Archive

Research Nut: Walnuts

Red blood cell omega-3 fatty acids and attention scores in healthy adolescents. 

Pinar-Martí, A., S. Fernández-Barrés, F. Gignac, C. Persavento, A. Delgado, D. Romaguera, I. Lázaro, E. Ros, M. López-Vicente, J. Salas-Salvadó, A. Sala-Vila, J. Júlvez, 2023. Red blood cell omega-3 fatty acids and attention scores in healthy adolescents. Eur. Child Adolesc. Psychiatry. 32(11):2187–2195. https://doi.org/10.1007/s00787-022-02064-w

Omega-3 fatty acids are critical for brain function. Adolescence is increasingly believed to entail brain vulnerability to dietary intake. In contrast to the abundant research on the omega-3 docosahexaenoic acid (DHA) in cognition, research on DHA and attention in healthy adolescents is scarce. In addition, the role of alpha-linolenic acid (ALA), the vegetable omega-3 fatty acid, is unexplored. We examined associations between DHA and ALA and attention function among a healthy young population. In this cross-sectional study conducted in 372 adolescents (13.8±0.9 years-old), we determined the red blood cell proportions of DHA and ALA by gas chromatography (objective biomarkers of their long-term dietary intake) and measured attention scores through the Attention Network Test. We constructed multivariable linear regression models to analyze associations, controlling for known confounders. Compared to participants at the lowest DHA tertile (reference), those at the highest DHA tertile showed significantly lower hit reaction time-standard error (higher attentiveness) (28.13 ms, 95% confidence interval [CI]= – 52.30; – 3.97), lower hit reaction time ( – 38.30 ms, 95% CI= – 73.28; – 3.33) and lower executive conflict response ( – 5.77 ms, 95% CI= – 11.44; – 0.09). In contrast, higher values were observed in those at the top tertile of ALA in hit reaction time compared to the lowest one (46.14 ms, 95% CI=9.90; 82.34). However, a beneficial association was observed for ALA, with decreasing impulsivity index across tertiles. Overall, our results suggest that DHA (reflecting its dietary intake) is associated with attention performance in typically developing adolescents. The role of dietary ALA in attention is less clear, although higher blood levels of ALA appear to result in lower impulsivity. Future intervention studies are needed to determine the causality of these associations and to better shape dietary recommendations for brain health during the adolescence period.

Effect of a Mediterranean diet or mindfulness-based stress reduction during pregnancy on child neurodevelopment: a prespecified analysis of the IMPACT BCN Randomized Clinical Trial. 

Crovetto, F., A. Nakaki, A. Arranz, R. Borras, K. Vellvé, C. Paules, M.L. Boutet, S. Castro-Barquero, T. Freitas, R. Casas, A. Martín-Asuero, T, Oller Guzmán, I. Morilla, A. Martínez-Àran, A. Camacho, M. Pasqual, M. Izquierdo Renau,  Ó.J. Pozo, A. Gomez-Gomez, R. Estruch,  E. Vieta , F. Crispi, E. Gratacós, 2023. Effect of a Mediterranean diet or mindfulness-based stress reduction during pregnancy on child neurodevelopment: a prespecified analysis of the IMPACT BCN Randomized Clinical Trial. JAMA Netw. Open. 6(8):e2330255. https://doi.org/10.1001/jamanetworkopen.2023.30255

Importance: Maternal suboptimal nutrition and high stress levels are associated with adverse fetal and childhood neurodevelopment. Objective: To test the hypothesis that structured interventions based on a Mediterranean diet or mindfulness-based stress reduction (MBSR) during pregnancy improve child neurodevelopment at age 2 years. Design, setting, and participants: This was a prespecified analysis of the parallel-group Improving Mothers for a Better Prenatal Care Trial Barcelona (IMPACT BCN) randomized clinical trial, which was conducted at a university hospital in Barcelona, Spain, from February 2017 to March 2020. A total of 1221 singleton pregnancies (19 to 23 weeks’ gestation) with high risk of delivering newborns who were small for gestational age were randomly allocated into 3 groups: a Mediterranean diet intervention, an MBSR program, or usual care. A postnatal evaluation with the Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III), was performed. Data were analyzed from July to November 2022. Interventions: Participants in the Mediterranean diet group received monthly individual and group educational sessions and free provision of extra virgin olive oil and walnuts. Those in the stress reduction group underwent an 8-week MBSR program adapted for pregnancy. Individuals in the usual care group received pregnancy care per institutional protocols. Main outcomes and measures: Neurodevelopment in children was assessed by Bayley-III at 24 months of corrected postnatal age. Results: A total of 626 children (293 [46.8%] female and 333 [53.2%] male) participated at a mean (SD) age of 24.8 (2.9) months. No differences were observed in the baseline characteristics between intervention groups. Compared with children from the usual care group, children in the Mediterranean diet group had higher scores in the cognitive domain (β, 5.02; 95% CI, 1.52-8.53; P = .005) and social-emotional domain (β, 5.15; 95% CI, 1.18-9.12; P = .01), whereas children from the stress reduction group had higher scores in the social-emotional domain (β, 4.75; 95% CI, 0.54-8.85; P = .02). Conclusions and relevance: In this prespecified analysis of a randomized clinical trial, maternal structured lifestyle interventions during pregnancy based on a Mediterranean diet or MBSR significantly improved child neurodevelopmental outcomes at age 2 years.

Antioxidant and anti-inflammatory properties of walnut constituents: focus on personalized cancer prevention and the microbiome.

Fan, N., J.L. Fusco, D.W. Rosenberg, 2023. Antioxidant and anti-inflammatory properties of walnut constituents: focus on personalized cancer prevention and the microbiome. Antioxidants. 12(5): 982. https://doi.org/10.3390/antiox12050982

Walnuts have been lauded as a ‘superfood’, containing a remarkable array of natural constituents that may have additive and/or synergistic properties that contribute to reduced cancer risk. Walnuts are a rich source of polyunsaturated fatty acids (PUFAs: alpha-linolenic acid, ALA), tocopherols, antioxidant polyphenols (including ellagitannins), and prebiotics, including fiber (2 g/oz). There is a growing body of evidence that walnuts may contribute in a positive way to the gut microbiome, having a prebiotic potential that promotes the growth of beneficial bacteria. Studies supporting this microbiome-modifying potential include both preclinical cancer models as well as several promising human clinical trials. Mediated both directly and indirectly via its actions on the microbiome, many of the beneficial properties of walnuts are related to a range of anti-inflammatory properties, including powerful effects on the immune system. Among the most potent constituents of walnuts are the ellagitannins, primarily pedunculagin. After ingestion, the ellagitannins are hydrolyzed at low pH to release ellagic acid (EA), a non-flavonoid polyphenolic that is subsequently metabolized by the microbiota to the bioactive urolithins (hydroxydibenzo[b,d]pyran-6-ones). Several urolithins, including urolithin A, reportedly have potent anti-inflammatory properties. These properties of walnuts provide the rationale for including this tree nut as part of a healthy diet for reducing overall disease risk, including colorectal cancer. This review considers the latest information regarding the potential anti-cancer and antioxidant properties of walnuts and how they may be incorporated into the diet to provide additional health benefits.

Nuts, Energy Balance and Body Weight.

Baer, D.J., M. Dalton, J. Blundell, G. Finlayson, F.B. Hu, 2023. Nuts, Energy Balance and Body Weight. Nutrients. 15(5):1162. doi: 10.3390/nu15051162.

Over several decades, the health benefits of consuming nuts have been investigated, resulting in a large body of evidence that nuts can reduce the risk of chronic diseases. The consumption of nuts, being a higher-fat plant food, is restricted by some in order to minimize weight gain. In this review, we discuss several factors related to energy intake from nuts, including food matrix and its impact on digestibility, and the role of nuts in regulating appetite. We review the data from randomized controlled trials and observational studies conducted to examine the relationship between nut intake and body weight or body mass index. Consistently, the evidence from RCTs and observational cohorts indicates that higher nut consumption does not cause greater weight gain; rather, nuts may be beneficial for weight control and prevention of long-term weight gain. Multiple mechanisms likely contribute to these findings, including aspects of nut composition which affect nutrient and energy availability as well as satiety signaling.

Mixed nuts as healthy snacks: effect on tryptophan metabolism and cardiovascular risk factors.

Yang, J., R. Lee, Z. Schulz, A. Hsu, J. Pai, S. Yang, S.M. Henning, J. Huang, J.P. Jacobs, D. Heber, Z. Li., 2023. Mixed nuts as healthy snacks: effect on tryptophan metabolism and cardiovascular risk factors. Nutrients. 15, 569; https://doi.org/10.3390/nu15030569.

We recently demonstrated that the consumption of mixed tree nuts (MTNs) during caloric restriction decreased cardiovascular risk factors and increased satiety. Tryptophan (Trp) metabolism has been indicated as a factor in cardiovascular disease. Here, we investigated the effect of MTNs on Trp metabolism and the link to cardiovascular risk markers. Plasma and stool were collected from 95 overweight individuals who consumed either MTNs (or pretzels) daily as part of a hypocaloric weight loss diet for 12 weeks followed by an isocaloric weight maintenance program for an additional 12 weeks. Plasma and fecal samples were evaluated for Trp metabolites by LC–MS and for gut microbiota by 16S rRNA sequencing. Trp–kynurenine metabolism was reduced only in the MTNs group during weight loss (baseline vs. week 12). Changes in Trp–serotonin (week 24) and Trp–indole (week 12) metabolism from baseline were increased in the MTNs group compared to the pretzel group. Intergroup analysis between MTN and pretzel groups does not identify significant microbial changes as indicated by alpha diversity and beta diversity. Changes in the relative abundance of genus Paludicola during intervention are statistically different between the MTNs and pretzel group with p < 0.001 (q = 0.07). Our findings suggest that consumption of MTNs affects Trp host and microbial metabolism in overweight and obese subjects.

Impact of dietary walnuts, a nutraceutical option, on circulating markers of metabolic dysregulation in a rodent cachectic tumor model.

Byerley, L. O., H.M. Chang, B. Lorenzen, J. Guidry, W.E. Hardman, 2022. Impact of dietary walnuts, a nutraceutical option, on circulating markers of metabolic dysregulation in a rodent cachectic tumor model. Biomed. Pharmacother. 155, 113728. https://doi.org/10.1016/j.biopha.2022.113728

Background: Nutraceutical foods, like walnuts which are rich in immunonutrients, can have medicinal benefits. Dietary walnuts have been shown to slow or prevent tumor growth in mice genetically programmed to grow breast or prostate tumors. This study investigated whether walnuts could exert the same preventable effect in a transplantable carcinoma rat model. Methods: Eighteen rats were randomly fed a diet containing walnuts (10% of food by weight), and 36 were fed a diet without walnuts (control) for 21 days. On day 22, 18 control diet rats were switched to the walnut diet. All other animals remained on their same diet. Within each diet group, 6 rats were implanted with the Ward colon carcinoma (TB), and 12 were sham-operated. Five days later, 6 sham-operated animals were weight-matched to a TB and then pair-fed for the remainder of the study. The remaining 6 sham-operated, or non-tumor-bearing rats, were ad-lib fed. Results: The tissue of the walnut-eating rats showed higher omega-3 fatty acid (immunonutrient) content which did not slow or prevent tumor growth or the loss of lean and fat mass typical of this TB model. In addition, blood glucose, insulin, IGF-1, and adiponectin levels were significantly lower in the TB, demonstrating metabolic dysregulation. Again, these changes were unaltered by consuming walnuts. Plasma proteomics identified six proteins elevated in the TB, but none could be connected with the observed metabolic dysregulation. Conclusion: Although walnuts’ rich immunonutrient content prevented tumor growth in genetically programmed mice models, there was no effect in this model.

Effects of a low-carbohydrate dietary intervention on hemoglobin A1c: a randomized clinical trial.

Dorans, K.S., L.A. Bazzano, L. Qi, H. He, J. Chen, L.J. Appel, C.S. Chen, M.H. Hsieh, F.B. Hu, K.T. Mills, B.T. Nguyen, M.J. O’Brien, J.M. Samet, G.I. Uwaifo, J. He, 2022. Effects of a low-carbohydrate dietary intervention on hemoglobin A1c: a randomized clinical trial. JAMA Netw. Open. 5(10), e2238645. https://doi.org/10.1001/jamanetworkopen.2022.38645

Importance: Low-carbohydrate diets decrease hemoglobin A1c (HbA1c) among patients with type 2 diabetes at least as much as low-fat diets. However, evidence on the effects of low-carbohydrate diets on HbA1c among individuals with HbA1c in the range of prediabetes to diabetes not treated by diabetes medications is limited. Objective: To study the effect of a behavioral intervention promoting a low-carbohydrate diet compared with usual diet on 6-month changes in HbA1c among individuals with elevated untreated HbA1c. Design, setting, and participants: This 6-month randomized clinical trial with 2 parallel groups was conducted from September 2018 to June 2021 at an academic medical center in New Orleans, Louisiana. Laboratory analysts were blinded to assignment. Participants were aged 40 to 70 years with untreated HbA1c of 6.0% to 6.9% (42-52 mmol/mol). Data analysis was performed from November 2021 to September 2022. Interventions: Participants were randomized to a low-carbohydrate diet intervention (target <40 net grams of carbohydrates during the first 3 months; <60 net grams for months 3 to 6) or usual diet. The low-carbohydrate diet group received dietary counseling. Main outcomes and measures: Six-month change in HbA1c was the primary outcome. Outcomes were measured at 0, 3, and 6 months. Results: Of 2722 prescreened participants, 962 underwent screening, and 150 were enrolled (mean [SD] age, 58.9 [7.9] years; 108 women [72%]; 88 Black participants [59%]) and randomized to either the low-carbohydrate diet intervention (75 participants) or usual diet (75 participants) group. Six-month data were collected on 142 participants (95%). Mean (SD) HbA1c was 6.16% (0.30%) at baseline. Compared with the usual diet group, the low-carbohydrate diet intervention group had significantly greater 6-month reductions in HbA1c (net difference, -0.23%; 95% CI, -0.32% to -0.14%; P < .001), fasting plasma glucose (-10.3 mg/dL; 95% CI, -15.6 to -4.9 mg/dL; P < .001), and body weight (-5.9 kg; 95% CI, -7.4 to -4.4 kg; P < .001). Conclusions and relevance: In this randomized clinical trial, a low-carbohydrate dietary intervention led to improvements in glycemia in individuals with elevated HbA1c not taking glucose-lowering medication, but the study was unable to evaluate its effects independently of weight loss. This diet, if sustained, might be a useful dietary approach for preventing and treating type 2 diabetes, but more research is needed.

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.