doses daily unless otherwise specified
all this is on a weight basis i am 115 lbs. so if the weight was half or 57.5 lbs you would halve the amount of the supplement.
the amounts are in elemental mineral equivalents to the amino acid chelate forms.
the thing about zinc is it is in the same column of the periodic table as cadmium and mercury
Sub-Group IIb : Transition Metal Elements
that is, it has a tendency to displace cadmium and mercury, the two electrons in the outer shell make these elements look similar chemically
but it is also a heavy metal and neurotoxic like both cadmium and mercury, so don't over do it
one mechanism for neurotoxicity is the disabling of the amyloid precursor protein (APP) generated for the purpose of exporting iron
genes for APP are expressed in neurons and is an iron oxidase and the loss of APP in cells and primary neurons causes iron levels to build, while increasing APP promotes the export of iron out of the neurons
in alzheimer's APP gets disabled by high levels of zinc that dissociate from the amlyoid plaques, but in my experience high levels of supplemental zinc have a similar effect w_k post
lead displaces zinc from sulfur-rich structural binding pockets in the proteins, causing them to fold improperly
lead preferentially binds to only three sulfurs in a trigonal pyramidal configuration, even when additional sulfurs are available.
zinc, on the other hand, binds sulfur in a four-coordinate, tetrahedral fashion study
zinc is one of the most basic things against yeast and biofilm, it is essential to biofilm formation but a super-abundance of it seems to impair fungal pathogens, perhaps because of the ability of the immune system to deliver high doses to its targets
chelators tend to pick up a lot of zinc, damaging proteins and depleting body levels
it also needs other cofactor minerals
zinc L-monomethionine is very well absorbed
dizziness, listing to one side, tingling in the skin and some degree of un-coordination might be something fairly specific to the L form in smaller doses compared to other forms and a sign of too much being taken
chelated zinc may have a place because of its spectrum of forms, but is much less well absorbed
inorganic forms of zinc like zinc citrate or oxide feed intestinal yeast in preference to being absorbed by the host
in fact my experience is if you do the minerals, enzymes and other supplements as per the compendium and undertake a dietetic rationality as per the BCD (which includes limiting your eating of seafood and fish) you will very slowly (four or five years ?) shed all the heavy metals in a way that is constructive and builds brain health
it can't be done more quickly than this without severe and subtle organ damage occuring, like in the brain, thryoid, kidneys and anything to do with hormones, a damage spectrum typical of chelation !
the prostate is the bodies most zinc rich organ and zinc deficiency is implicated in prostate cancer, though too much zinc supplementation is also associated with prostate cancer
i wonder if we are used to more zinc in the diet from eating animal prostates, in sausages or various offal dishes?
“ a daily supplement of 7 milligrams of zinc as zinc gluconate was associated with significant decreases in measures of anger - hostility and depression - dejection in young women ”
“ similar studies in lab animals showed that only females experienced increases in aggression levels when zinc deficient, and the new data appears to support this anger-reducing effect in women following zinc supplementation ” said the japanese researchers.
the best zinc in my experience is the L-optizinc from vitabase as it feeds gut bugs the least, but even that is not ideal as you need a smatter of different chelates to match what the diet might provide that do not seem to be satisfactorily supplied by the supplement market
too much zinc may contribute to osteoarthritis
“ zinc and copper ions are known to play important and contrasting roles in apoptosis, with zinc inhibiting the pro - apoptotic protein caspase-3 [..] while copper is understood to enhance apoptosis ”
zinc supplementation may offer some protection against box jellyfish stings, eileen and myself were taking 14mg of optizinc a day (much more than we do now!) and when in darwin (northern australia!) we went swimming and both of us got mildly stung by box jellyfish tentacles that were close to the waters edge and eileen was abit affected and i wasn't really at all, but we may have been saved from a more severe response by being quite “loaded” with zinc so to speak : o)
eileen says she did feel strange for awhile and we waited to see what would happen, the test is, does it get worse?, which fortunately didn't happen
i really think it may have been a closer call than we realised
some people worry about taking copper because of it supposedly being sequestered away in tissues and not showing up in test results
however what i have found with copper is if you are taking zinc and molybdenum as per the compendium you actually have trouble taking enough copper
however copper does seem to have a negative effect on the brain and stomach in single large doses, bascially i just take small amount of copper sebacate (5.5mg of copper sebacate/.75mg elemental copper) once a day or every two or three days !
zinc and molybdenum are very mobilizing of copper
“ one thing i wanted to tell you andrew is that i added copper sebacate to my youngest daughter's stack awhile ago after revisiting your compendium
i want to credit you for the remarkable elevation this brought her to
the connections she was able to make after having this added were pronounced and very new
i challenged it by removing the copper sebacate and she went back to losing the ability to make new intellectual and situational connections
[...] I just want to say again, thank you, Andrew for your work and sharing your incredible gift of self-awareness and knowledge of diet and supplements ”
however i do think that there is a need for a better zinc formulation with a more broad based selection of zinc forms, what that would be i don't know !
the L-optizinc is avaliable from vitabase, go with the 100 tablet bottle as this means a shorter open time for the bottle, there is a 250 tablet bottle which you could put a dry dessicant in when needed
a bit less of the vitabase is needed, like i'll take a quarter of a tablet, but that's a 20 milligram tablet so that's 5 mg for the vitabase compared to 7.5 mg for the source naturals racemic
i haven't tried it yet, but the jarrow L-optizinc formulation called “zinc balance” is likely ok !
for copper i use the source naturals copper sebacate and the solgar copper chelate
oxidizing and can destroy vitamins and food factors
you can, very occasionally, take 1/4 of a copper sebacate or chelate tablet first thing in the morning as an anti-biofilmic, however it can be rough on the stomach for which buffering by taking a teaspoon of double cream first is a possibility
however copper should not be taken just before bed or going to sleep because of possibly antagonising zinc and potentiating glutamate toxicity on the nerves especially the nerves in the eye or the neurons of visual center in the brain!
the oxidant effect of copper could be also contributing in this instance !
interestingly copper oxidises hemoglobin and LDL !
the benefits of copper !
taking a 1/4 copper sebacate in the morning before going to sleep again i woke several hours later with a most unusual dense static tangled mass like a very thin grey/black line that had been scribbled back and forth seen in the central macular area for a second or so before it disappeared !
wether this was in the visual center of the brain or the optic nerve or some (most likely) interaction i can't guess!
i don't think it is diabetic retinal blood vessel overgrowth because it was not in a branched pattern, but so exactly like a dense scribble by hand one might do it was amazing !
possibily there is some benefit to copper sebacate being scrunched over infections/holes in teeth as a anti-biofilmic !
too much zinc is not good for the brain, it displaces too much copper and zinc can act like a toxic heavy metal in excess
well it is actually a toxic heavy metal that is sequestered in little protective cages by the body biochemistry !
zinc may promote anti-fungal immune function but it also seems to depress the anti-viral immune function in medium to large amounts
so i take a quarter of a tablet of the vitabase l-optizinc every second, third or fourth day day and over that same period a quarter of a tablet of the solgar copper chelate and two times a quarter (separated) of the source natural's copper sebacate tablets
i suppose on average i am taking the 5 mg L-optizinc a quarter tablet once every three or four days which makes me think it's much better absorbed than zinc in food, since 5/3.5 = 1.4 mg a day compared to an rda of say 10 mg
i don't like taking just the one form of zinc (in this case monomethionine), so i also put a dab of the resolve brand nappy rash cream (australia) or daktozin (less preferred) between my toes for tinea when necessary (it's also an effective anti-biofilmic on the skin) which diffuses the immune stimulating zinc oxide nanoparticles into the blood !
being able to penetrate all body cells, there will be issues with zinc nanoparticles if the quantities absorbed are too large perhaps? anyway this is abit of an unknown area !
for three meals thats a total of 3/4 of an optizinc tablet which is 15 mg of elemental (equivalent) zinc, however i have gone down to just one meal of taking of zinc and copper a day, and will occasionally have rest days from both supplements
supplementation with every meal, while effective for yeast, is high enough to interfere with thyroid function, so on the one hand you have 15 mg a day total with meals and maybe a snack but are into the metabolically toxic area, particularly an impaired sulphur metabolism
on the other hand if only supplementing zinc and copper after one meal a day, there is one quarter of the zinc tablet a day with smidgens with some meals giving maybe a total of 6 mg a day which seems to be much better for the thyroid but less effective for yeast, so really you are modulating the amounts, i still keep zinc and copper roughly in ratio
the reason for smidgens is that the transport protein for stomach hydrochloric acid is zinc dependent so there may be an advantage to taking at least a small amount of zinc after some meals
estrogen promotes a copper based enzyme essential for the formation of collagen and connective tissue
women approaching, and in menopause, may benefit from copper supplementation, especially if they suffer from an enlarged heart.
when the heart enlarges, muscle cells are permanently lost as they clog with fat that is recruited to meet energy shortfalls, so enlargement is to be avoided at all costs.
the heart is basically muscle on an extremely extensive internal collagen scaffolding
eating lamb heart, liver and using a uvb lamp for skin vitamin d has greatly helped a woman i know with mitral valve and enlargement problems
iron levels need to be kept up which can be an issue for some, fresh, pasture grazed quality beef liver seems to be best for this
for straight mood improvement i would only take copper sebacate, but generally copper i find very helpful for the problematic acrimonial joint (ACJ) in my shoulder
copper chelate is better for joint and ligament issues
thats 5 mg of l-optizinc to 2.1 mg of copper sebacate and chelate which is a ratio of 2.4 and in that context the amount of copper in drinking water can be significant, i don't have any copper in my drinking water.
the acrimonial joint (ACJ) in my right shoulder is much better than it used to be and i think its the increased copper (it was actually sebacate i increased) in relation to the zinc and molybdenum that is helping
copper is part of a cofactor enzyme for the formation of collagen
eileen's comment is that copper salicylate “made my gut upset and head just felt a bit off ”
vitamin C needs to be kept well away from taking copper as it combines with copper to make free radicals
i was taking vitamin C for a while with copper sebacate and zinc under the mistaken impression i was helping passivate the copper, but the effect was the opposite and i feel much better having switched to taking vitamin e a bit before copper and zinc.
possibily it may help to up the copper occasionally, to make more copper/zinc superoxide dismutase (SOD) in the gut, which is a free radical antioxidant that is very helpful in ameliorating the fenton (iron) reaction in the intestine
so, to get a tad more occasionally, you can cut the copper sebacate into 1/3's by slicing a third off the outside diameter, then you have a piece that is a third and a larger piece that is 2/3's, cut the larger piece into half and voila, three pieces of 1/3
SOD has a different mode of action to vitamins. Dubbed 'the enzyme of life' when first discovered in 1968, it is the first antioxidant mobilised by the cell for defence. It is thought to be more powerful than antioxidant vitamins as it activates the body's production of its own antioxidants, including catalase and glutathione peroxidase.
SOD provides some protection against sunburn
i have read about wheat gliadin being a source of superoxide dismutase (SOD) which is a zinc/copper enzyme
i have read over the years of kids doing better with wheat back in thier diet when you not expect it, so maybe they are really short of copper and zinc or have metabolism problems with them
copper and iron are essential in the making of collagen and elastin
lead signifcantly decreases SOD and low copper (and high lead) are associated with cardiovascular problems
Li et al. (2006) measured paraoxonase 1 (PON1) in lead exposed workers and found an inverse association between lead exposure and the PON1 enzyme activity. This observation compliments some epidemiology and related experiments with animals, because low paraoxonase activity is associated with diabetes mellitus, familial hypercholesterolemia, ischemic heart disease, and metabolic syndrome (Klevay 2004). Paraoxonase, although studied most extensively because of its ability to detoxify organophosphate insecticides (James 2006; van Himbergen et al. 2006), has drawn increasing attention because it hydrolyzes homocysteine thiolactone, a vascular toxin that inhibits copper enzymes (Klevay 2006).
my note: lead inhibits copper enzymes
it is better to switch to chelated copper rather than continue with copper sebacate with a virus
it obviously feeds into a different pathway, like chelated copper is not as good for mood
the copper chelate may be considerably less destructive of vitamin a in the stomach and is therefore to be preferred if you are viral, and perhaps otherwise as well, but the sebacate does wonders for mood.
i have done four or five days in a row of only chelated copper because of having a virus but by the fifth or sixth day i was having a crashing depression which switching back to the copper sebacate fixed
molybdenum and copper may combine in the stomach so copper should be kept well clear of molybdenum when taken.
copper from drinking and cooking water from household copper pipes may be a significant source of copper and need accounting for in the amount of zinc and copper taken
zinc is a necessary cofactor for many viral proteins, and the ever1/ever2 gene complex appears to restrict the access of viral proteins to cellular zinc stores, limiting their growth.
so zinc can be pro-viral, probably a balance between what promotes the thymus and what promotes viruses
i have always broadly felt that copper is anti-viral and part of the reason may not just be copper dependent anti-viral enzymes but the effect copper has on deprecating zinc
there is is an interesting skin condition called epidermodysplasia verruciformis where these genes are unable to prevent access by viral protiens to host nuclear zinc and hpv gorws unchecked giving rise to huge cumualtive growths on the legs and arms mainly
i remember in 2002 when i came back from sightseeing in scotland and had started supplementing zinc and caught a bad flu from the woman next to me on the plane who was just dripping it and had that flu for two months and think that was due to taking zinc without copper
copper and zinc destroy vitamin a and beta carotene in the stomach
vitamin a and carotenes are very fragile and easily rendered useless by oxidation
this is not just in supplements about also in foods and especially just eaten food in the stomach
copper is particularly bad bad for this but so is zinc (i do not recommend an inorganic zinc btw like citrate or oxide)
however taking a bit of vitamin e (10 -20 iu?) after a meal and before taking the copper or zinc seems to dramatically help preserve the vitamin a and carotenes in the food as well other food factors including b's
i also suspect that this is a more general issue than just people taking supplements cause of the extensive use of copper piping for water now and the copper loading will be having a strong oxidising effect when used as cooking water and for drinks
with depletion of vit a and carotenes your immune system function just gets depressed and you get viral all the time with exposure, cfs'y
a who_knows post june 06 titled "an upper limit to copper"
have been taking 2 times a quarter of 3 mg copper sebacate twice daily (3 mg daily in total) plus a quarter of copper chelate at each of those time (1.25 mg total daily of chelate)
making a grand total of 4.25 mg daily of copper and its to much on balance, am dropping back to just the copper sebacate which makes 3 mg total daily
its interesting that the article says there is a relatively critical threshold above which the copper is basically retained though in my experience zinc and molybdenum do waste copper
copper does destroy vit a and maybe vit d as well
maybe a relatively critical threshold at which copper changes from be anti-viral to messing immune function
07/07/2005 - Regularly taking copper supplements could lead to excess levels of the mineral that may impact health, said a US researcher last week, calling for the current upper safe limit for the mineral to be lowered, reports Dominique Patton.
Judith Turnlund, a research chemist with the US Agricultural Research Service, has shown in recent studies that the body cannot excrete all of the copper when taken in amounts higher than that found in the diet. Further, excess copper could be associated with reduced immune function and lower antioxidant status, Dr Turnlund told NutraIngredients.com, although the mechanisms for this effect are not yet clear.
"We can't give all the answers yet but here are indications that we need to be cautious," she said. "Supplement companies need to push for more research and should be cutting back levels if they are currently working with 3 mg."
Turnlund's team, working at the ARS Human Nutrition Research Center in the University of California, Davis carried out a series of studies on adult men, giving them different copper intakes that ranged from 0.38 to 7.8 mg per day.
The researchers measured the doses excreted into the gastrointestinal tract and eliminated in the stools for 12 days after copper isotope infusions.
Although the amounts eliminated increased as intake increased, the researchers found that copper was consistently retained when intake reached 2 mg per day and increased further with increases in copper intake. Retention ranged from 0.3 to 0.9 mg per day.
"This is not a problem with usual dietary patterns but the data suggest that routine use of dietary copper supplements containing 2 mg or more per day could lead to accumulation of excess copper," Turnlund told an international symposium on trace elements in Northern Ireland last month (TEMA).
Excess copper could present health risks given the findings of earlier research by the same team, published in the American Journal of Clinical Nutrition (vol 79, pp1037-44) last year. The ARS researchers found that high copper diets over a long period (more than 150 days) altered on indicator of oxidant stress and several markers of immune function.
For the study, nine healthy men took 7.8 mg of copper a day for four and a half months. Blood analyses before and after the study found that the high copper intake interfered with levels of antioxidants.
Men on a high copper regime also had lower immunity than the control group, with reduced ability to fight off the Beijing strain of the flu.
"Seven mg of copper is too much but we don't yet have the data to elucidate the right level for supplementation," Dr Turnlund said.
The research raises key questions for upper safe levels of vitamins and minerals. In the US, the Food and Nutrition Board advises that up to 10 mg of copper daily is safe, while in Europe, the Scientific Committee of Food has set the USL at 5 mg.
Turnlund believes the US level should be lower.
"I was on the committee that set this level but we just didn't have the data at that time."
Copper, found in liver, nuts, sunflower seeds and oysters, is important for the brain, blood and bones and in the US, dietary intake recommendations used to be higher. This triggered its addition to multivitamins and supplements.
But Turnlund believes it is time reassess the amounts used in supplements.
"Copper in a normal diet will vary from day to day but my concern is with supplements. Often the multivitamins contain 2-3 mg per day, and if people are regularly taking several different supplements, their levels could be quite high," she said.
"The total body copper content of an average adult man is 80-100 mg. So if you were accumulating 1 mg per day, this total would double in just 100 days," she added.
More longer term studies looking at a modest level of copper supplementation are required to confirm the ARS findings.
i sent judith turnland the following email but no reply, actually she died of pancreatic cancer in 2009 and would have been 69 when i sent the email and may have been retired by then
I was interested to read your copper study about accumulation of copper with more than 2 mg a day
in fact in terms of supplementation, retained copper seems to be highly dependent on zinc and molybdenum supplementation
there still is a level above which copper is retained but with zinc methionine and copper sebacate supplementation the limit is more like 4 mg depending on body weight
the complexity of absorbtion profiles in different mineral chelate forms and the effect on gut flora seems little appreciated by researchers
copper is unusual in that the inorganic mineral forms are readily absorbed whereas the inorganic mineral forms of zinc are not and also inorganic forms of zinc strongly promote adverse gut biota (similarly for molybdenum)
zinc supplementation is fairly standard for children on autistic spectrum or with pervasive developmental disorders and experience indicates the need for it to be balanced up with copper in many cases
the problem with reducing the pill size of say copper is that you have an issue with supposedly inert fillers like mcs in fact feeding fermenting gut flora and it is a requirement to reduce the amount of filler as much as possible and this is done by cutting the pill down
if the amount of copper in the pill is reduced then you are getting more filler per unit copper which is destructive
given the decline in mineral content in todays foods and the escalating health issues in children as a result of fermenting gut flora issues, the limited digestibility of grains with breeding, and damage from vaccines given too young, it is disheartening to see the head in the sand attitude taken by nutritional schools and government departments.
if you don't think there a problem try and get a feel for the huge number of self injury issues among students at your university. its just horrendous in those age groups now.
a pecanbread thread (3/6/04)
Hi, how can you tell whether a mineral is in an organic or inorganic form? I'm assuming it's based on the ending that follows the name of each mineral but I don't know which is which. 'forliberty'
well you have to research a bit sometimes:
like i thought copper sebacate was a chelate but on researching found out it was a salt (inorganic). oxides are inorganic to.
basically organic minerals are chelated to an amino acid, like say magnesium glycinate is magnesium chelated to the amino acid glycine.
broad spectrum chelates are usually reacted with soy protein but not completely, so you have some degree of inorganic mineral which matters for magnesium
rice protein reacted full spectrum chelates can be good, like the solaray 50 mg manganese
there can be some very unsatisfactory chelates like the natures own magnesium chelate (here in australia) with a high degree of unreacted inorganic mineral magnesium.
i take 7-23 mg of optizinc (zinc methionine) a day. zinc depletes copper and lethargy and tendon pain can be an indication you have depleted too much copper. it pays to rest zinc occasionally, too much is neurotoxic. the source naturals optizinc tablets seem ok and i cut them into a quarter's and may take one to three a quarter's a day a bit after meals - bascially a a quarter of a tablet (7 mg optizinc) sometime after each meal buffering with vitamin c - sometimes i take more. too much zinc can also show as rsi type tendon pain. some kids with copper issues may not tolerate the small amount of copper in 'optizinc', there may be a formulation of zinc methionine somewhere without copper.
as an aside, zinc gluconate has the zn2+ ion which may help with colds or stomach conditions being antiviral if the virus is exposed directly to the zn2+ ion by say holding the tablet against the back of the roof of the mouth with the tongue where it gets absorbed and conveyed up into the nasal passages. zinc acetate supposedly has a higher zn2+ avaliablity but i haven't tried it. water oz zinc is zinc chloride mixed with water i think(very high zn2+ ion avaliablity?). i am unsure what the effect of taking these zn2+ forms regularly would be, it is possible that the anti viral action may upset the viral balance in the stomach or this may be a good thing, it is hard to say.
the source naturals optizinc tablets are what i use on a regular basis. i cut them into a quarter's and take say one to three quarters a day, a quarter 20 mins after a meal seems best and helps with digestion. zinc seems to turn on stomach acid. (16 june 04) when best to take the zinc seems variable, on a half empty stomach can also be useful once i took it half way through the night to good effect, and maybe sometimes just take 1/2 a tablet once a day.
inorganic zincs like water oz or zinc citrate feed yeast imo. the brainchild liquizinc which is half zinc citrate and half krebs chelates has had good reports, but this is for very severe malabsorbtion i suspect and i still am not keen on anything except the source naturals otpizinc and maybe occasional gluconate.
zinc picolinate seems to give vlcfa issues. vlcfa is 'very long chain fatty acids' and when i took zinc picolinate it gave me migraine. zinc picolinate may interere with the bodies metabolism of vlcfa's. i don't like any picolinate form of a mineral.
i have run into issues with the optizinc degrading after a while and releasing free zinc which feeds yeast and is not well absorbed
this was a 240 tab bottle and after a year it has reached this condition, it doesn't take much zinc methionine to degrade to zinc for it to feed yeast
just shows how bad inorganic zinc is as a yeast feeder
i would keep to the smaller 120 source naturals optizinc bottle, and maybe the bottles need a dried dessicant as well
don't ever get capsule optizinc because the powder is too uncompressed and lets the moisture get right through the capsule contents
vitamin d may change gene regulation to help control yeast but the trouble with winter is that vitamin d gene regulation also down regulates viral protection so from autumn things will just get worse as the blood vit d drops and the fruit released over winter from storage just gets more loaded with yeast
i am just about pasturising or cooking all fruit now (june 06 - winter)
basically summer is warm and moist which suits bacteria and fungus and has lots of vit d cause of the sun and winter is viral and has no vit d, so you can see which way evolutionary design would work in terms of vitamin d regulating genes.
whey has to be cut right back over winter to cause it is a yeast feeder, i take a teaspoon of plain whey with goats milk powder mixed in a drink with lemon juice or white vinegar about once every three or four days.
an enzymesandautism post(15/5/04) titled 'zinc needs copper - huge difference'
just a quarter of a tablet of source naturals copper sebacate and 12 hours later i feel more energised.........
bascially i need the zinc to keep yeast down and generally but it is depelting copper so much that i need copper as well.
basically the innate immune system of the gut with its abilty to dump its own enzymes on yeast and gut bugs is now working well enough that things are ok without OoO and continual treatment........
medicine is about 10 years behind on this i think. its the only long term solution and without a broad based suppelmentation esp minerals etc as per my web page you are just not going to get there.
copper sebacte is an inorganic salt of copper i think, since copper is biocidal, that is it is toxic to yeast and bugs being inorganic may not be an issue with it. i will find out i guess, i did see a copper glycinate on the net.
the blurb on the bottle says it is a enzyme co factor for many enzyme systems including the importanat superoxide dismutase and othe antioxidants. also a catalyst in the formation of heamaglobin and collagen
some kids may have high copper and not tolerate copper at first but the zinc will eventually pull the copper down so much that you need the copper.
but i did see a post by a mom with a child with high copper that needed MORE copper so i think its a bit trial and error.
[later - 25th august 04]
a likely high copper person (five amalgams?) i know taking zinc, molybdenum and other minerals was also taking matching copper sebacate and went a bit manic after three days or so and had to take more zinc to damp the manic which worked.
so i would say with likely high copper you start with zinc and molybdenum and add in small amounts of copper sebacate as is tolerated, using zinc and perhaps mloybdenum to step back any copper overshoot and lowering the copper dose.
please bear in mind that these supplements need to be give with the other minerals i talk about or you won't get the stability of effect the synergies provide.
even with high copper, the copper sebacate by providing a form that goes to the right metabolic pathways is an advantage
copper myelinates the nerves speeding things up and zinc demyelinates slowing things down. you can see this when you eat say fresh black salmon, an oily fish full of dha etc good for myelination and it relaxes the need for copper and even gives an extra dimension to it.
an enzymesandautism post(16/5/04)
it is seeming a rule that any mineral has to be in an amino acid chelate form which matches the way it absorbed in digestion from foods......
just got bit on copper sebacate(inorganic) which seems to feed yeast, will have find a chelate form, but i can certainly see i need the copper.
one of these copper bracelets might be a possibilty. i'm not sure if the copper from a bracelet is the right sort of copper at all as it is the same as in house copper piping and kids don't seem to do well on that at all. (later) i tried a copper bracelet and it seemed to make me cranky, i think you get about 1 mg of copper oxide a day from it and it takes about 6-7 hours to go though the skin.
from an enzymesandautism post(17/5/04) titled 'copper is ultra important'
basically it is essential in the myelination pathway and the last thing autism needs is more demyelination!!!!!!!!!!!!!
i'm not 100% happy with the effect of copper sebacate on the gut but it sure is acting quick and seems to get to the right pathways.
its going to take a month or so to sort out the forms but the benefit is so HUGE i will continue with it.
all this taking of zinc and molybdenum is depleting copper (if it was ever adequate in the first place) so no wonder kids are not really getting bettter on dan protocols etc since the emphasis is on reducing copper.
i am not sure what high hair copper means if it is actually a serum issue with copper not going into the cells or is actually high copper, i can see that drinking water from a copper pipe system in a house may mean you have high copper (there may be another issue of it not being the right form since it would be copper oxide),
anyway with copper sebacate, i am taking a a quarter (.75 mg) of source naturals copper sebacate a day and the effect of more energy and connectedness is very apparent within several day so i think that is the best way to test if it helps. actually i felt noticably better within several hours of first taking it.
"Copper activates a number of enzymes important to energy metabolism. It is the key mineral in lysyl oxidase, an enzyme which weaves together collagen and elastin. Copper assists in the formation of hemoglobin and red blood cells by facilitating iron absorption. It is involved in protein metabolism, the production of RNA, and the synthesis of phospholipids used in the formation of myelin sheaths. " from
from an enzymesandautism post(22/5/04) titled 'copper is antiviral'
copper appears to have the ability to disrupt viral RNA
inferring a bit from this
"Copper compounds that selectively damage RNA at picomolar concentrations could one day lead to safe antiviral agents for treating numerous diseases, including AIDS, according to James Cowan and colleagues at Ohio State University in Columbus. There are no cellular repair mechanisms for RNA so finding compounds that degrade it without interfering with DNA could lead to new antiviral agents without the side-effects associated with DNA damage. Aminoglycoside antibiotics, such as gentamicin and neamine, have been shown to block protein production in HIV by attaching themselves to viral RNA. Cowan and his team hoped to take this approach one step further by developing an inorganic compound that would not only interfere with protein translation by RNA but degrade it too. Previous efforts to destroy RNA with conventional drug types have required high temperatures, acid conditions and many hours at high concentration - hardly the ideal drug candidate. By complexing the aminoglycosides neomycin B and kanamycin A with copper ion, Cowan and his team hoped to be able to degrade RNA under much gentler, and ideally, physiological conditions. In a preliminary investigation the team chose an RNA segment, which they knew binds well to neomycin B. They treated it with the copper complexes of the two antibiotics at picomolar concentration, physiological pH and body temperature for about an hour. The products were then separated by gel electrophoresis. NMR analysis of the RNA aptamer with neomycin B shows the aminoglycoside to bind in the stem loop region. Autoradiography of the products resulting from cleavage by the copper complexes demonstrated specific cleavage points corresponding to the sites predicted by the NMR solution structure. They also found that the addition of ascorbic acid to the reaction mixture boosted the effectiveness of the cleavage process. They did not see any degradation of the RNA with copper ions alone or with just the antibiotics. The copper complex does not interact randomly with non-viral RNA nor DNA so they expect it to be a well targeted low dosage antiviral. Cowan says the new drug candidates could provide a useful and effective alternative to antisense drugs which attempt to disrupt DNA and RNA by binding but without degrading. Tests to demonstrate efficacy of the copper complexes against various viral RNA's, such as HIV and Dengue, are in progress. (Chemical Communications, 1999, 1147)" from
i think its a synergy thing, copper and zinc and co factors but if you are short of copper you will be susceptible to viruses.
from an enzymesandautism post(29/5/04) titled 'candex and oreganol for stomach yeast'
been having a bit of a problem with taking taking copper sebacate and this encouraging stomach yeast
took a candex on an empty stomach then after a surprising while you can sort feel the capsule burst, you get a tastes come back up into the mouth and thats the time to take the oreganol i think.
what is happening i think is that the copper is proving very accessiable to yeast(which being plants assimilate inorganic forms very well) amino acid chelates must reverse this situation.
from an enzymesandautism post(30/5/04)
have you taken copper sebacate? no.
it takes a while to form a picture of what it does and really am only just getting a picture now
its rather amazing, seems to amplify similar pathways as no fenol
really ramps on the emotions in a good way
you can't take to much or the nor adrenaline and adrenline pathways get too ramped............
so its not a bulk copper source
putting a heaped teaspoon of plain whey powder in quite warm milk seems to help with the bodies ability to digest it, actually seems to be an excellent source of slow release sugar....................
liver is a good bulk copper source...............
i think high copper hair tests are really a reflection of liver issues and lack of bile since copper is excreted through bile.........................
inorganic copper like copper from bracelets or drinking water from copper pipes is very reactive like mineral iron and a problem......................
from an enzymesandautism post(1/6/04) titled 'copper sebacate is a major winner'
it really improves mood, outlook and just feeling good about life..................
at 120 lbs i am taking a quarter of a source naturals copper sebacate tablet a day (on a full stomach?) which is 0.75 mg (full tablet is 3 mg)
think of it as a non toxic med and not a bulk source of copper, liver once a week will give bulk copper or possibly (and less preferred, copper glycinate)
the whole copper thing and issues with high copper arise from an impaired liver and not making enough bile to excrete surplus copper i think..................
inorganic copper or copper oxide from bangles or copper loaded water is very oxidsing like mineral iron and a big stress on body biochemistry.
copper sebacate is right up there with no fenol, lithium and selenium as super supplements.
an enzymesandautism post (4 june 04) titled 'dana no fenol copper sebacate'
i was just thinking your children might benefit from copper sebacate as it seems to have a similar effect to no fenol, i have halved the amount of no fenol with copper sebacate and between copper sebacate and zinc i am not using as much of the other enzymes.
i am not claiming copper sebacate is easily tolerated at the moment it seems best away from a full meal.
i seem to be eating less as well. copper and zinc are complementary i think, with the copper, less zinc seems needed anyway. one of the bodies important anti-oxidant enzymes uses both.
a mash of several posts (15-17th june 04) 'high copper kids?'
when the liver is not working properly it can no longer dump excess copper though the bile so an unbioavaliable form of copper seems to build up so the issue is really the bioavaliability of the copper.
probably with a high copper kid its best to start with optizinc or plain zinc methionine and say the solgar molybdenum chelate and add in say 1/8th to a quarter of a source naturals copper sebacate tablet as it is felt it is tolerated. because copper sebacate is a salt and can combine with molybdenum and zinc and possibly other minerals (manganese?) i take it separately away from other minerals on say a half full stomach
copper oxide is very reactive and not a good form at all.
probably trying copper is the only way to tell, if a kid was high copper and reacted unfavourably to copper sebacate THAT tells you a lot too, zinc and molybdenum need to bring down the un-bioavailiable copper so you can step in with the bioavailiable copper sebacate at some point.
copper is essential for the immune system and energy cycle, after a while you can see the difference with things like yeast as well as viral immunity.
zinc AND molybdenum are really the optimal combination for bringing down copper.
an enzymesand autism post (25 june 04)
is unbound copper
so its low copper in terms of what the body is using
the bodies copper transport mechanisms are not working properly, nor is the excretion through the liver and bile working properly
so you have the dual problem of too much copper around and not enough copper from impaired transport mechanisms
zinc methionine (optizinc) is extremely well absorbed. zinc citrate may encourage fermentation and is not suitable. occasionally substituting zinc gluconate for the zinc methionine may be of benefit, possibly anti viral.
also copper and zinc need to be separated a bit but not too much like say 10 minutes, but sometimes it pays to take the copper well away from the zinc, other times quite close, there are different synergies
for children you will need to divide the tablets up into maybe 1/8th to 1/16th of a source naturals tablet. you get the hang of these very fine divisions after a while, just know what the rough amount looks like and take several tablets and cut them up, you will lose a bit in waste.
some alternation of the copper sebacate with the solgar copper chelate is needed i think, see the who_knows post in the next section down (not far down, just after the next biggest gap, the who_knows post titled 'copper')
zinc and copper are a seesaw, more zinc and molybdenum require more copper, but zinc is a heavy metal and demyelinating and copper is oxidising, you want to take as little of both as you can get away with, you need them but they both have issues................ they are intrinsically unbalanced and cannot just be taken without regard to quanitity
copper sebacate is an inorganic salt and can combine with molybdenum, zinc, manganese and other minerals so i take it away from them. its just copper sebacate is inorganic so will bind with metals it likes. the other minerals are organic chelates so don't have the same affinity for metals they like.
what i particularly notice now that i have been taking the copper sebacate for a while is that i don't need the vitamin A like i used to, the copper can move it readily out of the liver when needed. if i feel there is a flu or something coming on i will take more copper sebacate. the nutricology germanium and the twin labs allergy a are also helpful for the flu. molybdenum helps move copper around the body.
a sign of too much copper is over activity or a touch manic, too much dopamine or noradrenalaine. also 'antsy' or figitidy or restless. there is quite a fine line between to much and to little copper and will vary, people will amalgams in will tolerate less.
copper oxide or the straight metallic forms are definitely a huge oxidising issue and not wanted. actually i think any form of copper is oxidising.
b vits in combination with copper may help with sleep i think
the number one supplementing mistake is zinc and molybdenum depleting copper and not balancing up with copper so copper sebacate needs to be supplemented. copper is a huge anti viral but needs to be in the right bioavaliable form and copper sebacate seems to do this. when the body presents a copper based enzyme to a virus the virus RNA transcription is dislocated.
the zinc-copper-selenium synergy is extremely potent at removing copper because of the promotion of metalliothionien, each MT can hold seven zinc's or thirteen coppers so you see that copper being less present in the body , yet more pulled out by mt, then............
molybdenum also holds copper in a lattice structure 'clatheration'............ e.g. tetrathiomolybdate
a who_knows post (8th feb 2005) titled 'copper...'
I do have a small problem with the copper I got.
It's Solgar's chelated copper (2.5 mg).
I think there's a relation between taking one tablet of it and me throwing up shortly thereafter in roughly 50% of the cases (depending on timing after a meal).
What does this mean? what happens? why the reaction?
my thinking now about copper is both the copper sebacate and the copper chelate are needed , haven't worked out the ratio's but maybe something like 2/5th's of the copper should be the copper chelate, it seems more anti-viral than the sebacate
maybe not the copper chelate every day, the sebacate is better tolerated but some chelate is necessary in there for disruption of vectoring and to promote balance
so you will need copper sebacate as well, say maybe takinga quarter of a tab of the copper chelate then well separated taking say 2 x a quarter (spaced) of the copper sebacate
that copper chelate is very tough on the stomach, one whole tablet would make me throw up to
an email exchange (26th july 04) on forms of zinc.
What are your thoughts on zinc picolinate? I read a paper that said it is quite bioavailable. Also, are ALL the mineral citrates yeast feeders? I give my daughter optizinc now but wondered about other options. C.
i think the issue with zinc picolinate is it preserves very long chain fatty acids which contribute to demyelination which is the ald (adrenoleukodystrophy) lorenzo oil thing. nothing is better absorbed than zinc methionine but i do worry about having too much of one form of zinc.
however demyelination is a general issue with zinc and this is why copper sebacate is important to re-promote myelination. you can need a suprising amount of copper sebacate.
it maybe that zinc picolinate goes preferentially to the brain and so unbalances the copper there contributing to demyelination? is copper an essential mineral in an enzyme that breaks down very long chain fatty acids? would copper sebacate rectify this and make it ok to take zinc picolinate?
the ratio of 1 to 10 copper to zinc that you mentioned before seems about right.
yeah all the mineral citrates are yeast feeders, its to do with the citrates being easily metabolised by stomach flora and hence the mineral also becomes very available to the flora.
i tried the now 50 mg zinc gluconate yesterday cutting the tablet down to the same dose as the optizinc or maybe a tad more and it goes well occasionally in place of the optizinc
a peacnbread thread (2 july 04) titled 'zink Study against hyperactivity'
I found the zink Study, but I am not able to send it.
But what I did find out is, that the daily zink-dosis was 150 mg and that there where no sideeffects with the treatment of the ADHD children.
Also it said, that it was a good treatment for older children. U.S.
bizarre. you try taking 150 mg a day for a while
What do you think will happen ??
zinc is a heavy metal, its quite toxic to biochemistry and the body has a special system to transport it called metallothione
if this system is overburdened then you get impairment of sulphur chemistry in a similar way to other heavy metals like mercury or lead.
copper would be seriously deficent to
i think the authors were confusing the lethargy from zinc toxicity with a reduction of adhd.
interestingly zinc may depelete manganese, actually i am not at all all sure zinc depeletes manganese.
"An essential mineral found in trace amounts in tissues of the body. Adults normally contain an average of 10 to 20 mg of manganese in their bodies, most of which is contained in bone, the liver and the kidneys. Manganese is essential to several critical enzymes necessary for energy production, bone and blood formation, nerve function and protein metabolism. It is involved in the metabolism of fats and glucose, the production of cholesterol and it allows the body to use thiamine and Vitamin E. It is also involved in the building and degrading of proteins and nucleic acid, biogenic amine metabolism, which involves the transmitting of nerve impulses."
manganese substituting for copper in healthy prion protien to form abnormal prions has been posited as a cause or contributing factor in mad cow disease and cjd, maybe the double whammy of low copper and manganese substituting for copper in prions makes these susceptible to infectious folding. so high manganese and low copper is not a good thing. organophosphate pesticides may chelate copper.
mark purdey's web page
science blog prion article
drawing of beta sheets flattening normal prion alpha helix's article
an enzymesandautism thread (7th july 04) titled 'Prof. Boyd Haley, PhD: Comments regarding the effectiveness of various chelators'
What do you think are the safest and most effective means for parents to chelate their mercury-poisoned children--both with a doctor and without? L.O.
Dr. Haley's answer (ed. from an email to L.O.) : I would recommend going the most natural route possible. We know how healthy children excrete mercury, they do so by first forming the glutathione-mercury complex and using metabolic produced energy to actively excrete the mercury-glutathione complex out of the body through the bilary transport system of the liver into the feces. Therefore, developing a diet that leads to increased intracellular reduced glutathione is important. This diet should also provide the needed minerals and vitamins and nutrients that allow the body to make energy (ATP or adenosine-triphosphate). Vitamin C is a good contributor to both of these needs. The child may also need supplementation of lipoic acid (used in the first step of the citric acid cycle and a strong binder of Hg2+, which inhibits its function and use). All mercury toxic individuals will likely be selenium deficient as Se2- binds Hg2+ very tightly forming HgSe (mercury selenide) which removes the selenium from bioavailability to the body.[snip]
lack of bioavialiable copper inhibits the energy cycle, so high copper which i take to be un-bioavailable copper and low copper both impair mercury removal though high copper will be worse with its high oxidation.
i think this just confirms what i am saying about the necessity of bio avialable copper and also that high doses of vitamin c which will mess with rather than enhance atp production are not a good idea.
from a (8th july 04) discussion of "Activation of methionine synthase by insulin-like growth factor-1 and dopamine: a target for neurodevelopmental toxins and thimerosal" deth pdf article
..... in the discussion it mentions that "Copper 2+ promotes methionine synthase activity and protects against the inhibitory effects of other metals, while copper 2+ chelation has an opposite effect. So I am wondering if DMPS is chelating my kids copper 2+ ? If it does...does anyone know were we could get a supplement of just copper 2+, b/c the other form of copper (Cu+) reduces methionine activity. I also wonder when you should dose it. P.
my comment 1:
yeah copper sebacate has has noticable effect improving dopamine (not a good idea to take too close to bed like no fenol, bit enervating, seems to have an effect about two hours after taking.........), from that paper i would say the cu 2+ must be its secret.
whey and copper sebacate would be a very potent combination since whey provides growth factors.
that must be the crux of the unbioavaliable/high copper problem too.................
all cu + copper and no cu 2+ from mercury and heavy metals.
yeah thats very signficant thanks
lead and cu + are almost as bad as mercury, cu + is also the copper oxide form in water and absorbed from copper bangles
so you have this very toxic form of copper, must be what bill walsh has really been on about all these years
zinc and molybdenum may reduce the total overall copper burden, hard to say the extent to which they may or may not help remedy cu + to cu 2+
i would imagine the vitamin d and probably especially skin vitamin d are other potent synergists with the whey and copper sebacate which would help explain the benefit of high sun in summer
makes the nerves grow too
my comment 2:
since most chelators seem to remove zinc what happens is that copper seems to be retained possibly in the cu+ form, so you have both too much and the wrong form of copper. the antioxidant effect of the chelator may save the situation in the on period, but during the off period the oxidation may be chronic. no wonder andy cutler is so keen on anti-oxidants and why its important to have reasonably constant blood levels of the chelator in the on period.
an enzymesandautism post (10th july 04) titled 'methylation, whey, vitamin d, copper, heavy metals'
an interesting paper that ties things together that are borne out in practical expereince.
the essentialness of cu 2+ (copper sebacate i think) and how it works with whey, zinc and also i infer vitmain d, especially skin vitamin d to methylate the genes and presumably right the gene expression back, and the toxicity of the oxide form cu +
from deth pdf article
Activation of methionine synthase by insulin-like growth factor-1 and dopamine: a target for neurodevelopmental toxins and thimerosal
Methylation events play a critical role in the ability of growth factors to promote normal development. Neurodevelopmental toxins, such as ethanol and heavy metals, interrupt growth factor signaling, raising the possibility that they might exert adverse effects on methylation. We found that insulin-like growth factor-1 (IGF-1)- and dopamine- stimulated methionine synthase (MS) activity and folate-dependent methylation of phospholipids in SH-SY5Y human neuroblastoma cells, via a PI3-kinase- and MAP-kinase-dependent mechanism. The stimulation of this pathway increased DNA methylation, while its inhibition increased methylationsensitive gene expression. Ethanol potently interfered with IGF-1 activation of MS and blocked its effect on DNA methylation, whereas it did not inhibit the effects of dopamine. Metal ions potently affected IGF-1 and dopamine-stimulated MS activity, as well as folate-dependent phospholipid methylation: Cu2 + promoted enzyme activity and methylation, while Cu+, Pb2 +, Hg2 + and Al3 + were inhibitory. The ethylmercury-containing preservative thimerosal inhibited both IGF-1- and dopamine-stimulated methylation with an IC50 of 1 nM and eliminated MS activity. Our findings outline a novel growth factor signaling pathway that regulates MS activity and thereby modulates methylation reactions, including DNA methylation. The potent inhibition of this pathway by ethanol, lead, mercury, aluminum and thimerosal suggests that it may be an important target of neurodevelopmental toxins.
interestingly i had dropped zinc for a day or two but went backwards and looking at bill walshes autism one presentation and metallothionein induction creating a choo choo train pumping zinc copper and heavy metals out.............
i think i am stuck with 7 to 15 mg of the optizinc a day to feed the very zinc high requirements of metallothionein induction
Zn3 Hg4 mt, Zn5 Cu2 mt are examples, bill walsh says 7 zinc atoms are needed for each metallothionein (mt) molecule
so this is basically what my supplementation is doing pumping out copper and heavy metals and replacing the unbioavaliable form of cu+ copper with the bioavaliable cu 2 +
then with whey vitamin d and other supplementation are getting remethylation of dna..................
some magnesium taurate helps as well to encourge bile flow
it's basically a natural chelation system and the few people that have followed this sytem have got very good results.
bill walshes easy to read power point presentation
an enzymesandautism thread (30 june 04)
from a reply by me to a post not shown here:
an issue with copper is wether there is significant copper oxide from house water
E's response (extracts):
2) We live in a newly remodeled house of two years and most probably have copper pipes. Our house water filter is by Multi-Pure.
5) Re: copper... it seems that my daughter's high copper of 53ug/g must indicate it is unbioavailable copper that is floating around and once I bring that down with the correct forms of zinc and molybdenum, then I can start on copper sebacate... is this correct?
is the multipure before the copper plumbing? the multipure is a carbon block filter. wow now i look at this again there is some sort of copper disaster area out there.
came across this interesting post
"Ours is in the refrigerator door. Right now that's all that's filtered.
As I said in the other thread, I used to have a whole house system and I turned it off. Sitting useless in the garage. Carbon type. LOVED IT!!! However, the water that came out of it also loved our copper plumbing. We noticed that we were leaching more copper than should be expected, so I got online and started looking. Apparently, water filtered this way will slowly degrade copper pipes. This can make the water a potential health hazard to those who drink it. Plus, it's not good for the plumbing either. So, to my shagrin, we turned it off. The excess copper sloughing stopped, but now our water smells like the city pool. Now looking into point-of-use for the shower.
According to what I've seen online, the whole-house filtering is pretty good with PVC plumbing, but bad news with copper."
another tricky thing with filters is if they overload they can then dump a lot of what was filtered out itno the water and you can end up with very toxic loads. presumably there are overflow mechanisms like with car oil filters but its something i would check out.
so i think the first step with the copper is to check this out and how much copper plumbing you do have.
an a-m-c post (25th july 04) titled 'filter for copper?'
On hair tests I have very high copper levels. The water in my house, though filtered through carbon, is blue, indicating high copper. Does anyone know of a water filter to reduce copper? J
a synopsis of the investigation that followed so its really only the solid block and pre coat carbon filters that will remove copper to some extent my reply and J's comments:
me: is that if the water has been standing a while?
J: um, maybe, though I use my water all the time.
me: just running the taps for a while to flush the pipes makes a huge difference.
J: I'll try that
me: what happens when you carbon filter the water is it makes it soft and the water after the filter picks up a lot of copper, filtering should be at the point of use like the kitchen or bathroom.
J: I have a sediment & charcoal filter at the water coming into the house, then I also have point of use filters at my sinks & shower/tub.
me: how long has it been like this? (editors note: J has a lot of health issues)
J: long as I can remember. I guess maybe I should change the entry filter to just a sediment filter.
copper is anti-viral because it is a co-factor in anti-viral enzymes and zinc is pro-viral because virues try to extract zinc for their replication from cell nuclei
there is a skin condition in humans that the body looks covered in scaley shells or similar from a genetic mutation which knocks out the bodies ability to deny viruses zinc in the skin cell nuclei, HPV in the case of the indonesian "treeman".
there is also a chinese man known as "the coral reef"
zinc and perhaps especially optizinc increases testosterone
and actually i think testersterone is a major player in promoting female sex drive
but maybe with low thyroid you don't get the hormones broken down quick enough
so u get a push pull effect of increasing testersterone from the zinc and a lower testersterone break down rate with hypothyroid
zinc tends to run out iodine, lowering thyroid, so standalone zinc or inadequate thyroid mineral cofactor supplementation could give rise to elevated testersterone levels
testosterone (as are all hormones) is derived from cholesterol, and zinc promoting testosterone may imply a benefical role for zinc in dealing with cholesterol
supplementing copper and zinc as per this page may help with forming copper/zinc superoxide dismutase which is a free radical antioxidant that is very helpful in ameliorating the fenton (iron) reaction in the intestine
Overexpression of Copper/Zinc- Superoxide Dismutase Protects from Kanamycin-Induced Hearing Loss Su-Hua Shaa, Gary Zajica, Charles J. Epsteinb, Jochen Schachta
The participation of reactive oxygen species in aminoglycoside-induced ototoxicity (inner ear ed.) has been deduced from observations that aminoglycoside-iron complexes catalyze the formation of superoxide radicals in vitro and that antioxidants attenuate ototoxicity in vivo. We therefore hypothesized that overexpression of Cu/Zn-superoxide dismutase (h-SOD1) should protect transgenic mice from ototoxicity. Immunocytochemistry confirmed expression of h-SOD1 in inner ear tissues of transgenic C57BL/6-TgN[SOD1]3Cje mice. Transgenic and nontransgenic littermates received kanamycin (400 mg/kg body weight/day) for 10 days beginning on day 10 after birth. Auditory thresholds were tested by evoked auditory brain stem responses at 1 month after birth. In nontransgenic animals, the threshold in the kanamycin-treated group was 45-50 dB higher than in saline-injected controls. In the transgenic group, kanamycin increased the threshold by only 15 dB over the respective controls. The effects were similar at 12 and 24 kHz. The protection by overexpression of superoxide dismutase supports the hypothesis that oxidant stress plays a significant role in aminoglycoside-induced ototoxicity. The results also suggest transgenic animals as suitable models to investigate the underlying mechanisms and possible strategies for prevention.
"Joan Selverstone Valentine, UCLA professor of chemistry and biochemistry, has studied the protein copper-zinc superoxide dismutase — since the 1970s, long before it was implicated in ALS in 1993. Since the link was discovered, Valentine's laboratory has made more than two dozen mutant, ALS-causing enzymes, most of which have only one wrong amino acid out of 153, to try to understand their properties and learn what makes them toxic.
"Some of the mutant proteins are very different from the normal protein, but others are virtually identical to the normal protein — yet they all cause the disease," said Valentine, "That was the real mystery. You wrack your brain: What is similar among all these proteins" They seem so different. How can they all cause the same disease?
the protein's copper and zinc may not be there at all.
If we keep the metals entirely out of the protein, we can explain the toxicity, since even the normal protein forms aggregate at physiological conditions when the metals are gone," Valentine said. "It was such a puzzle, but this hypothesis can solve it."
Copper-zinc superoxide dismutase, which was discovered in the 1960s, is an antioxidant enzyme that protects cells from free radicals, unstable atoms or molecules that can cause cell damage. The link with ALS came when researchers sequenced the genes of people who have the inherited form of ALS and found that some of them have mutations in the gene that codes for this enzyme. While the inherited form represents only a fraction of all ALS cases, this marked the first time there was any indication of a cause for any form of ALS, Valentine said.
For many years, Valentine's laboratory has studied the normal version of the protein. While the normal protein has copper and zinc, scientists can make it with no metals. When it is first made inside the cell, it has no metals and only acquires them later, Valentine said.
"We studied what happens to the protein if you have the metals, if you have no metals and if you have part of the metals," she said.
it is the metal-free protein that is likely to be toxic. The protein misfolds when the copper and zinc are not present, but folds properly when they are there.
"Before copper and zinc are inserted, the protein can misfold under physiological conditions," Valentine said.
There is evidence that ALS is associated with this misfolding of the protein, which becomes toxic in some way that is not known and has properties similar to misfolded proteins associated with other neurodegenerative disorders like Alzheimer's and Parkinson's diseases, Valentine said.
Is there a way to slow down this process to give the cell more time to eliminate the misfolded proteins in all of these diseases" Would a strategy to reduce or prevent protein misfolding work against these and other diseases" These are avenues for further investigation by researchers.
When Valentine first began working on copper-zinc superoxide dismutase, she was not a biochemist but a biological inorganic chemist and hardly knew what ALS was. She was interested in the enzyme, which is unique in that it has copper and zinc so close together.
Her laboratory isolated and characterized the enzyme, but Valentine was less interested in its biological properties than in the inorganic chemistry. She was more interested, for example, in how the protein influenced the reactivity of the copper or zinc, or how the copper and zinc influenced the structure of the enzyme. She and her colleagues were among the pioneers in taking the copper and zinc out and putting other metals in to see what would happen. Her laboratory put more emphasis on biological factors over time.
"When I moved to UCLA in 1980, we started working on copper-zinc superoxide dismutase in yeast, a model organism, using the then new tools of molecular biology to redesign the protein and make new mutant forms of the protein that would have different inorganic properties," she said. "We were making mutant forms of this enzyme to study, but with no connection to disease.
"I remember the day in March 1993 that the announcement came — it was on the front page of The New York Times — that ALS has been linked to superoxide dismutase (SOD), but the article didn't say which superoxide dismutase; I was hoping it was our enzyme. It took me all day to track down the scientists to find out which SOD it actually was. It was our SOD. It was a very exciting day."
"When we made the mutant proteins, each one seemed to be totally different," she said. "Some of the mutant proteins that cause the disease are identical to the normal protein in every property we measure."
copper (Cu(II)) prevents the deposition of Ab42 in b-sheets while iCu(II) abolishes the b-sheet structure of preformed amyloid fibrils of Ab42.
there is a similar finding for the other form of beta amyloid, Ab40, and together these observations strongly suggest that copper prevents both the formation and the accumulation of plaques in the brain. study
"copper damages a molecule known as LRP (low-density lipoprotein receptor-related protein), a molecule that acts like an escort service in the brain, shuttling amyloid-beta out of the brain and into the body" study
i think iodine, molybdenum, zinc and vitamin e go a long way to offsetting the effect described above, but it is of concern
the compendium copper intake is quite high
copper is needed for strong tendons
a fifty/fifty mix of copper sebacate and chelate may be best for tendon repair
"copper functions as a catalyst in the formation of the intramolecular bond in collagen and appears to be essential for formation of an intermediate aldehydic compound"
the research that follows was collated by eileen :
"copper deficiency impairs crosslink formation and results in gross pathology of bones, lungs and the cardiovascular system of many animal species."
"Lysyl oxidase (LO) is a copper-dependent amine oxidase that plays a critical role in the biogenesis of connective tissue matrices by crosslinking the extracellular matrix proteins, collagen and elastin."
"Recent studies of osteoporotic bone, for example, have demonstrated that subtle perturbations in the pattern of lysine hydroxylation result in changes in the cross-link profile. These alterations, specifically changes in the level of the pyrrolic cross-link, also correlate with the strength of the bone."
"lysyl oxidase was remarkably activated by estrogen in both skin and bone. Thus it is clear that estrogen stimulates the enzyme activity and accelerates the maturation of collagen and elastin in extracellular space."
"Copper's role in connective tissue is linked to the enzyme lysyl oxidase. From a biochemical perspective, copper is a cofactor for the enzyme and a determinant of its activity in connective tissues. Lysyl oxidase catalyses a post-translational oxidation of certain lysine and hydroxylysine residues. The peptidyl aldehydes so formed become active centres for the formation of cross-links in collagen and elastin. Less well understood is how copper controls the steady-state activity of lysyl oxidase; the enzyme fails in copper deficiency" (pmid: 6110524 )
"Both iron and copper play critical biochemical roles in the post-translational modifications of collagen and elastin. These modifications are essential to the maturation and structural integrity of these proteins. Iron functions in the hydroxylation of specific prolyl and lysyl residues in collagen, a process that must occur before the triple helix can form and be extruded from the cell. Copper functions in the oxidative deamination of specific lysyl residues in the soluble forms of both elastin and collagen. This process is essential for crosslink formation and the structural integrity of these proteins. there is no evidence that nutritional iron deficiency results in connective tissue pathology"
"The enzyme activity in the skin of hypophysectomized animals was markedly reduced as compared with the controls indicating directly the dependance of lysyl oxidase activity on pituitary gland hormones." (pmid: 8116)
wikipedia on lysyl oxidase (15th feb 2008)
"lysyl oxidase is an extracellular enzyme that catalyzes formation of aldehydes from lysine residues in collagen and elastin precursors. These aldehydes are highly reactive, and undergo spontaneous chemical reactions with other lysyl oxidase-derived aldehyde residues, or with unmodified lysine residues. This results in cross-linking collagen and elastin, which is essential for stabilization of collagen fibrils and for the integrity and elasticity of mature elastin. Complex cross-links are formed in collagen (pyrodininolines derived from three lysine residues) and in elastin (desmosines derived from four lysine residues) that differ in structure. The importance of lysyl oxidase-derived cross-linking was established from animal studies in which lysyl oxidase was inhibited either by nutritional copper-deficiency or by supplementation of diets with ß-aminopropionitrile (BAPN), an inhibitor of lysyl oxidase. This resulted in lathyrism , characterized by poor bone formation and strength, hyperextensible skin, weak ligaments, and increased occurrence of aortic aneurysms . These abnormalities correlated well with decreased cross-linking of collagen and elastin.
Lathyrogens, found in legumes such as chick peas and vetch, are derivatives of amino acids that act as metabolic antagonists of glutamic acid, Lathyrogens decrease collagen and elastin cross-linking by inhibiting lysine oxidase
if too much lathyrogens are consumed during pregnancy as happens in famine beset countries paralysis can occur in the child
eileen writes: "i suppose pelvic organ prolapse/urinary incontinance could be caused by lack of copper/pituitary hormones too"
“Copper is an essential trace element that acts as a cofactor for the physiological function of many proteins. Tiny amounts are contained in hundreds of copper-dependent proteins that perform essential biological functions in animals and humans.
Hypertrophy is an increase in the size of a tissue or organ. For the study, the researchers challenged two groups of mice for two months, resulting in cardiac hypertrophy—a condition in which the heart becomes bigger followed by disease. Enlarged hearts often occur in response to elevated blood pressure.
Both groups were fed the equivalent of the recommended dietary amount of copper for adults for the entire two months. But after the first month, the test group's diet was increased to contain the equivalent of three times the human recommended amount of dietary copper—an amount that was still just one-third of the equivalent safe upper limit for humans.
By four weeks, heart disease developed in all the mice, and by eight weeks, heart failure developed in the control mice. But the hearts of the mice receiving the extra copper returned to normal size and function, despite the fact that the cardiac challenge continued throughout the eight-week period.
In human hypertrophic heart disease, enlarged heart muscle leads to shortness of breath during exertion, discomfort caused by reduced blood supply to the heart muscle and/or abnormal heart rhythms.
They attributed the beneficial effects to increased production of cardiac blood vessels and to improved function of vascular endothelial growth factor, a molecule involved in function of the delicate lining of those blood vessels.
copper might be activating some kind of cardiac stem cell
liver is a good source of copper”
“ copper is a trace mineral found in all body tissues. it is vital in making elastin, a chief component of the elastic muscle fibers found throughout the body, especially in the heart and lungs. it is needed to build strong bones, connective tissue and joints.
copper is needed for the proper function of the enzyme lysyl oxidase, which is required in the crosslinking of collagen and elastin.”
“ both iron and copper play critical biochemical roles in the post-translational modifications of collagen and elastin. these modifications are essential to the maturation and structural integrity of these proteins.
iron functions in the hydroxylation of specific prolyl and lysyl residues in collagen, a process that must occur before the triple helix can form and be extruded from the cell.
copper functions in the oxidative deamination of specific lysyl residues in the soluble forms of both elastin and collagen.
this process is essential for crosslink formation and the structural integrity of these proteins.
while there is no evidence that nutritional iron deficiency results in connective tissue pathology, copper deficiency impairs crosslink formation and results in gross pathology of bones, lungs and the cardiovascular system of many animal species. ”
“ i discovered that the gliSODin by Bluebonnet really gave my daughter a lift after treatment of a micoplasma infection (and me as well).
but what goes wrong with collagen disorders such as Ehlers-Danlos Syndrome?
should my daughter continue taking supplemental SOD (gliSODin) in the hope that her copper and iron metabolism will improve enough for her cells to produce a more correct version of collagen/elastin? I realize this might be a rhetorical question, but does anything leap to mind? ”
i would say it's genetic and she will always be working to get adequate collagen production
pig skin is a good source of collagen, but it's difficult to digest, needs to be well cooked and pep taken with it
thanks for that info about the gliSODin by Bluebonnet, it looks like an effective supplement and as we all know, that is pretty rare !
yeah SOD is a huge antioxidant and why the compendium emphasises keeping a balance of zinc and copper
i do feel that unfortunately breeding has made wheat problematic
“ Long-lived structural proteins, collagen and elastin, undergo continual non-enzymatic crosslinking during aging and in diabetic individuals. This abnormal protein crosslinking is mediated by advanced glycation end products (AGEs) generated by non-enzymatic glycosylation of proteins by glucose. The AGE-derived protein crosslinking of structural proteins contributes to the complications of long-term diabetes such as nephropathy, retinopathy, and neuropathy. AGE-crosslinks have also been implicated in age-related cardiovascular diseases. ”
“ Early and advanced glycation end-products are increased in dietary copper deficiency ”
“ high blood sugar from diabetes reacting with proteins in the body is the major factor in AGE, which is why diabetes is so bad for it ”
The activity of chelated Cu(II) with four different aspirin-like drugs in various superoxide dismutase assays was examined. Prior to these studies the oxidation state of the involved copper was measured by x-ray photoelectron spectrometry and was found to be +II throughout. All copper complexes were able to suppress the xanthine-xanthine oxidase mediated reduction of both cytochrome c and nitroblue tetrazolium as well as the formazan formation by KO2 in a specific manner. The hydroxylation of benzo-[alpha]-pyrene as well as the demethylation of 7-ethoxycoumarin using induced hepatic rat microsomes could be successfully inhibited by the employed Cu(II) chelates. Cu(II)-acetylsalicylate was the most active copper complex. Our findings support the proposal that Cu(II) chelates are the active forms of aspirin-like anti-inflammatory agents
from that study i would take it that too much zinc and the consequent binding of zinc on the non-middle receptors of amylin was a clumping promotion factor
zinc and molybdenum, being copper depleters have to be balanced supplementally with copper, or you risk increasing dysfunction in the brain from more unstable prions (prions are a functional unit in the brain, its only certain misshapes which are contagious and destructive)
prions may have a protective role for neurons in the brain
over-supplementation of zinc chasing better anti-fungal protection but giving rise to general issues of impaired sulphur metabolism and brain issues like the above is almost the single biggest supplementation mistake
manganese can substitute for copper in prions study
this may be the reason for the spontaneous induction or susceptibility of prion diseases in areas with high manganese in the soil.
wether its a simple as that i don't know, but i did read a report of magnesium helping with brain issues in groote eylandt which has very high manganese and magnesium displaces manganese