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July 2004

LE Magazine July 2004

Legumes and soybeans: overview of their nutritional profiles and health effects.
Legumes play an important role in the traditional diets of many regions throughout the world. In contrast in Western countries beans tend to play only a minor dietary role despite the fact that they are low in fat and are excellent sources of protein, dietary fiber, and a variety of micronutrients and phytochemicals. Soybeans are unique among the legumes because they are a concentrated source of isoflavones. Isoflavones have weak estrogenic properties and the isoflavone genistein influences signal transduction. Soyfoods and isoflavones have received considerable attention for their potential role in preventing and treating cancer and osteoporosis. The low breast cancer mortality rates in Asian countries and the putative antiestrogenic effects of isoflavones have fueled speculation that soyfood intake reduces breast cancer risk. The available epidemiologic data are limited and only weakly supportive of this hypothesis, however, particularly for postmenopausal breast cancer. The data suggesting that soy or isoflavones may reduce the risk of prostate cancer are more encouraging. The weak estrogenic effects of isoflavones and the similarity in chemical structure between soybean isoflavones and the synthetic isoflavone ipriflavone, which was shown to increase bone mineral density in postmenopausal women, suggest that soy or isoflavones may reduce the risk of osteoporosis. Rodent studies tend to support this hypothesis, as do the limited preliminary data from humans. Given the nutrient profile and phytochemical contribution of beans, nutritionists should make a concerted effort to encourage the public to consume more beans in general and more soyfoods in particular.

Am J Clin Nutr . 1999 Sep;70(3 Suppl):439S-450S

Effect of genistein on in vitro and in vivo models of cancer.
In two-thirds of studies on the effect of genistein-containing soy materials in animal models of cancer, the risk of cancer (incidence, latency or tumor number) was significantly reduced. In addition, purified genistein delayed mammary tumor appearance in association with increased cell differentiation in mammary tissue in rats treated with 7, 12-dimethylbenz[a]anthracene when administered neonatally, inhibited phorbol ester-induced H2O2 production in a model of skin cancer, and inhibited aberrant crypt formation in a model of colonic cancer. In in vitro models, genistein inhibited the proliferation of human tumor cell lines in culture with a wide variation in IC50 values (2.6-79 mumol/L, or 1-30 micrograms/mL). In only a few cases was the IC50 below 13.2 mumol/L (5 micrograms/mL), the presumed upper limit for the serum genistein concentration in those on a high soy diet. In future studies, greater emphasis should be placed on the effect of genistein on nontransformed, normal cell lines from the tissues where cancer can occur rather than established tumor cell lines. Similarly, the effect of genistein on the progression and/or promotion of cancer may be more clearly examined using nontransformed cell lines transfected with specific oncogenes thought to be activated during oncogenesis.

J Nutr . 1995 Mar;125(3 Suppl):777S-783S

The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation.
CONTEXT: Raloxifene hydrochloride is a selective estrogen receptor modulator that has antiestrogenic effects on breast and endometrial tissue and estrogenic effects on bone, lipid metabolism, and blood clotting. OBJECTIVE: To determine whether women taking raloxifene have a lower risk of invasive breast cancer. DESIGN AND SETTING: The Multiple Outcomes of Raloxifene Evaluation (MORE), a multicenter, randomized, double-blind trial, in which women taking raloxifene or placebo were followed up for a median of 40 months (SD, 3 years), from 1994 through 1998, at 180 clinical centers composed of community settings and medical practices in 25 countries, mainly in the United States and Europe. PARTICIPANTS: A total of 7,705 postmenopausal women, younger than 81 (mean age, 66.5) years, with osteoporosis, defined by the presence of vertebral fractures or a femoral neck or spine T-score of at least 2.5 SDs below the mean for young healthy women. Almost all participants (96%) were white. Women who had a history of breast cancer or who were taking estrogen were excluded. INTERVENTION: Raloxifene, 60 mg, 2 tablets daily; or raloxifene, 60 mg, 1 tablet daily and 1 placebo tablet; or 2 placebo tablets. MAIN OUTCOME MEASURES: New cases of breast cancer, confirmed by histopathology. Transvaginal ultrasonography was used to assess the endometrial effects of raloxifene in 1781 women. Deep vein thrombosis or pulmonary embolism were determined by chart review. RESULTS: Thirteen cases of breast cancer were confirmed among the 5,129 women assigned to raloxifene vs 27 among the 2,576 women assigned to placebo (relative risk [RR], 0.24; 95% confidence interval [CI], 0.13-0.44; P<.001). To prevent 1 case of breast cancer, 126 women would need to be treated. Raloxifene decreased the risk of estrogen receptor-positive breast cancer by 90% (RR, 0.10; 95% CI, 0.04-0.24), but not estrogen receptor-negative invasive breast cancer (RR, 0.88; 95% CI, 0.26-3.0). Raloxifene increased the risk of venous thromboembolic disease (RR, 3.1; 95% CI, 1.5-6.2), but did not increase the risk of endometrial cancer (RR, 0.8; 95% CI, 0.2-2.7). CONCLUSION: Among postmenopausal women with osteoporosis, the risk of invasive breast cancer was decreased by 76% during 3 years of treatment with raloxifene.

JAMA . 1999 Jun 16;281(23):2189-97

Dietary effects on breast-cancer risk in Singapore.
It is suspected that diet influences the risk of getting breast cancer. A study of diet and breast cancer was done among 200 Singapore Chinese women with histologically confirmed disease and 420 matched controls. A quantitative food-frequency questionnaire was used to assess intakes of selected nutrients and foods 1 year before interview. Daily intakes were computed and risk analysed after adjustment for concomitant risk factors. In premenopausal women, high intakes of animal proteins and red meat were associated with increased risk. Decreased risk was associated with high intakes of polyunsaturated fatty acids (PUFA), beta-carotene, soya proteins, total soya products, a high PUFA to saturated fatty acid ratio, and a high proportion of soya to total protein. In multiple analysis, the variables which were significant after adjustment for each other were red meat (p less than 0.001) as a predisposing factor, and PUFA (p = 0.02), beta-carotene (p = 0.003), and soya protein (p = 0.02) as protective factors. The analysis of dietary variables in postmenopausal women gave uniformly non-significant results. Our finding that soya products may protect against breast cancer in younger women is of interest since these foods are rich in phyto-oestrogens.

Lancet . 1991 May 18;337(8751):1197-200

Soy isoflavones--benefits and risks from nature's selective estrogen receptor modulators (SERMs).
Phytoestrogens have become one of the more topical areas of interest in clinical nutrition. These non-nutrient bioactive compounds are ubiquitous to the plant kingdom and possess a wide range of biological properties that contribute to the many different health-related benefits reported for soy foods and flaxseeds--two of the most abundant dietary sources of phytoestrogens. Reviewed is the recent knowledge related to their pharmacokinetics and clinical effects, focusing mainly on isoflavones that are found in high concentrations in soy foods. Arguments are made for considering soy isoflavones as natural selective estrogen receptor modulators (SERMs) based upon recent data of their conformational binding to estrogen receptors. Rebuttal is made to several key and important issues related to the recent concerns about the safety of soy and its constituent isoflavones. This article is not intended to be a comprehensive review of the literature but merely highlight recent research with key historical perspectives.

J Am Coll Nutr . 2001 Oct;20(5 Suppl):354S-362S; discussion 381S-383S

Phytoestrogen intake and endometrial cancer risk.
BACKGROUND: The development of endometrial cancer is largely related to prolonged exposure to unopposed estrogens. Phytoestrogens (i.e., weak estrogens found in plant foods) may have antiestrogenic effects. We evaluated the associations between dietary intake of seven specific compounds representing three classes of phytoestrogens (isoflavones, coumestans, and lignans) and the risk of endometrial cancer. METHODS: In a case-control study from the greater San Francisco Bay Area, we collected dietary information from 500 African American, Latina , and white women aged 35-79 years who were diagnosed with endometrial cancer between 1996 and 1999 and from 470 age- and ethnicity-matched control women identified through random-digit dialing. Unconditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Isoflavone (OR = 0.59, 95% CI = 0.37 to 0.93 for the highest versus lowest quartile of exposure) and lignan (OR = 0.68, 95% CI = 0.44 to 1.1) consumptions were inversely related to the risk of endometrial cancer. These associations were slightly stronger in postmenopausal women (OR = 0.44, 95% CI = 0.26 to 0.77 and OR = 0.57, 95% CI = 0.34 to 0.97 for isoflavones and lignans, respectively). Obese postmenopausal women consuming relatively low amounts of phytoestrogens had the highest risk of endometrial cancer (OR = 6.9, 95% CI = 3.3 to 14.5 compared with non-obese postmenopausal women consuming relatively high amounts of isoflavones); however, the interaction between obesity and phytoestrogen intake was not statistically significant. CONCLUSION: Some phytoestrogenic compounds, at the levels consumed in the typical American-style diet, are associated with reduced risk of endometrial cancer.

J Natl Cancer Inst. 2003 Aug 6;95(15):1158-64