ArticleLiterature Review

Effect of carbohydrate-restricted dietary interventions on LDL particle size and number in adults in the context of weight loss or weight maintenance: a systematic review and meta-analysis

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Background LDL particle size and number (LDL-P) are emerging lipid risk factors. Nonsystematic reviews have suggested that diets lower in carbohydrates and higher in fats may result in increased LDL particle size when compared with higher-carbohydrate diets. Objectives This study aimed to systematically review available evidence and conduct meta-analyses of studies addressing the association of carbohydrate restriction with LDL particle size and LDL-P. Methods We searched 6 electronic databases on 4 January, 2021 for randomized trials of any length that reported on dietary carbohydrate restriction (intervention) compared with higher carbohydrate intake (control). We calculated standardized mean differences (SMDs) in LDL particle size and LDL-P between the intervention and control groups of eligible studies, and pooled effect sizes using random-effects models. We performed prespecified subgroup analyses and examined the effect of potential explanatory factors. Internal validity and publication bias were assessed using Cochrane's risk-of-bias tool and funnel plots, respectively. Studies that could not be meta-analyzed were summarized qualitatively. Results This review summarizes findings from 38 randomized trials including a total of 1785 participants. Carbohydrate-restricted dietary interventions were associated with an increase in LDL peak particle size (SMD = 0.50; 95% CI: 0.15, 0.86; P < 0.01) and a reduction in LDL-P (SMD = −0.24; 95% CI: −0.43, −0.06; P = 0.02). The effect of carbohydrate-restricted dietary interventions on LDL peak particle size appeared to be partially explained by differences in weight loss between intervention groups and exploratory analysis revealed a shift from small dense to larger LDL subclasses. No statistically significant association was found between carbohydrate-restricted dietary interventions and mean LDL particle size (SMD = 0.20; 95% CI: −0.29, 0.69; P = 0.37). Conclusions The available evidence indicates that dietary interventions restricted in carbohydrates increase LDL peak particle size and decrease the numbers of total and small LDL particles. This review was registered at www.crd.york.ac.uk/prospero/ as CRD42020188745.

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... Two small intervention studies (<50 participants) comparing consumption of glucose-, fructose-, and sugar-sweetened beverages within ranges of normal intake over 2-to 3-wk periods also observed that consumption of either fructose-or sugar-sweetened beverages led to lower LDL-P size (41,42). Several randomized controlled trials have examined the effect of low-carbohydrate diets on LDL-P size; a meta-analysis of 16 studies indicated that carbohydrate restriction reduces the number of small LDL-Ps (48). Our findings are consistent with these prior studies, where we observed higher concentrations of small LDL-Ps among the highest SSB consumers. ...
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Background Prospective cohort studies have found a relation between sugar-sweetened beverage consumption (SSB; sodas and fruit drinks) and dyslipidemia. There is limited evidence linking SSB consumption to emerging features of dyslipidemia, which can be characterized by variation in lipoprotein particle size, remnant-like particle (RLP), and apolipoprotein concentrations. Objective To examine the association between SSB consumption and plasma lipoprotein cholesterol, apolipoprotein, and lipoprotein particle size concentrations among US adults. Methods We examined participants from the Framingham Offspring Study (FOS) (1987–1995; n = 3047) and the Women's Health Study (1992; n = 26,218). Plasma LDL-C, apolipoprotein (apo) B, HDL-C, apoA1, triglyceride (TG), non-HDL-C, total: HDL-cholesterol ratio, and apoB: apoA1 concentrations were quantified in both cohorts, and apoE, apoC3, RLP-TG, and RLP-cholesterol concentrations in FOS only. Lipoprotein particle sizes were calculated from NMR signals for lipoprotein particle subclass concentrations (triglyceride-rich lipoprotein particles [TRL-P; very large, large, medium, small, and very small], LDL-particles [LDL-P; large, medium, and small], HDL-particles [HDL-P; large, medium, and small]). SSB consumption was estimated from food frequency questionnaire data. We examined the associations between SSB consumption and all lipoprotein and apoprotein measures in linear regression models, adjusting for confounding factors, such as lifestyle, diet, and traditional lipoprotein risk factors. Results SSB consumption was positively associated with LDL-C, apoB, TG, RLP-TG, RLP-C, non-HDL-C concentrations and total: HDL cholesterol and apoB: apoA1 ratio, and negatively associated with HDL-C and apoA1 concentrations (P-trend ranges from < 0.0001 to 0.003). After adjustment for traditional lipoprotein risk factors, SSB consumers had smaller LDL-P and HDL-P sizes, lower concentrations of large LDL-P and medium HDL-P, and higher concentrations of small LDL-P, small HDL-P, and large TRL-P (P-trend ranges from < 0.0001 to 0.0009). Conclusions Higher SSB consumption was associated with multiple emerging features of dyslipidemia that have been linked to higher cardiometabolic risk in US adults.
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Background: Previous studies have shown that increases in LDL-cholesterol resulting from substitution of dietary saturated fat for carbohydrate or unsaturated fat are due primarily to increases in large cholesterol-enriched LDL, with minimal changes in small, dense LDL particles and apolipoprotein B. However, individuals can differ by their LDL particle distribution, and it is possible that this may influence LDL subclass response. Objective: The objective of this study was to test whether the reported effects of saturated fat apply to individuals with atherogenic dyslipidemia as characterized by a preponderance of small LDL particles (LDL phenotype B). Methods: Fifty-three phenotype B men and postmenopausal women consumed a baseline diet (55%E carbohydrate, 15%E protein, 30%E fat, 8%E saturated fat) for 3 weeks, after which they were randomized to either a moderate carbohydrate, very high saturated fat diet (HSF; 39%E carbohydrate, 25%E protein, 36%E fat, 18%E saturated fat) or low saturated fat diet (LSF; 37%E carbohydrate, 25%E protein, 37%E fat, 9%E saturated fat) for 3 weeks. Results: Compared to the LSF diet, consumption of the HSF diet resulted in significantly greater increases from baseline (% change; 95% CI) in plasma concentrations of apolipoprotein B (HSF vs. LSF: 9.5; 3.6 to 15.7 vs. -6.8; -11.7 to -1.76; p = 0.0003) and medium (8.8; -1.3 to 20.0 vs. -7.3; -15.7 to 2.0; p = 0.03), small (6.1; -10.3 to 25.6 vs. -20.8; -32.8 to -6.7; p = 0.02), and total LDL (3.6; -3.2 to 11.0 vs. -7.9; -13.9 to -1.5; p = 0.03) particles, with no differences in change of large and very small LDL concentrations. As expected, total-cholesterol (11.0; 6.5 to 15.7 vs. -5.7; -9.4 to -1.8; p<0.0001) and LDL-cholesterol (16.7; 7.9 to 26.2 vs. -8.7; -15.4 to -1.4; p = 0.0001) also increased with increased saturated fat intake. Conclusions: Because medium and small LDL particles are more highly associated with cardiovascular disease than are larger LDL, the present results suggest that very high saturated fat intake may increase cardiovascular disease risk in phenotype B individuals. This trial was registered at clinicaltrials.gov (NCT00895141). Trial registration: Clinicaltrials.gov NCT00895141.
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Systematic reviews and meta-analyses have become increasingly important in health care. Clinicians read them to keep up to date with their field [1],[2], and they are often used as a starting point for developing clinical practice guidelines. Granting agencies may require a systematic review to ensure there is justification for further research [3], and some health care journals are moving in this direction [4]. As with all research, the value of a systematic review depends on what was done, what was found, and the clarity of reporting. As with other publications, the reporting quality of systematic reviews varies, limiting readers' ability to assess the strengths and weaknesses of those reviews. Several early studies evaluated the quality of review reports. In 1987, Mulrow examined 50 review articles published in four leading medical journals in 1985 and 1986 and found that none met all eight explicit scientific criteria, such as a quality assessment of included studies [5]. In 1987, Sacks and colleagues [6] evaluated the adequacy of reporting of 83 meta-analyses on 23 characteristics in six domains. Reporting was generally poor; between one and 14 characteristics were adequately reported (mean = 7.7; standard deviation = 2.7). A 1996 update of this study found little improvement [7]. In 1996, to address the suboptimal reporting of meta-analyses, an international group developed a guidance called the QUOROM Statement (QUality Of Reporting Of Meta-analyses), which focused on the reporting of meta-analyses of randomized controlled trials [8]. In this article, we summarize a revision of these guidelines, renamed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses), which have been updated to address several conceptual and practical advances in the science of systematic reviews (Box 1). Box 1: Conceptual Issues in the Evolution from QUOROM to PRISMA Completing a Systematic Review Is an Iterative Process The conduct of a systematic review depends heavily on the scope and quality of included studies: thus systematic reviewers may need to modify their original review protocol during its conduct. Any systematic review reporting guideline should recommend that such changes can be reported and explained without suggesting that they are inappropriate. The PRISMA Statement (Items 5, 11, 16, and 23) acknowledges this iterative process. Aside from Cochrane reviews, all of which should have a protocol, only about 10% of systematic reviewers report working from a protocol [22]. Without a protocol that is publicly accessible, it is difficult to judge between appropriate and inappropriate modifications.
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Avocados are a nutrient-dense source of monounsaturated fatty acids (MUFA) that can be used to replace saturated fatty acids (SFA) in a diet to lower low density lipoprotein cholesterol (LDL-C). Well-controlled studies are lacking on the effect of avocado consumption on cardiovascular disease (CVD) risk factors. A randomized, crossover, controlled feeding trial was conducted with 45 overweight or obese participants with baseline LDL-C in the 25th to 90th percentile. Three cholesterol-lowering diets (6% to 7% SFA) were fed (5 weeks each): a lower-fat diet (LF: 24% fat); 2 moderate-fat diets (34% fat) provided similar foods and were matched for macronutrients and fatty acids: the avocado diet (AV) included one fresh Hass avocado (136 g) per day, and the moderate-fat diet (MF) mainly used high oleic acid oils to match the fatty acid content of one avocado. Compared with baseline, the reduction in LDL-C and non-high-density lipoprotein (HDL) cholesterol on the AV diet (-13.5 mg/dL, -14.6 mg/dL) was greater (P<0.05) than the MF (-8.3 mg/dL, -8.7 mg/dL) and LF (-7.4 mg/dL, -4.8 mg/dL) diets. Furthermore, only the AV diet significantly decreased LDL particle number (LDL-P, -80.1 nmol/L, P=0.0001), small dense LDL cholesterol (LDL3+4, -4.1 mg/dL, P=0.04), and the ratio of LDL/HDL (-6.6%, P<0.0001) from baseline. Inclusion of one avocado per day as part of a moderate-fat, cholesterol-lowering diet has additional LDL-C, LDL-P, and non-HDL-C lowering effects, especially for small, dense LDL. Our results demonstrate that avocados have beneficial effects on cardio-metabolic risk factors that extend beyond their heart-healthy fatty acid profile. http://www.clinicaltrials.gov. Unique identifier: NCT01235832. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
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The DerSimonian and Laird approach (DL) is widely used for random effects meta-analysis, but this often results in inappropriate type I error rates. The method described by Hartung, Knapp, Sidik and Jonkman (HKSJ) is known to perform better when trials of similar size are combined. However evidence in realistic situations, where one trial might be much larger than the other trials, is lacking. We aimed to evaluate the relative performance of the DL and HKSJ methods when studies of different sizes are combined and to develop a simple method to convert DL results to HKSJ results. We evaluated the performance of the HKSJ versus DL approach in simulated meta-analyses of 2-20 trials with varying sample sizes and between-study heterogeneity, and allowing trials to have various sizes, e.g. 25% of the trials being 10-times larger than the smaller trials. We also compared the number of "positive" (statistically significant at p < 0.05) findings using empirical data of recent meta-analyses with > =3 studies of interventions from the Cochrane Database of Systematic Reviews. The simulations showed that the HKSJ method consistently resulted in more adequate error rates than the DL method. When the significance level was 5%, the HKSJ error rates at most doubled, whereas for DL they could be over 30%. DL, and, far less so, HKSJ had more inflated error rates when the combined studies had unequal sizes and between-study heterogeneity. The empirical data from 689 meta-analyses showed that 25.1% of the significant findings for the DL method were non-significant with the HKSJ method. DL results can be easily converted into HKSJ results. Our simulations showed that the HKSJ method consistently results in more adequate error rates than the DL method, especially when the number of studies is small, and can easily be applied routinely in meta-analyses. Even with the HKSJ method, extra caution is needed when there are = <5 studies of very unequal sizes.
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Very-low-carbohydrate diets or ketogenic diets have been in use since the 1920s as a therapy for epilepsy and can, in some cases, completely remove the need for medication. From the 1960s onwards they have become widely known as one of the most common methods for obesity treatment. Recent work over the last decade or so has provided evidence of the therapeutic potential of ketogenic diets in many pathological conditions, such as diabetes, polycystic ovary syndrome, acne, neurological diseases, cancer and the amelioration of respiratory and cardiovascular disease risk factors. The possibility that modifying food intake can be useful for reducing or eliminating pharmaceutical methods of treatment, which are often lifelong with significant side effects, calls for serious investigation. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possible mechanisms for the therapeutic actions of the ketogenic diet on different diseases. The present review also questions whether there are still some preconceived ideas about ketogenic diets, which may be presenting unnecessary barriers to their use as therapeutic tools in the physician's hand.European Journal of Clinical Nutrition advance online publication, 26 June 2013; doi:10.1038/ejcn.2013.116.
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Background: The number of circulating LDL particles is a strong indicator of future cardiovascular disease (CVD) events, even superior to the concentration of LDL cholesterol. Atherogenic (primarily LDL) particle number is typically determined either directly by the serum concentration of apolipoprotein B (apo B) or indirectly by nuclear magnetic resonance (NMR) spectroscopy of serum to obtain NMR-derived LDL particle number (LDL-P). Content: To assess the comparability of apo B and LDL-P, we reviewed 25 clinical studies containing 85 outcomes for which both biomarkers were determined. In 21 of 25 (84.0%) studies, both apo B and LDL-P were significant for at least 1 outcome. Neither was significant for any outcome in only 1 study (4.0%). In 50 of 85 comparisons (58.8%), both apo B and LDL-P had statistically significant associations with the clinical outcome, whereas in 17 comparisons (20.0%) neither was significantly associated with the outcome. In 18 comparisons (21.1%) there was discordance between apo B and LDL-P. Conclusions: In most studies, both apo B and LDL-P were comparable in association with clinical outcomes. The biomarkers were nearly equivalent in their ability to assess risk for CVD and both have consistently been shown to be stronger risk factors than LDL-C. We support the adoption of apo B and/or LDL-P as indicators of atherogenic particle numbers into CVD risk screening and treatment guidelines. Currently, in the opinion of this Working Group on Best Practices, apo B appears to be the preferable biomarker for guideline adoption because of its availability, scalability, standardization, and relatively low cost.
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Objective: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Design: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30
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To investigate the relative efficacy of four popular weight-loss programmes on plasma lipids and lipoproteins as measures of CVD risk. A multi-centred, randomised, controlled trial of four diets - Dr Atkins' New Diet Revolution, The Slim-Fast Plan, Weight Watchers Pure Points programme and Rosemary Conley's 'Eat yourself Slim' Diet and Fitness Plan - against a control diet, in parallel for 6 months. The trial was conducted at five universities across the UK (Surrey, Nottingham, Ulster (Coleraine), Bristol and Edinburgh (Queen Margaret University College)) and involved the participation of 300 overweight and obese males and females aged 21-60 years in a community setting. Significant weight loss was achieved by all dieting groups (5-9 kg at 6 months) but no significant difference was observed between diets at 6 months. The Weight Watchers and Rosemary Conley (low-fat) diets were followed by significant reductions in plasma LDL cholesterol (both -12.2 % after 6 months, P < 0.01), whereas the Atkins (low-carbohydrate) and Weight Watchers diets were followed by marked reductions in plasma TAG (-38.2 % and -22.6 % at 6 months respectively, P < 0.01). These latter two diets were associated with an increase in LDL particle size, a change that has been linked to reduced CVD risk. Overall, these results demonstrate the favourable effects of weight loss on lipid-mediated CVD risk factors that can be achieved through commercially available weight-loss programmes. No detrimental effects on lipid-based CVD risk factors were observed in participants consuming a low-carbohydrate diet.
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Background: Sugar-sweetened beverages (SSBs) have unfavorable effects on glucose and lipid metabolism if consumed in high quantities by obese subjects, but the effect of lower doses in normal-weight subjects is less clear. Objective: The aim was to investigate the effects of SSBs consumed in small to moderate quantities for 3 wk on LDL particle distribution and on other parameters of glucose and lipid metabolism as well as on inflammatory markers in healthy young men. Design: Twenty-nine subjects were studied in a prospective, randomized, controlled crossover trial. Six 3-wk interventions were assigned in random order as follows: 600 mL SSBs containing 1)40 g fructose/d [medium fructose (MF)], 2) 80 g fructose/d [high fructose (HF)], 3) 40 g glucose/d [medium glucose (MG)], 4) 80 g glucose/d [high glucose (HG)], 5) 80 g sucrose/d [high sucrose (HS)], or 6) dietary advice to consume low amounts of fructose. Outcome parameters were measured at baseline and after each intervention. Results: LDL particle size was reduced after HF by -0.51 nm (95% CI: -0.19, -0.82 nm) and after HS by -0.43 nm (95% CI: -0.12, -0.74; P < 0.05 for both). Similarly, a more atherogenic LDL subclass distribution was seen when fructose-containing SSBs were consumed (MF, HF, and HS: P < 0.05). Fasting glucose and high-sensitivity C-reactive protein (hs-CRP) increased significantly after all interventions (by 4-9% and 60-109%, respectively; P < 0.05); leptin increased during interventions with SSBs containing glucose only (MG and HG: P < 0.05). Conclusion: The present data show potentially harmful effects of low to moderate consumption of SSBs on markers of cardiovascular risk such as LDL particles, fasting glucose, and hs-CRP within just 3 wk in healthy young men, which is of particular significance for young consumers. This trial was registered at clinicaltrials.gov as NCT01021969.
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We recently showed that a hypocaloric carbohydrate restricted diet (CRD) had two striking effects: (1) a reduction in plasma saturated fatty acids (SFA) despite higher intake than a low fat diet, and (2) a decrease in inflammation despite a significant increase in arachidonic acid (ARA). Here we extend these findings in 8 weight stable men who were fed two 6-week CRD (12%en carbohydrate) varying in quality of fat. One CRD emphasized SFA (CRD-SFA, 86 g/d SFA) and the other, unsaturated fat (CRD-UFA, 47 g SFA/d). All foods were provided to subjects. Both CRD decreased serum triacylglycerol (TAG) and insulin, and increased LDL-C particle size. The CRD-UFA significantly decreased plasma TAG SFA (27.48 ± 2.89 mol%) compared to baseline (31.06 ± 4.26 mol%). Plasma TAG SFA, however, remained unchanged in the CRD-SFA (33.14 ± 3.49 mol%) despite a doubling in SFA intake. Both CRD significantly reduced plasma palmitoleic acid (16:1n-7) indicating decreased de novo lipogenesis. CRD-SFA significantly increased plasma phospholipid ARA content, while CRD-UFA significantly increased EPA and DHA. Urine 8-iso PGF(2α), a free radical-catalyzed product of ARA, was significantly lower than baseline following CRD-UFA (-32%). There was a significant inverse correlation between changes in urine 8-iso PGF(2α) and PL ARA on both CRD (r = -0.82 CRD-SFA; r = -0.62 CRD-UFA). These findings are consistent with the concept that dietary saturated fat is efficiently metabolized in the presence of low carbohydrate, and that a CRD results in better preservation of plasma ARA.
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Low-fat diets have been shown to increase plasma concentrations of lipoprotein(a) [Lp(a)], a preferential lipoprotein carrier of oxidized phospholipids (OxPLs) in plasma, as well as small dense LDL particles. We sought to determine whether increases in plasma Lp(a) induced by a low-fat high-carbohydrate (LFHC) diet are related to changes in OxPL and LDL subclasses. We studied 63 healthy subjects after 4 weeks of consuming, in random order, a high-fat low-carbohydrate (HFLC) diet and a LFHC diet. Plasma concentrations of Lp(a) (P < 0.01), OxPL/apolipoprotein (apo)B (P < 0.005), and OxPL-apo(a) (P < 0.05) were significantly higher on the LFHC diet compared with the HFLC diet whereas LDL peak particle size was significantly smaller (P < 0.0001). Diet-induced changes in Lp(a) were strongly correlated with changes in OxPL/apoB (P < 0.0001). The increases in plasma Lp(a) levels after the LFHC diet were also correlated with decreases in medium LDL particles (P < 0.01) and increases in very small LDL particles (P < 0.05). These results demonstrate that induction of increased levels of Lp(a) by an LFHC diet is associated with increases in OxPLs and with changes in LDL subclass distribution that may reflect altered metabolism of Lp(a) particles.
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Assessment of risk of bias is regarded as an essential component of a systematic review on the effects of an intervention. The most commonly used tool for randomised trials is the Cochrane risk-of-bias tool. We updated the tool to respond to developments in understanding how bias arises in randomised trials, and to address user feedback on and limitations of the original tool.
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Aims To assess the effects of walnuts on cardiometabolic outcomes in obese subjects and to explore underlying mechanisms using novel methods including metabolomic, lipidomic, glycomic, and microbiome analysis integrated with lipid particle fractionation, appetite‐regulating hormones and hemodynamic measurements. Materials and Methods 10 obese subjects were enrolled in this cross‐over, randomized, double‐blind, placebo‐controlled clinical trial. Patients participated in two 5‐day inpatient stays during which they consumed a smoothie containing 48g walnuts or a macronutrient‐matched placebo smoothie without nuts, with a one‐month washout period between the two visits. Results Walnut consumption improved aspects of the lipid profile, i.e. reduced fasting small and dense LDL particles (p<.02) and increased postprandial large HDL particles (p<.01). Lipoprotein Insulin Resistance Score, glucose and insulin AUC decreased significantly after walnut consumption (p<.01, p<.02, p<.04, respectively). Consuming walnuts significantly increased 10 N‐glycans, with 8 of them carrying a fucose core. Lipidomic analysis showed a robust reduction in harmful ceramides, hexosylceramides and sphingomyelins, which have been shown to mediate effects on cardiometabolic risk. Peptide YY AUC significantly increased after walnut consumption (p<.03). No major significant changes in hemodynamic, metabolomic analysis or in host health‐promoting bacteria such as Faecalibacterium were found. Conclusions These data provide a more comprehensive mechanistic perspective of the effect of dietary walnut consumption on cardiometabolic parameters. Lipidomic and lipid nuclear magnetic resonance spectroscopy analysis showed an early but significant reduction in ceramides and other atherogenic lipids with walnut consumption that may explain the longer‐term benefits of walnuts on insulin resistance, cardiovascular risk and mortality. This article is protected by copyright. All rights reserved.
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Scope The Mediterranean (MED) diet is considered to be beneficial, however the contribution of the MUFA component in these beneficial effects is unclear. Therefore, we wanted to disentangle the effects of MUFA from the other components in a MED diet. Methods and Results We performed a randomized fully controlled parallel trial to examine the effects of the consumption of a saturated fatty acid (SFA)‐rich diet, a MUFA‐rich diet, or a MED diet for eight weeks on serum metabolome, in 47 subjects at risk of the metabolic syndrome. We assessed 162 serum metabolites before and after the intervention, by using a targeted NMR platform. 52 metabolites were changed during the intervention (FDR p<0.05). Both MUFA and MED diet decreased exactly the same fractions of LDL, including particle number, lipid, phospholipid and free cholesterol fraction (FDR p <0.05). The MED diet additionally decreased the larger subclasses of VLDL, several related VLDL fractions, VLDL‐triglycerides, and serum‐triglycerides (FDR p<0.05). Conclusion Our findings clearly demonstrate that the MUFA component is responsible for reducing several LDL subclasses and fractions, and therefore causes a more anti‐atherogenic lipid profile. Interestingly, consumption of the other components in the MED diet show additional health effects. This trial was registered at clinicaltrials.gov as NCT00405197. This article is protected by copyright. All rights reserved
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Background: A limited number of studies have evaluated self-reported dietary intakes against objective recovery biomarkers. Objective: The aim was to compare dietary intakes of multiple Automated Self-Administered 24-h recalls (ASA24s), 4-d food records (4DFRs), and food-frequency questionnaires (FFQs) against recovery biomarkers and to estimate the prevalence of under- and overreporting. Design: Over 12 mo, 530 men and 545 women, aged 50-74 y, were asked to complete 6 ASA24s (2011 version), 2 unweighed 4DFRs, 2 FFQs, two 24-h urine collections (biomarkers for protein, potassium, and sodium intakes), and 1 administration of doubly labeled water (biomarker for energy intake). Absolute and density-based energy-adjusted nutrient intakes were calculated. The prevalence of under- and overreporting of self-report against biomarkers was estimated. Results: Ninety-two percent of men and 87% of women completed ≥3 ASA24s (mean ASA24s completed: 5.4 and 5.1 for men and women, respectively). Absolute intakes of energy, protein, potassium, and sodium assessed by all self-reported instruments were systematically lower than those from recovery biomarkers, with underreporting greater for energy than for other nutrients. On average, compared with the energy biomarker, intake was underestimated by 15-17% on ASA24s, 18-21% on 4DFRs, and 29-34% on FFQs. Underreporting was more prevalent on FFQs than on ASA24s and 4DFRs and among obese individuals. Mean protein and sodium densities on ASA24s, 4DFRs, and FFQs were similar to biomarker values, but potassium density on FFQs was 26-40% higher, leading to a substantial increase in the prevalence of overreporting compared with absolute potassium intake. Conclusions: Although misreporting is present in all self-report dietary assessment tools, multiple ASA24s and a 4DFR provided the best estimates of absolute dietary intakes for these few nutrients and outperformed FFQs. Energy adjustment improved estimates from FFQs for protein and sodium but not for potassium. The ASA24, which now can be used to collect both recalls and records, is a feasible means to collect dietary data for nutrition research.
Article
Background: Hypertriglyceridemia is a common condition in the United States and is often associated with other metabolic disturbances, including insulin resistance, metabolic syndrome, and a predominance of small dense LDL particles. Objective: The objective of this trial was to evaluate the effects of a combination of egg protein (Epro) and unsaturated fatty acids (UFAs) substituted for refined starches and added sugars on insulin sensitivity (primary outcome) and other cardiometabolic health markers in overweight or obese adults with elevated triglyceride (TG) concentrations. Methods: Subjects with elevated TG concentrations were given test foods prepared by using Epro powder (∼8% of energy) and vegetable oil (∼8% of energy; Epro and UFA condition) or test foods prepared by using refined starch and sugar (∼16% of energy; carbohydrate condition) in a randomized, double-blind, controlled-feeding, crossover trial (3 wk/condition, 2-wk washout). The Matsuda insulin sensitivity index (MISI), fasting lipids, and other cardiometabolic health markers were assessed at baseline and the end of each diet condition. Responses were compared by using repeated-measures ANCOVA. Results: Twenty-five participants [11 men, 14 women; mean ± SEM: age, 46.3 ± 2.4 y; body mass index (in kg/m²), 31.8 ± 1.0] with a median (interquartile range limits) fasting serum TG concentration of 173 mg/dL (159, 228 mg/dL) completed the trial. The MISI value increased 18.1% ± 8.7% from baseline during the Epro and UFA condition and decreased 5.7% ± 6.2% from baseline during the carbohydrate condition (P < 0.001). The disposition index increased 23.8% ± 20.8% during the Epro and UFA condition compared with a decrease of 16.3% ± 18.8% during carbohydrate (P = 0.042) and LDL peak particle size increased 0.12 nm (−0.12, 0.28 nm) with Epro and UFA compared with a decrease of 0.15 nm (−0.33, 0.12 nm) with carbohydrate (P = 0.019). TG and VLDL cholesterol concentrations were lowered by 18.5% (−35.7%, −6.9%) and 18.6% (−34.8%, −7.4%), respectively, after the Epro and UFA condition and by 2.5% (−13.4%, 17.0%) and 3.6% (−12.5%, 16.2%), respectively, after the carbohydrate diet condition (P < 0.002). Conclusions: The replacement of refined carbohydrates with a combination of Epro and UFA increased the MISI value and altered several markers of cardiometabolic health in overweight or obese adults with elevated TG concentrations. This trial was registered at clinicaltrials.gov as NCT02924558.
Article
Background: The DASH (Dietary Approaches to Stop Hypertension) dietary pattern, which is high in fruit, vegetables, and low-fat dairy foods, significantly lowers blood pressure as well as low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol. Objective: The study was designed to test the effects of substituting full-fat for low-fat dairy foods in the DASH diet, with a corresponding increase in fat and a reduction in sugar intake, on blood pressure and plasma lipids and lipoproteins. Design: This was a 3-period randomized crossover trial in free-living healthy individuals who consumed in random order a control diet, a standard DASH diet, and a higher-fat, lower-carbohydrate modification of the DASH diet (HF-DASH diet) for 3 wk each, separated by 2-wk washout periods. Laboratory measurements, which included lipoprotein particle concentrations determined by ion mobility, were made at the end of each experimental diet. Results: Thirty-six participants completed all 3 dietary periods. Blood pressure was reduced similarly with the DASH and HF-DASH diets compared with the control diet. The HF-DASH diet significantly reduced triglycerides and large and medium very-low-density lipoprotein (VLDL) particle concentrations and increased LDL peak particle diameter compared with the DASH diet. The DASH diet, but not the HF-DASH diet, significantly reduced LDL cholesterol, HDL cholesterol, apolipoprotein A-I, intermediate-density lipoprotein and large LDL particles, and LDL peak diameter compared with the control diet. Conclusions: The HF-DASH diet lowered blood pressure to the same extent as the DASH diet but also reduced plasma triglyceride and VLDL concentrations without significantly increasing LDL cholesterol. This trial was registered at clinicaltrials.gov as NCT01404897.
Article
Background: Measures of low-density lipoprotein (LDL) subfractions have been proposed as an independent risk factor for cardiovascular disease. Purpose: To review published studies that reported relationships between LDL subfractions and cardiovascular outcomes. Data Sources: MEDLINE (1950 to 5 January 2009), CAB Abstracts (1973 to 30 June 2008), and Cochrane Central Register of Controlled Trials (2nd quarter of 2008), limited to English-language studies. Study Selection: 3 reviewers selected longitudinal studies with 10 or more participants that reported an association between LDL subfractions and incidence or severity of cardiovascular disease and in which plasma samples were collected before outcome determination. Data Extraction: Data were extracted from 24 studies. The 10 studies that used analytical methods available for clinical use (all of which used nuclear magnetic resonance) had full data extraction, including quality assessment (good, fair, or poor). All studies were extracted by 1 researcher and verified by another. Data Synthesis: All 24 studies, and the subset of 10 nuclear magnetic resonance studies, were heterogeneous in terms of the specific tests analyzed, analytical methods used, participants investigated, and outcomes measured. Higher LDL particle number was consistently associated with increased risk for cardiovascular disease, independent of other lipid measurements. Other LDL subfractions were generally not associated with cardiovascular disease after adjustment for cholesterol concentrations. No study evaluated the incremental value of LDL subfractions beyond traditional cardiovascular risk factors or their test performance. Limitation: Publication bias was a possibility. Conclusion: Higher LDL particle number has been associated with cardiovascular disease incidence, but studies have not determined whether any measures of LDL subfractions add incremental benefit to traditional risk factor assessment. Routine use of clinically available LDL subfraction tests to estimate cardiovascular disease risk is premature.
Article
Objective. —To investigate the prospective association of low-density lipoprotein (LDL) particle diameter with the incidence of fatal and nonfatal coronary artery disease (CAD).Design. —A nested case-control study.Setting. —Cases and controls were identified from a population-based sample of men and women combining all of the 5 cross-sectional surveys conducted from 1979 to 1990 of the Stanford Five-City Project (FCP).Participants. —Incident CAD cases were identified through FCP surveillance between 1979 and 1992. Controls were matched by sex, 5-year age groups, survey time point, ethnicity, and FCP treatment condition. The sample included 124 matched pairs: 90 pairs of men and 34 pairs of women.Main Outcome Measures. —LDL peak particle diameter (LDL size) was determined by gradient gel electrophoresis on plasma samples collected during the cross-sectional surveys (stored at 70°C for 5-15 years). Established CAD risk-factor data were available from FCP baseline measurements.Results. —LDL size was smaller among CAD cases than controls (mean ±SD) (26.17±1.00nm vs 26.68±0.90nm;P<.001).The association was graded across control quintiles of LDL size. The significant case-control difference in LDL size was independent of levels of high-density lipoprotein cholesterol (HDL-C), non—HDL cholesterol (non-HDL-C), triglyceride, smoking, systolic blood pressure, and body mass index, but was not significant after adjusting for the ratio of total cholesterol (TC) to HDL-C (TC:HDL-C). Among all the physiological risk factors, LDL size was the best differentiator of CAD status in conditional logistic regression. However, when added to the physiological parameters above, the TC:HDL-C ratio was found to be a stronger independent predictor of CAD status.Conclusion. —LDL size was significantly smaller in CAD cases than in controls in a prospective, population-based study. These findings support other evidence of a role for small, dense LDL particles in the etiology of atherosclerosis.
Article
Background— Nuclear magnetic resonance (NMR) offers an alternative, spectroscopic means of quantifying LDL and of measuring LDL particle size. Methods and Results— We conducted a prospective nested case-control study among healthy middle-aged women to assess LDL particle size (NMR) and concentration (NMR) as risk factors for future myocardial infarction, stroke, or death of coronary heart disease. Median baseline levels of LDL particle concentration (NMR) were higher (1597 vs 1404 nmol/L; P = 0.0001) and LDL particle size (NMR) was lower (21.5 vs 21.8 nm; P =0.046) among women who subsequently had cardiovascular events (n=130) than among those who did not (n= 130). Of these 2 factors, LDL particle concentration (NMR) was the stronger predictor (relative risk for the highest compared with the lowest quartile=4.17, 95% CI 1.96–8.87). This compared with a relative risk of 3.11 (95% CI 1.55–6.26) for the ratio of total cholesterol to HDL cholesterol and a relative risk of 5.91 (95% CI 2.65–13.15) for C-reactive protein. The areas under the receiver operating characteristic curves for LDL particle concentration (NMR), total cholesterol to HDL cholesterol ratio, and C-reactive protein were 0.64, 0.64, and 0.66, respectively. LDL particle concentration (NMR) correlated with several traditionally assessed lipid and nonlipid risk factors, and thus adjustment for these tended to attenuate the magnitude of association between LDL particle concentration (NMR) and risk. Conclusions— In this cohort, LDL particle concentration measured by NMR spectroscopy was a predictor of future cardiovascular risk. However, the magnitude of predictive value of LDL particle concentration (NMR) was not substantively different from that of the total cholesterol to HDL cholesterol ratio and was less than that of C-reactive protein. Received May 20, 2002; revision received July 18, 2002; accepted July 19, 2002.
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A randomised, cross-over, controlled-feeding study was conducted to evaluate the cholesterol-lowering effects of diets containing pistachios as a strategy for increasing total fat (TF) levels v. a control (step I) lower-fat diet. Ex vivo techniques were used to evaluate the effects of pistachio consumption on lipoprotein subclasses and functionality in individuals (n 28) with elevated LDL levels ( ≥ 2·86 mmol/l). The following test diets (SFA approximately 8 % and cholesterol < 300 mg/d) were used: a control diet (25 % TF); a diet comprising one serving of pistachios per d (1PD; 30 % TF); a diet comprising two servings of pistachios per d (2PD; 34 % TF). A significant decrease in small and dense LDL (sdLDL) levels was observed following the 2PD dietary treatment v. the 1PD dietary treatment (P= 0·03) and following the 2PD dietary treatment v. the control treatment (P= 0·001). Furthermore, reductions in sdLDL levels were correlated with reductions in TAG levels (r 0·424, P= 0·025) following the 2PD dietary treatment v. the control treatment. In addition, inclusion of pistachios increased the levels of functional α-1 (P= 0·073) and α-2 (P= 0·056) HDL particles. However, ATP-binding cassette transporter A1-mediated serum cholesterol efflux capacity (P= 0·016) and global serum cholesterol efflux capacity (P= 0·076) were only improved following the 2PD dietary treatment v. the 1PD dietary treatment when baseline C-reactive protein status was low ( < 103μg/l). Moreover, a significant decrease in the TAG:HDL ratio was observed following the 2PD dietary treatment v. the control treatment (P= 0·036). There was a significant increase in β-sitosterol levels (P< 0·0001) with the inclusion of pistachios, confirming adherence to the study protocol. In conclusion, the inclusion of pistachios in a moderate-fat diet favourably affects the cardiometabolic profile in individuals with an increased risk of CVD.
Article
Estimates from individual studies included in a meta-analysis often are not in agreement, giving rise to statistical heterogeneity. In such cases, exploration of the causes of heterogeneity can advance knowledge by formulating novel hypotheses. We present a new method for visualizing between-study heterogeneity using combinatorial meta-analysis. The method is based on performing separate meta-analyses on all possible subsets of studies in a meta-analysis. We use the summary effect sizes and other statistics produced by the all-subsets meta-analyses to generate graphs that can be used to investigate heterogeneity, identify influential studies, and explore subgroup effects. This graphical approach complements alternative graphical explorations of data. We apply the method to numerous biomedical examples, to allow readers to develop intuition on the interpretation of the all-subsets graphical display. The proposed graphical approach may be useful for exploratory data analysis in systematic reviews. Copyright © 2012 John Wiley & Sons, Ltd. Copyright © 2012 John Wiley & Sons, Ltd.
Article
A THEROSCLEROSIS is generally considered to be the major disease of this era. Its consequences in the coronary, cerebral, and peripheral arteries, in the form o£ ocelu- sive phenomena, are responsible for more death and disability than any other disease. In spite of much study and research there is still no agreement con- cerning the sequence of pathogenetic events, etiol- ogy, or treatment of atheroselerosis. The not-too- rare oceurrence of coronary artery ocelusions (almost always a consequence of atheroselerosis) in young men from 20 to 40 years of age testifies to the fallacy of the idea, still prevalent, that atheroselerosis is a problem of the aged or senile. For the male it is a 1 This work was supported (in part) by the Atomic Energy Commission and the United States Public Health Service. The authors wish to acknowledge with gratitude the gener- ous and invaluable advice and assistance given by Profs. Hardin B. Jones and John H. Lawrence. A THEROSCLEROSIS is generally considered to be the major disease of this era. Its consequences in the coronary, cerebral, and peripheral arteries, in the form o£ ocelu- sive phenomena, are responsible for more death and disability than any other disease. In spite of much study and research there is still no agreement con- cerning the sequence of pathogenetic events, etiol- ogy, or treatment of atheroselerosis. The not-too- rare oceurrence of coronary artery ocelusions (almost always a consequence of atheroselerosis) in young men from 20 to 40 years of age testifies to the fallacy of the idea, still prevalent, that atheroselerosis is a problem of the aged or senile. For the male it is a
Article
Dietary fat plays an important role in the primary prevention of cardiovascular disease, but long-term (≥12 months) effects of different percentages of fat in the diet on blood lipid levels remain to be established. Our systematic review and meta-analysis focused on randomized controlled trials assessing the long-term effects of low-fat diets compared with diets with high amounts of fat on blood lipid levels. Relevant randomized controlled trials were identified searching MEDLINE, EMBASE, and the Cochrane Trial Register until March 2013. Thirty-two studies were included in the meta-analysis. Decreases in total cholesterol (weighted mean difference -4.55 mg/dL [-0.12 mmol/L], 95% CI -8.03 to -1.07; P=0.01) and low-density lipoprotein (LDL) cholesterol (weighted mean difference -3.11 mg/dL [-0.08 mmol/L], 95% CI -4.51 to -1.71; P<0.0001) were significantly more pronounced following low-fat diets, whereas rise in high-density lipoprotein (HDL) cholesterol (weighted mean difference 2.35 mg/dL [0.06 mmol/L], 95% CI 1.29 to 3.42; P<0.0001) and reduction in triglyceride levels (weighted mean difference -8.38 mg/dL [-0.095 mmol/L], 95% CI -13.50 to -3.25; P=0.001) were more distinct in the high-fat diet groups. Including only hypocaloric diets, the effects of low-fat vs high-fat diets on total cholesterol and LDL cholesterol levels were abolished. Meta-regression revealed that lower total cholesterol level was associated with lower intakes of saturated fat and higher intakes of polyunsaturated fat, and increases in HDL cholesterol levels were related to higher amounts of total fat largely derived from monounsaturated fat (of either plant or animal origin) in high-fat diets (composition of which was ∼17% of total energy content in the form of monounsaturated fatty acids, ∼8% of total energy content in the form of polyunsaturated fatty acids), whereas increases in triglyceride levels were associated with higher intakes of carbohydrates. In addition, lower LDL cholesterol level was marginally associated with lower saturated fat intake. The results of our meta-analysis do not allow for an unequivocal recommendation of either low-fat or high-fat diets in the primary prevention of cardiovascular disease.
Article
The effects of low-carbohydrate diets (≤45% of energy from carbohydrates) versus low-fat diets (≤30% of energy from fat) on metabolic risk factors were compared in a meta-analysis of randomized controlled trials. Twenty-three trials from multiple countries with a total of 2,788 participants met the predetermined eligibility criteria (from January 1, 1966 to June 20, 2011) and were included in the analyses. Data abstraction was conducted in duplicate by independent investigators. Both low-carbohydrate and low-fat diets lowered weight and improved metabolic risk factors. Compared with participants on low-fat diets, persons on low-carbohydrate diets experienced a slightly but statistically significantly lower reduction in total cholesterol (2.7 mg/dL; 95% confidence interval: 0.8, 4.6), and low density lipoprotein cholesterol (3.7 mg/dL; 95% confidence interval: 1.0, 6.4), but a greater increase in high density lipoprotein cholesterol (3.3 mg/dL; 95% confidence interval: 1.9, 4.7) and a greater decrease in triglycerides (-14.0 mg/dL; 95% confidence interval: -19.4, -8.7). Reductions in body weight, waist circumference and other metabolic risk factors were not significantly different between the 2 diets. These findings suggest that low-carbohydrate diets are at least as effective as low-fat diets at reducing weight and improving metabolic risk factors. Low-carbohydrate diets could be recommended to obese persons with abnormal metabolic risk factors for the purpose of weight loss. Studies demonstrating long-term effects of low-carbohydrate diets on cardiovascular events were warranted.
Article
This article aims at reviewing the recent findings that have been made concerning the crosstalk of carbohydrate metabolism with the generation of small, dense low-density lipoprotein (LDL) particles, which are known to be associated with an adverse cardiovascular risk profile. Studies conducted during the past few years have quite unanimously shown that the quantity of carbohydrates ingested is associated with a decrease of LDL particle size and an increase in its density. Conversely, diets that aim at a reduction of carbohydrate intake are able to improve LDL quality. Furthermore, a reduction of the glycaemic index without changing the amount of carbohydrates ingested has similar effects. Diseases with altered carbohydrate metabolism, for example, type 2 diabetes, are associated with small, dense LDL particles. Finally, even the kind of monosaccharide the carbohydrate intake consists of is important concerning LDL particle size: fructose has been shown to alter the LDL particle subclass profile more adversely than glucose in many recent studies. LDL particle quality, rather than its quantity, is affected by carbohydrate metabolism, which is of clinical importance, in particular, in the light of increased carbohydrate consumption in today's world.
Article
Background and aims: The well-established triglyceride (TG) lowering effect of fish oil is accompanied by an increase in LDL-cholesterol (LDL-C) concentration. Less is known about the differential impact on LDL particle distribution - the smaller particles being associated with a greater risk for atherosclerosis. We aimed to examine the changes in serum concentrations of four subclasses of LDL particles as well as shifts in LDL phenotype patterns (A, B, AB) among hypertriglyceridemic adults. Methods and results: This was a secondary analysis from a double-blind, parallel design, placebo controlled trial with 42 adults that experienced significant TG lowering and modest increases in total LDL-C concentrations after 12 weeks of 4 g/d EPA + DHA. Reduction in serum TG concentrations (mean ± SEM) was -26 ± 4% (-0.81 ± 10.12 mmol/L), p < 0.0001. Total LDL-C concentration increased by 13 ± 3% (+0.31 ± 0.08 mmol/L), p < 0.0001. The 12-week changes in concentrations of LDL1, LDL2, LDL3 and LDL4 were +0.06 ± 0.02 mmol/L [+2.2 ± 0.7 mg/dL], +0.07 ± 0.03 mmol/L [+2.6 ± 1.0 mg/dL], +0.16 ± 0.05 mmol/L [+6.3 ± 1.8 mg/dL], and +0.04 ± 0.04 mmol/L [+1.4 ± 1.7 mg/dL], respectively (+20 ± 5%, +64 ± 13%, +26 ± 6%, and +17 ± 9%), p < 0.05 for all but LDL4. Changes in LDL phenotype patterns A, B and A/B were negligible and not statistically significant. Conclusion: In this population of hypertriglyceridemic adults, dietary supplementation with fish oil resulted in an increase in total LDL-C concentration which was distributed relatively evenly across the range of smaller and more atherogenic as well as larger and less atherogenic LDL particles.
Article
High-fat, low-carbohydrate diets have been shown to raise plasma cholesterol levels, an effect associated with the formation of large low-density lipoprotein (LDL) particles. However, the impact of dietary intervention on time-course changes in LDL particle size has not been investigated. To test whether a short-term dietary intervention affects LDL particle size, we conducted a randomized, double-blind, crossover study using an intensive dietary modification in 12 nonobese healthy men with normal plasma lipid profile. Participants were subjected to 2 isocaloric 3-day diets: high-fat diet (37% energy from fat and 50% from carbohydrates) and low-fat diet (25% energy from fat and 62% from carbohydrates). Plasma lipid levels and LDL particle size were assessed on fasting blood samples after 3 days of feeding on each diet. The LDL particles were characterized by polyacrylamide gradient gel electrophoresis. Compared with the low-fat diet, plasma cholesterol, LDL cholesterol, and high-density lipoprotein cholesterol were significantly increased (4.45 vs 4.78 mmol/L, P = .04; 2.48 vs 2.90 mmol/L, P = .005; and 1.29 vs 1.41 mmol/L, P = .005, respectively) following the 3-day high-fat diet. Plasma triglycerides and fasting apolipoprotein B-48 levels were significantly decreased after the high-fat diet compared with the low-fat diet (1.48 vs 1.01 mmol/L, P = .0003 and 9.6 vs 5.5 mg/L, P = .008, respectively). The high-fat diet was also associated with a significant increase in LDL particle size (255.0 vs 255.9 Å;P = .01) and a significant decrease in the proportion of small LDL particle (<255.0 Å) (50.7% vs 44.6%, P = .01). As compared with a low-fat diet, the cholesterol-raising effect of a high-fat diet is associated with the formation of large LDL particles after only 3 days of feeding.
Article
The amount of cholesterol per low-density lipoprotein (LDL) particle is variable and related in part to particle size, with smaller particles carrying less cholesterol. This variability causes concentrations of LDL cholesterol (LDL-C) and LDL particles (LDL-P) to be discordant in many individuals. LDL-P measured by nuclear magnetic resonance spectroscopy, calculated LDL-C, and carotid intima-media thickness (IMT) were assessed at baseline in the Multi-Ethnic Study of Atherosclerosis, a community-based cohort of 6814 persons free of clinical cardiovascular disease (CVD) at entry and followed for CVD events (n = 319 during 5.5-year follow-up). Discordance, defined as values of LDL-P and LDL-C differing by ≥ 12 percentile units to give equal-sized concordant and discordant subgroups, was related to CVD events and to carotid IMT in models predicting outcomes for a 1 SD difference in LDL-C or LDL-P, adjusted for age, gender, and race. LDL-C and LDL-P were associated with incident CVD overall: hazard ratios (HR 1.20, 95% CI [CI] 1.08-1.34; and 1.32, 95% CI 1.19-1.47, respectively, but for those with discordant levels, only LDL-P was associated with incident CVD (HR 1.45, 95% CI 1.19-1.78; LDL-C HR 1.07, 95% CI 0.88-1.30). IMT also tracked with LDL-P rather than LDL-C, ie, adjusted mean IMT of 958, 932, and 917 microm in the LDL-P > LDL-C discordant, concordant, and LDL-P < LDL-C discordant subgroups, respectively, with the difference persisting after adjustment for LDL-C (P = .002) but not LDL-P (P = .60). For individuals with discordant LDL-C and LDL-P levels, the LDL-attributable atherosclerotic risk is better indicated by LDL-P.
Article
This pilot study compared weight loss and serum indicators of coronary artery disease (CAD) risk between 2 weight loss (energy-deficit) diets, one controlled for carbohydrate as a percentage of total calories and the other controlled for fat as percentage of total calories. Participants were randomized to 1 of 2 diets and fed on an outpatient basis for 70 days, after which they followed their diets using their own resources for an additional 70 days. Energy deficit for the diets was determined by indirect calorimetry with a 500- to 750-calorie per day adjustment. Weight and CAD risk indicators and serum lipid and C-reactive protein levels were measured at baseline, day 70, and day 140. The study was completed by 16 of 20 participants who were able to comply with the feeding portion of the study as well as with follow-up appointments during the second (self-management) period of the study. Participants lost weight in both diet groups (24.4 lbs, carbohydrate controlled; 18.5 lbs, fat controlled), and serum CAD risk factors decreased in both groups. There were no significant differences in CAD risk factors between diet groups, although there was a trend toward lighter low-density lipoprotein (LDL) size in the carbohydrate-controlled group. During the self-management portion of the study, weight loss stalled or regained from loss during the previous feeding period. The results, although underpowered, are consistent with recent studies in which macronutrient ratio of total calories in diet did not affect degree of weight loss and in which carbohydrate-controlled diets produced a predominance of lighter LDLs.
Article
To study the effects of the dietary fat content on cardiovascular disease risk factors in humans when the fatty acid composition and types of carbohydrates are kept constant. A controlled dietary study in healthy volunteers with 2 dietary groups and a parallel design consisting of 2 dietary periods was conducted. First, participants received a 2-week wash-in diet rich in saturated fatty acids (SFA; 47% of total fatty acids) and were then randomly assigned to either a high-fat (40% of energy) or a low-fat diet (29% of energy) for 4 weeks. Both diets were isocaloric, rich in monounsaturated fatty acids (MUFA; 51% of total fatty acids) and had similar fatty acid and carbohydrate compositions. Compared to the wash-in diet, the high-fat and low-fat diets significantly lowered LDL-cholesterol (-0.34 and -0.41 mmol/l, respectively; P < 0.001 for time effect in RM-ANOVA), and HDL-cholesterol (-0.13 and -0.18 mmol/l, respectively; P < 0.001 for time), without any differences between the high-fat and low-fat diets (P = 0.112 and P = 0.085 for time × group interaction in RM-ANOVA, respectively). The size of the major LDL fraction, the LDL susceptibility to oxidation and the plasma concentrations of oxidized LDL (ox-LDL) were significantly reduced by both the high-fat and low-fat diet, again without significant differences between the diets. The ratio of ox-LDL/LDL-cholesterol, serum triacylglycerols and urinary F2-isoprostanes were not significantly affected by the diets. A high-fat and a low-fat diet, both rich in MUFA, had similar effects on lipid-related cardiovascular disease risk factors in metabolically healthy men and women.
Article
Epidemiological studies have indicated a negative relation between low-fat dairy consumption and the metabolic syndrome. However, evidence from intervention studies is scarce. Our aim was to investigate the effects of daily consumption of low-fat dairy products on metabolic risk parameters in overweight and obese men and women. Thirty-five healthy subjects (BMI>27 kg/m(2)) consumed low-fat dairy products (500 mL low-fat milk and 150 g low-fat yogurt) or carbohydrate-rich control products (600 mL fruit juice and 3 fruit biscuits) daily for 8 weeks in random order. Compared with the control period, systolic blood pressure was decreased by 2.9 mm Hg (95% confidence interval (CI), -5.5 to -0.3 mm Hg; P=0.027), while the difference in diastolic blood pressure did not reach statistical significance (95% CI, -3.4 to 0.3 mm Hg; P=0.090). Low-fat dairy consumption decreased HDL-cholesterol concentrations by 0.04 mmol/L (95% CI, -0.07 to -0.01 mmol/L; P=0.021) and apo A-1 concentrations by 0.04 g/L (95% CI, -0.07 to -0.01 g/L; P=0.016) compared with control. Serum total cholesterol, LDL-cholesterol, apo B, triacylglycerols, non-esterified fatty acids, glucose, insulin, C-reactive protein and plasminogen activator inhibitor-1 were unchanged. We conclude that in overweight and obese subjects, daily intake of low-fat dairy products for 8 weeks decreased systolic blood pressure, but did not improve other metabolic risk factors related to the metabolic syndrome.
Article
Carbohydrate restriction (CR) has been shown to improve dyslipidemias associated with metabolic syndrome (MetS). We evaluated the effects of CR on lipoprotein subfractions and apolipoproteins in Emirati adults classified with the MetS. 39 subjects (15 men/24 women) were randomly allocated to a CR diet [20-25% energy from carbohydrate (CHO)] for 12 wk (CRD group) or a combination treatment consisting of CRD for 6 wk followed by the American Heart Association diet (50-55% CHO, AHA group) for an additional 6 wk. All subjects reduced body weight, LDL cholesterol and triglycerides (P<0.01). At baseline all subjects had low concentrations of medium VLDL and total HDL particles associated with the very low plasma triglycerides and HDL cholesterol in this population. After 12 wk, the large VLDL subfraction was decreased over time for subjects in the CRD group (P<0.01) while these changes were not observed in those subjects who changed to the AHA diet. The number of medium and small LDL particles decreased for all subjects rendering a less atherogenic lipoprotein profile. In agreement with these results, a significant decrease in apolipoprotein (apo) B was observed (P<0.01). The medium HDL subfraction and apo A-II, which can be considered pro-atherogenic, were also decreased over time in the CRD group only. These results suggest that weight loss favorably affects lipoprotein metabolism and that the CRD had a better effect on atherogenic VLDL and HDL than the low fat diet recommended by AHA.
Article
A previously described coefficient of agreement for nominal scales, kappa, treats all disagreements equally. A generalization to weighted kappa (Kw) is presented. The Kw provides for the incorpation of ratio-scaled degrees of disagreement (or agreement) to each of the cells of the k * k table of joint nominal scale assignments such that disagreements of varying gravity (or agreements of varying degree) are weighted accordingly. Although providing for partial credit, Kw is fully chance corrected. Its sampling characteristics and procedures for hypothesis testing and setting confidence limits are given. Under certain conditions, Kw equals product-moment r. The use of unequal weights for symmetrical cells makes Kw suitable as a measure of validity.
Article
Excess adiposity and high-carbohydrate diets have been associated with an atherogenic lipoprotein phenotype (ALP) characterized by increased concentrations of small, dense low-density lipoprotein (LDL) particles (pattern B). We tested whether weight loss and normalization of adiposity could reverse ALP in overweight men with pattern B. After consuming a moderate-carbohydrate, high-fat diet for 3 weeks, pattern B and nonpattern B (pattern A) men were randomized to a weight loss (n = 60 and n = 36, respectively) or control weight-stable arm (n = 20 and n = 17, respectively). Men in the weight loss arm consumed approximately 1,000 fewer calories per day over 9 weeks to induce an average approximately 9 kg weight loss. In the control group, weight stability was maintained for 4 weeks after randomization. Weight loss led to the conversion of pattern B to pattern A in 58% of baseline pattern B men. Among men who achieved BMIs of <25 kg/m(2) (62% of pattern B men vs. 83% of pattern A men), 81% of pattern B men converted to pattern A. Weight loss was associated with a significantly greater decrease in small, dense LDL subclass 3b in pattern B relative to pattern A men. The lipoprotein profiles of pattern A men who converted from pattern B were comparable to those of men with pattern A at baseline. Conversion of LDL subclass pattern B to pattern A and reversal of ALP can be achieved in a high proportion of overweight men by normalization of adiposity.
Article
LDL phenotype B is associated with obesity, insulin resistance, hypertriglyceridemia and oxidative stress. The effect of plasma n-3/n-6 PUFA ratio on LDL phenotype transformation was investigated. Patients with metabolic syndrome (n=99) received one of four isocaloric diets: (A) High-fat (38% energy) SFA-rich diet (HSFA); (B) High-fat (38% energy), MUFA-rich diet (HMUFA); (C), low-fat (LF) (28% energy), high-complex carbohydrate diet with 1.24g/d oleic sunflower oil (LFHCC) and (D): low-fat (28% energy), high-complex carbohydrate diet, with 1.24g/d LC n-3 PUFA (LFHCC n-3) for 12 weeks. Analysis of plasma lipid profile and LDL phenotype was done pre- and post-interventions. Post-dietary change of LDL density was a main effect observed in all groups. LFHCC n-3 and HFMUFA diets resulted in favorable alteration of LDL phenotype from B to A and decreased LDL density. In contrast, increased LDL density was observed in HSFA and LFHCC groups. The plasma pre-n3/n6 PUFA, Apo E change and pre-Apo CIII/CII ratios explained in 65% the post-dietary change of LDL density in diet LFHCC n-3 consumers. Study demonstrates efficacy of dietary n-3 PUFA to modify pro-atherogenic to less atherogenic LDL phenotype in patients with metabolic syndrome. Study identifier at ClinicalTrials.gov was NCT00429195.