“Who Shouldn’t Eat Soy?” When the Women’s Health
Initiative study found that menopausal women taking
hormone replacement therapy suffered higher rates of breast cancer,
cardiovascular disease, and overall harm, a call was made for safer alternatives. Yes, estrogen has positive effects,
the Women’s Health Initiative found, such as reducing menopausal
symptoms and improving bone health, reducing hip fracture risk,
but also negative effects: increasing the risk of blood clots
in the heart, brain, and lungs, as well as breast cancer. So ideally, to get the best of both
worlds, we’d need what’s called a selective estrogen
receptor modulator, something that has pro-estrogenic
effects in some tissues, like bone, but anti-estrogenic effects in
other tissues, like the breast. Drug companies are trying to
make them, but phytoestrogens, natural compounds in plants–
like genistein in soybeans, that are structurally
similar to estrogen– appear to function as natural selective
estrogen receptor modulators. How could something that looks like
estrogen act as an anti-estrogen? The original theory for how
soy phytoestrogens control breast cancer growth is that they
compete with our own estrogens for binding to the estrogen receptor. As you drip more and more soy
compounds on breast cancer cells in a Petri dish, less and less actual
estrogen is able to bind to them. So the estrogen-blocking
ability of phytoestrogens can help explain their anti-estrogenic
effects, but how do we then explain their pro-estrogenic effects
on other tissues like bone? How can soy have it both ways? The mystery was solved when
we discovered there are two types of estrogen receptors in the body,
and so how a target cell responds depends on which type of
estrogen receptors they have. This may be the key to understanding
the health-protective potential of soy phytoestrogens, the existence
of this newly discovered estrogen receptor–called
estrogen receptor beta, to distinguish it from the classic
estrogen receptor alpha– and unlike our body’s
own estrogen, soy phytoestrogens preferentially
bind to the beta receptors. If you have people eat about
a cup of cooked whole soybeans, within about 8 hours,
genistein levels in the blood reach about 20 to 50 nanomoles; that’s how much is circulating throughout
our body, bathing our cells. About half is bound up
to proteins in the blood, so the effective concentration
is about half that. So let’s see what that means
for estrogen receptor activation. This is the graph that explains the
mysterious health benefits of soy foods. Down around the effective levels
you’d get eating a cup of soybeans, there’s very little alpha activation,
but lots of beta activation. So now let’s look at where each of these
receptors are located in the human body. The way estrogen pills increase
the risk of fatal blood clots is by causing the liver to dump out
all these extra clotting factors. But guess what? The human liver only contains alpha
estrogen receptors, not beta receptors, and so maybe if we ate like 30 cups of
soybeans a day that could be a problem. But at the kinds of
concentrations one would get with just normal soy consumption, no wonder this is a problem with drug
estrogens, but not soy phytoestrogens. The effects on the uterus appear also
to be mediated solely by alpha receptors, which is presumably why no negative
impact has been seen with soy. So while estrogen-containing drugs may
increase the risk of endometrial cancer up to 10-fold, phytoestrogen-
containing foods are associated with significantly less
endometrial cancer, in fact, protective effects for these
types of gynecological cancers in general. Women who ate the most soy had
30% less endometrial cancer and appeared to cut their ovarian
cancer risk nearly in half. Soy phytoestrogens don’t appear to have
any effect on the lining of the uterus, but still can dramatically improve
menopausal symptoms. The Kupperman Index
is like a compilation of all 11 of the most common
menopausal symptoms. In terms of bone health, human bone
cells carry beta estrogen receptors, so we might expect soy
phytoestrogens to be protective. And indeed, they do seem to significantly
increase bone mineral density, consistent with population data
suggesting high consumption of soy products is associated
with increased bone mass. But can they prevent
bone loss over time? Soymilk was compared to a
transdermal progesterone cream. The control group lost significant
bone mineral density in their spine over the two year study period, but the
progesterone group lost significantly less and the two glasses of soymilk
a day group ended up actually better than
when they started. This is probably the most
robust study to date, comparing the soy
phytoestrogen genistein to a more traditional hormone
replacement drug regimen. In the spine, over a year, the
placebo group lost bone density, but gained in the phytoestrogen
and estrogen groups, and the same with the hip bones. The study clearly shows that the
soy phytoestrogen prevents bone loss and enhances new bone formation, in turn
producing a net gain of bone mass. But the only reason we care about bone mass
is that we want to prevent fractures. Is soy food consumption associated
with lower fracture risk? Yes. A significantly lower risk
of bone fracture associated with just a single
serving of soy a day, the equivalent of 5 to 7
grams of soy protein, or 20 to 30 milligrams
of phytoestrogens. So that’s just like
one cup of soymilk, or even better, a serving of a whole
soy foods like tempeh or edamame, or the beans themselves. We don’t have fracture data
on the soy supplements though, so if we seek the types of health benefits
we presume Asian populations get from eating whole and
traditional soy foods, maybe we should look
to eating those rather than taking unproven
protein powders or pills. Is there anyone who
should avoid soy? Well, some people have soy allergies. But a national survey found that
only about 1 in 2,000 people report a soy allergy. That is 40 times less than the most
common allergen, dairy milk, and about 10 times less than all
the other common allergens like fish, eggs, shellfish,
nuts, wheat, or peanuts.