Liver phases 1 and 2 detoxification pathways


The liver phases in a nutshell


 Your liver is your most important organ of detoxification. It continuously receives all forms of substances from your digestive tract and the rest of your body throughout the day. It has to deal with all these compounds,some of which are toxic and others which are useful. Your liver is very good at deciding what needs to be kept and what needs to be removed. It is like a massive chemical plant that manufactures certain compounds, detoxifies dangerous compounds, and directs substances all over the body for use, storage or excretion. Your liver makes use of two phases in order to carry out its work – phase 1 and phase 2. You can think of phase 1 as responsible for breaking things down and then sending the raw materials to phase 2 which builds new substances from the raw material by adding molecules to them (this is called conjugation).

Phase 1 uses several enzymes to break substances down. Think of this phase as the SUBTRACTION phase of metabolism, where the enzymes work to subtract molecules from substances and break them up into smaller more useful units, like digestion does in the gut. Phase 1 is utterly dependent on ENZYMES, whose speed of metabolism is in turn affected by things like genetics, exercise and the presence or absence of certain substances/supplements in the diet that can either speed them up (induce them) or slow them down (inhibit them). After the enzymes have broken down the substances, some very toxic end products (metabolites) remain and they must quickly be shunted to phase 2 pathways to make them safer for the body to use. Heavy metals in particular can make these enzymes dysfunctional.

Phase 2 is the ADDITION or CONJUGATION phase where new substances are added/conjugated to the toxic and good metabolites produced in phase 1 in order to make them easier to transport, more stabile and more functional for the body.
 Think of the phase 2 pathways like seven conveyor belts in constant motion extending from a central point, where the phase 1 empties its products. Specific substances are shunted towards a specific conveyor belt where particular enzymes are available for the addition of a ’special substance’ to create a new substance.
 Mostly these ’special substances’ are amino acids like glycine and taurine, and other substances, like glutathione, sulfate, and methyl. Each conveyor belt adds/conjugates a specific substance.

The seven parts (conveyor belts) of the phase 2 system are called:
 The Glycine pathway
 The Taurine pathway
 The Glutathione pathway
 The Sulphation (sulfation) pathway
 The Methylation pathway
 The Glucoronidation pathway
 The Acetylation pathway

You need to supply the ’special conjugation substances’ via your diet or the production lines come to a halt. If one conveyor belt stops because it is missing its ’special substance’, the other conveyor belts are equipped to deal with some of these jammed items that need conjugation. But certain compounds are restricted to only go down a specific pathway and production must wait until more of the ’special substance’ is provided. Even still, phase 1 does not stop production and it just keeps on going.

Since many of these ’special substances’ can be derived from big proteins that you eat, it shows why regular protein meals are vital for ill people. Sometimes your body is unable to go through all of the specific steps it needs to, in order to break complex proteins down fully and thereby provide phase 2 some of the seven particular ’special substances’. For example, sulphur (sulfur foods) are metabolized down through several steps in order to produce sulphate (sulfate), but some people are unable to complete the conversion of sulphur into sulphate, or they do it poorly, due to faulty or poisoned enzymes. In order to keep the Sulphation pathway moving, they must supply sulphate to the body via supplements taken on a daily basis, such as Magnesium sulphate (Epsom Salts) or Glucosamine sulphate. Different people will have different problems with different pathways.

You can think of the toxic metabolites from phase 1 as many freshly laid and fragile eggs from different birds that are churned out every second in the phase 1 factory. These eggs need to be quickly organised and sent down the correct conveyor belt or they will back-up and create a huge mess. Chicken eggs must go down the chicken egg conveyor belt, and geese eggs down the geese egg conveyor belt. So the eggs are swiftly organized onto specific conveyor phase 2 belts where workers (phase 2 enzymes) add certain ’special substances’, to create boxes and bubble wrap (taurine, glycine,sulphate) which stabilizes them and makes them ready for transport.

In Multiple Chemical Sensitivity (MCS) the phase 1 birds are making way to many eggs, while the phase 2 workers are overwhelmed and can’t keep up with the packing. This creates a bottle-neck at the beginning of the phase 2 conveyor belt and the eggs spill over and make a huge mess. When this happens in the body, the toxic metabolites that are bottle-necked at the beginning of phase 2 start to circulate and cause a lot of damage throughout the system. So when a person with MCS encounters certain compounds like perfumes or paint that need to be detoxified by the phase 2 system and it is not working, then they get a lot of symptoms. These individuals need help to slow down phase 1 pathways (e.g. with phase 1 inhibitors like niacinamide, 500-1000mg/day or grapefruit juice, several times per day or oregano oil, this also kills intestinal yeast and dosages vary) and support/speed up phase 2 pathways (e.g. with substances like sulphate or methyl groups). Grapefruit juice and curcumin (in tumeric, though people with high plasma cysteine and sulfur problems are cautioned by Andy Cutler, in Amalgam Illness, as curcumin raises plasma cysteine further ) are able to accomplish both of these tasks by slowing down phase 1 and speeding up phase 2 simultaneously. Here is a chart that shows the substances metabolised in the phase 1 pathways, and inducers and inhibitors of the specific enzymes.It takes quite a bit of personal experimentation to find out where exactly in your liver pathways you are having trouble.


Lab tests

Some labs such as Genova Labs (they used to be known as Great Smokies Lab) are able to test the ability of the liver to detoxify substances through its pathways, through their Liver Detoxification Profile. Here is an excellent article from the Genova on the liver detoxification test and its application.

There is a more comprehensive article on the liver pathways here… It is well worth reading.

So where do I start?
 One of the most important principles of detoxification is that you need to clean your bowels first. The phrase: “You need to clean downstream before you can clean upstream is often used’. It means: clean your intestines first, otherwise you will be sending dirty water from the gut to a clean chemical plant at the liver! This is a common cause for so called detoxification-illness.

Practically that means assess the ecology of the bowels with a stool test. Thereafter follow these common gut-cleaning principles:

First, Weed (remove offending foods and pathogens), then
 Seed (take appropriate pro-biotics), and thereafter
 Feed (eat the correct foods for your body).

Many people will have developed a leaky gut by the time they are ill, and so often the gut lining needs to be repaired during the initial weeding phase by using certain products containing glutamine, DLG (DeGlycerized Licorice so as to remove the cortisol retaining properties) and aloe (with the laxative properties removed). An example of a good product that can achieve this is Glutagenics by Metagenics.

Make sure you get your gut health better before taking compounds to assist your liver pathways. This is a vital step not to miss out!

Another vital consideration before beginning a detoxification program is to ensure that your metabolism is up to the task, by addressing your adrenals and thyroid. Your body temperature indicates just how well your adrenal and thyroid hormones are having an effect at a receptor level. You need your daily average (based on three oral temperatures taken around 9am, 12noon and 3pm) to measure 98.6 degrees F/37 degrees C and stabile for good health. If they are higher one day and lower the next, it indicates adrenal problems – because the adrenals control the stability of internal temperature. If they are low but stabile, it indicates thyroid problems – because the thyroid hormones (T3 in specific) lift the temperature. Saliva testing of the adrenals by DiagnosTechs Labs, and temperature testing and thyroid blood tests, will help you figure out if these glands are making sufficient adrenal and thyroid hormones to keep you healthy.

The thyroid labs will measure the glandular output (how much hormone is been secreted by the glands in the blood), while temperatures will measure the effectiveness of the hormones at a receptor level i.e. are the actually doing what they are supposed to.

To summarise:

  • Tackle your gut and hormone issues first,
  • Gut: get a stool test and use pro-biotics, diet, and supplements to heal the gut lining.
  • Work on your adrenals and thyroid via thyroid support, begin working with your body temperature, moving it closer towards 37 degrees (98.6F) and stabile
  • Address your liver pathways (as above), and
  • Continue down your detoxification path to remove offending metals e.g with oral chelation.