MTHFS defect (folinic acid intolerance) - request for genetic data

[Lotus97]

Not sure if anyone is still looking into this but thought I'd add mine in. I don't know if I really have any negative affects from Folic Acid. I've never taken it in high doses but my serum folate levels have always been high which makes me think I have a hard time converting it.

I hope someone who understands this will be able to go over the data at some point. There are a lot of knowledgeable people here so it seems likely that this will be of some use in the future. Did you mean folinic acid or folic acid? This thread is about folinic acid aka calicum folinate or 5-formyltetrafolicacid and not the folic acid that is in most supplements. From what I understand, folic acid would cause problems for people with MTHFR (not MTHFS) and/or DHFR polymorphisms. It would be a good idea for everyone to limit or avoid their folic acid intake because it doesn't serve any purpose and could still have a negative impact on people even if they don't have MTHFR or DHFR polymorphisms. Folinic acid on the other hand has been found to be beneficial for most people, but since some people are unable to process folinic acid we're trying to find out how prevalent this problem is and which genes are responsible.

 

[Paula Thomas]

Folic Acid, Folinic Acid, Folate, it's hard to keep them all straight. I have eliminated all my supplements that contain folic acid already and only use the good ones that have 5-MTHF or L-Methylfolate. I'm not sure about folinic acid, I don't think I've tried taking that.

 

[BFG]

I've taken methylfolate(quatrefolic) and took it for a couple months wihtout problems. Then I coudn't tolerate it and started to develop pains in my head and after I discontinued it, the symotoms dissapeared. I want to try folinic acid in the future. Do you think I would be able to tolerate it with these genes?



MTHFS, ST20-MTHFS 80136129 rs685487 A or G AA
MTHFS, ST20-MTHFS 80136288 rs8033649 A or C CC
MTHFS, ST20-MTHFS 80137560 rs8923 C or T TT
MTHFS, ST20-MTHFS 80138571 rs2733103 C or T CC
MTHFS, ST20-MTHFS 80138745 rs16971427 A or C AA
MTHFS, ST20-MTHFS 80141997 rs655473 A or G AA
MTHFS, ST20-MTHFS 80144197 rs17284990 C or T TT
MTHFS, ST20-MTHFS 80154571 rs16971450 A or G AA
MTHFS, ST20-MTHFS 80154982 rs6495446 C or T CT
MTHFS, ST20-MTHFS 80158042 rs7177659 A or C CC
MTHFS, ST20-MTHFS 80158159 rs6495449 A or G AG
MTHFS, ST20-MTHFS 80162265 rs17285431 A or C AA
MTHFS, ST20-MTHFS 80164053 rs6495451 C or T CT
MTHFS, ST20-MTHFS 80165368 rs2586154 A or G GG
MTHFS, ST20-MTHFS 80168282 rs12899781 G or T TT
MTHFS, ST20-MTHFS 80171971 rs16971478 A or G AA
MTHFS, ST20-MTHFS 80172133 rs2586153 C or T CC
MTHFS, ST20-MTHFS 80174388 rs2562744 A or C AC
MTHFS, ST20-MTHFS 80177687 rs2733106 A or G AA
MTHFS, ST20-MTHFS 80178283 rs12438477 A or C AC
MTHFS, ST20-MTHFS 80182050 rs12898642 C or T TT
MTHFS, ST20-MTHFS 80183766 rs2586182 A or C AA
MTHFS, ST20-MTHFS 80184657 rs2733088 A or G AG
MTHFS, ST20-MTHFS 80186340 rs12440798 C or T CC

 

[Lotus97]

I've taken methylfolate(quatrefolic) and took it for a couple months wihtout problems. Then I coudn't tolerate it and started to develop pains in my head and after I discontinued it, the symotoms dissapeared. I want to try folinic acid in the future. Do you think I would be able to tolerate it with these genes?

I'm not sure if you'll be able to tolerate folinic or not because I don't think we know which SNPs that have problems. Very few people have tested whether folinic acid is a problem. Freddd and Nandixon seem to be the only ones for sure that have a problem and Freddd hasn't had his SNPs tested.

I am curious about your experience with methylfolate. Were you taking B12 with the methylfolate? If so, how much and what type of B12 were you taking? And how much methylfolate were you taking with it?

 

[adyia]

I'm hoping this posts with the formatting correctly. Here are my 23andme results, put thru genetic genie. I'm currently doing a modified version of Freddds protocol. In the past when I've used folic acid or folate (not the active form) in vitamins I respond very badly (flu like symptoms, sore throat, congestion). My recent lab results indicate I am "excessive" in folate...my conclusion is I haven't been processing dietary folate into it's active form, hence the build up in my system. The lack of active folate results in my B12 deficiency symptoms which landed me here in the first place. I'm doing much better on methylfolate. I have the MTHFR A1298C +/- mutation, so this makes sense.
From what I've read, my MTHFR mutation, along with the CBS C699T +/+, and BHMT-08 +/+ lead to BH4 (tetrahydrobiopterin) depletion, which can lead to mast cell activation disorder. Anyone else with this issue? How do I check on it, treat it, ect?
On Freddds protocol I feel better in some ways, but am still having problems. I just got my 23andme results 2 days ago, so hoping it gives guidance. The CBS homozygous is concerning, which I read can lead to excess sulfur and ammonia levels. This again makes sense, as I landed in the ER due to sulfa drug allergy in the past. And a face mask containing sulfur made my acne 100X worse. Also very sensitive to soaps and shampoos which contain sodium laurel sulfate. With all this in mind, I'll reduce the high sulfur foods in my diet and see if I notice a difference. Right now I eat lots of onions, cauliflower, cabbage and the like.
I do hope someone actually looks at all this data from everyone at some point! Right now I'm kinda shooting in the dark, and I know others must also be struggling.
Gene & Variation rsID Alleles Result
COMT V158M rs4680 AG +/-
COMT H62H rs4633 CT +/-
COMT P199P rs769224 GG -/-
VDR Bsm rs1544410 CT +/-
VDR Taq rs731236 AG +/-
VDR Fok-I not found n/a n/a
MAO A R297R rs6323 TT +/+
ACAT1-02 rs3741049 GG -/-
MTHFR C677T rs1801133 GG -/-
MTHFR 03 P39P rs2066470 GG -/-
MTHFR A1298C rs1801131 GT +/-
MTR A2756G rs1805087 AA -/-
MTRR A66G rs1801394 AG +/-
MTRR H595Y rs10380 CT +/-
MTRR K350A rs162036 AG +/-
MTRR R415T rs2287780 CT +/-
MTRR S257T not found n/a n/a
MTRR A664A rs1802059 GG -/-
BHMT-01 not found n/a n/a
BHMT-02 rs567754 CC -/-
BHMT-04 rs617219 AA -/-
BHMT-08 rs651852 TT +/+
AHCY-01 rs819147 TT -/-
AHCY-02 rs819134 AA -/-
AHCY-19 rs819171 TT -/-
CBS C699T rs234706 AA +/+
CBS A360A rs1801181 GG -/-
CBS N212N rs2298758 GG -/-
SUOX S370S not found n/a n/a
NOS3 D298E not found n/a n/a
SHMT1 C1420T rs1979277 GG -/-
Gene & Variation

 

[Lotus97]

adyia
So you haven't taken folinic acid/calcium folinate then? Folinic acid is a reduced form of folate (unlike folic acid), but some people like Freddd can't process it. Freddd also has a problem with dietary folate, but according to dbkita dietary folate isn't folinic acid:

Folinic acid is a 5-formyl derivative of THF. The folates in vegetables are not folinic or folic acid (a fully oxidized synthetic folate, i.e. pteroylmonoglutamic acid). This is a notorious misconception in the research community. The folates in food are metabolites of THF packed within polyglutamates. In the intestinal lumen these polyglutmate dietary forms are broken down into monoglutamate variants which can then be converted to DHF and then THF by their respective enzymes. The DHFR enzyme is not present in humans for the synthetic folic acid it is present for processing dietary folates. Folinic acid is readily converted to 5,10 methylene THF without use of DHFR. That being said dietary folates parallel more with folic acid than with folinic acid with one crucial difference ... they can be processed in the intestinal lumen and the liver. Folic acid (I am pretty sure) being fully oxidized must be converted in the liver.

I don't think this changes the fact that high dietary folates could be an issue for some people who can not make use of them, have intestinal wall damage, or critical needs for 5mthf but let's be honest while maybe garden feasts are not a good idea, it is not wise probably to eschew vegetables entirely as a general rule."

Technically that was a little strong in the sense that animal and plant cells will have folinic acid in them. Just like TH4, L5mthf (say in liver), or 5,10 methylene THF, etc. But the dominant form that is ingested as dietary folates is the natural, non-oxidized folate (folic acid is the oxidized, synthetic version that can only be processed in the liver). Again this is cleaved of most glutamates in the intestine and further reduced to DHF in the intestines or liver. From there DHFR takes it to THF.

 

[adyia]

adyia
So you haven't taken folinic acid/calcium folinate then? Folinic acid is a reduced form of folate (unlike folic acid), but some people like Freddd can't process it. Freddd also has a problem with dietary folate, but according to dbkita dietary folate isn't folinic acid:

Hi Lotus,
There is Calcium folinate in my multi (Thorne). I actually tolerate it well. Thorne is the only multi I found I can tolerate. Others (with other folate forms and who knows what else) give me the flu-like symptoms mentioned above. I also take a B-complex daily with 5-methlyfolate (Quatrefolic) (Swansons Ultra Activated B, the only B-complex which I could tolerate), and a separate pill from Methyl Life which is 5-methylfolate (Quatrefolic). It sounds like a lot of methyfolate, but I've been pretty careful to titrate up, and so far, so good. I've had some improvement in my overall energy levels and mood.
I also can't tolerate high amounts of veggies without serious bloating and digestive issues (and the consequent fatigue). I don't know if this is the same as Freddds problem with dietary folate, or perhaps my sulfur sensitivity. I've experiment with diet a lot, and still have not found what suits me. I'm about to try limiting sulfur rich foods (due to CBS mutation) and see if it helps.

 

[adyia]

Does Freddd have his genetic results posted anywhere? That would be extremely interesting, and perhaps useful to those on his protocol.

 

[Lotus97]

Does Freddd have his genetic results posted anywhere? That would be extremely interesting, and perhaps useful to those on his protocol.

Haha. Many people would like to know as well, but he hasn't had his SNPs tested.

There is Calcium folinate in my multi (Thorne). I actually tolerate it well. Thorne is the only multi I found I can tolerate. I also can't tolerate high amounts of veggies without serious bloating and digestive issues (and the consequent fatigue). I don't know if this is the same as Freddds problem with dietary folate,

Freddd said that folinic acid causes him more problems that dietary folate, but I'm not sure what dosages he's taken of each. Since calcium folinate is the same as folinic acid then I assume you don't have a problem with folinic acid. Are you taking the full dose? (500 mcg of calcium folinate/folinic acid).

or perhaps my sulfur sensitivity. I've experiment with diet a lot, and still have not found what suits me. I'm about to try limiting sulfur rich foods (due to CBS mutation) and see if it helps.

Someone said they had more energy after following a CBS protocol. A lot of this stuff is trial and error. It's sometimes difficult determining cause and effect.

 

[PennyIA]

Not sure if this helps or not, but I'll throw mine into the mix. I haven't tried folinic acid yet, but would be willing to try some in the near future if it would help.

MTHFS:
MTHFS rs685487 GG
MTHFS rs8033649 CC
MTHFS rs8923 TT
MTHFS rs2733103 CT
MTHFS rs16971427 AA
MTHFS rs655473 AA
MTHFS rs17284990 CT
MTHFS rs16971450 AA
MTHFS rs6495446 CC
MTHFS rs7177659 AA
MTHFS rs6495449 GG
MTHFS rs17285431 AA
MTHFS rs6495451 CC
MTHFS rs2586154 AG
MTHFS rs12899781 TT
MTHFS rs16971478 AA
MTHFS rs2586153 CT
MTHFS rs2562744 AC
MTHFS rs2733106 AG
MTHFS rs12438477 CC
MTHFS rs12898642 TT
MTHFS rs2586182 AC
MTHFS rs2733088 AG
MTHFS rs12440798 CC
SHMT1 rs1979277 AG

I have gotten sick from taking Folic Acid, B6 and B12 (cyano). And am currently taking methylfolate (not for very long, though). I'm not sure how well I'm tolerating the methylfolate. Some bad days, but not sure it's tied to it or not (wired, jittery, high blood pressure, but still tired). It could just be detox getting going.

 

[Lotus97]

Not sure if this helps or not, but I'll throw mine into the mix. I haven't tried folinic acid yet, but would be willing to try some in the near future if it would help.

I'm not sure if it will help you or not. As you can see, a small percentage of people have problems with, but this is why Rich recommends it:
===================================================================
Folinic acid is helpful for a couple of reasons. One is that it is very versatile, in that it can be converted to other forms of folate. Normally, folates are needed to make nucleotides, but the folate metabolism is dysfunctional in ME/CFS because of the partial block of methionine synthase and the methyl trap, which drains folate from the cells when this reaction is partially blocked. One of the main reasons for including folinic acid in the protocol is to help with the production of nucleotides until the folate metabolism has been restored. The nucleotides are important for making new DNA and RNA for new cells, and also for making ATP.

Best regards,

Rich

​

 

[PennyIA]

I'm not sure if it will help you or not.

Oh, actually I was thinking in terms of helping the identfication of genetic intolerance as opposed to helping myself. Sorry for not being clearer. I am working on adopting a protocol specified by my MD who is MTHFR-proficient (ish, well, I hope he's good at it, jury is still out). But if you needed more data points, I'd be ok with adding it as well, just to see if I do tolerate it. It was always on my personal list of going to try it if things don't improve at some point anyway - to see if it would help me personally.

 

[Lotus97]

Oh, actually I was thinking in terms of helping the identfication of genetic intolerance as opposed to helping myself. Sorry for not being clearer. I am working on adopting a protocol specified by my MD who is MTHFR-proficient (ish, well, I hope he's good at it, jury is still out). But if you needed more data points, I'd be ok with adding it as well, just to see if I do tolerate it. It was always on my personal list of going to try it if things don't improve at some point anyway - to see if it would help me personally.

From what Rich is saying in that quote, it sounds like folinic acid is less necessary once you get methylation going. I did hear dbkita and Triffd say that they need to take folinic acid for a certain SNP they have (even thought they've been doing methylation for a long time). There was also a study done on CFS patients with Epstein Barr Virus using a very high dose of folinic acid and most people benefited from it. It would be good to know who it's going to cause problems for though and I can understand why some people are afraid to try it.

 

[BFG]

I'm not sure if you'll be able to tolerate folinic or not because I don't think we know which SNPs that have problems. Very few people have tested whether folinic acid is a problem. Freddd and Nandixon seem to be the only ones for sure that have a problem and Freddd hasn't had his SNPs tested.

I am curious about your experience with methylfolate. Were you taking B12 with the methylfolate? If so, how much and what type of B12 were you taking? And how much methylfolate were you taking with it?

I was taking b12, b right b complex and methylfolate. The b12 was jarrows and I was taking mega dose at the time at 20mg/day, but have now gone down to 2.5-5mg/day. So with the methylfolate in the b-right and methylfolate i was taking 800 mcg. I don't know how much folate supplementation I need, as I eat a lot of veggies, but I don;t know what other things are going on ie infections, toxins etc.

I havn't found many folinic acid supplements online, but saw in a different thread you posted about your kids multi by health products distributor inc and found that they also have the best formula I've seen in a mini multi, without the megadoses of b vitamins, no fillers, folinic acid and some good cofactors, but not sure about the aspartate in the boron. I am going to try this mini-multi out and see how I do. Have you tried this mini-multi?
http://www.integratedhealth.com/hpdspec/mini-multi.html

 

[Lotus97]

I was taking b12, b right b complex and methylfolate. The b12 was jarrows and I was taking mega dose at the time at 20mg/day, but have now gone down to 2.5-5mg/day. So with the methylfolate in the b-right and methylfolate i was taking 800 mcg. I don't know how much folate supplementation I need, as I eat a lot of veggies, but I don;t know what other things are going on ie infections, toxins etc.

I was told that the amount of methylfolate in B right is only 50 mcg (the rest is folic acid). I actually saw a post earlier today about someone else getting a headache. I was curious if yours was caused by methylfolate specifically or just methylation in general. Methylation could release toxins and also cause inflammation for people with viral or bacterial infections. It could also be from CBS issues. Based on what dbkita said about plant folate it's unclear how much of it you're able to convert into the reduced forms. Why were you taking a high dose of methylcobalamin? Is that for neuropathy?

I havn't found many folinic acid supplements online, but saw in a different thread you posted about your kids multi by health products distributor inc and found that they also have the best formula I've seen in a mini multi, without the megadoses of b vitamins, no fillers, folinic acid and some good cofactors, but not sure about the aspartate in the boron. I am going to try this mini-multi out and see how I do. Have you tried this mini-multi?
http://www.integratedhealth.com/hpdspec/mini-multi.html

All of Thorne's b complexes and multis have folinic acid. I guess if you want mostly coenzymated b vitamins then the mini multi might be good, but you do know the amount listed is for 4 capsules? I think their Mighty Multi or Multi Two (dose for 2 tablets or 4 capsules) is a better value unless you're already getting b vitamins from a b complex (or want less copper) in which case I'd understand why the mini multi would be more desirable. I take all my minerals and vitamins separately (it's cheaper that way) so I ended up buying this b complex which also has only folinic acid (and was on sale)
http://www.myvillagegreen.com/pathway-b-complex-50.html
I'm also taking two of these later in the day along with a small amount of P5P and R5P:
http://www.swansonvitamins.com/swanson-condition-specific-formulas-fibro-essentials-90-caps

 

[BFG]

I was told that the amount of methylfolate in B right is only 50 mcg (the rest is folic acid). I actually saw a post earlier today about someone else getting a headache. I was curious if yours was caused by methylfolate specifically or just methylation in general. Methylation could release toxins and also cause inflammation for people with viral or bacterial infections. It could also be from CBS issues. Based on what dbkita said about plant folate it's unclear how much of it you're able to convert into the reduced forms. Why were you taking a high dose of methylcobalamin? Is that for neuropathy?

All of Thorne's b complexes and multis have folinic acid. I guess if you want mostly coenzymated b vitamins then the mini multi might be good, but you do know the amount listed is for 4 capsules? I think their Mighty Multi or Multi Two (dose for 2 tablets or 4 capsules) is a better value unless you're already getting b vitamins from a b complex (or want less copper) in which case I'd understand why the mini multi would be more desirable. I take all my minerals and vitamins separately (it's cheaper that way) so I ended up buying this b complex which also has only folinic acid (and was on sale)
http://www.myvillagegreen.com/pathway-b-complex-50.html
I'm also taking two of these later in the day along with a small amount of P5P and R5P:
http://www.swansonvitamins.com/swanson-condition-specific-formulas-fibro-essentials-90-caps

I was taking high doses because it was what was working for me to reduce my symptoms (which you can read here http://forums.phoenixrising.me/inde...king-for-help-and-guidance.18676/#post-298001).
The more b12 I took the better my symptoms became. Until I felt that taking that high of b12 was not helping anymore so I redcued it down to where it felt best. I also read fredd and others who took high doses and talked to a very great doctor in the UK, Dr. Chandy, who told me he would often inject very high doses of methyl b12 to his patients.

The multi two does look more cost effective, but I'm reluctant due to the aspartic acid in there. I don;t do well with aspartame. I also have the thornes b complex, but don't feel too well when I take very high doses of the b's, that why I was lookong for a multi with b's on the lower side.

 

[Lotus97]

I was taking high doses because it was what was working for me to reduce my symptoms (which you can read here http://forums.phoenixrising.me/inde...king-for-help-and-guidance.18676/#post-298001).
The more b12 I took the better my symptoms became. Until I felt that taking that high of b12 was not helping anymore so I redcued it down to where it felt best. I also read fredd and others who took high doses and talked to a very great doctor in the UK, Dr. Chandy, who told me he would often inject very high doses of methyl b12 to his patients.

Are you concerned that you're just treating the symptoms by taking large amounts of methylcobalamin? Rich has said that you need to take methylfolate along with B12 of a more lasting improvement. While it's true that Freddd advocates high doses of B12 he also recommends that methylfolate be taken with it and also has additional methyl donors in his protocol, TMG and SAMe.

I read your post from last September. Have you made any progress in determining the cause(s) of your illness? That's actually more important than anything else (including methylation). Many people have improved from methylation, but if you're not addressing the underlying causes then methylation will only take you so far. Some people do make miraculous recoveries and the majority of the people doing methylation do improve to some degree, but I think some people are expecting too much from methylation.

The multi two does look more cost effective, but I'm reluctant due to the aspartic acid in there. I don;t do well with aspartame. I also have the thornes b complex, but don't feel too well when I take very high doses of the b's, that why I was looking for a multi with b's on the lower side.

I don't know what dose is right for you. I wouldn't recommend doing anything that doesn't make you feel good, but I didn't think Thorne's b complexes were that high in b vitamins. I'm not sure how much of the amino acids in protein are utilized (so maybe the aspartic acid would cause you problems), but a scoop of protein powder has 2500 mg of aspartic acid for example:
http://www.iherb.com/MLO-Natural-Milk-Egg-Protein-Powder-16-oz-454-g/6704

 

[BFG]

Are you concerned that you're just treating the symptoms by taking large amounts of methylcobalamin? Rich has said that you need to take methylfolate along with B12 of a more lasting improvement. While it's true that Freddd advocates high doses of B12 he also recommends that methylfolate be taken with it and also has additional methyl donors in his protocol, TMG and SAMe.

I read your post from last September. Have you made any progress in determining the cause(s) of your illness? That's actually more important than anything else (including methylation). Many people have improved from methylation, but if you're not addressing the underlying causes then methylation will only take you so far. Some people do make miraculous recoveries and the majority of the people doing methylation do improve to some degree, but I think some people are expecting too much from methylation.

I don't know what dose is right for you. I wouldn't recommend doing anything that doesn't make you feel good, but I didn't think Thorne's b complexes were that high in b vitamins. I'm not sure how much of the amino acids in protein are utilized (so maybe the aspartic acid would cause you problems), but a scoop of protein powder has 2500 mg of aspartic acid for example:
http://www.iherb.com/MLO-Natural-Milk-Egg-Protein-Powder-16-oz-454-g/6704

Yeah I was also taking TMG but stopped. From time to time I test to see how I feel on it and I don't know why but it makes me feel wired.

I also agree with you that addressing methylation is only one part of the big picture and others things should also be addressed. I recently just got a new health plan and seeing a new pcp. He has diagnosed me last week with CFS according to the CDC guidelines and I have high EBV titers and mildy enlarged spleen. I also have signs and symptoms of a Connective tissue disease and ruled out marfans syndrome,, might need to rule out EDS. CBC has shown High Neutrophil, low lymphocyte count and low Monocytes. My pcp has sent out a refferel to Dr Chia in Torrence, but I think the wait is going to be 5-6 months. So in the meantime I'm trying to pursue testing with my pcp for SIBO, LEaky gut, Lyme, and see what I can do from here.

 

[Lotus97]

Yeah I was also taking TMG but stopped. From time to time I test to see how I feel on it and I don't know why but it makes me feel wired.

There's two different reasons TMG could make you wired. One is by increasing methylation, but also by stimulating the BHMT pathway can cause a greater amount of dopamine to be converted into norepinephrine. Just curious, which Thorne b complex were you taking? I mentioned earlier that I thought the amount of b vitamins were low, but if you were taking Thorne's #6 b complex that does have a lot of B6 and P5P.

I also agree with you that addressing methylation is only one part of the big picture and others things should also be addressed. I recently just got a new health plan and seeing a new pcp. He has diagnosed me last week with CFS according to the CDC guidelines and I have high EBV titers and mildy enlarged spleen. I also have signs and symptoms of a Connective tissue disease and ruled out marfans syndrome,, might need to rule out EDS. CBC has shown High Neutrophil, low lymphocyte count and low Monocytes. My pcp has sent out a refferel to Dr Chia in Torrence, but I think the wait is going to be 5-6 months. So in the meantime I'm trying to pursue testing with my pcp for SIBO, LEaky gut, Lyme, and see what I can do from here.

That's good news about the EBV. A lot of people here have EBV or similar herpes viruses. If you haven't checked it out yet, Phoenix Rising has an entire forum dedicated to antivirals, antibiotics, and immune modulators
http://forums.phoenixrising.me/index.php?forums/antivirals-antibiotics-and-immune-modulators.4/

 

[Hip]

in theory, P-5-P and zinc should increase the activity and quantity of SHMT. Too much vitamin A (not beta-carotene) may decrease it..

Nandixon, would you by chance have any references for this inhibiting effect of vitamin A on SHMT? I take 25,000 iu of vitamin A daily, and I am +/- for SHMT1 C1420T (my full genotyping results given here). I think I may stop taking vitamin A for a while, to see if this helps with my methylation cycle.