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.
Eur J Clin Nutr. 2015. Red clover isoflavones enriched with formononetin lower serum LDL cholesterol-a randomized, double-blind, placebo-controlled study. Although postmenopausal combined hormone replacement therapy reduces the risk of hip fracture, long-term use may be associated with an increased risk of breast cancer, and in women more than 10 years after menopause it is associated with an increased risk of cardiovascular disease. Isoflavones, because of preferential binding to estrogen receptor beta, may retain the beneficial effects on bone but lessen the adverse effects on the breast. In a double-blind, randomized, placebo-controlled trial, 50 mg of Rimostil was given to women who were menopausal for at least 1 year. Bone mineral density of the spine, femoral neck and forearm and serum LDL cholesterol were measured at baseline and at 6-month intervals. The duration of follow-up was 2 years. There was no beneficial effect of Rimostil on bone density at any site. There was a 12% fall in serum LDL cholesterol in the Rimostil-treated arm, which was significantly greater than the 2% drop seen in the control arm.
Breast cancer protection, soy and isoflavones
Research 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.
Cancer, 2017. Dietary isoflavone intake and all-cause mortality in breast cancer survivors: The Breast Cancer Family Registry. Soy foods, isoflavones, and breast cancer. In this large, ethnically diverse cohort of women with breast cancer living in North America, a higher dietary intake of isoflavone was associated with reduced all-cause mortality.
Fertility in women, menstrual cycle
Fertil Steril. 2013. 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 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.
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). 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.
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
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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
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