↑, Ca↑, Vitamin C↓
tendinitis / tendonitis ( inflammation ) : Cuf↓, Ca↓, vitamin C↑

A similar distinction ( though not separation ! ) between arthrosis / arthritis has been elaborated by this author (2006, unpublished work ).

Some reputed authors ( Johns Hopkins Univ., 2006 ) stated that presently is no cure for arthritis ; methodologically, this statement is already history since whether the main cause of arthropathy is the hidden copper imbalance, each of the traditionally admitted causes such as infection ( Cu↑↓), inflammation ( Cu↓ ) and…even  joint’s laxity ( Cu↑→ Mn↓ = degeneration ), could be controlled by bringing / maintaining copper within the physiological range.
Recent studies showed that there is an established connection between the stress ( emotional ) level, degeneration and apoptosis, Ap ( programmed cell death ). It could be concluded that there are two main types of degeneration: apoptotic ( with zero or minimal inflammation) and necrotic ( with relative high inflammation), having a gradual transition between the two types. The EPSICO model develops these new alignments, suggesting a series of fruitful molecular approaches based on the following main etiologic equation of degeneration:
EPS→ (Cu↔MT)↑→Cuf↓, Zn↓, Mn↓, vit C↓→Mt !→ Ap↑→ Tissue Degeneration
In the above sequence Mt! represents the mitochondria as a sensor of perturbation of cellular homeostasis by the CIT.
The entity ( Cu↔MT)↑→Cuf ↓,Zn↓,Mn↓,( Se↓,Cr↓), vit.C↓, essential in any degeneration, has been designated by me as Degenerator. For instance , the copper overload determines the activation of caspase machinery ( “ silent degeneration ”) :
Cu↑→ XIAP↓→ ( caspase machinery )↑→ lowering the normal cell apoptotic threshold ( XIAP designates a certain X- protein from the IAPs group of inhibitors of Ap).
Also, Cu↑ plays a major role in the carcinogenesis and cell cycle dysregulation,via TP53 mutants. The TP53 or p53 ( proteine ) is tumor suppressive ( pro-apoptotic ) in Zinc-wild state, but becomes anti-apoptotic in mutant states mainly generated by ( Cu↔MT)↑, this way contributing to the apoptotic resistance of the cancerous cells ( don’t confuse the two opposite contribution of the copper overload to apoptosis : while the normal cells are “debilitated ” the cancerous cells are protected ). Important to know : beyond this anti-apoptotic contribution , intracellular copper overload induces cells transformation ( carcinogenesis ) through: a.  intense , uncompensated oxidative stress ( Cu ↑ →Zn ↓ ,Cuf ↓ → Cu,Zn SOD ↓ ) and  b.  Cu ↑ → Zn ↓, vitamin A ↓ ( abnormal differentiation and proliferation ).

5. Instead of conclusions: some methodological challenges

One could wonder how it was possible that for an almost a century since it was established the nutritional essentiality of copper ( 1920 ), the modern researchers to ignore the role of the intracellular copper overload as a generator of the chronic diseases, respectively to ignore the non-Cartesian , emotional root ( nature ) of all chronic disorders. The main explanation of this extremely critical overlook is given by not taking in consideration or by  underevaluation of the 3 following essential connections:

a. The stress ( EPS ) / Metallothionein. Without this primary link, the EPS could not to surpass the status of a subsidiary / modulator factor.

b.The Metallothionein / Copper = the biounavailability riddle (see § 5.2 ),
c. Excessive copper→ deficient ( functional ) copper
. The main copper deficiency proved to be not a nutritional one but a weird deficiency induced by the copper overload ( Cu↔MT )↑→ Cu f ↓.
Finally, there are presented some relevant details concerning these connections.

5.1 Stress / MT the missing link in the classical theory of stress
“ The stress from any source generates copper imbalance ” – this phrase full of metabolic signification ( bridging the emotional and physiological realms ) has remained for a longtime at the margin of the modern medical research, as a purely descriptive statement, rebel to any trial of causal approach. The chances of transposing this into a coherent and quantifiable biochemical mechanism have considerable increased with the discovery of MT as a unique chelator for some electrophile agents, especially the metal ions such as Cu+, Cu2+, Cd2+, Zn2+. Fundamental progress in connecting the stress ( as primary emotional factor ) and the epidemic of chronic illnesses has been achieved in two distinct / inseparable stages:
5.1.1. The knowledge of the structural-functional characteristics of MT ( 1985 – 2005 ).
Mammalian studies showed that MT can bind 7 divalent metal ions :
Cu, Cd, Zn ( or, alternatively, 12 monovalent copper ions ) per protein molecule in TWO DISTINCT DOMAINS ( clusters ): the alpha cluster or the carbon terminal domain ( including 11 cysteine residues) and the Beta cluster or the nitrogen terminal domain ( containing 9 cysteine residues ). It is remarkable that the chelation promoted by the two domains is done SEQUENTIALLY- the fixation of the cations on the Beta domain happens only after the alpha domain has been saturated with electrophile agents.This fact – due to the net difference of affinity attributed to the two domains – allows an efficient delimitation between the stable sequestration of toxic heavy metals ( Cd2+ , Cu↑ ) on the alpha domain and the homeostatic regulation of the essential metals ( Cuf, Zn ) essentially distributed on the Beta domain.
5.1.2. The second stage (2002 – 2006 ) dedicated to the verification of the hypothesis according to which the synthesis of the MT could be easily induced IN VIVO by glucocorticoid hormones, especially cortisol:

EPS → Cortisol ↑ → MT ↑

5.2 The Copper Biounavailability Riddlea new mineral ratio concept

The right solution of the copper biounavailability problem was late by several decades due to the preference given by the medical establishment to some plausible ( but false ) current analytical clichés such as: a. the copper deficiency is a very unlikely phenomenon, even in the case of a suboptimal nutrition and b. the copper overload cannot exist but in some exceptional cases ( mutations, accidents ). In this context, the copper biounavailability was sometimes looked at as… a simple biochemical curiosity or, at othertimes, it was considered as a sleeper phenomenon associated with dehydration. In reality, we deal with a new understanding of the mineral ratio concept, when the excess of one mineral ( intracellular Cu↑) determines the deficiency of the same mineral found in a different metabolic state ( Cu functional, intra- and extracellular). Note – in passing- that in mammals, the copper deficiency leads to the iron deficiency as Fe2+ , the only soluble, assimilable form : ( Cu ↔MT )↑ and / or Mo↑→ Cuf ↓ ( → Fe2+ ↓ ). This detail should be suggestive for Bovine Spongiform Encephalopathy ( Mad Cow disease ) research, and for its human counterpart ( Creutzfeld – Jakob disease ), both based on a deep imbalanced mineral metabolism ( Cu , Fe, Zn ).
The copper biounavailability conceived as sequestration, is based on the large difference of affinity of the coordinative bonds generated by the two domains (clusters ) of MT: relatively recent studies, due especially to the group led by the Swiss professor KAGI G. H. ( presently retired ) , showed that the Cadmium binding sites generated by the alpha domain of MT are 30 times more stable than those generated by the Beta domain. Transposing this result into the copper biochemistry ( important to know:  the affinity  of  Copper to MT is even  higher than that of the Cadmium ! ) one can conclude that copper from system becomes biounavailable, being preferentially fixed on the MT alpha domain ( sequestration ). Considering that excessive ionic ( free, soluble ) copper is much more dangerous than the functional copper deficiency, it results that the copper biounavailability represents a particularly valuable adaptive acquisition into the field of the oxidative metabolism, the evolution solving this vital problem through the so called chaperone effect of the MT. It can be stated that the only efficient answer of the living systems to the copper overload is the induction of MT ( MT ↑). This way a nonlinear risk was transformed by the evolution into a linear / chronic one, involving a transition from a potential hyperoxidative, acute toxicity to a chronic copper interference toxicity ( CIT ).Note:  MT becomes copper active  only in special ( overload ) situations,  the normal , physiological  copper works  without any MT involvment.
The well established inseparability between the intracellular excess and the induced deficiency of functional copper leads to the general conclusion that not the separation between  degeneration, infection and inflammation represents the right methodological solution since all these conditions ( symptoms ) suppose the intracellular copper imbalance. A better strategy – perhaps the only one – consists in bringing and maintaining the intracellular copper level within the normal, physiological range.


4 Responses to “Intracellular Copper Overload – the Western Metabolic Bomb”

  1. Deosebit acest articol, sunt fericit ca l-am cautat si invatat. Multumesc pentru acest articol deosebit ce contine nevoie de grija.

  2. Scott McGowan

    Dear Dr. Florin Florea Felecan,

    I’m writing this comment as an appeal for help, relating to this article.

    I have a very, very severe functional copper deficiency, to the extent that my body can no longer make SOD, as well as not being able to replenish collagen. I experience severe injuries from chemicals like car fumes, cigarette smoke, cleaning chemicals etc., to the extent that it harms my vascular system (sometimes in my brain causing all kinds of problems).

    I developed this problem after being very stressed over a long period and then drinking water from a copper cup (left overnight), which a friend recommended for grey hair.

    I reckon that the combination of extreme stress over a long period (and maybe continuing now), combined with drinking “heavy copper water” has imbalanced me so much that my functional copper is dangerously low now.

    I’ve tried balancing my minerals with zinc, manganese, molybdenum and chromium, but these all make my functional copper worse. I have low blood copper and low ceruloplasmin, so it seems that my copper is not available for making enzymes anymore.

    My body is breaking down every day (collagen disappearing in skin, joints, vascular system) and I cannot resist chemical injury. Also, this phenomena increases if I don’t eat carbohydrates every 30-60 minutes, and it makes more bubbles in my urine, so it seems that without “cuproenzymes” (copper-based enzymes), my body is in a meltdown situation…

    I realise that you are not a doctor, so I’m not expecting standard medical advice, but besides trying to consume the different minerals and reducing stress, I wondered what your idea would be…

    Can you help me please?

    • admin

      Hello, my friend !
      Of course I can / want to help you, but I need some minimal additional data about you as a biological / biochemical system.
      For instance :the duration of your problem; your age ( detoxification you very need is dependent – as intensity, for instance –
      from your ability to cope with the intermediary – toxic – products. I need too to know your acido-alkaline index: you can find
      it very simply:
      use a pH Testing Tape ( I suppose you are extremely acidic and we have to know exactly how low your pH is gone below 7 ):
      two readings are indicative for me = pH of saliva and pH of urine. Anyway according your description , you have the
      adrenal glands extremely weak ( there is a feed back : excess copper means weaker adrenals and , weak adrenals lead to more
      toxic copper; moreover , any form of stress results in new toxic copper deposits. The conclusion is obvious and non- negotiable :
      if you really want to control your problem first of all you have to eliminate immediately your stress source. You simplified your
      enzymatic status : because of low adrenal activity ( doubled invariably by o very low thyroid activity ) you miss not just some
      cupro-enzymes, but almost all enzymes are de-activated because of generalized lack of minerals.Don’t try to take mineral
      supplements ( Zinc , for instance makes copper higher ). Let me know some details and I’ll be back with some new,more elaborated
      suggestions. Take them, of course, just as a second opinion and not as an medical advise. Yours, F.Felecan

    • ashlee

      I can help you. You need to chelate the copper using a drug called Ammonium Tetrathiomolybdate (which is used in Wilson’s disease). You can order it from a company called Prochem (you need to tell them you are a business and using it for research purposes). I mixed my 10 grams of TTM with 20mL of almond oil (the compound quickly loses its potency in the presence of oxygen, so it’s important to do this). Then I put it in an eyedropper bottle and give myself two drops a day, which equals approximately 40mg (you can safely take up to 120mg/day). The half-life is 31 hours, so you only need to take it once a day (Andrew Hall Cutler PhD stresses the importance of taking chelators on their half-lives to prevent redistribution of metals). There are no side effects, except I am a bit more achy in all the spots I gathered that copper was affecting me (my neck and upper back), I’m a little more tired, but I have such an incredible ability to concentrate now and I’m really inspired and in a great, calm mood! I have been copper toxic all my life and now I’m finally getting my life back. It’s incredible. Good luck to you.

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