The Phases of Liver Detoxification
Your liver works very hard to keep you safe from toxins. It’s your primary and best defence against most of the toxic substances your body encounters from within and from the outside. The majority of these toxins are fat-soluble. Your body has tremendous difficulty trying to get rid of these fat-soluble chemicals. It can’t readily excrete them through your kidneys so it must instead rely heavily on your liver. Almost all drugs, chemicals, hormones and other substances your body generates are metabolised (broken down) through enzymatic pathways. Most of these take place inside your liver cells.
Your liver accomplishes the conversion of fat-soluble toxins to water-soluble ones in two phases. They are:
Phase I of Detoxification – Oxidation Reduction and Hydrolysis
This phase is predominantly carried out by the CYP (cytochrome P450) enzymes and to a much lesser extent by the MFO (mixed-function oxidase) enzymes. Both groups are found in the membranes of your hepatocytes (native liver cells). Within each of these two families of enzymes there are several enzyme members. Other reactions that happen in phase I include dehalogenation and hydration.
If your body is exposed to a certain chemical, your liver cells manufacture more CYP enzymes to deal with it. It’s your body’s way of shielding you from any harm caused by the chemical. These CYP enzymes use oxidation reduction and hydrolytic reactions to convert the harmful toxin into a less harmful (bearable) one.
However this process of conversion to a less harmful toxin carries its risks. Your liver cells produce a lot of free radicals which can consequently damage your liver cells when they’re produced in excessive. Taking antioxidants (such as vitamins C and E) can help to reduce or even prevent any damage.
Your CYP and MFO groups of enzymes aren’t always bulletproof. Some toxins are powerful enough to deactivate or hyper stimulate one or both enzyme systems. Imagine that. As an example, say you drank too much alcohol last night. Alcohol directly hyper stimulates your CYP enzymes so high levels of free radicals are produced. These can be very dangerous to the body if they’re not metabolised to water-soluble compounds by phase 2 of the detoxification pathway.
On the flipside, if you’re exposed to a substance that inhibits the CYP enzymes, you may have increased circulating levels of the toxic substance.
Here’s a quick reference table of substances that hyper stimulate or inhibit your CYP enzymes.
Hyper Stimulate CYP
Organophosphates (found in pesticides)
Paint & exhaust fumes
Dioxins and dioxin-like compounds (DLCs)
The flavonoid naringenin in grapefruit
Curcumin in turmeric
So if you’re exposed to these substances, you will produce more free radicals which can cause cell damage if not converted by phase 2 right away.
So if you’re exposed to these substances, you will have less CYP enzymes to detoxify harmful toxins so the toxins stay in the body longer and can cause damage.
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Your CYP group of enzymes handle the detoxification of the following substances:
- Antibiotics – macrolides
- Acetaminophen and theophylline
- Hormones – cortisol, estradiol, testosterone
- Beta-blockers – metoprolol, alprenolol, propranolol
- Diazepam and phenytoin
- Anaesthesia drugs used during surgery
- Ibuprofen and other NSAIDS (non-steroidal anti-inflammatory drugs)
- Antidepressant medications
Phase II of Detoxification – Conjugation
This second phase of detoxification by your liver involves your liver cells attaching another substance to the toxin. This is done to make the toxin water-soluble so that it can be excreted from your body through your kidneys (urine) or gallbladder (bile). Some of the substances that are used to conjugate toxins include sulphate, glucuronic acid, glycine and glutathione. The enzymes that are used to conjugate these substances include glutathione-S-transferase and UDP-glucuronyl transferase.
How to Make Liver Detoxification More Efficient
Your liver cells love and depend very much on sulphur-containing amino acids like cysteine for an efficient phase II. You will also need choline, inositol, glutamine and glycine to make this phase run smoothly. Check out the infographic below for nutrients to support each phase of your liver’s detox pathway.
What happens when one phase is faster than the other or out of sync?
When one phase is faster than the other, toxic products can accumulate in your body. If phase I is faster, toxic intermediates can flood your system. While if phase I is slower many toxins will continue to circulate in your body instead of being neutralised. The majority of the fat-soluble toxins hide themselves in organs rich in fat cells like your brain, breasts and your endocrine glands. Incorporation into these organs leads to a variety of problems like hormonal imbalances and brain disorders.
In summary, when your body takes in a toxin, it passes through your liver and undergoes two phases of detoxification. There are substances that can alter the course and speed of each phase. As a consequence, the metabolism of the toxin can be affected. Your liver is a remarkable organ. It can take an enormous amount of punishment before it screams timeout or waives a white flag. Don’t let that happen to your liver. Now that you know just how hard your liver works to detoxify your body, try your best to take good care of it, okay?