Mixed nut consumption improves brain insulin sensitivity: a randomized, single-blinded, controlled, crossover trial in older adults with overweight or obesity
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. Objective: 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, twenty-eight healthy adults (mean±SD; 65±3 years; BMI: 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 five clusters located in the left (difference in CBF responses to intranasal insulin: -4.5±4.7 mL/100g/min; P<0.001; -4.6±4.8 mL/100g/min; P<0.001; and -4.3±3.6 mL/100g/min; P=0.007) and right occipital lobe (-4.3±5.6 mL/100g/min; and -3.9±4.9 mL/100g/min; P=0.028). A fifth cluster was part of the left frontal lobe (-5.0±4.6 mL/100g/min; P<0.001). Peripheral insulin sensitivity was not affected. Intrahepatic lipid content (-0.7 %-point; 95%CI: -1.3 to -0.1; P=0.027), serum LDL cholesterol (-0.24 mmol/L; 95%CI: -0.44 to -0.04; P=0.019), and systolic blood pressure (-5 mmHg; 95%CI: -8 to -1; 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.
https://doi.org/10.1016/j.ajcnut.2023.12.010
EU and US Reach Deal to Extend Pause on Tariff Dispute
The tariff suspension will remain in force until the end of March 2025
Under an agreement announced on December 19, 2023, the European Union and the United States will extend the suspension of tariffs until March 31, 2025 in the context of a longstanding steel and aluminum dispute.
The dispute dates back to 2018, when the US introduced tariffs on European steel and aluminum and the EU responded by introducing rebalancing tariffs on imports of certain American products —including peanut butter and processed cranberry products— into the EU. In 2022, the parties reached an interim agreement under which the EU suspended its rebalancing tariffs until December 31, 2023, to allow time for negotiations towards a longer-term solution.
Under the deal announced this week, the EU-US trade dispute will be paused until after the 2024 American presidential election.
Consumption of tree nuts as snacks reduces metabolic syndrome risk in young adults: A randomized trial
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.
https://doi.org/10.3390/nu15245051
A Randomized, Placebo-Controlled Phase 1 Safety Study of OMIT in Adults with Peanut Allergy
Introduction: Oral Mucosal Immunotherapy (OMIT) uses a specially formulated toothpaste to deliver allergenic proteins to immunologically active areas of the oral cavity, a delivery mechanism which has the greatest potential for food allergy desensitization. OMIT presents advantages over other approaches to allergy immunotherapy due to its targeted delivery and simplified administration, supporting the goal of improved adherence. Methods: This study enrolled 32 adults, age 18-55, with peanut allergy in a 3:1 ratio to receive either an escalating dose of INT301 or placebo. Inclusion criteria included a positive SPT with a wheal diameter at least 3mm greater than control and/or psIgE ≥ 0.35 kU/L. Additionally, subjects were required to fail an oral food challenge ≤ 100 mg of peanut protein. During this 48-week trial, safety profile was monitored during the up-dosing and maintenance phases. Exploratory biomarkers were evaluated. Results: 100% of active subjects consistently tolerated the pre-specified protocol highest dose. No moderate nor severe systemic reactions in active participants. Non-systemic adverse reactions were mostly local (oral itching), mild and transient. 97% adherence to treatment with no dropouts due to study medication. Exploratory biomarkers were consistent with an immunologic response to treatment in a designated subset of subjects. Conclusion: In this phase 1 OMEGA trial, adherence and safety profile of INT301 successfully achieved the primary and secondary endpoints. OMIT appears to be a safe and convenient option for individuals with food allergies. Immunologic response to treatment suggests further evaluation. These results support continued development of INT301 in the pediatric population. https://doi.org/10.1016/j.anai.2023.10.023
Fast impedimetric immunosensing of IgGs associated with peanut and hazelnut allergens
Food allergies trigger a variety of clinical adverse symptoms and clinical evidence suggests that the presence of food allergy-related IgG can be helpful in the diagnosis when analyzed at the peptide-epitope level. To validate and select the peptides based on their specificity toward hazelnut or peanut epitopes, the authors of this study developed a silicon-based microchip coupled with click-chemistry bound peptides identified by the Fraunhofer Institute for Cell Therapy and Immunology. Peptides related to hazelnut and peanut allergies were identified and used to develop a silicon-based microchip. Peptides were coupled with click-chemistry to the sensor surface. The immunosensor was developed by electrografting diazotized amino phenylacetic acid and subsequently, dibenzocyclooctyne-amine (DBCO-NH2) was used as click-chemistry to allow coupling of the peptides with a C-terminal linker and azide structure. Energy-dispersive X-ray spectroscopy, electrochemical impedance spectroscopy (EIS), and fluorescence microscopy techniques have been used to analyze the bio-functionalization of the developed electrode. The peptide-epitope recognition was studied for seven allergen-derived peptides. The electrochemical responses were studied with sera from rabbits immunized with hazelnut and peanut powder. The microchips functionalized with the chosen peptides (peanut peptides T12 and EO13 and hazelnut peptides S4 and EO14 with an RSD of 4%, 3%, 9%, and 1% respectively) demonstrated their ability to specifically detect prevalent anti-nut related IgGs in rabbit sera in a range of dilutions from 1:500000 (0.0002%) until 1:50000 (0.002%). In addition, the other peptides showed promising differentiation abilities which can be further studied to perform multivariable detection fingerprint of anti-allergens in blood sera. https://doi.org/10.1016/j.bios.2023.115612
Desensitization and remission after peanut sublingual immunotherapy in 1- to 4-year-old peanut-allergic children: A randomized, placebo-controlled trial
Background: Prior studies of peanut sublingual immunotherapy (SLIT) have suggested a potential advantage with younger age at treatment initiation. Objective: We studied the safety and efficacy of SLIT for peanut allergy in 1- to 4-year-old children. Methods: Peanut-allergic 1- to 4-year-old children were randomized to receive 4 mg peanut SLIT versus placebo. Desensitization was assessed by double-blind, placebo-controlled food challenge (DBPCFC) after 36 months of treatment. Participants desensitized to at least 443 mg peanut protein discontinued therapy for 3 months and then underwent DBPCFC to assess for remission. Biomarkers were measured at baseline and longitudinally during treatment. Results: Fifty participants (25 peanut SLIT, 25 placebo) with a median age of 2.4 years were enrolled across 2 sites. The primary end point of desensitization was met with actively treated versus placebo participants having a significantly greater median cumulative tolerated dose (4443 mg vs 143 mg), higher likelihood of passing the month 36 DBPCFC (60% vs 0), and higher likelihood of demonstrating remission (48% vs 0). The highest rate of desensitization and remission was seen in 1- to 2-year-olds, followed by 2- to 3-year-olds and 3- to 4-year-olds. Longitudinal changes in peanut skin prick testing, peanut-specific IgG4, and peanut-specific IgG4/IgE ratio were seen in peanut SLIT but not placebo participants. Oropharyngeal itching was more commonly reported by peanut SLIT than placebo participants. Skin, gastrointestinal, upper respiratory, lower respiratory, and multisystem adverse events were similar between treatment groups. Conclusion: Peanut SLIT safely induces desensitization and remission in 1- to 4-year-old children, with improved outcomes seen with younger age at initiation. Keywords: Peanut allergy; SLIT; desensitization; food allergy; food immunotherapy; remission; sublingual immunotherapy. https://doi.org/10.1016/j.jaci.2023.08.032
A phase II study of Bruton's tyrosine kinase inhibition for the prevention of anaphylaxis
BACKGROUND. IgE-mediated anaphylaxis is a potentially fatal systemic allergic reaction for which there are no currently FDA-approved preventative therapies. Bruton’s tyrosine kinase (BTK) is an essential enzyme for IgE-mediated signaling pathways and is an ideal pharmacologic target to prevent allergic reactions. In this open-label trial, we evaluated the safety and efficacy of acalabrutinib, a BTK inhibitor that is FDA approved to treat some B cell malignancies, in preventing clinical reactivity to peanut in adults with peanut allergy. METHODS. After undergoing graded oral peanut challenge to establish their baseline level of clinical reactivity, 10 patients had a 6-week rest period, then received 4 standard doses of 100 mg acalabrutinib twice daily and underwent repeat food challenge. The primary endpoint was the change in patients’ threshold dose of peanut protein to elicit an objective clinical reaction. RESULTS. At baseline, patients tolerated a median of 29 mg of peanut protein before objective clinical reaction. During subsequent food challenge on acalabrutinib, patients’ median tolerated dose significantly increased to 4,044 mg (range 444–4,044 mg). 7 patients tolerated the maximum protocol amount (4,044 mg) of peanut protein with no clinical reaction, and the other 3 patients’ peanut tolerance increased between 32- and 217-fold. 3 patients experienced a total of 4 adverse events that were considered to be possibly related to acalabrutinib; all events were transient and nonserious. CONCLUSION. Acalabrutinib pretreatment achieved clinically relevant increases in patients’ tolerance to their food allergen, thereby supporting the need for larger, placebo-controlled trials.
https://doi.org/10.1172/JCI172335
Phase 3 Trial of Epicutaneous Immunotherapy in Toddlers with Peanut Allergy
Background: No approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown. Methods: We conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (the dose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months. The primary end point was a treatment response as measured by the eliciting dose of peanut protein at 12 months. Safety was assessed according to the occurrence of adverse events during the use of the peanut patch or placebo. Results: Of the 362 patients who underwent randomization, 84.8% completed the trial. The primary efficacy end point result was observed in 67.0% of children in the intervention group as compared with 33.5% of those in the placebo group (risk difference, 33.4 percentage points; 95% confidence interval, 22.4 to 44.5; P<0.001). Adverse events that occurred during the use of the intervention or placebo, irrespective of relatedness, were observed in 100% of the patients in the intervention group and 99.2% in the placebo group. Serious adverse events occurred in 8.6% of the patients in the intervention group and 2.5% of those in the placebo group; anaphylaxis occurred in 7.8% and 3.4%, respectively. Serious treatment-related adverse events occurred in 0.4% of patients in the intervention group and none in the placebo group. Treatment-related anaphylaxis occurred in 1.6% in the intervention group and none in the placebo group. Conclusions: In this trial involving children 1 to 3 years of age with peanut allergy, epicutaneous immunotherapy for 12 months was superior to placebo in desensitizing children to peanuts and increasing the peanut dose that triggered allergic symptoms. (Funded by DBV Technologies; EPITOPE ClinicalTrials.gov number, NCT03211247.).
https://doi.org/10.1056/NEJMoa2212895
Dietary intake and incidence risk of idiopathic pulmonary fibrosis: a Mendelian randomization study
Background: Dietary intake has been shown to have a causal relationship with various lung diseases, such as lung cancer and asthma. However, the causal relationship between dietary intake and idiopathic pulmonary fibrosis (IPF) remains unclear. We conducted a two-sample Mendelian Randomization (MR) study to investigate the causal relationship between dietary intake and IPF. Methods: The exposure datasets included meat, fruit, vegetable, and beverage intake from the UK Biobank. IPF data came from the EBI database of 451,025 individuals. All data in this study were obtained from the IEU Open GWAS Project. The inverse variance weighted (IVW), MR-Egger, and weighted median methods were used as the primary methods. Sensitivity analyses were performed to ensure the validity of the results. Results: Oily fish intake [odds ratio (OR):0.995; 95% confidence interval (CI): 0.993-0.998; p = 6.458E-05] and Dried fruit intake (OR:0.995;95%CI:0.991-0.998; p = 0.001) were discovered as protective factors. There was also a suggestive correlation between Beef intake (OR:1.006;95%Cl:1.001-1.012; p = 0.023) and IPF. Sensitivity analysis did not reveal any contradictory results. No causal relationship was found between IPF and the rest of the dietary exposures. Conclusions: Our study found that Oily fish and Dried fruit intake were associated with the risk of IPF, while Beef intake was suggestively associated with the risk of IPF. Other studies are still needed to confirm the results in the future.
https://doi.org/10.1186/s12890-023-02673-4
Walnut consumption and gut microbial metabolism: Results of an exploratory analysis from a randomized, crossover, controlled-feeding study
Background & aims: The effect of walnut-related modulation of gut microbiota composition on microbiota functionality is unknown. The aim was to characterize the effect of a walnut-enriched diet (WD), compared to a fatty acid-matched diet devoid of walnuts (WFMD) and a diet where oleic acid replaces alpha-linolenic acid (ORAD), on bacterial gene expression. Methods: A 3-period, randomized, crossover, controlled-feeding study was conducted. Participants were provided a 2-week run-in standard western diet (SWD; 50% kcal carbohydrate, 16% protein, 34% fat, 12% SFA). Following the SWD in random sequence order, participants were provided the WD, WFMD, and ORAD (48% carbohydrate; 17% protein; fat 35%; 7% SFA). The WD contained 18% of energy from walnuts (57 g/d/2100 kcal). The WFMD and ORAD were devoid of walnuts; liquid non-tropical plant oils were included in these diets. Metatranscriptomic analyses were performed as an exploratory outcome. Results: The analytical sample included 35 participants (40% female) with a mean ± SD age of 43 ± 10 y and BMI of 30.3 ± 4.9 kg/m2. The ⍺-diversity of taxa actively expressing genes, assessed by observed species (p = 0.27) and Pielou's Evenness (p = 0.09), did not differ among the diets. The ⍺-diversity of actively expressed genes was greater following the WD compared to the WFMD and ORAD as assessed by the observed genes and Pielou's Evenness metrics (p < 0.05). β-Diversity of the actively expressed genes differed following the WD compared to the WFMD (p = 0.001) and ORAD (p = 0.001); β-diversity did not differ between the WFMD and ORAD. Active composition analyses showed increased Gordonibacter (p < 0.001) activity following the WD vs. the ORAD. Greater expression of many genes was observed following the WD compared to the WFMD and ORAD. Following the WD, greater expression of metabolism-related genes encoding glycine amidinotransferase (GATM; K00613) and arginine deiminase (K01478) was observed compared to the WFMD. Greater expression of glycine amidinotransferase (GATM; K00613) by Gordonibacter was also observed following the WD vs. the WFMD and ORAD. Conclusion: Our results suggest walnut intake may increase endogenous production of homoarginine through gut microbiota-mediated upregulation of GATM, which is a novel mechanism by which walnuts may lower cardiovascular disease risk. However, given the exploratory nature replication is needed. https://doi.org/10.1016/j.clnu.2023.09.023