What does it really mean to detox, and what is Hepatic Bio-transformation?
Firstly, the information from this article comes in large part from direct quotation or paraphrasing (for brevity and clarification) of the live-chat on this subject, given by Dr. Kharrazian on facebook. It is now subsequently a video on YouTube entitled, « How To Detox Safely ».
The reason for this post is to clarify and categorize the enormous amount of information in that video, and to add additional clarifying information and links for people who are not part of the health and medical industry. Now, on to the good stuff!
WHAT REALLY IS DETOXING?
Detoxing is simply your body performing routine cleaning. It converts toxins into a *water-soluble metabolite that our body can excrete from our body in urine, sweat, and feces.
*(a molecule that can be dissolved in water)
Toxins come from everywhere. Cosmetics, air pollution, *formaldehyde from manufacturing, clothing production, food-born bacteria, even synthetic scents from cosmetics, candles, cleaning products, and perfume! The list goes on and on.
*formaldehyde exudes, or is « off-gassed » from newly manufactured clothing, furnishings, and appliances. These are only a few examples of chemical off-gassing
What are Obesogens?
Now, if these every-day toxins cannot be cleared from the body, they are either stored in adipocytes (fat cells) or they roam the body as free-radicals. Certain toxins like BPA, BPS or any other derived « BP » products are hard to clear from the body, so they’re stored in fat cells. They’re called obesogens because they actually make you fat!
What are Heavy Metals?
Heavy metals are also hard to clear. Lead (found in a lot of chocolate production), mercury (found in top-of-food-chain fish like tuna), and cadmium, (found in cigarette smoke), are also stored in the body.
Toxins and heavy metals need to be removed daily so they don’t roam your body as free radicals, causing damage and disease. So a healthy diet, proper sleep, and daily exercise are crucial.
The key goal with detoxing is to be able to clear out these chemicals and pollutants from normal every-day life.
So what are the mechanisms or ways in which we clear these out?
DETOX STARTS WITH ‘HEPA’
We are now entering the world of «DETOXING».
Detoxing is simply a general way to explain the body’s normal cleaning process. The true term is, HEPATIC-BIO-TRANSFORMATION HEPATIC, (from the latin ‘HEPA’, meaning, «Liver». «BIO» (biological; natural), « and “TRANSFORMATION”, to change.
Hepatic Bio-transformation must occur to keep you healthy. It happens when toxins are metabolized/converted, or «transformed» by your liver into compounds that can be eliminated in sweat, urine, and feces.
In the liver there are many different pathways where this happens. They have names depending on which pathway they are; glucoronidation, sulfation, acetylation, and methylation are some of these pathways. All of these pathway names refer to which process is happening to transform a toxin. They refer to what type of amino acid or chemical the pathway uses to convert the different toxins into something water soluble that can be eliminated.
One of the pathways is called glutathionylation. It needs Glutathione to process chemicals and ‘detox’ your body. According to askthescientists.com, Glutathione is one of the most numerous and important antioxidants in your body. So for that pathway to function, you need plenty of it! It’s found in large amounts in avocado, spinach, and asparagus.
So you know now that these pathways get rid of toxins, here’s how it all works.
YOUR LIVER AND HOW IT « DETOXES »
There are two phases your body needs to complete to convert toxins into harmless, water-soluble molecules.
PHASE 1 AND HOW IT WORKS
In Phase 1 – Toxins enter your body and are immediately funneled into a process called oxidation, reduction or hydroxylation. This simply means that there is a transfer of an electron on the toxin, or a slight change to the chain structure of the chemical to enable its transformation in a Phase 2 pathway. The toxin is now what’s called a ‘free radical’.
PHASE 2 AND HOW IT WORKS
In Phase 2 – The liver now takes this free radical and binds it to a different Amino Acid or metabolyte to make it water soluble. Once an Amino Acid or metabolyte binds to the toxin, that compound (toxin) becomes Water Soluble, then we can eliminate it!
Even excess hormones (and certain Endocrine Disruptors like BPA), need to go through these Phase 1 and 2 pathways to be removed.
EXAMPLES OF PHASE 2 PATHWAYS
There are many different pathways. One is Methylation. In the Methylation pathway, there are two carbons that are attached to the free radical to make it water soluble.
Another is Acetylation. In Acetylation, one carbon of Acetyl is attached to the free radical to make it water soluble.
Then there’s glutathione conjugation. The tripeptide amino acid, glutathione, binds to the Phase 1 metabolyte and makes it water soluble. These are just a few examples of many.
So, different free radicals go through different Phase 2 pathways. Some go through methylation, some go through glutathione conjugation, some go through glucoronidation.
WE NEED HEALTHY PHASES 1 AND 2
Problems can start if someone has impairments in Phase 2. For example if they don’t have enough Glutathione, then compounds which have been transformed into free radicals can’t be completed in Phase 2 to become water-soluble. Then these free-radicals can get into circulation and cause lots of inflammation and oxidative stress.
So in order for us to get rid of chemicals, these Phase 1 and Phase 2 pathways need to function at top efficiency. When chemicals go through Phase 1 and become free radicals, they actually become more inflammatory and more reactive than before.
Therefore, the process of Phase 1, which is necessary to change the structure of the toxin, creates a free-radical oxidative response. But it’s what must happen to get the toxin out of the body. This is why both Phase 1 AND Phase 2 need to be healthy and working correctly!
So it’s really important for us to have healthy Phase 2 pathways. So let’s talk about Phase 2 pathways. Phase 2 is like a coin sorter that separates coins into quarters, dimes, nickels, and pennies. Different chemicals have to go through different pathways just like the coins go into different slots.
So that’s the big picture of chemical Detoxification or Hepatic Bio-transformation.
DETOX IS DIFFERENT FOR EVERYONE
Now, we all have different degrees of efficiency in these pathways. Let’s look a little closer at how they work, because detox is not as simple as taking a botanical element like Chlorella or N-Acetyl Cysteine and thinking it’s going to make you better.
You really want to understand what’s happening and why there’s so much diversity. Some people respond differently to different toxins and chemicals, and other people respond to some treatments and don’t respond to other treatments. So first, let’s look at Genetics.
GENETICS AND HOW IT AFFECTS YOU ABILITY TO DETOX
The first key thing to understand is that because we’re all genetically different, we all have these different Phase 2 pathways – the coin sorter. Remember that each of these pathways clears out different chemicals. There are some genes and genetic differences that impact how effective each person is at clearing out certain pathways.
For example, some people have genetic uniquenesses where they can’t synthesize glutathione as much. Others can’t make enough glucaronic acid for the Phase 2. These are only two examples of many possible genetic differences.
There is a field of study called PHARMACOGENETICS, which is the STUDY OF GENETIC DETOX PATHWAYS. It studies the different genetic variations in our detox/liver bio transformation pathways. They call these pharmacogenetic pathways. These pathways can also change over time.
The field is still researching information, so until we come up with a system to genetically map everyone so we can achieve perfect health, you just need to remember a few things:
Certain chemicals are harder to metabolize by certain gene uniquenesses, and certain diseases have been associated with these gene uniquenesses. And this is where your environment combined with your genes can make you at risk for certain exposures and compromise your health.
This is why you need to focus on your health and wellness. Don’t put yourself at risk with poor diet, bad sleep habits, and a sedentary lifestyle.
GENETICALLY UNIQUE PATHWAY EXAMPLES
METHYLATION – In this pathway, if you had a genetic weakness where you didn’t have ideal methylation, and you also really became deficient in nutrients that support this pathway – *Folate and B12( see link below) – then if you get exposed to the particular free radical that has to be metabolized by methylation, then you can have some serious problems.
BPA DETOXING – We also know that certain diseases also have a hard time processing synthetic chemicals. For example, in patients that have Parkinson’s disease, we know they have a unique characteristic where they can’t metabolize BPA. Then that BPA in the system becomes reactive. And it can create an immuno-reactive response to something called ‘Alphas Nuclein’.
GLUCORONIDATION – Another example where a genetic problem can happen is with glucoronic acid. This is another Phase 2 Pathway. In order for the pathway glucoronidation to function, you have to make glucoronic-acid. So you have to have glucose in your cells.
Improve detox pathways by eating plenty of cruciferous vegetables!
People that are chronically hypo-glycemic, or have uncontrolled blood sugar issues and diabetes, their glucoronic-acid levels are not as efficient compared to healthy people. So now their blood sugar issue doesn’t allow glucose to get into the cell that needs that substrate (glucose) to make glucoronic acid. If you don’t have enough glucoronic acid you may not be able to metabolize chemicals that depend on that particular Phase 2 biotransformation pathway, aka glucoronidation.
YOUR LIFESTYLE AND DIET AFFECT YOUR PHASE 1 AND 2 PATHWAYS!
So you have your Phase 1 and Phase 2, and you have genetic differences which make you more or less efficient in these processing these pathways. Your lifestyle and diet can also play with your genes and make you either more or less efficient in processing these chemicals.
Let’s look at how to make these pathways as efficient as possible.
NEXT: THE NUTRIENTS THAT OPTIMIZE THE DETOX PATHWAYS
Now typically in these Phase 1 and Phase 2 pathways, we rely on some Key Nutrients to work.
So as we know from above, some people have genetic uniquenesses where they’re not efficient in one of the above pathways. The most common weakness is methyl-tetrahydrafolate polymorphase reductism*, about 20-25% of the US Population is affected. This means they don’t have efficient methylation pathways, (the adding of a two-carbon group) and they really needs higher amounts of things like Folate and B12 to make them more efficient compared to other people.
Your pathways are highly reliant on the body’s antioxidant system to be able to quench some of those toxic metabolytes and to play a role in this process. Anti-oxidants like flavonoids, tannins, and polyphenols are needed. Glutathione for Glutathione Conjugation, or garlic and onions for the Sulfation pathway when sulfur is attached to the free-radical. So you need your anti-oxidant system fit for the Phase 1 pathways, and you need plenty of Amino Acids and different vitamins and substrates in Phase 2.
When you look at what neutraceutical companies put in detox products that they produce and market to help clear out those pathways, they’re loaded with N-Acetyl Cysteine, Cysteine, Glutathione, B-Vitamins, like Folate and other B’s, and different anti-oxidants, Because those are the cofactors that are supportive of those Phase 1 and 2 pathways.
This means you need to eat vegetables and fruits of all colors, especially strongly colored foods like berries, carrots, beets, and dark leafy greens.
GUT DETOXIFICATION?!
Surprise! They’ve also found that these Phase 1 and 2 pathways that take place in the liver, also take place in the gut, by the bacteria!! This is called Microbiome Bio-transformation, read about the Microbiome in my article, What Is A Microbiome and How Do I promote Its Health And Diversity?
Bacterial Species in the gut (intestines) have enzymes just like the liver does. They clear out pollutants and toxins and turn them into a metabolytes capable of being eliminated in urine and feces.
This is why it’s absolutely crucial to have healthy and diverse bacteria living in your gut.
ln Mircobiome Bio-transformation, different bacterial species have different enzymes that impact different chemicals. So having a healthy microbiome diversity optimizes the different types of Bacteria, and all these different bacteria have different enzymes to metabolize different types of chemicals.
WHAT HAPPENS AFTER PHASE 1 AND 2?
So once the chemicals have gone through Phase 1 and 2, and become a metabloyte that is water soluble, the next step is that those compounds are funneled through portal pathways and are combined with Bile in your Gall Bladder. Your Gall Bladder has to contract (squeeze) to release the metabolytes that have been cleared in Phase 1 and 2, so that they can be pushed into the GI tract, where they can be combined with, and eliminated in, fecal material.
So Gall Bladder function is critical.
NORMAL ELIMINATION IS IMPORTANT!
Having normal bowel motility is important to eliminate these metabolytes. If they’re not eliminated, then they recirculate into your system. (MORE TO COME ON THIS TOPIC)
THE IMPORTANCE OF EXERCISE IN DETOXING
So, your metabolism performs the Phase 1 and 2 process – the detoxification/transformation of chemicals – but your lymphatic system has a role in removing these as well.
The metabolism detoxes by using Phase 1, which is highly dependent on Anti-oxidants, and Phase 2 which is highly dependent on sulfur, Amino Acids, B Vitamins and things like Glutathione etc. You also need microbiome diversity to help metabolize and detox chemicals. Once everything passes through these phases, it’s important to have healthy Gall-bladder and bowel function to eliminate all of these compounds.
But they’re not all eliminated in fecal matter. There are other pathways through your lymphatic system that are involved in removing toxins, such as sweating and urinating.
YOUR LYMPHATIC SYSTEM
The lymphatic system is crucial in getting these toxins moved to your liver so they can go through these Phase 1 and 2 processes. It moves these *metabolyzed compounds around as muscles contract.
*(the metabolyzed compounds are the now water-soluble toxins that went through Phase 1 and 2)
When muscles contract, the lymph nodes that are next to them cause movement of these metabolytes. So in order to have healthy metabolyte function, you have to have movement. That means a sedentary lifestyle (sitting around, desk jobs, etc) is not conducive to a healthy system. You also need sweating to help eliminate these metabolytes. Sweating, urinating, and fecal output are all part of this detoxification to eliminate these chemicals.
THE TOXIC WORLD AROUND US
So everyone is being exposed to different chemicals through air, water, food, cosmetics, cleaning products, synthetic chemicals, heavy elements like lead, cadmium (found in cigarette smoke, especially second-hand smoke). And if they’re not excreted, then they’re stored in fatty tissue. Your body is essentially trying to keep them away from critical organs to prevent damage. However, when they are stored in body fat they can promote obesity, this is known from well-published research.
We also know that toxic metabolytes like lead are stored in skeletal tissue. So if we can’t metabolize or transform these things, they stay there …until as you age and start to lose bone mass, this lead suddenly floods the bloodstream and can lead to neurological problems.
The other thing that happens when we can’t transform and metabolize chemicals through the Phase 1 and 2 pathways, is that they continue to cause inflammation and become free-radicals in our system. This decreases our anti-oxidant system, which in turn increases our risk for inflammation.
We also find that when these chemicals don’t get metabolized, they start to bind to proteins in our body. The most common protein in our body is albumin. Albumin is there to control our osmotic pressure, which is the ability of our blood vessels to maintain a certain pressure so that we don’t have swelling.
WHAT HAPPENS WHEN CHEMICALS AREN’T METABOLIZED?
So when chemicals aren’t metabolized and bind to proteins, they become adjuvents, or neo-antigens, which can trigger immune responses. Then your body makes anti-bodies to those antigens and those anti-bodies are highly assoicated with risks for different neuro-degenerative diseases and different auto-immune diseases. So it’s really important for us to detox.
So how do we get detox to happen?
We need all the pathways to be efficient, we need all the different « coin sorters » to work correctly. We need the Gall-bladder to function efficiently. We need a rich and diverse microbiome. We need lots of anti-oxidants and regular bowel movements. We need to make sure the lymphatic system is engaged by having daily exercise, and we need healthy amounts of sweating.
So this is the whole process of detoxification.
PHARMACOGENETICS, OR,
« WHAT IF I’M TAKING MEDICATION? »
So someone can go through life with some of their pathways genetically insufficient, or take medication, or be exposed to high amoungs of chemicals, and these pathways can get taxed.
And this combination of research with different medications causing adverse effects in detoxification, is a field of study called pharmacogenomics. They study how the different gene variations plus your medications can lead to adverse effects, because the body can’t metabolilze them.
AN EXAMPLE OF A POOR DETOX SYSTEM
So now we have our genes, plus our environment, plus these chemicals. So let’s look at a situation where someone goes on multiple medications or chemicals plus exposure to normal or increased environmental toxins. Their Phase 1 and 2 pathways get depleted. Let’s say they stop eating super foods, healthy foods, they’re eating the Standard American Diet (SAD), so they’re not getting high amounts of flavonoids and anti-oxidants in their diet. If they also smoke, that increases the free radical load. So now their Phase 1 pathways are compromised.
Now let’s say they don’t eat a lot of vegetables, don’t have enough sulfur, the sulfation pathway gets compromised. Let’s say they get pre-diabetic, they can’t get glucose in their cells, now their glucoronidation pathways get unbalanced.
Now let’s say they a COMT gene polymorphism, which happens to twenty five percent of the population. So they can’t methylate very well, (Methylation). Now they respond to toxic chemicals very differently.
Let’s say even further, since their diet is so bad, they don’t have microbiome diversity, so now they can’t bio-transform chemicals through their gut pathways, let’s say they have a sedentary lifestyle, they don’t move or exercise, so their lymphatic system is not working. And if they don’t exercise they also don’t sweat well.
So these things increase the so-called metabolyte load or ’toxic’ load, which causes inflammation and free radicals roaming around your body. These chemicals then get stuck in the circulation system and your body has to adapt, so it stores them in body fat which then increases weight gain. And it stores them in bone density, which can be a problem down the road when they start to have normal bone loss as they age.
Then don’t forget that some of these chemicals bind to proteins in our blood, in our circulation, like Albumin and they create new antigens and they cause this inflammatory response.
SO WHAT CAN WE DO TO HAVE EXCELLENT DETOX PATHWAYS?!
For Phase 1 pathways you have to have lots of super foods. Blueberries, raspberries, and foods with high amounts of anti-oxidants. Colorful food is so critical to provide those bio-flavinoids that are so important for everyone. Even taking anti-oxidants like Alpha-lipoic acid or Vitamin E or Glutathione are really important.
Sulphur and things like N-acetyl cysteine are really critical to metabolize compounds. We need sulphur to make glutathione for Phases 1 and 2, and for the bio-transformation that takes place in the gut. So, in addition to high anti-oxidants, you need lots of sulphur, especially when you get exposed to chemicals and multiple medications.
Make sure your microbiome is diverse. You must eat a diet diverse in vegetables and fruits to impact fibers that then lead to different bacteria being formed in your gut. So the more DIVERSE your fiber intake is, the more potential you have to diversify your gut microbiome. See the post, WHAT IS A MICROBIOME AND HOW DO I PROMOTE ITS HEALTH AND DIVERSITY?
And don’t forget movement and exercise which moves your lymphatic system, causes sweating, and gets your gastro-intenstinal motility working.
Conclusion…
Now you know the mechanisms of Hepatic Bio-Transformation! Don’t forget to exercise, eat plenty of deeply-colored fruits and vegetables, and get solid sleep!
To help with the last one, take a look at 7 Ways To Optimize Your Sleep.