High Iron and Low Manganese
*This article is not medical advice. Before starting on any health related regimen, seek the advice of your Primary Care Physician or an M.D.
Turns SOD2 into a Pro Oxidant Creating Gene…
Is it a Coincidence that the Drug Used to Silence Autism Inhibits the Stimulation of SOD2 ?
High iron, especially free unbound iron can cause significant oxidative stress when it combines with hydrogen peroxide, yielding the fenton reaction that produces very damaging hydroxyl radicals. This has been well known, published, and researched for decades.
However, I recently came across some research, that illuminates another HUGE issue with too much free unbound iron - it inserts itself in place of manganese into SOD2. Or, insufficient Manganese can also lead to iron insertion into SOD2. This disables SOD2 which is designed to detox Super Oxide (free radical) and instead results in a build up of super oxide, and also production of hydrogen peroxide.[1]. When iron is inserted into SOD2 instead of manganese it turns SOD2 into a Pro-Oxidant Peroxidase [2]- creating significant oxidative stress in the mitochondria, and silences its Super Oxide neutralizing activity.
Sirtuin genes SIRT1 and SIRT3 are both linked to SOD2 - and both stimulate SOD2. Is it a coincidence that the father of the "Cell Danger Response" theory, Robert Navioux, uses a drug to treat Autism (experimentally with success) - Suramin - that inhibits SIRT1 and SIRT3 !?. Suramin inhibits SIRT1 and SIRT3, say that again. Later I will detail another Sirtuin gene, SIRT4. Why is SIRT4 important ? Hint, it has to do with glutamate transport. Most cases in Autism, have excess glutamate. Hmm.
Please see my earlier blog article on Aluminum and how that may contribute to neurological issues, oxidative stress, and dysfunction in the heme pathway. Hint - Aluminum results in excess unbound free iron - because it inhibits the heme pathway (needed to bind iron). What do we find in the brains of folks diagnosed with Alzheimer's? Aluminum. What else inhibits the heme pathway ? Lead, Mercury. What else ? Elevated IL-10 (GI inflammation). What else ? Inhibition of the krebs cycle (needs succinyl CoA). What inhibits the krebs cycle - aside from nutritional depletion ? Lead, Mercury, and most importantly Aluminum. What else inhibits the heme pathway ? Low copper, low manganese. What else, c'mon. Glyphosate...... by inserting itself in place of glycine in the heme pathway (which shuts it down) - glycine is one of two substrates for the heme pathway. We are almost done, promise. What else can block the heme pathway ? Oxidized glutathione. One last thing - what else is needed for heme ? Sulfur (Alpha Lipoic Acid). If you don't have heme - your cyp450 enzymes wont work to detox, nor will Glutathione Peroxidase, Tryptophane metabolism, or the electron transport chain. There is more that won’t work, but don't you agree this enough ?
Add on top of that, Aluminum also disables ATPase enzymes required to pump Ca2+ out of the cell. High intracellular calcium over stimulates NMDA receptors which will cause neuronal death. Wonder why calcium channel inhibitors help Alzheimers (cats claw) or why oolong tea helps too (binds excess iron). Now you know how Percepta works on Alzheimer placque tangles! What else over stimulates the NMDA receptors ? Too much glutamate. What blocks glutamate transport ? Mercury and Ochratoxin A (SLC7A11), and porphyrin's that are produced from a blocked heme pathway! What else over stimulates the NMDA receptors ? Hydrogen sulfide, and too much acetyl Choline (found in ME / CFS), volatile organic compounds, mycotoxins, organo phosphates, hydro florocarbons. What do we find in Multiple Chemical Sensitivity cases ? Over stimulated NMDA receptors. Making sense yet ? And if you want to know what over stimulated NMDA receptors feel like - it’s what happens when you get a traumatic brain injury. This is why many ME / CFS folks feel like they have a concussion.
Perhaps RFK was onto something, in a way that he didn't quite understand. Where do we think Aluminum, Mercury, Lead, Glyphosate come from ? What is the magic bullet that inhibits the heme pathway thats not listed above ? Anti Fungals sprayed onto fruits and vegetables, to maximize yield - they kill the fungus by inhibiting the heme pathway in the fungus. It's why some people get brought to their knees if treating mold illness with anti fungals RX's. What place on earth uses the most anti fungals on their crops ? What place on earth uses the most glyphosate ? What place on earth did the autism epidemic start ? What place on earth has the highest levels of Aluminum in humans ? Hotel California, once you enter, you can never leave:).
Before you consider adding iron to your diet or supplement list - please do some checking on your iron AND manganese status. I see low iron often, and also way too high of iron also, balance is the key. Too much manganese isnt good either - high manganese can block the heme pathway and inhibits SLC1A3 (a Glutamate transporter). So now you see how “Mineral Balancing” really works - its not mystical or magic, there is a sweet spot. Finally, There is only one laboratory that measure intracellular iron on their micronutrient panel, which i find essential.
Food for thought,
Mike
References:
[1] J. Dafhne Aguirre and Valeria C. Culotta. J Biol Chem. 2012 Apr 20; 287(17): 13541–13548. Published online 2012 Jan 13. doi: 10.1074/jbc.R111.312181 PMCID: PMC3340200. PMID: 22247543
[2] Switch of mitochondrial superoxide dismutase into a prooxidant peroxidase in manganese-deficient cells and mice. By Douglas Ganini, et. al. .Cell Chem Biol. Author manuscript; available in PMC 2019 Apr 19. Cell Chem Biol. 2018 Apr 19; 25(4): 413–425.e6. doi: 10.1016/j.chembiol.2018.01.007. PMCID: PMC5910218. NIHMSID: NIHMS938468 PMID: 29398562