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Research Area: Cardiovascular Health

Glucoregulatory and cardiometabolic profiles of almond vs. cracker snacking for 8 weeks in young adults: A randomized controlled trial.

Dhillon, J., M. Thorwald, N. De La Cruz, E. Vu, S.A. Asghar, Q. Kuse, L.K. Diaz Rios, R.M. Ortiz, 2018. Glucoregulatory and cardiometabolic profiles of almond vs. cracker snacking for 8 weeks in young adults: A randomized controlled trial. Nutrients. 10, 960; doi:10.3390/nu10080960

The transition to nutritional independence makes new college students vulnerable to alterations in eating patterns, which can increase the risk of cardiometabolic disorders. The aim of the study was to examine the potential benefits of almond vs. cracker snacking in improving glucoregulatory and cardiometabolic profiles in new college students. A randomized controlled, parallel-arm, 8-week intervention of 73 college students (BMI: 18–41 kg/m2) with no cardiometabolic disorders was conducted. Participants were randomized into either an almond snack group (56.7 g/day; 364 kcal; n = 38) or Graham cracker control group (77.5 g/day; 338 kcal/d; n = 35). Chronic, static changes were assessed from fasting serum/plasma samples at baseline, and after 4 and 8 weeks. Acute, dynamic effects were assessed during a 2-h oral glucose tolerance test (OGTT) at 8 weeks. Almond snacking resulted in a smaller decline in HDL cholesterol over 8 weeks (13.5% vs. 24.5%, p < 0.05), 13% lower 2-h glucose area under the curve (AUC), 34% lower insulin resistance index (IRI) and 82% higher Matsuda index (p < 0.05) during the OGTT, despite similar body mass gains over 8 weeks compared with the cracker group. In general, both almond and cracker snacking reduced fasting glucose, and LDL cholesterol. Conclusions: Incorporating a morning snack in the dietary regimen of predominantly breakfast-skipping, first-year college students had some beneficial effects on glucoregulatory and cardiometabolic health. Almond consumption has the potential to benefit postprandial glucoregulation in this cohort. These responses may be influenced by cardiometabolic risk factor status.

The effect of long-term weight-loss intervention strategies on the dynamics of pancreatic-fat and morphology: An MRI RCT study.

Tene, L., I. Shelef, D. Schwarzfuchs, Y. Gepner, A.Y. Meir, G. Tsaban, H. Zelicha, A. Bilitzky, O. Komy, N. Cohen, N. Bril, M. Rein, D. Serfaty, S. Kenigsbuch, Y. Chassidim, B. Sarusy, U. Ceglarek, M. Stumvoll, M. Blüher, J. Thiery, M.J. Stampfer, A. Rudich, I. Shai, 2018. The effect of long-term weight-loss intervention strategies on the dynamics of pancreatic-fat and morphology: An MRI RCT study. Clinical Nutrition ESPEN. 24:82-89.

Background & aims: The ability to mobilize pancreatic-fat and the meaning of decreased fat in the pancreas remain controversial. We followed the dynamics of pancreatic-fat and its morphology during various long weight-loss induced lifestyle-interventions. Methods: In isolated workplace with monitored/provided lunch, we randomly assigned healthy persons with abdominal obesity or dyslipidemia for one of two 18-month equal-caloric diets: low-fat (LF) or Mediterranean/low-carbohydrate (Med/LC, with provided 1oz walnuts/day), with or without added moderate exercise (supervised gym membership). We used magnetic-resonance-imaging to quantify pancreatic-fat and morphology. Results: At baseline, 277 eligible participants (mean age = 48 years; 88% men; pancreatic-fat = 17.4 ± 5.1%) had higher pancreatic-fat in men (17.7 ± 4.9% vs 14.9 ± 5.5% in women; p = 0.004). Following 18-month intervention (adherence = 86.3%) and moderate weight-loss (mean = −3.0 ± 5.5 kg), pancreatic-fat decreased moderately but significantly (−0.26 ± 2.18% units; p = 0.049). Med/LC diet induced a greater decrease in pancreatic-fat compared to LF (p = 0.043), and the combination of Med/LC diet + exercise exhibited the highest reduction (−0.69% units) as compared to LF diet without exercise (+0.12%units; p = 0.027 between groups). In multivariate regression models, after further adjusted for visceral adipose-tissue (ΔVAT), pancreatic-fat loss associated with both decreases in pancreatic-morphology ratio (perimeter divided by area; beta = 0.361; p < 0.001) and superficial-subcutaneous adipose-tissue loss (beta = 0.242; p = 0.001), but not with changes in intrahepatic-fat (beta = −0.034; p = 0.638). Pancreatic-fat loss associated with increased intake of polyunsaturated-fat (beta = −0.137; p = 0.032), as with improved high-density lipoprotein-cholesterol (HDL; beta = −0.156; p = 0.023) and triglycerides/HDL ratio (beta = 0.162; p = 0.015), independently of ΔVAT, but not with glycemic–control parameters (e.g. HbA1c, HOMA-IR and HOMA-beta; p > 0.2 for all). Conclusions: Pancreatic-fat loss is mainly associated with improved lipid, rather than glycemic profiles. Med/LC diet, mostly with exercise, may benefit pancreatic-fat loss. Pancreatic-morphology could serve as a biomarker of pancreatic-fat state.

Daily walnut consumption favourably changed lipid profiles among Korean subjects with higher waist circumference.

Song, E.K., Y. Liu, H.S. Kim, H. Park, 2018. Daily walnut consumption favourably changed lipid profiles among Korean subjects with higher waist circumference. Acta Scientific Nutritional Health. 2.5:21-26.

Even though many studies have shown that walnuts have beneficial effects on lipid profiles in various populations, there have been limited data on the effects of walnuts in Korean populations. We examined not only the effects of walnut intake on lipid profiles among Korean adults but also focused on the sub-classification by waist circumference (WC). 89 subjects out of 119 completed trial with daily consumption of 45 g of walnuts for 16 weeks. Blood lipid profiles including triglycerides (TG), non-HDL cholesterol (non-HDL-C), LDL cholesterol (LDL-C), total cholesterol (TC), and HDL cholesterol (HDL-C), apolipoprotein B, anthropometric measurements (WC, weight, body mass index (BMI) and blood pressure) and glucose metabolism parameters including fasting blood sugar and insulin levels were assessed. Whose WC was greater than 85 cm for female and 90 cm for male were classified as higher WC group (n=48) and others were classified as normal WC group (n=41). Blood levels of non-HDL-C, LDL-C, TC and apolipoprotein B were improved after daily consumption of 45 g of walnuts (P=0.003, P=0.011, P=0.002, and P=0.012, respectively) compared to baseline levels. Systolic blood pressure, TG, non-HDL-C, LDL-C and TC were significantly decreased in the higher WC groups (P=0.048, P=0.002, P=0.002 and P=0.001, respectively) compared to normal WC group. The results suggest that consuming 45 g of walnuts daily for 16 weeks had beneficial effects on lipid profiles in general, and these results were even much stronger among the subjects with abdominal obesity as waist circumference compared to those with non-abdominal obesity.

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. Methods: In 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 .).