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Mechanisms underlying the cardiometabolic protective effect of walnut consumption in obese subjects: a cross‐over, randomized, double‐blinded, controlled inpatient physiology study.

Tuccinardi, D., O.M. Farr, J. Upadhyay, S.M. Oussaada, M.I. Klapa, M. Candela, S. Rampelli, S. Lehoux, I. Lázaro, A. Sala‐Vila, P. Brigidi, R.D. Cummings, C.S. Mantzoros, 2019. Mechanisms underlying the cardiometabolic protective effect of walnut consumption in obese subjects: a cross‐over, randomized, double‐blinded, controlled inpatient physiology study. Diabetes Obes Metab. 21(9):2086-2095.

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.

Replacing saturated fat with walnuts or vegetable oils improves central blood pressure and serum lipids in adults at risk for cardiovascular disease: a randomized controlled-feeding trial.

Tindall, A.M., K.S. Petersen, A.C. Skulas-Ray, C.K. Richter, D.N. Proctor, P.M. Kris-Etherton, 2019. Replacing saturated fat with walnuts or vegetable oils improves central blood pressure and serum lipids in adults at risk for cardiovascular disease: a randomized controlled-feeding trial. J Am Heart Assoc. 8(9):e011512. doi: 10.1161/JAHA.118.011512

Background: Walnuts have beneficial effects on cardiovascular risk factors, but it is unclear whether these effects are attributable to the fatty acid ( FA ) content, including α-linolenic acid ( ALA ), and/or bioactives. Methods and Results: A randomized, controlled, 3-period, crossover, feeding trial was conducted in individuals at risk for cardiovascular disease (n=45). Following a 2-week standard Western diet run-in (12% saturated FAs [ SFA ], 7% polyunsaturated FAs, 12% monounsaturated FAs), participants consumed 3 isocaloric weight-maintenance diets for 6 weeks each: a walnut diet ( WD ; 7% SFA , 16% polyunsaturated FAs, 3% ALA , 9% monounsaturated FAs); a walnut FA -matched diet; and an oleic acid-replaced- ALA diet (7% SFA , 14% polyunsaturated FAs, 0.5% ALA , 12% monounsaturated FAs), which substituted the amount of ALA from walnuts in the WD with oleic acid. This design enabled evaluation of the effects of whole walnuts versus constituent components. The primary end point, central systolic blood pressure, was unchanged, and there were no significant changes in arterial stiffness. There was a treatment effect ( P=0.04) for central diastolic blood pressure; there was a greater change following the WD versus the oleic acid-replaced-ALA diet (-1.78±1.0 versus 0.15±0.7 mm Hg, P=0.04). There were no differences between the WD and the walnut fatty acid-matched diet (-0.22±0.8 mm Hg, P=0.20) or the walnut FA-matched and oleic acid-replaced-ALA diets ( P=0.74). The WD significantly lowered brachial and central mean arterial pressure. All diets lowered total cholesterol, LDL (low-density lipoprotein) cholesterol, HDL (high-density lipoprotein) cholesterol, and non- HDL cholesterol. Conclusions: Cardiovascular benefits occurred with all moderate-fat, high-unsaturated-fat diets. As part of a low- SFA diet, the greater improvement in central diastolic blood pressure following the WD versus the oleic acid-replaced-ALA diet indicates benefits of walnuts as a whole-food replacement for SFA.

Walnuts and vegetable oils containing oleic acid differentially affect the gut microbiota and associations with cardiovascular risk factors: Follow-up of a randomized, controlled, feeding trial in adults at risk for cardiovascular disease.

Tindall, A.M., C.J. McLimans, K.S. Petersen, P.M. Kris-Etherton, R. Lamendella, 2019. Walnuts and vegetable oils containing oleic acid differentially affect the gut microbiota and associations with cardiovascular risk factors: Follow-up of a randomized, controlled, feeding trial in adults at risk for cardiovascular disease. J Nutr. 150(4):806-817.

Background: It is unclear whether the favorable effects of walnuts on the gut microbiota are attributable to the fatty acids, including α-linolenic acid (ALA), and/or the bioactive compounds and fiber. Objective: This study examined between-diet gut bacterial differences in individuals at increased cardiovascular risk following diets that replace SFAs with walnuts or vegetable oils.Methods: Forty-two adults at cardiovascular risk were included in a randomized, crossover, controlled-feeding trial that provided a 2-wk standard Western diet (SWD) run-in and three 6-wk isocaloric study diets: a diet containing whole walnuts (WD; 57-99 g/d walnuts; 2.7% ALA), a fatty acid-matched diet devoid of walnuts (walnut fatty acid-matched diet; WFMD; 2.6% ALA), and a diet replacing ALA with oleic acid without walnuts (oleic acid replaces ALA diet; ORAD; 0.4% ALA). Fecal samples were collected following the run-in and study diets to assess gut microbiota with 16S rRNA sequencing and Qiime2 for amplicon sequence variant picking. Results: Subjects had elevated BMI (30 ± 1 kg/m2), blood pressure (121 ± 2/77 ± 1 mmHg), and LDL cholesterol (120 ± 5 mg/dL). Following the WD, Roseburia [relative abundance (RA) = 4.2%, linear discriminant analysis (LDA) = 4], Eubacterium eligensgroup (RA = 1.4%, LDA = 4), LachnospiraceaeUCG001 (RA = 1.2%, LDA = 3.2), Lachnospiraceae UCG004 (RA = 1.0%, LDA = 3), and Leuconostocaceae (RA = 0.03%, LDA = 2.8) were most abundant relative to taxa in the SWD (P ≤ 0.05 for all). The WD was also enriched in Gordonibacter relative to the WFMD. Roseburia (3.6%, LDA = 4) and Eubacterium eligensgroup (RA = 1.5%, LDA = 3.4) were abundant following the WFMD, and Clostridialesvadin BB60group (RA = 0.3%, LDA = 2) and gutmetagenome (RA = 0.2%, LDA = 2) were most abundant following the ORAD relative to the SWD (P ≤ 0.05 for all). Lachnospiraceae were inversely correlated with blood pressure and lipid/lipoprotein measurements following the WD. Conclusions: The results indicate similar enrichment of Roseburia following the WD and WFMD, which could be explained by the fatty acid composition. Gordonibacter enrichment and the inverse association between Lachnospiraceae and cardiovascular risk factors following the WD suggest that the gut microbiota may contribute to the health benefits of walnut consumption in adults at cardiovascular risk. This trial was registered at clinicaltrials.gov as NCT02210767.

Relationship between long‐chain omega‐3 polyunsaturated fatty acid intake and ankle brachial index, pulse wave velocity and resting heart rate in a sample of overweight adults: A secondary analysis of baseline data in the HealthTrack study.

Senevirathne, A., E. Neale, G. Peoples, L. Tapsell, 2019. Relationship between long‐chain omega‐3 polyunsaturated fatty acid intake and ankle brachial index, pulse wave velocity and resting heart rate in a sample of overweight adults: A secondary analysis of baseline data in the HealthTrack study. Nutr Diet. 76(1):95-103.

Aim: The present study aimed to explore the association between dietary long-chain omega-3 polyunsaturated fatty acid (LCn3PUFA) intake and cardiovascular risk indicators (ankle brachial index, resting heart rate and brachial-ankle pulse wave velocity) in a clinical sample of overweight and obese participants volunteering for a weight loss trial. Methods: This was a secondary analysis of baseline data from the HealthTrack study (n = 351). LCn3PUFA intake was calculated via a diet history and the association with ankle brachial index, resting heart rate and brachio-ankle pulse wave velocity was explored using linear regression after controlling for covariates. Results: LCn3PUFA intake was inversely associated with ankle brachial index (R(2) change = 0.021, F change (1, 339) = 8.864, P < 0.05) and resting heart rate (R(2) change = 0.014, F change (1, 342) = 5.337, P < 0.05) but not with brachio-ankle pulse wave velocity (R(2) change = 0.001, F change (1, 339) = 0.725, P > 0.05). Conclusions: In this clinical sample of overweight adults, LCn3PUFA consumption was significantly associated with a lower resting heart rate, adding to the current evidence on the potential benefits of LCn3PUFA consumption. It also supports the value of targeting a diet rich in this nutrient when planning future dietetic approaches. Relationships with ankle brachial index and pulse wave velocity require further investigation. Future research should assess the effect of changes in dietary LCn3PUFA intake on novel cardiovascular risk indicators.