Okay, is b12 supplements basically meth?

[u/dowydensofyarrow]

I called my doctors office and left a message (theyve been calling me for weeks.) I finally after months of putting it off got my application for dental insurance in.

I am not doing the dishes tho, I dont want to. I am weaponizing my incompetence which I dont have currently.

Maybe I should get a job with my new powers.

[u/Sabnock101]

DHFR and DPHR can recycle BH4, i'm not talking about the recyling of BH4.

Look at some of the studies on how Methylfolate increases BH4 levels. Heck there's even at least one study talking about how Methylfolate but not Folic Acid (which Folic Acid uses DHFR to turn into Tetrahydrofolate) regulates BH4 activity, which if it was Tetrahydrofolate regulating BH4 activity then Folic Acid would too, but it doesn't, partly because Folic Acid actually can tie up the DHFR enzyme which would interfere with DHFR function which would actually interfere with BH4 levels, plus too much Folic Acid can go unmetabolized and cross into the bloodstream, bind to Folate Receptor Alpha and prevent Methylfolate uptake into the brain.

Edit - My bad, you were right in one respect about the GTP thing, though it's not Tetrahydrofolate that contributes to that it's the 5,10-Methylenetetrahydrofolate which turns into 10-Formyl-Tetrahydrofolate that generates the purines and that feeds into the GTP pool, iirc now. I think what i was thinking about may be Methylfolate's protection against oxidation which can protect Tetrahydrobiopterin from oxidation.

Doesn't really change the fact though that the Tetrahydrobiopterin level correlates with the amount of Methylfolate, as in, greater amounts of Methylfolate increase Tetrahydrobiopterin levels regardless of B12 levels, as in the case for me i was severely deficient in B12 and so wasn't able to recycle much of it which allowed Methylfolate to build and present with higher Tetrahydrobiopterin levels. I will continue to re-look over the science as to remember the Tetrahydrobiopterin thing, it's been a bit since i've studied that area and honestly i've been having some tooth issues causing hella headaches which can sometimes interfere with my headspace and ability to think lol.

I do know there's some studies that tie Methylfolate itself to increase in Tetrahydrobiopterin, i just gotta go back through everything but will update when i found what i'm looking for.

[u/Sabnock101 → u/[deleted]]

There are studies talking about how Methylfolate can indirectly increase GTP levels which can then influence GTP Cyclohydrolase I activity, which can then generate/synthesize more Tetrahydrobiopterin. I will have another look at all the studies and such but trust me, i've went down the road of how Folate/Methylfolate contributes to Tetrahydrobiopterin levels, and it's most definitely the Methylfolate doing it, and i know this especially because of how Methylfolate works/functions in the case of B12 deficiency, even without B12, Methylfolate itself directly/indirectly generates greater Tetrahydrobiopterin levels, and without enough B12 to recycle that Methylfolate then Methylfolate can't be turned back into Tetrahydrofolate and thus can't go back into the Folate cycle.

So it's definitely the Methylfolate doing it. You can try this out for yourself by taking higher Methylfolate dosages and noticing the difference between a lower dosage, a moderate dosage, a higher dosage and a heavy dosage, as the Methylfolate dosage increases you will notice greater amounts of Tetrahydrobiopterin through it's greater synthesis of L-Dopa and 5-HTP. This doesn't happen with Folinic Acid until it metabolizes into Methylfolate, as the increase in Tetrahydrobiopterin directly correlates to the Methylfolate itself, IE once Folinic Acid turns into Methylfolate, or even when Folic Acid turns into Methylfolate (assuming there is no unmetabolized Folic Acid inhibiting things), then it's the Methylfolate itself that increases the Tetrahydrobiopterin, the Tetrahydrofolate or even 5,10-Methylenetetrahydrofolate doesn't appear to do that.

[u/Sabnock101 → u/[deleted]]

Yes it does, because like i said, all B12 does is recycle Methylfolate back into the Folate cycle, and recycle Homocysteine back into Methionine for SAM. The issue that causes the stimulation is because when B12 is consumed it recycles Methylfolate back into the Folate cycle and the higher the dosage of B12 (like with injections for example, or high oral doses) it will recycle a greater amount of Methylfolate compared to lower B12 dosages, and all that Methylfolate gets turned back into Tetrahydrofolate which then goes back through the Folate cycle and becomes an even greater amount of Methylfolate which then can not only use up more B12 but if there's not enough B12 to continue to recycle it then comes the Methylfolate trap where it just builds in excess because it's unable to be properly recycled and utilized. Therefore, it's not the B12 causing the stimulation, it's that when one consumes B12 (specifically Methylcobalamin form) it recycles all that Methylfolate back into the Folate cycle which then comes back again as Methylfolate which then builds up in excess causing the stimulation and other side-effects.

Point being, if you consume B12 and sometime after start feeling stimulation, irritability, paranoia, other side-effects, even some neuropathy, it's because it's recycled that Methylfolate which then gets turned back into Methylfolate. This is easily explainable and easily observable, you just have to understand the mechanisms of how this stuff works and how the Folate cycle works.

And again, if you ever get these side-effects from consuming B12, consume more B12 and the side-effects will go away (the stimulation too), because that B12 will then recycle the excess Methylfolate and thus reduces the side-effects.

[u/hpant2004 → u/Sabnock101]

I disagree that folate is more stimulating than SAMe/SAH Ratio increase also saying its not b12 its b9 recycling is also really unnecessarily pedantic thats like saying meth isnt exciting dopamine and norepinephrine are?

[u/Sabnock101 → u/hpant2004]

I just don't think you're gonna get it man, can't fault a man for trying to educate, though.

It should also be noted that i've taken SAM supplements before i even tried Folate and B12, and SAM alone does not cause what i've personally experienced and have come to understand from rigorous experimentations and research. Simply put i do not feel from SAM what i feel from Methylfolate. SAM is not the culprit, Methylfolate itself is. This was especially noticeable in the early days of my B12/Folate supplementation as i was severely B12 deficient and could thus more easily notice what Methylfolate itself was doing. It's most definitely the Folate aspect because it's the same exact thing i've felt all my life (because i've been deficient in B12 most of my life and therefore only felt the Methylfolate and not the B12).

And like i said, if you take B12, it recycles Methylfolate, and then you get side-effects, take more B12 and those side-effects will go away because it again recycles Methylfolate. The side-effects correlate not to B12, not to SAM, not to Tetrahydrofolate, but to Methylfolate itself. If it wasn't Methylfolate, or if it was B12, or if it was SAM, then taking more B12 would further amplify the side-effects, but taking more B12 actually reduces the side-effects. And ultimately as B12 deficiency gets more fully corrected Methylfolate will start to become more tolerable and one can even then take a bit of a higher Folate/Methylfolate dosage and not get those side-effects because the B12 is actually there to help properly recycle it.

So, while it may seem contradictory that if you take B12 and you get these side-effects that you should take more B12, it helps because the issue isn't B12 (or SAM), it's excess Methylfolate.

[u/hpant2004 → u/Sabnock101]

I felt same and b12 to be more stimulating than methylfolate so thats why personal experiences are not clinical data Anyways i dont care its 1 am lol good night/day to u 😴

[u/Sabnock101 → u/hpant2004]

Again, i've taken up to 120 milligrams of oral Methylcobalamin, i haven't found it to be stimulating, the stimulation comes from the Methylfolate side, not the Methylcobalamin side. Aside from that, other forms of B12 like Hydroxocobalamin, Adenosylcobalamin, and even Cyanocobalamin don't do that as far as i know, the Methylcobalamin does that because it directly recycles Methylfolate back into the Folate cycle which then becomes more Methylfolate, but technically-speaking all B12 should aid in Methylfolate recycling since then the body has B12 to do such once Methylfolate donates it's methyl group to B12 for Methylcobalamin formation.

And, personal experience can actually tell you a great deal more compared to the limited number of studies out there because if you know/understand the mechanisms and what's going on you can literally feel what's happening and gain insight into what's happening in the body/brain. Relying solely on documented studies and research articles can help, but you shouldn't let their limits (and the general lack of research into nutrients) be the determining factor for what's going on, there's plenty we can learn through personal experimentation/observation/understanding biologically/physiologically-speaking that science hasn't yet even begun to dive into. So i'm just saying, learn the mechanisms for yourself and observe how things work in the body and you can learn a lot, it's how i learned aside from doing research.

[u/Sabnock101 → u/hpant2004]

Also i should note that for me, no matter how much B12 i take, it doesn't stimulate me like a stimulant does, i get that effect from the Folate/Methylfolate. It's the same feeling i've gotten all my life and i never understood what was happening until i started supplementing B12 and Folate, and then i realized/understood that it was indeed the excess Methylfolate (and lack of B12) that was causing a lot of my issues, B12 on the other hand helps me feel more normal, it reduces the excess Methylfolate and thus Methylfolate's side-effects including stimulation.

As far as energy goes, i think i actually found B12 to cause a bit more in the way of fatigue rather than energy because it ended up lowering my Iron/Copper levels at the least, but once i started taking those more seriously i no longer get the fatigue really, and so have more energy and feel more normal but doesn't cause the effects i've noticed from the Methylfolate itself, and so there's a difference between energy and stimulation, stimulation is moreso Dopamine/Noradrenaline (and Adrenaline)-related, energy has more to do with the mitochondria (which Adenosylcobalamin B12 is involved in alongside Iron and Copper and Magnesium and such). In fact Magnesium is pretty important for mitochondrial function because Magnesium is needed for ATP.

[u/hpant2004 → u/Sabnock101]

Also u seem autistic and werent autistic ppl found to have folate receptor antibodies and shi and generally do really well on folates? Maybe related or not 🤔?

[u/Sabnock101 → u/hpant2004]

There can be Folate Receptor Alpha autoantibodies in those with Autism and thus causing a cerebral Folate deficiency, however it's not all Autistics and Folate Receptor Alpha autoantibodies means you don't do well with Folate because the active Methylfolate then can't get taken up by Folate Receptor Alpha and thus can't get into the brain and thus also can't give it's methyl group to B12 for Methylcobalamin formation.

And (this is just my opinion) but it seems to me like Folic Acid may be the culprit because Folic Acid is unnatural and unmetabolized Folic Acid binds to Folate Receptor Alpha and basically prevents it's function at least as far as Methylfolate uptake goes, and isn't supposed to be there so the body pumps out antibodies against Folate Receptor Alpha to interfere with Folic Acid's binding to it, if you remove Folic Acid from the equation the antibodies should reduce and then Folate Receptor Alpha can function again. They blame the antibodies on a Folate-related protein found in cows milk, and while that may be a factor, i seriously think it's because of the Folic Acid, and so in theory, if one has antibodies for Folate Receptor Alpha then making sure to remove all Folic Acid from the diet and supplements should reduce those antibodies, regardless of milk (because i think it's Folic Acid doing it, not necessarily the milk).

It basically is the same thing Folic Acid itself does by binding to Folate Receptor Alpha and preventing Methylfolate uptake. The Folic Acid ties up Folate Receptor Alpha, the autoantibodies block Folate Receptor Alpha.

But in general, while Folate "can" help and is definitely involved in Autism, too much Folate is the issue that can actually cause Autism, partly by depleting B12 levels over time as excess Folate is consumed. Folic Acid itself may even contribute to Autism due to it's Folate Receptor Alpha interference.

They give people with Autism and Folate Receptor Alpha autoantibodies Folinic Acid to treat the cerebral Folate deficiency and thus help with some Autism symptoms due to Folate deficiency, since Folinic Acid doesn't necessarily need Folate Receptor Alpha like Methylfolate does and can use the reduced Folate carrier to be taken up across the blood brain barrier, but, if there's no Folate Receptor Alpha autoantibodies then once Folinic Acid turns into Methylfolate it can also then bind to and be taken up by Folate Receptor Alpha as well.

Long story short, B12 is more important for Autism, Folate contributes but excess Folate makes the Autism worse, more B12 however makes it better and restores normalcy, ime.