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Isoflavones are considered a type of nutritional supplement produced almost exclusively by the Fabaceae (Leguminosae or bean) family. They are a specific group of molecules that comprise what is called a phytochemical (natural plant chemical) found in foods like legumes, and herbs like red clover. Isoflavones are considered phytoestrogens, meaning that they are similar in structure to the female hormone, estrogen. Isoflavones are also considered anti-oxidant compounds. This means that they reduce damage due to oxygen (such as that caused by free radicals) and may help fight against certain types of cancer.
There have been multiple studies on the benefits and safety of isoflavones. In fact, isoflavones may be the most controversial natural supplement, when it comes to weighing the benefits against the risks because much of the medical research varies.
Health Benefits
When it comes to food items, soybeans contain the highest level of isoflavones. Herbal sources that are rich in isoflavones, including red clover (Trifolium pratense) and alfalfa (Medicago sativa). Like soy, red clover is considered a legume that contains phytoestrogens.
In their most common form, soy isoflavones include genistein, daidzein and glycetein. Isoflavones found in red clover include formononetin, biochanin A, daidzein, and genistein.
It’s important to note that taking a supplement source of isoflavones and eating a food/protein source of isoflavones—like tofu, tempeh, soy milk, miso, or other soybean products—produces different results (for benefits and side effects).
Isoflavones and Estrogen
Estrogens are hormones that influence sexual and reproductive development, primarily in women. Having a similar structure to estrogen allows isoflavones to bind with estrogen receptors. Depending on the hormone status of a person, isoflavones can affect a person in the same way that estrogen doesbyproducing either estrogenic or antiestrogenic effects.
In studies involving isoflavone supplements for menopausal symptoms, some benefit has been shown, such as improving fatigue and irritability and decreasing hot flashes. But, according to The Pharmaceutical Journal, although isoflavones are being marketed as an effective product for natural hormone replacement therapy (HRT), further research is needed and consumers should NOT use isoflavones for long-term HRT until more research is done to prove the safety and efficacy of the products.
In addition to providing menopause relief, isoflavones are said to prevent some types of cancer and protect the heart. Several studies have shown that soy protein supplementation (containing isoflavones) reduces both the total and low density (LDL) cholesterol in animal and human studies.
But there are conflicting study results on isoflavones—some showing benefits to health and others indicating harmful side effects.
Some case reports indicate that isoflavones in red clover help reduce hot flashes and anxiety during menopause. Although the herb is marketed as a dietary supplement called Promensil, the National Women’s Health Network reports that there is a lack of sufficient clinical research data to back up these claims. Red clover has, however, been found to have a cardiovascular benefit, raising good cholesterol called HDL.
Soy in the Diet
In Asia, where soy is eaten as a regular staple, the rate of heart disease, breast cancer, and prostate cancer is lower than in the U.S. But many Asians ingest soy differently than in Western countries.
For example, Asians notoriously eat much larger quantities of soy daily. It’s also common in the East to eat fermented forms of soy, including miso, tempeh, and tamari. It is thought that fermentation helps with the digestion of soy and may even promote the body’s ability to absorb isoflavones.
Many health experts feel that eating fermented soy in moderation may:
- • Increase bone density
- • Help to prevent breast and uterine cancers
- • Lower the incidence of prostate cancer
- • Lower bad cholesterol levels
- • Improve mental functioning
- • Reduce muscle soreness (particularly after exercise)
Medical Uses
There are many common medical uses for isoflavones. Conditions that may improve with the use of isoflavones vary.
Breast cancer: The research is mixed. Those who eat a high soy diet during adolescent years may have a lower risk of breast cancer later in life, but some studies show that isoflavones from soy can increase the risk of cancer.
Type 2 diabetes: The research says that eating soy protein or fermented soy may reduce blood sugar in those with diabetes.
Diarrhea in infants: Soy formula supplementation may shorten the duration of diarrhea (compared to drinking formula from cow’s milk). It’s important to note that in adults, soy fiber was NOT found to improve diarrhea.
High cholesterol: The clinical research evidence strongly suggests that isoflavones from soy reduce bad cholesterol called LDL. It’s important to note that ONLY the protein-based food sources of isoflavones such as tofu, tempeh, and other soy products were found to lower cholesterol; isoflavone supplements were not found to be effective.
High blood pressure: Eating soy may lower the blood pressure slightly and is suggested for those with slight increases in blood pressure, but NOT in people with severely elevated blood pressure.
Irritable bowel syndrome (IBS): Some research found that soy isoflavones may improve symptoms of IBS, such as abdominal pain.
Menopausal symptoms: Symptoms such as irritability, depression, and hot flashes may be lessened with the use of isoflavones. However, isoflavones were NOT found to be beneficial for night sweats.
Osteoporosis: In studies, soy protein from food sources and isoflavones in supplement form were both found to increase bone density.
There is NOT enough evidence to back the claims of using isoflavones to treat many medical conditions, including:
- • Alzheimer's disease
- • Asthma
- • Heart disease (such as stroke or heart attack)
- • Colic (in infants)
- • Crohn's disease
- • Endometrial cancer (cancer of the lining of the uterus)
- • Stomach cancer
- • Hepatitis C
- • Premenstrual syndrome (PMS)
- • Enlarged prostate
- • Prostate cancer
- • Rheumatoid arthritis
- • Thyroid cancer
- • Kidney disease
Studies
A 2016 review published in the British Journal of Pharmacology, reports that it has not been well-established whether plant-derived compounds (such as isoflavones) provide potential benefits that outweigh the risk factors.
Still, according to a study published in 2016 in the Journal of the American Medical Association examined 60 other studies and found that some plant-based therapies—such as isoflavones—worked to provide a modest reduction in hot flashes and vaginal dryness. However, the plant-based therapies were found to be ineffective for reducing night sweats.
Several studies, of both animals and humans, have shown that soy protein supplementation (containing isoflavones) may reduce both the total and low density (LDL) cholesterol.
A study published in the journal Nutrients reports, "As shown by this summary of abundant evidence, isoflavones exhibit impressive anti-inflammatory properties in various animal models, and even in humans, through increased antioxidative activities." The study authors go on to explain that due to the potentially harmful side effects of isoflavones—such as its immunosuppressive (lowering the immune response) and carcinogenic (cancer-causing) effects—the safety factor has not been established.
Possible Side Effects
Most of the side effects of isoflavones are associated with long-term use of supplements and not from dietary sources such as soy products. But epidemiological (the branch of medicine dealing with the incidence and control of disease) data have shown that there is a link between long term soy consumption and Kawasaki disease (KD), and that soy isoflavones are involved in the development of the disease.
Another study discovered that exposure to soy-based infant formula resulted in negative effects on the long-term development of infants.
Breast cancer cell growth has been linked with long-term exposure to genistein, resulting in what is called “soy protein isolate-induced tumors and advanced growth phenotypes.”
Animal studies have shown that evidence of the isoflavone genistein may have adverse effects on the developing female reproductive tract.
When ingested on a short-term basis (up to six months in duration) soy is considered possibly safe. Common side effects may include:
- • GI upset
- • Constipation, bloating and nausea
- • Allergic reactions (involving rash, itching, and in severe instances, anaphylaxis)
- • Loss of appetite
Swelling of the ankles and abdominal tenderness have been noted in high doses of isoflavones of four to eight milligrams per kilograms (mg/kg).
Long-term use of soy extract supplements may result in abnormal tissue growth in the uterus.
Precautions (Contraindications)
There is not enough clinical research data to support the safe use of soy products when pregnant or breastfeeding, particularly at higher doses.
There have been some preliminary research findings that link infant soy formula with delayed development in infants, but according to Drugs.com, “The National Toxicology Program (U.S. Department of Health and Human Services) has concluded that there is minimal concern for developmental effects in infants fed soy infant formula.” Long-term use of soy formula should always be discussed with the healthcare provider.
Children should not eat soy in large amounts. It’s uncertain whether soy is safe for kids at high doses.
Those with asthma or hay fever may have a higher risk of an allergic reaction to soy.
Those with breast cancer should discuss the use of isoflavone supplements with their oncologist or healthcare provider. The research data are mixed, and it’s possible that soy may act like estrogen and promote cancer cell growth in certain types of breast cancer.
Children with cystic fibrosis should avoid taking isoflavones because they may interfere with the way these kids process protein.
The use of isoflavones in people with diabetes should be discussed with the healthcare provider prior to use because soy products may lower blood sugar, interfering with diabetes medication.
Hypothyroidism may be worsened when using soy isoflavones.
Those with kidney stones should avoid taking soy isoflavones as they may increase a chemical, called oxalates, that contributes to kidney stones. Also, those with kidney conditions should avoid the use of phytoestrogens such as soy isoflavones, which could be toxic at high doses for those with kidney failure.
Drug Interactions
Isoflavones may adversely interact with some medications including:
- Monoamine oxidase inhibitors (MAOIs): A type of antidepressant which interacts adversely with fermented soy products
- Antibiotics may reduce the effectiveness of soy products by negatively impacting the natural gut flora needed to effectively process isoflavones.
- Estrogens such as Premarin, estradiol, and other HRT for menopause should not be taken with isoflavones because the isoflavones may decrease the effect of estrogen.
- Nolvadex (tamoxifen) is a drug used in the treatment of the type of cancer influenced by estrogen and should not be taken with isoflavones.
- Coumadin (warfarin) soy products may lower the effectiveness of Coumadin. Red clover may have blood-thinning properties and should not be taken with Coumadin.
Isoflavones may adversely impact the speed in which the liver metabolizes certain medications. These drugs include:
- • Tolbutamide (hypoglycemic agent)
- • Glipizide (hypoglycemic agent)
- • Phenytoin (anticonvulsant)
- • Flurbiprofen (anti-inflammatory agent)
- • Warfarin (anticoagulant)
Anyone taking prescription or over the counter medications should consult with the healthcare provider before taking isoflavones or any other herbal or nutritional supplement.
Dosage and Preparation
The following doses are backed by clinical research studies:
- For postmenopausal women: A supplement with least 54 mg of genistein (a soy isoflavone) per day is suggested for hot flashes.
- For IBS: A supplement of 40 mg of isoflavones per day for six weeks
- For protection against osteoporosis: A supplement of 80 mg per day of soy isoflavones was associated with a dosage that reduced bone loss in postmenopausal women (protecting against osteoporosis).
- For general supplementation: Drugs.com< suggests using a daily dose of 40 to 120 mg of isoflavones per day (from soy) or 40 to 80 mg per day of isoflavones (from red clover) for various conditions.
Note, the safety of the use of isoflavones, taken as a supplement, cannot be guaranteed when taken for a duration of longer than six months.
What to Look For
Since supplements are not regulated by the FDA, there are several things to look for to ensure quality and effectiveness in isoflavones and other natural supplements.
- Look for a product that is made into an extract and avoid powder supplements which may be much weaker in strength (but cheaper to make).
- Ensure that the strength and dosage of the isoflavone supplement align with recommendations from clinical research data. Those who are unsure should consult with the healthcare professional or pharmacist.
- Check the label to make sure that the product has active ingredients, such as natural phytoestrogens contained in isoflavones (in the extract form).
- Check to ensure that the product is quality-tested for safety and strength by a third party and made in the USA.
- Choose non-genetically modified: Make sure that the product selected is NOT from genetically modified (GMO) sources.
- Choose a company that backs its products with a 60-day guarantee to allow enough time to evaluate the effectiveness of the product.
Other Questions
What foods naturally contain isoflavones?
Isoflavones are found in:
- • Soybeans
- • Chickpeas
- • Fava beans
- • Pistachios
- • Peanuts
- • Other fruits and nuts
Soybeans contain the richest source of isoflavones.
Do products made from soy, such as soy sauce, contain isoflavones?
The highest level of isoflavones come from unprocessed sources of soy, such as edamame, tempeh, miso, soymilk, and tofu; however, soy sauce does NOT contain isoflavones.
Does red clover work better than soy for menopausal symptoms?
The isoflavones from red clover have phytoestrogens, which are known to help balance estrogen levels, but the research is mixed on how well red clover helps reduce symptoms of menopause. There have been more studies on soy isoflavones that support health benefits (including the treatment of menopausal symptoms).
A Word from Verywell
Although much of the clinical research data on isoflavones support its health benefits, such as promoting cardiac health, reducing menopausal symptoms and more, there is quite a bit of contradictory information. For example, some evidence supports the use of isoflavones for preventing breast cancer, yet, sever
Untitled Document
Most of the side effects of isoflavones are associated with long-term use of supplements and not from dietary sources such as soy products. But epidemiological (the branch of medicine dealing with the incidence and control of disease) data have shown that there is a link between long term soy consumption and Kawasaki disease (KD), and that soy isoflavones are involved in the development of the disease.
Another study discovered that exposure to soy-based infant formula resulted in negative effects on the long-term development of infants.
Breast cancer cell growth has been linked with long-term exposure to genistein, resulting in what is called “soy protein isolate-induced tumors and advanced growth phenotypes.”
Animal studies have shown that evidence of the isoflavone genistein may have adverse effects on the developing female reproductive tract.
When ingested on a short-term basis (up to six months in duration) soy is considered possibly safe. Common side effects may include:
- • GI upset
- • Constipation, bloating and nausea
- • Allergic reactions (involving rash, itching, and in severe instances, anaphylaxis)
- • Loss of appetite
Swelling of the ankles and abdominal tenderness have been noted in high doses of isoflavones of four to eight milligrams per kilograms (mg/kg).
Long-term use of soy extract supplements may result in abnormal tissue growth in the uterus.
Precautions (Contraindications)
There is not enough clinical research data to support the safe use of soy products when pregnant or breastfeeding, particularly at higher doses.
There have been some preliminary research findings that link infant soy formula with delayed development in infants, but according to Drugs.com, “The National Toxicology Program (U.S. Department of Health and Human Services) has concluded that there is minimal concern for developmental effects in infants fed soy infant formula.” Long-term use of soy formula should always be discussed with the healthcare provider.
Children should not eat soy in large amounts. It’s uncertain whether soy is safe for kids at high doses.
Those with asthma or hay fever may have a higher risk of an allergic reaction to soy.
Those with breast cancer should discuss the use of isoflavone supplements with their oncologist or healthcare provider. The research data are mixed, and it’s possible that soy may act like estrogen and promote cancer cell growth in certain types of breast cancer.
Children with cystic fibrosis should avoid taking isoflavones because they may interfere with the way these kids process protein.
The use of isoflavones in people with diabetes should be discussed with the healthcare provider prior to use because soy products may lower blood sugar, interfering with diabetes medication.
Hypothyroidism may be worsened when using soy isoflavones.
Those with kidney stones should avoid taking soy isoflavones as they may increase a chemical, called oxalates, that contributes to kidney stones. Also, those with kidney conditions should avoid the use of phytoestrogens such as soy isoflavones, which could be toxic at high doses for those with kidney failure.
Drug Interactions
Isoflavones may adversely interact with some medications including:
- Monoamine oxidase inhibitors (MAOIs): A type of antidepressant which interacts adversely with fermented soy products
- Antibiotics may reduce the effectiveness of soy products by negatively impacting the natural gut flora needed to effectively process isoflavones.
- Estrogens such as Premarin, estradiol, and other HRT for menopause should not be taken with isoflavones because the isoflavones may decrease the effect of estrogen.
- Nolvadex (tamoxifen) is a drug used in the treatment of the type of cancer influenced by estrogen and should not be taken with isoflavones.
- Coumadin (warfarin) soy products may lower the effectiveness of Coumadin. Red clover may have blood-thinning properties and should not be taken with Coumadin.
Isoflavones may adversely impact the speed in which the liver metabolizes certain medications. These drugs include:
- • Tolbutamide (hypoglycemic agent)
- • Glipizide (hypoglycemic agent)
- • Phenytoin (anticonvulsant)
- • Flurbiprofen (anti-inflammatory agent)
- • Warfarin (anticoagulant)
Anyone taking prescription or over the counter medications should consult with the healthcare provider before taking isoflavones or any other herbal or nutritional supplement. *
Note 1: Relevance of the Isoflavone Absorption and Testicular Function: A Systematic Review of Preclinical Evidence
Note 2: Isoflavones: Anti-Inflammatory Benefit and Possible Caveats
Note 3: Long-Term Exposure to Isoflavones Alters the Hormonal Steroid Homeostasis-Impairing Reproductive Function in Adult Male Wistar Rats