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Research Nut: Walnuts

Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial.

Yaskolka M.A., E. Rinott, G. Tsaban, H. Zelicha, A. Kaplan, P. Rosen, I. Shelef, I. Youngster, A. Shalev, M. Blüher, U. Ceglarek, M. Stumvoll, K. Tuohy, C. Diotallevi, U. Vrhovsek, F. Hu, M. Stampfer, I. Shai, 2021. Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial. Gut. 0:1–11. doi:10.1136/gutjnl-2020-323106.

Objective: To examine the effectiveness of green-Mediterranean (MED) diet, further restricted in red/ processed meat, and enriched with green plants and polyphenols on non-alcoholic fatty liver disease (NAFLD), reflected by intrahepatic fat (IHF) loss. Design: For the DIRECT-PLUS 18-month randomized clinical trial, we assigned 294 participants with abdominal obesity/dyslipidaemia into healthy dietary guidelines (HDG), MED and green-MED weight-loss diet groups, all accompanied by physical activity. Both isocaloric MED groups consumed 28 g/day walnuts (+440 mg/day polyphenols provided). The green-MED group further consumed green tea (3–4 cups/day) and Mankai (a Wolffia globosa aquatic plant strain; 100 g/ day frozen cubes) green shake (+1240 mg/day total polyphenols provided). IHF% 18-month changes were quantified continuously by proton magnetic resonance spectroscopy (MRS). Results: Participants (age=51 years; 88% men; body mass index=31.3 kg/m2; median IHF%=6.6%; mean=10.2%; 62% with NAFLD) had 89.8% 18 month retention-rate, and 78% had eligible follow-up MRS. Overall, NAFLD prevalence declined to: 54.8% (HDG), 47.9% (MED) and 31.5% (green-MED), p=0.012 between groups.  Despite similar moderate weight-loss in both MED groups, green-MED group achieved almost double IHF% loss (−38.9% proportionally), as compared with MED (−19.6% proportionally; p=0.035 weight loss adjusted) and HDG (−12.2% proportionally; p<0.001). After 18 months, both MED groups had significantly higher total plasma polyphenol levels versus HDG, with higher detection of Naringenin and 2-5-dihydroxybenzoic- acid in green-MED. Greater IHF% loss was independently associated with increased Mankai and walnuts intake, decreased red/processed meat consumption, improved serum folate and adipokines/lipids biomarkers, changes in microbiome composition (beta-diversity) and specific bacteria (p<0.05 for all). Conclusion: The new suggested strategy of green-Mediterranean diet, amplified with green plant-based proteins/polyphenols as Mankai, green tea, and walnuts, and restricted in red/processed meat can double IHF loss than other healthy nutritional strategies and reduce NAFLD in half.

Nut consumption and type 2 diabetes risk: a systematic review and meta-analysis of observational studies.

Becerra-Tomás, N., I. Paz-Graniel, P. Hernández-Alonso, D.J.A. Jenkins, C.W.C. Kendall, J.L. Sievenpiper, J. Salas-Salvadó, 2021. Nut consumption and type 2 diabetes risk: a systematic review and meta-analysis of observational studies. Am J Clin Nutr 00:1–12.

Background: Previous meta-analyses, with some methodological controversies, have assessed the relation between nut consumption and type 2 diabetes (T2D) risk and pointed to contradictory results, making desirable the performance of an updated meta-analysis. Objectives: We aimed to systematically review and meta-analyze all the published studies investigating the relations of total nuts and different types of nuts—i.e., walnuts, peanuts, peanut butter, and total tree nuts—with the prevalence and incidence of T2D. Methods: A systematic search was conducted in the PubMed and Cochrane databases through 12 August, 2020. The inverse variance method with fixed-effect models was used to pool data across studies, expressed as risk ratios (RRs) or ORs and 95% CIs for prospective cohort and cross-sectional studies, respectively. The Cochran Q test and I 2 statistics were used to test and quantify heterogeneity, respectively. Dose-response meta-analysis was also conducted. Results: Eight studies (5 prospective and 3 cross-sectional) were included in the quantitative synthesis. Meta-analyses of crosssectional studies and prospective cohort studies, comparing the highest with the lowest categories, revealed a nonsignificant association between total nut consumption and T2D. Meta-analyses of prospective cohort studies showed an inverse association between peanut butter consumption and T2D incidence (RR: 0.87; 95% CI: 0.77, 0.98; I 2 = 50.6%; Pheterogeneity = 0.16), whereas no association was observed between peanuts or tree nuts and T2D. There was no evidence of a linear dose-response or nonlinear dose-response gradient for total nut and peanut consumption in prospective cohort studies. The certainty of the evidence using NutriGrade was very low for all the exposures. Conclusions: Current results do not demonstrate an association of total nut, peanut, or tree nut consumption with T2D. Peanut butter consumption may be inversely associated with this disease. This review protocol was registered at www.crd.york.ac.uk/prospero/ as CRD42020149756.

Nut consumption for cognitive performance: A systematic review.

Theodore, L.E., N.J. Kellow, E.A. McNeil, E.O. Close, E.G. Coad, B.R. Cardoso, 2020. Nut consumption for cognitive performance: A systematic review. Adv Nutr. 00:1–16.

Diet is considered an important modifiable lifestyle factor capable of attenuating early cognitive changes in healthy older people. The inclusion of nuts in the diet has been investigated as a dietary strategy for maintenance of brain health across the lifespan. This review aimed to present up-to-date evidence regarding the association between nut intake and cognitive performance. Four databases (Ovid MEDLINE, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL) Plus, and Embase) were systematically searched from inception to April 2020. Eligible articles were interventional or observational studies in humans aged ≥18 y that measured the effects (or association) of nuts (almond, hazelnut, macadamia, pistachio, walnut, pecan, pine nut, Brazil nut, cashew, peanut) on cognitive outcomes. Out of the 2374 articles identified in the searches, 22 involving 43,793 participants met the criteria and were ultimately included in this review. Memory (immediate and delayed), attention, processing speed, executive function, and visual-spatial ability, as well as risk of mild cognitive impairment, were the outcomes investigated. Lack of consistency across the studies regarding study design, types of nut used, and cognitive outcomes measured resulted in inconsistent evidence that the regular consumption of mixed nuts has a protective effect on cognition in adults of different ages. Nonetheless, we observed that studies targeting populations with a higher risk of cognitive decline tended to find a more favorable outcome. Furthermore, homogeneous findings were observed in the studies that specifically addressed the association between walnut consumption and cognitive performance: out of the 6 studies, including 2 randomized controlled trials, only 1 did not find a positive association.

Effect of green Mediterranean diet on cardiometabolic risk; a randomised controlled trial.

Tsaban, G., A. Yaskolka Meir, E. Rinott, H. Zelicha, A. Kaplan, A. Shalev, A. Katz, A. Rudich, A. Tirosh, I. Shelef, I. Youngster, S. Lebovitz,  N. Israeli, M. Shabat, D. Brikner, E. Pupkin, M. Stumvoll, J. Thiery, U. Ceglarek, J.T. Heiker, A. Körner, K. Landgraf, M. von Bergen, M. Blüher, M.J. Stampfer, I. Shai, 2020. Effect of green Mediterranean diet on cardiometabolic risk; a randomised controlled trial. Heart. doi: 10.1136/heartjnl-2020-317802

Background: A Mediterranean diet is favourable for cardiometabolic risk. Objective To examine the residual effect of a green Mediterranean diet, further enriched with green plant-based foods and lower meat intake, on cardiometabolic risk. Methods: For the DIRECT-PLUS parallel, randomised clinical trial we assigned individuals with abdominal obesity/dyslipidaemia 1:1:1 into three diet groups: healthy dietary guidance (HDG), Mediterranean and green Mediterranean diet, all combined with physical activity. The Mediterranean diets were equally energy restricted and included 28 g/day walnuts. The green Mediterranean diet further included green tea (3–4 cups/day) and a Wolffia globosa (Mankai strain; 100 g/day frozen cubes) plant-based protein shake, which partially substituted animal protein. We examined the effect of the 6-month dietary induction weight loss phase on cardiometabolic state. Results: Participants (n=294; age 51 years; body mass index 31.3 kg/m2; waist circumference 109.7 cm; 88% men; 10 year Framingham risk score 4.7%) had a 6-month retention rate of 98.3%. Both Mediterranean diets achieved similar weight loss ((green Mediterranean −6.2 kg; Mediterranean −5.4 kg) vs the HDG group −1.5 kg; p<0.001), but the green Mediterranean group had a greater reduction in waist circumference (−8.6 cm) than the Mediterranean (−6.8 cm; p=0.033) and HDG (−4.3 cm; p<0.001) groups. Stratification by gender showed that these differences were significant only among men. Within 6 months the green Mediterranean group achieved greater decrease in low-density lipoprotein cholesterol (LDL-C; green Mediterranean −6.1 mg/dL (−3.7%), −2.3 (-0.8%), HDG −0.2 mg/dL (+1.8%); p=0.012 between extreme groups), diastolic blood pressure (green Mediterranean −7.2 mm Hg, Mediterranean −5.2 mm Hg, HDG −3.4 mm Hg; p=0.005 between extreme groups), and homeostatic model assessment for insulin resistance (green Mediterranean −0.77, Mediterranean −0.46, HDG −0.27; p=0.020 between extreme groups). The LDL-C/high-density lipoprotein cholesterol (HDL-C) ratio decline was greater in the green Mediterranean group (−0.38) than in the Mediterranean (−0.21; p=0.021) and HDG (−0.14; p<0.001) groups. High-sensitivity C-reactive protein reduction was greater in the green Mediterranean group (−0.52 mg/L) than in the Mediterranean (−0.24 mg/L; p=0.023) and HDG (−0.15 mg/L; p=0.044) groups. The green Mediterranean group achieved a better improvement (−3.7% absolute risk reduction) in the 10-year Framingham Risk Score (Mediterranean−2.3%; p=0.073, HDG−1.4%; p<0.001). Conclusions: The green MED diet, supplemented with walnuts, green tea and Mankai and lower in meat/poultry, may amplify the beneficial cardiometabolic effects of Mediterranean diet.

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, 2020. 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. 2020;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.

Walnut consumption and cardiac phenotypes: the coronary artery risk development in young adults (CARDIA) study.  

Steffen, L.M., S.Y. Yi, D. Duprez, X. Zhou, J.M. Shikany, D.R. Jacobs Jr., 2020. Walnut consumption and cardiac phenotypes: the coronary artery risk development in young adults (CARDIA) study.  Nutr Metab Cardiovasc Dis. S0939-4753(20)30381-1. doi: 10.1016/j.numecd.2020.09.001.  

Background and Aims: Observational studies and clinical trials have shown cardiovascular benefits of nut consumption, including walnuts. However, the relations of walnut consumption with systolic and diastolic function, risk factors for heart failure, are unknown.  We examined the associations of walnut consumption with cardiac structure and function parameters in black and white adults enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Methods and Results: After exclusions, the study population included 3,341 participants. Dietary intake was assessed using the CARDIA Diet History questionnaire at baseline, year 7 and year 20 exams.  Cardiac structure and function were measured by echocardiography at year 25. Multivariable linear regression evaluated the associations of walnut consumption with blood pressure (BP), heart rate, and cardiac phenotypes, adjusting for age, sex, race, lifestyle habits, and clinical characteristics. We found the majority of walnut consumers compared to non-consumers were females, whites, and more highly educated, and had lower waist circumference, diastolic BP, and heart rate, and higher diet quality score. Even though cardiac structure and function measures were generally within normal ranges among participants, walnut consumers had significantly better values for diastolic function parameters A wave, E/A ratio, septal and lateral e’ than non-consumers. Further adjustment for body mass index and diabetes status did not materially change the significance between walnut consumer groups. Systolic function parameters did not differ by walnut group.  Conclusion: Compared to non-consumers, walnut consumption is associated with better diastolic dysfunction in young to middle-aged adults.

Effects of diet-modulated autologous fecal microbiota transplantation on weight regain.

Rinott, E., I. Youngster, A.Y. Meir, G. Tsaban, H. Zelicha, A. Kaplan, D. Knights, K. Tuohy, F. Fava, M.U. Scholz, O. Ziv, E. Reuven, A. Tirosh, A. Rudich, M. Blüher, M. Stumvoll, U. Ceglarek, K. Clement, O. Koren, D.D. Wang, F.B. Hu, M.J. Stampfer, I. Shai, 2020. Effects of diet-modulated autologous fecal microbiota transplantation on weight regain. Gastroenterology. doi: https:// doi.org/10.1053/j.gastro.2020.08.041.

Background & Aims: We evaluated the efficacy and safety of diet-modulated autologous fecal microbiota transplantation (aFMT) for treatment of weight regain after the weight loss phase. Methods: In the DIRECT-PLUS weight loss trial (May 2017 through July 2018), abdominally obese or dyslipidemic participants in Israel were randomly assigned to (1) healthy dietary guidelines, (2) Mediterranean diet, and (3) green-Mediterranean diet weight-loss groups. All groups received free gym membership and physical activity guidelines. Both iso-caloric Mediterranean groups consumed 28g/day walnuts (+440mg/d polyphenols provided). The green-Mediterranean dieters further consumed green tea (3-4 cups/day) and a Wolffia-globosa (Mankai strain;100g/day) green shake (+800mg/day polyphenols provided). After 6 months (weight-loss phase), 90 eligible participants (mean age, 52 years; mean weight loss, 8.3 kg) provided a fecal sample that was processed into aFMT by frozen, opaque and odorless capsules. The participants were then randomly assigned to groups that received 100 capsules containing their own fecal microbiota or placebo until month 14. The primary outcome was regain of the lost weight over the expected weight regain phase (months 6–14). Secondary outcomes were gastrointestinal symptoms, waist-circumference, glycemic status and changes in the gut microbiome, as measured by metagenomic sequencing and 16s-rRNA. We validated the results in a parallel in-vivo study of mice specifically fed with Mankai, as compared to control chow diet. Results: Of the 90 participants in the aFMT trial, 96% ingested at least 80 of 100 oral aFMT or placebo frozen capsules over the transplantation period. No aFMTrelated adverse events or symptoms were observed. For the primary outcome, although no significant differences in weight regain were observed among the participants in the different lifestyle interventions during months 6–14 (aFMT, 30.4% vs. placebo, 40.6%;P=.28), aFMT significantly attenuated weight regain in the green Mediterranean group (aFMT, 17.1%, vs placebo, 50%; P=.02), but not in the dietary guidelines (P=.57) or Mediterranean diet (P=.64) groups (P for the interaction=.03). Accordingly, aFMT attenuated waist circumference gain (aFMT, 1.89cm vs placebo, 5.05cm;P=.01) and insulin rebound (aFMT, 1.46±3.6µIU/ml vs placebo, 1.64±4.7µIU/ml;P=.04) in the green Mediterranean group but not in the dietary guidelines or Mediterranean diet (P for the interaction=.04 and .03, respectively). The green-Mediterranean diet was the only intervention to induce a significant change in microbiome composition during the weight loss phase, and to prompt preservation of weight loss-associated specific bacteria and microbial metabolic pathways (mainly microbial sugar transport) following the aFMT. In mice, Mankaimodulated aFMT in the weight loss phase, compared with control diet aFMT, significantly prevented weight regain, and resulted in better glucose tolerance, during a high-fat-diet induced regain phase (P<.05 for all). Conclusions: Autologous FMT, collected during the weight loss phase and administrated in the regain phase, might preserve weight loss and glycemic control and is associated with specific microbiome signatures. High-polyphenols, green plant-based or Mankai diet better optimizes the microbiome for an aFMT procedure.

Effect of walnut consumption on markers of blood glucose control: A systematic review and meta-analysis.

Neale, E. V. Guan, L. Tapsell, Y. Probst, 2020. Effect of walnut consumption on markers of blood glucose control: A systematic review and meta-analysis. Br J Nutr. 1‐13. doi:10.1017/S0007114520001415

Type 2 diabetes mellitus is a chronic disease increasing in global prevalence. Although habitual consumption of walnuts is associated with reduced risk of CVD, there is inconsistent evidence for the impact of walnut consumption on markers of glycaemic control. This systematic review and meta-analysis aimed to examine the effect of walnut consumption on markers of blood glucose control. A systematic search of Medline, PubMed, CINAHL and Cochrane databases (to 2 March 2019) was conducted. Inclusion criteria were randomised controlled trials conducted with adults which assessed the effect of walnut consumption on fasting blood glucose and insulin, glycated Hb and homeostatic model assessment of insulin resistance. Random effects meta-analyses were conducted to assess the weighted mean differences (WMD) for each outcome. Risk of bias in studies was assessed using the Cochrane Risk of Bias tool 2.0. Sixteen studies providing eighteen effect sizes were included in the review. Consumption of walnuts did not result in significant changes in fasting blood glucose levels (WMD: 0·331 mg/dl; 95 % CI −0·817, 1·479) or other outcome measures. Studies were determined to have either ‘some concerns’ or be at ‘high risk’ of bias. There was no evidence of an effect of walnut consumption on markers of blood glucose control. These findings suggest that the known favourable effects of walnut intake on CVD are not mediated via improvements in glycaemic control. Given the high risk of bias observed in the current evidence base, there is a need for further high-quality randomised controlled trials.

Walnut polyphenol extracts inhibit Helicobacter pylori-induced STAT3Tyr705 phosphorylation through activation of PPAR-γ and SOCS1 induction.

Park, J.M., J.M. An, Y.M. Han, Y.J. Surh, S.J. Hwang, S.J. Kim, K.B. Hahm, 2020. Walnut polyphenol extracts inhibit Helicobacter pylori-induced STAT3Tyr705 phosphorylation through activation of PPAR-γ and SOCS1 induction. J Clin Biochem Nutr.67(3):248-256.

The health beneficial effects of walnut plentiful of n-3 polyunsaturated fatty acid had been attributed to its anti-inflammatory and anti-oxidative properties against various clinical diseases. Since we have published Fat-1 transgenic mice overexpressing 3-desaturase significantly mitigated Helicobacter pylori (H. pylori)-associated gastric pathologies including rejuvenation of chronic atrophic gastritis and prevention of gastric cancer, in this study, we have explored the underlying molecular mechanisms of walnut against H. pylori infection. Fresh walnut polyphenol extracts (WPE) were found to suppress the phosphorylation and nuclear translocation of signal transducer and activator of transcription 3 (STAT3) induced by H. pylori infection in RGM-1 gastric mucosal cells. Notably, H. pylori infection significantly decreased suppressor of cytokine signaling 1 (SOCS1), but WPE induced expression of SOCS1, by which the suppressive effect of walnut extracts on STAT3Tyr705 phosphorylation was not seen in SOCS1 KO cells. WPE induced significantly increased nuclear translocation nuclear translocation of PPAR-γ in RGM1 cells, by which PPAR-γ KO inhibited transcription of SOCS1 and suppressive effect of WPE on p-STAT3Tyr705 was not seen. WPE inhibited the expression of c-Myc and IL-6/IL-6R signaling, which was attenuated in the RGM1 cells harboring SOCS1 specific siRNA. Conclusively, WPE inhibits H. pylori-induced STAT3 phosphorylation in a PPAR-γ and SOCS1-dependent manner.

Identifying usual food choice combinations with walnuts: Analysis of a 2005-2015 clinical trial cohort of overweight and obese adults.

Guan, V., E. Neale, L. Tapsell, Y. Probst, 2020. Identifying usual food choice combinations with walnuts: Analysis of a 2005-2015 clinical trial cohort of overweight and obese adults. Front Nutr. 7:149. doi: 10.3389/fnut.2020.00149.

Consumption of nuts has been associated with a range of favorable health outcomes. Evidence is now emerging to suggest that walnuts may also play an important role in supporting the consumption of a healthy dietary pattern. However, limited studies have explored how walnuts are eaten at different meal occasions. The aim of this study was to explore the food choices in relation to walnuts at meal occasions as reported by a sample of overweight and obese adult participants of weight loss clinical trials. Baseline usual food intake data were retrospectively pooled from four food-based clinical trials (n=758). A nut-specific food composition database was applied to determine walnut consumption within the food intake data. The Apriori algorithm of association rules was used to identify food choices associated with walnuts at different meal occasions using a nested hierarchical food group classification system. The proportion of participants who were consuming walnuts was 14.5% (n=110). The median walnut intake was 5.14 (IQR 1.10 – 11.45) grams per day. A total of 128 food items containing walnuts were identified for walnut consumers. The proportion of participants who reported consuming unsalted raw walnut was 80.5% (n=103). There were no identified patterns to food choices in relation to walnut at the breakfast, lunch or dinner meal occasions. A total of 24 clusters of food choices related to walnuts were identified at others (meals). By applying a novel food composition database, the present study was able to map the precise combinations of foods associated with walnuts intakes at mealtimes using data mining. This study offers insights into the role of walnuts for the food choices of overweight adults and may support guidance and dietary behavior change strategies.