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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.

Effect of premeal pistachio supplementation on cardiometabolic risk factors among Asian Indian adults with prediabetes: A randomized controlled trial.

Ashwini, K., K. Abirami, R. Gayathri, S. Sasikala, V. Sudha, S. Shobana, R.G. Jeevan, K. Krishnaswamy, V. Deepika, M. Rajalakshmi, R.M.R. Bai, K. Parkavi, S. Padmavathi, R.M. Anjana, R. Unnikrishnan, F.B. Hu, W.C. Willett, J. Salas-Salvadó, S.N. Bhupathiraju, V. Mohan, 2025. Effect of premeal pistachio supplementation on cardiometabolic risk factors among Asian Indian adults with prediabetes: A randomized controlled trial. J Nutr. 155(3):899-909. https://doi.org/10.1016/j.tjnut.2024.12.005

Background: Asian Indians are susceptible to developing type 2 diabetes at a lower age and often consume diets that are high in glycemic load and low in healthy fats. Objectives: This study aimed to evaluate the effect of 30g prebreakfast and 30g predinner supplementation of pistachios for 12 wk on glycated hemoglobin (HbA1c), other glycemic markers, anthropometry, and lipid profile of Asian Indians with prediabetes. Methods: In a 12-wk parallel arm, randomized controlled trial, we recruited 120 participants with prediabetes based on American Diabetes Association criteria. The intervention group (n = 60) consumed 60g pistachios (30g prebreakfast and predinner) whereas the control group (n = 60) followed a routine diet that excluded nuts. At baseline and 12 wk, we collected blood samples for biochemical analysis, anthropometrics, and 24-h recalls. Participants wore a continuous glucose monitoring (CGM) sensor during the trial’s first and last 2 wk. Urinary N-methyl-trans-4-hydroxy-l-proline (MHP) was measured as a marker of pistachio consumption. Results: A total of 109 participants completed the study (follow-up rate = 90.8%). Compared with participants in the control group, those in the intervention group had significant reductions in HbA1c (mean between-group difference: −0.2; 95% confidence interval: −0.3, −0.1; P < 0.001] with no significant changes in fasting or 2-h post glucose load plasma glucose. Compared with the control group, the intervention group had significant reductions in serum triglyceride, waist circumference, lipid accumulation product, visceral adiposity index, and atherogenic index. Urinary MHP (mg/g creatinine) showed a 62% increase in the intervention compared with the control group (P < 0.05). CGM data revealed significant decreases in the incremental area under the curve, 2-h after breakfast (28%, p=0.01) and after dinner (17%, P = 0.002) in the intervention group compared to the control group. Conclusions: A 12-wk, premeal load of 60g pistachios lowers HbA1c and improves cardiometabolic profile among Asian Indians with prediabetes. This is among the first studies to investigate these effects in this ethnic group.

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.

Intake of pistachios as a nighttime snack has similar effects on short- and longer-term glycemic control compared with education to consume 1-2 carbohydrate exchanges in adults with prediabetes: A 12-wk randomized crossover trial.

Riley, T.M., P.M. Kris-Etherton, T.L. Hart, K.S. Petersen, 2024. Intake of pistachios as a nighttime snack has similar effects on short- and longer-term glycemic control compared with education to consume 1-2 carbohydrate exchanges in adults with prediabetes: A 12-wk randomized crossover trial. J Nutr. 154(4):1219-1231. https://doi.org/10.1016/j.tjnut.2024.01.021

Background: Nut intake is associated with better glycemic control and lower cardiovascular disease (CVD) risk. It remains unclear if nut intake timing affects glycemic control and CVD risk factors. Intake of pistachios as a nighttime snack may attenuate morning glucose production and lower fasting plasma glucose (FPG). Objectives: We assessed the effects of a nighttime (after dinner and before bedtime) pistachio snack (57g/d) on glycemic control markers, vascular health, lipids/lipoproteins, and diet quality compared with education to consume 1–2 carbohydrate (CHO) exchanges (usual care) in individuals with prediabetes. Methods: A 2-period, randomized crossover trial was conducted. Participants were provided 57g/d of dry roasted unsalted pistachios (319 kcal; fat 26g; CHO 16 g; protein 12 g; fiber 6 g) as a nighttime snack or received usual care for 12 wk. Primary (FPG) and secondary outcomes [hemoglobin A1c (HbA1c), insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), lipids/lipoproteins, vascular health, and Healthy Eating Index-2015 (HEI-2015)] were measured before and after each condition. Results: A total of 66 participants (50.9 ± 11.6 y, FPG: 106.2 ± 6.4 mg/dL) were randomly assigned, and 51 participants completed the trial. No between-condition differences in FPG {0.9 mg/dL [95% confidence interval (CI): −1.2, 3.1]}, HbA1c, insulin, HOMA-IR, lipids/ lipoproteins, blood pressure, or vascular health were observed. The HEI-2015 score was higher after the pistachio condition [6.8 points (95% CI: 1.5, 12.1)] than after usual care driven by higher component scores for seafood and plant proteins [2.0 points (95% CI: 1.0, 2.9)], refined grains [2.3 points (95% CI: 1.1, 3.5)], and the fatty acid ratio [1.7 points (95% CI: 0.0, 3.5)]. Conclusions: In adults with prediabetes, consuming 57 g/d of pistachios as a nighttime snack increased diet quality but had similar effects on glycemic markers, lipids/lipoproteins, blood pressure, and vascular health compared with the usual care comparator. Pistachios may be a healthful alternative to carbohydrate-rich nighttime snacks to increase alignment with Dietary Guidelines for Americans.

Pistachio (Pistacia vera L.) consumption improves cognitive performance and mood in overweight young adults: A pilot study.

Landaverde-Mejia, K., E. Dufoo-Hurtado, D. Camacho-Vega, M.E. Maldonado-Celis, S. Mendoza-Diaz, R. Campos-Vega, 2024. Pistachio (Pistacia vera L.) consumption improves cognitive performance and mood in overweight young adults: A pilot study. Food Chem. 457, 140211. https://doi.org/10.1016/j.foodchem.2024.140211

This pilot study evaluated the impact of pistachio consumption on cognitive performance and mood in overweight young adults. Pistachios were characterized (chemical and nutraceutical), and a baseline-final, uncontrolled nutritional intervention was performed (28 g of pistachio/28 days). Psychometric tests were applied to estimate cognitive performance and mood; anthropometric evaluation, biochemical analysis, and plasma antioxidant activity were included. The main component of nuts was lipids (48.1%). Pistachios consumption significantly (p ≤ 0.05) reduced waist circumference (−1.47 cm), total cholesterol (−10.21 mg/dL), LDL (−6.57 mg/dL), and triglycerides (−21.07 mg/dL), and increased plasma antioxidant activity. Pistachio supplementation improved risk tolerance (p ≤ 0.006) and decision-making strategy (p ≤ 0.002; BART-task), executive functions (BCST-task; p ≤ 0.006), and selective and sustained attention (Go/No-Go-test; p ≤ 0.016). The mood state was positively modulated (p ≤ 0.05) for anxiety, anger-hostility, and sadness-depression. These results show for the first time the benefits of pistachio consumption on cognitive performance and mood in overweight young adults.

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.

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.