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Pathological Detoxifiers and Environmental Illness

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Pathological DetoxifierA little while ago a member posted in the forums about a subject which hasn't been addressed specifically on the site before - 'pathological detoxifiers'.

I thought this subject deserved more attention as it can be a vital piece in the puzzle for those suffering from environmental illnesses including multiple chemical sensitivity (MCS), chronic fatigue syndrome (ME/CFS), and Gulf War syndrome.

To define what it means to be a pathological detoxifier first we need to understand the basics of how liver detoxification works:


Liver Detoxification

The detoxification of toxins by the liver basically occurs in two phases. Substances the liver must detoxify can be exogenous (from outside of the body) such as alcohol, drugs, pollutants, or endogenous (from inside the body) such as hormones.

Most toxins are fat-soluble which means they are easily absorbed and stored in the body (particularly fatty tissues, including the brain), but are difficult to get rid of. The overall aim of phases 1 and 2 of the liver detoxification system is to make toxins more water soluble so they can be easily excreted by the body in urine. Some remain predominantly fat-soluble and are excreted into bile and eventually removed from the body during a bowel movement.

Phase 1 mainly uses a class of enzymes known as the cytochrome P450 system to oxidise toxins and make them more easily excretable and/or easier for the phase 2 system to pick up and carry on the job. Some substances such as caffeine go through phase 1 and are then directly excreted in the urine without going through phase 2. Equally some toxins can bypass phase 1 and go straight into phase 2. In the most part however (and this will become important in terms of the pathological detoxifier), toxins pass through both phases of liver detoxification before the body can rid itself of them.

Phase 2 involves the binding, or "conjugation", of certain substances to the toxins coming out of phase 1 so they can be removed from the body. There are six different conjugation pathways - glutathione conjugation, amino acid conjugation (e.g. glycine, taurine), sulphation, glucuronidation, acetylation, and esterification. Glutathione conjugation is generally considered the most crucial but this is not to say the other pathways do not play an important role and all need to be functioning optimally for good health.

So basically - phase 1 prepares toxins for conjugation by phase 2 which renders the toxins safe and able to be excreted.


The Pathological Detoxifier 

Problems arise because when we are exposed to increased amounts of toxins this increases the rate at which phase 1 operates and it can usually continue to work at this rate indefinately. This isn't a problem if phase 2 pathways can keep up. Unfortunately in many people, if phase 1 activity remains elevated for a prolongd period the substances used by phase 2 tend to become depleted and phase 2 can no longer function efficiently and keep up with phase 1. When this situation exists in an individual they are said to be a pathological detoxifier. Substances coming out of phase 1 can't all be taken care of by phase 2, so instead they circulate throughout the body causing symptoms of toxicity and disease. What makes things worse is that substances produced by phase 1 are sometimes actually even more toxic than the original toxins being detoxified. This is why it is essential that phase 1 and phase 2 are in balance.

If you suffer from environmental illness or unexplained symptoms, or you feel "toxic"...it may be that you are a pathological detoxifier and you literally are toxic. Fortunately there is a simple test available from various functional medicine labs that can determine if this is the case. The test involves taking a small dose of caffeine, paracetamol, and aspirin, and then collecting urine over a specified amount of time. By measuring the amounts of detoxification products of these substances in your urine the lab can determine how quickly phase 1 and a number of phase 2 pathways are working.

I myself had a Detoxification Profile carried out by Great Smokies Diagnostic Lab (now Genova Diagnostics) back in 2000 to investigate the causes of my chronic fatigue syndrome. My results suggested a trend towards me being a pathological detoxifer. See the following blog:

Detoxification Profile Results - The Pathological Detoxifier and Chronic Illness

For information about treating imbalanced liver detoxification see this blog:

Foods and Supplements to Balance Phase 1 and Phase 2 Liver Detoxification 


Pathological Detoxifiers and Environmental IllnessDynamic Neural Retraining Program (DNRS)


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People in this conversation

  • Middlesbrough, UK

    You're welcome Jason. I've had a lot of positive feedback about this blog series so I'm glad it's been a good guide for yourself and others. To answer your question, it took maybe a month to see any noticeable improvement and I saw real benefits after 3 to 6 months. I think this is in-line with what has been seen in clinical studies on patients with more severe liver disease (fatty liver, hepatitis, cirrhosis etc).

    The product you've bought looks good as it has a high phosphatidyl choline content per serving (520mg) but I noticed the lecithin is still derived from soy beans like the alternatives - it's just that it is not genetically modified soy (Non-GMO). Is this why you chose it or do you have a soy allergy or intolerance?

    In any case, I hope you start seeing benefits from it soon.

  • Hi Maff,

    Thanks for this valuable information! I am looking into these phase 1 and phase 2 detoxification and ordered this product (because it's soy-free): http://www.iherb.com/Now-Foods-Sunflower-Lecithin-1200-mg-200-Softgels/23216
    It contains: Phosphatidyl Choline

    I wonder how long it took that you have noticed some positive effects from Phosphatidyl Choline?

  • Hi Heather,

    Welcome to the site and thank you for your excellent post! Sorry it has taken me so long to reply but I have been on holiday/vacation after completing my bachelor's degree in nutritional health.

    You make an excellent point about milk thistle (silymarin) and its inhibitory effects on glucuronidation. I should have included this somewhere. I think what I will do is add another blog post to this series listing foods, supplements, drugs and other substances that INHIBIT the various detoxification pathways.

    It's great to hear that your extensive research has paid off and calcium-d-glucurate has been so beneficial for you.

    I have to ask where you have read that reverse osmosis filtered water is highly acidic? Reverse osmosis effectively leaves only H2O itself which obviously has a neutral pH. However important minerals (typically alkaline) are removed in the process so if drinking water from a reverse osmosis filter it is essential to supplement with a multimineral and consume plenty of vegetables and fruits (if sugar is tolerated).

    I hope you continue to see improvements Heather and thanks again for posting - it would be great to read more from you in the future :)

    Comment last edited on about 8 years ago by Maff
  • Hi Mary,

    It is very difficult when your husband cannot tolerate many foods and supplements. It sounds like far infrared (FIR) saunas may be appropriate to remove the identified toxins from the body through the skin (in sweat).

    This in itself over time may help him tolerate more foods and supplements. For the time being I would suggest sticking to supplements such as silymarin (milk thistle) which both slow down Phase I while simulataneously increasing Phase II capacity. This would at least limit the number of supplements needed. Can he tolerate grapefruit or its juice? This contains a substance that potently inhibits Phase I even in modest amounts so would be worth a shot.

    Best wishes to you both and please let us know if you need more suggestions.

    Comment last edited on about 8 years ago by Maff
  • Hi Beth,

    No problem and thanks. I'll need all the luck I can get to get all my degree work handed in on time ;) Hopefully when I graduate I'll have time to update the out of date sections of the site and improve the quality of information.

    Very wise to look for information from as many sources as possible. I have been to countless doctors and other health care providers over the years and none alone has been able to help me significantly. They have all provided me with valuable information and insights that have helped me piece things together though.

    Great that your mother is a nutritional therapist. I'm sure she has seen a lot of patients with Candida so will know the issues and be able to help you. Plus she's your mum so you know she'll be doing everything she can! I guess that's how you got the detoxification profile kit so quickly?

    Take care and do let us know when you get your results!

    Comment last edited on about 8 years ago by Maff
  • Hi Beth,

    Sorry for taking my time in replying to your comments. I am in the final year of a bachelor's degree that will lead to me becoming a nutritional therapist so I'm very busy working on coursework and my dissertation at the moment.

    Thanks for the nice comment about the site :)

    Sorry to hear you're suffering badly at the moment. We are all in the same boat or have been so we know what you're going through!

    B56 is right on the money as always. PPC is definitely at the top of the list for supplements to improve liver health and support detoxification processes. There is a large amount of research backing up it's positive effects on the whole range of liver disorders. It has been found to help in alcoholic liver disease and therefore people suffering with Candida/yeast-related illness are likely to benefit as Candida and other yeast produce alcohol as part of their metabolism and this is then absorbed from the gut and travels to the liver where it can overwhelm detoxification pathways if this is a chronic situation.

    Another supplement with a similar amount of research behind it is SAMe. Both PPC and SAMe work in large part by increasing glutathione - the body's major antioxidant and detoxifying enzyme.

    I have to admit though, as B56 mentioned, that I've had problems with digestive upset when taking both PPC and SAMe. I now take lecithin with 35% phosphatidylcholine (PC) without any problems and it seems to help.

    I have also found that herbs which stimulate bile flow (known as choleretics) are very helpful. Production of bile in the liver and its excretion into the digestive tract are an essential part of the detoxification so it is important to keep it flowing. A choleretic herb I have found particularly helpful but which is not often mentioned for this purpose is Tribulus terrestris. However, studies have shown it both improves bile flow and also increases glutathione.

    I hope the detoxification profile sheds some light on your problems. Please let me know if I can help interpreting the results. You could even post your results in a blog entry if you have a scanner to scan them.

    It is certainly possible the symptoms you have had since taking the test are due to the aspirin and paracetemol. These drugs can temporarily increase intestinal permeability (causing "leaky gut") which puts extra strain on the liver. They are also of course directly toxic to the liver in large doses and are likely to be problematic at lower doses in people such as us (speaking from experience I know they can be as many drugs can - antibitotics and antifungals can be particularly bad!). The increased intestinal permeability is likely to be only temporary and both the gut and liver are good at repairing themselves so hopefully your symptoms will improve fairly quickly.

    I am still struggling to tolerate antifungals and get my health truly back on track myself. I have big problems with nervous system-related symptoms when I go on antifungals. I do believe we can all find our way back to health though so hang in there!

    Comment last edited on about 8 years ago by Maff
  • No problem, thanks for raising the topic in the first place :)

    Yes that is my experience as well. The term "pathological detoxifier" comes from the alternative medicine field and is not used in conventional medicine as far as I know.

    I had a battery of tests done by functional testing labs around the time of my detoxification profile all pointing to chronic toxic exposure, nutritional deficiencies, gut problems, and liver detoxification problems. I took them to various specialists - (immunologists etc) and they were all dismissed out of hand. I was incensed when the immunologist told me that if his own children had ME/CFS (he didn't believe in MCS) he wouldn't waste his money on these tests. I had a lot of the answers to my suffering in my hands and here was a highly intelligent and educated specialist simply dismissing them with no consideration. I am sure things will change but this will take time...

    There are signs they already are. I now have a GP (who also has a biochemistry degree) who is very open and believes 1. that both ME/CFS and MCS are physical illnesses and 2. a lot of the things I suggest as treatment approaches could well be useful but he is bound by guidelines so can't prescribe them. He tried prescribing the probiotic VSL#3 which costs close to Ăƒâ€šĂ‚Â£100 a month only to find it is not sanctioned by our local healthcare trust.

    I don't know if it was a typo but it's Austria not Australia that has joined Germany in recognizing MCS ;)

    P.S. I plan to write another blog this coming week on foods and nutritional supplements that address pathological detoxification.

    Comment last edited on about 8 years ago by Maff

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