Natural Standard Bottom Line Monograph, Copyright © 2013 (www.naturalstandard.com). Commercial distribution prohibited. This monograph is intended for informational purposes only, and should not be interpreted as specific medical advice. You should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.
While some complementary and alternative techniques have been studied scientifically, high-quality data regarding safety, effectiveness, and mechanism of action are limited or controversial for most therapies. Whenever possible, it is recommended that practitioners be licensed by a recognized professional organization that adheres to clearly published standards. In addition, before starting a new technique or engaging a practitioner, it is recommended that patients speak with their primary healthcare provider(s). Potential benefits, risks (including financial costs), and alternatives should be carefully considered. The below monograph is designed to provide historical background and an overview of clinically-oriented research, and neither advocates for or against the use of a particular therapy.
8-Prenylnaringenin (8-PN), biochanin A, coumestans, coumestrol, daidzein, enterodiol, enterolactone, equol, flax phytoestrogens, flaxseed, formononetin, genistein, glycitein, hop extract, Humulus lupulus L., isoflavones, isoflavonoid phytoestrogen, lignans, matairesinol, O-desmethylangolensin (O-DMA), prenylflavonoids, Pueraria lobata (kudzu), red clover, secoisolariciresinol diglucoside (SDG), soy.
Combination product examples: MenoHop®, PHYTO SOYA®, Promensil®, Rimostil®, SoyaVital®.
Note: This review does not include mycoestrogens, which are estrogenic fungal products and not intrinsic components of plants. They are found in pasture grasses and legumes infected by the fungal genus Fusarium.
The word "phytoestrogen" is derived from phyto, meaning "plant" and estrogen, because of the ability of these compounds to affect estrogenic activity in the body. Phytoestrogens are a diverse group of polyphenolic, nonsteroidal plant compounds that may cause both estrogenic and antiestrogenic effects. The estrogenic effects of phytoestrogens are similar, although less intense, than those of estrogens made by the human body. There are reportedly approximately 300 plant species containing phytoestrogen compounds that have some degree of estrogen activity.
The three major classes of phytoestrogens are isoflavones, lignans, and coumestans. Isoflavones are prominent in soy-based foods. Lignans are minor components of cell walls and fibers of seeds, fruits, berries, vegetables, grains, and nuts. Linseed (flaxseed) is a rich source of lignans. The primary coumestan is coumestrol. It is found in alfalfa and clovers, and in low levels in soybeans and peas.
Several population studies have indicated that phytoestrogens have health benefits. These include possible protection against menopausal symptoms and osteoporosis, as well as a potential reduction in breast cancer, prostate cancer, and cardiovascular disease risks. Both isoflavone and lignan phytoestrogens may have antioxidant activity.
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
Cardiovascular risk reduction (postmenopausal)
Evidence suggests that certain populations that consume large amounts of soy protein have lower cardiovascular morbidity and mortality. Soy protein has been reported to reduce serum lipid levels by up to 10%. Preliminary evidence suggests that soy protein is superior to isoflavones isolated from red clover for reduction of serum lipid levels. Additional research is needed in this area.
Foods rich in phytoestrogens may help alleviate symptoms of menopause, such as vaginal dryness, burning, itching, painful intercourse, and decreased interest in sex. Additional, well-designed studies are needed before firm conclusions may be made.
It has been theorized that phytoestrogens, such as isoflavonoids found in soy and red clover, may increase bone mineral density in postmenopausal women and reduce the risk of fractures. Further studies are required before a firm conclusion may be made.
Some evidence suggests that isoflavones may have a beneficial effect on cognitive function in postmenopausal women. Additional research is needed in this area.
Multiple studies have shown that dietary intake of phytoestrogens derived from soy, lignans, or red clover reduces the risk of osteoporosis in postmenopausal women by inhibiting bone resorption, stimulating bone formation, preventing bone loss, and increasing bone mineral content. Additional studies are needed before a conclusion can be made.
Approximately 30% of women afflicted with migraine have headaches associated with menstruation. Preliminary research suggests that a combination product containing soy, dong quai, and black cohosh may be effective in preventing menstrual migraines. Further research with phytoestrogens alone is needed.
In laboratory research, phytoestrogens had anticarcinogenic properties, such as growth arrest, and may have caused programmed cell death in prostate cancer cells. Additional research is needed in this area.
*Key to grades:A: Strong scientific evidence for this use; B: Good scientific evidence for this use; C: Unclear scientific evidence for this use; D: Fair scientific evidence against this use (it may not work); F: Strong scientific evidence against this use (it likely does not work).
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious and should be evaluated by a qualified health care professional.
Breast cancer, cardiovascular disease, colorectal cancer, hair loss, ovarian cancer, pregnancy (increased implantation rate in in vitro fertilization), uterine cancer, vaginal atrophy.
The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.
Adults (18 years and older)
For cardiovascular risk reduction (postmenopausal), phytoestrogens derived from 40 grams of crushed flaxseed have been taken by mouth daily for two months. The isoflavone genistein has been taken by mouth at a dose of 54 milligrams daily for 6-12 months. Ninety milligrams of isoflavones (1:1:0.2 genistein:daidzein:glycitein) has been taken by mouth daily in two divided doses for six weeks. Isoflavones from Pueraria lobata (kudzu) have been taken by mouth in a daily dose of 100 milligrams for three months. Isoflavonoids (114 milligrams) have been taken by mouth daily for three months. Phytoestrogens (30 grams of soy protein, 132 milligrams of isoflavones) have been taken by mouth daily for 12 weeks.
For cognitive function, 100 milligrams of isoflavones from Pueraria lobata (kudzu) has been taken by mouth daily for three months.
For menopausal symptoms, 100 or 250 micrograms of an extract of hops (Humulus lupulus L.) standardized to 8-prenylnaringenin (8-PN) have been taken by mouth daily for 12 weeks. Daily doses of Promensil® (82 milligrams of total isoflavones) or Rimostil® (57 milligrams of total isoflavones) have been taken by mouth for 12 weeks. Phytoestrogens in the form of isoflavones have also been taken by mouth in doses of 35 milligrams (one capsule of SoyaVital®) daily for 12 weeks. Phytoestrogens in the form of isoflavones have been taken by mouth in a dose of 35 milligrams daily in two divided doses (one PHYTO SOYA® capsule containing 175 milligrams of soy extract corresponding to 17.5 milligrams of isoflavones) for four months. Phytoestrogens in the form of isoflavones have also been taken by mouth in a dose of 118 milligrams daily in soy supplements for three months. Muffins containing 25 grams of soy (42 milligrams of isoflavones) or 25 grams of flaxseed (50 milligrams of lignans) have been taken by mouth daily for 16 weeks. Isoflavonoids have been taken by mouth in a dose of 114 milligrams daily for three months.
For osteoporosis prevention, 114 milligrams of isoflavonoids has been taken by mouth daily for three months. A daily dose of isoflavones from red clover (26 milligrams of biochanin A, 16 milligrams of formononetin, one milligram of genistein, and 0.5 milligram of daidzein) has been taken by mouth for one year. Genistein (54 milligrams) has been taken by mouth daily for one year.
For prostate cancer, 240 milligrams of clover phytoestrogens has been taken by mouth daily for two weeks prior to prostatectomy.
Children (under 18 years old)
There is no proven safe or effective dose for phytoestrogens in children.
For bone growth, isoflavone supplementation (50 milligrams Novasoy®) has been taken by mouth daily for six weeks
A qualified healthcare provider should be consulted regarding the choice of infant formula containing soy products, due to potential safety concerns.
The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.
Avoid with known allergy or hypersensitivity to the plant from which the phytoestrogen is derived, including, but not limited to, soy, hops, red clover, and flax.
Side Effects and Warnings
Phytoestrogens are likely safe when consumed in amounts commonly found in foods. Although not confirmed in humans, consumption of processed soy protein products may increase exposure to toxins and nitrites and lifetime exposure to plant estrogens may increase risk of certain cancers. Some experts suggest avoiding soy-based formulas in infants unless they are intolerant to cow's milk, due to estrogenic activity.
Phytoestrogens may cause depression, developmental disorders, gastrointestinal disturbances, headache, insomnia, low semen concentration, poor semen quality, premature breast development (in children fed soy formula), reduced bone mineralization (in children fed soy milk or formula), reduced sexual desire, and reduced sperm motility.
Phytoestrogen therapy (using genistein) may increase the risk of bleeding. Caution is advised in patients with bleeding disorders or those taking drugs, herbs, or supplements that may increase the risk of bleeding. Dosing adjustments may be necessary.
Phytoestrogens derived from soy supplements or flaxseed may cause decreases in fasting blood sugar, fasting insulin levels, and insulin resistance. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Blood glucose levels may need to be monitored by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.
Use cautiously in patients taking hormone replacement therapy or birth control pills, as phytoestrogens may have estrogenic effects.
Use cautiously in patients with thyroid disorders, as compounds in soybeans may affect thyroid function.
Use cautiously in men, as phytoestrogens may be associated with infertility.
Use cautiously in females attempting to become pregnant, as unfermented soy may disrupt hormone function and contribute to female infertility.
Use cautiously in children, due to insufficient available evidence.
Use cautiously in patients taking lipid-lowering medications, as phytoestrogens may cause changes in total cholesterol and other blood lipids.
Avoid in patients with estrogen-dependent tumors or endometrial hyperplasia.
Avoid during pregnancy or lactation, due to estrogenic effects
Avoid with known allergy or hypersensitivity to the plant from which the phytoestrogen is derived, including, but not limited to, soy, hops, red clover, and flax.
Pregnancy and Breastfeeding
Avoid levels higher than normally found in the diet during pregnancy or breastfeeding, due to estrogenic effects.
Isoflavone phytoestrogens may be transferred through breast milk from mothers to infants. High doses of isoflavones given to pregnant rats have resulted in tumors in female offspring, although this has not been tested in humans.
The substitution of soy formula for cow's milk in children during their first year of life may be associated with lower bone mineral density.
Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.
Interactions with Drugs
Phytoestrogen therapy (with genistein) may increase the risk of bleeding when taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants (blood thinners) such as warfarin (Coumadin®) or heparin, antiplatelet drugs such as clopidogrel (Plavix®), and nonsteroidal anti-inflammatory drugs such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®).
Phytoestrogens derived from soy supplements or flaxseed may result in decreases in fasting blood sugar, fasting insulin levels, and insulin resistance. Caution is advised when using medications that may also lower blood sugar. Patients taking insulin or drugs for diabetes by mouth should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.
Phytoestrogens may also interact with agents that affect the immune system, anticancer agents, anti-inflammatory agents, antimigraine agents, bisphosphonates, cardiovascular agents, estrogens, fertility agents, or lipid-lowering agents.
Interactions with Herbs and Dietary Supplements
Phytoestrogen therapy (using genistein) may increase the risk of bleeding when taken with herbs and supplements that are believed to increase the risk of bleeding. Multiple cases of bleeding have been reported with the use of Ginkgo biloba, and fewer cases with garlic and saw palmetto. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases.
Phytoestrogens derived from soy supplements or flaxseed may result in decreases in fasting blood sugar, fasting insulin levels, and insulin resistance. Caution is advised when using herbs or supplements that may also lower blood sugar. Blood glucose levels may require monitoring, and doses may need adjustment
Phytoestrogens may also interact with anticancer agents, anti-inflammatory agents, antimigraine agents, bone density conservation agents, cardiovascular herbs and supplements, fertility herbs and supplements, herbs and supplements that affect the immune system, hormonal herbs and supplements, lipid-lowering agents, probiotics, probiotic-containing foods, or zinc.
This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).
Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.
Berrino F, Bellati C, Secreto G, et al. Reducing bioavailable sex hormones through a comprehensive change in diet: the diet and androgens (DIANA) randomized trial. Cancer Epidemiol Biomarkers Prev 2001;10(1):25-33. View Abstract
Chiechi LM, Putignano G, Guerra V, et al. The effect of a soy rich diet on the vaginal epithelium in postmenopause: a randomized double blind trial. Maturitas 2003;45(4):241-246. View Abstract
Crisafulli A, Altavilla D, Marini H, et al. Effects of the phytoestrogen genistein on cardiovascular risk factors in postmenopausal women. Menopause 2005;12(2):186-192. View Abstract
D'Anna R, Baviera G, Corrado F, et al. The effect of the phytoestrogen genistein and hormone replacement therapy on homocysteine and C-reactive protein level in postmenopausal women. Acta Obstet Gynecol Scand 2005;84(5):474-477. View Abstract
Greany KA, Nettleton JA, Wangen KE, et al. Probiotic consumption does not enhance the cholesterol-lowering effect of soy in postmenopausal women. J Nutr 2004;134(12):3277-3283. View Abstract
Heyerick A, Vervarcke S, Depypere H, et al. A first prospective, randomized, double-blind, placebo-controlled study on the use of a standardized hop extract to alleviate menopausal discomforts. Maturitas 2006;54(2):164-175. View Abstract
Jayagopal V, Albertazzi P, Kilpatrick ES, et al. Beneficial effects of soy phytoestrogen intake in postmenopausal women with type 2 diabetes. Diabetes Care 2002;25(10):1709-1714. View Abstract
Lemay A, Dodin S, Kadri N, et al. Flaxseed dietary supplement versus hormone replacement therapy in hypercholesterolemic menopausal women. Obstet Gynecol 2002;100(3):495-504. View Abstract
Lissin LW, Oka R, Lakshmi S, et al. Isoflavones improve vascular reactivity in post-menopausal women with hypercholesterolemia. Vasc Med 2004;9(1):26-30. View Abstract
Messina M. The endometrial effects of isoflavones: a discussion paper. Complement Ther Clin Pract 2008;14(3):212-214. View Abstract
Mitchell JH, Cawood E, Kinniburgh D, et al. Effect of a phytoestrogen food supplement on reproductive health in normal males. Clin Sci (Lond) 2001;100(6):613-618. View Abstract
Peeters PH, Slimani N, Van Der Schouw YT, et al. Variations in plasma phytoestrogen concentrations in European adults. J Nutr 2007;137(5):1294-1300. View Abstract
Tuohy PG. Soy infant formula and phytoestrogens. J Paediatr Child Health 2003;39(6):401-405. View Abstract
Unfer V, Casini ML, Gerli S, et al. Phytoestrogens may improve the pregnancy rate in in vitro fertilization-embryo transfer cycles: a prospective, controlled, randomized trial. Fertil Steril 2004;82(6):1509-1513. View Abstract
Zava DT, Dollbaum CM, Blen M. Estrogen and progestin bioactivity of foods, herbs, and spices. Proc Soc Exp Biol Med 1998;217(3):369-378. View Abstract
Copyright © 2013 Natural Standard (www.naturalstandard.com)
The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.
March 22, 2017