Invest in ME Conference 12: First Class in Every Way
OverTheHills wraps up our series of articles on this year's 12th Invest in ME International Conference (IIMEC12) in London with some reflections on her experience as a patient attending the conference for the first time.
Discuss the article on the Forums.

MTHFR, SHMT and folinic acid?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by PeterPositive, Jan 13, 2014.

  1. PeterPositive

    PeterPositive Senior Member

    Messages:
    1,426
    Likes:
    1,033
    Hello,
    I am in need of a little help from the experts here, since I still can't wrap my head around all of the information I've found here.

    I have the MTHFR C699T +/+ mutation and SHMT1 +/- for which folinic acid is recommended (e.g. heartfixer, yasko). On the other hand folinic acid is not recommended for MTHFR by Dr.Lynch and others...

    I am not sure what to do. At the moment I am only using methyl-folate. (800mcg). I also have hetero MTR / MTRR double-whammy combo which might benefit from folinic acid.

    What do you recommend?

    Thanks
     
  2. Critterina

    Critterina Senior Member

    Messages:
    1,202
    Likes:
    700
    Arizona, USA
    @PeterPositive ,

    I think you're doing well to use the methylfolate instead of the folinic acid. I'm not sure that the MTR/MTRR will benefit from folinic if you also have the MTHFR C677T. Ask @Valentijn - she knows the research about how the MTHFR C677T and SHMT combination work and can point you to it.
     
    Last edited: Jan 14, 2014
  3. Freddd

    Freddd Senior Member

    Messages:
    4,940
    Likes:
    1,475
    Salt Lake City
    Hi PeterPositive,

    I would suggest that you do trials and find out for yourself how your body reacts rather than believing anybody's theories. If there is a noticeable difference then you need to figure out what that means. If it makes no difference at all you will save yourself all sorts of worrying. Doing alternating trials for several repetitions will make the difference obvious if there is a difference. You may not have any difference until some other supplements are on board. For instance, if you get increased folate deficiency symptoms on one and low potassium on the other the difference is obvious. If you get both low potassium and increased folate deficiency symptoms you also have an answer. If all you get are more deficiency symptoms on both and nothing else, the 'question' needs to be asked differently because the symptoms are paradoxical. The one you can be sure of is that methylfolate doesn't block methylfolate whereas folinic acid may block methylfolate or may work well and cause donut hole paradoxical folate deficiency. If you get increased folate deficiency symptoms on both on a low dose they may be of different causes. So a number of trials may be needed to distinguish which one can get healing going for you. If healing gets started on one and stops on the other you have an answer. Remember, results can appear contradictory because healing can start on some levels and have worse deficiency effects on other levels.
     
  4. Valentijn

    Valentijn Senior Member

    Messages:
    14,281
    Likes:
    45,812
    Do you mean MTHFR C677T or CBS C699T? The Yasko CBS SNPs do little or nothing and can be ignored, but MTHFR C677T would mean that methylfolate is much more effective than other forms of folate.
     
    Gloria H likes this.
  5. Valentijn

    Valentijn Senior Member

    Messages:
    14,281
    Likes:
    45,812
    Actually the information regarding MTHFR C677T is "science". It's been thoroughly researched and is known to cause specific problems, which can be dealt with in straight-forward ways. No guesswork needed: if it's +/+, then gene activity is at 30% of normal.
     
    flitza, SOC and Gloria H like this.
  6. PeterPositive

    PeterPositive Senior Member

    Messages:
    1,426
    Likes:
    1,033
    Thanks to all.
    Sorry, I wrote the wrong gene position, it is indeed MTHFR C677T +/+

    Sure, this is clear.
    The question is that methylfolate will not address the SHMT1 issue, if I understand it correctly. Hence the need for extra folinic acid. Unless it is "incompatible" with the supplementation of methylfolate, which it's not clear to me.

    I will experiment with a small dose, e.g. 200mcg and keep an eye on symptoms and homocysteine values.

    Thanks
     
    Last edited: Jan 14, 2014
  7. Freddd

    Freddd Senior Member

    Messages:
    4,940
    Likes:
    1,475
    Salt Lake City
    If it were as effective a "science" in it's interpretation as you imply people would be getting much better results. So what results should they get if they follow the advice based on this one thing. What are all the effects of having this and how does it allow pinpointing the protocol that produces people well along the road of healing.

    How about coming up with a protocol based on this and doing a 1 year A-B comparison with crossover for those not having substantial recovery at the end of the first year. Better yet let's use the 3 months that Rich suggested as plenty long to determine if what the person is doing is working well.

    I have seen nothing to suggest that other in the science of being able to produce this information bit that there is any effective science in it's application. Where are all the healing people?

    The only definitive way to tell which folate and cobalamin combinations are going to work for person x taking into account all of the person and their multitude of genetic differences is are several trials. THEN the person knows what works best for them, not according to somebody's hypothesis. Let's collect the data on results from people and apply some analysis.

    A person can start something and 3 months later decide that they are not having the predicted results and trying something else, yes, science include predictions and comparing results. Not just untested hypothesis. That type of design where the protocols are switched are called A-B crossover designs.

    Most hypotheses never make it as far as an established and validated theory. Hypothesis is a starting point. Then comes trials and analysis. Then comes modification of hypothesis. Then comes trials and analysis and modification of hypothesis. So were are the results and analysis. Of the people basing their protocol on this hypothesis how many will be approximately ready to start rehabilitation in a year?

    So why not explain the full protocol based on this hypothesis and trot out a bunch of people that have healed far enough to start rehabilitation via the specified protocol?
     
  8. Freddd

    Freddd Senior Member

    Messages:
    4,940
    Likes:
    1,475
    Salt Lake City
    Hi Peterpositive,

    Unless of course folinic acid causes you paradoxical folate deficiency which you can certainly find via a trial. Doses that are too small, like 200mcg can cause paradoxical folate deficiency if it is effective causing donut hole folate deficiency or because it blocks methylfolate. Or it does nothing in particular because of insufficient effective B12 or lack of other needed cofactors. It's not a trial that will produce you any useful answers and will leave things just as muddled afterwards
     
  9. Critterina

    Critterina Senior Member

    Messages:
    1,202
    Likes:
    700
    Arizona, USA
    Peter,

    When I was researching the biochemical pathways involved with the SHMT +/+ mutation, what I understood was that the SHMT keeps you from effectively converting folic acid to folinic acid - there are actually two steps in that reaction. So you can take folinic acid to compensate for the slow conversion from folic acid, but you still need to convert the folinic acid to methylfolate - the job of the C677T that is at 30% efficiency if you are +/+. So I can't see how taking folinic acid really would help you, since you're C677T +/+.

    I also found that there is another pathway with the serine-glycine conversion, that I don't really remember that well. It seemed to me that SHMT +/+ shouldn't be that big a problem because of this second pathway. But, as Valentijn points out, there is research to say that it's a problem if you are C677T compromise. There is no research on the combination I was interested in: SHMT and MTHFR A1296C. If you come across any studies about it, please pass it on!
     
  10. PeterPositive

    PeterPositive Senior Member

    Messages:
    1,426
    Likes:
    1,033
    Ok, thanks it makes sense.
    In other words we could say that folinic acid doesn't add any value if one is already taking methyl-folate? Is this correct?

    I guess my post originates from my lack of understanding in what role plays folinic acid in the body besides getting ultimately transformed into methyl-folate. If it's just one of the intermediate steps in the transformation then I guess using the end product is definitely the best idea.

    Thanks everyone for your help
     
    Critterina likes this.
  11. Critterina

    Critterina Senior Member

    Messages:
    1,202
    Likes:
    700
    Arizona, USA
    Peter,

    There are other pathways that folinic acid plays a role in. I just don't remember what they are. A good biochemistry textbook will be a good help. I have a second edition Lehninger (if I remember correctly, but I'm in a hotel and my texbook is at home). I'm sure later ones are better, but I like the style and explanations in that one.
     
    flitza likes this.
  12. kelly138

    kelly138

    Messages:
    95
    Likes:
    14
    folinic acid is used to form purines - don't ask me what that means or what they area but just a piece of info that has wandered in and out of this brain recently
     
    Critterina likes this.
  13. Freddd

    Freddd Senior Member

    Messages:
    4,940
    Likes:
    1,475
    Salt Lake City
    Hi PeterPositive,

    In other words we could say that folinic acid doesn't add any value if one is already taking methyl-folate? Is this correct?

    Yes. L-methylfolate is necessary and sufficient. Folinic acid is not necessary or sufficient for many. One of the posts by Rich described the pathway deriving all folate needs from l- Methylfolate. Where it is I don't know, but it was one of the posts not too long before his death. And of course, if a person can't use folinic acid they also can't use folic acid. Good Health.
     
  14. kelly138

    kelly138

    Messages:
    95
    Likes:
    14
  15. knackers323

    knackers323 Senior Member

    Messages:
    1,268
    Likes:
    358
    Is folinic acid needed by some?
     
  16. PeterPositive

    PeterPositive Senior Member

    Messages:
    1,426
    Likes:
    1,033
    Thank you.
    In this paper about folate metabolism:
    http://users.umassmed.edu/martin.marinus/Mph200/FolicAcidMetabolism.pdf

    there's a quick recap for each form in the reaction

    folate.png
    It would be correct to assume that supplementing only with methyl-folate would skips the "purine biosynthesis" step of the folinic acid. Of course the latter may also come from the diet, but with an SHMT1 mutation the conversion from DHF to folinic is not working well.
     
  17. Sea

    Sea Senior Member

    Messages:
    1,268
    Likes:
    2,650
    NSW Australia
    Looking at the diagram of the folate cycle that you linked to, the methylfolate is recycled and goes through the cycle again which is when all of the other forms and reactions would happen
     
  18. rubydragon

    rubydragon

    Messages:
    14
    Likes:
    4
    Peter, did you trial the folinic acid, and have you noticed any improvement with it, if so?

    The Yasko protocol I ran on my daughter (+/+ MTHFR A1298C and +/+ SHMT2) recommends starting it as a 1st level priority, before even adding in B12 and methylfolate. (Note: It is VERY difficult to trial these things on someone else's body!!)
     
  19. PeterPositive

    PeterPositive Senior Member

    Messages:
    1,426
    Likes:
    1,033
    I didn't because I see most people here don't recommend it for the C677T++ mutation. My doc also wanted me to use methylfolate. So that's what I am using now.

    Aslo I take a sublingual B complex every 2-3 days that has all active Bs and has a bit of folinic acid in it, 120mcg. So indeed I am taking a small dose of it. Doesn't seem to cause any troubles.

    I certainly have seen a difference between folic acid and methyl-folate. My homocysteine was going up with folic acid, now it's finally, slowly dropping.

    Probably your daughter doesn't have high Hcy levels, since A1298C doesn't seem to interfere much with that.
     
    rubydragon likes this.

See more popular forum discussions.

Share This Page