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

Discussion in 'Genetic Testing and SNPs' started by nandixon, Sep 3, 2012.

  1. Critterina

    Critterina Senior Member

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    Arizona, USA
    That's OK, Bluebell, I am. :rolleyes: I am crazy, that is. I just couldn't add my results by throwing them in a post. I have everyone's results in a spreadsheet except their tolerance or intolerance to folinic acid.
    Don't worry, but if you try folinic acid, let us know, because it may do some good in figuring this out. I think you may be right that it's more an SHMT1 issue than an MTHFS issue, but good data crunching will help.

    BTW, I am SHMT1 (+/+) (AA), unlike any of the others who have posted. And I'm
    rs7177659 AA like nandixon. So, if if either of these are the culprits, I should be most sensitive.

    So, now let me throw a wrench in the whole works. I took 800 mcg of folinic acid and the first day I thought "it can't possibly be this that's making me feel so good!" The second and third days I could hardly keep my eyes open. Not so much fatigue as almost narcolepsy (not really, but you get the idea.) Not being a informed as some of the people here, I've been following the AMRI website and was prepared that "energy production will falter" so I'd already planned to add L-carnitine, NADH, and ribose. The 4th and 5th days I did so, and didn't really have any trouble being overly sleepy. Today is the 6th day. I'm thinking the sleepiness may be coming back, but my allergies are so bad that it's hard to tell. For now, I'm saying I'm intolerant, but time will tell.

    Here's the file.
     

    Attached Files:

    nandixon likes this.
  2. Critterina

    Critterina Senior Member

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    merylg, did you ever figure out whether you were intolerant to folinic acid or if it was something else?
     
    merylg likes this.
  3. merylg

    merylg Senior Member

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    Sydney, NSW, Australia
    Sorry, no I never worked it out. I had to stop methylation protocols mainly because I became intolerant of B12 supplementation at any dose.
    I'm now having treatment prescribed by a LLMD & actually am on very few supplements. Any thing I try I will be running past him. He had me on Zinc picolinate but my stomach couldn't take that, so I stopped it. Apart from antibiotics & antifungal I'm only on Vit C 2x500mg, fish oil x 2, Prodophilus probiotic x 1 and Melatonin x 3 mg.

    I'd like to take some B1 Thiamine & B2 Riboflavin again, but I need to check with my Dr.
     
    Valentijn and Critterina like this.
  4. Critterina

    Critterina Senior Member

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    Thanks for your answer. I'm going to keep you as a 'maybe' on intolerance. Best wishes with your recovery!
     
    merylg likes this.
  5. Critterina

    Critterina Senior Member

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    The jury is still out. Wednesday I decided that I was intolerant. Thursday I stopped the 800 mch folinic acid and increased my MTHF from 2 mg to 3 mg. In less than 48 hrs my angular chelitis is back and my face has broken out. I'm going to give it a second chance, but at bedtime this time, when the sleepiness won't be a problem.
     
  6. HealthyCat

    HealthyCat

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    California
    I tried the SHMT spray as green shots recommended. I tried folinic acid and I couldn't tolerate it. The SHMT spray works great but it causes a very powerful detox. Dr Amy's site had verified this. The SHMT compound also causes a strong detox in folks with SHMT. The spray lets you take a smaller dose. Mind you, the recommended dose on the bottle is 5 sprays. I was doing that once per day for a week and it kicked off a strong detox.. I have only been able to tolerate one spray 2 X per day. If you can't tolerate that you can put one spray in water and sip it throughout the day.
     
  7. HealthyCat

    HealthyCat

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    Have you had your lithium levels checked. Dr Amy says having lithium levels in balance is key before adding in B12. There's a video on lithium on her site. They can be tested by blood or UEE.
     
  8. HealthyCat

    HealthyCat

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    California
    I tried the SHMT spray as green shots recommended. I tried folinic acid and I couldn't tolerate it. The SHMT spray works great but it causes a very powerful detox. Dr Amy's site had verified this. The SHMT compound also causes a strong detox in folks with SHMT. The spray lets you take a smaller dose. Mind you, the recommended dose on the bottle is 5 sprays. I was doing that once per day for a week and it kicked off a strong detox.. I have only been able to tolerate one spray 2 X per day. If you can't tolerate that you can put one spray in water and sip it throughout the day.
     
  9. rawcreamqueen

    rawcreamqueen

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    Bath, England
    As per my 23andme results as interpreted by livewello and mthfr support, i am normal/green for all SHMT snps but i am homozygous for MTHFS and hetero for a bunch of mthfr (mthfr a1298c and 5 other mthfr snps) and hetero for mtrr a66g, mtrr r415t, mtrr-11 a664a and 3 other mttr. i was going very slowly (titrating) on the dr rich protocol but could not add in methyl b12 nor 5mthr without getting very fatigued and down. i stopped those and stayed on 1/8th tab dibenzicode, 1000mcg perque hydroxy b12 and 200mcg megafolinic but the fatigue stayed and blues on and off came back. so i stopped all of those 3 days ago and don't know what to do!! i am hypothyroid(dxed by dr peatfield over here in uk 3 years ago) and was dxed chronic fatigue about 6.5 years ago, a year after getting MRSE and septicaemia (i was on rifampicin for 3months at home after the one month hospital stay). i feel i am 80% there in terms of health ....last year i felt i was 60% there. but very inconsistent still...and mood has been affected in the last 6 weeks or so and i cannot seem to tolerate 5htp (not even a small amount without getting really dissociative and depressed)..hence i turned to 23andme several months ago to see if that would give me further insight..been trying to read alot but difficult as brain fog came back while doing this methylation protocol!.but snps are difficult to interpret!! what should i be doing to be able to tolerate the b12 and the folinic /5mthr. i am comt +/- and vdr taq+/+ : per yasko i should be taking the 3 b12s with just a small bit of methyl b12. i have been on this methylation protocol about 2 months. prior to that i was cutting back oxalates as my snps suggest i had issues with oxalates (i also ate a very high oxalate diet for the last several years..) as per the yahoo group (low oxalate group). i had major dumping issues once i dropped my spinach and almonds....but better in the last week or so.

    i am on c.1.25grains of thyroid (thai thiroyd) a day, 1.5ml of ldn per night (that really helped my hashis when i started that in jan 2013). 1x thorne minerals , 1 x holistic health neurological health formula, 600mg mag citrate, 250mg liposomal vit c, 1 x drop of 5%lugols , 100mg selenium. and up to 3 days ago on some b12 and source naturals megafolinic. i am on 1/8th tsp progesterone cream per night (i am nearly 50). i cannot tolerate oestrogen supplementation - even smidges of otc creams without bloating/oedema even when i have shown very low in blood tests/saliva tests and when i had stopped my periods for 5 months this year and had low oestrogen symptoms. my basal temps are pretty normal as are my daytime temps.

    these are my methylation snps (i don't know how to upload my file!. sorry bear with me, first post!):
    hetero: ACE DEL16, ACAT 1-02, BHMT (x2 of these), BHMT 02, BHMT 04, BHMT R23Q, COMT, COMT H62H, COMT V158M, DAO, FOLR (x2 of these), FUT 2 (3 of these), GAD 1 x2, MTHTD1 C105T, MTHFR A1298C, MTHFR (x 5 of these), MTRR A66G, MTRR R415T, MTRR-11 A664A, MTRR (x3 of these), NOS 1, NOS 2, TCN 1, TYMS

    homoz: AGT m235t/c4072t, CBS A360A, GAD1 (x4 of these), MAO A R297R(livewello shows this as normal, mthfr/sterlings app shows this as homozygous), MTHFS, NOS 3 (x3 of these), PEMT, SLC 19A1 (x2 of these), VDR TAQ

    i am hoping for some guidance in terms of what to take and how to add in. in the fridge i do have nadh lozenges here, d ribose, dry form of vit e succinate, biocare b plex, fermented cod liver oil, dry form of vit a - just not taking them. i basically follow paul jaminet's perfect health diet (paleo with safe starches) for the last few years, am gluten free, drink raw milk and make my own raw milk milk kefir.
     
  10. Critterina

    Critterina Senior Member

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    rawcreamqueen,
    Congratulations on your first post! It sounds like you're not sure whether you're intolerant of folinic acid, since that's what you stayed on but the fatigue/blues remained.

    This is a pretty obscure place to ask for general help. I would recommend you start a new thread in this forum asking for input on your test results. If you need help doing that, I'm happy to help.
     
  11. HealthyCat

    HealthyCat

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    I have a mild familiarity with Dr Amy Yasko's protocal and I don't recognize some of those SNP's. Excuse my lack of knowledge. What's MTHFR x 5 of these, FUT, AGT. SLC? I was also on Jaminet's perfect health diet and I didn't do well on it. Too much protein. I am homozygous for CBS. I feel better when I eat grain and beans. Everyone is different. I just make sure I stay gluten free because gluten stimulates an autoimmune response in hashi's. It's probably a good idea for you to avoid it. The CBS RNA has been helpful for me. I take 3 drops 2 x a day. Go slow and don't ignore the steps. When I've pushed it, the supplements have made me ill. Dr Amy has her own version of a simplified protocal on her facebook page. It's excellent.
     
  12. rawcreamqueen

    rawcreamqueen

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    Bath, England
    thank you HealthyCat. I have dropped the protein to about 15- 20% of my daily total. i am still figuring stuff out - the snps are a minefield.....i used livewello and mthfrsupport for my 23andme results. i have read Amy Yasko - will re-read. my brain fog has gone!! i have been off the b12s and folinic since saturday. i don't know alot about Yasko's supplements bar the neurological health formula that i use (only 1 of those 5 days out of 7)- many seem very expensive over here in the UK! i have knocked out the very high and high oxalate foodstuffs/teas/supps out of my day - i didn't realise to go slow. i dropped my almost daily spinach and almonds immediately and was a 'rapid responder' - so have kept those out.

    Critterina. thank you! i will start a new post. i am trying to figure out how to attach my snp report so it will be easier for people to look at and give a broader picture rather than just post the mthfr snps. i am trying to understand the interplay - particularly with regards to the detox snps too and why my eyesight is total pants for the last 2 months in particular...
     
  13. HealthyCat

    HealthyCat

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    I haven't figured out how to attach my SNP's either. Your excellent diet is a great place to start. However, Dr Amy says diet alone is not enough to overcome SNP's. My experience tends to go along with that. Despite my excellent diet and lifestyle, I've had two forms of cancer.

    I'm wondering if the B12 was a methyl, because of your COMT status you would have trouble tolerating that. You also have to be careful of B5. There's a methyl form P5p. Luckily, you're +/+ on VDR taq and that helps moderate your methyl intolerance a bit.

    BHMT exacerbates CBS issues. BHMT is also your shortcut to methylation pathway. (Your short and long pathways have a number of blocks). The short is a good place to start. You might feel suprisingly good with the methylation support RNA (start with 1 drop a day, 1 time a day and if you feel okay go up to 1 drop 2 X a day) and 1 PC/PS/PE before bed. They work together. Vitaorgan would also help because you have so many BHMT SNP's. Dr Amy's supplements are expensive but the RNA lasts for months because you're only taking 1-3 drops 1 or 2 X a day, depending. Her supplements are excellent. I also find her prices are comparable or a little less with other supplements. For myself, I find getting well can be expensive but so was staying sick.

    Once again I recommend Dr Amy's simplified protocal. Here's a link http://www.scribd.com/doc/132017201/Dr-Amy-s-Simplified-Road-Map-to-Health Remember to go slow. It's better to titrate up than trigger a massive detox that overwhelms you and to try to figure out, what did it, and how to scale back. I know it can be hard to go slow if you have been unwell for a long time but this process can take 18 months or more. Dr Amy says it's a marathon, not a sprint and it's a roller coaster when you are in detox. I don't take all the supplements she recommends, everyone is different. But there's a reason she recommends them. You have to see how you do and sort through it. Do the steps, and get the tests that you can afford. They help a lot.

    PS I think I may have the ACE deletion too and opening up the shortcut aggravated it. I was kind of adrenaliney and my blood pressure went high, which isn't normal. I may have been generating to much aldesterone because of ACE. I started one oradrenal and one orakidney a day and that helped. Dr Amy also recommends stress RNA for that. I'm waiting for the results of a UTM/UEE test to figure out what's next in that regard. And also to see if my lithium levels are in balance so I start addressing the long route.
     
  14. rawcreamqueen

    rawcreamqueen

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    Bath, England

    thank you so much HealthyCat. i have been busy reading since getting home yesterday night after reading your reply. trying to comprehend the snps you mentioned better. i will definitely take your reminder on board. GO SLOW!!! i guess i should be grateful that i am a responder to all this as my bĂȘtes noires (of my CFS) have come back while on this protocol - particularly the depression, which had been gone for quite a while- practically all this year- reared its ugly head again on this methylation protocol. i have more tools now for dealing with this this time round...mindfulness techniques so luckily i get to practice them lots now!!!

    i will look into Dr Yasko's supps and i note you mention the methylation support RNA which she notes can be added in her simplified protocol although before i read that if one was could only afford one RNA dr yasko suggested to choose between the stress foundation one or the health foundation one rather than the methylation one...i don't know why and i don't understand how the RNAs work but i have read that people/people's children have been helped by them. the ingredients of the RNAs all look the same.

    i felt pretty good until mid afternoon yesterday. i had taken my neurological health formula (one) a few hours before. i don't know whether it was connected...i felt the heaviness come back (depression and slow thinking). i am planning to continue with the protocol.

    i will look into your recommendations and the simplified yasko v dr rich van K's - i was following his.

    really appreciate this as there is no one here that au fait with all of this.
     
  15. frenchmoxie

    frenchmoxie

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    Michigan
    I haven't taken a large dose of folinic acid, so I'm basing my symptoms off of the amount in the SHMT spray, which is around 50 mcg. I get extremely tired after using the spray, and so have to take it at night around bedtime. I'm thinking I might be intolerant to it.

    rs8923 15 80137560 TT
    rs2733103 15 80138571 CC
    rs16971427 15 80138745 AA
    rs655473 15 80141997 AA
    rs17284990 15 80144197 TT
    rs16971450 15 80154571 AA
    rs6495446 15 80154982 CC
    rs7177659 15 80158042 CC
    rs6495449 15 80158159 GG
    rs17285431 15 80162265 AA
    rs6495451 15 80164053 CC
    rs2586154 15 80165368 GG
    rs12899781 15 80168282 TT
    rs16971478 15 80171971 AA
    rs2586153 15 80172133 CC
    rs2562744 15 80174388 AA
    rs2733106 15 80177687 AA
    rs12438477 15 80178283 CC
    rs12898642 15 80182050 TT
    rs2586182 15 80183766 AA
    rs2733088 15 80184657 AA
    rs12440798 15 80186340 CC
    rs8033649 15 80136288 CC

    SHMT1
    rs1979277 17 18232096 AG
    SHMT2
    rs12319666 12 57624781 GG
    rs34095989 12 57627717 GG
     
  16. rawcreamqueen

    rawcreamqueen

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    I seem to tolerate folinic acid.

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

    SHMT1
    rs1979277 GG

    SHMT2
    rs12319666 GG
    rs34095989 GG

    I am still unable to tolerate even small doses of 5 mthf (1/8th tAblet of 800 mg metfolin ) without it leading to fatigue. Since I restarted the SMP (based on Dr Rich's protocol) I take 200 of folinic acid, 1/8 th of Adb12 sublingual and 500 mcg of sublingual OH B12. This week I am going to take these every other day as I am having issues with fatigue and mood swings from last week onwards.I don't think it's the folinic nor adb12 as I have held those doses steady. I did increase the OH b12 to 750mcg last week and was taking every day so maybe an issue as it converts to ME b12 in my system. I also feel that something is not right with my NDT dosage but i get issues when i lower below 0.875 grain. I also have gut issues - constipation for several weeks and now diarrhea, bloatedness. I had this when taking the MEb12 and 5mthf over the summer but with severe depression. I am looking at my detox phrase 1 and detox phrase 2 polymorphisms to see how I can improve that as they are definitely expressing! Does anyone know more about this area?
     
  17. Paula Thomas

    Paula Thomas

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    Could be the increase in B12. Hydroxy B12 made me have fatigue so I've been taking Adenosyl B12 instead and I seem to tolerate that better.
     
  18. rawcreamqueen

    rawcreamqueen

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    Bath, England
    Well I must get methyl folate from my diet(I eat medium and low oxalate diet based on paul jaminet's perfect health diet)..how much AD B12 do you take? Do you take 5mthf or folinic/both? I have no motivation, no zest for life and slight headaches, slight achy shoulders...I havent taken anything for 2 days (the b's I mean)
     
  19. Paula Thomas

    Paula Thomas

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    I use Holistic Health drops B12: 2000mcg and (6S)-5-Methyltetrahydrofolic acid 66.7mcg. That's 1 drop each in the morning sublingually.
     
  20. Journeyman

    Journeyman

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    I think its great that we can all pool our results together, in this new and relatively unexpolored/misunderstood field of nutritional genomics, to reach practical understandings that could make a huge difference in the quality of life for many here and those who will come searching for vital solutions in the future.

    My 23&Me results for MTHFS:

    MTHFS, ST20-MTHFS 80136129 rs685487 A or G AG
    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 CT
    MTHFS, ST20-MTHFS 80154571 rs16971450 A or G AA
    MTHFS, ST20-MTHFS 80154982 rs6495446 C or T CC
    MTHFS, ST20-MTHFS 80158042 rs7177659 A or C AC
    MTHFS, ST20-MTHFS 80158159 rs6495449 A or G GG
    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 CT
    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 CT
    Page 1 of 1

    I'm SHMT +/- with AG allele

    Now I know these posts are only as useful as your rating of observations following folinic acid intake, but even after careful observation I don't know if I am or not. Before I attempt to explain my existing observations I should let you know what I take: For a week now I've been on my new methylation protocol involving deadlock quartet components except using ALCAR instead of LCF as I'm still waiting on the LCF to arrive in the mail. That is:

    - Dr's Best Lithium Orotate (5mg/day since 8/11)
    - Solgar Metafolin (800mcg/tablet) x 4-5 tablets spread over the day (and kept separate from Vitamin C and potassium intake)
    - Enzyme Therapy sublingual MeB12 (2 x 1mg tablets in the morning and 1 in evening)
    - Anabol Naturals Dibencozide (half the capsule (5mg ADB12) in the morning and the rest in the evening (another 5mg)
    - Jarrow Sustain ALA (300mg x 2-3 times per day spread over the day)
    - Co-Q10 (mix of old generic brand I'm running out of (150mg/tablet) and new for a total of 300mg Co-Q10/day
    - Life Extension Foundation TMG (500mg) in the morning with the other components
    - LEF P-5P (30mg) - 1/3rd of their 100mg capsule in the morning and repeated in evening.
    - NOW Potassium gluconate (8 tablets a day spread over day and separate from the B12/Folate)
    - Zinc amino acid chelate (2 x 22mg in morning and evening) with 1 chromium picolinate (400mcg) in evening.
    General supps:
    - 1 x 500mg Korean Ginseng tablet standardised to provide 15mg of ginsenosides in the morning
    - 1 x Ginkgo Bilobo (6000mg - 28mg active) twice a day AM and PM
    - Calcium Citrate (3 x 250mg/day)
    - 2 x Saw Palmetto (each tablet standardised for 85% fatty sterols giving 128mg active ingredient) (ceased this as of morning of 10/11/13 to see if this has been the cause for my high fluid retention factor on a cellular health test and high Liver Function Test (AST in particular)

    So, to simplify the above: I think i've got a comprehensive methylation protocol with no gaps whatsoever? and I may be experiencing some detox from the months of Saw Palmetto intake that I've been on in the leadup to this point (Apparently it can cause liver issues in rare cases)

    So for two days now I've been feeling so tired in the morning that I've been having a 30-60min nap not long after breakfast which only involves half an apple, a chunk of freshly chopped pineapple, and 2 eggs with some mustard on top. I don't think this should contribute too much folinic acid (doesn't constitute a 'garden feast') as many term it.
    So I'm guessing the tiredness is due to the strong upramping of the methylation cycle as a result of the adB12/MeB12/3mg MeFol/TMG/ALCAR/ALA taken in the morning.

    For lunch I understand it should be the biggest meal of the day and so I have a meal based on a decent 200gm piece of meat with about 200gm of brussel sprouts and cabbage (steamed) which would supply an appreciable amount of dietary folates (I avoided saying folinic acid noting DBKita's useful post here: http://forums.phoenixrising.me/inde...ients-plus-biomarker.21745/page-6#post-344781

    I feel quite feeble after lunch, and one could be right in saying its because I've added all those dietary folates that my SHTM1+/- (AG) and MTHFS +/- (AC) is having trouble dealing with it resulting in folinic acid backcycle accumulation.. (thanks for this theory Nan Dixon) but after perusing this thread in great detail and some particularly pertinent comments from Lotus97 I realise that firstly we don't even know which allele of MTHFS or SHMT earnestly might cause a problem with dietary folates, and secondly, any symptoms which people are currently reporting as being 'folinic acid intolerance' might just as easily be overmethylation (which suggests the dietary folates are being processed just fine and so are contributing to the methylation cycle along with the existing methylfolates?)

    Whilst on this point I just want to clarify my understanding of dietary folates to date because it seems to cause an awful lot of confusion as to how they're processed. DBKita suggests that vegetables contain a bunch of THF's that are packed into polyglutamates. Tying this in with Lotus97's input: the SHTM1 related enzyme does the first stage of processing the THF to a DHF and then MTHF677 does the rest through its relation to the DHFR enzyme which converts the Dihidrofolate to methylfolate? Is this correct? I seem to recall Dr Lynch (MTHFR.net fame) video which tied in the MTHF677 defect to the DHFR problem which results in unmetabolised folates floating around...which will be highly relevant for any with the hetero or homo mutations and if we can confirm for sure that vegetable folate conversion invariably involves the use of the DHFR enzyme...

    I look forward to others contributing further to this thread so we can get some more clarity on this issue which has potentially important implications for all those looking to optimise diet and ensure their hard earned $$$ aren't being wasted on folate supplements...
     

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