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Research Nut: Walnuts

Red blood cell omega-3 status and longitudinal cognition in individuals at risk of Alzheimer’s disease.

Lázaro, I., A. Brugulat-Serrat, M. Suárez-Calvet, K. Fauria, C. Minguillon, J.D. Gispert, J.L. Molinuevo, W.S. Harris, G. Sánchez-Benavides, O. Grau-Rivera, A. Sala-Vila, 2025. Red blood cell omega-3 status and longitudinal cognition in individuals at risk of Alzheimer’s disease. J Nutr. S0022-3166(25)00576-0. doi: 10.1016/j.tjnut.2025.09.032.

Background. Many observational studies on dietary omega-3 fatty acids (FAs) and cognition focused on docosahexaenoic acid (DHA), because its significant role in brain. There is growing interest in whether other omega-3 FAs may also display cognitive benefits. Objectives. To examine the associations between the blood levels of three different omega-3 FAs (DHA; eicosapentaenoic acid [EPA]; and alpha-linolenic acid [ALA]) and 3-year changes in cognitive performance in a cohort of cognitively unimpaired individuals at high risk of Alzheimer’s disease (AD). Methods. Prospective longitudinal study conducted in 323 participants from the ALFA (ALzheimer and FAmilies) Study. We determined the baseline levels of omega-3 FAs in red blood cells (RBCs) using gas-chromatography. Participants underwent a comprehensive neuropsychological battery at baseline and after 3 yrs. We studied cognitive outcomes as rate of change between visits. We first constructed multivariate models to examine the association between RBC-DHA and the preclinical Alzheimer’s cognitive composite (PACC) score, also examining the effect of gender, APOE-ε4 carriership, and AD pathology (defined cerebrospinal fluid amyloid-beta and tau). As exploratory analysis, we examined associations between RBC-EPA and RBC-ALA with PACC, as well as those between omega-3 FAs and composite z-scores for attention, executive functioning, episodic memory, visual processing, and language domains. Results. RBC-DHA was associated with a positive (improved) global cognition (PACC) rate of change (estimate = 0.011, 95% confidence interval [CI] = 0.001;0.021, P = 0.024). No statistically significant interactions were observed for sex, APOE-ε4 carriership, or AD pathology. Higher RBC-ALA status was associated with positive rate of change (better performing) in visual processing (estimate = 0.425, 95% CI = 0.168;0.682, P = 0.001). Conclusions. In individuals at risk of AD, RBC-DHA and RBC-ALA showed positive associations with longitudinal cognition. These findings add to the observational evidence linking omega-3 FAs with improved brain health.

Novel proteomic signatures may indicate MRI-assessed intrahepatic fat state and changes: The DIRECT PLUS clinical trial.

Goldberg, D.T., A. Yaskolka Meir, G. Tsaban, E. Rinott, A. Kaplan, H. Zelicha, N. Klöting, U. Ceglarek, B. Iserman, I. Shelef, P. Rosen, M. Blüher, M. Stumvoll, O. Etzion, M.J. Stampfer, F.B. Hu, I. Shai, 2025. Novel proteomic signatures may indicate MRI-assessed intrahepatic fat state and changes: The DIRECT PLUS clinical trial. Hepatology. 81(1):198-211.   

Background and aims: We demonstrated in the randomized 18-month DIRECT PLUS trial (n = 294) that a Mediterranean (MED) diet, supplemented with polyphenol-rich Mankai duckweed, green tea, and walnuts and restricted in red/processed meat, caused substantial intrahepatic fat (IHF%) loss compared with 2 other healthy diets, reducing NAFLD by half, regardless of similar weight loss. Here, we investigated the baseline proteomic profile associated with IHF% and the changes in proteomics associated with IHF% changes induced by lifestyle intervention. Approach and results: We calculated IHF% by proton magnetic resonance spectroscopy (normal IHF% <5% and abnormal IHF% ≥5%). We assayed baseline and 18-month samples for 95 proteomic biomarkers. Participants (age = 51.3 ± 10.8 y; 89% men; and body mass index = 31.3 ± 3.9 kg/m 2) had an 89.8% 18-month retention rate; 83% had eligible follow-up proteomics measurements, and 78% had follow-up proton magnetic resonance spectroscopy. At baseline, 39 candidate proteins were significantly associated with IHF% (false discovery rate <0.05), mostly related to immune function pathways (e.g., hydroxy acid oxidase 1). An IHF% prediction based on the DIRECT PLUS by combined model (R2 = 0.47, root mean square error = 1.05) successfully predicted IHF% (R2 = 0.53) during testing and was stronger than separately inputting proteins/traditional markers (R2 = 0.43/0.44). The 18-month lifestyle intervention induced changes in 18 of the 39 candidate proteins, which were significantly associated with IHF% change, with proteins related to metabolism, extracellular matrix remodeling, and immune function pathways. Thrombospondin-2 protein change was higher in the green-MED compared to the MED group, beyond weight and IHF% loss (p = 0.01). Protein principal component analysis revealed differences in the third principal component time distinct interactions across abnormal/normal IHF% trajectory combinations; (p < 0.05 for all). Conclusions: Our findings suggest novel proteomic signatures that may indicate MRI-assessed IHF state and changes during lifestyle intervention. Specifically, carbonic anhydrase 5A, hydroxy acid oxidase 1, and thrombospondin-2 protein changes are independently associated with IHF% change, and thrombospondin-2 protein change is greater in the green-MED/high polyphenols diet.

Daily walnut consumption increases 6-sulfatoxymelatonin urinary levels and can improve sleep quality: a randomized crossover trial.

Zerón-Rugerio, M.F., A. Ibarra-Picón, M. Diez-Hernández, O. Comas-Basté, F.J. Pérez-Cano, T. Cambras, M. Izquierdo-Pulido, 2025. Daily walnut consumption increases 6-sulfatoxymelatonin urinary levels and can improve sleep quality: a randomized crossover trial. Food Funct. 2025 doi: 10.1039/d5fo00971e.

We aimed to study the potential impact of daily consumption of walnuts on urinary 6-sulphatoxymelatonin (6-SMT) levels and sleep quality parameters. We conducted an open-label randomized crossover trial (NCT04799821) in 76 young adults (24.1 ± 3.4 years; 85.5% women) who either ingested 40 g of walnuts daily during dinner (intervention) or refrained from eating walnuts or any other nuts (control) for 8 weeks, with a 2-week washout period. Outcome variables included the determination of 6-SMT in urine samples collected in two consecutive periods: evening (from 20:00 to 23:00) and nighttime (from 23:00 to 07:00), the measurement of sleep quality parameters (latency, wake after sleep onset, awakenings, and efficiency) and daytime sleepiness (Epworth Sleepiness Scale). Tryptophan and melatonin contents of the walnuts used for the intervention were quantified by high-performance liquid chromatography. The 8-week walnut intervention significantly increased evening urinary 6-SMT concentrations (p = 0.029) and improved sleep latency (p = 0.001), while no differences were found between the baseline and control conditions. Likewise, the walnut intervention resulted in increased global sleep quality (p = 0.002) and lower daytime sleepiness (p = 0.002). Partial correlation analyses indicated that during the intervention, evening urinary 6-SMT concentrations were significantly associated with higher sleep efficiency (p = 0.026) and an improved global sleep quality (p = 0.006). Our findings highlight the potential of walnuts as sleep-promoting foods among young adults. Specifically, we demonstrated that a daily serving of 40 g of walnuts increases urinary 6-SMT levels, reduces sleep latency, and improves global sleep quality. Further research is needed to fully understand the underlying mechanisms involved in the diet-sleep association.

Maternal nut and fish consumption during pregnancy and child risky decision-making at 11 years old.

Rivera, M.R., A. Pinar-Martí, I. Babarro, J. Ibarluzea, J. Vioque, S. Llop, A. Fernández-Somoano, A. Tardón, V. Pascual-Rubio, A. Fabregat-Sanjuan, S. Fernández-Barrés, D. Romaguera, M. Guxens, J. Julvez, 2025. Maternal nut and fish consumption during pregnancy and child risky decision-making at 11 years old. Eur Child Adolesc Psychiatry. doi: 10.1007/s00787-025-02750-5.

Antenatal diet may have a role in the development of impulsivity, and hence in risky decision-making. This study is assessing whether nut and fish consumption during pregnancy is associated with impulsivity and risky decision-making until pre-adolescence. This is a mother-child population-based birth cohort study, INMA (Infancia y Medio Ambiente) project (recruitment years 2004–2008). The final sample included 1386 healthy preadolescents and their mothers. The exposure variables included maternal nut and fish consumption during the first trimester of pregnancy from a validated food frequency questionnaire (FFQ). The main outcomes were impulsivity index (Attention Network Task, ANT) and the number of risky decision-making (Roulette Task). The association was estimated by multi-variable linear regression models. Children whose mothers were at the highest nut intake tertile showed less risky decision scores compared to those at the lowest tertile (β = -1.49, 95% CI = -2.85; -0.14; p-for-trend = 0.03). Fish consumption showed a positive association with ANT impulsivity index (the coefficient for second quintile compared to the lowest β = 65.73, 95% CI = 1.11; 130.35), with a p-value < 0.05 and a p-for-trend = 0.61. Although, no association was observed between fish consumption and risky decision-making outcome. Our study suggests that a higher nut intake during early pregnancy may be related with less risky decision-making in the 11-year-old children. Also, that a moderate intake of fish during early pregnancy seems to be associated with higher impulsivity in the offspring. The latter finding may be indicative of no benefits observed from seafood consumption.