Image Credit: Pixabay. This image has been modified.

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Where did this outdated notion that soy could increase breast cancer risk come from?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:

Discuss

Michael Greger M.D., FACLM

Michael Greger, M.D. FACLM, is a physician, New York Times bestselling author, and internationally recognized professional speaker on a number of important public health issues. Dr. Greger has lectured at the Conference on World Affairs, the National Institutes of Health, and the International Bird Flu Summit, testified before Congress, appeared on The Dr. Oz Show and The Colbert Report, and was invited as an expert witness in defense of Oprah Winfrey at the infamous "meat defamation" trial.


36 responses to “The Difference Between Alpha and Beta Receptors Explain Soy’s Benefits

Comment Etiquette

On NutritionFacts.org, you'll find a vibrant community of nutrition enthusiasts, health professionals, and many knowledgeable users seeking to discover the healthiest diet to eat for themselves and their families. As always, our goal is to foster conversations that are insightful, engaging, and most of all, helpful – from the nutrition beginners to the experts in our community.

To do this we need your help, so here are some basic guidelines to get you started.

The Short List

To help maintain and foster a welcoming atmosphere in our comments, please refrain from rude comments, name-calling, and responding to posts that break the rules (see our full Community Guidelines for more details). We will remove any posts in violation of our rules when we see it, which will, unfortunately, include any nicer comments that may have been made in response.

Be respectful and help out our staff and volunteer health supporters by actively not replying to comments that are breaking the rules. Instead, please flag or report them by submitting a ticket to our help desk. NutritionFacts.org is made up of an incredible staff and many dedicated volunteers that work hard to ensure that the comments section runs smoothly and we spend a great deal of time reading comments from our community members.

Have a correction or suggestion for video or blog? Please contact us to let us know. Submitting a correction this way will result in a quicker fix than commenting on a thread with a suggestion or correction.

View the Full Community Guidelines

  1. Can you address the difference between Vitamin K1 and Vitamin K2? Apparently, Natto is really high in Vitamin K2. Is it important for some people to get foods high in K2?

  2. Good article. I would love to see a similar article on soy and prostate cancer. I have read contradictory recommendations on soy consumption and prostate cancer, with some saying soy is beneficial and others saying it actually promotes prostate cancer.

  3. Phytoestrogens may also act as inhibitors of aromatase enzymes, which catalyze the conversion of androgens to estrogen in many human tissues.

    “In general, phytoestrogens act as aromatase inhibitors by (a) decreasing aromatase gene expression, (b) inhibiting the aromatase enzyme itself, or (c) in some cases acting at both levels of regulation.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699002/

    In fact, this is a treatment for breast cancer (after other treatments, such as surgery, radiation, and/or chemotherapy): aromatase inhibitors, which include tamoxifen and newer aromatase inhibitor drugs. Usually taken for 5-10 years.

  4. Hm. I read the research after getting diagnosed with breast cancer and increased my intake of soy. My tumour was just below the surface of the skin and within 2 weeks I developed a new nodule that I could feel quite clearly and the tumour started to feel a little uncomfortable, sort of achey. I stopped the soy and the nodule stopped developing, I had to wait another 4 weeks before surgery as there were more scans and investigations that had to be done but it didn’t grow any more and I had no more discomfort. My tumour was 8/8 on responsiveness to oestrogen, so maybe those of us with tumours that are very responsive may have a different reaction to soy than those with less responsive tumours. I’m a big believer in the effect of diet on health but in this case I would be a little wary of recommending soy to everyone just in case…

    1. Sara,

      You said that you increased your soy consumption and Dr. Greger did an IGF-1 video on soy and too many servings can undo the soy protective benefits by raising IGF-1.

      Five out of five studies it was beneficial, but if people eat too many servings per day the increase in IGF-1 undoes the benefit.

      Also, there are sources of soy that are not good for you.

      Edamame, Tempeh and Tofu and soy milk are all acceptable, but soy processed food is not healthy and doesn’t confer the same benefits.

      1. Deb,

        Thanks for your comment. I was having soy milk, tofu or edamame, I’m not really a fan of tempeh or processed soy foods. I guess the trouble is that as we are all individuals with our own biology it’s a bit hard to be completely prescriptive about how much is too much. I was eating a normal dietary amount, not going overboard, but for me in my situation that was possibly excessive. For others having soy does seem to be beneficial but for those like me that have, or had, tumours that are strongly oestrogen responsive perhaps we need to be more careful.

  5. Thankyou for some reason.. I have always wondered why young women with lots of hormones get ‘less’ breast cancer than ‘old’ women with fewer hormones get more breast cancer?
    Many thanks , Sharon B

    1. Sharon,

      It may take a while to accumulate DNA damage — mutations — which might then initiate cancer. Also, as I understand it, cancer is often very slow growing initially, perhaps kept in check by the immune system, but it accumulates additional mutations which allow it to escape the checks by the immune system. It is a complicated, and biologically fascinating, set of diseases. (And I say that having been diagnosed with breast cancer.)

    2. Hello Sharon,

      The issue isn’t actually about how much estrogen they’re exposed to at that moment, but the accumulation of exposure over their entire lives. That’s why women who had an early menarche (onset of menses) and late menopause have a higher risk of developing breast cancer, since they’ve had the longest exposure to higher estrogen levels.

      I hope this helps,
      Dr. Matt

  6. When I started menopause at the age of 50, I had a few hot flashes so extreme I felt I might be having a heart attack (intense sweating, pounding heart). I researched soy, then started drinking one or two cartons of soy milk a day plus stir-fried tofu two or three times a week. I never had another hot flash!

    BUT HERE’S THE CATCH!! – After about a year on my soy regime, I one day realized that I couldn’t remember my last normal bowel movement – either nothing or just a little bit of stringy stuff came out (gross, I know). I really didn’t think it could be the soy, but I had never had constipation before, and nothing else had changed.

    While awaiting a colonoscopy, I did more soy research and became alarmed. I stopped ingesting all soy products, even soy sauce. After maybe four weeks, my bowel movements returned to normal.

    The Moral? Maybe not all good foods are good for everyone. More likely, don’t overdo any food, not even possibly beneficial ones. You can die from drinking too much water

    1. J. Marshall,

      Yes, one or two cartons of soymilk per day, plus tofu is probably too much and too much will undo the benefit.

      I went WFPB (sometimes WFPB-ish, particularly the first year) and had soy milk in my green tea latte every day for maybe a year and a half, and, no, it didn’t hurt my bowel movements.

      I already did eat soy and what I will tell you is that I had zero hot flashes or any pain or excessive bleeding during menopause.

      I did have brain problems, and I am on the fence about whether that was related to menopause or not. Either way, I had out of control blood sugar and aluminum in my brain and high homocysteine for sure and clogged arteries, for double sure.

      But my friends who were older had warned me that women genuinely can feel “crazy” and like they have genuinely lost their minds during menopause. I was having hallucinations and psychotic breaks and night terrors and inverted day for night and I had a change in spacial relationships and other things, which have resolved.

      I am still sleeping most nights since I upped my Vitamin D dosage. I am amazed at how well that is still working. I do have some sleepless nights, but it is more like once a week or less – even with the increased responsibilities of the pandemic.

    1. It’s odd isn’t it. I eat soy all the time and have never had a kidney stone. My wife never eats soy but has suffered from kidney stones for years. I drink more fluids and consume less sodium than she. And no animal protein whereas she does. Perhaps the background diet is also relevant here.

      There appear to be multiple factors at work. I am not sure that kidney stones were ever a major problem in Asian societies that consumed a lot of tofu and other plant foods containing oxalates. Kidney stones do appear to be an increasing problem around the world though

      ‘There is strong evidence that diminished fluid and calcium consumption are risk factors.14,41–44 Increased oxalate consumption has also been demonstrated to promote stone formation. 45,46 Epidemiologic studies have demonstrated that increased sodium and animal protein intake have an equivocal impact on stone risk. However, a randomized prospective dietary intervention study demonstrated that reduction of sodium and animal protein and maintenance of normal dietary calcium intake attenuates stone activity in recurrent hypercalciuric stone formers.41 There is evidence that the consumption of animal protein has increased in a number of countries, paralleling the acceleration of stone disease.36–39 There are also studies that demonstrate an increased intake of sodium and sodium-rich foods in certain cohorts.47’
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931286/

      Dr G’s videos may also be helpful

      https://nutritionfacts.org/video/flashback-friday-how-to-prevent-and-treat-kidney-stones-with-diet/
      https://nutritionfacts.org/video/kidney-stones-and-spinach-chard-and-beet-greens-dont-eat-too-much/

      1. Tom,

        Thanks for posting that.

        I know that when they did the studies, it was spinach that was the vegetable that actually did cause them more than anything.

        There is a genetic predisposition issue with them is what I remember from those videos.

        The sodium thing is interesting.

        I have been thinking about sodium. I love soy sauce, but haven’t been using it because I know that soy sauce was considered not a good food by Dr. Greger, but it confused me because Miso was okay and soy sauce wasn’t okay and I thought Miso was okay because the potassium in soy balanced the sodium, but, somehow not in soy sauce. I know that it is important because in Japan, they had a lot of strokes in Japan related to sodium. That is discussed in Dr. Greger’s stroke series.

        So, is there more sodium in soy sauce or less potassium or was I wrong about why Miso was okay?

        1. I think Dr Greger said that while salt consumption is associated with gastric cancers and high BP, miso consumption is not. He thinks this may be because the protective effects of soy outweigh the harmful effects of sodium.

          Not sure if he has discussed soy sauce but Japanese style soy sauce is often up to 50% wheat and therefore wouldn’t have as much counterbalancing soy to offset the sodium.

      1. Soy that is organic, is never GMO. The GMO soy is used for animal feeds. Even if it doesn’t say organic, if it’s for human consumption, it is not GMO.

        1. She wrote ‘organically grown’ not ‘organic’. There is actually a difference in meaning.

          GMO plants can be conventionally grown or, conceivably, organically grown. Unlikely yes but it’s not impossible.

          It is illegal in the US to describe plants grown from GMO seeds as organic even if raised organically. However, this regulation recognises that a farmer could in practice choose to plant GMO seeds and raise/grow them organically. Cross contamination of organic crops by GMO seeds is also a known risk.

          For the students at the back of the class, however, let me state that my comment was intended as sarcasm

    1. If you have thyroid problems you should avoid unfermented soy. peanut products, cruciferous vegetables, and spinach and strawberries. People will tell you it’s OK to eat cruciferous vegetables and the others I’ve listed here, but I personally experience swelling at the thyroid when eating any of these. I’ve had Hashimoto’s thyroiditis since 2003. I do not take thyroid medicine and have kept my antibodies low via organic foods. Chamomile tea is the best at relieving thyroid discomfort and promoting thyroid health.

    2. This seems to be a case of throwing out the baby with the bath water. While there may be some concern about soy’s effect on hypothyroid meds, eliminating all soy products (& all their beneficial effects) may not be necessary. While there is some debate on the questions here is some research that you may find reassuring:
      https://www.ncbi.nlm.nih.gov/pubmed/16571087 Effects of soy protein and soybean isoflavones on thyroid function in healthy adults and hypothyroid patients: a review of the relevant literature.
      “…Some evidence suggests that soy foods, by inhibiting absorption, may increase the dose of thyroid hormone required by hypothyroid patients. However, hypothyroid adults need not avoid soy foods.”
      This article suggests an approach that seems to make sense- timing your soy intake to not interfere with medication absorption:
      https://www.mayoclinic.org/diseases-conditions/hypothyroidism/expert-answers/hyperthyroidism/faq-20058188ma
      Why not review both, then discuss with your doctor and of course monitor/report any symptoms with soy intake. Hope this helps.

  7. Ity should be noted in this article, but is not, that Japanese and Asians eat fermented soy, not soybeans. I believe this article is misleading. And what are the affects of extra estrogen from soy on men? Probably negative.

  8. Hello, in this article you don’t make the difference between “traditional” soy preparations such as tofu, miso, tempeh, tamari… and “westernized” soy preparations such as soy milk, soy cream, soy yoghurt… Could you please clarify? Thanks

Leave a Reply

Your email address will not be published. Required fields are marked *

Pin It on Pinterest

Share This