MTRR and Vitamin B12 Impact Your Homocysteine

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Over the last few years, there has been exploding information about epigenetics, SNPs, and methylation defects associated with the enzyme called “MTHFR.”  But there are other kids on the block you know, it’s not just all about methylation. There is another gene similar to MTHFR and it is abbreviated MTRR. The official name of this gene is 5-methyltetrahydrofolate-homocysteine methyltransferase reductase. I prefer MTRR, don’t you?

The MTRR gene provides the blue-print instructions to make an enzyme called methionine synthase reductase. The methionine synthase reductase enzyme tells another enzyme, methionine synthase what to do. Methionine synthase helps convert one amino acid into another. It converts the amino acid homocysteine into methionine. This pathway is termed the “transmethylation” pathway.

If there is a stall here, homocysteine builds up. Some of you have high homocysteine due to an MTRR gene SNP, and you’re not converting it into methionine. Here’s a screenshot of my friend’s SNPs for the MTRR gene, and you can see how some of them are heterozygous (+/-) indicating a potential problem but not severe because none of them are homozygous (+/+).


Homocysteine can be a neurotoxin and we already know it’s a risk factor for cardiovascular disease.

So MTRR turns on the first enzyme, which then turns on the second enzyme, when then converts homocysteine into something user friendly in the body, i.e. methionine. This MTRR gene activity and enzyme sequences turns on and off as the body needs but stalls out when vitamin B12 is depleted.

When MTRR is mutated, the body develops a problem and may accumulate homocysteine and become deficient in methionine. The SNP doesn’t cause this in everyone. It has to become activated so having the SNP doesn’t mean you have high homocysteine. If the gene SNP is turned on during pregnancy however, it can substantially increase the risk for a child to be born with Down’s syndrome or neural tube defects. That was shown in a “case control” study published in September 2014 of Molecular Biology Reports. The risk of having a child born with Down’s syndrome becomes even higher if you have a methylation SNP to go with that MTRR snp. Genetic testing easily uncovers these SNPs.

Now if you have been paying attention, some of this may sound a little familiar with MTHFR and homocysteine elevations. MTHFR is generally tied to reductions in natural folate, whereas MTRR is generally associated with vitamin B12 deficiency, but it isn’t black and white. Both of these genes require both vitamin B12 and folate or there are cramps in the pathway.  This explains why taking one or the other doesn’t always work.

Just like if you have a problem with MTHFR and inadequate natural folate, problems occur when inadequate natural or coenzyme vitamin B12 exists. Now, to be sure you realize, the forms of B12 commonly sold as “Cyanocobalamin” are synthetic forms of natural B12. Your body must convert that to “methylcobalamin, and then to “hydroxy” or “adenosyl” forms in order to fully use the B12. Cyanocobalamin is unfortunately found in most oral supplements, most prescribed B12 shots, and all fortified foods. If you are going to take B12, I urge you to pay a little more to buy the biologically activated forms of vitamin B12 like methylcobalamin, or  adenosycobalamin, or hydroxycobalamin which are harder to find. But the point is, natural B12 (and natural folate) may help you effectively deal with MTRR speed bumps if you have those.

Medications that deplete vitamin B12 are MTRR gene busters. Refer to my Drug Muggers book for the complete list. In the meantime, here are main categories of drug muggers which drain B12 from you. This will enhance a gene SNP in the MTRR pathway:

* Antacids and Acid blockers
* Corticosteroids (inhalers, oral, and topical)
* Multiple types of oral-dosed antibiotics (aminoglycosides, sulfa drugs, cephalosporins, macrolides, penicillin derivatives, quinolones and tetracycline derivatives)
* Anti-convulsant medications
* Metformin
* Oral contraceptives
* Potassium chloride
* Cholesterol lowering medications (bile acid sequestrants)
* Gout medications

MTRR gene speed bumps and compromised vitamin B12 status are linked with some serious disorders. Research shows links with Down’s Syndrome, acute childhood leukemia, pancreatic cancer, Crohn’s disease, congenital heart defects and more.

Now if you thinking what I am, how about identifying the gene defect risk, avoid the drug muggers (switch medication if possible), or at least restore the pathway with natural B12 supplements and consume it in natural foods found in animal foods, meat, fish, dairy, and eggs. If you are vegetarian and trying to conceive, you must work at this before getting pregnant. Cyanocobalamin will not do the trick.
If simple dietary nutrients like coenzyme B12 and folate can stop these genes from turning on and triggering disorders, it may stop a lifetime of illness and struggle.  Is it all about your genes? Heavens no, there are dozens of other factors involved so please compare the symptoms and clinical presentation and see if it matches up. Remember, having a gene SNP doesn’t mean you have a disease, in fact, most of the time a gene SNP does not cause the disease. You have to look at the entire puzzle, not just one piece of the puzzle. Feel free to leave me comments below.