Polymorphisms in the stearoyl-CoA desaturase gene modify blood glucose response to dietary oils varying in MUFA content in adults with obesity.

Diets varying in SFA and MUFA content can impact glycaemic control; however, whether underlying differences in genetic make-up can influence blood glucose responses to these dietary fatty acids is unknown. We examined the impact of dietary oils varying in SFA/MUFA content on changes in blood glucose levels (primary outcome) and whether these changes were modified by variants in the stearoyl-CoA desaturase (SCD) gene (secondary outcome). Obese men and women participating in the randomised, crossover, isoenergetic, controlled-feeding Canola Oil Multicenter Intervention Trial II consumed three dietary oils for 6 weeks, with washout periods of ˜6 weeks between each treatment. Diets studied included a high SFA/low MUFA Control oil (36·6 % SFA/28·2 % MUFA), a conventional canola oil (6·2 % SFA/63·1 % MUFA) and a high-oleic acid canola oil (5·8 % SFA/74·7 % MUFA). No differences in fasting blood glucose were observed following the consumption of the dietary oils. However, when stratified by SCD genotypes, significant SNP-by-treatment interactions on blood glucose response were found with additive models for rs1502593 (P = 0·01), rs3071 (P = 0·02) and rs522951 (P = 0·03). The interaction for rs3071 remained significant (P = 0·005) when analysed with a recessive model, where individuals carrying the CC genotype showed an increase (0·14 (sem 0·09) mmol/l) in blood glucose levels with the Control oil diet, but reductions in blood glucose with both MUFA oil diets. Individuals carrying the AA and AC genotypes experienced reductions in blood glucose in response to all three oils. These findings identify a potential new target for personalised nutrition approaches aimed at improving glycaemic control.

Diets Enriched with Conventional or High-Oleic Acid Canola Oils Lower Atherogenic Lipids and Lipoproteins Compared to a Diet with a Western Fatty Acid Profile in Adults with Central Adiposity.

BACKGROUND: Novel oils high in monounsaturated fatty acids (MUFAs) and low in saturated fatty acids (SFAs) are an alternative to partially hydrogenated oils high in trans-unsaturated fatty acids. There is widespread use of high-MUFA oils across the food industry; however, limited knowledge of their cardiovascular impact exists. OBJECTIVES: We investigated the effects of diets containing canola oil, high-oleic acid canola oil (HOCO), and a control oil blend (diet formulated to emulate a Western fat profile) on lipids, lipoproteins, and apolipoproteins (apos), as secondary outcomes of the trial. METHODS: In a multi-center, double-blind, randomized, 3-period crossover, controlled feeding trial, men (n = 44) and women (n = 75) with a mean age of 44 y, mean body mass index (BMI; in kg/m2) of 31.7, and an increased waist circumference plus ≥1 metabolic syndrome criteria consumed prepared, weight-maintenance diets containing canola oil [17.5% MUFAs, 9.2% polyunsaturated fatty acids (PUFAs), 6.6% SFAs], HOCO (19.1% MUFAs, 7.0% PUFAs, 6.4% SFAs), or control oil (10.5% MUFAs, 10.0% PUFAs, 12.3% SFAs) for 6 wk with ≥4-wk washouts. Fasting serum lipids were assessed at baseline and 6 wk. Diet effects were examined using a repeated measures mixed model. RESULTS: Compared with the control, canola and HOCO diets resulted in lower endpoint total cholesterol (TC; -4.2% and -3.4%; P < 0.0001), LDL cholesterol (-6.6% and -5.6%; P < 0.0001), apoB (-3.7% and -3.4%; P = 0.002), and non-HDL cholesterol (-4.5% and -4.0%; P = 0.001), with no differences between canola diets. The TC:HDL cholesterol and apoB:apoA1 ratios were lower after the HOCO diet than after the control diet (-3.7% and -3.4%, respectively). There were no diet effects on triglyceride, HDL cholesterol, or apoA1 concentrations. CONCLUSIONS: HOCO, with increased MUFAs at the expense of decreased PUFAs, elicited beneficial effects on lipids and lipoproteins comparable to conventional canola oil and consistent with reduced cardiovascular disease risk in adults with central adiposity. This trial was registered at www.clinicaltrials.gov as NCT02029833.

Assessing the impact of the diet on cardiometabolic outcomes: are multiple measurements post-intervention necessary?

The purpose of this study was to examine how using the mean of two consecutive measurements vs. one measurement post-treatment influences the sample size required to detect changes in cardiometabolic risk factors in dietary studies. For a given statistical power, using the mean of two measurements taken on consecutive days post-treatment instead of a single measurement significantly reduces the sample size required to observe changes in triglyceride, total apolipoprotein B100, and C-reactive protein concentrations in the context of a supplementation study. In the context of a controlled-feeding study, this gain is seen only in the case of change in triglyceride concentrations.

Diets Low in Saturated Fat with Different Unsaturated Fatty Acid Profiles Similarly Increase Serum-Mediated Cholesterol Efflux from THP-1 Macrophages in a Population with or at Risk for Metabolic Syndrome: The Canola Oil Multicenter Intervention Trial.

Background: Cholesterol efflux plays an important role in preventing atherosclerosis progression. Vegetable oils with varying unsaturated fatty acid profiles favorably affect multiple cardiovascular disease risk factors; however, their effects on cholesterol efflux remain unclear. Objective: The objectives of this study were to examine the effects of diets low in saturated fatty acids (SFAs) with varying unsaturated fatty acid profiles on serum-mediated cholesterol efflux and its association with the plasma lipophilic index and central obesity. Methods: The present study is a randomized, crossover, controlled-feeding study. Participants [men: n = 50; women: n = 51; mean ± SE age: 49.5 ± 1.2 y; body mass index (in kg/m2): 29.4 ± 0.4] at risk for or with metabolic syndrome (MetS) were randomly assigned to 5 isocaloric diets containing the treatment oils: canola oil, high oleic acid-canola oil, DHA-enriched high oleic acid-canola oil, corn oil and safflower oil blend, and flax oil and safflower oil blend. These treatment oils were incorporated into smoothies that participants consumed 2 times/d. For a 3000-kcal diet, 60 g of treatment oil was required to provide 18% of total energy per day. Each diet period was 4 wk followed by a 2- to 4-wk washout period. We quantified cholesterol efflux capacity with a validated ex vivo high-throughput cholesterol efflux assay. Statistical analyses were performed with the use of the SAS mixed-model procedure. Results: The 5 diets increased serum-mediated cholesterol efflux capacity from THP-1 macrophages similarly by 39%, 34%, 55%, 49% and 51%, respectively, compared with baseline (P < 0.05 for all). Waist circumference and abdominal adiposity were negatively correlated with serum-mediated cholesterol efflux capacity (r = -0.25, P = 0.01, r = -0.33, P = 0.02, respectively). Conclusion: Diets low in SFAs with different monounsaturated fatty acid and polyunsaturated fatty acid profiles improved serum-mediated cholesterol efflux capacity in individuals with or at risk for MetS. This mechanism may account, in part, for the cardiovascular disease benefits of diets low in SFAs and high in unsaturated fatty acids. Importantly, central obesity is inversely associated with cholesterol efflux capacity. This trial was registered at www.clinicaltrials.gov as NCT01351012.

Effects of canola and high-oleic-acid canola oils on abdominal fat mass in individuals with central obesity.

OBJECTIVE: To determine the effect of diets low in saturated fatty acids and high in monounsaturated fatty acids (MUFA) or polyunsaturated fatty acids on body composition in participants at risk for metabolic syndrome (MetS). METHODS: This study was a randomized, crossover, controlled feeding study. Participants (n = 101, ages 49.5 ± 1.2, BMI 29.4 ± 0.4 kg/m2 ) were randomized to five isocaloric diets containing treatment oils: Canola, CanolaOleic, CanolaDHA, Corn/Safflower, and Flax/Safflower. Each diet period was 4 weeks followed by a 2- to 4-week washout period. RESULTS: Canola (3.1 kg, P = 0.026) and CanolaOleic oil diets (3.09 kg, P = 0.03) reduced android fat mass compared with the Flax/Saff oil diet (3.2 kg), particularly in men. The decrease in abdominal fat mass was correlated with the reduction in blood pressure after the Canola (systolic blood pressure: r = 0.26, P = 0.062; diastolic blood pressure: r = 0.38, P = 0.0049) and CanolaOleic oil diets (systolic blood pressure: r = 0.39 P = 0.004; diastolic blood pressure: r = 0.45, P = 0.0006). The decrease in abdominal fat mass also was associated with a reduction in triglyceride levels after the CanolaOleic oil diet (r = 0.42, P = 0.002). CONCLUSIONS: Diets high in MUFA (compared with PUFA) reduced central obesity with an accompanying improvement in MetS risk factors. Diets high in MUFA may be beneficial for treating and perhaps preventing MetS.

The Relationship Between Parathyroid Hormone and 25-Hydroxyvitamin D During and After Pregnancy.

CONTEXT: There is debate about whether women may need greater vitamin D supplementation when pregnant. However, it is unclear whether the 25-hydroxyvitamin D (25-OH-D) concentration required for suppression of PTH (ie, suggesting vitamin D sufficiency) differs between pregnancy and the nongravid state. OBJECTIVE: To systematically characterize the relationship between 25-OH-D and PTH during and after pregnancy. DESIGN/SETTING/PARTICIPANTS: In this study, 468 women underwent serial assessment of serum 25-OH-D and PTH in late pregnancy, at 3 months postpartum, and at 12 months postpartum. At each visit, segmented regression analysis was performed to: 1) determine the best model to fit the relationship between 25-OH-D and PTH; and 2) identify the 25-OH-D threshold above which PTH is maximally suppressed. RESULTS: Serum 25-OH-D and PTH were inversely correlated at each of the pregnancy (r = −0.33; P < .0001), 3 months postpartum (r = −0.37; P < .0001), and 12 months postpartum (r = −0.34; P < .0001) assessments. In pregnancy, PTH first rises when 25-OH-D falls below 82 nmol/L (95% confidence interval, 61­103) and follows a linear relationship with declining 25-OH-D thereafter. In contrast, at both postpartum visits, there was a curvilinear relationship between 25-OH-D and PTH below the 25-OH-D threshold at which PTH is suppressed (71 nmol/L [61­81] at 3 months and 81 nmol/L [61­100] at 12 months). The 25-OH-D thresholds for PTH suppression in pregnancy and at 3 and 12 months postpartum were not significantly different from one another (all pairwise P ≥ .26). CONCLUSION: Although the shape of the relationship between 25-OH-D and PTH differs between pregnancy and the postpartum, the 25-OH-D thresholds for PTH suppression are similar, supporting comparable targets for vitamin D supplementation.

Traditional foods and 25(OH)D concentrations in a subarctic First Nations community.

BACKGROUND: Sub-optimal vitamin D status is common worldwide and the condition may be associated with increased risk for various chronic diseases. In particular, low vitamin D status is highly prevalent in indigenous communities in Canada, although limited data are available on the determinants of serum 25-hydroxyvitamin D (25(OH)D) concentrations in this population. The relationship between traditional food consumption and vitamin D status has not been well documented. OBJECTIVE: To investigate the determinants of serum 25(OH)D status in a First Nations community in Ontario, Canada, with a focus on the role of traditional food consumption and activities. METHODS: A cross-sectional analysis was conducted within the Sandy Lake Health and Diabetes Project (2003-2005). A total of 445 participants (>12 years of age) were assessed for serum 25(OH)D status, anthropometric and lifestyle variables, including traditional and non-traditional dietary practices and activities. Diet patterns were identified using factor analysis, and multivariate linear regression analysis was used to analyse the determinants of 25(OH)D concentrations. RESULTS: Mean serum 25(OH)D concentrations were 22.1 nmol/L (16.9, 29.9 nmol/L) in men and 20.5 nmol/L (16.0, 27.3 nmol/L) in women. Multivariate determinants of higher serum 25(OH)D included higher consumption of traditional and healthier market foods, higher wild fish consumption, male gender, spring/summer season of blood collection and more frequent physical activity. Significant negative determinants included hours of TV/day, higher BMI and higher consumption of unhealthy market foods. CONCLUSIONS: Traditional food consumption contributed independently to higher 25(OH)D concentrations in a First Nations community with a high prevalence of sub-optimal vitamin D status.

The persistence of maternal vitamin D deficiency and insufficiency during pregnancy and lactation irrespective of season and supplementation.

BACKGROUND: Pregnancy and lactation comprise a critical window spanning all seasons during which maternal vitamin D status potentially may influence the long-term health of the newborn. Women typically receive calcium/vitamin D supplementation through antenatal vitamins, but there has been limited serial evaluation of maternal vitamin D status across this critical window. DESIGN/PATIENTS/MEASUREMENTS: In this prospective observational cohort study, 467 women in Toronto, Canada, underwent measurement of serum 25-hydroxy vitamin D (25-OH-D) at mean 29·7 ± 2·9 weeks' gestation, 3 months postpartum and 12 months postpartum, enabling serial assessment across 3 seasons. At each assessment, vitamin D status was classified as deficiency (25-OH-D<50 nmol/l), insufficiency (25-OH-D≥50 nmol/l and <75 nmol/l) or sufficiency (25-OH-D≥75 nmol/l). RESULTS: The prevalence rates of vitamin D deficiency and insufficiency were 31·5% and 35·1% in pregnancy, 33·4% and 35·3% at 3 months, and 35·6% and 33·8% at 12 months postpartum, respectively. These high rates remained stable over time (P = 0·49) despite declining usage of antenatal calcium/vitamin D supplementation from pregnancy to 3 months to 12 months postpartum (P < 0·001). Indeed, on mixed model analyses, vitamin D deficiency and insufficiency in pregnancy were independently associated with decrements in average 25-OH-D over time of 49·6 nmol/l and 26·4 nmol/l, respectively (both P < 0·001). In contrast, season of baseline assessment and use of calcium/vitamin D supplements were independently associated with changes in 25-OH-D in the range of 3-5 nmol/l (both P < 0·008). CONCLUSIONS: The persistence of vitamin D deficiency/insufficiency during pregnancy and lactation, irrespective of season and supplementation, supports the emerging concept that current vitamin D supplementation in antenatal care is likely inadequate.

High-oleic canola oil consumption enriches LDL particle cholesteryl oleate content and reduces LDL proteoglycan binding in humans.

Oleic acid consumption is considered cardio-protective according to studies conducted examining effects of the Mediterranean diet. However, animal models have shown that oleic acid consumption increases LDL particle cholesteryl oleate content which is associated with increased LDL-proteoglycan binding and atherosclerosis. The objective was to examine effects of varying oleic, linoleic and docosahexaenoic acid consumption on human LDL-proteoglycan binding in a non-random subset of the Canola Oil Multi-center Intervention Trial (COMIT) participants. COMIT employed a randomized, double-blind, five-period, cross-over trial design. Three of the treatment oil diets: 1) a blend of corn/safflower oil (25:75); 2) high oleic canola oil; and 3) DHA-enriched high oleic canola oil were selected for analysis of LDL-proteoglycan binding in 50 participants exhibiting good compliance. LDL particles were isolated from frozen plasma by gel filtration chromatography and LDL cholesteryl esters quantified by mass-spectrometry. LDL-proteoglycan binding was assessed using surface plasmon resonance. LDL particle cholesterol ester fatty acid composition was sensitive to the treatment fatty acid compositions, with the main fatty acids in the treatments increasing in the LDL cholesterol esters. The corn/safflower oil and high-oleic canola oil diets lowered LDL-proteoglycan binding relative to their baseline values (p = 0.0005 and p = 0.0012, respectively). At endpoint, high-oleic canola oil feeding resulted in lower LDL-proteoglycan binding than corn/safflower oil (p = 0.0243) and DHA-enriched high oleic canola oil (p = 0.0249), although high-oleic canola oil had the lowest binding at baseline (p = 0.0344). Our findings suggest that high-oleic canola oil consumption in humans increases cholesteryl oleate percentage in LDL, but in a manner not associated with a rise in LDL-proteoglycan binding.

DHA-enriched high-oleic acid canola oil improves lipid profile and lowers predicted cardiovascular disease risk in the canola oil multicenter randomized controlled trial.

BACKGROUND: It is well recognized that amounts of trans and saturated fats should be minimized in Western diets; however, considerable debate remains regarding optimal amounts of dietary n-9, n-6, and n-3 fatty acids. OBJECTIVE: The objective was to examine the effects of varying n-9, n-6, and longer-chain n-3 fatty acid composition on markers of coronary heart disease (CHD) risk. DESIGN: A randomized, double-blind, 5-period, crossover design was used. Each 4-wk treatment period was separated by 4-wk washout intervals. Volunteers with abdominal obesity consumed each of 5 identical weight-maintaining, fixed-composition diets with one of the following treatment oils (60 g/3000 kcal) in beverages: 1) conventional canola oil (Canola; n-9 rich), 2) high-oleic acid canola oil with docosahexaenoic acid (CanolaDHA; n-9 and n-3 rich), 3) a blend of corn and safflower oil (25:75) (CornSaff; n-6 rich), 4) a blend of flax and safflower oils (60:40) (FlaxSaff; n-6 and short-chain n-3 rich), or 5) high-oleic acid canola oil (CanolaOleic; highest in n-9). RESULTS: One hundred thirty individuals completed the trial. At endpoint, total cholesterol (TC) was lowest after the FlaxSaff phase (P < 0.05 compared with Canola and CanolaDHA) and highest after the CanolaDHA phase (P < 0.05 compared with CornSaff, FlaxSaff, and CanolaOleic). Low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol were highest, and triglycerides were lowest, after CanolaDHA (P < 0.05 compared with the other diets). All diets decreased TC and LDL cholesterol from baseline to treatment endpoint (P < 0.05). CanolaDHA was the only diet that increased HDL cholesterol from baseline (3.5 ± 1.8%; P < 0.05) and produced the greatest reduction in triglycerides (-20.7 ± 3.8%; P < 0.001) and in systolic blood pressure (-3.3 ± 0.8%; P < 0.001) compared with the other diets (P < 0.05). Percentage reductions in Framingham 10-y CHD risk scores (FRS) from baseline were greatest after CanolaDHA (-19.0 ± 3.1%; P < 0.001) than after other treatments (P < 0.05). CONCLUSION: Consumption of CanolaDHA, a novel DHA-rich canola oil, improves HDL cholesterol, triglycerides, and blood pressure, thereby reducing FRS compared with other oils varying in unsaturated fatty acid composition. This trial was registered at www.clinicaltrials.gov as NCT01351012.

NF-kappaB -94Ins/Del ATTG polymorphism modifies the association between dietary polyunsaturated fatty acids and HDL-cholesterol in two distinct populations.

We previously showed that polymorphisms in the tumor necrosis factor (TNF)-alpha gene, which is regulated by nuclear factor kappa B (NF-kappaB), modify the association between dietary polyunsaturated fatty acid (PUFA) intake and circulating HDL-cholesterol. Our objective was to determine whether a common polymorphism in the NFKB1 gene (-94Ins/Del ATTG) interacts with PUFA intake to affect HDL-cholesterol in two distinct populations. Participants were diabetes-free young adults (n=593) and older individuals with diet-treated type 2 diabetes (n=103). The NF-kappaB polymorphism modified the association between dietary PUFA intake and HDL-cholesterol in both populations (p=0.02 and 0.005 for interaction). Among individuals with the Ins/Ins genotype, each 1% increase in energy from PUFA was associated with a 0.03+/-0.01 mmol/L (p for slope=0.009) and 0.06+/-0.02 mmol/L (p=0.02) increase in HDL-cholesterol among participants from the diabetes-free and diabetic populations. An inverse relationship was observed among those with the Del/Del genotype, which was significantly different from that of the Ins/Ins groups in both populations (p=0.02 and 0.006). No effects were observed for the Ins/Del genotype in either population (p>0.05). These findings show that this functional polymorphism in the NF-kB gene modifies the association between PUFA intake and plasma HDL-cholesterol in two distinct populations.

Effect of plant sterols in combination with other cholesterol-lowering foods.

The National Cholesterol Education Program Adult Treatment Panel III guidelines advocate effective combinations of cholesterol-lowering dietary components. This approach (dietary portfolio) produces large reductions in serum cholesterol, but the contribution of individual components remains to be established. We therefore assessed the effect of eliminating one out of the 4 dietary portfolio components. Plant sterols were selected because at 2 g/d, they have been reported to reduce low-density lipoprotein cholesterol (LDL-C) by 9% to 14%. Forty-two hyperlipidemic subjects were prescribed diets high in soy protein (22.5 g/1000 kcal), viscous fibers (10 g/1000 kcal), and almonds (23 g/1000 kcal) for 80 weeks. Subjects were instructed to take these together with plant sterols (1.0 g/1000 kcal) except between weeks 52 and 62. While taking the full dietary portfolio, including plant sterols, mean LDL-C reduction from baseline was 15.4% +/- 1.6% (P < .001). After sterol elimination, mean LDL-C reduction was 9.0% +/- 1.5% (P < .001). Comparable LDL-C reductions were also seen for the 18 subjects with a complete data set: on plant sterols, 16.7% +/- 3.1% (P < .001) and off plant sterols, 10.3% +/- 2.6% (P < .001), resulting in a 6.3% +/- 2.0% (P = .005) difference attributable to plant sterols. Compliance in this group of 18 was 67.0% +/- 5.9% for plant sterols and 61.9% +/- 4.8% for the other components. In combination with other cholesterol-lowering foods and against the background of a low-saturated fat diet, plant sterols contributed over one third of the LDL-C reduction seen with the dietary portfolio after 1 year of following dietary advice.

Assessment of the longer-term effects of a dietary portfolio of cholesterol-lowering foods in hypercholesterolemia.

BACKGROUND: Cholesterol-lowering foods may be more effective when consumed as combinations rather than as single foods. OBJECTIVES: Our aims were to determine the effectiveness of consuming a combination of cholesterol-lowering foods (dietary portfolio) under real-world conditions and to compare these results with published data from the same participants who had undergone 4-wk metabolic studies to compare the same dietary portfolio with the effects of a statin. DESIGN: For 12 mo, 66 hyperlipidemic participants were prescribed diets high in plant sterols (1.0 g/1000 kcal), soy protein (22.5 g/1000 kcal), viscous fibers (10 g/1000 kcal), and almonds (23 g/1000 kcal). Fifty-five participants completed the 1-y study. The 1-y data were also compared with published results on 29 of the participants who had also undergone separate 1-mo metabolic trials of a diet and a statin. RESULTS: At 3 mo and 1 y, mean (+/-SE) LDL-cholesterol reductions appeared stable at 14.0 +/- 1.6% (P < 0.001) and 12.8 +/- 2.0% (P < 0.001), respectively (n = 66). These reductions were less than those observed after the 1-mo metabolic diet and statin trials. Nevertheless, 31.8% of the participants (n = 21 of 66) had LDL-cholesterol reductions of >20% at 1 y (x +/- SE: -29.7 +/- 1.6%). The LDL-cholesterol reductions in this group were not significantly different from those seen after their respective metabolically controlled portfolio or statin treatments. A correlation was found between total dietary adherence and LDL-cholesterol change (r = -0.42, P < 0.001). Only 2 of the 26 participants with <55% compliance achieved LDL-cholesterol reductions >20% at 1 y. CONCLUSIONS: More than 30% of motivated participants who ate the dietary portfolio of cholesterol-lowering foods under real-world conditions were able to lower LDL-cholesterol concentrations >20%, which was not significantly different from their response to a first-generation statin taken under metabolically controlled conditions.

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.

The effect of combining plant sterols, soy protein, viscous fibers, and almonds in treating hypercholesterolemia.

Reductions in low-density lipoprotein-cholesterol (LDL-C) result from diets containing almonds, or diets that are either low in saturated fat or high in viscous fibers, soy proteins, or plant sterols. We have therefore combined all of these interventions in a single diet (portfolio diet) to determine whether cholesterol reductions could be achieved of similar magnitude to those reported in recent statin trials which reduced cardiovascular events. Twenty-five hyperlipidemic subjects consumed either a portfolio diet (n=13), very low in saturated fat and high in plant sterols (1.2 g/1,000 kcal), soy protein (16.2 g/1,000 kcal), viscous fibers (8.3 g/1,000 kcal), and almonds (16.6 g/1,000 kcal), or a low-saturated fat diet (n=12) based on whole-wheat cereals and low-fat dairy foods. Fasting blood, blood pressure, and body weight were obtained at weeks 0, 2, and 4 of each phase. LDL-C was reduced by 12.1% +/- 2.4% (P<.001) on the low-fat diet and by 35.0% +/- 3.1% (P<.001) on the portfolio diet, which also reduced the ratio of LDL-C to high-density lipoprotein-cholesterol (HDL-C) significantly (30.0% +/- 3.5%; P<.001). The reductions in LDL-C and the LDL:HDL-C ratio were both significantly lower on the portfolio diet than on the control diet (P<.001 and P<.001, respectively). Mean weight loss was similar on test and control diets (1.0 kg and 0.9 kg, respectively). No difference was seen in blood pressure, HDL-C, serum triglycerides, lipoprotein(a) [Lp(a)], or homocysteine concentrations between diets. Combining a number of foods and food components in a single dietary portfolio may lower LDL-C similarly to statins and so increase the potential effectiveness of dietary therapy.

Dose response of almonds on coronary heart disease risk factors: blood lipids, oxidized low-density lipoproteins, lipoprotein(a), homocysteine, and pulmonary nitric oxide: a randomized, controlled, crossover trial.

BACKGROUND: Although recent studies have indicated that nut consumption may improve levels of blood lipids, nuts are not generally recommended as snacks for hyperlipidemic subjects because of their high fat content. Furthermore, the effective dose is still unknown. METHODS AND RESULTS: The dose-response effects of whole almonds, taken as snacks, were compared with low-saturated fat (<5% energy) whole-wheat muffins (control) in the therapeutic diets of hyperlipidemic subjects. In a randomized crossover study, 27 hyperlipidemic men and women consumed 3 isoenergetic (mean 423 kcal/d) supplements each for 1 month. Supplements provided 22.2% of energy and consisted of full-dose almonds (73+/-3 g/d), half-dose almonds plus half-dose muffins, and full-dose muffins. Fasting blood, expired air, blood pressure, and body weight measurements were obtained at weeks 0, 2, and 4. Mean body weights differed <300 g between treatments. The full-dose almonds produced the greatest reduction in levels of blood lipids. Significant reductions from baseline were seen on both half- and full-dose almonds for LDL cholesterol (4.4+/-1.7%, P=0.018, and 9.4+/-1.9%, P<0.001, respectively) and LDL:HDL cholesterol (7.8+/-2.2%, P=0.001, and 12.0+/-2.1%, P<0.001, respectively) and on full-dose almonds alone for lipoprotein(a) (7.8+/-3.5%, P=0.034) and oxidized LDL concentrations (14.0+/-3.8%, P<0.001), with no significant reductions on the control diet. No difference was seen in pulmonary nitric oxide between treatments. CONCLUSIONS: Almonds used as snacks in the diets of hyperlipidemic subjects significantly reduce coronary heart disease risk factors, probably in part because of the nonfat (protein and fiber) and monounsaturated fatty acid components of the nut.

Effect of wheat bran on glycemic control and risk factors for cardiovascular disease in type 2 diabetes.

OBJECTIVE: Cohort studies indicate that cereal fiber reduces the risk of diabetes and coronary heart disease (CHD). Therefore, we assessed the effect of wheat bran on glycemic control and CHD risk factors in type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 23 subjects with type 2 diabetes (16 men and 7 postmenopausal women) completed two 3-month phases of a randomized crossover study. In the test phase, bread and breakfast cereals were provided as products high in cereal fiber (19 g/day additional cereal fiber). In the control phase, supplements were low in fiber (4 g/day additional cereal fiber). RESULTS: Between the test and control treatments, no differences were seen in body weight, fasting blood glucose, HbA(1c), serum lipids, apolipoproteins, blood pressure, serum uric acid, clotting factors, homocysteine, C-reactive protein, magnesium, calcium, iron, or ferritin. LDL oxidation in the test phase was higher than that seen in the control phase (12.1 +/- 5.4%, P < 0.034). Of the subjects originally recruited, more dropped out of the study for health and food preference reasons from the control phase (16 subjects) than the test phase (11 subjects). CONCLUSIONS: High-fiber cereal foods did not improve conventional markers of glycemic control or risk factors for CHD in type 2 diabetes over 3 months. Possibly longer studies are required to demonstrate the benefits of cereal fiber. Alternatively, cereal fiber in the diet may be a marker for another component of whole grains that imparts health advantages or a healthy lifestyle.

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 of high- and low-isoflavone (phytoestrogen) soy foods on inflammatory biomarkers and proinflammatory cytokines in middle-aged men and women.

This study sought to determine effects of high- and low-isoflavone soy protein foods on acute-phase proteins and proinflammatory cytokines and whether isoflavone phytoestrogens might act as estrogens, which enhance the immune response. Forty-one hypercholesterolemic men and postmenopausal women underwent three 1-month diets consisting of a low-fat dairy food control phase and high- and low-isoflavone soy food test phases (50 g/d and 52g/d soy protein, respectively, and 73 mg/d and 10 mg/d isoflavone, respectively). Diets were low in saturated fat (<5% of energy) and cholesterol (<50 mg/d). Fasting blood analytes and blood pressure were measured at the start and end of each phase. For the entire group of subjects, no treatment differences were observed for acute-phase proteins or proinflammatory cytokines. However, a significant interaction was noted between diet and sex. Assessing the results of men and women separately, women showed significantly higher interleukin-6 (IL-6) values after the high-isoflavone soy diet (P =.013) compared to control values. For women, the difference between the high- and low-isoflavone IL-6 values was significant using the unadjusted data (P =.048) but not after adjustment. No significant effects were seen for men or women in C-reactive protein (CRP), serum amyloid A (SAA), or tumor necrosis factor-alpha (TNF-alpha). Thus, high levels of isoflavone intake appear to increase serum concentrations of IL-6 in women. This finding may indicate an estrogenic effect of soy isoflavones in enhancing the immune response and provide a possible explanation through enhanced immune surveillance for lower incidence of certain cancers in soy-eating parts of the world.