Ema's 23andMe Results for Comment.

[Ema]

Valentijn - Hopefully this will work!

Thanks again...Ema

 

[Valentijn]

Valentijn - Hopefully this will work!

Looks good. Well, the file, not the results
The COMT results mean you're somewhat slow breaking down dopamine and the related neurotransmitters. Nothing too extreme though, and your MAO is normal, which should help a bit.

VDR is the usual problems making dopamine. Vitamin D and moderate methyl supplementation may help.

MTHFR is only effecting methylfolate production a little. Supplementing a little is probably okay, but you need to watch out for an excess of methyl groups. SHMT is also slowing down the production of methylfolate, as well as folinic acid. So it might help to throw some folinic acid into the mix.

MethylB12 might be a bit more of a problem, due to MTRR being downregulated somewhat in producing methylB12, and MTR being upregulated a bit in using up methylB12. So again, some supplementation of methylB12 might help, but be alert for a bad reaction if you do try it.

CBS looks pretty normal, which means you're processing homocysteine via the cysthionine pathway at a normal rate. But your BHMT is highly defective, meaning homocysteine can't be recycled back into methionine if necessary. AHCY may be helping by slowing down your production of homocysteine, and it doesn't sound like it should cause any problems itself. But it's probably a good idea to keep an eye on your homocysteine levels, in case a problem does pop up.

So vitamin D and folinic acid should help, and careful and moderate use of methylfolate and methylB12 may also help.

 

[Lotus97]

MTHFR is only effecting methylfolate production a little. Supplementing a little is probably okay, but you need to watch out for an excess of methyl groups. SHMT is also slowing down the production of methylfolate, as well as folinic acid. So it might help to throw some folinic acid into the mix.

MethylB12 might be a bit more of a problem, due to MTRR being downregulated somewhat in producing methylB12, and MTR being upregulated a bit in using up methylB12. So again, some supplementation of methylB12 might help, but be alert for a bad reaction if you do try it.

Ema was taking pretty high doses of both B12 and methylfolate with Freddd's protocol so I'm curious what her response was. I assume she was able to tolerate it otherwise she would have lowered her dose (?)

Part of the reason I'm curious is because I found a recent post from Rich about how he found that SNPs weren't always a good indicator of how a person reacts to methylation supplements. I'm planning to start a thread about that, but I haven't decided whether to start it in the SNP forums or the methylation forums.

 

[Ema]

Thanks Valentijn!

I wondered about that too, Lotus97. I did take a reasonably high dose of both mB12 and methylfolate and didn't have any issues. I have lowered them now though just because it seemed enough.

I started out at 8-10000 mcg of mB12 and 800 mcg of methylfolate (+800 mcg methyfolate from my B Complex) and stayed there for about a year. I'm taking 5000 mcg of mB12 now and only 400 mcg of methylfolate.

I did have issues with Deplin. I wasn't able to tolerate even a half tablet of Deplin without getting anxious.

So is folinic acid a better choice for me than the methylfolate? I don't get any of that at all in my supplements.

I never did very well with SAMe though. I think that is another methyl donor?

It's interesting about dopamine since things that affect dopamine generally seem to make me feel better. But maybe that is true for everyone? So the VDR indicates problems making dopamine but the COMT indicate issues breaking it down? Wouldn't that mean that I have more hanging around? I would have sworn I have less than average.

My homocysteine levels so far have been pretty low at 4-5. But apparently that is an issue as well at least according to this guy. I've never tested my urine sulfate. But I also don't think a vegan diet is beneficial for anyone. I wonder why they suggest cutting back on sulfur? I wonder if that includes magnesium sulfate (ie epsom salts) since I use those nearly every night.

For Low Homocysteine: Individuals with a low homocysteine level like mine usually have high levels of sulfate in the urine. You can test your own urine sulfate at home by using the simple “dip stick” strips manufactured by the Merck Company based in Germany (not to be confused with the U.S. pharmaceutical company Merck). A 100-strip container of the Sulfate (SO42-) Test can be purchased for $55 from Holistic Health International.

Low homocysteine and high urine sulfate suggests that you would also benefit from changing to a primarily vegan diet and cutting back on foods rich in sulfur compounds. To the extent you can, you should also limit drugs and nutritional supplements that contain large amounts of sulfur.

Read more: http://www.drsinatra.com/the-untold-truth-about-homocysteine-1#ixzz2UoaXPv5b

 

[Lotus97]

Thanks Valentijn!

I wondered about that too, Lotus97. I did take a reasonably high dose of both mB12 and methylfolate and didn't have any issues. I have lowered them now though just because it seemed enough.

I started out at 8-10000 mcg of mB12 and 800 mcg of methylfolate (+800 mcg methyfolate from my B Complex) and stayed there for about a year. I'm taking 5000 mcg of mB12 now and only 400 mcg of methylfolate.

I did have issues with Deplin. I wasn't able to tolerate even a half tablet of Deplin without getting anxious.

Isn't the lowest dose of Deplin 7.5 mg? So even half would have been much higher than your normal dose. And which brand of methylcobalamin are you taking now? (since Jarrow's is no longer any good).

I never did very well with SAMe though. I think that is another methyl donor?

Yes. SAMe is a methyl donor. So is choline, TMG, betaine hcl (same as TMG except for the hcl), phosphatidylserine, and phosphatidylcholine. Lecithin has choline and phosphatidylcholine. Most multis and b complexes also have choline. Also, B2/R5P and B6/P5P aren't methyl donors, but they are involved in folate metabolism so they will increase methylation.

So is folinic acid a better choice for me than the methylfolate? I don't get any of that at all in my supplements.

Methylfolate is what's needed for methylation. Most people can convert some folinic acid into methylfolate so theoretically a person could do methylation with only folinic acid, but since we don't know how much it would good to take methylfolate regardless of whether or not you're also taking folinic acid. Some people have a problem with folinic acid (although Rich thought is wasn't very common). It sounds like Rich is saying folinic acid is less necessary after you've been doing methylation for awhile (although dbkita said something about possibly taking folinic acid for his SNP even though he's been doing methylation a long time so maybe there are other reasons to take folinic), but I really don't know any more than what Rich is saying here:

Folinic acid is a buffer or storage form of folate that can be converted to other forms readily in most people.
The reason for including it in the simplified methylation protocol is that it can supply forms of folate needed to make new RNA and DNA while the methionine synthase enzyme is still running its reaction slowly. This reaction is fed directly by methylfolate, but until it goes through the reaction to produce tetrahydrofolate, it can't be used for forming other folates.

In order to use folinic acid a person must have a normally functioning MTHFS enzyme (not the same as MTHFR). If this enzyme is slow for genetic reasons, folinic acid can build up. and that will inhibit the SHMT reaction, which in turn will inhibit the normal production of MTHF, which in turn will hinder formation of DNA and formation of methylfolate.

According to Freddd, he cannot tolerate folinic acid, and there seem to be some others who can't, also. It would be helpful to pin down what SNP or SNPs are responsible for this.

Best regards,

Rich

There's more information about folinic acid in this thread:
http://forums.phoenixrising.me/inde...d-intolerance-request-for-genetic-data.19168/
(from Nandixon)

In January, Rich asked people to share their 23andMe results for the MTHFS gene to see if we can sort out which SNP or SNPs may be detrimental in ME/CFS. I didn't see where anyone responded. (You can find your MTHFS results by going to https://www.23andme.com/you/explorer/ and logging in and entering "MTHFS" for the gene name.)

It's important people contribute so we can try to figure out when folinic acid should be supplemented or avoided for certain people as part of a methylation protocol.

I may be intolerant to folinic acid (seems to cause exacerbation of fatigue, irritation of taste buds) and so am providing my DNA results. We need MTHFS results from as many other people as possible, though, whether intolerant or not.

If you could also include the one SHMT result that Yasko tests for, that may be helpful also. I'm heterozygous (AG) for that SNP (SHMT1 C1420T rs1979277), and the first day I took folinic acid it helped, as might be expected, but then I seemed to gradually get worse over several days (800-1600 mcg/day).

Below are Rich's personal MTHFS results with mine next to his in parentheses (he volunteered to be the DNA "standard"). At the time Rich was tested, 23andMe only gave results for 22 SNPs. They gave 24 for me. (36 are known?) There was only one instance of a flip in homozygosity between Rich's results and mine, rs7177659, and I discuss it after:

We're not likely to be so lucky right away that rs7177659 is the "bad" SNP, but it's interesting because having the hetero version (AC) for that SNP actually seems to be "normal" (58% frequency according to openSNP) and apparently results in a 29% decrease in cardiovascular disease risk compared to the homo versions (AA/CC). (This is from a May 2012 publication: http://jn.nutrition.org/content/early/2012/05/28/jn.111.157180.abstract - I don't have access to the full text; it's not mentioned in the abstract.)

So with respect to that SNP it might be that I have a detrimental down-regulation of MTHFS and Rich has a detrimental up-regulation (or vice versa). A down-reg would cause a build up of folinic acid and thus inhibition of SHMT (and several other enzymes outside the methylation cycle as well) and create an intolerance to supplementation. An up-reg can cause an increased turnover rate and depletion of cellular folate. Note: The C allele - what Rich has two copies of - is the ancestral (wild type) allele according to the NCBI data page.

Hopefully, if enough people contribute, we can figure out which SNP(s) is/are problematic. Thanks!

 

[Valentijn]

I did take a reasonably high dose of both mB12 and methylfolate and didn't have any issues. I have lowered them now though just because it seemed enough.

It's hard to guess really what the effect will be when things are adding an unknown amount of weight to both sides of the scale. Just that one result says methyl- might help, and the other result suggests some caution, because we don't really know to what extent each SNP is affecting each process. So if it helps, it's probably safe to take it, but because of the other results it's good to be on the lookout for adverse reactions, especially with higher doses.

I started out at 8-10000 mcg of mB12 and 800 mcg of methylfolate (+800 mcg methyfolate from my B Complex) and stayed there for about a year. I'm taking 5000 mcg of mB12 now and only 400 mcg of methylfolate.

I did have issues with Deplin. I wasn't able to tolerate even a half tablet of Deplin without getting anxious.

Deplin is a huuuge amount of methylfolate. More than ten times the normal amount, which seems pretty extreme considering your MTHFR results aren't that bad, and even the SHMT is just heterozyous.

So is folinic acid a better choice for me than the methylfolate? I don't get any of that at all in my supplements.

Your results indicate you might benefit from having both. But normal supplementation is probably enough, without any need for megadosing.

I never did very well with SAMe though. I think that is another methyl donor?

Yup, and it also breaks down into S-adenosyl-homocysteine (SAH), which has to be processed via CBS or BHMT. And your BHMT doesn't work, so you might be either 1) overloading the CBS processing and getting an excess of homocysteine or 2) getting too many toxic byproducts at once from properly processing the homocysteine via CBS. So it might be the extra methyl groups that are the problem, but since methylB12 wasn't a problem when you supplemented high doses, the homocysteine and/or its byproducts seems a more likely culprit.

It's interesting about dopamine since things that affect dopamine generally seem to make me feel better. But maybe that is true for everyone? So the VDR indicates problems making dopamine but the COMT indicate issues breaking it down? Wouldn't that mean that I have more hanging around? I would have sworn I have less than average.

Like with the methylfolate issue, it's a balancing act, and we don't get to see that much detail. Just that there's a problem sitting on either end, with no real idea of which problem is bigger. If you tolerate the methyl sources and feel better with things that increase dopamine, methylB12 can be one way to help raise dopamine.

My homocysteine levels so far have been pretty low at 4-5. But apparently that is an issue as well at least according to this guy. I've never tested my urine sulfate. But I also don't think a vegan diet is beneficial for anyone. I wonder why they suggest cutting back on sulfur? I wonder if that includes magnesium sulfate (ie epsom salts) since I use those nearly every night.

I agree regarding the diet. Meat is quite necessary, especially if there's any problem using carbohydrates or fats for producing energy. The sulfur recommendation is due to homocystiene breaking down to create even more sulfur-based products and ammonia via the CBS action of the cystiathionine pathway. In cases where that pathyway is overactive, the sulfur products and ammonia can build up. Your CBS results are pretty close to normal though, so if you are upregulated in processing homocysteine via the cystiathionine pathway, it's to a pretty mild extent - so I doubt radical dietary changes are required, so long as you're careful about avoiding things that can raise your homocysteine levels.