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detox diets & cytochrome P450 enzymes

Messages
78
I saw an integrative medicine doctor on Tuesday. He diagnosed me with CFS (no surprises there) and suggested I look up which of the cytochrome P450 liver enzymes metabolizes azithromycin (the antibiotic I took which caused my current crash), because apparently I'm deficient in it.

His "solution" to fixing these issues is to do the detox diet by metagenics, dry skin brushing and dry saunas (all for detox). I suspect he recommends the same things to a lot of people, something I have found is common with a lot of alternative docs. I am also afraid the diet would make me feel worse, though, and since I am gradually improving, although slowly, part of me doesn't want to mess with it.

Anyway, I just wondered if anyone had ever heard of cytochrome P450 enzymes before--it would go with the theory that ME/CFS is caused by a buildup of toxins.

Has anyone tried one of the detox diets (metagenics, standard process, etc.) and if so what was your experience?
 

xchocoholic

Senior Member
Messages
2,947
Location
Florida
I know I should know about p450 but that info is apparently tucked away at this moment. Lol fwiw tho we have numerous
detox mechanisms so I'm not sure we can actually blame just one for cfs.

I'm responding about the metagenics detox diet. I'm assuming you mean their detox powdered
meal replacement. I tried one container of that after I'd been on the gfcfsf + chemical free diet after 2 years
and because it's a rice base it made my blood glucose problems worse.

Imho, the wahls diet is a better option. Just slowly change out your current foods for her recommended foods.
We get more nutrients from foods that they can put in supplements. In case you haven't seen it we have a thread
here on dr wahls.

Tc .. X
 

richvank

Senior Member
Messages
2,732
HI, Kathy.

Azithromycin is not metabolized much by the cytochrome P450 enzymes. It is mostly excreted unchanged. About 6% of it goes out in the urine. Excretion in the bile is a "major route," but I don't know if the amount that goes out in the stools has actually been measured. There have been several studies to see if azithromycin interacts with other drugs that are metabolized by CYP3A, because other macrolide antibiotics do, but azithromycin does not appear to.

If you Google the "Flockhart table," you can see which cytochrome enzymes metabolize various drugs, and I think it only notes that azithromycin is NOT metabolized by the CYP3A enzymes.

Best regards,

Rich
 
Messages
78
Hi Rich,

Thank you so much for your response and the information about the Flockhart table. I am in awe of all the amazing work you do for everyone. I have a few questions:

1. I asked this MD if he had heard of methylation and he said yes, that the Metagenics detox diet (called the Clear Change program) would be "similar." I have to say, I'm a little skeptical, does this seem right to you? I definitely trust your opinion on this!

2. If azithromycin is not metabolized by these enzymes, what does that mean in terms of detoxification (e.g., would the methylation protocol still be an appropriate strategy)? Any thoughts on why someone with CFS would have a toxic reaction to azithromycin?

3. This doc mentioned a saliva test costing about $500 which would tell you which drugs your body can tolerate or not. I assume it is a type of DNA testing, is it like the Yasko testing I saw on her site (is it what is called nutrigenomics)?

I hope it's ok to ask all these questions, and that they are clear enough. Thanks again.

Kathy
 

richvank

Senior Member
Messages
2,732
***Hi, Kathy.

Thank you so much for your response and the information about the Flockhart table.

***You're welcome.

I am in awe of all the amazing work you do for everyone. I have a few questions:

1. I asked this MD if he had heard of methylation and he said yes, that the Metagenics detox diet (called the Clear Change program) would be "similar." I have to say, I'm a little skeptical, does this seem right to you? I definitely trust your opinion on this!

***I looked up the ingredients in the "Clear Change" supplement, and it contains some folic acid and B12, but they are at small dosages, so I don't think it is similar to the methylation treatment.

2. If azithromycin is not metabolized by these enzymes, what does that mean in terms of detoxification (e.g., would the methylation protocol still be an appropriate strategy)? Any thoughts on why someone with CFS would have a toxic reaction to azithromycin?

***Detoxication is only one of the things that is improved by the methylation treatment. It corrects a host of other things, also, because it treats the root issue in the pathophysiology of CFS. I don't know why azithromycin was a problem for you. Perhaps your liver needs some support.

3. This doc mentioned a saliva test costing about $500 which would tell you which drugs your body can tolerate or not. I assume it is a type of DNA testing, is it like the Yasko testing I saw on her site (is it what is called nutrigenomics)?

***No, the test you doc mentioned sounds more like it measures what is in the Genovations DetoxiGenomic Profile.
I don't know the current price of that.

I hope it's ok to ask all these questions, and that they are clear enough. Thanks again.

***Sorry I don't know about the azithromycin reaction. Maybe somebody else can comment about that.

***Best regards,

***Rich
 
Messages
78
Rich, thank you this is so helpful. I am glad I asked. I am thinking I will go back to another alternative MD who I have been seeing for many years to see if she will help me with the methylation protocol. Take care.
 

BEG

Senior Member
Messages
1,032
Location
Southeast US
Hi Kathy,

A doctor put me on the Z-pak (zithromycin). It was powerful because it was condensed into only 6 pills. I had a routine blood test while I was on it, and my liver enzymes had tanked. I had one doctor confess when it was over that he was quite concerned.

I did an online search for zithromycin and had many lawyer sites pop up. Some people do fine on it, but I would recommend that CFS patients stay away from it. BTY, I always thought since it was metabolized in the liver, it utilized p450. Just FYI, Tagamet, the common digestive aid, is metabolized by p450. Another one to avoid.
 
Messages
78
Hi BEG,

Thanks for your reply. I'm still learning about this p450 stuff, can you please explain why medications which are metabolized by p450 are ones to avoid? I thought there were different enzymes that fall under the p450 umbrella and the bad reactions are from the individual enzymes a person has that don't metabolize well. At least that is what I gathered from the 5-minute conversation I had with a doc I saw this week :).

Kathy
 

richvank

Senior Member
Messages
2,732
Hi, Kathy.

Drugs are foreign substances to the body, and it treats them as toxins and tries to get rid of them. A lot of them are oxidized in the liver by the CYP450 enzymes, of which there are many, but CYP 1, 2, and 3 types are the ones that metabolize drugs, CYP3A being responsible for metabolizing over half of the drugs.

People do have genetic polymorphisms in the genes that code for the CYP enzymes, and some of them can make it difficult to metabolize drugs. In such cases, a dosage that had been selected for the general population will result in the concentration going higher and staying longer in the blood in these people, and there can then be toxic effects of the drug.

Another issue is taking more than one drug that uses or suppresses the same CYP enzyme. That can have similar effects to the above.

Best regards,

Rich
 
Messages
78
Hi Karina,

My kids had pertussis and I freaked out a little, I didn't really need it. I only took the one dose, which is the first two pills of a z-pack. Sure wish I hadn't...

Kathy
 

BEG

Senior Member
Messages
1,032
Location
Southeast US
Hi BEG,

Thanks for your reply. I'm still learning about this p450 stuff, can you please explain why medications which are metabolized by p450 are ones to avoid? I thought there were different enzymes that fall under the p450 umbrella and the bad reactions are from the individual enzymes a person has that don't metabolize well. At least that is what I gathered from the 5-minute conversation I had with a doc I saw this week :).

Kathy

I wish I could elaborate. Sometime along the way I probably read something. Obvioiusly, I don't have thorough understanding of this p450 enzyme. However, several doctors I was seeing at the time were concerned. In fact, most concerned of all was my CFS specialist.

The next post by Rich gives a good explanation. You do a good job in your own post. I will say that the "tagamet" comment came from a doctor. She recommended taking something else.

I hope your crash is short lived and you soon feel better.
 
Messages
67
Location
NYC
Hi Karina,

My kids had pertussis and I freaked out a little, I didn't really need it. I only took the one dose, which is the first two pills of a z-pack. Sure wish I hadn't...

Kathy

ah, ok. that sucks. on the other hand, if you have a bacterial infection such as lyme, chlamydia pneumonia, etc, your negative reaction might actually be a good sign. so it would be a shame to avoid antibiotics in the future if those are what you'd really need for recovery. i hope you get a chance to test for various bacterial infections. good luck :)

ps: i took azithromycin for the first time last december and had a strange reaction- developed rashes and blisters on my feet, hands and throat- had to take steroids for weeks because i couldn't walk or eat. that may have been an allergic reaction of sorts, though.
 

undcvr

Senior Member
Messages
822
Location
NYC
I think that the P450 enzymes are at the heart of CFS and that it is a malfunctioning of these enzymes. Most of these enzymes are involved in Phase 1 and if that phase is sped up too much it can cause alot of the symptoms associated with CFS. Our bodies may not even be making the rite kind of P450 enzymes due to broken or easily hijacked pathways.

http://tuberose.com/Liver_Detoxification.html
 

richvank

Senior Member
Messages
2,732
Hi, all.

Another issue associated with the CYP enzymes in ME/CFS is that glutathione is depleted, and so is not able to help quench the oxidizing free radicals that are generated by the CYP enzymes as they react with toxins. Glutathione is involved in the detoxication system both in Phase I (with the CYP enzymes) and by serving in one of the Phase II pathways, by conjugating several categories of toxins.

Thus, depletion of glutathione, as well as causing many other problems in ME/CFS, wreaks havoc with the detox system and leads to buildup of body burdens of many toxins.

Best regards,

Rich
 

undcvr

Senior Member
Messages
822
Location
NYC
But there are reports of many pple with cfs who do not respond to glutathione supplementation. Both sublingual and S or R acetylated glutathione are absorbed intact so they are bioavailable. It seems obvious that glutathione supplementation should help in such cases, but it can make symptoms worse too.
 

richvank

Senior Member
Messages
2,732
Hi, undcvr.

That's true. Dr. Cheney thinks the reason is that PWMEs are low in NADPH (which he has measured in his patients), and that is needed by glutathione reductase to recycle glutathione. So when glutathione is added, it gets oxidized,and that shifts the GSH to GSSG ratio down, worsening the redox environment in the cells.

I don't favor direct boosting of glutathione on its own. I tried that from 1999 through 2004, and the results were as you stated. The way to raise glutathione is to correct the partial methylation cycle block, which is upstream of glutathione synthesis. We have lab evidence from our clinical trial that this works.

I have suggested boosting glutathione as an add-on to the methylation treatment to counter the excitotoxicity that many people experience on this treatment, which I suspect is due to an initial further drop in glutathione. More recently, I've suggested trying L-cystine (not cysteine) to boost production of glutathione in the brain during this treatment. This should not be done if a high body burden of mercury is suspected.

Best regards,

Rich