liver detox pathways chart

Every day I must get a dozen questions about the best way to “detox” the body.  I expect it, even welcome it.  After all, I AM The Detox Diva.  People want to know the best products work to detox their bodies.  More often than not they want to do, or have done and want to share their favorite products/recipes for fast liver cleanses.
Companies contact me to help “push” their snake oil products that promise a squeaky clean liver in 3-6-15 days.  After the urge to throw my computer out the window subsides I usually answer the reader explaining that there is not a one size fits all product that can properly cleanse the liver (no, not even milk thistle or dandelion tea) and answer the company kindly requesting they maybe perhaps need to understand exactly how the detoxification pathways work and how they can go totally wrong in the first place.  They usually respond too, telling me they have somehow figured out a way to skirt the process and miraculously carry toxins and used hormones straight out of the body.  Yeah, right, and George Clooney and I are getting married tomorrow on the moon!

So I thought today we would take a look at all the wonderful things your liver does in the body and a little about how it works.  This does carry a science nerd warning but I will be as succinct as possible.  Not only that, a few of the processes, we will be talking about in greater detail in subsequent posts.  (How estrogen detoxes through the methylation process and what happens when it chooses another path is a post all its own.)

Let’s talk about all the things your liver does for your body.

Wait, let’s back up for a moment and talk about toxins in the body, most of which enter the body as fat soluble toxins.  This means they dissolve only in oily or fatty solutions.  The body has major difficulty excreting fat soluble toxins.  Think, for a moment about pesticides and herbicides such as DDT, dioxin, 2,4,5-T, 2,3-D, PCB, and PCP.  These polycyclic hydrocarbons are so prevalent they are measurable in virtually all human fatty tissue in the US.  If you are overweight or obese, your fat cells are quite a bit larger than someone in a healthier weight range so you will store more of those toxins.

First and foremost the liver neutralizes harmful toxins in the body (endotoxins, made by your body like metabolic end products,bacteria, fungi, viruses and parasites from the blood and exotoxins, things like pesticides, herbicides, pharmaceutical and recreational drugs, food additives, insecticides and lest we forget, alcohol).

It filters the blood (as blood coming from the intestines contain quite high levels of fungi, parasites, bacteria and bacterial endotoxin, and antigen-antibody complexes and other miscellaneous toxic substances along with estrogen, and testosterone).  With a healthy liver, 99% of these toxins filter out the first time they pass through the liver.  A damaged liver, however, through chemical overload, alcoholism and other liver disorders, lets many of these toxins pass through without detoxing them.

The liver creates over 1 quart of bile a day and that bile serves as a carrier for many toxins to be taken to the intestines where both the bile and the toxins carried by it bind to fiber (think fruits and low ground veggies and that carrot salad) and excreted from the body.

This is where it starts to get good.  The detoxification “pathways” are divided into two processes Detox Pathways I &II (the latter is divided further into seven additional pathways but more on that later).

Detox Pathway I is an “addition” phase and is driven by enzymes called cytochrome P450 enzyme groups or Mixed Function Oxidase enzymes (MFOs).  The membrane system of liver cells called hepatocytes house these enzymes. These liver cells contain genetic code for many isoenzymes (types) of P450 which can be induced according to which type of chemical is introduced for detoxification.  This variation of isoenzyme provides a broad base of protection for a myriad of toxic chemicals.

Essentially, what happens is these toxic chemicals are rendered less harmful (in a healthy liver and detox pathway process) through various chemical processes such as reduction, oxidation, and hydrolysis. A toxin is often made water-soluble by cytochrome P450 during this process which means it can be more easily excreted through the kidneys.  The metabolic end product of the process creates free radicals. Everyone knows free radicals, in excess, can cause a lot of damage.  (Radical is the optimal word here.)  This is where antioxidant vitamins enter the picture.  Vitamins C and E and carotenoids all counter a lot of this damage (provided the rest of the liver is functioning as it should.)

Gluthathione, a master antioxidant, is required in phase i detoxification (which we will be discussing at length over the next few posts) to neutralize free radicals.  Glutathione (GSH) is oxidized to glutathione disulfide or GSSG) during this process.  Glutathione is also used in key phases of the Phase II detox process. When high levels of toxin exposure exists and there are too many free radicals generated so glutathione is depleted, the phases in Phase II that are dependent on glutathione are halted.  This is where oxidative stress and liver damage occurs.

When things go wrong in this phase less harmful chemicals can be turned into a more chemically active form of the chemical, occasionally even potentially carcinogenic substances.

What can go wrong in Phase I pathways?

An overload of certain chemicals can activate (effectively speeding up) Phase I pathways such as alcohol, steroids (including corticosteroids), barbiturates, caffeine, (can be a negative or positive), nicotine in cigarette smoke), paint and exhaust fumes (yep, what you smell can need detoxing), pesticides, herbicides, and insecticides, and even char-grilled meat.  This is called “induction”.

There are a few times when you want to speed up a sluggish Phase I pathway (we will be discussing this further in the next post) and you can accomplish this nutritionally by eating foods such as oranges, tangerines and lemons,(but never grapefruit juice!) cabbage, broccoli, and brussels sprouts, lots of protein, and herbs such as caraway and dill seeds.  Vitamins B1 and Vitamin C can also speed up a slow Phase I pathway.

There are many substances that actually inhibit cytochrome P450 and slow down Phase I detoxification.  This is problematic because toxic chemicals get to hang about in the body for longer than absolutely necessary before being detoxed. As an example, grapefruit juice decreases the rate of elimination of drugs from the bloodstream and has been found to substantially enhance their clinical activity (increasing their half life) and toxicity. Eight ounces of grapefruit juice contains enough of the flavonoid naringenin to decrease cytochrome P450 activity by a remarkable 30%. (This can be a good thing in some cases but more on that later.)

Drugs such asbenzodiazepines; antihistamines; cimetidine and other stomach-acid secretion blocking drugs (omeprazole, Nexium, and Zantac are killers!); ketoconazole; sulfaphenazole all work to inhibit cytochrome P450. Aging brings about a natural decline in the speed of Detox Pathway I and lack of exercise and/or poor circulation also aggravates the problem. (This is one of the few times speeding it up nutritionally is a good idea.)

There are times when slowing down cytochrome P450 (we will be discussing this further in the part 2 of this series) is necessary, such as when there are issues in Pathway II or any phase within Pathway II.  Curcumin, responsible for the bright yellow color in turmeric while helping stimulate Pathway II, inhibits cytochrome P450 as does Niacin (in the form of niacinamide) and can be an important fix for those with defects in any of the phases in Pathway II.   It IS possible to overdo it though, especially now that many people take turmeric by capsules rather than simply cooking with it.  This can overstimulate Pathway II or inhibit Pathway I to dangerous levels so you don’t want to overdo this if you are feeling unwell until you figure out which pathway needs detoxing. 

Tomorrow we will be discussing further the ins and outs of inducing and/or inhibiting Detox Pathway I and cytochrome P450 along with what could elicit the need for manipulating the pathway.

Think about Detox Pathway I and cytochrome P450 as a packaging facility responsible for making sure each product is packed in the right package, the right way, and sent to the right place for shipment.  If there is a glut of product, the packaging facility can pack the products in the wrong package or send them to the wrong shipping company.  If there are too many packages making their way to the shipping company (free radicals) this can cause the shipping company (Phase II pathway) to become bottlenecked.  If the packaging company is using outdated equipment  (age or poor health) the products (toxins) being packaged may fail to be packaged properly or sent to the right shipping company (phase in Detox Pathway II).  Thus the need to upgrade the company or induce cytochrome P450 may be needed for a time.

Although it is a virtual certainty, in this day and age, you can’t avoid chemical exposure, having a fully functioning liver that begins with Detox Pathway I and cytochrome P450 is a good start to balanced health.

14 replies
  1. Steve
    Steve says:

    In your 16th paragraph you have a sentence stating…
    “Curcumin, responsible for the bright yellow color in turmeric while helping stimulate Pathway II.”
    This seems like an incomplete sentence. Could you elaborate further?
    Looking forward to your next article on Liver detoxification.
    BTW, you have what I believe is one of the most informative nutritional websites on the web. Thank you for sharing your knowledge.

    Reply
    • thedetoxdiva
      thedetoxdiva says:

      Thanks for the catch. I think I was bleary eyed when I got to this paragraph….. It showed, unfortunately. Oh and thank you for the wonderful compliment. I love what I do and I love even more when people get something out of it! 🙂

      Reply
  2. Wendy Gardner
    Wendy Gardner says:

    Excellent article – you have the knack to translate what could be ‘ NASA scientist level/impossible to understand science’ into practical and logical English. Look forward to the next one.

    Reply
  3. Steve
    Steve says:

    Detox Diva, is it possible to accurately evaluate the true condition of one’s liver without the use of lab testing?

    Reply
    • thedetoxdiva
      thedetoxdiva says:

      That’s a loaded question. In my opinion, no, to fully EVALUATE (and I would even suggest a specific tests measuring methylation pathways) the condition of one’s liver is not possible BUT, through assessing symptoms, very specific symptoms, it IS very easy to make small (and sometimes big) tweaks to nutrition and some well placed supplements that CAN make big differences, even heal without those tests!

      Reply
      • Steve
        Steve says:

        I have a couple of reasons for asking. First, I’m trying to improve the health of my wife (late 50’s), two daughters (30s) and my own (late 50s), without the use of lab tests. Don’t get me wrong, I would love to have them, I just know my girls (for various reasons) will not get them. Second, my doctor would never take my request for a lab test seriously. At the present time he considers my health to be very good. That may be true, compared to most men my age, but I still think it can be better. That’s why I come to your website and others like it (although I consider yours to be unique), to find answers.
        Thank you again for your time!!!

        Reply
        • thedetoxdiva
          thedetoxdiva says:

          I maintain what I said…. It IS possible to make a HUGE dent, if not completely heal just going on symptoms. I rarely order tests. I do for EXTREME cases when nothing else works but yes, you can improve the health of you, your wife and your daughters without those tests. It’s not possible, for example, to KNOW, when I prescribe a supplement, if that is what is 100% going to change the way the gene is expressed but I am usually accurate to about 90% based on symptoms.

          Reply
  4. ecoguy
    ecoguy says:

    The best way to remove the mercury and other toxic heavy metals in pesticides, contaminated fish, seafood and dental amalgams is with the natural mineral detox called Zeolite which is proven to safely remove all heavy metals and radiation from the body. For more information do an online search for the single word Zeolite.

    Reply
    • thedetoxdiva
      thedetoxdiva says:

      Zeolite is NOT for everyone and it is not safe for those with impaired guts. Liquid zeolite also contains aluminum which can enter the blood stream. PLEASE do not use my website as a way to tout unfounded, untested supplements that are not completely safe for everyone.

      Reply
  5. rachael
    rachael says:

    I was diagnosed with having mild fatty liver through ab abdominal ultrasound 2 years ago. Read some very positive things about milk thistle so I tried it for three days a month ago and I experienced horrible anxiety. I stopped after that. I read that milk thistle can mimic effects of estrogen. Could that be why i had the anxiety?

    Reply
    • thedetoxdiva
      thedetoxdiva says:

      It absolutely could cause anxiety. Milk thistle should only be used when the rest of the detox systems of the body are working properly…. Downstream to up! Liver is the last. Milk thistle is way too strong if you have other issues!

      Reply
  6. Lola
    Lola says:

    Hello,

    I have just discovered your website and I’m amazed,I really love it! I have read on your Facebook that PUFAs cause Insulin Resistance and beta cell problems. Sad thing is that I was on paleo diet for over 2 years, eating too much nuts, paleo cakes made from nut flour and now I suffer from Hypothyroidism and Insulin Resistance and inflammation:(( I got Metformin for 1 year but did not help. So now I turned to natural solutions. Is there any help you think to get out of this state of health? I would like to also ask you that for how long one must keep each detox phase you explained above? Thank you!

    Reply
  7. Angela
    Angela says:

    Question about grapefruit: I see that grapefruit juice is not recommended for liver issues, but have seen that grapefruit (and other citrus) oils *are.* I know they’re not the same thing, but I just want to check! Thanks!

    Reply

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