Latest Research Shows Soy Foods help Prevent Bone Loss

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If you are not among those who are allergic to soy or have been diagnosed as having hypothyroidism, soy foods can be a great addition to your bone-building diet. Not only are soy foods excellent sources of magnesium and vitamin K1 (plus many are fortified with calcium), but they contain active compounds called isoflavones – genistein and ipriflavone, specifically — that greatly help lessen the activation of osteoclasts, the cells that break down bone.

Genistein improves the RANKL/OPG Ratio

What’s the RANKL/OPG ratio?

To explain this, we need to take a little trip “behind the scenes” for a look at these two molecules, one of which, RANKL, initiates a series of events that results in the production of osteoclasts ready to remove old bone, and another one, OPG, that shuts down this process.

When RANKL, which stands for receptor activator of nuclear factor-kappaB ligand, binds to a cellular receptor called RANK (receptor activator of nuclear factor-kappaB), this turns on nuclear factor-kappaB (NFkappaB), a seriously pro-inflammatory messenger. NFkappaB moves inside your cells and goes right to your DNA, where it sets off the production of a whole bunch of inflammatory actors—one of which is osteoclasts. You may remember we’ve said that anything that promotes chronic inflammation promotes bone loss. RANKL’s activation of NKkappaB, which in turn activates osteoclasts, is behind this connection.

If we want to keep our bones, we must keep RANKL under control. However, RANKL is not an altogether bad guy we can afford to totally eliminate (which is what denosumab, A.K.A. Prolia does – it totally shuts down RANKL). RANKL’s binding to RANK is also necessary for the activation of immune cells (our T and B cells, specifically), and we must have functional immune systems to survive. What good are great bones if we’re easy prey for destruction by infections or cancer? (More on this in our blog discussing of why you do not want to take denosumab.)

So, how do we safely put a leash on RANKL?  We send in its decoy receptor, osteoprotegerin (OPG), which also binds with RANKL, and thus blocks the interaction between RANKL and RANK, and the activation of NFkappaB. Pretty nifty how our body has worked out this balancing act for us, huh? I envision RANKL as a Conan, the Barbarian, kind of guy, and see OPG as standing for “Oh, Pretty Girl!” Enough OPG around and RANKL will be tamed. Not eliminated (so our immune cells will still mature), but tuned down.

So, what encourages this happy meeting of our cellular characters, RANKL and OPG? You guessed it –soy foods, specifically, a bioactive isoflavone compound in whole soy foods called genistein, which is well known to lessen inflammation. Now we know genistein is doing so, at least in part, by increasing OPG and decreasing RANKL. (Vitamin K2 – in its form as MK-7 – does so as well, but that’s another story – lots more to this, coming to you shortly in another blog.)

A two year-long placebo-controlled study of 389 osteopenic postmenopausal women in Italy found giving them genistein resulted in their having lower RANKL and higher OPG levels by the end of the first year, with further improvements in the ratio of RANKL/OPG by the end of the second year. [i]

In this study, genistein was given to 198 women; the remaining 191 women received a placebo. Both the supplement containing genistein and the placebo supplement contained calcium and vitamin D3, and all the women received the same information about healthy diet. A significant (-0.021) reduction in the RANKL/OPG ratio occurred in the women given genistein, while in the women receiving placebo, the RANKL/OPG ratio worsened (+0.004).

This bone-happy outcome is almost definitely due to genistein’s anti-inflammatory effects, which have been reported in numerous studies in relation to many other aspects of our physiology. For example:

Genistein inhibits activation of the pro-inflammatory enzyme COX-2. This is the enzyme inhibited by aspirin, ibuprofen, acetaminophen and other non-steroidal drugs, and the mechanism through which they provide pain relief.[ii]

Genistein lessens vascular inflammation, which is one of the ways soy foods help lower blood pressure.[iii]

Genistein has been referred to as an “anticancer agent,” since it lessens inflammation in cells throughout the body, and uncontrolled cellular inflammation promotes both the initiation and metastasis (spread) of cancer.[iv]

Genistein lessens inflammation in the kidneys, thus helping to prevent and treat kidney disease.[v], [vi], [vii]

Genistein lessens diabetes-related inflammation in blood vessels, nerves, and in the eyes (the retina, specifically).[viii], [ix]

Since inflammation plays such a key role in the production and activation of osteoclasts, it’s not surprising to learn that genistein helps prevent both, and in doing so, protects our bones.

Ipriflavone adds to genistein’s bone-protective benefits

But soy foods’ special benefits for bones don’t stop with genistein – the other major isoflavone in soy foods, ipriflavone, has also been shown—in many studies now — to prevent bone loss in postmenopausal women.

Soy isoflavone extracts have been shown to increase BMD in the spine – a recent meta-analysis (published in 2010) includes studies showing increases in spine BMD with isoflavone intake of more than 90 mg/day for 6 months of 28.5mg/cm(2) and 27 mg/cm(2). The authors of this review concluded: “Isoflavone intervention significantly attenuates bone loss of the spine in menopausal women. These favorable effects become more significant when more than 90 mg/day of isoflavones are consumed. And soy isoflavone consumption for 6 months can be enough to exert beneficial effects on bone in menopausal women.”[x]

The highly positive results of yet another recent study conducted on ipriflavone led the researchers to conclude that ipriflavone can inhibit bone resorption and promote bone formation, and is effective for the prevention and treatment of menopausal symptoms (hot flushes) as well as osteoporosis.[xi]

In the case of ipriflavone, the mechanism behind soy food’s bone protective effects is thought to be soy isoflavones’ chemical structure which is similar to that of human (bio-identical) estrogens (bi-est). Bio-identical hormone replacement therapy with bi-est is well known to increase BMD in menopausal women.[xii]

Why might this be? Again, a key way in which estrogen supports our ability to maintain healthy bones is by lessening inflammation, and thus osteoclast activation.[xiii]

The most recent (March 2012) medical journal paper to be published about the benefits of soy isoflavones for bone health is very impressive, in part because it is a “systematic review” – a meta-analysis of the results of many studies.[xiv]  This meta-analysis includes 14 randomized controlled trials that met the criteria of having their primary focus be the impact of soy isoflavones on osteoporosis in women.

What did these 14 trials show? Soy isoflavones significantly increased the bone mineral density (by 54%!) and decreased a marker of bone breakdown called urinary deoxypyridinoline (DPD) by 23% in the women in these studies, compared to where they were when the study began. The studies ranged in duration from just one month to two years. Greatest bone benefits were seen in postmenopausal women whose consumption of isoflavones, either in the form of supplements or as constituents of soy foods, was at least 75 mg/day.

Yet another even larger review, published December 2011, also looked at the impact of soy isoflavones on bone turnover markers in menopausal women – the time when bone loss accelerates to its highest pitch.[xv] This review was a meta-analysis of other meta-analyses of randomized controlled trials – so it included data from a lot of studies! The results: Soy isoflavones significantly decreased levels of the marker of bone breakdown noted above, deoxypyridinoline.  And, consuming soy isoflavones for just six months was long enough to significantly improve the women’s lumbar spine BMD.

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“Bone” appetite!

So, you’re probably wondering: Do I have to take a supplement or can I get 75-90 or even more mg of isoflavones per day by simply enjoying soy foods?

Good news – soy can help you eat our way to healthy bones. No need to spend money on a supplement. Just enjoy soy foods, and you can, as the table below shows—easily—get at least 75-90 mg of isoflavones each day.

Isoflavone Content of Commonly Eaten Soy Foods*

Food

Serving Size

Total  Isoflavones (mg)

Tempeh

3 ounces

37

Soybeans, dry roasted

1 ounce

37

Soybeans, boiled (Edamame)

½ cup

47

Soy milk

1 cup

30

Tofu

3 ounces

20

Soy “hot dog”

1 “soy dog”

11

Soy cheese, mozarella

1 ounce

2

*Adapted from Soy Isoflavones, Linus Pauling Institute, Micronutrient Information Center, accessed 4-15-12 @ http://lpi.oregonstate.edu/infocenter/phytochemicals/soyiso/

 

Be aware though that the isoflavone content of soy foods can vary considerably among brands and between lots of the same brand. However, the above values provide a decent estimate. Also, many brands list the amount of isoflavones they contain on the label.

One caveat – only consume ORGANIC soy. Soy foods not clearly labeled organic will be GMO – genetically modified. For lots of information on why you do not want to expose your body to GMO foods, here’s a link to the most comprehensive source of GMO health risk information on the web, the non-profit Institute for Responsible Technology: http://www.responsibletechnology.org/


References:

[i] Marini H, Minutoli L, Polito F, et al. OPG and sRANKL serum concentrations in osteopenic, postmenopausal women after 2-year genistein administration. J Bone Miner Res. 2008 May;23(5):715-20. PMID: 18433304
[ii] Maldonado-Rojas W, Olivero-Verbel J. Potential interaction of natural dietary bioactive compounds with COX-2. J Mol Graph Model. 2011 Sep;30:157-66. Epub 2011 Jul 12. PMID: 21803623
[iii] Babu PV, Si H, Fu Z, Zhen W, et al. Genistein Prevents Hyperglycemia-Induced Monocyte Adhesion to Human Aortic Endothelial Cells through Preservation of the cAMP Signaling Pathway and Ameliorates Vascular Inflammation in Obese Diabetic Mice.J Nutr. 2012 Apr;142(4):724-30. Epub 2012 Mar 7.PMID: 22399524
[iv] Ghiringhelli F, Rébé C, Hichami A, et al. Immunomodulation And Anti-Inflammatory Roles Of Polyphenols As Anticancer Agents. Anticancer Agents Med Chem. 2012 Jan 31. [Epub ahead of print] PMID: 22292769
[v] Elmarakby AA, Ibrahim AS, Faulkner J, et al. Tyrosine kinase inhibitor, genistein, reduces renal inflammation and injury in streptozotocin-induced diabetic mice. Vascul Pharmacol. 2011 Nov-Dec;55(5-6):149-56. Epub 2011 Jul 23. PMID: 2180712
[vi] Kim JM, Uehara Y, Choi YJ, et al. Mechanism of attenuation of pro-inflammatory Ang II-induced NF-κB activation by genistein in the kidneys of male rats during aging. Biogerontology. 2011 Dec;12(6):537-50. doi: 10.1007/s10522-011-9345-4. Epub 2011 Jun 29. PMID: 21713398
[vii] Palanisamy N, Kannappan S, Anuradha CV. Genistein modulates NF-κB-associated renal inflammation, fibrosis and podocyte abnormalities in fructose-fed rats. Eur J Pharmacol. 2011 Sep 30;667(1-3):355-64. Epub 2011 Jun 17. PMID: 21704028
[viii] Valsecchi AE, Franchi S, Panerai AE, et al. The soy isoflavone genistein reverses oxidative and inflammatory state, neuropathic pain, neurotrophic and vasculature deficits in diabetes mouse model. Eur J Pharmacol. 2011 Jan 15;650(2-3):694-702. Epub 2010 Nov 2. PMID: 21050844
[ix] Ibrahim AS, El-Shishtawy MM, Peña A Jr, et al. Genistein attenuates retinal inflammation associated with diabetes by targeting of microglial activation. Mol Vis. 2010 Oct 8;16:2033-42. PMID: 21042558
[x] Ma DF, Qin LQ, Wang PY, Katoh R. Soy isoflavone intake increases bone mineral density in the spine of menopausal women:meta-analysis of randomized controlled trials. Clin Nutr. 2008 Feb;27(1):57-64. Epub 2007 Dec 11.PMID: 18063230
[xi] Zhang X, Li SW, Wu JF, Dong CL, et al. Effects of ipriflavone on postmenopausal syndrome and osteoporosis. Gynecol Endocrinol. 2010 Feb;26(2):76-80. PMID: 19672742
[xii] Nielsen TF, Ravn P, Bagger YZ, et al. Pulsed estrogen therapy in prevention of postmenopausal osteoporosis. A 2-year randomized, double blind, placebo-controlled study. Osteoporos Int. 2004 Feb;15(2):168-74. Epub 2003 Nov 25.  PMID: 14647880
[xiii] Ratiani L, Parkosadze G, Cheishvili M, et al. Role of estrogens in pathogenesis of age-related disease in women of menopausal age. Georgian Med News. 2012 Feb;(203):11-6. PMID: 22466534
[xiv] Wei P, Liu M, Chen Y, Chen DC. Systematic review of soy isoflavone supplements on osteoporosis in women. Asian Pac J Trop Med. 2012 Mar;5(3):243-8. PMID: 22305793
[xv] Taku K, Melby MK, Nishi N, et al. Soy isoflavones for osteoporosis: an evidence-based approach. Maturitas. 2011 Dec;70(4):333-8. Epub 2011 Sep 29. PMID: 21958941


This article was written by Lara Pizzorno, author of “Your Bones”

Lara Pizzorno is a member of the American Medical Writers Association with 26+ years of experience writing for physicians and the public, am Editor of Longevity Medicine Review as well as Senior Medical Editor for SaluGenecists, Inc.More about Lara Pizzorno

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Posted in AlgaeCal Medical Advisors, Bone Health News, Featured, Osteoporosis Treatment News | Tagged , , , , , | 6 Replies
Lara Pizzorno

About Lara Pizzorno

A member of the American Medical Writers Association with 26+ years of experience writing for physicians and the public, am Editor of Longevity Medicine Review as well as Senior Medical Editor for SaluGenecists, Inc. In addition to reviewing the latest in longevity research for clinicians, Lara summarizes health & nutrition research for the Textbook of Natural Medicine e-dition, The World's Healthiest Foods (www.whfoods.org), Dr. Pizzorno's blog as WebMD's Integrative Medicine & Wellness Expert, and also blogs on EcoMii. Recent publications include: - Your Bones (Praktikos, April 2011) - Contributing author to the Textbook of Functional Medicine, (IFM, 2006) - Articles for Integrative Medicine: A Clinician's Journal (Innovisions Communications, Inc., 2005 through present) - Textbook of Natural Medicine (Elsevier, 2005, e-dition through present) - Lead author of Natural Medicine Instructions for Patients (Elsevier, 2002) - Co-author of The Encyclopedia of Healing Foods (Scribner's, 2005) - The World's Healthiest Foods Essential Guide for the healthiest way of eating (George Mateljan Foundation, 2006 through present) Lara graduated Phi Beta Kappa, magna cum laude from Wheaton College (Norton, MA, 1970), received her Master's in Religious Studies with Honors from Yale Divinity School (New Haven, CT, 1973), Master's in Literature from the University of Washington (Seattle, 1986), and has been a licensed massage therapist since 1986. Avocations include Pilates (currently working on Stott Pilates Instructor certification), motorcycling, organic gardening, healthy cooking. PublicationsYour Bones: How You Can Prevent Osteoporosis & Have Strong Bones for Life Naturally Book synopsis: When in her mid-forties, the author, now 63, was diagnosed with osteopenia--a loss of bone density that is the precursor to osteoporosis. Today, by following the recommendations discussed in this book, she has strong, healthy bones and will be the first woman in generations in her family not to die from osteoporosis. The bisphosphonate drugs prescribed for osteoporosis—eg Fosamax, Boniva -- should be your last choice: not only do they have numerous nasty side effects, they cause retention of old, brittle bone instead of creating new, healthy bone and actually promote fractures! Your Bones will teach you how to identify those factors in your life that are putting your bones at risk and will arm you with the cutting edge information you need to have healthy bones for life, naturally—relying on diet, exercise and supplements. Every statement this book is backed up with peer-reviewed medical research. Your Bones is an essential handbook for anyone wanting to prevent osteoporosis in later life. Available on Amazon

6 thoughts on “Latest Research Shows Soy Foods help Prevent Bone Loss

  1. Pingback: Vitamin K1 and K2 Boost Bone Formation, Lessen Bone Breakdown — AlgaeCal Bone Health Blog

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  3. jacki gutman on said:

    my osteoporosis is at the level of high risk for fracture. i have taken reclast x3yrs. & many other drugs with different results including, dexa improving for a yr. then falling. i took alot of soy products & became hypothyroid. when i reduced the soy intake , my thyroid became normal & stayed. i am fearful of taking soy but can get natto at my local asian store . how much should i take & how often. my doctor is pushing prolia….

    • Hi Jacki,res
      If you react to soy, natto is NOT a good idea for you. Take your K2 as a supplement (MK-7 form has been shown effective in the peer reviewed research at a very low dose, only 100 mcg/day. MK-7 would definitely be preferable for you rather than the MK-4 form for which the dose shown effective in the research is 15 mg/3 times per day.

  4. Nance Lee on said:

    Thanks! I was looking for data on soymilk vs cowmilk – hoping to reduce inflammation in a couple of troublesome joints. I have chondromalacia patellar in one knee and a healing metacarpal thumb fracture in one hand. Inflammation is not my friend!

    PS I think you mean “if you are among those who are allergic to MILK” in your first sentence.

    Thanks again!

    • Hi Nance,
      I have two suggestions for your joint inflammation –(1) N-acetyl-D-Glucosamine — this is the form into which our bodies convert glucosamine hydrochloride or glucosamine sulfate supplements before the glucosamine is able to be utilized within joint tissue. N-acetyl D-glucosamie is available as a supplement called Ultimate Glucosamine. I have NO CONNECTION with the company that produces this product; I met key doctors involved with this company at an A4M conference about 5 years ago now where the medical journal for which I am the Editor, Longevity Medicine Review, had a booth. At the time, I was wearing a brace on my left hand because my thumb joint was so inflamed (supposedly degenerative arthritis) that I could hardly use my hand. Within about 3 months of using Ultimate Glucosamine, my thumb joint was noticeably improved. Within 6 months, all pain was gone — and remains so. I continue to use Ultimate Glucosamine. You can find this product on line by doing a Google search for Ultimate Glucosamine.
      (2) Gluten intolerance is very frequently a cause of chronic joint inflammation. Go off all gluten containing grains for 6-8 weeks and see if your joint pain lessens. Gluten-containiing grains include not just wheat, but oats (unless labeled as gluten free), spelt, kamut, rye, and barley. Many processed food products contain gluten; you will need to read labels carefully on any processed foods you purchase; gluten hides out in products where you would not expect to find it, e.g., most ketchups and pizza sauces, soy sauce, even beer!

      In the first sentence you refer to in the Soy Foods Help Prevent Bone Loss post, I did not mean to limit reactions to soy to only soy milk. The issue is an immune response to the protein in soybeans — all food products made with soy beans will cause problems for persons who are intolerant to soy.

      Very much hope these suggestions are helpful, Lara

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