VERY simply stated, methylation is a process that happens in all cells of the body so that you’re able to make the chemicals you need to function. It is tightly linked to folate metabolism and requires vitamin B12.

What exactly needs methylation reactions? The short list would include cellular repair, detoxification, neurotransmitter production, proper immune system function, and specifically important in my case, inactivating histamine. Those are some important functions, indeed.

MTHFR stands for methyl-tetrahydrofolate reductase which is the enzyme which is responsible for methylation; there are several genetic variants which result in suboptimal methylation. I have one copy of C677T gene for MTHFR.

What problems that may be associated with MTHFR variants? Pull up a chair because there are many. Everything from chronic fatigue syndrome to depression.

Methotrexate is a folate antagonist. Given I have difficulty methylating and thereby converting to active folate, purposely taking a folate antagonist would just make my situation worse. This is the reason my functional medicine MD warned me against taking Methotrexate when she learned that this is the course of action my rheumatologist had advised to address the RA.

When I read the below email the day I was released from Kobe General Hospital after my unplanned-stay,

  • I just happened to come across today…. Carbamazepine in a folate antagonist. We know that you have issues with methylation based on testing that you are positive for one copy of abnormal C677T gene for MTHFR. For that reason you will have more trouble methylating and converting to active folate (about 60% of activity of a normal person). When patients are undermethylating, they will produce more histamine = rash, anaphylaxis, etc… This means that the carbamazepine could potentially be a key in your increase in histamine reactions.

which I have already quoted in a previous post, I thought several things:

• My anaphylaxis relating to Carbamazepine is likely due to the fact it is a folate antagonist. Wow, I wish I would’ve known this before we left. 🙂

• Looking at a list of drugs that should be avoided by people with MTHFR issues, I see medications that I have had anaphylaxis/allergic reactions to all through my life.

• I think of my rheumatologist trying to talk me into beginning Methotrexate BEFORE we went to Japan fall 2012 with the understanding that the anaphylaxis that occurred with Carbamazepine probably would have happened with Methotrexate, as well. (I don’t plan on doing that experiment to find out, however.)

Several weeks later my MD sent me the following video presentation by Benjamin Lynch, ND of www.MTHFR.Net

This is heavy on the biochemistry, so if you’re a geek like me, you’ll love it. Otherwise, skip it. Instead you may consider an impressive pictorial representation of methylation. You can find MTHFR in a blue box on the left-hand side of the center cog which represents the folate cycle. You may imagine that if that center cog is “broken” due to faulty copies of MTHFR, the cogs on either side are not going to work very well either.

Let’s just stop to consider that it is NOT standard protocol for traditional medicine doctors to test people for MTHFR variants BEFORE putting them on medication, which if folate antagonists, may make them worse or land them in the hospital with anaphylaxis.

My rheumatologist never mentioned this issue. I didn’t even know about this issue until I saw a functional medicine MD. Carbamazepine’s addition to the “drugs to avoid” list came across my MDs desk the day I was released from the hospital

Extra credit:
What’s the big deal?

According to Benjamin Lynch, ND of , these are the drugs to avoid if you have an MTHFR mutation:
Antacids (deplete B12)
Cholestyramine (deplete cobalamin and folate absorption) – common in gallbladder issues during pregnancy!
Colestipol (decrease cobalamin and folate absorption)
Methotrexate (inhibits DHFR)
Nitrous Oxide (inactivates MS)
Niacin (depletes SAMe and limits pyridoxal kinase = active B6) useful during times of over-methylation
Theophylline (limits pyridoxal kinase = active B6)
Cyclosporin A (decreases renal function and increases Hcy) Metformin (decreases cobalamin absorption)
Phenytoin (folate antagonist)
Carbamazepine (folate antagonist)
Oral Contraceptives (deplete folate)
Antimalarials JPC-2056, Pyrimethamine, Proguanil (inhibits DHFR)
Antibiotic Trimethoprim (inhibits DHFR)
Bactrim (inhibits DHFR)
Sulfasalazine (inhibits DHFR)
Triamterene (inhibits DHFR)

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