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American Journal of Clinical Nutrition, Vol. 88, No. 2, 298-304, August 2008
© 2008 American Society for Nutrition

ORIGINAL RESEARCH COMMUNICATION

Soy food consumption does not lower LDL cholesterol in either equol or nonequol producers1,2,3

Alicia A Thorp1, Peter RC Howe1, Trevor A Mori1, Alison M Coates1, Jonathan D Buckley1, Jonathan Hodgson1, Jackie Mansour1 and Barbara J Meyer1

1 From the Australian Technology Network Centre for Metabolic Fitness and Nutritional Physiology Research Centre, University of South Australia, South Australia, Australia (AAT, PRCH, AMC, and JDB); the Discipline of Physiology, University of Adelaide, South Australia, Australia (AAT); the School of Medicine and Pharmacology, University of Western Australia, Western Australia, Australia (TAM, JH, and JM); and the School of Health Sciences and Smart Foods Centre, University of Wollongong, Australia (BJM)

2 Supported by Australian Research Council Linkage Grant LP0349193 in partnership with Freedom Nutritional Products Limited.

3 Reprints not available. Address correspondence to PRC Howe, Nutritional Physiology Research Centre, University of South Australia, GPO Box 2471, Adelaide 5001, South Australia, Australia. E-mail: peter.howe{at}unisa.edu.au.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background:Health claims link soy protein (SP) consumption, through plasma cholesterol reduction, to a decreased risk of heart disease. Soy isoflavones (ISOs), particularly in individuals who produce equol, might also contribute to lipid lowering and thus reduce SP requirements.

Objective:The objective was to examine the contributions of SP, ISOs, and equol to the hypocholesterolemic effects of soy foods.

Design:Nonsoy consumers (33 men, 58 women) with a plasma total cholesterol (TChol) concentration >5.5 mmol/L participated in a double-blind, placebo-controlled, crossover intervention trial. The subjects consumed 3 diets for 6 wk each in random order, which consisted of foods providing a daily dose of 1) 24 g SP and 70–80 mg ISOs (diet S); 2) 12 g SP, 12 g dairy protein (DP), and 70–80 mg ISOs (diet SD); and 3) 24 g DP without ISOs (diet D). Fasting plasma TChol, LDL cholesterol, HDL cholesterol, and triglycerides (TGs) were measured after each diet.

Results:TChol was 3% lower with the S diet (–0.17 ± 0.06 mmol/L; P < 0.05) than with the D diet, and TGs were 4% lower with both the S (–0.14 ± 0.05 mmol/L; P < 0.05) and SD (–0.12 ± 0.05 mmol/L; P < 0.05) diets. There were no significant effects on LDL cholesterol, HDL cholesterol, or the TChol:HDL cholesterol ratio. On the basis of urinary ISOs, 30 subjects were equol producers. Lipids were not affected significantly by equol production.

Conclusions:Regular consumption of foods providing 24 g SP/d from ISOs had no significant effect on plasma LDL cholesterol in mildly hypercholesterolemic subjects, regardless of equol-producing status.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Health claims approved for soy foods in the United States and United Kingdom (1, 2) link daily consumption of 25 g soy protein (SP) to a reduced risk of heart disease through a lowering of LDL cholesterol. The substantive evidence underpinning the approval of these health claims came from a meta-analysis by Anderson et al (3), which reported that regular consumption of soy lowered total cholesterol (TChol) by 9.3%, LDL cholesterol by 12.9%, and triglycerides (TGs) by 10.5% without affecting HDL cholesterol. However, the average consumption of SP associated with these benefits was 47 g/d, which is almost double that recommended in the US health claim. Moreover, Anderson et al found no relation between reductions in cholesterol and the level of SP intake, which suggests that some component other than the protein in soy, such as isoflavones (ISOs), may contribute to the cholesterol-lowering effect. This hypothesis was not addressed in the meta-analysis and the US Food and Drug Administration (FDA) stipulated in its health claim statement that evidence did not support a significant role for ISOs in the cholesterol-lowering effects of SP (4).

In contrast with the position of the FDA, the American Heart Association scientific advisory Statement for Healthcare Professionals on SP and CVD stated that, whereas there was some evidence that substituting SP for animal protein could reduce TChol and LDL cholesterol, the benefit could not be attributed solely to SP. Instead, they recommended the daily consumption of ≥25 g SP/d and its associated phytochemicals to improve lipid profiles in individuals with hypercholesterolemia (4). Consistent with this, several recent meta-analyses have reported that the greatest reductions in cholesterol, particularly in LDL cholesterol, are achieved when SP and ISOs are delivered concurrently (5–8). However, other studies have failed to show any relation between the level of intake of ISOs and the magnitude of reduction in LDL cholesterol (9–14).

Setchell (15) hypothesized that the inconsistency in results from trials investigating the effects of SP delivered in combination with ISOs may be related to the ability of individuals to convert the soy ISO daidzein into equol through bacterial fermentation in the large intestine, compared with 50–55% of Asian populations (16). In a relatively small study, Meyer et al (17) demonstrated retrospectively that the lipid-lowering effects of soy containing both SP and ISOs were limited to equol producers. Thus, when consumed in combination with ISOs, equol producers may require less SP than is recommended in the current health claims to achieve reductions in LDL cholesterol.

This study investigated whether the postulated hypocholesterolemic benefit of SP could be attained by consuming foods with a similar ISO content but with half the recommended SP content and whether these benefits were limited to equol producers.


   SUBJECTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Subjects
A randomized, double-blind, placebo-controlled triple crossover dietary intervention trial of 18 wk duration was undertaken as a multicenter collaboration between the University of South Australia, the University of Western Australia and the University of Wollongong. The protocol for the intervention was approved by, and followed in accordance with, ethical standards of each institution's Human Research Ethics Committee. All participants provided written informed consent before participation.

Adult volunteers (age: 18–80 y) with a fasting plasma TChol concentration ≥5.5 mmol/L at screening but who were otherwise healthy were recruited from the general community by advertisement between June 2004 and July 2005. Eligibility was initially assessed by phone interview and a diet and lifestyle questionnaire. Potential participants were then invited to attend a screening visit to measure fasting TChol with a finger-prick test with the use of an automated analyzer (Reflotron; Roche Diagnostics, Basal, Switzerland). Potential participants were excluded if they were smokers, were pregnant, were diabetic, had a history of cardiovascular disease (CVD), had major surgery in the past 3 mo, had a blood pressure >170/100 mm Hg, had liver or renal disease, took hormone replacements, took lipid-lowering or antihypertensive medications, or regularly ate soy products or plant sterol margarines. Participants were also excluded if they were unwilling to consume the test foods or had an allergy to dairy or soy products.

Study foods
The following foods were prepared for use in the intervention trial (Freedom Nutritional Products Limited, Taren Point, NSW, Australia): plain and flavored (chocolate and coffee) milks, instant custard, apricot and bran-flavored cookies, chocolate snack bars, and dried pasta. The foods were low in saturated fat and cholesterol to ensure that they met current dietary guidelines (18). Each product was prepared in 3 versions containing equivalent amounts of protein (8 g/serving) from soy (S), dairy (D) or soy and dairy (SD). The ISO content of the foods was confirmed according to a modified version of the method of Pettersson and Kiessling (19). ISOs were analyzed by HPLC (Prominence model SIL-20 A; Shimadzu, Tokyo, Japan) with electrochemical detection (VT-03 Electrochemical Flow Cell; INTRO, Antec Leyden) by using a hydrogen reference working electrode. Concentrations were determined by reference to peak areas for internal standards of daidzein (Sigma D-7802; Sigma, St Louis, MO), equol (Plantech, Reading, UK), and genistein (Sigma G-664) applied at a range of concentrations. The S and SD foods contained ISOs (14.1–43.7 mg aglycone equivalents/serving). The contents of ISO aglycone equivalents of the trial foods are shown in Table 1Go.


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  		TABLE 1 Isoflavone content of trial foods

 
Study design
The intervention trial consisted of three 6-wk-long dietary treatments administered according to a Latin square design. In view of the short half-life of circulating ISOs and the relatively short time frame required to induce stable changes in plasma blood cholesterol, specifically in LDL cholesterol (3 wk); a washout period between intervention periods was considered unnecessary.

Each dietary treatment consisted of 3 servings/d of the trial foods, which contributed 24 g protein to the subjects' daily protein intake. Diet S, which approximated the 25 g SP/d intake recommended in the current health claim, provided 24 g SP with 71.4 ± 1.9 mg ISO aglycone equivalents/d. Diet SD provided 12 g dairy protein and 12 g SP with 76 ± 1.5 mg ISO aglycone equivalents/d; diet D was a control diet providing 24 g dairy protein and 0.5 ± 0.1 mg ISO aglycone equivalents/d.

Subjects were block matched into 3 groups balanced for age, sex, and fasting TChol. Each group was then randomly assigned to an order in which they would consume the 3 diets. Compliance was measured on the basis of food records, on which the subjects were required to record daily the quantities and types of trial foods consumed.

Testing was performed on 2 consecutive mornings at baseline and after completing each 6-wk diet treatment. Throughout the intervention, participants agreed not to consume any foods known to contain soy. To minimize any increase in energy intake, the subjects were advised to substitute the trial foods for similar foods in their habitual diets. To ensure that subjects followed this instruction, validated food-frequency questionnaires (FFQs; Victorian Cancer Council) (20–22) were completed at the end of each of the 3 diet phases and assessed for macronutrient intake.

Urinary isoflavone analysis
An overnight urine sample was provided by subjects at the end of each diet phase to quantify urinary concentrations of genistein, daidzein, and equol. ISOs were extracted from urine samples by using a modification of the method of King and Bursill (23) and identified by HPLC with electrochemical detection. An isocratic mobile phase solution of 45:55:1 ammonium acetate (0.1 mol/L; pH 4.6), HPLC grade methanol, and 25 mmol/L EDTA disodium salt with 50 mmol/L KCl was used to run 50-µL samples at 0.8 mL/min for 60 min. Concentrations were determined by comparison with relative peak areas of external standards.

Identification of equol producers
Equol producers were identified according to the method of Setchell and Cole (24), whereby the urinary S-equol:daidzein ratio for each subject at the end of the S and SD diet phases were averaged and expressed as log10. Subjects who exhibited a log10 value above –1.75 were deemed to be equol producers (24).

Blood collection and analyses
Duplicate blood samples were taken by venipuncture from an antecubital vein on 2 consecutive mornings after an overnight fast (>10 h). Blood was collected into tubes containing EDTA, which were centrifuged at 3000 x g for 10 min at 4 °C and stored at –80 °C until analyzed. Plasma concentrations of TChol, HDL cholesterol, and TGs were measured in duplicate using a spectrophotometric autoanalyser (Konelab, Model 20xTi; Thermo Electron, Waltham, MA) with the manufacturer's assay kits, quality controls, and reagents. LDL cholesterol was calculated according to the Friedewald equation (25).

Anthropometric measurements
The subject's height and weight were measured at baseline and at the end of each 6-wk diet phase. Weight was recorded to the nearest 0.01 kg with a digital scale (Tanita UltimateScale, model 2000; Tanita Corporation, Tokyo, Japan). Height was measured to the nearest 0.1 cm with a wall-mounted stadiometer (Seca 220; Vogel and Halke, Hamburg, Germany). Body mass index (BMI) was calculated as weight (in kg) divided by height2 (in m).

Data analyses and statistical considerations
Data were analyzed by using STATISTICA for WINDOWS software (version 5.1; StatSoft Inc, Tulsa, OK). One-way analysis of variance (ANOVA) with repeated measures was used to examine the overall effects of the different diet treatments on the dependent variables. To determine the effects of the diet treatments on the dependent variables, and their interaction with sex and/or equol status, 3-factor ANOVA with repeated measures was used. To determine the effect of subject's habitual diets on the dependent variables, one-factor ANOVA was used with macronutrient intake expressed as a changing covariate. When ANOVA showed significant main effects, the differences between means were determined post hoc by using Tukey's honestly significant difference test. The test for the difference between two proportions was used to determine whether there was a difference in the population of equol producers of each sex. Relations between variables were determined by using linear regression. Statistical significance was set at P < 0.05. All data in tables and graphs are shown as means ± SEM unless stated otherwise.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
One hundred sixty-seven individuals attended a clinic visit for screening. Of these, 126 met the entry criteria and commenced the study. Ninety one subjects completed the 18-wk intervention. Inability to comply with the protocol (n = 26), poor tolerance of study foods (n = 4), change in work commitments (n = 3), and interstate or overseas travel (n = 2) were the primary reasons cited by the 35 subjects who withdrew. The baseline anthropometric and lipid measurements for those who completed the intervention trial are shown in Table 2Go. Experimental foods, particularly the milks, instant custard, and cookies, were well received. Compliance with consumption of 3 servings/d of the foods was similar with all diets (D diet: 97 ± 0.6%; SD diet: 97 ± 0.5%; S diet: 96 ± 0.7%).


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  		TABLE 2 Baseline characteristics of subjects who completed the intervention trial1

 
Plasma lipid concentrations at the end of each diet treatment are shown in Table 3Go, and changes in the S and SD diet groups relative to those in the D diet group are shown in Figure 1Go. ANOVA showed significant treatment effects on TChol (P = 0.014) and TGs (P < 0.001), but not on LDL cholesterol (P = 0.22) or HDL cholesterol (P = 0.72). Post hoc analysis showed that, compared with the D diet, TChol was 3% lower during diet S (P = 0.01), and TGs were 3.5% and 4% lower during diet SD (P = 0.03) and diet S (P = 0.009), respectively, with no difference between the SD and S diet groups (P = 0.94). The ratios of TChol:HDL cholesterol in response to the D, SD, and S diets were 5.05, 5.01, and 4.76, respectively. Despite a trend for the ratio of TChol:HDL cholesterol to be lower with the S treatment than with the SD and D treatments, this difference was not statistically significant (P = 0.06). Anthropometric measures did not change during the study period; the results for weight are shown in Table 4Go.


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  		TABLE 3 Plasma lipid concentrations at the end of each diet phase1

 

Figure 1
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  		FIGURE 1. Mean (±SEM) changes in plasma lipids after consumption of the soy and dairy (SD) and soy (S) diets compared with the dairy (control) diet. One-factor ANOVA with repeated measures was used to analyze the data. *Significant changes, P < 0.05 (Tukey's honestly significant difference post hoc test).

 

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  		TABLE 4 Macronutrient intakes of all 91subjects assessed with a food-frequency questionnaire and the weight of subjects by diet1

 
Approximately 33% (30/91) of subjects were equol producers (Table 2Go). Of the equol-producing individuals, 11 were men and 19 were women, and there was no difference in the proportion of equol producers between sex (P = 0.93). Equol production status did not influence the effects of the diet treatments on blood lipids, as indicated by the lack of any significant interactions between diet treatment and equol production status on changes in TChol, TGs, LDL cholesterol, or HDL cholesterol (P > 0.68 for all).

The experimental food products for the S and SD diets provided varying amounts of ISOs (Table 1Go), resulting in significantly different ISO intakes during the different dietary phases (D diet < S diet < SD diet; P < 0.05), as shown in Table 4Go. There were no significant correlations, however, between changes in ISO intakes and changes in lipid variables across all subjects or in the subgroup of equol producers.

Analysis of FFQs showed that consumption of saturated fat was significantly higher during the D diet than during the SD and S diets (P > 0.01; Table 4Go). Unsaturated fat intake was higher during the S diet than during the SD (P = 0.04) and D (P = 0.01) diets. Moreover, the ratio of unsaturated to saturated fat intake differed significantly between all treatment phases (P < 0.01): S diet > SD diet > D diet. When the consumption of intervention foods was removed from the FFQ data for each treatment, saturated fat intake was consistent across the diets (P = 0.60), which indicated that the elevation in saturated fat intake during the D diet was a direct result of consuming the intervention foods rather than a change in background diet. Sugar intake was also significantly lower with the S diet than with the D and SD diets (P < 0.01); however, when sugar intake was controlled for, the changes in TGs across the diets remained significant (P = 0.01).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
In the present study, consumption of novel foods designed to approximate the intake of SP recommended by the US FDA health claim and the UK Joint Health Claims Initiative (JHCI), together with the associated ISO content, had no effect on LDL cholesterol. It was anticipated that subjects would, at the very least, experience a reduction in LDL cholesterol while consuming the S diet, because recent reviews and meta-analyses (26, 27) predict a 3–5% reduction in LDL cholesterol from an intake of 25 g SP/d. A small reduction in TChol was observed with the S diet, although saturated fat intake differed between diets and may have contributed to this effect on TChol.

LDL cholesterol is one of the most comprehensively studied CVD risk factors and a principal criterion on which the National Cholesterol Education Program estimates risk and recommends therapy for CVD (28). Moreover, the reduction in LDL cholesterol observed in numerous trials provided the foundation for the FDA's declaration that regular soy consumption could reduce a person's risk of heart disease. LDL-cholesterol concentrations in the mild hypercholesterolemic subjects in the current study, however, failed to be significantly reduced with either the SD or S diets.

A similar, smaller-scale study (29) recently reported a 5% reduction in LDL cholesterol with the consumption of 25 g SP/d, which was consistent with the average 6.8% reduction reported in the meta-analysis of Anderson et al (3). Importantly, however, their subjects had substantially higher baseline LDL-cholesterol concentrations (averaging 4.8 ± 0.5 mmol/L compared with 3.60 ± 0.7 mmol/L in the present study). The difference in LDL cholesterol in response to 25 g SP/d may be related to the subjects' baseline LDL-cholesterol concentrations, which suggests that a clinically relevant reduction in LDL cholesterol might only be obtained in subjects with baseline concentrations that would qualify for statin treatment. Furthermore, the mean SP intake in the meta-analysis by Anderson et al (3), which delivered clinically significant lipid reductions was 47 g/d—almost twice that proposed by the FDA and the JHCI. The failure of the SD and S diets to achieve clinically significant reductions in LDL cholesterol cannot be attributed to deviations from the study protocol. Compliance, as determined from self-reported food records, was >96% for all diets over the course of the intervention, which indicates that subjects were consuming the intended doses of SP and ISOs during the treatment phases. However, basing subject compliance solely on self-reported food intake data was a potential limitation of this study, and subjects could have overreported the amount of trial foods they actually consumed.

Despite similar trends in LDL cholesterol and TChol reduction with the S diet, only TChol was significantly reduced. The failure of the LDL cholesterol reduction to reach statistical significance with the S diet was due to the study being underpowered to detect the smaller than anticipated change of 1.2%. Given the concomitant reduction in plasma TGs and the trend for a reduction in the TChol:HDL cholesterol ratio, the reduction in TChol could be explained by a reduction in VLDL.

TChol was not reduced with the SD diet, despite the foods providing a significantly greater daily intake of ISO aglycone equivalents (76 ± 1.5 mg/d). The 3% TChol reduction observed with the S diet (0.17 ± 0.06 mmol/L) is consistent with reductions reported in subjects with normal baseline cholesterol concentrations who consumed similar quantities of SP and ISOs (5). Controlling for baseline TChol in the current study did not alter the extent of TChol reduction, despite the high correlation between initial TChol concentrations and reductions in LDL cholesterol and TChol in the meta-analysis by Anderson et al (3). However, the range of baseline TChol concentrations was considerably higher in the meta-analysis than in the present study.

Despite counseling subjects to maintain their normal dietary habits throughout the intervention, macronutrient intakes, based on FFQ data, differed between treatments. Notably, the saturated fat intake of the subjects was significantly higher with the D diet than with the SD and S diets as a direct result of consuming the intervention foods rather than a change in background diet. Given that there was no significant decrease in LDL-cholesterol concentrations, it is likely that the modest 3% reduction in TChol observed with the S diet was due to a reduced saturated fat intake coupled with an increased intake of unsaturated fat. This speculation parallels that of Gardner et al (29, 30), who reported that between one-third and one-half of the LDL-lowering effect observed when consuming soy milk was attributable to its decreased saturated fat and cholesterol and increased polyunsaturated fat content compared with dairy milk. Furthermore, the magnitude of the LDL cholesterol reduction observed was not shown to be attributable to SP intake.

No significant change was observed in HDL cholesterol with the S and SD treatments. The inability to see a benefit in HDL cholesterol with treatment may have been related to the length of the diets, because evidence indicates that ISO supplementation for >6 wk is necessary to mediate significant improvements (31).

In the present study, plasma TGs were reduced significantly after both the SD and S diets. Although increased sugar in the diet increases TGs (32, 33) and sugar intake varied across dietary treatments, the lower sugar intakes from the SD and S diets did not account for the decrease in TGs when controlled for across the diets. A likely explanation for the TG reduction with the SD and S diets was the inclusion of ISOs, which can activate peroxisome proliferator–activated receptors, which leads to decreased TG concentrations via increased fatty acid oxidation (34, 35). The ISO genistein has also been shown to activate peroxisome proliferator–activated receptor-{gamma}, which results in an up-regulation of adipogenesis that involves the uptake of fatty acids from plasma and subsequent redistribution into adipocytes (36).

The food products manufactured for the current trial are the first of their kind to be used to investigate whether a lesser intake of SP than that recommended by the FDA and JHCI can mediate hypocholesterolemic effects when consumed in combination with a full complement of ISOs. It has been consistently shown that cholesterol reduction is enhanced when SP and ISOs are delivered in combination, which indicates an interactive effect between the components. Contrary to views held by the American Heart Association's Scientific Advisory Committee and the lack of evidence supporting a dose-response relation between SP consumption and cholesterol reduction, the current health claims dismiss any contributory effect of ISOs.

Several trials have used differently processed forms of soybean (whole, fermented, or unfermented) or products derived from soy flour (textured SP) or soymilk (tofu and yogurt) with varying quantities of ISOs and compared the effects of these foods on blood lipids with the effects of foods containing animal protein (17, 29, 30, 37–39). However no trials to date have looked at the impact on cholesterol of soy foods in which SP has been partially replaced with more palatable dairy protein while retaining the full complement of ISOs. The present study sought to assess the impact of the consumption of such foods on plasma lipids.

Interestingly, changes in lipids were not correlated with mean daily ISO intake. This is consistent with the findings of several studies (11, 14) in which supplementation with isolated ISOs was shown to have no effect on blood lipids. In contrast, a recent study by Clerici et al (40) showed significant improvements in TChol and LDL cholesterol when 33 mg ISOs/d in aglycone form were provided in a pasta food matrix over an 8-wk period. If the aglycone form is required to mediate this benefit, studies such as ours using glycoside conjugates, which require digestion by gastrointestinal bacteria to become biologically active, can be expected to have more variable outcomes.

In the present study, because of some difference in foods chosen in the different diet phases, mean daily ISO intake was marginally higher with the SD diet than with the S diet. However, given that ISOs were not related to changes in blood lipids, this slight difference in ISOs between diet treatments is unlikely to be of any concern.

An objective of this study was to determine whether equol production enhanced the hypocholesterolemic effects of the soy foods. The study by Meyer et al (17) was the first human intervention to investigate retrospectively the correlation between equol production and the lipid-lowering benefits of soy supplementation. Despite only a relatively small number of equol producers (n = 8) in the study population (n = 23), they showed significant reductions in the lipid profiles of equol producers compared with nonequol producers. Of the 91 subjects who completed the present study, 30 were equol producers, which is the largest cohort identified in a dietary intervention investigating the effect of soy on cholesterol reduction. However, when subjects were categorized as either equol or nonequol producers, there was no significant difference in their responses to the dietary treatments. Our finding confirms that of another recent, but smaller, study that also showed no difference in the effect of SP on the blood lipids of equol producers and nonequol producers (29).

The current study found that the regular consumption of foods providing 24 g SP/d or, alternatively, 12 g SP/d plus an equal amount of ISOs did not significantly decrease LDL-cholesterol concentrations in mildly hypercholesterolemic subjects. This outcome was unrelated to the ability of individuals to produce equol. A 3% reduction in plasma TChol was observed with the S diet, compared with the D diet, but could be accounted for by an increased saturated fat intake with the D diet as a result of the test foods. The results of this study call into question the ability of SP to significantly reduce cholesterol and the risk of heart disease as stated in current health claims for soy foods. Consumption of soy foods can improve plasma TGs, although this benefit may be attributable to ISOs rather than to SP in the diets.


   ACKNOWLEDGMENTS
 
We are grateful to Roger King for his expert guidance concerning the isoflavone analysis.

The authors' responsibilities were as follows—BJM, PRCH, and TAM: initiated, designed, and attracted grant support for the study; AAT and JM: recruited subjects and conducted the study visits at each center; PRCH, JDB, AMC, TAM, and JH: supervised the study visits at each center; BJM: supervised the lipid analyses; AAT: conducted the laboratory and statistical analyses and prepared the manuscript; and PRCH, TAM, AMC, JDB, JH, and BJM: reviewed the manuscript. None of the authors had a potential conflict of interest.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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Received for publication February 8, 2008. Accepted for publication April 19, 2008.





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