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Research Nut: Walnuts

Mixed tree nut snacks compared to refined carbohydrate snacks resulted in weight loss and increased satiety during both weight loss and weight maintenance: A 24-week randomized controlled trial.

Wang, J., S. Wang, S.M. Henning, T. Qin, Y. Pan, J. Yang, J. Huang, C.-H. Tseng, D. Heber,  Z. Li, 2021. Mixed tree nut snacks compared to refined carbohydrate snacks resulted in weight loss and increased satiety during both weight loss and weight maintenance: A 24-week randomized controlled trial. Nutrients. 13(5), 1512; doi.org/10.3390/nu13051512

Mixed tree nuts (MTNs) are an excellent source of protein and healthy fat contributing to satiety. However, their relatively high caloric content might not be beneficial in a weight loss diet. The present study was designed to test whether including MTNs in a weight loss and maintenance program interferes with weight management compared to a refined carbohydrate pretzel snack (PS). We performed a randomized, controlled, two-arm study in 95 overweight individuals consuming 1.5 oz of MTNs or PS daily as part of a hypocaloric weight loss diet (−500 kcal) over 12 weeks followed by an isocaloric weight maintenance program for 12 weeks. Participants in both groups experienced significant weight loss (12 weeks: −1.6 and −1.9 and 24 weeks: −1.5 and −1.4 kg) compared to baseline in the MTN and PS groups, respectively. However, there was no difference in weight loss and other outcome parameters between the MTN and PS groups. The MTN group showed a significant increase in satiety at 24 weeks. Both groups had a decrease in diastolic blood pressure at 12 weeks. Participants in the MTN group showed significant decreases in heart rate at 4, 12, and 24 weeks. Plasma oleic acid was significantly increased at 12 and 24 weeks in the MTN group but only at 12 weeks in the PS group. Plasma MCP-1 was decreased significantly in the MTN group at 4 weeks. In summary, participants in both groups lost weight, but only the MTN intervention increased satiety at 24 weeks, enhanced retention, decreased heart rate, and increased serum oleic acid at 24 weeks.

Acute consumption of pecans decreases angiopoietin-like protein-3 in healthy males: a secondary analysis of randomized controlled trials.

Guarneiri, L.L., M.O. Spaulding, A.R. Marquardt, J.A. Cooper, C.M. Paton, 2021. Acute consumption of pecans decreases angiopoietin-like protein-3 in healthy males: a secondary analysis of randomized controlled trials. Nutr Res. 92:62-71. https://doi.org/10.1016/j.nutres.2021.06.001

Angiopoietin-like proteins (ANGPTL)-3 and -4 regulate lipid metabolism, but the effect of tree nuts of varying fatty acid composition on post-meal responses is unknown. The purpose of the study was to conduct a secondary analysis of two studies on ANGPTL3 and -4 responses to meals containing different tree nuts. We hypothesized that the pecan-containing meal would mitigate postprandial rises in ANGPTL3 compared to the traditional meal without nuts in males, but not females. In addition, we hypothesized that there would be no other differences between any other treatments in ANGPTL3 or -4 responses. The two studies were double-blind, randomized crossover trials. Twenty-two adults (10=male, 12=female) completed study 1, which compared meals containing pecans vs. no nuts (control), and thirty adults (14=male, 16=female) completed study 2, which compared meals containing black walnuts, English walnuts (EW), or no nuts (control). Blood was collected at fasting, 30, 60, 120, and 180min postprandially. In study 1, ANGPTL3 was suppressed more in pecan vs. control in males (iAUC: -579.4±219.4 vs. -128.4±87.1pg/mL/3h, P<.05). In study 2, there was no difference in ANGPTL3 between black walnuts vs. EW, but ANGPTL3 was suppressed more in control vs. black walnuts in females only (iAUC: -196.4±138.4 vs. 102.1±90.1pg/mL/3h, P<.05). There were no differences in ANGPTL4 between treatments. In conclusion, adding pecans to a meal decreased ANGPTL3 in males, but not females. These data highlight the importance of investigating the impact of nutrients and sex on postprandial ANGPTL3 ad -4 responses to better understand their ability to reduce cardiovascular disease risk.

Hazelnut Allergy.

Calamelli, E., A. Trozzo, E. Di Blasi, L. Serra, P. Bottau, 2021. Hazelnut Allergy. Medicina (Kaunas). 57(1):67. d https://doi.org/10.3390/medicina57010067

Background and Objectives: Hazelnuts are frequently involved in IgE-mediated reactions and represent the main culprit of nut allergy in Europe. The clinical presentation varies from mild symptoms limited to the oropharynx [oral allergy syndrome (OAS)], due to the cross-reaction with homologues in pollen allergens and more severe events caused by the primary sensitization to highly stable molecules contained in hazelnuts. The aim of this review is to summarize the most relevant concepts in the field of hazelnut allergy and to provide a practical approach useful in the clinical practice Materials and Methods: References were identified by PubMed searches dating from January 2000 up to November 2020 using the search terms: “component resolved diagnosis” and “Hazelnut allergy. Results: The storage proteins Cor a 9 and Cor a 14 resulted highly specific for primary hazelnut allergy and strongly associated with severe reactions, while the cross reactive Cor a 1, an homolog of the birch Bet v1, were related to OAS. Any cut-off has shown a specificity and sensitivity pattern as high as to replace the oral food challenge (OFC), which still remains the gold standard in the diagnosis of hazelnut allergy. To date there is still no definitive treatment. Hazelnut free-diet and treatment of symptoms with emergency management, including the prescription of auto-injective epinephrine, still represent the main approach. Oral allergen immunotherapy (AIT) appears a promising therapeutic strategy and the definition of individual clinical threshold would be useful for sensitized individuals, caregivers, and physicians to reduce social limitation, anxiety, and better manage food allergy. Conclusions: An accurate diagnostic work-up including clinical history, in vivo and in vitro test including component resolved diagnosis and OFC are essential to confirm the diagnosis, to assess the risk of a severe reaction, and to prescribe an adequate diet and treatment.

Effects of diet-modulated autologous fecal microbiota transplantation on weight regain.

Rinott, E., I. Youngster, A.Y. Meir, G. Tsaban, H. Zelicha, A. Kaplan, D. Knights, K. Tuohy, F. Fava, M.U. Scholz, O. Ziv, E. Reuven, A. Tirosh, A. Rudich, M. Blüher, M. Stumvoll, U. Ceglarek, K. Clement, O. Koren, D.D. Wang, F.B. Hu, M.J. Stampfer, I. Shai, 2021. Effects of diet-modulated autologous fecal microbiota transplantation on weight regain. Gastroenterology. 160(1):158–173.

Background & Aims: We evaluated the efficacy and safety of diet-modulated autologous fecal microbiota transplantation (aFMT) for treatment of weight regain after the weight loss phase. Methods: In the DIRECT-PLUS weight loss trial (May 2017 through July 2018), abdominally obese or dyslipidemic participants in Israel were randomly assigned to (1) healthy dietary guidelines, (2) Mediterranean diet, and (3) green-Mediterranean diet weight-loss groups. All groups received free gym membership and physical activity guidelines. Both iso-caloric Mediterranean groups consumed 28g/day walnuts (+440mg/d polyphenols provided). The green-Mediterranean dieters further consumed green tea (3-4 cups/day) and a Wolffia-globosa (Mankai strain;100g/day) green shake (+800mg/day polyphenols provided). After 6 months (weight-loss phase), 90 eligible participants (mean age, 52 years; mean weight loss, 8.3 kg) provided a fecal sample that was processed into aFMT by frozen, opaque and odorless capsules. The participants were then randomly assigned to groups that received 100 capsules containing their own fecal microbiota or placebo until month 14. The primary outcome was regain of the lost weight over the expected weight regain phase (months 6–14). Secondary outcomes were gastrointestinal symptoms, waist-circumference, glycemic status and changes in the gut microbiome, as measured by metagenomic sequencing and 16s-rRNA. We validated the results in a parallel in-vivo study of mice specifically fed with Mankai, as compared to control chow diet. Results: Of the 90 participants in the aFMT trial, 96% ingested at least 80 of 100 oral aFMT or placebo frozen capsules over the transplantation period. No aFMTrelated adverse events or symptoms were observed. For the primary outcome, although no significant differences in weight regain were observed among the participants in the different lifestyle interventions during months 6–14 (aFMT, 30.4% vs. placebo, 40.6%;P=.28), aFMT significantly attenuated weight regain in the green Mediterranean group (aFMT, 17.1%, vs placebo, 50%; P=.02), but not in the dietary guidelines (P=.57) or Mediterranean diet (P=.64) groups (P for the interaction=.03). Accordingly, aFMT attenuated waist circumference gain (aFMT, 1.89cm vs placebo, 5.05cm;P=.01) and insulin rebound (aFMT, 1.46±3.6µIU/ml vs placebo, 1.64±4.7µIU/ml;P=.04) in the green Mediterranean group but not in the dietary guidelines or Mediterranean diet (P for the interaction=.04 and .03, respectively). The green-Mediterranean diet was the only intervention to induce a significant change in microbiome composition during the weight loss phase, and to prompt preservation of weight loss-associated specific bacteria and microbial metabolic pathways (mainly microbial sugar transport) following the aFMT. In mice, Mankai modulated aFMT in the weight loss phase, compared with control diet aFMT, significantly prevented weight regain, and resulted in better glucose tolerance, during a high-fat-diet induced regain phase (P<.05 for all). Conclusions: Autologous FMT, collected during the weight loss phase and administrated in the regain phase, might preserve weight loss and glycemic control and is associated with specific microbiome signatures. High-polyphenols, green plant-based or Mankai diet better optimizes the microbiome for an aFMT procedure.

Neural correlates of future weight loss reveal a possible role for brain-gastric interactions.

Levakov G, Kaplan A, Yaskolka Meir A, Rinott E, Tsaban G, Zelicha H, Meiran N, Shelef I, Shai I, Avidan G., 2021. Neural correlates of future weight loss reveal a possible role for brain-gastric interactions. Neuroimage. 224:117403. doi: 10.1016/j.neuroimage.2020.117403.

Lifestyle dietary interventions are an essential practice in treating obesity, hence neural factors that may assist in predicting individual treatment success are of great significance. Here, in a prospective, open-label, three arms study, we examined the correlation between brain resting-state functional connectivity measured at baseline and weight loss following 6 months of lifestyle intervention in 92 overweight participants. We report a robust subnetwork composed mainly of sensory and motor cortical regions, whose edges correlated with future weight loss. This effect was found regardless of intervention group. Importantly, this main finding was further corroborated using a stringent connectivity-based prediction model assessed with cross-validation thus attesting to its robustness. The engagement of senso-motor regions in this subnetwork is consistent with the over-sensitivity to food cues theory of weight regulation. Finally, we tested an additional hypothesis regarding the role of brain-gastric interaction in this subnetwork, considering recent findings of a cortical network synchronized with gastric activity. Accordingly, we found a significant spatial overlap with the subnetwork reported in the present study. Moreover, power in the gastric basal electric frequency within our reported subnetwork negatively correlated with future weight loss. This finding was specific to the weight loss related subnetwork and to the gastric basal frequency. These findings should be further corroborated by combining direct recordings of gastric activity in future studies. Taken together, these intriguing results may have important implications for our understanding of the etiology of obesity and the mechanism of response to dietary intervention.

Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial.

Yaskolka M.A., E. Rinott, G. Tsaban, H. Zelicha, A. Kaplan, P. Rosen, I. Shelef, I. Youngster, A. Shalev, M. Blüher, U. Ceglarek, M. Stumvoll, K. Tuohy, C. Diotallevi, U. Vrhovsek, F. Hu, M. Stampfer, I. Shai, 2021. Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial. Gut. 0:1–11. doi:10.1136/gutjnl-2020-323106.

Objective: To examine the effectiveness of green-Mediterranean (MED) diet, further restricted in red/ processed meat, and enriched with green plants and polyphenols on non-alcoholic fatty liver disease (NAFLD), reflected by intrahepatic fat (IHF) loss. Design: For the DIRECT-PLUS 18-month randomized clinical trial, we assigned 294 participants with abdominal obesity/dyslipidaemia into healthy dietary guidelines (HDG), MED and green-MED weight-loss diet groups, all accompanied by physical activity. Both isocaloric MED groups consumed 28 g/day walnuts (+440 mg/day polyphenols provided). The green-MED group further consumed green tea (3–4 cups/day) and Mankai (a Wolffia globosa aquatic plant strain; 100 g/ day frozen cubes) green shake (+1240 mg/day total polyphenols provided). IHF% 18-month changes were quantified continuously by proton magnetic resonance spectroscopy (MRS). Results: Participants (age=51 years; 88% men; body mass index=31.3 kg/m2; median IHF%=6.6%; mean=10.2%; 62% with NAFLD) had 89.8% 18 month retention-rate, and 78% had eligible follow-up MRS. Overall, NAFLD prevalence declined to: 54.8% (HDG), 47.9% (MED) and 31.5% (green-MED), p=0.012 between groups.  Despite similar moderate weight-loss in both MED groups, green-MED group achieved almost double IHF% loss (−38.9% proportionally), as compared with MED (−19.6% proportionally; p=0.035 weight loss adjusted) and HDG (−12.2% proportionally; p<0.001). After 18 months, both MED groups had significantly higher total plasma polyphenol levels versus HDG, with higher detection of Naringenin and 2-5-dihydroxybenzoic- acid in green-MED. Greater IHF% loss was independently associated with increased Mankai and walnuts intake, decreased red/processed meat consumption, improved serum folate and adipokines/lipids biomarkers, changes in microbiome composition (beta-diversity) and specific bacteria (p<0.05 for all). Conclusion: The new suggested strategy of green-Mediterranean diet, amplified with green plant-based proteins/polyphenols as Mankai, green tea, and walnuts, and restricted in red/processed meat can double IHF loss than other healthy nutritional strategies and reduce NAFLD in half.

Nut consumption and type 2 diabetes risk: a systematic review and meta-analysis of observational studies.

Becerra-Tomás, N., I. Paz-Graniel, P. Hernández-Alonso, D.J.A. Jenkins, C.W.C. Kendall, J.L. Sievenpiper, J. Salas-Salvadó, 2021. Nut consumption and type 2 diabetes risk: a systematic review and meta-analysis of observational studies. Am J Clin Nutr 00:1–12.

Background: Previous meta-analyses, with some methodological controversies, have assessed the relation between nut consumption and type 2 diabetes (T2D) risk and pointed to contradictory results, making desirable the performance of an updated meta-analysis. Objectives: We aimed to systematically review and meta-analyze all the published studies investigating the relations of total nuts and different types of nuts—i.e., walnuts, peanuts, peanut butter, and total tree nuts—with the prevalence and incidence of T2D. Methods: A systematic search was conducted in the PubMed and Cochrane databases through 12 August, 2020. The inverse variance method with fixed-effect models was used to pool data across studies, expressed as risk ratios (RRs) or ORs and 95% CIs for prospective cohort and cross-sectional studies, respectively. The Cochran Q test and I 2 statistics were used to test and quantify heterogeneity, respectively. Dose-response meta-analysis was also conducted. Results: Eight studies (5 prospective and 3 cross-sectional) were included in the quantitative synthesis. Meta-analyses of crosssectional studies and prospective cohort studies, comparing the highest with the lowest categories, revealed a nonsignificant association between total nut consumption and T2D. Meta-analyses of prospective cohort studies showed an inverse association between peanut butter consumption and T2D incidence (RR: 0.87; 95% CI: 0.77, 0.98; I 2 = 50.6%; Pheterogeneity = 0.16), whereas no association was observed between peanuts or tree nuts and T2D. There was no evidence of a linear dose-response or nonlinear dose-response gradient for total nut and peanut consumption in prospective cohort studies. The certainty of the evidence using NutriGrade was very low for all the exposures. Conclusions: Current results do not demonstrate an association of total nut, peanut, or tree nut consumption with T2D. Peanut butter consumption may be inversely associated with this disease. This review protocol was registered at www.crd.york.ac.uk/prospero/ as CRD42020149756.

Nut consumption for cognitive performance: A systematic review.

Theodore, L.E., N.J. Kellow, E.A. McNeil, E.O. Close, E.G. Coad, B.R. Cardoso, 2020. Nut consumption for cognitive performance: A systematic review. Adv Nutr. 00:1–16.

Diet is considered an important modifiable lifestyle factor capable of attenuating early cognitive changes in healthy older people. The inclusion of nuts in the diet has been investigated as a dietary strategy for maintenance of brain health across the lifespan. This review aimed to present up-to-date evidence regarding the association between nut intake and cognitive performance. Four databases (Ovid MEDLINE, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL) Plus, and Embase) were systematically searched from inception to April 2020. Eligible articles were interventional or observational studies in humans aged ≥18 y that measured the effects (or association) of nuts (almond, hazelnut, macadamia, pistachio, walnut, pecan, pine nut, Brazil nut, cashew, peanut) on cognitive outcomes. Out of the 2374 articles identified in the searches, 22 involving 43,793 participants met the criteria and were ultimately included in this review. Memory (immediate and delayed), attention, processing speed, executive function, and visual-spatial ability, as well as risk of mild cognitive impairment, were the outcomes investigated. Lack of consistency across the studies regarding study design, types of nut used, and cognitive outcomes measured resulted in inconsistent evidence that the regular consumption of mixed nuts has a protective effect on cognition in adults of different ages. Nonetheless, we observed that studies targeting populations with a higher risk of cognitive decline tended to find a more favorable outcome. Furthermore, homogeneous findings were observed in the studies that specifically addressed the association between walnut consumption and cognitive performance: out of the 6 studies, including 2 randomized controlled trials, only 1 did not find a positive association.

Effect of green Mediterranean diet on cardiometabolic risk; a randomised controlled trial.

Tsaban, G., A. Yaskolka Meir, E. Rinott, H. Zelicha, A. Kaplan, A. Shalev, A. Katz, A. Rudich, A. Tirosh, I. Shelef, I. Youngster, S. Lebovitz,  N. Israeli, M. Shabat, D. Brikner, E. Pupkin, M. Stumvoll, J. Thiery, U. Ceglarek, J.T. Heiker, A. Körner, K. Landgraf, M. von Bergen, M. Blüher, M.J. Stampfer, I. Shai, 2020. Effect of green Mediterranean diet on cardiometabolic risk; a randomised controlled trial. Heart. doi: 10.1136/heartjnl-2020-317802

Background: A Mediterranean diet is favourable for cardiometabolic risk. Objective To examine the residual effect of a green Mediterranean diet, further enriched with green plant-based foods and lower meat intake, on cardiometabolic risk. Methods: For the DIRECT-PLUS parallel, randomised clinical trial we assigned individuals with abdominal obesity/dyslipidaemia 1:1:1 into three diet groups: healthy dietary guidance (HDG), Mediterranean and green Mediterranean diet, all combined with physical activity. The Mediterranean diets were equally energy restricted and included 28 g/day walnuts. The green Mediterranean diet further included green tea (3–4 cups/day) and a Wolffia globosa (Mankai strain; 100 g/day frozen cubes) plant-based protein shake, which partially substituted animal protein. We examined the effect of the 6-month dietary induction weight loss phase on cardiometabolic state. Results: Participants (n=294; age 51 years; body mass index 31.3 kg/m2; waist circumference 109.7 cm; 88% men; 10 year Framingham risk score 4.7%) had a 6-month retention rate of 98.3%. Both Mediterranean diets achieved similar weight loss ((green Mediterranean −6.2 kg; Mediterranean −5.4 kg) vs the HDG group −1.5 kg; p<0.001), but the green Mediterranean group had a greater reduction in waist circumference (−8.6 cm) than the Mediterranean (−6.8 cm; p=0.033) and HDG (−4.3 cm; p<0.001) groups. Stratification by gender showed that these differences were significant only among men. Within 6 months the green Mediterranean group achieved greater decrease in low-density lipoprotein cholesterol (LDL-C; green Mediterranean −6.1 mg/dL (−3.7%), −2.3 (-0.8%), HDG −0.2 mg/dL (+1.8%); p=0.012 between extreme groups), diastolic blood pressure (green Mediterranean −7.2 mm Hg, Mediterranean −5.2 mm Hg, HDG −3.4 mm Hg; p=0.005 between extreme groups), and homeostatic model assessment for insulin resistance (green Mediterranean −0.77, Mediterranean −0.46, HDG −0.27; p=0.020 between extreme groups). The LDL-C/high-density lipoprotein cholesterol (HDL-C) ratio decline was greater in the green Mediterranean group (−0.38) than in the Mediterranean (−0.21; p=0.021) and HDG (−0.14; p<0.001) groups. High-sensitivity C-reactive protein reduction was greater in the green Mediterranean group (−0.52 mg/L) than in the Mediterranean (−0.24 mg/L; p=0.023) and HDG (−0.15 mg/L; p=0.044) groups. The green Mediterranean group achieved a better improvement (−3.7% absolute risk reduction) in the 10-year Framingham Risk Score (Mediterranean−2.3%; p=0.073, HDG−1.4%; p<0.001). Conclusions: The green MED diet, supplemented with walnuts, green tea and Mankai and lower in meat/poultry, may amplify the beneficial cardiometabolic effects of Mediterranean diet.

Walnuts and vegetable oils containing oleic acid differentially affect the gut microbiota and associations with cardiovascular risk factors: Follow-up of a randomized, controlled, feeding trial in adults at risk for cardiovascular disease.

Tindall, A.M., C.J. McLimans, K.S. Petersen, P.M. Kris-Etherton, R. Lamendella, 2020. Walnuts and vegetable oils containing oleic acid differentially affect the gut microbiota and associations with cardiovascular risk factors: Follow-up of a randomized, controlled, feeding trial in adults at risk for cardiovascular disease. J Nutr. 2020;150(4):806-817.

Background: It is unclear whether the favorable effects of walnuts on the gut microbiota are attributable to the fatty acids, including α-linolenic acid (ALA), and/or the bioactive compounds and fiber. Objective: This study examined between-diet gut bacterial differences in individuals at increased cardiovascular risk following diets that replace SFAs with walnuts or vegetable oils. Methods: Forty-two adults at cardiovascular risk were included in a randomized, crossover, controlled-feeding trial that provided a 2-wk standard Western diet (SWD) run-in and three 6-wk isocaloric study diets: a diet containing whole walnuts (WD; 57-99 g/d walnuts; 2.7% ALA), a fatty acid-matched diet devoid of walnuts (walnut fatty acid-matched diet; WFMD; 2.6% ALA), and a diet replacing ALA with oleic acid without walnuts (oleic acid replaces ALA diet; ORAD; 0.4% ALA). Fecal samples were collected following the run-in and study diets to assess gut microbiota with 16S rRNA sequencing and Qiime2 for amplicon sequence variant picking. Results: Subjects had elevated BMI (30 ± 1 kg/m2), blood pressure (121 ± 2/77 ± 1 mmHg), and LDL cholesterol (120 ± 5 mg/dL). Following the WD, Roseburia [relative abundance (RA) = 4.2%, linear discriminant analysis (LDA) = 4], Eubacterium eligensgroup (RA = 1.4%, LDA = 4), LachnospiraceaeUCG001 (RA = 1.2%, LDA = 3.2), Lachnospiraceae UCG004 (RA = 1.0%, LDA = 3), and Leuconostocaceae (RA = 0.03%, LDA = 2.8) were most abundant relative to taxa in the SWD (P ≤ 0.05 for all). The WD was also enriched in Gordonibacter relative to the WFMD. Roseburia (3.6%, LDA = 4) and Eubacterium eligensgroup (RA = 1.5%, LDA = 3.4) were abundant following the WFMD, and Clostridialesvadin BB60group (RA = 0.3%, LDA = 2) and gutmetagenome (RA = 0.2%, LDA = 2) were most abundant following the ORAD relative to the SWD (P ≤ 0.05 for all). Lachnospiraceae were inversely correlated with blood pressure and lipid/lipoprotein measurements following the WD. Conclusions: The results indicate similar enrichment of Roseburia following the WD and WFMD, which could be explained by the fatty acid composition. Gordonibacter enrichment and the inverse association between Lachnospiraceae and cardiovascular risk factors following the WD suggest that the gut microbiota may contribute to the health benefits of walnut consumption in adults at cardiovascular risk. This trial was registered at clinicaltrials.gov as NCT02210767.