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I know that the question was not directed at me but I have MTRR x4. Plus MTHFR C677T and TCN2. I have an idea that these do not play nicely together.

Do you have the mtrr mutation?

I only have 2 comments: methylcobalamin needs to be sublingual as gut does not absorb i think. i love pure encapsulations brand; lasts a long time. 2. i take lithium as one poster already mentioned but now it is throwing my thyroid off and 3. i would search phoenixrising.me frre forums. they are excellent geneticists. too hi mma is not good.

I needed to change multivitamins - I went to Pure Encapsulation Multivitamin - because the other one was not absorbing and was actually making me sick

I had high levels of B12 and signs of deficiency. I was taking cyanocobalamin and folic acid and yet my homocysteine was high. This is the place where a better Dr would have realized that there was something wrong with methylation, as opposed to my Dr who had never heard of it before.
I have TCN2++ and a harder time getting B12 into the cells and then MTHFR C677T++ so that methyl groups are less available and then MTRR++ x 4 that makes attachment of methyl to B12 (to drive the methylation pathway) less likely to occur. I take 2 needles a day and feel much better. My blood level is not measurable. I avoid folic acid, taking methylfolate instead.

There are different forms of b12. I have issues with elevated methylcobalamom but noticed it was helpful to supplement adenosylcobalamom. If you get headaches from too much b12 take a niacin supplement to mop it up. The headache and weird sickly feeling resolves quickly. My theory is that the body doesn't readily convert b12 into the needed forms and the wrong type builds up.

Supplement lithium orotate to be able to utilize the B12 in your blood.

Hi, I haven't read any other responses, so apologies in advance if I'm just repeating what others have said. I am homozygous for this FUT gene, AND have extremely high levels of both B12 and Folate. My understanding is that this is because I also have the MTHFR mutation, so I can't activate either folate or B12 (MTHFR enzyme takes a methyl group from folate and gives it to B12 and this activates both). As a consequence, my RBC folate and total B12 levels are extremely high (3 to 4X the upper limit). However, when I eventually got my active b12 (holotranscobalamin) tested, it was only just within normal limits (i.e. on the lower end). I take both methyl-B12 and active Folate (5-MTHF), but I'd recommend you either read Amy Yasko's book on nutrigenomics and methylation, or see a Dr who is familiar with this work. I'm lucky that I did as it has helped me a lot, as well as changed my career direction - I'm back at uni studying to become a dietitian with an interest in nutrigenomics. Good luck!

@JR2160: A lot of good info :-) However, it is my impression that before a person implements for an example amino acids and methyl-donors like methyl-folate/5-MTHF and methyl-B12 as a part of her/his supplement regime, it might be a good idea for that person to check out the various SNPs related to the entire methyl cycle (COMT, CBS, MTRR, SUOX etc.) For an example being MTHFR C677T +/+ doesn't automatically lead to an increased level of homocysteine. I'm MTHFR C677T +/+ and my homocysteine is too low; probably due to a combination of my unique set of SNPs, my lifestyle, load of toxins etc. Also some people have a hard time processing sulfate, which means they - at least for a while - need to avoid or at least limit the intake of sulfate-rich foods and supplements such as red meats, eggs, N-AcetylCysteine, milk thistle etc.

What I mean is... a person s individual intake of supplements and diet must be exactly... individual. The more I - as a layperson - learn about nutrigenomics, the more I understand, how individual our needs are. Or as the Lucretius saying goes: One Man s Poison Is Another Man s Cure (or something like that)

Best ... More

@JR2160: A lot of good info :-) However, it is my impression that before a person implements for an example amino acids and methyl-donors like methyl-folate/5-MTHF and methyl-B12 as a part of her/his supplement regime, it might be a good idea for that person to check out the various SNPs related to the entire methyl cycle (COMT, CBS, MTRR, SUOX etc.) For an example being MTHFR C677T +/+ doesn't automatically lead to an increased level of homocysteine. I'm MTHFR C677T +/+ and my homocysteine is too low; probably due to a combination of my unique set of SNPs, my lifestyle, load of toxins etc. Also some people have a hard time processing sulfate, which means they - at least for a while - need to avoid or at least limit the intake of sulfate-rich foods and supplements such as red meats, eggs, N-AcetylCysteine, milk thistle etc.

What I mean is... a person s individual intake of supplements and diet must be exactly... individual. The more I - as a layperson - learn about nutrigenomics, the more I understand, how individual our needs are. Or as the Lucretius saying goes: One Man s Poison Is Another Man s Cure (or something like that)

Best,
Susanne :-) Less

I didn't bother to get it tested either, apparently the methylcobalamin will help to reduce the elevated serum levels. Do you know if you have the MTHFR variation. If so here are 10 tips I found:

1. Avoid taking folic acid blocking or depleting drugs, such as birth control pills or Methyltrexate
2. Avoid taking proton pump inhibitors, like Prilosec or Prevacid or antacids, like Tums, which may block essential Vitamin B12 absorption
3. Have your homocysteine measured, which if elevated may indicate a problem with methylation or a deficiency of B12 or folate. If your homocysteine is elevated, limit your intake of methionine-rich foods
4. Avoid eating processed foods, many of which have added synthetic folic acid. Instead eat whole foods with no added chemicals or preservatives.
5. Get your daily intake of leafy greens, like spinach, kale, Swiss chard or arugula, which are loaded with natural levels of folate that your body can more easily process.
6. Eat hormone-free, grass-fed beef, organic pastured butter or ghee, and eggs from free-range, non-GMO fed chickens.
7. Remove any mercury amalgams with a trained biologic dentist. Avoid aluminium exposure in antiperspirants or cookware. Avoiding heavy metal or other toxic exposure ... More

I didn't bother to get it tested either, apparently the methylcobalamin will help to reduce the elevated serum levels. Do you know if you have the MTHFR variation. If so here are 10 tips I found:

1. Avoid taking folic acid blocking or depleting drugs, such as birth control pills or Methyltrexate
2. Avoid taking proton pump inhibitors, like Prilosec or Prevacid or antacids, like Tums, which may block essential Vitamin B12 absorption
3. Have your homocysteine measured, which if elevated may indicate a problem with methylation or a deficiency of B12 or folate. If your homocysteine is elevated, limit your intake of methionine-rich foods
4. Avoid eating processed foods, many of which have added synthetic folic acid. Instead eat whole foods with no added chemicals or preservatives.
5. Get your daily intake of leafy greens, like spinach, kale, Swiss chard or arugula, which are loaded with natural levels of folate that your body can more easily process.
6. Eat hormone-free, grass-fed beef, organic pastured butter or ghee, and eggs from free-range, non-GMO fed chickens.
7. Remove any mercury amalgams with a trained biologic dentist. Avoid aluminium exposure in antiperspirants or cookware. Avoiding heavy metal or other toxic exposure is important.
8. Make sure you supplementing with essential nutrients, like methyl-B12, methyl-folate, TMG, N-acetylcysteine, riboflavin, curcumin, fish oil, Vitamins C, D, E, and probiotics. If you are double homozygous for MTHFR mutations, you should proceed very cautiously with methyl-B12 and methyl-folate supplementation as some people do not tolerate high doses. Introduce nutrients one by one and watching for any adverse reactions. Use extreme caution when supplementing with niacin, which can dampen methylation.
9. Make time for gentle detox regimens several times per week. These could include infrared sauna, epsom salt baths, dry skin brushing, and regular exercise or sweating.
10. If you have a known genetic mutation, share the information with parents, children and other family members and encourage them to be tested, too! The easiest way is to order through 23andMe online ( 125).
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@NI1578 : That's really interesting. I haven't spoken to my naturopath yet, but from what you and others at this thread now are saying, I think I will ask for a MMA test next time I see her. Thanks so much for sharing :-)

@Susanne Stender - I just saw my naturopathic doctor and she was satisfied with my MMA test - she said I did not need to take the Spectracell test and I was not B12 deficient at a cellular level. It could be the high serum levels are from years of supplementing with non-active forms of B12 but the methylcobalamin that I have been using seems to be working.

@JR2160 and @US2699: Highly appreciate your inputs. Thanks :-)

Btw @JR2160: May I ask, from where have you got the info about high copper levels related to MTHFR mutations? I have had Chronic Fatigue Syndrome for many years, and it wasn't until last year I found out that I am suffering from a bad case of copper toxicity; probably the main reason behind my CFS. Also I am MTHFR 677 +/+, so your info really intrigues me...

Hello, I also have very high b12 levels and am now supplementing with methylfolate and methylcobalamin. Here is some of my findings:

Serum B12 is often not a good test for the B12 levels that you are actually able to utilize. You can have high serum B12 and actually be deficient.
High B12 serum levels can mean that you are absorbing b12 through the gut wall, but cannot then utilize it due to a defect in your methylation pathway.
The only two B12 test that are useful are urinary MMA (methylmelonic acid) test (for aB12) and homocysteine (for mB12, P5P, mfolate). The serum B12 test shows active and inactive B12 all lumped together. If you can't use inactive B12 it will accumulate in the blood and will be there a long time.
Methionine is an essential amino acid obtained from protein in the diet. Some methionine is turned into homocysteine. The body turns much of this homocysteine back into methionine with the help of vitamin B12. If someone is B12-deficient, homocysteine levels will increase because this reaction cannot take place. Keeping homocysteine at levels associated with lower rates of disease requires both adequate B12 and folate. Low vitamin B6 ... More

Hello, I also have very high b12 levels and am now supplementing with methylfolate and methylcobalamin. Here is some of my findings:

Serum B12 is often not a good test for the B12 levels that you are actually able to utilize. You can have high serum B12 and actually be deficient.
High B12 serum levels can mean that you are absorbing b12 through the gut wall, but cannot then utilize it due to a defect in your methylation pathway.
The only two B12 test that are useful are urinary MMA (methylmelonic acid) test (for aB12) and homocysteine (for mB12, P5P, mfolate). The serum B12 test shows active and inactive B12 all lumped together. If you can't use inactive B12 it will accumulate in the blood and will be there a long time.
Methionine is an essential amino acid obtained from protein in the diet. Some methionine is turned into homocysteine. The body turns much of this homocysteine back into methionine with the help of vitamin B12. If someone is B12-deficient, homocysteine levels will increase because this reaction cannot take place. Keeping homocysteine at levels associated with lower rates of disease requires both adequate B12 and folate. Low vitamin B6 status can also cause elevated homocysteine in some people.
High homocysteine levels are associated with high cholesterol.
If you have high levels of folate or b12, but signs of deficiencies then look for gene mutations MTHFR 1298AC & MTHFR 677T
It is estimated that 40%-60% of the population have a MTHFR defective gene.
People with an MTHFR variation have issues converting folic acid into the form necessary - L-methylfolate - for it to be active in the methylation cycle. This results in a slowing down of methylation, which affects neurotransmitters and the body s ability to detoxify. The methyl cycle is the backbone of our physiology. Methyl Cycle abnormalities explain why you are sick from environmental toxins while the guy next door is just fine.
A common finding, when you have an MTHFR defect, is a high levels of copper, which will conversely mean your zinc levels will fall. And since the ratio of these two metals is highly important, correcting the problem is crucial.
People with MTR & MTRR variation have problems with methylation and recycling of B12.
Those with the genotype rs4654748 are more likely to have reduced levels of B6. I test positive for this on deeper analysis using translated results from the website livwello.


What is the difference between the 677 and 1298 gene mutation?

Mutation 677 This mutation is most commonly associated with heart disease, heart attack, stroke, blood clots, peripheral neuropathy, anaemia, miscarriages, congenital birth defects, and more.

Mutation 1298 This mutation is most commonly associated with chronic illnesses, such as; depression, fibromyalgia, chronic fatigue syndrome, migraines, IBS (Irritable Bowel Syndrome), Memory loss, Alzheimer's and Dementia, OCD, Bipolar, Schizophrenia, and more.
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There are three natural B 12's,Hydroxycobalamin,methylcobalamin,and Adenosyl cobalamin.And there is a synthetic form,Cyanocobalamin,that has the cobalamin attached to a cyano group and must be modified in the body prior to its use.When you test for B12,you do not know the distribution of the figure among all kinds of B12.The metabolism of cobalamyns is fairly complicated.Chances are you're not converting B 12 to its active form well, thus it accumulates.Methyl B12 is an assential cofactor in the Methionine syntase reaction to recycle homocysteine into methionine,thus Methyl B12 sustains Methylation reactions,key for more than 200 reactions of methylation,for instance,making carnitine,creatine,Phopholipids,Biliary acids,recycling Bh4...Adenosylcobalamin is for mitocondrial energy.Depending on your health condition,I would supplement methyl or Adenosyl,or Hydroxi if you have a great oxidative stress.
If in doubt,check out the genes that codify for B12 metabolism enzymes.it is also useful to check your folate status and VCM in blood sample.If VCM is high,then you have B12/folate deficiency regardless of the numbers,and please do not supplement with Cyano anyway.Good luck

J Ramos.Physician

Thanks, @UK1203 :-)

However, it looks like the company only provides services for American citizens. Does anyone know, if any European labs offer the same kind of test (I'm from Denmark)?

Thanks, @@UK1203 - My doctor refuses to dig deeper into the B12 issue. Her response to my high B12 level was "take less." I had to order the MMA test on my own through an independent blood testing lab. I'm finally seeing a different doctor next week so will bring this up. Thanks!

Spectracell Labs offers blood testing for intracellular levels of many nutrients. It must be ordered through a doctor or chiropractor.

@@NI1578: okay, I see what you mean. I think I'll ask my fortunately highly talented naturopath what she knows about the subject next time I see her. if she has a suggestion, I'll make sure to post it on this thread :-)

@Susanne - one caveat: it's possible my MMA was normal because I took the test a month or so after I started supplementing with methylcobalamin. So it may still be a good measure. I just wasn't sure where it left me in figuring out whether or how much to supplement with methycobalamin.