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@@NI1578: Interesting! So I guess the crucial question is:

How (and where) does one get tested properly for B12 at a cellular level?

Anyone out there knows?

@Susanne - A common recommendation is to get a Methylmalonic Acid (MMA) Test done. However, for me, my results were totally normal and I'm now back to square one in trying to figure out why by B12 levels are so high and whether I'm actually deficient at a cellular level. So I too am looking for information on how to test for active B12 levels.

@@NI1578: I got tested (provocation urine test) last year and again this summer for heavy metals and copper. I suffer from a bad case of copper overload, even though my last test showed that the amount of copper in me seems to decrease fast. But thanks for your advice. I really appreciate it :-)

Getting tested is always a good idea. Actually, after having read this thread, I strongly consider having my level of intracellular B12 tested. Never even knew it was possible. My blood levels have always been high, even though my genes say that I don't absorb B12 well. Hmmm makes me a bit suspicious

Anyone knows the best method of getting B12 at cellular level tested?

@susanne stender - probably best to get your copper levels checked. I'm homozygous C677T MTHFR and tested on the low end for normal on copper. Copper is one of the key trace minerals for high histamine folks like me.

So much interesting info here. Thanks, all. Will probably try low dosage lithium orotate after having read this thread.

@Julie Patrick: Do you remember, where you have got the info about MTHFR mutations and copper excess? Being copper toxic and MTHFR 677 homozygous that piece of information is especially interesting for me. And the link

http://ajcn.nutrition.org/content/26/6/657.full.pdf

...from which book is it from? Thanks a lot in advance :-)

I too am homozygous for C677T MTHFR and have elevated B12 and the FUT2 gene which helps with intestinal absorbtion of B12. I too have had problems with anemia...which resolved when I began treating the MTHFR with methylfolate, etc. Interestingly, folks with MTHFR have problems with elevated copper which spars with iron...but taking molybdenum has reversed this problem for me.

http://ajcn.nutrition.org/content/26/6/657.full.pdf

From [PMID 18776911OA-icon.png]: We identified a strong association (p = 5.36 x 10(-17)) between rs492602 in the FUT2 gene and plasma vitamin B(12) levels in a genome-wide scan (n = 1,658) and an independent replication sample (n = 1,059) from the Nurses' Health Study. Women homozygous for the rs492602(C) allele (in dbSNP orientation) had higher B(12) levels. This allele is in strong linkage disequilibrium with the FUT2 nonsecretor variant encoding W143X, suggesting a plausible mechanism for altered B(12) absorption and plasma levels.
Neighbor rs601338
Distance 257
GWAS
SNP rs492602
PubMedID [PMID 18776911OA-icon.png]
Condition Plasma level of vitamin B12
Gene FUT2
Risk Allele G
pValue 5.00E-017
OR 0.09
95% CI 0.07-0.11) pg/ml decreas

I have no idea what this means but I just copied this from Promethease as I to have this gene. I am on B12 injections have massively high blood levels but macrocytosis in my blood cells and I have MTHFRC677T going on.

Yeah, ok. There could be some test to distinguish cellular levels, but I think the studies are only looking at blood levels. I'm not sure if there's studies with links either way about cellular levels. FUT2 is about gut absorption, I think.

@QJ2313 I think the various references are not properly distinguishing between blood or serum levels and cellular levels of B12. The Livewello site does not specify which (hence leading to the confusion). My serum B12 is off the charts but all evidence points to my cellular levels of B12 being low.

@UK1203, please Google Rs602662, and you'll find ample evidence that Livewello is mistaken here. Livewello says AA homozygotes have LOWER than normal B12, however, SNPedia (which lists study references), says AA homozygotes have HIGHER than normal B12.

This gene is related with gut absorption, not blood-to-cell absorption, I think. Anyways, all the evidence shows AA Rs602662 is associated with higher B12, not lower.

LiveWello is NOT incorrect. As a few others have said, I also have extremely high blood levels of B12 and a FUT2 mutation. My Functional MD recently did the SpectraCell panel, and my cellular level of B12 is very low. If you cannot absorb the B12, it will collect in your blood.

I think Livewello HAS A MISTAKE HERE. I am also homozygous for rs602662 FUT2 mutation AA. Livewello says "People with homozygotes (AA) and heterozygotes (AG) polymorphisms in the FUT2 gene have 15% lower vitamin B12 levels because it is not efficiently absorbed in their intestines." But I think it should read "homozygotes (GG) and heterozygotes (AG)", meaning normal population, rather than AA mutation. AA mutation causes higher than normal B12, according to SNPedia and other sources.

Being homozygous AA rs602662, I can verify that my blood levels were tested as ">1999pg/mL" on a reference scale 211-946pg/mL. In other words, my B12 is off the charts. I take daily Methyl-B12, although I'm not sure I should. I also don't experience any effects from B12, like energy or anxiety or whatever. If I don't take B12 for a month or so, and then take it prior to sleep, I do notice very vivid dreams for only the first night upon starting to take it (I've reproduced it many times).

Anyways, to the original commenter, I think he's been misinformed by Livewello. Hopefully they fix their mistake.

Try added a low dose of over the counter Lithium (5 mg or less). It will help with B12 absorption. It worked great for me. Took it in addition with B vitamin, helped greatly. Now taking every other day.

In my case it was due to having one copy each of the A1298C and the C677T. I was told by a doctor that I later contacted about the results of the B12 blood test, before I had the 23andme testing, that having high B12 blood levels should have triggered the doctor that did that test to order the MTHFR testing, because that result is a marker for MTHFR mutations. If you have not checked your data to see if you have the A1298C or C677T you may wish to do so. Then the advice previously to go to mthfr.net is a good idea.

Thanks, all. Very helpful comments and suggestions!

As I stated previously, Having rs492602 (C;C or A;A) may be causing better intestinal absorption of B12...so which polymorphism is the author asking about? I too have high plasma B12. I have not gotten more testing because I have HIGH ENERGY which correlates with my labs.

If you are fatigued and you are referring to another polymorphism then you can get additional testing to see if your B12 is actually reaching the cells. Methylmalonic Acid (MMA) Test. Methylmalonic acid is produced when certain amino acids break down in the body. Methylmalonic Acid is used to help detect early and/or mild vitamin B12 deficiency, especially at the tissue level. The test is $68
http://www.mylabsforlife.com/BloodTests/alllabsalpha

Yes I can explain this. The blood test measures the amount of vitamin b12 circulating in your blood but does not measure the amount that is actually bioavailable to your cells. Nor does ot necesarily tell you whih type of b12 is circulating. If you have a mutuation which impairs your ability to metabolise (or methylate) the b12 in your blood then this could lead to this result. You could effectively have a b12 deficiencyat the cellular level yet a standard blood test will show normal or even high circulating levels of b12 in your blood. Methylcobalamin is the more bioavailable form of b12 whereas many supplements contain a form of b12 which needs to be converted to a more bioavailable form before it can actually be used by the body's cells. If you are not producing the correct enzymes in sufficient quantities due to carrying a mutation 8n the gene that codes for the enzyme then you may have a b12 deficiency despite high circulating blood b12 levels. You should always consult a knowledgeable doctor before supplementing but if you ARE going to supplement with b12 you should definitely do so with the methylcobalamin version.

Try mthfr.net really good resource I'm sure you can get your answer there

Yes sometimes low lithium levels is an issue but often times it is not. I have had plenty of clients with high blood B12 levels ( low absorption) AND sufficient lithium levels - I recommend Hair Metal Analysis testing as a good way to find out your lithium levels and see if this is a contributing factor. If you enter genetic info into Amy Yasko software it will tell you the best form of B12 to take for your specific genetics - everyone absorbs differently. Methyl form is most widely absorbed however older people and some genetic SNP's only do well with hydroxy and adeno.

Methylcobalamin is the most bioavailable form because it requires requires little to no conversion. It's readily available for your body to utilize. Some can not tolerate MB12 well and switch to HydroxyB12 which seems to be somewhat smoother for those people. My son can not tolerate Mb12 and uses HB12 with great results but MB12 is what I use because I can't tolerate HB12. Different strokes for different folks. But the above comment suggesting lithium orotate is an excellent suggestion. Also if you supplement with folic acid be sure and use the bioavailable form 5MTHF or you could be in the same situation and have all this folic acid lingering in your body but if your body can't metabolize and use it.