[Paleopsych] Phase 2 detoxification

[Steve Hovland]

Dietary risk factors for CA
1. High fat diet (strongly associated with colorectal and prostate cancer, 
hypothetically related to Breast CA
2. Low fiber diet
3. Processed foods - high fat, bad fat (see below) - antinutrients
Chemotherapy - Not !!
Rather - Chemoprevention (prevent disease).
Able to measure amount of damage to our DNA
1. Free radicals (Reactive Oxygen Species - ROS)
a. High dose pesticides
b. Tobacco/2nd hand smoke/other carcinogens
Cancer develops over many decades
1. We have abnormal cells produced consistently.
2. Several mechanisms to identify and destroy these cells before they cause 
a tumor.
a. Detoxifying enzymes (Phase 1, Phase 2)
b. Immune recognition
c. Tumor suppressor genes (i.e., P53)
d. NK cells-natural killer cells, (non-T, non-B)
3. These systems can break down in the following pattern of carcinogenesis:
initiation?promotion?progression.
4. Need to stimulate protective systems.
Detoxification - break down carcinogens to prevent DNA damage (liver).
1. Phase 1 Enzymes - Hydroxylation
a. Cytochrome P450 system (50-100 enzymes)
b. Many toxins are now more carcinogenic (after hydroxylation) and 
chemically active with DNA so Phase 2 must be active to detoxify these 
products.
2. Phase 2 Enzymes - Conjugation
a. Glutathione-S-transferase, UDP-glucuronyl-transferase, Glutathione 
peroxidase, Quinone, reductase (all are glutathione dependent).
Ageing is associated with a decrease in plasma antioxidants (glutathione) 
and an increase in oxidative products (lipid hydroperoxide) even in the 
healthy as demonstrated in the above graph, Lancet 1998.
b. Stimulate these detoxifying enzymes: Polyphenols (green tea), Silymarin 
(milk-thistle), Sulforaphane (broccoli), Tumeric (curry).
c. Ellagic acid (strawberries, raspberries, grapes, walnuts) - stimulate 
Phase 2 enzymes while modulating Phase 1 enzyme activity.

http://www.med.und.nodak.edu/depts/surgery/nutrition/dietary.htm