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Research Nut: Walnuts

Angiopoietin-1 protects 3T3-L1 preadipocytes from saturated fatty acid-induced cell death.

Son, Y., J.M. Cox, J.L. Stevenson, J.A. Cooper, C.M. Paton, 2020. Angiopoietin-1 protects 3T3-L1 preadipocytes from saturated fatty acid-induced cell death. Nutr Res. 76:20-28.

Cross talk between endothelial cells and adipocytes is vital to adipocyte functions, but little is known about the mechanisms or factors controlling the process. Angiogenesis is a critical component linking the endothelium to healthy adipogenesis, yet it is not known if or how it is involved in adipocyte physiology. Therefore, the purpose of this study was to determine the effect of angiopoietin-1 (Ang-1) and -2 (Ang-2) as well as their receptor, Tie-2, on adipocyte physiology. 3T3-L1 pre- and mature adipocytes were found to express Ang-1, Ang-2, and Tie-2, which decrease upon polyunsaturated fatty acid treatment. Furthermore, 3T3-L1 cells treated with recombinant Ang-1 or Ang-2 increased expression of the antiapoptotic gene Bcl-x and decreased expression of the proapoptotic gene Casp-8. Next, preadipocytes were treated with saturated fatty acids (SFAs) to induce cell stress. SFA-mediated splicing of X-box-binding protein-1 was reduced by co-treatment with Ang-1, and cell viability was improved in the presence of SFAs + Ang-1. Taken together, these results indicate that Ang-1 may protect preadipocytes from SFA-induced apoptosis and endoplasmic reticulum stress.

Effect of a 2-year diet intervention with walnuts on cognitive decline. The Walnuts and Healthy Aging (WAHA) study: a randomized controlled trial.

Sala-Vila, A., C. Valls-Pedret, S. Rajaram, N. Coll-Padrós, M. Cofán, M. Serra-Mir, A.M. Pérez-Heras, I. Roth, T.M. Freitas-Simoes, M. Doménech, C. Calvo, A. López-Illamola, E. Bitok, N.K. Buxton, L. Huey, A. Arechiga, K. Oda, G.J. Lee, D. Corella, L. Vaqué-Alcázar, R. Sala-Llonch, D. Bartrés-Faz, J. Sabaté, E. Ro, 2020. Effect of a 2-year diet intervention with walnuts on cognitive decline. The Walnuts and Healthy Aging (WAHA) study: a randomized controlled trial. Am J Clin Nutr. pii: nqz328. doi: 10.1093/ajcn/nqz328. [Epub ahead of print]

Background: Walnut consumption counteracts oxidative stress and inflammation, 2 drivers of cognitive decline. Clinical data concerning effects on cognition are lacking. Objectives: The Walnuts and Healthy Aging study is a 2-center (Barcelona, Spain; Loma Linda, CA) randomized controlled trial examining the cognitive effects of a 2-y walnut intervention in cognitively healthy elders. Methods: We randomly allocated 708 free-living elders (63-79 y, 68% women) to a diet enriched with walnuts at ∼15% energy (30-60 g/d) or a control diet (abstention from walnuts). We administered a comprehensive neurocognitive test battery at baseline and 2 y. Change in the global cognition composite was the primary outcome. We performed repeated structural and functional brain MRI in 108 Barcelona participants. Results: A total of 636 participants completed the intervention. Besides differences in nutrient intake, participants from Barcelona smoked more, were less educated, and had lower baseline neuropsychological test scores than those from Loma Linda. Walnuts were well tolerated and compliance was good. Modified intention-to-treat analyses (n = 657) uncovered no between-group differences in the global cognitive composite, with mean changes of -0.072 (95% CI: -0.100, -0.043) in the walnut diet group and -0.086 (95% CI: -0.115, -0.057) in the control diet group (P = 0.491). Post hoc analyses revealed significant differences in the Barcelona cohort, with unadjusted changes of -0.037 (95% CI: -0.077, 0.002) in the walnut group and -0.097 (95% CI: -0.137, -0.057) in controls (P = 0.040). Results of brain fMRI in a subset of Barcelona participants indicated greater functional network recruitment in a working memory task in controls. Conclusions: Walnut supplementation for 2 y had no effect on cognition in healthy elders. However, brain fMRI and post hoc analyses by site suggest that walnuts might delay cognitive decline in subgroups at higher risk. These encouraging but inconclusive results warrant further investigation, particularly targeting disadvantaged populations, in whom greatest benefit could be expected.

Changes in nut consumption and subsequent cardiovascular disease risk among US men and women: 3 large prospective cohort studies.

Liu, X., M. Guasch-Ferré, J.P. Drouin-Chartier, D.K. Tobias, S.N. Bhupathiraju, K.M. Rexrode, W.C. Willett, Q. Sun, Y. Li, 2020. Changes in nut consumption and subsequent cardiovascular disease risk among US men and women: 3 large prospective cohort studies.
J Am Heart Assoc. 9(7):e013877. doi: 10.1161/JAHA.119.013877. Epub 2020 Apr 1.

Background: we aim to evaluate the association of within-individual changes in consumption of total and specific types of nuts and the subsequent risk of incident cardiovascular disease (CVD) in US men and women. Methods and Results: We included 34 103 men from the HPFS (Health Professionals Follow-Up Study) (1986-2012), 77 815 women from the NHS (Nurses’ Health Study) (1986-2012), and 80 737 women from the NHS II (1991-2013). We assessed nut consumption every 4 years using validated food frequency questionnaires. We used multivariable Cox proportional hazards regression models to examine the association between 4-year changes in nut consumption and risk of confirmed CVD end points in the subsequent 4 years. Per 0.5 serving/day increase in total nut consumption was associated with lower risk of CVD (relative risk [RR], 0.92; 95% CI, 0.86-0.98), coronary heart disease (RR, 0.94; 95% CI, 0.89-0.99), and stroke (RR, 0.89; 95% CI, 0.83-0.95). Compared with individuals who remained nonconsumers in a 4-year interval, those who had higher consumption of total nuts (≥0.5 servings/day) had a lower risk of CVD (RR, 0.75; 95% CI, 0.67-0.84), coronary heart disease (RR, 0.80; 95% CI, 0.69-0.93), and stroke (RR, 0.68; 95% CI, 0.57-0.82) in next 4 years. Individuals who decreased nut consumption by ≥0.50 servings/day had a higher risk of developing CVD (RR, 1.14; 95% CI, 0.99-1.32), coronary heart disease (RR, 1.06; 95% CI, 0.88-1.28), and stroke (RR, 1.28; 95% CI, 1.02-1.60) when compared with those who maintained their nut consumption. Conclusions: Increasing total consumption of nuts and intake of individual types of nuts (eg, walnuts, other tree nuts, and peanuts) was associated with a subsequent lower risk of CVD. These data support the role of nut intake in the primary prevention of CVD.

Consumption of Nuts at Midlife and Healthy Aging in Women.

Freitas-Simoes, T.M., M. Wagner, C. Samieri, A. Sala-Vila, F. Grodstein, 2020. Consumption of Nuts at Midlife and Healthy Aging in Women. J Aging Res. https://doi.org/10.1155/2020/5651737.

Background: Nut consumption may reduce age-related diseases and lead to better health and well-being in aging. Many conditions of aging develop over decades, and thus earlier lifestyle factors may particularly influence later health. Methods: In 1998 and 2002, we administered food frequency questionnaires to assess nut consumption (peanuts, walnuts, and other nuts and peanut butter) in women in the Nurses’ Health Study in their 50 s/early 60 s. In 2012, those who survived beyond 65 years with no chronic diseases, no reported memory impairment, no physical disabilities, and intact mental health were considered “healthy agers.” We used multivariable logistic regression to estimate odds ratios for healthy versus usual aging, controlled for sociodemographic, behavioral, dietary, and other potential confounding factors. Results: Of 33,931 participants at midlife, 16% became “healthy agers.” After age adjustment, we observed a significant association between total nut consumption at midlife and higher odds of healthy aging, with strongest associations observed excluding peanut butter (odds ratio (OR) = 1.46, 95% confidence interval (CI) 1.32–1.62, ≥3 servings/week versus none). Findings were attenuated after further control for covariates, including overall diet quality (OR = 1.14, 95% CI 1.02–1.28, P trend = 0.05). For nut types, we found statistically significantly higher odds of healthy aging across peanuts, walnuts, and other nuts after age adjustment. After full control for confounders, only walnut consumption remained associated with healthy aging (P trend = 0.0001); for example, the OR was 1.20 (95% CI 1.00–1.44) for ≥2 servings/week versus none. Conclusions: Women consuming nuts at midlife have a greater likelihood of overall health and well-being at older ages. Nut consumption may represent a simple intervention to explore and promote healthy aging.

Colon cancer prevention with walnuts: a longitudinal study in mice from the perspective of a gut enterotype-like cluster.

Chen Y., M. Nakanishi, E.J. Bautista, V. Qendro, E. Sodergren, D.W. Rosenberg, G.M. Weinstock, 2020. Colon cancer prevention with walnuts: a longitudinal study in mice from the perspective of a gut enterotype-like cluster. Cancer Prev Res (Phila). 13(1):15-24.

There is limited understanding of how walnut consumption inhibits the development of colorectal cancer. A possible mechanism may involve alterations to the gut microbiota. In this study, the effects of walnut on gut microbiota were tested in a mouse tumor bioassay using the colonotropic carcinogen, azoxymethane (AOM) added to the total Western diet (TWD). 16S rRNA pyrosequencing identified three enterotype-like clusters (E1, E2, and E3) in this murine model. E1, E2, and E3 are associated with AOM exposure, walnut consumption, and TWD diet, respectively. E2 and E3 showed distinct taxonomic and functional characteristics, while E1 represented an intermediate state. At the family level, E1 and E3 were both enriched with Bacteroidaceae, but driven by two different operational taxonomic units (OTU; OTU-2 for E1, OTU-4 for E3). E2 was overrepresented with Porphyromonadaceae and Lachnospiraceae, with OTU-3 (family Porphyromonadaceae) as the “driver” OTU for this cluster. Functionally, E3 is overrepresented with genes of glycan biosynthesis and metabolism, xenobiotic metabolism, and lipid metabolism. E2 is enriched with genes associated with cell motility, replication and repair, and amino acid metabolism. Longitudinally, E2 represents the gut microbial status of early life in these mice. In comparison with E1 and E3, E2 is associated with a moderate lower tumor burden (P = 0.12). Our results suggest that walnuts may reduce the risk of colorectal cancer within a Western diet by altering the gut microbiota. Our findings provide further evidence that colorectal cancer risk is potentially modifiable by diet via alterations to the microbiota.

Walnut-associated fatty acids inhibit LPS-induced activation of BV-2 microglia.

Carey, A.N., D.R. Fisher, D.F. Bielinski, D.S. Cahoon, B. Shukitt-Hale, 2020. Walnut-associated fatty acids inhibit LPS-induced activation of BV-2 microglia. Inflammation. 43(1):241-250.

Walnuts have high levels of the omega-3 fatty acid alpha-linolenic acid (C18:3n-3, ALA) and the omega-6 fatty acid linoleic acid (C18:2n-6, LA). Previous research has demonstrated that pre-treatment of BV-2 microglia with walnut extract inhibited lipopolysaccharide (LPS)-induced activation of microglia. As an extension of that study, the effects of walnut-associated fatty acids on BV-2 microglia were assessed. BV-2 murine microglia cells were treated with LA, ALA, or a combination of LA+ALA prior to or after exposure to LPS. Nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) were measured in cell-conditioned media. Cyclooxeganse-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression were assessed in BV-2 microglia. Both LA and ALA protected against LPS-induced increases in NO, iNOS, COX-2, and TNF-alpha when used before LPS exposure. When BV-2 microglia were treated with fatty acids after LPS, only COX-2 and TNF-alpha were significantly attenuated by the fatty acids. There was no synergism of LA+ALA, as the LA+ALA combination was no more effective than LA or ALA alone. Fatty acids, like those found in walnuts, may protect against production of cytotoxic intermediates and cell-signaling molecules from microglia and may prove beneficial for preventing age- or disease-related neurodegeneration.

Effects of supplementing the usual diet with a daily dose of walnuts for two years on metabolic syndrome and its components in an elderly cohort.

Al Abdrabalnabi, A., S. Rajaram, E. Bitok, K. Oda, W.L. Beeson, A. Kaur, M. Cofán, M. Serra-Mir, I. Roth, E. Ros, J. Sabaté, 2020. Effects of supplementing the usual diet with a daily dose of walnuts for two years on metabolic syndrome and its components in an elderly cohort. Nutrients. 11;12(2). pii: E451. doi: 10.3390/nu12020451.

Accumulating evidence links nut consumption with an improved risk of metabolic syndrome (MetS); however, long-term trials are lacking. We examined the effects of a daily dose of walnuts for two years on MetS in a large elderly cohort. A total of 698 healthy elderly participants were randomly assigned to either a walnut supplemented or a control diet. The participants in the walnut group were provided with packaged walnuts (1, 1.5, or 2 oz. or ~15% of energy) and asked to incorporate them into their daily habitual diet. The participants in the control group were asked to continue with their habitual diet and abstain from eating walnuts and other tree nuts. Intake of n-3 fatty acid supplements was not permitted in either group. Fasting blood chemistries, blood pressure, and anthropometric measurements were obtained at baseline and at the end of intervention. A total of 625 participants (67% women, mean age 69.1 y) completed this two-year study (90% retention rate). Triglycerides decreased in both walnut (-.94 mg/dl) and control (-0.96 mg/dl) groups, with no significant between-group differences. There was a non-significant decrease in systolic and diastolic blood pressure in the walnut group (-1.30 and -0.71 mm Hg, respectively) and no change in the control group. Fasting blood glucose decreased by ~1 point in both the walnut and control groups. There were no significant between-group differences in the development or reversion of MetS. In conclusion, supplementing the diet of older adults with a daily dose of walnuts had no effect on MetS status or any of its components, although the walnut group tended to have lower blood pressure.

Effect of tree nuts consumption on serum lipid profile in hyperlipidemic individuals: A systematic review.

Altamimi, M., S. Zidan, M. Badrasawi, 2020. Effect of tree nuts consumption on serum lipid profile in hyperlipidemic individuals: A systematic review. Nutrition and Metabolic Insights.  13: 1–10.

Many epidemiological studies have regularly connected nuts intake with decreased risk for coronary heart disease. The primary mechanism by which nuts protect against cardiovascular disease is through the improvement of lipid and apolipoprotein profile. Therefore, numerous dietary intervention studies investigated the impact of nut consumption on blood lipid levels. Many studies have shown that nut intake can enhance the lipid profile in a dose-response way among individuals with increased serum lipids. This systematic review examines the effectiveness of nuts on the lipid profile among patients with dyslipidemia from different age groups. A total of 29 interventional studies from 5 databases met the inclusion criteria. In all, 20 studies were randomized controlled clinical trials, whereas 9 were crossover-controlled clinical trials. Participants included in the studies were different in terms of age, sex and, serum lipid profile. The studies were inconsistent in the type of tree nuts, duration, dose, and the nut forms. All studies indicated changes in the lipid profile after the intervention particularly on the total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, total cholesterol/high-density lipoprotein. Interventional periods ranged from 3 weeks up to 12 months with doses ranged from 15 to 126gm. In conclusion, this review provides an evidence of favorable effect of nuts consumption of serum lipid profile.

Comparative effects of different types of tree nut consumption on blood lipids: a network meta-analysis of clinical trials.

Liu, K., S. Hui, B. Wang, K. Kaliannan, X. Guo, L. Liang, 2020. Comparative effects of different types of tree nut consumption on blood lipids: a network meta-analysis of clinical trials. Am J Clin Nutr. 111(1):219-227.

Background: Recent evidence has confirmed that nuts are one of the best food groups at reducing LDL cholesterol and total cholesterol (TC). However, the comparative effects of different types of nuts on blood lipids are unclear. Objectives: This network meta-analysis of randomized clinical trials aimed to assess the comparative effects of walnuts, pistachios, hazelnuts, cashews, and almonds on typical lipid profiles. Methods: We conducted literature searches to identify studies comparing ≥2 of the following diets-walnut-enriched, pistachio-enriched, hazelnut-enriched, cashew-enriched, almond-enriched, and control diets-for the management of triglycerides (TGs), LDL cholesterol, TC, and HDL cholesterol. Random-effects network meta-analyses, ranking analyses based on the surface under the cumulative ranking (SUCRA) curves, and sensitivity analyses according to the potential sources of heterogeneity across the included studies were performed for each outcome. Results: Thirty-four trials enrolling 1677 participants were included in this study. The pistachio-enriched diet was ranked best for TG (SUCRA: 85%), LDL cholesterol (SUCRA: 87%), and TC (SUCRA: 96%) reductions. For TG and TC reductions, the walnut-enriched diet was ranked as the second-best diet. Regarding LDL cholesterol reduction, the almond-enriched diet was ranked second best. The pistachio-enriched and walnut-enriched diets were more effective at lowering TG, LDL cholesterol, and TC compared with the control diet. Regarding TG and TC reductions, the pistachio-enriched diet was also more effective than the hazelnut-enriched diet. For TG reduction, the walnut-enriched diet was better than the hazelnut-enriched diet. However, these findings are limited by the low quality of evidence ratings. In addition, the quality of this network meta-analysis was limited by the small number and generally poor reporting of available studies. Conclusions: The pistachio-enriched and walnut-enriched diet could be better alternatives for lowering TGs, LDL cholesterol, and TC compared with other nut-enriched diets included in this study. The findings warrant further evaluation by more high-quality studies. This network meta-analysis was registered at www.crd.york.ac.uk/PROSPERO as CRD42019131128.

Edible nuts for memory.

Arslan, J., A.-U.-H. Gilani, H. Jamshed, S.F. Khan, M.A. Kamal, 2020. Edible nuts for memory. Curr Pharm Des. 26(37):4712-4720.

Nuts hold prime significance throughout the world as they offer multiple health benefits owing to their highly nutritious profile. A number of scientific studies have demonstrated their actions against inflammation, oxidative damage, the aging process, as well as dementia or memory loss. However, only walnuts, followed by almonds, hazelnuts and pistachios, have shown promising results in empirical studies for memory improvements. So, the current review focuses on presenting hypotheses regarding anti-dementia property of nine different nuts: almond, walnut, pistachio, Brazil nut, peanut, pecans, cashew, hazelnut, and chestnut. The nutritious profile of nuts contains essential fats (mostly mono- and poly-unsaturated fatty acids), proteins (source for arginine, lysine and tryptophan), vitamins (riboflavin, folate, and various tocopherols), fibers, minerals (calcium, sodium, magnesium, phosphorus and potassium) and trace elements (copper, zinc, and selenium). Interestingly, the constituents of natural products, nuts being an excellent example, work synergistically and/or in a side-effect neutralizing manner. These latter properties can make nuts an alternate therapy for humankind to fight against memory loss.