The Difference Between Alpha and Beta Receptors Explain Soy’s Benefits

“[S]oyfoods have become controversial in recent years…even among health professionals…exacerbated by misinformation found on the Internet.” Chief among the misconceptions is that soy foods promote breast cancer because they contain a class of phytoestrogen compounds called isoflavones, as I explore in my video, Is Soy Healthy for Breast Cancer Survivors? Since estrogens can promote breast cancer growth, it is natural to assume that phytoestrogens might, too, but most people do not realize there are two different types of estrogen receptors in the body, alpha and beta. Unlike actual estrogen, soy phytoestrogens “preferentially bind to and activate ERβ,” estrogen receptor beta. “This distinction is important because the [two types of receptors] have different tissue distributions within the body and often function differently, and sometimes in opposite ways. This appears to be the case in the breast,” where beta activation has an anti-estrogenic effect, inhibiting the growth-promoting effects of actual estrogen—something we’ve known for more than ten years.

The effects of estradiol, the primary human estrogen, on breast cells are “completely opposite” to those of soy phytoestrogens, which have “antiproliferative effects on breast cancer cells…even at [the] low concentrations” we get in our bloodstream after eating just a few servings of soy. This makes sense, given that after eating a cup of soybeans, the levels in our blood cause significant beta receptor activation, as you can see at 1:27 in my video.

Where did this outdated notion that soy could increase breast cancer risk come from? The concern was based largely on research that showed that the main soy phytoestrogen, genistein, stimulates the growth of mammary tumors in a type of mouse—but, it turns out, we’re not mice. We metabolize soy isoflavones very differently from rodents. As you can see at 2:00 in my video, the same soy phytoestrogens led to 20 to 150 times higher levels in the bloodstream of rodents. The breast cancer mouse in question had 58 times higher levels. What does this mean for us? If we ate 58 cups of soybeans a day, we could get some significant alpha activation, too, but, thankfully, we’re not hairless athymic ovariectomized mice and we don’t tend to eat 58 cups of soybeans a day.

At just a few servings of soy a day, with the excess beta activation, we would assume soy would actively help prevent breast cancer. And, indeed, “[s]oy intake during childhood, adolescence, and adult life were each associated with a decreased risk of breast cancer.” Those women who ate the most soy in their youth appeared to grow up to have less than half the risk. This may help explain why breast cancer rates are so much higher in the United States than in Asia, where soy foods are more commonly consumed. Yet, when Asians come to the United States and start eating and living like Americans, their breast cancer risk shoots right up. Women in their 50s living in Connecticut, for example, are way at the top of the breast cancer risk heap, as you can see at 3:00 in my video, and have approximately ten times more breast cancer than women in their 50s living in Japan. It isn’t genetic, however. When Japanese women move to the United States, their breast cancer rates go up generation after generation as they assimilate into American culture.

Are the anti-estrogenic effects of soy foods enough to actually change the course of the disease? We didn’t know until the first human study on soy food intake and breast cancer survival was published in 2009 in the Journal of the American Medical Association, suggesting that “[a]mong women with breast cancer, soy food consumption was significantly associated with decreased risk of death and [breast cancer] recurrence.” That study was followed by another study, and then another, each with similar findings. That was enough for the American Cancer Society, which brought together a wide range of cancer experts to offer nutrition guidelines for cancer survivors, concluding that, if anything, soy foods should be beneficial. Since then, two additional studies have been published for a total of five—five out of five studies that tracked more than 10,000 breast cancer patients—and they all point in the same direction.

Pooling all of the results, soy food intake after breast cancer diagnosis was associated with both reduced mortality and reduced recurrence—that is, a longer lifespan and less likelihood that the cancer comes back. This improved survival was for women with estrogen receptor negative tumors and estrogen receptor positive tumors, and for both younger women and for older women.

Pass the edamame.


Flaxseeds are protective for likely the same reasons. For more on this, see my videos Flaxseeds and Breast Cancer Survival: Epidemiological Evidence and Flaxseeds and Breast Cancer Survival: Clinical Evidence.

What about women who carry breast cancer genes? I touched on that in BRCA Breast Cancer Genes and Soy and Should Women at High Risk for Breast Cancer Avoid Soy?.

What about genetically modified soy? See GMO Soy and Breast Cancer.

Who Shouldn’t Eat Soy? An excellent question I answer in that video.

For even more information on soy, see:

Not all phytoestrogens may be protective, though. See The Most Potent Phytoestrogen Is in Beer and What Are the Effects of the Hops Phytoestrogen in Beer?.

In health,
Michael Greger, M.D.

PS: If you haven’t yet, you can subscribe to my free videos here and watch my live presentations:

How Not to Die from Cancer

After Dr. Dean Ornish conquered our number-one killer, heart disease, he moved on to killer number-two. What happens if cancer is put on a plant-based diet? Ornish and colleagues found that the progression of early-stage prostate cancer could be reversed with a plant-based diet and other healthy lifestyle behaviors.

If the blood of those eating the Standard American Diet is dripped onto cancer cells growing in a petri dish, cancer growth is cut down about 9 percent. And if they’ve followed a plant-based diet for a year? Their blood can slash cancer growth by 70 percent. So the blood circulating thgouhout the bodies of those eating plant-based diets had nearly eight times the stopping power when it came to suppressing cancer cell growth.

That was for cell growth of prostate cancer, the leading cancer-killer specific to men. In younger women, breast cancer is the top cancer-killer. Researchers wanted to repeat the study with women using breast cancer cells, but they didn’t want to wait a whole year to get the results. Women are dying now. So they figured they’d see what a plant-based diet could do after just two weeks against three different types of human breast cancer.

As you can see in my video How Not to Die from Cancer, the study showed cancer growth started out at 100 percent, but then dropped after the subjects ate a plant-based diet for 14 days. A layer of breast cancer cells was laid down in a petri dish, and then blood from women eating the Standard American Diet was dripped on it. As you can see in the video, even the blood of women eating pretty poor diets had some ability to break down cancer. After just two weeks of eating healthfully, though, blood was drawn from those same women—so they effectively acted as their own controls—and was dripped on a new carpet of breast cancer cells. You can see for yourself that only a few individual cancer cells remained. Their bodies cleaned up. After only 14 days on a plant-based diet, their bloodstream became that much more hostile to cancer.

Slowing down the growth of cancer cells is nice, but getting rid of them all together is even better. This is what’s called apoptosis, programmed cell death. After eating healthfully, the women’s own bodies were able to somehow reprogram the cancer cells, forcing them into early retirement.

In my video, you can see what’s called TUNEL imaging, which allows researchers to measure DNA fragmentation, or cell death. With this technology, dying cancer cells appear as little white spots. From the start of the study, you can see one small white speck in the upper left of the image, showing that the blood of an average woman on a typical American diet can knock off a few breast cancer cells. After 14 days of healthy, plant-based living, however, her blood turned that one small white speck into a multitude of white spots. It’s as if she’s an entirely different woman inside! The same blood now coursing through these women’s bodies gained the power to significantly slow down and even stop breast cancer cell growth after just two weeks of eating a plant-based diet.

What kind of blood do we want in our body? What kind of immune system? Do we want blood that just rolls over when new cancer cells pop up, or do we want blood circulating to every nook and cranny of our body with the power to slow down and stop them?

The dramatic strengthening of cancer defenses shown in the study was after 14 days of a plant-based diet—and exercise.The researchers had the women walking 30 to 60 minutes a day. Given there were two factors, how do we know what role the diet played? Researchers decided to put it to the test.

In my video, you can see a chart that first shows how blood taken from those who ate a plant-based diet and had a routine of mild exercise, such as walking every day, over an average of 14 years, exhibited significant cancer cell clearance. The researchers then compared the substantial cancer-stopping power of plant eaters to that of an average sedentary American, which you can see is basically nonexistent.

The researchers also analyzed a third group. Instead of 14 years on a plant-based diet, they had 14 years on a Standard American Diet, but they also had 14 years of daily, strenuous, hour-long exercise, like calisthenics. They wanted to know if you exercised hard enough and long enough could you rival some strolling plant eaters.

The answer? There’s no question that exercise helped, but literally 5,000 hours in the gym was no match for a plant-based diet.

Once again using TUNEL imaging to analyze cancer cell death, the researchers found that even if you are a couch potato eating fried potatoes, your body isn’t totally defenseless. Your bloodstream can kill off some cancer cells, which you can see in my video as a couple white spots in the first image of that series. If you exercise for 5,000 hours, you can kill many more cancer cells, evidenced by the many more white specks appearing throughout that image. But nothing appears to kick more cancer tush than a plant-based diet, as that image is filled with white spots indicating cancer cells killed off.

Why is this the case? We think it’s because animal proteins, such as meat, egg white, and dairy protein, increase the level of insulin-like growth factor-1 (IGF-1), a cancer-promoting growth hormone involved in the “acquisition or progress of malignant tumors.”

In my video, you can see the results of a study that nailed IGF-1 as the villain. Just as in the previous studies, subjects went on a plant-based diet and cancer-cell growth dropped, while cancer-cell death shot up. This experiment, however, had a kicker: It added back to the cancer just the amount of IGF-1 that had been banished from your body as a result of eating and living healthier. In doing so, it effectively erased the “diet and exercise” effect. It’s as if the subjects had never started eating healthfully at all, with the cancer-cell growth rates and death rates returning to the same levels as before the plant-based diet intervention.

The reason one of the largest prospective studies on diet and cancer found “the incidence of all cancers combined was lower among vegetarians than among meat eaters” may be because they eat less animal protein, and thereby end up with less IGF-1, which means less cancer growth.

How much less cancer growth? A study found that middle-aged men and women with high protein intakes had a 75 percent increase in overall mortality and a fourfold increase in the risk of dying specifically from cancer. Does the protein source matter? Yes. It was specifically animal protein, which makes sense, given their higher IGF-1 levels.

The academic institution where the study was done sent out a press release with a memorable opening line: “That chicken wing you’re eating could be as deadly as a cigarette.” It went on to explain that “eating a diet rich in animal proteins during middle age makes you four times more likely to die from cancer…—a mortality risk factor comparable to smoking.”

What was the response to the revelation that diets high in meat, eggs, and dairy could be as harmful to health as smoking? One nutrition scientist replied it was “‘potentially even dangerous’ to compare the effects of smoking with the effect of meat and cheese,” but why? Because, they argued, a smoker might think “‘why bother quitting smoking if my cheese and ham sandwich is just as bad for me?’”

This reminds me of a famous Philip Morris cigarette ad that tried to downplay the risks of second-hand smoke. The ad included a chart with “everyday activities” and “reported relative risk,” in an attempt to say second-hand smoke wasn’t all that bad. The chart showed that while it increases the risk of lung cancer by 19 percent, drinking one or two glasses of milk every day may be three times as bad with a 62 percent higher risk of lung cancer. Lung cancer risk could be doubled if you frequently cook with oil, and heart disease risk tripled if you eat non-vegetarian or multiplied six-fold by eating lots of meat and dairy. Philip Morris’s conclusion? “Let’s keep a sense of perspective.” The “risk of lung cancer from second-hand tobacco smoke [was put] well below the risk reported by other studies for many everyday items and activities.”

That’s like saying, “Don’t worry about getting stabbed, because getting shot is so much worse.” Two risks don’t make a right.

Of course, you’ll note Philip Morris stopped throwing dairy under the bus once it purchased Kraft Foods.


The first time someone visits NutritionFacts.org can be overwhelming. With videos on more than 2,000 health topics, where do you even begin? Imagine stumbling onto the site not knowing what to expect and the new video-of-the-day is about how a particular spice can be effective in treating a particular form of arthritis. It would be easy to miss the forest for the trees, which is precisely why I created a series of overview videos that are essentially taken straight from my live, hour-long 2016 presentation How Not to Die: Preventing, Arresting, and Reversing Our Top 15 Killers.

The other videos in this overview series are:

Inspired to learn more about the role diet may play in preventing and treating cancer? Check out these other popular videos on the topic:

I’ve also produced an entire series on mammograms. You can find all of those videos here.

In health,
Michael Greger, M.D.

PS: If you haven’t yet, you can subscribe to my free videos here and watch my live, year-in-review presentations:

Vitamin D Supplements for Reducing Cancer Mortality

It all started with a famous study entitled “Do sunlight and vitamin D reduce the likelihood of colon cancer?” that was published in 1980. Johns Hopkins University researchers were trying to figure out why states like New Mexico and Arizona have only about half the colon cancer rates of states like New York, New Hampshire, and Vermont. Could it be because New Mexicans and Arizonans get so much more sun? The researchers proposed that perhaps vitamin D, known as the sunshine vitamin, is a protective factor against colon cancer. Since then, sun exposure has also been associated with lower rates of 14 other types of cancer.

As I discuss in my video Do Vitamin D Supplements Reduce the Risk of Dying from Cancer?, vitamin D may also affect cancer survival. Higher blood levels of vitamin D were associated with lower mortality of patients with colorectal cancer. How much lower? Nearly half the mortality. And, the higher the vitamin D levels, the lower the death rate appeared to fall. This may explain why the survival rate from colon cancer may depend in part “on the season of diagnosis.” The risk of rapid death is lowest if you’re diagnosed in the fall after you’ve spent the summer building up your vitamin D stores. Other risk factors could be seasonal, too. For example, perhaps people are taking advantage of the fall harvest and eating healthier, which might explain lower risk in the autumn. Additionally, “[a]lcohol intake is a risk factor and may be highest in the winter season…” What about physical activity? In the summer, we may be more likely to be outside running around, not only getting more sun, but also getting more exercise, which may itself be protective.

These kinds of studies just provide circumstantial evidence. Establishing a cause-and-effect relationship between colon cancer and vitamin D deficiency using observational studies is challenging because of confounding factors, such as exercise habits—so-called lurking variables. For example, there may be a tight correlation between ice cream sales and drowning deaths, but that doesn’t mean ice cream causes drowning. A more likely explanation is that there is a lurking third variable, like hot weather in summertime, that explains why drowning deaths are highest when ice cream consumption is also at its highest.

This actually happened with hormone replacement therapy. Women taking drugs like Premarin appeared to have 50 percent less risk of heart disease, so doctors prescribed it to women by the millions. But, if we dig a little deeper into the data, we find that, indeed, women taking estrogen had 50 percent lower risk of dying from heart disease, but they also had a 50 percent lower risk of dying from accidents and homicide, so it probably wasn’t the drug. The only way to know for sure is to put it to the test in a randomized, clinical trial, where half the women are given the drug and we see what happens. A decade later, such a study was done. Instead of having a 50 percent drop in risk, within a year of being given the hormone pills, heart attack and death rates shot up 50 percent. In retrospect, the lurking variable was likely socioeconomic class. Poor women are less likely to be prescribed hormone replacement therapy and more likely to be murdered and die of heart disease. Because of the lurking variable, a drug we now know to be dangerous had initially appeared to be protective.

Besides lurking variables, there’s also the possibility of reverse causation. Perhaps low vitamin D levels didn’t worsen the cancer. Instead, maybe the cancer worsened the vitamin D levels. This may be unlikely, since tumors don’t appear to directly affect vitamin D levels, but cancer treatment might. Even simple knee surgery can cause vitamin D levels to drop dramatically within hours, thought to be due simply to the inflammatory insult of cutting into someone. So, maybe that could help explain the link between lower vitamin D and lower survival. And, cancer patients may be spending less time running around the beach. So, yes: Higher vitamin D levels are associated with improved survival in colorectal cancer, and the same has been found for breast cancer. In fact, there is about double the risk of breast cancer recurrence and death in women with the lowest vitamin D levels. What’s more, higher vitamin D levels are associated with longer survival with ovarian cancer, as well as having better outcomes for other cancers like lymphoma. But, the bottom-line, as we learned with hormone replacement, is that we have to put it to the test. There weren’t a lot of randomized controlled trials on vitamin D supplements and cancer, however…until now.

We now have a few randomized controlled trials, and vitamin D supplements do indeed appear to reduce the risk of dying from cancer! What dose? Researchers suggest getting blood levels up to at least about 75 nanomoles per liter. These levels are not reached by as many as three-quarters of women with breast cancer nor achieved by a striking 97 percent of colon cancer patients .

Getting up to these kinds of levels—75 or, perhaps even better, 100 nanomoles—might require about 2000 to 4000 IU of vitamin D a day, levels of intake for which there appear to be no credible evidence of harm. Regardless of what the exact level is, the findings of these kinds of studies may have a profound influence on future cancer treatment.


What about just getting sun instead? Be sure to check out my six-part video series:

It’s better, of course, to prevent colon cancer in the first place. See, for example:

For more on that extraordinary story about Premarin and hormone replacement therapy, see How Did Doctors Not Know About the Risks of Hormone Therapy?

In health,
Michael Greger, M.D.

PS: If you haven’t yet, you can subscribe to my free videos here and watch my live, year-in-review presentations: