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Sacks, Frank

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Sacks, Frank
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    Associations of Plasma Phospholipid SFAs with Total and Cause-Specific Mortality in Older Adults Differ According to SFA Chain Length1234
    (American Society for Nutrition, 2016) Fretts, Amanda M; Mozaffarian, Dariush; Siscovick, David S; King, Irena B; McKnight, Barbara; Psaty, Bruce M; Rimm, Eric; Sitlani, Colleen; Sacks, Frank; Song, Xiaoling; Sotoodehnia, Nona; Spiegelman, Donna; Lemaitre, Rozenn N
    Background: Not much is known about the relations of circulating saturated fatty acids (SFAs), which are influenced by both metabolic and dietary determinants, with total and cause-specific mortality. Objective: We examined the associations of plasma phospholipid SFAs with total and cause-specific mortality among 3941 older adults from the Cardiovascular Health Study, a population-based prospective study of adults aged ≥65 y who were followed from 1992 through 2011. Methods: The relations of total and cause-specific mortality with plasma phospholipid palmitic acid (16:0), stearic acid (18:0), arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) were assessed using Cox proportional hazards models. Results: During 45,450 person-years of follow-up, 3134 deaths occurred. Higher concentrations of the plasma phospholipid SFAs 18:0, 22:0, and 24:0 were associated with a lower risk of total mortality [multivariable-adjusted HRs (95% CIs)] for the top compared with the bottom quintile: 0.85 (0.75, 0.95) for 18:0; 0.85 (0.75, 0.95) for 22:0; and 0.80 (0.71, 0.90) for 24:0. In contrast, plasma 16:0 concentrations in the highest quintile were associated with a higher risk of total mortality compared with concentrations in the lowest quintile [1.25 (1.11, 1.41)]. We also found no association of plasma phospholipid 20:0 with total mortality. Conclusions: These findings suggest that the associations of plasma phospholipid SFAs with the risk of death differ according to SFA chain length and support future studies to better characterize the determinants of circulating SFAs and to explore the mechanisms underlying these relations.
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    Frequency of consuming foods predicts changes in cravings for those foods during weight loss: The POUNDS Lost Study
    (2017) Apolzan, John W.; Myers, Candice A.; Champagne, Catherine M.; Beyl, Robbie A.; Raynor, Hollie A.; Anton, Stephen A.; Williamson, Donald A.; Sacks, Frank; Bray, George A.; Martin, Corby K.
    Objective: Food cravings are thought to be the result of conditioning or pairing hunger with consumption of certain foods. Methods: In a two-year weight loss trial, subjects were randomized to one of four diets that varied in macronutrient content. The Food Craving Inventory (FCI) was used to measure cravings at baseline, 6, and 24 months. Also, food intake was measured at those time points. To measure free-living consumption of food items measured in the FCI, items on the FCI were matched to the foods consumed from the food intake assessments. Secondarily, we analyzed the amount of food consumed on food intake assessments from foods on the FCI. Results: 367 subjects who were overweight and obese were included. There was an association between change from baseline FCI item consumption and change in cravings at months 6 (p<0.001) and 24 (p<0.05). There was no association between change from baseline amount of energy consumed per FCI item and change in cravings. Conclusions: Altering frequency of consuming craved foods is positively associated with cravings; however, changing the amount of foods consumed does not appear to alter cravings. These results support the conditioning model of food cravings and provide guidance on how to reduce food cravings.
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    The Effects of Carbohydrate, Unsaturated Fat, and Protein Intake on Measures of Insulin Sensitivity: Results from the OmniHeart Trial
    (American Diabetes Association, 2013) Gadgil, Meghana D.; Appel, Lawrence J.; Yeung, Edwina; Anderson, Cheryl A.M.; Sacks, Frank; Miller, Edgar R.
    OBJECTIVE Impaired insulin sensitivity increases the risk of cardiovascular disease. Although calorie restriction and weight loss increase insulin sensitivity, the effects of modifying macronutrient composition on insulin sensitivity are uncertain. The purpose of this study is to determine the effects on insulin sensitivity of a carbohydrate-rich diet (CARB; similar to the Dietary Approaches to Stop Hypertension [DASH] diet), a protein-rich diet (PROT; protein predominantly from plant sources), and an unsaturated fat–rich diet (UNSAT; predominantly monounsaturated). RESEARCH DESIGN AND METHODS This study was a randomized, controlled, three-period, crossover feeding study. The study participants were 164 individuals with prehypertension or stage 1 hypertension without diabetes. Diets were administered for 6 weeks each, with a washout period between diets of 2–4 weeks. Weight was held constant throughout the study. For our primary outcome, we calculated the quantitative insulin sensitivity check index (QUICKI) using the end-of-period fasting serum glucose and insulin. QUICKI is a validated measure of insulin sensitivity. The primary analyses used generalized estimating equations. RESULTS At baseline, mean (SD) BMI was 30.2 (6.1) kg/m2, and mean (SD) QUICKI was 0.35 (0.04). The UNSAT diet increased QUICKI by 0.005, more than the CARB diet (P = 0.04). PROT had no significant effect compared with CARB. CONCLUSIONS A diet that partially replaces carbohydrate with unsaturated fat may improve insulin sensitivity in a population at risk for cardiovascular disease. Given the well-recognized challenges of sustaining weight loss, our results suggest an alternative approach for improving insulin sensitivity.
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    FTO Genotype and 2-Year Change in Body Composition and Fat Distribution in Response to Weight-Loss Diets: The POUNDS LOST Trial
    (American Diabetes Association, 2012) Zhang, Xiaomin; Qi, Qibin; Zhang, Cuilin; Hu, Frank; Sacks, Frank; Qi, Lu
    Recent evidence suggests that the fat mass and obesity-associated gene (FTO) genotype may interact with dietary intakes in relation to adiposity. We tested the effect of FTO variant on weight loss in response to 2-year diet interventions. FTO rs1558902 was genotyped in 742 obese adults who were randomly assigned to one of four diets differing in the proportions of fat, protein, and carbohydrate. Body composition and fat distribution were measured by dual-energy x-ray absorptiometry and computed tomography. We found significant modification effects for intervention varying in dietary protein on 2-year changes in fat-free mass, whole body total percentage of fat mass, total adipose tissue mass, visceral adipose tissue mass, and superficial adipose tissue mass (for all interactions, P < 0.05). Carriers of the risk allele had a greater reduction in weight, body composition, and fat distribution in response to a high-protein diet, whereas an opposite genetic effect was observed on changes in fat distribution in response to a low-protein diet. Likewise, significant interaction patterns also were observed at 6 months. Our data suggest that a high-protein diet may be beneficial for weight loss and improvement of body composition and fat distribution in individuals with the risk allele of the FTO variant rs1558902.
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    Effect of Dietary Composition of Weight Loss Diets on High Sensitivity C-Reactive Protein: The Randomized POUNDS LOST Trial
    (2012) Nicklas, Jacinda M.; Sacks, Frank; Smith, Steven R.; Leboff, Meryl; Rood, Jennifer C.; Bray, George A.; Ridker, Paul
    Overweight and obesity are associated with increased high sensitivity C-reactive protein (hsCRP) levels. The purpose of this study was to determine if weight loss diets differing in fat, protein, or carbohydrate composition differentially reduce hsCRP. POUNDS (Preventing Overweight Using Novel Dietary Strategies) LOST was a two-year trial of overweight and obese adults randomly allocated to one of four weight loss diets with targeted percentages of energy derived from fat, protein, and carbohydrates (20,15,65%;20,25,55%;40,15,45%;40,25,35%, respectively). hsCRP was measured at baseline, 6, and 24 months among 710 participants, and adiposity as measured by dual X-ray absorptiometry (N=340) or abdominal computed tomography (N=126) was correlated with hsCRP change. At 6 months, hsCRP was reduced in all trial participants by −24.7% (IQR +7%,−50%), weight by −6.7% (IQR −3%,−11%), and waist circumference by −6.0% (IQR −3%,−10%) (all P<.002), with no significant differences according to dietary composition. The percent change in hsCRP at 6 and 24 months correlated modestly with change in weight, waist circumference, fasting insulin, fasting glucose, HOMA, and most lipid levels. Reductions in hsCRP persisted despite an approximate 50% regain of weight by 24 months. The percent change in hsCRP at 24 months significantly correlated with changes in total body fat (r=0.42), total abdominal adiposity (r=0.52), subcutaneous abdominal adiposity (r=0.52), visceral adiposity (r=0.47), and hepatic tissue density (r=−0.34) (all P<0.0006). In conclusion, weight loss decreased hsCRP by similar magnitude, irrespective of dietary composition. Clinicians concerned about inflammation and cardiovascular risk should recommend weight loss diets most likely to succeed for their patients.
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    Apolipoprotein E in VLDL and LDL With Apolipoprotein C‐III is Associated With a Lower Risk of Coronary Heart Disease
    (Blackwell Publishing Ltd, 2013) Mendivil, Carlos O.; Rimm, Eric; Furtado, Jeremy; Sacks, Frank
    Background: Low‐density lipoprotein (LDL) with apolipoprotein C‐III (apoC‐III) is the lipoprotein species that most strongly predicts initial and recurring coronary heart disease (CHD) events in several cohorts. Thus, a large portion of the CHD risk conferred by LDL may be attributable to LDL that contains apoC‐III. Very‐low‐density lipoprotein (VLDL) and LDL with apoC‐III have varying amounts of apoE. We hypothesized that a high content of apoE lessens the adverse influence of apoC‐III on the risk of CHD because it promotes the clearance of VLDL and LDL from plasma. Methods and Results: We studied 2 independent cohorts, the Nurses' Health Study, composed of women, and the Health Professionals Follow‐up Study, composed of men. These cohorts contributed to this study 322 women and 418 men initially free of CVD who developed a fatal or nonfatal myocardial infarction during 10 to 14 years of follow‐up and matched controls who remained free of CHD. The apoE content of LDL with apoC‐III was inversely associated with CHD after multivariable adjustment (relative risk for top versus bottom quintile 0.53, 95% CI 0.35 to 0.80). The apoE content of VLDL with apoC‐III had a similar inverse association with CHD. The highest risks were associated with a high apoB concentration and a low apoE content of LDL with apoC‐III or of VLDL+LDL with apoC‐III. The observed associations were in both male and female cohorts and independent of traditional CHD risk factors and of C‐reactive protein. Conclusions: An increased apoE content in VLDL and LDL with apoC‐III was associated with a lower risk of CHD. Strategies to enrich VLDL and LDL in apoE are worth exploring for the prevention of CHD.
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    Effect of diet composition and weight loss on resting energy expenditure in the POUNDS LOST study
    (2012) de Jonge, Lilian; Bray, George A.; Smith, Steven R.; Ryan, Donna H.; de Souza, Russell; Loria, Catherine M.; Champagne, Catherine M.; Williamson, Donald; Sacks, Frank
    Weight loss reduces energy expenditure, but it is unclear whether dietary macronutrient composition affects this reduction. We hypothesized that energy expenditure might be modulated by macronutrient composition of the diet. The POUNDS LOST study, a prospective, randomized controlled trial in 811 overweight/obese people who were randomized in a 2×2 design to diets containing 20en% or 40en% fat and 15en% or 25en% (diets with 65%, 55%, 45% and 35% carbohydrate) provided the data to test this hypothesis. Resting energy expenditure (REE) was measured at baseline, 6 and 24 months using a ventilated hood. REE declined at 6 months by 99.5±8.0 kcal/d in men and 55.2±10.6 kcal/d in women during the first 6 months. This decline was related to the weight loss, and there was no difference between the diets. REE had returned to baseline by 24 months, but body weight was still 60% below baseline. Measured REE at 6 months was significantly lower than the predicted (−18.2±6.7 kcal/d) and was the result of significant reductions from baseline in the low fat diets (65% or 55% carbohydrate), but not in the high fat diet groups. By 24 months the difference had reversed with measured REE being slightly but significantly higher than predicted (21.8±10.1 kcal/d). In conclusion, we found that REE fell significantly after weight loss but was not related to diet composition. Adaptive thermogenesis was evident at 6 months, but not at 24 months.
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    Plasma Pentraxin 3 Levels Do Not Predict Coronary Events but Reflect Metabolic Disorders in Patients with Coronary Artery Disease in the CARE Trial
    (Public Library of Science, 2014) Miyazaki, Tetsuro; Chiuve, Stephanie; Sacks, Frank; Ridker, Paul; Libby, Peter; Aikawa, Masanori
    Chronic inflammation closely associates with obesity, metabolic syndrome, diabetes mellitus, and atherosclerosis. Evidence indicates that the immunomodulator pentraxin 3 (PTX3) may serve as a biomarker of these cardiometabolic disorders, but whether PTX3 predicts cardiovascular complications is unknown. We examined the association of plasma PTX3 levels with recurrent coronary events via a prospective, nested, case-control design in the CARE trial. Among 4159 patients who had a prior myocardial infarction 3 to 20 months before enrollment and also had total cholesterol levels <240 mg/dL and LDL cholesterol levels between 115 and 175 mg/dL, we measured plasma PTX3 levels at baseline by high-sensitivity ELISA in 413 cases with recurrent myocardial infarction or coronary death during a 5-year follow-up period, and in 366 sex- and age-matched controls. Cases with recurrent coronary events and controls had similar PTX3 levels, and PTX3 did not predict recurrent coronary events — a finding that contrasts with that of C-reactive protein (CRP) and serum amyloid A (SAA) in this cohort. We then associated PTX3 levels with metabolic disorders. Low plasma PTX3 levels correlated with high body-mass index, waist circumference, and triglycerides; and with low HDL cholesterol. Overall, PTX3 levels correlated inversely with the number of metabolic syndrome components. PTX3 levels also correlated inversely with apoCIII and tissue plasminogen activator, but did not associate with CRP. Although the study further links low PTX3 levels with various features associated with metabolic syndrome, the results do not indicate that PTX3 can predict recurrent coronary events among MI survivors.
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    ApoC-III and visceral adipose tissue contribute to paradoxically normal triglyceride levels in insulin-resistant African-American women
    (BioMed Central, 2013) Sumner, Anne E; Furtado, Jeremy; Courville, Amber B; Ricks, Madia; Younger-Coleman, Novie; Tulloch-Reid, Marshall K; Sacks, Frank
    Background: African-Americans are more insulin-resistant than whites but have lower triglyceride (TG) concentrations. The metabolic basis for this is unknown. Our goal was to determine in a cross-sectional study the effect of insulin resistance, visceral adipose tissue (VAT) and the apolipoproteins, B, C-III and E, on race differences in TG content of very low density lipoproteins (VLDL). Methods: The participants were 31 women (16 African-American, 15 white) of similar age (37 ± 9 vs. 38 ± 11y (mean ± SD), P = 0.72) and BMI (32.4 ± 7.2 vs. 29.3 ± 6.0 kg/m2, P = 0.21). A standard diet (33% fat, 52% carbohydrate, 15% protein) was given for 7 days followed by a test meal (40% fat, 40% carbohydrate, 20% protein) on Day 8. Insulin sensitivity index (SI) was calculated from the minimal model. VAT was measured at L2-3. The influence of race, SI, VAT and apolipoproteins on the TG content of VLDL was determined by random effects models (REM). Results: African-Americans were more insulin-resistant (SI: 3.6 ± 1.3 vs. 5.6 ± 2.6 mU/L-1.min-1, P < 0.01) with less VAT (75 ± 59 vs. 102 ± 71 cm2, P < 0.01). TG, apoB and apoC-III content of light and dense VLDL were lower in African-Americans (all P < 0.05 except for apoC-III in light VLDL, P = 0.11). ApoE content did not vary by race. In REM, VAT but not SI influenced the TG concentration of VLDL. In models with race, SI, VAT and all apolipoproteins entered, race was not significant but apoC-III and VAT remained significant determinants of TG concentration in light and dense VLDL. Conclusions: Low concentrations of apoC-III and VAT in African-Americans contribute to race differences in TG concentrations. Trial registration ClinicalTrials.gov Identifier: NCT00484861
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    Racial differences between African-American and white women in insulin resistance and visceral adiposity are associated with differences in apoCIII containing apoAI and apoB lipoproteins
    (BioMed Central, 2014) Wang, Liyun; Sacks, Frank; Furtado, Jeremy; Ricks, Madia; Courville, Amber B; Sumner, Anne E
    Background: African-Americans have higher HDL, less visceral adipose tissue (VAT) and lower triglyceride (TG) and apoCIII concentrations than whites, despite being more insulin-resistant. We studied in African-American and white women the influences of insulin resistance and VAT on the apoAI concentrations of two HDL subspecies, one that contains apoCIII that is associated with increased risk of coronary heart disease (CHD) and one that does not have apoCIII that is associated with decreased CHD; and on the apoCIII concentrations of HDL and of the apoB lipoproteins. Methods: The participants were 32 women (14 African-Americans, 18 white) of similar age (39 ± 12 vs. 42 ± 11y). Mean BMI was 34 kg/m2 in the African-Americans compared to 30 in the whites. A standard diet (33% fat, 52% carbohydrate, 15% protein) was provided for 7 days followed by a test meal (40% fat, 40% carbohydrate, 20% protein) on Day 8. Insulin sensitivity index (SI) was calculated from the minimal model. Results: After controlling for SI, African-Americans have a higher mean apoAI level in HDL with apoCIII compared with whites (12.9 ± 2.8 and 10.9 ± 2.9 mg/dL, respectively, P = 0.05). SI was associated with higher apoAI in HDL with apoCIII, whereas VAT was not associated with this HDL subspecies. This pattern of results was reversed for apoCIII concentrations in apoB lipoproteins. After adjusting for SI, African-Americans had lower apoCIII in apoB lipoproteins. SI was associated with lower apoCIII in total apoB lipoproteins, whereas VAT was associated with higher apoCIII in all the apoB lipoproteins. Additional adjustment for VAT tended to reduce the difference in apoCIII between the groups. Conclusions: African-American women have a higher HDL with apoCIII level than whites when controlled for insulin sensitivity. African-Americans have lower insulin sensitivity. Insulin sensitivity is associated with higher levels of HDL with apoCIII. ApoCIII levels in VLDL are lower in African-American women than whites, also affected by insulin sensitivity which is associated with low apoCIII in VLDL. VAT has a strong association with apoCIII in apoB lipoproteins but not with apoAI in HDL with apoCIII. Trial registration ClinicalTrials.gov Identifier: NCT00484861