Patient Handout: The Science of Soy

A stroll through nearly any american grocery store or pharmacy yields ample proof of the soybean's increasing role in the U.S. diet. Food packaging offers statements about products' soy content and the purported associated health benefits. Products such as tofu, soy milk, soy-based infant formula, and meatless "texturized vegetable protein" burgers are widely available. Shelves of dietary supplements and nutraceuticals are stocked with isoflavones, naturally occurring estrogen-like compounds found in soy. The general impression is one of certainty that both soy and soy isoflavones deliver many health benefits, including prevention of cardiovascular disease, cancer, and osteoporosis, as well as treatment of menopausal symptoms. The science is less absolute, however, and still evolving.

Soy provides a complete source of dietary protein, meaning that, unlike most plant proteins, it contains all the essential amino acids. According to the American Soybean Association, 3.14 billion bushels (85.5 million metric tons) of soybeans were harvested in the United States in 2004. Approximately half of the harvest was exported, and most of the remainder was crushed to produce oil and protein meal for domestic use. An April 2006 report from the USDA Economic Research Service indicates that only a small amount of whole soybeans are used to produce soy foods, and just 2% of soy protein meal is used for human consumption; the rest is used for animal feed.

The Soyfoods Association of North America reports that U.S. sales of soy foods reached $3.9 billion in 2003, continuing an 11-year trend of 15% average annual increases. According to the United Soybean Board's 2004-2005 Consumer Attitudes About Nutrition report, 25% of Americans consume soy foods or beverages at least once per week, and 74% view soy products as healthy.

Nevertheless, Americans as a whole still consume very little soy protein. Based on 2003 data from the UN Food and Agriculture Organization, per-capita soy protein consumption is less than 1 g per day in most European and North American countries, although certain subpopulations such as vegetarians, Asian immigrants, and infants fed soy-based formula consume more. The Japanese, on the other hand, consume an average 8.7 g of soy protein per day; Koreans, 6.2-9.6 g; Indonesians, 7.4 g; and the Chinese, 3.4 g.

Traditional soy foods include tofu, which is produced by puréeing cooked soybeans and precipitating the solids, and miso and tempeh, which are made by fermenting soybeans with grains. "Second generation" soy products involve chemical extractions and other processing, and include soy protein isolate and soy flour. These products become primary ingredients in items such as meatless burgers, dietary protein supplements, and infant formula, and are also used as nonnutritive additives to improve the characteristics of processed foods.

Health Effects of Soy

Soybeans and soy foods contain a variety of bioactive components, including saponins, protease inhibitors, phytic acid, and isoflavones. Isoflavones belong to a class of compounds generally known as phytoestrogens, plant compounds that have estrogen-like structures.

The dominant isoflavone in soy is genistein, with daidzein and glycitein composing the remainder. Within soy, isoflavones are almost entirely bound to sugars, producing the respective compounds genistin, daidzin, and glycitin. Soy isoflavones have been linked with numerous health effects, but the strength of the relationships and whether the effects are beneficial are strongly debated.

Soy isoflavones are frequently referred to as weak estrogens, and depending upon the specific circumstance, they can act as agonists, partial agonists, or antagonists to endogenous estrogens (such as estradiol) and xenoestrogens (including phytoestrogens) at estrogen receptors. They are not especially potent, however, and activity varies by tissue concentration, cell type, hormone receptor type, and stage of differentiation. In addition to their estrogen receptor activity, isoflavones may also interfere with steroid metabolism by inhibiting aromatase, hydroxysteroid dehydrogenase, and steroid a-reductase, and by altering the ratio of estradiol metabolites. Soy isoflavones may also act as antioxidants; inhibitors of proteases, tyrosine kinases, and topoisomerases; inducers of Phase I and/or Phase II enzymes such as cytochrome P450s, glutathione S-transferase, quinone reductase, and inhibitors of angiogenesis.

Isoflavone Variables and Risks

Soy research is complicated because there's considerable variation in isoflavone exposure among people classified as soy consumers. Agronomic factors (such as the soybean cultivar and the environmental conditions under which the crop grew) affect a food's isoflavone profile, as does the way a soy food is processed. For example, soy protein concentrate produced by alcohol extraction may have only 12.5 mg total isoflavones per 100 g, in contrast to the nearly 199.0 mg total isoflavones per 100 g of full-fat roasted soy flour. Additionally, the fact that most of the isoflavones in food occur bound to sugar affects how they are digested.

Once genistin enters the digestive tract, it releases its sugar and becomes "free" genistein. Some of this free genistein is absorbed. However, most is reconjugated into glucuronides or sulfates, the primary circulating forms of genistein, which are thought to have either low or no biological activity. Only a very small amount of free genistein escapes conjugation by the liver and circulates in that form.

Finessing Investigations

On balance, it does not seem that soy and its constituent isoflavones have met original expectations. Clinical results with regard to soy's ability to reduce the risk of cardiovascular disease have been inconsistent; a review in the February 2006 issue of Circulation indicated there was little to no effect. The only apparent impact of soy and soy isoflavones on cardiovascular disease risks seems to be a slight reduction in low-density lipoproteins in individuals who had very high levels of cholesterol. An August 2005 report from the DHHS Agency for Healthcare Research and Quality, Effects of Soy on Health Outcomes, also concluded that there was little evidence to support a beneficial role of soy and soy isoflavones in bone health, cancer, reproductive health, neurocognitive function, and other health parameters.

Nevertheless, there remain tantalizing clues that soy may benefit human health. For example, in vitro studies with human breast cancer cells suggest that genistein may induce detoxification enzymes and inhibit growth of both estrogen receptor-positive and estrogen receptor-negative cancers. Additionally, in vitro studies demonstrate that genistein inhibits prostate cancer cell growth, and epidemiologic studies continue to find an inverse relationship between consumption of isoflavone-rich foods and prostate cancer. Rodent models and in vitro systems have suggested beneficial effects on bone density; similar results have not been observed in humans, although clinical trials have shown a promising effect on biomarkers of bone turnover.

Although there has been comparatively little research on the effects of soy and isoflavones on cognition and other brain activity, Thomas Clarkson, a professor of comparative medicine at the Wake Forest University School of Medicine, says this area may also hold some promise. "Our group has done some work [in monkeys] showing that [soy] modifies serotonin metabolism in a direction that should be useful in the prevention of depression," he says.

What most researchers do agree on is that we are only just beginning to truly understand the nature of soy, and that much more research is needed before it is possible to make firm health recommendations. "If you look at nutritional research in general," says Jay Kaplan, head of comparative medicine at Wake Forest University School of Medicine, "there are kinds of proteins that are described as being ‘bioactive.' Most people had assumed that if soy is bioactive, it's because of the isoflavones. We're no longer certain of that at all."

Source: Barrett R. The science of soy: What do we really know? EHP Student Edition. 2006;A352-A358. [Accessed September 10, 2007 at www.ehponline.org].