I Ecture 16

Question 1

Phytoestrogens

Answer 1

-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

Question 2

Isoflavones

Answer 2

• 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

Question 3

Isoflavone precursors

Answer 3

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

Question 4

Is flavone intake

Answer 4

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

Question 5

Is of lavone absorption

Answer 5

Intestinal bacteria are key to is of Lavon absorption
- antibiotic use will prevent absorption

1. Precursors:
   - biochanin A
   - for mononetin
2. Is flavone glycosides:
   - Genistin
   - daidzin
   -Glycitin

3, isoflavone aglycones:
- genistein
- daidzein
- glycitein
- absorption can happen

4. Isoflavone metabolites:
   -P-ethylphenol
   - equal, ODMA
   - absorption

Isoflavones are present in foods as glycosides except fermented foods (aglycones)

Question 6

Is of flavones after absorption

Answer 6

• 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

Question 7

Uniqueness of equol

Answer 7

• 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

Question 8

Potential health effects of soy is flavones

Answer 8

• Relate to estrogen
• hormone dependent cancers
• CVD
• osteoporosis
• menopausal symptoms

Question 9

Isoflavones & animals

Answer 9

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

Question 10

estrogenic potency of isoflavones
Important

Answer 10

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

Question 11

Isoflavones and estrogen: estrogenic or anti-estrogenic
Important

Answer 11

• 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

Question 12

Isoflavones & breast cancer prevention

Answer 12

• 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

Question 13

Isoflavones and breast cancer

Answer 13

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

Question 14

Isoflavones and cancer mechanism

Answer 14

Reduced concentrations of reproductive hormones
- interactions with estrogen receptor
- inhibiting enzymes involved in hormone synthesis

_Antioxidant effects
- inhibit angiogenesis, protein tyrosine kinase
- increase apoptosis

Question 15

Say is of flavones and CVD

Answer 15

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

Question 16

Is o flavones and osteoporosis

Answer 16

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 )

Question 17

Soy is flavones and menopausal symptoms

Answer 17

Studies shown soy is of lavorus; - decrease not flush frequency and severity
- key issue is placebo effect
- other issues: time, subjectivity

Question 18

Is flavones : in soy or extracted

Answer 18

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

Question 19

Soy & infants

Answer 19

• 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

Question 20

Soy is flavones and thyroid function

Answer 20

-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

Question 21

Lignans

Answer 21

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 )

Question 22

Coumestans

Answer 22

A class of phytoestrogens
Little known
Found in sprouts, clover
Main coumestan:coumesterol
- can bind to er, therefore considered a class of phytoestrogen

Question 23

Phytoestrogen classification review

Answer 23

Phytoestrogens are a group of phytochemicals

3 classes of phytoestrogens
1. Is flavones
- genisitein, daidzein, glycitein
2. lignans
- plant lignans, mammalian
3. Coumestans
- coumestrol