May 1, 2018 – Isoflavone-rich Soy Protein Reduces CVD Risk
During the 1990s, there was much interest in establishing whether it was the protein or isoflavones in soybeans, or a combination of both, that were responsible for cholesterol reduction. Similar questions were raised about other health outcomes. The advent of isoflavone supplements greatly helped determine which proposed health benefits were due specifically to these soybean constituents. However, some researchers opted to get at the isoflavone vs protein question by stripping the isoflavones from soy protein and comparing this stripped protein with soy protein containing a full complement of isoflavones.
Such is the approach used by Sathyapalan and colleagues from the University of Hull in a six-month study involving 200 young postmenopausal women. They compared the effects of 15 g isolated soy protein devoid of isoflavones (ISP-) with the same amount of protein that contained 66 mg isoflavones (ISP+). In statistically significant results, ISP+ lowered systolic blood pressure and fasting glucose and insulin levels and decreased insulin resistance, relative to ISP-. Based on these favorable changes in cardiovascular disease risk factors (CVD), the investigators estimated the 10-year risk of CVD mortality was reduced by 42%. There were no changes in lipid levels, which is not surprising given the intervention consisted of only 15 g soy protein. Although the findings suggest isoflavones are responsible for the observed changes in risk factors, it is possible that they resulted from an interaction between the protein and isoflavones. Also, removing all of the isoflavones from soy protein can change its tertiary structure, which could influence the results. In any event, the findings show that soy protein, which is naturally rich in isoflavones, reduces CVD risk.
Source: Sathyapalan et al. Nutrition Metabolism and Cardiovascular Diseases, 2018
March 28, 2018 – Soy Infant Formula Update
By Mark Messina, PhD, MS
Since soy infant formula (SIF) first became widely available in the 1960s, more than 20 million Americans have reportedly used this formula during infancy.1 Current estimates are that about 12% of formula-fed infants use SIF.2 Studies consistently show that infants fed SIF experience normal growth and development, a conclusion reached by the American Academy of Pediatrics in its review of the scientific literature.3
Despite its long history of successful use, in recent years there has been renewed interest in understanding the health effects of SIF primarily because it is a rich source of isoflavones.4 Isoflavones are naturally-occurring plant compounds that are commonly classified as phytoestrogens although they differ substantially from the hormone estrogen.5
An example of the research interest in SIF is a recent study, named the Infant Feeding and Early Development (IFED) study, conducted by a team of investigators lead by Virginia A. Stallings, MD, Children’s Hospital of Philadelphia.6 For this study, 410 mother-infant pairs were recruited from eight Philadelphia hospitals between 2010 and 2013. To qualify, the infants of mothers had to fit into one of three feeding categories: 1) almost exclusively (≥90% of calories) breast fed; 2) almost exclusively ((≥90% of calories) SIF fed or; 3) almost exclusively (≥90% of calories) cow milk formula fed. Of the 410 mother-infant pairs enrolled in this 36-week investigation (28 weeks for boys) only 283 pairs or 69% completed the study.
The investigators examined several different parameters, but especially those that are thought to be sensitive to hormonal influences. Data were collected every couple of weeks at the beginning of the study and then every four weeks thereafter.
Over the course of the study weight gain was similar among the three feeding groups. Several parameters that served as a proxy to estimate potential differences in sexual development were also assessed. Examples include serum estrogen levels and follicle stimulating hormone levels (measured in girls only), where no differences were detected. Changes in the vaginal maturation index (VMI), assessed by observing cells of the sex organs, were observed in all groups, over time. Subtle differences were noted at the end of the study; VMI was higher in girls fed SIF than those who were breast fed or fed cow milk formula. The VMI is determined by measuring the amount of each of the three main types of cells in the vaginal wall. The higher VMI suggests that the vaginal wall was exposed to higher amounts of estrogen-like compounds. The volume of the uterus was also higher in SIF-fed infants in comparison to both of the other groups although infants fed cow-milk also had a higher volume than breast-fed infants.
In contrast to these findings, there were no differences in breast bud diameter in girls or boys among the three feeding groups. And in contrast to the differences noted among girls, there were no differences among the three groups in the maturation index in boys. In boys, the maturation index was determined by measuring the cells of the urethra, which is the vessel that carries urine out of the body from the bladder.
The IFED investigators concluded that it is unclear as to whether the subtle differences observed in estrogen-responsive tissues will be associated with any future health consequences. These changes may be transient and thus not relevant for long-term health. But the research team called for more research to be conducted. This suggestion is certainly reasonable.
To better understand the possible implications of the IFED study, it is useful to put this research into perspective and also to compare it to other similarly-conducted research. It is important to recognize that the mother-infant pairs were not randomly allocated to one of the three feeding groups, as would be the case in a clinical trial. Rather, the mothers chose on their own to feed their infants in the way they did. As a result, a number of maternal characteristics substantially differed among the three groups.
For example, about 80% of the mothers of formula-fed infants were black, whereas nearly half of the women who breast fed were white. Another big difference was educational level; 29% of the women who fed their infants SIF didn’t graduate from high school, whereas all of the breast-feeding mothers did. Because of these types of differences, which were beyond the control of the investigators, observational studies like this one are not able to establish cause and effect relationships. Thus, this study isn’t able to prove that the differences among the infants solely resulted from the way in which they were fed. Observational studies are an important part of the scientific literature, but they often serve primarily as a basis for generating hypotheses that can be tested in clinical trials.
Another important point to consider is that the subtle differences among the three groups of infants might be transient. In fact, in boys there were differences among the three groups at six weeks of age but not by the end of the study. In agreement with this possibility are the results from a similar study conducted at the University of Arkansas for Medical Sciences, called the Beginnings study. This study found that at four months of age, the ovaries of infants fed cow milk formula were larger than the ovaries of infants who were breast fed (no difference between SIF-fed and breast-fed infants were noted)7 but by five years of age, these differences had disappeared.8 That study also found, in agreement with findings from the IFED study, that at five years of age, there were no differences among the three groups in breast bud diameter. However, whereas the IFED study found differences among girls in the volume of the uterus at 36 weeks of age, the Beginnings study found no differences at five years of age.8 There were also no differences among the three groups in the volume of the testes or prostate among boys, which were not measured by the IFED investigators.8
Another recently-published study from Israel also helps to provide some perspective on the possible developmental impact of infant feeding. This study compared the likelihood of early puberty onset among 29 infants who consumed SIF for an average of two years with 60 infants who did not consume SIF.9 Arguably, early puberty is a more clinically relevant endpoint than the kinds of parameters evaluated in the IFED study. The investigators found there were no differences between the two groups as 13.8% of SIF-fed infants and 13.3% of the infants in the control group were classified as having precocious puberty, early puberty or premature adrenarche. Besides its small size, one limitation of this study was that the infants in the SIF group were breastfed for an average of almost eight months.
In summary, it is important to emphasize that it is unclear as to whether any of the observed differences among infants in the IFED study will have any long-term consequences. Furthermore, if they do, it could be that the subtle differences between infants fed SIF and the other infants could actually lead to benefits. To this point, very preliminary research showed that girls who were fed SIF were less likely to develop breast cancer as adults.10 Clearly, more research is needed before any definitive conclusions can be made. But given its long history of successful use, SIF still remains a practical, safe, and valid choice for mothers who decide not to breast feed or to use cow milk formula.
- Merritt RJ, Jenks BH. Safety of soy-based infant formulas containing isoflavones: the clinical evidence. J Nutr. 2004;134(5):1220S-4S.
- Rossen LM, Simon AE, Herrick KA. Types of infant formulas consumed in the United States. Clin Pediatr (Phila). 2016;55(3):278-85.
- Bhatia J, Greer F. Use of soy protein-based formulas in infant feeding. Pediatrics. 2008;121(5):1062-8.
- McCarver G, Bhatia J, Chambers C, et al. NTP-CERHR expert panel report on the developmental toxicity of soy infant formula. Birth Defects Res B Dev Reprod Toxicol. 2011;92(5):421-68.
- Oseni T, Patel R, Pyle J, et al. Selective estrogen receptor modulators and phytoestrogens. Planta Med. 2008;74(13):1656-65.
- Adgent MA, Umbach DM, Zemel BS, et al. A longitudinal study of estrogen-responsive tissues and hormone concentrations in infants fed soy formula. J Clin Endocrinol Metab. 2018.
- Gilchrist JM, Moore MB, Andres A, et al. Ultrasonographic patterns of reproductive organs in infants fed soy formula: comparisons to infants fed breast milk and milk formula. J Pediatr. 2010;156(2):215-20.
- Andres A, Moore MB, Linam LE, et al. Compared with feeding infants breast milk or cow-milk formula, soy formula feeding does not affect subsequent reproductive organ size at 5 years of age. J Nutr. 2015.
- Sinai T, Ben-Avraham S, Guelmann-Mizrahi I, et al. Consumption of soy-based infant formula is not associated with early onset of puberty. Eur J Nutr. 2018.
- Boucher BA, Cotterchio M, Kreiger N, et al. Soy formula and breast cancer risk. Epidemiology. 2008;19(1):165-6.
February 21, 2018 – Soymilk Comes Out On Top
After their evaluation of the nutritional attributes of a variety of plant milks, two Canadian researchers, S.K. Vanga and V. Raghavan, reached a non-too startling conclusion: “Soy milk is the best alternative for replacing cow’s milk in human diet.”1
Surprisingly, this rather obvious conclusion generated a huge amount of favorable press for soymilk. After all, it isn’t exactly a secret that rice milk, almond milk and coconut milk each have about 1 gram of protein per serving whereas soymilk typically has about 7 grams. Not unexpectedly, a similar review published about a year ago reached similar conclusions.2 That study received no press.
The main two factors contributing to the rise in the popularity of almond milk are its desirable taste profile and its lower caloric density (in comparison to soymilk). The positive health buzz around almonds is probably also a factor. Surprisingly, Vanga and Raghavan1 don’t spell out the reason for the low caloric density of almond milk. Based on the amount of calories in almond milk it is quite evident that most almond milk is very low in almonds. According to the Almond Board of California (http://www.almonds.com/sites/default/files/all_about_almonds%5B1%5D.pdf), one serving (one ounce) of almonds is comprised of 23 almonds and provides 6 grams of protein. Therefore, a cup of almond milk that provides only 1 gram of protein is comprised of only about 4 almonds. For the most part, the nutrient contribution of almond milk comes primarily from fortification. And therefore, the health benefits of almonds aren’t relevant to the vast majority of almond milk sold in the United States.
- Vanga SK, Raghavan V. How well do plant based alternatives fare nutritionally compared to cow’s milk? J Food Sci Technol. 2018;55:10-20.
- Singhal S, Baker RD, Baker SS. A Comparison of the Nutritional Value of Cow’s Milk and Nondairy Beverages. J Pediatr Gastroenterol Nutr. 2017;64:799-805.
January 16, 2018 – Epidemiologic evidence indicates soy intake reduces risk of prostate cancer
A systematic review and meta-analysis of the epidemiologic data by University of Illinois researchers makes a convincing case that the intake of soyfoods, likely because they are such rich sources of isoflavones, reduces the risk of developing prostate cancer. In total, 30 articles were included in the review. The meta-analysis for soy intake included 16 studies, nine case-control and seven cohort studies. Seven of the 16 studies were conducted in North America and eight in Asia (one study was conducted in Europe).
When comparing extremes of soy intake, the relative risk for the North American and Asian studies was 0.72 and 0.71, respectively, with both values being statistically significant. Although both the case-control and cohort studies showed statistically significant reductions in risk, the relative risk was 0.61 for the former and only 0.90 for the latter. In general, case-control studies tend to show more robust results than cohort studies but it is the latter that carry more weight within the epidemiologic community. There was also a striking difference between the results for unfermented and fermented soyfoods, with the relative risk for the former being 0.66 (95% CI: 0.52, 0.83) and the latter being 0.86 (95% CI: 0.66, 1.13).
Somewhat surprisingly, circulating levels of genistein and daidzein were not associated with the risk of prostate cancer. However, it should be noted, as was pointed out by the authors of this analysis, that peak circulating isoflavone levels can occur as soon as 30 minutes or as long as 6 hours after feeding. Therefore, even among individuals with similar isoflavone intakes, circulating isoflavones levels can vary quite markedly depending upon when soyfoods were consumed in relation to blood sampling. In contrast to the lack of effect of blood levels, dietary intakes of genistein and daidzein (the two primary isoflavones in soybeans) were inversely related to risk, although only among Asian studies. The lack of effect in North American studies could be because isoflavone intake is so low in populations outside of Asia. Finally, no relationship was found between soy intake and risk of advanced prostate cancer, although only a few studies examined this relationship.
In conclusion, epidemiologic evidence suggests that soy intake reduces risk of developing prostate cancer but the evidence is derived primarily from case-control rather than prospective studies.
Applegate CC, Rowles JL, Ranard KM et al. (2018) Soy consumption and the risk of prostate cancer: An updated systematic review and meta-analysis. Nutrients 10.
December 28, 2017 – Soy Protein Lowers Total Cholesterol in Subclinical Hypothyroid Patients
By Mark Messina, PhD, MS
British investigators have just published research1 that is especially timely given that the FDA is considering revoking the soy protein health claim. For this study, 80 adult subclinical hypothyroid patients were randomly assigned to receive either 30 g/d soy protein or 30 g/d casein, although only 42 patients completed the study. The high dropout rate was anticipated.
After eight weeks on their respective diets, there was an eight week washout period which was followed by another eight week period during which time the study participants consumed the alternate protein. The soy protein was devoid of isoflavones as a result of being repeatedly washed with alcohol.
The results showed that in comparison to the casein control, soy protein had no effect on thyroid function but favorably affected a number of disease markers. For example, soy protein lowered fasting glucose, insulin resistance, total cholesterol, triglycerides and highly sensitive C-reactive protein, the latter being a marker of inflammation. LDL-cholesterol was not statistically significantly reduced. However, relative to baseline, it was decreased by 3.1% in response to soy protein, whereas it was increased by 3% in response to casein, for a difference of 6.1%. Clearly, the lack of statistical significance has more to do with the small sample size than the effect size. Like many studies that have evaluated the cholesterol-lowering effect of soy protein, LDL-cholesterol was not the primary outcome of interest. In this case, the study was powered to determine differences in thyroxine levels.
- Sathyapalan T, Javed Z, Rigby AS, Kilpatrick ES, Atkin SL. Soy protein improves cardiovascular risk in subclinical hypothyroidism: A randomized double-blinded crossover study. Journal of the Endocrine Society. 2017;1:423-30.
December 21, 2017 – Isoflavones, Compounded Bioidentical Hormones, and the Alleviation of Menopausal Symptoms
By Mark Messina, PhD, MS
Soyfoods and the isoflavones isolated from soybeans, which are available in supplement form, are one of several nonhormonal treatments for hot flashes. These types of “alternative treatments” are especially popular among women, who for any number of reasons, have decided not to use conventional hormone therapy (HT). Interest in alternatives to HT has increased as interest in HT has decreased. Many women began to sour on HT as a result of the findings from the Women’s Health Initiative Trial published in 2002.1 This trial, which involved over 10,000 women, found that the harms of HT outweighed the benefits.
Considerable research shows isoflavones significantly alleviate hot flashes reducing frequency by approximately 50% to 60%.2 Although not as potent as HT,3 despite a very recently published study involving over 300 women suggesting they are,4 isoflavones are still going to markedly improve the quality of life of women suffering from hot flashes. However, despite the impressive data, many women who shunned HT have opted for compounded bioidentical hormones (cBHT) rather than isoflavones to alleviate their menopausal symptoms. According to a 2016 survey of American pharmacists, an estimated 26 to 33 million cBHT prescriptions are filled annually with total sales estimated at $1.3 to $1.6 billion.5
Here is some background information on cBHT that might be helpful: Simply put, bioidentical hormone preparations are medications that contain hormones that are an exact chemical match to those made naturally by humans. Some bioidentical hormones are made by drug companies and approved by the FDA. However, other bioidentical hormone preparations are made at special pharmacies commonly referred to as compounding pharmacies, which make the preparations on an individual basis for each patient. Those “custom-made” preparations aren’t approved by the FDA.
In a recent viewpoint published in JAMA Internal Medicine, Stuenkel, and Manson6 emphasize that evidence in support of the efficacy and benefits of cBHT is lacking. Similarly, they note that safety data are lacking. An additional concern is the lack of standardization for cBHT in that analyses have shown there is substantial variation in the content of cBHT products.7 This variation is worrisome because, for example, inadequate progesterone administration to women taking estrogen therapy increases risk of developing endometrial cancer.
Not surprisingly, virtually every medical society that provides guidance to clinicians treating women who are perimenopausal and postmenopausal recommends against prescribing cBHT.6 Nevertheless, cBHT is often perceived as natural and therefore safer than FDA-approved products, although this belief is not supported by evidence.7
Every woman needs to decide for herself which treatment for menopausal symptoms makes most sense. Certainly, based on a wealth of data, soybean isoflavones should be a highly considered option for women suffering from hot flashes.
- Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288:321-33.
- Taku K, Melby MK, Kronenberg F, Kurzer MS, Messina M. Extracted or synthesized soybean isoflavones reduce menopausal hot flash frequency and severity: systematic review and meta-analysis of randomized controlled trials. Menopause. 2012;19:776-90.
- Crisafulli A, Marini H, Bitto A, et al. Effects of genistein on hot flushes in early postmenopausal women: a randomized, double-blind EPT- and placebo-controlled study. Menopause. 2004;11:400-4.
- Tit DM, Pallag A, Iovan C, Furau G, Furau C, Bungau S. Somatic-vegetative symptoms evolution in postmenopausal women treated with phytoestrogens and hormone replacement therapy. Iranian Journal Public Health. 2017;46:1528-34.
- Pinkerton JV, Constantine GD. Compounded non-FDA-approved menopausal hormone therapy prescriptions have increased: results of a pharmacy survey. Menopause. 2016;23:359-67.
- Stuenkel CA, Manson JE. Compounded bioidentical hormone therapy: Does the regulatory double standard harm women? JAMA Internal Medicine. 2017;177:1719-20.
- Santoro N, Braunstein GD, Butts CL, Martin KA, McDermott M, Pinkerton JV. Compounded bioidentical hormones in endocrinology practice: An endocrine society scientific statement. J Clin Endocrinol Metab. 2016;101:1318-43.
November 30, 2017 – Isoflavones Alleviate Menopausal Symptoms Similar to Hormone Therapy
By Mark Messina, PhD, MS
The effect of soybean isoflavones on menopausal symptoms such as hot flashes has been investigated for more than 20 years. The most recent trial found that isoflavones alleviate hot flashes and night sweating to a similar extent as hormone therapy and that both treatments are significantly better than the placebo.
For this study, 325 women clinically diagnosed with specific postmenopausal symptomatology and not previously treated with phytoestrogens or hormone replacement therapy (HRT), were divided into 3 groups. One group received a placebo, one group a combination of estrogen and progestin, and one group 40 mg isoflavones per day. Hot flashes and night sweats were recorded at baseline and at 6 and 12 months. The investigators presented the results as the percentage of women whose symptoms were completely eliminated, were improved, or that remained unchanged. At study conclusion, 77%, 78% and 35% of the women in the isoflavone, HRT and placebo group, respectively, reported that their symptoms either improved or were completely eliminated. The 35% value for the placebo group is consistent with other studies showing a typical placebo response ranging from about 20 to 40%.
The strengths of this study include its large size and long duration and that it included both a placebo and positive control (HRT). However, there were some important weaknesses. One, the numerical changes in frequency and severity of hot flashes were not reported. Two, menopausal symptoms were only reported at three time periods over the entire year. And three, the definition of “improved” was not provided. Still, it is clear from the results that soybean isoflavones alleviate menopausal symptoms and offer an efficacious option for women wanting hot flash relief without having to take hormones.
Tit DM, Pallag A, Iovan C et al. (2017) Somatic-vegetative Symptoms Evolution in Postmenopausal Women Treated with Phytoestrogens and Hormone Replacement Therapy. Iranian journal of public health 46, 1528-1534
November 9, 2017 – Isoflavones and Advanced Prostate Cancer: Finding Lacks Biological Plausibility
By Mark Messina, PhD, MS
An analysis from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) revealed that isoflavone intake was associated with an approximate two-fold increased risk of developing advanced prostate cancer.1 Among the 27,004 U.S. men in this study, 287 cases of advanced prostate cancer were identified over the 11.5 year follow up period. Although the association between isoflavones and advanced prostate cancer was statistically significant, it completely lacks biological plausibility.
Not unexpectedly, the median isoflavone intake of the men in this study was extremely low. In fact, it was only 0.42 mg/day. To put that number into perspective, one cup of soymilk made from whole soybeans contains about 25 mg isoflavones, or about 60 fold more than the median intake in the PLCO. Even in the fifth quintile, the isoflavone intake range was from only 0.75 mg to 2.03 mg per day. Even allowing for the effects of long-term consumption, it is inconceivable that such low isoflavone intakes could exert a physiological effect. Furthermore, the relationship between isoflavone intake and risk was monotonic.
Risk was increased by 60% when comparing the second isoflavone intake quintile with the first. The intake range for quintile 2 was 0.18 to 0.31 mg/day. Aside from the extreme difficulty of accurately measuring such low intakes, is someone to believe that the equivalent of consuming approximately 3.5 cups of soymilk per year will increase risk of advanced prostate cancer by 60 percent? The inability of Western epidemiologic studies involving the general population to provide insight into the health effects of soyfoods and soybean isoflavones was pointed out more than two decades ago.2 Nevertheless, these studies continue to be published.
- Reger MK, Zollinger TW, Liu Z, Jones JF, Zhang J. Dietary intake of isoflavones and coumestrol and the risk of prostate cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Int J Cancer. 2017.
- Messina M. Western soy intake is too low to produce health effects. Am J Clin Nutr. 2004;80:528-9.
October 31, 2017 – The Scientific Data Are Clear: Soy Protein Provides Heart Health Benefits
Soy protein lowers blood cholesterol levels according to years of scientific evidence 1-10 and the conclusions of the U.S. Food and Drug Administration (FDA) and health agencies in Canada 11 and 11 other countries.12
Nevertheless, the FDA recently announced it is proposing to change the existing heart health claim for soy protein. The possible change to a “qualified” health claim indicates that while the FDA believes the scientific evidence still supports consumption of soy protein as a means of lowering blood cholesterol levels, it recognizes there is some inconsistency in the results of recent clinical trials. However, no adverse effects were observed in these studies.
Such inconsistency is not at all unexpected as there is no nutrition research area where clinical studies have produced entirely consistent findings. This is true even for the effects of sodium on blood pressure13,14 and calcium on bone mineral density15,16 and yet reducing the intake of sodium is routinely recommended by nutritionists as a means of reducing risk of heart disease and increasing calcium intake as a means of preventing osteoporosis.
The Soy Nutrition Institute (SNI) intends to provide data and comment to the FDA during the 75-day comment period that was opened by the FDA with the announcement of the possible change to the soy protein health claim. In addition to commenting on the cholesterol lowering effects of soy protein, other benefits will be highlighted in SNI comments.
While the mechanism behind the ability of soy protein to lower cholesterol levels in humans remains elusive, it has been observed that soyfoods can help to lower cholesterol levels by replacing commonly consumed sources of dietary protein because of the favorable change in the fatty acid content of the diet.1 In fact, the cholesterol lowering effect of soybean oil was recently recognized by the FDA in the form of a heart health claim.17 Furthermore, there is intriguing evidence that there may be components of soybeans and soyfoods aside from the fat and protein that favorably affect a number of coronary heart disease risk factors.18-21
Soyfoods provide ample amounts of high-quality protein, so regardless of someone’s risk of developing coronary heart disease, adding soyfoods to the diet makes nutritional sense.22 Importantly, the nutrition community recognizes that to markedly reduce cholesterol levels and coronary heart disease risk requires adopting a comprehensive dietary approach. Because of their varied nutritional and health attributes, soyfoods and soy protein have been key components of comprehensive dietary approaches that have led to dramatic reductions in cholesterol.23-28
Therefore, from a public health perspective, regardless of any possible change to the existing soy protein heart health claim the clinical evidence indicates that soyfoods can make important contributions to heart-healthy diets.
For more information about the nutrition and health attributes of soyfoods visit www.thesoynutritioninstitute.com.
- Jenkins DJ, Mirrahimi A, Srichaikul K, et al. Soy protein reduces serum cholesterol by both intrinsic and food displacement mechanisms. J Nutr. 2010;140:2302S-11S.
- Zhan S, Ho SC. Meta-analysis of the effects of soy protein containing isoflavones on the lipid profile. Am J Clin Nutr. 2005;81:397-408.
- Harland JI, Haffner TA. Systematic review, meta-analysis and regression of randomised controlled trials reporting an association between an intake of circa 25 g soya protein per day and blood cholesterol. Atherosclerosis. 2008;200:13-27.
- Anderson JW, Bush HM. Soy protein effects on serum lipoproteins: A quality assessment and meta-analysis of randomized, controlled studies. J Am Coll Nutr. 2011;30:79-91.
- Benkhedda K, Boudrault C, Sinclair SE, Marles RJ, Xiao CW, Underhill Food Risk Analysis Communication. Issued By Health Canada’s Food Directorate. Health Canada’s Proposal to Accept a Health Claim about Soy Products and Cholesterol Lowering. Int Food Risk Anal J. 2014;4:22 | doi: 10.5772/59411.
- Tokede OA, Onabanjo TA, Yansane A, Gaziano JM, Djousse Soya products and serum lipids: a meta-analysis of randomised controlled trials. Br J Nutr. 2015;114:831-43.
- Yang B, Chen Y, Xu T, et al. Systematic review and meta-analysis of soy products consumption in patients with type 2 diabetes mellitus. Asia Pacific J Clinical Nutr. 2011;20:593- 602.
- Hooper L, Kroon PA, Rimm EB, et al. Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2008;88:38- 50.
- Reynolds K, Chin A, Lees KA, Nguyen A, Bujnowski D, He J. A meta-analysis of the effect of soy protein supplementation on serum lipids. Am J Cardiol. 2006;98:633-40.
- Weggemans RM, Trautwein EA. Relation between soy-associated isoflavones and LDL and HDL cholesterol concentrations in humans: a meta-analysis. Eur J Clin Nutr. 2003;57:940-6.
- Summary of Health Canada’s Assessment of a Health Claim about Soy Protein and Cholesterol Lowering. Bureau of Nutritional Sciences Food Directorate Health Products and Food Branch. https://canada.ca/en/health-canada/services/food-nutrition/food- labelling/health-claims/assessments/summary-assessment-health-claim-about-protein- cholesterol-lowering.html.
- Xiao CW. Health effects of soy protein and isoflavones in humans. J Nutr. 2008;138:1244S-9S.
- Graudal NA, Hubeck-Graudal T, Jurgens G. Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and The Cochrane database of systematic reviews. 2011:CD004022.
- Lelong H, Galan P, Kesse-Guyot E, Fezeu L, Hercberg S, Blacher J. Relationship between nutrition and blood pressure: a cross-sectional analysis from the NutriNet-Sante Study, a French web-based cohort study. Am J Hypertens. 2015;28:362-71.
- Lanou AJ, Berkow SE, Barnard ND. Calcium, dairy products, and bone health in children and young adults: a reevaluation of the evidence. Pediatrics. 2005;115:736-43.
- Tai V, Leung W, Grey A, Reid IR, Bolland MJ. Calcium intake and bone mineral density: systematic review and meta-analysis. BMJ. 2015;351:h4183.
- Qualified Health Claim Petition – Soybean Oil and Reduced Risk of Coronary Heart Disease (Docket No. FDA-2016-Q-0995). https://fda.gov/downloads/Food/IngredientsPackagingLabeling/LabelingNutrition/UCM56 8508.pdf.
- Pase MP, Grima NA, Sarris J. The effects of dietary and nutrient interventions on arterial stiffness: a systematic review. Am J Clin Nutr. 2011;93:446-54.
- Li SH, Liu XX, Bai YY, et al. Effect of oral isoflavone supplementation on vascular endothelial function in postmenopausal women: a meta-analysis of randomized placebo- controlled trials. Am J Clin Nutr. 2010;91:480-6.
- Li Y, Zhang H. Soybean isoflavones ameliorate ischemic cardiomyopathy by activating Nrf2-mediated antioxidant responses. Food & Function.
- Liu XX, Li SH, Chen JZ, et al. Effect of soy isoflavones on blood pressure: A meta- analysis of randomized controlled trials. Nutrition, metabolism, and cardiovascular diseases : NMCD. 2012;22:463-70.
- Hughes GJ, Ryan DJ, Mukherjea R, Schasteen CS. Protein digestibility-corrected amino acid scores (PDCAAS) for soy protein isolates and concentrate: Criteria for evaluation. J Agric Food Chem. 2011;59:12707-12
- Jenkins DJ, Jones PJ, Frohlich J, et al. The effect of a dietary portfolio compared to a DASH-type diet on blood pressure. Nutrition, Metabolism CVD: NMCD. 2015;25:1132-9.
- Jenkins DJ, Jones PJ, Lamarche B, et al. Effect of a dietary portfolio of cholesterol- lowering foods given at 2 levels of intensity of dietary advice on serum lipids in hyperlipidemia: a randomized controlled trial. JAMA. 2011;306:831-9.
- Jenkins DJ, Kendall CW, Faulkner D, et al. A dietary portfolio approach to cholesterol reduction: combined effects of plant sterols, vegetable proteins, and viscous fibers in hypercholesterolemia. Metabolism. 2002;51:1596-604.
- Jenkins DJ, Kendall CW, Faulkner DA, et al. Long-term effects of a plant-based dietary portfolio of cholesterol-lowering foods on blood pressure. Eur J Clin Nutr. 2008;62:781-8.
- Jenkins DJ, Kendall CW, Marchie A, et al. Effects of a dietary portfolio of cholesterol- lowering foods vs lovastatin on serum lipids and C-reactive protein. JAMA. 2003;290:502-10.
- Jenkins DJ, Kendall CW, Marchie A, et al. Direct comparison of a dietary portfolio of cholesterol-lowering foods with a statin in hypercholesterolemic participants. Am J Clin Nutr. 2005;81:380-7.
About the Soy Nutrition Institute
The mission of the Soy Nutrition Institute is to identify soy and health research priorities, provide evidence-based information on the impact of soybeans and soy components on human health through a variety of education and outreach efforts and, as funds may be available, facilitate the development and funding of targeted research projects.
The Soy Nutrition Institute is a collaborative organization begun in 2004 through the initiative of the United Soybean Board and soy industry leaders, including global corporations and national associations. Members meet at least twice annually to review and discuss research related to soy and health. Emerging issues are examined with presentations from experts in the field. Literature reviews and primary research are commissioned by SNI, as funding allows.
October 2017 – Taiwanese case-control study finds higher isoflavone intake associated with protection against breast cancer
Research into the effects of isoflavones on breast cancer risk has been underway for 30 years. The most meaningful epidemiologic investigations of this relationship have come from Asian countries because of their higher isoflavone intake relative to the West. The most recent Asian observational study to examine the link between isoflavones and breast cancer is a small case-control study from Taiwan.1 The study in question involved 233 cases and 236 age-matched controls. The food frequency questionnaire used to assess dietary intake included 28 frequently-consumed food items. Participants also indicated whether they were vegetarians.
There were no significant differences between cases and controls for age, education, family history, oral contraceptive usage, or regular exercise. However, the cancer group presented with both a higher body mass index and an older age of primiparity.
Dietary analysis identified five dietary patterns: 1) meat 2) processed meat 3) fruit/vegetable/soybean 4) dessert/sugar and 5) fermented food. Multivariate logistic regression showed that meat/fat and processed meat dietary patterns were associated with an increased breast cancer risk (odds ratio (OR): 2.22, 95% CI 1.67–2.94, P < 0.001; OR: 1.49, 95% CI 1.09–2.04, P = 0.013, respectively). Conversely, vegetarian diet and high isoflavone intake were inversely associated with breast cancer risk (P < 0.05).
Not unexpectedly, vegetarians had a higher daily soy isoflavone intake than non-vegetarians (25.9 ± 25.6 mg vs. 18.1 ± 15.6 mg, P < 0.001). Importantly, women who consumed daily >22 mg were 63% less likely to develop breast cancer in comparison to women consuming less than this amount (OR 0.37, 95% CI: 0.24, 0.60, P < 0.001).
The results of this study clearly suggest soyfood intake is protective against breast cancer although the small size of this study and the fact that it utilized a case-control rather than a prospective design limit the utility of the findings.
- Chang YJ, Hou YC, Chen LJ, Wu JH, Wu CC, Chung KP. Is vegetarian diet associated with a lower risk of breast cancer in Taiwanese women? BMC Public Health. 2017;17:800.
October 2017 – Soybean Oil May Provide Diabetes Protection
Newly published evidence indicates that consuming linoleic acid, the primary fatty acid in soybeans, is protective against diabetes.1
Linoleic acid is an essential omega-6 polyunsaturated fat. It is the primary omega-6 fat in the diet. Health authorities recognize that linoleic acid lowers blood cholesterol levels and as a result, risk of coronary heart disease. The cholesterol-lowering effect of linoleic acid is acknowledged by the American Heart Association and the 2015-2020 Dietary Guidelines. Furthermore, soybean oil was recently awarded a health claim for coronary heart disease based on its ability to lower blood cholesterol levels.
Less is known about the role that linoleic acid may have in protecting against other chronic diseases such as diabetes. The incidence of diabetes has increased dramatically over the past 20 years in large part because of the skyrocketing rates of obesity. Most people with diabetes, about 90% are overweight.
To gain insight into the relationship between linoleic acid and diabetes, an international team of researchers conducted a comprehensive statistical analysis of 20 different population studies from ten countries.1 This analysis involved nearly 40,000 participants. All of the participants were free of diabetes at enrollment. During the period the participants were followed, 4,347 individuals developed diabetes.
When the investigators looked at levels of linoleic acid in the body, such as in adipose tissue, it was found that those with the highest levels were 35% less likely to develop diabetes. These findings strongly suggest consuming linoleic acid will protect against this disease.
This new analysis is especially noteworthy not only because of its size but because the researchers relied upon levels of linoleic acid in the body as the primary metric, rather than the amount of linoleic acid the study participants reported eating. Accurately assessing dietary intake is very difficult.
This new research indicates that dietary sources of linoleic acid, such as soybean oil, will not only lower risk of coronary heart disease but will protect against diabetes as well.
- Wu JHY, Marklund M, Imamura F, et al. Omega-6 fatty acid biomarkers and incident type 2 diabetes: pooled analysis of individual-level data for 39 740 adults from 20 prospective cohort studies. Lancet Diabetes Endocrinology. 2017.
The impact of soyfood intake on the prognosis of breast cancer patients has been hotly debated for the past 20 years. However, this debate has largely been resolved in support of the safety and possibly even benefits of soyfoods. Clinical data show that soyfoods don’t adversely affect breast tissue and prospective epidemiologic data show that post-diagnosis soy intake reduces recurrence and mortality. Now, newly published rat research from Georgetown University suggests that genistein, the primary isoflavone in soybeans, affects the efficacy of tamoxifen. However, a closer look at the data reveals why this study isn’t relevant to women.
First of all, the rats in this study were exposed to far more genistein than women could ever be exposed to via the intake of soyfoods. The diet itself contained 500 ppm genistein. Steady state blood levels of genistein were about 4.4 uM. Work in humans suggests that steady state levels in response to 500 ml soymilk per day are about 0.5 uM. Furthermore, whereas nearly all (>99%) of the genistein in the serum of humans is conjugated and therefore biologically inactively, only about 96% of genistein in rat serum is conjugated. When the calculations are done it could be that rats were exposed to 100 times more genistein than would be the case for women consuming two servings of soyfoods per day.
In the Georgetown experiment genistein enhanced the efficacy of tamoxifen in rats exposed to genistein prior to treatment with this drug whereas efficacy was inhibited if genistein was given only beginning at the same time that treatment began. However, the population studies aren’t consistent with these findings. For example, among Chinese breast cancer patients, soyfoods don’t enhance the efficacy of tamoxifen.
When considering all of the data, the positions of the American Cancer Society and American Institute for Cancer Research still hold, breast cancer patients can safely consume soyfoods.
Research from Singapore provides support for the increasingly accepted belief that omega-6 polyunsaturated fat (PUFA) isn’t pro-inflammatory. For decades, conventional wisdom has been that omega-6 PUFA such as linoleic acid (LA) increase inflammation because it was converted to arachidonic acid (AA) in vivo. A number of pro-inflammatory eicosanoids are synthesized from AA. However, it is now recognized that the endogenous conversion of LA to AA is highly inefficient such that increasing LA intake was insignificant effects on AA levels. This line of thinking is supported by the results of an analysis of Singapore Chinese adults. This cross-sectional study involved 269 healthy, ethnic Chinese participants.
Multivariable linear regression showed that higher intake of red meat was associated with higher plasma AA concentrations. In contrast, high intake of PUFA or PUFA-rich oils was associated with higher plasma alpha-linolenic acid (ALA) but not with plasma AA. Higher intakes of soy were associated with higher ALA. These results indicate that it is only preformed AA, that is, the AA found in foods such as meat, which increases endogenous levels of AA and therefore, potentially increases inflammation.
January 2017 – Soy Reduces CVD Events
Clinical studies indicate that soyfoods and various soybean components favorably affect CVD risk factors. For example, soy protein lowers LDL-cholesterol and possibly also blood pressure. Isoflavones improves the functioning of endothelium. And the fat in soyfoods, because it is comprised mostly of polyunsaturated fatty acids, will lower cholesterol when replacing saturated fat in the diet. Of course, what matters is not whether soy affects markers of CVD but CVD events, that is, strokes and heart attacks.
To determine whether soy does in fact reduce events, Chinese researchers conducted a meta-analysis of 17 observational studies that involved over 17,000 strokes and heart attacks. Higher soy intake was associated with a statistically significant 17% reduction in risk of having a CVD event. However, most of the protection was observed in case-control, not prospective studies. It should also be recognized that the epidemiologic data may actually underestimate the potential benefits of soy because even Asian study participants likely aren’t consuming enough soy for maximum benefit.
January 2017 – PUFA Reduces MS Risk
Multiple sclerosis (MS) is an unpredictable, often disabling disease of the central nervous system that disrupts the flow of information within the brain, and between the brain and body. Not much is known about how diet might affect the development and/or progression of this disease. New research suggests that polyunsaturated fat (PUFA) may have some benefits in this regard. The results come from an analysis of 80,920 women from the Nurses’ Health Study (1984-2004) and 94,511 women from the Nurses’ Health Study II (1991-2009) who reported on diet using a validated food frequency questionnaire every 4 years. During the follow up period 479 women developed MS. After adjusting for a host of potential confounders, higher intake of total PUFA at baseline was associated with a statistically significant one-third reduction in risk. Sub-analysis indicated that protective effects were due primarily to alpha-linolenic acid. Interestingly, neither EPA nor DHA were protective. Because of its widespread use, soybean oil accounts for over 40% of the US intake of alpha-linolenic acid.
November 2016 – Dairy fat increases cardiovascular disease risk
November 2016 – Estrogen therapy associated with reduced breast cancer risk
October 2016 – Plant protein reduces overall mortality
September 2016 – Isoflavones benefit polycystic ovary syndrome patients
September 2016 – Isoflavones reduces hot flashes more than SSRIs
July 2016 – Polyunsaturated fat improves glycemic control
June 2016 – No effect of soy isoflavones on PSA
Dec 14, 2015 – SNI Filed Additional Comments to the FDA
Nov 02, 2015- A growing body of evidence suggests soy has antidepressant effects
According to the WHO 350 million people suffer from depression. Several clinical trials have found soybean isoflavones exert antidepressant effects. Impressively, one study found isoflavones were as efficacious as selective serotonin reuptake inhibitors. Now a study from China shows soyfood intake is inversely related to depression. The study involved 1,717 people at least 65 years of age living in rural Northeast China. In comparison to individuals rarely consuming soyfoods, those consuming soy at least 4 times per were much less likely to report being depressed (3.6% vs. 12.5%, P<0.05). The odds ratio (plus 95% confidence intervals) for those consuming soy 2-3 times per week vs rarely consuming soy were 0.50 (0.34, 0.74). Source: J Nutr Health Aging. 19: 884-93 (2015).
October 2015 – The EPA issues glyphosate report
Jul 21, 2015- Adaptation to the iron-inhibiting effects of phytate
Phytate, which is found in whole grains and legumes including soy, is known to inhibit the absorption of divalent minerals such as iron. Since plant-based diets are typically high in these foods some concern has been raised about the iron status of vegetarians. However, nearly all studies show that vegetarian iron status is normal although iron stores are usually lower in comparison to that of non-vegetarians. One reason for the normal iron status may be because new research indicates there is adaption to the mineral-inhibiting effects of phytate. This notion contrasts with findings from a study published nearly 30 years ago.
For this new study, 32 nonanemic females, 18-35 y of age, with normal body mass index but with suboptimal iron stores were matched for serum ferritin concentration and randomly assigned to high-phytate or low-phytate groups, in a parallel design study. Each subject consumed high- or low-phytate foods with at least 2 of their daily meals for 8 weeks and the serum iron response over 4 hours after a test meal containing 350 mg of phytate was measured at baseline and postintervention. The serum iron response to the test meal increased in the high-phytate group at postintervention, resulting in a 41% increase in the area under the curve (AUC). In contrast, no effect was observed in the low-phytate group (21% decrease in AUC). These results strongly suggest that iron bioavailability from diets rich in high-phytate foods has been underestimated.
Armah SM, Boy E, Chen D, et al. Regular consumption of a high-phytate diet reduces the inhibitory effect of phytate on nonheme-iron absorption in women with suboptimal iron stores. J Nutr. (2015).
Jul 03, 2015 – Soy and luteal phase deficiency (female fertility)
Luteal phase deficiency (LPD) refers to inadequate progesterone secretion by the corpus luteum, which may render the endometrium less receptive to implantation and result in infertility or early pregnancy loss. The prevalence of LPD ranges from 4 to 9% in healthy women of reproductive age. The BioCycle Study (2005-2007) prospectively enrolled 259 women from Western New York state, and followed them for one (n = 9) or two (n = 250) menstrual cycles. Participants completed baseline questionnaires, four 24-h dietary recalls per cycle and daily diaries capturing vigorous exercise, perceived stress and sleep; they also provided up to eight fasting serum samples during clinic visits timed to specific phases of the menstrual cycle using a fertility monitor. Cycles were included for this analysis if the peak serum luteal progesterone was >1 ng/ml and a urine or serum luteinizing hormone surge was detected.
In separate macro- and micronutrient adjusted models, increased fiber and isoflavone intake showed modest positive associations with LPD: fiber (per g), adjusted odds ratio: 1.10 (95% CI: 0.99, 1.23), P = 0.07; and isoflavones (per 10 mg), adjusted odds ratio: 1.38 (95% CI: 0.99, 1.92), P = 0.06. Although this study found an association between isoflavone intake and LPD, the first through fourth quartile isoflavone intake cutoffs were < 0.26 mg/day, >0.26 to 0.57 mg/day, >0.57 to 1.66 mg/day, and >1.66 mg/day, respectively. Relationships between health outcomes and such low isoflavone intakes almost certainly have no causal basis.
Andrews MA, Schliep KC, Wactawski-Wende J, et al. Dietary factors and luteal phase deficiency in healthy eumenorrheic women. Hum Reprod. (2015).
Jun 29, 2015 – Isoflavones may limit binge drinking
Kudzu is one of the few plants besides soybeans to contain large amounts of isoflavones. Readings of historical Chinese texts (Li, 1590–1596; Sun, circa 600 AD) reveal that extracts of the kudzu root have been used to treat alcoholism and drunkenness since at least 600 AD. Recent analysis of the kudzu root has revealed it contains 3 active isoflavones that have antidipsotropic (anti-drinking) activity: daidzin, daidzein,and puerarin. Of the total isoflavone content in soybeans, approximately 40% is comprised of daidzein/daidzein.
In the current study, 20 men participated in a placebo-controlled, double-blind, between subjects design experiment (n=10/group) that tested the effects of kudzu extract for its ability to alter alcohol consumption in a natural settings laboratory. A single dose of kudzu extract (2 g total with an active isoflavone content of 520 mg) or placebo was administered 2.5 hours before the onset of a 90 minute afternoon drinking session during which participants had the opportunity to drink up to 6 beers ad libitum. During the baseline session, the placebo-randomized group consumed 2.7+/-0.78 beers before treatment and increased consumption to 3.4+/-1.1 beers after treatment. The kudzu group significantly reduced consumption from 3.0+/-1.7 at baseline to 1.9+/-1.3 beers after treatment. The placebo-treated group opened 33 beers during baseline conditions and 38 following treatment whereas the kudzu-treated group opened 32 beers during baseline conditions and only 21 following treatment. Additionally, kudzu-treated participants drank slower.
The results of this study show for the first time that a kudzu extract limits male alcohol consumption during an afternoon of drinking. It is not possible to determine from the experimental design the kudzu components responsible for the effect but previous work in animals and humans points to isoflavones. There is sufficient data to investigate the effects of soy extracts on binge drinking.
Penetar DM, Toto LH, Lee DY, et al. A single dose of kudzu extract reduces alcohol consumption in a binge drinking paradigm. Drug Alcohol Depend. (2015).
Jun 17, 2015 – Male soy intake does not impair fertility
Male factor etiology may be a contributing factor in up to 60% of infertility cases. Clinical studies show that neither soyfood nor isoflavone intake affects sperm or semen parameters. However, a pilot epidemiologic study from the Harvard University School of Public published in 2008 found that soy intake was associated with low sperm concentration although not sperm count. That epidemiologic study had quite a few weaknesses but it received considerable attention nonetheless. In contrast to those results, the current study found that high soy intake by the male partners of couples undergoing fertility treatment with in vitro fertilization was unrelated to unrelated to fertilization rates, the proportions of poor quality embryos, accelerated or slow embryo cleavage rate, and implantation, clinical pregnancy and live birth. A total of 182 men participated in this study.
Although the results from Western epidemiologic studies involving the general population are usually of questionable value because of the generally low soy intake, in this study mean isoflavone intake in the highest intake group, which was comprised of 33 men, was 24 mg/day, an amount equivalent to approximately one serving per day and more than twice the isoflavone intake in the aforementioned 2008 study. The results of this in vitro fertilization study when combined with the results of clinical studies should resolve the issue of whether soy intake impairs male fertility.
Minguez-Alarcon L, Afeiche MC, Chiu YH, et al. Male soy food intake was not associated with in vitro fertilization outcomes among couples attending a fertility center. Andrology. (2015).
Jun 01, 2015 – Snack Rich in Soy Protein Reduces Appetite and Satiety
The purpose of this research was to compare a 260 calorie high-protein or high-fat afternoon snacks vs. no snacking on appetite, food intake, mood, and cognition in adolescents with an average age of 17 years. Consuming a snack rich in soy protein but not a high-fat snack delayed eating initiation in comparison to not consuming a snack. The soy-protein-snack also reduced appetite to a greater extent than the high-fat snack. Not surprisingly, the soy-protein-snack resulted in a greater increase in protein intake and also tended to reduce confusion-bewilderment and increase cognitive flexibility. These results suggest that consuming soy protein in the afternoon will help to improve diet quality and may help to maintain ideal body weight.
Leidy HJ, Todd CB, Zino AZ, et al. Consuming high-protein soy snacks affects appetite control, satiety, and diet quality in young people and influences select aspects of mood and cognition. J Nutr. (2015).
May 25, 2015 – Plasma genistein levels associated with lower risk of developing prostate cancer and prostate cancer metastasis
According to the results of small Chinese epidemiologic study, soy intake reduces risk of both developing prostate cancer and reduces risk of prostate cancer metastasis. For this study, 100 men underwent a prostate biopsy to determine whether cancer was present. Results showed that among the 46 men determined to have cancer, median plasma genistein concentration was significantly lower than the median concentration in the men without prostate cancer. Furthermore, the age-adjusted odds ratio of prostate cancer risk comparing plasma genistein level above the median to below the median was 0.31 (95% CI 0.13-0.71). In addition, among the men whose cancer had metastasized the median plasma genistein concentration was significantly lower that it was in men whose cancer had not metastasized. This latter finding is supportive of clinical data suggesting genistein has the potential to inhibit metastasis.
Wu Y, Zhang L, Na R, et al. Plasma genistein and risk of prostate cancer in Chinese population. Int Urol Nephrol. (2015).
Apr 08, 2015 – Development of triple null soybeans
Research has led to the development of soybeans that are markedly reduced in three proteins, the
Kunitz trypsin inhibitor (TI), soybean agglutinin (lectin) and immunodominant soybean allergen P34 protein. Although the commercial implications of this research are unclear, this soybean variety could help to increase soyfood consumption.
Schmidt MA, Hymowitz T, Herman E. Breeding and characterization of soybean Triple Null; a stack of recessive alleles of Kunitz Trypsin Inhibitor, Soybean Agglutinin, and P34 allergen nulls. Plant Breeding, 2015
Mar 24, 2015 – In young girls high urinary genistein is associated with serum proteins reflective of a decreased cancer risk
For this study investigators identified two groups of prepubertal girls. Based on quintiles, one group included those who excreted the highest amounts of genistein and the lowest amounts of bisphenol A (BPA) and the other excreted the highest amounts of BPA and the lowest amounts of genistein. BPA is generally classified as an endocrine disrupter. The results showed that in the blood of girls with high urinary genistein concentrations, two proteins with cancer associations were down regulated: endothelin-converting enzyme (ECE-1) and eukaryotic translation initiation factor 3 subunit J (EIF-3). ECE-1 has been implicated in the pathogenesis of a range of disease states including breast, gynecological and urological cancers, cardiovascular disease and Alzheimer’s disease. EIF-3 has been found elevated in human breast, cervical, esophageal, and lung cancers, suggesting a potential role in malignant transformation and cell growth control. On the other hand, nucleolar 7 and PR domain zinc finger 5 (PRDM5) are proteins that are up regulated in high-genistein girls. Nucleolar 7 and PRDM5 have been reported to regulate the cell cycle. The nucleolar 7 gene is reported to be a candidate tumor suppressor gene in cervical cancer that modulates the angiogenic phenotype. PRDM5 has growth suppressive activities and is silenced in breast, ovarian, liver, lung, colon, and other cancers. In contrast to the results in the high-genistein girls, protein changes in the high-BPA group were reflective of an increased cancer risk.
Wang J, Betancourt A, Jenkins S. et al. Altered Blood Proteome in Girls with High Urine Concentrations of Bisphenol A, Genistein, Mono-Ethyl Hexylphthalate and Mono-Benzyl Phthalate. MOJ Proteomics & Bioinformatics 2, 2015.
Feb 23, 2015 – Hot flashes last a lot longer than commonly perceived
Vasomotor symptoms (VMS), including hot flashes and night sweats, are hallmarks of the menopausal transition and can significantly affect quality of life. Up to 80% of women experience VMS during the menopause transition and most rate them as moderate to severe. VMS are one of the chief menopause-related problems for which US women seek medical treatment. The expected duration of VMS is important to women making decisions about possible treatments.
To provide data on duration researchers associated with the SWAN surveyed women reporting symptoms to gather information about duration. The Study of Women’s Health Across the Nation (SWAN) is a multiracial/multiethnic observational study of the menopausal transition among 3302 women enrolled at 7 US sites. From February 1996 through April 2013, women completed a median of 13 visits. Analyses included 1,449 women with frequent VMS.
Key findings of this survey are that the median duration of symptoms was 7.4 years. However several factors markedly affected whether a given woman experienced symptoms to a greater or lesser extent than the median. For example, the median duration for women who began experiencing symptoms during the perimenopausal period was >11.8 years whereas the duration of symptoms for women who experienced them only beginning postmenopause was only 3.4 years. There was also a big difference among ethnicities as the median duration for Black, Hispanic, White, Chinese and Japanese women was 10.1, 8.9, 6.5, 5.4 and 4.8 years, respectively. (Note, previously published research shows isoflavones effectively alleviate hot flashes Menopause 19: 776-790, 2012).
Avis NE, Crawford SL, Greendale G, et al. Duration of Menopausal Vasomotor Symptoms Over the Menopause Transition. JAMA Intern Med. (2015).c
Feb 18, 2015 – Protein Digestibility-Corrected Amino Acid Scores (PDCAAS) versus Digestible Indispensable Amino Acid Scores (DIAAS)
The FAO has held recent discussions about replacing the protein digestibility–corrected amino acid score (PDCAAS) with the digestible indispensable amino acid score (DIAAS) although it is likely that the PDCAAS will remain the assay used by regulatory bodies for evaluating protein quality for several more years. There are two primary differences between the PDCAAS and the DIAAS. One, as the name implies, is that the digestibility of individual amino acids rather than the entire protein is used in the calculation of protein quality. The other is that digestibility is to be determined at the end of the small intestine (ileal digestion) rather than the large intestine (fecal digestion).
Soy protein is a very high-quality protein with PDCAAS values ranging from about 0.9 to 1.0 for different soy products. This research by Rutherford et al. shows that soy protein is a high-quality protein when evaluated using the DIAAS. The digestibility of the indispensable amino acids ranged from approximately 90 to 98% and the content of the sulfur amino acids (the limiting amino acids in soy protein) for the two soy proteins evaluated averaged about 26.5 mg/g. This value compares favorably to the FAO recommended scoring pattern of 27 mg/g protein for children 6 months to 3 years of age and 23 mg/g protein for children older than 3 years, adolescents and adults. Consequently, DIAAS value for soy protein was approximately 0.9, which was much higher than the other plant proteins evaluated. Proteins with scores above 0.8 are considered high-quality proteins.
This research by Rutherford et al. is also notable because they found that 98% of the lysine was available. The FAO has recommended that available or reactive lysine be determined in proteins because of the potential for processing to convert lysine to lysinoalanine, a form of lysine unusable for protein synthesis. Although exposure to high alkaline conditions can cause this conversion to occur, the work by Rutherford et al. shows little conversion occurs in commercial soy proteins.
Rutherfurd SM, Fanning AC, Miller BJ, et al. Protein digestibility-corrected amino acid scores and digestible indispensable amino acid scores differentially describe protein quality in growing male rats. J Nut. (2015).
Feb 11, 2015 – Rodents metabolize isoflavones differently than humans raising questions about their utility as a model for evaluating the health effects of soyfoods
The isoflavone genistein has been shown to stimulate the growth of existing mammary tumors in ovariectomized athymic mice implanted with estrogen-sensitive human breast cancer cells. However, these results contrast with the human research in that clinical studies show that isoflavone exposure has no impact on markers of breast cancer risk and prospective epidemiologic studies show post-diagnosis soy intake reduces recurrence and improves survival. Furthermore, it has been established that rodents metabolize isoflavones differently than humans which raises questions about the utility of using rodents for evaluating isoflavones.
This study from the Netherlands provides additional data showing rodent and human isoflavone metabolism differs. The Dutch researchers found that under similar experimental conditions, rat breast tissue S9 fraction was about 30 times more potent in deconjugating isoflavone glucuronides to their respective aglycones than was the human breast tissue S9 fraction. The S9 fraction refers to the supernatant fraction obtained from an organ homogenate by centrifuging at 9000 g for 20 minutes in a suitable medium; this fraction contains cytosol and microsomes. The microsome component of the S9 fraction contains cytochrome P450 isoforms (phase I metabolism) and other enzyme activities. The cytosolic portion contains the major part of the activities of transferases (phase II metabolism).
The finding that in comparison to the human breast tissue, rat breast tissue more effectively deconjugates isoflavone glucuronides is extremely important because only when isoflavones are in their aglycone form are they able to bind to estrogen receptors and exert estrogen-like effects. Upon absorption, isoflavones are conjugated primarily with glucuronic acid in the liver and intestine. Consequently, about 98% of the isoflavones in the circulation are conjugated and mostly biologically inactive. However, as this research shows, the mammary gland of the rat very efficiently deconjugates the glucuronide thereby producing an active form of isoflavones. Therefore, using rodents to study isoflavones can lead to erroneous conclusions about the effects of these soybean constituents in humans.
Islam MA, Bekele R, Vanden Berg JH, et al. Deconjugation of soy isoflavone glucuronides needed for estrogenic activity. Toxicol In Vitro. (2015).
Jan 30, 2015 – Isoflavone intake is associated with lower bone mineral density (BMD) among breast cancer survivors
Current estimates indicate that there are more than 2.9 million breast cancer survivors in the United States and more than 5 million worldwide. Breast cancer patients often have acute estrogen deprivation, due to premature ovarian failure following adjuvant chemotherapy, which increases risk of rapid bone loss and fracture. Additionally, anti-estrogenic endocrine therapies contribute to bone health issues; aromatase inhibitors exert negative effects on bone health due to estrogen depletion, and tamoxifen negatively affects BMD in premenopausal women.
In this cross-sectional study, the relationship between isoflavone intake and BMD was examined in a subset of participants (N=1,587) from the Shanghai Breast Cancer Survival Study (SBCSS). Women were divided into quartiles according to their isoflavone intake with women in the first intake quartile consuming less than 28.96 mg/d while those in the fourth quartile consumed more than 62.64 mg/d. When all women were included in the analysis, the odds ratio for osteoporosis/osteopenia (based on T score for proximal forearm BMD) for women in the fourth quartile was 1.69 (p for trend, 0.03).
These results suggest that isoflavones may have exerted an anti-estrogenic effect in breast cancer survivors. This finding contrasts with epidemiologic research involving healthy women which found isoflavone intake was associated with a reduce risk of fracture. Nevertheless, this new finding provides a possible explanation for previously published results from the SBCSS showing that higher isoflavone intake among breast cancer patients was associated with a decreased risk of recurrence and mortality. Therefore, although breast cancer survivors on a high-soy-diet may be less likely to succumb to their disease they may need to take additional measures to prevent bone loss.
Baglia ML, Gu K, Zhang X, et al. Soy isoflavone intake and bone mineral density in breast cancer survivors. Cancer Causes Control. (2015).
Jan 13, 2015 – Health Canada announces intention to issue health claim for soy protein
Health Canada’s Food Directorate has announced its intention to award a health claim for soyfoods and coronary heart disease based on the hypocholesterolemic effects of soy protein. Health Canada concluded that soy protein lowers LDL-cholesterol approximately 4 percent. The US FDA, in 1999, was the first regulatory body to formally acknowledge the benefits of soy protein although since that time, 10 other countries have done likewise. In evaluating the literature, Health Canada implicitly rejected claims that soyfoods might be harmful to some people other than the relatively small percentage of adults who are allergic to soy protein.
Food Risk Analysis Communication Issued By Health Canada’s Food Directorate. Health Canada’s Proposal to Accept a Health Claim about Soy Products and Cholesterol Lowering. Karima Benkhedda, Cynthia Boudrault, Susan E. Sinclair, Robin J. Marles, Chao Wu Xiao and Lynne Underhill.
Dec 09, 2014 – The World Cancer Research Fund International identifies a possible link between soy intake and better survival from breast cancer
Nov 16, 2014 – Soy isoflavones improve dry mouth
Dry mouth, which is characterized by decreased salivation, has a number of causes; the involvement of estrogen has been suggested as symptoms typically develop in middle-aged females. However, there is a lack of consensus regarding the treatment of this condition. Because soy isoflavones share some properties in common with the hormone estrogen, Japanese researchers evaluated the effects of isoflavones on impaired salivary secretion in patients with dry mouth. Soy isoflavones (25 mg/day) were administered for two months to 15 study participants with an average age of about 70 years. The results showed a significant improvement based on the saliva flow rate and self-completed questionnaire, thus suggesting the usefulness of isoflavones in improving the symptoms of salivary gland hypofunction.
Ryo K, Takahashi A, Tamaki Y, et al. Therapeutic effects of isoflavones on impaired salivary secretion. J Clin Biochem Nutr. 55,168-173 (2014).
Oct 28, 2014 – Soymilk lowers blood pressure
Recently published meta-analyses have found that soy protein modestly lowers both systolic and diastolic blood pressure. However, because blood pressure changes were not the primary focus of many of these studies, more research is needed before definitive conclusions about the hypotensive effects of soy protein can be made. The latest research to evaluate the soy and blood pressure relationship is an acute study that garnered quite a bit of media attention and generated some controversy.
In this intervention study, elderly participants drank 500 milliliters of soymilk provided in either glass bottles or cans. Two hours following consumption of the soymilk in glass bottles, systolic and diastolic blood pressure decreased by 7.9 and 3.5 mmHg, respectively. These differences were statistically significant. However, when soymilk was provided in cans, the drop in blood pressure was much more modest; systolic and diastolic blood pressure decreased by only 2.9 and 2.8 mmHg, respectively. The authors attributed this difference in response to soymilk to a hypertensive effect of bisphenol-A (BPA). BPA is a chemical used in the production of polycarbonate plastic and epoxy resins, which are used on the inner coating of cans.
One obvious limitation of this study is its short duration. One can only speculate as to whether soymilk would lower blood pressure when consumed over a much longer period of time although other studies have found that to be the case. Also, it is somewhat surprising that the drop in blood pressure in participants consuming soymilk in one can and one glass bottle was similar to the drop in blood pressure in those drinking soymilk in bottles only. Nevertheless, this study adds to the evidence that soyfoods are hypotensive.
Bae S and Hong YC. Exposure to bisphenol A from drinking canned beverage increases blood pressure: Randomized crossover trial. Hypertension. (2014).
Jun 01, 2014 – More educated needed about the Protein Digestibility Corrected Amino Acid Score
In 1991, the Joint FAO/WHO Expert Consultation on Protein Quality Evaluation recommended adopting the protein digestibility corrected amino acid score (PDCAAS) as the assay of choice for evaluating protein quality.3 This assay determines protein quality by comparing the amino acid content of a protein with the reference pattern for indispensable amino acids (IAAs) and correcting for digestibility. This PDCAAS has become the standard method for protein quality evaluation in the United States. In 1993, the US Food and Drug Administration adopted it for nutrition labeling of proteins in foods.
However, a recent survey of dietitians in Missouri reported that few dietitians can correctly identify the PDCAAS as the accepted assay for evaluating protein quality. In fact, only 18% of the respondents were familiar with this method and only 10% correctly identified it as the method used by the FDA for nutrition labeling. On the positive note, 97% of the respondents correctly identified wheat and rice as incomplete proteins although 25% of the respondents incorrectly identified peanut protein as complete and 27% were not able to identify soy protein as a complete protein. Extensive work published in 2011 shows the quality of soy protein products (soy protein concentrate and isolated soy protein) to be similar to animal protein.
Hughes GJ, Kress KS, Armbrecht ES, et al. Initial investigation of dietitian perception of plant-based protein quality. Food Sci Nutr. 2,371-9 (2014).
May 29, 2014 – Soyfoods protective against esophageal cancer
Esophageal cancer is the eighth most common malignancy and the sixth leading cause of cancer-related deaths worldwide. Furthermore, the incidence is increasing in developed countries. To determine whether soyfood intake affects the risk of esophageal cancer, Chinese researchers determined the relationship between soy and isoflavone intake and risk of this cancer in a high-esophageal cancer region of China. This study, which involved 359 cancer patients and 380 hospital-based controls found that patients consumed significantly less total soy than controls (mean 83.3 vs 57.2 g/d). Information on soy intake was obtained by personal interview. Furthermore, the adjusted odds ratio was 0.33 when comparing those in the third soyfood intake tertile with those in the first. Inverse associations with apparent dose-response relationships were also found between isoflavone intakes and esophageal cancer risk. Since this study involved Chinese participants, it is unlikely soy was simply a marker for a more healthful diet. Thus, the results suggest fairly modest soy intakes may be protective against esophageal cancer.
Tang L, Lee AH, Xu F, et al. Soya and isoflavone intakes associated with reduced risk of oesophageal cancer in north-west China. Public Health Nutr 2014;1-5.
Apr 15, 2014 – Soy protective against ovarian cancer
Ovarian cancer has the eighth highest incidence of all cancers in women, and is the second most common gynecological malignancy. The 5-year prevalence rate for ovarian cancer has exceeded half a million cases worldwide. Rates of this cancer are much higher in the United States and Europe than in Asia, suggesting that soyfood intake might be protective against this disease. Therefore, a case-control study was conducted in southern China to evaluate this hypothesis. Five hundred incident patients with histologically confirmed cancer of the ovary and 500 controls (mean age 59 years) were recruited from four public hospitals in Guangzhou. Information on habitual consumption of soyfoods, including soybean, soymilk, fresh tofu, dried tofu, and soybean sprout, was obtained face-to-face from participants through a validated and reliable semi-quantitative food frequency questionnaire. Isoflavone intakes were then estimated using the USDA nutrient database. The ovarian cancer patients reported lower consumption levels of total soyfoods (110.7 vs. 75.3 g/day). Furthermore, logistic regression analyses showed that regular intake of soyfoods was associated with a 71% reduction in risk when comparing women who consumed at least 120 g/day relative to those less than 61 g/day. Similarly, isoflavone intakes were inversely associated with the ovarian cancer risk, with significant dose-response relationships. These results agree with the existing data so a strong epidemiologic case now exists for soy being protective against ovarian cancer. Furthermore, since estrogen therapy markedly increases risk of ovarian cancer that soyfoods are protective illustrates that soy differs from estrogen and may in fact, be exerting an antiestrogenic effect on the ovaries.
Andy H. Lee, Dada Su, Maria Pasalich, Li Tang, Colin W. Binns, Liqian Qiu. Soy and isoflavone intake associated with reduced risk of ovarian cancer in southern Chinese women. Nutr Research 2014
Apr 02, 2014 – Legume fiber and legumes associated with a reduced prostate cancer risk
Prostate cancer mortality rates vary markedly throughout the world and migration data show that when men move from low-risk to high-risk countries, the offspring of these men acquire the risk of those in their adopted homeland. These data suggest lifestyle factors play a role in the etiology of prostate cancer. Among the various possible factors, much attention has focused on diet although the relationship between diet and prostate cancer risk remains unclear. New data suggest that dietary fiber may have a protective effect, but also that not all fibers are equal in this regard. French researchers evaluated the relationship between fiber intake and prostate cancer risk among 3313 men who were followed for a median period of 12.6 years. During that time, 139 men developed prostate cancer. Prostate cancer risk was inversely associated with total dietary fiber intake; when comparing men in the fourth versus first intake quartile, risk was reduced by 53% (P = 0.001). A similar benefit was associated with insoluble fiber and legume fiber. Independent of fiber, legume intake was also shown to be protective. In contrast, no associations between prostate cancer risk and intakes of soluble, cereal, vegetable and fruit fiber were reported. Although soy intake was not a focus of the current study, previous research indicates that soyfoods may reduce risk of developing prostate cancer by as much as 50 percent. Most evidence suggests it is the isoflavone content of soy that is responsible for protection against prostate cancer. However, this French study suggests that both the fiber provided by some soyfoods and the isoflavones may play a role in reducing prostate cancer risk.
Deschasaux M, Pouchieu C, His M, et al. Dietary total and insoluble fiber intakes are inversely associated with prostate cancer risk. J Nutr 2014.
Mar 26, 2014 – Isoflavone gel improves vaginal atrophy
Vaginal atrophy is a common condition in postmenopausal women associated with vaginal and/or urinary symptoms such as vaginal dryness, itching, discomfort and dyspareunia (painful intercourse), dysuria (painful urination), urinary urgency and frequency. Estrogen is a dominant regulator of vaginal physiology. Estrogen-receptors are present in the vaginal tissues of both pre-menopausal and postmenopausal women. In a 12 week placebo-controlled study a vaginal isoflavone gel was shown to significantly improve symptoms of vaginal atrophy, benefits which were supported by changes in vaginal cytology. While these findings have no direct implications for soyfoods, they do show that the isoflavones in soybeans are biologically active.
Lima S et al. Effects of Glycine max (L.) Merr. soy isoflavone vaginal gel on epithelium morphology and estrogen receptor expression in postmenopausal women: A 12-week, randomized, double-blind, placebo-controlled trial. Maturitas 2014.
Mar 06, 2014 – Soyfoods protective against ovarian cancer
Existing epidemiologic evidence indicates that soyfood intake reduces risk of ovarian but only limited research has been conducted. To examine this relationship in detail, Chinese investigators conducted a case-control study involving 1,000 women (mean age, 59) from Guangzhou, the capital city of Guangdong Province of southern China.
Information on habitual consumption of soyfoods, including soybean, soymilk, fresh tofu, dried tofu, and soybean sprout, was obtained face-to-face from participants through a validated and reliable semi-quantitative food frequency questionnaire. Isoflavone intakes were then estimated using the USDA nutrient database. The ovarian cancer patients consumed on average much less soy than their healthy counterparts, 75.3 grams per day versus 110.7 grams per day. When divided women into tertiles, according to the amount of soy consumed, those in the highest intake group (≥120 grams per day) were 71% (odds ratio, 0.29; 95% confidence interval 0.20 to 0.42) less likely to have ovarian cancer than were women in the lowest intake group (<61 grams per day). Isoflavone intake was also inversely associated with the ovarian cancer risk, with significant dose-response relationships being noted.
Lee Andy H., Su Dada, Pasalich Maria, Tang Li, Binns Colin W., Qiu Liqian, Soy and isoflavone intake associated with reduced risk of ovarian cancer in southern Chinese women, Nutrition Research (2014), doi: 10.1016/j.nutres.2014.02.005.
Feb 25, 2014 – Soy infant formula a safe and healthful choice
A comprehensive systematic review and meta-analysis by a team of researchers from five countries concludes that soy infant formula is a safe option and that the patterns of growth, bone health and metabolic, reproductive, endocrine, immune and neurological functions in infants using soy formula are similar to those observed in children fed cow’s milk-based formula or human milk. This position is concurs with that of the American Academy of Pediatrics and agrees with the view of the lead investigator of the Beginnings Study, which is evaluating the development, nutritional status, and health of formula-fed children from birth through puberty. According to Thomas M. Badger, PhD, Director, Arkansas Children’s Nutrition Center, “there is no evidence of the adverse estrogenic effects that prompted the debate over potential estrogenic effects of soy infant formula and there is no reason to restrict soy infant formula use for infants where appropriate.”
Vandenplas Y, Castrellon PG, Rivas R, et al. Safety of soya-based infant formulas in children. Br J Nutr 2014;1-21.
Feb 10, 2014 – Soy and cognition
The relationship between soy intake and cognitive function has been rigorously investigated for 20 years. The evidence overall is conflicting with some clinical studies showing improvement in one or more measures of cognition whereas a couple of epidemiologic studies suggest just the opposite. A just published review represents the most comprehensive look at the data to date. The authors concluded that “… the evidence to date is not sufficient to make any recommendations about the association between dietary intake of soy isoflavones and cognition in older adults.” It is unlikely given the amount of data already published, that at least in the near future this conclusion is likely to change.
Soni M, Rahardjo TB, Soekardi R, et al. Phytoestrogens and cognitive function: a review. Maturitas 2014.
Jan 23, 2014 – Soy improves memory in mice
The usefulness of animal studies for predicting effects in humans is a hotly debated topic. Consequently, whether the finding that soybean saponins improved chemically-induced memory impairment in mice will be replicated should clinical studies be conducted is unclear. Nevertheless, this study serves to illustrate that classically-defined “antinutrients” can have beneficial effects.
Hong SW, Yoo DH, Woo JY, et al. Soyasaponins Ab and Bb Prevent Scopolamine-Induced Memory Impairment in Mice without the Inhibiton of Acetylcholinesterase. J Agric Food Chem 2014;
Jan 07, 2014 – Soy phytosterols benefit hip osteoarthritis (OA) patients
Results of a 3-year trial found that 300 mg/d of a combination consisting of 2/3 soy phytosterols and 1/3 avocado phytosterols reduced the number of hip osteoarthritis patients whose condition had worsened (patients whose loss of joint space width was 0.5 mm or more) over the study period. Osteoarthritis is the most common joint disorder, with hip OA being reported by one in 10 individuals older than 65.
Maheu E, Cadet C, Marty M, et al. Randomised, controlled trial of avocado-soybean unsaponifiable (Piascledine) effect on structure modification in hip osteoarthritis: the ERADIAS study. Ann Rheum Dis 2014;73:376-84.