1
Soyfoods are a unique dietary source of isoflavones,
a phytoestrogen that may offer women heart health
benefits and may help alleviate hot flashes during
menopause.
Soyfoods offer health benefits for all
consumers, but studies show that
postmenopausal women may reap
particular benefits. This fact sheet
discusses recent research into the benefits
and safety of soy for women, from heart
disease to hot flashes.
Traditional soyfoods such as tofu and miso have been widely used in
many East Asian countries for centuries and have been consumed by
health-conscious individuals in Western countries for several decades. In
recent years, because of the purported health benefits, increased numbers
of Westerners have decided to incorporate soy into their diets. Soyfoods
hold particular appeal for postmenopausal women because they are such
uniquely rich sources of isoflavones, one type of phytoestrogen.
Isoflavones exhibit estrogen-like effects under certain experimental
conditions and are posited to reduce the risk of coronary heart disease,
1

osteoporosis,
2
certain forms of cancer
3
and may alleviate menopause-
related hot flashes.
4
Consequently, many women view soyfoods as natural

intake is less
than 3 mg/day in the United States and other Western countries.
11, 12, 14-17

Using weighted, 2-day food consumption data for the U.S. population from
the National Health and Nutrition Examination Survey (NHANES) 2007-
2008, the United States Department of Agriculture recently estimated that
daily per capita isoflavone intake is 0.68 mg/day.
18

Isoflavones occur in soybeans as glycosides (a sugar molecule is attached
to the isoflavone backbone);
19
upon ingestion, the sugar is hydrolyzed
thereby allowing absorption to occur.
20
In fermented soyfoods such as
miso, tempeh and natto, substantial amounts of the isoflavones occur as
aglycones due to bacterial hydrolysis. The three isoflavones genistein,
daidzein and glycitein and their respective glycosides account for
approximately 50 percent, 40 percent and 10 percent, respectively, of the
total isoflavone content of soybeans.
19

Each gram of soy protein in soybeans and traditional soyfoods is
associated with approximately 3.5 mg of isoflavones.
10
In this document,
isoflavone amounts are expressed in aglycone equivalent weights.
Consequently, one serving of a traditional soyfood, such as 3-4 oz of tofu

23
While estrogen binds to and transactivates both ERα and ERβ
equally, isoflavones preferentially bind to and transactivate ERβ.
24-27
This
difference in binding and transactivation between isoflavones and estrogen
is important because the two estrogen receptors have different tissue
distributions and, when activated, can have different and sometimes even
opposite physiological effects. This appears to be the case in the breast,
where ERβ transactivation is thought to inhibit the proliferative effects of
ERα transactivation.
28, 29
The preference of isoflavones for ERβ is one reason they exert tissue-
selective effects, and for this reason, isoflavones are classified as selective
estrogen receptor modulators (SERMs).
30-32
In tissues that possess
estrogen receptors, SERMs exert estrogen-like effects in some cases
but no effects or antiestrogenic effects in others. The pharmaceutical
industry has for many years been actively developing SERMs.
33
Widely
used SERMs include tamoxifen, used in breast cancer treatment, and
raloxifene, which is used for treatment of osteoporosis.
34
In addition to
being classified as phytoestrogens and SERMs, the European Food Safety
Authority has recently proposed a new classification for compounds such
as isoflavones, which is “endocrine active substances.”
35

as one factor. The low incidence of hot flashes in Japan gave rise to initial
speculation that isoflavones could be useful in their prevention.
62

Even Chinese-American and Japanese-American women are about
one-third less likely to report experiencing hot flashes than Caucasian
women.
63
Interestingly, among Asian women, chilliness and shoulder
aches are much more commonly reported menopausal symptoms than
hot flashes. Recent evidence suggests, however, that Japanese women are
reluctant to report having hot flashes.
64
To this point, one study found that
hot flash frequency was lower among Japanese compared to Caucasian
women when based on a subjective determination (personal diary), but
not when determined objectively by measuring sternal and nuchal skin
conductance.
65
Sources of Soy Protein
Soyfood Serving size
Grams of
soy protein
Fortified soymilk 1 cup 6-7
Soy cereal
1 ¼ cup 7
Soy yogurt, vanilla
1 cup 6
Soy breakfast patty
2 patties 11

77
Estrogen therapy reduces postmenopausal
bone loss and hip fracture risk by approximately one-third.
6
Recent data
shows that the protective effects against hip fracture are lost within two
years of cessation of estrogen therapy.
78
Initial speculation that soyfoods
might promote bone health in postmenopausal women was based on the
estrogen-like effects of isoflavones and early research showing that the
synthetic isoflavone, ipriflavone, exerted skeletal benefits.
79

Since 1995, more than 50 clinical trials have examined the impact of
isoflavone-rich soyfoods or isoflavone supplements on the alleviation
of menopause-related hot flashes. In recent years, investigators have
gravitated toward the use of supplements rather than soyfoods to enhance
compliance and reduce the complexity of study design. The results of
these trials have produced inconsistent results. Although some recent
reviews and analyses of the literature have concluded that isoflavone-rich
products alleviate hot flashes,
4, 66
most have found that the data does not
allow for definitive conclusions to be made even though more trials than
not showed benefit.
67, 68
Some inconsistency in the literature is expected
given the small sample size of many trials and the variable placebo
response. However, several more specific explanations for the seemingly

and glycitein. Several lines of evidence, including relative estrogen
receptor binding and transactivation, indicate that genistein is more potent
than daidzein or glycitein and there is evidence that genistein is more
potent than the other isoflavones for alleviating hot flashes.
73, 74
The most comprehensive statistical analysis of the literature, which was
only recently published, clearly supports the efficacy of isoflavones
for alleviating hot flashes.
75
This systematic review and meta-analysis
included 19 and 17 studies, respectively, and included only studies
involving isoflavone supplements derived from soy. The meta-analysis of
the data on hot flash frequency, which included 13 studies involving 1,196
women, found isoflavones were consistently efficacious, reducing the
number of hot flashes per day about 21 percent more than the reduction
in the placebo group. Similarly, in the nine trials involving 988 women
that evaluated hot flash severity, isoflavones reduced symptoms by
about 26 percent more than the reduction in the placebo group. For both
measures, the effect of isoflavones was highly statistically significant.
When considering the combined effect of the placebo and isoflavones,
the overall reduction in frequency and severity was approximately 50
percent. Furthermore, subanalysis indicated that isoflavone supplements
providing at least 18 mg genistein were more than twice as efficacious
as supplements lower in genistein. As noted previously, genistein is the
predominant isoflavone in soybeans.
Collectively, this data makes a convincing case that isoflavones can be of
help to women who experience hot flashes. The level of relief provided by
The relatively low hip-fracture rates in Asian countries have also been cited
as evidence for the skeletal benefits of isoflavones, but other factors may
help explain these rates.

35,000 postmenopausal Singaporean women during the 7-year follow up
period.
94

In a third prospective epidemiologic study involving Seventh-day
Adventists, a religious denomination that includes a high proportion
of vegetarians, soymilk intake was significantly inversely related to
osteoporosis.
95
In this study, which involved 337 postmenopausal women,
participants had their bone health assessed using broadband ultrasound
attenuation of the calcaneus two years after completing a lifestyle and
dietary questionnaire at enrollment. Compared with women who did not
drink soymilk, women drinking soymilk once a day or more had 56 percent
lower odds of osteoporosis (defined as defined as a T-score <-1.8).
However, the protective effect of soymilk was likely due to its calcium
rather than isoflavone content since dairy product intake was similarly
protective. Although the results of these three studies are intriguing,
definitive conclusions about the skeletal effects of soyfoods can only be
based on the results from appropriately designed clinical studies.
Since the first clinical study to examine the effects of an isoflavone-rich
product on bone mineral density (BMD) in postmenopausal women was
published in 1998,
96
more than 25 trials have provided results (for reviews,
see references) although many involved small numbers of subjects and
were conducted for relatively short durations.
97, 9 8
Ideally, studies of bone
health should be at least 2-3 years in duration. The results from the clinical

another 1-year trial failed to show that either isoflavone supplements or
isoflavone-rich soy protein affected bone loss in U.S. postmenopausal
women.
104
Similarly, a recently published 2-year study found that soy
protein, regardless of isoflavone content, failed to prevent bone loss in
postmenopausal women, although this study had a large dropout rate and
many women were non-compliant with the intervention.
105

According to the American Cancer Society, breast
cancer patients can consume up to 3 servings of
soyfoods daily.
Lastly, the most important results were from three very large studies, two of
which were two years
106, 107
in duration whereas the third was three years in
duration.
108
Two of these were conducted in the U.S.
106, 107
and one in Taiwan.
108

Isoflavone intake from supplements was 80 and 120 mg/day in one study,
109

200 mg/day in another
107
and 300 mg/day in the third.

Additionally, subanalysis of the results revealed that among women
who were fewer than 5 years, 5-10 years, and more than 10 years post-
menopause, CIMT progression was reduced by 68 (p=0.05), 17 (p=0.51)
and 9 percent (p=0.77), respectively. It is notable that progression was
reduced so significantly in early postmenopausal women for two reasons.
First, it adds substantially to the biological plausibility of the findings, and
second, it provides clear insight into the soy component responsible for
the beneficial effects. The pronounced effect in early menopausal women
suggests isoflavones were primarily responsible for the reduced CIMT
progression. Over the past 10 years, a hypothesis has emerged, referred
to as the “estrogen timing hypothesis.” This maintains that exposure to
estrogen-like compounds leads to dramatic coronary and cognitive benefits
when begun soon after menopause, but has less effect in later years.
125
Asian countries where soyfoods are generally perceived as health foods.
Another explanation is that in the epidemiologic studies, isoflavone intake
occurred via the consumption of traditional soyfoods, whereas the clinical
studies have generally used soy extracts. However, there is no evidence
that this difference matters with respect to skeletal effects. It may also
be that the effects noted in the epidemiologic studies result from lifelong
intake as opposed to the relatively short-term intervention periods begun
in adulthood in the clinical studies. At the same time, there is no direct
evidence supporting this suggestion.
At this point, the evidence that isoflavones provide skeletal benefits is
unimpressive. Soyfoods have other benefits in this regard, however, since
they provide high quality protein,
110
which may promote bone health.
111, 112


119-122
Furthermore,
isoflavones improve impaired endothelial function in postmenopausal
women.
123
Lastly, the most important study came from the Women’s
Isoflavone Soy Health (WISH). This 3-year study involved 350 healthy
postmenopausal women ages 45-92, and found that isoflavone-rich soy
protein inhibited the progression of subclinical atherosclerosis.
124

Subclinical atherosclerosis can be assessed using ultrasound to measure
the thickness of the carotid arteries—which are located on both sides
of the neck beneath the jawline and provide the main blood supply to the
brain. The thickness of the carotid artery is referred to as carotid intima-
media thickness or CIMT. Typically, CIMT increases or progresses over
time; the extent of progression reflects risk of future coronary events.
Participants in the WISH study were randomly assigned to groups
consuming either 25 g of isolated soy protein per day or 25g of milk
protein. The soy protein provided 99 mg of isoflavones (expressed in
aglycone equivalent weight).
Soyfoods may offer protection against heart
disease, as they are low in saturated fat and high in
polyunsaturated fats.
6
Breast Cancer
There has been rigorous investigation of the role of soyfoods in
reducing breast cancer risk. A recent meta-analysis found that, in Asian
epidemiologic studies, higher soy intake was associated with a 29
percent decreased risk of breast cancer.

135
More importantly,
isoflavone-containing products have been found to stimulate the growth
of mammary tumors in ovariectomized athymic mice implanted with
estrogen-sensitive breast cancer cells.
136
Stimulation appears to result
primarily from exposure to the isoflavone genistein.
137
In this model,
genistein was also found to inhibit the efficacy of tamoxifen and the
aromatase inhibitor, letrozole.
138
Interestingly, more highly processed soy
products stimulate tumor growth to a greater extent than less processed
ones, despite containing similar amounts of genistein.
139
In fact, soy flour,
the least processed product to be evaluated, does not result in tumor
stimulation.
However, the relevance of this processing effect is in question because
it has now been established that, in athymic mice, processing affects
genistein pharmacokinetics in a way that leads to greater tumor
stimulation, which is not the case in humans.
140, 141
Also, Japanese
researchers, using the previously described mouse model, found that
genistein did not stimulate tumors.
142
Prior to implantation, the cancer cells

the median follow-up period of approximately 3.9 years, the hazard ratio
associated with the highest quartile of soy protein intake was 0.71 for total
mortality and 0.68 for recurrence compared with the lowest quartile of intake.
In fact, in this study, high soy intake was as protective as tamoxifen use.
In the second study, which was conducted in the U.S. and involved nearly
2,000 breast cancer patients, over the 6-year follow-up period, results
suggested that isoflavone intake may have improved prognosis overall,
and, in particular, among those women taking tamoxifen.
148
However,
among patients who had not previously used tamoxifen, there was an
increased risk associated with higher genistein intake but relatively
few women fell into this category. This raises the possibility that these
findings may have occurred by chance. In a second Chinese study,
Human data suggests that isoflavones do not exert
stimulatory effects on breast tissue, such as tissue
density or cell proliferation in vivo, which are both
markers of breast cancer risk.
Clinical evidence indicates that neither soyfoods nor
isoflavones adversely affect breast tissue.
7
which was conducted in Harbin among postmenopausal women with
estrogen receptor positive and progesterone receptor positive tumors, soy
consumption was associated with an approximate 30 percent decrease
in recurrence although overall mortality was not affected.
149
Interestingly,
although there was no interaction between tamoxifen and soy intake,
which is consistent with the results of the SBCSS, soy intake enhanced
the efficacy of anastrozole, an aromatase inhibitor. These findings are

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The 69 farmer-directors of USB oversee the investments of the soy checkoff to maximize profit opportunities for all U.S. soybean farmers. These volunteers invest
and leverage checkoff funds to increase the value of U.S. soy meal and oil, to ensure U.S. soybean farmers and their customers have the freedom and infrastructure
to operate, and to meet the needs of U.S. soy’s customers. As stipulated in the federal Soybean Promotion, Research and Consumer Information Act, the USDA