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Clinical Studies on Soy/Soya on:


Menopause:
Soy isoflavones have been shown to ameliorate the effects of menopause. A recent six-year study involving 1,106 women in Japan demonstrated that soy does appear to reduce the occurrence of hot flashes associated with menopause.

Soy product intake and hot flashes in Japanese women: results from a community-based prospective study.

Nagata C, Takatsuka N, Kawakami N, Shimizu H.

Department of Public Health, Gifu University School of Medicine, Gifu, Japan.

The association between soy product intake and the occurrence of hot flashes was examined in a cohort of 1,106 female residents of Takayama, Gifu, JAPAN: The women were aged 35-54 years and premenopausal at their entry into the study in 1992. Diet, including intake of soy products and isoflavones, was assessed by means of a validated semiquantitative food frequency questionnaire at study entry. A follow-up mail questionnaire asking about experiences of hot flashes was sent in 1998. During the 6 years of the study period, 101 women had new moderate or severe hot flashes according to the Kupperman test of menopausal distress. After data were controlled for age, total energy intake, and menopausal status, hot flashes were significantly inversely associated with consumption of soy products in terms of both total amount (highest tertile of soy product intake (g/day) vs. lowest: hazard ratio = 0.47; 95% confidence interval: 0.28, 0.79; p for trend = 0.005) and isoflavone intake (highest tertile of isoflavone intake (mg/day) vs. lowest: hazard ratio = 0.42; 95% confidence interval: 0.25, 0.72; p for trend = 0.002). These data suggest that consumption of soy products has a protective effect against hot flashes.


Osteoporosis: Osteoporosis is a disease that primarily affects older women in which the bones become porous and fracture easily. Japanese women, who generally consume soy products, have half the rate of hip fractures as U.S. women. A study involving 85 postmenopausal Japanese women showed soy to be associated with a higher bone density and a decreased rate of bone resorption (the decrease of bone density), thereby slowing the onset of osteoporosis.*

Given the large body of evidence supporting a variety of benefits of soy, and since the typical American diet consists of very little soy products, you may want to consider supplementing your diet with the most active part of the soybean -- Soy Isoflavone capsules from GeroSoya.

Effect of soy protein on bone metabolism in postmenopausal Japanese women.

Horiuchi T, Onouchi T, Takahashi M, Ito H, Orimo H.

Department of Endocrinology, Tokyo Metropolitan Geriatric Hospital, Japan.

We conducted a cross-sectional study of the effects of soybean protein intake on bone mineral density and biochemical markers in 85 postmenopausal Japanese women. Nutrients in the diet of postmenopausal Japanese women visiting the osteoporosis unit, including subjects with normal lumbar spine bone mineral density (L2-4 BMD), were investigated by questionnaire, and the calculated daily energy, protein, soy protein and calcium intake were obtained. L2-4 BMD was measured with dual-energy X-ray absorptiometry, and assays done of serum alkaline phosphatase (ALP) and serum intact osteocalcin (IOC) as bone formation markers and urinary pyridinoline (UPYR) and urinary deoxypyridinoline (UDPYR) as bone resorption markers. Soy protein intake was significantly associated with the Z-score for L2-4 BMD (r = 0.23,p = 0.038) and UDPYR (r = -0.23, p = 0.034). Stepwise multiple regression analyses showed that soy protein intake is significantly associated with the Z-score for L2-4 BMD (beta = 0.225, p = 0.04) and UDPYR (beta = -0.08, p = 0.03) among four nutritional factors. These results suggest that high soy protein intake is associated with a higher bone mineral density and a lower level of bone resorption, but further studies are needed to confirm the causal dynamic mechanisms.


Heart Disease: A recent study involving monkeys demonstrated that the isoflavone component of soy protein significantly reduces cholesterol levels and the risk of atherosclerosis. A substantial amount of additional evidence that soy reduces unhealthy LDL-Cholesterol levels while either not affecting or increasing healthy HDL-Cholesterol levels is summed up in an analysis of 38 controlled clinical trials. In fact, the evidence has been so overwhelming as to the benefits of soy with regard to heart disease that the FDA has concluded that soy may reduce the risk of coronary heart disease by lowering blood cholesterol levels and has authorized the labeling of food to state this finding.

Effects of soy isoflavones on atherosclerosis: potential mechanisms.

Anthony MS, Clarkson TB, Williams JK.

Comparative Medicine Clinical Research Center, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157-1040, USA. manthony@wfubmc.edu

It has long been recognized that coronary heart disease rates are lower in Japan, where soy consumption is common, than in Western countries. In experimental studies, atherosclerosis was reduced in animals fed diets containing soy protein compared with those fed diets with animal protein. Recently, several lines of evidence have suggested that the components of soy protein that lower lipid concentrations are extractable by alcohol (eg, the isoflavones genistein and daidzein). We recently evaluated the relative effect of the soy protein versus the alcohol-extractable components of soy on cardiovascular disease and its risk factors. Young male and female cynomolgus monkeys were fed diets that contained either 1) casein-lactalbumin as the source of protein (casein), 2) soy protein isolate from which the isoflavones were alcohol extracted (SPI-), or 3) isoflavone-intact soy protein (SPI+). The SPI+ group had significant improvements in LDL cholesterol and HDL cholesterol. Only HDL cholesterol was significantly improved in the SPI- group males compared with the casein group. The casein group had the most atherosclerosis, the SPI+ group had the least, and the SPI- group was intermediate but did not differ significantly from the casein group. Potential mechanisms by which soy isoflavones might prevent atherosclerosis include a beneficial effect on plasma lipid concentrations, antioxidant effects, antiproliferative and antimigratory effects on smooth muscle cells, effects on thrombus formation, and maintenance of normal vascular reactivity.

Meta-analysis of the effects of soy protein intake on serum lipids.

Anderson JW, Johnstone BM, Cook-Newell ME.

Metabolic Research Group, Veterans Affairs Medical Center, Lexington, KY 40511, USA.

BACKGROUND. In laboratory animals, the consumption of soy protein, rather than animal protein, decreases serum cholesterol concentrations, but studies in humans have been inconclusive. In this meta-analysis of 38 controlled clinical trials, we examined the relation between soy protein consumption and serum lipid concentrations in humans. METHODS. We used a random-effects model to quantify the average effects of soy protein intake on serum lipids in the studies we examined and used hierarchical mixed-effects regression models to predict variation as a function of the characteristics of the studies. RESULTS. In most of the studies, the intake of energy, fat, saturated fat, and cholesterol was similar when the subjects ingested control and soy-containing diets; soy protein intake averaged 47 g per day. Ingestion of soy protein was associated with the following net changes in serum lipid concentrations from the concentrations reached with the control diet: total cholesterol, a decrease of 23.2 mg per deciliter (0.60 mmol per liter); 95 percent confidence interval, 13.5 to 32.9 mg per deciliter [0.35 to 0.85 mmol per liter]), or 9.3 percent; low-density lipoprotein (LDL) cholesterol, a decrease of 21.7 mg per deciliter (0.56 mmol per liter); 95 percent confidence interval, 11.2 to 31.7 mg per deciliter [0.30 to 0.82 mmol per liter]), or 12.9 percent; and triglycerides, a decrease of 13.3 mg per deciliter (0.15 mmol per liter; 95 percent confidence interval, 0.3 to 25.7 mg per deciliter [0.003 to 0.29 mmol per liter]), or 10.5 percent. The changes in serum cholesterol and LDL cholesterol concentrations were directly related to the initial serum cholesterol concentration (P < 0.001). The ingestion of soy protein was associated with a nonsignificant 2.4 percent increase in serum concentrations of high-density lipoprotein (HDL) cholesterol. CONCLUSIONS. In this meta-analysis we found that the consumption of soy protein rather than animal protein significantly decreased serum concentrations of total cholesterol, LDL cholesterol, and triglycerides without significantly affecting serum HDL cholesterol

Food labeling: health claims; soy protein and coronary heart disease. Food and Drug Administration, HHS. Final rule.

[No authors listed]

The Food and Drug Administration (FDA) is authorizing the use, on food labels and in food labeling, of health claims on the association between soy protein and reduced risk of coronary heart disease (CHD). Based on its review of evidence submitted with comments to the proposed rule, as well as evidence described in the proposed rule, the agency has concluded that soy protein included in a diet low in saturated fat and cholesterol may reduce the risk of CHD by lowering blood cholesterol levels.


Cancer: Soy isoflavones have demonstrated a significant anti-cancer effect. This statement is supported by the fact that the Japanese breast cancer mortality rate is one-fourth that of the U.S. A recent controlled study found that soy was associated with an almost 50 percent decreased risk of breast cancer in premenopausal women. Soy has also been shown to inhibit chemically induced mammary cancer in rats. More than 100 in vitro (outside the body) studies have confirmed that soy isoflavones inhibit the growth of a wide range of cancer cells, including breast, colon, lung, leukemia and prostate cells.

Protection against breast cancer with genistein: a component of soy.

Lamartiniere CA.

Department of Pharmacology and Toxicology and the Comprehensive Cancer Center, University of Alabama at Birmingham, 35294, USA. coral.lamartiniere@ccc.uab.edu

Breast cancer is the most common cancer in women. Because genetics is believed to account for only 10-15% of breast cancer cases, the environment, including nutrition, is thought to play a significant role in predisposing women to this cancer. Studies of Asian women suggest that those who consume a traditional diet high in soy products have a low incidence of breast cancer, but that among emigrants to the United States, the second generation, but not the first, loses this protection. These findings suggest a possible common mechanism of action for breast cancer protection from early, specific nutritional exposure. Genistein, an isoflavone found in soy, has been reported to have weak estrogenic and antiestrogenic properties, to be an antioxidant, to inhibit topoisomerase II and angiogenesis, and to induce cell differentiation. In studies of the mammary glands of immature rats, we showed that genistein up-regulates the expression of the epidermal growth factor receptor shortly after treatment, which may be responsible for the increased cell proliferation seen at that age. We hypothesize that the early genistein action promotes cell differentiation that results in a less active epidermal growth factor signaling pathway in adulthood that, in turn, suppresses the development of mammary cancer. We speculate that breast cancer protection in Asian women consuming a traditional soy-containing diet is derived from early exposure to soybean products containing genistein. We believe that early events are essential for the benefits of cancer protection.

Inhibitory effects of Bifidobacterium-fermented soy milk on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced rat mammary carcinogenesis, with a partial contribution of its component isoflavones.

Ohta T, Nakatsugi S, Watanabe K, Kawamori T, Ishikawa F, Morotomi M, Sugie S, Toda T, Sugimura T, Wakabayashi K.

Cancer Prevention Division, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo, Japan.

High consumption of soybean and soybean-related products is hypothesized to contribute to protection against breast cancer. Soybean is a rich source of genistein, a putative cancer chemopreventive agent. Fermented soy milk (FSM), which is made of soy milk fermented with the Bifidobacterium breve strain Yakult, contains larger amounts of the isoflavone aglycones genistein and daidzein than unfermented soy milk. In the present study, we examined the effects of FSM and its component isoflavone mixture (genistein:daidzein 4:1) on 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP)-induced mammary carcinogenesis in rats. Starting at 7 weeks of age, female Sprague-Dawley rats were given PhIP at a dose of 85 mg/kg body wt by intragastric administration four times a week for 2 weeks. They were fed control high fat basal diet or experimental high fat diet containing 10% FSM or 0.02 or 0.04% isoflavone mixture during and after carcinogen exposure. The incidences (percentage of rats with tumors) of mammary gland tumors were 71% in the control diet group, 51% in the FSM group and 68 and 61% in the groups treated with isoflavone mixture at 0.02 and 0.04%, respectively. Mammary tumor multiplicities (number of tumors per rat) were 1.2 +/- 0.2 for 10% FSM, 2.2 +/- 0.4 for 0.02% isoflavone mixture and 1.5 +/- 0.3 for 0.04% isoflavone mixture, being clearly smaller than the control diet value (2.6 +/- 0.5). Furthermore, feeding of FSM and the isoflavone mixture at both doses reduced the sizes of mammary tumors. Since the amounts of isoflavones in 10% FSM are approximately equivalent to those in the 0.02% isoflavone mixture, the chemopreventive activity of FSM could be partly attributable to the presence of isoflavones such as genistein and daidzein.

Soy intake and cancer risk: a review of the in vitro and in vivo data.

Messina MJ, Persky V, Setchell KD, Barnes S.

National Cancer Institute, National Institutes of Health, Bethesda, MD.

International variations in cancer rates have been attributed, at least in part, to differences in dietary intake. Recently, it has been suggested that consumption of soyfoods may contribute to the relatively low rates of breast, colon, and prostate cancers in countries such as China and Japan. Soybeans contain a number of anticarcinogens, and a recent National Cancer Institute workshop recommended that the role of soyfoods in cancer prevention be investigated. In this review, the hypothesis that soy intake reduces cancer risk is considered by examining relevant in vitro, animal, and epidemiological data. Soybeans are a unique dietary source of the isoflavone genistein, which possesses weak estrogenic activity and has been shown to act in animal models as an antiestrogen. Genistein is also a specific inhibitor of protein tyrosine kinases; it also inhibits DNA topoisomerases and other critical enzymes involved in signal transduction. In vitro, genistein suppresses the growth of a wide range of cancer cells, with IC50 values ranging from 5 to 40 microM (1-10 micrograms/ml). Of the 26 animal studies of experimental carcinogenesis in which diets containing soy or soybean isoflavones were employed, 17 (65%) reported protective effects. No studies reported soy intake increased tumor development. The epidemiological data are also inconsistent, although consumption of nonfermented soy products, such as soymilk and tofu, tended to be either protective or not associated with cancer risk; however, no consistent pattern was evident with the fermented soy products, such as miso. Protective effects were observed for both hormone- and nonhormone-related cancers. While a definitive statement that soy reduces cancer risk cannot be made at this time, there is sufficient evidence of a protective effect to warrant continued investigation.

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