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Research Nut: Hazelnuts

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.

Effects of enzymatic hydrolysis combined with pressured heating on tree nut allergenicity.

Cuadrado, C., C. Arribas, A. Sanchiz, M.M. Pedrosa, P. Gamboa, D. Betancor, C. Blanco, B. Cabanillas, R. Linacero, 2024.  Effects of enzymatic hydrolysis combined with pressured heating on tree nut allergenicity. Food Chem. 451:139433. https://doi.org/10.1016/j.foodchem.2024.139433

Hazelnut, pistachio and cashew are tree nuts with health benefits but also with allergenic properties being prevalent food allergens in Europe. The allergic characteristics of these tree nuts after processing combining heat, pressure and enzymatic digestion were analyzed through in vitro (Western blot and ELISA) and in vivo test (Prick-Prick). In the analyzed population, the patients sensitized to Cor a 8 (nsLTP) were predominant over those sensitized against hazelnut seed storage proteins (Sprot, Cor a 9 and 14), which displayed higher IgE reactivity. The protease E5 effectively hydrolyzed proteins from hazelnut and pistachio, while E7 was efficient for cashew protein hydrolysis. When combined with pressured heating (autoclave and Controlled Instantaneous Depressurization (DIC)), these proteases notably reduced the allergenic reactivity. The combination of DIC treatment before enzymatic digestion resulted in the most effective methodology to drastically reduce or indeed eliminate the allergenic capacity of tree nuts.

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.

Impact of heat and pressure processing treatments on the digestibility of peanut, hazelnut, pistachio and cashew allergens.

Arribas, C., A. Sanchiz, M.M. Pedrosa, S. Perez-Garcia, R. Linacero, C. Cuadrado, 2024. Impact of heat and pressure processing treatments on the digestibility of peanut, hazelnut, pistachio and cashew allergens. Foods. 13(22):3549. https://doi.org/10.3390/foods13223549

Abstract: Food processing can alter protein biochemical properties, impacting immunoreactivity and allergenicity. A key feature of food allergens is their resistance to enzymatic digestion, particularly by pepsin and trypsin. This study compares the digestomes of raw and heat- and/or pressure-treated peanuts, hazelnuts, pistachios and cashews using the INFOGEST harmonized digestion protocol and analyzing their IgE-binding capacity through in vitro methods. Protein patterns from controls and digestomes were resolved by SDS-PAGE and tested with sera from allergic patients, confirmed by competitive ELISA for hazelnuts and peanuts. The results indicate that processing methods differently affect the gastrointestinal (GI) digestion of these allergens. Simulated GI digestion caused a significant destruction of protein structures, reducing but not eliminating IgE reactivity for all four nuts. Boiling for 60 min did not change the SDS-PAGE profiles, but it did stimulate enzymatic activity, decreasing IgE binding capacity. In contrast, applying heat and pressure led to a nearly complete inhibition of allergenic potential during simulated digestion. These findings suggest that employing intense food processing techniques and investigating the gastrointestinal effects of highly allergenic nuts could be crucial steps toward developing new hypoallergenic formulations.

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.