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Just got my Methylation and Detox Profile Results: can the Experts Kindly Provide Commentary Please

Hip

Senior Member
Messages
17,824
Just received my 23andme genotyping results, and having downloaded the raw data file of my gene results (available here on the 23andme website), and having run this file through the Genetic Genie website (here), I obtained my methylation and detox profile results, were are both given below.

I'd be most grateful if the interpretation experts here on Phoenix Rising could make some comments regarding my results.

Methylation Analysis Results
Methylation Analysis Results.jpg




Detox Profile Results
Detox Profile Results.jpg



In general, when I try high dose vitamin B12 injections or high dose B12 sublingually, I don't experience very much in terms of benefits. I have tried methylcobalamin, adenosylcobalamin and hydroxocobalamin, often all together.

Similarly, when I try the full methylation protocol, including vitamin B12, methylfolate, P5P, glutathione, phosphatidylserine, fish oil, vitamin B complex, I also don't seem to get much benefit.

I get neither much benefit, nor experience any negative symptoms, such as Herxheimer or detox symptoms.

When I first started taking high dose vitamin B12 fro my ME/CFS several years ago, the improvements I experienced then were a little better; but now, taking B12 or doing a methylation protocol hardly makes any difference.

So I wonder of one or more parts of my methylation cycle is blocked?
 
Messages
8
Hi Hip,
May I ask how you did such test? Is it a blood test, where do you actually do it?
I infer from your post that the results don't come with some kind of interpretation. I'd like to try this test but I have so far felt overwhelmed by its complexity. I hope someone can help you out with the results.

I did a methylation panel at the ELN which showed abnormalities in certain methylation metabolites from which one can see whether there is a block. In my case there was a block which improved on the simplified methylation protocol. However, like you, I did not have any positive or negative reactions I was aware of.
I have been on this protocol for a while, twice actually with a long break in between. After I started chelating metals I had to go back on methylation in order to be able to carry on. I guess methylation it's part of a bigger puzzle.
 

Hip

Senior Member
Messages
17,824
Hi Hip,
May I ask how you did such test? Is it a blood test, where do you actually do it?

You need to get your genes tested first, by 23andme.com. They send you a test tube, you provide them with a saliva sample, pay them $99, and six weeks later, you get your gene results back. You then upload these results to the Genetic Genie website, and hey presto, within a few minutes, Genetic Genie gives you the above methylation analysis results.

The hard thing is trying to understand and interpret the methylation analysis results, as there is a big learning curve to this interpretation, which is why I have asked the help of the experts here.
 

caledonia

Senior Member
You need to treat the First Priority mutations first. So that would be SHMT, then CBS if that's expressed (doesn't seem like it though because the methyl donors didn't cause any problem), then onto MTHFR, MTRR and the rest.

Have you tried TMG, such as in Yasko's General Neurological Health Formula? That would act on the BHMT shortcut pathway. I got some energy from that within a day or two. I have similar BHMT SNPs to you.

There can be a honeymoon period of 6-8 weeks (if I'm remembering correctly) where nothing seems to be happening, then Bam. How long did you try the supps?

Like the other poster said, you can do the ELN (HDRI methylation panel) to see how your methylation is functioning. The SNPs are potentials - they may or may not be expressed. The panel would tell you that.

There is also a comprehensive functional test called Nutreval which can show you if your methylation is blocked, and also tests for gut problems, Krebs cycle, metals, minerals, fatty acids and neurotransmitters. In fact, I'm going to be taking this one myself in the next week or so. I've already done the HDRI methylation panel and things are sure screwed up.

One other thought. There could be gut problems blocking supplements. You're bypassing the stomach with the B12, but not with the other supps.
 

Patrick*

Formerly PWCalvin
Messages
245
Location
California
Hip, from BHMT 01 on down to the end of the Methylation Analysis, our results are exactly the same. Mine are here.

We are both +/- for the CBS A360A mutation, which can be confusing. Supposedly if a person has a CBS mutation, he/she needs to address that first because it is an "open gate" where all the methylation supports will simply dump out the gate until it is closed. Closing the gate involves reducing sulfer in the diet and ammonia, through flushes. But, there is apparently some controversy about whether CBS is as big of a deal as Dr. Yasko thinks it is. (See posts #17-19 in this thread). But even if it is a "big deal", the A360A mutation is the more mild form of the CBS mutation (something like 1/40th as bad as the CBS C669T mutation), and we are both heterozygous (+/-) for A360A, meaning it's not even clear if that mutation affects us at all.

But it's a risk to move forward without addressing CBS because if it is a problem, then everything else we try will be in vain. Considering how costly these supplements are, that's an expensive gamble. So I'm playing it safe and following Yasko's plan of addressing CBS first, just to be safe.

I am just starting over with a new Methylation protocol based on Amy Yasko's book Autism: Pathways to Recovery. Like you, a high dose B-12 protocol did nothing for me in the past, so I'm hoping this "full protocol" will do the trick. If nothing else, I'm going to be better about ordering tests and monitoring the levels of different methylation components to try to fine tune it. I just finished outlining my basic plan, which is here.

Good luck.
 

Hip

Senior Member
Messages
17,824
Have you tried TMG, such as in Yasko's General Neurological Health Formula? That would act on the BHMT shortcut pathway. I got some energy from that within a day or two. I have similar BHMT SNPs to you.

Yes, I did try adding TMG (trimethylglycine) to my methylation regimen for a few weeks, but I did not notice any improvements from TMG.

There can be a honeymoon period of 6-8 weeks (if I'm remembering correctly) where nothing seems to be happening, then Bam. How long did you try the supps?

I've tried the methylation protocol on a number of occasions, but on each occasion, it was not longer than around a month; so I guess it could be that I did not take the protocol for long enough.
 

Hip

Senior Member
Messages
17,824
Hip, from BHMT 01 on down to the end of the Methylation Analysis, our results are exactly the same. Mine are here.

We are both +/- for the CBS A360A mutation, which can be confusing. Supposedly if a person has a CBS mutation, he/she needs to address that first because it is an "open gate" where all the methylation supports will simply dump out the gate until it is close. Closing the gate involves reducing sulfer in the diet and ammonia, through flushes. But, there is apparently some controversy about whether CBS is as big of a deal as Dr. Yasko thinks it is. (See posts #17-19 in this thread). But even if it is a "big deal", the A360A mutation is the most mild form of the CBS mutation (something like 1/40th as bad as the CBS C669T mutation), and we are both heterozygous (+/-) for A360A, meaning it's not even clear if that mutation affects us at all.

But it's a risk to move forward without addressing CBS because if it is a problem, then everything else we try will be in vain. Considering how costly these supplements are, that's an expensive gamble. So I'm playing it safe and following Yasko's plan of addressing CBS first, just to be safe.

That's interesting Patrick. I guess it would make sense to play it safe, and be a bit careful with sulfur. I often use sulfur containing supplements, like L-taurine (2 gram dose) and glutathione, so I will cut these out now.

On this list of high sulfur foods, it seems that there is quite a few foods that you have to avoid/cut down on. How strict are you with your low sulfur diet?


I have a question general: when you look at your gene mutations, are the potential problem genes only the ones in which you have a double mutation (+/+) in the same gene variant? For example, I have the MTHFR C677T gene variant as a +/+ double mutation.

Or can there also be potential problems in genes in which you have no double mutations, but you have more than one single mutation (+/-) present? For example, I have the BHMT 02, BHMT 04, and BHMT 08 gene variants all as single mutations (+/-), so I have a total of three mutations in the BHMT gene.

In other words, can a series of single mutations in the same gene be potentially just as problematic as one double mutation?
 

Hip

Senior Member
Messages
17,824
I would also like to ask what peoples' views are on this guy, Dr Ben Lynch, who says on his mthfr.net website that:
"I believe the MTHFR gene mutation is a highly significant public health problem that is completely ignored. Yet, millions are suffering from pulmonary embolisms, addictions, fibromyalgia, miscarriages, schizophrenia, severe depression, cancer and autism to name a few."

Is this exaggeration and hyperbole, or is there some truth to it?
 

LaurieL

Senior Member
Messages
447
Location
Midwest
Hi Hip,

Been looking at your mutational profile, and your methylation SNP's have been discussed in others. But wow!!! What a detox profile you have!!! I am wondering if your CYP's have anything to do with your lack of response? I really want to get into your detox profile a bit more. I am not an interpretational expert......Thanks for your patience.

Laurie
 

LaurieL

Senior Member
Messages
447
Location
Midwest
Would you do me a fav?? Would you go to 23andme and under your name when you log in, click on raw data and plug in rs4147565 and get those results for me? I don't know why genetic genie doesn't include this one, and there are a couple of others as well.

Laurie
 

Patrick*

Formerly PWCalvin
Messages
245
Location
California
That's interesting Patrick. I guess it would make sense to play it safe, and be a bit careful with sulfur. I often use sulfur containing supplements, like L-taurine (2 gram dose) and glutathione, so I will cut these out now.

On this list of high sulfur foods, it seems that there is quite a few foods that you have to avoid/cut down on. How strict are you with your low sulfur diet?


I have a question general: when you look at your gene mutations, are the potential problem genes only the ones in which you have a double mutation (+/+) in the same gene variant? For example, I have the MTHFR C677T gene variant as a +/+ double mutation.

Or can there also be potential problems in genes in which you have no double mutations, but you have more than one single mutation (+/-) present? For example, I have the BHMT 02, BHMT 04, and BHMT 08 gene variants all as single mutations (+/-), so I have a total of three mutations in the BHMT gene.

In other words, can a series of single mutations in the same gene be potentially just as problematic as one double mutation?


So far, I've eliminated about half of the sulfur rich foods that I used to eat. I'm starting with a moderate reduction and hoping that's all that's required. Most signs point to CBS/BHMT being only a slight issue for me.

About your other question, heterozygous mutations (+/-) can be a problem, but there's not as much certainty as with homozygous mutations (+/+). If you have a homozygous mutation (+/+), you know with 100% certainty that you are affected by that mutation. With heterozygous mutations, it's not as clear, but your odds increase with multiple single mutations (like the way we both are +/- for BHMT 02, 04, and 08.). So then you have to look for clues in your blood work and urine samples to determine if you are actually affected by that particular mutation and to what extent.

I believe that when a person has CBS and BHMT mutations together, there's a greater chance of having high sulfur & ammonia levels, so there's probably a good chance for both of us that we're affected. Then it becomes a question of how much.

EDIT: After I wrote this post, I went back over Yasko's book and Heartfixer and pulled out 6 clues to whether CBS & BHMT mutations are a problem, then I put together a little analysis based those six clues. Since we have the same CBS and BHMT mutations, it might help you to do a similar analysis.
 

Hip

Senior Member
Messages
17,824
Wow!!! What a detox profile you have!!! I am wondering if your CYP's have anything to do with your lack of response? I really want to get into your detox profile a bit more.

Is that "Wow" in a good way, or is it "Wow" meaning "Oh-oh"....?!

Would you do me a fav?? Would you go to 23andme and under your name when you log in, click on raw data and plug in rs4147565 and get those results for me? I don't know why genetic genie doesn't include this one, and there are a couple of others as well.

I just plugged in rs4147565 on the raw data page of the 23andme, and got these results:

Gene ..... Position .... SNP ........ Versions ... Genotype
GSTM1 .... 110231777 ... rs4147565 .. A or G ..... GG

The SNPedia page for this SNP is here.

Thanks for looking into this Laurie.
 

caledonia

Senior Member
I would also like to ask what peoples' views are on this guy, Dr Ben, who says on his mthfr.net website that:

Is this exaggeration and hyperbole, or is there some truth to it?

Not an exaggeration!

About 40% of the population has MTHFR mutations. Most people eat bread and cereals with synthetic folic acid added to it and many people also take cheap supplements with folic acid. The folic acid is not well absorbed by those with MTHFR mutations, in addition it will deplete the good kind of folate. In addition it will float around unused and potentially cause cancer.

In addition, we live in a very polluted world which can cause glutathione depletion which is especially a problem for those with MTHFR mutations who are already depleted to start with. There are many health consequences for glutathione depletion.

Now look at the rise of "modern diseases" - cancer, autism, ME/CFS, fibromyalgia, anxiety, depression, etc. etc. These things were almost unheard of 100 years ago (I have verified that with geneological research - most people were dying from strokes, heart attacks or infectious disease).

These things combined make those with MTHFR mutations the "canaries in the coalmine". I've seen methylation results for probably at least 40-50 people with ME/CFS and only one did not have MTHFR (but had other serious methylation cycle mutations).
 

dannybex

Senior Member
Messages
3,561
Location
Seattle
You need to treat the First Priority mutations first. So that would be SHMT, then CBS if that's expressed (doesn't seem like it though because the methyl donors didn't cause any problem), then onto MTHFR, MTRR and the rest.

Have you tried TMG, such as in Yasko's General Neurological Health Formula? That would act on the BHMT shortcut pathway. I got some energy from that within a day or two. I have similar BHMT SNPs to you.
...

The SNPs are potentials - they may or may not be expressed. The panel would tell you that.

Excellent points. Jill James told me that she considers the CBS mutation to be 'adaptive', and her small study with autistic kids showed even though they had the CBS issue, that folinic and TMG helped improve their glutathione levels -- no restriction of sulfur was required.
 

Hip

Senior Member
Messages
17,824
About 40% of the population has MTHFR mutations. Most people eat bread and cereals with synthetic folic acid added to it and many people also take cheap supplements with folic acid. The folic acid is not well absorbed by those with MTHFR mutations, in addition it will deplete the good kind of folate. In addition it will float around unused and potentially cause cancer.

In addition, we live in a very polluted world which can cause glutathione depletion which is especially a problem for those with MTHFR mutations who are already depleted to start with. There are many health consequences for glutathione depletion.
I just found this interesting hypothesis postulating that the reason there is such a high percentage (40%) of MTHFR mutations in the population is because these mutations confer protection from viral infection.

The evolutionary biologist Paul W. Ewald talks about the fact that genetic mutations will persist in populations if they provide a compensating benefit. For example, he says that the genes that cause sickle cell disease have persisted down generations, in spite of causing this disease, as these genes also protect against malaria, which is a serious killer in many parts of the world.

So the reason that so many people have MTHFR mutations might be because this mutation provided this compensating benefit of protecting against viral infection. The struggle against infectious diseases has always been one of the toughest survival challenges for the human species, and any gene that helps in this struggle will likely be conserved over generations of humans.

Although if MTHFR mutations do provide protection against viral infection, and this protection is due to altered cytokine responses, I wonder if these altered cytokine responses might also predispose to developing chronic diseases such as ME/CFS from viral infection? That is to say, if for example a MTHFR mutation produces more pro-inflammatory cytokines that help fight off acute infections, might such pro-inflammatory cytokines also cause chronic diseases in the case of chronic infections?
 

caledonia

Senior Member
So I wonder of one or more parts of my methylation cycle is blocked?

I had forgotten about this until now - here's one really simple thing you can try: you may have low stomach acid, in which case supplements won't absorb well. You can do the "baking soda burp test" to verify if your stomach acid is high or low (google it). If it's low, take betaine hydrochloride with each meal. At one point I was taking 2 capsules with each meal. If you feel a burning sensation, then it's too much.

Or just take the betaine and see if you can tolerate it.

Now that I've gotten methylation going a bit, I don't need to do this any more.
 

Dreambirdie

work in progress
Messages
5,569
Location
N. California
Or just take the betaine and see if you can tolerate it.

Now that I've gotten methylation going a bit, I don't need to do this any more.

Good point. I had to take betaine for many years. Now that my digestion is better, I rarely ever need it.

Though I am not sure how methylation is connected to stomach acid?
 

Hip

Senior Member
Messages
17,824
I had forgotten about this until now - here's one really simple thing you can try: you may have low stomach acid, in which case supplements won't absorb well. You can do the "baking soda burp test" to verify if your stomach acid is high or low (google it). If it's low, take betaine hydrochloride with each meal. At one point I was taking 2 capsules with each meal. If you feel a burning sensation, then it's too much.

Or just take the betaine and see if you can tolerate it.

Now that I've gotten methylation going a bit, I don't need to do this any more.

I just tried the burp test with sodium bicarbonate, and I failed it (no burps at all), so it seems I may have low stomach acid.

I will get some betaine hydrochloride, and try taking the methylation protocol supplements with my meals along with betaine hydrochloride, to see if that makes a difference.

Thanks for that tip, Caledonia.