Mehtylation for Dummies

[LNN]

I started this on the lyme forum in response to someone who wished there was a "Methylation for Dummies" they could read. It's by no means the whole picture but maybe it will explain why I think it's been so helpful for my family...

 

Methylation Diagram"]Methylation Diagram[/url]

 

Ok, this is very rough and my explanation may not be perfectly correct in the true medical sense, but I took the diagram Yasko and others use and added some comments in red.

 

My comments are aimed at the C677T mutation of the MTHFR gene. I don't have as much knowledge on how the A1298 mutation effects everything, because no one in my family carries it and also because there's way less written about it. But I wanted to try to explain why knowing if you have a MTHFR gene mutation matters to a Pandas or lyme kid. (it also matters to people with a family history of heart disease, stroke, macular degeneration or history of miscarriages, but I'm not getting into all that).

 

The thing that effects our kids the most are neuropsych and detox issues. Our kids tend to have problems with seratonin and/or dopamine, both of which are shown on the circle I numbered #3. You can see that the MTHFR gene plays a role in how your body synthesizes tryptophan into seratonin and tyrosine into dopamine.

 

On the far right circle, where I have #1, you see how MTHFR plays a role. MTHFR is what makes folate (the inactive form of B9) into methylfolate (the bioavailable/active form). At the point in the circle where you see homocysteine, your body uses methylfolate and methylB12 to recycle homocysteine into SAMe, which in turn gets turned into seratonin (it also does other things but seratonin is the part I'm highlighting).

 

If B6 (the active form is P-5-P) is present, MTHFR also influences how much homocysteine gets converted into cycsteine, which then gets synthesized into glutathione (among other things). Glutathione is the master detox agent.

 

You'll also see (at the bottom of the circle on the right) sulfite. This is where the transsulfuration pathway starts. It too plays a role in detox. But I don't know enough to speak about it intelligently. I mention it as a starting point for your own research if you struggle with sulfa drugs like bactrim.

 

There are many other genes - some known and studied, some not - some you can test for commercially, some not - that influence these circles. MTHFR is not the be all and end all for helping your kid to stop being crazy. But this illustrates why some of us have found good results when we supplement with methylfolate and/or methylB12. Since MTHFR converts folate into methylfolate, if you have one mutation on C677 (heterozygous), your body only does this conversion at about 40-60% efficiency. If you have two mutations of C677 (homozygous), you only do this conversion at about 10% efficiency. So you can see where you'd have trouble making enough seratonin and/or dopamine. You might also struggle to make enough glutathione, which becomes in high demand during periods of infection, mold illness or other stressor on the immune and detox systems.

 

An SSRI (which can help some kids) only makes your existing seratonin last longer in the synapse between your neurons. Bypassing a faulty MTHFR gene by supplementing with already-converted methylfolate helps your body create more seratonin to begin with. Be aware that if you're using an SSRI or supplementing with tryptophan or maybe even melatonin, you may need to reduce or eliminate these other things as time goes on. I learned that the hard way this summer. I didn't reduce tryptophan and was giving too much methylfolate and ended up with a crazed, evil, bipolar child.

 

Treating MTHFR is like being the little Dutch boy and plugging one hole in the dike. If it's your only leak, it can work wonders for getting the cycles working properly again. if you have other leaks (other gene mutations) than other steps might also be needed.

 

Hope this helps.

[dcmom]

Thanks LLM- I will have to reread this a few times.

 

As you might know, I have two pandas kids- one has one copy of this mutation (hetero) and the other does not.

 

My question is how you think this relates to pandas- which is where I get stuck. Our pandas symptoms generally recede completely when well, and return with illness. If the body was not detoxing, it would make me think there would always be symptoms present. Or is it that the body needs to detox when sick?

 

Does homocysteine level play into this for you? In other words, from my quick reading it seems homocysteine could be normal (it is in my dd) but there could still be an issue down the line.... is this how you see it? (I know the homocysteine levels are used a lot in the evaluation of heart disease/ stroke risk).

 

Thanks!!!

 

(I have been considering trying to supplement with methylfolate- but I am stubbornly resistant to supplements....)

[LNN]

I don't think methylation is the only thing at play in Pandas kids. I don't think if you bypass one known gene mutation that you've cured Pandas. I suspect my DD will still be susceptible to issues when she gets sick. But I do think that if you have this mutation, there's an extra strain on things like your body's ability to produce enough glutathione, enough SAMe, especially when illness puts demands on some of the things that are produced by methylation. There just isn't enough to go around. So for my DD, supplementing with methylfolate (a small amount), it helps increase the supply of important materials in the system.

 

There's something written here http://mthfr.net/mthfr-mutations-are-more-than-high-homocysteine/2011/09/20/ about why using homocysteine levels isn't necessarily the right benchmark.

 

Yes, I do think the body needs to detox more when sick. Glutathione removes damaged cells as well as toxins released by bacteria. You have macrophages that are eating up bacteria like little pac men and then need to be eliminated from the body. So illness would certainly increase your need for glutathione. Methylfolate, combined with methylB12, encounters homocysteine and one of two processes occurs: that homocysteine is either recycled in the methylation cycle back into methionine and then SAMe (which then becomes seratonin) OR it converts homocysteine into cysteine which then gets converted into glutathione. Well, if your body needs more glutathione during illness, then it's pushing more of the methylfolate/methylB12 down the pathway that leads to more glutathione, potentially leaving a shortage of methylfolate/methylB12 on the other pathway that creates SAMe (and also creates ATP - which is cell energy - which could be why you feel so tired when you're sick - not enough methylfolate/methylB12 to satisfy both pathways). This is one reason why docs will give methylB12 shots to lyme patients who are chronically tired.

 

So should you supplement your DD? You need to follow your gut. I personally think that not supplementing with a low amount of methylfolate for my own DD and myself is playing Russian Roulette. The incidence of heart disease, stroke and macular degeneration are extremely high in my family tree. To know that we have a genetic defect that we can bypass - I feel obligated to do what I can in that regard, Pandas or not. I think I'd be supplementing methylfolate regardless of whether it helped DDs behaviors, just out of a sense of protecting her from future health risks. But I'm also big on orthomolecular medicine and supplements. So that's my personal bias. I can't say it should be everyone's answer.

[Dedee]

Thanks LLM for your constant assistant with this complex issue. As you know we recently started with Lyme treatment. My daughter is having extreme herxing and this week-end was a whirl wind of rages and mood swings. I believe her MTHFR / methylation issues have something to do with how bad her herx reaction is. I am trying to detox as much as possible. Practically kept her in an epson salt bath for hours in the evenings. But as you know, when she relapses, one of her symptoms is her issues with taking medications. So it has been really hard just to get her to take what she is supposed to much less other detoxing agents. She is drinking lots of lemon water and I am able to get motrin in twice daily. I am hoping this herx will ease up soon.

 

Anyway, thanks again for all the helpful information.

 

dedee

[dcmom]

Thanks LLM- that helps.

 

We have our semi annual visit to Dr T coming up, and I will discuss this issue. And the possibility of supplementing.

 

Having two pandas kids who have had an almost identical course of illness, makes me question the relationship of MTHRFR to pandas for us- however I have read up on the other issues this can cause in the future, so I am interested in being sure to prevent them (if necessary). In my family tree, everyone has been really healthy! But, my husband's side does have a history of stroke. I think it would be interesting/ helpful to test my husband and myself to see which of us carries the gene. If he does, it would certainly seem like a possible smoking gun. If I do, well, I might become more skeptical

 

I have become a bit of a "chicken" in the last year (with pandas). Things have been great, or under control, for the most part so I am always afraid to "rock the boat".

 

But I do appreciate your patience with explanations and reasoning. I am not trying (in any way) to challenge you- just figure this out for my kiddos.

[LNN]

E - No, I don't feel "challenged". I respect your reluctance to rock the boat and I also know your kids have much better diets than mine. So I think it's an individual decision influenced by a number of personal factors. It would be interesting to test your DH. If he has a mutation, using a supplement could potentially lower his stroke risk. It's one of those insurance things - you'd likely see "nothing" as a response. But silently, he could be dodging a bullet.

 

Dee- you may want to contact your LLMD and talk about ways to reduce the abx - maybe fewer days per week (sometimes abx are taken 2x/week or some sort of on/off rotation) or maybe a lower dose? It's one thing to push thru a herx of muscle pain or anger. But when it interferes with her ability to take meds, it might be time to back down or go slower. You might also ask about alpha lipoic acid or resveratrol to help with detox once she's past her pill issue. Keeping you in my thoughts...

[norcalmom]

LLM,

Speaking as the Dummy that asked for it -Thank you!! It was very generous of you to post the diagram and explain it. I was reading Singleton's "The Lyme Disease Solution" last night and he mentioned something that I could get my head around regarding this - and motivate me enough to care enough to invest the time to really read your diagram and try to understand it.

 

If you aren't Lyme - don't dismiss this. It has to do with chronic infection of any kind.

 

Natural Killer Cells (a key component of the immune system) need glutithione to function. They cannot perform without it. Without high levels of NK cells, your immune system is disabled, and leads to inability to fully clear infections. There are things that lead to less glutithione production (see LLMs comments on MTHFR mutations) and things that enhance it. So in addition to helping with clearing toxins, and regulate seratonin, proper functioning mythylation helps the bodies immune system kill off infection (because good amounts of glutithione = better production of NK cells = better ability to clear infection). So for those of you (like me maybe?) that are trying to figure out if they should care about detox or mutations, if our kids have recurring or chronic infections, maybe we should care.

 

So, I may still be a Dummy, but things are starting to click. Thanks for beating the drum LLM. Its starting to get through my thick skull!

 

PS - singleton states that acetminophin is horrible for glutithione. (along with alcohol and smoking..I assume our kids aren't doing that) . Since many of us use anti-inflatories, I thought I'd just mention that you may want to use something other than Tylenol if you have the option.

[LNN]

Norcal - I'm glad you're starting to put pieces together. My passion for methylation is that not everyone will have the same issues, but somewhere along one of these 4 circles, you may very well find something that's been your road block and you may see a way to build a detour. For you, it might very well be along the transsulfuration pathway and glutathione/oxidative stress. For one of my kids, it revolved around B6 (which also plays a role with glutathione) and zinc (the immune system's bullets). For the other kid, it was MTHFR.

So I don't beat the drum because I have "the" answer. It's just that understanding this diagram offers so many possibilities to explore that could give you "aha" moments.

 

You can find some good Youtube videos on methylation and oxidative stress that explain it better than I can.

 

BTW - your comment on tylenol and glutathione - one of the worst pieces of advice my former pediatrician ever gave me was to give tylenol after a vaccination to help with any crankiness. Tylenol reduces your ability to detox the aluminum, thimerasol, etc that can come with a vaccine. Don't want to get into the whole vaccine issue on this thread, but if you do vaccinate, never give tylenol afterward.

[mdmom]

Thanks LLM - you are one smart cookie. I had to dig deep for my pre-med undergrad brain to understand even a smidge of the diagram. But I have Lyme brain that often makes it impossible to wrap my head around anything besides dispensing pills these days

 

In your opinion, why don't you hear more on this forum about supplementing with IV glutathione? My non-PANDAS daughter (she's Lyme and co-infections) was tested through Great Plains Lab and found to have a very low glutathione level (lowest the LLMD had ever seen) so we started supplementing with 1x/week 5ml glutathione. I cannot tell if it is helping and the doc doesn't think we should test levels again right now.

 

My PANDAS/Lyme son is low too, but not as low as my daughter and unfortunately I had to choose only one child to try the glutathione on - it's $95 per dose.

 

I know you posted a few weeks back about over-methylation issues. How does one know if there is too much of a good thing?

[LNN]

Thanks LLM - you are one smart cookie. I had to dig deep for my pre-med undergrad brain to understand even a smidge of the diagram. But I have Lyme brain that often makes it impossible to wrap my head around anything besides dispensing pills these days

 

In your opinion, why don't you hear more on this forum about supplementing with IV glutathione? My non-PANDAS daughter (she's Lyme and co-infections) was tested through Great Plains Lab and found to have a very low glutathione level (lowest the LLMD had ever seen) so we started supplementing with 1x/week 5ml glutathione. I cannot tell if it is helping and the doc doesn't think we should test levels again right now.

 

My PANDAS/Lyme son is low too, but not as low as my daughter and unfortunately I had to choose only one child to try the glutathione on - it's $95 per dose.

 

I know you posted a few weeks back about over-methylation issues. How does one know if there is too much of a good thing?

No pre-med background for me. I was a communications/art/business major, so take my interpretation of medical issues with a healthy bit of skepticism and always run it by your doc or your own research. I've been known to make mistakes now and again.

 

As for IV glutathione, it's something I see a lot in lyme land and even in regular integrative discussions. I just don't think the Pandas docs are tuned into detox issues. Methylation is not a big focus in conventional medicine (outside of cancer circles) and it's only with the progress of DNA mapping in the past decade that something like MTHFR is even starting to be understood. Just my personal opinion, but I think by looking at Pandas as autoimmune (and I'm not saying it isn't), it sorta leads you to look at things in terms of shutting things off, at suppression. My big "spiritual awakening" on methylation and my own experiences treating my kids has convinced me that - for my kids - supporting the body's systems has been more helpful than suppression. So if, when my son was in a bad place, we'd been able to do IV Glutathione, way back before we'd been bled dry by medical expenses, to do it over again, I'd jump at the chance to do IV Gluthathione. I just don't think it's an idea that's well understood in conventional medicine yet (but I do think it's changing and I think the more that parents bring these idea into the doctors' offices, the more parallels are found between ASD lyme and Pands, the more it will start to be discussed). JMHO

 

For your son, you can research glutathione precursors. My son takes alpha lipoic acid during herxes to help in this regard. But there are other things you can use too.

 

As for too much of a good thing - probably true in all aspects of life. For my daughter, when the things that had helped were suddenly not helping at all, it was a clue that we'd tipped the scales. I think it you do a dose of something and it works for awhile and then you start thinking maybe you need to increase, maybe also ask if you need to actually decrease. This is true for SSRIs in our kids. I think it's probably true for other things too. It's making me much more methodical and "scientific". X is supposed to make Y happen. I didn't get the response I expected. Why? There's always a reason why.

 

Just FYI - my DD had worked up to 800mcg of methylfolate and 500mg tryptophan. After we stopped supplements to do the urine test and her bipolar stopped almost in its track, she took a 1 week holiday and she improved each day. But at the end of the week, the scale started tipping and mood swings started to come back, not as severe, but there. So I broke the "no supplelents" drought and gave her 200mcg of methylfolate (but no tryptophan). We tweaked for a week and now she seems to be stable if we do 200mcg methylfolate every other day, no tryptophan. During times of stress or illness, this may change. So I now use her behaviors to guide. I know this must make me sound like a complete nut, playing mad scientist with my kid. I do have my LLMDs input but even he concedes that it's all so highly individual and will change day to day based on health, diet, seasonal environment, stress - that you try to find that spot where the body gets just enough - s spot that's never in the exact same place one day to the next. I am trying to evaluate our supplements and only use what's necessary. But what that means changes sometimes. Funny, the more I learn, the fewer absolutes I find. I'm having to become much more comfortable with shades of gray (and I don't mean the books!)

[Kiera]

LLM Thanks for all the great info. Really that chart looks like MTHFR for "Rocket Scientists!!" LOL! One quick question, when finally getting on the right supplementation to treat the MTHFR, broadly speaking, do you know how long it takes to correct the deficits? And for those taking psych drugs, at what point could we consider lowering them as the supplements kick in? Tx.

[LNN]

LLM Thanks for all the great info. Really that chart looks like MTHFR for "Rocket Scientists!!" LOL! One quick question, when finally getting on the right supplementation to treat the MTHFR, broadly speaking, do you know how long it takes to correct the deficits? And for those taking psych drugs, at what point could we consider lowering them as the supplements kick in? Tx.

 

You might find some good answers to some of this on www.mthfr.net. He's a doctor - I'm so, so not!

Yasko talks about seeing a very brief honeymoon and then something akin to a herx response. But she's vague about time frames.

Rich Van Konyenberry also writes a lot about methylation and chronic fatigue. You can google his stuff and see if time frames are discussed. I know he did a research study that spanned 4-6 months. Most people saw improvements in the first two months, I think. But I don't think they were on any psych drugs.

 

As for tapering down on meds...obviously I'd get the prescribing doctor on board. I only wanted to mention it as something to keep an eye on. In hindsight, I started seeing the need to taper down on things after 3-4 weeks and again about a month after that. But I didn't recognize the signs until later. The signs of "too much" looked a lot like the signs of "too little" and I was actually tempted to add more into the system instead of backing down like I should have. Do a search in mthfr.net about niacin. That helped my DD put an end to Evil Child when I finally realized my over-zealousness was the root of the Evil. But I'm not exactly sure how you'd manage things with an SSRI or other psych med.