Life Extension Magazine July 2010
Is Soy Safe?
By Oscar Rodriguez
Rarely has a nutritional source gained such rapid acceptance and drawn the kind of hostile scrutiny focused on soy. No sooner did the FDA take the highly unusual step of allowing a health claim to be made for soy as a food in 1999,1,2 than it came under attack by a vocal minority of “concerned citizens”—some of whom were found to represent a narrow segment of the food industry threatened by soy’s profits.3
Thanks to their efforts, considerable misinformation now contaminates the discussion of soy’s real impact on health. Instead of enjoying the broad range of benefits, many aging individuals are unnecessarily fearful of consuming soy products.
The good news is that the popularity and “controversy” surrounding soy have resulted in considerable clinical study and research, giving rise to a wealth of scientific literature that validates soy’s health-promoting potential.
In this article, you will find out how soy became the subject of controversy—and why it shouldn’t be. You will discover the latest findings on soy and its components, including isoflavones and soy protein. You will also learn how just 15-20 grams of soy per day, (or 50-90 mg of soy isoflavones) can operate at the cellular level to provide a formidable defense against cardiovascular disease, numerous forms of cancer, osteoporosis, and menopausal symptoms.4
Soy and Estrogen: The Real Story
At the center of the controversy surrounding soy is the “estrogen-like” molecular profile of some soy-based compounds—and whether they increase the risk of certain hormone-dependent cancers and other adverse effects associated with hormonal imbalance.
Soy contains antioxidant polyphenols (plant-based compounds) known as isoflavones. Isoflavones are considered “phytoestrogens” or “dietary estrogens” because of their molecular similarity to estrogen as estradiol (17-β-estradiol), the female sex hormone. The ability of isoflavones to “mimic” some of estrogen’s effects has led many doctors and scientists to characterize isoflavones as “weak estrogens.”
This is incorrect, according to Dr. Mark F. McCarty, an internationally recognized expert in soy isoflavones.5 Advances in our understanding of how the body responds to estrogen (and estrogen-like compounds) explains why.
Estrogen exerts its influence upon cells directly through the presence of estrogen receptors. Until relatively recently, only one receptor was known to exist, now called the estrogen receptor alpha or ER-alpha. Overexpression of ER-alpha has been implicated in a variety of cancers in humans, including breast cancer, ovarian cancer, endometrial cancer, and colon cancer.6-9
In the late 1990s,5,10 a second estrogen receptor was discovered, now known as ER-beta. Expression of this receptor appears to counteract many of the cancer-causing activities of ER-alpha.10
As Dr. McCarty points out, genistein, one of the most abundant isoflavones in soy, is a highly potent activator of ER-beta. Critics of soy regard isoflavones’ action on estrogen receptors as the source of concern, without recognizing there is more than one type of estrogen receptor in the body, and that they exert very different effects.
This highly selective mode of action explains why soy isoflavones promote beneficial estrogen-like effects in tissues where the ER-beta receptor predominates, but do not provoke the harmful effects of conventional estrogen replacement therapy in tissues where the ER-alpha receptor predominates.
For example, soy isoflavones have been shown to exert positive effects in tissues such as bone, vascular endothelium (blood vessel lining), and breast cells without the negative effects in those and other tissues such as liver and uterus, where side effects of estrogen therapy have been observed.5 In fact, in breast tissue possessing both estrogen receptor types, ER-beta is now known to exert a restraining influence on cell proliferation stimulated by estrogen at ER-alpha sites, reducing the risk of breast cancer.10 This balance helps to explain why soy isoflavones do not increase breast cancer risk despite their estrogen-like activity.5
Dozens of epidemiological (population-level) studies document the broad array of health benefits associated with a high-soy diet.11-13 Diets rich in soy isoflavones are associated with lower rates of cardiovascular disease, osteoporosis, cancer, and obesity-related complications such as type 2 diabetes.14-16
Soy isoflavones have relaxing effects on blood vessels, mediated by their influence on nitric oxide synthase (NOS), as well as powerful antioxidant effects, which together explain their potential for treatment and prevention of hypertension and stroke.11,17 Acting via yet another distinct mechanism, the isoflavones modulate signaling in pathways that control the interaction of oxidant stress with inflammation, leading to upregulation of detoxifying and antioxidant defense genes.18
The cumulative weight of the evidence for soy’s health benefits led to the remarkable decision by the FDA to approve a food-labeling health claim for products containing 25 grams of soy proteins in the prevention of coronary heart disease in 1999.14 This claim was based on a wealth of clinical trials as well as epidemiological data showing that high soy isoflavone intake could reduce LDL cholesterol, inhibit pro-inflammatory cytokines, reduce cell adhesion proteins, inhibit platelet aggregation, and improve blood vessel reactivity.19 Many nations throughout the world have now similarly endorsed soy products based on these data.10
Dr. Mark Messina, a noted soy expert at the Department of Nutrition at the Loma Linda University School of Public Health, has summarized soy’s remarkable benefits and provides specific recommendations on optimal soy intake. Messina suggests, based on the totality of available data and practical dietary standards, that aging individuals should ingest 15-20 grams of soy per day, including 50-90 mg of isoflavones—recommendations that have been echoed by other researchers worldwide.20 He adds that an intake of 25 grams per day of soy protein can be specifically used for cholesterol reduction.
Protection from Cardiovascular Disease
Soy products, both soy protein isolates and soy isoflavones, induce profoundly beneficial effects on the human cardiovascular system. Early human studies showed that long-term intake of soy protein rich in isoflavones could improve blood lipid profiles, at least in part by increasing expression of receptor molecules that take up LDL cholesterol.21 In fact, soy protein and isoflavones have universally been shown to lower LDL cholesterol and triglycerides, while some studies have also documented increases in beneficial HDL cholesterol as well.22,23 Along with phytic acid, another soy component, soy isoflavones significantly lower homocysteine levels and positively influence other biomarkers of cardiovascular disease risk.24-27
These benefits are obtained through multiple mechanisms of action.28,29 The various constituents of soy favorably regulate expression of numerous genes, including those involved in:
These effects appear to be universal, benefiting young and the old, male and female, normal weight and obese.31-34
As the central role of inflammation in cardiovascular disease emerged, scientists became interested in how soy consumption might affect the inflammatory process.28 They found that short-term soy consumption reduces some markers of inflammation while increasing plasma levels of vessel-relaxing nitric oxide in postmenopausal women with metabolic syndrome, and improves signs of the metabolic syndrome in general.35,36 Soy protein also increases the activity of paraoxonase 1 (PON1), the natural antioxidant compound found in HDL cholesterol that prevents the inflammatory oxidation of cholesterol.37 In a preclinical model, genistein inhibited the inflammatory control complex called nuclear factor-kappaB (NF-kB) and reduced expression of a molecule essential to production of atherosclerotic plaques.38
Another factor that contributes to the risk of a cardiovascular event such as heart attack or stroke is the tendency of platelets to aggregate, or clump together, forming clots that can obstruct blood flow. Platelet aggregation is a complex, multi-step process involving a number of signaling molecules—and soy isoflavones act to reduce the density of vital receptors for one such molecule, thromboxane A2, in direct proportion to the isoflavone concentration in blood.39 Thromboxane plays a central role in potentially lethal blood clot formation.
Short peptides (protein fragments) in soy proteins are among those recently shown to act against angiotensin-converting enzyme (ACE), thereby helping to safely lower blood pressure.40 Genistein inhibits the release of calcium within vascular smooth muscle cells, and helps to block constriction.41 These effects directly mimic those of many prescription blood pressure medications and, along with their direct influence on nitric oxide synthesis and other endothelial health factors, account for the additional vascular benefits conferred by soy products.42,43
Several nutritional intervention studies in both animals and humans further indicate that consumption of soy protein reduces body weight and fat mass, in addition to the beneficial effects on lipid profiles.44 The effect on blood lipid profile was recently shown to be dramatically enhanced by the addition of a prebiotic mixture to soy.45 This study, conducted among a group of adults with high lipid levels, capitalized on the fact that intestinal bacteria can metabolize soy components to produce equol, a powerful lipid-lowering compound that many adults have trouble producing. The people on the prebiotic plus soy branch of the study experienced significant improvements in their lipid profiles not seen when either prebiotic or soy was taken alone.
Combating Metabolic Syndrome
The current epidemic of obesity and type 2 diabetes increases overall risk for cardiovascular disease and other metabolic complications. Soy components have direct benefits on several of the parameters that go awry in the development of metabolic syndrome. For example, soy proteins lower lipids, improve kidney function, and reduce urinary protein losses in type 2 diabetics with kidney disease.46,47
Soy protein combined with isoflavones improves blood sugar control, reduces insulin resistance, and lowers serum lipids in diabetic patients, and can also reduce serum CRP levels and restore lipid profiles towards normal.48-51 These effects may account for the observation that including soy in the diet can improve features of the metabolic syndrome in adults.36
In a group of obese type 2 diabetics, replacement of animal-derived protein with soy protein helped improve hemoglobin A1c (a measure of long-term blood sugar control), reduced dependence on glucose-lowering drugs, lowered CRP levels, and triggered significant weight loss.52 And soy isoflavones, particularly daidzein, can enhance gene expression of the vital metabolic regulatory protein PPARgamma, which helps cells absorb and use glucose.53
Replacing animal-derived proteins with soy-based meals can lower body weight and fat mass, while reducing LDL cholesterol even more than would be expected from weight loss alone, and can improve body composition, increasing the ratio of lean body mass to fat.54,55 Even more exciting, soy product and isoflavone intakes were directly associated with a lower risk of developing type 2 diabetes in a group of overweight women!56