I Ecture 16 Flashcards
Phytoestrogens
-Phytochemicals
- naturally found in plants
- non steroidal plant compound that can exert estrogen effects
- 3 major classes:
Isoflavones
Lignin
Coumestans
- structures are similar to estrogen and anti estrogen structure
Isoflavones
- Major class of phytoestrogens
- legumes, soybeans, soy products, red clover
- 3 major is flavones in soy:
-Glycoside forms;
1. genistin
2. Daidzin
3, glycitin
Aglycone forms (de conjugated)
1. Genistein
2. Daidzein
3. Glycitein
Usually 60/30/10 proportions
Isoflavone precursors
Present in red clover and can be converted to is of flavones
- formononetin : precursor for daidzein
- biochanin A: precursor for genistein
Converted in intestines since nothing is absorbed yet
Is flavone intake
Asian intake way more man western
Important concept for intake: units
- want aglycone units
Isoflavones have a database
- helps with quantities and associated disease risk
- Can’t help w bioavailability
Is of lavone absorption
Intestinal bacteria are key to is of Lavon absorption
- antibiotic use will prevent absorption
- Precursors:
- biochanin A
- for mononetin - Is flavone glycosides:
- Genistin
- daidzin
-Glycitin
3, isoflavone aglycones:
- genistein
- daidzein
- glycitein
- absorption can happen
- Isoflavone metabolites:
-P-ethylphenol
- equal, ODMA
- absorption
Isoflavones are present in foods as glycosides except fermented foods (aglycones)
Is of flavones after absorption
- Portal circulation to liver
- conjugation with glucoronic acid or sulfate
- travel into circulation to exert biological effects
- therefore when analyzed in biological
Fluid as the first step is to deconjugate the glucuronic acid or sulfate to yield the aglycone
Uniqueness of equol
- Metabolite of daidzein
- only 30-40% of population excrete equol in their urine
- one of the most potent isoflavones
- binds estrogen receptor with higher affinity than other is of flavones
- longer half life, stays in circulation longer
-Inversely associated with breast cancer risk
Potential health effects of soy is flavones
- Relate to estrogen
- hormone dependent cancers
- CVD
- osteoporosis
- menopausal symptoms
Isoflavones & animals
Clover disease
- fertility problems linked to female sheep
- attributed to isoflavone precursors in clover they ate
- clover is high in formononetin which is an is oflavome precursor for which isoffavone?
- equol
- no reports of fertility problems in humans related to is of flavones but reports of hormonal and anti hormonal effects
estrogenic potency of isoflavones
Important
Able to bind to the estrogen receptor
- potency is much less than endogenous estrogen (1/1000th )
- potency defined by affinity for estrogen receptor
- to make up for weakness, their quantities in the blood are 1000 times greater
Isoflavones and estrogen: estrogenic or anti-estrogenic
Important
- Is flavone structure similar to estradiol
- whether there are estrogenic or anti-estrogenic effects depends on level of endogenous estrogen present
High endogenous estrogens ( premenopausal women):
- is of flavones compete with endogenous estrogens for ER
- but isofiavones are weaker estrogens
-Is oflavores would exert net anti-estrogenic effect
- relevant for breast cancer prevention
Low endogenous estrogens (post menopausal women)
- isoflavones do not need to compete for Er
- net estrogen effect since they can be in large quantities to make up for weakness
- relevant for menopausal symptoms, bone health, cv system
Isoflavones & breast cancer prevention
- Anti-estrogenic effect of is flavones thought to contribute towards reduction in BC risk
- inverse relationship between BC risk and:
- dietary intake of isoflavones
-Urinary excretion of is of iavoms - blood conc of is of flavones
Above are all good biomarkers of intake
Isoflavones ave bidavailable and can reach breast tissue
- bioavailability is key to realization of health effects of phytochemicals
Isoflavones and breast cancer
Age of exposure is a key concept that may explain the inconsistencies among soy is flavone, breast cancer studies in adults
- early life events contribute most toward breast cancer risk
Genistein exposure at different life stages in rats showed
- prepubertal had least tumors( most protected )
- adult had most tumors (no protective effect)
Inverse association between soy intake in adolescence and adult breast cancer risk
- also protective effect against prostate cancer
Isoflavones and cancer mechanism
Reduced concentrations of reproductive hormones
- interactions with estrogen receptor
- inhibiting enzymes involved in hormone synthesis
_Antioxidant effects
- inhibit angiogenesis, protein tyrosine kinase
- increase apoptosis
Say is of flavones and CVD
Blood lipid studies snow evidence that led to approval of a health claim in USA & Canada
- soy protein and coronary heart disease
- note the claim is for soy protein not the is is of flavones specifically
Extracted is of flavones do not lower blood lipids
- key idea of whether efficacy is compromised when photochemical is an extracted or isolated form
Is o flavones and osteoporosis
Most relevant to post menopausal women
- decline in estrogen production that occurs is a big contributing factor
Initial interest in isoflavones and osteoporosis risk came from Asia
Studies assessed blood and urinary biomarkers of bone turnover
- favourable effects (increased bone formation, decreased bone resorption )
Soy is flavones and menopausal symptoms
Studies shown soy is of lavorus; - decrease not flush frequency and severity
- key issue is placebo effect
- other issues: time, subjectivity
Is flavones : in soy or extracted
Relates to efficacy:
- extracted isotlavones do not lower serum lipids
- but may affect other health biomarkers
Relates to safety;
- widespread availability of extracted is isoflavones in dietary supplement form
Relates to qualify assurance;
- need to make sure amount is there
New studies snow a curvilinear relationship between soy is of lavone intake from food and their plasma concentration/bioavailabil
- blood levels increased with consumption but then reached a plateau
-Hypothesized that absorption is a saturable process
- possibly more difficult to obtain pharmacological levels with food but also means safety not much of a concern
Soy & infants
- no indications of any adverse effects in soy fed children
- higher levels of is of flavones but no negative effects
- infants do not produce equol
Soy is flavones and thyroid function
-Isoflavones inhibit thyroid peroxidase by acting as an alternative substrate for iodine in cell culture and rat studies
- studies results showed no or very little change in thyroid hormone
- even thou gh thyroid peroxidase is inhibited, is flavone supplements not associated with changes in thyroid function
Soy can interfere with absorption of levothyroxine (thyroid medication) and foods nigh in calcium or fibre
- recommended to take meds in morning or on empty stomach
Lignans
A class of phytoestrogens
- more widespread in plants then icoflavoms, especially flaxseed.
Plant lignans:
- seco
- matairesinol
Plant lignans are precursors of mammalian lignans:
- enterodiol
- enter lactone
- both present in biological fluids there fore measured for bioavai/ability, not plant forms
Figure on slide 58
Health effects similar to soy ( breast cancer risk, DVD risk )
Coumestans
A class of phytoestrogens
Little known
Found in sprouts, clover
Main coumestan:coumesterol
- can bind to er, therefore considered a class of phytoestrogen
Phytoestrogen classification review
Phytoestrogens are a group of phytochemicals
3 classes of phytoestrogens
1. Is flavones
- genisitein, daidzein, glycitein
2. lignans
- plant lignans, mammalian
3. Coumestans
- coumestrol
