Liver detox pathways
The liver phases in a nutshell
Your liver is your most important organ of detoxification and continuously processes 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 very toxic and others which are beneficial, and decide what to do with them. Your liver is very good at deciding what needs to be kept and what needs to be removed. It functions just like a complex chemical plant that manufactures new compounds, detoxifies dangerous compounds, and directs substances all over the body for use, storage or excretion.
Your liver makes use of two pathways in order to carry out its detoxification work – phase 1 and phase 2 pathways.
You can think of:
- Phase 1 as being responsible for breaking things down into smaller raw materials. These are then shunted to….
- Phase 2, which builds new substances from the raw materials, by adding molecules to them (this process is called conjugation).
- phase 1 breaks down &
- phase 2 adds-on
Phase 1 is the ‘SUBTRACTION’ phase of metabolism, where the enzymes work to subtract molecules from substances and break them up into smaller more useful units, just like the process of food digestion in the gut. Phase 1 is completely dependent on these 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 some of the substances, some very toxic end products (metabolites) remain and they must quickly be shunted to phase 2 pathway in order 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 of metablism, 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 stable and/or more functional for the body.
You can think of the phase 2 pathways like you would seven conveyor belts in constant motion extending outwards from a central point, where the phase 1 pathways empty their byproducts. Specific substances are shunted towards a specific conveyor belt where particular enzymes are waiting to add something else and create a new substance. Mostly specific amino acids are added, such as glycine and taurine are added, as well as other substances such as glutathione, sulfate, and methyl. Each conveyor belt is named after the substance it adds/conjugates.
The seven parts of the phase 2 system are thus called:
- The Glycine pathway
- The Taurine pathway
- The Glutathione pathway
- The Sulphation (sulfation) pathway
- The Methylation pathway
- The Glucoronidation pathway
- The Acetylation pathway
Where do these conjugation substances, used in phase 2, come from?
We must supply them via our diet and/or make them in our body through enzyme-dependent chemical reactions.
Since many of these conjugation substances can be derived from big proteins that you eat, it helps explain why regular protein-dense meals are considered so helpful for chronically ill/toxic people.
But sometimes your body is simply unable to go through all of the specific steps required, in order to break down complex proteins and thereby provide phase 2 with the the conjugation substances it needs to keep the process going. For example, sulfur foods are metabolized down through several steps in order to produce sulfate, but some people are unable to complete the conversion of sulfur into sulfate, or they do it poorly, due to faulty or poisoned enzymes. Since they can’t manufacture sulfate efficiently, such individuals must supply sulfate endogenously (from outside of the body), through supplements taken on a daily basis, such as magnesium sulfate (Epsom Salts) or glucosamine sulphate, in order to keep the phase 2 sulfation pathway moving.
We thus need to continually supply the special conjugation substances required in phase 2 via our diet or internal metabolism, or the production process lines come to a halt. If one conveyor belt stops because it is missing its special substance, the other conveyor belts are sometimes equipped to deal with the overflow from the jammed production. But certain compounds are fussy, and will only go down one specific pathway, and production must simply wait until more of the conjugation substance is provided. If these compounds that are hanging around are toxic, they can cause health problems whilst they await the phase 2 pathway to get going again.
Even still, despite this block in the phase 2 production line , the phase 1 production process does not let up, and it just keeps on going and going, making more toxic compounds and causing a bottle-neck, and leading to issues such as Multiple Chemical Sensitivity (MCS).
You can think of these toxic metabolites from phase 1 as many freshly laid, fragile eggs from different livestock, that are churned out every second in the phase 1 process. These eggs need to be quickly organized 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. And so, in a healthy system, the eggs are swiftly organized onto specific conveyor belts in the phase 2 pathway, where workers (phase 2 enzymes) add conjugation substances, such as egg boxes and bubble wrap to stabilizes the eggs, and makes them ready for transport. Without the protective packaging that phase 2 provides, the eggs from phase 1 will cause a lot of trouble!
In Multiple Chemical Sensitivity (MCS) the phase 1 birds are making way too many eggs, while the phase 2 workers are overwhelmed and can’t keep up with the packing. When phase 1 is moving too fast in this way, it creates a bottle-neck at the beginning of the phase 2 conveyor belt and the eggs spill over and make a huge mess. Sometimes it is a genetic cause, and other times an environmental, as some chemicals cause phase 1 to move even faster, such exposure to the preservatives BHT and BHA, or the herbs licorice and ginseng.
Either way, when this happens in the body, the toxic metabolites that are bottle-necked at the beginning of phase 2 start to circulate and cause damage throughout the system. So when a person with MCS encounters certain chemicals like perfumes or paint that need to be detoxified by the phase 2 system and it is not working for the above reasons, they experience a lot of symptoms.
In order to help with the symptoms of Multiple Chemical Sensitivity (MCS) these individuals need to:
- Avoid chemicals that speed up phase 1 (see Dr Andy Cutler’s book Amalgam Illness: Diagnosis and Treatment pg. 40-43 for a complete list of phase 1 and 2 inducers and inhibitors)
- Slow down phase 1, with phase 1 inhibitors, such as niacinamide (500-1000mg/day).
- Speed up & support phase 2 (e.g. with substances like magnesium sulfate or methyl support)
But, two specific substances have the added benefit of helping to modulate both liver phases at the same time i.e. they slow down phase 1 and speed up phase 2 simultaneously, making them most helpful for MCS:
- Grapefruit juice (250ml 3-4 times per day)
- Oregano oil, (dosages vary).
Combining the above with the phase 1 inhibitor, niacinamide, is often where most people need to start.
Since many foods can either induce or inhibit the liver pathways, it takes quite a bit of personal experimentation to find out where exactly in your liver pathways you are having trouble.
Some foods that are said to positively affect the liver pathways, fall into the high-thiol or high sulfur category, as explained by Dr Andy Cutler. It is very important that all individuals suffering with MCS, or who suspect heavy metal toxicity, do a sulfur food exclusion trial in order to find out if you have problems with sulfur foods. This can make a chronically ill person feel instantly better, by avoiding thiols in foods, that act as heavy metal mobilizers, making susceptible people feel ill much of the time.
Ideally, make sure you get your gut health better before taking compounds to assist your liver pathways. This is an extremely helpful step not to miss out!
The phrase: “you need to clean downstream before you can clean upstream” is often used, to imply that you should clean your bowels first, before tackling your liver (or at least at the same time). Otherwise, you will be sending dirty water from the gut to the clean chemical plant which is the liver. This is a common cause for so called ‘detoxification-illness’.
Practically, that means addressing the following:
1) FOOD EXCLUSION TESTS:
- SULFUR FOODS: do 10-day sulfur food exclusion trial in order to ascertain if you have problems with sulfur foods, which implies heavy metal toxicity according to Dr Andy Cutlers principles.
- ELIMINATION DIET: once you have figured out if sulfur foods are a problem or not, continue with a more comprehensive elimination diet, as described by the Institute of Functional Medicine. This will further exclude foods that are causing problems.
- take probiotics regularly, varying the brands. Only select brands where the manufacturer lists the precise strain of bacteria on the label, as these companies tend to produce better products, as they make the effort to source specific strains e.g. B. lactis Bi-07, where the Bi-07 implies a specfic strain of B. lactis.
3) STOOL TEST: Whenever possible, test the ecology of the bowels with a stool test. However, step 1 and 2 above are vastly more important than a stool test, which is very helpful to catch unusual and unexpected pathogens.
Many chronically sick people will have developed a leaky gut, and so often the gut lining needs to be repaired/supported during the above process by using certain products containing glutamine, DLG (Deglycerized Licorice) and aloe (with the laxative properties removed). An example of a good product that can achieve this is Glutagenics by Metagenics.
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 stable 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 stable, 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 they actually doing what they are supposed to.
- Tackle your gut first – do the SULFUR EXCLUSION TRIAL first and then the ELIMINATION DIET thereafter.
- Get on probiotics and glutamine supplements to heal the gut lining
- Look into your hormonal system. Support your adrenals first using an Adrenal Cortical Extract, and thereafter look towards your thyroid health, in order to begin moving your body temperature, closer towards 37 degrees C (98.6F) and towards stability.
- Address your liver pathways if necessary, through the use of grapefruit juice, niacinamide and oregano oil
- Detoxify heavy metals only with oral chelation, once all amalgams have been safely removed.