Why does B12 not work for me?

[TigerLilea]

@TigerLilea That is scary that your iron went up to that after menopause. I still bleed completely regularly, and this is recent: Ferritin 288 (10-232 normal). I think you are right about not taking what your body doesn't need. My regular local doctor always told me I didn't need vitamins as I eat very healthy.

It's normal for a women's ferritin to rise after menopause as there are no more monthly periods. And 121 is a good level for ferritin - puts it right in the normal range for "iron deficiency unlikely". They changed our ranges here in Canada, well at least in BC, and now anything under 50 is considered too low and anything between 50 to 100 is considered a possible problem depending on symptoms.

 

[Strawberry]

Dr Lynch has a neat supplement called B Minus which has all b vitamins minus folate and b12: https://www.amazon.com/Riboflavin-Pantothenic-Formulated-Seeking-Health/dp/B00HZUNQ9K/ref=sr_1_1_s_it?s=hpc&ie=UTF8&qid=1475784782&sr=1-1&keywords=b minus. His supplements are quality since he formulates them.

That b minus is almost identical to my methylpro. Mine has a few more things though, probably doesn't matter. Link to my methylpro is in my first post.

 

[Strawberry]

It's normal for a women's ferritin to rise after menopause as there are no more monthly periods. And 121 is a good level for ferritin - puts it right in the normal range for "iron deficiency unlikely". They changed our ranges here in Canada, well at least in BC, and now anything under 50 is considered too low and anything between 50 to 100 is considered a possible problem depending on symptoms.

It is perfect for you, but scary for me! If I can't figure out what is causing that high ferritin, it might make life miserable once I hit menopause.

BC? We must be neighbors!

 

[CCC]

@CCC My methylpro has 25 mg of B2 and 15 mg of methylfolate. Is that enough, or not? I have also tried magnesium to no avail. My iron is sky high (which concerns me as I am nearing the age of pre menopause) so that (IMO) leaves me with manganese? And Lithium?[/QUOTE]

For B12: read the low-and-slow write up of how to approach this B12 thing (it's in @caledonia signature). I can't tell you how much is enough. Not because I'm stubborn, but because everyone here is different.

Iron: have you been tested for haemochromatosis? Left untreated, it can make you very, very fatigued. The treatment is easy: give blood (it's a therapeutic 'donation', so they'll take the blood even if they have to throw it out).

Other stuff that might be helpful:
If you go back to Freddd's or @caledonia 's basics, you'll see they all suggest a good multimineral, a good multiB (like Jarrow BRight or similar) and some quantity of folate, starting with a very low amount of folate to avoid all sorts of problems. After that, it's up to your body. We need A and E, in the forms recommended by Freddd/caledonia. We also need lots of B2 and now a little manganese - which isn't the case for everyone. And zinc is proving to be a real challenge.

 

[Strawberry]

For B12: read the low-and-slow write up of how to approach this B12 thing (it's in @caledonia signature). I can't tell you how much is enough. Not because I'm stubborn, but because everyone here is different.

Iron: have you been tested for haemochromatosis? Left untreated, it can make you very, very fatigued. The treatment is easy: give blood (it's a therapeutic 'donation', so they'll take the blood even if they have to throw it out).

I've read the low and slow, but doesn't that refer to people that get reactions? I've read her links at least a half dozen times, but my memory is no good... Nothing ever clicks.

And for the haemochromatosis, I haven't been tested, but I probably should. I'm 100% northern European. Doctors don't test for it until after menopause, and I want to get on top of this high ferritin before I hit menopause. I don't need to get worse than I am! Even though I am mild to moderate cfs, enough is enough. Also for what its worth, I used to be anemic. I had to take iron when I was a little kid, and often as an adult. I'm not sure when this stopped and switched to high. I haven't supplemented iron for years.

 

[Mary]

@Mary, do you think it was the brand you were taking? I've heard a few people say that this brand worked for them but not another brand for multiple supplements.

Are you talking about the brand of B12? I don't think it was the brand per se that caused the problem. I did injections from a compounding pharmacy but it was only 3 times a week and I don't think it was enough. I tried several different brands of sublingual MB12. I think it was a matter of absorption and for some reason I absorb the liquid methylcobalamin better than the sublingual tablets. And many people swear by transdermal B12 for absorption.

 

[alicec]

Here are my homo:

Three of those SNPs do something, though not a lot.

The MTHFR A1298C SNP has a modest slowing effect on the enzyme.

BHMT R239Q is a missense mutation which changes the structure of the protein but studies have shown that this has no significant effect on the amount of enzyme produced or on its activity.

The MTHFS SNP is a slight upregulation.

None of the other SNPs amount to anything and even these three have only a modest to negligible effect.

He has a whole chapter on this homo A1298C, and says it's the hardest of the methylation-related polymorphisms to treat.

This is a gross exaggeration which I suspect is based on the incorrect reading of research and erroneous claims about this SNP made by Yasko.

The SNP is extremely common, millions of people around the world have it and they certainly don't all need "treating".

Active B12 supplementation has certainly been helpful for many people so is worth persisting with. I would endorse the thoughts of others - many things need to be in place for the system to work well.

Your methylfolate dose of 15 mg is quite large. Maybe there is a balance issue.

Regarding high ferritin, only about 10% elevated ferritin is due to iron overload. More commonly it is due to inflammation, infection and various other causes. Mildly elevated ferritin (300-1000 ug/L) usually means just continue monitoring. >1000 is cause for concern and definitely needs thorough investigation.

23andme looks at haemachromatosis SNPs so you should be able to check there to see if this is an issue for you.

Iron studies should help to better define iron status. The single best measure is transferrin saturation - >45% is strongly suggestive of iron overload. Here is an article on the issue.

 

[Strawberry]

Bluebonnet liquid methylcobalamin - 5000 mcg.

Dang, I just looked this up. It has food coloring...... That wipes it off the list for me.

 

[Strawberry]

@alicec If my snps aren't that bad, then could it be more of a co-mineral deficiency/imbalance, or do you think that the original answer of lithium could help?

BTW, I guess we can forget the discussion of ferritin. I never checked to see if it was tested in May, and it was. Everything right smack dab in the middle where it should be. I must have had inflammation when I went to California last December. How embarrassing!

Back to the methylfolate, if you think it is high, is there a ratio of folate to mB12? Dr K. did have me on very high levels of b12 when I was self injecting. And it seems others here have done well on the methylpro products. Maybe I should try a different methylpro pill without folate?

I get so danged confused with this.

 

[TigerLilea]

It is perfect for you, but scary for me! If I can't figure out what is causing that high ferritin, it might make life miserable once I hit menopause.

BC? We must be neighbors!

I'm in Metro Vancouver.

High ferritin can be an indication of something like rheumatoid arthritis or an inflammatory condition. Has your doctor done any further testing?

 

[Tammy]

I like global healing liquid B12. ( 80%methyl, 20% adeno). (No additives) Methylfolate will help drive B12 into the cells.

 

[alicec]

could it be more of a co-mineral deficiency/imbalance, or do you think that the original answer of lithium could help?

I really don't know whether lithium has any significant role in B12 transport. The few scientific studies which might shed some light on it are behind pay walls and not of sufficient interest to me to pay for.

I most certainly don't accept the promotion of lithium orotate by Amy Yasko. She has made so many serious errors that I don't consider her a reliable source of information.

Trace minerals could indeed be significant. Various people on PR, including myself, have found that depletion of different trace minerals over time has interfered with the effectiveness of active B12/folate.

There is no fixed ratio of B12 to folate that is advisable - it is something that needs to be determined empirically. Some people do seem to benefit from big doses like 15 mg or more, but many get by on much less.

I was just pointing out that you are taking quite a high dose. It may or may not matter.

Getting active B12/folate to work well and continue working can be tricky and the balance seems to change over time.

 

[Kierkegaard]

This is a gross exaggeration which I suspect is based on the incorrect reading of research and erroneous claims about this SNP made by Yasko.

The SNP is extremely common, millions of people around the world have it and they certainly don't all need "treating".

I should qualify that this refers to patients who come to see him, so clearly there's gene expression and who knows how many other correlates with this polymorphism with this qualification.

As for prevalence, how many are homozygous for a1298c?

As for Yasko, I know she's botched the interpretation of a reference for her claims about CBS. What else do you think she's misinterpreted?

What minerals were depleted and how did you test for them? I'm thinking of asking my doc for a Nutraeval test, unless there's something more comprehensive out there.

 

[Valentijn]

As for prevalence, how many are homozygous for a1298c?

8.7% of the general population, which comes out to approximately 644 million people. It's also not doing anything special which other MTHFR mutations don't do, and if taking the other common MTHFR SNP (C677T) into account, the normal reduction in enzyme activity is 32%. Homozygous A1298C causes a 39% reduction, so MTHFR function with it is still quite close to average.

"Gene expression" in the context of methylation is pretty much entirely a bullshit excuse by spin-doctors or people who don't understand genetics at all, usually when confronted with the information that the SNPs they're blaming don't have the impact that they claim. If the influence isn't due to the SNPs on the gene itself, it's happening due to an external process - and still has nothing to do with A1298C or any other particular SNP. And when gene expression is altered, it's the entire gene which is affected - and again, this is not due to any particular SNP on the gene nor is it having any impact on any specific SNP. So basically, gene expression has nothing to do with specific SNPs, beyond the actual impact which that SNP always has on the gene.

Yasko has "misinterpreted" pretty much everything. If I look at results from her testing service or Cenetic Genie, the only things I consider to be of interest regarding methylation are MTRR A66G, MTHFR A1298C, and MTHFR C677T. And it sounds like the effect of even MTHFR A1298C is getting badly exaggerated. There are a few other SNPs on her test which can have a big impact (missense mutations) but they're exceedingly rare.

 

[alicec]

this refers to patients who come to see him, so clearly there's gene expression and who knows how many other correlates with this polymorphism with this qualification.

Makes no difference. He is attributing symptoms to the presence of the SNP but there is no evidence that the SNP causes the problems. It is a very common SNP so undoubtedly a number of patients would have it. Nor does it have anything to do with so-called expression of the SNP. It is part of the gene and is expressed when the gene is expressed.

@Valentijn has covered the prevalence and the fact that most of the SNPs that Yasko makes claims about are pretty much irrelevant. Many of them are synonymous - ie they cause no change to the protein product of the gene, so have no effect.

I'll just mention too the claims this SNP affects the backwards reaction of MTHFR which in turn is involved in regeneration of BH4, along with the related claim that BH4 gets used up in processing ammonia.

Both claims are incorrect. The first is based on misreading of a research paper which had created experimental conditions to make the enzyme run backwards, using qBH2 as a reactant (not the same as BH2). There is no evidence that MTHFR runs backwards in the body, nor does it act to regenerate BH4. Two other enzymes do that - DHFR (dihydrofolate reductase) which converts BH2 to BH4, and DHPR (dihydropteridine reductase) which converts qBH2 to BH4.

BH4 has no role whatsoever in the urea cycle, where ammonia is processed. Yasko seems to have completely misread the NOS reaction, which does involve BH4 and somehow conflated it with the urea cycle. There are a couple of shared reactants but they are two separate metabolic pathways.

What minerals were depleted and how did you test for them

Determining mineral status can be very difficult. In my case I determined empirically that I responded mainly to boron, though later addition of calcium, molybdenum and manganese also seemed to help restore the beneficial effect of B12/folate (which had petered out).

I interpreted the positive response as meaning these minerals had become depleted, though I can't say for sure that this is the reason. I did have lowish boron, molybdenum and manganese on a hair test; true calcium status is very difficult to determine. The only real sign of lowish calcium status I had was high 1,25 diOH vit D to 25 OH D ratio

Freddd found he developed severe copper depletion. He interpreted this and other trace mineral depletion as part of refeeding syndrome. It is a reasonable interpretation of the phenomenon though there are so many unknowns around why and how active B12/folate really works that it is not possible to say for sure.

 

[Mary]

Dang, I just looked this up. It has food coloring...... That wipes it off the list for me.

Sorry to hear that! The Global Healing liquid B12 that @Tammy mentions looks interesting. Also you might check this one out: http://www.iherb.com/Garden-of-Life-MyKind-Organics-B-12-Organic-Spray-Raspberry-2-oz-58-ml/58126

My energy also picked up when I added in P-5-P (co-enzymated B6). Nutreval testing showed a rather major deficiency. It might be useful if you could get Nutreval testing done. I know it's very hard flying in the dark, trying to figure out what's going on.

BTW, my B12 numbers are always very high and that's due to the fact that I have a difficult time absorbing it, so it just floats around not getting into the cells. But again, I do better with the liquid B12 than sublingual or injections. You also might check out transdermal B12. Here's a rather lengthy thread all about it, but you don't have to read the whole thing: http://forums.phoenixrising.me/inde...2-oils-view-vs-rich-vans-view-thoughts.43539/

 

[alicec]

I just looked this up. It has food coloring

Are you sure about that? The red colour of the product is the natural colour of the vitamin (from the cobalt).

 

[Strawberry]

Wow, so much to take in here.

So what it appears that this is boiling down to, is some mineral deficiency. Since I don't have the nerve to try this and that on a whim, would it be better to get a hair test or nutreval or ___?

And revisiting folate... Am I best off eliminating the methylpro and getting a b complex that doesn't have folate, and taking folate separately?

@alicec You popped up while I was posting! I can't be sure, it was a review that said it had artificial color and flavors. I couldn't find a list of ingredients... You are right though, I remember now from injecting that it is QUITE red. But I don't know what it tastes like, and if flavoring is natural or artificial. I guess I could try a bottle, and give it to someone if I don't tolerate it.

 

[alicec]

if flavoring is natural or artificial

They say natural raspberry flavour.

I have used this product topically as a cheap way of taking relatively high doses. Just mix in the palm of the hand with a dob of body lotion and rub into the soft skin of abdomen, thighs, inner arms etc.

This gives much better uptake than sublingual.

Since I don't have the nerve to try this and that on a whim, would it be better to get a hair test or nutreval or ___?

In the end you probably do need to determine things empirically but a nutreval or other OAT test could certainly be helpful in revealing metabolic slow points.

Determining mineral status can be difficult. RBC values are useful for at least some, urine for those that are normally excreted via the kidney (less so for those excreted via the bowel, though a high urine value for these could mean excess which is spilling over). Hair mineral tests can be difficult to interpret.

And revisiting folate... Am I best off eliminating the methylpro and getting a b complex that doesn't have folate, and taking folate separately

Depends on how much effort you want to put into this. You may need to take the whole thing apart - ie individual B vitamins, to see if changing proportions makes a difference. Also don't overlook the possibility of sublingual active B2 and B6 (and maybe others). I found a big difference between swallowed and sublingual. The latter were far more potent.

Unfortunately there is no easy answer and we don't even know if you would respond better to B12 in different circumstances. Some people have benefitted greatly but not all. Only you can decide if you think it is worth the effort of pursuing further.

 

[Strawberry]

They say natural raspberry flavour.

I have used this product topically as a cheap way of taking relatively high doses. Just mix in the palm of the hand with a dob of body lotion and rub into the soft skin of abdomen, thighs, inner arms etc.

This gives much better uptake than sublingual.

How much do you use when you do it topically? I might try this.

And as for how much effort do I want to put into this? I have too little energy for effort, so I want to say zero! but I would like to get B vitamins to help more.