Sunday, November 3, 2013

A bad MTHFR (shut yo' mouth!) -- all about a common genetic mutation that you might have, and probably would like to know about

This post has two parts:
1. The "Funny" Part
2. The Informative Part

You can skip down to The Informative Part without any issue at all and still learn something that might save your life. You may laugh more, however, if you start at the beginning with Part 1.

Or not.

Part 1.

The usual pre-class chatter was taking place in the genetics lab that morning when the aged, learned, very-British professor hobbled into class quietly, walked to the front of the lab, and started banging his cane on the table to get all of our attention. The students, from the very-smart people in the front to the table in the back where my lab partner John and I sat -- often confused, always amused -- immediately hushed up.

(In a very-British accent) "TOO. MANY. FRUIT FLIES. ARE. EEE-SCAPING!!" the professor bellowed. He smacked his cane down on the table a couple more times for effect.

The entire class turned around and looked at me and John.

"What?" he and I jointly exclaimed silently via shrugged shoulders and the sort of utterly unconvincing facial expression that makes the pronouncement that one, really, Has. No. Idea. what you could possibly mean by such an accusation, and possibly even adds a "You bad, assuming maker-of-assumptions, you" to the gesture.

John and I were biology majors. I don't know why. I wasn't a very good one. (To get some idea, I am a lawyer now, and although we don't talk about that here (ever!), let's just say that the laws of biology are not part of my practice). I don't think John was very good at it either, because, although I have lost track of him, I know that his chosen career path -- while shockingly straightlaced and law-abiding after our college years -- also was not ultimately in the sciences.

We also had no time for the sort of annoying pre-med majors that seemed to dominate that particular biology department's student body, and who seemed to have the next thirty years of their lives plotted out on logarithmic paper with pie charts, slides, diagrams and what a famous folk singer would call "eight-by-ten colour glossy pictures with circles and arrows and a paragraph on the back of each one" explaining their significance.

So, our genetics-lab m.o. was pretty simple. We would do the same stupid assignments full of stupid experiments involving stupid fruit-fly copulation (and, obviously, did so while missing a still-not-recovered thesaurus) as the rest of You People, but -- much like in freshman-year general-bio lab when John and I removed all the intestines from our fetal pig and from the fetal pigs of the other two teams at our lab table and stuffed them all inside our friend Karen's pig across the class, just to, ya know, be funny, and which was *really* funny when Karen started throwing the "extras" at us across the room -- we felt that we needed to lighten up the stuffiness of the situation a bit.

When you place fruit flies in a glass jar full of "medium" (not a paranormal thing... it's a food thing, I think), you don't need to set up a dating service, play Barry White, or even ply the little fellows with intoxicants in order to get them in the mood for lovin'. Fruit flies don't wear T-shirts that say, "Beer: getting ugly people laid since forever." They don't take medications that lead to disabling four-hour erections. And they don't pretend to like that new Arcade Fire album just to impress the leggy blonde across the glass jar. They just mate their little fruit-fly bootays right off as soon as you let 'em at each other. Then they lay their (little) fruit-fly eggs, and the eggs hatch, causing the burgeoning scientists to "log" the results -- you know, like: "Two wingless green-eyed flies mated and their offspring were 72% wingless/green-eyed, 24% winged/green-eyed, and 4% awesome [or something]." Then comes the boring part. Or the let's-feign-moral-outrage-and-get-all-animal-rightsy-even-though-they-aren't-technically-animals part....

You kill them when you're done.

The ensuing slaughter isn't a complicated process. You just gas the flies with lots of extra ether to kill them -- instead of the smaller dose that you use to knock them out before placing them together for motorbooty action.

This is where John and I took The Path Less Traveled.

What we learned was this: by simply employing the smaller knockout dose of ether to the flies, instead of killing them, one could place the little buggers almost anywhere before they awoke. "Almost anywhere" amounted to the lab-table desk drawers of our more-annoying/humor-challenged classmates. So, each morning Kip R. DoRight and his future wife, Mrs. Do-Right-to-be (both of whom are now successful doctors, so, yeah, who actually "won", you might ask? A fair question), would come into class, say something snuggly-wuggly (and altogether nauseating) to each other, open their lab-desk drawers to place something inside (undoubtedly the aforementioned logarithmic life-plan graphs with photos) and, as they did so, what appeared to be some significant percentage of All the Fruit Flies in the Universe would fly out of the drawer.

The flies went everywhere. They were seen in places in the biology department over the next few months where no fruit fly had previously ever dared wander.

It probably was not a nice thing to do. I probably, if given time to absorb what a jerk I sound like for even recounting this story, ought to be ashamed of myself. But really, given the stuffiness of the rest of the situation (and by "the situation," I mean everything about being a biology major in that school at that time), it was a veritable laugh riot to see the ensuing chaos.

I could tell you other stories, but they would only reinforce the point that I have now taken many paragraphs to reach: I didn't learn very much in genetics that year, which was many (over 30) years ago. My burning desire to understand, as best I could, some recent lab results made me have to make up for that deficiency fairly quickly.

Part 2.

The Introduction

So... when I recently went to a paleo doc, got some bloodwork done and it came back with "two heterozygous mutations on the MTHFR gene," my first, fully-informed, reaction was: (1) "heterozygous... OK, excellent; these genes can get married even in backwards states," and (2) "the MOTHERFUCKER gene!?!?!.... (drummer guy makes fake 1970s wah-wah-pedal guitar sound and employs Isaac Hayes voice) ... I'm just talkin' bout Shaft!"

Not all that "informed" of a reaction, actually. So I went to Dr. Google.

(A side note on Dr. Google. He will tell you almost anything about anything, providing often-contradictory advice leading the average hypochondriacal drummer to believe he is dying TODAY!!! I'm not saying this happened -- of course not -- but be careful of that, hmmm?)

What I had learned from my doc was that, in shorthand, the mutations meant that I should take a methyl-folate supplement, but my Google research led to me to believe there were even a few additional points to consider. So, put on yer science goggles (I have an extra-thick pair to make up for college behavior) and let's learn something.

Basic Genetic Hoo-Hah

I don't want to go very deep with the science-y explanations, but a little bit of basic genetics is important to understand here in order to "get" what comes thereafter -- including understanding some of the terminolgy used in the links I provide)....

Each time there is "genetic stuff" to think about, we are talking about getting half of said stuff from mom and half from dad. My research, and a little help from a reader, tells me that the two mutations that I have on the MTHFR gene -- C667T and A1298C -- are specific mutations (Cysteine to Threonine at amino acid 667 and Alanine to Cysteine at amino acid 1298) within the protein produced from the gene.

At the C667 location on the gene. a "normal" person would get a C from both parents, resulting in a C/C designation. A "heterozygous" mutation means you got a C from one parent and T from the other (a C/T, aka what I have). A "homozygous" mutation would be a T/T -- a T from each parent. Easy and simple to understand, right?

Likewise, at the A1298 locus, a "normal" person would be A/A, a heterozygous mutation (me! again!) would be A/C, and a homozygous mutation would be C/C. Again... Easy to understand, right?

So, to recap the basics, any person could be normal for both genes, mutant for both, or mutant for one or the other. And within the individual mutations, those could be heterozygous or homozygous at either of the loci (plural of locus... really, not just Steve Latin). Because I have a heterozygous mutation at both loci, my mutations are so-called "compound heterozygous."

MTHFR mutations

Hope I haven't lost you yet, because that is just the entry-level terminology. Let's jump to The Almost Really Important Part:

MTHFR mutations are present in a lot of the population. The lab that did my bloodwork tells me that the estimated frequency of mutations at the C677 locus is: 39.8% of people have the heterozygous C/T mutation and 10.9% have the homozygous T/T. At the A1298 locus, 30% of people have the heterozygous A/C mutation and between 7 and 12% are homozygous C/C mutants.

What that means is that there is a slightly better than one in two chance that you have the mutation at C677 and just under that same chance of a A1298 mutation.

Here's the Really Important Part: what it all means to your health.

The shortcut for the Really Important Part: read this.
It's written by a doc, tells you a lot of info, and, really, isn't funny at all.
But the (allegedly) funny part of my post was many paragraphs ago, so you may do better with hers.

However, I will try to give you my own synopsis:

Either one of these mutations means that you do not process B vitamins, particularly folic acid (synthetic folate), properly. In fact, if you eat foods enriched with folic acid -- and go look at almost anything grainy in a package and it has folic acid in there; so does almost every multivitamin out there -- you are quite possibly messing yourself up. Your body can't process the folic acid. The folic acid, unprocessed, can then linger and causes inflammation and a rise in homocysteine levels. That can then lead to any and all of the doom/gloom scenarios listed, like (mostly stolen from that article):

Addictions: smoking, drugs, alcohol
Down’s syndrome
Frequent miscarriages
Male & female infertility
Pulmonary embolism and other blood clots
Depression & anxiety
Bipolar disorder
Chronic Fatigue Syndrome
Chemical Sensitivity
Parkinson’s disease
Irritable Bowel Syndrome
Spina bifida
Breast cancer
Multiple Sclerosis
Myocardial Infarction (Heart Attack)
Methotrexate Toxicity
Nitrous Oxide Toxicity

Holy motherfucker gene, Batman. That's an ugly list.
Blood clots, cardiac trouble, stroke, MS, Parkinson's, dementia, other mental problems, and on and on and on. For a guy whose dad had dementia and a couple strokes, this becomes somewhat concerning.

So.... What should you do? Ideally, get tested for the mutations. My understanding is that the saliva test at 23 and Me only checks for the mutations at C677 but not at A1298. (But maybe they will tell you differently; ask them). Going to see a paleo doc is a good option. He or she can have an NMR (nuclear magnetic resonance, I believe) blood panel run and it will test for both mutations.

Then you will know what, if anything, to possibly do from there. There is a long list of possible supplements, dietary changes, etc. that the site provides for those with the mutations at C677C. That same site also provides a shorter list of potentially appropriate things to do for those with the mutation at the A1298 locus. (The research on the A1298 locus has not been as extensive, so far).

And I am not suggesting that you supplement without a doc's advice, by the way. Quite the contrary. If you have this mutation, you should be talking about it with your doctor. (I have, and it turns out that my homocysteine level, and other signs of inflammation, are all rock-bottom. Whoo! Power of paleo! So I will keep eating paleo, but also am now taking a couple supplements that the doc suggested).

But a couple things seem super-clear from all of those suggestions at if you have either mutation -- and let's remember that over 50% of the population has the mutation at C677 without even considering the presence of the mutation at A1298 -- you should not ever be eating gluten, probably shouldn't be eating dairy from cows and should not be eating things or taking supplements with folic acid in them. Those folks (me!) have to get their folate either through the real-food chain, or from supplementation with methyl-folate, which bypasses the part of the conversion cycle that your (and my) mutant body can't engage in.

I repeat: That means over half the population shouldn't ever be eating gluten, dairy from cows, taking standard multivitamins, drinking energy drinks loaded with B-vitamins, or eating any other folic-acid-supplemented food (and yes, folate is essential to pregnancy/fetal-development, so, if you are a woman considering getting pregnant, you might think you really would want to know if your body can process folic acid properly or not, or whether you need to supplement with methyl-folate instead under your doc's supervision).

If I didn't know about these mutations already, I would want to know. I would get tested.

But let's say that you are a strict paleo eater, figure that you feel great and just don't want to know. I think that, considering much of the remedy for these mutations involves what is essentially strict paleo eating, you could rationally choose ignorance about the mutations because of your spectacular diet.

But I am betting there are a whole bunch of you who aren't so spectacular about your paleo eating and have no idea if you have either mutation. You might even be eating gluten, dairy from cows or folic-acid-enhanced foods on a regular basis. Are your homocysteine levels raging? You have no idea.

That approach strikes me as a bit of Russian roulette, healthwise. Look, these mutations were just discovered in the last ten years or so. Research is still young, and I suspect someday the research is going to show clearly that these mutations are playing a significant role in the astronomical increase in the number of any of that laundry list of maladies above. Right now, it merely suggests it. But I personally know six people with multiple sclerosis. That's insane. Autism is through the roof. Something is going on that didn't used to be going on. And modern wheat, with its concentrated gluten dose, along with (well-meaning, but perhaps misguided or imperfect) folic-acid supplementation of our processed-food supply, very well may have something to do with it.

Ultimately, as always, what you do with this info is your call. But, it's one of those areas in which the research is so new that the safe choice -- I'll even say the smart choice -- seems to be either to opt in favor of either very strict paleo without testing, or getting tested and dealing with the results from there.

- Posted using BlogPress from my iPad


  1. This is the most entertaining, yet very well-explained, post I've seen yet! I'm there with you on the compound sucks but what can you do?

  2. Eat paleo? :) And I live for comments that encourage my "funny" side, so thanks.

  3. So so interested to read this. I have recently tested heterozygous for MTHFR 1298C. So it looks like those two Pulmonary Embolisms I had weren't so random after all...

    Are you on a b12/methylfolate protocol? I've just started and interested to see what changes it makes. I also have the B12 and Iron levels "of a vegan", so intrigued to see what changes occur...

  4. The folks over at will tell you that hetero for 1298 only is not a very big deal. It's homozygous for either or hetero for both that seem to be the bigger deals. But I imagine a folate regimen can't hurt. And yeah, I am on one.

  5. Hahaha this is excellent ! Not that the actual problem is funny... I am being tested tomorrow. d: This is the first post about this topic that made me smile. Thanks.

  6. I have been mostly sleeping for the last 10 years, and have a lot of autoimmune diseases, I have motherfucker -C577C , I had 2 strokes , and I had thought this would be the last year on Earth for me .I started taking a compounded vitamin B, with amino acids etcetera... - first pill, I woke up WOW, , so far I think I won the big lottery ;-) good luck everybody!

  7. I really enjoyed reading this post. Very entertaining and even more so informative and well-written. It all makes so much sense (and I LOVE it when that happens) - I got chills while reading your second to last paragraph that touched on the eerie correlation between our country's obscene gluten intake and the astronomical increase in the diagnosis of autism. You're so right....something is most certainly going on!

  8. I really enjoyed reading your post. I have been reading so much lately on this subject just found out about a month or so ago that I am compound hetero like you. For the last year or so I have been trying to transition my entire family over to the paleo diet, it is not easy.... Do you have any suggestions to make the transition easier? I know that my homocystiene and folate levels are within normal range. I recently started taking a folate prenatal that doesnt have folic acid in it. Before I found out I was taking extra folic acid because I thought I wasnt getting enough of it, little did I know I was doing my body more damage and making my symptoms worse. I suggest to anyone that is just finding this diagnosis out to do as much research as they possibly can and also dont just take the doctors word for what you need to do. I dont say that because I dont trust my doctor or any doctor for that matter but I do know when I was first going over my lab results and that mthfr popped up I had no idea about it and I work in a doctors office so I asked one of the nurse practitioner to help me understand it. She suggested taking extra folic acid. So all I am saying just be aware its not well known and sometimes their suggestions can be more harmful then help. Sorry to go on and on. Just thought I would comment even though this post is several years old, I appreciated what you wrote and how you made it fun and easy to read.

  9. I know I'm a little late to this game, but this is the best post I have seen yet. I have the same diagnosis you have - heterozygous C667T and A1298C, testing done in May 2015. Let me tell you....I've been eating both dairy and gluten. I had no idea. I took Deplin 15 mg, that was terrible. Crazy? Present! I discontinued that. I guess I go full swing paleo now. Thanks for the post.

  10. This is great!! I too am ++ MTHFR C667T I have a Dr that is knowledgeable and I have stopped eating processed food with folic acid added and no dairy, no commercial wheat with high amounts of gluten, and started on a Vitamin regime recommended by her. My family has lots of stroke, glaucoma, blood and some cardiovascular disease so I am glad I am starting now. What I wonder is what has happened to all that synthetic folic acid that I have taken in for the last 60 years..D

  11. Yeah, I wonder the very same thing. I've known about this for a little over two years now. Sadly, during the first 51 years, I was horsing down bread and other folic-acid containing items like there was no tomorrow. Fortunately, my homocysteine levels are good.

  12. Was your Dr easily open to checking your homocysteine level. I am not sure my Dr is open to thinking out of the traditional medicine box.

  13. Just to clarify I have a Primary Care Dr and a Woman's Wellness Dr. the Women's Wellness Dr is the one who is very knowledgeable about the MTHFR concerns. It is my Primary Care Dr that may not be open to assessing these issues.

  14. One more thought, how can get the food industry to change synthetic folic acid in flour and processed foods to methylfolate, anyone up to start a petition?

  15. I go to a paleo/primal doc and he runs extensive bloodwork as a matter of course. Homocysteine, insulin, LDL particle number and size, all kinds of inflammatory markers, Omega6/3 ratio, etc.

    As for getting the food industry to stop putting folic acid in food, that won't happen. It was put in there to stop birth defects -- and actually has been pretty successful that way. But it is inflammatory to about half the population because of MTHFR mutations. The easier solution is just not to eat processed foods.

  16. My 3 year old daughter was recently diagnosed compound heterogeneous she was so sick right around Christmas that she was hospitalized and no one could figure out what was wrong with her. High inflammation levels constant fevers random rashes the minute you touched her and joint pain. She really didn't eat a lot of processed food but a few months before she got sick I started her on a Flintstone vitamin. She is finally getting better it's amazing that one can get sick so quickly and that regular pcps don't think of this mutation you basically have to go to a naturalpath