Detoxification Flashcards
(118 cards)
What are factors for an increased risk in breast cancer
Xenoestrogens Pollutants Xenobiotics Menopause Stress
How is menopause a risk factor for Breast cancer
spikes estrogen relative to progesterone
excessive stimulation through estrogen receptor
How is stress a risk factor for Breast Cancer
Emotions: more cause most damage Physical and surgical- less often Decrease in melatonin Decrease thyroid Cortisol and Dhea out of balance
How does the tumor contribute to breast cancer
tumor becomes like ovary- produces estrogen- and is primarily the source of inflammation
How is the breast tumor a source of inflammation
as its forming need a good source of glucose
over stimulates the insulin receptors leading to insulin resistance
LH/FSH increase-> PCOS-> testosterone-> estradiol
How does estrogen metabolism become a cancer risk
most estrogen hormones in body are estrosulfate
Key Enzymes: CYP1B1- in liver, kidney and other tissue
CYP1A1: both enzymes move estrogen through pathways
4-OH-E1(E2) with COMT-Methylation of 2-A-4-OH-E1(E2) coverts estrogen or estrodial- is bad but not terrible, if patient methylate well will clear them-
If not methylating well, above reaction will down regulate and lead to cancer
How does estrogen metabolism and pollutant lead to cancer
If making too many estrogens with exposure to pollutants-> induce enzymes that will make bad estrogen and cause DNA formation which leads to DNA damage which results in cacner
What factors contribute to DENA formation, damage and ultimately cancer
Trans Fats- more easily oxide estrogen
Heavy metals: mercury, arsenic: oxidize estrogen
What testing is available for Estrogen
Serum and Plasm
Urine( liquid and dry)
Saliva
What is significant about Estrogen vs Estradiol in terms of metabolism and cancer risk
Harmful if metabolized in the wrong way
Progesterone is natural anti-estrogen
Higher levels of estrogen can have higher levels of catechol of estrogen
What is a common Urinary profile in breast cancer patients
- increased estradiol and estrone
- increased 4-OH-E1 and 4-OH-E2
- decreased ratio of 4-MeO-E1/r-OH-E1
- decreased pregnanediol
- Increased ratio of pregnane/pregnene
- Decreased testosterone and dHT
- Increased EPI testosterone
- Decreased DHEA
Increased diurnal cortisol flat
What are lifestyle changes that reduce risk of breast cancer
Lots of organic veggies- crucious veggies- improve estrogen metabolism
avoid pollutants
Exercise
Get adequate sleep
If hormone deficient- take necessary hormones
DIM- indole-3-carbionol or diindolymethane
omega 3 FA
green algae
Whats the pathway for Estrogen metabolism
E1-SO4-> sulfatase->E1->(17B-HSD-Type1)-E2
Conversely: E2-> (17B-HSD2)->(Sulfotransferase)->E1- SO4
What happens when E1-SO4 is converted to E1
depends on the SNP for processing. If CYP1B1 then issues occur, if CYP1A1 more normal and safer outcome
How does CYP1B1 affect estrogen metabolism in the body
E1->( CYp1B1)-becomes 4-OH-E1(E2) which if appropriate methylation will become metabolites: 2 and 4 MeO-E1(E2)
If not methylating well will become 4-Quinone-E1(E2) and if appropriate GST-GSH conjugation of 2 and 4 quinone E1(E2) will become metabolites- if not will produce DNA adduct formation-> DNA damage mutation-> cancer
How does CYP1A1 affect estrogen metabolism
E1 with CYP1A1-> either 2 OH-E1(E2) or 16-OH-E1. Would like to become 16 as it is metabolized appropriately becoming E3 and binds to protein and no affect on the body. If an issue with CYP1A1 and ability to detox- 2-OH-E1(E2) -> 2-Quinonine-E1(E2)- DNA adduct formation and DNA repair
How is cortisol a factor for Breast Cancer patients
Normal profile: cortisol high in am and low at night
Breast cancer patients- flat line diurnal cortisol and high at night
What key hormones make up the matrix for Breast cancer- estrogen matrix
Testosterone Estrogen Progesterone Cortisol DHEA
Where is estrogen found
produced in ovaries and metabolized in liver
What are benefits of estrogen
metabolism functions correctly vessel and skin increase bone formation increase hepatic production of binding protein increase HDL Decrease LDL Increase cortisol: SHBG Increase Cholesterol in bile Promote lung function
What are 2 key estrogen metabolites
2-Hydroyestrone( 2-OHE1)- inhibit cancer growth- implies balanced metabolism: via reasonable intake of veggies and flaxseed
16-a-hydroxyestrone( 16-a-OHE1)- encourages tumor development- bad estrogen- lupus, breast cancer, levels can rise in response to obesity and alcohol, genetics play a role, is modifiable by measuring estrogen
What is important about 2:16 alpha-Hydroxyestrone ratio
Higher ration less risk for estrogen related cancers
Serum great than .4 is considered to be beneficial
What are mechanisms of heavy metal toxicity
metals generate many of deletions effects through the formation of free radicals, resulting in DNA damage, lipid peroxiding depletion of protein sulfydrase
are everywhere- appear mediated through mitochondrial damage from glutathione depletion
why be concerned about heavy metal toxicity
toxic to all living creature everywhere in environment increase in health damage if not removed may take years for sx to appear causes many diseases and blocks healing mercury is usually hidden as the cause