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Effect of individualised dietary advice for weight loss supplemented with walnuts on blood pressure: the HealthTrack study.

Ndanuko, R.N., L.C. Tapsell, K.E. Charlton, E.P. Neale, M.J. Batterham, 2018. Effect of individualised dietary advice for weight loss supplemented with walnuts on blood pressure: the HealthTrack study. Eur J Clin Nutr. 72(6):894-903.

BACKGROUND/OBJECTIVES: In addition to weight-loss, healthy dietary patterns and lower sodium intakes can help reduce blood pressure (BP), but individualised dietary advice may be necessary to achieve these effects. This study aimed to examine the impact of individualised dietary advice on BP in the intensive phase of a weight-loss trial. SUBJECTS/METHODS: Secondary analysis of baseline and 3-month data from the HealthTrack randomised controlled trial (n = 211). Participants were randomly assigned to one of three dietary advice groups: general advice (control), individualised advice (intervention group, I), or intervention group supplemented with 30 g walnuts/day (IW). Resting BP and 24-h urine sodium and potassium were measured. Dietary intake was evaluated through diet history interviews. RESULTS: Unadjusted SBP reduced significantly in all groups (IW and I groups P < 0.001; control group P = 0.002) and DBP in IW and I groups (P < 0.001). Compared to controls, the reductions in BP were 3-4 mmHg greater in the I and IW groups, but this only reached significance for DBP in the I group (-3.3 mmHg; P = 0.041). After controlling for age, sex, medication, weight-loss, physical activity and smoking, only the IW group showed a significant association between SBP reduction and increased urinary potassium (β = -0.101, P = 0.044), decreased sodium:potassium ratio (β = 2.446, P = 0.037) and increased consumption of seed and nut products and dishes (β = -0.108, P = 0.034). CONCLUSIONS: Dietary patterns with distinctive foods and lower sodium:potassium ratios may enhance the effects of weight-loss on BP. The patterns were best achieved with individualised dietary advice and food supplements.

Considerations to facilitate a US study that replicates PREDIMED.

Jacobs, D.R. Jr., K.S. Petersen, K. Svendsen, E. Ros, C.B. Sloan, L.M. Steffen, L.C. Tapsell, P.M. Kris-Etherton, 2018. Considerations to facilitate a US study that replicates PREDIMED. Metabolism. pii: S0026-0495(18)30118-5. doi: 10.1016/j.metabol.2018.05.001. [Epub ahead of print]

The PREDIMED clinical trial provided strong evidence that a Mediterranean dietary pattern (MedDiet) could help prevent cardiovascular disease (CVD) events in high risk middle-aged/older people. This report considers the feasibility of replicating PREDIMED in the U.S., including recommendations for dietary and behavioral principles. A 14-point Mediterranean diet Adherence Score (MEDAS) guided the PREDIMED MedDiet recommendations. At baseline MEDAS points were ~8.5. During intervention this score increased to nearly 11 in MedDiet vs. 9 in control. In the MedDiet groups, only about 0.5 points of the net 2 point MEDAS increase was attributable to the gratis supplements of olive oil or nuts. An issue in a U.S. replication is the large difference in typical U.S. versus Spanish diet and lifestyle. A typical U.S. diet would achieve a MEDAS of 1-2. A replication is scientifically feasible with an assumption such as that the MedDiet reflects a continuum of specific food choices and meal patterns. As such, a 2 point change in MEDAS at any point on the continuum would be hypothesized to reduce incident CVD. A conservative approach would aim for a randomized 4 point MEDAS difference, e.g. 5-6 points vs. an average U.S. diet group that achieved only 1-2 points.

Effects of walnut consumption on blood lipids and other cardiovascular risk factors: an updated meta-analysis and systematic review of controlled trials.

Guasch-Ferré, M., J. Li, F.B. Hu, J. Salas-Salvadó, D.K. Tobias, 2018. Effects of walnut consumption on blood lipids and other cardiovascular risk factors: an updated meta-analysis and systematic review of controlled trials. Am J Clin Nutr. doi: 10.1093/ajcn/nqy091. [Epub ahead of print]

BACKGROUND: Intervention studies suggest that incorporating walnuts into the diet may improve blood lipids without promoting weight gain. OBJECTIVE: We conducted a systematic review and meta-analysis of controlled trials evaluating the effects of walnut consumption on blood lipids and other cardiovascular risk factors. Design: We conducted a comprehensive search of PubMed and EMBASE databases (from database inception to January 2018) of clinical trials comparing walnut-enriched diets with control diets. We performed random-effects meta-analyses comparing walnut-enriched and control diets for changes in pre-post intervention in blood lipids (mmol/L), apolipoproteins (mg/dL), body weight (kg), and blood pressure (mm Hg). RESULTS: Twenty-six clinical trials with a total of 1059 participants were included. The following weighted mean differences (WMDs) in reductions were obtained for walnut-enriched diets compared with control groups: -6.99 mg/dL (95% CI: -9.39, -4.58 mg/dL; P < 0.001) (3.25% greater reduction) for total blood cholesterol (TC) and -5.51 mg/dL (95% CI: -7.72, -3.29 mg/dL; P < 0.001) (3.73% greater reduction) for low-density lipoprotein (LDL) cholesterol. Triglyceride concentrations were also reduced in walnut-enriched diets compared with control [WMD = -4.69 (95% CI: -8.93, -0.45); P = 0.03; 5.52% greater reduction]. More pronounced reductions in blood lipids were observed when walnut interventions were compared with American and Western diets [WMD for TC = -12.30 (95% CI: -23.17, -1.43) and for LDL = -8.28 (95% CI: -13.04, -3.51); P < 0.001]. Apolipoprotein B (mg/dL) was also reduced significantly more on walnut-enriched diets compared with control groups [WMD = -3.74 (95% CI: -6.51, -0.97); P = 0.008] and a trend towards a reduction was observed for apolipoprotein A [WMD = -2.91 (95% CI: -5.98, 0.08); P = 0.057]. Walnut-enriched diets did not lead to significant differences in weight change (kg) compared with control diets [WMD = -0.12 (95% CI: -2.12, 1.88); P = 0.90], systolic blood pressure (mm Hg) [WMD = -0.72 (95% CI: -2.75, 1.30); P = 0.48], or diastolic blood pressure (mm Hg) [WMD = -0.10 (95% CI: -1.49, 1.30); P = 0.88]. Conclusions: Incorporating walnuts into the diet improved blood lipid profile without adversely affecting body weight or blood pressure.

Effect of distinct lifestyle interventions on mobilization of fat storage pools: The CENTRAL MRI randomized controlled trial.

Gepner, Y., I. Shelef, D. Schwarzfuchs, H. Zelicha, L. Tene, A. Yaskolka Meir, G. Tsaban, N. Cohen, N. Bril, M. Rein, D. Serfaty, S. Kenigsbuch, O. Komy, A. Wolak, Y. Chassidim, R. Golan, H. Avni-Hassid, A. Bilitzky, B. Sarusi, E. Goshen, E. Shemesh, Y. Henkin, M. Stumvoll, M. Blüher, J. Thiery, U. Ceglarek, A. Rudich, M.J. Stampfer, I. Shai, 2018. Effect of distinct lifestyle interventions on mobilization of fat storage pools: The CENTRAL MRI randomized controlled trial. Circulation. 137(11):1143-1157. doi: 10.1161/CirculationAHA.117.030501.

Background: We aimed to assess whether distinct lifestyle strategies can differentially affect specific body adipose depots. Methods: We performed an eighteen-month randomized controlled trial among 278 sedentary adults with abdominal obesity (75%) or dyslipidemia in an isolated workplace with a monitored provided lunch. Participants were randomized to iso-caloric low-fat (LF) or Mediterranean/low-carbohydrate (MED/LC) diet+28g walnuts/day with/without added moderate physical activity (PA;80% aerobic; supervised/free gym membership). Overall primary outcome was body fat re-distribution, and the main specific endpoint was visceral adipose tissue (VAT). We further followed the dynamics of different fat depots [deep/superficial subcutaneous (D/SSAT), liver, pericardial, muscle, pancreas and renal-sinus] by magnetic-resonance-imaging. Results: Of 278 participants (age=48y; 89%men, body-mass-index=30.8kg/m2), 86% completed the trial, with good adherence. The LF group preferentially decreased reported fat intake (-21.0% vs. -11.5% for the MED/LC; P<0.001), and the MED/LC group decreased reported carbohydrates intake (-39.5%vs. -21.3% for the LF;P<0.001). The PA+ groups significantly increased the metabolic-equivalents (METs)/week vs. the PA- groups (19.0 vs. 2.1;P=0.009). Whereas final moderate weight loss was indifferent, exercise attenuated the waist circumference rebound with the greatest effect in MED/LCPA+ group (P<0.05). VAT (-22%), intra-hepatic (-29%), and Intra-pericardial (-11%) fats declines were higher than pancreatic and femur intermuscular fats (1-2%) loss. Independent of weight loss, PA+ with either diet had a significantly greater effect on decreasing VAT [mean-of-difference=-6.67cm2;95%CI:(-14.8 to -0.45) compared with PA-]. The MED/LC diet was superior to LF in decreasing intra-hepatic, intra-pericardial and pancreatic fats (P<0.05 for all). In contrast, renal-sinus and femoral-intermuscular fats were not differentially altered by lifestyle interventions, but by weight loss per-se. In multivariate models, further adjusted for weight loss, losing VAT or intra-hepatic fat were independently associated with improved lipid profile, losing deep-SAT with improved insulin sensitivity and losing superficial-SAT remained neutral except of association with decreased leptin. Conclusions: Moderate weight loss alone inadequately reflects the significant lifestyle effects on atherogenic and diabetogenic fat depots. The MED/LC diet mobilizes specific ectopic fat depots, and exercise has an independent contribution to VAT loss. Fat depots exhibit diverse responsiveness and are differentially related to cardiometabolic markers. Distinct lifestyle protocols may uniquely induce fat mobilization from specific anatomical sites.

The red blood cell proportion of arachidonic acid relates to shorter leukocyte telomeres in Mediterranean elders: A secondary analysis of a randomized controlled trial.

Freitas-Simoes, T.M., M. Cofán, M.A. Blasco, N. Soberón, M. Foronda, D. Corella, E.M. Asensio, M. Serra-Mir, I. Roth, C. Calvo, C. Valls-Pedret, R.P. Casaroli-Marano, M. Doménech, S. Rajaram, J. Sabaté, E. Ros, A. Sala-Vila, 2018. The red blood cell proportion of arachidonic acid relates to shorter leukocyte telomeres in Mediterranean elders: A secondary analysis of a randomized controlled trial. Clin Nutr. pii: S0261-5614(18)30074-8. doi: 10.1016/j.clnu.2018.02.011. [Epub ahead of print]

BACKGROUND & AIMS: Shortening of leukocyte telomere length (LTL) is a biomarker of aging. Epidemiologic studies of LTL in relation to dietary fatty acids have reported conflicting results. The red blood cell (RBC) fatty acid status is a valid objective biomarker of long-term dietary intake of C18:2n-6, C18:3n-3 and long-chain n-3 polyunsaturated fatty acids (C20:5n-3 and C22:6n-3). In healthy older individuals, we investigated whether LTL relates to the RBC proportions of the main dietary polyunsaturated fatty acids (PUFA), and to the RBC proportion of arachidonic acid (C20:4n-6), a fatty acid that can generate pro-inflammatory lipid mediators once released from cell membranes. DESIGN: Cross-sectional study in 344 subjects (mean age 68.8 y, 68.6% women) who participated in a randomized controlled trial testing whether a diet enriched in walnuts can delay the onset of age-related diseases (https://clinicaltrials.gov/ct2/show/NCT01634841). At baseline, we assessed LTL by high-throughput quantitative fluorescence and determined fatty acids in RBCs by gas chromatography. RESULTS: In multivariate models adjusted for age and gender, the RBC proportions of dietary PUFA were unrelated to LTL. In contrast, the RBC proportion of arachidonic acid inversely related to LTL (regression coefficient [95% confidence interval], -0.10 (-0.19 to -0.01), P = 0.023). CONCLUSION: An increasing proportion of C20:4n-6 in RBCs is associated with shorter telomeres. Further research is needed to investigate the role of this fatty acid and its derived lipid mediators in the aging process.

A walnut-enriched diet affects gut microbiome in healthy Caucasian subjects: A randomized, controlled trial.

Bamberger, C., A. Rossmeier, K. Lechner, L. Wu, E. Waldmann, S. Fischer, R.G. Stark, J. Altenhofer, K. Henze, K.G. Parhofer, 2018. A walnut-enriched diet affects gut microbiome in healthy Caucasian subjects: A randomized, controlled trial. Nutrients. 10(2). pii: E244. doi: 10.3390/nu10020244.

Regular walnut consumption is associated with better health. We have previously shown that eight weeks of walnut consumption (43 g/day) significantly improves lipids in healthy subjects. In the same study, gut microbiome was evaluated. We included 194 healthy subjects (134 females, 63 ± 7 years, BMI 25.1 ± 4.0 kg/m²) in a randomized, controlled, prospective, cross-over study. Following a nut-free run-in period, subjects were randomized to two diet phases (eight weeks each); 96 subjects first followed a walnut-enriched diet (43 g/day) and then switched to a nut-free diet, while 98 subjects followed the diets in reverse order. While consuming the walnut-enriched diet, subjects were advised to either reduce fat or carbohydrates or both to account for the additional calories. Fecal samples were collected from 135 subjects at the end of the walnut-diet and the control-diet period for microbiome analyses. The 16S rRNA gene sequencing data was clustered with a 97% similarity into Operational Taxonomic Units (OTUs). UniFrac distances were used to determine diversity between groups. Differential abundance was evaluated using the Kruskal-Wallis rank sum test. All analyses were performed using Rhea. Generalized UniFrac distance shows that walnut consumption significantly affects microbiome composition and diversity. Multidimensional scaling (metric and non-metric) indicates dissimilarities of approximately 5% between walnut and control (p = 0.02). The abundance of Ruminococcaceae and Bifidobacteria increased significantly (p < 0.02) while Clostridium sp. cluster XIVa species (Blautia; Anaerostipes) decreased significantly (p < 0.05) during walnut consumption. The effect of walnut consumption on the microbiome only marginally depended on whether subjects replaced fat, carbohydrates or both while on walnuts. Daily intake of 43 g walnuts over eight weeks significantly affects the gut microbiome by enhancing probiotic- and butyric acid-producing species in healthy individuals. Further evaluation is required to establish whether these changes are preserved during longer walnut consumption and how these are linked to the observed changes in lipid metabolism.

Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts.

Estruch, R., E. Ros, J. Salas-Salvadó, M.-I. Covas, D. Corella, F. Arós, E. Gómez-Gracia, V. Ruiz-Gutiérrez, M. Fiol, J. Lapetra, R.M. Lamuela-Raventos, L. Serra-Majem, X. Pintó, J. Basora, M.A. Muñoz, J.V. Sorlí, J.A. Martínez, M. Fitó, A. Gea, M.A. Hernán, M.A. Martínez-González, PREDIMED Study Investigators, 2018. Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts. N Engl J Med.  378(25):e34. doi: 10.1056/NEJMoa1800389. Epub 2018 Jun 13.

Background: Observational cohort studies and a secondary prevention trial have shown inverse associations between adherence to the Mediterranean diet and cardiovascular risk. MethodsIn a multicenter trial in Spain, we assigned 7447 participants (55 to 80 years of age, 57% women) who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was a major cardiovascular event (myocardial infarction, stroke, or death from cardiovascular causes). After a median follow-up of 4.8 years, the trial was stopped on the basis of a prespecified interim analysis. In 2013, we reported the results for the primary end point in the Journal. We subsequently identified protocol deviations, including enrollment of household members without randomization, assignment to a study group without randomization of some participants at 1 of 11 study sites, and apparent inconsistent use of randomization tables at another site. We have withdrawn our previously published report and now report revised effect estimates based on analyses that do not rely exclusively on the assumption that all the participants were randomly assigned. Results: A primary end-point event occurred in 288 participants; there were 96 events in the group assigned to a Mediterranean diet with extra-virgin olive oil (3.8%), 83 in the group assigned to a Mediterranean diet with nuts (3.4%), and 109 in the control group (4.4%). In the intention-to-treat analysis including all the participants and adjusting for baseline characteristics and propensity scores, the hazard ratio was 0.69 (95% confidence interval [CI], 0.53 to 0.91) for a Mediterranean diet with extra-virgin olive oil and 0.72 (95% CI, 0.54 to 0.95) for a Mediterranean diet with nuts, as compared with the control diet. Results were similar after the omission of 1588 participants whose study-group assignments were known or suspected to have departed from the protocol. Conclusions: In this study involving persons at high cardiovascular risk, the incidence of major cardiovascular events was lower among those assigned to a Mediterranean diet supplemented with extra-virgin olive oil or nuts than among those assigned to a reduced-fat diet. (Funded by Instituto de Salud Carlos III, Spanish Ministry of Health, and others; Current Controlled Trials number, ISRCTN35739639 .).

The effects of daily intake timing of almond on the body composition and blood lipid profile of healthy adults.

Liu, Y., H.-J. Hwang, H. Ryu, Y.-S. Lee, H.-S. Kim, H. Park, 2017. The effects of daily intake timing of almond on the body composition and blood lipid profile of healthy adults. Nutrition Research and Practice. 11(6):479-486.

BACKGROUND/OBJECTIVES: Timing of almond intake during a day may result differently in the perspectives of body composition and changes of lipid profile. The current study was conducted to compare the effects of daily almond intake as a preload versus as a snack on body composition, blood lipid profile, and oxidative and inflammation indicators among young Korean adults aged 20-39 years old. SUBJECTS/METHODS: Participants were randomly assigned to one of three groups: a pre-meal almond group (PM), a snack almond group (SN) in which participants were instructed to consume 56 g of almonds either as a preload before meals or as a snack between meals, respectively, and a control group (CL) in which participants were provided high-carbohydrate iso-caloric control food. Measurements were performed at baseline, weeks 8 and 16. RESULTS: A total of 169 (M 77 / F 92) out of the 227 participants completed the study between June 2014 and June 2015 (n=58 for PM; 55 for SN; and 56 for CL). A significant decrease in body fat mass was observed in the PM group at both weeks 8 and 16 compared with the CL. There were significant intervention effects on changes of body fat mass (P=0.025), body fat percentages (P=0.019), and visceral fat levels (P<0.001). Consuming almonds as a daily snack reduced the levels of total cholesterol (P=0.043) and low-density lipoprotein (LDL) cholesterol (P=0.011) without changing high-density lipoprotein (HDL) cholesterol compared with the CL. CONCLUSION: Almond consumption as a preload modified body fat percentages, whereas snacking on almonds between meals improved blood lipid profiles.

Effect of nut consumption on vascular endothelial function: A systematic review and meta-analysis of randomized controlled trials.

Xiao, Y., W. Huang, C. Peng, J. Zhang, C. Wong, J.H. Kim, E.-K. Yeoh, 2017. Effect of nut consumption on vascular endothelial function: A systematic review and meta-analysis of randomized controlled trials. Clinical Nutrition. http://dx.doi.org/10.1016/j.clnu.2017.04.011

Objective: Nut consumption has consistently been found to be associated with a reduced risk of cardiovascular diseases (CVD) and mortality in prospective studies. However, its effect on endothelial function, a prognostic marker of CVD, is still controversial in clinical trials. This meta-analysis of randomized controlled trials (RCTs) aimed to quantitatively assess the effect of nuts on vascular endothelial function. Methods: Major electronic databases were searched for published RCTs that reported the effect of nuts on flow mediated dilation (FMD) as a measurement of endothelial function in the adult population (age eighteen years or over). We calculated the pooled estimates of weighted mean differences (WMDs) and their 95% confidence intervals (CIs) by using random-effects models. Results: A total of nine papers (10 trials) involving 374 participants were included. The pooled estimates found that nut consumption significantly improved FMD (WMD: 0.41%; 95% CI: 0.18%, 0.63%; P = 0.001). Moderate and marginally significant heterogeneity was observed among the studies (I2 = 39.5%, P = 0.094). Subgroup analyses indicated that walnuts significantly improved FMD (WMD: 0.39%; 95% CI: 0.16%, 0.63%; P = 0.001). In addition, nut consumption had a significant effect on FMD in the trials with study duration <18 weeks, nut dose <67 g/d, or subjects with baseline FMD ≥8.6%. Conclusions: Nut consumption significantly improved endothelial function. However, the beneficial effect was limited to walnuts. More studies examining the effect of other nuts on endothelial function are needed in the future.

Inclusion of almonds in a cholesterol-lowering diet improves plasma HDL subspecies and cholesterol efflux to serum in normal-weight individuals with elevated LDL cholesterol.

Berryman, C.E, J.A. Fleming, P.M. Kris-Etherton, 2017. Inclusion of almonds in a cholesterol-lowering diet improves plasma HDL subspecies and cholesterol efflux to serum in normal-weight individuals with elevated LDL cholesterol. J. Nutr. 147(8). doi: 10.3945/jn.116.245126.

Background: Almonds may increase circulating HDL cholesterol when substituted for a high-carbohydrate snack in an isocaloric diet, yet little is known about the effects on HDL biology and function. Objective: The objective was to determine whether incorporating 43 g almonds/d in a cholesterol-lowering diet would improve HDL subspecies and function, which were secondary study outcomes. Methods: In a randomized, 2-period, crossover, controlled-feeding study, a diet with 43 g almonds/d (percentage of total energy: 51% carbohydrate, 16% protein, and 32% total and 8% saturated fat) was compared with a similar diet with an isocaloric muffin substitution (58% carbohydrate, 15% protein, and 26% total and 8% saturated fat) in men and women with elevated LDL cholesterol. Plasma HDL subspecies and cholesterol efflux from J774 macrophages to human serum were measured at baseline and after each diet period. Diet effects were examined in all participants (n = 48) and in normal weight (body mass index: <25; n = 14) and overweight or obese (≥25; n = 34) participants by using linear mixed models. Results: The almond diet, compared with the control diet, increased α-1 HDL [mean ± SEM: 26.7 ± 1.5 compared with 24.3 ± 1.3 mg apolipoprotein A-I (apoA-I)/dL; P = 0.001]. In normal-weight participants, the almond diet, relative to the control diet, increased a-1 HDL (33.7 6 3.2 compared with 28.4 ± 2.6 mg apoA-I/dL), the α-1 to pre–β-1 ratio [geometric mean (95%CI): 4.3 (3.3, 5.7) compared with 3.1 (2.4,4.0)], and non–ATP-binding cassette transporter A1 cholesterol efflux (8.3% ± 0.4% compared with 7.8% ± 0.3%) and decreased pre–β-2 (3.8 ± 0.4 compared with 4.6 ± 0.4 mg apoA-I/dL) and α-3 (23.5 ± 0.9 compared with 26.9 ± 1.1 mg apoA-I/dL) HDL (P < 0.05). No diet effects were observed in the overweight or obese group. Conclusions: Substituting almonds for a carbohydrate-rich snack within a lower-saturated-fat diet may be a simple strategy to maintain a favorable circulating HDL subpopulation distribution and improve cholesterol efflux in normal-weight individuals with elevated LDL cholesterol.