B12: a simple 5-second poll for everyone

[Aerose91]

B12 deficiency, via the "methylfolate trap", leads to elevated homocysteine, especially if vitamin B6 is also low.

In neurological conditions, you have to test for high homocysteine in the cerebrospinal fluid, not in the blood, as there can be a localized B12 deficiency in the brain, but not in the rest of the body.

For more information, see:
https://pubmed.ncbi.nlm.nih.gov/9310111/

Thanks

 

[Learner1]

Would high or low homocysteine indicate low B-12?

Typically high, but it could also indicate B6 or folate deficiency, which is why testing methylmalonic acid is needed. (Or all 3.)

B12 deficiency, via the "methylfolate trap", leads to elevated homocysteine, especially if vitamin B6 is also low.

Plain old B12 deficiency will as well.

However, one can have low homocysteine and B12 deficiency at the same time if methionine is low.

@Pyrrhus Do you know of a other way to confirm one has a methyl trap? Measuring homocysteine won't do it.

In neurological conditions, you have to test for high homocysteine in the cerebrospinal fluid, not in the blood, as there can be a localized B12 deficiency in the brain, but not in the rest of the body.

Good to know, but for most of us, even with ME/CFS, it's not necessary to have an expensive and invasive lumbar puncture to test CSF. This would be likely be ordered by a neurologist if the simpler tests didn't help with the diagnosis.

 

[Pyrrhus]

Plain old B12 deficiency will as well.

However, one can have low homocysteine and B12 deficiency at the same time if methionine is low.

@Pyrrhus Do you know of a other way to confirm one has a methyl trap? Measuring homocysteine won't do it.

Thank you for your question.

First, a point of clarification:
When I use the term "methylfolate trap", I am NOT referring to any of the "methyl trap" hypotheses put forward by Ben Lynch, Amy Yasko, Rich Van Konynenburg, or by @Freddd that have floated around Phoenix Rising for years. Although these hypotheses are clearly related to and clearly inspired by the original "methylfolate trap", they are distinct hypotheses.

I am only talking about the original "methylfolate trap" that accompanies B12 deficiency, which predicts that B12 deficiency can lead to elevated homocysteine. The clearest description of the original "methylfolate trap" is the 1981 paper by Weir:
https://www.thelancet.com/journals/lancet/article/PIIS0140673681906504/fulltext

Basically, the original "methylfolate trap" describes how the body misinterprets B12 deficiency as a methionine deficiency, triggering metabolic changes that had evolved to protect the supply of methionine, but which inadvertently trap folate in the methylfolate state. If there is B6 deficiency at the same time, the "methylfolate trap" predicts elevated homocysteine as well. This is probably exactly the same as what you meant by "plain old B12 deficiency".

I don't know of any simple way to test for the "methylfolate trap", but there was a thorough test of the "methylfolate trap" in a 2006 case study:
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2141.2005.05913.x

I hope I was clear. Apologies if I wasn't.

 

[Pyrrhus]

By the way, if anyone is interested in the purpose of this poll:

I had previously noticed at least 2 distinct subsets of ME patients:
1) Those who crash terribly from even minute quantities of B12 and are constantly looking for ways to reduce the dosage as much as possible
2) Those who get an energy boost from large quantities of B12 and are constantly looking for ways to increase the dosage as much as possible

I found this dichotomy fascinating and, as a first step to understanding these two subsets, I wanted to get a rough idea of how large these subsets are. That was the purpose of this poll.

No poll is perfect, and @ebethc and @Learner1 have already pointed out some limitations of this poll. But I think it's safe to conclude that most current members of PR probably had no effect from B12 the first time they tried it.

 

[Aerose91]

Typically high, but it could also indicate B6 or folate deficiency, which is why testing methylmalonic acid is needed. (Or all 3.)

Plain old B12 deficiency will as well.

However, one can have low homocysteine and B12 deficiency at the same time if methionine is low.

@Pyrrhus Do you know of a other way to confirm one has a methyl trap? Measuring homocysteine won't do it.

Good to know, but for most of us, even with ME/CFS, it's not necessary to have an expensive and invasive lumbar puncture to test CSF. This would be likely be ordered by a neurologist if the simpler tests didn't help with the diagnosis.

My homocysteine always comes back low but methylmalonic acid also low. Does that indicate adequate b12?

 

[ebethc]

No poll is perfect, and @ebethc and @Learner1 have already pointed out some limitations of this poll.

I've often thought that the best polls/survey potential in this community would be from from ppl who have left the community... I don't know if anyone running the site has a list of email and could x-ref w site analytics to come up w a survey list (or if this is even okay, per the ToS), but I would help and I think this would be of enormous value to researchers (potentially, hopefully ).. I think that where the real "gold" is in PR survey potential...But, I've learned in surveys I've done for work, assumptions can be wrong and that's part of the reason that you do a survey... Ideally, you find people who have been "successful" & moved forward in some way and apply that to other users who are spinning in a cul-de-sac...

what I'm curious about:

1. treatment:
why did you leave PR? (improved health, found a more suitable community, ??, etc.)
where are you on the disability scale? (10 point scale)
have you had a new diagnosis? if so, what is it? where were you treated? etc.

2. PR uex/content:
what did you learn from PR?
how could PR improve?
would you recommend PR to a friend?
what other communities and sites have you visited, and how do/did you benefit from them?

etc..etc..

BTW, for those of you who are new, there was a big split in the community a few years ago, so there is a big group of former users whose PoV is known... What I'm most interested in is finding ppl who have had some kind of improvement, vs philosophical differences...

 

[Pyrrhus]

1. treatment:
why did you leave PR? (improved health, found a more suitable community, ??, etc.)
where are you on the disability scale? (10 point scale)
have you had a new diagnosis? if so, what is it? where were you treated? etc.

2. PR uex/content:
what did you learn from PR?
how could PR improve?
would you recommend PR to a friend?
what other communities and sites have you visited, and how do/did you benefit from them?

Excellent ideas. There is probably a wealth of experience from current and former PR members and lurkers, but extracting that experience is certainly difficult.

 

[Aerose91]

I've often thought that the best polls/survey potential in this community would be from from ppl who have left the community... I don't know if anyone running the site has a list of email and could x-ref w site analytics to come up w a survey list (or if this is even okay, per the ToS), but I would help and I think this would be of enormous value to researchers (potentially, hopefully ).. I think that where the real "gold" is in PR survey potential...But, I've learned in surveys I've done for work, assumptions can be wrong and that's part of the reason that you do a survey... Ideally, you find people who have been "successful" & moved forward in some way and apply that to other users who are spinning in a cul-de-sac...

what I'm curious about:

1. treatment:
why did you leave PR? (improved health, found a more suitable community, ??, etc.)
where are you on the disability scale? (10 point scale)
have you had a new diagnosis? if so, what is it? where were you treated? etc.

2. PR uex/content:
what did you learn from PR?
how could PR improve?
would you recommend PR to a friend?
what other communities and sites have you visited, and how do/did you benefit from them?

etc..etc..

BTW, for those of you who are new, there was a big split in the community a few years ago, so there is a big group of former users whose PoV is known... What I'm most interested in is finding ppl who have had some kind of improvement, vs philosophical differences...

What was the split about

 

[Pyrrhus]

What was the split about

See: https://forums.phoenixrising.me/thr...point-of-view-when-responding-to-posts.54002/

 

[pechius]

The first time I took methgl b12... wow. Immediate effect, but I couldn't tolerate it im the long term due to various side effects. Same with methyl folate.

I found out over a long time that my inability to tolerate methyl b12 and methyl folate (I could easily tolerate hydroxy b12 and benefit a lot from that as well) was probably related to nutrient deficiencies. I can't say 100% which was the most important, but it seems that it was molybdenum, it could've been vit A, because it's needed for an enzyme that is involved in using glycine as a methyl buffer or selenium, because of the antioxidant side of things. Not sure yet.

I'm taking the following supplements and find that they work quite well and help tremendously with muscle weakness and help me tolerate methyl folate and methylB12:
1. Taurine(best supplement ever, helps with everything! but I think it tanked my probably already deficient molybdenum and lost some of its efficacy temporarily)
2. Collagen (mostly because of glycine)
3. Pure glycine before bed (methyl bufer, helps a little with sleep)
4. B6, B2(for mthfr), B3, folate (200mcg currently)
5. Methyl b12, 1mg sublingual
6. TMG 500mg (seems like TMG without folate or folate without TMG doesn't work for me)
7. Selenium (life extension) methyl selenocysteine 200mcg. Very important for me
8. Zinc sulphate 7.5mg, the only form that I can tolerate and it works best.
9. Calcium hydroxyapatite
10. Vitamin D
11. Molybdenum, 150mcg every other day
12. Vitamin A, depends on how much liver I eat. Maybe 20 000 IU a week

 

[Learner1]

My homocysteine always comes back low but methylmalonic acid also low. Does that indicate adequate b12?

Homocysteine and methionine recycle each other. Your homocysteine is low because you ran out of methionine. This is not good - you need some of both. You might try taking 1g l-methionine for a couple of months, which should bring both homocysteine and methionine up. Then, if homocysteine is high, you'd want to look into whether your deficient in B6, folate, or MB12

My homocysteine went down to 3 when I was short of methionine, and has been around 6 or 7 since I took the methionine. I keep an eye on it. It's been a couple years and it's drifting lower again, but my homocysteine is still 6.5, so I don't need it yet.

And, if you're short of methionine, you might investigate whether you might be short of other aminos. They all have important jobs to do, and every time I've been short of one, I've been short of a few more, with accompanying symptoms or odd lab values. The pattern of aminos I was short in matched what the ME/CFS researchers found. I did s customized amino supplement for awhile as I was low in so many, then upped my protein intake to 1.8g/kg body weight for awhile, and have backed off a little recently.

Good luck!

 

[Aerose91]

Homocysteine and methionine recycle each other. Your homocysteine is low because you ran out of methionine. This is not good - you need some of both. You might try taking 1g l-methionine for a couple of months, which should bring both homocysteine and methionine up. Then, if homocysteine is high, you'd want to look into whether your deficient in B6, folate, or MB12

My homocysteine went down to 3 when I was short of methionine, and has been around 6 or 7 since I took the methionine. I keep an eye on it. It's been a couple years and it's drifting lower again, but my homocysteine is still 6.5, so I don't need it yet.

And, if you're short of methionine, you might investigate whether you might be short of other aminos. They all have important jobs to do, and every time I've been short of one, I've been short of a few more, with accompanying symptoms or odd lab values. The pattern of aminos I was short in matched what the ME/CFS researchers found. I did s customized amino supplement for awhile as I was low in so many, then upped my protein intake to 1.8g/kg body weight for awhile, and have backed off a little recently.

Good luck!

I did a methylation panel and my methionine came back totally fine. I wonder if I'm recycling homocysteine through the BHMT pathway.

Does low methylmalonic acid relate to B12 levels?

 

[Learner1]

Methylmalonic acid is a very good test for B12. If it's high you are deficient in B12. If it's low B12 is ok.

 

[Aerose91]

Got it, thank you

 

[Wishful]

As someone else pointed out, I probably got some B12 in a multivitamin and didn't notice any significant effect. I know I had a B12 injection in the first few months of ME, and it had no effect. 10+ years later, a doctor recommended B12 tablets, and the first time with that induced strong suicidal moods. When I tried it months or years later, it had no effect. Hmmm, how quickly do B12 tablets expire?

 

[Leah_Heisel]

The first time I tried B12 as a supplement is was as methylcobalamin. I can't remember the dosage but I believe it was 1,000 mcg. First day was great. Second day, still pretty good. Problems began soon after and I stopped immediately. I can only describe what I felt as manic anxiety. My thoughts were moving so fast they felt as if they were tripping over themselves and I did not feel in control of much. Very unsettling.

Fast forward to now. I am seeing a functional med doc who is also a chiro and treats autistic patients as well as hEDS, which I also have. She knows a lot about methylation. More than my brain can digest so I decided to go w/ her recommendations. She started me w/ 50mg of niacin partly to see if I would flush and according to her, see what my histamine levels were at. The first time I flushed and then had about 30 minutes of feeling manic again but then felt clear headed and with good energy. She wanted me to do this every other day while taking 250mcg of adeno b12 every 3-4 days and then eventually add in 15mg p5p with the b12. I did this for several weeks and the first two weeks I had positive results but then I started having emotional outbursts - feeling irritated, angry, sad and weepy at a moments notice. I was also very tired, partially from so much emotional energy spent I think. Then I had a day where it felt as though I were disassociated from my body for about 30 minutes. Hugely unnerving. I stopped all the b supplements and have an appointment with her tomorrow for a tmj adjustment and will bring this up but I don't know that anyone is going to be able to convince me it's safe to get back in the B Vitamin waters ...

 

[Pyrrhus]

She started me w/ 50mg of niacin partly to see if I would flush and according to her, see what my histamine levels were at. The first time I flushed and then had about 30 minutes of feeling manic again but then felt clear headed and with good energy. She wanted me to do this every other day while taking 250mcg of adeno b12 every 3-4 days and then eventually add in 15mg p5p with the b12.

Sorry to hear about your vitamin B roller coaster ride! I think many people here can relate.

Did your functional medicine doc ever ask you to take folate or methyl-folate? It seems rather unusual for someone who knows a lot about methylation to advise taking B12 and B6/P5P, but not folate...

 

[bread.]

Seems like an odd question maybe, but, do people that use b12 supplements get highly raised b12 blood labs? I red that should not be the case and raised b12 in blood can be a sign of malignancy?

 

[pattismith]

B12 deficiency, via the "methylfolate trap", leads to elevated homocysteine, especially if vitamin B6 is also low.

In neurological conditions, you have to test for high homocysteine in the cerebrospinal fluid, not in the blood, as there can be a localized B12 deficiency in the brain, but not in the rest of the body.

For more information, see:
https://pubmed.ncbi.nlm.nih.gov/9310111/

That's interesting, I got a two weeks remission with my very first B12 trial, then it stopped working.

My husband who has post chemotherapy neuropathy/fatigue did well with hydroxycobalamine injections, but it worked much much better when he added Nicotinamide Riboside + Caffeine

 

[Hufsamor]

When i tried b12 shots, I got slightly hyper. Like the kind of energy you get from too much coffee. And after three months I had a big crash.