Methylation Cycle dysfunction a possible part of benzo withdrawal picture

[[Sm...]]

This has a dizzying amount of information

 

http://www.tuberose.com/Liver_Detoxification.html

[[Sw...]]

Sniff,

 

The liver detox link is great!  :thumbsup:thanks so much, now I have reading to do.

 

Sweet pea

 

[[Se...]]

Smiff

I think the CYP 450 enzyme has been highly overlooked in the Bb community. Yes it varies from person to person greatly. I am convinced this is where people's windows and waves partly come from during their taper.... How the body is metabolizing everything that enters the body.  Soaps, food, supplements, toxins, they are all metabolized through the liberation some point or another. From my personal experience, My first time around with my Klonopin taper, I was able to either potentiating or induce my dose based on what I ate and how closely I ate/ eat certain foods to my dose. Fats are HUGE in valium dosing. Along with a lot of fruits and veggies people don't realize. A lot of info I read came from cancer websites where patients undergoing chemo are advised to avoid certain things. Specifics are given for lots of foods and which CYP450 Enzyme is affected. I know my situation is extremely sensitive. Many others may not be.

Also had read that under starvation conditions, the body basically either creates more CYP450 enzymes or makes them more sensitized. I can't remember. But I know during this process my body has encountered many "starvation conditions".

I think that once off the benzos with a fair bit of time lag for the drug to detox from the body, things can be looked at differently.

There's just too much to know to unravel what The Great Creator has intricately designed in us! And I  realizing more and more that everybody is different... In so many ways.

I would LOVE to not have to worry about my eating. But as a diabetic I do. So that complicates things greatly. I know that If I go into a state of de realization I will potentially not survive as I would be unable to manage my insulin. This is a bizarre tightrope to walk and any info or contributions that people make are greatly appreciated!

Have a blessed Holiday!

 

 

 

[[Co...]]

Dies 23andme test cyp450?

[[...]]

Selah,

 

A good full report is on Livewello, get all four parts of Health Coach 7!

 

[Guest [Ma...]]

There is definitely a link between taper experience and ones genetic ability to detox meds.

I had the following tested:

Genelex labs - CYP & NAT2 (klonopin pathway) tested

23 and me - raw data for genetic expression

Livewello - interpretation of raw data from 23 and me

NutrEval - nutritional testing from Genova labs

Spectracell - cellular testing

 

All very helpful but not curative.

This I formation would have been extremely helpful prior to beginning any meds. The Genelex report clearly identifies vulnerable pathways.

[[Se...]]

Cool - yes several of the Cyp 450 enzymes. 23ans me has crazy amounts of info the decifering is the hard part.

 

GMIT - is the Health coach 7 part of Livewello? Do you have to pay extra for each part? Will have to have my husband check out. Thanks!

 

Marina - was the Genelex ordered for you or did you do yourself and did your insurance cover it? Would love to have a more concise test/results I could present to my doctors. Sorry you are having such a rough time! This is challenging on so many levels! Will keep you and all in my prayers!

 

Blessings

Selah

 

[Guest [Ma...]]

Selah,

It is a rough road. Hope yours will be much smoother!

Arm yourself with information and find an integrative internist if possible.

I researched and ordered the tests from Genelex independently, presented to a physician who then ordered the Spectracell & NutrEval from Genova labs.

Www.genelex.com

Pharmacogenetic testing

They will provide a comprehensive liver pathway medication profile to use when consulting a physician in the future, for all meds. I have found this invaluable with my particular sensitivities.

[[...]]

Selahessentialoils, you can run a whole bunch of reports, they are free! Sign on to Livewello and go to Gene Reports, choose the ones you want and install them!

 

[[jj...]]

Hey there Smiff.

 

I've been reading through this and a couple of other sites as well. One thing that I'm still not understanding is if you are saying that you believe that Methylation Cycle dysfunction is the cause of benzodiazepine withdrawal or if you are saying that benzo w/d is deregulating the MC. One thing that I'm sort of worried about is that some people may end up thinking that benzo withdrawal is something that you can go out and get DNA testing for and then it can be "cured".

 

There's a few problems with this. 1) DNA coding turns out to have very little utility in either treating or prognosticating disease with the exception of a very few conditions. That's why the human genome project ended up as being more or less a bust (far more questions were raised than answered) and wound up spawning the current interest in epigenetics. This is particularly true when it comes to the complexity of something like the Methylation Cycle, and while the folks that are offering testing and cures based on the results may be sincere, the scientific backing is well.. this than robust here. 2) While there does appear to be a great deal of overlap in the symptoms claimed to be caused by MC dysfunction and benzo withdrawal, there are enough things that are unique to benzo withdrawal that make them appear to be separate syndromes. Even if we are looking for something that accounts for excess glutamate, the current theory of downregulation of gaba receptors and upregulation of glutamate receptors directly related to benzo use seems to be a far more parsimonious explanation. 3) If supplements and dietary changes are needed to correct MC dysregulation, then it becomes unclear why the vast majority of people recover from benzo withdrawal regardless of diet and then we also have the problem of supplements revving up withdrawal symptoms rather than relieving them.

 

My larger concern is that people might feel like they need expensive specialists, testing, supplements and food to recover when if fact, what is needed more than anything is time and a supportive environment. Just my thoughts 

[[...]]

Gene mutations can cause difficulty in the Methylation Cycle (among other things)...assisting the cycle can make some people feel better in general, which may also assist those in wd feel better. I do not believe that this causes benzo wd or that benzos cause the deregulation! We are born with Gene mutations, and there are things that can assist our bodies to, if you will, work around these mutations

 

My opinion is...

 

1) finding your mutations and assisting the cycle may be beneficial in benzo wd, but there is no sure way of knowing.

 

2) please refer to MTHFR.net and Dr. Amy Yasko's site for information, assisting The Methylation Cycle has improved autism in children (dramyyasko.com).

 

3) no one should believe this is a quick and/or easy answer to benzo wd healing, but it may assist healing, it's truly unknown.

 

4) do not get tested if you are not comfortable with it, or if you are looking for "quick and easy" answers to healing during benzo wd. Do not spend money on anything you are uncomfortable with!

 

Time and a supportive environment may be all that's necessary, or maybe...just maybe, assisting the Methylation Cyle can help!

 

Honestly, it's just unknown! It's just a theory that we like to ponder!

[[Sm...]]

Hey there Smiff.

 

I've been reading through this and a couple of other sites as well. One thing that I'm still not understanding is if you are saying that you believe that Methylation Cycle dysfunction is the cause of benzodiazepine withdrawal or if you are saying that benzo w/d is deregulating the MC. One thing that I'm sort of worried about is that some people may end up thinking that benzo withdrawal is something that you can go out and get DNA testing for and then it can be "cured".

 

There's a few problems with this. 1) DNA coding turns out to have very little utility in either treating or prognosticating disease with the exception of a very few conditions. That's why the human genome project ended up as being more or less a bust (far more questions were raised than answered) and wound up spawning the current interest in epigenetics. This is particularly true when it comes to the complexity of something like the Methylation Cycle, and while the folks that are offering testing and cures based on the results may be sincere, the scientific backing is well.. this than robust here. 2) While there does appear to be a great deal of overlap in the symptoms claimed to be caused by MC dysfunction and benzo withdrawal, there are enough things that are unique to benzo withdrawal that make them appear to be separate syndromes. Even if we are looking for something that accounts for excess glutamate, the current theory of downregulation of gaba receptors and upregulation of glutamate receptors directly related to benzo use seems to be a far more parsimonious explanation. 3) If supplements and dietary changes are needed to correct MC dysregulation, then it becomes unclear why the vast majority of people recover from benzo withdrawal regardless of diet and then we also have the problem of supplements revving up withdrawal symptoms rather than relieving them.

 

My larger concern is that people might feel like they need expensive specialists, testing, supplements and food to recover when if fact, what is needed more than anything is time and a supportive environment. Just my thoughts 

 

Yea J, you are right to point out of all of these things, I should say from the outset I  certainly absolutely 100% don't mean to suggest you can be cured of benzo wd.

 

You know I am not even sure if I think it has anything to do with benzo wd. I only started thinking about it because I found some dietary, and gut, changes I made possibly, maybe was helping me and I looked into the world of these particular dietary changes - autism, CFS protocols - and I came across the methylation cycle. As you can see this a pretty tenuous link/beginning but it was one that led me to find it interesting. You make a number of very good points though and I will try to address a few of the particularly important ones.

"One thing that I'm still not understanding is if you are saying that you believe that Methylation Cycle dysfunction is the cause of benzodiazepine withdrawal or if you are saying that benzo w/d is deregulating the MC."

Like I said I don't think methylation cycle dysfunction is the cause of benzodiazepine withdrawal nor do I think benzo wd alone could deregulate it. I do need to reiterate here that any of my thoughts on this matter are infant thoughts. They aren't fully formed and I hold them without any conviction. They are more questions that had been swirling in my head for a few months. What are those infant thoughts inclined toward when I think on any possible connection between MC and complicated benzo wd? I have wondered whether I always had an issue with MC firstly and whether it is possible this was further deregulated given the strains to the body/cycle during benzo wd. My further musings have led me to wonder if any of the symptoms of benzo wd (definitely a unique phenomenon which alone explains the symptoms - although not all of the theories of benzo wd are complete) could have been exacerbated, or complicated, by any of these genetic dispositions in the MC cycle. On that I have no clue. I am merely musing.

 

"This is particularly true when it comes to the complexity of something like the Methylation Cycle, and while the folks that are offering testing and cures based on the results may be sincere, the scientific backing is well.. this than robust here."

 

J can you give me some readings on this. My brother - who incidentally just became a consultant gastroenterologist - said the same thing. 'There is no diagnostic or therapeutic usefulness to genetic testing' he said. I'm not saying it isn't true, though obviously there are people who as you say sincerely believe they can do diagnostic work based on genetic results. So any help you can give me to understanding the discrepancy and why genetic testing has no diagnostic, or therapeutic, value would be very much appreciated.

 

...there are enough things that are unique to benzo withdrawal that make them appear to be separate syndromes.

 

My infant thoughts on this incline me to say they are absolutely 100% separate, but plausibly (maybe?) not completely unrelated in everyone, syndromes.

 

Even if we are looking for something that accounts for excess glutamate, the current theory of downregulation of gaba receptors and upregulation of glutamate receptors directly related to benzo use seems to be a far more parsimonious explanation.

 

Absolutely agree with you except the apparent huge range of severity, and length, of symptoms remains problematic

 

If supplements and dietary changes are needed to correct MC dysregulation, then it becomes unclear why the vast majority of people recover from benzo withdrawal regardless of diet and then we also have the problem of supplements revving up withdrawal symptoms rather than relieving them.

 

This is a very good point and I'm not sure I have a satisfactory answer. I'm not sure I'm even saying there is a connection between the two syndromes. My only possible thoughts on it are this: in the MC dysregulation world they do seem to think you can go along with normal life and have just 'normal' levels of tiredness, inflammatory illnesses etc for much of the time but that you can get seriously sick under certain circumstances when there are critical overloads on the system. Now as you can see that is a pretty helpful theory because it makes it completely unfalsifiable. 'You are fine?! Ah well that is cause you haven't reached a critical level of dysregulation, and even if you decide to not treat it you very well may get this and this very common diseases relating to aging and inflammation'.

I should note here again though that I think they are different phenomena. Benzo wd is benzo wd and it will happen no matter what. So absolutely you'd heal from it no matter what, even if there was a connection to MC. What I've wondered on is why the discrepancy among individuals in severity and longevity. Here again it isn't clear, even among the people interested in this, that you'd have to supplement to eventually get back to baseline. Theoretically it is a system that, as it deals with the shunting off of chemicals produced particularly under stressful conditions, may only be falling into dysfunction when there is excesses of said particular chemicals. As you say benzo withdrawal will, in the vast vast majority of people, heal no matter what so there would theoretically no longer be a situation where the body's systems for degrading glutamate, adrenaline, cortisol, homo-cysteine, ammonia etc is under the same pressure. Any predisposition for MC issues would potentially then fall back to baseline. This whole MC polymorphisms are problems idea would be rather problematic if everyone thought you needed supplements throughout a lifetime. The polymorphisms we are talking about aren't super uncommon and they would have been rather more problematic if people stayed overtly dysfunctional, and ill, over a lifetime without the advent of recent supplementation.

 

"My larger concern is that people might feel like they need expensive specialists, testing, supplements and food to recover when if fact, what is needed more than anything is time and a supportive environment. Just my thoughts  "

 

Yes, I 100% agree J and I do hope no-one takes my musings beyond what they are: the mere musings - nothing more - of some random over the internet who is technically crazy   

Time and a supportive environment is absolutely what we ultimately need 

 

 

Thanks for pointing these out J. They are excellent points and rightly show this is far far from a solid theory both in and outside of the benzo wd world.

[[Sm...]]

Why so quiet peeps? Be honest: Is it because I pointed out I'm technically crazy?

I do have a diagnosis of PTSD so yea that would make me technically crazy I guess 

 

In any case, someone I know says Baylissa Johns said methylation was involved which is why we must be careful with diet. So that is something from someone who is not technically crazy.. I think 

 

Hope you are all well

 

Cool has the dietary changes made any impact?

 

G, still going strong? You are brave to take those methyl groups still in withdrawal. I'm not sure when I'll be willing to take them.

 

love

Smiff 

[[...]]

Smiff, I actually felt better when I started those! After doing my micronutrient testing and finding all my deficiencies I'm also using many supplements, which I started each verryyyy slowly! I intend to only supplement to get things back in balance, then I will back off ost of them!

 

How are you?

 

[[Sm...]]

Smiff, I actually felt better when I started those! After doing my micronutrient testing and finding all my deficiencies I'm also using many supplements, which I started each verryyyy slowly! I intend to only supplement to get things back in balance, then I will back off ost of them!

 

How are you?

 

 

Glad you are doing better on them Maybe I will be brave enough to try them once I get my 22andme back, which hasn't arrived yet for a swab OY!

 

In cog fog about a fortnight ago I took 1mg of methylcobalamin. I know that is a lot. I just took the sublingual tablet without reading the label because my cog fog was so bad and I had to be human for a christmas thing. The outcome was interesting. I did have an increase in anxiety (maybe methyl trapping?) but oddly my sleep was fantastic for -5 days. Since then though my sleep has been poor. Anyway, I'll wait till I get my results and see what to do from there. Unlike you I'm still on a benzo though I'm down to the 2s now thankfully.

 

I'm ok other than that G 

[[...]]

Yes, I suppose having some healing under my belt could possibly make a difference.

 

I hope you improve soon! Can't wait for your results!

 

[[On...]]

Very interesting reading, and very timely, too.

 

Benzos nearly killed me within 4 months of a mere .5  Ativan once a day while waiting to get a "new patient" appointment with a cardiologist. The symptoms were legion within 3 weeks, including burning spine, skin, spontaneous oxygen desaturation  that required supplemental oxygen, and weight loss down to 77 pounds.

 

I do believe methylation issues play a part for me.  Keeping glutamate levels low seems to help but only to a degree. I still feel every single .005 drop in diazepam.

 

Today, having reached the "low" dose of 1.4 mg, I decided to switch to once a day dosing. Many others have done this with either no perceived problems or with an actual improvement of symptoms.

 

Expecting a nice "relaxed relief" from a single dose of 1.4, I was shockingly disappointed by horrible spinal burning and rib pain within 30 minutes of dosing. I have NOT had this symptom since my 2 daily divided doses have gotten below .9 mg each. Wth??? My pain has increased exponentially as the day has progressed.

 

I am guessing this is a pretty good sign that diazepam is literally toxic for me, that my liver does not process it well. To add to this fiasco, it is now the end of the day and I am also suffering terrible muscle tightening like a cold turkey and my throat is closing up, making it hard to breathe and giving me a monster headache.

 

When I am recovered from this misstep enough to do mthfr testing, I probably will just to have the info.  And I won't be taking my doses once a day until I am close to 1 mg. 

 

Thanks for taking the time to post this info, smiff.  It is helpful to at least have another potential explanation for why this ordeal has been so doggone difficult for me. And I was always the strong one up until this, giving birth with ease at home twice and being the super healthy one.  When Benzos were scripted to me, I was walking 3-5 miles a day, biking, dancing, and very active. Now I'm just wanting to survive to see life free of Benzos once again.

[[Sm...]]

Yes I know what you mean: it really is amazing how much physical dysfunction can be wrought on us by these drugs.

I too was a fit hot yogi who danced semi professionally. Just at the moment I struggle to stand very long because my gut makes me double over with pain (time to get back serious with my diet and probiotics).

 

I think the high nutrient, low inflammation diet isn't overly controversial even if we don't have genetic markers that show methylation problems.

 

In any case I'm sorry this is hurting you so. At least we know there will be an end. 

[[Se...]]

Hi all.

Found this link that sums up in a small nutshell about the MTHFR gene mutation.

 

http://www.stopthethyroidmadness.com/mthfr/

 

Very informative regarding glutathione, detox pathway basics, Zinc,copper, iron, etc. also gives useful links to input your 23and me tests in.

Hope it helps some.

 

Selah

 

 

[[Sm...]]

oo good one Selah

 

This one is a good run down or MTHFR too http://holisticprimarycare.net/topics/topics-a-g/functional-medicine/1353-mthfr-mutation-a-missing-piece-in-the-chronic-disease-puzzle

[[Se...]]

Hi Smiff

I am part of the Magnesium Advocacy Group on Facebook. Run by Morley Robbins. Lots of great info. Recently someone posted on why they couldn't take magnesium Glycinate and how it made them anxious and unable to sleep. Talked about Gaba and Glutamate. Lots of stuff and how it relates to different CBS and COMT mutations. This includes some peoples inability to use Epsom salts because of the sulfate in it. I think this is not just about methylation but the other genes that interact. I have no idea how to post it here but will try. You have to join the group to see all the posts. Not all are great and you have to weed through the debates. But unbelievably knowledgeable people there including Benzo withdrawal peeps.

I think it's all related and why so many people have such different reactions to different things.

The down side is for someone without BW it's a monster to try to unravel and I find myself utterly overwhelmed because all the vitamins I know I need to take or experiment with are very touchy while tapering. Ugh! Frustrating and overwhelming!

Taking it slow...I know I have to dose 3 times a day,and am sure it has to do with my SNP irregularities etc. I  really should be 4 but my Cyp enzymes interact with everything! So having to sort through this is like "trying to herd cats" as my husband would say!

Blessings

Selah

 

[[Sm...]]

These are for me just to record and read later.. when I have time.. not sure when that actually is 

 

ex-dependent behavioral effects of Mthfr deficiency and neonatal GABA potentiation in mice

Levav-rabkin, Tamar ; Blumkin, Elinor ; Galron, Dalia ; Golan, Hava M

Behavioural brain research, 2011, Vol.216(2), pp.505-13 [Peer Reviewed Journal]

 

Association between MTHFR C677T polymorphism and depression: An updated meta-analysis of 26 studies

Wu, Yi-Le ; Ding, Xiu-Xiu ; Sun, Ye-Huan ; Yang, Hui-Yun ; Chen, Jian ; Zhao, Xue ; Jiang, Yu-Hong ; Lv, Xiao-Ling ; Wu, Zhen-Qiang

Progress in neuro-psychopharmacology & biological psychiatry, 2013, Vol.46, pp.78-85 [Peer Reviewed Journal]

 

Folate, vitamin B12, homocysteine, and the MTHFR 677C->T polymorphism in anxiety and depression: the Hordaland Homocysteine Study

Bjelland, Ingvar ; Tell, Grethe S ; Vollset, Stein Emil ; Refsum, Helga ; Ueland, Per Magne

Archives of general psychiatry, 2003, Vol.60(6), pp.618-26 [Peer Reviewed Journal]

 

Involvement of gene polymorphisms of the folate pathway enzymes in gene expression and anticancer drug sensitivity using the NCI-60 panel as a model

European Journal of Cancer, Sept, 2009, Vol.45(13), p.2391(11) [Peer Reviewed Journal]

 

Alcohol-induced one-carbon metabolism impairment promotes dysfunction of DNA base excision repair in adult brain

Fowler, Anna-Kate ; Hewetson, Aveline ; Agrawal, Rajiv G ; Dagda, Marisela ; Dagda, Raul ; Moaddel, Ruin ; Balbo, Silvia ; Sanghvi, Mitesh ; Chen, Yukun ; Hogue, Ryan J ; Bergeson, Susan E ; Henderson, George I ; Kruman, Inna I

The Journal of biological chemistry, 2012, Vol.287(52), pp.43533-42 [Peer Reviewed Journal]

 

Evidence that interactive effects of COMT and MTHFR moderate psychotic response to environmental stress

Peerbooms, O. ; Rutten, B. P. F. ; Collip, D. ; Lardinois, M. ; Lataster, T. ; Thewissen, V. ; Mafi Rad, S. ; Drukker, M. ; Kenis, G. ; Van Os, J. ; Myin‐germeys, I. ; Van Winkel, R.

Acta Psychiatrica Scandinavica, 2012, Vol.125(3), pp.247-256 [Peer Reviewed Journal]

 

 

[[bu...]]

Started reading, I have all of the stuff going on you mentioned in the beginning. been unravelling my diet and toxins for years.

 

I need to get straight about supplements but have a migraine as we speak so I will read rest of posts early tomorrow.

Background, started with fibro maybe before klonopin but maybe not until after I started on it. I have a ton of allergies and intolerances. Now RA as well as adrenal and thyroid disfunction. Trying desperately to get a hold on this and taper at the same time!

 

I saw mention of fish and paleo, what about the contamination of fish and meat sources? I have dairy and egg allergy and have been vegetarian most of my life, not turning that boat around. Current state of the meat, fish and dairy industries have me convinced not to eat them either way.

 

Yet I fed myself klonopin all of these years, so yeah. Working on that one!

[[Se...]]

Butterfly1

Sorry to hear about your struggles! There is a book I have been reading called "Could It be B12? An Epidemic of Misdiagnosis" by Dr. Jeffrey Stuart and Sally Pacholok. Very intriguing info. B12 deficiency is widely undetected and the normal ranges the doctors use when tested are evidently too low.

Especially being a vegetarian. This also ties in with methylation. May be worth getting yours checked out. Different B12 forms affect people differently based on gene mutations. Just a thought.

Blessings

Selah

 

[[Sm...]]

Hi Smiff

I am part of the Magnesium Advocacy Group on Facebook. Run by Morley Robbins. Lots of great info. Recently someone posted on why they couldn't take magnesium Glycinate and how it made them anxious and unable to sleep. Talked about Gaba and Glutamate. Lots of stuff and how it relates to different CBS and COMT mutations. This includes some peoples inability to use Epsom salts because of the sulfate in it. I think this is not just about methylation but the other genes that interact. I have no idea how to post it here but will try. You have to join the group to see all the posts. Not all are great and you have to weed through the debates. But unbelievably knowledgeable people there including Benzo withdrawal peeps.

I think it's all related and why so many people have such different reactions to different things.

The down side is for someone without BW it's a monster to try to unravel and I find myself utterly overwhelmed because all the vitamins I know I need to take or experiment with are very touchy while tapering. Ugh! Frustrating and overwhelming!

Taking it slow...I know I have to dose 3 times a day,and am sure it has to do with my SNP irregularities etc. I  really should be 4 but my Cyp enzymes interact with everything! So having to sort through this is like "trying to herd cats" as my husband would say!

Blessings

Selah

 

oo yes I'll have to have a look at that group!

Interestingly I had a reaction to Magnesium biglycinate just a week or so ago. I had heard of possible reactions - glyciene can activate NMDA receptors - so it wasn't super unexpected. It felt like a classic glutamate storm : waves of anxiety and electrical tingling through my body.

 

Yes the COMT enzyme is very interesting (COMT is part of methylation though). Turns out I do have a polymorphism on that thankfully.

 

That is right: My 23andMe is in!

 

I am homogenous MTHFR C67TT

I do have at least one GAD polymorphism

I do have a homogenous MAO polymorphism which I don't really understand yet (but I dont' like it since MAO is the enzyme for eliminating serotonin, adrenaline and dopamine with COMT doing adrenaline and dopamine)

I do also have a heterogenous COMT polymorphism and a DAAO.

At this point I think I better stop reading cause I dunno how I'm remotely sane with that much neurotransmitter dysfunction (based on the methylation enzymes that are either over active or under active)

 

Yes I think you are right there are lots of genes at work in benzo wd from many areas. Methylation has a dizzying amount of areas it is part of though (both MAO, GAD and COMT are parts of methylation and they are virtually all related to neurotransmitters)

 

What CYP information do you have? I did have some CYP polymorphisms but I don't really know what they mean. I don't really know what most of this means