LindsayI know, I know. I’m like the billionth person to make a pun between mthfr, the curse word, and the MTHFR genetic mutation. But as a lover of 1990’s gangsta rap, I have to. All those mthfrs would be disappointed if I didn’t. So, in the words of Notorious BIG, come on, mthfr, come on. Let’s go.
As an advanced warning, there’s a lot to say about MTHFR, and even more about my genetic shitshow, so I’m barely cracking the mthfr-ing surface here about MTHFR. I will provide links to resources for more information at the bottom. Because in the words of Dr. Dre, I’m robbin like a mthfr. But I ain’t lynchin.
If you are not familiar with MTHFR (it’s all the mthfr-ing rage right now), MTHFR is a gene that contains the instructions for making the
methylenetetrahydrofolate reductase enzyme. That’s a big mthfr-ing mouthful, and thus it was shortened to MTHFR.
The methylenetetrahydrofolate reductase enzyme is necessary for methylation – a metabolic functions that repairs DNA and switches genes on and off. It is also involved in a process that allows your body to use folate (vitamin B9), and converts homocysteine, an amino acid, to methionine, another amino acid which produces certain molecules necessary for normal cell function. There are at least 40 MTHFR variations, but you primarily hear about two SNPs – A1298C and C677T. Individuals who have mutations in the A1298C or C677T variants (more so in the C677T) may have difficulty converting folate into a form your body can process. Simply having the mutation doesn’t automatically result in issues. In fact, most of us have at least one mutation.
There’s a mthfr-ing point to all this MTHFR rambling. At my neurologist appointment a few weeks ago where I was diagnosed with small fiber neuropathy, the doctor ran a bunch of blood tests to eliminate other potential causes, such as an autoimmune panel, vitamin B6 test (toxicity can cause SFN), and vitamin B12 (a deficiency can cause SFN). Those were all normal. However, we also tested my folate, which came back high. Super high. Over twice the top of the normal reference range. My doctor said folate is tested to look for a deficiency and that there isn’t any concern for high folate. After all, folate is a water soluble vitamin.
I wasn’t convinced that high folate had no significance, however, especially when it’s that high. I don’t know that it has anything to do with neuropathy, but I think it means something. So I started researching high folate. There isn’t much out there, and most of what there is, agrees with my neurologist that high folate isn’t a concern.
But eventually I came across an article that mentioned high folate can mask a vitamin B12 deficiency. This seems to be especially true in those with the MTHFR mutation. As I mentioned above, a vitamin B12 deficiency CAN cause neuropathy. I had the 23andme test run many years ago and still have my raw data. I checked for mutations, and I have a heterozygous A1298C mutation. But my vitamin B12 level was normal – right smack in the middle of the range. So my high folate isn’t masking the symptoms of a B12 deficiency.
But as I researched more, I found out that sometimes B12 tests can produce a false normal result. When a B12 deficiency is present, homocysteine (the amino acid mentioned above) builds up in the blood. A high homocysteine level can suggest a B12 deficiency. Methylmalonic acid (MMA) can also be tested to discover a vitamin B12 deficiency. While homocysteine blood tests are fairly common, MMA tests are rarely ordered by doctors. In the interest of saving time, I ordered both tests myself from Walk in Lab and paid out of pocket.
Both came back normal. Which suggests my vitamin B12 level is normal, and a deficiency isn’t responsible for my neuropathy.
So I continued to research high folate. There’s a difference between folate and folic acid – folate is naturally found in leafy greens, edamame, lentils, and asparagus, among other foods, whereas folic acid is a synthetic form of folate that is added to cereals, breads, and other foods. It was discovered that a folate deficiency can lead to neural tube and other newborn complications. Thus, the United States implemented a mandatory folic acid enrichment program in 1996 which required the addition of folic acid to flour.
Folic acid, the synthetic form, is generally thought to be safe. However, those with a MTHFR mutation, especially the C677T variant, do not tolerate folic acid well. Those individuals may be unable to convert folic acid into 5-MTHF, the active form of folate, and it can accumulate and become hazardous.
Current blood tests do not differentiate between natural folate and synthetic folic acid. So I’m not sure if my elevated folate blood test is actually caused by high folate, or if folic acid is building up in my blood because I can’t process it, which could mean I actually have low usable folate. I don’t have the C677T variant, but I also think my high folate results need to be investigated further.
Next step is to try and get micronutrient testing. More on that mthfr next time.
If you have an MTHFR mutation, talk to your doctor about whether you need to supplement with methyl-folate and methyl-cobalamin (methyl-B12).
“yo weekly, monthly and yearly
until them dumb mthfr see clearly
that I’m down with the capital C-P-T
boy you can’t f**k with me . – NWA
Smell ya later.
– Linds
Resources:
Ben Lynch is like the mthfr-ing MTHFR guru. I’m currently reading his book, but would also suggest his website for more info –
http://mthfr.net/
Dr. Lynch also gives a very thorough explanation of Folic Acid and MTHFR on YouTube –
https://www.youtube.com/watch?v=cWFPRI6X7P4
What is a MTHFR mutation – Wellness Mama website –
https://wellnessmama.com/27148/mthfr-mutation/
MTHFR: What the bleep is it? – Aviva Romm, MD –
https://avivaromm.com/mthfr-what-the-bleep/
The hazards of excessive folic acid intake in MTHFR gene mutation carriers: An obstetric and gynecological perspective –
https://www.oatext.com/the-hazards-of-excessive-folic-acid-intake-in-mthfr-gene-mutation-carriers-an-obstetric-and-gynecological-perspective.php
You certainly went through a lot trying to figure out the high folate conundrum. Where b12 is involved (I have pernicious anaemia) it can be complicated, and you’re right about false negatives and folate masking b12 deficiency etc, so I think it’s good you armed yourself with information and got further tests. Just a shame there’s no easier way to differentiate the folate, like whether it’s because of high folate itself or a folic acid build-up because you’re not processing it. Let us know how you get on with micronutrient testing, I’ll keep my fingers crossed, Linds.
And I think you did a mthfr-ing good job with this post, it helps raise awareness of a mthfr of a condition that many don’t know about.
Caz xx
Hi Caz, I didn’t know you have pernicious anaemia. Do you have to take vitamin B12 supplements? If so, do you do pills or the shots?
P.S. I love when people continue my mthfr-ing jokes. So thanks for that 🙂
What a journey! I have low B12, low folate, high homocysteine (all of these are since MECFS onset). I know right!? All the luckiness coming my mthfr way 😉 Hoping you get to the bottom of it. I supplement with a sublingual methyl B12 and am awaiting labs to potentially start a methyl folate as well. Hoping your neuropathy is any bit better? I’m so behind here in blog world. :/
Yikes – low B12 and folate, and high homocysteine is a lot to deal with! Have you been tested for MTHFR or other genetic mutations? I recently started taking a B12 sublingual and am hoping that makes a difference!
I just happened to check here and saw you replied. For some reason I’m not notified. So my apologies if you’ve answered before I seemed rude by not answering!! Yes, I have several genetic mutations. I ran my raw data from Ancestry.Com through Genetic Genie (it’s free) and it shows you all your mutations with relation to a certain part of your genes. A homeopath had also told me I had MTHFR so I knew. Hoping the B12 helps you!! My previous rheumatologist said your levels should be in the 900s with the supplement, still struggling to get mine up there, but atleast they are better than they were with no supplementation.
How very interesting as my folate libels are always super high in blood tests too. I now take methyl b12 which has lifted my b12 from low normal to mid normal. I took folic acid in my pregnancies as advised for all pregnant women these days and after my second pregnancy, when things slowly began going downhill for me health wise, was when my folate levels were extremely high on my blood test. I don’t eat the fortified cereal or bread now and I’ve purchased methylfolate to take but it makes me feel yuck and there’s an art to taking it which I haven’t worked out as it all sounds so complex. I’m fine with the methyl b12 though. I hope you can work it out better than I have and getbon top of your high folate. Mine has come down some by avoiding synthetic folic acid. I feel like this could be where our problems all began sometimes!