23andme analysis and treatment (COMT/VDR/MAO)

[twincity]

The CBS SNPs have little or no impact. Hence it doesn't make any sense to "treat" them.

Hi there. If the SNPs have little or no impact, what should I be looking for instead? How would I go about identifying the issues that are causing the problems?

Any pointers on what I treat and how (from your point of view) would be greatly appreciated.

 

[Valentijn]

Hi there. If the SNPs have little or no impact, what should I be looking for instead? How would I go about identifying the issues that are causing the problems

If you're just interested in methylation, I have lists of the SNPs with an actual impact (based on reading the research) at:
http://forums.phoenixrising.me/index.php?threads/interesting-mthfr-variations.24543/
http://forums.phoenixrising.me/index.php?threads/interesting-mtrr-variations.24551/
http://forums.phoenixrising.me/index.php?threads/interesting-mtr-variations.24572/
http://forums.phoenixrising.me/index.php?threads/interesting-cbs-variations.24492/
http://forums.phoenixrising.me/index.php?threads/interesting-bhmt-and-bhmt2-variations.24512/
http://forums.phoenixrising.me/index.php?threads/interesting-ahcy-variations.24498/
http://forums.phoenixrising.me/index.php?threads/interesting-acat1-and-acat2-variations.24494/
http://forums.phoenixrising.me/index.php?threads/interesting-comt-variations.24672/
http://forums.phoenixrising.me/index.php?threads/interesting-vdr-variations.24480/

If you're looking for potential issues instead of just focusing on presumed issues, I have a small program at http://sourceforge.net/projects/analyzemygenes/ which creates a list of you rarest 23andMe results. Homozygous results, "i" numbers, and stuff with under 1% prevalence are generally the more interesting ones. They can be looked up on dbSNP to see what genes they're on and if there's any existing research: http://www.ncbi.nlm.nih.gov/SNP/

 

[twincity]

If you're just interested in methylation, I have lists of the SPNs with an actual impact (based on reading the research)

Thanks for that. Very helpful.

If CBS isn't a thing (or has no impact), are there any thoughts on why foods like broccoli, peas, eggs, sulphur-rich foods trigger the wired-but-exhausted, twitchy symptoms in people like me? Could it be related to the effects of the COMT SNP?

 

[Valentijn]

If CBS isn't a thing (or has no impact), are there any thoughts on why foods like broccoli, peas, eggs, sulphur-rich foods trigger the wired-but-exhausted, twitchy symptoms in people like me? Could it be related to the effects of the COMT SNP?

I doubt it's related to COMT either. Sometimes we just don't know, and that's that, at least until more research has been done.

 

[Gondwanaland]

If CBS isn't a thing (or has no impact), are there any thoughts on why foods like broccoli, peas, eggs, sulphur-rich foods trigger the wired-but-exhausted, twitchy symptoms in people like me? Could it be related to the effects of the COMT SNP?

I have been giving a lot of thinking to this issue since my husband is 1x +/+CBS and 2x +/+ COMT and has sulfur intolerance.

One possible reason is if the person is also copper deficient, and sulfur consumption could worsen this condition. Well, copper is a double sword supplement, since it converts dopamine into noradrenaline, and +/+ COMTers can't tolerate that well.

Also there are several theories about how most people is copper toxic but with oxidized (unavailable) form of copper, so supplementation is really tricky and should be kept at mcg scale. The tipping point is also very hard to predict. I have seen my husband from feeling very well upon supplementing 600mcg copper (+ 8mg Zn, 500mcg Mn, 80mcg Se) to unwell just after 1 week of supplementation.

Other possible connection is that copper is also a cofactor of enzymes that break down histamines, and sulfur chelates copper out causing symptoms.

I don't know, just thinking out loud.

 

[twincity]

I doubt it's related to COMT either. Sometimes we just don't know, and that's that, at least until more research has been done.

If I don't know, how do I treat it? Is there a standard approach you recommend?

 

[Valentijn]

If I don't know, how do I treat it? Is there a standard approach you recommend?

I'd suggest that you discuss your symptoms with your doctor. Licensed Naturopathic Doctors (NDs) are often willing to investigate and help treat such issues.

Or just avoid foods if you think they're causing you problems. There's no need to invent an explanation for why it helps ... if it helps, it helps, and that can be good enough

 

[twincity]

It would be great to hear from anyone else who finds sulphur-rich foods trigger symptoms.

If there is a reason for it, I'd prefer to know. When I avoid the foods I'm sick, and when I don't I'm a complete mess. If I can find out why I can't tolerate the foods I might get a better idea of what is causing the underlying sickness in the first place.

 

[pogoman]

It would be great to hear from anyone else who finds sulphur-rich foods trigger symptoms.

If there is a reason for it, I'd prefer to know. When I avoid the foods I'm sick, and when I don't I'm a complete mess. If I can find out why I can't tolerate the foods I might get a better idea of what is causing the underlying sickness in the first place.

I already replied in your thread but theres a good chance your sulfur issues are separate from the others.
I am documented allergic to Septra which is a sulfonamide antibiotic, I also have bad reactions like fatigue and brain fog when I have repeatedly tried sulfur related supplements.
sam-e, methionine, msm and others all disagree with me.
yet I am homozygous for mthfr which some sulfur compounds are recommended.
go figure.

 

[picante]

It would be great to hear from anyone else who finds sulphur-rich foods trigger symptoms.

If there is a reason for it, I'd prefer to know. When I avoid the foods I'm sick, and when I don't I'm a complete mess. If I can find out why I can't tolerate the foods I might get a better idea of what is causing the underlying sickness in the first place.

Are you using any methylation supplements? (B12, methylfolate, L-carnitine, etc)?

These actually triggered my problems with high-thiol foods. I have a theory about where the cycle is going awry for me. Will write more later. Gotta go dig in the garden right now.

 

[TheChosenOne]

Hi twincity. Don't mind the trolls on the forum.
About CBS, there is a lot of discussion about it, but like Valentijn said, there is a lot of things we don't know. CBS may or may not be a problem. What I notice is that most people with CBS mutations do seem to have problems with sulfur foods.
You have COMT mutations, which makes supplementation much more difficult. You also have AHCY mutations, which makes COMT worse. I'd start with methylfolate and hydroxyB12. I woudn't take methylB12. You might get benefits from small doses of TMG (because of BHMT).

 

[picante]

This diagram by the Neurological Research Institute has been posted here, there and everywhere. Here is one site where you can see it more clearly: http://hopefulgeranium.blogspot.com/2012/12/rich-von-konynenberg-rip-methylation.html

Direct your attention to where it says "Homocysteine" at the bottom of the right-most circle. Below that is the transsulfuration pathway. It might be upregulated somewhat for those with CBS mutations. I do not have the C699T mutation, although I may have others (I had 3 "no calls" on that gene).

Methylation Cycle

More homocysteine drains down that pathway when there is a bottleneck on the routes around and/or through that methylation circle. I have gene snps (MTRR and BHMT) indicating possible bottlenecks on both routes.

But in my case, I was happily eating eggs and chard and sauerkraut ... until I started methylation supps. Then I was back to the old days (before I got on thyroid hormone) of gut bloatation / grogginess. And too many thiols could trigger a neck spasm/headache/nausea, another old symptom returning.

Here's my hypothesis: Rebooting the folate & methylation cycles gradually used up the riboflavin in my body, among other things. Riboflavin (the FAD form) is a co-factor at the junction of those two circles. It's a co-factor for a few hundred of our enzyme reactions. And what do I need to convert riboflavin to FAD? Things I don't have much of: thyroid hormones and aldosterone, for starters.

This was explained to me in December, but I'm still struggling with it: http://forums.phoenixrising.me/inde...lerating-it-how-to-get-out-of-the-maze.37492/

There are three neurotoxins on that pathway: homocysteine, ammonia, and sulfite. These explain why my brain wanders into Dorothy's poppy field. Ten years ago (before I started T3) I had super-high urine ammonia and extreme taurine wasting. It would be nice if more of that homocysteine would convert to glutathione, but it doesn't seem to, and I don't know why.

I hope this helps you understand what might be going on for you, @twincity.

There's no way I'm giving up on methylation, because it gets rid of my low-back arthritis! That tells me it's very effective with inflammation.

 

[twincity]

Thanks for the info.

I haven't yet started a methylation protocol yet. I wanted to get on top of the other issues first.

I've had thyroid checked out. All ok. Same with homocysteine. But I still have these awful issues with overstimulated nervous system and constant gastritis-like gut inflammation.

From what I can see, nobody can agree on why people are sulphur/thiol sensitive. It's unclear. So time to crack on treating the issues I think I know about. Hopefully it is a symptom of an underlying methylation issue that I can treat. This is my rough plan of action:

COMT/MAO:

- I need to raise the activity of the COMT/MAO enzymes, in order to normalise my levels of serotonin, dopamine and adrenaline. So I'm going to be taking B2 (as per http://forums.phoenixrising.me/index.php?threads/sustained-release-methylation-protocol-srmp.36344/), low dose Lithium Orotate, Magnesium and Pregnenolone.

METHYLATION:

- Once I've stabilsed my COMT/MAO activity, I'll start the sustained release methylation protocol under the watchful eye of my doctor (Dr Hembury, in Bristol).

In the meantime I'll continue to avoid high sulphur/thiol grub, and see how I get on. I'll keep you updated.

 

[picante]

I've had thyroid checked out. All ok.

Good! One less thing to deal with.

Same with homocysteine.

When homocysteine is draining down the transsulfuration pathway, blood levels usually come out fine. Mine are mid-range. The instructions for the blood test are to eat a low-methionine diet for 1-2 days, which I did. I'm hypothesizing that the result would be much higher when I'm eating my usual foods, and I'd like to see my levels when I'm all groggy from eating thiols/methionine.

Thanks for the link to the thread. I need to get back over there and read, since my husband has the same COMT & MAO-A snps you do.

Good luck with this! I'll follow your progress on the other thread.

 

[ahmo]

It would be great to hear from anyone else who finds sulphur-rich foods trigger symptoms.

I don't tolerate sulfur/high thiol foods. This first became evident when I was 6 months on GAPS diet and having increasing rosacea-like symptoms on my face. When I stopped histamines, this cleared about 50%, overnight. When I quit high-thiol, the remaining irritation cleared. I also have had terrible excitotoxic reactions to supps containing sulfur.

It's now 3 years on, and I've just been able to eat some garlic. My sense is that adding FMN form of B2 has made the difference. This would be in line w/ picante's obversation,

Here's my hypothesis: Rebooting the folate & methylation cycles gradually used up the riboflavin in my body, among other things.

Additionally, from the beginning of the year I did intensive fungal/bacterial clearing, and protyolytic enzymes. I also was detoxxing metals for 2 years. Whatever has made the difference, I'm very grateful that change is possible.

 

[picante]

@twincity, @ahmo, I just found this explanation from Rich Van K: http://forums.phoenixrising.me/inde...dication-stop-working.5515/page-2#post-118565

Partial quote:

The methylation cycle is at the beginning of the sulfur metabolism. It is fed by methionine, which comes in as part of protein in the diet. Homocysteine is produced from methionine (via SAMe and SAH) in the methylation cycle, and then methionine synthase "decides" how much should be converted back to methionine, to stay in the methylation cycle. In the liver and kidneys, the BHMT reaction also converts some homocysteine back to methionine. The rest of the homocysteine enters the transsulfuration pathway, which is downstream.

The way that methionine synthase does its "deciding" is that the cobalt ion in the cobalamin that is its cofactor gets oxidized at a rate that depends on the state of oxidative stress in the cells. The more oxidizing this state is, the more often the cobalt ion gets oxidized, and that temporarily shuts down the methionine synthase reaction and diverts the homocysteine flow into the transsulfuration pathway, which helps to make more glutathione, which counters the oxidative stress. Unfortunately, in ME/CFS this delicate mechanism gets overwhelmed, and the oxidative stress becomes more severe, so that glutathione doesn't recover and get control of it. The result is that methionine synthase becomes partially blocked, and the sulfur metabolites drain down the transsulfuration pathway, into sulfoxidation, and get excreted too much as taurine and sulfate, which depletes methionine. The whole sulfur metabolism becomes dysfunctional, and that takes down the cell-mediated immune response as well as the detoxication system.

 

[twincity]

@twincity, @ahmo, I just found this explanation from Rich Van K: http://forums.phoenixrising.me/inde...dication-stop-working.5515/page-2#post-118565

Thanks Picante, that's brilliant. Looks like I'll need to address methylation before the sulphur issues will start to resolve. I'll pursue the initial B2 dosing as well, just in case that helps too.

 

[twincity]

Quick update for y'all.

Over the past couple of years I've had persistent, chronic Gastritis. Debilitatingly so. Full-on stomach, oesophageal and sinus inflammation at the slightest provocation (e.g. eating anything, travelling in a car, shouting). It strangles my voice. Makes me dizzy. Makes me feel awful.

My theory is that it is caused by something called Visceral Hypersensitivity (see http://goo.gl/bssUXO and http://goo.gl/2XdsuP) - caused by the excess of norephedrine, dopamine and serotonin in my system due to the COMT/MAO issues.

I've tried everything to get the gut healing:

- My diet is now severely restricted (no dairy etc - I eat like a nutritionist), but pretty much everything now results in post-meal dizziness and discomfort
- PPI's gave me a slight improvement then made it worse.
- SSRIs didn't help (thanks NHS GPs for that one - nearly drove me insane)
- Nissen Fundoplication surgery didn't help (!!! what fun that experience was)
- Gaviscon didn't help (and why would it - it only provides a barrier between the contents of the stomach and the oesophagus and that's not what Gastritis is about)
- Mastic Gum didn't help at all
- NAG didn't help
- L-Glutamine didn't help.
- Slippery Elm didn't help.
- Marshmallow Root didn't help.
- Sea buckthorn didn't help.
- Licorice didn't help (and in fact made me feel terrible due to the fact it inhibits COMT activity - v bad for me).
- Probiotics DO help, to reduce bloating, but not the stomach and above.
- Charcoal DOES help, a bit, again to reduce bloating.

Below are the things that are now helping, and giving me my life (and brain) back. And this is why I'm now on here ready to get cracking on the remaining conditions that have been the cause of all this (COMT & methylation):

- Bismuth Subsalicylate, via Pepto Bismol
- Digestive enzymes with meals (standard OTC ones e.g. Lamberts Digestizyme)

That's it! As I have hypersensitivity of the gut lining, I needed something to coat and protect my gut (stomach and above), and something to help me digest food. Pepto Bismol and digestive enzymes do that for me. I can eat freely (and sensibly, obvs) again - it's awesome (apart from the occasional black tongue in the morning, which is an interesting side effect of Pepto Bismol - one I can live with though).

Hopefully my gut will have a chance to heal now. But of course, I need to address the cause or it will return. I'll let you know how that goes. Hope this helps someone out there with mysterious gut issues.

[Maybe I should post this as a new thread - which I might do, but it's part of my treatment story so I thought I'd better put it here.]

 

[Gondwanaland]

@twincity take a look into oxalates. Perhaps gradually reducing your daily oxalate intake and going back to dairy will improve things.

I got worse too trying to eat "healthier" and unknowingly more than doubled my oxalate intake.

 

[TheChosenOne]

Bloating can be related to the lack of stomach acid. I used to have serious bloating problems, which I fixed by using stomach acid supplements and lowering my protein intake.