Role of liver in metabolism

In Pathways to Detox Pt. 1 we talked about cytochrome P450 enzymes and their role in liver detox pathway I. Detox pathway I is an “conversion” phase, meaning it generally converts something from a fat soluble toxin to make it more water soluble and rendering it less harmful to the body. It does this through a process or processes such as oxidation, hydrolysis, and/or reduction.

Depending on the chemical (the body is ever so intelligent) and its genetic code knows  exactly which isoenzyme of cytochrome P450 to induce. In fact, over 50% of medications ingested today are metabolized in some way by cytochrome P450.  If everything is moving along smoothly and the toxic overload isn’t abnormally high, these toxins are excreted through the kidneys and urinary tract mainly.

That’s the big “IF”!!  

So what could go wrong?  Let me count the ways.  First, toxic overload is common these days.  “A pill for every ill” (how many people take statin drugs and stomach acid reducers like candy these days??)  has seen to that as has overfarming/ moncrops and the use of pesticides, insecticides, and herbicides (a lot of them even in our personal care products….  triclosan, anyone??) and, potentially, GMOs, second hand smoke, parasites, fungi, you name it, it all contributes to toxin overload.

“How has it gotten so out of hand?”, you might ask.  A long time ago we used pretty innocuous pesticides, our crops were rotated, our soil mineral dense, the most we took for medicine is an aspirin , and we didn’t have complicated ingredients lists for food containing everything under the sun that act as endocrine disruptors and contribute to toxin overload.  Now everything from our toothpaste to deodorant, floor cleaner to furniture polish to sheets on our bed or clothes on our back (are you sleeping on solvents?) contribute to too many poisons making their way into our bodies.

Now you know the hows and whys of cytochrome P450 and Detox Pathway 1 so let’s talk about the need to speed up or induce or slow down or inhibit phase 1 detox pathways.

For more details on which toxins inhibit or induce Cytochrome P450 read Path(ways) to Detox Pt. 1  Today we are talking about why you might want to speed up or slow down this pathway and what you can do to make that happen.

Inducing or speeding up is detox pathway I and cytochrome P450 is often needed when there is an overload of toxins entering the body such as times when there are no organic fruits and vegetables available and one is exposed to pesticides.  If one lives in a congested polluted area exposed to exhaust fumes, or when one is in the middle of a remodel on a house and are exposed to paint fumes or fiberglass.  If one takes steroids or smokes cigarettes these are all substances not only that can speed up the detox pathway I (in order to neutralize these substances) but can induce to such a point where it can clog both detox pathways I and II.

To support Detox Pathway I the limonene in lemons, oranges and tangerines are helpful. These support both Detox Pathways I and II. (Grapefruits, however, achieve the opposite and slow down or inhibit cytochrome P450.)  Niacin, Vitamin B1, and Vitamin C are the nutrients that most support an efficient Detox Pathway I.  Both caraway and dill (high in limonene as well) are herbs that induce cytochrome P450.

One of the most important nutrients in the support of Detox Pathway I is glutathione, “the master antioxidant” (we will be talking about its effect in a post all on its own).  Glutathione helps neutralize the free radicals created by Detox Pathway I.  If, however, the toxic load is high enough, glutathione is depleted (and free radicals run amok) affecting one of the key phases of detox pathway II effectively causing a slow down of detox pathway II which will cause a bottleneck in the whole process of detoxification.

How do you know if you need to induce your detox pathway I?  Because caffeine is directly neutralized by cytochrome P450 if caffeine has no effect on you, you probably have a rather overactive detox pathway to begin with so you will want to watch what you eat or take so as to avoid inducing it any further.  If you feel more awake but not jittery or have any other negative reactions, your detox pathway I is balanced and if you have many symptoms ranging from being jittery, headaches, get shaky or even experience anxiety, you more than likely have a need to speed up cytochrome P450.

Because aging is a huge factor in a general slowing down of cytochrome P450 and Detox Pathway I these nutrients become increasingly important.

Inhibition of Detox Pathway I has a place as well.  Remember in Pt. 1 when we likened the detoxification pathways of the liver to a packaging facility.  The role of cytochrome P450 is to sort the products (toxins), package the product in the right box (using processes such as oxidation, hydrolysis, and/or reduction) and make sure the boxes (free radicals) get to the right shipping company (Detox Pathway II process) for proper shipping to the right location (final elimination).

Sometimes the products are sorted and packed in the right box but Guido the box sorter has called in sick and there are just too many boxes to sort properly to the right shipping company.  (Too many free radicals are produced, not enough nutrients and precursors to antioxidants are present and glutathione is depleted.)  When the pathways involved in Detox Pathway II are “log jammed” there is an immediate need to inhibit cytochrome P450 while, hopefully, stimulating Detox Pathway II along the way.

Grapefruit juice can and does (through the flavonoid naringenin) inhibit cytochrome P450 a whopping 30%.  Be aware it can also increase toxicity and clinical activity quite a bit.   Grapefruit juice does not increase Detox Pathway II so using this juice to inhibit cytochrome P450 can challenge the body.

Curcumin, the compound responsible for the yellow color in turmeric, is powerful because it inhibits phase I while stimulating phase II. Certain types of cancer (caused by free radical damage) can be prevented or the incidence greatly minimized with the use of turmeric. Curcumin has been found to reduce the negative effects of known carcinogens such as benzopyrene (found in grilled meat), and prevent those carcinogens from inducing cancer in several animal studies. The theory behind this is that curcumin has  anti-carcinogenic effects by lowering the activation of carcinogens while increasing the detoxification process of those that happen to be activated. Curcumin also has a powerful ability to inhibit the growth of cancer cells. As most of the cancer-inducing chemicals in cigarette smoke are only truly carcinogenic during the period between activation by phase I and final detoxification by phase II (so anywhere in between the time it enters the body and time it is detoxed by the liver) , therefore increasing your turmeric intake can help neutralize the cancer-causing effects of tobacco.

Capsaicin form chili pepper; eugenol from clove oil; quercetin from onions all have inhibition of Detox Pathway I properties and can help stimulate Detox Pathway II.

We will be discussing Detox Pathway II and its processes in subsequent posts.

“So what foods help maintain liver detox pathway balance?”

General Liver Detoxification Nutrients

Foods to aid detoxification::
Beetroot and artichoke: helps with liver drainage
Broccoli, cauliflower and other cruciferous vegetables (well cooked, of course): these aid cytochrome P450 activity
Protein from pastured animals and collagen/gelatin
Radish, watercress: rich in sulphur
Albion family vegetables: leeks, garlic, onions
A daily carrot salad which has fiber that binds to certain toxins and used hormones and carries them out of the body.

Supplements to aid liver detoxification::
B-complex vitamins: necessary co-factors used in Phase 1 detoxification
Digestive enzymes: may be necessary to ensure that protein is adequately digested and
glycine is readily available
Essential fatty acids
N-acetyl cysteine (NAC): an immediate precursor to glutathione, a potent antioxidant and
among the most import detoxification nutrients for the liver
Acetyl-glutathione or glutathione suppositories
Selenium, zinc, magnesium and manganese; possibly iron and copper if used with caution
Taurine (a useful combination product is magnesium taurate)
Vitamins C and E and beta carotene.

When the Detox Pathways I and II are running efficiently (and it is possible to make that happen with proper nutrition and some well placed supplements) a myriad of symptoms magically vanish!
Inositol & Methionine: lipotropic agents (help with the breakdown of fat in metabolism) that
work to transport fat out of the liver.

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