What besides methylation could drive a high need for B12?

[garyfritz]

I have a bunch of methylation-related SNPs -- see my sig. And I have some significant symptoms that respond almost instantly to B12. But I'm not convinced my symptoms are due to methylation or ME.

As I've posted before, I have a ferocious appetite for B12. I'm using a triple dose of the B12oil, which is equivalent to about 4.5mg adenoB12 and 1.5mg methylB12, injected, per day. And sometimes that's not enough. The B12oils guy says he hasn't personally encountered anybody who uses as much as I do.

But I don't think I have ME. I don't show any of the symptoms like exercise intolerance. I can do pretty strenuous exercise (yardwork, hiking, expert skiing, etc) for hours, and not have any unusual / inappropriate problems afterwards. At least nothing unusual for an out-of-shape 60-yr-old.

I'm also not convinced this is a methylation issue. I didn't get any response to Freddd's DQ, except the B12.

So my question is -- what's up with me and B12??

I think it's definitely connected to my SNPs. I've recently started sending my 84-yr-old mother some of the B12oil, and she says she gets immediate relief from it. She also says HER mother used to get B12 injections in the 1950's, and it was always very obvious when her shot was running out. So it definitely seems to be hereditary.

I suspect my symptoms (restless legs, daytime fight/flight-like reactions and crawl-out-of-my-skin feelings, night-time agitation and near-seizure-like twitching/thrashing with nightmarish mental state, etc etc) are just B12-deficiency symptoms. But I'm wondering what causes the deficiency, and if there is anything I can do about it other than shovel in more and more B12. Greg the B12oils guy has suggested several ancillary nutrients (B1, B2, selenium, iodine, others) but none have made any noticeable difference. Only B12 seems to have any effect, and its effect is immediate and dramatic. And BTW I don't seem to be "loading up my tank" of B12 reserves as Greg expected I would. I've been doing the triple-dose for a year now and I'll still see symptoms within a day if I go off the B12. (Though I suppose it's possible I need a 4-5x dose to have enough surplus to start stockpiling it!)

I'm very thankful I found B12 when my lifelong but occasional RLS issues suddenly exploded into a constellation of related symptoms 3-4 years ago. I can't imagine how insane I would be by now without it. And I probably avoided significant neural damage by providing enough B12 to keep my symptoms in check. But I would really like to understand the mechanism behind this. I'd like to know if there's anything I can do to address the problem and prevent it from getting worse as I get older. Any suggestions?

Thanks!!
Gary

 

[Lynn_M]

Garyfritz,
Have you ruled out pernicious anemia? Ever had a MMA test?

 

[garyfritz]

Hi @Lynn_M -- yes, I was tested for intrinsic factor, and my MMA (Methylmalonic Acid, right?) tested normal, 0.6 when it was supposed to be < 1.9. I had a urine MAP test (Metabolic Analysis Profile) that said I had a high need for B1, but my B12 was fine. (And yes, I've tried taking 100mg/day of B1 -- no effect.) The only things in that test that were really out of whack were Benzoic acid and 5-OH-indoleacetic Acid.

 

[ahmo]

I've read several times that lithium helps in B12 absorption. Might be worth a trial, but not the answer to your question.

 

[garyfritz]

Tried it. Pure Encapsulations 5mg lithium orotate 1x/day, if I remember right, for several months. Didn't notice any difference.

 

[ahmo]

 

[dannybex]

@garyfritz, are you taking any folate? They usually work together, and both folinic and methylfolate have helped my fight/flight symptoms. Could be a lot better, but they're better than 3-4 years ago. In fact folate has decreased my noise hypersensitivity considerably, and is also sometimes connected to RLS.

 

[garyfritz]

Yup @dannybex, I usually take 1600 mcg/day of methyl folate. That's about the only other thing that has noticeable effects. Sometimes I wake in the night with agitation and B12 doesn't help. A 400mcg methyl folate tab usually does the trick. I first figured this out after eating a whole bunch of deep-dish pizza. Woke up and B12 didn't work, and I thought, hmm, there was probably a whole lot of folic acid in that crust... took some MF and I was asleep in a few minutes.

 

[garyfritz]

Thanks for the suggestions, everyone. It looks like I've already tried or addressed the things you could think of.

I figure this community is the largest and deepest reservoir of B12 expertise I'm likely to encounter. Most doctors know little or nothing beyond the RDA. Greg at B12oils has very deep knowledge but my case has stumped him. I had hoped that someone here might have encountered similar symptomology and might have some pointers or ideas I hadn't already tried, but apparently my situation is unusual. A few people here have said they have somewhat similar symptoms, but nobody seems to understand the mechanism or what to do about it -- except loading up more and more B12 and hoping it doesn't get worse.

I consider myself very fortunate. My problems are minor compared to what many of you face. And with sufficient B12 I can lead a pretty normal life with very few real issues. Hopefully I have prevented severe neural damage by stumbling across B12 early in my condition's progression. But my problems ARE very unpleasant and crazy-making, and I worry that my condition could worsen with age. So I'll keep looking...

 

[dannybex]

Yup @dannybex, I usually take 1600 mcg/day of methyl folate. That's about the only other thing that has noticeable effects. Sometimes I wake in the night with agitation and B12 doesn't help. A 400mcg methyl folate tab usually does the trick. I first figured this out after eating a whole bunch of deep-dish pizza. Woke up and B12 didn't work, and I thought, hmm, there was probably a whole lot of folic acid in that crust... took some MF and I was asleep in a few minutes.

Sounds like you found the answer. B12 (or too much relative to folate) is stimulating or agitating, and folate resolves this. I've found the same thing (after years of experiments) that folate (either methyl or folinic) is calming and actually can make me sleep too hard.

 

[Gondwanaland]

I first figured this out after eating a whole bunch of deep-dish pizza.

I have been wondering if methylation is about insulin resistance.

 

[garyfritz]

@dannybex, I was taking B12 for 2-3 years before I started taking methyl folate, and I didn't really have any agitation problems. (Unless I didn't get enough B12.) But maybe I was still changing and still figuring things out.

I think it's probably better to take some folate to balance the B12, and the 1600mcg / day I take seems to work fine. Usually when I wake with agitation, it "wants" B12. But sometimes B12 doesn't feed it, and it "wants" folate. I just try to give it whatever will let me calm down and sleep... but I've never noticed folate making me sleep extra deeply or long. (I wish !!)

No idea, @Gondwanaland. I have a family history of diabetes but I have no clue if that's involved in my issues.

 

[Gondwanaland]

No idea, @Gondwanaland. I have a family history of diabetes but I have no clue if that's involved in my issues.

I have always wondered why folks following a low carb diet report the same beneficial effects of a smooth-going methylation regime.

 

[mgk]

The symptoms you mentioned remind me of problems with the MAO gene. I used to have them too (especially the twitching) and accidentally discovered that taking adb12 would resolve them (still don't know why that worked). Then @Sherpa turned me on to the actual cause. See here:

http://forums.phoenixrising.me/inde...s-need-for-magnesium.35144/page-2#post-567059

I haven't had them since I started supplementing extra B2. I should mention here that there was already a sizable dose of B2 in my B complex, but I found that an extra 1-2 doses of B2 by itself had a different effect. I have in my notes this quote from the B12 Oils guy which might explain why:

[...]

With nearly all the mutations, the mutations mean that the enzyme can lose hold of the co-factor if the concentration drops. Thus, if an enzyme needs FAD (from vitamin B2) and there is a mutation in the enzyme, it is critical that you keep the levels of the vitamins very high.

[...]

The other major snp you have is in MAO. This is the most common double mutation seen in CFS and ASD. You need MAO to break down dopamine, nor-epinephrine and epinephrine. You can find out how bad this is by using Dr Google to look at the side effects of MAO inhibitors. It is pretty bad and curiously it is very similar to many of the symptoms that are listed on the B12 deficiency symptom list that you can see at http://b12oils.com/deficiencyfrm.htm If you fill out the form I can let you know which of the symptoms may be entirely due to MAO. To overcome this you need to supplement with lots of vitamin B2, BUT you need to have an active thyroid function to do this as you can't turn B2 into FAD and FMN if you thyroid is not working well.

Source

In other words, it's not that we have a B2 deficiency necessarily, rather that the intermittent low-normal levels may cause the cofactor to detach from the enzyme, so we need to maintain high levels. I do this by separating my doses: morning, noonish, night.

 

[garyfritz]

@mgk, I do have +/+ MAO A R297R (and a bucketload more), soo... I haven't quite figured out what to do about it. I have supplemented with B2 but I don't know if I'm taking the right forms. These days I'm taking http://www.douglaslabs.com/b-complex.html, which contains 20mg of R-5-P. Currently I take it in the morning, but last summer I was splitting it morning & night. That was a royal pain (since it's a powder in a gelcap) so I gave up on that. Maybe I need to revisit that -- maybe with a B multi that comes in a splittable tablet!!

Initially methylB12 totally erased my night-time thrashing, but over time I seemed to need adB12 as well. I tried various forms of Mg about 10-15 yrs ago and it seemed to help a little, but not much. I think I might try the Jigsaw SRT Mg, as I sporadically have a number of the Mg symptoms (hives, stiff neck, calf cramping, loss of sexual desire, in addition to the twitching).

 

[mgk]

@mgk, I do have +/+ MAO A R297R (and a bucketload more), soo... I haven't quite figured out what to do about it. I have supplemented with B2 but I don't know if I'm taking the right forms. These days I'm taking http://www.douglaslabs.com/b-complex.html, which contains 20mg of R-5-P. Currently I take it in the morning, but last summer I was splitting it morning & night. That was a royal pain (since it's a powder in a gelcap) so I gave up on that. Maybe I need to revisit that -- maybe with a B multi that comes in a splittable tablet!!

I don't have a definitive answer about the right B2 form either. Some people report amazing results with the active form FMN, whereas some seem to do fine with regular old riboflavin. I suspect it has something to do with thyroid function since thyroid hormone is required to convert riboflavin into the active form.

Personally, I tried FMN but didn't notice any difference from riboflavin. My multi has 25mg as a mix of riboflavin and r-5-p. I also have a separate plain riboflavin supplement which I get as tablets and split into 25mg doses. I take the multi in the morning and the others around noon and night for a total of 75mg.

I tried various forms of Mg about 10-15 yrs ago and it seemed to help a little, but not much. I think I might try the Jigsaw SRT Mg, as I sporadically have a number of the Mg symptoms (hives, stiff neck, calf cramping, loss of sexual desire, in addition to the twitching).

By the way, the post I linked to isn't a list of Mg deficiency symptoms, it's actually a list of side effects from MAO inhibitor medications (used for treating depression). Because our MAO enzyme is slow, we have a natural MAO inhibitor built-in, so in theory it's a rough estimate of what happens to us, especially when the enzyme is functioning slower than its usual slow.

 

[garyfritz]

I don't have a definitive answer about the right B2 form either. Some people report amazing results with the active form FMN, whereas some seem to do fine with regular old riboflavin. I suspect it has something to do with thyroid function since thyroid hormone is required to convert riboflavin into the active form.

I didn't realize until I read that thread that the B-multi I've been taking actually contains R-5-P = FMN instead of "regular" B2. So I've been taking FMN for quite a while and didn't know it. And didn't notice anything from it.

I'm another one that shows many/most hypothyroid symptoms but my test results are normal, so who knows how that fits in with the "must have normal thyroid function" comments.

By the way, the post I linked to isn't a list of Mg deficiency symptoms, it's actually a list of side effects from MAO inhibitor medications (used for treating depression). Because our MAO enzyme is slow, we have a natural MAO inhibitor built-in, so in theory it's a rough estimate of what happens to us, especially when the enzyme is functioning slower than its usual slow.

Yeah, that post went from magnesium, to adb12, to MAO issues in 3 paragraphs. I think I got lost.

 

[ahmo]

I'm another one that shows many/most hypothyroid symptoms but my test results are normal

Thyroid experts tend to discount the lab results, and the the levels considered normal. I gave up testing for thyroid, as I'd been hypothyroid most of my life, on Synthroid, and my tests were generally within the norm. But you'd need some good guidance to start taking any form of thyroid. Maybe iodine could be useful.


http://www.amymyersmd.com/2015/08/thyroid-health-part-vi-the-iodine-thyroid-connection/

5 Lies About Your Thyroid Disease That You’re Likely to Hear

http://thyroid.about.com/od/thyroidbasicsthyroid101/a/5lies.htm

Izabella Wentz, Pharmacologist http://www.thyroidpharmacist.com/

http://thyroidbook.com/ Datis Kharrazian

https://www.youtube.com/user/TheRLCLabs Several Hypothyroid vids, incl Dragone



http://thyroidbook.com/blog/iodine-and-hashimotos/

 

[garyfritz]

Thanks @ahmo, I'll check into that. But my MD tried me on Synthroid? Westhroid? and I didn't notice any differences, so we gave up on that route...

 

[garyfritz]

Greg the B12oils expert told me he has over 800 people using the oil, and I use more oil than any of the other 800 people. How lovely to be so special.

Greg had an interesting observation... I don't need as much B12 during the day. I use one squirt of the oil in the morning, and that lasts me 15-16 hours with very few symptoms. Then I take TWO squirts at bedtime, and often only 4-5 hours later I'll wake up with agitation, RLS, etc. I need a bit more B12 to get back to sleep. (Usually 1/4 of a 5mg Country Life will do it.)

I mentioned this to Greg and he said "You will definitely need methyl B12 to make melatonin, which occurs at night. Also if you are chewing up B12, once you stop eating, or taking folate, the consumption will go up. Possibly (and it is very hard to tell this) you saturate your uptake system, and then clog it with Bad-inactive B12 (due to lack of 5MTHF), you then need to displace it with methyl B12. Another possibility is that you have unidentified SNPs that make your MTRR and MTFR enzymes really really poor at working when B12 or folate drops."

I take 800mcg of 5MTHF (Metafolin) at bedtime, so I doubt that's the problem. I wonder if there is something amiss in my melatonin-production system that gobbles up tons of B12? That might explain the increased demand during the night...

Any insights there?