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Institute on Nutraceuticals and Functional Foods, Laval University, Ste-Foy, Québec, Canada, G1K 7P4 and * Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111
2To whom correspondence should be addressed. E-mail: benoit.lamarche{at}inaf.ulaval.ca.
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ABSTRACT |
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 TOP ABSTRACT SUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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KEY WORDS: • soy protein • isoflavones • lipoproteins • lipids • LDL size
The diet currently recommended by the American Heart Association (AHA),3 which is low in saturated fat, trans fat, and cholesterol (1), was shown to be efficacious in decreasing plasma total cholesterol (C), LDL-C, triglycerides (TG) and the total C:HDL-C ratio, in a meta-analysis of nutritional interventions conducted in free-living subjects (2). Although well documented, these beneficial effects are modest at best, and it has been argued that the addition of other nutrients or dietary constituents such as soy protein might lead to further improvements in the cardiovascular disease (CVD) risk profile. The recognition of the effects of soy protein on traditional CVD risk factors emerged after the publication of several studies that demonstrated the hypocholesterolemic (3–5) and antiatherogenic (6,7) properties of soy. In a meta-analysis of 38 controlled studies, Anderson et al. (8) reported that the daily consumption of an average of 47 g of soy protein led to clinically meaningful reductions in total C, LDL-C and TG concentrations of 9.3, 12.9, and 10.5%, respectively. Although the mechanisms underlying the hypocholesterolemic and antiatherogenic properties of soy protein remain unclear, studies have reported a greater reduction in blood lipids when soy protein was combined with isoflavones compared with when it was depleted in isoflavones (3,4,9–11). However, when isoflavones from soy were consumed without its protein component, the lipid-lowering effect was generally not observed (12). Hence, there is still limited evidence supporting the independent effect of soy isoflavones on blood cholesterol and the reduction of atherosclerosis.
It was reported that the presence of small, dense LDL particles is associated with an increased risk of CVD (13,14). Also, recent evidence from the large Quebec Cardiovascular Study indicated that an increased proportion of cholesterol within small LDL particles increases the risk of CVD even in the presence of relatively normal LDL-C concentrations (15). Although LDL particle diameter may be modulated through dietary interventions, particularly by modifying the fat and carbohydrate content of the diet (16,17), little is known about the effects of other dietary constituents. The independent contribution of soy protein and isoflavones to the cholesterol distribution among different LDL subclasses has not been documented.
The purpose of the present study was to compare the effects of soy protein diets enriched in (soy/+) or depleted in (soy/-) isoflavones vs. animal protein diets with (animal/+) or without (animal/-) added isoflavones on various electrophoretic characteristics of LDL particles, including LDL peak particle diameter (LDL-PPD) and the cholesterol distribution among the small, medium and large LDL subclasses.
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SUBJECTS AND METHODS |
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TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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The study protocol and the effect of the four experimental diets were described previously (18). For the present analyses, a subsample of 36 subjects (20 women and 16 men) from the 42 recruited for the original study (18) were included in the analysis of LDL size characterization. Six subjects were excluded because plasma was not available for all of the dietary phases. Inclusion criteria were as follows: >50 y old; LDL-C concentrations > 3.36 mmol/L; and postmenopausal (for women) (Table 1). Subjects taking medications known to affect lipoprotein metabolism were excluded from the study. The study protocol was approved by the Human Investigation Review Committee of New England Medical Center and Tufts University.
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Subjects consumed each of four experimental diets in random order as well as in a double-blind fashion; the diets were as follows: 1) soy protein depleted of isoflavones (soy/-); 2) soy protein enriched in isoflavones (soy/+); 3) animal protein with no added isoflavones (animal/-); and 4) animal protein with added isoflavones (animal/+), for periods of 6 wk each, separated by 2- to 4-wk washout periods. Participants were specifically instructed to maintain their usual levels of physical activity throughout the study period and to inform the staff of any change in physical activity patterns. Crude assessment of changes in physical activity levels indicated that activity patterns varied very little during the dietary phases. Blood samples were obtained during the last week of each period. All food and drink was provided to the subjects and packaged to take home. Body weight of subjects was stable throughout the study.
Experimental diets.
The four experimental diets were designed to be similar in their protein, carbohydrate, total fat, fatty acid profile, fiber, and cholesterol contents. This was achieved by using as many of the same foods as possible, substituting isolated soy protein for common sources of animal protein (two thirds of the daily protein intake, 10% of total energy), and adjusting the fatty acid profile of the diet, using commercially available fats and oils, to be similar. The variable protein component in the soy/- and soy/+ diets was contributed by specially prepared batches of isolated soy protein, one depleted (0.12 mg aglycone/g protein) and one enriched (1.96 mg aglycone/g protein) in isoflavones (Protein Technologies). The isolated soy protein was incorporated into sauces, cereals, casseroles, baked goods, and deserts that were provided to the subjects as a component of each meal. The protein component of the animal/- and animal/+ diets was provided by milk and meat. Isoflavones, in the form of a powdered concentrate (Archer Daniels Midland Company) were mixed into different food items of the animal/+ diet. Chemical analysis confirmed that the soy and animal protein diets with isoflavones were formulated to have similar levels of isoflavones (soy/+ diet, 46 mg aglycone isoflavones/4.2 MJ; animal/+ diet, 52 mg aglycone isoflavones/4.2 MJ). The distribution of genistein, daidzein and glycetin did not differ between the soy/+ and animal/+ diets. Food items low and high in isoflavones were indistinguishable with respect to appearance and taste. The mean daily soy protein intake was 55 g for women and 71 g for men. The mean daily isoflavone intake was 108 mg for women and 139 mg for men (Table 2).
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Blood samples were collected and analyzed as previously described (19,20). Data on the effects of soy protein and isoflavones on the lipid profile were reported previously (18).
LDL particle size characterization.
Nondenaturing 2–16% polyacrylamide gradient gel electrophoresis of whole plasma was performed to assess LDL particle diameter by using procedures previously described (15). LDL particle diameter was determined using polyacrylamide gradient gels prepared in batches of 8 in our laboratory. Aliquots of 4 µL plasma samples were mixed in a 1:1 volume ratio to a sampling buffer containing 20% sucrose and 0.25% bromophenol blue. A 15-min prerun at 75 V preceded electrophoresis of the plasma samples at 150 V for 3 h. According to standardized procedures, gels were stained with Sudan black and stored in a solution made of 9% acetic acid and 20% methanol until analysis by the Imagemaster 1-D Prime computer software version 3.01 (Amersham Pharmacia Biotech). LDL particle diameter was computed from the extrapolation of the relative migration of plasma standards of known diameter. LDL peak particle diameter (PPD) was identified within each densitometric scan as the most important LDL subclass. An integrated LDL particle size, which corresponds to the weighted mean size of all subclasses in an individual, was also computed, using a modification of the procedures described by Tchernof et al. (21). It is calculated as the sum of the diameter of each LDL subclass weighted, multiplied by its relative proportion. Analysis of pooled plasma standards showed that measurement of LDL peak and mean particle diameters was highly reproducible, with an interassay CV of 0.6%. The relative proportion of LDL having a diameter < 25.5 nm (termed LDL% <25.5 nm) was ascertained by computing the relative area of the LDL densitometric scan < 25.5 nm. The absolute concentration of cholesterol among LDL < 25.5 nm (termed LDL-C<25.5 nm) was calculated by multiplying the total plasma LDL cholesterol concentrations by the LDL%<25.5 nm, as described earlier (15). A similar approach was used to determine the concentration of cholesterol in LDL particles with a diameter between 25.5 and 26.0 nm (medium LDL particles) and > 26.0 nm (large LDL particles). The CV associated with the measurement of LDL%<25.5 nm and LDL%>26.0 nm was 12 and 9.3%, respectively.
Statistical analyses.
Statistical analyses were performed using the Statistical Analysis System, version 8.2 (SAS Institute). Plasma TG data were log-transformed before statistical analyses. Descriptive statistics and univariate correlations were first performed to summarize the effects of each experimental diet on the subjects. A two-way ANOVA for a Latin-square design with main effects of dietary protein type and isoflavone content with subjects as a repeated measure was carried out. Inclusion of terms reflecting a diet order effect in the statistical model did not affect the results (not shown). Thus, random effect terms were not included in the final analysis to keep the model as simple as possible. Also, inclusion of a "diet x sex" interaction term in the models indicated that sex did not modulate the LDL size response to soy vs. animal protein (not shown). Differences were considered significant at P < 0.05.
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RESULTS |
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TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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The daily consumption of >50 g soy protein resulted in a small but significant decrease in plasma total C and in a more pronounced decrease in TG (Table 3). Plasma LDL-C concentrations tended to be reduced (P = 0.07) by soy protein in our subsample of 36 subjects. This is not entirely consistent with the significant reduction reported in the entire sample of 42 subjects (18). However, the absolute reduction in plasma LDL-C concentrations associated with soy protein (vs. animal protein) were of similar magnitude in both samples [subsample of 36 subjects, 
LDL-C = -0.11 mmol/L and entire sample of 42 subjects, LDL-C = -0.12 mmol/L (18)]. Hence, the lack of a significant soy-induced reduction in LDL-C concentrations can be attributed to the reduced power of the analysis because of the smaller number of subjects in the subanalysis. The dietary isoflavones, either as a component of the soy protein diet or added to the animal protein diet, significantly decreased plasma total C, which was likely due to the significant decrease in VLDL-C concentrations (Table 3).
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Soy protein diets significantly increased LDL-PPD as well as the LDL integrated size compared with animal protein diets (Table 4). Consumption of isoflavones, as part of the soy protein diet or added to the animal protein diet, did not affect the LDL-PPD or the LDL integrated size. A correlation analysis indicated that the changes in plasma TG concentrations associated with soy protein (vs. animal protein) were marginally correlated with the changes in LDL-PPD (r = -0.32, P = 0.06) but that the soy-induced changes in plasma LDL-C concentrations were not correlated with changes in measures of LDL-PPD (r < 0.13).
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The consumption of soy protein significantly decreased LDL%<25.5 nm and significantly increased LDL%>26.0 nm (Table 4, Fig. 1). In a similar manner, soy protein significantly decreased LDL-C<25.5 nm and significantly increased LDL-C>26.0 nm. Correlation analyses showed that soy-induced changes in plasma TG levels (vs. animal protein) were correlated with concurrent changes in LDL-C<25.5 nm concentrations (r = 0.36 P = 0.03) but not with changes in LDL-C>26.0 nm concentrations (r = 0.05, P = 0.78) or LDL%>26.0 nm (r = -0.12, P = 0.47). The correlations between soy protein-induced change in LDL-C concentration and changes in LDL%<25.5 nm (r = -0.28, P = 0.09) or LDL%>26.0 nm (r = 0.32, P = 0.06) were not significant. Isoflavones did not affect any of the electrophoretic characteristics of the LDL particles.
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DISCUSSION |
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TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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The purpose of the present study was to investigate the effect of dietary soy protein on various electrophoretic characteristics of LDL particles, including the LDL-PPD and the cholesterol distribution among small and large LDL subclasses, and to examine the extent to which these effects may be mediated by the isoflavone component of soy. Our results suggest that the consumption of a soy protein diet may induce cardioprotective and beneficial changes in the LDL size phenotype compared with an animal protein-based diet, and that those effects are independent of the isoflavone component of soy.
LDL particle size.
Our results indicated that the LDL-PPD and the LDL integrated size increased after consumption of the soy protein diets compared with the animal protein diets. Changes in these small dense LDL phenotypes were particularly apparent in individuals with small LDL particles after consumption of the animal/- "baseline" diet. Because small, dense LDL particles have been associated with an increased CVD risk (13–15), results of the present study suggest a beneficial effect of soy protein on the CVD risk profile and further confirm results observed in other nutritional studies in which individuals with smaller LDL-PPD appear to respond more favorably to dietary changes (27). To our knowledge, two studies have investigated the effects of soy protein, incorporating various amounts of isoflavones, on LDL-PPD. Those studies were conducted in free-living normolipidemic premenopausal (10) and normolipidemic or mildly hypercholesterolemic postmenopausal women (11) who consumed their usual diet. The diets in these studies were supplemented with one of the three isolated soy protein beverage powders accounting for slightly less than half of the daily protein intake and providing either no (7.1 mg/d), low (65 mg/d), or high (132 mg/d) levels of isoflavones (10,11). Neither study reported a significant change in LDL-PPD as a result of incorporating isolated soy protein beverage powders into the diet. It must be emphasized that our study was conducted under controlled conditions during which all food was provided to the participants. The isolated soy protein also accounted for a greater proportion (two thirds) of the daily protein intake, whereas the mean daily isoflavone intake was 108 and 139 g for women and men, respectively, depending on the amount of energy necessary to maintain body weight. The fact that both men and women participated in our study is not likely to explain the disparate results between our study and those of Wangen et al. (11) and Merz-Demlow et al. (10) because we did not observe an interaction between gender and diet on LDL-PPD. Also, the diets in those two studies did not affect TG concentrations, which were reduced in the present study after consumption of soy protein diets. Indeed, our data are consistent with the concept that diet-induced variations in plasma TG concentrations are strongly correlated with concurrent changes in LDL peak particle size (28).
LDL cholesterol distribution.
The present study emphasizes the importance of further characterizing LDL particles to elucidate the effect of dietary interventions on cardiovascular risk. Indeed, although the variation in plasma LDL-C concentrations was not as large as it was expected to be on the basis of data from previous intervention studies, dietary soy protein resulted in a clinically meaningful redistribution of cholesterol from small to large LDL particles. We demonstrated recently that the cholesterol concentration in LDL particles with a diameter < 25.5 nm was strongly and independently associated with an increased risk of ischemic heart disease (IHD) in men (15). This led us to conclude that further characterization of LDL particles, in addition to the traditional lipid profile, may improve our ability to predict IHD events (15). Our thorough examination of the LDL particle phenotype highlighted additional benefits of soy protein on the CVD risk profile in comparison with animal protein, which would not have been fully apparent had we examined only the LDL-C concentrations. The lack of change in LDL-PPD in previous studies (10,11) may have obscured other beneficial effects associated with the consumption of soy protein, such as a desirable redistribution of cholesterol from smaller to larger particles as seen in the present study.
Potential mechanisms of action.
To the best of our knowledge, this is the first study indicating that soy protein has beneficial effects on LDL electrophoretic characteristics. Although potential mechanisms of action can be proposed, they are purely speculative because no data exist to support them. Among those speculations are changes in intravascular hepatic lipase and lipoprotein lipase activities, but the very few studies that have examined this issue showed that soy protein had little or no effect on postheparin lipase activities (29,30). The reduced hepatic TG synthesis associated with soy protein consumption in rats may also be considered as a mechanism (31). Changes in lipase activities and in hepatic TG synthesis could partially explain the effect of soy protein on plasma TG concentrations and hence, on LDL particle size. One study found that soy protein did not affect cholesteryl ester transfer protein activity (30). Finally, previous studies suggested that the consumption of soy protein may increase LDL receptor expression in humans (3). This may contribute to reducing the intravascular residence time of LDL, thus increasing the probability of these particles being subjected to intravascular hydrolysis, a process that promotes the formation of small dense LDL. However, no significant correlation was found between the changes induced by the soy protein diet on LDL-C concentrations and the proportion of small LDL particles (LDL%<25.5 nm) or LDL-PPD. This suggests that the soy-induced beneficial effects on LDL electrophoretic characteristics may be explained by mechanisms that are mainly independent of those responsible for the reduction in LDL-C concentrations.
Clinical relevance.
It may be argued that the changes in LDL size in the present study are not large enough to have clinical relevance. Available data from in vitro as well as epidemiological studies indicate the opposite. It was demonstrated that a decrease in LDL size of only 0.1 nm may be associated with a loss of several molecules at the surface of the LDL macromolecular complex. These changes modified the tertiary conformation of apolipoprotein B, a conformation that is required to maintain homeostatic surface pressure of the particle, thereby affecting the chemical and physical properties of LDL (32). These changes may also represent one of the key mechanisms underlying the prolonged residence time of small LDL compared with larger LDL particles observed in previous studies (33). In addition, data from the Quebec Cardiovascular Study suggested that a small shift in LDL-PPD toward smaller particles was associated with a significant 2.2-fold increase in the 5-y risk of ischemic heart disease in men (34). In the present study, the mean LDL-PPD increase of 
0.1 nm between animal- and soy-protein diets would translate into a 5% reduction in the 5-y risk of IHD according to data from the Quebec Cardiovascular Study. Recent data from the Quebec Cardiovascular Study indicated that each 0.5 mmol/L increase in the cholesterol content of small LDL particles translated into a 5% increase in the 5-y risk of IHD (15). Our data suggest that the daily incorporation of relatively high levels of soy protein-containing food (>50 g/d) in the diet, through significant redistribution of small toward large LDL particles, may translate into a clinically meaningful reduction in IHD risk. Those beneficial effects on the LDL electrophoretic characteristics would occur only with sustained high intakes of soy protein over time, which are not yet part of the North American diet.
In conclusion, our results suggest an additional positive effect of soy protein on LDL particle size, an important CVD risk factor. Data showed that a soy protein-containing diet has positive effects on LDL particle size and leads to a favorable redistribution of cholesterol among each LDL subclass compared with an animal protein-based diet. Our extended analysis also suggests that individuals with smaller LDL-PPD at baseline would benefit more from an increase in soy protein intake. Those effects do not appear to be gender specific. Furthermore, the present study also indicated that the beneficial effects of soy protein on these electrophoretic characteristics of LDL are not due to the isoflavone component of soy.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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3 Abbreviations used: AHA, American Heart Association; animal/+, animal protein diets with added isoflavones; animal/-, animal protein diets with no added isoflavones; C, cholesterol; CVD, cardiovascular disease; IHD, ischemic heart disease; LDL-C<25.5 nm, absolute concentration of cholesterol among LDL < 25.5 nm; LDL-C25.5–26.0 nm, absolute concentration of cholesterol among LDL with a diameter between 25.5 and 26.0 nm; LDL-C>26.0 nm, absolute concentration of cholesterol among LDL > 26.0 nm; LDL%<25.5 nm, proportion of LDL with a diameter < 25.5 nm; LDL%25.5–26.0 nm, proportion of LDL with a diameter between 25.5 and 26.0 nm; LDL%>26.0 nm, proportion of LDL with a diameter > 26.0 nm; PPD, peak particle diameter; soy/-, soy protein diets depleted in isoflavones; soy/+, soy protein diets enriched in isoflavones; TG, triglyceride.
Manuscript received 31 October 2003. Initial review completed 15 November 2003. Revision accepted 3 December 2003.
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LITERATURE CITED |
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TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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1. Krauss, R. M., Eckel, R. H., Howard, B., Appel, L. J., Daniels, S. R., Deckelbaum, R. J., Erdman, J. W., Kris-Etherton, P. & Goldberg, I. J., et al (2000) AHA Dietary Guidelines. Revision 2000: a statement for healthcare professionals from the nutrition committee of the American Heart Association. Circulation 102:2284-2299.
2. Yu-Poth, S., Zhao, G., Etherton, T., Naglak, M., Jonnalagadda, S. & Kris-Etherton, P. M. (1999) Effects of the National Cholesterol Education Program’s Step I and Step II dietary intervention programs on cardiovascular disease risk factors: a meta-analysis. Am. J. Clin. Nutr. 69:632-646.
3. Baum, J. A., Teng, H., Erdman, J. W., Weigel, R. M., Klein, B. P., Persky, V. W., Freels, S., Surya, P. & Bakhit, R. M., et al (1998) Long term intake of soy protein improves blood lipid profiles and increases mononuclear cell low-density-lipoprotein receptor messenger RNA in hypercholesterolemic, postmenopausal women. Am. J. Clin. Nutr. 68:545-551.[Abstract]
4. Crouse, J. R., III, Morgan, T., Terry, J. G., Ellis, J., Vitolins, M. & Burke, G. L. (1999) A randomized trial comparing the effect of casein with that of soy protein containing varying amounts of isoflavones on plasma concentrations of lipids and lipoproteins. Arch. Intern. Med. 159:2070-2076.
5. Teixeira, S. R., Potter, S. M., Weigel, R., Hannum, S., Erdman, J. W. & Hasler, C. M. (2000) Effects of feeding 4 levels of soy protein for 3 and 6 wk on blood lipids and apolipoproteins in moderately hypercholesterolemic men. Am. J. Clin. Nutr. 71:1077-1084.
6. Anthony, M. S., Clarkson, T. B., Bullock, B. C. & Wagner, J. D. (1997) Soy protein versus soy phytoestrogens in the prevention of diet-induced coronary artery atherosclerosis of male cynomolgus monkeys. Arterioscler. Thromb. Vasc. Biol. 17:2524-2531.
7. Kritchevsky, D. (1995) Dietary protein, cholesterol and atherosclerosis: a review of the early history. J. Nutr. 125:589S-593S.
8. Anderson, J. W., Johnstone, B. M. & Cook-Newell, M. E. (1995) Meta-analysis of the effects of soy protein intake on serum lipids. N. Engl. J. Med. 333:276-282.
9. Gardner, C. D., Newell, K. A., Cherin, R. & Haskell, W. L. (2001) The effect of soy protein with or without isoflavones relative to milk protein on plasma lipids in hypercholesterolemic postmenopausal women. Am. J. Clin. Nutr. 73:728-735.
10. Merz-Demlow, B. E., Duncan, A. M., Wangen, K. E., Xu, X., Carr, T. P., Phipps, W. R. & Kurzer, M. S. (2000) Soy isoflavones improve plasma lipids in normocholesterolemic, premenopausal women. Am. J. Clin. Nutr. 71:1462-1469.
11. Wangen, K. E., Duncan, A. M., Xu, X. & Kurser, M. S. (2001) Soy isoflavones improve plasma lipids in normocholesterolemic and mildly hypercholesterolemic postmenopausal women. Am. J. Clin. Nutr. 73:225-231.
12. Nestel, P. J., Yamashita, T., Sasahara, T., Pomeroy, S., Dart, A., Komesaroff, P., Owen, A. & Abbey, M. (1997) Soy isoflavones improve systemic arterial compliance but not plasma lipids in menopausal and perimenopausal women. Arterioscler. Thromb. Vasc. Biol. 17:3392-3398.
13. Lamarche, B., Tchernof, A., Moorjani, S., Cantin, B., Dagenais, G. R., Lupien, P. J. & Després, J. P. (1997) Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men. Prospective results from the Québec cardiovascular study. Circulation 95:69-75.[Medline]
14. Gardner, C. D., Fortmann, S. P. & Krauss, R. M. (1996) Association of small low-density lipoprotein particles with the incidence of coronary artery disease in men and women. J. Am. Med. Assoc. 276:875-881.[Abstract]
15. St-Pierre, A. C., Ruel, I. L., Cantin, B., Dagenais, G. R., Bernard, P. M., Després, J. P. & Lamarche, B. (2001) Comparison of various electrophoretic characteristics of LDL particles and their relationship to the risk of ischemic heart disease. Circulation 104:2295-2299.
16. Dreon, D. M., Fernstrom, H. A., Campos, H., Blanche, P., Williams, P. T. & Krauss, R. M. (1998) Change in dietary saturated fat intake is correlated with change in mass of large low-density-lipoprotein particles in men. Am. J. Clin. Nutr. 67:828-836.[Abstract]
17. Dreon, D. M., Fernsrom, H. A., Williams, P. T. & Krauss, R. M. (1997) LDL subclass patterns and lipoprotein response to a low-fat, high-carbohydrate diet in women. Arterioscler. Thromb. Vasc. Biol. 17:707-714.
18. 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 without and with isoflavones in moderately hypercholesterolemic subjects. Arterioscler. Thromb. Vasc. Biol. 22:1852-1858.
19. McNamara, J. R. & Schaefer, E. J. (1987) Automated enzymatic standardized lipid analyses for plasma and lipoprotein fractions. Clin. Chim. Acta 166:1-8.[Medline]
20. Warnick, G. R., Benderson, J. & Albers, J. J. (1982) Dextran sulfate-Mg++ precipitation procedure for quantitation of high-density lipoprotein cholesterol. Clin. Chem. 28:1379-1388.
21. Tchernof, A., Lamarche, B., Prud’homme, D., Nadeau, A., Moorjani, S., Labrie, F., Lupien, P. J. & Després, J. P. (1996) The dense LDL phenotype. Association with plasma lipoprotein levels, visceral obesity, and hyperinsulinemia in men. Diabetes Care 19:629-637.[Abstract]
22. Department of Health and Human Services, Food and Drug Administration () Food labeling: health claims; soy protein and coronary heart disease http://vm.cfsan.fda.gov/lrd/fr991026.html [accessed 10/29/2003].
23. Erdman, J. W. (2000) Soy protein and cardiovascular disease: a statement for healthcare professionals from the nutrition committee of the AHA. Circulation 102:2555-2559.
24. Jenkins, D.J.A., Kendall, C.W.C., Jackson, C.J.C., Connelly, P. W., Parker, T., Faulkner, D., Vidgen, E., Cunnane, S. C., Leiter, L. A. & Josse, R. G. (2002) Effects of high- and low-isoflavone soyfoods on blood lipids, oxidized LDL, homocysteine, and blood pressure in hyperlipidemic men and women. Am. J. Clin. Nutr. 76:365-372.
25. Wiseman, H., O’Reilly, J.D.O., Adlercreutz, H., Mallet, A. I., Bowey, E. A., Rowland, I. R. & Sanders, T.A.B. (2000) Isoflavone phytoestrogens consumed in soy decrease F2-isoprostane concentrations and increase resistance of low density lipoprotein to oxidation in humans. Am. J. Clin. Nutr. 72:395-400.
26. Anthony, M. S., Clarkson, T. B. & Williams, J. K. (1998) Effects of soy isoflavones on atherosclerosis: potential mechanisms. Am. J. Clin. Nutr. 68(suppl.):1390S-1393S.[Abstract]
27. Krauss, R. M. & Dreon, D. M. (1995) Low-density-lipoprotein subclasses and response to a low-fat diet in healthy men. Am. J. Clin. Nutr. 62:478S-487S.
28. Lamarche, B., Lemieux, I. & Després, J. P. (1999) The small, dense LDL phenotype and the risk of coronary heart disease: epidemiology, patho-physiology and therapeutic aspects. Diabetes Metab. 25:199-211.[Medline]
29. Vessby, B., Karlstrom, B., Lithell, H., Gustafsson, I. B. & Werner, I. (1982) The effects on lipid and carbohydrate metabolism of replacing some animal protein by soy-protein in a lipid-lowering diet for hypercholesterolemic patients. Hum. Nutr. Appl. Nutr. 36:179-189.[Medline]
30. Higashi, K., Abata, S., Iwamoto, N., Ogura, M., Yamashita, T., Ishikawa, O., Ohslzu, F. & Nakamura, H. (2001) Effects of soy protein on levels of remnant-like particles cholesterol and vitamin E in healthy men. J. Nutr. Sci. Vitaminol. 47:283-288.
31. Demonty, I., Deshaies, Y., Lamarche, B. & Jacques, H. (2002) Interaction between dietary protein and fat in triglyceride metabolism in the rat: effects of soy protein and menhaden oil. Lipids 37:693-699.[Medline]
32. McNamara, J. R., Small, D. M., Li, Z. & Schaefer, E. J. (1996) Differences in LDL subspecies involve alterations in lipid composition and conformational changes in apolipoprotein B. J. Lipid Res. 37:1924-1935.[Abstract]
33. Packard, C. J., Demant, T., Stewart, J. P., Bedford, D., Caslake, M. J., Schwertfeger, G., Bedynek, A., Shepherd, J. & Seidel, D. (2000) Apolipoprotein B metabolism and the distribution of VLDL and LDL subfractions. J. Lipid Res. 41:305-318.
34. Lamarche, B., St-Pierre, A., Ruel, I., Cantin, B., Dagenais, G. R. & Després, J. P. (2001) A prospective population based study of LDL particle size as a risk factor for ischemic heart disease in men. Can. J. Cardiol. 17:859-865.[Medline]
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S. Shrestha, J. S. Volek, J. Udani, R. J.Wood, C. M. Greene, D. Aggarwal, J. H. Contois, B. Kavoussi, and M. L. Fernandez A Combination Therapy Including Psyllium and Plant Sterols Lowers LDL Cholesterol by Modifying Lipoprotein Metabolism in Hypercholesterolemic Individuals J. Nutr., October 1, 2006; 136(10): 2492 - 2497. [Abstract] [Full Text] [PDF]
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 M. Takahashi, T. Sekine, N. Kuba, S. Nakamori, M. Yasuda, and H. Takagi The Production of Recombinant APRP, an Alkaline Protease Derived from Bacillus pumilus TYO-67, by In Vitro Refolding of Pro-enzyme Fixed on a Solid Surface J. Biochem., October 1, 2004; 136(4): 549 - 556. [Abstract] [Full Text] [PDF]
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