![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
,2
* Department of Nutrition, Harvard School of Public Health, Boston, MA;
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands;
** Department of Epidemiology, Harvard School of Public Health, Boston, MA;
Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA
2To whom correspondence should be addressed. E-mail: y.t.vanderschouw{at}umcutrecht.nl.
 |
ABSTRACT |
|---|
 TOP ABSTRACT SUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
KEY WORDS: • isoflavones • lignans • cardiovascular risk factors • men • cross-sectional study
Increased intake of soy protein may have blood lipid–lowering effects in animals (1,2) and humans (3). In a recent meta-analysis of 38 studies, supplementation with soy protein compared with animal (meat and dairy) protein decreased triacylglycerols (TG)3 by 10.5% and nonsignificantly increased HDL cholesterol (HDL-C) by 2.4%. Total and LDL cholesterol (LDL-C) decreased 9.3 and 12.9%, respectively (3). This effect occurred in men as well as women, and is generally ascribed to the isoflavones in the soy, although other components, e.g., saponins or soy peptides (4), have also been held responsible. However, in a recent study, there were no significant effects of isoflavones on plasma lipid levels either constituent to soy protein or supplemental to animal protein (5).
Isoflavones are 1 of 3 main groups of phytoestrogens, plant-derived substances that are structurally related to 17ß-estradiol. The other main groups are coumestans and lignans. The major isoflavones are genistein, daidzein, formononetin, and biochanin A. The major coumestan is coumestrol, whereas the major dietary lignans are matairesinol and secoisolariciresinol. Active metabolites of dietary lignans, enterolactone and enterodiol, are produced by colonic bacteria. Isoflavones and coumestrol bind to the estrogen receptor (ER)-
at low levels compared with endogenous estrogen (6–8), but have almost comparable affinity for ER-ß (6); lignans, however, do not bind to either ER (9).
In traditional Asian diets, soy intake is usually high, ranging from 75 to 150 g/d which corresponds to an intake of isoflavones of 30–60 mg/d (10). In most Western diets in which the consumption of soy foods is limited, mean intakes of isoflavones (mainly from beans and peas, tea and coffee and nuts), and lignans (mainly from breads, cereals, rice and grain and fruits) are in the magnitude of several milligrams per day (11–13). Studies on the cardiovascular effects of isoflavones and lignans at these lower levels in Western populations are scarce. In 2 studies among postmenopausal women, intake of phytoestrogens even within this low range was associated with an improved cardiovascular risk profile (11).
Among men in Japan (14) and Hong Kong (15), where soy consumption is traditionally high, higher intake of soy products was associated with lower total serum cholesterol, consistent with supplementation studies. To the best of our knowledge, studies of habitually lower phytoestrogen intake in relation to cardiovascular risk factors in men are not available.
To evaluate further the relation between regular dietary phytoestrogen intake and cardiovascular risk factors in men, we studied participants aged 47 to 80 y enrolled in the Health Professionals Follow-up Study (HPFS).
|
SUBJECTS AND METHODS |
|---|
|
TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
Research design. From the 18,225 men who provided a blood sample between 1993 and 1995, we excluded 8922 men who did not complete all questionnaire information on diet, cigarette smoking, alcohol consumption, and physical activity from 1986 to 1994. Because disease conditions may influence body weight and cardiovascular disease (CVD) risk factors, we also excluded 208 men with CVD, diabetes, gastric or duodenal ulcer, liver disease, and cancer (except nonmelanoma skin cancer). From the remaining men, we randomly sampled 468 (47–83 y of age) based on their self-reported alcohol consumption because the original purpose of the study sample was to examine CVD risk factors related to drinking patterns. The sample is a stratified random sample selected to represent 8 distinct alcohol consumption patterns for a separate study of biomarkers of alcohol consumption. We accounted for alcohol consumption categories in our analyses to avoid biases that occur from oversampling of participants who consume alcohol. Details on the selection process and other background information related to the blood samples can be found elsewhere (16).
Dietary information.
Data on mean nutrient intake were derived from a self-administered FFQ (1994). For each food, a commonly used unit or portion size was specified, and participants were asked how often, on average, they consumed that amount of each food over the past year. There were 9 possible responses ranging from never or <1 time/mo up to 
6 times/d. We computed nutrient intake by multiplying the consumption frequency of each food by the nutrient content of the specified portion, using composition values from the Harvard University Food Composition Database, based primarily on USDA sources (17), supplemented with other data. The correlation for nutrients estimated by the FFQs and those measured by 2 wk of diet recording ranged from 0.37 for polyunsaturated fat to 0.92 for vitamin C with supplements (mean = 0.65, P < 0.01) after adjusting for total energy and for within-person variation in intake (18).
As previously described in detail (12), by using published information, we calculated and assigned values for daidzein, genistein, formononetin, biochanin A, matairesinol, and secoisolariciresinol for each food item on the FFQ according to the following protocol. All values found in the literature were converted to mg/100 g food. Values expressed on a dry weight basis were converted to wet weight basis either by using moisture content for that particular food or by using adjustments for the method of preparation. When the specific phytoestrogen content was reported as "a trace" or "traceable," a value of 0.00001 mg/100 g was used. This value is based on the sensitivity of the method used. When several values were reported from literature sources, we used the highest value. If wet and dry weights were reported from different original sources in the literature, we used the wet weight. If the questionnaire listed similar food items on the same line, we preferentially used the phytoestrogen data for the most commonly eaten food item for which data were available, and alternatively, a value for one of the other food items. If there was no information about the phytoestrogen content of a food item, a value was assigned using data of a similar food item if available; if no information could be found, the value 0 was assigned. The amount of phytoestrogen in breakfast cereals was estimated using the fiber content of the cereal as an indicator of the phytoestrogen content, following the Nutrition Data system of the University of Minnesota. The mean phytoestrogen content of wheat, triticale, and rye was used to estimate the amount of phytoestrogen per gram of fiber. Each phytoestrogen content of a food item was then scored on 1 of 7 categories described in Table 1, and we multiplied the phytoestrogen score of each food item by the serving size of the food. Finally, values for each food item were multiplied by the frequency of consumption of that food item and summed across all foods to obtain the total dietary intake of each phytoestrogen for each individual.
|
Other variables. Each participant was asked to report his height to the closest inch at baseline and his current weight in pounds at baseline and on each biennial questionnaire. The validity of the self-reported anthropometric measures is described elsewhere (20). We calculated BMI as the ratio of body weight to body height squared (kg/m2).
On the 1986 baseline questionnaire, current and past smokers were asked to report when they began smoking and the mean number of cigarettes smoked during each decade of their life. Past smokers were asked about time since quitting. Current smoking status was assessed at each biennial follow-up.
Alcohol intake was calculated by summing the frequency and amounts of beer, red wine, white wine, and spirits as reported by the participants on the FFQ. The reproducibility and validity of alcohol consumption measured by self-administered questionnaire was evaluated in detail within the HPFS (21).
Each biennial questionnaire measured the average time spent weekly at 4 sedentary activities and 10 specified leisure time physical activities during the past year. Metabolic equivalents (METs) for the task were defined for each type of physical activity as a multiple of the energy requirement of sitting quietly for 1 h. In a validation study of this questionnaire, vigorous activity assessed by the questionnaire was correlated with resting pulse (r = –0.45, P < 0.01) and postexercise pulse (r = –0.41, P < 0.01) (22).
In each biennial questionnaire, participants could indicate whether they have hypertension or hypercholesterolemia; we also asked about a family history of coronary heart disease before age 65 y.
Measurements of biochemical variables. To reduce extraneous between-person variation, we requested blood samples after fasting. However, if the men were not fasting, a questionnaire was sent requesting information on the date and time the sample was drawn and the time elapsed since the preceding meal. Blood samples were collected in three 10-mL liquid EDTA blood tubes, placed on ice packs in styrofoam containers, and returned to our laboratory via overnight courier; >95% of the samples arrived within 24 h. Upon arrival, the blood samples were centrifuged at 1530 x g for 20 min and divided into aliquots for storage in liquid nitrogen (–150°C). Fewer than 15% of the samples were slightly hemolyzed and very few were moderately hemolyzed (<3%), lipemic (<1%), or not cooled upon arrival (<0.5%). We found excellent stability during transport conditions for plasma leptin (23) and for other more standard clinical measures (24).
Measurements of plasma insulin, C-peptide, hemoglobin A1c (HbA1c), leptin, total cholesterol, TG, HDL-C, LDL-C, apolipoprotein (apo) A1 and apoB, and lipoprotein (a) [Lp(a)]) concentrations were made using standard methods, as described elsewhere (16).
Statistical analyses. Distributions of anthropometric measures, dietary and lifestyle characteristics, biochemical variables, and atherogenic and thrombogenic CVD risk factors were expressed according to the quartile distributions of total phytoestrogen intake of participants in 1994. Because of the skewed distribution of the individual phytoestrogens, we calculated geometric means and their 95% CI.
In multivariate linear regression models, we evaluated the relations between isoflavone and lignan intake and CVD risk factors after adjusting for different lifestyle and dietary variables. To the univariate model, we then added the lifestyle and dietary variables first one by one and then together to evaluate the changes in the regression coefficient for isoflavone or lignan intake. All models included age, cigarette smoking (pack-years), BMI, physical activity (mean METs/wk) (in quartiles), hypertension (yes/no), hypercholesterolemia (yes/no), and family history of coronary heart disease. The final model also included intake of total energy, total fat, vegetable protein, total fiber, alcohol, vitamin C, and folate.
All analyses with TG, insulin, and C-peptide were restricted to men who provided a blood sample while fasting (time since last meal before blood draw > 6 h, n = 268).
Whether associations with isoflavone or lignan intake differed across levels of traditional risk factors was tested by adding an interaction term between phytoestrogen intake and traditional risk factor to the model also containing at least the 2 individual variables.
|
RESULTS |
|---|
|
TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
In general, phytoestrogen intake was low (mean: 
1 mg/d). Genistein and secoisolariciresinol were the greatest contributors to total phytoestrogen intake (Table 2). Men in the highest quartile of total phytoestrogen intake were more physically active, had a lower intake of total fat and a higher intake of alcohol, total fiber, and vitamin C (Table 3).
|
|
|
For insulin and C-peptide, there were significant trends for lower levels with increasing lignan intake [for insulin, difference in means for Q4 compared with Q1 = –32.57 pmol/L (95% CI –56.60; –8.54), or –11% (95% CI –55%; –8%), P for trend = 0.02, and for C-peptide, difference in means = –0.18 nmol/L (95% CI –0.32; –0.04), or –25% (95% CI –44; –6%), P for trend = 0.01; Table 5]. Because the magnitudes of the differences were similar for the less extensive models and the final extensive models, we presented only the final models for isoflavones as well as lignans.
|
15 vs. >15 g/d), age (60 vs. >60 y) or BMI (25 vs. >25 kg/m2) did not significantly modify the observed associations as assessed by interaction terms. |
DISCUSSION |
|---|
|
TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
We chose to use a FFQ to quantify the mean exposure to dietary phytoestrogens in the previous year because foods containing high amounts of phytoestrogens are most likely to be consumed weekly or monthly, and not on a daily base. One of the major disadvantages of using biochemical indicators such as urinary excretion or serum levels to measure phytoestrogen exposure is the short period of intake (24 h) that is reflected by these measurements (25). The FFQ that we used was not specifically validated for assessment of phytoestrogen intake. However, the questionnaire proved to be valid for estimation of the foods that contribute importantly to the intake of isoflavones and lignans, including specific fruits, vegetables, legumes, coffee, tea, nuts, and grain products (26,27).
Data reported on the phytoestrogen content of foods in the literature are still limited and preliminary. Moreover, differences in phytoestrogen content of food items between types, brands, or different countries are not known because most measurements were performed in one country using only a few types or brands. To avoid the suggestion of precision for which the currently available data are too limited and too preliminary, we scored the highest value reported in the literature into 7 categories, instead of using the exact measurements of phytoestrogen content reported in the literature. By using categories instead of exact amounts of phytoestrogen content, these differences do not influence our results as long as they are within a 10-fold range of the data we used for our classification. Although the potential for error is much greater in the top 3 categories than in the bottom 3 shown in Table 1, we chose not to make more categories for foods with higher phytoestrogen content because they are seldom consumed in a Western diet. Furthermore, we divided the cohort into quartile categories of intake and did not use continuous data on phytoestrogen intake. This reduces the influence of extreme data points, but also reduces the power to detect an association.
Error in exposure measurement could have occurred due to missing phytoestrogen data for some of the food items consumed in the Western diet. However, for almost all vegetable food items in the questionnaire, data were available for daidzein, genistein, matairesinol, and secoisolariciresinol. Data for formononetin, biochanin A, and coumestrol are still scarce, but will become more available in the future. The industrial use of soybean meal could contribute to the presence of phytoestrogens in food items such as donuts and white bread, although the processing of soybean meal might reduce the amounts of phytoestrogens in these products (28). However, the amount of soy additives varies by type and brand of food, and most FFQs do not capture such levels of detail. Several other research groups quantified the dietary intake of phytoestrogens (11,28,29) and although estimates of isoflavone and lignan intake varied across studies because of differences in FFQs and phytoestrogen databases, in general, the reported intake is similar in comparable populations.
Residual confounding due to unmeasured or unknown factors and in particular confounding due to other dietary constituents is a potentially important bias in this study. However, the availability of extensive FFQ data on other nutrients enabled adjustment in the multivariate analyses. We adjusted for dietary fiber intake because dietary phytoestrogens are present in foods that contain fiber, and dietary fiber intake is inversely associated with cardiovascular risk factors. We adjusted for alcohol intake because alcohol is associated with both phytoestrogen intake and several CVD risk factors in this population (30). Moreover, we adjusted for physical activity, smoking, BMI, vitamin C, and folate intake to control confounding caused by a healthy lifestyle, which is associated with increased phytoestrogen intake as well as reduced CVD risk. However, even after extensive adjustment for these variables, a causal interpretation of our findings is inherently restricted by the cross-sectional nature of the design.
Our findings for the lipid variables are in conflict with those of previous studies (3,14,31). A major difference is the dose of phytoestrogens. The study of Anderson et al. (3) was a meta-analysis of 38 intervention studies with a mean of 47 g of soy protein, comparable to 66 mg isoflavones/d (as estimated by Y.T.vdS.), whereas the study of Hermansen et al. (31) was an intervention with >165 mg isoflavones from 50 g soy protein daily. Although the study of Nagata et al. (14) focused on usual intake, it was conducted in Japan, where intake of soy and soy products is habitually high and the mean intake of isoflavones is 20 mg/d. Thus, the intake of isoflavones in the present study in which 90% of the men consumed <7 mg/d may have been too low to exert effects on cardiovascular risk factors. Because soy foods were not a main food group contributing to isoflavones in this population, it might be more relevant to compare our findings with studies investigating isolated isoflavones (32–36). Results are not consistent here, although increased lipid levels with increased isoflavone intake were not reported.
Even within with a similar range of Western diets, intake of isoflavones was associated with blood lipids among postmenopausal women (11). This may be due to the higher number of ERs in postmenopausal women compared with men, but the levels of expression of ER- and -ß in different vascular beds in normal women and men have not been well characterized (37). Gender differences were reported in lung and brain tissue (38,39), but they were absent in adipose fat tissue (40). Confounding by unmeasured variables may also account for the findings in women.
Hyperinsulinemia is associated with insulin resistance and with the development of diabetes, hypertension, and coronary heart disease. In an intervention study in cynomolgus monkeys (2) and small studies in humans (41,42), there were no effects of soy isoflavone supplementation on fasting insulin, which contradicts one study on usual intake in American postmenopausal women (11).
Because increased lignan intake was associated with an improved lipid profile in postmenopausal women (13), our results are unexpected. Studies of lignans and cardiovascular risk factors in men are limited. Supplementation with flaxseed, rich in secoisolariciresinol, reduced total serum cholesterol in 25 men (43), but flaxseed also contains n-3 fatty acids and fiber, and the study was uncontrolled. However, in our study, the main food groups contributing to lignans were coffee and tea, and not flax seed; therefore it is not clear whether results from studies with flax seed can be extrapolated to studies examining other lignan sources.
Enterolactone, the human metabolite of the dietary lignans, moderately to weakly inhibits human estrogen synthetase (aromatase) by binding to the active site of the P450 enzyme (44,45). Thus, a high intake of lignans may play a role in increasing serum lipids in women by lowering estrogen levels. What this means in men is still unclear, but our finding have to be replicated and the mechanism further explored if lignans in low doses do indeed affect blood lipids in men. Similarly, our findings with insulin and C-peptide, which suggest that higher lignan intake may reduce insulin secretion, have to be confirmed.
In conclusion, our study indicates that usual intakes of isoflavones in U.S. men are not strongly associated with a beneficial cardiovascular risk profile. Furthermore, our study suggests that a diet high in lignans, even in the relatively low range of U.S. consumption, might be associated with increased LDL-C and apoB, and with reduced fasting insulin and insulin secretion. These associations warrant further investigation.
|
FOOTNOTES |
|---|
3 Abbreviations used: apo, apolipoprotein; CVD, cardiovascular disease; ER, estrogen receptor; HbA1c, hemoglobin A1c; HDL-C, HDL cholesterol; HPFS, Health Professionals Follow-up Study; LDL-C, LDL cholesterol; MET, metabolic equivalent; TG, triacylglycerol.
Manuscript received 12 August 2004. Initial review completed 27 September 2004. Revision accepted 29 October 2004.
|
LITERATURE CITED |
|---|
|
TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
|---|
1. Anthony, M. S., Clarkson, T. B., Hughes, C. L., Jr, Morgan, T. M. & Burke, G. L. (1996) Soybean isoflavones improve cardiovascular risk factors without affecting the reproductive system of peripubertal rhesus monkeys. J. Nutr. 126:43-50.
2. Wagner, J. D., Cefalu, W. T., Anthony, M. S., Litwak, K. N., Zhang, L. & Clarkson, T. B. (1997) Dietary soy protein and estrogen replacement therapy improve cardiovascular risk factors and decrease aortic cholesteryl ester content in ovariectomized cynomolgus monkeys. Metabolism 46:698-705.[Medline]
3. Anderson, J. W., Johnstone, B. M. & Cook Newell, M. E. (1995) Meta-analysis of the effects of soy protein intake on serum lipids. [see comments]N. Engl. J. Med. 333:276-282.
4. Potter, S. M. (1995) Overview of proposed mechanisms for the hypocholesterolemic effect of soy. J. Nutr. 125:606S-611S.
5. Lichtenstein, A. H., Jalbert, S. M., Adlercreutz, H., Goldin, B. R., Rasmussen, H., Schaefer, E. J. & Ausman, L. M. (2002) Lipoprotein response to diets high in soy or animal protein with and without isoflavones in moderately hypercholesterolemic subjects. Arterioscler. Thromb. Vasc. Biol. 22:1852-1858.
6. Kuiper, G. G., Carlsson, B., Grandien, K., Enmark, E., Haggblad, J., Nilsson, S. & Gustafsson, J. A. (1997) Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 138:863-870.
7. Zava, D. T., Dollbaum, C. M. & Blen, M. (1998) Estrogen and progestin bioactivity of foods, herbs, and spices. Proc. Soc. Exp. Biol. Med. 217:369-378.[Abstract]
8. Baker, V. A., Hepburn, P. A., Kennedy, S. J., Jones, P. A., Lea, L. J., Sumpter, J. P. & Ashby, J. (1999) Safety evaluation of phytosterol esters. Part 1. Assessment of oestrogenicity using a combination of in vivo and in vitro assays. Food Chem. Toxicol. 37:13-22.[Medline]
9. Saarinen, N. M., Warri, A., Makela, S. I., Eckerman, C., Reunanen, M., Ahotupa, M., Salmi, S. M., Franke, A. A., Kangas, L. & Santti, R. (2000) Hydroxymatairesinol, a novel enterolactone precursor with antitumor properties from coniferous tree (Picea abies). Nutr. Cancer 36:207-216.[Medline]
10. Chen, Z., Zheng, W., Custer, L. J., Dai, Q., Shu, X. O., Jin, F. & Franke, A. A. (1999) Usual dietary consumption of soy foods and its correlation with the excretion rate of isoflavonoids in overnight urine samples among Chinese women in Shanghai. Nutr. Cancer 33:82-87.[Medline]
11. Goodman-Gruen, D. & Kritz-Silverstein, D. (2001) Usual dietary isoflavone intake is associated with cardiovascular disease risk factors in postmenopausal women. J. Nutr. 131:1202-1206.
12. de Kleijn, M. J., van der Schouw, Y. T., Wilson, P. W., Adlercreutz, H., Mazur, W., Grobbee, D. E. & Jacques, P. F. (2001) Intake of dietary phytoestrogens is low in postmenopausal women in the United States: The Framingham Study. J. Nutr. 131:1826-1832.
13. Boker, L. K., van der Schouw, Y. T., de Kleijn, M. J., Jacques, P. F., Grobbee, D. E. & Peeters, P. H. (2002) Intake of dietary phytoestrogens by Dutch women. J. Nutr. 132:1319-1328.
14. Nagata, C., Takatsuka, N., Kurisu, Y. & Shimizu, H. (1998) Decreased serum total cholesterol concentration is associated with high intake of soy products in Japanese men and women. J. Nutr. 128:209-213.
15. Ho, S. C., Woo, J. L., Leung, S. S., Sham, A. L., Lam, T. H. & Janus, E. D. (2000) Intake of soy products is associated with better plasma lipid profiles in the Hong Kong Chinese population. J. Nutr. 130:2590-2593.
16. Fung, T. T., Rimm, E. B., Spiegelman, D., Rifai, N., Tofler, G. H., Willett, W. C. & Hu, F. B. (2001) Association between dietary patterns and plasma biomarkers of obesity and cardiovascular disease risk. Am. J. Clin. Nutr. 73:61-67.
17. U.S. Department of Agriculture, ARS (1999) USDA Nutrient Database for Standard Reference, Release 13, SR13 1999 http://www.nal.usda.gov/fnic/foodcomp/Data/SR13/dnload/sr13dnld.html [accessed 20 October 2004].
18. Rimm, E. B., Giovannucci, E. L., Stampfer, M. J., Colditz, G. A., Litin, L. B. & Willett, W. C. (1992) Reproducibility and validity of an expanded self-administered semiquantitative food frequency questionnaire among male health professionals. Am. J. Epidemiol. 135:1114-1126.
19. Willett, W. & Stampfer, M. (1998) Implications of total energy intake for epidemiologic analyses. Willett, W. eds. Nutritional Epidemiology 1998:273-301 Oxford University Press New York, NY. .
20. Rimm, E. B., Stampfer, M. J., Colditz, G. A., Chute, C. G., Litin, L. B. & Willett, W. C. (1990) Validity of self-reported waist and hip circumferences in men and women. Epidemiology 1:466-473.[Medline]
21. Giovannucci, E., Colditz, G., Stampfer, M. J., Rimm, E. B., Litin, L., Sampson, L. & Willett, W. C. (1991) The assessment of alcohol consumption by a simple self-administered questionnaire. Am. J. Epidemiol. 133:810-817.
22. Chasan-Taber, S., Rimm, E. B., Stampfer, M. J., Spiegelman, D., Colditz, G. A., Giovannucci, E., Ascherio, A. & Willett, W. C. (1996) Reproducibility and validity of a self-administered physical activity questionnaire for male health professionals. Epidemiology 7:81-86.[Medline]
23. Chu, N. F., Makowski, L., Hotamisligil, G. S. & Rimm, E. B. (1999) Stability of human plasma leptin concentrations within 36 hours following specimen collection. Clin. Biochem. 32:87-89.[Medline]
24. Pai, J. K., Curhan, G. C., Cannuscio, C. C., Rifai, N., Ridker, P. M. & Rimm, E. B. (2002) Stability of novel plasma markers associated with cardiovascular disease: processing within 36 hours of specimen collection. Clin. Chem. 48:1781-1784.
25. Watanabe, S., Yamaguchi, M., Sobue, T., Takahashi, T., Miura, T., Arai, Y., Mazur, W., Wahala, K. & Adlercreutz, H. (1998) Pharmacokinetics of soybean isoflavones in plasma, urine and feces of men after ingestion of 60 g baked soybean powder (kinako). J. Nutr. 128:1710-1715.
26. Feskanich, D., Rimm, E. B., Giovannucci, E. L., Colditz, G. A., Stampfer, M. J., Litin, L. B. & Willett, W. C. (1993) Reproducibility and validity of food intake measurements from a semiquantitative food frequency questionnaire. J. Am. Diet. Assoc. 93:790-796.[Medline]
27. Willett, W. C. (1998) Invited commentary: comparison of food frequency questionnaires. Am. J. Epidemiol. 148:1157-1159.
28. Horn-Ross, P. L., Barnes, S., Lee, M., Coward, L., Mandel, J. E., Koo, J., John, E. M. & Smith, M. (2000) Assessing phytoestrogen exposure in epidemiologic studies: development of a database (United States). Cancer Causes Control 11:289-298.[Medline]
29. Pillow, P. C., Duphorne, C. M., Chang, S., Contois, J. H., Strom, S. S., Spitz, M. R. & Hursting, S. D. (1999) Development of a database for assessing dietary phytoestrogen intake. Nutr. Cancer 33:3-19.[Medline]
30. Rimm, E. B., Klatsky, A., Grobbee, D. & Stampfer, M. J. (1996) Review of moderate alcohol consumption and reduced risk of coronary heart disease: is the effect due to beer, wine, or spirits. Br. Med. J. 312:731-736.
31. Hermansen, K., Sondergaard, M., Hoie, L., Carstensen, M. & Brock, B. (2001) Beneficial effects of a soy-based dietary supplement on lipid levels and cardiovascular risk markers in type 2 diabetic subjects. Diabetes Care 24:228-233.
32. Dewell, A., Hollenbeck, C. B. & Bruce, B. (2002) The effects of soy-derived phytoestrogens on serum lipids and lipoproteins in moderately hypercholesterolemic postmenopausal women. J. Clin. Endocrinol. Metab. 87:118-121.
33. Han, K. K., Soares, J. M., Jr, Haidar, M. A., de Lima, G. R. & Baracat, E. C. (2002) Benefits of soy isoflavone therapeutic regimen on menopausal symptoms. Obstet. Gynecol. 99:389-394.
34. Hale, G., Paul-Labrador, M., Dwyer, J. H. & Merz, C. N. (2002) Isoflavone supplementation and endothelial function in menopausal women. Clin. Endocrinol. 56:693-701.[Medline]
35. Uesugi, T., Fukui, Y. & Yamori, Y. (2002) Beneficial effects of soybean isoflavone supplementation on bone metabolism and serum lipids in postmenopausal Japanese women: a four-week study. J. Am. Coll. Nutr. 21:97-102.
36. Hsu, C. S., Shen, W. W., Hsueh, Y. M. & Yeh, S. L. (2001) Soy isoflavone supplementation in postmenopausal women. Effects on plasma lipids, antioxidant enzyme activities and bone density. J. Reprod. Med. 46:221-226.[Medline]
37. Mendelsohn, M. E. & Karas, R. H. (1999) The protective effects of estrogen on the cardiovascular system. N. Engl. J. Med. 340:1801-1811.
38. Fasco, M. J., Hurteau, G. J. & Spivack, S. D. (2002) Gender-dependent expression of alpha and beta estrogen receptors in human nontumor and tumor lung tissue. Mol. Cell Endocrinol. 188:125-140.[Medline]
39. Ishunina, T. A., Kruijver, F. P., Balesar, R. & Swaab, D. F. (2000) Differential expression of estrogen receptor alpha and beta immunoreactivity in the human supraoptic nucleus in relation to sex and aging. J. Clin. Endocrinol. Metab. 85:3283-3291.
40. Pedersen, S. B., Bruun, J. M., Hube, F., Kristensen, K., Hauner, H. & Richelsen, B. (2001) Demonstration of estrogen receptor subtypes alpha and beta in human adipose tissue: influences of adipose cell differentiation and fat depot localization. Mol. Cell Endocrinol. 182:27-37.[Medline]
41. Duncan, A. M., Merz, B. E., Xu, X., Nagel, T. C., Phipps, W. R. & Kurzer, M. S. (1999) Soy isoflavones exert modest hormonal effects in premenopausal women. J. Clin. Endocrinol. Metab. 84:192-197.
42. Duncan, A. M., Underhill, K. E., Xu, X., Lavalleur, J., Phipps, W. R. & Kurzer, M. S. (1999) Modest hormonal effects of soy isoflavones in postmenopausal women. J. Clin. Endocrinol. Metab. 84:3479-3484.
43. Demark-Wahnefried, W., Price, D. T., Polascik, T. J., Robertson, C. N., Anderson, E. E., Paulson, D. F., Walther, P. J., Gannon, M. & Vollmer, R. T. (2001) Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal levels, prostate-specific antigen, and histopathologic features. Urology 58:47-52.[Medline]
44. Adlercreutz, H., Bannwart, C., Wahala, K., Makela, T., Brunow, G., Hase, T., Arosemena, P. J., Kellis, J. T., Jr & Vickery, L. E. (1993) Inhibition of human aromatase by mammalian lignans and isoflavonoid phytoestrogens. J. Steroid Biochem. Mol. Biol. 44:147-153.[Medline]
45. Makela, T. H., Wahala, K. T. & Hase, T. A. (2000) Synthesis of enterolactone and enterodiol precursors as potential inhibitors of human estrogen synthetase (aromatase). Steroids 65:437-441.[Medline]
This article has been cited by other articles:
|
|
 |
|
  M. K Jensen, P. Koh-Banerjee, M. Franz, L. Sampson, M. Gronbaek, and E. B Rimm Whole grains, bran, and germ in relation to homocysteine and markers of glycemic control, lipids, and inflammation 1 Am. J. Clinical Nutrition, February 1, 2006; 83(2): 275 - 283. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
