5-MTHF Methylation question

[cobbiemommy]

OKay..... After doing my research, DS has a variant of H109R on the LETM1 gene. This means he has an inborn defect of dimethylglycine dehydrogenase (DMGDH) which has to do with folate and the binding of histadine to arginine. The end result is that the body does not methylate properly.

 

There are prescription forms of L5-MTHF available at dosages that are 99% absorbed. These can be in doses from 7.5 mg to 15 mg. Until that time, we are going with a supplement purchased online. The big question is for those who have went before me...What dosage??? Do you ramp up or just jump right in on whole dose?

 

Secondary to that, at what point did you see benefits???

 

While I am not happy there is a genetic issue, I am kind of happy to know there is a possible treatment.

 

Have a good night!

Cobbie

[Hopeny]

LLM has posted pretty extensively on this and there is lots of good info on the board if you search her posts. Her advice per her research and Yasko was to start very small, if I recall 400 MICROgrams. I was giving DD (9, 67 pounds) 5 MG and it seems it may have brought back compulsive skin picking. After reading the most recent posts on this I dropped down to less than 1 MG and skin picking greatly diminished (maybe 80-90%) gone. my DD has 677T one copy. My advice would be to go LOW....

[LNN]

I'm confused. If your DS doesn't have a MTHFR mutation, why would you supplement with methylfolate? If his MTHFR is normal, his body is able to convert/methylate folate into methylfolate on its own. This isn't where his methylation roadblock is. So adding more methylfolate into the system could possibly produce symptoms of over-methylation.

 

I don't know anything about LETM1. But what you're describing is the Krebs Cycle (aka the ammonia cycle) and the BH4 cycle, not the MTHFR cycle.

http://www.google.com/imgres?imgurl=http://www.dramyyasko.com/wp-content/uploads/2010/06/diagram.png&imgrefurl=http://www.dramyyasko.com/diagrams-listing/&h=524&w=703&sz=207&tbnid=GweZCjMXEoeinM:&tbnh=88&tbnw=118&zoom=1&usg=__PzsVr1NdSbtnDDpOc4yKjbTOEX8=&docid=3BsVKWnakbowUM&sa=X&ei=mckHUfKjE4PO0QGVkYGADQ&ved=0CDUQ9QEwAQ&dur=377

(I so wish I could insert the picture and not just a link)

 

There are 4 cycles involved - think of 4 cogs of a clock, with interlocking sprockets. The cog on the far left is the Krebs/ammonia cycle. This involves eliminating ammonia/urea from the body and has something to do with energy production, tho I've not studied this circle in any detail. The next cog is the BH4 cycle. Arginine is involved where the Krebs cycle interacts with the BH4 cycle. The BH4 cog is where the body uses DMG/TMG/BH4 to convert tryptophan into serotonin and tyrosine into dopamine. These seem to be the two cycles you'd care about with the LETM1 issues you describe.

 

The third cog from the left is the folate cycle. This is where MTHFR is involved, converting folate into methylfolate and then joining forces with methylB12. From there, you move to the 4th cog - the Methionine or "methylation" cycle to create ATP (cell energy) and homocycsteine (which later gets converted into cycteine, then combines with B6 to eventually create glutathione for detox). While the 4th cog is sometimes called the "methylation" cycle, the entire process actually involves many, many methylation processes and methylation also occurs in many other processes in the body. So sometimes the term methylation is used in a broad sense and other times it's used to refer to a very specific cycle. Gets confusing.

 

Anyway, my confusion is that I don't see where you'd supplement with methylfolate if your roadblock was in the first two cogs. Those cogs require proper methylation of arginine, nitros oxide, BH4, TMG/DMG, tryptophan, tyrosine, and probably others I'm not familiar with.

 

However, if your doctor wants you to try methylfolate, I'm not trying to suggest I'm any expert or give medical advice. If you opt to supplement with methylfolate though, absolutely build up rather than jump in at a high dose. Yasko and Ben Lynch (mthfr.net) use 400 MICROgrams as a rough end goal for children and 800mcg for adults. But it's very individual. My DD only needs 67micrograms of methylfolate every other day. More than that and she gets angry, sad, anxious, has rapid mood cycles, oppositional - not pretty. I think she'd be locked up if we tried to give her milligrams of the stuff, let alone 7.5-10 mgs. Because she needs such a low dose, we use Yasko's methylmate B, which comes in drops, so you can adjust doses much easier. One drop = approx 67mcg. Others here use a combo that has both methylfolate + methylB12 - Thorne's Methylguard I think. But since I need the liquid in order to do such a low dose, we use the methylmate B drop of methylfolate plus 1000mcg of methylB12 sublingual tablet. As a general rule, you should always supplement both methylfolate plus methylB12 - they need each other.

 

Hope I didn't confuse the issue for you.

Edited January 29, 2013 by LLM

[cobbiemommy]

I'm confused. If your DS doesn't have a MTHFR mutation, why would you supplement with methylfolate? If his MTHFR is normal, his body is able to convert/methylate folate into methylfolate on its own. This isn't where his methylation roadblock is. So adding more methylfolate into the system could possibly produce symptoms of over-methylation.

 

I don't know anything about LETM1. But what you're describing is the Krebs Cycle (aka the ammonia cycle) and the BH4 cycle, not the MTHFR cycle.

http://www.google.com/imgres?imgurl=http://www.dramyyasko.com/wp-content/uploads/2010/06/diagram.png&imgrefurl=http://www.dramyyasko.com/diagrams-listing/&h=524&w=703&sz=207&tbnid=GweZCjMXEoeinM:&tbnh=88&tbnw=118&zoom=1&usg=__PzsVr1NdSbtnDDpOc4yKjbTOEX8=&docid=3BsVKWnakbowUM&sa=X&ei=mckHUfKjE4PO0QGVkYGADQ&ved=0CDUQ9QEwAQ&dur=377

(I so wish I could insert the picture and not just a link)

 

There are 4 cycles involved - think of 4 cogs of a clock, with interlocking sprockets. The cog on the far left is the Krebs/ammonia cycle. This involves eliminating ammonia/urea from the body and has something to do with energy production, tho I've not studied this circle in any detail. The next cog is the BH4 cycle. Arginine is involved where the Krebs cycle interacts with the BH4 cycle. The BH4 cog is where the body uses DMG/TMG/BH4 to convert tryptophan into serotonin and tyrosine into dopamine. These seem to be the two cycles you'd care about with the LETM1 issues you describe.

 

The third cog from the left is the folate cycle. This is where MTHFR is involved, converting folate into methylfolate and then joining forces with methylB12. From there, you move to the 4th cog - the Methionine or "methylation" cycle to create ATP (cell energy) and homocycsteine (which later gets converted into cycteine, then combines with B6 to eventually create glutathione for detox). While the 4th cog is sometimes called the "methylation" cycle, the entire process actually involves many, many methylation processes and methylation also occurs in many other processes in the body. So sometimes the term methylation is used in a broad sense and other times it's used to refer to a very specific cycle. Gets confusing.

 

Anyway, my confusion is that I don't see where you'd supplement with methylfolate if your roadblock was in the first two cogs. Those cogs require proper methylation of arginine, nitros oxide, BH4, TMG/DMG, tryptophan, tyrosine, and probably others I'm not familiar with.

 

However, if your doctor wants you to try methylfolate, I'm not trying to suggest I'm any expert or give medical advice. If you opt to supplement with methylfolate though, absolutely build up rather than jump in at a high dose. Yasko and Ben Lynch (mthfr.net) use 400 MICROgrams as a rough end goal for children and 800mcg for adults. But it's very individual. My DD only needs 67micrograms of methylfolate every other day. More than that and she gets angry, sad, anxious, has rapid mood cycles, oppositional - not pretty. I think she'd be locked up if we tried to give her milligrams of the stuff, let alone 7.5-10 mgs. Because she needs such a low dose, we use Yasko's methylmate B, which comes in drops, so you can adjust doses much easier. One drop = approx 67mcg. Others here use a combo that has both methylfolate + methylB12 - Thorne's Methylguard I think. But since I need the liquid in order to do such a low dose, we use the methylmate B drop of methylfolate plus 1000mcg of methylB12 sublingual tablet. As a general rule, you should always supplement both methylfolate plus methylB12 - they need each other.

 

Hope I didn't confuse the issue for you.

Thank you LLM, and this is why I should stick to History and not try medicine! I was interpreting what I read in the wrong way, but it makes a lot more sense this way. Our appt is not until mid March and I thought I would get a head start on the research. (Bad plan) I will go back and slowly reread about the Kreb's cycle...

 

I hope I can pick your brain in the future...

 

Sincerely,

Cobbie

[Hopeny]

Llm I just saw that methyl mate has rosemary in it. We had a dog that actually developed seizures from rosemary in food so I completely avoid it. I am going to try the Thorne version. I need to read all of your posts and get my head around this. My dd has LOW glututhiaone as i recall from testing so I need to think through all of this and discuss with Dr O on our next consult.

[LNN]

Hope - thanks for the rosemary tip. Something I'll have to keep in the back of my mind. Ironically, DD is having an EEG tomorrow - she had a strange clonus reaction a few weeks ago - probably from too much cold medicine - but she also had a febrile seizure 3 yrs ago (also due to antihistamine the minute clinic told me to give her when she really had the flu). So doing the EEG to make sure there's no underlying problem. Not that an every other day drop of methylmate is giving her a high amount of rosemary, but still good to have in my mental library of strangely connected things.

 

Let me know what dr O has to say. Jealous...

[Hopeny]

Hope - thanks for the rosemary tip. Something I'll have to keep in the back of my mind. Ironically, DD is having an EEG tomorrow - she had a strange clonus reaction a few weeks ago - probably from too much cold medicine - but she also had a febrile seizure 3 yrs ago (also due to antihistamine the minute clinic told me to give her when she really had the flu). So doing the EEG to make sure there's no underlying problem. Not that an every other day drop of methylmate is giving her a high amount of rosemary, but still good to have in my mental library of strangely connected things.

 

Let me know what dr O has to say. Jealous...

I googled the Rosemary thing for humans because of the dog history and found a link http://www.epilepsy.com/epilepsy/alternative_oils. I knew Eucalyptus and camphor were a problem but now see all of these can be an issue. I think it just takes a minute amount, it is used as a preservative in dog food. I am pretty surprised that Yasko has it in that supp given the target audience. Hope the EEG goes well.

[LNN]

Very interesting site you sent me to. They also mention ephedrine as a problem, which is what we've seen from giving her antihistamines when she's recently had a fever. She takes an antihistamine daily for allergies but when she gets something more often for a cold/flu, she's had clonus issues. If the EEG comes back with abnormalities (they wouldn't give me any info after the test - have to wait for the dr to call next week), I'll have to switch to Lynch's product http://www.seekinghealth.com/liposomal-b12.html which is also in drops. His is 50mcg/drop. Wonder how I'll give 1.5 drops??

[Hopeny]

The drop thing always seems a little uncertain so I guess you can use a healthy drop . In doing some research on quercetin I believe it has antihistamine properties, may not be strong enough though. I am going to try 50 mcg. My dd is definitely better with much less.