Cytochrome P450 Drug Metabolization Polymorphisms

There's a concept called "allostatic load" which describes how you hit a tipping point and the downward cascade accelerates. You were probably near that tipping but and had you been older, or had one more stressor, would have gone over. No doubt many people succumb without ever having had any idea what precipitated their final decline. I lived in Oregon not too long ago and the major 'health' megaplex I went to in Portland had so many seriously sickly looking people going in and out that it looked like the Court of Miracles. The vast majority were seriously overweight. That's a trend that it it can be even slightly reversed much suffering will be averted.
As far as this issue causing endocrine disorders, its easy to start over-generalizing once you get momentum. Quite possible, or a complicating factor, much like how a fatty liver wrecks so many things, but the root cause of most endocrine problems probably unlikely.
We'd all like a unified field theory to explain all misery but its never going to materialize is my guess.
Once I get some more clarification of an issue I'm dealing with I'll look into this, mainly as a way to help weight loss. Shedding 30 lbs would help a lot of things.
This won't explain everything, but its a very good jump on a lot of problems.
https://en.wikipedia.org/wiki/Allostatic_load

Allostatic load -- This perfectly explains what was happening to me! I had my own theory about this, but had no idea that there was a name for it.

I bet this is one factor of, maybe even the main contributing factor to, epigenetic switches being turned on, and perhaps also the cause of conditions such as fibromyalgia.

I truly-and-firmly believe that I was on-the-edge on my final decline. Years and years of feeling more and more ill and battling doctors all while trying to have a normal life (and the stressors of failing at that). It was at this point in August 2015 that I came home from yet another doctor's appointment crying because I was told once again that I my tests had come back normal and nothing was wrong with me. I finally stopped crying and got mad enough at the situation to call Mayo Clinic and ask if I could come. Thankfully, my insurance requires no referrals to see other doctors.

Looking back now, it's as if P450 drugs caused me to have a pseudo-acromegaly (with high but not super-high GH and IGF1 levels, which is usually the case, and lacking all physical symptoms). Another good example is that it caused me to have a buffalo hump, yet I always had normal cortisol levels, so no Cushings. When my PCP examined me on August 1, he lifted my hair and quickly said, "Oh my gosh, it's gone!" The hump was there for years, and was still there when he saw me the previous mid-April.

And I do realize that it could be that I, as an individual, have a super-wonky set of polymorphisms even compared to most people out there. For example, 33% of caucasians like me are CYP2D6 Poor, BUT are they also CYP2C9 Poor/Intermediate and also CYP2C19 Intermediate, etc.? When I came to Mayo a year ago, I was on 12 medications; the more medications you are on, the more likely these issues are likely to occur. BUT, my P450 symptoms actually started in 2005 after adding Celexa to the Nexium that I had started in 2004. (An additional theory I have is that this seems to occur to those of German ancestry more than other caucasians.)

Feeling better is great, but seeing all of my physical symptoms completely disappear from ceasing these drugs seems to have been the most fascinating factor for doctors. Knowing that I have lost 50 pounds in six months solely from ceasing metoprolol, omeprazole, ranitidine, and duloxetine has stunned them.

When you get a chance, please do look into this for yourself. One thing that my Mayo pharmacist said that struck me was, "I feel that every person should have this testing done." I feel that he's spot-on with this. He said that for all of the people he had tested from August 2015 through February 2016, most people had at least one polymorphism.

One other battle that I'm still in is getting doctors and pharmacists to realize that there are non-P450 metabolized medications that also inhibit/induce these enzymes. Currently, they stay inside-the-box and don't consider other meds; they assume that a drug metabolized elsewhere in the body won't affect things, and they also neglect to consider that things like vitamins. I know these things do because I lived it and felt this happen to me -- and the symptoms were exactly the same with these drugs as they were for metoprolol, omeprazole, ranitidine, and duloxetine. I think the problem is that they look things up on sites like clinicalpharmacology.com, which lacks information. Knowing that my clinical symptoms didn't match what my Mayo pharmacist was telling me (i.e., non-P450 drugs don't affect this), I did more research and was able to locate a Canadian database that acknowledges that these other drugs and supplements indeed do inhibit/induce, and this exactly-matches my clinical symptoms regarding taking non-P450 drugs / vitamins and inhibiting/inducing P450 enzymes. (It's called http://www.drugbank.ca, and it was developed by their government and their genome institutes. It's also acknowledged by some P450 doctors and pharmacists in Germany that I correspond with. These people have another database and also a tool that I'm looking into. The tool let's you enter your specific polymorphisms and medications and it will give you severity results.)

@dawn_giacabazi @johnwburns @alysebrunella @colleenyoung -- I wanted to share the attached photo with you. This is what cytochrome P450 drugs did to me because of my inability to properly-metabolize them. I started ceasing them in January 2016, and by July I had lost 50 pounds -- any stopping these P450-metabolized drugs is the only lifestyle change I made. Though I am still detoxing from them, I will be forever grateful to my Mayo doctors for listening to me and suggesting that I have these tests. What my home doctors couldn't figure out for 12 years, Mayo figured out in only six months.

Interestingly, in December 2015, I was in the patient cafeteria at Mayo and saw a young woman walking by looking for place to sit, so I waved her over to sit with me. We talked about medical stuff, as is normal in that cafeteria, I told her that Mayo was going to perform these Pharmacogenomic tests on me, and I told her that it sounded like she had many of the same issues I was having. We decided to become Facebook friends.

She was able to get into my doctor in Allergy/Immunology, and they decided to perform the testing on her. (I'm not sure why they sent me to the Center for Individualized Medicine but they ordered the tests for her directly from their department.) Anyway, it ends up that she has three of the exact same polymorphisms I have, plus some that I wasn't tested for (and I have polymorphisms that she doesn't have). We are now forever-friends and slowly-building our own community of information to help people.

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*** Looks like the site removed the sides of my photo. I'll try to revise and repost. Regardless, it still gives you a good idea regarding what happened to me.

Incredible @kdubois. Thank you for sharing so openly.
PS: I'm afraid that the photo attachment tool on Connect clips all images to the pre-set size.

Amazing!! Thank you for sharing and pray your encouraging success rings loud a amounts many!!

PgX is truly an amazing tool
Dawn