Phytoestrogens

1
Phytoestrogens

• Roxann Harvey

2
Human Diet

• Contain various plant derived non steroidal weak
  estrogenic compounds
• Phytoestrogens can be divided into 3 classes
  isoflavonoids, coumestans, and mammalian lignans
• Isoflavonoids ex. Biochanin A and genistein and
  coumenstans are formed in numerous edible plants,
  especially in soy and other leguminous plants
• Mammalian lignans ex. Enterolactone and
  enterodiol are derived from unrefined grain

3
Soy Breast Cancer

• Soy estrogens rich in plant estrogens are used
  by American women for relieving menopause
  symptoms
• Soy estrogens are thought to have the same
  benefits without the breast cancer risk of
  synthetic hormones
• Soy is rich in phytoestrogens, weakly estrogenic
  non-steroidal compounds
• Soy is known to produce estrogenic isoflavones

4
Asian Women Soy

• Asian women typically consume soy based diets and
  have a low incidence of breast cancer possibly
  by reducing estrogen levels
• Asian women living in Asia have been found to
  have estrogen levels up to 40 lower than U.S
  females
• They also demonstrate a fivefold lower risk of
  developing breast cancer

5
Phytoestrogens

• Phytoestrogens are a class of several different
  chemicals produced by a variety of plants
• Soys possible anticancer potential is associated
  with its rich supply of phytoestrogens
  genistein in particular
• Several in vitro studies have shown genistein
  suppresses estrogenic activity
• Genistein may inhibit estrogenic activity by
  blocking estrogen metabolizing enzymes

6
Urine Concentrations

• Phytoestrogens appear in high concentrations in
  the urine of Asian women, who have low rates of
  breast cancer
• Phytoestrogens are found in low concentrations in
  the urine of breast cancer patients

7
Genistein

• Some animal experiments and studies with human
  breast cancer cells have found genisteins
  ability to suppress cell growth
• Genistein is structurally similar to steroidal
  estrogens and binds to estrogen receptors
• In contrast, other studies in vivo and in vitro
  models have found genistein to be estrogenic
• Dose may explain the paradox of genisteins
  estrogenic and anti-estrogenic properties

8
Genistein Dosage

• Some studies have demonstrated that only doses
  higher than can be received by only consuming soy
  based foods provide protection against breast
  cancer, similar to the drug tamoxifen
• Doses that can be achieved with consuming foods
  high in soy, genistein stimulates human breast
  cancer cell growth
• However, a study of postmenopausal American
  women given 38 grams of soy protein isolate daily
  for 5 months ( amount in a high soy diet) showed
  no changs
• Another study by Donna Baird,an epidemiologist,
  found no changes in postmenopausal women but
  there was evidence of vaginal cell changes as a
  result of estrogens

9
Animal Models Genistein

• In utero rat studies have found that exposure to
  genistein but not to soy increases the risk of
  breast cancer
• Ovariectomized mice post menopause model
  suggest that genistein increases breast cancer
  risk
• No increase is seen in animals exposed during
  their reproductive stage
• Rats exposed genistein before puberty show low
  breast cancer risk

10
Timing is Everything

• Asian women eat a soy based diet throughout
  pregnancy and do not raise their daughters risk
  of breast cancer
• It is speculated that Asian womens protection
  originates from life long exposure
• Other components of soy such as saponins and
  phytic acids may temper genisteins estrogenic
  effects in humans

11
Female Estrogen Levels

• Hypothesized that genisteins variable effects
  may be a function of womens estrogen levels
• Before puberty when estrogen is low- genisein
  may act as an estrogen
• Animal and human studies suggest that estrogen
  exposure before puberty reduces breast cancer
  risk
• Phytoestrogens may promote the rapid growth of
  mammary cells in women of all ages
• However, older women may already have malignant
  cells in their breasts which make them more
  likely to develop cancer

12
Soy produces isoflavonoids

• Isoflavonoids are a class of plant estrogens
• Have an adverse affect on sexual development
• In one experiment researchers fed female rats a
  diet containing the isoflavonoid coumestrol The
  female offspring had early and irregular menstual
  cycles and the male offspring did not gain weight
  as fast as the controls before puberty. Deficits
  in mating behavior were also exhibited
• The offspring received the coumestrol from the
  mothers milk
• Another experiment by Whitten showed that
  coumenstrol induced uterine growth, thereby
  demonstrating estrogen activity

13
Dangers of Soy

• Soy isoflavones given during development can
  cause several forms of estrogen toxicity in
  experimental animals
• Genistein has been found to cause uterine
  adenocarcinoma in adult mice, following neonatal
  treatment
• Since earlier diethylstilbestrol (DES) studies
  showed the same effect, equal doses of genistein
  and DES ( the positive control) were used and
  found to have equivalent tumor incidences
• These findings suggest that the estrogenic
  activity and not the chemical structure is
  responsible for the malignant outcomes

14
Effects of Soy

• In a controlled trial, women receiving a dose of
  30 g of soy flour a day had clear estrogenic
  effects including lengthening of the menstrual
  cycle
• Infants on soy infant formula receive a dose of
  phytoestrogens that is 5 times higher than the
  dose causing estogenic effects in women
• Although approximately 20 of American infants
  are consuming soy formula, no comprehensive
  studies have been done yet

15
Effects of Genistein

• Genistein binds to the estrogen receptor
• It is estrogenic in vivo and is an estrogenic
  developmental toxicant
• Genistein is an estrogenic carcinogen in rodents
  and may translate over to human subjects

16
Possible Effects of Soy on Human Thyroid Health

• Similar total genistein concentrations in rat
  serum in one experiment were similar to those in
  human, suggesting a similar tissue exposure
• Therefore human isoflavone consumption could
  produce isoflavone levels in the thyroid
  sufficient to inactivate human thyroid peroxidase
  a heme-containg enzyme that catalyzes both
  reactions required for thyroid hormone synthesis

17
Pyhtoestrogens with high estrogen receptor binding

• Soy Milk
• Licorice
• Clover
• Mandrake
• Bloodroot
• Thyme
• Yucca
• Tumeric
• Haps
• Verbena
• Yellow dock
• Sheep sorrel

18
References

• Gpotrpgemoc and Estrogenic Activity of Soy
  Isoflavones Daniel R. Doerge and Daniel M
  Sheehan (2002)
• Diety Estrogens Act through Estrogen Receptor
  Mediated Processes and Show No Antiestrogenicity
  in Cultured Breast Cancer Cells Makela et al.,
  (1994)
• Extra Ingredients Hormones in Food John
  McCarthy (1994)
• Estrogenic Activity of Natural and Synthetic
  Estrogens in Human Breast Cancer Cells in
  Culture David Zava et. al., ( 1997)
• Soy and Breast Cancer Cynthia Waham (2000)