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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.

Validation of the NUT CRACKER diagnostic algorithm and prediction for cashew and pistachio co-allergy.

Goldberg, M.R., M.Y. Appel, K. Tobi, M.B. Levy, N. Epstein-Rigbi, M. Holmqvist, J. Östling, L. Nachshon, J. Lidholm, A. Elizur, 2024. Validation of the NUT CRACKER diagnostic algorithm and prediction for cashew and pistachio co-allergy. J Allergy Clin Immunol Pract. 12(5):1273-1282.

Background: Because of the high cross-sensitization among tree nuts, the NUT CRACKER (Nut Co-reactivity-Acquiring Knowledge for Elimination Recommendations) study proposed a diagnostic algorithm to minimize the number of required oral food challenges (OFCs). Objective: To validate the algorithm for cashew and pistachio allergy and determine markers for allergic severity. Methods: Patients (n = 125) with a median age of 7.8 (interquartile range, 5.9-11.2) years with suspected tree nut allergy were evaluated prospectively with decision tree points on the basis of skin prick test (SPT), basophil activation test (BAT), and knowledge of the coincidence of allergies. Validation of allergic status was determined by OFC. Markers of clinical severity were evaluated using the combined original and prospective cohort (n = 187) in relationship to SPT, BAT, and Ana o 3-sIgE. Results: Reactivity to cashew in SPT, BAT, and Ana o 3-sIgE and the incidence of abdominal pain on challenge were significantly higher in dual-allergic cashew/pistachio patients (n = 82) versus single cashew allergic patients (n = 18) (P = .001). All 3 diagnostic tests showed significant inverse correlation with log10 reaction doses for positive cashew OFC. The algorithm reduced overall the total number of OFCs by 72.0%, with a positive predictive value and negative predictive value of 93.0% and 99.0%, respectively. Cashew false-positives were observed primarily in hazelnut-allergic patients (P = .026). In this population, Ana o 3-specific IgE could diagnose cashew allergy with a sensitivity of more than 90% and a specificity of more than 95%. Conclusions: The NUT CRACKER diagnostic algorithm was validated and reduced the number of diagnostic OFCs required. Markers for severity phenotypes may guide oral immunotherapy protocols, improving the risk/benefit ratio for patients.

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.

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.

Cashew nut (Anacardium occidentale L.) and cashew nut oil reduce cardiovascular risk factors in adults on weight-loss treatment: a randomized controlled three-arm trial (Brazilian Nuts Study).

Meneguelli, T.S., A.C.P. Kravchychyn, A.L. Wendling, A.P. Dionísio, J. Bressan, H.S.D. Martino, E. Tako, H.H.M. Hermsdorff, 2024. Cashew nut (Anacardium occidentale L.) and cashew nut oil reduce cardiovascular risk factors in adults on weight-loss treatment: a randomized controlled three-arm trial (Brazilian Nuts Study). Front Nutr. 11:1407028. https://doi.org/10.3389/fnut.2024.1407028

Introduction: Cashew nut contains bioactive compounds that modulate satiety and food intake, but its effects on body fat during energy restriction remains unknown. This study aimed to assess the effects of cashew nut and cashew nut oil on body fat (primary outcome) as well as adiposity, cardiometabolic and liver function markers (secondary outcomes). Materials and methods: An eight-week (8-wk) randomized controlled-feeding study involved 68 adults with overweight/obesity (40 women, BMI: 33 ± 4 kg/m2). Participants were randomly assigned to one of the energy-restricted (−500 kcal/d) groups: control (CT, free-nuts), cashew nut (CN, 30 g/d), or cashew nut oil (OL, 30 mL/d). Body weight, body composition, and blood collection were assessed at the baseline and endpoint of the study. Results: After 8-wk, all groups reduced significantly body fat (CT: −3.1 ± 2.8 kg; CN: −3.3 ± 2.7 kg; OL: −1.8 ± 2.6 kg), body weight (CT: −4.2 ± 3.8 kg; CN: −3.9 ± 3.1 kg; OL: −3.4 ± 2.4 kg), waist (CT: −5.1 ± 4.6 cm; CN: −3.9 ± 3.9 cm; OL: −3.7 ± 5.3 cm) and hip circumferences (CT: −2.9 ± 3.0 cm; CN:−2.7 ± 3.1 cm; OL: −2.9 ± 2.3 cm). CN group reduced liver enzymes (AST: −3.1 ± 5.3 U/L; ALT:−6.0 ± 9.9 U/L), while the OL-group reduced LDL-c (−11.5 ± 21.8 mg/dL) and atherogenic index (−0.2 ± 0.5). Both intervention groups decreased neck circumference (CN: −1.0 ± 1.2 cm; OL: −0.5 ± 1.2 cm) and apo B (CN: −6.6 ± 10.7 mg/dL; OL: −7.0 ± 15.3 mg/dL). Conclusion: After an 8-wk energy-restricted intervention, all groups reduced body fat (kg), weight, and some others adiposity indicators, with no different effect of cashew nut or cashew nut oil. However, participants in the intervention groups experienced additional reductions in atherogenic marker, liver function biomarkers, and cardiovascular risk factors (neck circumference and apo B levels), with these effects observed across the OL group, CN group, and both intervention groups, respectively.

Development of cashew and pistachio ladders through a food-processing approach. 

Shwe Yee, N., H.K. Ng, J. Zeng, J. Bao, D.E. Campbell, P.J. Turner, N.A. Lee, 2024. Development of cashew and pistachio ladders through a food-processing approach. Foods. 13(21):3440. https://doi.org/10.3390/foods13213440

Following successful oral immunotherapy (OIT) for peanut allergy using boiled peanuts (BOPI trial), this study investigated the potential of wet-thermal-processing-induced allergen modifi cation, specifically soaking and boiling (1–4 h) to reduce the allergenicity of cashew and pistachio allergens. In addition, this study provides a foundation of understanding for developing safer forms of cashew/pistachio administration for application in OIT by gradual exposure to increasing doses of modified allergens with reduced potency as an “allergen ladder”. An SDS-PAGE analysis and an intrinsic-fluorescence spectroscopy revealed altered tertiary structures of the allergens, leading to their denaturation and even degradation. Notably, the reduction in both allergen-specific polyclonal IgG and human-specific IgE (sIgE) binding correlated with the treatment time, with the most significant decrease observed after 4 h of boiling. In contrast, shorter soaking treatments showed negligible effects on the IgE-binding capacity of these nuts, therefore indicating a further need for optimization. These findings indicate that extended boiling effectively reduced the amounts of the highly potent allergenic component Ana o 3 in cashew and Pis v 1 in pistachio, as confirmed by ELISA using polyclonal anti-Ana o 3 antibodies, and an immunoblot showed decreased IgE epitope binding in cashew and pistachio allergens, which further modified their allergenic profiles. This approach shows promise as a viable method for offering a safer therapeutic option for cashew/pistachio allergy.

Safety of oral immunotherapy for cashew nut and peanut allergy in children – a retrospective single-centre study.

Breiding, M., M. Soomann, M. Roth, J. Trück, F. Bellutti Enders, 2024. Safety of oral immunotherapy for cashew nut and peanut allergy in children – a retrospective single-centre study. Swiss Med Wkly. 154(11):3691. https://smw.ch/index.php/smw/article/view/3691

AIM OF THE STUDY: Oral immunotherapy (OIT) is increasingly used for the treatment of childhood food allergies, with limited data available on cashew nut OIT. This real-life study investigated the safety and feasibility of cashew nut OIT, comparing it with peanut OIT, with a focus on the up-dosing process. METHODS: We analyzed cashew nut (n = 24) and peanut (n = 38) OIT cases with treatment initiated between 2018 and 2022 at the University Children’s Hospital Basel. All patients who commenced therapy within this time frame were enrolled without prior selection. Two different starting protocols were used. Within the up-dosing protocol, the nut intake was incrementally increased by 20–30% every 2 weeks until reaching a maintenance dose of 1g of nut protein. After consuming the maintenance dose regularly for 18–24 months, a second oral food challenge was performed. Patients who passed this challenge were considered desensitized. The safety of the therapy was evaluated based on the severity of adverse reactions during the up-dosing phase. Symptom severity was evaluated using the validated ordinal food allergy severity scale (o-FASS-5). RESULTS: Over the study period, 33% of cashew nut-allergic and 63% of peanut-allergic patients experienced mild to moderate allergic reactions. Severe allergic reactions occurred in five peanut-allergic children with high baseline allergen-specific IgE levels. Six patients with peanut, and none with cashew nut OIT, discontinued the therapy due to adverse reactions. The mean duration to reach the maintenance phase was longer for children with asthma or another food allergy. Among children who already underwent the second oral food challenge, desensitization was achieved in 91% (11 out of 12) of cashew nut- and 73% (11 out of 15) of peanut-allergic patients. CONCLUSION: Cashew nut OIT had a low severity of adverse reactions and was generally well-tolerated. However, patient characteristics influenced side effect risk and treatment duration, emphasizing the need for individualized OIT strategies.

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. MethodsIn 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.