Equol [7-hydroxy-3-(4'-hydroxyphenyl)-chroman] is a nonsteroidal estrogen of the isoflavone class. It is exclusively a product of intestinal bacterial metabolism of dietary isoflavones and it possesses estrogenic activity, having affinity for both estrogen receptors, ERalpha and ERbeta. Equol is superior to all other isoflavones in its antioxidant activity. It is the end product of the biotransformation of the phytoestrogen daidzein, one of the two main isoflavones found in abundance in soybeans and most soy foods. Once formed, it is relatively stable; however, equol is not produced in all healthy adults in response to dietary challenge with soy or daidzein. Several recent dietary intervention studies examining the health effects of soy isoflavones allude to the potential importance of equol by establishing that maximal clinical responses to soy protein diets are observed in people who are good "equol-producers." It is now apparent that there are two distinct subpopulations of people and that "bacterio-typing" individuals for their ability to make equol may hold the clue to the effectiveness of soy protein diets in the treatment or prevention of hormone-dependent conditions. In reviewing the history of equol, its biological properties, factors influencing its formation and clinical data, we propose a new paradigm. The clinical effectiveness of soy protein in cardiovascular, bone and menopausal health may be a function of the ability to biotransform soy isoflavones to the more potent estrogenic isoflavone, equol. The failure to distinguish those subjects who are "equol-producers" from "nonequol producers" in previous clinical studies could plausibly explain the variance in reported data on the health benefits of soy.

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The Clinical Importance of the Metabolite Equol—A Clue to the Effectiveness of Soy and Its Isoflavones

Substantial evidence indicates that diets high in plant-based foods may explain the epidemiologic variance of many hormone-dependent diseases that are a major cause of mortality and morbidity in Western populations. There is now an increased awareness that plants contain many phytoprotectants. Lignans and isoflavones represent two of the main classes of phytoestrogens of current interest in clinical nutrition. Although ubiquitous in their occurrence in the plant kingdom, these bioactive nonnutrients are found in particularly high concentrations in flaxseeds and soybeans and have been found to have a wide range of hormonal and nonhormonal activities that serve to provide plausible mechanisms for the potential health benefits of diets rich in phytoestrogens. Data from animal and in vitro studies provide convincing evidence for the potential of phytoestrogens in influencing hormone-dependent states; although the clinical application of diets rich in these estrogen mimics is in its infancy, data from preliminary studies suggest beneficial effects of importance to health. This review focuses on the more recent studies pertinent to this field and includes, where appropriate, the landmark and historical literature that has led to the exponential increase in interest in phytoestrogens from a clinical nutrition perspective.

Dietary Isoflavones: Biological Effects and Relevance to Human Health

Objectives. We investigated whether vasomotor symptom reporting or patterns of change in symptom reporting over the perimenopausal transition among women enrolled in a national study differed according to race/ethnicity. We also sought to determine whether racial/ethnic differences were explained by sociodemographic, health, or lifestyle factors.Methods. We followed 3198 women enrolled in the Study of Women’s Health Across the Nation during 1996 through 2002. We analyzed frequency of vasomotor symptom reporting using longitudinal multiple logistic regressions.Results. Rates of vasomotor symptom reporting were highest among African Americans (adjusted odds ratio [OR]=1.63; 95% confidence interval [CI]=1.21, 2.20). The transition to late perimenopause exhibited the strongest association with vasomotor symptoms (adjusted OR = 6.64; 95% CI = 4.80, 9.20). Other risk factors were age (adjusted OR=1.17; 95% CI=1.13, 1.21), having less than a college education (adjusted OR = 1.91; 95% CI = 1.40, 2.61), increasing...

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Longitudinal Analysis of the Association Between Vasomotor Symptoms and Race/Ethnicity Across the Menopausal Transition: Study of Women’s Health Across the Nation

Soy protein and isoflavones (phytoestrogens) have gained considerable attention for their potential role in improving risk factors for cardiovascular disease. This scientific advisory assesses the more recent work published on soy protein and its component isoflavones. In the majority of 22 randomized trials, isolated soy protein with isoflavones, as compared with milk or other proteins, decreased LDL cholesterol concentrations; the average effect was approximately 3%. This reduction is very small relative to the large amount of soy protein tested in these studies, averaging 50 g, about half the usual total daily protein intake. No significant effects on HDL cholesterol, triglycerides, lipoprotein(a), or blood pressure were evident. Among 19 studies of soy isoflavones, the average effect on LDL cholesterol and other lipid risk factors was nil. Soy protein and isoflavones have not been shown to lessen vasomotor symptoms of menopause, and results are mixed with regard to soy's ability to slow postmenopausal bone loss. The efficacy and safety of soy isoflavones for preventing or treating cancer of the breast, endometrium, and prostate are not established; evidence from clinical trials is meager and cautionary with regard to a possible adverse effect. For this reason, use of isoflavone supplements in food or pills is not recommended. Thus, earlier research indicating that soy protein has clinically important favorable effects as compared with other proteins has not been confirmed. In contrast, many soy products should be beneficial to cardiovascular and overall health because of their high content of polyunsaturated fats, fiber, vitamins, and minerals and low content of saturated fat.

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Soy Protein, Isoflavones, and Cardiovascular Health An American Heart Association Science Advisory for Professionals From the Nutrition Committee

Dietary phytoestrogens and health.

The effect of dietary soy supplementation on hot flushes.

Dietary soy supplementation and phytoestrogen levels.

BACKGROUND AND AIM Postmenopausal modification of the lipid profile plays a major role in the risk of ischemic heart disease. Lifestyle counseling and estrogen replacement therapy have all been proposed as first-line measures, but there is no agreement on the best way to treat climacteric dyslipidemia. Soybean-based diet seems particularly attractive in this context, given its cholesterol lowering potential, its hypothetical anticancerous effects and possible modification of climacteric symptoms. METHODS AND RESULTS We evaluated the effect of 60 g isolated soy protein (ISP) daily on the lipid profile of 104 postmenopausal women (53.3 +/- 3.3 years) in a double-blind, parallel, placebo-controlled (caseinate) trial, as part of a broader assessment of the effect of ISP on climacteric symptomatology. Serum total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, apo A-I, apo B and lipoprotein (a) were determined before and after a 12-week diet modification. Seventy-seven women completed the trial. Both soy and placebo determined a significant reduction in total cholesterol (-0.42 +/- 0.79 and -0.40 +/- 0.57 mmol/L) and LDL-cholesterol (-0.35 +/- 0.72 and -0.31 +/- 0.54 mmol/L), but only soy had a significant lowering effect on apo B and the LDL-cholesterol/HDL-cholesterol ratio (-6% and -8% from baseline respectively); lipoprotein (a) plasma levels were not significantly changed by either treatment. Forty-four women were dyslipidemic at baseline; those with increased LDL concentrations showed a somewhat greater improvement in their lipoprotein profile (LDL-cholesterol and apo B reduction) with soy rather than placebo. No further information emerged when the subjects were divided into three apo E phenotypes. CONCLUSIONS We conclude that diet supplementation with 60 g ISP is slightly better than caseinate in favorably modifying the lipoprotein metabolism of postmenopausal women; this effect is more evident in hypercholesterolemic subjects.

Plasma lipoproteins in soy-treated postmenopausal women: a double-blind, placebo-controlled trial.

The menopausal transition: a dynamic approach to the pathogenesis of neurovegetative complaints

Hormone replacement therapy (HRT) is the treatment of choice for neurovegetative climacteric symptoms. In some women, however, HRT may either be contraindicated, or the patients themselves may prefer a non-hormonal form of treatment. Trazodone is a drug that acts a weak, but specific, inhibitor of the uptake of 3H-serotonin and is generally used for its antidepressant effects. In this study we have observed the efficacy of oral Trazodone (75 mg/day) in the treatment of the climacteric symptoms in 25 menopausal patients recruited at the Menopause Clinic of Ferrara University Hospital. The symptoms were scored from 0 to 3 according to presence and intensity. The patients were all complaining of climacteric neurovegetative symptoms (average symptom score 2.43). Symptoms scores were recorded before starting treatment and then again after 3 months. The appeared to be particularly effective on the intensity of anxiety (OR: 0.08, CI: 0-0.080), insomnia (OR: 0.15, CI: 0.02-0.71), and irritability (OR: 0.29, CI: 0.04-1.48). The intensity of hot flushes appeared reduced but was not statistically significant (OR: 0.52, CI: 0.08-1.87). However, the average total score of symptoms appearing in the Kupperman scale was reduced (-14%) after treatment. Trazodone should be kept in mind as a possible alternative to HRT. This drug can be particularly useful for those patients whose climacteric symptoms have a marked connotation of anxiety rather than for hot flushes or when HRT are contraindicated.

P. Albertazzi

Papers

The effect of dietary soy supplementation on hot flushes.

Dietary soy supplementation and phytoestrogen levels.

Plasma lipoproteins in soy-treated postmenopausal women: a double-blind, placebo-controlled trial.

The menopausal transition: a dynamic approach to the pathogenesis of neurovegetative complaints

Trazodone: a non-hormonal alternative for neurovegetative climacteric symptoms