Re: The importance of our Detoxifiction Pathways

[Guest guest]

Hi Pam,

Does fluconazole actually affect the P450 pathways in humans then???

Or is it just specific to the P450 in bugs like yeasts and borrelia?

Cheers,

Carol

> 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

[Guest guest]

very interesting stuff pam right on time.

I hope you are better. I am not keeping up much here as the head is

still frassled and computer time is down due to physical work as a part

of the detox. my head is still hurting but seems to moving in the right

direction. I think a little bit of shit is stuck somewhere but has

moved. Im going to try L-carntine and ALA next.

bleu

> 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

>

>

>

>

>

>

>

>

>

>

>

>

[Guest guest]

> Hi Pam,

>

> Does fluconazole actually affect the P450 pathways in humans then???

> Or is it just specific to the P450 in bugs like yeasts and borrelia?

>

> Cheers,

> Carol

>

Hi Carol

I think it would definitely affect the P450 pathway in humans along

with a huge amount of other drugs. I am sure this is why some of us

feel so ill when taking certain drugs.

Luckily I have got rid of the mercury toxicity I had and chelated most

of it out but I do have concerns for people who have got loads of

amalgams and problems with bugs, yeast etc. Of course it might not be

mercury but I do not that people with CFS have huge problems with

various heavy metals being retained and not excreted and I also know

that some of them have been diagnosed with borrelia too. Thinking

about the detox system being messed up really explains this now.

I have had a good 2 weeks and think it might be connected to the whey

protein with lactoferrin that I am taking and also the Perfect Foods

green drinks I am have twice a day. Just hoping the flucanzole

doesn't mess things up too much.

Pam