Isoflavone supplement health benefit, effective for menopause symptom relief?
Feb 21 2014 by Ray Sahelian, M.D.

Isoflavones are types of flavonoids found in plants. The main sources in the diet are soy products, beans, peas, nuts, grain products, coffee, tea and certain herbs such as red clover and kudzu extract. Currently 40 to 50mg of isoflavones (biochanin A, daidzein, formononetin and genistein) are recommended as daily intake. This recommendation is based on the daily intake of phytoestrogens in a traditional Japanese diet.

Of all common plant foods, soybeans appear to have by far the highest concentrations, specifically the soy isoflavones daidzein, genistein, and glycitein. Genistein is one of the best known and studied isoflavones. Others include aglycon, glucoconjugate, dihydrodaidzein, O-desmethylangolensin, and equol. Isoflavones are also found in kudzu. In addition to soy, isoflavones are found in a number of plants, including raisins and currants.

buy Soy Isoflavones - Daidzein and Genistein

Soy Isoflavones have been the focus of scientific research for several decades. Studies have shown that they can bind to the same receptor sites as estrogen. Soy is a significant dietary source of isoflavones; however, the amount of soy foods necessary to meet the body's needs can be difficult to incorporate into today's diet. In Asia, where soy is a staple, the daily isoflavone intake can be up to 20 times that of a Western diet. Source Naturals isoflavone rich soybean powder yields a consistent standardized soy isoflavone content. This unique chemical-free process requires approximately 400 pounds of soybeans to yield just one pound of finished product.

Supplement facts:
Amount per 2 tablets
Isoflavone - 2 g
Soybean Powder (Soylife) Yielding:
   Daidzein - 34 mg
   Glycitein - 20 mg
   Genistein - 8 mg
   Total Isoflavones - 62 mg

Buy this Soy Isoflavone product, for more information

How are isoflavones different than 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. Considerable interest has focused on the use of soy-based products, isolated soy isolates, and synthetic isoflavones as estrogen substitutes in postmenopausal women, in particular to inhibit loss of bone mass. In a review of clinical trials and epidemiologic studies of the effect of soy isoflavones on bone, a researcher concluded: "Fifteen clinical trials were identified that examined the effects of isoflavones or isoflavone-rich soy protein on bone mineral density. Most trials were conducted for 1 year or less and involved relatively few participants per group. The findings from these studies are inconsistent but generally suggest that isoflavones reduce bone loss in younger postmenopausal women. Similarly, the limited epidemiologic data generally show that among Asian populations, isoflavone intake is associated with higher bone mineral density."

Benefits
Blood vessel health and cholesterol

Isoflavones improve vascular reactivity in post-menopausal women with hypercholesterolemia.
Vasc Med. 2004.
This randomized clinical trial was designed to assess the effects of dietary isoflavones on vascular reactivity, lipid levels, and markers of inflammation in post-menopausal women. Forty post-menopausal, hypercholesterolemic women who did not take estrogen replacement therapy were recruited for this study of isoflavone supplementation. After 6 weeks of 90 mg of isoflavones daily versus placebo, women receiving treatment demonstrated improved responsiveness to nitroglycerin, an assessment of endothelium-independent vasodilation. Lipid levels were unchanged. In conclusion, dietary soy isoflavones may have cardiovascular benefit in the form of improved vascular reactivity, but not by lowering cholesterol, for women who do not take estrogen replacement therapy.

Meta-analysis of the effects of soy protein containing isoflavones on lipid profile
American Journal of Clinical Nutrition, 2005.
Convincing evidence shows that soy protein intake has beneficial effects on lipid changes, but it is unclear which components of soy protein are responsible. We conducted a meta-analysis to identify and quantify the effects of soy protein containing isoflavones on lipid profile. Soy protein with isoflavones intact was associated with significant decreases in serum total cholesterol, LDL cholesterol, and triacylglycerols, and significant increases in serum HDL cholesterol. Soy protein containing isoflavones significantly reduced serum total cholesterol, LDL cholesterol, and triacylglycerol and significantly increased HDL cholesterol, but the changes were related to the level and duration of intake and the sex and initial serum lipid concentrations of the subjects.

Fertility in women, menstrual cycle
Fertil Steril. 2013 December. Usual dietary isoflavone intake and reproductive function across the menstrual cycle. To assess the association of total isoflavone intake with ovulatory function, including sporadic anovulation in healthy premenopausal women. Participants included 259 healthy regularly menstruating women aged 18-44 years. Serum concentrations of E2, free E2, P, LH, FSH, and SHBG and sporadic anovulation in healthy premenopausal women. Isoflavone intake was not associated with E2, free E2, P, LH, and FSH concentrations. Consumption in the highest quartile (Q4: 1.6-78.8 mg/d) was significantly associated with greater SHBG concentrations, compared with the first quartile. Dietary isoflavone intake among young premenopausal women was not related to sex hormone concentrations or anovulation, but was associated with minimally increased SHBG concentrations. These results suggest potential endocrine effects with no subsequent effects on ovulation, easing concerns regarding their impacts on fertility.

Hair growth
There is a possibility that they may influence hair growth.

Immune function
Soy isoflavones modulate immune function in healthy postmenopausal women
American Journal of Clinical Nutrition, 2006.
Postmenopausal women aged 50–65 y enrolled in this 16-wk double-blind, placebo-controlled trial were randomly assigned to 1 of 3 experimental groups: 1) control, 706 mL cow milk a day plus a placebo supplement; 2) soymilk, 71 mg isoflavones derived from 706 mL soymilk/d plus a placebo supplement; and 3) supplement, 70 mg isoflavones in a supplement plus 706 mL cow milk/d. Isoflavone intervention in postmenopausal women resulted in higher B cell populations and lower plasma concentrations of 8-hydroxy-2-deoxy-guanosine, an oxidative marker of DNA damage. Isoflavone treatment did not significantly influence concentrations of interferon {gamma}, interleukin 2, tumor necrosis factor {alpha}, or C-reactive protein in plasma or of 8-isoprostane in urine. Conclusions: Soymilk and supplemental isoflavones modulate B cell populations and appear to be protective against DNA damage in postmenopausal women.

Isoflavone menopause treatment
When given in adequate doses to postmenopausal women, soy that contains isoflavone improves menopausal symptoms and related quality of life. Studies on the benefits of soy for relieving menopausal symptoms have produced mixed results. In one study, a research group used a standardized soy product which contains 160 milligrams of total soy isoflavones. Postmenopausal women were assigned to the treatment product or placebo daily for three months. The average age of the women was 55 years and they had been off hormone replacement therapy for at least six months prior to entering the study. Compared with placebo, soy therapy led to a 40-percent reduction in psychosocial complaints involving mood and depression, a 36-percent reduction in hot flashes and night sweats, as well as and a 30-percent reduction in other physical symptoms, primarily low energy. For more information on menopause and natural treatment options.

Isoflavone treatment for acute menopausal symptoms.
Menopause. 2007. 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, isoflavones, estrogen and breast cancer
Research in monkeys suggests that the natural soy isoflavones do not increase markers of breast cancer risk in postmenopausal women. In fact, they may provide a protective effect in some women. Even at high doses, there was no evidence that the estrogen -like compounds in soy, called 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. There has been much debate about whether higher levels of dietary soy are safe or beneficial for postmenopausal women. Some evidence has suggested that soy isoflavones may protect against the more powerful estrogen produced by the body, which is an important risk factor for breast cancer in postmenopausal women. For example, population studies show that women who consume diets high in soy generally have lower rates of breast cancer. Researchers evaluated the effects of dietary isoflavones in the presence of different levels of estrogen by rotating 31 postmenopausal cynomolgus monkeys through eight different diets. Each diet contained one of four different isoflavone doses along with either a low or a high dose of estrogen. Isoflavone doses were equivalent to the following human levels: no isoflavones, 60 milligrams (comparable to the typical Asian diet), 120 milligrams (the highest levels that can be consumed through diet alone), or 240 milligrams (levels obtained through supplements). Estrogen doses were designed to mimic either a low or high-estrogen environment found in postmenopausal women. Estrogen levels in postmenopausal women can vary depending on their amounts of body fat, which produces estrogen, and whether they are taking hormone therapy. In the low estrogen environment, no evidence of increased proliferation was seen at any level of isoflavone exposure, even at doses almost several times higher than in a typical Asian diet. In the high estrogen environment, there was higher breast cell proliferation both when isoflavones weren't in the diet and when they were present in lower doses. However, the addition of high levels of dietary soy isoflavones tended to block estrogen effects in breast tissue. This finding suggests that postmenopausal women with too much estrogen may derive the greatest benefit from soy.

Lung cancer
In a large-scale, population-based, prospective study in Japan, isoflavone intake was associated with a decreased risk of lung cancer in never smokers. American Journal of Clinical Nutrition, 2010.

Prostate cancer prevention
Chemoprevention of prostate cancer by isoflavonoids. Recent Results Cancer Res. 2014.

Asian Pac J Cancer Prev. 2013. Influence of isoflavone intake and equol-producing intestinal flora on prostate cancer risk. The age-adjusted incidence rate of prostate cancer (PCa) has been reported to be lower among Asians than Western populations. A traditional Japanese meal, high in soybean products or isoflavones, may be associated with a decreased risk of PCa. Equol, which is converted from daidzein by human intestinal flora, is biologically more active than any other isoflavone aglycone.

Nutr Rev. 2010. Clinical pharmacology of isoflavones and its relevance for potential prevention of prostate cancer. St. George Hospital Clinical School, UNSW, Kogarah, New South Wales, Australia.

Mechanism of action
Data from epidemiological reports and laboratories have shown that isoflavones have multi-biological and pharmacological effects in animals and humans. These include estrogenic and anti-estrogenic effects, influencing cell signaling 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.

Potential health benefits
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 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.

Isoflavones and heart health
Dietary isoflavones are thought to be of benefit in cardiovascular condtions because of their structural similarity to estrogen. The reduction of concentrations of circulating inflammatory markers by estrogen may be one of the mechanisms by which premenopausal women are protected against cardiovascular disease. Isoflavones improve C reactive protein concentrations.

Isoflavone supplement use and fat free muscle mass
Six months of isoflavone supplement increases fat-free mass in obese-sarcopenic postmenopausal women: a randomized double-blind controlled trial.
Eur J Clin Nutr. 2007.
The aim of this study was to verify if six months of isoflavone supplementation could increase fat-free mass (FFM) and muscle mass index (MMI=appendicular FFM/height(2)) in obese-sarcopenic postmenopausal women. Eighteen sarcopenic-obese women completed the study (12 on isoflavones and six on placebo). Body composition was measured by dual-energy X-ray absorptiometry. Subjects ingested 70 mg of isoflavones per day (44 mg of diadzein, 16 mg glycitein and 10 mg genestein) or a placebo for 24 weeks. The isoflavone group increased significantly appendicular, leg FFM and MMI, but not the placebo group. Six months of isoflavone supplementation increased FFM and MMI in obese-sarcopenic postmenopausal women.

Menopause
Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women: a randomized controlled trial.
JAMA. 2004.
Postmenopausal estrogen therapy has been posited to have some beneficial effects on aging processes, but its use has risks. Isoflavones, estrogenlike compounds naturally occurring in plant foods, might confer positive effects with fewer adverse effects. To investigate whether soy protein with isoflavones improves cognitive function, bone mineral density, and plasma lipids in postmenopausal women. Double-blind, randomized, placebo-controlled trial of 202 healthy postmenopausal women aged 60 to 75 years, recruited from a population-based sample in the Netherlands, conducted between April 2000 and September 2001. Participants were randomly assigned to receive 25.6 g of soy protein containing 99 mg of isoflavones (52 mg genistein, 41 mg daidzein, and 6 mg glycetein or total milk protein as a powder on a daily basis for 12 months. Cognitive function was assessed using the following instruments: dementia, Mini-Mental State Examination; memory, Rey Auditory Verbal Learning Test, immediate recall, delayed recall, and recognition, the Digit Span forward and reversed, and the Doors test; complex attention tasks, Digit Symbol Substitution and Trailmaking, A1, A2, and B; and verbal skills, Verbal Fluency A and N, animals and occupations, and the Boston Naming Task. Bone mineral density of the hip and lumbar spine was assessed using dual-energy x-ray absorptiometry scanning. Lipid assessment included lipoprotein(a), total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglycerides. A total of 175 women completed the baseline and at least 1 postintervention analysis and were included in the modified intent-to-treat analysis. Cognitive function, bone mineral density, or plasma lipids did not differ significantly between the groups after a year. This double-blind randomized trial does not support the hypothesis that the use of soy protein supplement containing isoflavones improves cognitive function, bone mineral density, or plasma lipids in healthy postmenopausal women when started at the age of 60 years or later.

Osteoporosis
Soymilk, isoflavones, and osteoporosis
Soymilk or progesterone for prevention of bone loss. A 2 year randomized, placebo-controlled trial.
Eur J Nutr. 2004.
Given concerns over the use of hormone replacement therapy, women are seeking natural alternatives to cope with the symptoms and effects of menopause. The bone sparing effects of soy protein and its isoflavones is well established in animal studies, while previous human studies on soy and bone have yielded variable outcomes due in part to their short duration of study. The aim of the study was to compare for the first time the long-term effects of soymilk, with or without isoflavones with natural transdermal progesterone, or the combination, on bone mineral density in the lumbar spine and hip. Daily intake of two glasses of soymilk containing 76 mg isoflavones prevents lumbar spine bone loss in postmenopausal women. Transdermal progesterone had bone-sparing effects but when combined with soy milk a negative interaction between the two treatments occurs resulting in bone-loss to a greater extent than either treatment alone.

Soymilk or progesterone for prevention of bone loss. A 2 year randomized, placebo-controlled trial.
Eur J Nutr. 2004.
Given concerns over the use of hormone replacement therapy (HRT), women are seeking natural alternatives to cope with the symptoms and effects of menopause. The bone sparing effects of soy protein and its isoflavones is well established in animal studies, while 5 previous human studies on soy and bone have yielded variable outcomes due in part to their short duration of study. Progesterone has been suggested as a bone-trophic hormone, but the effect of long-term, low dose transdermal progesterone is unknown. AIM. The aim of the study was to compare for the first time the long-term effects of soymilk, with or without isoflavones with natural transdermal progesterone, or the combination, on bone mineral density in the lumbar spine and hip. Postmenopausal, Caucasian women with established osteoporosis or at least 3 risk-factors for osteoporosis, were randomly assigned, double-blind to one of four treatment-groups: soymilk containing isoflavones, transdermal progesterone, or the combination of soy+ and TDP or placebo (isoflavone-poor soymilk, soy/ and progesterone-free-cream TDP/, n = 22). All subjects received comparable intakes of calcium, minerals and vitamins. Bone mineral content (BMC) and density (BMD) were measured in lumbar spine and hip by using dual-energy X-ray absorptiometry (DEXA) at baseline and after 2 years. The percentage change in lumbar spine BMD and BMC respectively, did not differ from zero in the soy+ group and TDP+ group but significant bone loss occurred in the control groupand the combined treatment group. No significant changes occurred for femoral neck BMD or BMC. Daily intake of two glasses of soymilk containing 76 mg isoflavones prevents lumbar spine bone loss in postmenopausal women. Transdermal progesterone had bone-sparing effects but when combined with soy milk a negative interaction between the two treatments occurs resulting in bone-loss to a greater extent than either treatment alone.

Prostate cancer
Soy isoflavones in the treatment of prostate cancer.
Nutr Cancer. 2003.
Epidemiological studies suggest an inverse association between soy intake and prostate cancer risk. We have previously observed that soy isoflavone genistein induces apoptosis and inhibits growth of both androgen-sensitive and androgen-independent prostate cancer cells in vitro. To determine the clinical effects of soy isoflavones on prostate cancer we conducted a pilot study in patients with prostate cancer who had rising serum prostate-specific antigen (PSA) levels. Patients with prostate cancer were enrolled in the study if they had either newly diagnosed and untreated disease under watchful waiting with rising PSA (group I) or had increasing serum PSA following local therapy (group II) or while receiving hormone therapy (group III). The study intervention consisted of 100 mg of soy isoflavone (Novasoy) taken by mouth twice daily for a minimum of 3 or maximum of 6 mo. Forty-one patients were enrolled (4 in group I, 18 in group II, and 19 in group III) and had a median PSA level of 13 ng/ml. Thirty-nine patients could be assessed for response. Soy isoflavone supplementation was given for a median of 5.5 (range 0.8-6) mo per patient. Although there were no sustained decreases in PSA qualifying for a complete or partial response, stabilization of the PSA occurred in 83% of patients in hormone-sensitive (group II) and 35% of hormone-refractory (group III) patients. There was a decrease in the rate of the rise of serum PSA in the whole group with rates of rise decreasing from 14 to 6% in group II and from 31 to 9% in group III following the soy isoflavone intervention. Serum genistein and daidzein levels increased during supplementation. No significant changes were observed in serum levels of testosterone, IGF-1, IGFBP-3, or 5-OHmdU. These data suggest that soy isoflavones may benefit some patients with prostate cancer.

Stroke
Isoflavone, a substance found in soybeans, chickpeas, legumes and clovers, may improve artery function in stroke patients. After 12 weeks of isoflavone supplement, at a dose of 80 milligrams a day, there was improved blood flow in the brachial artery, which is especially important in patients who have suffered ischaemic stroke -- which is caused by blood clots or other obstructions. Eighty percent of the patients in the Hong Kong study began the experiment with an impaired blood flow, but after 12 weeks, there was an improvement in the arteries of the isoflavone-treated patients compared with those on placebos.

Side effects of isoflavones, safety, danger
No significant side effects have yet been reported from isoflavones from soy or other plants. To be on the safe side, supplements should be limited to 30 to 50 mg of isoflavones a day until long term studies are done.

A multicenter, randomized, double-blind, placebo-controlled 24-mo trial was conducted to assess the effects of daily supplementation with 80 or 120 mg aglycone equivalent soy hypocotyl isoflavones plus calcium and vitamin D on the health of 403 postmenopausal women. At baseline and after 1 and 2 y, clinical blood chemistry values were measured and a well-woman examination was conducted, which included a mammogram and a Papanicolaou test. After 2 y of daily isoflavone exposure, all clinical chemistry values remained within the normal range. The only variable that changed significantly was blood urea nitrogen, which increased significantly after 2 y but not after 1 y in the supplementation groups. Isoflavone supplementation did not affect blood lymphocyte or serum free thyroxine concentrations. No significant differences in endometrial thickness or fibroids were observed between the groups. Two serious adverse events were detected (one case of breast cancer and one case of estrogen receptor–negative endometrial cancer), which was less than the expected population rate for these cancers. Am J Clin Nutr 2011.

Isoflavones research study
Reproductive toxicity assessment of chronic dietary exposure to soy isoflavones in male rats.
Reprod Toxicol. 2004.
Epidemiologic and experimental data suggest that consumption of diets that are rich in isoflavones may decrease cancer risk in the breast, prostate, and other tissues. Isoflavones such as genistein and daidzein are structurally similar to endogenous estrogens, and demonstrate both estrogenic and weak anti-estrogenic activities; these activities may underlie the impaired fertility and reproductive tract disorders reported in animals exposed to high doses of isoflavones. To identify possible effects of isoflavones on male fertility, we evaluated reproductive parameters in Wistar-Unilever rats. Our data suggest that the reproductive system of adult male rats is relatively insensitive to isoflavone toxicity at dose levels that demonstrate significant activity in cancer chemoprevention, and that male reproductive function is unlikely to be affected by long-term administration of isoflavones for cancer prevention or other purposes.

Questions
Your article states that isoflavone intake is associated with higher bone mineral density in Asian populations. What? Asian women are well known to have a higher rate of osteoporosis, and they eat more soy than women of other ethnic groups. Question #2: Your article states that no significant side effects have yet been reported from soy isoflavones. Then why does France ban the importation and domestic sale of soy based infant formulas?
    There are many factors that influence osteoporosis, primarily exercise, calcium intake, vitamin D intake, and estrogen. Women who have more fatty tissue are likely to have more estrogen since some estrogen is made in fat cells. Hence, focusing on one isolated compound, such as isoflavone intake, in terms of generalizing this to osteoporosis risk is not taking a comprehensive viewpoint.
   You would have to ask the French government for their rational. Ipriflavone intake in adults, when done so in reasonable amounts as part of an overall healthy diet that includes a variety of foods, does not present any risk in adults. Exclusive consumption of one type of food in infants is a different matter.

I am currently writing a piece on the benefits of soy products and isoflavones. I understand there are great health benefits especially for women and saw that you had noted: "Soy isoflavone daily value not established." I'm sure this varies depending on the individual woman, but my main question is: How much is too much? Is there a point where the intake of too much soy isoflavones could be dangerous in anyway to our health? Or is it simply like taking too much of a vitamin where our body will just flush out what we don't need? I am hoping to include your medical opinions in the article.
    Water is a necessity to life, but excessive water intake can cause seizures. There are countless beneficial substances in various foods, and the idea is to be reasonable in our consumption. There are a number of different legumes available and it is a good idea to eat a variety as opposed to too much of just one type. I have not come across any specific studies regarding the harm of excessive soy consumption, but it is possible that allergies or hormonal imbalances could occur from too high a consumption of isoflavones. There is no point that tips intake into the "too much" category, but a few ounces of soy products a day is reasonable. With the wide variety of foods available to the average consumer in a grocery store, there is no point in ingesting more than four to six ounces of soy products a day. In fact, two or three ounces a few times a week seems fine. In order to know for sure what would happen if high doses of isoflavones are ingested daily for prolonged periods, several multi-year studies would need to be done and I have not come across such prospective longitudinal human studies.