Atherosclerosis of titanium implant origin, causing dementia

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Help me comprehend this literature, any insights appreciated thank you :)

Exposure to Ti4Al4V Titanium Alloy Leads to Redox Abnormalities, Oxidative Stress, and Oxidative Damage in Patients Treated for Mandible Fractures

Glossary:
Antioxidant enzymes (glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase-1 (SOD)) Nonenzymatic antioxidants (reduced glutathione (GSH) and uric acid (UA))
Total antioxidant capacity (TAC), ferric reducing ability of plasma (FRAP), and total oxidant status (TOS)​

Some excerpts:
In patients with titanium implants, mandibular movements triggered by strong muscles cause micromovements of the fixed bone fragments, which increases the friction between the miniplates and the screws. This phenomenon is responsible for the corrosion of titanium fixations and the release of titanium ions to the tissues/organs surrounding the implants [3]. In our investigation, the deposition of titanium particles in the study group was observed in the form of gray periosteal discolourations adjacent to the titanium miniplates and screws (data not shown)
I wonder if the metal ions circulate up into the brain, reducing catalase activity up there? How important is catalase to cognition I wonder? In the mandible per the study catalase (CAT) function appears to be impaired by around 58%.
The increased activity/concentration of antioxidants (↑SOD, ↑UA, ↑TAC, and ↑FRAP) in the mandibular periosteum of patients with titanium mandibular fixations, compared to the controls, suggests an adaptive reaction of the body in response to excessive ROS production (↑TOS) due to exposure to Ti6Al4V titanium alloy and its wear products. As Wang et al. [25] demonstrated, titanium ions released from implants may stimulate phagocytes (mainly macrophages) and osteoclasts to produce increased amounts of ROS and RNS. By participating in phagocytosis, they can also increase the activity of NADPH oxidase (NOX) [35] which is the main source of free radicals in the cell. High concentrations of ROS can initiate inflammation at the implantation site (by increasing the production of proinflammatory cytokines), which additionally (by positive feedback) increases the production of free oxygen radicals [5, 9, 29]. In our study, the induction of antioxidant defence mechanisms was observed not only in the periosteum but also in the plasma (↑UA) and erythrocytes (↑CAT) of the patients in the study group.
Interestingly, we have observed a significantly lower CAT activity in the periosteum of the patients in the study group versus healthy controls. The decrease in CAT activity may be explained by the exhaustion of the ability to neutralize hydrogen peroxide in the conditions of an overproduction of this tissue. In patients with titanium fixations of the mandible, a higher production of H2O2 may occur as the direct effect of titanium on the periosteal cells [5, 6, 33] or due to an increase in SOD activity that produces a large amount of hydrogen peroxide as a by-product of the dismutation reaction. This is confirmed by the results of our study (↑SOD in the mandible of the patients in the study group) and may be partially explained by the lack of changes in GPx specific activity.
In chemistry metal acts as a catalyst for many reactions... in addition to the metal ions inhibiting catalase (CAT) [2] from decomposing H2O2, this study says the titanium is also causing more H2O2 to be produced?
Despite the increased defence capacity of the antioxidant systems (↑SOD, ↑UA, ↑TAC, and ↑FRAP), we can observe an increased oxidative damage of proteins (↑AGE and ↑AOPP) and lipids (↑4-HNE) in the mandibular periosteum contacting Ti6Al4V titanium alloy. These changes suggest that the body is not able to protect itself effectively against oxidative stress and free radical damage of cells at the site of implantation of miniplates and screws. Importantly, the observed increase in oxidative stress biomarkers did not depend on the time span between osteosynthesis and the removal of the mandibular fixations.
What does this last sentence mean? Years after the oxidation problems are still in the local area and body?
Supplementation with antioxidants would also be helpful in patients treated with titanium fixations; however, further research is needed in this area.
Took me what, 10+ years of progressive debilitating brain fog sans support/savings to figure this one out... Woman I love left me during this traumatic time as I declined.

So Vitamin E (tocopherol & tocotrienol, not tocopheryl) substantially helps me (age 30 now). I first tried tocopheryl (age ~28-29) and that gave me bad migraine each time (past expiry date though). I then tried trimethylglycine and that brought my cognition back to pre-titanium-implantation, it was AMAZING. But had depreciating returns over the next two days, 4th day no effect at all even when I tried more. Month later tried it again and it worked, but same depreciating returns. So I began looking into antioxidants and revisiting the concepts of mini-strokes and atherosclerosis (which began SOON AFTER the implant placements age ~21), which 2 primary doctors both blew off said observed phenomena as "anxiety", calling me "young and healthy" (age ~21-24 when I saw them). I'll tell you what I'll told them, the veins in my neck (carotoid arteries) would at times feel sick (in correlation with my reduced cognition and general sick feeling), they'd enlarge and feel "poofy", and I would describe my blood as feeling like poison. I told them my suspicion it was the dental implants. I believe in both cases they tested my thyroid (doctors never tested more blood work than that, they'd ran that specific test 8+ times through my life all negatives...). One did test my "shortness of breath", I felt like I couldn't breathe, the feeling like you get when you've held your breath much longer than you should have, then your brain is very uncomfortable for some time, but your brain experiences that discomfort all the time. His breathing test was $400+ (he told me it was cheap when I expressed concerns about cost and about it being not related to my problems, the asshole, month worth of my labor down the drain) and just tested lung capacity and CO2 exhast or whatever... it wasn't logically related to my complaints at all, and his office called back in a dismissive way saying "test was negative therefore nothing was wrong with me".

Any heavy metal ion (such as copper cations in copper(II) sulfate) can act as a noncompetitive inhibitor of catalase [2].
So this stuff about catalase (CAT) seems most important. I recall reading with a different enzyme if it is inhibited for long enough then it is marked for disassembly... and is "cleaned up", I imagine as a way of clearing out dysfunctional/degraded enzymes. What do you think?

A search on this forum for titanium implants didn't yield much, ping @alex3619 . I do wonder how much dementia is caused by these titanium implants, especially considering old rich people probably elect to get these implants & hip replacements only to get dementia and think it's just cause they're getting old...

I suppose my symptoms may also have gut or allergy origin. I know I'm allergic to nickel (hives from metal watchband). And was on antibiotics for years due to infections from these dental implants- I know this seriously killed my gut, constant diarrhea unless I ate same thing every day, couldn't digest many things I used to be able to it would run straight through, pickles, mustard, coleslaw, and many more good foods I wasn't able to gain nutrition from anymore and risked sudden septic explosions at school/work/anywhere :'(

Oh, an oral surgeon also wouldn't remove my dental implants. As my symptoms didn't exist in literature he searched, he called my observations imaginary and myself delusional, gave me yet another prescription of antibiotics (had 16+ Rx'd for this issue...) and sent me out the door... I don't have any faith in U.S. society anymore.
Seeing that reduced glutathione (GSH) is reduced both at the titanium implant site and in plasma makes me think that supplementation of it and cofactors would be advisable (examine.com says to use stuff like NAC and ALA as direct supplementation of glutathione is more expensive and doesn't enter the cell?). Rhodiola Rosea looks great too (says it helps antioxidant enzymes do their thing), if you have any other recommendations for antioxidants let me know please, especially if you can think of why trimethylglycine doesn't work for long (has to be staggered). These dental implants really f'd up my life, I didn't even want them in the first place.

EDIT: Doing transdermal Alpha-lipoic acid, mixed in whatever oil/lotion I have laying around, applied to head/face/body. Feels good! I started doing transdermal because in powder it burns mouth & doesn't dissolve into water or mix in a drink well, also has much longer "half-life" given transdermally. Need to get NAC & Rhodiola Rosea. Maybe the depreciating returns of trimethylglycine was due to it being a glycine source for glutathione and other stuff ran out so more glycine didn't help anymore? Previously I was thinking it was an allergic/inflamation response, elevated homocysteine, and trimethylglycine lowered the elevated homocysteine. A different oral surgeon (seen age ~25-26) didn't know what was going on either and biopsied some tissue by the implant, the pathologist said chronic inflammation... I don't recall the exact words used.
 
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Pyrrhus

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. A different oral surgeon (seen age ~25-26) didn't know what was going on either and biopsied some tissue by the implant, the pathologist said chronic inflammation...
If you have chronic inflammation surrounding the problem implant, and it doesn’t respond to antibiotics, then the implant needs to be removed. (But you already knew that.) This is true regardless of whether the titanium alloy is leaking particles or not.

If the problem implant is, as you previously mentioned, penetrating the sinus cavity, then it may have been improperly implanted. (But you already knew that as well.)

I know it is hard, emotionally and financially, to seek out yet more oral surgeons, but the reality is that that is just what we sometimes have to do to find someone who knows what they’re talking about.

The fact that you have a second implant without surrounding inflammation lessens the likelihood of an allergic component to the inflammation around the problem implant. (Which is unlikely anyway for titanium alloys.)

Until the problem implant is removed and the area heals, it will be impossible to tell whether the implant inflammation is contributing to your cognitive difficulties. If the titanium alloy was, in fact, leaking particles or ions then it is reasonable to assume that there may be some lingering effects, which may resolve on their own.

But you may also find that there is something else entirely going on, and your cognitive difficulties may end up having nothing to do with the implant. (I’m sure you know this already, as well.)

As for NAC, If your purpose is to maintain intracellular glutathione levels, I think NAC is a worthwhile and low-risk supplement at relatively low doses such as 200-600mg per day. Some people purposefully take much higher doses for the sedative effect, and I’m not sure what the consequences of that might be.

Everybody has the potential to react differently, so you should also read about other people’s NAC experiences. The easiest way to do this is with a Google Site Search:
Go to google.com and search for “NAC site:" followed by "phoenixrising.me”. (No space between the colon and the ‘p’ of phoenixrising)

Hope this helps.
 
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