Xeno/estrogens link to CFS/Fibromyalgia - Success!!

Gestalt

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This story relates to my girlfriend who had Dermatomyositis/Psoriases/Eczema and how what worked for her, helped me with my CFS/Fibromyalgia.

Story 1 - Girlfriend (Non - CFS/ME):
When my girlfriend was about 10 years old, she contracted what was diagnosed at the time as Dermatomyositis. She couldn't keep food down, and became incredibly weak, couldn't walk down stairs, and almost starved to death. The Doctors in a last ditch effort gave her steroids and the state of her health improved quickly, to the point she was free of problems until she was about 20 years old. Then at 20 she began battling a flare up of Psoriases/Eczema which subsided after a year. Keeping food down wasn't an issue at this time. Same thing happened when she was 26. And now again at 29 the Psoriases like symptoms & Eczema came back.

I hunted down the best Naturopath I could find and he recommended she do the DetoxiGenomic Profile from Genova Diagnostics.

Here are her results:
gf liver detox genetic results.jpg


What's important to note here are the polymorphisms on the genes coding for Estrogen metabolism.

-CYP1B1 - Up-regulated.....responsible for 4-hydroxylation of estrogen
-CYP3A4 - Down-regulated (40% supposed) ........responsible for metabolism of cortisol, estrogen, testosterone, etc.
-COMT - Down-regulated (40% supposed)..........responsible for estrogen metabolism

Now how does this all relate to each other?
estradiol metabolism.jpg

Follow the orange arrows for the dominant pathway given the stated polymorphisms.

The combination of polymorphisms CYP3A4 and COMT have the effect of double down regulation on the production of good estrogen and an up-regulation via the most damaging pathway. A double whammy of sorts. Not good.

The polymorphism up-regulation on CYP1B1 exacerbates the problem by shuttling estrogen down for Quinone production massively increasing oxidative stress and putting a huge unnecessary load on Glutathione. My current theory is that this is what the root cause is behind dermatomycoytis, psoriases and eczema.

So what to do about it? - Supplements:
- I3C & DIM - These provide nutritional workarounds by helping estridol convert into the favorable 2-hyroxy-estradiol instead of the harmful 4-hyroxy-estradiol. In effect they support the CYP3A4 pathway.
- Calcium D-Glucarate- Supports the glucoronosyl transferase enzyme

Within 2 days of taking these, she had massive improvements in decreasing her symptoms and after a couple of weeks is almost completely healed. Success #1 !!!

Story 2 - Me the guy with CFS/Fibromyalgia
I came down with CFS/Fibromyalgia when I was 15 years old. I am 27 now, so I have been battling this for almost half my life. My primary symptoms are chronic fatigue, tired but wired, anxiety, excessive high body temperature...especially at night, muscle achiness, brain fog, poor concentration, poor memory, headaches, no appetite for 3 hours after waking- nausea associated with this, IBS, allergies & very poor recovery after exercise. I am textbook ME/CFS/Fibromyalgia. In contrast to my gf, I do not have Dermatomyositis/Psoriases/Eczema. My skin is fine and for the most part has been most of my life.

What I decided to do was take all the same supplements that my girlfriend was taking just to see what would happen. Within 24 hours, I had a huge burst of energy, brain fog cleared up, concentration improved and muscle achiness diminished. My emotions felt more stable and waking up in the morning I felt somewhat rejuvenated and not like I had been hit by a semi- truck which was the norm for me. Success #2!! I hit the gym, my cardio endurance improved, and when lifting weights my strength had also improved. Oddly my upper body sweats more now as well, and I appear to release heat better. Wow, I was elated. I hadn't felt like this in over a decade.

And then a few days later I had a setback. Fatigue started to return and I became exhausted. What I didn't mention is I had also started taking Sulforaphane (I figure may as well take all the broccoli supplements) and then subsequently learned it was an inhibitor of CYP3A4. Not good. So myself and my gf (who was also temporarily set back) stopped taking it and the benefits I3C & DIM began to return quickly.

Now I myself have not yet done the DetoxiGenomic Profile so I am merely guessing I have a somewhat similar of a genetic profile to my girlfriend. I have the test on order so hopefully in about 1 month's time I'll have a better idea of what's going on for myself from a genetic stand point.

For now my theory is that a lot of my CFS/Fibromyalgia is somehow linked to Xenoestrogens. The big assumption I am making here is that xenoestrogens are metabolized using more or less the same pathways as estrogen and that supporting those pathways may help. In retrospect I remembered the CFS/Fibromyalgia started almost right after I did a stint of Accutane when I was 15. Accutane is a potent xenoestrogen. And the CFS/Fibromyalgia symptoms I experienced for the last 10 years all line up quite well with the symptoms of a male with low effective testosterone and estrogen dominance. I currently believe that Accutane may have started a negative feedback loop of some kind.

I wrote an extensive article on Xenoestrogens and posted it to my website here:
---> http://www.gestaltreality.com/2012/05/19/fake-estrogen-a-modern-health-epidemic/ <---

Now while I have made drastic improvements I still do not feel quite 100%. I have Amy Yasko's Comprehensive Methylation Panel on order for myself and my gf, so I can address perhaps other underlying and potentially related issues.

Important Note: I have other problems that I have had since birth which indicate issues with Methylation prior to the onset of CFS/Fibromyalgia. My mother used thyroid meds to get pregnant with me, her mother died of thyroid cancer, my grandpa on my dad's side has prostate issues and his mother had b12 issues, my dad and his mother both got grey hair in their late 20's, my cousin on my dad's side has CFS....all of these things are linked with polymorphisms in methylation. So thus I have a sneaking suspicion I inherited issues from both my parents in regards to this. The toxic exposure (Accutane), again just made everything worse and was the straw that broke the camel's back so to speak and began the CFS. I was a colicky baby, had dry bleeding skin, numerous allergies, anxiety, and nightmares since I was born. All this got worse with the onset of CFS. As a child I also apparently reacted violently to MMR vaccinations.

Note I also recently added this:
- SAMe - Supports COMT in enhancing the methylation of 2 and 4-hydroxy-estradiol instead of quinone production.

It seems to be really helping my gf as well. And for myself I "think" it helps.

I have tried a gazillion supplements over the last decade or so, and been to countless doctors/Naturopath's and tried many therapies & diets. I even went to the Mayo clinic and after $10,000 worth of work they told me I was perfectly healthy according to their tests and to go home and learn to live with it. Yea right!

So far what I have found has worked for me was massive doses of glutamine 10-20g a day. This increased my energy from about 30% to 60% and a high protein diet took me to about 70%. The glutamine was a magic bullet in terms of the insane catabolism I had experienced with the associated achy muscular pain which had been virtually debilitating. Also acidophilus worked as well. And now the I3C & DIM. The journey continues.

I am curious if anyone else has experimented with IC3 & DIM? Again this may not work for everyone, depending on your genetic predispositions. The DIM I got is a very potent kind, double strength from Enzymatic Therapy. Supposedly the best.
 

ukxmrv

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I'd like to thank you Gestalt for your very thorough and informative post!

Hope someone will be able to comment on this properly as it's over my head but I am slowly working through it and looking bits up.
 
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O ok, I know Indole 3, but isn't I3C converted to DIM when taken so would there be a need to take both if you are taking DIM?
I'm interested in the dosages of C-D-Glucarate and DIM you and your g/f are on?
 

Gestalt

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I-3-C by AOR 200 mg 3 x a day
D-Glucarate by AOR 200mg 2x day
Estro-Balance by Enzymatic Therapy DIM from Indoplex 120mg 2x a day

And yes I3C converts to DIM, but I don't know what the conversion rate is and what's required for conversion.

I3C can breakdown into other forms as well. So it may offer differential benefits. DIM is just one form, and thus taking both supplements nets you the benefits of both. I tend to take a "more the better" approach.

I3C breakdown.jpg

http://clincancerres.aacrjournals.org/content/10/15/5233.full
 

Beyond

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This is fucking amazing, you are a hero. We were chasing genetic mutations and enviromental toxins as the root cause for months in some forums of desperate people and now this thread only confirms it!!! Now every case its different. I got my problems from Odaban (aluminum) and not Accutane but the rest of the story, including prone-to-be-sick family and very bad reactions to vaccines are exactly the same. I am gonna detox aluminum and mercury while getting the detoxi pannel and the yasko one. You maybe havent thought of the scope of your discoveries but there are hundreds of desperate post accutane/propecia etc users in boards and you have find a cure for some or most of them. My estradiol its high in all test btw. And in any case, you have find a great way to combat the increasing pollution of xenoestrogens.

Bravo!!
 

Beyond

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So, do you think with the Genova and the Yasko we can cover all the mutations, at least the crucial ones?

How much its the Genova, I cant see the price on the website.

I like your new age speculations on your web, have you read montalk.com? Good stuff.
 

globalpilot

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Thank you very much for posting this. Rich V pointed out I have a problem metabolizing estrogen based on my genovations resutls years ago. I have not done anything about it other than try to address the resulting oxidative stress. This gives something additional to look at. Thank you!
 

Gestalt

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Beyond - Yes I think the Genova and Yasko Genetic tests should get you all the crucial results you need. The Genova test runs somewhere between $600-$900. I'm always on the lookout for more/better tests. If anyone knows of some, please let me know.

freshveggies - I have no idea what SNP's 23andme tests. Can you find an exact list somewhere?
 

drex13

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23 and me provides results on both CYP1B1 and CYP3A4, but I don't know which SNP specifically we would be looking for. Someone is going to have to figure that out and do a conversion, like the Yasko to 23andme conversion. And figure out which genotype is normal, and which isn't.
 

place

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I'm a little confused...are saying that if one overloads their system with synthetic estrogen that it could potentially help?
 

globalpilot

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There is a test that may be very worthwhile here :
http://www.metametrix.com/test-menu/profiles/hormones/estronex
It measures various metabolites of estrogen including those in the diagram as above. I'm going to invest in this before trying the supplements.
I do have the polymorphisms that would lead to bad estrogen but will test first anyways.

Does anyone know if measuring the metabolites also includes the xenoestrogens ?

Gestalt - is your theory that you have BOTH the genetic mutations and xenoestrogens contributing to your fatigue ? ie. both are necessary.
 

Gestalt

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I'm a little confused...are saying that if one overloads their system with synthetic estrogen that it could potentially help?
I'm not sure how you came to that conclusion, but no, synthetic estrogen is not helpful.

There is a test that may be very worthwhile here :
http://www.metametrix.com/test-menu/profiles/hormones/estronex
It measures various metabolites of estrogen including those in the diagram as above. I'm going to invest in this before trying the supplements.
I do have the polymorphisms that would lead to bad estrogen but will test first anyways.
Does anyone know if measuring the metabolites also includes the xenoestrogens ?
Gestalt - is your theory that you have BOTH the genetic mutations and xenoestrogens contributing to your fatigue ? ie. both are necessary.
As far as I am aware the metabolism of xenoestrogens has not been definitively studied. Thus we really have no idea how the body rids itself of them. The assumption I am making and most people at large, is that xenoestrogens are metabolized along the same pathways as real estrogen's. If your ability to metabolize real estrogen is compromised then it is assumed xenoestrogen metabolism is also compromised, leading to elevated levels of both.

My theory is that both genetic mutations and xenoestrogens are problems independent of each other. However when the two occur together it compounds the problem.

You could hypothetically have no genetic mutations and xenoestrogens would still have a negative effect.
You could have genetic mutations and no xenoestrogens and still have issues, due to your body's compromised ability to detoxify it's own self created estrogen.
 
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Hi Gestalt, I found your thread as I have a theory that my post accutane fatigue is also caused high oestrogen or a compromised oestrogen metabolism. We run a big thread here http://www.musclechatroom.com/forum/showthread.php?20097-Official-Accutane-Thread and someone posted a link here.

You say that glutamine and protein diet have taken you to 70%, but how has your theory worked out since taking DIM, i3c and dgluconate? What are your thoughts on taking an aromotase inhibitor to lower E2 in the first place? I know it will also lower good oestrogen but I was thinking that maybe the E2 metabolism is compromised or sluggish as total E2 is too high so E2 metabolism isn't able to keep up?
 

richvank

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Hi, Gestalt and the group.

With regard to Accutane, here's something else to consider: Accutane has been found to raise the gene expression of the enzyme glycine N-methyl transferase. The effect of this is to lower the ratio of SAMe to SAH, and that lowers the methylation rates of the methyltransferase reactions, including the ones that methylate DNA and thus silence gene expression.

I have encountered several people who became chronically ill after Accutane (or Roaccutane in Australia) treatment. I think that what might have happened is that the gene expression for glycine N-methyltransferase got "stuck" high because of a positive feedback mechanism. Since methylfolate downregulates glycine N-methyltransferase at the biochemical level, taking a fairly high dosage of it may break this vicious circle.

Best regards,

Rich
 

richvank

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This story relates to my girlfriend who had Dermatomyositis/Psoriases/Eczema and how what worked for her, helped me with my CFS/Fibromyalgia.

Story 1 - Girlfriend (Non - CFS/ME):
When my girlfriend was about 10 years old, she contracted what was diagnosed at the time as Dermatomyositis. She couldn't keep food down, and became incredibly weak, couldn't walk down stairs, and almost starved to death. The Doctors in a last ditch effort gave her steroids and the state of her health improved quickly, to the point she was free of problems until she was about 20 years old. Then at 20 she began battling a flare up of Psoriases/Eczema which subsided after a year. Keeping food down wasn't an issue at this time. Same thing happened when she was 26. And now again at 29 the Psoriases like symptoms & Eczema came back.

I hunted down the best Naturopath I could find and he recommended she do the DetoxiGenomic Profile from Genova Diagnostics.

Here are her results:
View attachment 3530

What's important to note here are the polymorphisms on the genes coding for Estrogen metabolism.

-CYP1B1 - Up-regulated.....responsible for 4-hydroxylation of estrogen
-CYP3A4 - Down-regulated (40% supposed) ........responsible for metabolism of cortisol, estrogen, testosterone, etc.
-COMT - Down-regulated (40% supposed)..........responsible for estrogen metabolism

Now how does this all relate to each other?
View attachment 3531
Follow the orange arrows for the dominant pathway given the stated polymorphisms.

The combination of polymorphisms CYP3A4 and COMT have the effect of double down regulation on the production of good estrogen and an up-regulation via the most damaging pathway. A double whammy of sorts. Not good.

The polymorphism up-regulation on CYP1B1 exacerbates the problem by shuttling estrogen down for Quinone production massively increasing oxidative stress and putting a huge unnecessary load on Glutathione. My current theory is that this is what the root cause is behind dermatomycoytis, psoriases and eczema.

So what to do about it? - Supplements:
- I3C & DIM - These provide nutritional workarounds by helping estridol convert into the favorable 2-hyroxy-estradiol instead of the harmful 4-hyroxy-estradiol. In effect they support the CYP3A4 pathway.
- Calcium D-Glucarate- Supports the glucoronosyl transferase enzyme

Within 2 days of taking these, she had massive improvements in decreasing her symptoms and after a couple of weeks is almost completely healed. Success #1 !!!

Story 2 - Me the guy with CFS/Fibromyalgia
I came down with CFS/Fibromyalgia when I was 15 years old. I am 27 now, so I have been battling this for almost half my life. My primary symptoms are chronic fatigue, tired but wired, anxiety, excessive high body temperature...especially at night, muscle achiness, brain fog, poor concentration, poor memory, headaches, no appetite for 3 hours after waking- nausea associated with this, IBS, allergies & very poor recovery after exercise. I am textbook ME/CFS/Fibromyalgia. In contrast to my gf, I do not have Dermatomyositis/Psoriases/Eczema. My skin is fine and for the most part has been most of my life.

What I decided to do was take all the same supplements that my girlfriend was taking just to see what would happen. Within 24 hours, I had a huge burst of energy, brain fog cleared up, concentration improved and muscle achiness diminished. My emotions felt more stable and waking up in the morning I felt somewhat rejuvenated and not like I had been hit by a semi- truck which was the norm for me. Success #2!! I hit the gym, my cardio endurance improved, and when lifting weights my strength had also improved. Oddly my upper body sweats more now as well, and I appear to release heat better. Wow, I was elated. I hadn't felt like this in over a decade.

And then a few days later I had a setback. Fatigue started to return and I became exhausted. What I didn't mention is I had also started taking Sulforaphane (I figure may as well take all the broccoli supplements) and then subsequently learned it was an inhibitor of CYP3A4. Not good. So myself and my gf (who was also temporarily set back) stopped taking it and the benefits I3C & DIM began to return quickly.

Now I myself have not yet done the DetoxiGenomic Profile so I am merely guessing I have a somewhat similar of a genetic profile to my girlfriend. I have the test on order so hopefully in about 1 month's time I'll have a better idea of what's going on for myself from a genetic stand point.

For now my theory is that a lot of my CFS/Fibromyalgia is somehow linked to Xenoestrogens. The big assumption I am making here is that xenoestrogens are metabolized using more or less the same pathways as estrogen and that supporting those pathways may help. In retrospect I remembered the CFS/Fibromyalgia started almost right after I did a stint of Accutane when I was 15. Accutane is a potent xenoestrogen. And the CFS/Fibromyalgia symptoms I experienced for the last 10 years all line up quite well with the symptoms of a male with low effective testosterone and estrogen dominance. I currently believe that Accutane may have started a negative feedback loop of some kind.

I wrote an extensive article on Xenoestrogens and posted it to my website here:
---> http://www.gestaltreality.com/2012/05/19/fake-estrogen-a-modern-health-epidemic/ <---

Now while I have made drastic improvements I still do not feel quite 100%. I have Amy Yasko's Comprehensive Methylation Panel on order for myself and my gf, so I can address perhaps other underlying and potentially related issues.

Important Note: I have other problems that I have had since birth which indicate issues with Methylation prior to the onset of CFS/Fibromyalgia. My mother used thyroid meds to get pregnant with me, her mother died of thyroid cancer, my grandpa on my dad's side has prostate issues and his mother had b12 issues, my dad and his mother both got grey hair in their late 20's, my cousin on my dad's side has CFS....all of these things are linked with polymorphisms in methylation. So thus I have a sneaking suspicion I inherited issues from both my parents in regards to this. The toxic exposure (Accutane), again just made everything worse and was the straw that broke the camel's back so to speak and began the CFS. I was a colicky baby, had dry bleeding skin, numerous allergies, anxiety, and nightmares since I was born. All this got worse with the onset of CFS. As a child I also apparently reacted violently to MMR vaccinations.

Note I also recently added this:
- SAMe - Supports COMT in enhancing the methylation of 2 and 4-hydroxy-estradiol instead of quinone production.

It seems to be really helping my gf as well. And for myself I "think" it helps.

I have tried a gazillion supplements over the last decade or so, and been to countless doctors/Naturopath's and tried many therapies & diets. I even went to the Mayo clinic and after $10,000 worth of work they told me I was perfectly healthy according to their tests and to go home and learn to live with it. Yea right!

So far what I have found has worked for me was massive doses of glutamine 10-20g a day. This increased my energy from about 30% to 60% and a high protein diet took me to about 70%. The glutamine was a magic bullet in terms of the insane catabolism I had experienced with the associated achy muscular pain which had been virtually debilitating. Also acidophilus worked as well. And now the I3C & DIM. The journey continues.

I am curious if anyone else has experimented with IC3 & DIM? Again this may not work for everyone, depending on your genetic predispositions. The DIM I got is a very potent kind, double strength from Enzymatic Therapy. Supposedly the best.