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Research Nut: Walnuts

Walnut inclusion in a palm oil-based atherogenic diet promotes traits predicting stable atheroma plaque in Apoe-deficient mice.

Lázaro, I., J. Bobi, M. Cofán, G. Kapravelou, A.J. Amor, J. Surra, C. Gómez-Guerrero, E. Ortega, J. Osada, A.P. Dantas, A. Sala-Vila, 2023. Walnut inclusion in a palm oil-based atherogenic diet promotes traits predicting stable atheroma plaque in Apoe-deficient mice. Front. Nutr. 10:1079407. https://doi.org/10.3389/fnut.2023.1079407

Introduction: The lower rates of cardiovascular disease in Southern Europe could be partially explained by the low prevalence of lipid-rich atheroma plaques. Consumption of certain foods affects the progression and severity of atherosclerosis. We investigated whether the isocaloric inclusion of walnuts within an atherogenic diet prevents phenotypes predicting unstable atheroma plaque in a mouse model of accelerated atherosclerosis. Methods: Apolipoprotein E-deficient male mice (10-week-old) were randomized to receive a control diet (9.6% of energy as fat, n = 14), a palm oil-based high-fat diet (43% of energy as fat, n = 15), or an isocaloric diet in which part of palm oil was replaced by walnuts in a dose equivalent to 30 g/day in humans (n = 14). All diets contained 0.2% cholesterol. Results: After 15 weeks of intervention, there were no differences in size and extension in aortic atherosclerosis among groups. Compared to control diet, palm oil-diet induced features predicting unstable atheroma plaque (higher lipid content, necrosis, and calcification), and more advanced lesions (Stary score). Walnut inclusion attenuated these features. Palm oil-based diet also boosted inflammatory aortic storm (increased expression of chemokines, cytokines, inflammasome components, and M1 macrophage phenotype markers) and promoted defective efferocytosis. Such response was not observed in the walnut group. The walnut group’s differential activation of nuclear factor kappa B (NF-kappaB; downregulated) and Nrf2 (upregulated) in the atherosclerotic lesion could explain these findings. Conclusion: The isocaloric inclusion of walnuts in an unhealthy high-fat diet promotes traits predicting stable advanced atheroma plaque in mid-life mice. This contributes novel evidence for the benefits of walnuts, even in an unhealthy dietary environment.

Effect of nuts on gastrointestinal health. 

Mandalari, G., T. Gervasi, D.W. Rosenberg, K.G. Lapsley, D.J. Baer, 2023. Effect of nuts on gastrointestinal health. Nutrients. 15(7):1733. https://doi.org/10.3390/nu15071733

Nuts are high nutrient-dense foods containing healthy lipids, dietary fiber, and bioactive phytochemicals, including vitamins and minerals. Although the beneficial effect of nut consumption on different chronic diseases has been well documented, especially in relation to their cardiometabolic benefits, less scientific evidence is available on their possible beneficial effects on gastrointestinal health. In this narrative review, we summarize the most important findings and new research perspectives in relation to the importance of nut consumption on gastrointestinal health. The integrity of the cell wall structure, cell size and particle size after mastication are known to play a crucial role in energy, nutrient and bioactive release from nuts during digestion, therefore affecting bioaccessibility. Other mechanisms, such as cell wall composition, thickness and porosity, as well as stability of the membranes surrounding the oil bodies within the cell, are also important for energy extraction. As the undigested nutrients and phytochemicals are delivered to the colon, effects on gut microbiota composition are predicted. Although the overall effect of nut consumption on microbial alpha- and beta-diversity has been inconsistent, some scientific evidence suggests an increase in fecal butyrate after almond consumption, and a beneficial role of walnuts on the prevention of ulcerative colitis and protection against the development of gastric mucosal lesions.

Dietary walnuts preserve aspects of health span and alter the hippocampal lipidome in aged high-fat diet-fed mice.

Novaj, A., M.G. Engel, R. Wang, K. Mao, X. Xue, Y. Amir, G. Atzmon, D.M. Huffman, 2023. Dietary walnuts preserve aspects of health span and alter the hippocampal lipidome in aged high-fat diet-fed mice. Int. J. Mol. Sci. 24(3), 2314. https://doi.org/10.3390/ijms24032314

Evidence continues to accrue that aging and its diseases can be delayed by pharmacologic and dietary strategies that target the underlying hallmarks of the aging process. However, identifying simple, safe, and effective dietary strategies involving the incorporation of whole foods that may confer some protection against the aging process is also needed. Recent observational studies have suggested that nut consumption can reduce mortality risk in humans. Among these, walnuts are particularly intriguing, given their high content of n-3 fatty acids, fiber, and antioxidant and anti-inflammatory compounds. To this end, 12-month-old male CB6F1 mice were provided either a defined control low-fat diet (LFD), a control high-fat diet (HFD), or an isocaloric HFD containing 7.67% walnuts by weight (HFD + W), and measures of health span and related biochemical markers (n = 10-19 per group) as well as survival (n = 20 per group) were monitored. Mice provided the HFD or HFD + W demonstrated marked weight gain, but walnuts lowered baseline glucose (p < 0.05) and tended to temper the effects of HFD on liver weight gain (p < 0.05) and insulin tolerance (p = 0.1). Additional assays suggested a beneficial effect on some indicators of health with walnut supplementation, including preservation of exercise capacity and improved short-term working memory, as determined by Y maze (p = 0.02). However, no effect was observed via any diet on inflammatory markers, antioxidant capacity, or survival (p = 0.2). Ingenuity Pathway Analysis of the hippocampal transcriptome identified two processes predicted to be affected by walnuts and potentially linked to cognitive function, including estrogen signaling and lipid metabolism, with changes in the latter confirmed by lipidomic analysis. In summary, while walnuts did not significantly improve survival on a HFD, they tended to preserve features of health span in the context of a metabolic stressor with aging.

Effect of walnut consumption on neuropsychological development in healthy adolescents: a multi-school randomised controlled trial. 

Pinar-Martí, A., F. Gignac, S. Fernández-Barrés, D. Romaguera, A. Sala-Vila, I. Lázaro, O.T. Ranzani, C. Persavento, A. Delgado, A. Carol, J. Torrent, J. Gonzalez, E. Roso, J. Barrera-Gómez, M. López-Vicente, O. Boucher, M. Nieuwenhuijsen, M.C. Turner, M. Burgaleta, J. Canals,  V. Arija, X. Basagaña , E. Ros, J. Salas-Salvadó , J. Sunyer, J. Julvez, 2023. Effect of walnut consumption on neuropsychological development in healthy adolescents: a multi-school randomised controlled trial. EClinicalMedicine. 59, 101954. https://doi.org/10.1016/j.eclinm.2023.101954

Background: Omega-3 fatty acids are critical for neuropsychological functioning. Adolescence is increasingly believed to entail brain vulnerability to dietary intake. The potential benefit on adolescent neurodevelopment of consuming walnuts, a source of omega-3 alpha-linolenic acid (ALA), remains unclear. Methods: We conducted a 6-month multi-school-based randomized controlled nutrition intervention trial to assess whether walnut consumption has beneficial effects on the neuropsychological and behavioral development of adolescents. The study took place between 04/01/2016 and 06/30/2017 in twelve different high schools in Barcelona, Spain (ClinicalTrials.gov Identifier: NCT02590848). A total of 771 healthy teenagers aged 11–16 years were randomized into two equal groups (intervention or control). The intervention group received 30 g/day of raw walnut kernels to be incorporated into their diet for 6 months. Multiple primary endpoints concerning neuropsychological (working memory, attention, fluid intelligence, and executive function) and behavioral (socioemotional and attention deficit hyperactivity disorder [ADHD] symptoms) development were assessed at baseline and after intervention. Red blood cell (RBC) ALA status was determined at baseline and 6 months as a measure of compliance. Main analyses were based on intention-to-treat using a linear mixed-effects model. A per-protocol effect of the intervention was analysed using inverse-probability weighting to account for post-randomization prognostic factors (including adherence) using generalized estimating equations. Findings: In intention-to-treat analyses, at 6 months there were no statistically significant changes between the intervention and control groups for all primary endpoints. RBC ALA (%) significantly increased only in the intervention group, coefficient = 0.04 (95% Confidence Interval (CI) = 0.03, 0.06; p < 0.0001). The per-protocol (adherence-adjusted) effect on improvement in attention score (hit reaction time variability) was −11.26 ms (95% CI = −19.92, −2.60; p = 0.011) for the intervention group as compared to the control group, improvement in fluid intelligence score was 1.78 (95% CI = 0.90, 2.67; p < 0.0001), and reduction of ADHD symptom score was −2.18 (95% CI = −3.70, −0.67; p = 0.0050). Interpretation Our study suggested that being prescribed eating walnuts for 6 months did not improve the neuropsychological function of healthy adolescents. However, improved sustained attention, fluid intelligence, and ADHD symptoms were observed in participants who better complied with the walnut intervention. This study provides a foundation for further clinical and epidemiological research on the effect of walnuts and ALA on neurodevelopment in adolescents.

Adding walnuts to the usual diet can improve diet quality in the United States: diet modeling study based on NHANES 2015-2018. 

Spence, L.A., B. Henschel, R. Li, C.D. Tekwe, K. Thiagarajah, 2023. Adding walnuts to the usual diet can improve diet quality in the United States: diet modeling study based on NHANES 2015-2018. Nutrients. 15(2):258. https://doi.org/10.3390/nu15020258

Background: The under-consumption of calcium, potassium, fiber, and vitamin D is considered a U.S. public health concern. Shifts in eating patterns that increase the consumption of vegetables, fruits, whole grains, nuts/seeds, and dairy products can help achieve the recommended intakes of these nutrients, leading to healthier diets. Objective: We assessed the impact of adding 1 ounce (28.35 g) of walnuts to usual diets on diet quality and nutrients of concern, including magnesium, fiber, and potassium. Methods: We utilized 24 h dietary recalls obtained from the What We Eat in America, National Health and Nutrition Examination Survey (NHANES) and modeled the addition of 1 ounce (28.35 g) of walnuts to the usual diets of no-nut consumers. No-nut consumers aged _4 years (n = 7757) from the 2015–2018 NHANES study were included. Population percentages with intakes below the estimated average requirement (EAR) values for calcium, magnesium, folate, and vitamin E and above the adequate intake (AI) values for potassium and fiber were examined. Diet quality was assessed using the Healthy Eating Index-2015 (HEI-2015). The National Cancer Institute method was used to estimate the usual and modeled intakes. Significant differences between usual (current) and modeled intakes were determined using non-overlapping 95% confidence intervals. All analyses included sample weights to account for the NHANES survey design. Results: Adding 1 ounce (28.35 g) of walnuts to the usual diet resulted in significant reductions in the percentages of adults with intakes below the EAR for magnesium and folate (69.6% vs. 52.0%; 49.2% vs. 40.6%, respectively), and increased the percentage of adults above the AI for potassium (22.8% vs. 26.5%). A similar trend was observed among children (4–18 years). HEI scores improved significantly from 49.1 (95% CI: 48.0–50.4) to 58.5 (95% CI: 57.5–59.6) in children and from 52.4 (95% CI: 51.0–53.8) to 59.2 (95% CI: 58.0–60.5) in adults. Conclusions: Adding 1 ounce (28.35 g) of walnuts to the usual diet of no-nut consumers improved the diet quality and adequacy of some under-consumed nutrients.

Long-term consumption of nuts (including peanuts, peanut butter, walnuts, and other nuts) in relation to risk of frailty in older women: evidence from a cohort study.

Wang, R., M.T. Hannan, M. Wang, A.W. Schwartz, E. Lopez-Garcia, F. Grodstein, 2023. Long-term consumption of nuts (including peanuts, peanut butter, walnuts, and other nuts) in relation to risk of frailty in older women: evidence from a cohort study. J. Nutr. 153(3): 820–827.

Background: Adherence to a healthy diet is inversely associated with frailty. However, the relationship between nuts, a key food group of Mediterranean diet, and frailty is unclear. Objectives: This study aimed to evaluate the association between nut consumption and frailty in an aging female population. Methods: This population-based observational study included nonfrail women (60 y old) in the NHS from 11 states of the United States.

Outcome was incident frailty, defined as having 3 of the FRAIL components (fatigue, lower strength, reduced aerobic capacity, multiple chronic conditions, and significant weight loss) and assessed every 4 y from 1992 to 2016. From 1990 to 2014, FFQs were used to assess the intakes of peanuts, peanut butter, walnuts (added in 1998), and other nuts at 4-y intervals. Exposure was total nut consumption, calculated as the sum of intakes of peanuts, peanut butter, walnuts, and other nuts and categorized into <1 serving/mo, 1–3 servings/mo, 1 serving/wk, 2 4 servings/wk, and 5 servings/wk. The relations of intakes of peanuts, peanut butter, and walnuts with frailty were also investigated separately. Cox proportional hazards models were used to assess the associations between nut consumption and frailty after adjusting for age, smoking, BMI, EI, diet quality, and medication use. Results: Among 71,704 participants, 14,195 incident frailty cases occurred over 1,165,290 person-years. The adjusted HR (95% CI) for consuming 5 servings/wk of nuts was 0.80 (0.73, 0.87), as compared with <1 serving/mo. Higher intakes of peanuts and walnuts, but not peanut butter, were also inversely associated with frailty. Conclusions: This large prospective cohort study showed a strong and consistent inverse association between regular nut consumption and incident frailty. This suggests that nut consumption should be further tested as a convenient public health intervention for the preservation of health and well-being in older adults.

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.

Long-term consumption of nuts (including peanuts, peanut butter, walnuts, and other nuts) in relation to risk of frailty in older women: evidence from a cohort study.

Wang, R., M.T. Hannan, M. Wang, A.W. Schwartz, E. Lopez-Garcia, F. Grodstein, 2023. Long-term consumption of nuts (including peanuts, peanut butter, walnuts, and other nuts) in relation to risk of frailty in older women: evidence from a cohort study. J Nutr. 153(3):820-7. https://doi.org/10.1016/j.tjnut.2023.01.003

Background: Adherence to a healthy diet is inversely associated with frailty. However, the relationship between nuts, a key food group of Mediterranean diet, and frailty is unclear. Objectives: This study aimed to evaluate the association between nut consumption and frailty in an aging female population. Methods: This population-based observational study included nonfrail women (60 y old) in the NHS from 11 states of the United States. Outcome was incident frailty, defined as having 3 of the FRAIL components (fatigue, lower strength, reduced aerobic capacity, multiple chronic conditions, and significant weight loss) and assessed every 4 y from 1992 to 2016. From 1990 to 2014, FFQs were used to assess the intakes of peanuts, peanut butter, walnuts (added in 1998), and other nuts at 4-y intervals. Exposure was total nut consumption, calculated as the sum of intakes of peanuts, peanut butter, walnuts, and other nuts and categorized into <1 serving/mo, 1-3 servings/mo, 1 serving/wk, 2-4 servings/wk, and ≥ 5 servings/wk. The relations of intakes of peanuts, peanut butter, and walnuts with frailty were also investigated separately. Cox proportional hazards models were used to assess the associations between nut consumption and frailty after adjusting for age, smoking, BMI, EI, diet quality, and medication use. Results: Among 71,704 participants, 14,195 incident frailty cases occurred over 1,165,290 person-years. The adjusted HR (95% CI) for consuming ≥ 5 servings/wk of nuts was 0.80 (0.73, 0.87), as compared with <1 serving/mo. Higher intakes of peanuts and walnuts, but not peanut butter, were also inversely associated with frailty. Conclusions: This large prospective cohort study showed a strong and consistent inverse association between regular nut consumption and incident frailty. This suggests that nut consumption should be further tested as a convenient public health intervention for the preservation of health and well-being in older adults.