As soy isoflavone intake increased, the risk of death decreased. Women at the highest levels of soy isoflavone intake (> 16.3 mg isoflavones/day) had a 54% reduction in risk of death.

Commentary: This is the third epidemiologic study to report no adverse effects of soy foods on the prognosis of breast cancer. Soy foods, which contain isoflavones, a phytoestrogen, show both antiestrogenic and estrogen-like properties. The confusion and controversy has been that many studies have shown that isoflavones may protect against an initial breast cancer but in a very few laboratory studies certain isoflavone components of soy have been able to enhance the proliferation of breast cancer cells in select doses, and have been able to both promote and inhibit mammary tumor growth in rats.

However, in 2009, some clarity began to emerge for breast cancer patients. In breast cancer survivors, one study in Asian women (the Shanghai Breast Cancer Survival Study) and the other in U.S. women (the Life after Cancer Epidemiology study), suggest that soy containing foods do not negatively affect breast cancer prognosis, do not counteract the effect of the breast cancer drug tamoxifen and may in fact provide potential benefits in decreasing risk of recurrence or death from breast cancer.

The current study has explored this issue further, by examining data from a randomized controlled trial, the WHEL study. The results of this study, and the two previous in 2009, should give practitioners and women alike, great reassurance in the safety of soy consumption for women with who have/have had a diagnosis of breast cancer. We no longer need to advise against soy consumption for breast cancer survivors. This is great news given all the potential health benefits of soy for bone health, cardiovascular health and soy as a part of a whole foods and healthy diet.

Reference

Caan B, Natarajan L, Parker B, et al. Soy food consumption and breast cancer prognosis. Cancer Epidemiol Biomarkers Prev 2011;20(5):854-858.

In each of the studies, women who consumed the highest dietary intake of soy had a lower risk for endometrial and ovarian cancers compared with the women who had the lowest intake.

Commentary: It is not surprising to see this report as we have seen previous observational studies with similar results, showing lack of endometrial proliferation, endometrial safety and/or reduced risk of endometrial cancer. Only one previous study that I’m aware of, did demonstrate that after 5 years, but not after one year or 3 years, who were given 150 mg per day of soy isoflavone tablets had an increased occurrence of endometrial hyperplasia (but no cases of atypical hyperplasia or endometrial cancer).[ii]

The mechanisms whereby soy appears to have an influence on lowering the risk of hormonal cancers, including breast, appear to be multiple. These include: through its ability to bind to certain estrogen receptors and actually have an estrogen blocking effect, raising sex hormone-binding globulin which decreases circulating estrogens, affecting selected enzyme pathways which result in anti-carcinogenic effects, direct tumor growth inhibition, and having antioxidant effects.

My advice: for most women, and for those who are not allergic to soy or have indigestion with soy products, I recommend 1-2 servings per day of the following soy foods: cooked soy beans, roasted soy nuts, soy milk, tofu, tempeh, edamame, tofu pate (my favorite).

[i] Myung S- K et al. Soy intake and risk of endocrine-related gynaecological cancer: A meta-analysis. BJOG 2009 Dec; 116:1697

[ii] Unfer V, et al. Endometrial effects of long-term treatment with phytoestrogens: a randomized, double-blind, placebo-controlled study. Fertility and Sterility 2004;82:145-148). 150 mg of soy isoflavones per day is above the average intake in an Asian diet (ranging from about 40-90 mg per day

Soybeans contain a class of compounds called phytoestrogens, comprising mostly genistein, daidzein and glycitein, all of which have a biochemical structure similar to 17- beta estradiol.  The binding of isoflavones to estrogen receptors is preferential for the estrogen receptor beta and thus indicates that soy isoflavones act as selective estrogen modulators.  Daidzein is similar in shape to a drug called Ipriflavone, which is used in Europe to treat osteoporosis.  In the U.S., Ipriflavone is available as a nutritional supplement. 

Bone mineral density (BMD) is the gold standard for determining fracture risk due to non-traumatic events.  Bone turnover is an independent predictor of fracture risk.  While research on the effects of soy on bone metabolism has been inconsistent, many positive studies do exist that suggest a role for soy in slowing bone turnover and increasing bone density in women.  Soy appears to have an estrogenic effect on bone in some experimental evaluations. The bone density of ovariectomized rats was evaluated in a study in which soy replaced casein in the diet and compared to another group that received estrogen. The addition of soy inhibited bone loss, although not to the same extent as was achieved with the estrogen treatment.  Another study of ovariectomized rats also reported a positive effect of the soy phytoestrogen, genistein in maintaining bone.  These authors also reported that genistein suppresses osteoclasts, the cells responsible for bone resorption, both in the test tube and in vivo.  Arjmandi also did a double-blind, randomized, and controlled trial using 40g of soy protein containing isoflavones over 3 months in postmenopausal women.  Bone resorption was decreased, when compared to milk protein.

Several human studies have provided further insight and comfort in the possible role of soy in our bone health. A study conducted at the University of Illinois found that menopausal women had an increase in mineral levels and density in their lumbar spines after taking 55-90 mg of soy isoflavones for six months.  The placebo group showed the lowest bone density and the greatest bone loss, while the estrogen group showed the highest bone density and the slowest bone loss. What was surprising was that the isoflavone diet was effective in preventing bone loss in the fourth lumbar vertebra and, although less so, in the right hip. Soy isoflavones seem to have more of an effect on trabecular bone (more predominant in the spine) than on cortical bone (more predominant in the hip). The soy did not show as great of ability in preventing bone loss as the estrogen group, but the positive effect it showed is encouraging. 

An analysis of the relationship of soy isoflavone intake and bone mineral density was conducted from the Study of Women’s Health Across the Nation, a US cohort study of women aged 42-52 years.  For African-American and Caucasian women, median intakes of genistein were too low to pursue analyses. For Chinese women, no association between genistein and bone mineral density was found. Premenopausal, but not perimenopausal Japanese women whose intakes were greater had a higher bone density of the spine and femoral neck. The mean spinal bone density of those women in the highest group was 7.7% greater than that of women in the lowest group. Bone density of the femoral neck was 12% greater in the highest intake group versus the lowest.
 
Other positive studies on soy and bone density also give some credence to the role of soy and bone health. In a study estimating the daily intakes of soy isoflavones in the diets of 478 postmenopausal Japanese women who reported soy consumption, high consumption of soy products was associated with increased bone mass.

A recent meta-analysis further increases our optimism about using soy to inhibit bone resorption.  Nine studies with a total of 432 menopausal women were evaluated in this meta-analysis.  Amount of soy intake varied amongst the nine studies from 37 mg of isoflavones per day to 118 mg of isoflavones per day. Testing for urinary peptides (deoxypyridinoline), a marker of bone turnover, demonstrated that those who consumed isoflavones had a decrease in these biomarkers of -2.08nmol/mmol, when compared to those who did not consume isoflavones.  In five of the studies where isolated soy protein was used there was no significant effect on urinary deoxypyridinoline.  In the current analysis, a significant reduction in urinary deoxypyridinoline was not observed in those studies with isoflavones of less than 90 mg/day.  In a review of the research in 2003, the author concluded that 90 mg of isoflavones per day is required to achieve benefits on bone health.

In contrast to the positive studies, several clinical trials using a variety of soy protein isolate formulations found no clinically important effects of soy on bone metabolism and bone turnover markers.  Further inconsistent research can be seen with several clinical trials using soy protein or isoflavones demonstrating a positive effect on BMD, while others have not had positive findings.

I mentioned variations in dosing, duration, soy formulations used, and different study populations as possible reasons for inconsistent results on the effects of soy isoflavones on bone turnover and bone density.  But, another significant consideration may be due to how the isoflavones are metabolized in the gut.  In the meta-analysis mentioned above which analyzed nine studies the significant effects on urinary peptides occurred in Asian women but not Caucasian women.  This may be due to the conversion of daidzein into its active metabolite equol by intestinal flora, and by the fact that only one-third of Caucasian women can metabolize isoflavones into equol, whereas more than half of Asian women possess this ability. 

Soy isoflavones may also have more of an effect in post-menopausal women than in pre or perimenopausal women.  In one study, 53.3 mg of isoflavones per day was associated with an increase in bone density in postmenopausal women, but not pre-menopausal women.

A nutritional influence of soy foods that may be overlooked is the amount of calcium in some of these foods or in diets that contain soy foods. A diet that includes greater amounts of soy products can account for a meaningful amount of calcium, and some soy foods can offer as much, or more, calcium than a serving of dairy products.
 

CALCIUM CONTENT OF SELECTED SOY FOODS

With the inconsistent research, it is difficult to draw confident conclusions about the role of soy in bone health.  My clinical advice is to increase soy foods as part of a regular diet in prevention strategies for all pre, peri and postmenopausal women.  For all women who have significant risk factors for osteoporosis, I would in addition, recommend soy supplementation so that their total daily soy isoflavone intake would deliver approximately 90 mg of soy isoflavones per day.  For treatment of peri and postmenopausal women who already have osteoporosis, I would not consider soy an adequate treatment alone.  For these women who already have osteoporosis, I am in favor of proven conventional therapies to reduce fracture risk in addition to the 90 mg per day of soy isoflavones and typical supplementation including calcium, vitamin D and other potential nutrients (K, boron, magnesium, manganese, and more), and dietary and exercise advice.

References
  Weaver C, Cheong J.  Soy isoflavones and bone health: the relationship is still unclear.  J Nutr 2005; 135:1243-1247.

  Setchell K.  Soy isoflavones-benefits and risk from nature’s selective estrogen receptor modulators (SERMS).  J Am Coll Nutr 2001; 20: 354S-362S.

  Garnero P, Hausherr E, Chapuy M, et al.  Markers of bone resorption predict hip fracture in elderly women: the EPIDOS Prospective Study.  J Bone Miner Res 1996; 11:1531-1538.

  Arjmandi B, Alekel L, Hollis B, Amin D, Stacwicz-Sapuntzakis M, Guo, Kukreja S.  Dietary soybean protein prevents bone loss in an ovariectomized rat model of osteoporosis.  J Nutr 1996;126:161-167.

  Blair H, Jordan S, Peterson T, Barnes S.  Variable effects of tyrosine kinase inhibitors on avian osteoclastic activity and reduction of bone loss in ovariectomized rats. J Cell Biochem  1996;61:629-637.

  Arjmandi B, Khalil D, Smith B, et al.  Soy protein has a greater effect on bone in postmenopausal women not on hormone replacement therapy, as evidenced by reducing bone resorption and urinary calcium excretion. J Clin Endocrinol Metab  2003; 88: 1048-1054.

  Erdman J, Stillman R, Lee K, Potter S.  Short-term effects of soybean isoflavones on bone in postmenopausal women.  Program and Abstract Book, Second International symposium on the Role of Soy in Preventing and Treating Chronic Disease.  Brussels, Belgium, 1996.

  Greendale G, FitzGerald G, Huang M, et al.  Dietary soy isoflavones and bone mineral density: Results from the study of women’s health across the nation. Amer J Epidemiology 2002;155(8):746-754.

  Somekawa Y, Chiguchi M, Ishibashi T, Takeshi A. Soy intake related to menopausal symptoms, serum lipids, and bone mineral density in postmenopausal Japanese women. Obstet Gynecol  2001;97:109-115.

  Ma DF, Qin LQ, Want P-Y, Katoh R.  Soy isoflavone intake inhibits bone resorption and stimulates bone formation in menopausal women:  meta-analysis of randomized controlled trials.  European J of Clinical Nutrition 2008; 62:155-161.

  Branca F.  Dietary phyto-oestrogens and bone health.  Proc Nutr Soc 2003; 62: 877-887.

  Wangen K, Duncan A, Merz-Demlow B, et al.  Effects of soy isoflavones on markers of bone turnover in premenopausal and postmenopausal women.  J Clin Endocrinol Metab 2000; 85:3043-3048.

  Knight D, Howes J, Eden J, Howes L.  Effects of menopausal symptoms and acceptability of isoflavone-containing soy powder dietary supplementation. Climacteric 2001; 4:13-18.

  Dalais F, Ebeling P, Kotsopoulos D, McGrath B, Teede H.  The effects of soy protein containing isoflavones on lipids and indices of bone resorption in postmenopausal women.  Clin Endocrinol 2003; 58:704-709.

  Potter S, Baum J, Teng H, et al.  Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women.  Am J Clin Nutr 1998; 68:1375S-1379S.
  Alekel D, Germain A, Peterson C, et al.  Isoflavone-rich soy protein attenuates bone loss in the lumbar spine of perimenopausal women.  Am J Clin Nutr 2000; 72:844-852.

  Morabito N, Crisafulli A, Vergara C, et al.  Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women:  a randomized double-blind placebo controlled study. J Bone Miner Res 2002; 17:1904-1912.

  Chen Y, Ho S, Lam S, Ho S, Woo J.  Soy isoflavones have a favorable effect on bone loss in Chinese postmenopausal women with lower bone mass: a double-blind, randomized, controlled trial. J Clin Endocrinol Metab 2003;88:4740-4747.

  Lydeking-Olsen E, Beck-Jensen J, Setchell K, Holm-Jensen T.  Soymilk or progesterone for prevention of bone loss: a 2 year randomized, placebo-controlled trial. Eur J Nutr 2004;43:246-257.

  Gallagher J, Satpathy R, Rafferty K, Haynatzka V.  The effect of soy protein on bone metabolism.  Menopause 2004; 11:290-298.

  Kreijkamp-Kaspers S, Kok L, et al.  Effects of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women.  JAMA 2004; 292:65-74.

  Mei J, Yeung S, Kung A.  High dietary phytoestrogen intake is associated with higher bone mineral density in postmenopausal but not premenopausal women. J Clin Endocrinol Metab 2001; 86:5217-5221.

Compared with the placebo group, symptoms of hot flashes and excessive sweating significantly reduced after 3 months and weakness, palpitations, limb paresthesias and total symptoms significantly decreased after 6 months, (P< 0.05) but only in the equol producers. At 3 months, total scores had decreased by 66% in the EP group, 54% in the non-EP group and 59% in the placebo group. At 6 months, symptom scores had decreased by 84% in the EP group, 58%in the non-EP group and 66 % for the placebo group.

Jou H-J, Wu S-S, Change F-W, Ling P-Y, Chue K, Wu W-H. Effect of intestinal production of equol on menopausal symptoms in women treated with soy isoflavones. Intl J Gynecology and Obstetrics (2008), doi: 10.1016/j.ijgo. 2008.01.028

Commentary: The research on soy’s ability to relieve menopause symptoms has produced quite mixed results. Differences in study doses, different proportions of genistein and daidzein used in the study medication, and differences in the study population have been used to explain the discrepancies. Study populations who may have a higher percentage of women who are equol producers have been previously suspected to be the determining factor in the effectiveness of soy isoflvaones, but the current study seems to be the first to demonstrate more clearly that a woman’s ability to produce equol determines her response to soy isoflavone supplementation. Daidzein and genestien are the two most significant phytoestrogens in soy. Daidzein is converted to equol, a metabolite of daidzein, by bacterial flora in the gut. It may be appropriate to test for equol production prior to treatment of perimenopausal and menopausal women to achieve the most success, and/or improve gut flora so that the individuals can more easily transform soy isoflavones to equol. This can be done with improving one’s diet to whole foods nutrition, reducing sugar to a minimum, consuming mostly unsaturated fats, and possibly taking probiotics as a nutritional supplement or in quality yogurts.

Soybeans contain a class of compounds called phytoestrogens, comprising mostly genistein, daidzein and glycitein, all of which have a biochemical structure similar to 17 beta estradiol. The binding of isoflavones to estrogen receptors is preferential for the estrogen receptor beta and thus indicates that soy isoflavones act as selective estrogen modulators. Daidzein is similar in shape to a drug called Ipriflavone which is used in Europe to treat osteoporosis. In the U.S., Ipriflavone is available as a nutritional supplement.

Bone mineral density (BMD) is the gold standard for determining fracture risk due to nontraumatic events. Bone turnover is an independent predictor of fracture risk.

While the effects of soy on bone metabolism has been inconsistent, many positive studies do exist that suggest a role for soy in slowing bone turnover and bone density in women. Soy appears to have a pro estrogen effect on bone in some experimental evaluations. The bone density of ovariectomized rats was evaluated in which soy replaced casein in the diet, compared to another group that received estrogen. The addition of soy inhibited bone loss, although not to the same extent as was achieved with the estrogen treatment. Another study of ovariectomized rats also reported a positive effect of the soy phytoestrogen genistein in maintaining bone. These authors also reported that genistein suppresses the bone losing cells (osteoclasts), both in the test tube and in vivo. Arjmandi also did a double-blind, randomized, controlled trial using 40g of soy protein containing isoflavones over 3 months in postmenopausal women. Bone resorption was decreased, when compared to milk protein.

Several human studies have provided further insight and comfort in the possible role of soy in our bone health. A study conducted at the University of Illinois found that menopausal women had an increase in mineral levels and density in their lumbar spines after taking 55-90 mg of isoflavones for six months. The placebo group showed the lowest bone density and the greatest bone loss, while the estrogen group showed the highest bone density and the slowest bone loss. What was surprising was that the soybean diet was effective in preventing bone loss in the fourth lumbar vertebra and, although less so, in the right hip as well. Soybean seems to have more of an effect on trabecular bone (more predominant in the spine) than on cortical bone (more predominant in the hip). The soy did not show as great an ability in preventing bone loss as the estrogen group, but the positive effect it showed is encouraging.

A study of the relation of soy isoflavone intake and bone mineral density was conducted within the Study of Women’s Health Across the Nation, a US cohort study of women aged 42-52 years. For African-American and Caucasian women, average intakes of genistein was too low to pursue analyses. For Chinese women, no association between genistein and bone mineral density was found. Pre-menopausal, but not peri-menopausal, Japanese women whose intakes were greater had a higher bone density of the spine and femoral neck. Mean spinal bone density of those women in the highest group was 7.7% greater than that of women in the lowest group. Bone density of the femoral neck was 12% greater in the highest intake group versus the lowest.

Other positive studies on soy and bone density also give some credence to the role of soy and bone health. In a study estimating the daily intakes of soy isoflavones in the diets of 478 postmenopausal Japanese women who reported soy consumption, high consumption of soy products was associated with increased bone mass.

A very recent analysis of nine studies further increases our optimism about using soy to inhibit bone resorption. Nine studies with a total of 432 menopausal women were evaluated for meta-analysis. Amount of soy intake varied amongst the nine studies from 37 mg of isoflavones per day to 118 mg of isoflavones per day. Testing for urinary peptides (deoxypyridinoline) of bone turnover demonstrated that when all nine study results are combined, those who consumed isoflavones had a decrease in these biomarkers of -2.08 nmol/mmol when compared to those who did not consume isoflavones. In five of the studies, isolated soy protein was used, as a group, there was no significant effect on urinary deoxypyridinoline. In the current analysis, significant reduction in urinary deoxypyridinoline did not occur in those studies with isoflavones of less than 90 mg/day. In a review of the research in 2003, the author concluded that 90mg of isoflavones per day is required to achieve benefits on bone health.

In contrast to the positive studies, several clinical trials using a variety of soy protein isolate formulations found no clinically important effects of soy on bone metabolism and bone turnover markers. Further inconsistent research can be seen with several clinical trials using soy protein or isoflavones demonstrating a positive effect on BMD, while others have not had positive findings.

I mentioned variations in dosing, duration, soy formulations used, and different study populations as possible reasons for inconsistent results on the effects of soy isoflavones on bone turnover and bone density. But, another significant consideration may be due to how the isoflavones are metabolized in the gut. In the recent study mentioned about analyzing nine studies 10 the significant effects on urinary peptides occurred in Asian women but not Caucasian women. This may be due to the conversion of isoflavones into its active metabolite equol in intestinal flora, and that only one-third of Caucasian women can metabolize isoflavones into equol, whereas more than half of Asian women possess this ability.

Soy isoflavones may also have more of an effect in post-menopausal women than in pre or perimenopausal women. In one study, 53.3 mg of isoflavones per day was associated with an increase in bone density in postmenopausal women, but not pre-menopausal women.

An area of soy foods that may be overlooked, is the amount of calcium in some soy foods. A diet that includes greater amounts of soy products can account for a meaningful amount of calcium, and some soy foods can offer as much or more calcium than a serving of dairy products.

With the inconsistent research, it is difficult to draw confident conclusions about the role of soy in bone health. My clinical advice is to increase soy foods as part of a regular diet in prevention strategies for all pre, peri and postmenopausal women. For all women who have significant risk factors for osteoporosis, I would in addition, recommend soy supplementation so that their total daily soy isoflavone intake would deliver approximately 90 mg of soy isoflavones per day. For treatment of peri and postmenopausal women who already have osteoporosis, I would not consider soy an adequate treatment alone. In addition to the 90 mg per day of soy isoflavones and typical supplementation including calcium, vitamin D and other potential nutrients (K, boron, magnesium, manganese, and more), dietary and exercise advice, for these women who already have osteoporosis, I am in favor of proven conventional therapies to reduce fracture risk.

References

• Weaver C, Cheong J. Soy isoflavones and bone health: the relationship is still unclear. J Nutr 2005; 135:1243-1247.
• Setchell K. Soy isoflavones-benefits and risk from nature’s selective estrogen receptor modulators (SERMS). J Am Coll Nutr 2001; 20: 354S-362S.
• Garnero P, Hausherr E, Chapuy M, et al. Markers of bone resorption predict hip fracture in elderly women: the EPIDOS Prospective Study. J Bone Miner Res 1996; 11:1531-1538.
• Arjmandi B, Alekel L, Hollis B, Amin D, Stacwicz-Sapuntzakis M, Guo , Kukreja S. Dietary soybean protein prevents bone loss in an ovariectomized rat model of osteoporosis. J Nutr 1996;126:161-167.
• Blair H, Jordan S, Peterson T, Barnes S. Variable effects of tyrosine kinase inhibitors on avian osteoclastic activity and reduction of bone loss in ovariectomized rats. J cell Biochem. 1996;61:629-637.
• Arjmandi B, Khalil D, Smith B, et al. Soy protein has a greater effect on bone in postmenopausal women not on hormone replacement therapy, as evidenced by reducing bone resorption and urinary calcium excretion. J Clin Endocrinol Metab 2003; 88: 1048-1054.
• Erdman J, Stillman R, Lee K, Potter S. Short-term effects of soybean isoflavones on bone in postmenopausal women. Program and Abstract Book, Second International symposium on the Role of Soy in Preventing and Treating Chronic Disease. Brussels, Belgium, 1996.
• Greendale G, FitzGerald G, Huang M, et al. Dietary soy isoflavones and bone mineral density: Results from the study of women’s health across the nation. Amer J Epidemiology 2002;155(8):746-754.
• Somekawa Y, Chiguchi M, Ishibashi T, Takeshi A. Soy intake related to menopausal symptoms, serum lipids, and bone mineral density in postmenopausal Japanese women. Obstet Gynecol 2001;97:109-115.
• Ma D-F, Qin L-Q, Want P-Y, Katoh R. Soy isoflavone intake inhibits bone resorption and stimulates bone formation in menopausal women: meta-analysis of randomized controlled trials. European J of Clinical Nutrition 2008; 62:155-161.
• Branca F. Dietary phyto-oestrogens and bone health. Proc Nutr Soc 2003; 62: 877-887.
• Wangen K, Duncan A, merz-Demlow B, et al. Effects of soy isoflavoens on markers of bone turnover in premenopausal and postmenopausal women. J Clin Endocrinol Metab 2000; 85:3043-3048.
• Knight D, Howes J, Eden J, Howes L. Effects of menopausal symptoms and acceptability of isoflavone-containing soy powder dietary supplementation. Climacteric 2001; 4:13-18.
• Dalais F, Ebeling P, Kotsopoulos D, McGrath B, Teede H. The effects of soy protein containing isoflavones on lipids and indices of bone resorption in postmenopausal women. Clin Endocrinol 2003; 58:704-709.
• Potter S, Baum J, Teng H, et al. Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr 1998; 68:1375S-1379S.
• Alekel D, Germain A, Peterson C, et al. Isoflavone-rich soy protein attenuates bone loss in the lumbar spine of perimenopausal women. Am J Clin Nutr 2000; 72:844-852.
• Morabito N, Crisafulli A, Vergara C, et al. Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: a randomized double-blind placebo controlled study. J Bone Miner Res 2002; 17:1904-1912.
• Chen Y, Ho S, Lam S, Ho S, Woo J. Soy isoflavones have a favorable effect on bone loss in Chinese postmenopausal women with lower bone mass: a double-blind, randomized, controlled trial. J Clin Endocrinol Metab 2003;88:4740-4747.
• Lydeking-Olsen E, Beck-Jensen J, Setchell K, Holm-Jensen T. Soymilk or progesterone for prevention of bone loss: a 2 year randomized, placebo-controlled trial. Eur J Nutr 2004;43:246-257.
• Gallagher J, Satpathy R, Rafferty K, Haynatzka V. The effect of soy protein on bone metabolism. Menopause 2004; 11:290-298.
• Kreijkamp-Kaspers S, Kok L, et al. Effects of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women. JAMA 2004; 292:65-74.
• MeiJ, Yeung S, Kung A. High dietary phytoestrogen intake is associated with higher bone mineral density in postmenopausal but not premenopausal women. J Clin Endocrinol Metab 2001; 86:5217-5221

The TLC diet plus soy nuts was associated with a 45% decrease in hot flashes, when compared to the TLC diet alone, in women with > 4.5 hot flashes per day. With treatment, there were 4.1 hot flashes per day in the TLC plus soy nut group vs 7.5 hot flashes per day in the TLC diet alone group. Soy nuts were also associated with a significant improvement in other menopausal symptom quality of life issues including psychosocial scores.

Welty F, Lee K, Lew N, et al. The association between soy nut consumption and decreased menopausal symptoms. J Women’s Health 2007;16(3): 361-369

Commentary: Numerous previous studies have shown inconsistent reductions in menopausal symptoms with soy preparations, whether it be soy foods, soy beverage, soy powders or soy isoflavone capsules/tablets. In this study, it may be that the complex of a whole soy bean with a significant amount of soy protein and isoflavones were responsible for greater relief relative to most other studies. This study was not blinded, so a placebo response must be considered.