A question of Balance : Phase 1 and Phase 2
In the scheme of liver detoxification, there are a lot of ‘ducks in a row’ that need to be in place for the process to work and not increase potential damage caused by exo- and endotoxins.
The CYP450 enzymes act as Phase 1, transforming toxins from fat-soluble to water-soluble in order to be processed by Phase 2 conjugation pathways for elimination. This process can make some chemicals more inflammatory and even carcinogenic. It can overwhelm and deplete antioxidant levels.
If Phase 2 of liver detoxification is not balanced or up to par, a ‘normal’ level of Phase 1 function can become a serious problem. This is even more the case with high levels of toxin exposure, as this stimulates the production and release of higher levels of CYP450 enzymes, thereby increasing the secondary free radical metabolites and the tissue damage they incur.
This often appears in screening results as high levels of oxidative stress, such as superoxide, which indicates a pattern of imbalance between Phase 1 and Phase 2 that is destructive and symptom causing, particularly if antioxidant levels that are meant to regulate the intermediary metabolites become exhausted or deficient. Genetics can also have an impact on this imbalance between Phase 1 and 2.
Inhibitory factors of Phase 1 -
Can result in longer exposure to drugs, toxins, hormones, histamines etc
Low calorie intake
Fasting
Protein deficiency
Phos choline deficiency
Antihistamines
Grapefruit compounds
Deficiencies of Vit A and C
Bacterial toxins
Induction of Phase 1
Excess toxin and xenobiotic exposure
High protein diet
Pesticides, Chemicals and and toxic damage to CYP450
The role of pesticides in causing dysfunction in this Enzyme system cannot be overstated. That is because most pesticides are in fact created to target and destroy these enzymes in plants and they can have the same effect on the human enzyme system.
Take a minute to absorb this. The implications are huge. Pesticides are designed to destroy part of the system that is fundamental to multiple metabolic and detoxification processes. Going organic may be one of the most important health choices you can make.
Having said this, any high or long lasting toxic exposure can be enough to cause long lasting damage to this pathway. Specific chemicals and toxins known to have caused lifelong damage to the CYP450 enzymes pathways include chemotherapy, pesticides and heavy metals, with mercury being one of the worst offenders in causing permanent damage.
This is where homeopathic treatment that targets toxic build up in the body can make such a difference in the case of chronic disease. It works to focus the body’s natural healing ability to clear not just the toxic residue that remains in the body, but also addresses the epigenetic imprint of that toxin on the body. This means it can reverse the ‘genetic switches’ that have been affected by toxic exposure, and which can permanently impact the way the body functions even when a toxin has been chelated and cleared from the tissues. The ‘Miasma’, or genetic ‘stain’ can remain, and homeopathy is one of the only medicines that has the ability to ‘unflip the gene switch’.
Some of the toxins and substances that CYP450 acts upon (substrates) or that influence its function
Nicotine
Steroids
Cruciferous vegetables
Aflatoxins/Mycotoxins (toxins produced by fungi that infect food)
Hydrocarbons
Estrogen
BPA and Phthalates
Paint fumes
Pesticides, herbicides, fungicides (like Glyphosate)
SSRIs
Dioxins
charcoal broiled foods
coumarin
steroids
adrenal hormones
Ethanol
st john wort
testosterone
Acetaminophen (Tylenol)
ketamine
caffeine
lidocaine
erythromycin
cyclosporin
ketoconazole
testosterone
estradiol
cortisone
Alprenolol
bopindolol
carvedilol
metoprolol
propranolol
Amitriptyline
clomipramine
desipramine
nortriptyline
Codeine
dextrometh- orphan
ethylmorphine
4-methoxyamphetamin
Phenytoin
ibuprofen
naproxen
oxicam drugs
S-warfarin
Diazepam (eg Valium)
hexobarbitone
imipramine
alcohol
chlorzoxazone
enfluraneT