Archive

Research Nut: Walnuts

Systemic inflammation and the inflammatory context of the colonic microenvironment is improved by urolithin A.

Moussa, M.R., N. Fan, J. Birk, A.A. Provatas, P. Mehta, Y. Hatano, O.K. Chun, M Darooghegi Mofrad, A. Lotfi, A. Aksenov, V.N. Motta, M. Zenali, H. Vaziri, J.J. Grady, M. Nakanishi, D.W. Rosenberg, 2025. Systemic inflammation and the inflammatory context of the colonic microenvironment is improved by urolithin A. Cancer Prev Res (Phila). https://doi.org/10.1158/1940-6207.capr-24-0383

Diet affects cancer risk and plant-derived polyphenols exhibit cancer-preventive properties. Walnuts are an exceptional source of polyphenolic ellagitannins, converted into urolithins by gut microflora. This clinical study examines the impact of urolithin metabolism on inflammatory markers in blood and colon polyp tissue. We evaluate the effects of walnut consumption on urinary urolithins, serum inflammatory markers and immune cell markers in polyp tissues obtained from 39 subjects. Together with detailed food frequency data, we perform integrated computational analysis of metabolomics data combined with serum inflammatory markers and spatial imaging of polyp tissues using imaging mass cytometry. LC-MS/MS analyses of urine and fecal samples identifies a widely divergent capacity to form nine urolithin metabolites in this patient population. Subjects with higher urolithin A formation exhibit lower levels of several key serological inflammatory markers, including C-peptide, sICAM 1, sIL6R, Ghrelin, TRAIL, sVEGFR2, PDGF and MCP2, alterations that are more pronounced in obese individuals for siCAM-1, ENA-78, Leptin, GLP-1 and MIP-1D. There is a significant increase in levels of PYY associated with urolithin A formation, whereas TNF-α levels show an opposite trend, recapitulated in an in vitro system with ionomycin/PMA-stimulated PBMCs. Spatial imaging of colon polyp tissues shows altered cell cluster patterns, including a significant reduction of vimentin and CD163 expression associated with urolithin A. The ability to form urolithin A is linked to inflammation, warranting further studies to understand the role of urolithins in cancer prevention.

The impact of a walnut-rich breakfast on cognitive performance and brain activity throughout the day in healthy young adults: a crossover intervention trial.

Bell, L., G.F. Dodd, M. Jeavons, D.R. Fisher, A.R. Whyte, B. Shukitt-Hale, C.M. Williams, 2025. The impact of a walnut-rich breakfast on cognitive performance and brain activity throughout the day in healthy young adults: a crossover intervention trial. Food Funct. 16(5):1696-1707. https://doi.org/10.1039/d4fo04832f

A healthy diet is essential for optimal brain health and many bioactives from food are linked to cognitive benefits. To examine whether walnuts led to cognitive improvements throughout the day, 32 healthy young adults, aged 18-30, were tested in a double-blind, crossover pilot study, to compare the effects of a breakfast containing 50 g walnuts with a calorie-matched control containing no nuts. Cognition, mood, blood, and EEG measures were recorded at baseline and 2, 4, and 6 hours postprandially. Mood ratings for negative affect appeared worse following walnuts compared to control, possibly due to a general dislike of the intervention. However, walnuts elicited faster reaction times throughout the day on executive function tasks. Memory recall performance at 2 hours was worse for walnuts compared to control, but by 6 hours this finding was reversed with walnuts outperforming the control. EEG PSD analysis revealed differences in frontoparietal activity in the walnut condition compared to the control condition during memory recall and during executive function performance. These results may reflect between-treatment differences in cognitive effort or attentional processes while performing the tasks. Blood analysis revealed lower circulating non-esterified fatty acids and small increases in glucose availability following consumption of walnuts compared to control, suggesting enhanced glucose availability as one possible mechanism of action. Further investigations of other potential mechanisms are needed. Overall, these findings provide evidence for reaction time benefits throughout the day following a walnut-rich breakfast, while memory findings were mixed with benefits only observed later in the day. However, more research is needed into how diets containing walnuts might regulate cognitive improvements in humans postprandially and over the longer term.

Upcycling commercial nut byproducts for food, nutraceutical, and pharmaceutical applications: A comprehensive review.

Alasalvar, C., G. Huang, B.W. Bolling, P.A. Jantip, R.B. Pegg, X.K. Wong, S.K. Chang, E. Pelvan, A.C. de Camargo, G. Mandalari, A. Hossain, F. Shahidi, 2025. Upcycling commercial nut byproducts for food, nutraceutical, and pharmaceutical applications: A comprehensive review. Food Chem. 467:142222. https://doi.org/10.1016/j.foodchem.2024.142222

This article presents a comprehensive overview of upcycling commercial nut byproducts (such as almond, Brazil nut, cashew, hazelnut, macadamia, peanut (also known as a legume), pecan, pine nut, pistachio, and walnut) for food, nutraceutical, and pharmaceutical applications. Upcycling nut byproducts, namely husk/hull, hard shell, brown skin, defatted flour/meal/cake, pine cone, cashew nut shell liquid, cashew apple, walnut septum, and dreg/okara, has great potential, not only to reduce/minimise waste, but also to fit within the circular economy concept. Each byproduct has its own unique functional properties, which can bring significant value. These byproducts can be used as value-added ingredients to promote better health and well-being, due to their rich sources of diverse bioactive components/phytochemicals, polysaccharides, fibre, lignin, prebiotics, oils, proteins, bioactive peptides, minerals, and vitamins, among other components. This comprehensive review provides a basis for future research and development of product applications for nut byproducts. More studies are needed on novel product development to valorise nut byproducts.

Consumption of tree nuts as snacks stimulates changes in plasma fatty acid profiles and adipose tissue gene expression in young adults at risk for metabolic syndrome

Widmer, A., K. Lillegard, K. Wood, M. Robles, R. Fan, F. Ye, J.R. Koethe, H.J. Silver, 2025. Consumption of tree nuts as snacks stimulates changes in plasma fatty acid profiles and adipose tissue gene expression in young adults at risk for metabolic syndrome. Clinical Nutrition. (48)25 – 34. https://doi.org/10.1016/j.clnu.2025.03.002.

Background and aims: The prevalence of metabolic syndrome has been increasing in young adults, concomitant with the occurrence of increased abdominal adiposity. We previously reported that consuming tree nuts, as replacement for typical high-carbohydrate snacks, reduces visceral fat and waist circumference in young adults who have one or more metabolic syndrome risk factors. We aimed to investigate the effects of tree nuts snack consumption on plasma and adipose tissue fatty acid profiles along with changes in the expression of adipose tissue genes involved in thermogenesis, glycemia, adipocyte signaling, lipolysis, and immunity. Methods: A randomized parallel-arm 16-week intervention trial was conducted in 84 adults aged 22-36 years. Participants in both groups were provided with caloric goals for weight maintenance, daily menus, and pre-portioned snacks at every other week visits with study registered dietitians. Changes in dietary fatty acid intakes, plasma and abdominal subcutaneous adipose tissue (SAT) triglycerides fatty acid profiles using gas-liquid chromatography, and the expression of 241 genes in abdominal SAT were evaluated. Results: Consuming tree nuts snacks increased mono- and polyunsaturated fatty acid intakes yielding a 9-fold greater dietary unsaturated to saturated fat ratio. The tree nuts snack group also had significantly greater improvements in plasma 16:1/16:0 ratio; plasma phospholipids oleic and gamma linolenic acid content; plasma diglycerides, triglycerides, and cholesterol esters oleic acid content; and total plasma monounsaturated fatty acids. While abdominal SAT only showed trends for increased oleic acid content and unsaturated to saturated fat ratio, the tree nuts snacks participants had altered expression of 13 genes in abdominal SAT that have roles in nutrient sensing, energy homeostasis, and vulnerability to obesity. Conclusions: Replacing typical high-carbohydrate snacks with tree nuts results in more favorable dietary, plasma, and adipose tissue fatty acid profiles that could aid in preventing the development of excess adiposity and cardiometabolic disease states including metabolic syndrome.

Dietary walnuts prevented indomethacin-induced gastric damage via AP-1 transcribed 15-PGDH, Nrf2-mediated HO-1, and n-3 PUFA-derived Resolvin E1.

Park, J.M., K.B. Hahm, 2024. Dietary walnuts prevented indomethacin-induced gastric damage via AP-1 transcribed 15-PGDH, Nrf2-mediated HO-1, and n-3 PUFA-derived Resolvin E1. Int J Mol Sci. 25(13):7239. https://doi.org/10.3390/ijms25137239.

Non-steroidal anti-inflammatory drugs (NSAIDs), the most highly prescribed drugs in the world for the treatment of pain, inflammation, and fever, cause gastric mucosal damage, including ulcers, directly or indirectly, by which the development of GI-safer (-sparing) NSAIDs relates to unmet medical needs. This study aimed to document the preventive effects of walnut polyphenol extracts (WPEs) against NSAID-induced gastric damage along with the molecular mechanisms. RGM-1 gastric mucosal cells were administered with indomethacin, and the expressions of the inflammatory mediators between indomethacin alone or a combination with WPEs were compared. The expressions of the inflammatory mediators, including COX-1 and COX-2, prostaglandin E2, 15-hydroxyprostaglandin dehydrogenase (15-PGDH), and antioxidant capacity, were analyzed by Western blot analysis, RT-PCR, and ELISA, respectively. HO-1, Nrf-2, and keap1 were investigated. The in vivo animal models were followed with in vitro investigations. The NSAIDs increased the expression of COX-2 and decreased COX-1 and 15-PGDH, but the WPEs significantly attenuated the NSAID-induced COX-2 expression. Interestingly, the WPEs induced the expression of 15-PGDH. By using the deletion constructs of the 15-PGDH promoter, we found that c-Jun is the most essential determinant of the WPE-induced up-regulation of 15-PGDH expression. We confirmed that the knockdown of c-Jun abolished the ability of the WPEs to up-regulate the 15-PGDH expression. In addition, the WPEs significantly increased the HO-1 expression. The WPEs increased the nuclear translocation of Nrf2 by Keap-1 degradation, and silencing Nrf2 markedly reduced the WPE-induced HO-1 expression. We found that the WPE-induced HO-1 up-regulation was attenuated in the cells harboring the mutant Keap1, in which the cysteine 151 residue was replaced by serine. These in vitro findings were exactly validated in indomethacin-induced gastric rat models. Daily walnut intake can be a promising nutritional supplement providing potent anti-inflammatory, antioxidative, and mucosa-protective effects against NSAID-induced GI damage.

Key Area: Gut Health

Effects of walnut consumption for 2 years on older adults’ bone health in the Walnuts and Healthy Aging (WAHA) trial.

Oliver-Pons, C., A. Sala-Vila, M. Cofán, M. Serra-Mir, I. Roth, C. Valls-Pedret, M. Domènech, E. Ortega, S. Rajaram, J. Sabaté, E. Ros, G. Chiva-Blanch, 2024. Effects of walnut consumption for 2 years on older adults’ bone health in the Walnuts and Healthy Aging (WAHA) trial. J Am Geriatr Soc. 72(8):2471-2482. https://doi.org/10.1111/jgs.19007

Background: Nutritional strategies to maintain bone health in aging individuals are of great interest. Given the beneficial nutrient composition of walnuts, rich in alpha-linolenic (the vegetable n-3 fatty acid) and polyphenols, their regular consumption might be a dietary option to reduce age-related bone loss. We determined whether daily walnut consumption improves bone mineral density (BMD) and circulating biomarkers of bone turnover. Methods: The Walnuts and Healthy Aging study (WAHA) is a two-center, parallel, randomized controlled trial evaluating the effect of a diet enriched with walnuts at ≈15% energy compared with a control diet for 2 years on age-related health outcomes in healthy men and women aged 63–79 years. Changes in BMD were a prespecified secondary outcome only at the Barcelona node of the trial, where 352 participants were randomized. Retention rate was 92.6%. Primary endpoints were 2-year changes in BMD at the spine and the nondominant femoral neck, determined by dual-energy X-ray absorptiometry (DXA). Secondary endpoints were 2-year changes in bone turnover biomarkers (adrenocorticotropic hormone, Dickkopf WNT signaling pathway inhibitor-1, osteoprotegerin, osteocalcin, osteopontin, sclerostin, parathyroid hormone, and fibroblast growth factor-23), which were quantified in 211 randomly selected participants. Results: The walnut diet versus the control diet had no effect on 2-year changes in BMD at the spine (0.15% vs. 0.35%, p = 0.632) and femoral neck (−0.90% vs. −0.70%, p = 0.653), or on bone turnover biomarkers. Results were similar in participants treated or not with bone resorption inhibitors or those with or without osteoporosis/osteopenia at inclusion. Conclusions: Compared with the usual diet, a diet enriched with walnuts at 15% of energy for 2 years failed to improve BMD or circulating markers of bone metabolism in healthy older people.

Correlation between intestinal microbiota and urolithin metabolism in a human walnut dietary intervention.

Liu H, Birk JW, Provatas AA, Vaziri H, Fan N, Rosenberg DW, Gharaibeh RZ, Jobin C, 2024. Correlation between intestinal microbiota and urolithin metabolism in a human walnut dietary intervention. BMC Microbiol. 24(1):1–10. https://doi.org/10.1186/s12866-024-03626-5

This study is to investigate the relationship between the intestinal microbiota and urine levels of the ellagic acid derived polyphenols, the urolithins, in a cohort of subjects following a three-week walnut dietary intervention. We longitudinally collected fecal and urine samples from 39 subjects before and after walnut consumption (2 oz per day for 21 days). 16S RNA gene sequencing was performed on fecal DNA to study the association between microbiota composition and the levels of nine urolithin metabolites, which were measured using UHPLC/Q-TOF–MS/MS. Fecal microbial composition was found to be significantly different between pre- and post-walnut intervention (beta diversity, FDR-p = 0.018; alpha diversity, p = 0.018). Roseburia, Rothia, Parasutterella, Lachnospiraceae UCG-004, Butyricicoccus, Bilophila, Eubacterium eligens, Lachnospiraceae UCG-001, Gordonibacter, Paraprevotella, Lachnospira, Ruminococcus torques, and Sutterella were identified as the 13 most significantly enriched genera after daily intake of walnuts. We observed 26 genera that were significantly associated with 7 urolithin metabolites, with 22 genera positively correlating after walnut supplementation (FDR-p ≤ 0.05). PICRUSt analysis showed that several inferred KEGG orthologs were associated with 4 urolithin metabolites after walnut intake. In this study, we found that walnut supplementation altered urolithin metabolites, which associates with specific changes in bacterial taxa and inferred functional contents.

Omega-3 blood biomarkers relate to brain glucose uptake in individuals at risk of Alzheimer’s disease dementia.

Lázaro, I., O. Grau-Rivera, M. Suárez-Calvet, K. Fauria, C. Minguillón, M. Shekari, C. Falcón, M. García-Prat, J. Huguet, J.L. Molinuevo, J.D. Gispert, A. Sala-Vila, 2024. Omega-3 blood biomarkers relate to brain glucose uptake in individuals at risk of Alzheimer’s disease dementia. Alzheimers Dement (Amst). 16(3):e12596. https://doi.org/10.1002/dad2.12596

Introduction: Brain glucose hypometabolism is a preclinical feature of Alzheimer’s disease (AD). Dietary omega-3 fatty acids promote brain glucose metabolism, but clinical research is incipient. Circulating omega-3s objectively reflect their dietary intake. Methods: This was a cross-sectional study in 320 cognitively unimpaired participants at increased risk of AD dementia. Using lipidomics, we determined blood docosahexaenoic (DHA) and alpha-linolenic (ALA) acid levels (omega-3s from marine and plant origin, respectively). We assessed brain glucose metabolism using [18-F]-fluorodeoxyglucose (FDG) positron emission tomography (PET). Results: Blood ALA directly related to FDG uptake in brain areas known to be affected in AD. Stronger associations were observed in apolipoprotein E ε4 carriers and homozygotes. For DHA, significant direct associations were restricted to amyloid beta-positive tau-positive participants. Discussion: Blood omega-3 directly relate to preserved glucose metabolism in AD-vulnerable brain regions in individuals at increased risk of AD dementia. This adds to the benefits of omega-3 supplementation in the preclinical stage of AD dementia. Highlights: Blood omega-3s were related to brain glucose uptake in participants at risk of Alzheimer’s disease (AD) dementia. Complementary associations were observed for omega-3 from marine and plant sources. Foods rich in omega-3 might be useful in early features of AD.

A cross-sectional study on the association of walnut consumption with obesity and relative fat mass among United States adolescents and young adults in NHANES (2003–2020).

Gletsu-Miller, N., Henschel, B., Tekwe, C.D. and Thiagarajah, K., 2024. A cross-sectional study on the association of walnut consumption with obesity and relative fat mass among United States adolescents and young adults in NHANES (2003–2020). Curr Dev in Nutr. 8(8), p.104407. https://doi.org/10.1016/j.cdnut.2024.104407

Background: Walnuts contain nutrients and phytochemicals that can promote metabolic health. However, the high energy content of walnuts along with other nuts raises the concern that consuming nuts promotes obesity. Objectives: We sought to investigate the associations between consumption of walnuts as well as other nuts and measures of obesity in adolescents and young adults. Methods: This study included 8874 adolescents (12–19 y) and 10,323 young adults (20–39 y) from 8 waves of National Health and Nutrition Examination Survey data (2003–2020). The associations of consumption of 1) walnuts only (WO); 2) walnuts with other nuts (WON); 3) other nuts (ON); and 4) no nuts (NN) with obesity status and relative fat mass (RFM) were assessed using logistic and linear regressions stratified by age group and sex. Sample weights were used in all statistical analyses. Results: The mean daily intake of walnuts was not different between the 2 walnut consumption groups within each age group (adolescents: 2.18 [standard error (SE) 0.14] g; P = 0.917; young adults: 4.23 [0.37] g; P = 0.682). The WON group had the lowest prevalence of obesity (adolescents: 8.3%; young adults: 21.1%) while the NN group had the highest prevalence (adolescents: 24.1%; young adults: 35.4%). The models indicated lower odds of obesity in adolescent girls (odds ratio [OR]: 0.27; P < 0.05) and young adult women (OR: 0.58; P < 0.05) who consumed WON than in those who consumed NN. In both young women and girls, RFM was significantly lower in the WON and ON groups than the NN group (P < 0.001). In young men, WON consumption was also associated with a lower RFM (OR: −1.24; 95% confidence interval: −2.21, −0.28) compared with NN consumption. Conclusions: For adolescent girls and young women, dietary intake of walnuts combined with other nuts has the strongest inverse association with measures of obesity.

Original article: adolescent dietary patterns derived using principal component analysis and neuropsychological functions: a cross-sectional analysis of Walnuts Smart Snack cohort.

Ayala-Aldana, N., A. Pinar-Martí, M. Ruiz-Rivera, S. Fernández-Barrés, D. Romaguera, J. Casanova-Mollà, N. Solà-Valls, J. Julvez, 2024. Original article: adolescent dietary patterns derived using principal component analysis and neuropsychological functions: a cross-sectional analysis of Walnuts Smart Snack cohort. Eur Child Adolesc Psychiatry. 2024 Sep 18. https://doi.org/10.1007/s00787-024-02577-6

A balanced diet is relevant for neuropsychological functioning. We aimed to analyze the association between dietary patterns and neuropsychological outcomes in a sample of healthy adolescents of the Walnuts Smart Snack (WSS) cohort from Barcelona city. We performed principal components analysis (PCA) to determine dietary patterns in the adolescent sample using a food frequency questionnaire (60 items). Multiple linear regression models were performed to analyze the association between PCA dietary patterns with neuropsychological outcomes: Strengths and Difficulties (SDQ) externalizing and internalizing scores, Attention Network Test (ANT) Impulsivity Index and Emotional Recognition Task (ERT) scores. We additionally adjusted the models for child sex, age, body mass index (BMI), physical activity and maternal education. Six dietary patterns were identified in PCA analyses. “low consumption of calorie-dense foods” dietary pattern had a negative association (protective) with the both SDQ outcomes (p value < 0.001) and “Nuts” dietary pattern showed a negative (protective) association with impulsivity index (β1= −24.60, 95% CI = −36.80, −12.41, p value < 0.001). Overall, our main results suggest that healthy dietary patterns, including higher intakes of “nuts” and a preference of “low consumption of calorie-dense foods” dietary patterns, could provide a beneficial association with neuropsychological functions during the adolescence period. The associations may include improvements of externalizing and internalizing problem symptoms, and impulsivity.