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MTHFD1?
- Thread starter Bdeep86
- Start date
bertiedog
Senior Member
- Messages
- 1,740
- Location
- South East England, UK
I also have this double mutation which renders MTHFD1 non functioning and I think this is common amongst a European community.
If it is combined with other mutations in MTHFR (from memor)y I think it can be more of an issue. I am heterozygous for MTHFR 1298C and when I did a 24 hour urine test for female hormones a couple of years ago, although I had a fairly high range for the type of oestrogen that can lead to cancers my body had methylated it to virtually zero. I have taken a low dose of estrogel for 20 years, hence the test.
This really was unexpected but good to know because of my family history. The comment from Genova was that it showed I had a good lifestyle and diet! The diet thing I can go along with because I am very careful what I eat but the life style thing surprised me. I am lucky that most days I can walk with my dog and I am nothing like affected as many here for which I am grateful but I still found this reassuring as I have to spend a good portion of each day flat on my back resting.
BTW There is a lot of cancer in my family, with my mother having died from ovarian cancer, both my grandmothers had breast cancer with one dying from it and my brother has had prostate cancer which is treatable for the past 4 years and so I think it's highly likely that these combined mutations put us at greater risk of a disease like cancer. I have been aware of my bad genetics for some time now and would say that I have paid much greater attention to my diet for the past 21 years (I am 74 now and have had full blown ME since 2000 but the first hit was in 1979 after 2 weeks of flu. My nervous system never recovered from it with chronic migraine and vertigo attacks which were completely disabling. Thankfully I don't get the vertigo anymore but still have chronic migraines.
Hope I haven't been too pessimistic but no point in not being honest.
Pam
If it is combined with other mutations in MTHFR (from memor)y I think it can be more of an issue. I am heterozygous for MTHFR 1298C and when I did a 24 hour urine test for female hormones a couple of years ago, although I had a fairly high range for the type of oestrogen that can lead to cancers my body had methylated it to virtually zero. I have taken a low dose of estrogel for 20 years, hence the test.
This really was unexpected but good to know because of my family history. The comment from Genova was that it showed I had a good lifestyle and diet! The diet thing I can go along with because I am very careful what I eat but the life style thing surprised me. I am lucky that most days I can walk with my dog and I am nothing like affected as many here for which I am grateful but I still found this reassuring as I have to spend a good portion of each day flat on my back resting.
BTW There is a lot of cancer in my family, with my mother having died from ovarian cancer, both my grandmothers had breast cancer with one dying from it and my brother has had prostate cancer which is treatable for the past 4 years and so I think it's highly likely that these combined mutations put us at greater risk of a disease like cancer. I have been aware of my bad genetics for some time now and would say that I have paid much greater attention to my diet for the past 21 years (I am 74 now and have had full blown ME since 2000 but the first hit was in 1979 after 2 weeks of flu. My nervous system never recovered from it with chronic migraine and vertigo attacks which were completely disabling. Thankfully I don't get the vertigo anymore but still have chronic migraines.
Hope I haven't been too pessimistic but no point in not being honest.
Pam
- Messages
- 24
I have MTHFD1 hetero, paired with hetero MTHFR 677CT (folate), an MTR mutation (B12), and hetero CBS 699CT (homocysteine/sulfur). I'm researching MTHFD1 and just found this thread, so thought I'd comment.
TL;DR version in bold.
From what I understand/remember, MTHFD1 utilizes choline to assist MTHFR in recycling folate / generating MTHF. So people who over-focus on MTHFR mutations while having an MTHFD1 mutation might be missing a big part of the picture.
My theory a couple months ago was that supporting choline intake would support my folate+methionine cycles as a whole. Can't say I've had much success, as it seems my folate is still becoming deficient on a semi-regular basis, even while taking 1.25g choline at bedtime. (I took it at bedtime hoping it would help with sleep, since taking 1-3mg of an MTHF tablet before bed or upon early insomnia usually helps. If I'm slow to fall asleep, or wake up after specifically 5 hours, it's often low folate/MTHF, or perhaps low serotonin via low BH4 via low folate.)
According to the Chris Masterjohn genetic choline calculator (using a 23andMe file for example), I needed 8 eggs worth of choline, which I believe was 2.5g/day. So at bedtime I'm getting half my genetic needs, and the goal was to take the other half during the day, but I've fallen short of that.
When I first tested choline with a 2g dose, I did notice a prompt improvement in roughly-folate-related symptoms (tingling-sizzling-fizzy eyes and tongue, fatigue, hazy mind, brain fog). Maybe I need to test taking higher multi-gram doses. It's just hard to intake that much choline.
I'm using NOW choline + inositol which works, when it works. I've also had good experience with sunflower lecithin.
Phosphatadylcholine did not work. I also have PEMT mutations and figured this would be a useful supplement, but if it is useful, it wasn't noticeable in my symptoms.
So in sum, I theorize that MTHFD1 can be tossed aside and taking MTHF can compensate for it, since its only job, from what I understand, is to use up choline to assist MTHFR in recycling folate / making MTHF. And naturally this has consequences down the line, impacting MTR(R) with B12 recycling, and that then impacting efficacy of the methionine cycle as a whole.
For reference, I take Life Extensions Optimized Folate which I can often find for $15 a bottle on Vitamin Shoppe I believe. I am not partial to brands, only efficacy. There was only one other form of MTHF that worked for me and it stopped being stocked on Amazon. Powder capsules of 5mg and 10mg didn't even work for me. So I've settled on taking these Life Extension 1mg tablets, sublingually under the tongue. I get the sense that swallowing/digesting them doesn't work, making me wonder if I have folate absorption issues; or maybe I really just need that much MTHF. I average 5mg, with 1-3mg on the low end and 8mg on the top end, before I begin noticing distinct over-methylation symptoms (such heavy sleepiness, which is honestly more soothing than undermethylation wired-tiredness).
There were a couple times where taking B2 helped me, but it hasn't been consistent. (Where it noticeably helped was in resolving the disgust-rage symptom I now associate directly with SAM-e/methionine deficiency, meaning it would've helped folate cycling which reached the methionine cycle.)
Maybe MTHFR mutations paired with MTHFD1 mutations imply an even higher need for MTHF intake, because whereas MTHFR is slow recycling of folate / production of MTHF, I get the sense that MTFHD1 failures might be totally preventing recycling, as the Folate Cycle is a multi-step cycle involving MTHFD1 three times!
I just looked up the pathway, and forgot that I also have DHFR mutation, which IIRC means I can't utilize folic acid well. I'm surprised my DNA is still functioning with this catastrophe of a folate cycle! But it does explain why I've had chronic serotonin + dopamine deficiency issues (BH4 impairment from low folate), and why I likely need so much MTHF.
MTHF might as well be an essential nutrient for me.
Pathway reference: https://ndupdate.com/mthfr_ben_lynch/
TL;DR version in bold.
From what I understand/remember, MTHFD1 utilizes choline to assist MTHFR in recycling folate / generating MTHF. So people who over-focus on MTHFR mutations while having an MTHFD1 mutation might be missing a big part of the picture.
My theory a couple months ago was that supporting choline intake would support my folate+methionine cycles as a whole. Can't say I've had much success, as it seems my folate is still becoming deficient on a semi-regular basis, even while taking 1.25g choline at bedtime. (I took it at bedtime hoping it would help with sleep, since taking 1-3mg of an MTHF tablet before bed or upon early insomnia usually helps. If I'm slow to fall asleep, or wake up after specifically 5 hours, it's often low folate/MTHF, or perhaps low serotonin via low BH4 via low folate.)
According to the Chris Masterjohn genetic choline calculator (using a 23andMe file for example), I needed 8 eggs worth of choline, which I believe was 2.5g/day. So at bedtime I'm getting half my genetic needs, and the goal was to take the other half during the day, but I've fallen short of that.
When I first tested choline with a 2g dose, I did notice a prompt improvement in roughly-folate-related symptoms (tingling-sizzling-fizzy eyes and tongue, fatigue, hazy mind, brain fog). Maybe I need to test taking higher multi-gram doses. It's just hard to intake that much choline.
I'm using NOW choline + inositol which works, when it works. I've also had good experience with sunflower lecithin.
Phosphatadylcholine did not work. I also have PEMT mutations and figured this would be a useful supplement, but if it is useful, it wasn't noticeable in my symptoms.
So in sum, I theorize that MTHFD1 can be tossed aside and taking MTHF can compensate for it, since its only job, from what I understand, is to use up choline to assist MTHFR in recycling folate / making MTHF. And naturally this has consequences down the line, impacting MTR(R) with B12 recycling, and that then impacting efficacy of the methionine cycle as a whole.
For reference, I take Life Extensions Optimized Folate which I can often find for $15 a bottle on Vitamin Shoppe I believe. I am not partial to brands, only efficacy. There was only one other form of MTHF that worked for me and it stopped being stocked on Amazon. Powder capsules of 5mg and 10mg didn't even work for me. So I've settled on taking these Life Extension 1mg tablets, sublingually under the tongue. I get the sense that swallowing/digesting them doesn't work, making me wonder if I have folate absorption issues; or maybe I really just need that much MTHF. I average 5mg, with 1-3mg on the low end and 8mg on the top end, before I begin noticing distinct over-methylation symptoms (such heavy sleepiness, which is honestly more soothing than undermethylation wired-tiredness).
There were a couple times where taking B2 helped me, but it hasn't been consistent. (Where it noticeably helped was in resolving the disgust-rage symptom I now associate directly with SAM-e/methionine deficiency, meaning it would've helped folate cycling which reached the methionine cycle.)
Maybe MTHFR mutations paired with MTHFD1 mutations imply an even higher need for MTHF intake, because whereas MTHFR is slow recycling of folate / production of MTHF, I get the sense that MTFHD1 failures might be totally preventing recycling, as the Folate Cycle is a multi-step cycle involving MTHFD1 three times!
I just looked up the pathway, and forgot that I also have DHFR mutation, which IIRC means I can't utilize folic acid well. I'm surprised my DNA is still functioning with this catastrophe of a folate cycle! But it does explain why I've had chronic serotonin + dopamine deficiency issues (BH4 impairment from low folate), and why I likely need so much MTHF.
MTHF might as well be an essential nutrient for me.
Pathway reference: https://ndupdate.com/mthfr_ben_lynch/
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