Archive

Research Nut: Walnuts

Transcriptome profiling analysis of the response to walnut polyphenol extract in Helicobacter pylori-infected cells.

Park, J.M., Y.M. Han, H.J. Lee, S.J. Hwang, S.J. Kim, K.B. Hahm, 2021. Transcriptome profiling analysis of the response to walnut polyphenol extract in Helicobacter pylori-infected cells. J Clin Biochem Nutr. doi.org/10.3164/jcbn.20-128.

Dietary intervention to prevent Helicobacter pylori (H. pylori)-associated gastric diseases seems to be ideal with no risk of bacterial resistance, safe long-term intervention, and correcting pathogenic mechanisms including rejuvenation of precancerous atrophic gastritis and anti-mutagenesis. A transcriptome as set of all RNAs transcribed by certain tissues or cells demonstrates gene functions and reveals the molecular mechanism of specific biological processes against diseases. Here, we have performed RNAseq and bioinformatic analysis to explain proof of concept that walnut intake can rescue from H. pylori infection and explore unidentified mode of actions of walnut polyphenol extract (WPE). As results, BIRC3, SLC25A4, f3 transcription, VEGFA, AZU1, HMOX1, RAB3A, RELBTNIP1, ETFB, INPP5J, PPME1, RHOB, TPI1, FOSL1, JUND.RELB, KLF2, MUC1, NDRG1, ALDOA, ENO1, PFKP, GPI, GDF15, and NRTN genes were newly discovered to be enriched with WPE, whereas CCR4, BLNK, CCR7, CXCR4, CDO1, KLSG1, SELE, RASGRP2, PIK3R3, TSPAN32, HOXC-AS3, HCG8, BTNL8, and CXCL3 genes as inhibitory targets by WPE in H. pylori infection. We identified additional genes what WPE afforded actions of avoiding H. pylori-driven onco-inflammation and rejuvenating precancerous atrophic gastritis. Conclusively, after applying RNAseq analysis in order to document walnut intake for precision medicine against H. pylori infection, significant transcriptomic profiling applicable for validation were drawn.

Association of walnut consumption with total and cause-specific mortality and life expectancy in U.S. adults.

Liu, X., M. Guasch-Ferré, D.K. Tobias, Y. Li, 2021. Association of walnut consumption with total and cause-specific mortality and life expectancy in U.S. adults. Nutrients. 13(8), 2699. https://doi.org/10.3390/nu13082699

Walnut consumption is associated with health benefits. We aimed to (1) examine the association between walnut consumption and mortality and (2) estimate life expectancy in relation to walnut consumption in U.S. adults. We included 67,014 women of the Nurses’ Health Study (1998–2018) and 26,326 men of the Health Professionals Follow-up Study (1998–2018) who were free of cancer, heart disease, and stroke at baseline. We used Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During up to 20 years of follow-up, we documented 30,263 deaths. The hazard ratios for total mortality across categories of walnut intake (servings/week), as compared to non-consumers, were 0.95 (95% confidence interval (CI), 0.91, 0.98) for <1 serving/week, 0.94 (95% CI, 0.89, 0.99) for 1 serving/week, 0.87 (95% CI, 0.82, 0.93) for 2–4 servings/week, and 0.86 (95% CI, 0.79, 0.93) for >=5 servings/week (p for trend <0.0001). A greater life expectancy at age 60 (1.30 years in women and 1.26 years in men) was observed among those who consumed walnuts more than 5 servings/week compared to non-consumers. Higher walnut consumption was associated with a lower risk of total and CVD mortality and a greater gained life expectancy among U.S. elder adults.

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

Levakov, G., A. Kaplan, A. Yaskolka Meir, E. Rinott, G. Tsaban, H. Zelicha, N. Meiran, I. Shelef, I. Shai, G. Avidan, 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.

Walnuts, long-chain polyunsaturated fatty acids, and adolescent brain development: Protocol for the walnuts smart snack dietary intervention trial.

Julvez, J., F. Gignac, S. Fernández-Barrés, D. Romaguera, A. Sala-Vila, O.T. Ranzani, C. Persavento, A. Delgado, A. Carol, J. Torrent, J. Gonzalez, E. Roso, J. Barrera-Gómez, M. López-Vicente, R. Garcia-Esteban, O. Boucher, J. Forns, M. Burgaleta, N. Sebastián, J. Canals, V. Arija, X. Basagaña, E. Ros, J. Vendrell, J. Salas-Salvadó, J. Sunyer, 2021. Walnuts, long-chain polyunsaturated fatty acids, and adolescent brain development: Protocol for the walnuts smart snack dietary intervention trial. Front. Pediatr. 9:593847. doi: 10.3389/fped.2021.593847

Background: Adolescence, when the most complex behaviors are refined to adult sophistication, represents a major window of opportunity and vulnerability for neuropsychological development. To support and protect this complex and active brain growth, different nutritional components considered essential need to be acquired from the diet. For instance, omega-3 fatty acids are mainly obtained from seafood, seeds, and walnuts. Known for their rich lipid profile, walnuts contain sizable amounts of an essential fatty acid, alpha-linolenic acid (ALA), the vegetable omega-3 fatty acid that is the precursor of two longer-chain omega-3 polyunsaturated fatty acids (omega-3 PUFA): docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids. While there is growing evidence of neuropsychological improvements in the young developing brain associated with omega-3 PUFA intake, few studies have examined whether consuming walnuts during adolescence entails similar beneficial effects. There is a need to further explore the ways in which walnuts influence youthful brain function, particularly for the long-term. Thus, we designed the WALNUTs study (WSS), a population-based randomized controlled trial conducted in adolescents in Barcelona, Spain. We hypothesize that walnut intake will increase omega-3 PUFA tissue availability (particularly ALA) to a level that enhances the neuropsychological development during adolescence. Methodology/Design: We conducted a 6-month population-based randomized controlled trial in teenagers (n = 800) and we aimed to determine the effectiveness of the intervention (four walnuts per day, or 30 kernel g, ~1.5g of ALA) in enhancing brain neuropsychological and socio-emotional development compared to a control group with no walnut intervention. Before randomization, different neuropsychological tests were recorded for all participants, and blood samples (in a subsample of participants) were collected to measure omega-3 PUFA levels at baseline, and all again, after randomization and the intervention. The data is now collected and we will conduct linear regression models to assess the effect of the intervention. Discussion: The WALNUTs (WSS) study results will allow us to better understand the role of plant-based omega-3 PUFA intake from regular walnut consumption on neuropsychological development during adolescence. Results could be translated into nutritional public health recommendations targeting teenagers.

Low-carbohydrate dietary pattern on glycemic outcomes trial (ADEPT) among individuals with elevated hemoglobin A1c: study protocol for a randomized controlled trial.

Dorans, K.S., L.A. Bazzano, L. Qi, H. Hua, L.J. Appel, J.M. Samet, J. Chen, K.T. Mills, B.T. Nguyen, M.J. O’Brien, I.U. Uwaifo, J. He, 2021. Low-carbohydrate dietary pattern on glycemic outcomes trial (ADEPT) among individuals with elevated hemoglobin A1c: study protocol for a randomized controlled trial. Trials 22, 108. https://doi.org/10.1186/s13063-020-05001-x.

Background: Type 2 diabetes mellitus (T2DM) is a major cause of morbidity and mortality globally. Strong evidence supports the importance of diet and other lifestyle factors in preventing T2DM. Among individuals with T2DM, low carbohydrate diets lead to decreases in hemoglobin A1c (HbA1c). However, research on the effects of low carbohydrate diets on glycemic outcomes among individuals not currently on glucose-lowering medications who have elevated HbA1c is limited. Methods: The objective of this randomized controlled trial is to study the effect of a healthy low-carbohydrate diet achieved through behavioral intervention and key food supplementation compared with usual diet on HbA1c and other metabolic risk factors among individuals with HbA1c from 6.0 to 6.9% who are not on glucose-lowering medications. In this parallel trial, 150 participants will be randomized to the intervention or control group for 6 months. The healthy low-carbohydrate diet target is < 40 g of net carbohydrates during the first 3 months and < 40 to 60 net grams for months 3 to 6. This diet is characterized by abundant unsaturated fat and protein, high-fiber foods such as non-starchy vegetables and nuts, and minimal refined carbohydrates. The primary outcome is the difference in HbA1c change from baseline to 6 months in the intervention compared with usual diet group. Secondary outcomes include differences between groups in 6-month changes in fasting glucose, systolic blood pressure, total-to-high-density lipoprotein (HDL) cholesterol ratio, and body weight. Exploratory outcomes include differences in 6-month changes in fasting insulin, homeostasis model assessment of insulin resistance, diastolic blood pressure, waist circumference, and 10-year cardiovascular disease risk. An intention-to-treat analysis will be used. Discussion: We expect that the results from this study will lead to new approaches for developing and implementing dietary approaches (other than the most commonly used reduced fat diet) that will substantially reduce risk of cardiometabolic disease among adults with or at high risk of T2DM. The study intervention involves behavioral counseling and promotes consumption of dietary components thought to reduce risk of cardiometabolic disease and has expected applicability in clinical practice.

Walnut intake, cognitive outcomes and risk factors: a systematic review and meta-analysis.

Cahoon, D., S.P. Shertukde, E.E. Avendano, J. Tanprasertsuk, T.M. Scott, E.J. Johnson, M. Chung, N. Nirmala, 2021. Walnut intake, cognitive outcomes and risk factors: a systematic review and meta-analysis. Annals of Medicine, 53:1, 971-997, DOI: 10.1080/07853890.2021.1925955.

Background: Walnuts contain nutrients that are associated with improved cognitive health. To our knowledge, no review has systematically examined the effects of walnuts on cognitive function and risk for cognitive decline. Objective To conduct a systematic review and meta-analysis evaluating the effects of walnut intake on cognition-related outcomes and risk-factors for cognitive decline in adults. Methods: Medline®, Commonwealth Agricultural Bureau, and Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) and observational studies published until April 2020 on walnut intake, cognition (e.g. cognitive function, stroke, and mood), and selected risk factors for cognitive decline (e.g. glucose homeostasis and inflammation). Risk-of-bias and strength-of-evidence assessments were conducted using standard validated tools. Random-effects meta-analyses were conducted when ≥3 studies reported quantitative data for each outcome. Results: 32 RCT and 7 observational study publications were included. Meta-analysis of cognition-related outcomes could not be conducted due to heterogeneity of tests. None of the 5 cognition RCTs found significant effects of walnuts on overall cognition, although 3 studies found improvements on subdomains and/or subgroups. All 7 observational studies found significant associations and a dose-response relationship between walnut intake and cognition-related outcomes. Meta-analyses of 27 RCTs reporting glucose homeostasis and inflammation outcomes, selected risk factors for cognitive decline, did not show significant effects of walnut intake. Conclusions: Due to the non-uniformity of tests for cognition-related outcomes, definitive conclusions regarding the effect of walnut consumption on cognition could not be reached. Additionally, evidence does not show associations between walnut intake and glucose homeostasis or inflammation, cognitive decline risk-factors. High-quality studies with standardized measures are needed to clarify the role of walnuts in cognitive health.

Are fatty nuts a weighty concern? A systematic review and meta-analysis and dose–response meta-regression of prospective cohorts and randomized controlled trials.

Nishi, S.K., E. Viguiliouk, S. Blanco Mejia, C.W.C. Kendall, R.P. Bazinet,  A.J. Hanley, E.M. Comelli, J. Salas Salvado, D.J.A. Jenkins, J.L. Sievenpiper, 2021. Are fatty nuts a weighty concern? A systematic review and meta-analysis and dose–response meta-regression of prospective cohorts and randomized controlled trials. Obes Rev. doi: 10.1111/obr.13330.

Nuts are recommended for cardiovascular health, yet concerns remain that nuts may contribute to weight gain due to their high energy density. A systematic review and meta-analysis of prospective cohorts and randomized controlled trials (RCTs) was conducted to update the evidence, provide a dose-response analysis, and assess differences in nut type, comparator and more in subgroup analyses. MEDLINE, EMBASE, and Cochrane were searched, along with manual searches. Data from eligible studies were pooled using meta-analysis methods. Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). Certainty of the evidence was assessed by Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Six prospective cohort studies (7 unique cohorts, n = 569,910) and 86 RCTs (114 comparisons, n = 5873) met eligibility criteria. Nuts were associated with lower incidence of overweight/obesity (RR 0.93 [95% CI 0.88 to 0.98] P < 0.001, “moderate” certainty of evidence) in prospective cohorts. RCTs presented no adverse effect of nuts on body weight (MD 0.09 kg, [95% CI -0.09 to 0.27 kg] P < 0.001, “high” certainty of evidence). Meta-regression showed that higher nut intake was associated with reductions in body weight and body fat. Current evidence demonstrates the concern that nut consumption contributes to increased adiposity appears unwarranted.

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.

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.