• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of, and finding treatments for, complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia, long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

Opinions on Dr Lynch's comment regarding folinic acid and MTRR & MTR

juniemarie

Senior Member
Messages
383
Location
Albuquerque
Not sure what to make of Ben Lynch's statement regarding folinic acid. Has anyone with MTRR & MTR found folinic helpful?


"Methylfolate is needed to bypass the MTHFR mutation and folinic acid is needed in case there is any MTR/MTRR inhibition for any reason – along with other folate snps beyond MTHFR."
 

ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
I only have hetero MTRR, but folinic never helped me. In fact,, I've had to cut out my cooked green veg, as the veg folinic was blocking my methylfolate, creating adrenal stress. When I stopped the veg, my Mfolate need < from 25mg to 15mg/day.

Fred's just made this comment:
http://forums.phoenixrising.me/inde...n-protocol-what-should-i-do-next.31582/unread
I'm very sorry to say there is no "simplified" Active B12 protocol. However, it can be started in certain pieces. Let's look at the simplest way.

First, the Active B12 Protocol is based on maximizing the probability that a person gets healing started and eliminating, up front, all those things that might interfere. So for instance Folinic acid, just like folic acid, MIGHT be a cause for the whole thing not working....
 

juniemarie

Senior Member
Messages
383
Location
Albuquerque
But I have both MTRR & MTR and am +/+ for both of them. I think they must be having an impact, perhaps much more than MTHFR which I am only -/+. But its almost impossible to find much info on them. I find info about how they work and what they do in the process but thats about it. I eat no green veggies,hardly any other veggies so not getting any folinic at this time….just trying to understand these to SNP's Unfortunately Dr Lynch gave not explanation as to why???
 

juniemarie

Senior Member
Messages
383
Location
Albuquerque
OK Sorry I am not +/+ for both of those I am +/+ for 2 MTRR SNP's below is what Heartfixer has to say. I need read this carefully but it seems he suggests Hydroxy and Methyl B12
I would appreciate any explanations that may make his statement clearer to me. I have a hard time understanding this
stuff. My intuition tells me that I have been missing a piece of my puzzle and given that I have 2 of these seems like something I need to pay attention to.

MTRR: Methionine Synthase Reductase

A66G

 +/- (A/G)  +/+(A/A)

A substituted for G at site 66.

H595Y

 +/- (H/Y)  +/+(H/H)

H substituted for Y at site 595.

Function

Generates the Methyl-B12 used by MTR to convert 5-Methyl-THF into Methionine.

Findings

Homocysteine levels will likely be elevated.

Problem

Methyl-B12 cannot be generated to allow MTR to convert Homocysteine and 5-Methyl-THF into Methionine. Homocysteine toxicity will occur as well as impaired formation of S-Adenosyl Methionine (SAMe) such that methylation in general will be impaired

Treatment

1. Supplement with B12, Hydroxy-B12 if Methyl groups are in excess or Methyl-B12 if they are not, or a combination of the above.
2. Supplement the backdoor Homocysteine to Methionine pathway (via BHMT) with TMG (trimethylglycine), phosphatidylserine, or phosphatidylcholine. Avoid dimethylglycine (DMG) which would actually slow down the Homocysteine to Methionine conversion.

Monitoring

None except Homocysteine levels if elevated pre-treatment

Modifier

MTR – if abnormal will need even more B12, as this is an up regulation, increasing the demand for Methyl-B12 (see graphic below).

Modifier

COMT: if +/+ or +/- there will be delayed breakdown of Dopamine via Methylation so there will be extra Methyl groups available so we would tend to use Hydroxy rather than Methyl-B12
VDR Bsm/Taq: -/- is normal and allows for higher levels of dopamine and higher methyl group status, so here you would tend to use Hydorxy-B12, while +/+ VDR status leads to lower dopamine and Methyl status such that Methyl-B12 would be more appropriate than the hydroxyl-B12 form. So if you are (+) for COMT and (-) for VDR you will have high dopamine levels and lots of Methyl groups, while is you are COMT (-) and VDR (+) you will have low dopamine levels and lower levels of available Methyl groups so you would tend to use Methyl-B12 to help overcome the defect in MTRR.
 

ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
@juniemarie
confused-3316.gif
 

juniemarie

Senior Member
Messages
383
Location
Albuquerque
As to other suggestions he makes I can add phos/choline/serine. Tried TMG So what exactly is he saying in regards to VDR status. I am +/- for that. Does something to dopamine. All I know is if I throw my system off balance I get dark depression
 

caledonia

Senior Member
Not sure what to make of Ben Lynch's statement regarding folinic acid. Has anyone with MTRR & MTR found folinic helpful?


"Methylfolate is needed to bypass the MTHFR mutation and folinic acid is needed in case there is any MTR/MTRR inhibition for any reason – along with other folate snps beyond MTHFR."

I have MTR/MTRR. I tolerate folinic ok. Technically, folinic is involved in the folate cycle not the methionine cycle (where B12 is), so I'm not sure why he's saying that.
 

caledonia

Senior Member
OK Sorry I am not +/+ for both of those I am +/+ for 2 MTRR SNP's below is what Heartfixer has to say. I need read this carefully but it seems he suggests Hydroxy and Methyl B12

He's actually talking about COMT here. He's saying, to take B12 for MTR/MTRR (in general), but take hydroxy if you have COMT and are sensitive to too many methyl groups (causing mood swings).
 

caledonia

Senior Member
As to other suggestions he makes I can add phos/choline/serine. Tried TMG So what exactly is he saying in regards to VDR status. I am +/- for that. Does something to dopamine. All I know is if I throw my system off balance I get dark depression

The latest suggestion for BHMT (is that what you're referring to?) is to take sunflower lecithin which contains phosphatidylcholine and will convert to TMG. The sunflower is used to avoid soy. Direct TMG supplementation might be too much.

VDR taq works with COMT to affect dopamine, which can affect mood.

If VDR Bsm has mutations that could affect vitamin D levels, so supplement with D3 if you're low. Low D can affect mood.
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
Modifier

MTR – if abnormal will need even more B12, as this is an up regulation, increasing the demand for Methyl-B12 (see graphic below).
I was following you up to this point. Yes, MTR is an up-regulation. Does it become deactivated earlier/sooner because of the mutation? I have never seen anyone suggest that. Evidence please? Theoretically, it could, or it could have no effect or the opposite effect. What I would suspect is that it increases the requirement for methylfolate. Of course, if it's limited by the availability of MB12, you'd have to take that into consideration

BTW, I tolerate folinic acid with my MTR +/- and MTRR +/+. At first it made me extremely sleepy, but then it didn't. I decided that it was not a good supplement for me due to my MTHFR A1298C. With that SNP, I have less BH4, and taking folinic acid only uses up BH4.

Also BTW, phosphatidyl serine (choline, etc.) will make low adrenal function worse. So that has to be taken into consideration.

Cheers!
Crit
 

Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
It apparently decreases already-low cortisol, which can lead to or increase insomnia and hypoglycemia and other symptoms or low cortisol.
 
Messages
10
I also have MTR/MTRR mutations and am hopeful that this could be the cause of a lot of my fatigue-related issues. It sounds like our bodies are attempting to function on almost no B12 at all without tons of supplementation.

Question: How much b12 & folate are people taking/finding success with? Based on my research, it sounds like we need at least 20K mg of B12 p/day. Does that sound right? How are people dividing their doses between the different kinds of B12 and folate?

2nd Question: Also, there was a lot of talk above about forms of folate other than methylfolate impacting people negatively. Are people with MTR/MTRR mutations more likely to have issues with this or no? (I'm curious b/c I'm currently on the Simplified Yasko Protocol and am taking supplements w/multiple types of folate. I have not tried taking just methylfolate yet...)

Finally, I noticed recently that the Sunflower Lecithin I bought to avoid soy and Phosphatidyl Serine happened to have Phosphatidyl Choline in it - which has probably been draining my already low adrenals. :( Yet another potential pitfall to look out for.

PS - Glad to find some other MTR/MTRR + people to compare notes with!
 

xena

Senior Member
Messages
241
I am mtrr ++and do well with Folinic and food folate.. ... I think maybe because the mtrr doesn't regenerate thf fast enough to drive NOS? Not sure but definitely do better with both