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Research Nut: Walnuts

Dietary walnut supplementation alters mucosal metabolite profiles during DSS-induced colonic ulceration.

Nakanishi, M., A. Matz, C. Klemashevich, D.W. Rosenberg, 2019. Dietary walnut supplementation alters mucosal metabolite profiles during DSS-induced colonic ulceration.  Nutrients. 11(5). pii: 1118. doi: 10.3390/nu11051118

Walnuts contain a complex array of natural compounds and phytochemicals that exhibit a wide range of health benefits, including protection against inflammation and colon cancer. In this study, we assess the effects of dietary supplementation with walnuts on colonic mucosal injury induced in mice by the ulcerogenic agent, dextran sodium sulfate (DSS). C57Bl/6J mice were started on the Total Western Diet supplemented with freshly-ground whole walnuts (0, 3.5, 7 and 14% g/kg) 2 weeks prior to a 5-day DSS treatment and walnut diets were continued throughout the entire experimental period. Mice were examined at 2 days or 10 days after withdrawal of DSS. In a separate study, a discovery-based metabolite profiling analysis using liquid chromatography tandem mass spectrometry (LC-MS/MS) was performed on fecal samples and colonic mucosa following two weeks of walnut supplementation. Dietary walnut supplementation showed significant effects in the 10-day post-DSS recovery-phase study, in which the extent of ulceration was significantly reduced (7.5% vs. 0.3%, p < 0.05) with 14% walnuts. In the metabolite-profiling analysis, walnuts caused a significant increase in several polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA) and 9-oxo-10(E),12(E)-octadecadienoic acid (9-oxoODA), as well as kynurenic acid. In colon tissue samples, walnuts caused a significant increase in the levels of S-adenosylhomocysteine (SAH) and betaine, important components of fatty acid β-oxidation. These metabolite changes may contribute in part to the observed protection against DSS-induced inflammatory tissue injury.

Energy extraction from nuts: walnuts, almonds, pistachios.

McArthur, B., R. Mattes, 2019. Energy extraction from nuts: walnuts, almonds, pistachios. Br J Nutr. 17:1-21.

The bioaccessibility of fat has implications for satiety and postprandial lipidemia. The prevailing view holds that the integrity of plant cell wall structure is the primary determinant of energy and nutrient extraction from plant cells as they pass through the gastrointestinal tract. However, comparisons across nuts (walnuts, almonds, pistachios) with varying physical properties do not support this view. In this study, masticated samples of three nuts from healthy adults were exposed to a static model of gastric digestion followed by simulated intestinal digestion. Primary outcomes were particle size and lipid release at each phase of digestion. Walnuts produced a significantly larger particle size post-mastication compared to almonds. Under gastric and intestinal conditions, the particle size was larger for walnuts compared to pistachios and almonds (P<0.05). However, the masticated and digesta particle sizes were not related to the integrity of cell walls nor lipid release. The total lipid release was comparable between nuts after the in vitro intestinal phase (P>0.05). Microstructural examination showed ruptured and fissured cell walls that would allow digestion of cellular contents and this may be governed by internal cellular properties such as oil body state. Furthermore, the cell walls of walnuts tend to rupture rather than separate and as walnut tissue passes through the gastrointestinal track, lipids tend to coalesce reducing digestion efficiency.

Walnut phenolic extract inhibits nuclear factor kappaB signaling in intestinal epithelial cells, and ameliorates experimental colitis and colitis-associated colon cancer in mice.

Koh, S.J., Y.I. Choi, Y. Kim, Y.S. Kim, S.W. Choi, J.W. Kim, B.G. Kim, K.L. Lee, 2019. Walnut phenolic extract inhibits nuclear factor kappaB signaling in intestinal epithelial cells, and ameliorates experimental colitis and colitis-associated colon cancer in mice.
Eur J Nutr. 58(4):1603-1613.

Purpose: Walnuts (Juglans regia) are known to have anti-cancer and immunomodulatory effects. However, little information is available on the effects of walnut phenolic extract (WPE) on intestinal inflammation and colitis-associated colon cancer. Methods: COLO205 cells were pretreated with WPE and then stimulated with tumor necrosis factor (TNF)-α. In the acute colitis model, wild type mice (C57BL/6) were administered 4% dextran sulfate sodium (DSS) for 5 days. In the chronic colitis model, interleukin (IL)-10-/- mice were administered with either the vehicle or WPE (20 mg/kg) by oral gavage daily for 2 weeks. In an inflammation-associated tumor model, wild type mice were administered a single intraperitoneal injection of azoxymethane followed by three cycles of 2% DSS for 5 days and 2 weeks of free water consumption. Results: WPE significantly inhibited IL-8 and IL-1α expression in COLO205 cells. WPE attenuated both the TNF-α-induced IκB phosphorylation/degradation and NF-κB DNA binding activity. The administration of oral WPE significantly reduced the severity of colitis in both acute and chronic colitis models, including the IL-10-/- mice. In immunohistochemical staining, WPE attenuated NF-κB signaling in the colons of both colitis models. Finally, WPE also significantly reduced tumor development in a murine model of colitis-associated colon cancer (CAC). Conclusions: WPE ameliorates acute and chronic colitis and CAC in mice, suggesting that WPE may have potentials for the treatment of inflammatory bowel disease.

Daily walnut intake improves metabolic syndrome status and increases circulating adiponectin levels: randomized controlled crossover trial.

Hwang, H.J., Y. Liu, H.S. Kim, H. Lee, Y. Lim, H. Park, 2019. Daily walnut intake improves metabolic syndrome status and increases circulating adiponectin levels: randomized controlled crossover trial. Nutr Res Pract. 13(2):105–114.

Background/Objectives: Several previous studies have investigated whether regular walnut consumption positively changes heart-health-related parameters. The aim of this study was to investigate the effects of daily walnut intake on metabolic syndrome (MetS) status and other metabolic parameters among subjects with MetS. Materials/Methods: This study was a two-arm, randomized, controlled crossover study with 16 weeks of each intervention (45 g of walnuts or iso-caloric white bread) with a 6-week washout period between interventions. Korean adults with MetS (n = 119) were randomly assigned to one of two sequences; 84 subjects completed the trial. At each clinic visit (at 0, 16, 22, and 38 weeks), MetS components, metabolic parameters including lipid profile, hemoglobin A1c (HbA1c), adiponectin, leptin, and apolipoprotein B, as well as anthropometric and bioimpedance data were obtained. Results: Daily walnut consumption for 16 weeks improved MetS status, resulting in 28.6%-52.8% reversion rates for individual MetS components and 51.2% of participants with MetS at baseline reverted to a normal status after the walnut intervention. Significant improvements after walnut intake, compared to control intervention, in high-density lipoprotein cholesterol (HDL-C) (P = 0.028), fasting glucose (P = 0.013), HbA1c (P = 0.021), and adiponectin (P = 0.019) were observed after adjustment for gender, age, body mass index, and sequence using a linear mixed model. Conclusion: A dietary supplement of 45 g of walnuts for 16 weeks favorably changed MetS status by increasing the concentration of HDL-C and decreasing fasting glucose level. Furthermore, consuming walnuts on a daily basis changed HbA1c and circulating adiponectin levels among the subjects with MetS.

mRNA expression data in breast cancers before and after consumption of walnut by women.

Hardman, W.E., D.A. Primerano, M.T. Legenza, J. Morgan, J. Fan, J. Denvir, 2019. mRNA expression data in breast cancers before and after consumption of walnut by women. Data in Brief. 25:104050. doi: 10.1016/j.dib.2019.104050

This article contains supporting data for the research paper entitled: ‘Dietary walnut altered gene expressions related to tumor growth, survival, and metastasis in breast cancer patients: a pilot clinical trial’ [1] Hardman et al., 2019. Included are tables for all mapped genes and all unmapped loci identifications that were significantly changed in breast cancers by consumption of walnut for about 2 weeks. All gene networks that were identified by Ingenuity Pathway Analyses as modified are shown in table 3. Files containing the raw reads, along with a shell script describing the complete data analysis pipeline, were deposited to the Gene Expression Omnibus (GEO) at the National Center for Biotechnology Information (NCBI) and can be obtained via accession number GSE111073.

Dietary walnut altered gene expressions related to tumor growth, survival, and metastasis in breast cancer patients: a pilot clinical trial.

Hardman, W.E., D.A. Primerano, M.T. Legenza, J. Morgan, J. Fan, J. Denvir, 2019. Dietary walnut altered gene expressions related to tumor growth, survival, and metastasis in breast cancer patients: a pilot clinical trial. Nutr Res. 66:82-94.

Consumption of walnuts has slowed breast cancer growth and/or reduced the risk of mammary cancer in mice. The benefit against cancer was associated with altered expression of genes for cancer growth and survival. We hypothesized that walnut consumption would alter gene expression in pathologically confirmed breast cancers of women in a direction that would be expected to decrease breast cancer growth and survival, as was seen in mice. The study was a non-placebo, two-arm, clinical trial. Women with breast lumps large enough for research and pathology biopsies were recruited and randomized to walnut consuming or control groups. Immediately after biopsy collection, women in the walnut group began to consume two ounces of walnuts per day until follow-up surgery. Pathological studies confirmed that lumps were breast cancer in all women who remained in the trial. At surgery, about two weeks after biopsy, additional specimens were taken from the breast cancers. Changes in gene expression in the surgical specimen compared to baseline were determined in each individual woman in walnut-consuming (n=5) and control (n=5) groups. RNA-Seq expression profiling revealed that expression of 456 identified genes was significantly changed in the tumor due to walnut consumption. Ingenuity Pathway Analysis showed activation of pathways that promote apoptosis and cell adhesion, and inhibition of pathways that promote cell proliferation and migration. These results support the hypothesis that, in humans, walnut consumption could suppress growth and survival of breast cancers.

The Alternative Healthy Eating Index and physical function impairment in men.

Hagan, K.A., F. Grodstein, 2019. The Alternative Healthy Eating Index and physical function impairment in men. J Nutr Health Aging. 23(5):459-465.

Objectives: Physical function is increasingly recognized as integral to healthy aging, in particular as a core component of mobility and independent living in older adults. Thus, it is important to identify strategies for the prevention of physical function decline. Design: Longitudinal cohort study. Setting and Participants: A total of 12,658 men from the Health Professionals Follow-Up Study were followed from 2008–2012. Measurements: We examined the association between the Alternative Healthy Eating Index-2010 (AHEI), a measure of diet quality combining 11 dietary components (vegetables, fruits, nuts and legumes, red and processed meats, sugar-sweetened beverages and fruit juices, alcohol, whole grains, omega-3 fatty acids, polyunsaturated fatty acids, trans fatty acids, sodium), and impairment in physical function, as measured by the SF-36. Multivariable logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (CI) of impairment in physical function. Results: In the multivariable-adjusted model, each 10-point increase in total AHEI score was associated with a 10% lower odds of impairment in physical function (OR=0.90, 95% CI: 0.86,0.95), and in the categorical analysis, men with AHEI scores in the top quintile had a 26% lower odds (OR=0.74, 95% CI:0.63,0.86) compared with men in the bottom quintile. For individual AHEI components, higher intake of vegetables (p-trend=0.01), nuts and legumes (p-trend<0.01), polyunsaturated fatty acids (p-trend<0.01) and lower intake of red and processed meats (p-trend=0.03) and sugar-sweetened beverages (p-trend=0.01) were significantly associated with lower odds of physical impairment. For specific foods, higher consumption of lettuce, broccoli, blueberries, peanuts, walnuts and other nuts were associated with lower odds of impairment. Conclusions: In this large cohort of older men, better overall diet quality was significantly associated with a lower odds of impairment in physical function. Given the value of physical function to healthy aging and quality of life, this may represent a particularly compelling public health rationale for older men to improve their diet.

Mediterranean-style diet in pregnant women with metabolic risk factors (ESTEEM): A pragmatic multicentre randomised trial.

H Al Wattar, B., J. Dodds, A. Placzek, L. Beresford, E. Spyreli, A. Moore, F.J. Carreras, F. Austin, N. Murugesu, T.J. Roseboom, M. Bes-Rastrollo, 2019. Mediterranean-style diet in pregnant women with metabolic risk factors (ESTEEM): A pragmatic multicentre randomised trial. PLoS Med. 16(7):e1002857. doi:10.1371/journal.pmed.1002857

Background: Pregnant women with metabolic risk factors are at high risk of complications. We aimed to assess whether a Mediterranean-style diet reduces adverse pregnancy outcomes in high-risk women. Methods and findings: We conducted a multicentre randomised trial in 5 maternity units (4 in London and 1 in Birmingham) between 12 September 2014 and 29 February 2016. We randomised inner-city pregnant women with metabolic risk factors (obesity, chronic hypertension, or hypertriglyceridaemia) to a Mediterranean-style diet with high intake of nuts, extra virgin olive oil, fruits, vegetables, non-refined grains, and legumes; moderate to high consumption of fish; low to moderate intake of poultry and dairy products; low intake of red and processed meat; and avoidance of sugary drinks, fast food, and food rich in animal fat versus usual care. Participants received individualised dietary advice at 18, 20, and 28 weeks’ gestation. The primary endpoints were composite maternal (gestational diabetes or preeclampsia) and composite offspring (stillbirth, small for gestational age, or admission to neonatal care unit) outcomes prioritised by a Delphi survey. We used an intention-to-treat (ITT) analysis with multivariable models and identified the stratification variables and prognostic factors a priori. We screened 7,950 and randomised 1,252 women. Baseline data were available for 593 women in the intervention (93.3% follow-up, 553/593) and 612 in the control (95.6% follow-up, 585/612) groups. Over a quarter of randomised women were primigravida (330/1,205; 27%), 60% (729/1,205) were of Black or Asian ethnicity, and 69% (836/1,205) were obese. Women in the intervention arm consumed more nuts (70.1% versus 22.9%; adjusted odds ratio [aOR] 6.8, 95% confidence interval [CI] 4.3–10.6, p ≤ 0.001) and extra virgin olive oil (93.2% versus 49.0%; aOR 32.2, 95% CI 16.0–64.6, p ≤ 0.001) than controls; increased their intake of fish (p < 0.001), white meat (p < 0.001), and pulses (p = 0.05); and reduced their intake of red meat (p < 0.001), butter, margarine, and cream (p < 0.001). There was no significant reduction in the composite maternal (22.8% versus 28.6%; aOR 0.76, 95% CI 0.56–1.03, p = 0.08) or composite offspring (17.3% versus 20.9%; aOR 0.79, 95% CI 0.58–1.08, p = 0.14) outcomes. There was an apparent reduction in the odds of gestational diabetes by 35% (aOR 0.65, 95% CI 0.47–0.91, p = 0.01) but not in other individual components of the composite outcomes. Mothers gained less gestational weight (mean 6.8 versus 8.3 kg; adjusted difference −1.2 Kg, 95% CI −2.2 to −0.2, p = 0.03) with intervention versus control. There was no difference in any of the other maternal and offspring complications between both groups. When we pooled findings from the Effect of Simple, Targeted Diet in Pregnant Women With Metabolic Risk Factors on Pregnancy Outcomes (ESTEEM) trial with similar trials using random effects meta-analysis, we observed a significant reduction in gestational diabetes (odds ratio [OR] 0.67, 95% CI 0.53–0.84, I2 = 0%), with no heterogeneity (2 trials, 2,397 women). The study’s limitations include the use of participant reported tools for adherence to the intervention instead of objective biomarkers. Conclusions: A simple, individualised, Mediterranean-style diet in pregnancy did not reduce the overall risk of adverse maternal and offspring complications but has the potential to reduce gestational weight gain and the risk of gestational diabetes.

The beneficial effects of Mediterranean diet over low-fat diet may be mediated by decreasing hepatic fat content.

Gepner, Y., I. Shelef, O. Komy, N. Cohen, D. Schwarzfuchs, N. Bril, M. Rein, D. Serfaty, S. Kenigsbuch, H. Zelicha, A.Y. Meir, 2019. The beneficial effects of Mediterranean diet over low-fat diet may be mediated by decreasing hepatic fat content. J Hepatol. 71(2):379-388.

Background & Aim: It is unclear if a reduction in hepatic fat content (HFC) is a major mediator of the cardiometabolic benefit of lifestyle intervention, and whether it has prognostic significance beyond the loss of visceral adipose tissue (VAT). In the present sub-study, we hypothesized that HFC loss in response to dietary interventions induces specific beneficial effects independently of VAT changes. Methods: In an 18-month weight-loss trial, 278 participants with abdominal obesity/dyslipidemia were randomized to low-fat (LF) or Mediterranean/low-carbohydrate (MED/LC + 28 g walnuts/day) diets with/without moderate physical activity. HFC and abdominal fat-depots were measured using magnetic resonance imaging at baseline, after 6 (sub-study, n = 158) and 18 months. Results: Of 278 participants (mean HFC 10.2% [range: 0.01%-50.4%]), the retention rate was 86.3%. The %HFC substantially decreased after 6 months (-6.6% absolute units [-41% relatively]) and 18 months (-4.0% absolute units [-29% relatively]; p <0.001 vs. baseline). Reductions of HFC were associated with decreases in VAT beyond weight loss. After controlling for VAT loss, decreased %HFC remained independently associated with reductions in serum gamma glutamyltransferase and alanine aminotransferase, circulating chemerin, and glycated hemoglobin (p <0.05). While the reduction in HFC was similar between physical activity groups, MED/LC induced a greater %HFC decrease (p = 0.036) and greater improvements in cardiometabolic risk parameters (p <0.05) than the LF diet, even after controlling for VAT changes. Yet, the greater improvements in cardiometabolic risk parameters induced by MED/LC were all markedly attenuated when controlling for HFC changes. Conclusions: %HFC is substantially reduced by diet-induced moderate weight loss and is more effectively reduced by the MED/LC diet than the LF diet, independently of VAT changes. The beneficial effects of the MED/LC diet on specific cardiometabolic parameters appear to be mediated more by decreases in %HFC than VAT loss. Lay Summary: High hepatic fat content is associated with metabolic syndrome, type 2 diabetes mellitus, and coronary heart disease. In the CENTRAL 18-month intervention trial, a Mediterranean/low-carbohydrate diet induced a greater decrease in hepatic fat content than a low-fat diet, conferring beneficial health effects that were beyond the favorable effects of visceral fat loss. ClinicalTrials.gov Identifier: NCT01530724.

Effect of a walnut diet on office and 24-hour ambulatory blood pressure in elderly individuals: findings From the WAHA randomized trial.

Domènech, M., M. Serra-Mir, I. Roth, T. Freitas-Simoes, C. Valls-Pedret, M. Cofán, A. López, A. Sala-Vila, C. Calvo, S. Rajaram, J. Sabaté, 2019. Effect of a walnut diet on office and 24-hour ambulatory blood pressure in elderly individuals: findings From the WAHA randomized trial. Hypertension. 73(5):1049-1057.

Nut consumption lowers blood cholesterol and is associated with reduced cardiovascular disease, but effects on blood pressure (BP) are inconsistent. We assessed the 2-year effects of a walnut diet versus a control diet on office BP and 24-hours ambulatory BP in free-living elders participating in the Walnuts and Healthy Aging study, a randomized trial testing the effects of walnuts at ≈15% energy on age-related disorders. In a prespecified analysis, we enrolled 305 participants, of whom 236 (75%) completed the study (65% women; age, 69 years; 60% with mild hypertension). Walnuts were well tolerated, and compliance was >98%. Mean baseline office BP was 128/79 mm Hg. Adjusted changes from baseline in mean office systolic BP were −4.61 mm Hg (95% CI, −7.43 to −1.79 mm Hg) in the walnut group and −0.59 mm Hg (−3.38 to 2.21 mm Hg) in controls (P=0.051). Respective changes in mean systolic 24-hour ambulatory BP were −3.86 mm Hg (CI, −5.45 to −2.26 mm Hg) and −2.00 mm Hg (CI, −3.58 to −0.42 mm Hg; P=0.111). No changes in diastolic BP were observed. In participants in the upper tertile of baseline 24-hour ambulatory systolic BP (>125 mm Hg), mean 2-year systolic 24-hour BP was −8.5 mm Hg (CI, −12 to −5.0 mm Hg) in the walnut group and −2.5 mm Hg (CI,−6.3 to 1.3 mm Hg) in controls (P=0.034). During the trial, participants in the walnut group required less uptitration of antihypertensive medication and had better overall BP regulation than controls. Walnut consumption reduces systolic BP in elderly subjects, particularly in those with mild hypertension.