• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of, and finding treatments for, complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia, long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

OAT, PLEASE INTERPET

Kathevans

Senior Member
Messages
689
Location
Boston, Massachusetts
I have been feeling ramped up, heart pounding, trouble getting to sleep.
It took me a long time to understand--and the helpful guidance of Greg Russell-Jones (the famous B12 Oils guy: PhD in Biochem)--that this racing of mind and heart can be not only too much B-12 or Folate, but also the stimulation of the adrenals, which occurs when B12 is taken after there has been a physical deficiency. The adrenals begin to release what Greg calls 'adrenal precursors' as they heal, among these aldosterone and adrenaline. The adrenaline can cause this initial night time wakefulness. I had to go through a couple of months, possibly longer, of feeling tired, beginning to doze off, turning off the light and bam! Wide awake! Alert again. Sometimes till 3:00 a.m. or longer.

I'm happy to say that currently this seems to be gone. I use the B12 Oils, started by working up the MeB12 tablets to 7,000mcg or so, then pulsed back and forth between the two. I still occasionally go back to the sublinguals and find that they don't cover symptoms nearly as well--which is to say tingling in my legs. But I'm still a work in progress, more with regard to folate at the moment (thanks for the earlier discussion on folate vs. folinic and the folate cycle, guys!)

Also, I know I've stated elsewhere that Greg says you need three things to make active B2--to recycle that folate: iodine, selenium and molybdenum. I found I was very low in molybdenum and spent 2 months titrating up to 150mcg/day, which Greg says ought to fill up my tanks.
 

Jimbo39

Senior Member
Messages
405
Location
San Deigo, CA
that this racing of mind and heart can be not only too much B-12 or Folate, but also the stimulation of the adrenals, which occurs when B12 is taken after there has been a physical deficiency.

It's good to know that it's part of the healing process tho it can be extremely annoying, the lack of sleep that is.

But I'm still a work in progress, more with regard to folate at the moment (thanks for the earlier discussion on folate vs. folinic and the folate cycle, guys!)

Whats the name of this thread? I feel completely overwhelmed trying to understand the folate cycle. I believe folinic is a type of folate? From my limited understanding, @alicec please correct me if I'm wrong, folinic or 5-formyl THF is produced from 5-10 methenyl THF with the help of the SHMTI enzyme and B6.

I know how you feel about a work in progress. It seems that how things should work doesn't necessarily apply to our bodies.

Also, I know I've stated elsewhere that Greg says you need three things to make active B2--to recycle that folate: iodine, selenium and molybdenum. I found I was very low in molybdenum and spent 2 months titrating up to 150mcg/day, which Greg says ought to fill up my tanks.

Yes, I think this has something to do with T3 and molyb converting FNM to FAD. I'm not sure what you mean by recycling.
 

Kathevans

Senior Member
Messages
689
Location
Boston, Massachusetts
I'm not sure what you mean by recycling.
Yes, interestingly, I'm not sure what I mean either! My assumption is that it gets used over again. That's what it sounds like, isn't it? I do know that when the B2 becomes active you actually 'get' the folate, or get to use it, and therefore need less. Perhaps @Johnmac or @ahmo could chime in on this. I know his need for folate lowered drastically as his B2 became more functional; possibly hers as well. This has been the case for me, too. I seem to need less folate than I did before I began to work on the B2. In fact, at this point, I'm wondering if I need any folate...

Just trying to 'read' my body. It's a pretty dense book to get through!
 

alicec

Senior Member
Messages
1,572
Location
Australia
For some B12 promotes inflammation (acne),

The inflammation comes from the increased need for folate - ie it is a folate deficiency symptom.

Some people use hydroxoB12, others methylB12 and andenosylB12. Is this a matter of preference? Do some people react badly to methyl i.e. Over methylation?

It's more a matter of response, ie which things work empirically.

I think high dose hydroxyB12 is probably doing different things - eg scavenging nitric oxide.

Personally I think the concept of over methylation is a bit dubious. There can be many reasons for sensitivity to methylB12 and methylfolate.

Theoretically, according to what is known of cobalamin uptake and processing in the cell, which form you take shouldn't matter since the methyl/adenosyl/hydroxyl group is cleaved off inside the cell and the cobalamin is then directed to either methyl or adenosylB12 synthesising pathways as needed. The detail of this is discussed here.

BUT, as mentioned here, there is evidence that cobalamin is taken up by a different mechanism also (passive diffusion) and I don't think we know much about what happens next with this mechanism.

According to Freddd who has read a lot more of the cobalamin literature than I have looked at, it is the passive diffusion mechanism which is important in the high dose supplement route. Furthermore it is his hypothesis that much of the study of B12 has been sent down a blind alley by the initial misidentification of cyanocobalamin as B12. Actually this was a laboratory artefact which meant that the active forms of the vitamin were missed.

Freddd thinks that many of the pathways defined by the early research are default, basic survival pathways. Other pathways are used when the active vitamins are supplied in sufficient amounts.

As far as I know there is not much research support for Freddd's idea because no-one has been really looking. He formulated it mainly based on his experience of using the active vitamins.

In my, and many others' experiences, the form you take does make a difference. Whether it is because of Freddd's theories or something else is just not known. There is much about cobalamin metabolism that is just not understood.
 

alicec

Senior Member
Messages
1,572
Location
Australia
I feel completely overwhelmed trying to understand the folate cycle. I believe folinic is a type of folate? From my limited understanding, @alicec please correct me if I'm wrong, folinic or 5-formyl THF is produced from 5-10 methenyl THF with the help of the SHMTI enzyme and B6.

The folate cycle IS complicated and I don't think you need to worry too much about the detail. Essentially it is a way of funnelling single carbon units (methyl groups) into different metabolic pathways, leading to synthesis of various useful molecules.

Folinic is a storage form of folate. It is formed as you say. The enzyme MTHFS converts it back to 5,10 methenyl THF.
 

caledonia

Senior Member
I have been feeling ramped up, heart pounding, trouble getting to sleep. I'm taking 1/4 MeCb, folate, and AdoClb. 1/2 Pure Encapsulation B complex (taken in 2 doses).

@caledonia mentioned B12 can cause adrenaline surges tho I don't know how this works. I wonder if those who are tapering/withdrawing from benzos and are prone to cortisol surges might be more sensitive to B12?

I haven't started taking LCF. Could this be a contributing factor?

I've tapered from benzos three times. For me, after I reduce a dose, I feel kind of unstable with some low level type anxiety, but then invariably, one week after the reduction, I get a big increase in anxiety or an outright panic attack. If I can make it through that, then I'm stabilized. Then I wait maybe another week before reducing again. It takes some time to work up the courage to face having more anxiety and panic attacks.

The various B vitamins can be overstimulating. So now you're combining possibly stimulating supplements with withdrawals from a med may already be causing similar type issues. (not sure what your benzo withdrawal symptoms are?)

My suggestion would be to keep the B vitamin doses low while you're tapering from the benzo or maybe not even take them at all until you're sure how you're reacting to the benzo withdrawal. Everyone is different, but the B vitamin doses listed would be way too much for me.

Or you could wait until you're in a stable spot from your taper - hold your taper amount the same and then spend some time experimenting with B vitamins, so you're only changing one thing at at time. That way, you know what is doing what.

If you're having trouble with the taper, there are some forums for tapering antidepressants in general, and also benzos in particular which may be able to help. Surviving Antidepressants and Benzo Buddies are two that come to mind.

ps. carnitine is another thing which could charge you up.
 

Jimbo39

Senior Member
Messages
405
Location
San Deigo, CA
The inflammation comes from the increased need for folate - ie it is a folate deficiency symptom.

That's good to know. I was like "What? B12 causes inflammation?"

I couldn't understand the links but it's reassuring to know there's at least two pathways in which cobalamin is used.
 

alicec

Senior Member
Messages
1,572
Location
Australia
I'm not sure what you mean by recycling.

Recycling of folate. Methyl folate is used by the enzyme methionine synthase (MTR), which converts it to THF. THF can enter all parts of the folate cycle including being used again by methionine synthase.

However for this latter reaction to happen, it needs to be remethylated by the MTHFR enzyme which uses FAD as a cofactor.

One of Greg's concerns is that FAD is difficult to make and if it is in short supply, the MTHFR reaction will not function well and there will be difficulty keeping up the supply of methylfolate to MTR. This will be evidenced by a high need for methylfolate supplementation with active B12 supplementation.
 

Jimbo39

Senior Member
Messages
405
Location
San Deigo, CA
do know that when the B2 becomes active you actually 'get' the folate, or get to use it, and therefore need less.

It's encouraging to know that B2 is working for you. This confirms Alicec's last post about the need for FAD (from FMN) driving the need for more B12.

Just trying to 'read' my body. It's a pretty dense book to get through!

I know! For me it's been so hard because my body's so messed up. I envy those who can tell when they are lacking or have too much of something.
 

Jimbo39

Senior Member
Messages
405
Location
San Deigo, CA
get a big increase in anxiety or an outright panic attack. If I can make it through that, then I'm stabilized.

I know what you mean. In fact probably 90% of those on Benzo Buddies complain about anxiety and insomnia being their biggest w/d symptoms. I suppose it may have to do with a lack of GABA or rather the down regulation of GABA receptors causing glutamate to go wild.

not sure what your benzo withdrawal symptoms are?)

If I taper too fast, I get gut and neck pain. The gut pain is more peripheral like the vagus nerve. I also get brain fog (but not much lately). And of course insomnia. I don't get panic attacks anymore.

Everyone is different, but the B vitamin doses listed would be way too much for me.

How much do you take? Have you ever tried pushing thro? I'm just wondering if these symptoms might be an indication of B deficiency and your body's trying to correct those blocks in your methylation cycle?
 

Kathevans

Senior Member
Messages
689
Location
Boston, Massachusetts
One of Greg's concerns is that FAD is difficult to make and if it is in short supply, the MTHFR reaction will not function well and there will be difficulty keeping up the supply of methylfolate to MTR. This will be evidenced by a high need for methylfolate supplementation with active B12 supplementation.
Exactly. What's interesting is the testing I've had to do to begin to arrive at the amount of Methylfolate I need. And not a surprise, really.

I waited about 5 weeks into my supplementation of molybdenum--Greg was always admonishing me to be patient; he always says it takes about a month for the process to really work (and I suspect it may even then start out slowly)--before I began to add in the folate I believed I needed. And so over the next 5 weeks I titrated up to over 2mg of folate a day until the symptoms I thought I was helping became intolerable. And so back down again. And when no folate again didn't seem like the answer, I went back up over the last week or so. This time, though, I've reached only 800mcg/day before feeling I might have over-shot my limit.

This suggests that as my body is functioning better, most likely getting more FAD on board, I need less and less of the folate. The wonder to me is that in the end I may find that I need no folate at all. At this point I wouldn't be surprised.

My alternadoc is about to have me repeat the NutrEval test which I haven't done in over a year and a half as I struggled with this methylation stuff. It will be interesting to see if I have any methionine, as I had very low to negligible at the time of the last test (and assuming this is what you're talking about!). Thank you @alicec.

I'm sure there will be much more to compare. Then I'll see if there are new deficiencies I need to address!
 

caledonia

Senior Member
If I taper too fast, I get gut and neck pain. The gut pain is more peripheral like the vagus nerve. I also get brain fog (but not much lately). And of course insomnia. I don't get panic attacks anymore.

Pain is an interesting response. Never would have thought that would happen. Brain fog and insomnia seem right. I'm glad you don't get panic attacks any more.

How much do you take? Have you ever tried pushing thro? I'm just wondering if these symptoms might be an indication of B deficiency and your body's trying to correct those blocks in your methylation cycle?

Ridiculously small - 20mcg of methylcobalamin and 4 mcg of adenosylcobalamin per day. About 1mcg of folate per week. There's also some methionine and SAMe in the multi I'm taking, so maybe about the same of each of those as the folate.

I tried increasing but depending on the supplement it made me either get overstimulated or crash, so I backed off.

I'm working on the other aspect of methylation blocks instead - removing metals. It's like two sides of the same coin. You can either supplement deficiencies or remove toxins. Both will help methylation.
 

Jimbo39

Senior Member
Messages
405
Location
San Deigo, CA
Exactly. What's interesting is the testing I've had to do to begin to arrive at the amount of Methylfolate I need. And not a surprise, really.

By testing do you mean trial and error?

I waited about 5 weeks into my supplementation of molybdenum--Greg was always admonishing me to be patient; he always says it takes about a month for the process to really work (a

It's great Greg is willing to help you. I feel like I'm shooting in the dark. I'm taking 200 mcg molyb. How much are you taking?

This time, though, I've reached only 800mcg/day before feeling I might have over-shot my limit.

This is very courious to me. What are the symptoms of "over-shooting" your limit? Do you feel better when you add more cofactors (B2, B6, minerals)? Do you think a compromised thyroid may factor into this?

This suggests that as my body is functioning better, most likely getting more FAD on board, I need less and less of the folate. The wonder to me is that in the end I may find that I need no folate at all. At this point I wouldn't be surprised.

When you say folate do you mean metafolin? Or are you including MeCb and AdoCbl?

will be interesting to see if I have any methionine, as I had very low to negligible at the time of the last tes

Yes, I think this is the goal for all of us, to convert homocysteine to methionine. But first we need B2 at MTHFR.
 

Jimbo39

Senior Member
Messages
405
Location
San Deigo, CA

Jimbo39

Senior Member
Messages
405
Location
San Deigo, CA
I'm working on the other aspect of methylation blocks instead - removing metals. It's like two sides of the same coin. You can either supplement deficiencies or remove toxins. Both will help methylation.

This is a huge challenge. I agree, I probably wouldn't tackle both as B therapy will also cause detox.
 

Kathevans

Senior Member
Messages
689
Location
Boston, Massachusetts
I'm working on the other aspect of methylation blocks instead - removing metals. It's like two sides of the same coin. You can either supplement deficiencies or remove toxins. Both will help methylation.
For years I began my day with Sonne's Bentonite Clay #7, I believe, and noticed recently that my levels of mercury from a youthful mouthful of amalgam went from .0503 in 2010 to .0100 in 2014. Maybe this was just the passage of time, but I like to think it helped...

It's a great supplement to have on hand for stomach upset, too, indigestion and so forth.

By testing do you mean trial and error?
Yes. In my experience it takes a lot of it to figure out what works for you. And then, too, your body is constantly changing...

I'm taking 200 mcg molyb. How much are you taking?
Greg says that you need about 75-100mcg/day to keep the cycle going, and that 150mcg/day ought to help refill a deficit. But I know there are people who take much more. I think you, @alicec, mentioned taking a huge dose at one time--1000mcg (am I right or making this up or was it someone else?!) and noticed a huge difference. I assume this was not a regular thing, however. I have also seen a supplement, I think one of Bed Lynch's for 500mcg of moly, so there must be some science behind it--not that I know what it is.

This is very curious to me. What are the symptoms of "over-shooting" your limit? Do you feel better when you add more cofactors (B2, B6, minerals)? Do you think a compromised thyroid may factor into this?
A compromised thyroid can affect many things. Fortunately it's one thing that seems to be working right for me. Over time, the cofactors seem to make a difference. I'm still working on this.

And when I over-shoot the folate, I have a tightening of my trapezius, neck and facial muscles. But then, this may be because of other deficiencies. I seem to have low'ish copper, for example, which is where my molybdenum was until I began supplementing. In the last few years, I've titrated up on magnesium (ca 400mg/day), zinc (22-25mg/day), Vit D (2,000 things/day), molybdenum (150mcg/day), manganese (about 2.5mg every day or two), and now selenium (I eat the 3 Brazil Nuts/day, but my digestion is not great and so have begun this journey, currently quite low at 8mcg/day).

Actually, if I've over-shot the folate, taking B2 makes me feel worse because I am 'recycling' it and I can actually feel it start to occur within 5 or 10 minutes of sucking on the Source Naturals sublingual. This happened last night and I was up till about 4 a.m. with my standard insomnia and felt, well, sort of strung out for a while.

But I will be honest, it's very difficult to know what to attribute to what, as you, yourself have found. Often in retrospect what you initially suspect, may be off the mark. That's why I keep an Excell chart with doses and reactions. Even then, it's a bit of a mystery. Over time things become a bit clearer.

One hopes!
 

caledonia

Senior Member
This is a huge challenge. I agree, I probably wouldn't tackle both as B therapy will also cause detox.

I think it's good to have even a little methylation going if you can to help with metal chelation. But there are ways around it even if you can't tolerate B vitamins.

Namely glutamine and glycine, precursors to NAC, precursor to glutathione. You may not be able to tolerate NAC or glutathione if you have mercury and are sensitive to sulfur/thiols.
 

Jimbo39

Senior Member
Messages
405
Location
San Deigo, CA
But I will be honest, it's very difficult to know what to attribute to what, as you, yourself have found. Often in retrospect what you initially suspect, may be off the mark. That's why I keep an Excell chart with doses and reactions. Even then, it's a bit of a mystery. Over time things become a bit clearer.

I keep a journal too. I'm pretty sure my reaction was attributed to B12 because I've been on multi-Vit/min and b complexes for over a year. Then again, who knows? It seems when methylation improves, it'll drive the need for certain minerals so it's a constant catch up game.
 

Jimbo39

Senior Member
Messages
405
Location
San Deigo, CA
Namely glutamine and glycine, precursors to NAC, precursor to glutathione. You may not be able to tolerate NAC or glutathione if you have mercury and are sensitive to sulfur/thiols.

I used to take NAC but quit because of the possibility of methyl trapping. I wonder if supplying the cofactors, at least in the long run, would be better than supplementing with end products. But you're right, if someone can't tolerate Bs, they have to look for alternatives.