Archive

Research Nut: Walnuts

Identification of new allergens in macadamia nut and cross-reactivity with other tree nuts in a Spanish cohort.

Gutiérrez-Díaz, G., D. Betancor, J. Parrón-Ballesteros, R.G. Gordo, E.S. Castromil-Benito, E. Haroun, M. Vázquez de la Torre, J. Turnay, M. Villalba, J. Cuesta-Herranz, C. Pastor-Vargas, 2024. Identification of new allergens in macadamia nut and cross-reactivity with other tree nuts in a Spanish cohort. Nutrients. 16(7):947. https://doi.org/10.3390/nu16070947

The consumption of macadamia nuts has increased due to their cardioprotective and antioxidant properties. However, this rise is consistent with an increase in the cases of macadamia nut allergy, leading to severe reactions. Although two Macadamia integrifolia allergens (Mac i 1 and Mac i 2) have been identified in Australian and Japanese patients, the allergenic sensitization patterns in Western European populations, particularly in Spain, remain unclear. For this purpose, seven patients with macadamia nut allergy were recruited in Spain. Macadamia nut protein extracts were prepared and, together with hazelnut and walnut extracts, were used in Western blot and inhibition assays. IgE-reactive proteins were identified using MALDI-TOF/TOF mass spectrometry (MS). Immunoblotting assays revealed various IgE-binding proteins in macadamia nut extracts. Mass spectrometry identified three new allergens: an oleosin, a pectin acetylesterase, and an aspartyl protease. Cross-reactivity studies showed that hazelnut extract, but not walnut extract, inhibited macadamia nut oleosin-specific IgE binding. This suggests that oleosin could be used as marker for macadamia-hazelnut cross-reactivity. The results show an allergenic profile in the Spanish cohort different from that previously detected in Australian and Japanese populations. The distinct sensitization profiles observed highlight the potential influence of dietary habits and environmental factors exposure on allergenicity.

Current options in the management of tree nut allergy: A systematic review and narrative synthesis.

Pasioti, M., P. Xepapadaki, A.G. Mathioudakis, J. Lakoumentas, E. Efstathiou, N.G. Papadopoulos, 2024. Current options in the management of tree nut allergy: A systematic review and narrative synthesis. Pediatr Allergy Immunol. 35(5):e14132. doi: 10.1111/pai.14132.

Tree nut allergy is a lifelong and potentially life-threatening condition. The standard of care is strictly avoiding the culprit nut and treating accidental reactions symptomatically. To evaluate potential therapeutic options for desensitizing patients with IgE-mediated tree nut allergy, we systematically searched three bibliographic databases for studies published until January 2024. We looked for active treatments of IgE-mediated allergy to tree nuts (walnut, hazelnut, pistachio, cashew, almond, pecan, macadamia nut, and brazil nut). We focused on allergen-specific immunotherapy (AIT) using oral (OIT), sublingual (SLIT), epicutaneous (EPIT), or subcutaneous (SCIT) delivery, or other disease-modifying treatments. We found 19 studies that met our criteria: 3 studies investigated sublingual immunotherapy, 5 studied oral immunotherapy to a single tree nut, and 6 used multi-food oral immunotherapy with or without omalizumab. The remaining studies investigated the effectiveness of monoclonal antibodies or IgE-immunoadsorption in multi-food allergic patients, including patients with tree nut allergy. The heterogeneity of the studies prevented pooling and meta-analysis. Oral immunotherapy, single or multi-nut, with or without omalizumab, was the most studied approach and appears effective in conferring protection from accidental exposures. Omalizumab monotherapy is the only approved alternative management for reducing allergic reactions that may occur with accidental exposure.

Tolerance of peanuts and tree nuts in Spanish children with exclusive sensitization to lipid transfer proteins.

De Agrela-Mendes, I., M. Pedrosa, C. Gómez-Traseira, E. Phillips-Anglés, M. Rodríguez-Álvarez, S. Quirce, 2024. Tolerance of peanuts and tree nuts in Spanish children with exclusive sensitization to lipid transfer proteins. Pediatr Allergy Immunol. 35(7):e14204. doi: 10.1111/pai.14204.

Background: Allergy to peanuts and tree nuts is a common cause of food allergy in Spain, with lipid transfer proteins (LTP) being the most frequently recognized panallergen. LTP sensitization often leads to multiple food group sensitivities, resulting in overly restrictive diets that hinder patient’s quality of life. This study aimed to assess the tolerance of peanuts and tree nuts (hazelnuts and walnuts) in children sensitized to LTP, potentially mitigating the need for such diets. Methods: This prospective study enrolled individuals diagnosed with allergy to peanuts, hazelnuts, or walnuts. Data were collected from medical records, including demographics and clinical history. Allergological assessment comprised skin prick tests using commercial extracts and the nuts in question, alongside measurements of total and specific IgE to nuts and their primary molecular components. Participants showing positive LTP sensitization without sensitization to seed storage proteins underwent open oral nut challenges. Results: A total of 75 individuals labeled as allergic to peanuts, 44 to hazelnuts, and 51 to walnuts were included. All of them underwent an open oral provocation test with the incriminated nut, showing a high tolerance rate. Peanut was tolerated by 98.6% of patients, 97.72% tolerated hazelnut, and 84.3% tolerated walnut. Conclusion: The findings suggest that the majority of patients allergic to peanuts, hazelnuts, or walnuts, due to LTP sensitization and lacking IgE reactivity to seed storage proteins, can tolerate these nuts. This supports the need for personalized nut tolerance assessments to avoid unnecessary dietary restrictions.

Efficacy of walnut supplementation in managing overweight and obesity: A meta-analysis of randomized clinical trials.

Liu, W., E. Li, M. Hu, 2024. Efficacy of walnut supplementation in managing overweight and obesity: A meta-analysis of randomized clinical trials. J. Funct. Foods. Volume 122, 106515. https://doi.org/10.1016/j.jff.2024.106515.

This study aimed to assess how effective walnut supplementation is in managing overweight and obesity. A thorough search of PubMed, Embase, and Cochrane Central Register of Controlled Trials was carried out until March 2024. Two reviewers independently examined the suitability of studies and assessed the quality of reporting in the randomized controlled trials (RCTs) that were included. The results indicated that adding walnuts to the diet significantly lowered total cholesterol (TC) levels (p < 0.0001) and low-density lipoprotein-cholesterol (LDL-C) levels (p < 0.001). However, there was no notable difference in weight loss (p > 0.05) and body mass index (BMI) (p > 0.05) between those who received walnut supplementation and the control groups. Based on the RCT data, it appears that walnut supplementation can effectively decrease TC and LDL-C levels. Additionally, it seems to be a safe choice for individuals who are overweight or obese, as it did not have an adverse effect on body weight.

Mixed nut consumption improves brain insulin sensitivity: a randomized, single-blinded, controlled, crossover trial in older adults with overweight or obesity.

 Nijssen, K.M., R.P. Mensink, J. Plat, D. Ivanov, H. Preissl, P.J. Joris, 2024. Mixed nut consumption improves brain insulin sensitivity: a randomized, single-blinded, controlled, crossover trial in older adults with overweight or obesity. Am J Clin Nutr. 119(2):314-323. https://doi.org/10.1016/j.ajcnut.2023.12.010

Background: Improving brain insulin sensitivity, which can be assessed by measuring regional cerebral blood flow (CBF) responses to intranasal insulin, may prevent age-related metabolic and cognitive diseases. Objectives: This study aimed to investigate longer-term effects of mixed nuts on brain insulin sensitivity in older individuals with overweight/obesity. Methods: In a randomized, single-blinded, controlled, crossover trial, 28 healthy adults (mean ± standard deviation: 65 ± 3 years; body mass index: 27.9 ± 2.3 kg/m2) received either daily 60-g mixed nuts (15 g of walnuts, pistachio, cashew, and hazelnuts) or no nuts (control) for 16 weeks, separated by an 8-week washout period. Throughout the study, participants were instructed to adhere to the Dutch food-based dietary guidelines. During follow-up, brain insulin action was assessed by quantifying acute effects of intranasal insulin on regional CBF using arterial spin labeling magnetic resonance imaging. Furthermore, effects on peripheral insulin sensitivity (oral glucose tolerance test), intrahepatic lipids, and cardiometabolic risk markers were assessed. Results: Body weight and composition did not change. Compared with control, mixed nut consumption improved regional brain insulin action in 5 clusters located in the left (difference in CBF responses to intranasal insulin: -4.5 ± 4.7 mL/100 g/min; P < 0.001; -4.6 ± 4.8 mL/100 g/min; P < 0.001; and -4.3 ± 3.6 mL/100 g/min; P = 0.007) and right occipital lobes (-4.3 ± 5.6 mL/100 g/min; and -3.9 ± 4.9 mL/100 g/min; P = 0.028). A fifth cluster was part of the left frontal lobe (-5.0 ± 4.6 mL/100 g/min; P < 0.001). Peripheral insulin sensitivity was not affected. Intrahepatic lipid content (-0.7%-point; 95% CI: -1.3%-point to -0.1%-point; P = 0.027), serum low-density lipoprotein cholesterol concentration (-0.24 mmol/L; 95% CI: -0.44 to -0.04 mmol/L; P = 0.019), and systolic blood pressure (-5 mm Hg; 95% CI: -8 to -1 mm Hg; P = 0.006) were lower after the mixed nut intervention. Conclusions: Longer-term mixed nut consumption affected insulin action in brain regions involved in the modulation of metabolic and cognitive processes in older adults with overweight/obesity. Intrahepatic lipid content and different cardiometabolic risk markers also improved, but peripheral insulin sensitivity was not affected.

Effects of longer-term mixed nut consumption on lipoprotein particle concentrations in older adults with overweight or obesity.

Nijssen, K.M.R., M.A. Chavez-Alfaro, P.J. Joris, J. Plat, R.P. Mensink, 2024. Effects of longer-term mixed nut consumption on lipoprotein particle concentrations in older adults with overweight or obesity. Nutrients. 17(1):8. https://doi.org/10.3390/nu17010008

Background: Recently, we reported that longer-term mixed nut intake significantly reduced serum total and low-density lipoprotein (LDL)-cholesterol, but these markers may not fully capture lipoprotein-related cardiovascular disease (CVD) risk. Objectives: This randomized, controlled, single-blinded, crossover trial in older adults with overweight or obesity examined the effects of longer-term mixed nut consumption on lipoprotein particle size, number, and lipid distribution. Methods: Twenty-eight participants (aged 65 ±3years; BMI 27.9 ± 2.3 kg/m2) completed two 16-week periods (control [no nuts] vs. mixed nuts (60 g/day: 15g of walnuts, pistachios, cashews, and hazelnuts), separated by an 8-week washout. Plasma lipoprotein particle numbers, sizes, and lipid distributions across subclasses were analyzed using high-throughput nuclear magnetic resonance (NMR) spectroscopy. Results: Mixed nut consumption significantly reduced Apolipoprotein B (ApoB) concentrations (−0.07 g/L; p = 0.009), total cholesterol (−0.27 mmol/L; p = 0.047), non-HDL cholesterol (−0.28 mmol/L; p = 0.022), and total triacylglycerol (TAG) (−0.27 mmol/L; p = 0.008). Total very large-density lipoprotein (VLDL) particle numbers decreased by 24 nmol/L (p < 0.001), with reductions observed across all VLDL subclasses. Total LDL particle numbers (p = 0.044), specifically intermediate-density lipoprotein (IDL) (p = 0.002) and large LDL particles (p = 0.015), were also reduced, while HDL particle numbers and sizes were unaffected. The mixed nut intervention significantly reduced cholesterol concentrations across all VLDL subclasses and IDL (all p < 0.01), with no changes in LDL or HDL subclasses. TAG concentrations showed reductions across all lipoprotein subclasses (all p < 0.05). Conclusions: Longer-term mixed nut consumption may lower CVD risk in older adults and favorable shifts in ApoB-containing lipoprotein subclasses towards a less atherogenic profile.

Consumption of tree nuts as snacks reduces metabolic syndrome risk in young adults: a randomized trial.

Sumislawski, K., A. Widmer, R.R. Suro, M.E. Robles, K. Lillegard, D. Olson, J.R. Koethe, H.J. Silver, 2023. Consumption of tree nuts as snacks reduces metabolic syndrome risk in young adults: a randomized trial. Nutrients. 15(24):5051. doi: 10.3390/nu15245051.

Metabolic syndrome (MetSx) and its chronic disease consequences are major public health concerns worldwide. Between-meal snacking may be a modifiable risk factor. We hypothesized that consuming tree nuts as snacks, versus typical carbohydrate snacks, would reduce risk for MetSx in young adults. A prospective, randomized, 16-week parallel-group diet intervention trial was conducted in 84 adults aged 22-36 with BMI 24.5 to 34.9 kg/m2 and ≥1 MetSx clinical risk factor. Tree nuts snacks (TNsnack) were matched to carbohydrate snacks (CHOsnack) for energy (kcal), protein, fiber, and sodium content as part of a 7-day eucaloric menu. Difference in change between groups was tested by analysis of covariance using general linear models. Multivariable linear regression modeling assessed main effects of TNsnack treatment and interactions between TNsnack and sex on MetSx score. Age, BMI, and year of study enrollment were included variables. There was a main effect of TNsnack on reducing waist circumference in females (mean difference: -2.20 ± 0.73 cm, p = 0.004) and a trend toward reduced visceral fat (-5.27 ± 13.05 cm2, p = 0.06). TNsnack decreased blood insulin levels in males (-1.14 ± 1.41 mIU/L, p = 0.05) and multivariable modeling showed a main effect of TNsnack on insulin. Main effects of TNsnack on triglycerides and TG/HDL ratio were observed (p = 0.04 for both) with TG/HDL ratio reduced ~11%. A main effect of TNsnack (p = 0.04) and an interaction effect between TNsnack and sex (p < 0.001) on total MetSx score yielded 67% reduced MetSx score in TNsnack females and 42% reduced MetSx score in TNsnack males. To our knowledge, this is the first randomized parallel-arm study to investigate cardiometabolic responses to TNsnacks versus typical CHOsnacks among young adults at risk of MetSx. Our study suggests daily tree nut consumption reduces MetSx risk by improving waist circumference, lipid biomarkers, and/or insulin sensitivity-without requiring caloric restriction.

Association of tree nut consumption with cardiovascular disease and cardiometabolic risk factors and health outcomes in US adults: NHANES 2011-2018.

Lopez-Neyman, S. M., N. Zohoori, K.S. Broughton, D.C. Miketinas, 2023. Association of tree nut consumption with cardiovascular disease and cardiometabolic risk factors and health outcomes in US adults: NHANES 2011-2018. Curr. Dev. Nutr. 7(10):102007. https://doi.org/10.1016/j.cdnut.2023.102007

Background: Tree nuts are nutrient dense, and their consumption has been associated with improvements in health outcomes. Objective: To estimate the usual tree nut intake and examine the association between tree nut consumption and cardiometabolic (CM) health outcomes in a nationally representative sample of US adults. Methods: Cross-sectional data were analyzed from a sample of 18,150 adults aged ≥ 20y who provided at least one reliable 24-h dietary recall and had complete data for the variables of interest in the NHANES 2011-2018. Tree nut consumers were defined as those consuming ≥ ¼ ounce/d (7.09 g). The National Cancer Institute Method was used to estimate the usual tree nut intake among consumers. Measurement error calibrated regression models were used to assess the association between tree nut consumption and each health outcome of interest. Results: Approximately 8% of all participants (n = 1238) consumed tree nuts and had a mean ± SE usual intake of 39.5 ± 1.8 g/d. Tree nut consumers were less likely to have obesity (31% vs. 40%, P < 0.001) and low high-density lipoprotein cholesterol (22% vs. 30%, P < 0.001) compared with nonconsumers. Moreover, tree nut consumers had a lower mean waist circumference (WC) (97.1 ± 0.7 vs. 100.5 ± 0.3 cm, P < 0.001) and apolipoprotein B (87.5 ± 1.2 vs. 91.8 ± 0.5 mg/dL, P = 0.004) than nonconsumers. After adjusting models for demographics and lifestyle covariates, the difference in WC between average intake (33.7 g/d) and low threshold intake (7.09/g) of tree nuts was -1.42 ± 0.58 cm (P = 0.005). Conclusions: Most US adults do not consume tree nuts, yet modest consumption was associated with decreased prevalence of cardiovascular disease and CM risk factors and improvement for some health outcome measures.

Effect of walnut supplementation on dietary polyphenol intake and urinary polyphenol excretion in the walnuts and healthy aging study.

Amen, R. I., Sirirat, R., Oda, K., Rajaram, S., Nwachukwu, I., Cofan, M., Ros, E., Sabate, J., & Haddad, E. H. (2023). Effect of walnut supplementation on dietary polyphenol intake and urinary polyphenol excretion in the walnuts and healthy aging study. Nutrients. 15(5):1253. https://doi.org/10.3390/nu15051253

Among all tree nuts, walnuts contain the highest total polyphenols by weight. This secondary data analysis examined the effect of daily walnut supplementation on the total dietary polyphenols and subclasses and the urinary excretion of total polyphenols in a free-living elderly population. In this 2-year prospective, randomized intervention trial (ID NCT01634841), the dietary polyphenol intake of participants who added walnuts daily to their diets at 15% of daily energy were compared to those in the control group that consumed a walnut-free diet. Dietary polyphenols and subclasses were estimated from 24 h dietary recalls. Phenolic estimates were derived from Phenol-Explorer database version 3.6. Participants in the walnut group compared to the control group had a higher intake of total polyphenols, flavonoids, flavanols, and phenolic acids in mg/d (IQR): 2480 (1955, 3145) vs. 1897 (1369, 2496); 56 (42,84) vs. 29 (15, 54); 174 (90, 298) vs. 140 (61, 277); and 368 (246, 569) vs. 242 (89, 398), respectively. There was a significant inverse association between dietary flavonoid intake and urine polyphenol excretion; less urinary excretion may imply that some of the polyphenols were eliminated via the gut. Nuts had a significant contribution to the total polyphenols in the diet, suggesting that a single food like walnuts added to habitual diet can increase the polyphenol intake in a Western population.

A polyphenol-rich green Mediterranean diet enhances epigenetic regulatory potential: the DIRECT PLUS randomized controlled trial. 

Hoffmann, A., A.Y. Meir, T. Hagemann, P. Czechowski, L. Müller, B. Engelmann, S.B. Haange, U. Rolle-Kampczyk, G. Tsaban, H. Zelicha, E. Rinott, A. Kaplan, I. Shelef, M. Stumvoll, M. Blüher, L. Liang, U. Ceglarek, B. Isermann, M. von Bergen, P. Kovacs, M. Keller, I. Shai, 2023. A polyphenol-rich green Mediterranean diet enhances epigenetic regulatory potential: the DIRECT PLUS randomized controlled trial. Metabolism. 145:155594. https://doi.org/10.1016/j.metabol.2023.155594S.

Background: The capacity of a polyphenol-enriched diet to modulate the epigenome in vivo is partly unknown. Given the beneficial metabolic effects of a Mediterranean (MED) diet enriched in polyphenols and reduced in red/processed meat (green-MED), as previously been proven by the 18-month DIRECT PLUS randomized controlled trial, we analyzed the effects of the green-MED diet on methylome and transcriptome levels to highlight molecular mechanisms underlying the observed metabolic improvements. Methods: Our study included 260 participants (baseline BMI = 31.2 kg/m2, age = 5 years) of the DIRECT PLUS trial, initially randomized to one of the intervention arms: A. healthy dietary guidelines (HDG), B. MED (440 mg polyphenols additionally provided by walnuts), C. green-MED (1240 mg polyphenols additionally provided by walnuts, green tea, and Mankai: green duckweed shake). Blood methylome and transcriptome of all study subjects were analyzed at baseline and after completing the 18-month intervention using Illumina EPIC and RNA sequencing technologies. Results: A total of 1573 differentially methylated regions (DMRs; false discovery rate (FDR) < 5 %) were found in the green-MED compared to the MED (177) and HDG (377) diet participants. This corresponded to 1753 differentially expressed genes (DEGs; FDR < 5 %) in the green-MED intervention compared to MED (7) and HDG (738). Consistently, the highest number (6 %) of epigenetic modulating genes was transcriptionally changed in subjects participating in the green-MED intervention. Weighted cluster network analysis relating transcriptional and phenotype changes among participants subjected to the green-MED intervention identified candidate genes associated with serum-folic acid change (all P < 1 × 10-3) and highlighted one module including the KIR3DS1 locus, being negatively associated with the polyphenol changes (e.g. P < 1 × 10-4), but positively associated with the MRI-assessed superficial subcutaneous adipose area-, weight- and waist circumference- 18-month change (all P < 0.05). Among others, this module included the DMR gene Cystathionine Beta-Synthase, playing a major role in homocysteine reduction. Conclusions: The green-MED high polyphenol diet, rich in green tea and Mankai, renders a high capacity to regulate an individual’s epigenome. Our findings suggest epigenetic key drivers such as folate and green diet marker to mediate this capacity and indicate a direct effect of dietary polyphenols on the one‑carbon metabolism.