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A 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 

Following on from my blog - Pathological Detoxifiers and Environmental Illness which explained the process of detoxification in the liver and when someone might be termed a 'pathologicial detoxifier' - I wanted to share the results of my own Detoxification Profile and explain how the results related to my illness at the time and subsequent developments.

The Detoxification Profile uses caffeine, paracetamol, and aspirin, to determine how well phase1 and some of the most important phase 2 liver detoxification pathways are functioning.

 

My Detoxification Profile Results

 

 

Interpretation

As you can see, although my phase 1 is within the reference range, it is towards the upper end of normal. In combination with this my phase 2 glutathione conjugation is borderline low. The other phase 2 pathways are all what Genova ,I believe, now classes as high and indicates increased toxic exposure. 

Other testing revealed my d-glucaric acid was high (another marker of increased toxic exposure) along with a cysteine deficiency. Cysteine is the sulphur-containing amino acid that is not only a component of glutathione, but also dertermines the rate at which it can be manufactured by the body.

The trend towards increased rate of phase 1 detoxification coupled with that towards deficient glutathione conjugation suggests I was at the time a mild pathological detoxifier. Interestingly, I went on to develop multiple chemical sensitivity (MCS) just over a year after this detoxification profile was carried out!

At the time of the test I had suffered from chronic fatigue syndrome (ME/CFS) for 10 years and had been diagnosed with fungal type dysbiosis/intestinal Candida overgrowth by various doctors including Dr. Keith Eaton, a consultant allergist and respected researcher in environmental medicine, following a Comprehensive Digestive Stool Analysis (CDSA) by Great Smokies Diagnostic Laboratory (now Genova Diagnostics) and blood ethanol  levels testing by Biolab (UK).

It seems a logical hypothesis that my trend towards being a pathological detoxifier was caused by chronic exposure to ethanol, acetaldehyde, and other chemical waste products of Candida, the infection with which resulted from impaired immunity associated with ME/CFS. Glutathione is the major phase 2 pathway dealing with the detoxification of alcohol which would explain its depletion. Further testing at Biolab also showed increased activity of specific phase 1 cytochrome P450 enzymes that deal with alcohol, specifically CYP 2A and 4.

 

I believe anyone suffering from environmental illnesses or unexplained symptoms should have a Detoxification Profile done if they are not getting help elsewhere. There are many nutritional and herbal supplements that can be used to restore balance to the detoxification pathways, reduce the toxic burden on the body, and restore health if there is indeed an imbalance detected.

 

For information about treating imbalanced liver detoxification see this blog:

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