Detox

So I am learning about detoxification. It is a complex subject and I am only grappling at the surface. It has been my experience that I heal in cycles, worsening symptoms lead to improvements in health. It is as if my body is purging a toxin. I have tested and isolated every factor I could think of to moderate these down swings, to not avail, confirming, to me, that I am "clearing" something.

So why and I not detixifying adequately?

Well, the liver is the primary organ responsible for breaking down toxins. but what I am learning is that there are three phases of liver detoxification, and any one pahse working more quickly, or more slowly, than the other, causes problems. Phase one aggressively converts toxins into checmically reactive forms. Phase two metabilizes those forms and Phase three well, Phase three is excretion in bile. I think.

Phase I, is run, as best i can tell, on what are called cytochrome P450 enzymes, rather than the Phase II enzymes, which work much more slowly to detoxify substances. Some 50-100 enzymes make up the cytochrome P450 system. Each enzyme works best in detoxifying certain types of chemicals, but with considerable overlap in activity among the enzymes. THis is an intersting note I found:

Patients with underactive phase I detoxification will experience caffeine intolerance, intolerance to perfumes and other environmental chemicals, and an increased risk for liver disease, [editor note- my liver enzymes ar eusually elevated] while those with an overactive system will be relatively unaffected by caffeine drinks. One way of objectively determining the activity of phase I is to measure how efficiently a person detoxifies caffeine. Using this test, a surprising fivefold difference in the detoxification rates of apparently healthy adult has been discovered. Liver Detoxification

Are all you histapeniacs listening out there? Chemical sensitivites, intolerance to drugs, liver problems? It seems interesting doesn't it that this closely mirrors the Pfeiffer center's group characteristics for histapenia. histadelics, there is something there for you too...check it out "unaffected by caffeine". Yeah E, you know I am looking at you. Stuff is an elixer for her.

So lets suppose that histapenics are slow in phase one, and histadelics are fast.

By the way, most of this information is courtesy of wisewitch, who holds one of the best informed websites on the web regarding nutrition and human health. I cannot recommend it enough [read: she has forgotten more today than I have learned all together]. It takes a bit of courage on your part to wade in. If you are of the "I want to get better, but I hate chemistry" camp, you are not going to find easy predigested answers there. You will have to chew your own food. Still, if you want great and not just good, she is a prime resource. Be nice to her though, She is dumping hundreds of hours into her blog to help us for no pay.

http://wisewtich.blogspot.com

Ok, back to the liver Phase 1:

Subtances that promote Phase I detox:

Cytochrome P450 is induced by some toxins and by some foods and nutrients. However, stimulation of phase I is contraindicated if the patient's phase II systems are underactive.

• the brassica family, i.e. cabbage, broccoli, and Brussels sprouts, contains chemical constituents that stimulate both phase I and phase II detoxification enzymes. One such compound is indole-3-carbinol, which is also a powerful anti-cancer chemical. It is a very active stimulant of detoxifying enzymes in the gut as well as the liver. The net result is significant protection against several toxins, especially carcinogens. This helps to explain why consumption of cabbage family vegetables protects against cancer.
• Oranges and tangerines (as well as the seeds of caraway and dill) contain limonene, a phytochemical that has been found to prevent and even treat cancer in animal models.

Substances that activate Phase I detoxification:

• Drugs: alcohol; nicotine in cigarette smoke; Phenobarbital; sulfonamides; steroids
• Foods: cabbage, broccoli, and brussels sprouts; charcoal-broiled meats; high-protein diet; oranges and tangerines (but not grapefruits)
• Nutrients: niacin; vitamin B1; vitamin C
• Herbs: caraway and dill seeds
• Environmental toxins: carbon tetrachloride; exhaust fumes; paint fumes; dioxin; pesticides

"Substances that Inhibit phase I detoxification:
Drugs: benzodiazepines; antihistamines; cimetidine and other stomach-acid secretion blocking drugs; ketoconazole; sulfaphenazole
Foods: naringenin from grapefruit juice; curcumin from turmeric; capsaicin from chili pepper; eugenol from clove oil; quercetin from onions
Botanicals: curcuma longa (curcumin); capsicum frutescens (capsaicin); eugenia caryophyllus (eugenol); calendula officianalis
Other: aging; toxins from inappropriate bacteria in the intestines"

Histapeniacs? are you reading this? Antihistamines slow Phase one. Hmmmmm. class, anyone want to take a swing at this? Niacin? High protein diet? sound familiar?

"As someone who has problems getting to sleep and big problems
waking up in the mornings, I was interested to discover melatonin
is metabolised by this particular enzyme. " -WW

There it is again...another common characteristic of histapeniacs...the inability to awaken easily in the morning. Maybe this is becuase we are not metabolizing our lil' buddy melatonin. Hmmm.

Phase II detoxification (slower than phase one). The body's approches to a certain role, i.e. detoxification, are often called "pathways". This is important when reading about these subjects. It appears there are multiple ways to produce a given result and some are favored, and some are redundancies built in. There are essentially six phase II detoxification pathways:
Glutathione conjugation
· Amino acid conjugation
· Methylation
· Sulfation
· Acetylation
· Glucuronidation

Ok, I am gong out of a limb here. I am going to guess, becuase of Mythlation, that histapenics are ok with Phase two, perhaps too aggressive, but not phase one, and histadelics nail phase I, but then cannot get rid of the stuff in Phase two. This would explain a lot fo the skin problems I see on histadelics. I could be totally off here.

Nutrients needed by phase II detoxification enzymes
Glutathione conjugation: Glutathione, vitamin B6
Amino acid conjugation: Glycine
Methylation: S-adenosyl-methionine
Sulfation: Cysteine, methionine, molybdenum
Acetylation: Acetyl-CoA
Glucuronidation: Glucuronic acid

This is a bit mixed. of course histapeniacs, according to the PTC, are heavily methylated, but this is where I get confused. sit down for this, but college chemistry books tell us that you that to convert homocysteine to methionine, which then becomes SAMe and donates the dreaded (for histapeniacs) methyl groups, you need..folic acid and b-12. Somebody is screwed up here. I dont know who. but the fact is, my jury, made up regrettably of my peers, is out on that. Still, I note taht the PTC has prescribed Vit b6, and glyciene, and that Zn promotes glutathione.

Glutathione is available through two routes: diet and synthesis. Dietary
glutathione (found in fresh fruits and vegetables, cooked fish, and meat) is
absorbed well by the intestines and does not appear to be affected by the
digestive processes. Dietary glutathione in foods appears to be efficiently
absorbed into the blood. However, the same may not be true for glutathione
supplements.In healthy individuals, a daily dosage of 500 mg of vitamin C may be
sufficient to elevate and maintain good tissue glutathione levels.

Hmm, this is interesting...

Sulfation
Sulfation is the conjugation of toxins with sulfur-containing
compounds. The sulfation system is important for detoxifying several drugs, food
additives, and, especially, toxins from intestinal bacteria and the environment.
In addition to environmental toxins, sulfation is also used to detoxify some
normal body chemicals and is the main pathway for the elimination of steroid and
thyroid hormones. Since sulfation is also the primary route for the elimination
of neurotransmitters, dysfunction in this system may contribute to the
development of some nervous system disorders.

Sulfation was already on my list on "to learn about" since the PTC prescribed phenolic enymes, which break down phenols, which are ordinarly broken down by sulfates. Maybe I was too hasty in the "phase II ok for histapenics" conclusion. Still, methionine is needed for sulfation, and supposedly histapenics have a lot of that. I dont know.

Inducers of phase II detoxification enzymes
Glutathione conjugation: Brassica family foods (cabbage, broccoli, Brussels sprouts); limonene-containing foods (citrus peel, dill weed oil, caraway oil)
Amino acid conjugation: Glycine
Methylation: Lipotropic nutrients (choline, methionine, betaine, folic acid, vitamin B12)
Sulfation: Cysteine, methionine, taurine
Acetylation: None found
Glucuronidation: Fish oils, cigarette smoking, birth control pills, Phenobarbital, limonene-containing foods

Inhibitors of phase II detoxification enzymes
Glutathione conjugation: Selenium deficiency, vitamin B2 deficiency, glutathione deficiency, zinc deficiency
Amino acid conjugation: Low protein diet
Methylation: Folic acid or vitamin B12 deficiency
Sulfation: Non-steroidal anti-inflammatory drugs (e.g. aspirin), tartrazine (yellow food dye), molybdenum deficiency
Acetylation: Vitamin B2, B5, or C deficiency
Glucuronidation: Aspirin, probenecid

reads like a checklist of histapenic supplments, but do not taht ciggarettes, most favored by histadelics, induce phase II detoxification.

Pahse III is bile production. Bile. from the liver, stored in the gall bladder. Somehow I recall that Ceruplasmin is involved. I have to check that out.

Impairment of bile flow within the liver can be caused by a variety of
agents and conditions. These conditions are often associated with alterations of
liver function in laboratory tests (serum bilirubin, alkaline phosphatase, SGOT, LDH, GGTP, etc.) signifying cellular damage. However, relying on these tests alone to evaluate liver function is not adequate, since, in the initial or subclinical stages of many problems with liver function, laboratory values
remain normal. Among the symptoms people with enzymatic damage complain of
are: Fatigue; general malaise; digestive disturbances; allergies and chemical sensitivities; premenstrual syndrome; constipation.

Hmmmmmmmm. My PMS is fine, but that is interesting. AS noted above, my AST and SGOT are always slightly elevated, and my billirubin is high. If this researches leads to something, I want a refund from all the hospitals who have wasted my time on cr*p I could figure out. I am sick of funding thier student loan payments.

regrettably methionine is listed as the only supplment aiding in bile production, but I have to tell you that I am recently feeling like the methionine and methly cycle is more complex than the PTC is telling me. I dont know on that one.