Parkinson’s disease, neuro degenerative diseases, inflammatory conditions, allergies, autoimmunity, hypertension, diabetes/metabolic syndrome are associated with toxic body burden. Disease does not just manifest itself overnight. Most of the disease does breaking the healthcare budget are lifestyle diseases. Not to worry, we were given a liver to combat disease. It’s working 24 seven to detoxify all the horrible things that we do to ourselves. So that requires a lot of energy in the form of ATP as well as being highly nutrient dependent. Most people these days are deficient in certain enzyme pathways that do the actual detoxifying.
Over millions of years, our liver has evolved to handle an increasing number of demands, metabolizing toxins found in food and the environment. It would be nice if all toxins that entered the body would be water soluble, but that’s not the case. Many of the substances taken in by the liver are exclusively fat soluble, making them much harder for the liver to metabolize. These toxins will cling to fatty cells and membranes, staying in your body for days, weeks, or years.
These toxins can release in times of stress, causing symptoms such as headaches, memory loss, fatigue, and nausea. The body has two mechanisms, or detoxification pathways, to breakdown fat soluble toxins into water soluble chemicals so that they can be easily excreted, but without some extra prompting, this functioning may not be able the handle the demands of daily life.
Too many toxins can slow down the liver’s functioning, leading to an increase of toxins within the body. The brain, breast and adrenal glands are organs with higher levels of fatty tissue, making these favorite places for toxins to hang out. This can lead to brain toxicity and hormonal imbalances, leading to damaging side effects like cognitive issues, fatigue, as well as contributing to infertility and even the development of some kinds of cancer.
There are two main mechanisms of liver detoxification: phase 1 and phase 2. While there are 10 families of enzymes in phase 1 the cytochrome P450 enzyme is the majority of activity. In phase 2 detoxification the methods used by the liver to clean up the battlefield are: sulfation, glucuronidation, methylation, glutathione conjugation, amino acid conjugation, acetylation.
Phase one detoxification includes oxidation, reduction, and hydrolysis and is catalyzed by enzymes classified as P-450 that reside on the membrane of liver cells. Generally, these enzymes are triggered by proximity to specific chemicals, causing a mechanism of protection that safeguards against many different kinds of toxins.
When toxin levels get too high, over-activity of the phase one liver detoxification can occur, causing a dangerously high level of free radicals that must be further metabolized by phase two to protect against cell damage. When too many substances, like alcohol, saturated fats, and paint fumes, to name a few, are processed by phase one of the liver detox process, the byproducts of metabolism can become overwhelming for the liver to handle safely. Avoiding toxins that cause phase one detoxification over-activity can be to your benefit, leading to a more balanced phase two process.
Phase two detox is also known as the conjugation pathway, in which the liver adds additional chemicals, to toxic chemicals that have already been processed by phase one, in order to render them harmless. This step makes the toxins water soluble, allowing for easy excretion and removal from the body.
Efficient phase two detox requires certain substances, including sulfur-containing amino acids and nutrients like glycine, glutamine, and choline. These substances are not always found in foods like cruciferous vegetables, garlic, certain dark leafy greens because of modern farming methods. It is important to support and balance both phases of liver detoxification because if phase two is slower than phase one, then the toxins processed by the phase one are in a state that can cause much more harm in the body. Phase two of liver detox might be impaired due lack of micronutrients in fast food diets.
Nearly all tissues have some form of detoxification activity but the liver will be the primary spot. First pass metabolism happens as a compound travels through the digestive track and experiences the natural digestive and absorptive processes. This can degrade particular compounds and render them less effective or less potent such as drugs or hormones. This can complicate administration of therapy says there is so much diversity in each persons microbiome in conjunction with those that have this biosis. A good way to bypass first pass metabolism is with sublingual, intravenous, intramuscular injections. The outcomes are molecules that were once active are now inactive or vice versa, toxic drugs to non-toxic again vice versa, and lipid toxins become water-soluble.
35 years ago that was what I was taught. To make things worse for everyone there is now a phase 3 detoxification method. It is made up of over 300 unique proteins that are highly concentrated in the small intestinal epithelium but also present in the kidneys and liver. The goal of this phase 3 is to reduce Xenobiotic load on the system, specifically the liver. Just like phase 2 being too slow to handle phase 1 causes problems, a sluggish phase 3 will down regulate phase 2 and that will cause a meltdown at the phase 1 level.
The cytochrome P450 super family of enzymes associated with phase 1 is responsible for the oxidation of almost 90% of currently used drugs. Humans have 57 genes that will encode for CYP450. I included that because that means it’s very important when we have 57 genes dedicated to a process.
In case all this confused you, what it means is a very important factor to remaining healthy is to be drinking a lot of water because the poisons you consume can only come out of you when they are wet. The incredibly complex steps of the enzyme systems all have the same end result, waste water is being created.
A very popular poison is benzene. It was known in 1948 that the only absolutely safe concentration for benzene is zero. Unfortunately for us, our phase 1 detox system converts benzene to highly toxic intermediates that are linked to different leukemia’s, chromosomal damage, other cancers, and birth defects. Benzo pyrene is a hydrocarbon present in cigarettes, coal, burning wood, and some foods. While your body is trying to detoxify benzene an intermediate byproduct called epoxide is created and it can bind to DNA and it is very carcinogenic. Some common symptoms of benzene toxicity are: dizziness, drowsiness, headaches, cancer, tachycardia, vomiting, coma, death. Our body when trying to breakdown benzene creates S-phenylmercapturic acid and this can be detected in urine so you can get yourself tested.
At this point you are probably wondering why codeine works better for some people than others. It is a class of pro-drugs meaning codeine needs to be converted into morphine for its intended purpose of painkilling. This is accomplished by our cytochrome enzymes and they require certain micronutrients to perform. So if you want to get a better buzz off your cough medicine you might want to consider getting healthy first with B vitamins, vitamin C, flavonoids, phospholipids, indoles, coumarins, methylxanthines(found in tea, coffee, cocoa), selenium, iron, zinc, copper, magnesium.
Again, some reactive intermediates are more harmful than the original substrate especially with regard to medications. A fast phase 1 compared to phase 2 increases intermediate reactivity and reactive oxygen species formation.(ROS). ROS are not good. Also known as the superoxide radical O2-. Another example is peroxynitrite. The good news is we can make superoxide disputatious and catalase which are antioxidants that work to counteract the damage from the reactive oxygen species a.k.a. free radicals. L-carnitine is a great supplement to promote this pathway.
Peroxynitrite interacts with lipids and DNA. This is related to: fibromyalgia, systemic lupus erythematosus, Alzheimer’s, asthma, depression, autism, arthritis, atherosclerosis, celiac disease, pulmonary fibrosis, and more. This is an incredibly damaging free radical. I try and protect myself from this by using supplements of SOD, catalase, vitamins A, C, E, Tocotrienols, coenzyme Q 10,EGCG from green tea, B complex and sublingual B12.
Lipopolysaccharides (LPS) also known as lipoglycans and endotoxins, can decrease hepatic cytochrome P450 mediated drug metabolism. The presence of endotoxins in the blood is called endotoxemia. It can lead to septic shock, if the immune response is severely pronounced. This is linked to obesity.
I understand a lot of this is very complicated but mixed in with the complications are the nutrient antidotes. There will be more nutrients to come. Eventually you’ll figure out that the stuff will help you sleep better.
Stay tuned for part 4.