Phytoestrogens

Phytoestrogen/Drug Interactions:

  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: According to a study conducted to evaluate the effects of phytoestrogen on cardiovascular risk markers in postmenopausal women, fibrinogen levels may decrease after genistein phytoestrogen therapy (6).
  • Antidiabetic agentsAntidiabetic agents: In humans, treatment with phytoestrogens derived from soy supplements or flaxseed may result in decreases in fasting blood glucose, fasting insulin levels, and insulin resistance in postmenopausal women (6; 7; 8).
  • Anti-inflammatory agentsAnti-inflammatory agents: In vitro, the isoflavones genistein and daidzein enhanced the cyclooxygenase-2 (COX-2) protein and subsequent prostacyclin production through estrogen receptor activation (a potent vasodilator) in a model using cultured human umbilical vein endothelial cells (33). Additionally, 5-lipooxygenase (5-LOX), a mediator of inflammation, was more highly expressed in persons consuming phytoestrogens derived from soy (42).
  • AntilipemicsAntilipemics: In humans, dietary phytoestrogens derived from soy supplements may lower total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels, and increase high-density lipoprotein cholesterol levels (11; 12; 7).
  • Antimigraine agentsAntimigraine agents: In humans, phytoestrogen treatment may reduce the frequency of menstrually associated migraine attacks (44).
  • AntineoplasticsAntineoplastics: In humans, isoflavones and lignans from soy supplements may decrease estrogen synthesis and alter the estrogen metabolism away from genotoxic metabolites toward inactive metabolites and thereby may exert cancer-preventive effects in women (45; 46). In another study, isoflavone supplementation showed a significant increase in genistein and daidzein concentration in prostate tissue, which may reduce prostate cancer risk (28).
  • BisphosphonatesBisphosphonates: In postmenopausal women, isoflavone phytoestrogens were associated with inhibition of osteoclastic bone resorption, attenuation of bone loss, and stimulation of osteoblastic bone formation (26; 25; 27; 47).
  • Cardiovascular agentsCardiovascular agents: In vitro, genistein treatment may have favorable effects on certain cardiovascular markers, such as a significant reduction in serum lipid levels, fasting glucose, fasting insulin, insulin resistance, osteoprotegerin (OPG), and fibrinogen (6; 17; 7; 8).
  • EstrogensEstrogens: In postmenopausal women, 8-prenylnaringenin (8-PN), the phytoestrogen derived from hops (Humulus lupulus L.), may have potent estrogenic activity and effects on menopausal symptoms (14). Other forms of phytoestrogens, such as isoflavones derived from soy supplements (PHYTO SOYA?) or red clover (Promensil?, Rimostil?), and lignans derived from linseed were found to have a similar positive impact on climacteric symptoms due to estrogenic effects (19; 21; 22; 48). It is unclear if phytoestrogen consumption alters the effectiveness of birth control pills that contain estrogen.
  • Fertility agentsFertility agents: In humans, the use of phytoestrogens for luteal phase support in patients undergoing in vitro fertilization-embryo transfer (IVF-ET) may have favorable outcomes, such as a significant increase in implantation rate, clinical pregnancy rate, and ongoing pregnancy or delivered rate (3).
  • ImmunosuppressantsImmunosuppressants: In postmenopausal women, a high dietary intake of phytoestrogens derived from soy proteins may significantly increase interleukin-6 (IL-6) values. This finding may indicate an estrogenic effect of soy isoflavones in enhancing the immune response and provide a possible explanation through enhanced immune surveillance for the lower incidence of certain cancers in soy-eating populations. However, no significant effects were seen for men or women on acute-phase proteins and other proinflammatory cytokines such as C-reactive protein (CRP), serum amyloid A (SAA), or tumor necrosis factor-alpha (TNF-alpha) after phytoestrogen consumption (49).

    • Phytoestrogens/Herb/Supplement Interactions:

  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: According to a study conducted to evaluate the effects of phytoestrogen on cardiovascular risk markers in postmenopausal women, fibrinogen levels may decrease after genistein phytoestrogen therapy (6).
  • Anti-inflammatory agentsAnti-inflammatory agents: In vitro, the isoflavones genistein and daidzein enhanced the cyclooxygenase-2 (COX-2) protein and subsequent prostacyclin production through estrogen receptor activation (a potent vasodilator) in a model using cultured human umbilical vein endothelial cells (33). Additionally, 5-lipooxygenase (5-LOX), a mediator of inflammation, was more highly expressed in persons consuming phytoestrogens derived from soy (42).
  • AntilipemicsAntilipemics: In humans, dietary phytoestrogens derived from soy supplements may lower total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels, and increase high-density lipoprotein cholesterol levels (11; 12; 7).
  • Antimigraine agentsAntimigraine agents: In humans, phytoestrogen treatment may reduce the frequency of menstrually associated migraine attacks (44).
  • AntineoplasticsAntineoplastics: In humans, isoflavones and lignans from soy supplements may decrease estrogen synthesis and alter the estrogen metabolism away from genotoxic metabolitestoward inactive metabolites and thereby may exert cancer-preventive effects in women (45; 46). In another study, isoflavone supplementation showed a significant increase in genistein and daidzein concentration in prostate tissue, which may reduce prostate cancer risk (28).
  • Bone density conservation agentsBone density conservation agents: In postmenopausal women, isoflavone phytoestrogens were associated with inhibition of osteoclastic bone resorption, attenuation of bone loss, and stimulation of osteoblastic bone formation (26; 25; 27; 47).
  • Cardiovascular herbs and supplementsCardiovascular herbs and supplements: In vitro, genistein treatment may have favorable effects on certain cardiovascular markers, such as significant reduction in serum lipid levels, fasting glucose, fasting insulin, insulin resistance, osteoprotegerin (OPG), and fibrinogen (6; 17; 7; 8).
  • Fertility herbs and supplementsFertility herbs and supplements: In humans, the use of phytoestrogens for luteal phase support in patients undergoing in vitro fertilization-embryo transfer (IVF-ET) may have favorable outcomes, such as significant increase in implantation rate, clinical pregnancy rate, and ongoing pregnancy or delivered rate (3).
  • Hormonal herbs and supplementsHormonal herbs and supplements: In postmenopausal women, 8-prenylnaringenin (8-PN), the phytoestrogen derived from hops (Humulus lupulus L.), may have potent estrogenic activity and exert favorable effects on menopausal symptoms (14). Other forms of phytoestrogens, such as isoflavones derived from soy supplements (PHYTO SOYA?) or red clover (Promensil?, Rimostil?), and lignans derived from linseed were found to have similar positive impacts on climacteric symptoms due to estrogenic effects (19; 21; 22; 48). It is unclear if phytoestrogen consumption alters the effectiveness of birth control pills that contain estrogen.
  • HypoglycemicsHypoglycemics: In postmenopausal women, treatment with phytoestrogens derived from soy supplements or flaxseed may result in decreases in fasting blood glucose, fasting insulin levels, and insulin resistance (6; 7; 8).
  • ImmunomodulatorsImmunomodulators: In postmenopausal women, high dietary intake of phytoestrogens derived from soy proteins may significantly increase interleukin-6 (IL-6) values. This finding may indicate an estrogenic effect of soy isoflavones in enhancing the immune response and provide a possible explanation through enhanced immune surveillance for the lower incidence of certain cancers in soy-eating populations. However, no significant effects were seen for men or women on acute-phase proteins and other proinflammatory cytokines such as C-reactive protein (CRP), serum amyloid A (SAA), or tumor necrosis factor-alpha (TNF-alpha) after phytoestrogen consumption (49).
  • ProbioticsProbiotics: In humans, consumption of probiotic supplements consisting of Lactobacillus acidophilus and Bifidobacterium longum for two months did not significantly alter the excretion status of equol, a metabolite of daidzein phytoestrogen (50). In an another similar study, plasma phytoestrogen concentrations and the number of equol producers did not differ between the subjects receiving only soy protein supplements or subjects receiving soy protein supplements along with probiotic diets consisting of 109 colony-forming units of Lactobacillus acidophilus and Bifidobacterium longum, and 15-30mg of fructooligosaccharide (51).
  • ZincZinc: According to secondary sources, soy may interfere with zinc absorption.

    • Phytoestrogens/Food Interactions:

  • Probiotic-containing foodsProbiotic-containing foods: Phytoestrogens are metabolized by the intestinal bacteria and enzymes, and any alterations in these may affect the phytoestrogen metabolism. According to clinical evidence, consumption of probiotic supplements consisting of Lactobacillus acidophilus and Bifidobacterium longum for two months did not significantly alter the excretion status of equol, a metabolite of daidzein phytoestrogen (50). In an another similar study, plasma phytoestrogen concentrations and the number of equol producers did not differ between the subjects receiving only soy protein supplements or subjects receiving soy protein supplements along with probiotic diets consisting of 109 colony-forming units of Lactobacillus acidophilus and Bifidobacterium longum, and 15-30mg of fructooligosaccharide (51).

    • Phytoestrogens/Lab Interactions:

  • Alkaline phosphate levelsAlkaline phosphate levels: In humans, genistein therapy for 6-12 months resulted in significant increases in bone-specific alkaline phosphate levels, indicative of reduced bone resorption and increase in bone formation (27).
  • Coagulation panelsCoagulation panels: Fibrinogen levels were observed to be significantly decreased after genistein phytoestrogen therapy in a study conducted to evaluate the effects of phytoestrogen on cardiovascular risk markers in postmenopausal women (6).
  • Cortisol levelsCortisol levels: Dietary consumption of flaxseed, which contains large quantities of a lignan phytoestrogen precursor secoisolariciresinol diglucoside (SDG), was associated with significant decrease in plasma cortisol levels in postmenopausal women (52).
  • C-reactive protein (CRP) levelsC-reactive protein (CRP) levels: In postmenopausal women, genistein treatment for six months did not alter the plasma CRP levels, a marker of cardiovascular risk, but this marker was significantly raised after conventional hormonal replacement therapy (15).
  • Estrogen levelsEstrogen levels: In postmenopausal women, phytoestrogens such as isoflavones derived from soy supplements were found to have positive impact on climacteric symptoms due to estrogenic effects (48). In premenopausal women, isoflavones and lignans from soy supplements may decrease estrogen synthesis and alter the estrogen metabolism away from genotoxic metabolitestoward inactive metabolites and thereby may exert cancer-preventive effects (46).
  • Glucose levelsGlucose levels: A significant decrease in the fasting blood glucose, fasting insulin levels, and insulin resistance was observed after treatment with phytoestrogens derived from soy supplements or flaxseed in several clinical trials conducted in postmenopausal women (6; 7; 8).
  • Homocysteine levelsHomocysteine levels: In postmenopausal women, genistein treatment for six months did not alter the circulating homocysteine levels, an independent marker of cardiovascular risk (15).
  • Lipid panelLipid panel: In postmenopausal women, several studies reported that dietary phytoestrogens derived from soy supplements significantly lowered total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels and increased high-density lipoprotein cholesterol levels, due to its hypolipidemic effects (11; 12; 7). In infants, there was a significant increase in the cholesterol fractional synthesis rates in infants that received soy milk-based formula compared to infants that received human milk or cow's milk (53).
  • Osteocalcin levelsOsteocalcin levels: In postmenopausal women, genistein therapy for 6-12 months caused a significant increase in osteocalcin (bone Gla protein) levels, indicative of reduced bone resorption and increased bone formation (27).
  • Phytoestrogen levelsPhytoestrogen levels: 8-Prenylnaringenin (8-PN), the phytoestrogen derived from hops (Humulus lupulus L.), caused potent estrogenic activity and exerted favorable effects on menopausal symptoms in postmenopausal women (14). Other forms of phytoestrogens, such as isoflavones derived from red clover, had a similar positive impact on climacteric symptoms, due to estrogenic effects (28).