Minerals and neurodegeneration (Good/Bad)...
Skyguy2005 07 May 2017
I though I'd post a bit about minerals. Which minerals are most heavily implicated in neurodegeneration? My non-expert summary would be:
Neurodegenerative: Copper, Iron, Manganese, Aluminium, Lead, Arsenic, Mercury
Not Sure: Zinc
Neuroprotective: Molybdenum, Magnesium
E.g. there has been a lot of evidence that copper favours neurodegeneration, with some ambiguity.
https://www.ncbi.nlm...pubmed/22024360
https://www.ncbi.nlm...les/PMC4030141/
http://www.cureffi.o...-prion-disease/
https://www.ncbi.nlm...pubmed/21619885
https://www.scienced...30819171636.htm
Magnesium may be protective:
http://nri.bjmu.edu....71507939207.pdf
https://www.ncbi.nlm...pubmed/24625803
Molybdenum may be protective as it antagonises copper.
Dorian Grey 07 May 2017
Zinc is antagonistic to copper, which along with iron are the ultimate pro-oxidants.
Myelin sheath's of neurons are 80% lipid in composition and these metals act as catalyst's for lipid oxidation.
Copper plumbing and iron fortification of foods results in excess levels of these minerals accumulating with age.
Manage these two toxic minerals well, & half the battle of neurological inflammaging is won.
Curcumin, Quercetin & IP6 (Inositol Hexaphosphate) are your natural iron/copper chelators.
Great Thread!
Edited by synesthesia, 07 May 2017 - 08:28 PM.
Skyguy2005 07 May 2017
I also thought that even though plant foods are containing copper, they are also the highest sources of molybdenum (especially beans). tetrathiomolybdate is used for chelating copper in case of toxicity. This link http://www.whfoods.c...trient&dbid=128 says that the top 8 foods containing molybdenum are lentils, peas, lima beans, kidney beans, soybeans, black beans, pinto beans, and garbanzo beans. Oats barley and nuts contain some, but 10-fold less than beans.
Dorian Grey 07 May 2017
Phytic Acid (the food name for IP6 / Inositol Hexaphosphate) is also a good chelator of copper.
Whole grains, nuts, legumes the richest source.
I just posted on Ferrotoxic Disease over in Aging Theories.
http://www.longecity...isease-omnibus/
Edited by synesthesia, 08 May 2017 - 12:03 AM.
adamh 08 May 2017
Lets not forget the fact that copper is an essential mineral, you have to have it. Like anything else too much is no good and neither is too little. Another very important factor is organic or non organic in form. Organic copper is what you get from plants, we need around 2mg cu per day. Inorganic copper is the bad form, things like cuperic oxide and various other forms of copper not seen in living things. Get your copper from a good source and use the right amount.
Many multi vitamins have the wrong form of copper in them. If it does not say the type, its probably inorganic. If it does tell you the form then look it up to see if its a good one or bad one.
Iron too is essential, we would die without any iron in our bodies same as having no copper. Low to medium levels of iron are best. Men and post menopausal women should avoid multis that have added iron.
The same could be said for the other minerals mentioned. Get a reasonable amount in your diet or with supplements but do not go overboard and try for good forms of the minerals. Food sources are generally best.
Dorian Grey 08 May 2017
Sorry I don't have a link, but from what I've read trace minerals are almost never deficient, (the exception being iron in menstruating females) but often become unbalanced, usually by an excess of a given trace that antagonizes the effect of its counterpart. Too much (supplemental) zinc for instance, interfering with copper utilization.
I avoid supplementing trace min's for this reason as it's easy to do more harm than good. Dietary manipulation of trace minerals on the other hand, is a lot safer and worth exploring. Modest chelation, with natural chelators like curcumin, quercetin & phytic acid (IP6) intrigue me, as I believe trace minerals are so easily replaced through normal diet, drawing down excesses through chelation should be helpful in maintaining a proper balance.
Magnesium appears to be the most common (macromineral) mineral deficiency, so I do supplement this modestly with mag-taurate.
Copper (through copper plumbing) and iron (through fortification) in men are examples of minerals that typically accumulate and result in imbalances, so I focus on correcting this through dietary and chelation protocols.
My humble opinion, but fairly logical.
Edited by synesthesia, 08 May 2017 - 02:46 AM.
Skyguy2005 08 May 2017
Let's look for copper and all cause mortality. I found five studies.
https://www.ncbi.nlm...pubmed/16570028
1. Zinc, copper, and magnesium and risks for all-cause, cancer, and cardiovascular mortality.
High copper values (4th quartile) were associated with a 50% increase in RRs for all-cause deaths (RR = 1.5; 95% confidence interval = 1.1-2.1), a 40% increase for cancer mortality (1.4; 0.9-2.2), and a 30% increase for cardiovascular mortality (1.3; 0.6-2.8) compared with low values (1st quartile). High magnesium values were negatively related to mortality with a 40% decrease in RR for all-cause (0.6; 0.4-0.8) and cardiovascular deaths (0.6; 0.2-1.2) and by 50% for cancer deaths (0.5; 0.3-0.8). Additionally, subjects with a combination of low zinc and high copper values had synergistically increased all-cause (2.6; 1.4-5.0) and cancer (2.7; 1.0-7.3) mortality risks. Similarly, combined low zinc and high magnesium values were associated with decreased all-cause (0.2; 0.1-0.5) and cancer (0.2; 0.1-0.8) mortality risks.
http://jamanetwork.c...article/1105975
2. Dietary Supplements and Mortality Rate in Older Women: The Iowa Women's Health Study
Results In multivariable adjusted proportional hazards regression models, the use of multivitamins (hazard ratio, 1.06; 95% CI, 1.02-1.10; absolute risk increase, 2.4%), vitamin B6 (1.10; 1.01-1.21; 4.1%), folic acid (1.15; 1.00-1.32; 5.9%), iron (1.10; 1.03-1.17; 3.9%), magnesium (1.08; 1.01-1.15; 3.6%), zinc (1.08; 1.01-1.15; 3.0%), and copper (1.45; 1.20-1.75; 18.0%) were associated with increased risk of total mortality when compared with corresponding nonuse. Use of calcium was inversely related (hazard ratio, 0.91; 95% confidence interval, 0.88-0.94; absolute risk reduction, 3.8%). Findings for iron and calcium were replicated in separate, shorter-term analyses (10-year, 6-year, and 4-year follow-up), each with approximately 15% of the original participants having died, starting in 1986, 1997, and 2004.
http://link.springer...0522-009-9251-1
3. Plasma copper/zinc ratio: an inflammatory/nutritional biomarker as predictor of all-cause mortality in elderly population
Cu/Zn ratio may be considered an important clinical inflammatory-nutritional biomarker as well as a significant predictor of all-cause mortality in over 70-year-olds.
http://digitalcommon...chcres_articles
4. High Serum Cu and Cu/Zn Ratios Correlate with Impairments in Bone Density, Physical Performance and Overall Health in a Population of Elderly Men With Frailty Characteristics
http://www.tandfonli...762.2014.901510
5. Copper, ceruloplasmin, and long-term cardiovascular and total mortality (The Ludwigshafen Risk and Cardiovascular Health Study)
Background. Copper and its main transport protein ceruloplasmin have been suggested to promote the development of atherosclerosis. Most of the data come from experimental and animal model studies. Copper and mortality have not been simultaneously evaluated in patients undergoing coronary angiography. Methods and results. We examined whether serum copper and ceruloplasmin concentrations are associated with angiographic coronary artery disease (CAD) and mortality from all causes and cardiovascular causes in 3253 participants of the Ludwigshafen Risk and Cardiovascular Health Study. Age and sex-adjusted hazard ratios (HR) for death from any cause were 2.23 (95% CI, 1.85–2.68) for copper and 2.63 (95% CI, 2.17–3.20) for ceruloplasmin when we compared the highest with the lowest quartiles. Corresponding hazard ratios (HR) for death from cardiovascular causes were 2.58 (95% CI, 2.05–3.25) and 3.02 (95% CI, 2.36–3.86), respectively. Further adjustments for various risk factors and clinical variables considerably attenuated these associations, which, however, were still statistically significant and the results remained consistent across subgroups. Conclusions. The elevated concentrations of both copper and ceruloplasmin are independently associated with increased risk of mortality from all causes and from cardiovascular causes.
Copper seems to consistently be shit!! I didnt cherry pick or anything. I look for copper and it's aaaall bad. I look for magnesium and its all good.
Edited by Skyguy2005, 08 May 2017 - 07:19 PM.
adamh 08 May 2017
Of course high levels of copper are bad for you, I already mentioned that and most of us knew it. No need for voluminous studies for what is more or less common knowledge. My post was simply to point out that copper is indeed an essential mineral and we can't do without it, same with iron and all the others mentioned. A safe balance is what we need and iron supplements are of no benefit to most of the population.
The other thing I wanted to bring out is the form that the minerals come in which can affect bioavailability as well as potential toxicity. Here is a quote from an article
http://www.livestron...er-supplements/
"Organic copper in food is processed by the liver and transported and stored in a safe manner, whereas copper supplements -- including chelated forms -- largely bypass the liver and enter the bloodstream directly, according to a study published in a 2009 edition of the "Journal of the American College of Nutrition." High blood levels of copper are toxic, especially to the brain. Copper toxicity has been linked to Alzheimer’s disease and cirrhosis of the liver"
So we want to not only avoid excess copper we want to avoid inorganic forms of it such as metalic copper and compounds without carbon. For example, copper leached out of copper plumbing found in many homes is inorganic and not good. A reverse osmosis filter will take out most of that.
Quite often when the public becomes aware of a problem with a substance or food, they go overboard. For example when cholesterol and saturated fats were indicated as being a problem people wanted to avoid all of it but we now know that some saturated fats are good and needed. Again it comes down to balance rather than completely avoiding something.
Magnesium is a great thing and most people are somewhat deficient in it. Organic forms will be easier to absorb but even mg can be overdone and can reach toxic levels though that is rare.
Dorian Grey 09 May 2017
The issue of balance becomes interesting when one takes a look at what imbalances occur most often. When it comes to copper, it appears an excess is quite common.
http://www.acu-cell.com/crcu.html
"Of thousands of patients tested since the mid 1970s from different continents around the world, nearly 90% exhibited a chemical profile that in addition to their own unique chemistry, contained an underlying pattern that reflected the impact of elevated copper levels on various opposing nutrients, which include Vitamin C, chromium, sulfur, nickel, molybdenum, and hesperidin, an essential flavonoid, among others."
If copper excess/imbalance is known to dominate large percentages of the population, is it not wise to attempt to ameliorate this imbalance and the negative impact it may have on health?
Age related iron accumulation, due to a lifetime of consuming iron fortified foods is the other common imbalance...
https://freetheanima...everything.html
Would it not make sense to monitor iron by adding a ferritin test to routine labs and take measures to keep ferritin out of triple digits, where it begins to become problematic?
Regarding magnesium toxicity, we dose pregnant women in pre-term labor with mag sulfate with a 4-6 gram loading dose which is maintained at 2-3 grams per hour IV (up to 80 grams/day), often for extended periods. This does not harm either mother or child.
Edited by synesthesia, 09 May 2017 - 06:53 AM.
pamojja 09 May 2017
Regarding magnesium toxicity, we dose pregnant women in pre-term labor with mag sulfate with a 4-6 gram loading dose which is maintained at 2-3 grams per hour IV (up to 80 grams/day), often for extended periods. This does not harm either mother or child.
Wow, 80 g/d! Thanks for that assurance. I need above 2 g/d of oral elemental magnesium just to keep painful muscle-cramps away for years, and was wondering if there is a toxic level ever for Mg.
Skyguy2005 09 May 2017
So we want to not only avoid excess copper we want to avoid inorganic forms of it such as metalic copper and compounds without carbon. For example, copper leached out of copper plumbing found in many homes is inorganic and not good. A reverse osmosis filter will take out most of that.
Quite often when the public becomes aware of a problem with a substance or food, they go overboard. For example when cholesterol and saturated fats were indicated as being a problem people wanted to avoid all of it but we now know that some saturated fats are good and needed. Again it comes down to balance rather than completely avoiding something.
Agreed that supplemental/leached/inorganic copper is the problem. For one thing people have not evolved with it.
Probably avoiding cholesterol is not a bad idea - thats basically veganism in a nutshell - although not perfect. I dont think overreacting is really possible anyway for dietary copper unless you were really stupid. It's in mushrooms, green veg and legumes and whole grains which anyone with a brain is eating anyway. It's pretty much in anything that doesn't contain saturated fat and cholesterol, ironically!
Diet-wise I can only see to avoid shellfish (clams, oysters, cockles, mussels, but not scallops) and organ meats. This is probably good to do anyway (BMAA, cholesterol).
Reacting/overreacting to environmental exposure to non-dietary copper - which is presumably a big factor as it's fairly ubiquitous/consistent in most foods - maybe thats reasonable. Maybe copper in pipes is a massive factor, as big as eating too much meat, in alzheimers.
Edited by Skyguy2005, 09 May 2017 - 06:36 PM.
adamh 10 May 2017
So we want to not only avoid excess copper we want to avoid inorganic forms of it such as metalic copper and compounds without carbon. For example, copper leached out of copper plumbing found in many homes is inorganic and not good. A reverse osmosis filter will take out most of that.
Quite often when the public becomes aware of a problem with a substance or food, they go overboard. For example when cholesterol and saturated fats were indicated as being a problem people wanted to avoid all of it but we now know that some saturated fats are good and needed. Again it comes down to balance rather than completely avoiding something.
Agreed that supplemental/leached/inorganic copper is the problem. For one thing people have not evolved with it.
Probably avoiding cholesterol is not a bad idea - thats basically veganism in a nutshell - although not perfect. I dont think overreacting is really possible anyway for dietary copper unless you were really stupid. It's in mushrooms, green veg and legumes and whole grains which anyone with a brain is eating anyway. It's pretty much in anything that doesn't contain saturated fat and cholesterol, ironically!
Diet-wise I can only see to avoid shellfish (clams, oysters, cockles, mussels, but not scallops) and organ meats. This is probably good to do anyway (BMAA, cholesterol).
Reacting/overreacting to environmental exposure to non-dietary copper - which is presumably a big factor as it's fairly ubiquitous/consistent in most foods - maybe thats reasonable. Maybe copper in pipes is a massive factor, as big as eating too much meat, in alzheimers.
What you get in veggies is almost certainly going to be the organic form of copper which is much better than inorganic. Since we do need some copper, its best to get it from those sources. Multis with copper should be viewed with suspicion and if they do not state its organic sourced, then avoid.
Cholesterol in excess is not good, but if there is none in the diet our bodies will produce some because its needed. We need some saturated fats just not too much. The brain is made up mostly of fat, you don't want to lose that do you? lol. Likewise our organs have a healthy amount of fat in their makeup, its just when we overdo it that it becomes a problem. They have studied primitive societies that ate most of their calories from fat and they did not seem to have a high rate of illness. But they ate less calories than we do and got more exercise.
Edited by adamh, 10 May 2017 - 01:14 AM.
normalizing 10 May 2017
i was cut short of donating blood because i wasnt born in US, now i wonder how to get rid of excess iron :/
Dorian Grey 10 May 2017
i was cut short of donating blood because i wasnt born in US, now i wonder how to get rid of excess iron :/
Curcumin, Quercetin, & IP6 are your natural iron chelators. Cilantro in foods too. Drinking coffee or tea with meals will inhibit absorption of dietary iron. This is particularly effective for non-heme iron typical in iron fortified foods.
Breakfast cereals are absolutely loaded with iron fortification, so you might want to avoid these. Take Vitamin-C on an empty stomach, as C greatly increases absorption of dietary iron, particularly from fortified foods.
If ferritin is up near the top of normal range, a referral to a hematologist for therapeutic phlebotomy is also an option.
GP's tend to poo-poo high iron, but hematologist's are usually quite open minded about treating this.
normalizing 10 May 2017
on separate note i just found this study suggesting garlic's alicin antibacterial action is both inhibiting zinc AND copper; http://pubs.acs.org/...cs.jafc.7b00250
it seems most people talk ill of copper on here, but it will seem zinc also plays role in some negative effects and while both copper and zinc work in balancing ratio for good health, it would mean inhibiting them both together is actually good!
pamojja 10 May 2017
Probably avoiding cholesterol is not a bad idea - thats basically veganism in a nutshell - although not perfect.
Cholesterol in excess is not good, but if there is none in the diet our bodies will produce some because its needed.
My experience too. Was vegan from age 10 and avoided fat. With age 41 was diagnosed a PAD due to 80% stenosis at my abdominal aorta. I added in eggs, fish and loads of fats again (about 68% of calories), along with comprehensive supplementation. LDL, HDL and trigs improved in average 40%. Moreover, a 60% government certified walking-disability has again been revoked.
Skyguy2005 10 May 2017
Cholesterol in excess is not good, but if there is none in the diet our bodies will produce some because its needed. We need some saturated fats just not too much. The brain is made up mostly of fat, you don't want to lose that do you? lol.
The brain is made up mostly of brain, should we eat brains for food? I wouldn't trust to that logic.
Avoiding fatty acids is not a good idea as that includes olives, nuts and all the unsaturated fatty acids esp. oleic and omega 3. Avoiding or at least moderating cholesterol in the diet there is plenty of evidence for. Pescetarian is a good balance as it is less cholesterolish, and contains good fatty acids (plus more selenium, which may be deficient in a vegan diet).
on separate note i just found this study suggesting garlic's alicin antibacterial action is both inhibiting zinc AND copper; http://pubs.acs.org/...cs.jafc.7b00250
it seems most people talk ill of copper on here, but it will seem zinc also plays role in some negative effects and while both copper and zinc work in balancing ratio for good health, it would mean inhibiting them both together is actually good!
I'm not sure zinc deserves the reputation of copper but it can interact with proteins and increase misfolding. Also, zinc is something like 5-fold more common in beef and lamb than in chicken or turkey, which is something of a red flag.
Edited by Skyguy2005, 10 May 2017 - 04:00 PM.
Heisok 10 May 2017
This is an excellent, and important topic. I wanted to research deeper before posting, but have not had a chance. Sorry. At this stage, these are just possibilities which I am proposing, and really questions.
Like any way of eating, I would think that a Pescetarian diet needs to be carefully thought out as to choices. My understanding is that some fish contains Mercury. Maybe that could hurt ones brain. Looking for lower mercury species of fish might be advisable.
There has been some discussions about Aluminum being an issue for some. Perhaps a form of Silica might be a path. Two Longecity discussions about sources including water, and supplements. Also some comments about the different forms of Silicon for supplementation. These have included posters which I greatly respect.
http://www.longecity...um-from-body/ "Silicon rich mineral water purges aluminium from body"
http://www.longecity...ne-take-silica/ "does anyone take silica?"
Edited by Heisok, 10 May 2017 - 05:55 PM.
normalizing 10 May 2017
if you are taking lots of supplements then its very likely you are dosing quite high on the silica as well. check ingredients, supplements always contain silica plus magnesium stearate. the two major "inactives"
Skyguy2005 11 May 2017
http://journals.plos...al.pone.0153513
Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans
We found that increasing zinc levels in vivo with excess dietary zinc supplementation decreased the mean and maximum lifespan, whereas reducing zinc levels in vivo with a zinc-selective chelator increased the mean and maximum lifespan in C. elegans. We determined that the lifespan shortening effects of excess zinc required expression of DAF-16, HSF-1 and SKN-1 proteins, whereas the lifespan lengthening effects of the reduced zinc may be partially dependent upon this set of proteins. Furthermore, reducing zinc levels led to greater nuclear localization of DAF-16 and enhanced dauer formation compared to controls, suggesting that the lifespan effects of zinc are mediated in part by the insulin/IGF-1 pathway.
...
Secondly, reducing zinc levels were shown to slow the normal age-dependent increase in protein aggregation within the worm, which is a common feature of the disease of aging. The reasons for this are also unclear, but could involve direct effects, such as the removal of excess zinc ions from aggregated proteins. In numerous other disease models, zinc has been shown to modulate protein aggregation, including the promotion of beta amyloid aggregates in models of Alzheimer disease [76,77] and even urinary concretions in a D. melanogaster [78]. Moreover, the use of zinc-selective metal chelators has been shown to be efficacious in improving proteostasis and overall morbidity [79,80].
To balance out stuff about copper being bad. Maybe zinc supplementation is also bad? Increasing protein aggregation sounds like neurodegeneration to me.
Obviously nobody especially me knows what all this means. Personally it inspires me to avoid not only copper and iron but also zinc in supplements, and just eat good and drink green tea (+ whatever other chelators like Ginkgo and Turmeric).
Edited by Skyguy2005, 11 May 2017 - 06:38 PM.
Skyguy2005 12 May 2017
Curcumin, Quercetin, & IP6 are your natural iron chelators. Cilantro in foods too. Drinking coffee or tea with meals will inhibit absorption of dietary iron. This is particularly effective for non-heme iron typical in iron fortified foods.
What's your opinion on alpha-lipoic acid?
Dorian Grey 12 May 2017
I've taken ALA off and on over the years. Haven't read about it for a while, but seemed to recall it had a short half life. Read it's good for chelating mercury, but I've had that removed from my mouth years ago.
I prefer SAM-e (s adenosylmethionine) to help bump glutathione, as SAM-e helps keep arthritis in check too, which is good at my age.
https://www.ncbi.nlm...pubmed/15102339
Nothing against the ALA though.
Edited by synesthesia, 12 May 2017 - 02:45 AM.
Skyguy2005 12 May 2017
how is gingko a chelator?
Magic. No seriously flavonoids (the 24% in Ginkgo 24/6).
http://onlinelibrary....200800299/full (Ginkgo)
https://www.ncbi.nlm...pubmed/12592672 (flavonoids like quercetin, myricetin which are found in Ginkgo)
http://www.fasebj.or...act/20/4/A197-a (kaempferol)
http://pubs.acs.org/...nalCode=jafcau (kaempferol)
Most evidence is on flavonoids found of the sort found in Ginkgo. I could only find one study specifically saying Ginkgo chelates metals, which said it chelates iron.
Ginkgo also contains (+)-catechin, (-)-epicatechin, (-)-gallocatechin, (-)-epigallocatechin, so it has a bit of overlap with green tea. Again, these are known chelators.
https://www.ncbi.nlm...pubmed/24759072
Edited by Skyguy2005, 12 May 2017 - 08:46 PM.
Omega 3 Snake Oil 13 May 2017
How does curcumin chelate copper?
Also I started a thread on bioavailable copper, please weigh in if you can: http://www.longecity...ailable-copper/
Dorian Grey 13 May 2017
How does curcumin chelate copper?
Also I started a thread on bioavailable copper, please weigh in if you can: http://www.longecity...ailable-copper/
https://www.ncbi.nlm...pubmed/26902401
Curcumin is a biologically active copper chelator with antitumor activity
normalizing 14 May 2017
lots of mentions on copper and zinc in high amounts being detrimental, but so far i havent see any study supporting copper in even moderate amounts being beneficial in any way. so i checked on zinc and it seems most people get it wrong, its actually pretty beneficial even in high doses given certain conditions, like the ones ill list here;
Skyguy2005 16 May 2017
What about chlorella? I've heard about chlorella binding to heavy metals, on the other hand it is rich in iron and zinc.
If you take chlorella are you chelating iron/zinc, are you taking iron/zinc, or does it cancel out?
Edited by Skyguy2005, 16 May 2017 - 04:55 PM.
Dorian Grey 17 May 2017
Well, the Japanese love chlorella, & they outlive most other modern industrial cultures, so I expect it can't be all bad.
Anything that contains a boat-load of iron is off my list though, particularly when there are other well established detox/chelation options like curcumin, quercetin & IP6.
If I was going to try this, I'd check my ferritin before, and every few months after starting this, to see if it destabilized iron stores.
Edited by synesthesia, 17 May 2017 - 02:51 AM.