Monday, September 23, 2013

MTHFR Gene Mutation: Common in Autism, Autoimmune Diseases, Chronic fatigue, Fibromyalgia, PANDAS , Thyroid Disease

“Holy MTHFR!” from

If I say MTHFR, then Methylenetetrahydrofolate Reductase are the two words that pop into your brain, right? No? Well, hopefully after reading this, you’ll see more than that swear word that caught your attention.
If I next mention bipolar struggles, rapid mood swings, depression, anxiety, heart disease, strokes, macular degeneration, miscarriages – and any of these issues hit home for you, then read on, because you might just want to know about MethyleneTetraHydroFolate Reductase – better known by its abbreviation – MTHFR.
MTHFR is a gene and like all genes, it acts as a light switch – turning on or turning off various body processes. In this case, MTHFR takes folate (vitamin B9) and methylates (converts) it into methylfolate (5-methylTHF). Hardly seems like a big deal, does it? Yet, if you belong to an autism, Pandas, Lyme or chronic fatigue group, you’ve probably noticed a big buzz around this thing called methylation. While the past decade has seen MTHFR studied in terms of cardiovascular disease and cancer, it turns out it might also be a very big deal for those raising kids with developmental, neurological or behavioral symptoms and for those fighting chronic infections.

A lot of parents raising kids with challenges are already overwhelmed – too overwhelmed to start stuffing their brains with hard to pronounce words describing hard to understand biochemistry. But you can think of methylation as a kind of metabolism. Imagine the insides of a clock with many cogs, each cog regulating specific chemical reactions. This is an over-simplified diagram of the methylation cycle:

The cogs in this picture turn in your body billions of times per second. But quick, before your eyes glaze over, find the MTHFR in the middle of the picture. Got it? The MTHFR gene sits at a critical point. If you have a glitch that keeps this gene from doing its job, the cogs on both sides of the picture are going to get mucked up. Instead of the light switch being on or off, it’s stuck in some sort of dimmer switch mode, functioning, but not nearly as well as it should be. The proper interaction of methylfolate and Methyl-B12 is what drives your body’s ability to fuel every cell in your body with energy (this is what’s going on in the green and red cogs). Methyl-B12 regulates certain T-cells that may play a role in some autoimmune diseases. Improper methylation can also raise your levels of homocysteine (look to the bottom of the red cog on your right).  This can greatly increase your risks for heart disease, stroke, macular degeneration, dementia and some cancers (e.g. lung, colon and leukemia). It also impedes your ability to manufacture glutathione (bottom right of diagram), the body’s master antioxidant (the “sanitation engineer”) that plays a critical role in autism treatments, chronic Lyme disease and some tic disorders. While there isn’t enough research to say for certain, some MTHFR literature discusses a possible role of MTHFR mutations and increased miscarriages. Insufficient levels of methylfolate are linked to neural tube defects, which is why pregnant women are told to take supplements of folic acid. But if your body has a faulty MTHFR gene and can’t properly convert folate into methylfolate, then this advice may not be having the intended benefits.

So you can see why this one little gene is a big deal. And you can find some pretty decent articles on the web on why treating an MTHFR mutation is so important for many health issues. But there’s one more important role that MTHFR plays. One that doesn’t get nearly enough ink. Look to the left of the MTHFR circle. See the blue cog labeled “BH4 cycle”? MTHFR plays a direct role in how well the BH4 cycle works – and the BH4 cycle controls those two neurotransmitters that are so essential to people with behavioral and emotional challenges – serotonin and dopamine. This has a huge potential impact for how some kids might be helped – kids whose parents are averse to psychotropic medications as well as kids for whom medications have been ineffective or caused serious side effects.

After months of studying everything I could get my hands on, I came to realize that given my long family history of heart disease and depression, this microscopic chemical conductor, aptly named MTHFR, might be the cause of a lot of suffering along my family tree.

Testing MTHFR is actually very simple. Most commercial labs in the U.S. can test for it.  Go to your local lab’s website, find their test menu (usually under the section for doctors) and search on “mthfr” or “methylfolate” or some similar phrase. This should bring you the test code number that you can ask your physician to order. The list price for my test was $150 but my insurance negotiated rate was $50 and since we’d met our annual deductible, my 20% portion of the bill was $10.

The results for one of my children came back normal. So the source of his hurdles lay elsewhere. MTHFR, no matter how important, is certainly not the single root of all evil. But my other child showed one mutation (called a polymorphism) on her MTHFR gene. At least 24 mutations have been identified on the MTHFR gene. Only two are well studied at this point – mutations labeled C677T and A1298T. My daughter had one mutation of C677T, making her heterozygous. (If she had two mutations of C677T, she’d be homozygous).
In the U.S., it’s estimated that roughly 45% of the population may have at least one mutation of MTHFR, though your heritage can increase or decrease your individual risk. While exact numbers are hard to verify, one mutation on C677T means you’re probably methylating (converting) folate into methylfolate at 40-60% efficiency. 

If you have two mutations, that number drops to approximately 10% efficiency.

In my personal experience, this is a pretty big deal when it comes to dealing with anxiety and depression. (I couldn’t find estimates for A1298C mutations and much less is written about this. It seems to play a greater role in gut health. For more details, you’ll need to watch Dr. Amy Yasko’s videos. It’s well beyond my ability to do justice to A1298C.)

By following the green cog counterclockwise to the blue cog, you can see the impact on serotonin and dopamine and why knowing about this gene can be important to those who struggle with mood and behavioral disorders.

So what to do about it?
Those who’ve studied methylation extensively have developed various protocols depending on what ailment they’ve focused on. But the common thread for those with a C677T mutation is that if your body can’t convert folate into methylfolate properly, then you can help your body around this hurdle by taking a supplement that already contains methylfolate (not regular folate) to make up for the shortage.  (Think of using instant mashed potatoes where the hard work has already been done for those of us who are cooking-challenged – except unlike potatoes, methylfolate from a store is just as good as “home-made”).

Because this is an emerging field of research, little guidance is out there regarding dosage and step by step how-to’s. There’s no vetted resource to tell you the proper dosage of 5-methylTHF to give an adult, let alone a child. I know one child who’s doing well at less than 100mcg/day (that’s micrograms) and a teen who’s on 10mg/day (that’s milligrams) of Deplin (a prescription form of methylfolate). This is an enormous range for dosage. Most sources I’ve come across discuss ranges of 100-400mcg for a child and 800mcg-1mg for an adult. But many factors are at play and it’s best to work with a physician if possible. Unfortunately, the whole field of epigenetics is so new that few clinicians have much experience in this area. So you may need to do a lot of research alongside an open-minded doctor. We started out slow – very slow, then gradually built up dosage under the guidance of my daughter’s doctor. Even with a doctor’s help, there was still an element of guesswork involved, in the same way doctors work with any patient to zero in on an ideal dosage for any medication.

Supplementing with methylfolate has made a huge difference for my daughter (and has also helped my own health). Over a few months, my daughter’s anxiety, mood cycling and sadness evaporated. So we kept tweaking. At the two month mark, we unwittingly went too high and endured a period of extreme anger, serious depression, food refusal, rapid mood swings, oppositional defiance and truly ugly times – the very things that drove us to our supplementation trial to begin with. Confused, I was ready to give up. But then, almost by accident, we stumbled onto the problem when I stopped the methylfolate in order to do a lab test. Within 24 hours of being methylfolate-free, my daughter’s issues melted away. Hmmm. She became pretty stable – for about a week. Had we been on the wrong path? Then things started to head south again. That feeling of panic returned to the pit of my stomach – that feeling just before you plunge over the peak of the rollercoaster track and you start screaming for your life.

So I re-started the methylfolate at a low dose – and things got good again. It felt like the sun had come back out from behind the clouds. So we built back up once more, not as high as before but just to the point where things got a little dicey again. When warning signs of a meltdown showed on the horizon, I used the advice from one of the MTHFR researchers and gave a small dose of niacinamide (vitamin B3), which has the effect of using up methyl groups (think of it as a sponge mopping up a spill). Within the hour, things were calm again – and stayed that way. Over the course of a few weeks, we zeroed in on the dose of methylfolate that seemed to work best. It will inevitably change as my daughter grows and when her body may need extra resources, like when she’s fighting an illness. It will always be a little bit of an experiment, in the same way that dosing of an SSRI or psychotropic medication is never carved in stone. After all, what fun would parenting be if you were allowed to figure things out and then get on with your life?

Our experiment has been going on for awhile now and I’m happy to report that things have stayed pretty stable. I did find that in addition to methylfolate, my daughter also needs methyl-B12, because both are necessary to keep the methylation cycle functioning properly. If you only take one without the other, you can develop what’s called a folate trap and you can end up thinking you’re on the wrong track when you’re really not. I’ve also tried to keep my daughter away from things fortified with regular folate – things like cereals and multi-vitamins. Her body just can’t handle the regular stuff and if she consumes too much, we end up paying for it with glimpses of the bad old days. Things we once used to help with anxiety have gone by the wayside. My own methylfolate supplement has lowered my blood pressure to the point where I may be able to stop taking prescription medication. I’ll never know if I’ve averted some other ailment, such as the macular degeneration that robbed my father of his eyesight or the strokes that crippled my grandmother or the congestive heart disease that killed my uncle. But I know that both my daughter and I have improved our own odds significantly. Best of all, as winter brings shorter days, it isn’t bringing the depression and sense of dread that has often come with it. Is this all because of a supplement? Hard to say. I’m sure having a happy child plays a role in many ways. But unless things take a dramatic change for the worse, I’m feeling like we’ve found a key piece of our behavioral and health puzzles.

MTHFR is by no means the Holy Grail. The entire field of epigenetics promises to bring even greater gifts and ideas and more than a few dead ends. But for now, this one little gene has proven to be one big deal in my family.