Soy protein and casein in cholesterol-enriched diets: effects on plasma lipoproteins in normolipidemic subjects

The effect of dietary plant protein vs animal protein on plasma lipoproteins was investigated in a crossover study. Eleven normal subjects consumed formula diets containing 20% of calories as soy protein or casein, 27% as fat, and 53% as carbohydrate: the average cholesterol intake was 500 mg/d. After an initial decrease in plasma cholesterol and low-density-lipoprotein cholesterol (LDL-C) on both diets, the concentration of LDL-C stabilized during the soy-protein diet at a 16% lower level than on the casein diet (p less than 0.02) whereas the concentration of high-density-lipoprotein cholesterol (HDL-C) was 16% higher (p less than 0.01). In a similar earlier study with a cholesterol intake of less than 100 mg/d, casein and soy protein had indistinguishable effects on lipoprotein levels. Our two studies together suggest that the level of cholesterol intake may determine whether plant and animal dietary proteins have similar or different effects on plasma LDL and HDL concentrations.     

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.     

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.     

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.     

High-protein diets in hyperlipidemia: effect of wheat gluten on serum lipids, uric acid, and renal function.

BACKGROUND: The metabolic effects of diets high in vegetable protein have not been assessed despite much recent interest in the effect of soy proteins in reducing serum cholesterol. OBJECTIVE: We assessed the metabolic effects of diets high in vegetable protein (specifically, wheat gluten) on serum lipids, uric acid concentrations, and renal function. DESIGN: Twenty hyperlipidemic men and women consumed isoenergetic test (high-protein) and control metabolic diets for 1 mo in a randomized crossover design. In the high-protein diet, 11% of the total dietary energy from starch in the control bread was replaced by vegetable protein (wheat gluten), resulting in 27% of total energy from protein compared with 16% in the control diet. In other respects, the 2 diets were identical. RESULTS: Compared with the control, the high-protein diet resulted in lower serum concentrations of triacylglycerol (by 19.2 +/- 5.6%; P = 0.003), uric acid (by 12.7 +/- 2.0%; P < 0.001), and creatinine (by 2.5 +/- 1.1%; P = 0.035) and higher serum concentrations of urea (by 42.2 +/- 5.8%; P < 0.001) and a higher 24-h urinary urea output (by 99.2 +/- 17.2%; P < 0.001). No significant differences were detected in total or HDL cholesterol or in the renal clearance of creatinine. LDL oxidation, assessed as the ratio of conjugated dienes to LDL cholesterol in the LDL fraction, was lower with the high-protein diet (by 10.6 +/- 3.6%; P = 0.009). CONCLUSIONS: High intakes of vegetable protein from gluten may have beneficial effects on cardiovascular disease risk by reducing oxidized LDL, serum triacylglycerol, and uric acid. Further studies are required to assess the longer-term effects on renal function.     

Lipid response to a low-fat diet with or without soy is modified by C-reactive protein status in moderately hypercholesterolemic adults

Recent evidence suggests that individuals with high concentrations of C-reactive protein (CRP), a marker of inflammation, are less responsive to cholesterol-lowering diets. CRP concentrations are increased by oral estrogen; however, the effect of soy phytoestrogens on inflammation has not been studied comprehensively, especially in women receiving hormone replacement therapy (HRT). This study was conducted to determine whether adding soy to a low-fat, high-fiber diet affects CRP and interleukin (IL)-6, and to examine the association between CRP levels and lipid response in moderately hypercholesterolemic adults (men = 18, postmenopausal women = 14; 6 receiving HRT). After a 3-wk run-in period with consumption of a Step I diet (27% total fat, 7% saturated fat, 275 mg cholesterol), participants were randomly assigned to diets containing 25 g/d soy protein (+ 90 mg/d isoflavones) or 25 g/d milk protein for 6 wk in a crossover design. Lipids and lipoproteins, CRP, and IL-6 were measured at the end of each diet and participants were categorized into high (>3.5 mg/L) or low CRP groups based on a median split. The addition of soy or milk protein to the Step I diet did not affect lipids or inflammatory markers. Regardless of protein source, those with low CRP exhibited significant decreases in LDL cholesterol (-3.5%) and the LDL:HDL cholesterol ratio (-4.8%), whereas those with high CRP had significant increases in LDL cholesterol (+4.8%), the LDL:HDL cholesterol ratio (+5.2%), apolipoprotein B (+3.8%), and lipoprotein(a) (+13.5%) compared with the run-in diet. These results suggest that inflammation may not only attenuate lipid responses, but also aggravate dyslipidemia in hypercholesterolemic subjects consuming a cholesterol-lowering diet.     

Low-fat and high-monounsaturated fatty acid diets decrease plasma cholesterol ester transfer protein concentrations in young, healthy, normolipemic men

BACKGROUND: Cholesterol ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL to apolipoprotein (apo) B-containing lipoproteins. The possible atherogenic role of this protein is controversial. Diet may influence plasma CETP concentrations. OBJECTIVE: The objective was to determine whether the changes in plasma lipids observed after consumption of 2 lipid-lowering diets are associated with changes in plasma CETP concentrations. DESIGN:: We studied 41 healthy, normolipidemic men over 3 consecutive 4-wk dietary periods: a saturated fatty acid-rich diet (SFA diet: 38% fat, 20% saturated fat), a National Cholesterol Education Program Step I diet (NCEP Step I diet: 28% fat, 10% saturated fat), and a monounsaturated fatty acid-rich diet (MUFA diet: 38% fat, 22% monounsaturated fat). Cholesterol content (27.5 mg/MJ) was kept constant during the 3 periods. Plasma concentrations of total, LDL, and HDL cholesterol; triacylglycerol; apo A-I and B; and CETP were measured at the end of each dietary period. RESULTS: Compared with the SFA diet, both lipid-lowering diets significantly decreased plasma total and LDL cholesterol, apo B, and CETP. Only the NCEP Step I diet lowered plasma HDL cholesterol. Positive, significant correlations were found between plasma CETP and total (r = 0.3868, P < 0.0001) and LDL (r = 0.4454, P < 0.0001) cholesterol and also between changes in CETP concentrations and those of total (r = 0.4543, P < 0.0001) and LDL (r = 0.4554, P < 0.0001) cholesterol. CONCLUSIONS: The isoenergetic substitution of a high-saturated fatty acid diet with an NCEP Step I or a high-monounsaturated fatty acid diet decreases plasma CETP concentrations.     

Effects of isoenergetic high-carbohydrate compared with high-fat diets on human cholesterol synthesis and expression of key regulatory genes of cholesterol metabolism

BACKGROUND: High-carbohydrate diets improve plasma cholesterol concentrations but increase triacylglycerol concentrations; the latter effect increases the risk of cardiovascular disease (CVD). Triacylglycerol concentrations increase only during very-high-carbohydrate diets consisting mainly of simple sugars. OBJECTIVE: We compared the CVD risk profile, cholesterol metabolism, and glucose tolerance of 7 healthy subjects during 2 isoenergetic diets: a high-fat, low-carbohydrate diet (HF diet) and a moderately high-carbohydrate, low-fat diet (HC diet). DESIGN: In a randomized crossover study, we measured the effects of the HF diet [40% carbohydrate and 45% fat (15% saturated, 15% monounsaturated, and 15% polyunsaturated)] and HC diet [55% carbohydrate (mainly complex) and 30% fat (10% saturated, 10% monounsaturated, and 10% polyunsaturated)] (3 wk each) on plasma lipid concentrations, oral glucose tolerance, cholesterol synthesis rate, and the messenger RNA (mRNA) concentrations of beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase, the LDL receptor, and the LDL-receptor-related protein (LRP). RESULTS: Compared with the HF diet, the HC diet lowered total, LDL, and HDL cholesterol (P < 0.05 for all) without modifying the ratio of LDL to HDL cholesterol; triacylglycerol concentrations were unchanged. Lower cholesterol concentrations occurred despite a higher cholesterol synthesis rate (P < 0.05) and higher HMG-CoA reductase mRNA concentrations (P < 0.05). LDL receptor mRNA concentrations were unchanged, LRP mRNA concentrations were lower (P < 0.01), and oral glucose tolerance was better (P < 0.05) with the HC diet. CONCLUSION: The beneficial effects of the HC diet on glucose tolerance and plasma cholesterol concentrations without increases in triacylglycerol show that this diet had favorable effects on both insulin sensitivity and the plasma lipid profile.     

Moderate alcohol consumption lowers risk factors for cardiovascular disease in postmenopausal women fed a controlled diet

BACKGROUND: Moderate alcohol consumption (1-2 drinks/d) may decrease cardiovascular disease risk in postmenopausal women by improving lipid profiles. OBJECTIVE: We measured the effect of moderate alcohol consumption on lipids and lipoproteins in postmenopausal women. DESIGN: Postmenopausal women (n = 51) consumed 0 (control), 15 (1 drink), and 30 (2 drinks) g alcohol (ethanol)/d for 8 wk each as part of a controlled diet in a randomized crossover design. The control diet provided approximately 15%, 53%, and 32% of energy from protein, carbohydrate, and fat, respectively. The energy provided from alcohol in the 15- and 30-g alcohol diets was replaced with energy from carbohydrate. RESULTS: Compared with concentrations after the control diet, plasma LDL cholesterol decreased from 3.45 to 3.34 mmol/L (P = 0.04) and triacylglycerol from 1.43 to 1.34 mmol/L (P = 0.05) after 15 g alcohol/d. There were no additional significant decreases in either lipid after an increase in alcohol intake from 15 to 30 g/d. Compared with concentrations after the control diet, plasma HDL cholesterol increased nonsignificantly from 1.40 to 1.43 mmol/L after 15 g alcohol/d but increased to 1.48 mmol/L after 30 g alcohol/d (P = 0.02). Apolipoprotein A-I increased significantly and apolipoprotein B decreased significantly after 30 g alcohol/d relative to the concentration after the control diet. CONCLUSIONS: Consumption of 15-30 g alcohol/d by postmenopausal women apparently decreases cardiovascular disease risk by improving lipid profiles. Plasma LDL-cholesterol and triacylglycerol concentrations improve after 15 g alcohol/d; plasma HDL cholesterol improves only after 30 g alcohol/d.     

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.     

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.     

Dietary soy beta-conglycinin (7S globulin) inhibits atherosclerosis in mice

Although beta-conglycinin (7S globulin), a major soy storage protein, stimulates the expression of LDL receptors and the degradation of LDL by hepatocytes in vitro, the in vivo effects of dietary beta-conglycinin on the cardiovascular system are unknown. We assessed the effects of dietary beta-conglycinin and other soy peptide fractions on the development of atherosclerosis in atherosclerosis-susceptible mice. At 6 wk of age, male and ovariectomized female apolipoprotein (apo) E-null mice and LDL receptor-null, apoB transgenic mice were assigned randomly to treatment groups that differed only in the source of dietary protein: 1) casein/lactalbumin, 2) isoflavone-containing soy protein isolate, 3) beta-conglycinin, 4) glycinin (11S globulin, another major soy storage protein), 5) beta-conglycinin-devoid soy protein, and 6) W008 (a peptide fraction produced by hydrolysis and precipitation of soy protein isolate). After 4 mo, aortic atherosclerosis (cholesteryl ester content) and plasma lipoprotein cholesterol concentrations were quantified using GLC. Relative to mice fed casein/lactalbumin-based diets, the extent of atherosclerosis was reduced in ovariectomized female mice fed all soy protein-containing diets. Relative to mice fed isoflavone-containing soy protein isolate, atherosclerosis was reduced only in mice fed the beta-conglycinin-containing diet. Mean reductions were 39 and 67% (all P <0.05) in male and ovariectomized female apoE null mice and 66% (P < 0.05) in male LDL receptor null mice. These effects were unrelated to variation in isoflavone content of the protein source and only minimally related to plasma lipoprotein cholesterol concentrations. We conclude that a diet rich in beta-conglycinin has atheroprotective effects that greatly exceed those of isoflavone-containing soy protein isolate and do not depend on LDL receptors or influences on plasma lipoproteins.     

A very low-fat diet is not associated with improved lipoprotein profiles in men with a predominance of large, low-density lipoproteins

BACKGROUND: We found previously that men with a predominance of large LDL particles (phenotype A) consuming high-fat diets (40-46% fat) show less lipoprotein benefits of low-fat diets (20-24% fat) than do men with a high-risk lipoprotein profile characterized by a predominance of small LDL (phenotype B). Furthermore, one-third of men with phenotype A consuming a high-fat diet converted to phenotype B with a low-fat diet. OBJECTIVE: We investigated effects of further reduction in dietary fat in men with persistence of LDL subclass phenotype A during both high- and low-fat diets. DESIGN: Thirty-eight men who had shown phenotype A after 4-6 wk of both high- and low-fat diets consumed for 10 d a 10%-fat diet (2.7% saturates) with replacement of fat with carbohydrate and no change in cholesterol content or ratio of polyunsaturates to saturates. RESULTS: In 26 men, phenotype A persisted (stable A group) whereas 12 converted to phenotype B (change group). LDL cholesterol did not differ from previous values for 20-24%-fat diets in either group, whereas in the change group there were higher concentrations of triacylglycerol and apolipoprotein B; greater mass of HDL, large LDL-I, small LDL-III and LDL-IV, and HDL3; lower concentrations of HDL cholesterol, apolipoprotein A-I; and lower mass of large LDL-I and HDL2. CONCLUSIONS: There is no apparent lipoprotein benefit of reduction in dietary fat from 20-24% to 10% in men with large LDL particles: LDL-cholesterol concentration was not reduced, and in a subset of subjects there was a shift to small LDL along with increased triacylglycerol and reduced HDL-cholesterol concentrations.     

Increased plasma concentrations of lipoprotein(a) during a low-fat, high-carbohydrate diet are associated with increased plasma concentrations of apolipoprotein C-III bound to apolipoprotein B-containing lipoproteins

BACKGROUND: Low-fat, high-carbohydrate (LFHC) diets have been shown to increase plasma concentrations of lipoprotein(a) [Lp(a)] and of triacylglycerol- rich lipoproteins (TRLs). OBJECTIVE: We tested whether increases in plasma Lp(a) induced by an LFHC diet are related to changes in TRLs. DESIGN: Healthy men (study 1; n = 140) consumed for 4 wk each a high-fat, low-carbohydrate diet (HFLC; 40% fat, 45% carbohydrate) and an LFHC diet (20% fat, 65% carbohydrate). Plasma lipids; lipoproteins; apolipoprotein (apo) B, A-I, and C-III; and Lp(a) were measured at the end of each diet. In a second group of men following a similar dietary protocol (study 2; n = 33), we isolated apo(a)-containing particles by immunoaffinity chromatography and determined the concentrations of apo C-III in ultracentrifugally isolated subfractions of apo B-containing lipoproteins. RESULTS: In study 1, plasma concentrations of Lp(a) (P < 0.001), triacylglycerol (P < 0.001), apo B (P < 0.005), apo C-III (P < 0.005), and apo C-III in apo B-containing lipoproteins (non-HDL apo C-III) (P < 0.001) were significantly higher with the LFHC diet than with the HFLC diet. Stepwise multiple linear regression analysis showed that the association of changes in Lp(a) with changes in non-HDL apo C-III was independent of changes in body mass index, apo B, LDL cholesterol, and HDL cholesterol. Plasma lipid and lipoprotein changes were similar in study 2, and we found that both total apo C-III and the apo C-III content of apo(a)-containing particles were increased in a TRL fraction consisting predominantly of large VLDL particles [TRL-apo(a)]. CONCLUSIONS: The increase in plasma Lp(a) with an LFHC diet is significantly associated with an increase in non-HDL apo C-III. Enrichment of TRL-apo(a) with apo C-III may contribute to this dietary effect on Lp(a) concentrations.     

Comparison of the effect of dietary fat restriction with that of energy restriction on human lipid metabolism

BACKGROUND: Dietary fat and energy have been implicated as factors controlling circulating total and LDL-cholesterol concentrations. Whether these factors work independently or synergistically in regulating human cholesterol metabolism remains to be fully elucidated. OBJECTIVE: The objective was to determine whether the effects of fat restriction on circulating lipid concentrations and synthesis differ from those of energy restriction in hypercholesterolemic subjects fed controlled diets. DESIGN: Eleven men (LDL > 3.6 mmol/L) participated in a randomized crossover study. Subjects consumed 4 prepared diets, each for 4 wk and separated by 6 wk, that contained either typical amounts of fat and energy (TF), low amounts of fat but adequate energy (LF), low amounts of fat and energy through carbohydrate restriction (LFE), or typical amounts of fat and low energy through carbohydrate restriction (LE). RESULTS: Body weights declined (P < 0.001) after the LE and LFE diets. Total cholesterol concentrations were not significantly different between the diets. LDL cholesterol was lower (P < 0.05) after the LF and LFE diets (8.2% and 8.0%, respectively) than after the TF diet. The LE diet increased HDL cholesterol (46.8%) and decreased triacylglycerols (22.7%), whereas the LF diet increased triacylglycerols (23.6%), relative to the TF diet. LDL:HDL decreased after the LE and LFE diets (P < 0.05). Cholesterol fractional synthesis rates after the LF, LE, and LFE diets were lower (35.2%, 27.7%, and 25.5%, respectively; P < 0.05) relative to the TF diet. CONCLUSION: Reductions in both dietary fat and energy may modify LDL cholesterol by lowering cholesterol biosynthesis; however, the increase in HDL cholesterol and the suppression of triacylglycerol concentrations and LDL:HDL suggests that favorable plasma lipid profiles were also achieved through energy restriction alone.     

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.     

A comparison of the effects of 2 doses of soy protein or casein on serum lipids,serum lipoproteins,and plasma total homocysteine in hypercholesterolemic subjects

BACKGROUND: Studies have shown that soy protein reduces some atherogenic lipid and lipoprotein concentrations, although lipoprotein(a) concentrations may be increased. The dose response of soy protein has not been established; neither has its effect on plasma total homocysteine. OBJECTIVE: Our objective was to evaluate the effect of 2 doses of soy protein on lipid, lipoprotein, and homocysteine concentrations. DESIGN: Four to 24 wk after being instructed to consume a lipid-lowering diet, 130 men and women with LDL-cholesterol concentrations > or = 4 mmol/L were studied during a parallel group trial in which 4 interventions were assigned randomly. Thirty grams isolated soy protein (ISP) and 10 g cotyledon fiber or 50 g ISP and 16.6 g cotyledon fiber or equivalent doses of casein and cellulose were consumed daily as a beverage for 16 wk. RESULTS: When the 2 groups who consumed ISP were compared with the 2 groups who consumed casein, the differences in the net changes from baseline to week 16 in the concentrations of LDL cholesterol and plasma total homocysteine were -0.26 mmol/L (95% CI: -0.43, -0.09 mmol/L; P = 0.01) and -0.8 micromol/L (-1.4, -0.2 micromol/L; P = 0.005), respectively. The effect of the ISP dose was not significant. There were no significant differences between the 2 ISP and the 2 casein groups in changes in lipoprotein(a), HDL-cholesterol, or triacylglycerol concentrations. CONCLUSIONS: Adding 30-50 g soy protein/d to a lipid-lowering diet significantly reduced LDL-cholesterol concentrations without increasing lipoprotein(a) concentrations. Plasma total homocysteine concentrations also decreased, suggesting a novel, possibly antiatherosclerotic effect.     

Direct comparison of a dietary portfolio of cholesterol-lowering foods with a statin in hypercholesterolemic participants

BACKGROUND: 3-Hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors reduce serum cholesterol and are increasingly advocated in primary prevention to achieve reductions in LDL cholesterol. Newer dietary approaches combining cholesterol-lowering foods may offer another option, but these approaches have not been compared directly with statins in the same persons. OBJECTIVE: The objective was to compare, in the same subjects, the cholesterol-lowering potential of a dietary portfolio with that of a statin. DESIGN: Thirty-four hyperlipidemic participants underwent all three 1-mo treatments in random order as outpatients: a very-low-saturated-fat diet (control diet), the same diet plus 20 mg lovastatin (statin diet), and a diet high in plant sterols (1.0 g/1000 kcal), soy-protein foods (including soy milks and soy burgers, 21.4 g/1000 kcal), almonds (14 g/1000 kcal), and viscous fibers from oats, barley, psyllium, and the vegetables okra and eggplant (10 g/1000 kcal) (portfolio diets). Fasting blood samples were obtained at 0, 2, and 4 wk. RESULTS: LDL-cholesterol concentrations decreased by 8.5+/-1.9%, 33.3+/-1.9%, and 29.6+/-1.3% after 4 wk of the control, statin, and portfolio diets, respectively. Although the absolute difference between the statin and the portfolio treatments was significant at 4 wk (P=0.013), 9 participants (26%) achieved their lowest LDL-cholesterol concentrations with the portfolio diet. Moreover, the statin (n=27) and the portfolio (n=24) diets did not differ significantly (P=0.288) in their ability to reduce LDL cholesterol below the 3.4-mmol/L primary prevention cutoff. CONCLUSIONS: Dietary combinations may not differ in potency from first-generation statins in achieving current lipid goals for primary prevention. They may, therefore, bridge the treatment gap between current therapeutic diets and newer statins.     

Contribution of postprandial lipemia to the dietary fat-mediated changes in endogenous lipoprotein-cholesterol concentrations in humans

BACKGROUND: Dietary fats alter LDL and HDL cholesterol while serving as precursors of postprandial triacylglycerol-rich lipoproteins (TRLs). OBJECTIVE: We hypothesized that the saturated fatty acid (SFA)-mediated increase and the polyunsaturated fatty acid (PUFA)-mediated decrease in endogenous lipoprotein cholesterol are promoted by postprandial TRLs. DESIGN: We performed a 16-d crossover diet study to examine the effect of PUFA-rich [ratio of PUFAs to SFAs (P:S) = 2.0] and SFA-rich (P:S = 0.25) diets on fasting and postprandial plasma lipid and lipoprotein-cholesterol concentrations in 16 normolipidemic subjects. RESULTS: Fasting plasma cholesterol decreased significantly after a PUFA-rich diet because of a decrease in LDL (-12.3%; P < 0.05) and HDL (-3.8%; NS), but did not change after an SFA-rich diet. The appearance of postprandial TRLs in plasma at 4 h was linked to a significant lowering of both LDL (-7.4%) and HDL (-4.8%) after a PUFA-rich diet; no such effect was observed after the SFA-rich diet. At 7 h, LDL and HDL cholesterol returned to near fasting concentrations without postprandial TRL accumulation after a PUFA-rich diet but with a significant postprandial TRL accumulation after an SFA-rich diet. Thus, the in vivo postprandial clearance of cholesterol in LDL+HDL was greater after a PUFA-rich diet than after an SFA-rich diet. The appearance of postprandial TRLs in plasma increased the cholesteryl ester transfer protein-mediated transfer of cholesteryl ester from LDL+HDL to TRLs in vitro without a significant influence from dietary fat. CONCLUSION: Dietary fat-mediated alterations in the rate of hepatic removal of postprandial TRLs, which carry cholesterol accepted from LDL+HDL via cholesteryl ester transfer protein in vivo, may contribute to the dietary fat-mediated change in endogenous lipoprotein cholesterol.     

Effects of a soy-protein beverage on plasma lipoproteins in children with familial hypercholesterolemia

The effects of soy protein (35% of protein energy) given as a beverage and those of cow-milk proteins were investigated on plasma lipoprotein concentrations in children with familial hypercholesterolemia (FH). Subjects were randomly assigned to either the soy-protein or cow-milk-protein experimental period, with subsequent crossover after a washout period, each period lasting 4 wk. Diets were planned to provide 20% energy as protein, 28% as fat (polyunsaturated:monounsaturated:saturated fatty acids, 1:3:3) and less than 200 mg cholesterol/d. No changes were observed in either plasma cholesterol, low-density-lipoprotein cholesterol, or apolipoprotein concentrations. However, the soy beverage significantly reduced the concentrations of triglyceride and very-low-density-lipoprotein cholesterol (P less than 0.05) and significantly increased the concentrations of high-density-lipoprotein cholesterol (HDL-C) and HDL3-C (P less than 0.04 and P less than 0.03, respectively). These results indicate that the administration of soy protein may induce clinically beneficial effects in children with FH.