Detoxification can be dangerous as well as beneficial – here’s why
Detox’s, and especially New Year detox’s, where people tend to go extra hardcore, fill me with fear.
I’ve seen it in our Functional Medicine and Nutritional Therapy clinics too many times.
Heavily marketed detox’s that claim to rejuvenate and revitalise after a period of over indulgence, often leaving people with more digestive issues, headaches and weight gain then they started out with.
What’s liver detoxification all about?
Firstly, liver detoxification is a real thing (!).
The liver filters more than a litre of blood every minute, and is responsible for turning normal waste products and toxins into a form that the body can easily excrete.
Liver detoxification processes are a normal function that happens all the time, every day.
So you may wonder why we would want or need to interfere with, or do anything specifically to support, these ‘normal’ processes that are already occurring.
One way to look at it, is considering the efficiency of those detoxification processes.
The detox reactions in the liver are controlled by enzymes, and these enzymes dictate how fast (or slow) the reactions will occur.
We can’t assume that we have a good level of enzymes in the first place.
Our individual genetics determine how well we will produce specific enzymes (something that we can test for, through DNA testing of the genes that code for these enzymes).
Another factor to consider is the total toxic load, i.e. the amount of substances the liver has to metabolise (detox) at any given time.
Poor liver detoxification (also referred to as metabolic detoxification) can lead to:
leading to a wide range of signs and symptoms.
You can find some examples of these below, but this is only a small example of the signs and symptoms that can be associated with sub-optimal liver detoxification processes:
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The liver is responsible for metabolising potentially toxic chemicals or substances from inside and outside of the body.
Most of the toxins are fat-soluble, which means they dissolve only in fat or oil, and not in water, making them difficult to excrete from the body.
Being fat-soluble, many of these substances can be stored in adipose (fat) tissue or in the membrane of cells (which are made of fatty acids).
The toxins may then only be released when someone experiences weight loss (more specifically fat loss), or during periods of high stress, high exercise, or fasting.
When the fat-soluble toxins aren’t efficiently dealt with by the liver, they can contribute to symptoms such as headaches, fatigue, skin issues, cognitive issues, and many more.
When it comes to liver detoxification, the key aim is for the liver to turn these fat-soluble toxins, into water-soluble toxins, so they can easily be excreted from the body.
To achieve this, there are three phases of liver detoxification.
Let’s dive into each of these phases:
And here’s a more in-depth graphic of the essential nutrients needed for effective detoxification, as well as the reactions and pathways involved:
As you can see, there are a lot of factors involved in detoxification, and if you don’t have all of these factors in place, it can lead to compromised detoxification.
In our clinical experience, this can be a factor in many of the health problems we help our clients with.
And for many people who are following a ‘detox program’ in the search for better health and increased energy, getting it wrong can lead to short and long term health problems.
Phase 1 liver detoxification
During phase 1, toxins from the environment, waste products / toxins produced in the body, and those absorbed through contaminated food and water, are converted to less harmful substances via a family of enzymes, called the Cytochrome (CYP) P450 enzymes.
Individual detoxification capacity can be explained by not having enough of a particular CYP450 enzyme (genetically), or not having sufficient nutrient cofactors for these enzymes to function optimally.
Vitamins act as cofactors for CYP450 enzymes, enabling the enzymes to function and facilitate the phase 1 detoxification reaction.
Phase 1 end products are more water soluble, but they also become less stable, i.e., become more reactive, producing more free radicals, and contributing to increased oxidative stress.
This means that phase 1 intermediate products (or metabolites) can be more harmful than the ‘original’ toxin.
Due to the high levels of free radicals produced during phase 1 reactions, your antioxidant status is important.
Some phase 1 metabolites are excreted through the kidneys at this stage.
But the majority of phase 1 products need to undergo phase 2 metabolism rapidly, to minimise harm to the liver.
Many detoxes such as juice cleanses only promote phase 1 pathways, but if phase 2 isn’t also responding quickly enough, this can lead to a greater toxic load, or to put it another way, toxins can be backed up in your body with no where to go.
This is not good – and it can be a big problem for health (and weight loss).
Phase 2 detoxification
Phase 2 detoxification is also known as the conjugation pathway.
This is where products from phase 1 are bound to a molecule to make it less reactive, and therefore less harmful.
The end products of phase 2 also become more water-soluble so they can be safely removed from the body.
The availability of amino acids (the building blocks of protein) is a critical factor for liver detoxification processes, and particularly for phase 2 reactions.
Therefore any ‘detox’ program that excludes protein – for instance juice only or water only detox programmes – are essentially not promoting phase 2 detoxification and can result in a greater toxic load in your body.
Have you ever done a juice fast and felt amazing for a short while, before feeling a whole lot worse?
Remember – if only phase 1 is supported, then potentially there is more oxidative stress, and the potential for more harm, because phase 2 isn’t fast enough to mop up these phase 1 metabolites.
If food is being excluded e.g., a juice only fast, then taking amino acids in supplement form is important.
A low protein diet is also a nightmare for effective phase 2 detoxification.
Or you could be getting enough protein rich foods, but you have low stomach acid levels, or low pancreatic digestive enzymes, and so the protein-rich foods you are eating, are not being digested and absorbed properly.
Most phase 2 enzymes are dependent on a protein called nuclear factor erythroid-derived 2 (Nrf2), a master regulator of antioxidant response.
The presence of oxidative stress (like that produced by the products of phase 1 reactions), activates Nrf2, which then turns on the genes for phase 2 enzymes.
Certain foods can directly activate Nrf2, like sulforaphane from broccoli.
The enzymes responsible for phase 2 liver reactions, are working to bind a molecule (substrate) to the end products from phase 1. These are called ‘conjugation’ reactions.
The phase 2 enzymes and their functions
So this section is pretty terminology dense, and you don’t necessarily need to grasp it to understand why detoxification can be harmful.
If it’s not for you, feel free to skip down to the section on phase 3 detoxification.
UDP-glucuronosyltransferases (UGTs) catalyse the glucuronidation reactions, where a glucuronic acid is attached to a toxin, making it less reactive and more water soluble.
Oestrogens are metabolised via this pathway, as well as many environmental chemicals, such as:
Glutathione S-transferases (GST) catalyse the transfer of glutathione (an important antioxidant produced in the liver) to certain phase 1 metabolites.
This important pathway deals with:
GSTs also function as an antioxidant and help to reduce oxidative stress.
Sufotransferases (SULTs) attach sulphate to phase 1 metabolites.
This phase 2 pathway plays an important role in pharmaceutical medication and environmental toxin detoxification.
Another key phase 2 reaction is called methylation.
The enzymes responsible for methylation are called methyltransferase enzymes. In methylation reactions, a methyl group (which molecularly, is a very simple hydrogen and carbon molecule) is attached to phase 1 metabolites.
Important methyltransferase enzymes include methyl-tetrahydrofolate reductase (MTHFR) and COMT (Catechol O-methyltransferase).
SAMe (S-adenosyl-L-methionine) is the most abundant methyl donor – provides a methyl group to facilitate methylation.
This pathway aids in the detoxification of some environmental chemicals including heavy metals, stress hormones and oestrogen metabolites.
Some amino acids conjugate with phase 1 metabolites.
The enzymes Acyl-CoA synthetase and acyl-CoA amino acid N-acyltransferases attach an amino acid (e.g. glycine and glutamine) to some environmental and industrial chemicals (xenobiotics).
The N-acetyltransferase (NAT) enzymes are responsible for acetylation.
In acetylation, an acetyl Co-A molecule is added to toxins.
Caffeine and some medications like benzodiazepines and sulphonamides (broad spectrum antibiotics) are examples of substances that are detoxified via acetylation.
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Phase 3 detoxification
Phase 3 transporters (carrier proteins) are responsible for enabling the phase 2 end products to be carried out of the cells, ready for elimination from the body.
Phase 3 transporters are found in many tissues, including the liver, intestines, kidneys and brain.
In the liver, the phase 3 transporters move conjugated products (from phase 2) out of the cells and into the bile for elimination through the stools.
In the kidneys and intestinal tract, phase 3 transporters remove phase 2 conjugated products from the blood to be eliminated through the kidneys and eventually out in the urine.
are just a few suggestions for supporting optimal phase 3 detoxification.
So what can go wrong during your detox?
Basically, when doing a detox, what you don’t want to do is release lots of stored toxins from your fat into your bloodstream (phase 1), and then there not be anywhere for them to go because your phase 2 or phase 3 isn’t doing its thing.
If you do that, all the toxins you just released re-circulate around your body, potentially causing tissue damage.
And that’s both not what you intended with your ‘healthy’ detox, and it’s not good news for your health.
So it’s a good idea to know what you’re doing, and remember that the consequences of screwing your healthy detox up can include:
And it’s no joke – we see these consequences in our clinics regularly.
Of course, that won’t stop your average insta influencer or C rated celeb from selling you on a detox programme that could do you more harm than good.
Detox is a multi million (even billion) dollar industry, and don’t kid yourself for a second that your health matters more than their profit.
How to do your detox properly
When trying to optimise detoxification processes, it’s important to work to support all three phases simultaneously, or in the reverse order – phase 3, then phase 2 and then phase 1.
For instance, if you’re struggling with constipation, then this should be addressed first.
If the bowels are not moving regularly, then you run the risk of toxins being reabsorbed into the system (a process called entero-hepatic recirculation).
That’s not good news, and can cause more harm than the ‘original’ toxin.
If you’re not passing stools a minimum of once a day, it may not be a good idea starting any kind of detox, until this is fixed.
to help with bowel motility.
Natural laxatives to help get things moving include magnesium citrate and vitamin C (in supplement form).
If only phase 1 liver detoxification pathways are supported, for example through juice fasts, or other types of fasts that restrict protein intake, hopefully you can see how this could be disastrous for your health, and that sufficient support for phase 2 is also required at the same time.
Vitamin, mineral, protein and phytonutrient status are all key to ensuring that the liver enzymes have all the cofactors they need to function, and to ensure efficient, non-harmful detoxification.
A good level of antioxidants is also important, to ensure that the free radicals produced by the detoxification reactions (that cause oxidative stress and tissue damage) are appropriately dealt with, before the oxidative stress can cause more damage.
A broad and varied diet helps to obtain all the necessary nutrients to support phase 1, 2 and 3 detoxification pathways.
Individual differences in detoxification capacity can be explored through functional testing, such as genetic SNP testing for detoxification enzymes, oxidative stress markers and testing levels of detoxification pathway metabolites.
For those suffering from chronic conditions such as:
pinpointing enzymes that are not functioning optimally due to your unique genetics can be a real game changer.
Supplemental support can be tailored specifically to your individual needs, improving the efficiency and efficacy of detoxification, reducing oxidative stress, reducing inflammation, and allowing cellular function to ‘reboot’.
Unwanted signs and symptoms commonly seen after a detox-gone-wrong include:
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Your body is undergoing detoxification processes all the time, and you’re detoxing all the time, including right now.
Detox programs or cleanses, are focused periods of time when detoxification processes are enhanced.
But it’s not for everyone.
If you take medications, have a diagnosed condition or have a weak or compromised immune system, then seek professional advice before starting a detox program.
Pregnant or breast-feeding women should not follow a detox program.
Also, consider what toxins you are trying to eliminate from the body, as different toxins are metabolised differently by the liver.
Are you trying to remove heavy metals (cadmium e.g. from cigarette smoking, mercury, aluminium, etc) for instance?
Hormones? Pesticides? Phthalates (found in plastics)?
Bacterial toxins or caffeine?
These are all important considerations when. thinking about detoxification, otherwise that ‘healthy’ detox program could do more harm than good.
To your optimised, healthy future,
Dee & the Coho Health team
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