Most research on MTHFR mutations point to the C677T homozygous mutation and how it causes elevated levels of homocysteine.
There is very little research in regards to the A1298C MTHFR mutations.
Then compound that with even less information on what to do successfully with A1298C mutations.
Then compound the issue that there is very little research done with heterozygous MTHFR mutations. The only research I’ve seen about heterozygous MTHFR mutations is basically summarized as, “No big thing.”
Well. I think absolutely the other way. Research or no research. Doctors just need to think a little outside the box and realize there are other things that must be at play here because those with heterozygous MTHFR mutations are NOT doing well!
When doctors discover elevated homocysteine levels in their patients, that may trigger them to order a MTHFR Genetic Test. At least, the doctors who know about MTHFR would order it.
Elevated homocysteine levels are typically found in those with homozygous C677T mutations.
But MTHFR mutations are way more than just elevated homocysteine; in fact, those with MTHFR mutuations may demonstrate normal levels of homocysteine.
Many doctors do nothing with MTHFR mutations if homocysteine levels are WNL (within normal limits).
This is what patients commonly hear over and over again (this is taken directly from a doctor’s email to their patient – and the patient posted this on a public forum):
MTHFR was positive for 1 copy of C677T and negative (normal) for A1298C. This means you are heterozygous for MTHFR. This has NO increased risk or coronary disease and clotting. This is a common finding in the general population. Your homocysteine level was normal so therefore no risk for you with clotting. If you would have have 1 copy for each of the above mutations, then there is some increased risk and treating with blood thinners would be the approach.
Is this the right thing to do?
Not in my mind.
To be fair to the doctor, she is correct based on what research is stating based on these types of MTHFR mutations.
But the issue is many women with heterozygous C677T are miscarrying over and over yet their homocysteine levels are ‘normal.‘
Something else must be checked as there is obviously something being missed here.
Doctors just cannot go with the flow and say, “You’re fine. There’s no risk with your MTHFR mutation because you have low levels of homocysteine.”
Dig some more.
Think outside the box.
Why isn’t it right to just use homocysteine as a guide to see how MTHFR mutations are affecting people?
Because homocysteine is NOT the most sensitive marker for cardiovascular risk.
Plasma S-adenosylhomocysteine appears to be a much more sensitive indicator of the difference between patients with cardiovascular disease and control subjects than is homocysteine.
Then add this to further the blow:
Homocysteine-lowering vitamins do not lower plasma S-adenosylhomocysteine in older people with elevated homocysteine concentrations.
Yes, this was a study with older men but it shows that we need to evaluate pregnant women and s-adenosylhomocysteine.
Thankfully, some researchers are thinking outside the box and they have done something significant regarding the human umbilical vein and s-adenosylhomocysteine:
The aim of this study was to estimate the relationship of endothelial dysfunction induced by intracellular S-adenosylhomocysteine (SAH) accumulation and DNA methylation in human umbilical vein endothelial cells (HUVEC)…..These findings suggest that SAH can act as the potential molecular biological marker in the promotion of atherogenesis.
What does that mean?
That means that if a mother has elevated s-adenosylhomocysteine levels, the umbilical vein and any tiny blood vessel in a developing fetus can become blocked due to atherosclerosis.
Typically, atherosclerosis takes years to develop. However, we are talking tiny capillary-sized arteries in a fetus. This means that it will not take long at all to develop atherosclerosis in a developing fetus if a mother’s s-adenosylhomocysteine levels are elevated.
I’m not done yet.
…results may show s-adenosylhomocysteine (SAH) might cause cellular DNA damage in hepatic and microglia cells by DNA hypomethylation, resulting in irreversible DNA damage and increased cell cytotoxicity. We suggest that SAH is a better marker of cell damage than homocysteine (Hcy) in hepatic and microglia cells…We suggest that SAH is a better marker of cell damage than Hcy in hepatic and microglia cells.
That’s huge. That means that s-adenosylhomocysteine causes significant cellular damage including the neurological system’s cells.
This may partially explain the scores of women who have heterozygous C677T or heterozygous A1298 mutations and have miscarried numerous times.
Here are some forum posts I’ve found:
I have had 3 miscarriages since January, one being a twin pregnancy. I just recently found out that I tested positive for Heterozygous MTHFR C677T. I saw a specialist (RE) at the Cleveland Clinic last week that told me this was niot causing my miscarriages. I have been tested and tested and tested and this is the ONLY thing I am positive for. I have seen that many people take baby aspril or take shots of heperan along with extra folic and B vitamins. PLEASE HELP! I just don’t know who to believe and who not to believe.
Makes you wonder what would have happened if the doctor tested for s-adenosylhomocysteine instead of homocysteine. It also makes you wonder what would have happened if this woman took 5-MTHF, methylB12, P5P, TMG, R5P, baby aspirin and fish oil.
I just miscarried at 15 weeks. I came back with the same results…heterozygote C677T and everything else tested negative. I spoke to my doctor tonight and she is going to send us to a perinatologist (sp?) if and when we do get pregnant again. She said that studies have been inconclusive but that some Dr.s would put one on a blood thinner. I would recommend a referral to a high-risk dr. Good luck and God bless you and your family. My heart is with you.
Here is a woman who tests positive for heterozygous A1298C:
Hi, I am 33 years old and have had 3 miscarriages in the last 2 years. After numerous tests, one came back positive. I am positive for the Heterozygous A1298C mutation of MTHFR. What does this mean for me having children? I have a perfectly healthy 13 year old, and had no problems with my pregnancy with her. All of the research on line talks about the C677T mutation or a combo of the two. I want info on just the Heterozygous A1298C and what I need to do? I am so worried, and don’t know where to go for help!
There are countless women out there with heterozygous C677T mutations and heterozygous A1298C mutations that are miscarrying or having other symptoms highly related to the homozygous C677T mutation.
This tells me that testing is inaccurate for MTHFR care.
I highly recommend doctors and patients demand testing for the more sensitive laboratory values when patients come back positive for ANY MTHFR mutation:
- S-adenosylhomocysteine (SAH)
- Methylmalonic acid (MMA)
- More testing as I discover it will be posted. I’m not satisfied with these two.
This also tells me that we need to use more than just folic acid in treating any MTHFR mutations.
I highly recommend doctors utilize a wide-net approach to lowering homocysteine – AND s-adenosylhomocysteine in their patients.
Doctors that only use folic acid in high doses for MTHFR mutations are doing a major disservice to their patients.
Doctors that are not doing anything for heterozygous MTHFR mutations are doing a disservice to their patients.
We need more doctors who handle patients like this – proactively:
I also had 3 miscarriages in a row. Doctors have run 3D ultrasounds, genetic tests on my husband and I, etc. The only thing that came back was heterozygous for C677T. I am with a fertility specialist now who said he will treat this with folic acid supplements and baby aspirin when we start the IVF process. Hopefully this will help.
I wish the doctor ran the blood tests I suggest above along with providing 5-MTHF, methylB12, fish oil, TMG and other nutrients which suppport the breakdown of homocysteine.
But – the main point of that doctor is he is taking action. He is not simply sitting on his haunches and saying there is no risk because you have heterozygous MTHFR C677T.
The lab test you can have your doctor order to check the main areas of homocysteine metabolism and methylation are in the Methylation Profile Test by Doctor’s Data.
Please perform a study measuring levels of s-adenosylhomocysteine in those with MTHFR mutations who have ‘normal homocysteine’ levels. I’ll share the Nobel Prize with you.
Have you miscarried and only tested heterozygous A1298C or heterozygous C677T? Please comment below.
What do you think of this more specific lab test: s-adenosylhomocysteine?
Pulling for you,
1. Kerins et al, Plasma S-adenosylhomocysteine is a more sensitive indicator of cardiovascular disease than plasma homocysteine, Americal Journal of Clinical Nutrition
2. MedHelp.Org and Search Terms: A1298C heterozygous, C677T heterozygous
3. Sample Methylation Lab Test from Doctor’s Data
4. Yahoo Forum on Pregnancy and Immunology
5. Green et al, Homocysteine-lowering vitamins do not lower plasma S-adenosylhomocysteine in older people with elevated homocysteine concentrations, British Journal of Nutrition
6. Yu et al, Relationship of impairment induced by intracellular S-adenosylhomocysteine accumulation with DNA methylation in human umbilical vein endothelial cells treated with 3-deazaadenosine, International Journal of Experimental Pathology
7. Liu et al, Effects of S-adenosylhomocysteine and homocysteine on DNA damage and cell cytotoxicity in murine hepatic and microglia cell lines, Journal of Biochemical and Molecular Toxicology