ALLNatural Smooth Change

Reduce the Symptoms of Menopause

Genistein, a compound present in ALLNatural Smooth Change, starts to reduce the incidence of hot flushes within one month of supplementation and after 12 months of usage reduces flushes by 56%. Many studies have shown that Genistein can help reduce hot flushes and night sweats in postmenopausal women.

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The Health Benefits of ALLNatural Smooth Change

Soy isoflavones are the principle components of Smooth Change. They are phytoestrogens (plant estrogens) that are found in soybeans. Soy isoflavones have been safely consumed for centuries in Asia and have many health benefits.

Soy Isoflavones reduce the frequency and severity of hot flushes in pre- and post-menopausal women and provide an excellent alternative to hormones.  Other benefits of Soy Isoflavones include:

Bone Health

After menopause, bone reabsorption (breakdown) outpaces the building of new bone. Soy isoflavones provide an excellent means of maintaining bone health and reducing incidence of breaks and fracture.

Heart Disease

A daily intake of soy isoflavones may decrease blood cholesterol by 10% and reduce the risk of coronary heart disease by up to 30%.

Blood Pressure

Soy isoflavones have been shown to help reduce blood pressure in hypertensive (high blood pressure) populations.

Cancer

Soy isoflavones result in lower incidence of cancers, particularly the hormone related cancers including breast, colon and prostate cancers.

Viral Infection

The isoflavone, genistein, has been shown to have anti-virus activity against the common cold and other viruses.

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Authorized for Sale by Health Canada

ALLNatural Smooth Change is of high quality, high strength and non-GMO. ALLNatural Nutritional Products Inc. has been issued a Natural Product Number (NPN 80023124), a requirement by Health Canada for the sale of nutraceuticals. This number insures you that the product has been reviewed and approved by Health Canada and it is safe, effective and of high quality.

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Frequently Asked Questions

Soy isoflavones are a group of phytoestrogens (plant estrogens) found in soybeans. Soy isoflavones have been consumed for centuries in Asia and have been shown to have many benefits that apply to bone health, heart disease, cancer protection, and menopausal symptoms.

Labels on some isoflavone supplements may be incomplete, confusing or inaccurate. Many products list the weight of both types of isoflavones (aglycone and glycoside form), not the weight of the aglycone that serves as the active ingredient. Health Canada requires that the content of isoflavones, as given on the label, be reported as their aglycone content. Some products labels provide no information about the amounts of isoflavone present and, if they do, they are often incorrect.

Nurmi et al. (2002) analyzed 15 products for their isoflavone content. One of the 15 products contained the level of isoflavones claimed with the values of most products being 30 to 50% of those claimed. The four products that did not make claims for their content of isoflavones had very low concentrations of isoflavones (usually only 10% of the others). This data clearly suggests that many isoflavone products do not contain the claimed amount of isoflavones .HPLC analysis is considered to be the good standard for isoflavone analysis. Also, many products that are currently being sold are not licensed for sale by Health Canada. Health Canada requires that all nutraceutical products be issued a Natural Product Number (NPN), that this number be given on the label, and that the daily recommended dose and reported form of the product be correct. Consumers should only purchase products that have been issued a NPN by Health Canada and are produced by a reputable Company.

Yes. Total isoflavones content must be expressed in aglycone isoflavone equivalents (AIEs) on the product label and in the potency section of the Health Canada Product Licence Application (PLA) with claims being made on their beneficial bone health effects. Additionally, genistein/genistin compounds (including genistein, genistin, acetyl genistin, and malonyl genistin) content must also be expressed in AIEs on the product label and in the potency section of the PLA when claims are being made on its ability to reduce the severity of menopausal symptoms. The recommended total isoflavones intake is 75-125 mg AIE, per day. Please see Health Canada’s website for more information.

Many studies have attempted to identify the factors in soy protein responsible for its effect on thyroid function in animals and humans, but with conflicting results.

Several clinical trials in pre-menopausal and post-menopausal women with sufficient iodine intakes and high intakes of soy isoflavones demonstrated that there are no clinically significant changes in circulating thyroid hormone levels.  In another study, it concluded that soy supplementation did not affect thyroid end points. Seven weeks of 5g/day seaweed supplementation, a good source of iodine, was associated with a small but statistically significant increase in TSH. They concluded that soy protein isolate supplementation which contains soy isoflavones was not associated with changes in serum thyroid hormone concentrations.

The beneficial effects of soy isoflavones are supported by a Meta-analysis carried out by Taku et al. Asia Pac J Clin Nutr 19(1):33-34, 2010. They analysed results involving 1240 menopausal women on the effects of ingesting soy isoflavones (SIF) on lumbar spine bone mineral density (BMD). This combination analysis of 11 previous scientific studies currently has provided the most comprehensive and accurate assessment of the benefits of SIFs for bone health.

The Meta-analysis demonstrated that ingestion by menopausal women of about 82 mg of SIF (in the aglycone form) per day for 6 to 12 month significantly increased spine BMD by 12.4% compared with the controls without SIF (p<0.001, a probability of being wrong in only in 1 in 1,000 trials). No adverse effects were observed. The authors concluded that their “Meta-analysis suggests that soy isoflavone supplements can be used not only to offset the bone loss that occurs naturally in women after menopausal, but are also applicable for complementary or alternative use in patients with post-menopausal osteoporosis who are unwilling to take or unable to tolerate the side effects of estrogen or/and biophosphonate therapies”.

In the above studies the intake of calcium and vitamin D met daily requirements.

Science and Research

Summary of the Literature on Soy Isoflavones

Soy products have been consumed for centuries in Asia and have been shown to have many health promoting benefits.

Soy isoflavones (SIFs) belong to a class of diphenol phytoestrogens (plant estrogens) that occur naturally in plants such as soybeans. Most SIFs contain a mixture of compounds based on the three basic isoflavones with the common names genistein, daidzein and glycitein with the first two being the most important. These forms do not contain glucose and other esters and are called aglycones (isoflavones without glucose residues).

Health Canada requires that all products in the market report the content of isoflavones as their content of aglycones as this provides a simple means of directly comparing different products. The SIFs have structural and functional similarities to human estrogen (17ß-estrodiol) but in contrast to 17ß-estrodiol they have both weak estrogenic and weak anti-estrogenic effects, both of which are beneficial.

SIFs have been shown to have protective effects against a number of clinical diseases including bone disease (osteoporosis), menopausal symptoms of hot flushes, coronary heart disease and several different cancers, especially those that are hormonally induced.

The scientific evidence has confirmed the safety of SIF at levels typically consumed in soy-based diets. It has also been shown that SIF intake does not adversely affect thyroid function in healthy individuals. There have been more than 3000 scientific peer reviewed publications on isoflavones since 2000 (Google Scholar) which is an indication of their importance to human health and well being.

Amount and Duration of Soy Isoflavones Intake

Soy isoflavones, in order to receive their full benefits, should be taken over long periods of time at the Health Canada recommended a rate of 100 mg/day (aglycone equivalent) or 2 capsules/day.

ALLNatural Nutritional Products Inc. has been issued a licence from Health Canada to market its soy isoflavones under the brand names of Bone Health and Smooth Change. The Natural Health Product Numbers (NPNs), a requirement for sale of the products, are 80016300 and 80023124.

The following sections provide detailed information as taken from the recent scientific literature on what soy isoflavones are, their mode of action in the body and their beneficial effects and safety. A link to the abstract and in some cases the full publication can be accessed by clicking on the quoted reference. The list of topics is given in the Table of contents.

Soy products have been consumed for centuries in Asia and have been shown to have many health benefits. Fifty years ago, the US and Canadian consumers did not care about soy or its active components, the isoflavones. But now are taking soy pills, soy milk, soy energy bars, soy supplements, etc., in large quantities.

By 2005, North Americans were spending about $4.7 billion on soy foods; an 844% increase over 1990 (Consumer Reports, 2004). The reason for this large increase in intake of soy supplements is that a large body of evidence shows that soy and its products have many health benefits for most people, especially the isoflavones that are a natural constituent of soy. ANNP’s products provide a convenient means of obtaining the recommended daily intake of soy isoflavones.

Soy isoflavones belong to a class of diphenol compounds known as phytoestrogens (plant estrogens) that occur naturally in many plants, of which there are approximately 230 individual types. They are most commonly found in legumes, with soybeans having one of the highest amounts of these compounds. Dried soy beans, an excellent source of isoflavones, contain about 200 mg soy isoflavones per 100 g soy beans.

There is a large variability in the isoflavone composition amongst soybeans and soy-based food products with most dietary sources containing a mixture of derivatives based on the three isoflavones with the common names genistein, daidzein and glycitein. However,the same isoflavones also exist as glucosides (contain glucose esters), acetyl glucosides, or malonyl glucosides in addition to the free phenolic or aglycone (without glucose) form.

Soybeans contain approximately three times as much genistin as daidzin, and a small amount of glycitin. After consumption, these glycoside forms are enzymatically converted (hydrolyzed) in the gut to the aglycone isoflavones; genistein, daidzein and glycitein. The most important soy isoflavones are daidzein and genistein. The chemical structures of these compounds are as shown in the following diagram in the gut to the active aglycone isoflavones (Anderson et al., 1999Scambia et al., 2000).

Daidzein and GenisteinSoy isoflavones (soy isoflavones) have structural and functional similarities to the human estrogen, 17ß-estradiol, except they have variable estrogen-like biological activities. They, in contrast to 17B-estradiol, have both weak estrogenic and weak anti-estrogenic effects, both of which are beneficial.

Soy isoflavones and other phytoestrogens can bind to estrogen receptors, mimicking the effects of estrogen in some tissues while antagonizing (blocking) the effects of estrogen in others (Zava and Duwe, 1997).

The extent to which soy isoflavones exert estrogenic and anti-estrogenic effects in humans is currently the focus of considerable scientific research. When the natural levels of estrogen are high, for example during adolescence, the isoflavones competitively inhibit the binding of estrogen with the specific estrogenic receptors. This reduces the efficacy of the natural form of estrogen.

This antagonism is especially beneficial in individuals who are sensitive to estrogen induced cancers such as breast and vaginal cancers as the isoflavones compete with endogenous estrogen for binding to its receptors and thereby reduce its biological effects. The traditionally high intake of soy isoflavones by Asian women has been hypothesized to be one of the factors responsible for their reduced incidence of estrogen-induced cancers.

In contrast to soy isoflavones antagonistic properties in pre-menopausal women, they also have beneficial effects in post-menopausal women since they are able to stimulate the formation of cells capable of synthesizing bone cells, thereby reducing the effects of osteoporosis (bone weakness). The ability to regenerate new bone forming cells (osteoblasts) is reduced in menopausal women as a result of a greatly reduced secretion of estrogen but is re-stimulated in individuals consuming soy isoflavones.

Soy isoflavones, because of their phytoestrogenic effects, have also been shown to reduce menopausal signs (hot flushes) in women and to help build bone synthesizing cells in elderly men. Isoflavones, therefore, have several beneficial effects in both pre- and post-menopausal women as well as in men.

Some of the protective effects of the soy isoflavones against a number of clinical diseases include bone disease (osteoporosis) (Brynin, 2002Ye et al., 2006Marini et al., 2007Ma et al., 2008a and 2008bIshimi et al., 2009Taku et al., 2010a), menopausal symptoms of hot flushes (Anderson et al., 1999Scambia et al., 2000Nahas et al., 2007Taku et al., 2012), coronary heart disease and blood pressure (Anderson et al., 1995Lichtenstein 1998Zhuo et al., 2004Sacks et al., 2006Taku et al., 2007 and 2010b); and breast, endometrial, prostate and lung cancers (Messina et al., 1994Schabath et al., 2005Lee et al., 2009Koh et al., 2011Wu et al., 2008).

D’Anna et al. (2007) demonstrated that genistein, a compound present in soy isoflavones, reduces the incidence of hot flushes in post-menopausal women within one month of supplementation and reach a peak after 12 months (a 56% reduction in the number of hot flushes).

Taku et al. (2012) also carried out a Meta-analysis on the ability of soy isoflavones (SIF) to alleviate hot flushes in pre- and post-menopausal women. This combination analysis of 11 previous scientific studies has provided the most comprehensive and accurate assessment to date of the benefits of SIF in reducing the effects of menopausal symptoms. The Meta-analysis revealed that the ingestion of soy isoflavones (medium, 54 mg per day; aglycone equivalents) for 6 weeks to 12 months, significantly reduced (p ANNPs suggested daily dosage of SIF is 100 mg/day (50 mg SIF aglycone × 2).

The higher recommended ANNP dosage compared to the median value for the Taku et al. (2012) study would be similar to that in some of the studies included in their Meta-analysis. Consult your health care practitioner in regards to dosage used.

Zhuo et al (2004) carried out a Meta-analysis of 8 randomized control trials in humans on the ability of SIFs to lower serum LDL cholesterol. They demonstrated that SIFs have the ability to significantly lower LDL cholesterol in the soy containing foods and that this effect was independent of soy protein.

Taku et al. (2007) carried out a meta-analysis evaluating the effects of SIFs on blood lipid profiles in humans. This combined analysis of 11 previous scientific studies has currently provided the most accurate and comprehension assessment of the benefits of SIF on blood lipids. They reported that soy isoflavones (102 mg aglycone form) were able to significantly reduce serum total cholesterol (1.77%, P<0.02) and LDL (bad) cholesterol, (3.6%, P<0.0001) but did not change HDL (good) cholesterol.

Reductions in LDL-cholesterol were larger in hypercholesterolemic than normal cholesteteroalemic subjects. Previous studies showing the beneficial effects of SIF on the protective effects of SIF against heart disease were reported by Anderson et al. (1995). Lichtenstein (1998) and Sacks et al., (2006).

A daily intake of 2 capsules of ANNP’s isoflavone will provide 100 mg/SIF in the aglycone form.

General

High dietary intake of soy isoflavones appears to be associated with a lower incidence of cancers, particularly the hormone related cancers including breast cancer (Wu et al., 2008Lee et al., 2009Koh et al., 2011), prostate cancer (Kurahashi et al., 2007Miyanaga et al., 2012), and lung cancer (Schabath et al., 2005Shimazu et al., 2010).

Breast Cancers

A study by Lee et al. (2009) provided strong evidence that soy food intake, a rich source of SIFs, provide a protective effect against premenopausal breast cancer. Koh et al (2011) reported that polymorphisms (mutations) in two genes (MDM2 and p53) play a role in breast cancer carcinogenesis and that SIFs have the ability to down-regulation (reduce) the effect of the two genes and, therefore, provide a protective effect against breast cancer. The same research groups in a previous study (Wu et al., 2008), reported that post-menopausal women with above average intake of soy had a 20% reduction in breast cancer risk compared with women having a lower intake of SIFs.

Prostate Cancer

Kurahashi et al. (2007) conducted a population-based prospective study on 43,509 Japanese men ages 45 to 74 years who had a high and low incidence of prostate cancer. They reported that there was a dose-depended decrease in the risk of localized cancer with the relative risks for men in the highest quartile of genistein (a SIF), daidzein (a SIF) and soy food consumption (a good source of SIFs) compared with the lowest quartile of 52% [95% confidence control (95% CI), 0.30-0.90], 50% (95% CI, 0.29-0.88), and 52% (95% CI, 0.29-0.90), respectively.  They concluded that SIF intake was associated with a decrease risk of localized prostate cancer.

In another study, Miyanaga et al. (2012) carried out a phase II trial on the effect of oral isoflavone intake (60 mg/day) for 12 months on its ability to prevent prostate cancer. They reported that the incidence of cancer in 53 patients aged 65 or more was significantly lower than that in the placebo group (28% versus 57%, P=0.03). In addition SIFs were safe and well tolerate.

Lung Cancer

Schabath et al. (2005) examined the relationship between dietary intake of phytoestrogens and risk of lung cancer in patients with and without lung cancer. The patients in the highest quartile of isoflavones intakes were associated with a reduction in risk of lung cancer of 32% (95% confidence interval) compared to the lowest quartile. They concluded that the epidemiologic evidence indicate that dietary phytoestrogens which include SIFs are associated with a decrease in risk of lung cancer, especially in never and current smokers.

Shimazu et al. (2010) carried out a long term cohort study on about 76,000 men and women 45 to 74 years of age over eleven years on the relationship between SIF intake and incidence of lung cancer. They reported that the incidence of lung cancer in the highest versus lowest quartile of isoflavone intake was significantly reduced (43%) for men and women that never smoked. This data suggests that isoflavone intake reduces the risk of lung cancer in never smokers.

What is Osteoporosis?

Osteoporosis results in loss of calcium and other minerals from bones causing them to become overly porous and brittle. Men and women start to lose bone at a significant rate starting in midlife. However, women experience accelerated bone loss following menopause placing them at a high risk for fractures. Osteoporosis is a major health threat to more than 40 million North Americans, 80% of whom are women, and is responsible for more than 2 million fractures per year. Almost one-quarter of patients over 50 years of age with hip fractures die within one year.

General role of calcium, vitamin D and phytoestrogens and estrogen in the prevention of Osteoporosis

Intake of calcium rich foods or calcium supplements, and vitamin D to help with the absorption of calcium, and exercise are important factors in the prevention of osteoporosis especially in menopausal women. These, however, are not enough as it is also necessary to maintain and increase the amount of the estrogen-stimulated bone-building tissue (osteoblasts) (Setchell and Lydeking-Ulsen, 2003).

General benefits of phytoestrogens

Isoflavones like HRT have been shown to be highly effective as discussed above in promoting the synthesis of bone producing cells but, in contrast to estrogen therapy, they do not increase but reduce the incidence of hormone related cancers and heart disease.

These additional positive benefits are the reason why soy isoflavone should be preferably used. Overall, scientific evidence as shown in the following section demonstrates that soy isoflavone are an excellent means of maintaining bone health and reducing incidence of breaks and fractures in menopausal women.

Prevention of Osteoporosis; recent scientific evidence

Several large scientific studies have demonstrated that soy isoflavones (SIFs) were effective in preventing osteoporosis in post-menopausal women and to some extent in elderly men (Brynin et al., 2002Ye et al., 2006Marini et al., 2007Ma et al., 2008a and 2008bIshimi et al., 2009Taku et al., 2010a).

Taku et al. (2010a) in his study carried out a Meta-analysis involving 1240 menopausal women on the effects of ingesting soy isoflavones (SIF) on lumbar spine bone mineral density (BMD). This combination analysis of 11 previous scientific studies currently has provided the most comprehensive and accurate assessment of the benefits of SIFs for Bone Health.

The Meta-analysis demonstrated that ingestion by menopausal women of about 82 mg of SIF (in the aglycone form) per day for 6 to 12 month significantly increased spine BMD by 2.4% compared with the controls without SIF in (P<0.001, a probability of being wrong in only in 1 in 1,000 trials).

No adverse effects were observed.  The authors concluded that their “Meta-analysis suggests that soy isoflavone supplements can be used not only to offset the bone loss that occurs naturally in women after menopause, but are also applicable for complementary or alternative use in patients with post-menopausal osteoporosis who are unwilling to take or unable to tolerate the side effects of estrogen or/and biophosphonate therapies”.

More recently studies have demonstrated that the isoflavone, genistein, has anti-viral activity against the common cold virus and other viruses such as rotavirus (Andres et al., 2007), and provides protection against certain toxins such as the estrogenic xenobiotic chemical bisphenol A (Dolinoy et al., 2007), hypertension (high blood pressure) (Taku et al., 2010b) and also against enlargement of the male prostate gland.

Some studies have suggested that the consumption of soy products may adversely affect thyroid function and that soy isoflavones may be responsible for some of this effect (Doerge and Sheehan, 2002). To clarify this possible effect (Bruce et al., 2003) investigated the effect of daily soy isoflavone (SIFs) supplements (approximately 50 mg SIF tablets 3 times/day) on thyroid function in idodine repleted post-menopausal women.

They found no evidence that the consumption of SIFs advertisely affected the level of thyroid related hormones (TSH, T3 and T4). Ryan-Bochers et al. (2008) evaluated the effects of SIFs obtained from either soy milk or a SIF supplement (70 mg SIF/day) on circulatory TSH (thyroid stimulating hormone) in healthy, well nourished post-menopausal women over a 16-week intervention period. They reported that there was no difference (P<0.05) in baseline TSH values of participants with or without SIFs (2.5 ± 0.5 mU/L).  They concluded that soy isoflavones at the intake levels of their study does not adversely affect thyroid function in healthy well nourished post-menopausal women.

Marini et al. (2012) in a review concluded that the isoflavone, genistein, shows a good profile of safety on the thyroid.

For centuries, soy has been a regular part of the diet in many Asian countries. Hence, isoflavones, naturally occurring components of soy, have long been consumed in substantial quantities by these populations. An international team of health experts, in a detailed review on the safety of soy isoflavones, have confirmed the safety of soy isoflavones (Munro et al., 2003).

They concluded, “when viewed in its entirety, that the scientific evidence support the safety of isoflavones as typically consumed in soy-based diets, or in soy containing isolates such as the isoflavones when consumed as a supplement”.

Andres, A. et al. Isoflavones at Concentrations Present in Soy Infant Formula Inhibit Rotavirus Infection in VitroJ Nutr 137:2068-2073, 2007. http://jn.nutrition.org/content/137/9/2068.full.pdf+html

Anderson, J. W. et al. Meta-analysis of the effects of soy protein intake on serum lipids, The New England Journal of Medicine 333:276-282, 1995.

Anderson, J. J. et al. Review article: Health potential of soy isoflavones for menopausal women, Public Health Nutrition 2:489-504, 1999.

Brynin, R. Soy and its isoflavones: a review of their effects on bone density,  Alternative Medicine Review 7:317-327, 2002.

Bruce, B. et al. Isoflavone Supplements Do Not Affect Thyroid Function in Iodine-Replete Postmenopausal Women. J. Med Food 6:309-316, 2003. http://online.liebertpub.com/doi/abs/10.1089/109662003772519859

Consumer Reports, Soy cutting through the confusion. Consumer Reports 28-31, 2004.

D’Anna, R., et al. Effects of the phytoestrogen genistein on cardiovascular risk factors in postmenopausal women, Menopause 14:648-655, 2007.

Doerge, D. R. and D. M. Sheehan. Goitrogenic and estrogenic activity of soy isoflavones. Environ Health Perspect 110:349–353, 2002. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1241182/pdf/ehp110s-000349.pdf

Dollinoy, D. C. et al. Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development. PNAS 104(32):13056-13061, 2007. http://www.pnas.org/content/104/32/13062.full.pdf+html

Ishimi, Y. et al. Systematic review and verification of preventive effects of soy constituents on lifestyle-related diseases: Isolated soy isoflavone supplements for postmenopausal bone loss: Meta-Analysis of randomized controlled trials (Part II). Soy Protein Research, 12: 11-21, 2009. http://www.fujioil.co.jp/daizu/srj/eng/headline/docu/vol30e.html#2

Koh, W-P. et al. Combined effects of MDM2, SNP309 and TP53 R72P polymorphisms, and soy isoflavones on breast cancer risk among Chinese women in Singapore. Breast Cancer Res Treat 130:1011-1019, 2011. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3404431/pdf/nihms392380.pdf

Kurahashi, N. et al. Soy product and isoflavone consumption in relation to prostate cancer in Japanese men. Cancer Epidemiol Biomarkers Prev 16:538-545, 2007. http://cebp.aacrjournals.org/content/16/3/538.full.pdf

Lee, S-A. et al. Adolescent and adult soy food intake and breast cancer risk: results from the Shanghai Women’s Health Study. Am J Clin Nutr 89:1920-1926, 2009. http://www.ajcn.org/content/89/6/1920.full

Lichtenstein, A. H. Soy protein, isoflavones and cardiovascular disease risk, Journal of Nutrition 128:1589-1592, 1998.

Marini, H. et al. Effects of the Phytoestrogen Genistein on Bone Metabolism in Osteopenic Postmenopausal Women – A Randomized Trial, Annals of Internal Medicine 146:839-847, 2007.

Marini, H. et al.  Update on genistein and thyroid: an overall message of safety. Frontiers in Thyroid Endocrinol 3:1-4, 2012.http://www.frontiersin.org/Thyroid_Endocrinology/10.3389/fendo.2012.00094/full

Ma, D-F. et al. Soy isoflavone intake increases bone mineral density in the spine of menopausal women: Meta-analysis of randomized trials. Clin Nutr 27:57-64, 2008a. http://www.sciencedirect.com/science/article/pii/S0261561407001902

Ma, D-F. et al. Soy isoflavone intake inhibits bone resorption and stimulates bone formation in menopausal women: Meta-analysis of randomized trials. Europ Clin Nutr 62:155-161, 2008b. http://www.nature.com/ejcn/journal/v62/n2/abs/1602748a.html

Messina, M. J. et al. Soy intake and cancer risk: a review of the in vitro and in vivo data. Nutr Cancer 21: 113-131, 1994. http://www.ncbi.nlm.nih.gov/pubmed/8058523

Miyanaga, N. et al. Prostate Cancer Chemoprevention Study: An investigative randomized control study using purified isoflavones in men with rising prostate-specific antigen. Cancer Sci. 103:125-130, 2012. http://onlinelibrary.wiley.com/doi/10.1111/j.1349-7006.2011.02120.x/full

Munro, I. C. et al.  Soy Isoflavones: A Safety Review, Nutrition Review 1:1-13, 2003.

Nahas E. A. P. et al. Efficacy and safety of a soy isoflavone extract in postmenopausal women: A randomized, double-blind, and placebo-controlled study. Maturitas 58:249-258, 2007. http://www.megawecare.co.th/file/research/Efficacy%20and%20safety%20of%20a%20soy%20isoflavone%20extract_42.pdf

Ryan-Borchers, T. et al. Effects of Dietary and supplement forms of isoflavones on thyroid function in healthy postmenopausal women. Top Clin Nutr 23:13-22, 2008. http://public.wsu.edu/~fournier/Research/Thyroid_Soy%20Publication%202008%20Proof.pdf

Sacks, F. M., et al. Soy Protein, Isoflavones, and Cardiovascular Health. A Summary of a Statement for Professionals From the American Heart Association Nutrition Committee, Arteriosclerosis, Thrombosis, and Vascular Biology. 26:1689-1692, 2006.

Scambia  N. et al. Clinical effects of a standardized soy extract in postmenopausal women: a pilot study. Menopause 7:105-111, 2000.

Schabath, M. B. et al. Dietary phytoestrogens and lung cancer risk. J Am Med Assoc  294:1493-1504, 2005. http://jama.jamanetwork.com/article.aspx?articleid=201594

Setchell, K. D. R. and E. L.Vdeking-Olsen. Dietary phytoestrogens and their effect on bone: evidence from in vitro and in vivo, human observational and dietary intervention studies.   Am J Clin Nutr 78:593s-609s, 2003. http://www.ajcn.org/content/78/3/593S.full.pdf+html

Shimazu, T. et al. Isoflavone intake and risk of lung cancer: a prospective cohort study in Japan. Am J Clin Nutr 91:722-728, 2010. http://www.ajcn.org/content/91/3/722.full.pdf

Taku, K. et al. Soy isoflavone lower total and LDL cholesterol in humans: a meta-analysis of 11 randomized controlled trials. Am J Clin Nutr 85:1148-1156, 2007.  http://www.ajcn.org/content/85/4/1148.full

Taku, K. et al. Effect of soy isoflavone extract supplements on bone mineral density in menopausal women: meta-analysis of randomized controlled trials. Asia Pac J Clin Nutr. 19(1):33-42, 2010a. http://www.ncbi.nlm.nih.gov/pubmed/20199985

Taku, K. et al. Effects of soy isoflavone extract supplements on blood pressure in adult humans: systematic review and meta-analysis of randomized placebo-controlled trials. J Hypertension 28:1971-1982, 2010b. http://journals.lww.com/jhypertension/Abstract/2010/10000/Effects_of_soy_isoflavone_extract_supplements_on.1.aspx

Taku, K. et al. Extracted or synthesized soybean isoflavones reduces menopausal hot flash frequency and severity: systematic review and meta-analysis of randomized controlled trials. Menopause 19(7):776-790, 2012. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2621412/

Wu, A. H. et al. Soy intake and breast cancer risk in Singapore Chinese Health StudyBr J Cancer 99:196-200, 2008. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2453029/

Ye, Y-B.  et al. Soy isoflavones attenuate bone loss in early postmenopausal Chinese women – A single-blind randomized, placebo-controlled trial, European Journal of Nutrition 45:327-334, 2006.

Zava, D. T. and G. Duwe. Estrogenic and antiprofiliferative properties of genstein and other flavonoids in human breast cancer cells in vitroNutrition and Cancer. 27:31-40, 1997.

Zhuo, X-G. et al. Soy isoflavone intake lowers serum LDL cholesterol: A Meta-analysis of 8 randomized trials in humans. J. Nutr 134:2395-2400, 2004. http://jn.nutrition.org/content/134/9/2395.full.pdf+html

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