Isoflavone supplement dosage and health benefit
What is the proper dosage for long term health?
Are there risks or danger to excess isoflavone flavonoid supplement intake or consuming soy  products?

 Isoflavones are types of flavonoids found in plants. The main sources are soy products, beans, peas, nuts, grain products, coffee, tea and certain herbs such as red clover. Genistein is one of the best known and studied isoflavones. Other isoflavones include daidzen, aglycon, glucoconjugate and equol. Compounds in plants that have estrogen-like properties are called phytoestrogens. Most isoflavones have phytoestrogenic properties.
   Most studies of soy and cholesterol have tested foods made from purified soy proteins containing mainly isoflavone glycosides. Fermented soy foods have mainly isoflavone aglycons and account for a high proportion of the soy protein source in Asia, where there is an inverse relationship between soy intake and serum cholesterol.

Mechanism of action of isoflavones
Data from epidemiological reports and laboratories have shown that isoflavones have multi-biological and pharmacological effects in animals and humans. These include estrogenic and antiestrogenic effects, influencing cell signalling conduction, as well as cell growth and death. Isoflavones also regulate gene transcription, modulate transcription factors, act as antioxidants, as well as alter some enzyme activities.

How are isoflavones different that phytoestrogens?
Compounds in plants that have estrogen-like properties are called phytoestrogens. Most, but not all, isoflavones have phytoestrogenic properties. Although not steroids, isoflavones have a molecular structure that resembles that of estradiol closely enough that they have partial agonist or antagonist effects on estrogen receptors in humans, and thus they fall into a class of plant molecules referred to as phytoestrogens.

Potential health benefits of isoflavones
Isoflavones are proposed to have health benefits in a variety of human conditions, including coronary heart disease, menopause, osteoporosis, endocrine-responsive cancers, and cyclic mastalgia (monthly breast pain). Many isoflavones have estrogen-like properties and, because of a favorable side-effect profile, may be ideal alternatives to hormone replacement therapy with respect to cardiovascular benefits. Increased isoflavone intake affects estrogen metabolism by altering the steroid hormone concentrations and menstrual cycle length, thereby demonstrating a potential to reduce the risk for breast carcinoma.   

Heart health
Pasta naturally enriched with isoflavone aglycons from soy germ reduces serum lipids and improves markers of cardiovascular risk.
J Nutr. 2007 Oct. Clinica di Gastroenterologia ed Epatologia, Università degli Studi di Perugia, Perugia, Italy 06100.
The aim of this study was to compare a novel soy germ pasta, naturally enriched in isoflavone aglycons as a result of the manufacturing process, with conventional pasta for effects on serum lipids and other cardiovascular risk markers. In this randomized, controlled, parallel study design of 62 adults with hypercholesterolemia who consumed a Step II diet that included one 80-g serving/d of pasta, we measured serum lipids, high sensitivity C-reactive protein (hsCRP), urinary isoprostanes, and brachial artery flow-mediated vasodilatation at baseline and after 4 and 8 wk. The pasta delivered 33 mg of isoflavones and negligible soy protein and led to a serum isoflavone concentration of 222 nmol/L; 69% of subjects were equol producers. Soy germ pasta reduced serum total and LDL cholesterol more than conventional pasta, representing reductions from baseline of 7% and 8%, respectively. Arterial stiffness and hsCRP decreased and improvements in all the above risk markers were greatest in equol producers. All measures returned to baseline when patients were switched to conventional pasta. In conclusion, pasta naturally enriched with isoflavone aglycons and lacking soy protein had a significant hypocholesterolemic effect beyond a Step II diet and improved other cardiovascular risk markers.

Mastalgia
A double-blind randomized controlled trial of isoflavones in the treatment of cyclical mastalgia.
Ingram DM. Sir Charles Gairdner Hospital, Hospital Avenue, Perth, Western Australia, 6009, Australia.
Breast. 2002 Apr;11(2):170-4.
Cyclical mastalgia is very common in Western populations and is believed to have an hormonal basis. Simple measures such as vitamins or evening primrose oil are not very effective, yet the disease rarely warrants anti-oestrogen therapies. Isoflavones are a subgroup of phytoestrogens which we hypothesized might be a simple and effective means of therapy as they act as a weak anti-oestrogen in pre-menopausal women and have no side-effects. A double-blind randomized control trial of either placebo, 40 mg or 80 mg of isoflavones was undertaken after an initial 2 month single-blind 'Placebo Lead-in' to exclude women with a significant placebo response. Eighteen women were randomized to the treatment phase of the trial. Nine of the 12 women on treatment had a worthwhile improvement in their pain compared to only two of six on placebo. The reduction in pain was 13% for placebo, 44% for 40 mg of isoflavone per day and 31% for 80 mg per day. There have been no previous clinical studies of isoflavones for the treatment of mastalgia and the benefit demonstrated in this study adds another valuable arm to therapy.

Isoflavones and menopause symptoms
The field of hormone replacement or herbal therapy during or after menopause is very complicated and there are yet no clear guidelines, nor is there a consensus among the medical community as to the best way to treat symptoms and prevent disease. However, the medical community is gradually realizing that hormone replacement with synthetic hormones is not beneficial as once thought, and is probably even harmful. isoflavones may be helpful in some women.

Isoflavone treatment for acute menopausal symptoms.
Menopause. 2007 May-Jun;14(3 Pt 1):468-73. Department of Biosciences and Nutrition, Karolinska Institutet, Novum, Huddinge, Sweden.
The association of a lower incidence of postmenopausal symptoms with high intake of soybeans in Asian women suggests that phytoestrogens are an alternative to estrogen therapy. The main effective compounds in soybean are isoflavones, which have a higher binding affinity to estrogen receptor beta than to estrogen receptor alpha. The aim of present study was to evaluate the effects of isoflavone treatment in postmenopausal women. Sixty healthy postmenopausal women were randomly assigned into two groups to receive 60 mg isoflavones or placebo daily for 3 months. In women receiving 60 mg isoflavones daily, hot flashes and night sweats were reduced by 57% and 43%, respectively. The treatment did not change the levels of circulating estradiol or follicle-stimulating hormone. Isoflavones did not affect expression levels of steroid receptors; estrogen receptors alpha, beta, and betacx; progesterone receptors A and B; or the proliferation marker Ki67. No side effects on body weight or lipoprotein lipids were observed. This short-term prospective study implies that isoflavones could be used to relieve acute menopausal symptoms.

Soy isoflavone intake increases bone mineral density in the spine of menopausal women: Meta-analysis of randomized controlled trials.
Clin Nutr. 2007 Dec 4. Department of Social Medicine & Health Education, School of Public Health, Peking University, Beijing 100083, PR China; Department of Human Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi 409-3898, Japan.
We identified randomized controlled trials related to the effects of soy isoflavone intake on spine bone mineral density or spine bone mineral content and performed meta-analysis with Review Manager 4.2 software. Ten studies with a total of 608 subjects were selected for meta-analysis. The spine bone mineral density in subjects who consumed isoflavones increased significantly in comparison to that in subjects who did not consume isoflavones. Isoflavone intervention significantly attenuates bone loss of the spine in menopausal women. These favorable effects become more significant when more than 90mg/day of isoflavones are consumed. And soy isoflavone consumption for 6 months can be enough to exert beneficial effects on bone in menopausal women.

Isoflavones and weight loss
A daily serving of soy may help postmenopausal women avoid gaining fat around the middle. In a study of 18 postmenopausal women, those who drank a soy-based shake every day for three months tended to gain less abdominal fat than those who had a milk-based shake. Soy contains compounds called isoflavones that are structurally similar to estrogen and bind to estrogen receptors in fat tissue. So in theory, soy isoflavones could help regulate body fat metabolism. Soy protein may affect abdominal fat distribution. Fertility and Sterility, December 2007.

Estrogen -Like Compounds in Plants and Breast Cancer
Research in monkeys suggests that the natural plant estrogens found in soy - called isoflavones - do not increase breast cancer risk in postmenopausal women. In fact, they may provide a protective effect. Even at high doses, there was no evidence that isoflavones stimulate cell growth or other markers for cancer risk in breast tissue. Women who have higher levels of estrogen hormone may actually gain a protective effect from higher doses of soy isoflavones. Population studies show women who consume diets high in soy generally have lower rates of breast cancer. You can consume isoflavones from soy, other plants, or take a supplement. It is very difficult to estimate a good amount to take as a supplement since no long term human trials are available.

Soy isoflavones and osteoporosis
Soy isoflavones may be used as an alternative to menopausal hormone therapy because they are structurally and functionally related to 17beta-estradiol. Soy isoflavones influence both osteoblasts and osteoclasts through genomic and nongenomic pathways. Research suggests soy isoflavones have beneficial effects on bone mineral density, bone turnover markers, and bone mechanical strength in postmenopausal women. However, there are conflicting results related to differences in study design, estrogen status of the body, metabolism of isoflavones among individuals, and other dietary factors.

Prostate cancer
Consumption of the estrogen-like isoflavone substances found in soy may reduce the risk of developing early prostate cancer, but isoflavones appear to be associated with advanced disease if prostate cancer does occur. Isoflavones found in traditional foods that Japanese eat throughout life may be protective against prostate cancer. Dr. Norie Kurahashi and associates from the National Cancer Center, Tokyo, investigated the association between dietary isoflavones and risk of prostate cancer in a study of Japanese men, who generally consume large amounts of soy products and have a low rate of prostate cancer. The study involved some 43,500 men followed from 1995 through 2004. During that time, 307 of them were diagnosed with prostate cancer. Consumption of isoflavones (principally genistein, but also daidzein and soy foods) was associated with a decreased risk of early prostate cancer. Genistein and daidzein, however, were associated with an increased risk of advanced prostate cancer. The protective effect of isoflavones for early prostate cancer was clearest among men over 60 years old, the researchers note, as was the association of isoflavone with an increased risk of advanced prostate cancer. "We suggest that isoflavones delay the progression from latent cancer to clinically significant prostate cancer in Japanese who consume isoflavones regularly throughout life," Kurahashi said. "However, we do not know when or how isoflavones affect latent or (early) prostate cancer development and whether isoflavones can be used in the treatment or...prevention of this cancer." More studies are needed "to clarify what period in life soy consumption exerts an effect against prostate cancer and what type of prostate cancer it can prevent. Cancer Epidemiology, Biomarkers & Prevention, March 2007.

Inulin and isoflavones
Inulin in the diet or taken as a supplement increases the plasma concentrations of the soybean isoflavones daidzein and genistein. It appears that the absorption of these isoflavones is facilitated by inulin.

 Readers ask questions
Q. Does the herb tribulus terrestris extract have any isoflavones? i take this herb a few times a week along with isoflavone supplements for menopause and I don't want to be exposed to more.
   A. Not that we know of.

Q. I used to one or two cartons of soy milk per day, which can amount to 400mg of isoflavones a day! It adversely affected my cognition and fluid speaking abilities. I cut out soy three weeks ago and started supplementing with the iodine supplement Iodoral. I want to include soy in my diet because of the health benefits of isoflavones, especially daidzein and its DHT blocking abilities, but I don't want to overdo it. I've been researching the average amount of isoflavones consumed per day in Japan and I've found ranges from 10mg to 100mg, typically around 35mg. Some soy isoflavones supplements call for 200mg a day. Would going over 50mg really be bad or would it be more beneficial? Can 400mg be overcome by enough iodine? My other question is one that has boggled my mind for a while. If isoflavones in soy act as goitrogens and block the uptake of iodine to the thyroid, how exactly do they block uptake of iodine? Do the isoflavones bind to the iodine themselves or do the isoflavones bind to receptors in the thyroid so that iodine cannot bind? And if one consumes a bit of soy or other goitrogenic foods each day, how can one achieve maximum thyroid health benefits when there's always going to be something blocking the uptake of iodine, requiring more iodine? Does that make sense? I have two soy isoflavone supplements, one from Whole Foods that has 25mg isoflavones per capsule with recommended two capsules a day and another supplement from Walgreens that contains 55mg isoflavones per capsule and says to take 2 to 4 per day, which could equal 220mg isoflavones a day, which seems much more than the Japanese average. How much should I take?
   A. We have not studied in detail the influence of soy products and isoflavones on thyroid health. Researchers do not have enough experience and long term data with the public use of soy isoflavone supplements to determine the long term benefits and risks. Hence, it would be a good idea to not take too high a dosage until we learn more about the influence of these supplements on various physiological functions. We are not in a position to suggest a specific isoflavone dosage since that would be role of your health care provider or your decision based on your review of the information available.

Q. I take a joint formula product by the name of Joint Power Rx for arthritis and was wondering if soy isoflavone pills would reduce the benefits of these supplements or enhance the benefits
   A. We don't think isoflavone flavonoids from soy would have a major interaction with the products you mention.