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Research Nut: Walnuts

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.

Energy extraction from nuts: walnuts, almonds, pistachios.

McArthur, B., R. Mattes, 2020. Energy extraction from nuts: walnuts, almonds, pistachios. Br J Nutr. 123(4):361-371.

The bioaccessibility of fat has implications for satiety and postprandial lipidemia. The prevailing view holds that the integrity of plant cell wall structure is the primary determinant of energy and nutrient extraction from plant cells as they pass through the gastrointestinal tract. However, comparisons across nuts (walnuts, almonds, pistachios) with varying physical properties do not support this view. In this study, masticated samples of three nuts from healthy adults were exposed to a static model of gastric digestion followed by simulated intestinal digestion. Primary outcomes were particle size and lipid release at each phase of digestion. Walnuts produced a significantly larger particle size post-mastication compared to almonds. Under gastric and intestinal conditions, the particle size was larger for walnuts compared to pistachios and almonds (P<0.05). However, the masticated and digesta particle sizes were not related to the integrity of cell walls nor lipid release. The total lipid release was comparable between nuts after the in vitro intestinal phase (P>0.05). Microstructural examination showed ruptured and fissured cell walls that would allow digestion of cellular contents and this may be governed by internal cellular properties such as oil body state. Furthermore, the cell walls of walnuts tend to rupture rather than separate and as walnut tissue passes through the gastrointestinal track, lipids tend to coalesce reducing digestion efficiency.

Circulating omega-3 fatty acids and incident adverse events in patients with acute myocardial infarction.

Lázaro, I., F. Rueda, G. Cediel, E. Ortega, C. García-García, A. Sala-Vila, A. Bayés-Genís, 2020. Circulating omega-3 fatty acids and incident adverse events in patients with acute myocardial infarction. J Am Coll Cardiol. 76(18):2089-2097.

Background: Dietary omega-3 eicosapentaenoic acid (EPA) has multiple cardioprotective properties. The proportion of EPA in serum phosphatidylcholine (PC) mirrors dietary EPA intake during previous weeks. Circulating EPA in ST-segment elevation myocardial infarction (STEMI) relates to smaller infarct size and preserved long-term ventricular function. Objectives: The authors investigated whether serum-PC EPA (proxy for marine omega-3 consumption) levels at the time of STEMI were associated with a lower incidence of major adverse cardiovascular events (MACE), all-cause mortality, and readmission for cardiovascular (CV) causes at 3 years’ follow-up. We also explored the association of alpha-linolenic acid (ALA, proxy for vegetable omega-3 intake) with all-cause mortality and MACE. Methods The authors prospectively included 944 consecutive patients with STEMI (mean age 61 years, 209 women) undergoing primary percutaneous coronary intervention. We determined serum-PC fatty acids with gas chromatography. Results During follow-up, 211 patients had MACE, 108 died, and 130 were readmitted for CV causes. A Cox proportional hazards model adjusted for known clinical predictors showed that serum-PC EPA at the time of STEMI was inversely associated with both incident MACE and CV readmission (hazard ratio [HR]: 0.76; 95% confidence interval [CI]: 0.62 to 0.94, and HR: 0.74; 95% CI: 0.58 to 0.95, respectively, for a 1-standard deviation [SD] increase). Serum-PC ALA was inversely related to all-cause mortality (HR: 0.65; 95% CI: 0.44 to 0.96, for a 1-SD increase). Conclusions: Elevated serum-PC EPA and ALA levels at the time of STEMI were associated with a lower risk of clinical adverse events. Consumption of foods rich in these fatty acids might improve the prognosis of STEMI.

Walnut consumption, plasma metabolomics, and risk of Type 2 diabetes and cardiovascular disease.

Guasch-Ferré, M., P. Hernández-Alonso, J.P. Drouin-Chartier, M. Ruiz-Canela, C. Razquin, E. Toledo, J. Li, C. Dennis, C. Wittenbecher, D. Corella, R. Estruch, M. Fitó, E. Ros, N. Babio, S.N. Bhupathiraju, C.B. Clish, L. Liang, M.A. Martínez-González, F.B. Hu, J. Salas-Salvadó, 2020. Walnut consumption, plasma metabolomics, and risk of Type 2 diabetes and cardiovascular disease. J Nutr. doi: 10.1093/jn/nxaa374.

Background: Walnut consumption is associated with lower risk of type 2 diabetes (T2D) and cardiovascular disease (CVD). However, it is unknown whether plasma metabolites related to walnut consumption are also associated with lower risk of cardiometabolic diseases. Objectives: The study aimed to identify plasma metabolites associated with walnut consumption and evaluate the prospective associations between the identified profile and risk of T2D and CVD. Methods: The discovery population included 1833 participants at high cardiovascular risk from the PREvención con DIeta MEDiterránea (PREDIMED) study with available metabolomics data at baseline. The study population included 57% women (baseline mean BMI (in kg/m2): 29.9; mean age: 67 y). A total of 1522 participants also had available metabolomics data at year 1 and were used as the internal validation population. Plasma metabolomics analyses were performed using LC-MS. Cross-sectional associations between 385 known metabolites and walnut consumption were assessed using elastic net continuous regression analysis. A 10-cross-validation (CV) procedure was used, and Pearson correlation coefficients were assessed between metabolite weighted models and self-reported walnut consumption in each pair of training–validation data sets within the discovery population. We further estimated the prospective associations between the identified metabolite profile and incident T2D and CVD using multivariable Cox regression models. Results: A total of 19 metabolites were significantly associated with walnut consumption, including lipids, purines, acylcarnitines, and amino acids. Ten-CV Pearson correlation coefficients between self-reported walnut consumption and the plasma metabolite profile were 0.16 (95% CI: 0.11, 0.20) in the discovery population and 0.15 (95% CI: 0.10, 0.20) in the validation population. The metabolite profile was inversely associated with T2D incidence (HR per 1 SD: 0.83; 95% CI: 0.71, 0.97; P = 0.02). For CVD incidence, the HR per 1-SD was 0.71 (95% CI: 0.60, 0.85; P < 0.001). Conclusions: A metabolite profile including 19 metabolites was associated with walnut consumption and with a lower risk of incident T2D and CVD in a Mediterranean population at high cardiovascular risk.

A walnut diet in combination with enriched environment improves cognitive function and affects lipid metabolites in brain and liver of aged NMRI mice.

Esselun, C., B. Dilberger, C.V. Silaidos, E. Koch, N.H. Schebb, G.P. Eckert, 2020. A walnut diet in combination with enriched environment improves cognitive function and affects lipid metabolites in brain and liver of aged NMRI mice. Neuromolecular Med. doi:10.1007/s12017-020-08639-7.

This in vivo study aimed to test if a diet enriched with 6% walnuts alone or in combination with physical activity supports healthy ageing by changing the oxylipin profile in brain and liver, improving motor function, cognition, and cerebral mitochondrial function. Female NMRI mice were fed a 6% walnut diet starting at an age of 12 months for 24 weeks. One group was additionally maintained in an enriched environment, one group without intervention served as control. After three months, one additional control group of young mice (3 weeks old) was introduced. Motor and cognitive functions were measured using Open Field, Y-Maze, Rotarod and Passive Avoidance tests. Lipid metabolite profiles were determined using RP-LC-ESI(-)-MS/MS in brain and liver tissues of mice. Cerebral mitochondrial function was characterized by the determination of ATP levels, mitochondrial membrane potential and mitochondrial respiration. Expression of genes involved with mito- and neurogenesis, inflammation, and synaptic plasticity were determined using qRT-PCR. A 6% walnut-enriched diet alone improved spatial memory in a Y-Maze alternation test (p < 0.05) in mice. Additional physical enrichment enhanced the significance, although the overall benefit was virtually identical. Instead, physical enrichment improved motor performance in a Rotarod experiment (p* < 0.05) which was unaffected by walnuts alone. Bioactive oxylipins like hydroxy-polyunsaturated fatty acids (OH-PUFA) derived from linoleic acid (LA) were significantly increased in brain (p** < 0.01) and liver (p*** < 0.0001) compared to control mice, while OH-PUFA of α-linolenic acid (ALA) could only be detected in the brains of mice fed with walnuts. In the brain, walnuts combined with physical activity reduced arachidonic acid (ARA)-based oxylipin levels (p < 0.05). Effects of walnut lipids were not linked to mitochondrial function, as ATP production, mitochondrial membrane potential and mitochondrial respiration were unaffected. Furthermore, common markers for synaptic plasticity and neuronal growth, key genes in the regulation of cytoprotective response to oxidative stress and neuronal growth were unaffected. Taken together, walnuts change the oxylipin profile in liver and brain, which could have beneficial effects for healthy ageing, an effect that can be further enhanced with an active lifestyle. Further studies may focus on specific nutrient lipids that potentially provide preventive effects in the brain.

Investigating walnut consumption and cognitive trajectories in a representative sample of older US adults.

Bishop, N., K. Zuniga, 2020. Investigating walnut consumption and cognitive trajectories in a representative sample of older US adults. Public Health Nutrition, 1-12. doi:10.1017/S1368980020001287

Objective: Existing research suggests walnut intake may be associated with better cognitive function in older adults, yet few studies utilise longitudinal data from observational studies of ageing populations. Our objective was to estimate the association between whole walnut intake and cognitive change in a representative sample of older Americans. Design: Secondary analysis of the Health and Retirement Study and Health Care and Nutrition Study. Walnut consumption was defined as a categorical measure (none, low intake (0·01–0·08 1 oz. servings per day) and moderate intake (>0·08 1 oz. servings per day)) and cognitive function was measured using the Telephone Interview for Cognitive Status. Latent growth modelling estimated the association between walnut consumption and trajectories of cognitive status over a 4-year observational period. Sensitivity analyses assessing non-random dropout and Monte Carlo power analyses were conducted to contextualise results. Setting: The USA. Participants: A sample of 3632 US adults aged 65 years and older. Results: Those reporting any walnut consumption had greater cognitive scores at baseline than those not consuming walnuts (low walnut consumption, b = 1·53, se = 0·21, P < 0·001; moderate walnut consumption, b = 2·22, se = 0·27, P < 0·001), but walnut consumption was not associated with cognitive change. Walnut consumption was positively associated with socioeconomic status and health behaviours as well as intake of nutrients identified to have neuroprotective benefits. Conclusions: We identified an association between walnut consumption and cognitive function in older adults, although we did not find that walnut consumption was protective against age-related cognitive decline.