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Research Nut: Walnuts

Walnut oil reduces Aβ levels and increases neurite length in a cellular model of early Alzheimer disease. 

Esselun, C., F. Dieter, N. Sus, J. Frank, G.P. Eckert, 2022. Walnut oil reduces Aβ levels and increases neurite length in a cellular model of early Alzheimer disease. Nutrients. 14(9):1694. https://doi.org/10.3390/nu14091694

Background: Mitochondria are the cells’ main source of energy. Mitochondrial dysfunction represents a key hallmark of aging and is linked to the development of Alzheimer’s disease (AD). Maintaining mitochondrial function might contribute to healthy aging and the prevention of AD. The Mediterranean diet, including walnuts, seems to prevent age-related neurodegeneration. Walnuts are a rich source of α-linolenic acid (ALA), an essential n3-fatty acid and the precursor for n3-long-chain polyunsaturated fatty acids (n3-PUFA), which might potentially improve mitochondrial function. Methods: We tested whether a lipophilic walnut extract (WE) affects mitochondrial function and other parameters in human SH-SY5Y cells transfected with the neuronal amyloid precursor protein (APP695). Walnut lipids were extracted using a Soxhlet Extraction System and analyzed using GC/MS and HPLC/FD. Adenosine triphosphate (ATP) concentrations were quantified under basal conditions in cell culture, as well as after rotenone-induced stress. Neurite outgrowth was investigated, as well as membrane integrity, cellular reactive oxygen species, cellular peroxidase activity, and citrate synthase activity. Beta-amyloid (Aβ) was quantified using homogenous time-resolved fluorescence. Results: The main constituents of WE are linoleic acid, oleic acid, α-linolenic acid, and γ- and δ-tocopherol. Basal ATP levels following rotenone treatment, as well as citrate synthase activity, were increased after WE treatment. WE significantly increased cellular reactive oxygen species but lowered peroxidase activity. Membrane integrity was not affected. Furthermore, WE treatment reduced Aβ1–40 and stimulated neurite growth. Conclusions: WE might increase ATP production after induction of mitochondrial biogenesis. Decreased Aβ1–40 formation and enhanced ATP levels might enhance neurite growth, making WE a potential agent to enhance neuronal function and to prevent the development of AD. In this sense, WE could be a promising agent for the prevention of AD.

Interplay of walnut consumption, changes in circulating miRNAs and reduction in LDL-cholesterol in elders.

Gil-Zamorano, J., M. Cofán, M.C. López de Las Hazas, T. García-Blanco, A. García-Ruiz, M. Doménech, M. Serra-Mir, I. Roth, C. Valls-Pedret, S. Rajaram, J. Sabaté, E. Ros, A. Dávalos, A. Sala-Vila, 2022. Interplay of walnut consumption, changes in circulating miRNAs and reduction in LDL-cholesterol in elders. Nutrients. 14(7):1473. https://doi.org/10.3390/nu14071473

The mechanisms underlying the lipid-lowering effect of nuts remain elusive. This study explores whether one-year supplementation with walnuts decreases LDL-cholesterol (LDL-C) by affecting the expression of circulating microRNAs (c-miRNA). In this sub-study of the Walnuts and Healthy Aging (WAHA) trial, we obtained fasting serum at baseline and at 1 year from 330 free-living participants (63–79 year, 68% women), allocated into a control group (CG, abstinence from walnuts, n = 164) and a walnut group (WG, 15% of daily energy as walnuts, ~30–60 g/day, n = 166). Participants in the WG showed a 1 year decrease in LDL-C (−9.07, (95% confidence interval: −12.87; −5.73) mg/dL; p = 0.010 versus changes in the CG). We conducted a miRNA array in eight randomly selected participants in the WG who decreased in LDL-C. This yielded 53 c-miRNAs with statistically significant changes, 27 of which survived the correction for multiple testing. When validating them in the full population, statistical significance lasted for hsa-miR-551a, being upregulated in the WG. In mediation analysis, the change in hsa-miR-551a was unrelated to LDL-C decrease. Long-term supplementation with walnuts decreased LDL-C independently of the changes in c-miRNA. The hsa-miR-551a upregulation, which has been linked to a reduced cell migration and invasion in several carcinomas, suggests a novel mechanism of walnuts in cancer risk.

The effects of walnuts and academic stress on mental health, general well-being and the gut microbiota in a sample of university students: a randomised clinical trial.

Herselman, M. F., S. Bailey, P. Deo, X.F. Zhou, K.M. Gunn, L. Bobrovskaya, 2022. The effects of walnuts and academic stress on mental health, general well-being and the gut microbiota in a sample of university students: a randomised clinical trial. Nutrients. 14(22):4776. https://doi.org/10.3390/nu14224776

Poorer mental health is common in undergraduate students due to academic stress. An interplay between stress and diet exists, with stress influencing food choices. Nutritional interventions may be effective in preventing mental health decline due to complex bidirectional interactions between the brain, the gut and the gut microbiota. Previous studies have shown walnut consumption has a positive effect on mental health. Here, using a randomized clinical trial (Australian New Zealand Clinical Trials Registry, #ACTRN12619000972123), we aimed to investigate the effects of academic stress and daily walnut consumption in university students on mental health, biochemical markers of general health, and the gut microbiota. We found academic stress had a negative impact on self-reported mood and mental health status, while daily walnut consumption improved mental health indicators and protected against some of the negative effects of academic stress on metabolic and stress biomarkers. Academic stress was associated with lower gut microbial diversity in females, which was improved by walnut consumption. The effects of academic stress or walnut consumption in male participants could not be established due to small numbers of participants. Thus, walnut consumption may have a protective effect against some of the negative impacts of academic stress, however sex-dependent mechanisms require further study.

The effect of a high-polyphenol Mediterranean diet (Green-MED) combined with physical activity on age-related brain atrophy: the Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT PLUS).

Kaplan, A., H. Zelicha, A. Yaskolka Meir, E. Rinott, G. Tsaban, G. Levakov, O. Prager, M. Salti, Y. Yovell, J. Ofer, S. Huhn, F. Beyer, V. Witte, A. Villringer, N. Meiran, T.B. Emesh, P. Kovacs, M. von Bergen, U. Ceglarek, M. Blüher, M. Stumvall, F.B. Hu, M.J. Stampfer, A. Friedman, I. Shelef, G. Avidan, I. Shai, 2022. The effect of a high-polyphenol Mediterranean diet (Green-MED) combined with physical activity on age-related brain atrophy: the Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT PLUS). Am. J. Clin. Nutr. 115(5):1270–1281. https://doi.org/10.1093/ajcn/nqac001

Background: The effect of diet on age-related brain atrophy is largely unproven. Objective: To explore the effect of a Mediterranean diet higher in polyphenols and lower in red/processed meat (Green-MED diet) on age-related brain atrophy. Methods: This 18-month clinical trial longitudinally measured brain structure volumes by magnetic-resonance-imaging using hippocampal-occupancy (HOC) and lateral-ventricle-volume (LVV) expansion scores as neurodegeneration markers. Abdominally obese/dyslipidemic participants were randomly assigned to (1)-healthy dietary guidelines (HDG), (2)-Mediterranean (MED) diet, or (3)-Green-MED diet (MED diet higher in polyphenols and lower in red/processed meat). All subjects received free gym memberships and physical activity guidance. Both MED groups consumed 28g/day walnuts (+440 mg/d polyphenols). The Green-MED group consumed green-tea (3-4 cups/day) and Mankai (Wolffia-globosa strain, 100g frozen-cubes/day) green shake (+800mg/day polyphenols). Results: Among 284 participants (age = 51years; 88% men; BMI = 31.2kg/m2; apolipoprotein E-ε4 genotype = 15.7%), 224 (79%) completed the trial with eligible whole-brain MRIs. The pallidum (-4.2%), third ventricle (+3.9%), and LVV (+2.2%) disclosed the largest volume changes. Compared to younger participants, atrophy was accelerated among those ≥ 50 years [HOC change = -1.0±1.4% vs. -0.06±1.1%; 95% confidence-interval (CI):0.6, 1.3; p<0.001; LVV change = 3.2±4.5% vs. 1.3±4.1%; 95%CI:-3.1, -0.8;p = 0.001]. In subjects ≥50years, HOC decline and LVV expansion were attenuated in both MED groups, with the best outcomes among Green-MED diet participants, as compared to HDG (HOC: -0.8±1.6% vs. -1.3±1.4%;95%CI: -1.5, -0.02;p = 0.042, LVV: 2.3±4.7% vs. 4.3±4.5;95%CI;0.3, 5.2;p = 0.021). Similar patterns were observed among younger subjects. Improved insulin sensitivity over the trial was the strongest parameter associated with brain atrophy attenuation (p<0.05). Greater Mankai, green-tea and walnuts intake and less red and processed meat were significantly and independently associated with reduced HOC decline (p<0.05). Elevated urinary levels of the Mankai-derived polyphenols: urolithin-A (r = 0.24;p = 0.013) and tyrosol (r = 0.26;p = 0.007) were significantly associated with lower HOC decline. Conclusions: A Green-MED, high-polyphenol diet, rich in Mankai, green tea and walnuts and low in red/processed meat is potentially neuroprotective for age-related brain atrophy.