The importance of our Detoxifiction Pathways

[Guest guest]

After all the important info regarding drugs that inhibit or induce

the P450 pathways I thought I would look over the notes I have from

2 conference calls I took 2 years ago with Great Smokies, the first

being an Introductory course and the 2nd the Advanced course. Below

are some simplified notes that might be helpful –

• Elimination is the removal from the body via faeces, urine

sweat and/or exhalation of detoxified compounds, xenobiotics and

endogenous toxins and metabolic waste products

• Compromised detox frequently affects the immune system

(frequent colds, night sweats, allergies), neurological tissues,

endocrine system

• If the system is overloaded or if any stage of detox or

excretion is impaired Total Toxic Load increases

• Symptom picture of general toxicity: Malaise, chronic

fatigue, headaches, joint and muscle pain, nausea, chronic mucous

production

• Consequences of chronically impaired detox – free radical

damage, depletion of glutathione, sulphate and other critical

nutrients resulting in an accumulation of toxic intermediate

metabolites, less sulphur is available for the building of body

tissue

• Phase 1 detox: P450 enzymes

• The family of P450 enzyme systems is quite diverse with

specific enzymes systems being inducible by particular drugs or

metabolites (Penny has put a list of these in the Files section)

• If this phase becomes upregulated or induced then there is

increased exposure to toxins and increased production of free

radicals (more toxins and free radicals for the body to clear)

• If this phase becomes downregulated or inhibited then there

is impaired detox activity and a back-up of toxins will develop that

will cause problems in Phase 2. There will be sluggish hepatic

functioning. NB hypothyroidism inhibits both Phases 1 and 2

• NB, all bugs inhibit Phase 1

• Amongst many other drugs listed in the Files section

flucanzole inhibits this Phase 1 pathway

• Heavy metals including mercury inhibit P450 as does

insufficient nutrient co-factors like B1, B2, B3, Mg, Iron,

Molybdenum, essential fatty acids

• Phase 2 detox pathways include glutathione conjugation,

glycine conjugation, sulphation and glucuronidation.

• If one of the pathways becomes blocked or congested the body

will try and compensate and other pathways may also break down

• Best way to raise glutathione is whey products. When there

is insufficient glutathione conjugation it is difficult for the body

to remove toxins from the body. Induced P450 activity because of a

large amount of compounds to be detoxed would stress glutathione

conjugation. (I would think that this is why some of us have

problems with flucanzole as one example)

• Insufficient nutrient co-factors would cause insufficient

glutathione (reduced glutathione, N-acetylcysteine, glycine, l-

methionine, L-glutamine. )

• Decreased sulphation could be caused by an overabundance of

oestrogens, cortisol, DHEA and would make it difficult to remove

toxins from the body

• Insufficient sulphation might be due to; excess exposure to

xenobiotics or free radicals, inadequate dietary sulphate available,

insufficient nutrient co-factors, L-methionine, L-cysteine, N-

acetylcysteine, reduced glutathione. Again there would be

difficulty in removing toxins from the body.

• Insufficient sulphation might also be due to upregulated

P450 activity or an excess of B6 and molybdenum

• Insufficient glucuronidation may be caused by insufficient

carbohydrate reserves or insulin sensitivity

• Insufficient glucuronidation may also be caused by possible

free radical damage to the mitochondria (I believe green foods were

mentioned as extremely beneficial)

• Insufficient nutrient co-factors, L-glutamine, aspartic

acid, niacin, Vitamin B6, Iron and Magnesium, plus hypothyroidism

delays this enzyme system

• Insufficient glycine conjugation may be caused by

insufficient glycine available, or insufficient co-factors,

cysteine, pantothenic acid, magnesium or underlying kidney disease

• Phase 1 and 2 need to be in balance, if Phase 1 inhibited

then all the rubbish is sitting around making us putrid and very

toxic. It needs to be moving but not too fast to stress Phase 2.

When the toxins aren't being moved out correctly they recirculate

creating extra toxicity and possible damage to our DNA, RNA,

cellular structures, mitochondria and enzymes.

• Final note, increased sweating can be a symptom of toxic

overload on the body.

All the above comes from the first Conference Call and when I get

time I will post anything relevant from the 2nd course. Hope this

is helpful. Pam