16 Phytoestrogens Flashcards
3 main categories of phytoestrogens
Isoflavons
lignans
coumestans
Good qualities of a biomarker
Feasibility Specificity ** Sensitivity ** Invasiveness Cost Validated Reference Ranges
Classic definition of phytoestrogens?
Non-steroidal plant compound able to exert estrogenic effects
(naturally occurring)
Phytoestrogens are structurally similar to?
endogenous estrogen (Estradiol) synthetic E and anti-E
Food sources of isoflavons
*soy beans and soy products
legumes
clover
Isoflavones are found in what forms?
Glycoside (typical food form)
Aglycone (fermented foods, absorbed in this form)
- carb group removed
3 major isoflavones present in soy?
Genistin / Genistein
Daidzin / Daidzein
Glycitin / Gycitein
(60/30/10 proportions)
What is present in clover?
isoflavone precursors:
- formononetin
- daidzein - Biochanin A
- genistein
Formononetin
isoflavone precursor of daidzein
Biochanin A
Isoflavone Precursor of genistein
Where are isoflavone precursors converted to isoflavones?
Intestine
Important concept to consider when estimating isoflavone intakes?
Glycoside vs Aglycone form
- glycoside form has carb group still attached
- would overestimate intake
Isoflavone Database
to increase “accuracy” of intake estimates and relation of intake to disease risk
Key physiological feature that effects isoflavone absorption
Intestinal bacteria
what effects intestinal bacteria
antibiotics
pro/prebiotics
travel (food consumption)
Foods that would have isoflavone in its aglycone form?
fermented foods
- ex. soy sauce
Absorption form of aglycones?
aglycone
isoflavone metabolites
Important isoflavone metabolite
Equol
- from daidzein
- only 30%-40% of population has gene to produced intestinal bacteria for the conversion
- higher in asia
Equol compared to other isoflavones and isoflavone metabolites?
- potent
- binds with higher affinity
- longer half-life
- inversely associated with breast cancer
Potential health benefits of soy isoflavones?
Cancer (hormone dependent) CVD Osteoporosis Menopausal Symptoms Cognitive function
Clover disease
Red clover - high in formononetin
- in Australian sheep
- fertility problems
Isoflavone and fertility
Studies show effects in animals
BUT no studies in humans
(more studies in females)
Estrogenic Potency of Isoflavones
potency 1/1000
found in blood 1000x great amounts
(E = pico, iso = nano to low micro amounts)
Isoflavones have similar structure to what estrogen?
estradiol
estrogenic vs anti-estrogenic effect of isoflavone dependent on ?
concentration of endogenous estrogen
Effect of isoflavone when endogenous estrogen is high
Anti-Estrogenic Effect
- isoflavones compete for estrogen receptors
- weaker than estrogens
Effect of isoflavone when endogenous estrogen is low
Estrogenic Effect
- DON’T compete for estrogenic receptors
breast cancer inverse relation to isoflavone based on what 3 parameters?
Dietary Intake
Urinary excretion
Blood concentration
Other than intake and biomarker parameters, what other importance factor relates to breast cancer and isoflavones
age of exposure
- puberty best time
- both puberty and adult is best
relation between rostate cancer and isoflavones?
Inverse relation shown but conflicting data in human studies
Animal studies showed reduced risk, and reduction of size in existing tumors
Isoflavon mechanisms on cancer reduction?
- Reduced concentration of reproductive hormone
- antioxidant effects
- inhibit tyrosine kinase
- inhibit angiogenesis
- inhibit DNA topoisomerase
- induce apoptosis
Inhibition of angiogenesis
reduced blood flow to cancer cells
inhibition of DNA topoisomerase
destabalizes cancer cells
Soy and CVD
Soy “PROTEIN” associated with reduced:
- total cholesterol
- LDL-cholesterol
- triglycerides
- aortic stiffness
increased:
- systemic arterial compliance
- LDL resistance to oxidation
Difference in extracted soy isoflavones? what does this mean?
No Effects on
- total cholesterol
- LDL, HDL
- Triglycerides
supports need for presence in “soy protein”
People at highest risk of osteoporosis? Typical treatment?
Postmenopausal women
- hormone replacement therapy
Why we originally related isoflavones to osteoporosis
Asian women significantly lower hip fractures to white women
Soy isoflavone relation (with respect to osteoporosis)?
Increase Bone Marrow Density
Soy isoflavone used as an alternative to what treatment?
Hormone replacement therapy
HRT
Problems with studies of isoflavones on menopausal symptoms?
HUGE placebo effect
- seasonally different
- self reported data (difficult to measure)
Graphical representation of soy isoflavone intake and plasma concentrations and bioavailability
Curvilinear
- plateaus
- saturable
Lignin food sources
- high in flaxseed
- whole grains, fruits, veggies, seeds
more widespread than isoflavones
Plant vs Mammalian ligans
plant lignans are precursors for mammalian lignans
- only some plant absorbed, most converted to mammalian
Plant lignans
Secoisolariciresinol (SECO)
Mateaiesinal
- in lignan rich foods
Mammalian Lignans
Enterodiol
Enterolactone
- in biological fluids
What plant lignan makes what mammalian lignans
SECO –> Enterodiol
Matairsinol –> Enterolactone
Lignin Health Effects
Human data: (very little available) -Breast cancer -CVD Animal Data: -osteoperosis -colon cancer
Coumestan food sources
sprouts: bean, alfalfa, soybean
clover
Main coumestan? Features?
Coumestrol
- similar to estradiol
- can bind to ERs
Pharmakinetics
branch of pharmacology dedicated to determine fates of substances admitted to an organism externally (drugs, nutrients, toxins etc)
