Saturday, November 8, 2008

MTHFR

For those not suffering from infertility and not well versed in genetic disorders the title to my entry probably sounds like a really dirty sentence. As some of you might know I have consulted with SIRM and have had some blood work done. The first half of my blood work came back and I have
Compound Heterozygous MTHF. It's extremely hard to explain. Basically it means my body doesn't absorb folic acid...but it's not that simple either. Here is a blip from a web site that pretty much explains what it is: (please bare in mind that this breifly talks about men and how MTHFR effects them but none the less I still think it's quite informative.

***

Fortunately, most symptoms of MTHFR are surprisingly easy to treat. All it usually takes is some extra folic acid, a common B vitamin.

Most of the studies on folic acid and the MTHFR mutation have been done in women. But at least three have been done in men. These studies are too early to be conclusive but they suggest a link between low folic acid, the MTHFR mutation and male fertility.

To understand this link, we first need to learn about MTHFR. And how low levels of folic acid can affect our DNA, fertility, and risk for miscarriage.

MTHFR is a gene that makes a protein called methylenetetrahydrofolate reductase (now you see why we call it MTHFR). The MTHFR mutation is actually just a certain version of the gene.

This version leads to a weaker MTHFR protein. And people with weak MTHFR proteins need extra folic acid.

We know that folic acid is important for all sorts of things. You’ve probably heard doctors tell women to take their B vitamins when they are pregnant. Or even thinking about getting pregnant. Lots of our foods are now fortified with these vitamins too.

These B vitamins are recommended for the reasons we talked about before. Extra folic acid can help prevent miscarriages and protect developing babies from getting birth defects. And as I said, women with the MTHFR mutation need even more.


The MTHFR protein converts something called homocysteine into methionine. When MTHFR is not working properly you can get a buildup of homocysteine in the blood and not have enough methionine.

Folic acid fits into this because MTHFR doesn’t do its job alone. It needs to work with folic acid to turn homocysteine into methionine. This is actually why folic acid can help people with weak MTHFR. Extra folic acid pushes the reaction along so that the build up of homocysteine goes away.

OK, so having a weak MTHFR protein leads to an increase in homocysteine levels and a decrease in methionine. And both of these can lead to DNA damage in different ways (click here to learn more).


** this is what you find when you "click here"***

One of the effects of increased homocysteine build up may be more lost pregnancies. One number I saw was that 21% of women with high homocysteine levels have recurrent pregnancy loss! But if this is true (and I haven't seen the hard data to confirm it), is it because of chromosomal abnormalities? Or something else?

Hard to say. There are a couple of ideas out there for how high homocysteine levels might affect a pregnancy. There is some evidence that clots form more easily in these women’s blood. Too much clotting can lead to problems like cystic hygromas which are known to affect pregnancies.

Another possible consequence of high homocysteine levels is chromosomal problems. DNA is often thought of as unchanging but it is actually pretty dynamic. While the A, G, C, and TÂ’s rarely change, something called DNA methylation can change a lot.

DNA is decorated with little chemical groups called methyls. These methyl groups can affect whether a gene is turned on or off. They can also affect whether a chromosome goes to the right place when a cell divides.

The connection here is that high homocysteine levels decrease your pool of methyl groups. What this means is that there is less methyl around so your DNA might not get enough. What folic acid does is provide extra methyl groups to the pool.

It certainly looks like women with the MTHFR mutation have more babies with Down syndrome when they don’t get extra folic acid. But, is there a connection with other chromosomal problems?

No one knows for sure. In one study, researchers failed to find a connection between the MTHFR mutation you mention and any other trisomies except, possibly trisomy 18. However, the researchers couldn’t tell from that study whether the mothers had had enough extra folic acid in their diet to overcome their mutation.

As you can probably tell, more research needs to be done. For now, no research has shown that extra folic acid can help prevent trisomies in the absence of some health problem like the MTHFR mutation.

**

Here is some more information. Just for the record I'm Compound Heterozygous MTHFR for 677CT & 1298AC

MTHFR = methylenetetrahydrofolate reductase

The gene MTHFR encodes the protein/enzyme MTHFR.
Its job is to convert one form of folate (5,10-methylenetetrahydrofolate) to another form of folate (5-methyltetrahydrofolate). 5-methyltetrahydrofolate is used to convert homocysteine (a "bad" amino acid) to methionine (a "good" amino acid). Therefore, if MTHFR is not doing its job as well, homocysteine will not be converted to methionine and will be elevated in plasma. Normal plasma homocysteine levels are generally quoted as between 5 and 12 uM (uM = micromoles per litre). Elevated homocysteine has been associated with a variety of multi-factorial diseases.

Folate is a generic term referring to a family of related molecules that are interconverted between each other by a number of enzymes (including MTHFR). Folic acid is the synthetic, easily absorbed form of folate. Food has been fortified with folic acid for the past decade in North America. The recommended daily intake of folic acid is 400 ug/day (ug = micrograms). MTHFR does NOT affect how folic acid is absorbed into your body --> it affects what folate forms are in your body.

In general, if you have a mutation is a gene, there are a number of consequences.
Sometimes, the gene mutation has no effect whatsoever on the protein - therefore the protein can still do its job.
Sometimes, the gene mutation has a little effect on the protein - the protein still does its job, but not as well.
Sometimes, the gene mutation results in very very little or no protein - these are serious mutations.

The 677C-->T mutation

This mutation is an example of one that has a moderate effect on the protein. It is called a "polymorphism" which means that it is a common mutation.
The C is the normal allele (copy of the gene).
The T is the variant allele (copy of the gene).
The T mutation in the MTHFR DNA causes the MTHFR protein to be "thermolabile". This basically means that it is less stable. Folate can increase the stability of thermolabile MTHFR to a level similar to that of normal MTHFR --> that's why it is important to take a BIT extra folic acid if you are 677TT.

677CC is the "normal" or "wildtype" genotype
677TT individuals (homozygous) are said to have mild MTHFR deficiency
677CT individuals (heterozygotes) are almost the same as normal individuals because the normal MTHFR can make up for the thermolabile MTHFR.

The 1298A-->C mutation

This is also a polymorphism and has little to no affect on the protein.
The A is the "normal" or more common allele.
The C is the "variant" or less common allele.
The C mutation does not appear to affect the MTHFR protein. It does not result in thermolabile MTHFR and does not appear to affect homocysteine levels.

Compound Heterozygotes

Mutations at 677 and 1298 are both in the same gene, MTHFR. They are at different locations in the same gene. Some studies have shown that the MTHFR protein in people with the genotype 677CT 1298AC does its job a bit less well than the normal MTHFR.

MTHFR Polymorphisms & Disease

There are MANY studies associating MTHFR polymorphisms with various diseases. Sometimes one study will say one thing, another study will say another thing. It is important to remember that these problems (NTDs, miscarriages, cancer) are MULTIFACTORIAL - they have a combination of causes. MTHFR polymorphisms alone will not be the sole cause of them.

In terms of "severity" of genotype for various conditions:
677TT > compound heterozygous > every other genotype

NTDs - it is clear that folic acid deficiency increases the risk of having a baby with neural tube defects such as spina bifida.
Miscarriages - some studies have shown an association between MTHFR and miscarriages - some have not.
Cancer - 677TT genotype may help protect against colorectal cancer and some leukemias.

Severe mutations in MTHFR

These are very very rare (about 50 worldwide).
Severe mutations result in little or no MTHFR protein being produced. They are different from the above-mentioned polymorphisms.
The result in motor and gait abnormalities, mental retardation, decreased lifespan, etc.


**

This effects more then just fertility. A few of the symptoms are depression, anxiety & migrain headaches. All of which I suffer from. It can also cause other problems down the road like alzheimer's, problems with your heart, clotting disorders etc. Of course the symptoms all depend on what variation of MTHFR you have. One part of the info above says mine does it's job a "bit" less well then normal MTHFR then towards the bottom in "sevarity" it is in the middle so who really knows. All I know is I'll be booking an appointment with a hematologist just to make sure we keep this under control. Since this effects my over all health I'll be making an appointment as soon as my husband and I get back from vacation.

Side note: yesterday was our 5 year anniversary and we are going on vacation from Tuesday through Saturday. I can't wait. We are doing the same thing we do every year...but it's our ritual. :) We go back to where we honey mooned. Well it's late so I should head to bed.





19 comments:

Jeni Pelletier said...

How do you feel now that you know what exactly it is? I can't believe that it is that complicated, and I also can't believe that it affects you in other ways. It does explain your anxiety, headaches and some depression I've seen you with.
I will keep praying for you and your hubby. I miss you so much!!!!
Happy Anniversary! Hope you have a great time!!!

Just Meim said...

I'm glad that you were able to find this out. At least you know that it is treatable. Hopefully knowing will be a huge blessing for you!

Jennifer said...

I must chime in here. I am Homozygous MTHFR (1298AC) - discovered after extensive testing was done after my 1st failed IVF.

After starting to take extra folic acid (folgard - 2 pills/day), one baby aspirin/day, and tried our FET cycle (after 2 fresh IVF's)...I got pregnant and gave birth to a healthy baby boy.

I continued the folgard and BA thru my pregnancy (I discontinued BA around 36 wks). I also took daily injections of a blood thinner called Lovenox until around 15/16 wks...in case clotting was a factor that was contributing to my previous losses (3 miscarriages). This seemed to work to help get me pregnant and stay pregnant!

Good luck!

Jocelyn Aucoin said...

THANK YOU for this post! I just found out I have the MTHFR mutation, too... after two miscarriages and some bloodwork. I am not sure if it's homo or hetero yet. But the part about your post I found most interesting is that this can result in depression, anxiety and migraines! I have suffered with the latter two for years... since puberty... so over 15 years. Am really hoping to find some answers.

Sades said...

I read you post today 8/1/2010. I notice it has been quite awhile since your initial post. I really appreciate reading it. I had 2 miscarriages both at about 6- 7 weeks. After the second miscarriage I got lucky and blood work was done that revealed I was homo 1298AC MTHFR. but my homocysteine levels were normal. So my OB referred me to a heme. During the 3 weeks leading up to the heme appointment I stopped taking all my vitamins because I wanted to see if the vitamins were preventing the high levels of homocysteine ( at that time I just found out and did not know half as much as I know now) The heme told me that when I get pg again to start taking 40 mg of lovenox daily, plus folic acid at least 1mg, and baby asa. Well, we got pregnant shortly after that! I continued with the regimen he prescribed to me. at my 20 week ultrasound it was discovered our baby had a severe form of spina bifida. It was discovered that I was not taking enough folic acid. 1 mg is not enough. My OB told me to take 2 folgard (folic acid/vitamin b complex/ daily, plus I'm taking a prenatal vitamin called Neevo (made for people with MTHFR mutation), lovenox, and baby asa. We waited 6 months, so I could stock up the folic acid levels in my body. We started trying in June and got pg! I am now 9 weeks and scared to death. I pray we have avoided spina bifida, and other trisomies. Anyone out there have a similar situation, and end up with a healthy baby? Thanks for listening!

Sades said...

I read your post today 8/1/2010. I notice it has been quite awhile since your initial post. I really appreciate reading it. I had 2 miscarriages both at about 6- 7 weeks. After the second miscarriage I got lucky and blood work was done that revealed I was homo 1298AC MTHFR. but my homocysteine levels were normal. So my OB referred me to a heme. During the 3 weeks leading up to the heme appointment I stopped taking all my vitamins because I wanted to see if the vitamins were preventing the high levels of homocysteine ( at that time I just found out and did not know half as much as I know now) The heme told me that when I get pg again to start taking 40 mg of lovenox daily, plus folic acid at least 1mg, and baby asa. Well, we got pregnant shortly after that! I continued with the regimen he prescribed to me. at my 20 week ultrasound it was discovered our baby had a severe form of spina bifida. It was discovered that I was not taking enough folic acid. 1 mg is not enough. My OB told me to take 2 folgard (folic acid/vitamin b complex/ daily, plus I'm taking a prenatal vitamin called Neevo (made for people with MTHFR mutation), lovenox, and baby asa. We waited 6 months, so I could stock up the folic acid levels in my body. We started trying in June and got pg! I am now 9 weeks and scared to death. I pray we have avoided spina bifida, and other trisomies. Anyone out there have a similar situation, and end up with a healthy baby? Thanks for listening!

Amy said...

yeah 1 mg is what woman with OUT MTHFR are supposed to take. Anyone with any form of MTHFR is supposed to take at least 2.5 mg of folic acid a day.

Anonymous said...

NEWSFLASH: If you have this MTHFR polymorphism, it means you CANNOT convert "folic acid" into folate.

You need methylfolate in supplement form, not folic acid. In fact, folic acid may create more problems than if you had not taken any at all. Folic acid is a synthetic form of folate.

METHYLFOLATE. As in Metafolin, etc.

Dr. Sheryl Wagner said...

Remember that is you have a genetic MTHFR problem you can pass this on to your children. It is responsible for much more than infertility such as schizophrenia, ADD, depression and more. so it will be very important to remember this and have your child tested genetically so they don't have to deal with these debilitating illnesses. The other answer is to adopt, although you never know if you will be getting a child with a genetic defect that way either.

kirsti said...

I just read your post. Googling MTHFR. I was diagnosed this past spring. I actually take MTHF drops, but thorne also makes a pill, also there is something called deplin that is a patented drug. My dr. Told me that my body had folic acid in it, so if I had a blood test done, my levels would lo normal, but my body does not process it. So folic acid is processed by the body, turning it into MTHFR. So since my body does not process it, taking more folic acid does not help, I need to have the already processed version. So much more has been found out about this genetic disease, and more people are being diagnosed!!!

Sades said...

I just got a comment from Kirsten today. The comment brought me to a blog site, where I read my old post in 2010. After 3 losses, (2 due to spontaneous abortions, and 1 due to severe neural tube defect), I was on my 4th pregnancy and 9 weeks when I posted. I am happy to report back that my 4th pregnancy made it, I was induced at 37 weeks, and I had a healthy baby girl on 2/14/2011. She is now 7 and a half months, and meeting all her milestones. I was taking a prenatal vitamen called NEEVO (has folic acid in a broken down form), and 2 folgard a day, plus the baby aspirin, and 40 mg of lovenox daily. At 35 weeks I switched from lovenox to heparin.
Just thought I would comment answering my own question that there is hope of having a healthy pregnancy and baby after a few losses.

Anonymous said...

We are just learning about MTHFR as we have found both of our parents each have a mutation, and my sister has both.

One of my brothers had a child with spina bifida. She is categorized as L1, which as I understand it, is the worst. However, my sister-in-law has fostered her independence and upper body strength and you would NOT believe how wonderful this little girl does.

She is 11 now, and climbs serious mountains using walking sticks (basically climbs them on the strength of her shoulders to keep swinging her legs forward. I was climing a mountain with her this summer (Flattop Mountain in Anchorage for anyone who is familiar. It is quite difficult. She could not scale the final stone part.) People coming down and meeting us would stop and stare at her as she swung her legs forward a step at a time...some even moved to tears to say "you are my inspiration!!" She is amazing. She is also working to qualify as a downhill skier for the Special Olympics. She skis on a chair that has a single ski under it, and routinely whips down double black diamond runs.

In her home, she crawls on her hands and knees up and down the stairs and all over. Very mobile and not held back at all. She has no ability to use her legs, so this is on hip and upper body strength.

Bottom line for anyone who has MTHFR and finds out their baby has spina bifida...this is not the end of the world that you might think it is. My sister in law used some pretty politically incorrect tactics, such as letting the girl when she was a toddler crawl behind her through the dirt on walks. I felt terrible for the little girl at the time, but it was JUST what she needed. It is hard to make them do for themselves, but you HAVE to do it. Seriously, those first years are so important to not coddle them but to teach them to do for themselves.

There is hardly anyone in the family today who can win against her in arm wrestling. And she is an adorable, precious amazing girl.

Yes, she has had lots of surgeries and needed a shunt. She has a couple of medical issues that take a little extra time to pay attention to. None of that is the end of the world. Today, except for the fact she needs to snap on her leg braces and grab her pink walking sticks, she is just as mobile and goes everywhere my kids go.

I wish people facing a lifetime with a child with spina bifida could just see this child. Yes, it took so much strength of mind and more time for the mother to make sure her daughter was doing for herself, but WHAT an amazing outcome. It's not the easiest path, but a rewarding outcome is worth the effort.

Anonymous said...

I had two previous MC in 2011 first was in Aug second was in Dec after that luckily my dr decided to test me to see what might have been causing them and I was diagnosed with Homozygous MTHFR 1298AC. I am very happy I found this blog. It's been almost a year since I found out about my gene mutation, I am looking into the Neevo DHA prenatals because of this post, I have yet to become pregnant again but I don't think I could handle another loss. Please don't ever take this blog down! we all have to stick together!

Susan Laney said...

I highly recommend that anyone who is homozygous for C677T take Cerefolin NAC. Yes, it is expensive and, unfortunately, most insurance companies won't pay for it since it is a "medical food." However, it has totally revitalized every part of me since I started on it about a year ago. I am 62 years old and in the best shape of my entire life. Mental acuity has come back, energy levels high, weight loss, eyesight improved, blood pressure 110/60. The ONLY side effect, if you can call it that, is an increase in lucid dreaming. I have seen doctors actually tell people with MTHFR to take MORE folic acid. Big mistake. What you need is folate, which is the methylated form of folic acid. Before my later in life MTHFR diagnoses, I was diagnosed periodically with just about every AI out there. My thyroid didn't function properly, and I had polycystic ovarian disease. (Had two normal pregnancies after having my first ovary removed at age 20.) I have been on HRT since age 37 when I had a total hysterectomy. Fortunately, I go to an integrative medicine doctor who really listens to me. I was also diagnosed with MGUS about 12 years ago. Since starting on the Cerefolin, my MGUS has all but disappeared. Hematologists need to be aware of the possible connection between MTHFR and MGUS! Maybe it will save someone from developing multiple myeloma or other blood cancers.

Anonymous said...

It's funny I posted on 9/22 and just found out today I am pregnant. 3 weeks 4days along and I am FREAKING out! My insurance ended so now I have to use medicaid to get into the dr until I get a new insurance provider and I AM SO SCARED they will not understand my MTHFR issues and wont give me what I need. is there anything OTC I can take in the mean time to help ease my mind?! Thanks!

Amy said...

This is what I take. http://www.iherb.com/Olympian-Labs-Inc-Expecting-Mother-Premium-Multivitamin-with-5-mg-Folic-Acid-60-Capsules/23803

Some say you need something special but I haven't found anything OT that is special for MTHFR yet. Haven't honestly put to much thought into it since we are not really trying any more:

Anonymous said...

I just wanted to let people know they can buy methyl folate / metafolin in a good health food store. I just found out I have one mutated 1298AC gene after having two back to back early miscarriages. I do have two healthy, totally normal and wonderful children who are 3 and 5 - and I can't believe how lucky I am (even more than I knew before !) to have them here with no knowledge of this before. Anyhow, my doctor also recommended just taking extra folic acid (in addition to my RAW foods pregnancy vitamin) - but I happened to be at the health store buying it and asked the owner if any brands better, etc and he casually mentioned that about half the population has some sort of difficulty metabolizing folate and they now had a partially metabolized form you could take. I actually feel much better on it / we'll see how it affects pregnancy...I'm very nervous now and glad to have something I can do to be proactive at least!!!

Colleen Shaffer said...

Just found out I have one A1298C mutation. I agree with Amy and Kirsti - multiple geneticists are telling me NOT to take folic acid as my body cannot break it down. Instead I need to take FOLATE. Not the same thing. Extra folic acid can cause harm to people with MTHFR. Hope you are doing very well - I found your blog looking for MTHFR info! :)

daisy said...

Susan Laney, How can I possibly find you and talk to you..I was diagnosed with MGUS last year, I think exposure to lyme disease triggered it--but the doc who was testing for lyme ran the gene mutation test on me and I am compound heterez, my son is compound homogo ---I am being followed by an oncologist and mgus is considered pre myeloma...I would like to consult with your doctor...this is fascinating to me that you got rid of the mgus..I've been taking curucumin..please help!! thanks