Soy isoflavones lower serum total and LDL cholesterol in humans: a meta-analysis of 11 randomized controlled trials

BACKGROUND: Clinical trials have reported the cholesterol-lowering effects of soy protein intake, but the components responsible are not known. OBJECTIVE: This meta-analysis was primarily conducted to evaluate the precise effects of soy isoflavones on lipid profiles. The effects of soy protein that contains enriched and depleted isoflavones were also examined. DESIGN: PUBMED was searched for English-language reports of randomized controlled trials published from 1990 to 2006 that described the effects of soy protein intake in humans. Eleven studies were selected for the meta-analysis. RESULTS: Soy isoflavones significantly decreased serum total cholesterol by 0.10 mmol/L (3.9 mg/dL or 1.77%; P = 0.02) and LDL cholesterol by 0.13 mmol/L (5.0 mg/dL or 3.58%; P < 0.0001); no significant changes in HDL cholesterol and triacylglycerol were found. Isoflavone-depleted soy protein significantly decreased LDL cholesterol by 0.10 mmol/L (3.9 mg/dL or 2.77%; P = 0.03). Soy protein that contained enriched isoflavones significantly decreased LDL cholesterol by 0.18 mmol/L (7.0 mg/dL or 4.98%; P < 0.0001) and significantly increased HDL cholesterol by 0.04 mmol/L (1.6 mg/dL or 3.00%; P = 0.05). The reductions in LDL cholesterol were larger in the hypercholesterolemic subcategory than in the normocholesterolemic subcategory, but no significant linear correlations were observed between reductions and the starting values. No significant linear correlations were found between reductions in LDL cholesterol and soy protein ingestion or isoflavone intakes. CONCLUSIONS: Soy isoflavones significantly reduced serum total and LDL cholesterol but did not change HDL cholesterol and triacylglycerol. Soy protein that contained enriched or depleted isoflavones also significantly improved lipid profiles. Reductions in LDL cholesterol were larger in hypercholesterolemic than in normocholesterolemic subjects.     

Dietary soy and soy isoflavones have gender-specific effects on plasma lipids and isoflavones in golden Syrian f(1)b hybrid hamsters

The specific components of soy responsible for its beneficial effects on plasma lipids are unknown. Golden Syrian F(1)B Hybrid hamsters (75 male, 74 female) were evaluated for the effect of dietary soy and soy isoflavones on plasma lipids. They were fed the following diets for 16 wk: casein/lactalbumin (C/L), soy protein with isoflavones [Soy(+)], soy protein with isoflavones removed [Soy(-)], Soy(-) plus isoflavone extract (IF), and C/L + IF. At necropsy, plasma total cholesterol, HDL cholesterol (HDLC), LDL + VLDL cholesterol (LDL + VLDLC), isoflavones, and uterine and accessory gland weights were measured. Male hamsters fed the three soy-containing diets had lower LDL + VLDLC concentrations than those fed the two C/L diets (P < 0.01), and those fed Soy(-) + IF did not differ from those fed Soy(+). In females, diet did not affect plasma LDL + VLDLC concentration. Females fed Soy(+) or Soy(-) had higher HDLC (P < 0.05) than those fed C/L. HDLC was not affected by diet in males. Due to higher equol production (P < 0.01), males had greater plasma isoflavone concentrations (P < 0.01) than females. There was a positive association between plasma total isoflavones and LDL + VLDLC (r = 0.65, P < 0.05) in females. These data suggest gender differences in plasma lipid and isoflavone responses to soy- based diets in Syrian F(1)B Hybrid hamsters, which offer an opportunity to explore effects of sex hormones on isoflavone metabolism and the effects of isoflavones on lipid metabolism.     

The effect of soy protein with or without isoflavones relative to milk protein on plasma lipids in hypercholesterolemic postmenopausal women

BACKGROUND: Clinical trial data and the results of a meta-analysis suggest a hypocholesterolemic effect of soy protein. The effect may be partially attributable to the isoflavones in soy. Few studies have examined the separate effects of soy protein and isoflavones. OBJECTIVE: The objective of this study was to determine the effect of soy protein and isoflavones on plasma lipid concentrations in postmenopausal, moderately hypercholesterolemic women. DESIGN: This was a randomized, double-blind, placebo-controlled clinical trial with 3 treatment groups. After a 4-wk run-in phase during which the women consumed a milk protein supplement, the subjects were randomly assigned to 12 wk of dietary protein supplementation (42 g/d) with either a milk protein (Milk group) or 1 of 2 soy proteins containing either trace amounts of isoflavones (Soy- group) or 80 mg aglycone isoflavones (Soy+ group). RESULTS: LDL-cholesterol concentrations decreased more in the Soy+ group (n = 31) than in the Soy- group (n = 33) (0.38 compared with 0.09 mmol/L; P = 0.005), but neither of these changes was significantly different from the 0.26-mmol/L decrease observed in the Milk group (n = 30). The results for total cholesterol were similar to those for LDL cholesterol. There were no significant differences in HDL-cholesterol or triacylglycerol concentrations between the 3 groups. CONCLUSIONS: The difference in total- and LDL-cholesterol lowering between the 2 soy-protein supplements suggests an effect attributable to the isoflavone-containing fraction. However, the unexpected LDL-cholesterol lowering observed in the Milk group, and the fact that there was no significant difference between either soy group and the Milk group, suggests that changes may have been due to other factors related to participation in the study.     

Effect of soy protein varying in isoflavone content on serum lipids in healthy young men

BACKGROUND: Previous research supports a role for soy protein in reducing serum lipids; however, few studies involved healthy male subjects or focused on soy isoflavones (or did both). OBJECTIVE: The objective was to ascertain the effects of soy protein varying in isoflavone content on serum lipids in healthy young men. DESIGN: Thirty-five males (x +/- SD age: 27.9 +/- 5.7 y) consumed milk protein isolate (MPI), low-isoflavone soy protein isolate (low-iso SPI; 1.64 +/- 0.19 mg aglycone isoflavones/d), and high-isoflavone SPI (high-iso SPI; 61.7 +/- 7.4 mg aglycone isoflavones/d) for 57 d each, separated by 4-wk washout periods, in a randomized crossover design. Blood samples were collected at the beginning and end of each treatment period, and total, LDL, and HDL cholesterol; triacylglycerols; apolipoprotein (apo) B; apo A-I; and C-reactive protein (CRP) were measured in serum. Twenty-four-hour urine samples were collected for 3 consecutive days at the end of each treatment period and analyzed for isoflavones. RESULTS: Urinary isoflavones were significantly greater with consumption of the high-iso SPI than with that of the low-iso SPI or MPI. The differences between the 3 treatments with respect to individual serum lipids were not significant, but the ratios of total to HDL cholesterol, LDL to HDL cholesterol, and apo B to apo A-I were significantly lower with both SPI treatments than with MPI treatment. CONCLUSION: Soy protein, regardless of isoflavone content, modulates serum lipid ratios in a direction beneficial for cardiovascular disease risk in healthy young men.     

Soy isoflavones improve plasma lipids in normocholesterolemic and mildly hypercholesterolemic postmenopausal women

BACKGROUND: Soy-protein consumption is known to reduce plasma total and LDL cholesterol concentrations. However, the responsible soy component or components and the magnitude of effects in normocholesterolemic and mildly hypercholesterolemic subjects are unclear. OBJECTIVE: The present study examined the effects of soy isoflavone consumption on plasma concentrations of triacylglycerol, apolipoprotein (apo) A-I, apo B, lipoprotein(a), and total, LDL, and HDL cholesterol and on LDL peak particle diameter in normocholesterolemic and mildly hypercholesterolemic postmenopausal women. DESIGN: In a randomized crossover trial, fasting plasma samples were obtained from 18 postmenopausal women throughout three 93-d periods of daily isolated soy protein (ISP) consumption providing an average of 7.1 +/- 1.1 (control), 65 +/- 11 (low isoflavone), or 132 +/- 22 (high isoflavone) mg isoflavones/d. RESULTS: Compared with values measured during the control diet, the plasma LDL cholesterol concentration was 6.5% lower (P < 0.02) during the high-isoflavone diet and the ratio of LDL to HDL cholesterol was 8.5% and 7.7% lower during the low- and high-isoflavone diets, respectively (P < 0.02). Isoflavone consumption did not significantly affect plasma concentrations of total or HDL cholesterol, triacylglycerol, apo A-I, apo B, or lipoprotein(a) or the LDL peak particle diameter. CONCLUSIONS: Consumption of isoflavones as a constituent of ISP resulted in small but significant improvements in the lipid profile in normocholesterolemic and mildly hypercholesterolemic postmenopausal women. Although the effects were small, it is possible that isoflavones may contribute to a lower risk of coronary heart disease if consumed over many years in conjunction with other lipid-lowering strategies.     

Relation between soy-associated isoflavones and LDL and HDL cholesterol concentrations in humans: a meta-analysis

BACKGROUND: Differences in isoflavone content of soy protein may explain the absence of a dose-response relation between soy protein intake and blood cholesterol concentrations. OBJECTIVE: To study specifically the effect of soy-associated isoflavones on cholesterol concentrations in well-controlled trials substituting soy protein with dairy or animal protein. DESIGN: Studies were identified by MEDLINE searches (1995 - 6 June 2002) and reviewing reference lists. Studies were included if they had a control group or treatment, experimental diets only differed in the amounts of soy protein and isoflavones and were each fed for at least 14 days. A total of 10 studies met these criteria, providing 21 dietary comparisons. SUBJECTS:: Studies comprised 959 subjects (336 men and 623 women), average age ranged from 41 to 67 y and baseline cholesterol concentration from 5.42 to 6.60 mmol/l. INTERVENTIONS: The intake of soy-associated isoflavones increased by 1-95 mg/day and the intake of soy protein increased by 19-60 g/day. RESULTS: Feeding daily 36 g soy protein with 52 mg soy-associated isoflavones on average decreased low-density lipoprotein (LDL) cholesterol by -0.17+/-0.04 mmol/l (mean+/-s.e.) and increased high-density lipoprotein (HDL) cholesterol by 0.03+/-0.01 mmol/l. There was no dose-response relation between soy-associated isoflavones and changes in LDL cholesterol (R=-0.33, P=0.14) (Pearson correlation coefficient) or HDL cholesterol (R=-0.07, P=0.76) or their ratio. CONCLUSIONS: Consumption of soy-associated isoflavones is not related to changes in LDL or HDL cholesterol.     

Soy food consumption does not lower LDL cholesterol in either equol or nonequol producers

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.     

Soy protein favorably affects LDL size independently of isoflavones in hypercholesterolemic men and women

We assessed the independent effect of soy protein relative to animal protein and of isoflavones on various electrophoretic characteristics of LDL particles. LDL particles were characterized by polyacrylamide gradient gel electrophoresis in 36 moderately hypercholesterolemic men and women (LDL cholesterol > 3.36 mmol/L). All subjects consumed in random order each of the four diets (soy protein depleted of isoflavones, soy protein enriched in isoflavones, animal protein with no added isoflavones, and animal protein with added isoflavones) for 6 wk. Consumption of soy protein was associated with a larger LDL peak particle size relative to animal protein (P < 0.01). Soy protein also decreased the cholesterol levels in LDL < 25.5 nm by 12.3% (P < 0.001) and increased cholesterol levels in LDL > 26.0 nm by 14.3% (P < 0.05) relative to animal protein. Isoflavones did not affect these LDL particle characteristics. Soy protein shifted LDL particle distribution to a less atherogenic pattern and this effect is independent of soy's isoflavone component.     

Soy isoflavones improve plasma lipids in normocholesterolemic, premenopausal women

BACKGROUND: Soy consumption is known to reduce plasma total cholesterol and LDL cholesterol in hypercholesterolemic subjects, but the responsible soy components and the effects in normocholesterolemic subjects remain unclear. OBJECTIVE: The effects of soy isoflavone consumption on plasma total cholesterol, HDL-cholesterol, LDL-cholesterol, triacylglycerol, apolipoprotein A-I, apolipoprotein B, and lipoprotein(a) concentrations and on LDL peak particle diameter were examined in normocholesterolemic, premenopausal women. DESIGN: Thirteen healthy, normocholesterolemic, free-living, premenopausal female volunteers took part in this randomized, crossover-controlled trial. Each subject acted as her own control. Three soy isoflavone intakes (control: 10.0 +/- 1.1; low: 64.7 +/- 9.4; and high: 128.7 +/- 15.7 mg/d), provided as soy protein isolate, were consumed for 3 menstrual cycles each. Total cholesterol, HDL cholesterol, LDL cholesterol, and triacylglycerol were measured over the menstrual cycle. Apolipoprotein A-I, apolipoprotein B, lipoprotein(a), and LDL peak particle diameter were evaluated in the midluteal phase. RESULTS: Total cholesterol, HDL-cholesterol, and LDL-cholesterol concentrations changed significantly across menstrual cycle phases (P < 0.005). During specific phases of the cycle, the high-isoflavone diet lowered LDL cholesterol by 7.6-10.0% (P < 0.05), the ratio of total cholesterol to HDL cholesterol by 10.2% (P < 0.005), and the ratio of LDL to HDL cholesterol by 13.8% (P < 0.002). CONCLUSIONS: Isoflavones significantly improved the lipid profile across the menstrual cycle in normocholesterolemic, premenopausal women. Although of small magnitude, these effects could contribute to a lower risk of developing coronary heart disease in healthy people who consume soy over many years.     

Soy protein intake by perimenopausal women does not affect circulating lipids and lipoproteins or coagulation and fibrinolytic factors

Soy protein favorably alters serum lipids and lipoproteins in hypercholesterolemic individuals, thereby reducing cardiovascular disease risk. The primary purpose was to determine the effect of soy protein (40 g/d) on circulating lipids and lipoproteins or coagulation and fibrinolytic factors in normocholesterolemic and mildly hypercholesterolemic perimenopausal women. We also determined the contribution of coagulation and fibrinolytic and other factors (e.g., body size and composition; serum estrogens, ferritin, iron; dietary intake) to lipid profiles. Subjects were randomly assigned to treatment: isoflavone-rich soy (n = 24), isoflavone-poor soy (n = 24), or whey control (n = 21) protein. We measured circulating lipids and lipoproteins at baseline, wk 12 and wk 24, and coagulation/fibrinolytic factors at baseline and wk 24. Coagulation and fibrinolytic factors were not adversely affected by treatment. Treatment did not alter lipid profiles in mildly hypercholesterolemic (n = 30) or in all subjects combined. Time significantly (P < 0.001) affected serum total cholesterol, triacylglycerol, LDL cholesterol and HDL cholesterol concentrations. We could not attribute changes over time to various factors, but at baseline accounted for 57% of the variability in HDL cholesterol (P < or = 0.0001) and for 50% in the total to HDL cholesterol ratio (P < or = 0.0001). Dietary vitamin E and % energy from fat had positive effects, whereas plasma plasminogen activator inhibitor-1, fibrinogen, body weight and serum ferritin had negative effects on HDL and total to HDL cholesterol. Isoflavone-rich or isoflavone-poor soy protein had no effect on lipid profiles or coagulation and fibrinolytic factors, whereas the effect of time suggested that the hormonal milieu during the menopausal transition may have overridden any detectable treatment effect on lipids. The relationship between coagulation factors and serum lipids should be examined further as indices of cardiovascular disease risk in midlife women.     

Soy, soy phytoestrogens and cardiovascular disease

Dietary soy protein has been shown to have several beneficial effects on cardiovascular health. The best-documented effect is on plasma lipid and lipoprotein concentrations, with reductions of approximately 10% in LDL cholesterol concentrations (somewhat greater for individuals with high pretreatment LDL cholesterol concentrations) and small increases in HDL cholesterol concentrations. Dietary soy protein improves flow-mediated arterial dilation of postmenopausal women but worsens that of men. Soy isoflavone extracts improve systemic arterial compliance, an indicator of atherosclerosis extent. Complete soy protein but not alcohol-washed soy protein reduces atherosclerosis of postmenopausal monkeys. No definite experimental evidence exists currently to establish that the cardiovascular benefits of soy protein are accounted for by its isoflavones.     

Soy isoflavone intake lowers serum LDL cholesterol: a meta-analysis of 8 randomized controlled trials in humans

Clinical trials have noted hypocholesterolemic effects of soy protein intake, but the components responsible are not known. This meta-analysis of 8 randomized controlled trials was conducted to more precisely evaluate the effects of isoflavones on blood LDL cholesterol concentration independently of soy protein level. PubMed was searched for English-language "randomized controlled trial" articles published from 1966 to 2003 that described the effects of soy protein isolate (SPI) intake with measured isoflavone levels on blood lipids in humans using the search terms "soy protein," "isoflavones," and "cholesterol." From 31 articles identified by the search, 8 articles (with 10 low vs. high isoflavone comparisons) were selected for the meta-analysis. Subjects in each comparison consumed similar dietary fat, cholesterol, and fiber; the reported body weight of subjects did not change significantly during treatment. Serum LDL cholesterol concentration in subjects who consumed SPI (mean 50 g/d) with high isoflavone content (mean intake 96 mg/d) decreased by 0.15 mmol/L (95% CI: 0.08 to 0.23 mmol/L; P < 0.0001) compared with those who consumed the same SPI level with low isoflavone content (mean intake 6 mg/d). Decreases in serum LDL cholesterol concentration in hypercholesterolemic and normocholesterolemic subjects were 0.18 mmol/L (95% CI: 0.01 to 0.35 mmol/L; P = 0.03) and 0.14 mmol/L (95% CI: 0.06, 0.23 mmol/L; P = 0.0008), respectively. With identical soy protein intake, high isoflavone intake led to significantly greater decreases in serum LDL cholesterol than low isoflavone intake, demonstrating that isoflavones have LDL cholesterol-lowering effects independent of soy protein.     

Effects of the National Cholesterol Education Program's Step I and Step II dietary intervention programs on cardiovascular disease risk factors: a meta-analysis

BACKGROUND: Plasma lipid and lipoprotein responses have been variable in dietary intervention studies. OBJECTIVE: The objective of this study was to evaluate the effects of the National Cholesterol Education Program's Step I and Step II dietary interventions on major cardiovascular disease risk factors using meta-analysis. DESIGN: MEDLINE was used to select 37 dietary intervention studies in free-living subjects published from 1981 to 1997. RESULTS: Step I and Step II dietary interventions significantly decreased plasma lipids and lipoproteins. Plasma total cholesterol (TC), LDL cholesterol, triacylglycerol, and TC:HDL cholesterol decreased by 0.63 mmol/L (10%), 0.49 mmol/L (12%), 0.17 mmol/L (8%), and 0.50 (10%), respectively, in Step I intervention studies, and by 0.81 mmol/L (13%), 0.65 mmol/L (16%), 0.19 mmol/L (8%), and 0.34 (7%), respectively, in Step II intervention studies (P < 0.01 for all). HDL cholesterol decreased by 7% (P = 0.05) in response to Step II but not to Step I dietary interventions. Positive correlations between changes in dietary total and saturated fatty acids and changes in TC and LDL and HDL cholesterol were observed (r = 0.59, 0.61, and 0.46, respectively; P < 0.001). Multiple regression analyses showed that for every 1% decrease in energy consumed as dietary saturated fatty acid, TC decreased by 0.056 mmol/L and LDL cholesterol by 0.05 mmol/L. Moreover, for every 1-kg decrease in body weight, triacylglycerol decreased by 0.011 mmol/L and HDL cholesterol increased by 0.011 mmol/L. Exercise resulted in greater decreases in TC, LDL cholesterol, and triacylglycerol and prevented the decrease in HDL cholesterol associated with low-fat diets. CONCLUSION: Step I and Step II dietary interventions have multiple beneficial effects on important cardiovascular disease risk factors.     

Probiotic consumption does not enhance the cholesterol-lowering effect of soy in postmenopausal women

Numerous studies report that soy lowers cholesterol. Probiotic bacteria were also reported to lower total cholesterol (TC) and LDL cholesterol (LDL-C). We hypothesized that by altering intestinal microflora, probiotic consumption may also change phytoestrogen metabolism and enhance the effects of soy. To evaluate the independent and interactive effects of probiotic bacteria and soy on plasma TC, LDL-C, HDL cholesterol (HDL-C), and triglycerides (TG), 37 women with a baseline TC of 5.24 mmol/L were given the following 4 treatments for 6 wk each in a randomized crossover design: soy protein isolate (26 +/- 5 g soy protein containing 44 +/- 8 mg isoflavones/d); soy protein isolate + probiotic capsules (10(9) colony-forming units Lactobacillus acidophilus DDS-1 and Bifidobacterium longum); milk protein isolate (26 +/- 5 g milk protein/d); and milk protein isolate + probiotic. Soy consumption decreased plasma TC by 2.2% (P = 0.02) and LDL-C by 3.5% (P = 0.005), increased HDL-C by 4.2% (P = 0.006) and tended to decrease TG (P = 0.07) compared with milk protein intake. When divided according to initial TC concentration, soy effects were observed only in hypercholesterolemic women (TC > 5.17 mmol/L). In this subgroup, soy treatments decreased plasma TC by 3.3% (P = 0.01), LDL-C by 4.5% (P = 0.004), and TG by 10.6% (P = 0.02), and increased HDL-C by 4.2% (P = 0.02). When subjects were divided on the basis of plasma and urine concentrations of the isoflavone metabolite, equol, equol producers and nonproducers did not differ in baseline lipids or in the effects of soy. Probiotics did not lower cholesterol or enhance the effects of soy. These results confirm a beneficial effect of soy on plasma cholesterol in mildly hypercholesterolemic postmenopausal women independent of equol production status, but do not support an independent or additive effect of these particular probiotic bacteria.     

Modest protective effects of isoflavones from a red clover-derived dietary supplement on cardiovascular disease risk factors in perimenopausal women, and evidence of an interaction with ApoE genotype in 49-65 year-old women

Data suggest that soy protein, a source of isoflavones, may have favorable effects on cardiovascular risk factors. Women (n = 205), ages 49-65 y, were randomized into this double blind, placebo-controlled trial of 43.5 mg red clover-derived isoflavones/d. A total of 177 women completed the trial. There were no differences between treatments for changes from baseline to 12 mo in total cholesterol, LDL cholesterol, triglycerides, HDL cholesterol, systolic and diastolic blood pressures, fibrinogen, and plasminogen activator inhibitor type 1 (PAI-1) (P >/= 0.1). Interactions between treatment and menopausal status were significant for changes in triglycerides and PAI-1 (P = 0.02 and P = 0.01), and changes were significant among perimenopausal women. In the isoflavone and placebo groups, changes in triglycerides were -0.2 +/- 0.6 and 0.4 +/- 0.6 mmol/L, P = 0.02, and changes in PAI-1 were -3.06 +/- 5.88 and 4.95 +/- 6.25 IU/L, P = 0.004, respectively. Interactions between apolipoprotein E (apoE) genotype and treatment tended to be significant for changes in total and LDL cholesterol (P = 0.06 and P = 0.05), and differences between treatments were significant in E2/E3 women. In the isoflavone and placebo groups, changes in total cholesterol were -0.61 +/- 0.79 and 0.18 +/- 0.79 mmol/L, P = 0.03, and changes in LDL cholesterol were -0.84 +/- 0.79 and -0.04 +/- 0.69 mmol/L, P = 0.02, respectively. Although there were potentially beneficial changes in triglycerides and PAI-1 among perimenopausal women consuming isoflavones, this study suggests that isoflavones alone are not responsible for the well-documented effects of soy protein on blood lipids. A larger study is required to confirm the effect modification by apoE genotype.     

Effects of high- and low-isoflavone soyfoods on blood lipids,oxidized LDL,homocysteine, and blood pressure in hyperlipidemic men and women

BACKGROUND: Many of the benefits of soy have been attributed to soy isoflavones. OBJECTIVE: The objective was to determine the effects of high- and low-isoflavone soy-protein foods on both lipid and nonlipid risk factors for coronary artery disease (CAD). METHODS: Forty-one hyperlipidemic men and postmenopausal women participated in a study with three 1-mo diets: a low-fat dairy food control diet and high- (50 g soy protein and 73 mg isoflavones daily) and low- (52 g soy protein and 10 mg isoflavones daily) isoflavone soyfood diets. All 3 diets were very low in saturated fat (< 5% of energy) and cholesterol (< 50 mg/d). Fasting blood samples were drawn and blood pressure was measured at the start and end of each diet. RESULTS: No significant differences were seen between the high- and low-isoflavone soy diets. Compared with the control diet, however, both soy diets resulted in significantly lower total cholesterol, estimated CAD risk, and ratios of total to HDL cholesterol, LDL to HDL cholesterol, and apolipoprotein B to A-I. No significant sex differences were observed, except for systolic blood pressure, which in men was significantly lower after the soy diets than after the control diet. On the basis of blood lipid and blood pressure changes, the calculated CAD risk was significantly lower with the soy diets, by 10.1 +/- 2.7%. CONCLUSION: Substitution of soyfoods for animal products, regardless of isoflavone concentration, reduces the CAD risk because of both modest reductions in blood lipids and reductions in oxidized LDL, homocysteine, and blood pressure.     

Effects on blood lipids of a blood pressure-lowering diet: the Dietary Approaches to Stop Hypertension (DASH) Trial.

BACKGROUND: Effects of diet on blood lipids are best known in white men, and effects of type of carbohydrate on triacylglycerol concentrations are not well defined. OBJECTIVE: Our goal was to determine the effects of diet on plasma lipids, focusing on subgroups by sex, race, and baseline lipid concentrations. DESIGN: This was a randomized controlled outpatient feeding trial conducted in 4 field centers. The subjects were 436 participants of the Dietary Approaches to Stop Hypertension (DASH) Trial [mean age: 44.6 y; 60% African American; baseline total cholesterol: < or = 6.7 mmol/L (< or = 260 mg/dL)]. The intervention consisted of 8 wk of a control diet, a diet increased in fruit and vegetables, or a diet increased in fruit, vegetables, and low-fat dairy products and reduced in saturated fat, total fat, and cholesterol (DASH diet), during which time subjects remained weight stable. The main outcome measures were fasting total cholesterol, LDL cholesterol, HDL cholesterol, and triacylglycerol. RESULTS: Relative to the control diet, the DASH diet resulted in lower total (-0.35 mmol/L, or -13.7 mg/dL), LDL- (-0.28 mmol/L, or -10.7 mg/dL), and HDL- (-0.09 mmol/L, or -3.7 mg/dL) cholesterol concentrations (all P < 0.0001), without significant effects on triacylglycerol. The net reductions in total and LDL cholesterol in men were greater than those in women by 0.27 mmol/L, or 10.3 mg/dL (P = 0.052), and by 0.29 mmol/L, or 11.2 mg/dL (P < 0.02), respectively. Changes in lipids did not differ significantly by race or baseline lipid concentrations, except for HDL, which decreased more in participants with higher baseline HDL-cholesterol concentrations than in those with lower baseline HDL-cholesterol concentrations. The fruit and vegetable diet produced few significant lipid changes. CONCLUSIONS: The DASH diet is likely to reduce coronary heart disease risk. The possible opposing effect on coronary heart disease risk of HDL reduction needs further study.     

Plasma antioxidant capacity in response to diets high in soy or animal protein with or without isoflavones

BACKGROUND: Several clinical trials have suggested that soy intake decreases oxidative stress. Soy isoflavones have antioxidant properties in vitro, but results of supplementation in clinical trials are inconclusive. OBJECTIVE: The objective was to evaluate the independent effects of soy protein and soy-derived isoflavones on plasma antioxidant capacity and biomarkers of oxidative stress. DESIGN: Forty-two hypercholesterolemic (LDL cholesterol > 3.36 mmol/L) subjects aged >50 y were provided with each of 4 diets in random order in a crossover design. Diets varied in protein source (10% of energy, soy or animal) and isoflavone content (trace or 50 mg/1000 kcal) and were consumed for 42 d each. Plasma antioxidants, protein carbonyls, malondialdehyde, total antioxidant performance, LDL oxidizability, and urinary F(2)-isoprostanes were measured at the end of each dietary phase. RESULTS: Plasma antioxidant concentrations were not significantly different, regardless of dietary treatment, except for isoflavones, which were higher after isoflavone supplementation (P = 0.0001). Although plasma total antioxidant performance was 10% higher with soy protein intake, regardless of dietary isoflavones (P = 0.0003), soy protein did not significantly affect most individual markers of oxidative stress (LDL oxidizability, urinary F(2)-isoprostanes, malondialdehyde, or protein carbonyls in native plasma). However, soy protein was associated with modestly lower concentrations of protein carbonyls in oxidized plasma. There was no significant effect of isoflavones on LDL oxidation, urinary F(2)-isoprostanes, or protein carbonyl groups, although, paradoxically, the plasma malondialdehyde concentration was significantly higher after the isoflavone-rich diets (P = 0.04). CONCLUSIONS: Diets relatively high in soy protein or soy-derived isoflavones have little effect on plasma antioxidant capacity and biomarkers of oxidative stress.     

Blood lipid and oxidative stress responses to soy protein with isoflavones and phytic acid in postmenopausal women

BACKGROUND: Postmenopausal women are at risk of cardiovascular disease (CVD) as a result of unfavorable blood lipid profiles and increased oxidative stress. Soy protein consumption may help protect against these risk factors. OBJECTIVE: Our objective was to ascertain the effect of the soy protein components isoflavones and phytate on CVD risk in postmenopausal women. DESIGN: In a double-blind 6-wk study, 55 postmenopausal women were randomly assigned to 1 of 4 treatments with soy protein (40 g/d) isolate (SPI): low phytate/low isoflavone (LP/LI); normal phytate/low isoflavone (NP/LI); low phytate/normal isoflavone (LP/NI); or normal phytate/normal isoflavone (NP/NI). Blood lipids (total, LDL, and HDL cholesterol and triacylglycerol) and oxidative stress indexes (protein carbonyls, oxidized LDLs, and 8-iso-prostaglandin-F(2alpha)) were measured at baseline and 6 wk. RESULTS: The oxidative stress indexes were not significantly affected by either phytate or isoflavones. Phytate treatment had a minimal but nonsignificant effect in reducing protein carbonyls and 8-iso-prostaglandin-F(2alpha); the reductions were 6-8% and 4-6% in the NP/LI and NP/NI groups and 1-4% and 3-4% in the LP/LI and LP/NI groups, respectively. Similarly, circulating lipids were not significantly affected by either phytate or isoflavones. The decline in total (6%-7% compared with 2%-4%) and LDL (10%-11% compared with 3%-7%) cholesterol did not differ significantly between the normal- and low-isoflavone groups, respectively. CONCLUSION: In postmenopausal women, neither phytate nor isoflavones in SPI have a significant effect of reducing oxidative damage or favorably altering blood lipids.     

Pasta naturally enriched with isoflavone aglycons from soy germ reduces serum lipids and improves markers of cardiovascular risk

Most studies of soy and cholesterol have tested foods made from purified soy proteins containing mainly isoflavone glycosides. Fermented soy foods have mainly isoflavone aglycons and account for a high proportion of the soy protein source in Asia, where there is an inverse relationship between soy intake and serum cholesterol. The aim of this study was to compare a novel soy germ pasta, naturally enriched in isoflavone aglycons as a result of the manufacturing process, with conventional pasta for effects on serum lipids and other cardiovascular risk markers. In this randomized, controlled, parallel study design of 62 adults with hypercholesterolemia who consumed a Step II diet that included one 80-g serving/d of pasta, we measured serum lipids, high sensitivity C-reactive protein (hsCRP), urinary isoprostanes, and brachial artery flow-mediated vasodilatation at baseline and after 4 and 8 wk. The pasta delivered 33 mg of isoflavones and negligible soy protein and led to a serum isoflavone concentration of 222 +/- 21 nmol/L; 69% of subjects were equol producers. Soy germ pasta reduced serum total and LDL cholesterol by 0.47 +/- 0.13 mmol/L (P = 0.001) and 0.36 +/- 0.10 mmol/L (P = 0.002) more than conventional pasta, representing reductions from baseline of 7.3% (P = 0.001) and 8.6% (P = 0.002), respectively. Arterial stiffness (P = 0.003) and hsCRP (P = 0.03) decreased and improvements in all the above risk markers were greatest in equol producers. All measures returned to baseline when patients were switched to conventional pasta. In conclusion, pasta naturally enriched with isoflavone aglycons and lacking soy protein had a significant hypocholesterolemic effect beyond a Step II diet and improved other cardiovascular risk markers.