B12/Folic Acid and D3/K2 Supplementation

Please note that folic acid is not a natural form of folate and while we can convert it into a useable form, the process is not without problems.

Folic acid is processed by the enzyme dihydrohydrofolate reductase (DHFR) in a two step reaction. First folic acid is converted to dihydrofolate (DHF), which is the natural substrate for the enzyme DHFR. Then, in the normal reaction for the enzyme, DHF is conveted to tetrahydrofolate (THF) which can then feed into the folate cycle.

As this paper shows, DHFR processes folic acid about 1,300 times as slowly as its natural substrate DHF. Furthermore, there is an approximately 5 fold variation in activity of the enzyme among individuals.

So everyone processes folic acid very slowly and some people do it extremely slowly. This means that even modest doses of folic acid can readily accumulate.

As the paper shows, folic acid at even modest levels saturates the DHFR enzyme and inhibits its activity. This means that in the presence of folic acid, the natural substrate DHF accumulates. DHF in turn inhibits several other folate cycle enzymes, including MTHFR (which provides folate for B12 dependant methionine synthase) and thymidylate synthase.

Thus accumulating folic acid can interfere in the wider folate cycle.

The five-fold variation in natural DHFR activity means that the extent of interference will vary among individuals and of course, the higher the folic acid dose, the more likely interference will occur.

So it seems wise to avoid folic acid and stick to natural folate supplements (methylfolate and/or folinic).

The linked paper canvases reasons for the variable response to B12 among patients. One they don't consider is the capacity of folic acid to interfere in the folate cycle and hence in B12 dependant enzymes.

 

Please note that folic acid is not a natural form of folate and while we can convert it into a useable form, the process is not without problems.

Folic acid is processed by the enzyme dihydrohydrofolate reductase (DHFR) in a two step reaction. First folic acid is converted to dihydrofolate (DHF), which is the natural substrate for the enzyme DHFR. Then, in the normal reaction for the enzyme, DHF is conveted to tetrahydrofolate (THF) which can then feed into the folate cycle.

As this paper shows, DHFR processes folic acid about 1,300 times as slowly as its natural substrate DHF. Furthermore, there is an approximately 5 fold variation in activity of the enzyme among individuals.

So everyone processes folic acid very slowly and some people do it extremely slowly. This means that even modest doses of folic acid can readily accumulate.

As the paper shows, folic acid at even modest levels saturates the DHFR enzyme and inhibits its activity. This means that in the presence of folic acid, the natural substrate DHF accumulates. DHF in turn inhibits several other folate cycle enzymes, including MTHFR (which provides folate for B12 dependant methionine synthase) and thymidylate synthase.

Thus accumulating folic acid can interfere in the wider folate cycle.

The five-fold variation in natural DHFR activity means that the extent of interference will vary among individuals and of course, the higher the folic acid dose, the more likely interference will occur.

So it seems wise to avoid folic acid and stick to natural folate supplements (methylfolate and/or folinic).

The linked paper canvases reasons for the variable response to B12 among patients. One they don't consider is the capacity of folic acid to interfere in the folate cycle and hence in B12 dependant enzymes.

 

I haven't read the linked paper yet so this may already be covered in there. What you said about folic acid is what I was about to say about Cyanocobalamin. It is the synthetic form of the vitamin and it seems that some can convert it to usable form and others can't. That can be due to genetic differences.

 

from what i am learning there is a link in all the tests and treatment with all things being balanced out. so yes there are some with genetic defaults so that they are not able to translate and absorb the folic and or b12. it quite complicated the relationship between the folic acid which can hide the b12 deficiency in the blood tests.

@b12unme @b12info are both great sources of info and there is as i have said a great facebook group pagewhich has info on the balance of iron folic etc that are needed.

eg to much b12 can lower potasium which can lead to another condition which leaves you weak muscles.

for me taking the normal folic acid does not help but boods get better. false result. as that hides other problems.

so i am taking both mtfhr and b12.

i wonder that the gut problems with pwme dont allow for absortion and we are linked to leaky gut and that leads to other illnesses due to malabsorbtion

it complicated

 

I know that! I read somewhere that 2/3 of post-menopausal women cannot metabolize folic acid. What I should have said was most people take folate with B12.

 

Merged thread
Once again on B12 / folate...

When I browse the symptoms of B12 and/or folate deficiency I see things I have suffered with for years. Tinnitus, palpatations, tongue inflammation, etc. Now I know these overlap with ME symptoms, but I want to try supplementation and see if there is any effect.

Before visiting these forums I had no idea what a complex subject this was, and I am still not clesr what the best option is for me RE supplementation.

I have had serum folate and B12 tests in the past. The B12 was in the upper range, and folate towards the lower suggested range.

Last spring I had a month on high strength sublingual B12. I felt like it was perhaps one of the only times I'd felt some noticable change from supplementation. However, around that time some visual problems that had started up seemed to get worse - for example I got black floaters. I wasn't sure if this was related to the methycobalamin.

If I was try supplementation again, I am wondering: What are your experiences with B12 and folate supplementation? Has anyone had any problems or benefits taking the two together?

Thanks!

Note. I have not had any genetic testing to check for gene mutations etc.

 

I am feeling better since I started injectable methylcobalamin. I also take methylfolate. IIRC, it is dangerous to take one without the other. I mean B12 and folate. They don't have to be those specific forms.

 

High B12 has not been found to be harmful. As for your floaters i can't say if its related or coincidental. I take 1000mcg methylcobalamin daily. It gives a bit of energy and reversed my B12 deficiency.
I found the only effect of folate is to reduce my headaches, a very good result. I use mehtylfolate because there are concerns that folic acid over the long term may cause harm, its not bioidentical to the folate from vegetables.

 

I' m tagging @JaimeS as i believe that she has had issues with B12.

My aunt cannot take B12 she has had a horrendous reaction on both occasions that she tried. I don' t know which version she took - methylated versions may be an issue for some people.

This is unusual as most of the literature suggests that this should not happen.

 

I take a multi-B called Terry's Naturally Healthy Feet & Nerves.

My GP chided me, saying it was impossible that I felt better on it, since my B12 levels were normal, and scoffed when I said I felt better when they were on the high end of normal.

Less than a week later, my neurologist told me that a lot of his patients said the same, and that I should continue doing what I was doing.

I feel like it should be increased and decreased with activity. I 'need more' on days where I'm pushing physically or cognitively. I'm sure not everyone will feel the same.

My bad reaction was the result of perhaps a medical mishap. Dr DeMeirlier recommended a B12 injection at a much higher dose than one usually receives in the US. He also insisted it not have a particular kind of preservative, because ME patients have so many sensitivities.

My US doctor also scoffed (a new doc by this point!). She said no one gave B12 injections at such a strength. She said the preservative was in all US B12 injections. I shrugged and took the injection.

For 5-15 minutes I felt the bare edge of healthiness and it was a near-religious experience.

Then I began to feel something was going dreadfully wrong. I was driving home and began to wonder if I was going to make it. I started to shake. Honestly, it didn't feel like it was the preservative, a 'poisoning' or sensitivity response; it felt as though I had "burned through" the B12 at an intense rate and now it was gone. Metabolic cycles had revved and now they were being asked once again to come to a halt.

I had a phenomenal crash.

The doctor offered me more injections but I couldn't imagine feeling that awesome for five minutes only to have it yanked out from under me, and the crash was one of my worse ones.

Terry's Naturally is an absolute lifesaver, though. Helps with CNS, peripheral nervous system issues, and on and on. I don't get the same effect from other supplements. I think it might be the benfotiamine, which isn't in a lot of B complexes -- it's a "semi-B" that was once called B9.

All of this is my own personal experience and shouldn't be taken as medical advice.

 

Merged thread
B12/Folic Acid and D3/K2 Supplementation

My B12 and D are low, like many people with or without ME/CFS.

I was able to raise them both to normal levels with supplementation.

I went to Vitacost.com and found BTotal, a liquid sublingual. This has all the B's (except B1 which I take separately) and Folate.

They have their own brand of D3 gel caps so I take 2,000 2x a day. They also have a D3/K2 supplement which is a sublingual tablet but you can only take one of these a day as it has all the K2 you need and you should not take more K2 than this. It may be that this one sublingual will be all you need to raise your D but I need to take more so I use the D3 gel caps also.

Taking D2 is not recommended as the body needs to convert it to D3 to use it. I imagine D2 is OK for people that don't really have low levels of D OR get SO MUCH in Rx form that converting it is not an issue especially if they don't have other chronic health issues which may tax the bodies normal mechanisms of converting D2 to D3.

 

You can take K2 till you go bankrupt it won't do any harm. Except to your pocketbook
Its best to stick to D3.
You can also add A to create more osteocalcin which the K2 activates to prevent osteoporosis. If you have unemerged wisdom teeth you will have a problem with K2 especially combined with A.
A, D3, E and a few others you can take too much of, i would monitor or research the highest safe levels if your going to take them regularly.

 

I looked up the ingredients of what you were taking. It contains folic acid, not folate (assuming I found the right product). They aren't the same. This is worth reading on the subject :

https://chriskresser.com/folate-vs-folic-acid/

 

For B12 it is my experience that supplements do raise the level in the blood. However despite my numbers being fine (even marked 'high'), switching to injections did make a difference. Not a big one in my case, but enough to consider jabbing myself in the leg worth it.
Having 'enough' B12 in your system doesn't always mean you can use it properly. I've read MTHFR mutations which can cause issues with metabolizing B12 are fairly common (in the general population, I don't know how frequent it is found with ME).

If I remember correctly this study https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0124648 was part of the rationale to let me try injections.

Not saying you need to get injections, there are also lots of people who don't see any benefits, but it could be worth looking into.

 

I've read that about 50% of the world's population has an MTHFR mutation of some sort, which can be inherited from one or both parents, but that 50% figure varies a lot depending on the source of the info, and the population under discussion.

This website is worth poking around in :

http://mthfr.net/

It is a commercial site with things to sell, but it has loads of free info on MTHFR.

I was always under the impression that for a gene mutation to survive in the population it must confer some advantage to the people who have it. For example, I heard that having sickle cell disease reduces the risk of developing malaria - I could be wrong though - I can't remember my source. I don't know any advantages to having an MTHFR mutation at all, and yet it is so common that I feel there must be one that hasn't yet been discovered, or (more likely) I just haven't come across it in my reading.

It is essential to have good levels of folate in order to use B12. For someone with an MTHFR mutation taking folic acid does not qualify as taking a folate supplement - such people can't reliably convert folic acid to folate. But there are quite a few reasons for not being able to use B12 as it should be used by the body. In people with issues in using B12 they can have high levels from supplementation, but still suffer B12 deficiency symptoms. This article is worth reading, but is heavy going :

Title : The pathophysiology of elevated vitamin B12 in clinical practice

Link : https://www.researchgate.net/public..._of_elevated_vitamin_B12_in_clinical_practice

There is an option to download the full PDF file from that link.

 

There are also different types of B12. My daughter does tolerate methylcobalamin but some do not.

If you have gut issues you may have issues with B12. It may simply feed a colony of bacteria.

I know of some people taking B and multi vitamins by " patches" - similar to nicotine ones- this bypasses the gut and seems to be effective. I suspect dosage may be a bit more difficult to modulate though.

 

The ones I know of are (1) cyanocobalamin, (2) hydroxocobalamin, (3) methylcobalamin and (4) adenosycobalamin. I'm sure I've read there are several others but they don't get mentioned much and I have never seen them available as treatments or supplements.

(1) is artificial and doesn't occur in nature. I'm not sure about (2). (3) and (4) are the active forms of vitamin B12 in the body.

A Pernicious Anaemia Forum I occasionally read, which also has members with B12 deficiency but no PA, has people with all sorts of tolerances - some do sort-of-okay with supplements, most have to have injections, some use mouth sprays, some use patches. Also there are people who tolerate one of the forms of B12 above but can't tolerate another one. (1) is the form generally used to inject people in the US who have PA. (2) is the form generally used to inject people in the UK with PA. In both cases there are people who only do well with (3) or (4). As far as I can tell there are lots of situations and its a very messy subject.

 

Merged thread
Hi folks,

Was wondering if anyone has self treated with B12 injections? I am looking to trial this. I tick many of the boxes for issues with B12 (fatigue, glossitis, vision issues) though my serum B12 is in the normal range.

I am minded to try and source hydroxocobalamin and self inject. Anyone done similar? And if so, is there a reputable source?

 

@InitialConditions I have tried B12 injections administered by a nurse. Dr was happy to try it. We tried 1 dose a month for 3 months though I did later learn more frequent doses are recommended for ME. I didn’t have astonishing results. There were many challenges in my life at the same time and I do wonder if it made me less prone to a crash so dr and I have filed it away as something we might re-visit. I’m now trialing oral drops although I realise injections are the recommended method of delivery for ME. I believe it is B12 levels in the cerebrospinal fluid rather than levels in the blood that is at issue with ME. If it is not too inconvenient, receiving doses by a nurse should eliminate issues you might have about reputable sources or any self-injection issues you might have.