Victronix
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Yes, it could be the folate, worth a try without it. That way you can try it out separately to see how it is, and control the dosage of it, if you decide to do it.
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Let me correct something in my earlier reply. Only monoglutamate forms can enter cells but both folinic acid and methylfolate inside celks are polyglutamated. I think this is true of other intracellular folate derivatives as well. Hence why most ingested dietary folates are polyglutamated. That being said in animals methylfolate is the dominant circulating form of folate. I also stick by my assertion that fokate derivative distributions between plants and animals are very different. On the other hand any glutamate lowering effects of folinic acid or methyfolate is likely due to other mechanisms not simply intracellular storage. Besides excitotoxicity is about extracellular glutamate in the neuronal gap not inside the cells. Hence the reason people drink coffee. As an aside I see people post that they have perceived glutamate excitoxicity but drin coffee ... if glutamate was overloaded then drinkinf coffee would set off a firestorm. Had that happen twice due to coffee. Both times I wanted basically to die.I probably should have posted the quote. What I meant is that he said folinic acid would lower glutamate because it's polyglutamated (or at least he thought it was at one time). I didn't want to post it here because like I said I wasn't sure if it was accurate since he only mentioned it once in 2010 (even though he talked about glutamate induced excitotoxicity many times since then). This is what he said:
"Another factor is that folinic acid is polyglutamated when it is inside the cells, and this can help to lower the amount of free glutamate, which is an excitotoxin."
As an aside I see people post that they have perceived glutamate excitoxicity but drin coffee ... if glutamate was overloaded then drinkinf coffee would set off a firestorm. Had that happen twice due to coffee. Both times I wanted basically to die.
Caffeine
Regular coffee drinkers are at markedly lower risk for Parkinson’s disease [169], and two epidemiological studies suggest that Alzheimer’s disease may also be less common in coffee drinkers [170,171]. Caffeine has well documented neuroprotective effects in a range of rodent models, including those for Parkinson’s disease,
stroke, and excitotoxicity [172]; moreover, caffeine is reported to decrease the toxicity of b amyloid to cultured cerebellar neurons in vitro [173]. This protection appears to reflect inhibition of adenosine type 2A receptors (A2A), widely expressed in the brain [172]. In particular, such receptors are found on microglial cells, and selective agonists for this receptor promote induction of COX-2 in these cells [174]. Thus, it is conceivable that caffeine neuroprotection reflects, at least in part, down-regulation of COX-2 expression in microglia. However, the main impact of A2A antagonists on neurodegeneration may reflect a down-regulation of glutamate release from excitatory synapses; evidently, adenosine plays a physiological role in promoting the extracellular glutamate excess that mediatesexcitotoxicity [175–178].
Other people have said the folate in meat is methylfolate. I wasn't referring to anything you said. I just asked because I figured you probably knew the answer.So plant folate isn't folinic acid, but is meat methylfolate?
Dietary folates are technically any folate derivative. But the majority ingested from plants is not THF, not folinic acid, and not l5mtthf. They are simply folate (the natural non oxidized polyglutamated form of folic acid). It is pretty clear if you look at the diagram in the link I put in my post. So no plant folates is NOT meat methylfolate. I never said that sorry.
I'm not sure what happened. I was taking 1600+ folic acid, 200 mcg methylcobalamin orally, and TMG (as betaine hcl), but as soon as I started taking methylfolate I had serious problems. I also do have problems with too much sublingual B12 (without folate). That could partially be due to the fact that I do get a lot of dietary folate including some from meat.I understand your reluctance about methylfolate but if you really are processing the folic acid than the endgame is essentially to convert to methylfolate ignoring the parts that get drained into making DNA / RNA. You may be reacting to methyl donors of any type.
Rich said inflammation from methylation could be from infection. Do you know if there are other reasons why methylation can cause inflammation? And does it still cause inflammation even if you're not overmethylating?This may suggest inflammatory processes
My 23andMe results will be here in 6-8 weeks so you're welcome to place bets. Just a side note on that. My saliva for the test kit was slightly yellow due to a sublingual I took earlier. I didn't feel like doing the saliva sample again so I just sent it in. Now I'm sort of freaking out that it will mess up the results.or maybe COMT++ intolerance.
First you're my doctor, now my psychiatrist? Ok, I'll humor you I guess. I was very active and athletic when I was young. I wasn't really driven academically until I got to high school, but I was into sports and video games before that. I think I have Asperger's to a certain degree. At least 2 online tests I took say I have Asperger's. I was bullied in elementary school so I think I was mildly depressed since then. Assuming my tick bite at age 16 was where my illness began, within a year or two I was severely depressed and had major insomnia. I've had insomnia my whole life though. I do have a lot of mental energy. I wouldn't say I have much mental anxiety, but I do have an active mind. I have both ADD and OCD to a certain extent so my research is a bit chaotic to say the least.Before you got sick, what was your mood generally like? Happy a lot? So much so it made other people sick? A lot of drive? Mental energy? Just curious.
NE and ammonia are other possibilities for example. You can read some other posts distinguishing NE vs glutamate.Hmm. I guess I'm misunderstanding something, as this says caffeine is good for excitotoxicity.
Down-regulation of microglial activation may represent a practical strategy for combating neurodegenerative disorders
I concede that my glutamate issues are indeed "perceived" - I have no proof that is what drives my problem. But something makes my brain to go haywire, and it correlates with known excitotoxins - but caffeine is not one of them.
I'm not sure what happened. I was taking 1600+ folic acid, 200 mcg methylcobalamin orally, and TMG (as betaine hcl), but as soon as I started taking methylfolate I had serious problems. I also do have problems with too much sublingual B12 (without folate). That could partially be due to the fact that I do get a lot of dietary folate including some from meat.
My plan is to slowly increase folinic acid first since it serves other functions besides converting to methylfolate, but mainly because there's some b complexes and multivitamins with only folinic acid which I'd like to take instead of taking all my b vitamins separately and/or taking b complexes with folic acid. Even if I am converting folic acid to active folates (it certainly didn't block methylfolate), folic acid still uses up NADPH and ties up the DHFR enzyme which is needed for BH4. I'm just not sure if 100-200 mcg of folic acid is enough to cause problems.
Rich said inflammation from methylation could be from infection. Do you know if there are other reasons why methylation can cause inflammation? And does it still cause inflammation even if you're not overmethylating?
My 23andMe results will be here in 6-8 weeks so you're welcome to place bets. Just a side note on that. My saliva for the test kit was slightly yellow due to a sublingual I took earlier. I didn't feel like doing the saliva sample again so I just sent it in. Now I'm sort of freaking out that it will mess up the results.
First you're my doctor, now my psychiatrist? Ok, I'll humor you I guess. I was very active and athletic when I was young. I wasn't really driven academically until I got to high school, but I was into sports and video games before that. I think I have Asperger's to a certain degree. At least 2 online tests I took say I have Asperger's. I was bullied in elementary school so I think I was mildly depressed since then. Assuming my tick bite at age 16 was where my illness began, within a year or two I was severely depressed and had major insomnia. I've had insomnia my whole life though. I do have a lot of mental energy. I wouldn't say I have much mental anxiety, but I do have an active mind. I have both ADD and OCD to a certain extent so my research is a bit chaotic to say the least.
I translate that to be 25 mg folinic acid tid-quid which in medical speak means 75-100 mg per day total. But I may be wrong.I wonder what this scientific study means when they specify the amounts of folinic acid? This is what it said: "Folinic acid was used at a 25 mg dose level 3-4 times daily for 1-2 months..."
Did this mean that the whole dose for the whole day was 25 mg? Or was the dose for the whole day 100 mg?
Most bottles selling Folinic Acid holds about 2 days worth, so one must buy quite a bit it seems.
Please help explain.
Thanks.
Rich said inflammation from methylation could be from infection. Do you know if there are other reasons why methylation can cause inflammation? And does it still cause inflammation even if you're not overmethylating?
NE and ammonia are other possibilities for example. You can read some other posts distinguishing NE vs glutamate.
Sorry I don't buy that article. Caffeine affects glutamate transport flooding the extracellular gap so the neurons fire and people feel "good" mentally. Of course there is tolerance that builds up but that is a separate issues.
They are talking about something very different. Different pathway. They are talking about microglial activation which is the CNS equivalent of immune cells and inflammation. Very important to neurodegenerative disorders. Does not invalidate the heightened activity of GLT transporters.
Just so I don't seem like a total methylation n00b, I was taking 1600 mcg folic acid and 200 mcg methylcobalamin orally before I learned about methylation. My multi had 800 mcg folic acid and my b complex had 400 mcg folic acid/100 mcg methylcobalamin which I took twice a day. My first methylation "attempt" was unintentional. The company simply added 50 mcg of methylfolate to the formula. So I was taking that twice a day for a total of 100 mcg methylfolate and no other methyl donors except the 200 mcg oral dose of methylcobalamin and 1000+ mg of TMG (as betaine hcl). That was enough to cause serious problems. I didn't go into detail because I've mentioned this a few times already in various threads.That is a lot of folic acid with just a bit of mb12, especially oral. Adding methylfolate on top of that is begging for a folate trap imo.
I mentioned it only to try explain why such a low dose of B12 seems to affect me even though until recently I wasn't taking any other folate except from food. And the other only methyl donor being betaine hcl. I don't know much about SNPs, but based on my sensitivity to even hydroxocobalamin it seems likely that I'm COMT. Probably my current state of health also affects how I respond to methylation supplements. If I had tried methylation a year ago when I was making a recovery maybe I would have had an easier time.DIetaty folate in meat is extremely small. We already discussed the forms you get in veggies. I eat 3500-4000 calories a day all meat, nuts, and veggies with a bit of fruit and the total amount of folate is under 350 mcg or so. Not much.
I wasn't insulted. Just a little surprised, but I know you well enough to assume you were going somewhere with it. I can understand why you want to back away from being labeled "doctor" with liabilities and whatnot, but I just making a joke. You do seem to know more than my doctor and she's the best doctor I've ever had, but again I don't actually consider you "giving me medical advice" so don't worry. I really do appreciate your in-depth answers though. I've learned so much in such a short amount of time. And yet it seems there's so much left to learn. I told you before that you seem to have an answer for every question. Well, I seem to have a question for every answer.I am neither your doctor nor your psychiatrist. The questions I asked about mood were specific to COMT. That is all I was asking about, sorry. I intended no insult.
I probably was like that as a young kid, but I also had a hard time adjusting to life even before my illness. It's hard to say what my true personality is. Like I said before, I have Asperger's to a certain extent coupled with depression at an early age so it's hard to know who I really am.People with COMT mutations tend to be more joyful, ebullient, and happy
In high school and college I was very active. I was in the honors program, played sports, worked part time, did theater. It was only a matter of time until my crash, but even after I started getting sick I kept pushing myself. I've been running on empty for a long time. I assume it's the NE giving me the "energy" based on what you've said to me in the past. Since my relapse at the end of last summer my blood pressure has been getting higher even though I'm on Lisinopril. It doesn't seem like a coincidence that my NE symptoms started around the same time.but can be prone to mood swings especially if coupled with MAO mutations. They tend to have very high dopamine and NE levels, summoning NE to get tasks done, etc. We will have to see what your tests show.
Do you have CV symptoms with BP and pulse when you are wired? Or is it more sensory related? Just curious.True. I have amassed a lot of links to random papers regarding glutamate and I remembered that one when you mentioned coffee, but you're right - it's a different pathway.
Well, I can tell when it's NE because there's both a physical and mental reaction, but telling the difference between glutamate and ammonia.. no idea. It could be both, for all I know. As I said, I have trouble with even small amounts of known excitotoxins, but no issue at all with a reasonable amount caffeine. But I also have excitotoxicity issues seemingly out of nowhere, which unfortunately makes the source/cause hard to pin down.
I wasn't insulted. Just a little surprised, but I know you well enough to assume you were going somewhere with it. I can understand why you want to back away from being labeled "doctor" with liabilities and whatnot, but I just making a joke. You do seem to know more than my doctor and she's the best doctor I've ever had, but again I don't actually consider you "giving me medical advice" so don't worry. I really do appreciate your in-depth answers though. I've learned so much in such a short amount of time. And yet it seems there's so much left to learn. I told you before that you seem to have an answer for every question. Well, I seem to have a question for every answer.
In high school and college I was very active. I was in the honors program, played sports, worked part time, did theater. It was only a matter of time until my crash, but even after I started getting sick I kept pushing myself. I've been running on empty for a long time. I assume it's the NE giving me the "energy" based on what you've said to me in the past.
Do you have CV symptoms with BP and pulse when you are wired? Or is it more sensory related? Just curious.