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Research Nut: Walnuts

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. 00:1–9.

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.

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.

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 oxylipinlevels (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.

Effects of 2-Year walnut-supplemented diet on inflammatory biomarkers.

Cofán, M., S. Rajaram, A. Sala-Vila, C. Valls-Pedret, M. Serra-Mir, I. Roth, T.M. Freitas-Simoes, E. Bitok, J. Sabaté, E. Ros, 2020.  Effects of 2-Year walnut-supplemented diet on inflammatory biomarkers. J Am Coll Cardiol. 76(19):2282–2284

Robust epidemiological evidence suggests that regular nut consumption is associated with lower cardiovascular disease (CVD) risk. As summarized in a recent meta-analysis of 19 prospective studies (1),when  comparing extreme quantiles of total nut consumption (2.5 to 28 g/day), total CVD and CVD mortality were  15% and 23% lower, respectively. Walnut consumption independent from other nutsrevealed similar inverse associations with CVD in 3 studies

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.

Dietary walnut as food factor to rescue from NSAID-induced gastrointestinal mucosal damages.

An, J.M., E.H. Kim, H. Lee, H.J. Lee, K.B. Hahm, 2020. Dietary walnut as food factor to rescue from NSAID-induced gastrointestinal mucosal damages. Arch Biochem Biophys. 689:108466. doi: 10.1016/j.abb.2020.108466. Epub 2020 Jun 23.

Nuclear factor erythroid-derived 2-like 2 (Nrf-2) is transcription factor implicated in the antioxidant response element-mediated induction of endogenous antioxidant enzyme such as heme oxygenase-1 (HO-1), glutamatecysteine ligase, and NAD(P)H quinone dehydrogenase 1, among which HO-1 is an enzyme catalyzing the degradation of heme.producing biliverdin, ferrous iron, and carbon monoxide. In the stomach, as much as regulating gastric acid secretions, well-coordinated establishment of defense system stands for maintaining gastric integrity. In previous study, author et al. for the first time discovered HO-1 induction was critical in affording faithful gastric defense against various irritants including Helicobacter pylori infection, stress, alcohol, nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, and toxic bile acids. In this review article, we can add the novel evidence that dietary walnut intake can be reliable way to rescue from NSAIDs-induced gastrointestinal damages via the induction of HO-1 transcribed with Nrf-2 through specific inactivation of Keap-1. From molecular exploration to translational animal model of indomethacin-induced gastrointestinal damages, significant induction of HO-1 contributed to rescuing from damages. In addition to HO-1 induction action relevant to walnut, we added the description the general actions of walnut extracts or dietary intake of walnut regarding cytoprotection and why we have focused on to NSAID damages.

Profiling anticancer and antioxidant activities of phenolic compounds present in Black Walnuts (Juglans nigra) using a high-throughput screening approach.

Ho, K.-V., A. Roy, S. Foote, P.H. Vo, N. Lall, C.-H. Lin, 2020. Profiling anticancer and antioxidant activities of phenolic compounds present in Black Walnuts (Juglans nigra) using a high-throughput screening approach. Molecules. 25, 4516; doi:10.3390/molecules25194516

Our recent studies have demonstrated multiple health-promoting benefits from black walnut kernels. These biological functions of black walnuts are likely associated with their bioactive constituents. Characterization of phenolic compounds found in black walnut could point out underexplored bioactive activities of black walnut extracts and promote the development of novel applications of black walnut and its by-products. In the present study, we assessed bioactivity profiles of phenolic compounds identified in the kernels of black walnuts using a high-throughput screening (HTS) approach. Black walnut phenolic compounds were evaluated in terms of their total antioxidant capacity, antioxidant response element (ARE) induction, and anticancer activities. The anticancer activities were identified by evaluating the effects of the phenolic compounds on the growth of the tumorigenic alveolar epithelial cells (A549) and non-tumorigenic lung fibroblast cells (MRC-5). Out of 16 phenolic compounds tested, several compounds (penta-O-galloyl-β-d-glucose, epicatechin gallate, quercetin, (–)-epicatechin, rutin, quercetin 3-β-d-glucoside, gallic acid, (+)-catechin, ferulic acid, syringic acid) exerted antioxidant activities that were significantly higher compared to Trolox, which was used as a control. Two phenolic compounds, penta-O-galloyl-β-d-glucose and quercetin 3-β-d-glucoside, exhibited antiproliferative activities against both the tumorigenic alveolar epithelial cells (A549) and non-tumorigenic lung fibroblast cells (MRC-5). The antioxidant activity of black walnut is likely driven not only by penta-O-galloyl-β-d-glucose but also by a combination of multiple phenolic compounds. Our findings suggested that black walnut extracts possibly possess anticancer activities and supported that penta-O-galloyl-β-d-glucose could be a potential bioactive agent for the cosmetic and pharmaceutical industries.

Association of total nut, tree nut, peanut, and peanut butter consumption with cancer incidence and mortality: A comprehensive systematic review and dose-response meta-analysis of observational studies.

Naghshi, S., M. Sadeghian, M. Nasiri, S. Mobarak, M. Asadi, O. Sadeghi, 2020. Association of total nut, tree nut, peanut, and peanut butter consumption with cancer incidence and mortality: A comprehensive systematic review and dose-response meta-analysis of observational studies. Adv Nutr. 0:1–16.

Data on the association of nut intake with risk of cancer and its mortality are conflicting. Although previous meta-analyses summarized available findings in this regard, some limitations may distort their findings. Moreover, none of these meta-analyses examined the dose-response associations of total nut intake with the risk of specific cancers as well as associations between specific types of nuts and cancer mortality. Therefore, this study aimed to summarize available findings on the associations of total nut (tree nuts and peanuts), tree nut (walnuts, pistachios, macadamia nuts, pecans, cashews, almonds, hazelnuts, and Brazil nuts), peanut (whole peanuts without considering peanut butter), and peanut butter consumption with risk of cancer and its mortality by considering the above-mentioned points. We searched the online databases until March 2020 to identify eligible articles. In total, 43 articles on cancer risk and 9 articles on cancer mortality were included in the current systematic review and meta-analysis. The summary effect size (ES) for risk of cancer, comparing the highest with lowest intakes of total nuts, was 0.86 (95% CI: 0.81, 0.92, P < 0.001, I2 = 58.1%; P < 0.01), indicating a significant inverse association. Such a significant inverse association was also seen for tree nut intake (pooled ES: 0.87, 95% CI: 0.78–0.96, P < 0.01, I2 = 15.8%; P = 0.28). Based on the dose-response analysis, a 5-g/d increase in total nut intake was associated with 3%, 6%, and 25% lower risks of overall, pancreatic, and colon cancers, respectively. In terms of cancer mortality, we found 13%, 18%, and 8% risk reductions with higher intakes of total nuts, tree nuts, and peanuts, respectively. In addition, a 5-g/d increase in total nut intake was associated with a 4% lower risk of cancer mortality. In conclusion, our findings support the protective association between total nut and tree nut intake and the risk of cancer and its mortality.

Metabolic syndrome features and excess weight were inversely associated with nut consumption after 1-year follow-up in the PREDIMED-Plus study.

Julibert, A., M. del Mar Bibiloni, L. Gallardo-Alfaro, M. Abbate, M.Á. Martínez-González, J. Salas-Salvadó, D. Corella, M. Fitó, J.A. Martínez, Á.M. Alonso-Gómez, J. Wärnberg, J. Vioque, D. Romaguera, J. Lopez-Miranda, R. Estruch, F.J. Tinahones, J. Lapetra, L. Serra-Majem, N. Cano-Ibañez, V. Martín-Sánchez, X. Pintó, J.J. Gaforio, P. Matía-Martín, J. Vidal, C. Vázquez, L. Daimiel, E. Ros, C. Sayon-Orea, N. Becerra-Tomás, I.M. Gimenez-Alba, O. Castañer, I. Abete, L. Tojal-Sierra, J. Pérez-López, L. Notario-Barandiaran, A. Colom, A. Garcia-Rios, S. Castro-Barquero, R. Bernal, J.M. Santos-Lozano, C.I. Fernández-Lázaro, P. Hernández-Alonso, C. Saiz, M.D. Zomeño, M.A. Zulet, M.C. Belló-Mora, J. Basterra-Gortari, S. Canudas, A. Goday, J.A. Tur, PREDIMED-PLUS investigators, 2020. Metabolic syndrome features and excess weight were inversely associated with nut consumption after 1-year follow-up in the PREDIMED-Plus study. J Nutr. 00:1–10.

Background: High nut consumption has been previously associated with decreased prevalence of metabolic syndrome (MetS) regardless of race and dietary patterns. Objectives: The aim of this study was to assess whether changes in nut consumption over a 1-y follow-up are associated with changes in features of MetS in a middle-aged and older Spanish population at high cardiovascular disease risk. Methods: This prospective 1-y follow-up cohort study, conducted in the framework of the PREvención con DIeta MEDiterránea (PREDIMED)-Plus randomized trial, included 5800 men and women (55-75 y old) with overweight/obesity [BMI (in kg/m2) ≥27 and <40] and MetS. Nut consumption (almonds, pistachios, walnuts, and other nuts) was assessed using data from a validated FFQ. The primary outcome was the change from baseline to 1 y in features of MetS [waist circumference (WC), glycemia, HDL cholesterol, triglyceride (TG), and systolic and diastolic blood pressure] and excess weight (body weight and BMI) according to tertiles of change in nut consumption. Secondary outcomes included changes in dietary and lifestyle characteristics. A generalized linear model was used to compare 1-y changes in features of MetS, weight, dietary intakes, and lifestyle characteristics across tertiles of change in nut consumption. Results: As nut consumption increased, between each tertile there was a significant decrease in WC, TG, systolic blood pressure, weight, and BMI (P < 0.05), and a significant increase in HDL cholesterol (only in women, P = 0.044). The interaction effect between time and group was significant for total energy intake (P < 0.001), adherence to the Mediterranean diet (MedDiet) (P < 0.001), and nut consumption (P < 0.001). Across tertiles of increasing nut consumption there was a significant increase in extra virgin olive oil intake and adherence to the MedDiet; change in energy intake, on the other hand, was inversely related to consumption of nuts. Conclusions: Features of MetS and excess weight were inversely associated with nut consumption after a 1-y follow-up in the PREDIMED-Plus study cohort. This trial was registered at isrctn.com as ISRCTN89898870.