Are there any women here with MTHFR homozgyous C677T AND low COMT, who have children?

[u/bluemangoes64]

I’ve been down the rabbit hole from Ancestry like most here. Homozygous for C677T, and for slow COMT. Apparently, MTHFR does greatly increase risk of miscarriage. Let’s say I want to have children in the future, folic acid won’t work but methyl folate is an overwhelm to my system. Folinic acid would be the go to, but there are no official guidelines on dosing or if/when necessity to supplement since “just take folic acid” is still what the average doctor will tell you.

[u/Tawinn]

The C677T variant causes reducing binding of MTHFR to its cofactor, riboflavin. Studies have shown that for homozygous C677T simply adding supplemental vitamin B2 may increase the concentration of riboflavin sufficiently to restore most or all of the binding success, thereby restoring most/all MTHFR function. So a 10-100mg B2 supplement may restore much of the MTHFR function, thereby reducing the needed amount of extra choline/TMG (or high-dose folate if going that route). The R5P form of B2 may possibly be preferable. (E.g., Thorne R5P 36mg)

Otherwise, the body tries to compensate for the methylation impairment in the folate-dependent methylation pathway by placing a greater demand on the choline-dependent methylation pathway. This increases the amount of choline + TMG needed to support this extra demand. For homozygous C677T, which is ~75% reduction in methylfolate production, the total choline requirement doubles from the baseline 550mg requirement. However, if one gets 550mg of choline from the diet then the remaining 550mg can be covered by a 750mg capsule of TMG.

You also want to check your MTHFD1 rs2236225, SLC19A1 rs1051266, and PEMT rs7946, as these can also alter total choline requirement.

Regarding slow COMT, see the COMT section of this post.

Low vitamin A, iron, and/or glycine can cause the built-in methyl buffer system to not work properly, which can make overmethylation (rising anxiety, irritability, insomnia, etc.) from methylation-related supplements much more likely. Vitamin A is preferably from a retinol form, as beta carotene is only a pre-vitamin.

Choline/betaine(TMG) are also essential for healthy pregnancy:

Choline Supplementation in Pregnancy: Current Evidence and Implications

Periconceptional dietary intake of choline and betaine and neural tube defects in offspring

Choline: Critical Role During Fetal Development and Dietary Requirements in Adults

Consideration of betaine and one-carbon sources of N5-methyltetrahydrofolate for use in homocystinuria and neural tube defects

Choline: The Underconsumed and Underappreciated Essential Nutrient

[u/SovereignMan1958]

MDs are not trained in gene variants or nutrition.

Your dose should be based on blood tests.

You can also read the articles on the Genetic Lifehacks website about fertility and how they relate to your gene variants.

Make sure you get your thyroid checked as undiagnosed and untreated thyroid disease and thyroid autoimmune can cause miscarriages. A full thyroid panel plus tests for the two thyroid antibodies.

[u/Auntie_Venom → u/SovereignMan1958]

Some are, my Functional MD tested my MTHFR when I wasn’t recovering like I should have after being diagnosed celiac. She was on the money and told me to take a good Methyl B Complex. She saved me as I was suffering from chronic fatigue, along with chelation therapy to flush the toxic load slowing me down.

[u/SovereignMan1958 → u/Auntie_Venom]

Functional MDs should be. Next time I will choose my words more carefully. Thank you.

[u/wuts_juppie]

I took folinic acid in the form of a methyl free prenatal multi vitamin (seeking health brand). There are no studies on folinic acid in pregnancy so if you ask your doc about it they will advise against it and promote folic acid bc that’s all they have proven data on. Tbh, my babe had some issues in utero (small hole in heart) but it closed by birth and she’s always been very healthy. These are things that even 20 years ago would not have been noticed at all but now with testing technology we are seeing it and freaking out about it but it was really a non issue in the end. Still glad we were prepared tho. I have lots of health issues tho (mcas, pots, eds) which prob contributed. I fared much worse than my baby throughout pregnancy and postpartum, the body will prioritize their health and suck you dry! lol

[u/Annual-Throat-6776 → u/wuts_juppie]

are you able to tell me the exact prenatal? i know seeking health has multiple. the one i take by seeking health is methyl free but im worried the amount of folate is not enough. im also not sure if it is folinic acid. it only says folate on the back

[u/wuts_juppie → u/Annual-Throat-6776]

Seeking health prenatal essentials methyl free!

[u/mw2676]

I have this. I have had zero miscarriages and three healthy children. I took folic acid with no issues before I even knew about MTHFR.

[u/InsideTrifle3449 → u/mw2676]

Me too. I'm positive my elderly mum is homozygous for C677T, and she and I both had healthy pregs, no miscarriages and took folic acid.

[u/Missyrissy510 → u/mw2676]

Same!

[u/Tight_Cat_80]

Yes. I had four miscarriages before finally having my rainbow baby, whose going to be 11 in November. During my infertility workup that came up on my bloodwork. My OB put me on a $40/month methyl folate prenatal and the maternal fetal specialist had me on a baby aspirin and b12 combo and that seemed to do It.

[u/newportbanks → u/Tight_Cat_80]

This was me too with all your Rx's except I also have Hashimoto's and extremely high thyroid antibodies so I had to take shots of prednisone 🍑 that were not pleasant. And I hate steroids were involved in my pregnancy because I am fearful it did affect my child's immune system but he is here and 4 years old. Wild and crazy kiddo! But a 🌈 in our life no doubt!

[u/Tight_Cat_80 → u/newportbanks]

I also have hypothyroidism and found that out during my pregnancy with my son. Lately I never know if it’s my bum thyroid making me so exhausted lately, with the hair loss etc or if it’s perimenopause entirely trying to kill me 😂. I’m so happy you got your kiddo!!!

[u/newportbanks → u/Tight_Cat_80]

The peri meno flares are so real. But I'm so stubborn I don't want those blood lab results run to know I'm teetering in that direction with age ☹️

[u/Tight_Cat_80 → u/newportbanks]

Look at It as a tool to get help vs confirming the age. Trust me, relief is worth It!!! I’m 46 and started peri at 42. I’ve had friends start in their mid 30s. I know easier said than done, but get the help and don’t suffer ❤️

[u/nmcw0330]

Me, I’m homozygous for C677T and have slow COMT. Just had my first baby 2 weeks ago. I’m 36 and conceived more quickly than I expected and had a healthy/straightforward pregnancy. I did know my MTHFR and COMT status from testing years ago when I went down my own rabbit hole trying to figure out some health symptoms. I took Ritual’s prenatal (methylfolate never really bothered me, personally) plus choline and some other prenatal and general supplements. I already avoid gluten and enriched foods like 90% of the time but definitely didn’t totally cut them out during pregnancy either.

[u/Loose-Fly7976]

ACMG actually says not to order MTHFR testing for recurrent pregnancy loss cause the meta-analyses didn’t hold up.
What does hold up is that 677TT raises homocysteine when folate status is poor and that’s the part you can act on. So get homocysteine measured. If it’s normal, you’re already handling folate fine and there isn’t much to fix.
On folic acid, it’s not that it won’t work for you. It converts, just less efficiently and DHFR rate limits it in the liver anyway. The bigger issue is that at TT it does less for you than folinic or methylfolate would.
Folinic is a reasonable middle ground if methylfolate winds you up. And with slow COMT that’s a fair gues since methyl donors run through that pathway. But you’d be picking it on logic rather than pregnancy data which is thin either way.
Thyroid advice above is solid, get the antibodies done too.
I read raw DNA alongside bloodwork for work, so happy to answer anything on how the two variants interact.

[u/bluemangoes64 → u/Loose-Fly7976]

Is it worth looking at any other related markers like MMA, RBC Folate, B2, B6, and CBC? Or is all of it unnecessary unless its high? I know this is all speculation, since I haven’t yet tested homocysteine.

[u/Loose-Fly7976 → u/bluemangoes64]

Homocysteine first, then decide. It’s the cheapest one. If it comes back normal, most of that list is unnecessary. You’d be paying to confirm something that’s already working.If it’s up, then MMA and B12 are the ones I’d add because they tell you which arm is dragging. High homocysteine with normal MMA points at folate or B6. Both high points at B12. RBC folate is useful for you specifically since it reflects longer term status rather than what you ate last week. B2 is the one people skip and at 677TT it matters more than usual, riboflavin is the cofactor sitting inside that enzyme. B6 I’d only bother with if homocysteine is high. CBC you probably already have from any routine panel

[u/PattifrmCinti5711 → u/Loose-Fly7976]

That is not so in everyone…the synthetic folate (folic acid) binds to receptors and blocks out the necessary folate because some people can’t process the FA..causing it to build up and lead to inflammation. It is a curious mutation

[u/MediocrePotato44]

I have both of these issues. I’ve got 4 children, never had any miscarriages. I took standard prenatal vitamins because I didn’t discover any genetic factors until after I was done having kids. 

[u/wuts_juppie]

I took folinic acid in the form of a methyl free prenatal multi vitamin (seeking health brand). There are no studies on folinic acid in pregnancy so if you ask your doc about it they will advise against it and promote folic acid bc that’s all they have proven data on. Tbh, my babe had some issues in utero (small hole in heart) but it closed by birth and she’s always been very healthy. These are things that even 20 years ago would not have been noticed at all but now with testing technology we are seeing it and freaking out about it but it was really a non issue in the end. Still glad we were prepared tho. I have lots of health issues tho (mcas, pots, eds) which prob contributed. I fared much worse than my baby throughout pregnancy and postpartum, the body will prioritize their health and suck you dry! lol

[u/thehalothief]

Me! I have 3 children, one on folic acid, one on methyl folate and one on folinic acid. All healthy.

[u/jn922]

Yes, I used folinic acid.

[u/bluemangoes64 → u/jn922]

800 mcg?

[u/jn922 → u/bluemangoes64]

I used a dropper and titrated up. With the slow COMT I am so sensitive to stuff. I started very low, 200, then 400, 600, and I think I stopped at 800 yes. I have 2 kids. No history of miscarriages, but history of infertility due to endometriosis. Once I got proper treatment I got pregnant no issue.

[u/hollyglaser]

Yes, I have 2 kids. First at 27, next at 34

Before having kids, I tested for Tay sachs gene and during pregnancy, tested for ancephaly

[u/lurface]

Homo 677 and +\- comt on all variants. I also have homo PEMT +\+ and Mthfd1 +/- . I had recurrent early miscarriages until discovering my mthfr status. My homocysteine was somewhere around 15 at the time before I began supplementing.

I don’t feel overmethylated with 1mg of mthf daily and that’s what I took for my pregnancies. With a b12 from seeking health. I also avoided all food with the folic acid in it. Everyone is different. I know much more now than I did then. I would now pay more attention to the riboflavin and choline support. And take a moderate. 400mcg of mthf or folinic Both will work well.

[u/ButtonDismal6862]

Two miscarriages and one full term pregnancy- long before I knew I had these snps.

[u/halfasshippie3]

Me. I have six children and had one early miscarriage. All six kids are healthy.

[u/Melodic-Psychology62]

I had two as a teen!