Archive

Research Area: Nutrient and Bioactive Composition

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.

Metabolic influence of walnut phenolic extract on mitochondria in a colon cancer stem cell model.

Choi, J., P.K. Shin, Y. Kim, C.P. Hong, S.W. Choi, 2019. Metabolic influence of walnut phenolic extract on mitochondria in a colon cancer stem cell model. Eur J Nutr. 58(4):1635-1645.

Purpose: Walnut phenolic extract (WPE) reduces proliferation and enhances differentiation of colon cancer stem cells (CSCs). The present study investigated the metabolic influence of WPE on the mitochondrial function of colon CSCs to determine its underlying mechanism. Methods: CD133+CD44+ HCT116 colon cancer cells were selected by fluorescence-activated cell sorting and were treated with or without 40 µg/mL WPE. RNA-sequencing (RNA-Seq) was performed to identify differentially expressed genes (DEGs), which were further validated with RT-PCR. WPE-induced alterations in mitochondrial function were investigated through a mitochondrial stress test by determining cellular oxygen consumption rate (OCR), an indicator of mitochondrial respiration, and extracellular acidification rate (ECAR), an indicator of glycolysis, which were further confirmed by glucose uptake and lactate production tests. Results: RNA-Seq analysis identified two major functional clusters: metabolic and mitochondrial clusters. WPE treatment shifted the metabolic profile of cells towards the glycolysis pathway (ΔECAR = 36.98 mpH/min/ptn, p = 0.02) and oxidative pathway (ΔOCR = 29.18 pmol/min/ptn, p = 0.00001). Serial mitochondrial stimulations using respiration modulators, oligomycin, carbonyl cyanide-4 (trifluoromethoxy) phenylhydrazone, and rotenone/antimycin A, found an increased potential of mitochondrial respiration (ΔOCR = 111.5 pmol/min/ptn, p = 0.0006). WPE treatment also increased glucose uptake (Δ = 0.39 pmol/µL, p = 0.002) and lactate production (Δ = 0.08 nmol/µL, p = 0.005). Conclusions: WPE treatment shifts the mitochondrial metabolism of colon CSC towards more aerobic glycolysis, which might be associated with the alterations in the characteristics of colon CSC.

Walnuts change lipoprotein composition suppressing TNFa-stimulated cytokine production by diabetic adipocyte.

Borkowski, K., S.J. Yim, R.R. Holt, R.M. Hackman, C.L. Keen, J.W. Newman, G.C. Shearer, 2019. Walnuts change lipoprotein composition suppressing TNFa-stimulated cytokine production by diabetic adipocyte. J Nutr Biochem. 68:51-58.

Walnut consumption can provide both vascular and metabolic health benefits, and walnut-induced changes in lipoprotein particle chemical payloads may be responsible for these health benefits. To explore this possibility with a focus on metabolic health, this study investigated the impact of walnut consumption on lipoprotein lipid composition and changes in LDL anti-inflammatory properties, as reported by inflamed adipocyte. Hypercholesterolemic, postmenopausal females were treated with 40 g/day (i.e., 1.6 servings/day; n=15) of walnuts for 4 weeks. Fatty acids and their oxygenated metabolites, i.e., oxylipins, were quantified in isolated lipoproteins. Human primary adipocytes were exposed to LDL and TNFα-stimulated adipokine production was measured. Walnut treatment elevated α-linolenic acid and its epoxides in all lipoproteins and depleted mid-chain alcohols in VLDL and LDL, but not HDL. Walnuts also reduced TNFα-induced diabetic adipocyte production of IL-6 (−48%, P=.0006) and IL-8 (−30%, P=.01), changes inversely correlated with levels of α-linolenic acid-derived epoxides but not α-linolenic acid itself. In conclusion, modest walnut consumption can alter lipoprotein lipid profiles and enhance their ability to inhibit TNFα-dependent pro-inflammatory responses in human diabetic primary adipocytes. Moreover, this study suggests the oxylipins, rather than the parent fatty acids, mediate LDL action of adipocytes.

Polyphenols in almond skins produced during almond blanching process modulate plasma biomarkers of oxidative stress in healthy humans.

Chen, C.-Y.O., P.E. Milbury, J.B. Blumberg, 2019. Polyphenols in almond skins produced during almond blanching process modulate plasma biomarkers of oxidative stress in healthy humans. Antioxidants. 8, 95. doi: https://www.mdpi.com/2076-3921/8/4/95/pdf

Almond skins are a waste byproduct of blanched almond production. Polyphenols extracted from almond skins possess antioxidant activities in vitro and in vivo. Thus, we examined the pharmacokinetic profile of almond skin polyphenols (ASP) and their effect on measures of oxidative stress. In a randomized crossover trial, seven adults consumed two acute ASP doses (225 mg (low, L) or 450 mg (high, H) total phenols) in skim milk or milk alone. Plasma flavonoids, glutathione peroxidase (GPx), glutathione (GSH), oxidized GSH (GSSG), and resistance of low-density lipoprotein (LDL) to oxidation were measured over 10 h. The H dose increased catechin and naringenin in plasma, with maximum concentrations of 44.3 and 19.3 ng/mL, respectively. The GSH/GSSG ratio at 3 h after the H doses was 212% of the baseline value, as compared to 82% after milk (p = 0.003). Both ASP doses upregulated GPx activity by 26–35% from the baseline at 15, 30, 45, and 120 min after consumption. The in vitro addition of α-tocopherol extended the lag time of LDL oxidation at 3 h after L and H consumption by 144.7% and 165.2% of that at 0 h compared to no change after milk (p≤0.05). In conclusion, ASP are bioavailable and modulate GSH status, GPx activity, and the resistance of LDL to oxidation.

Consumption of Brazil nuts with high selenium levels increased inflammation biomarkers in obese women: A randomized controlled trial.

G.B.S. Duarte, B.Z. Reis, M.M. Rogero, E. Vargas-Mendez, F.B. Júnior, C. Cercato, S.M.F. Cozzolino, 2019. Consumption of Brazil nuts with high selenium levels increased inflammation biomarkers in obese women: A randomized controlled trial. Nutrition. 63-64:162-168.

Objective: Increased inflammatory response is an important factor in the pathophysiology of obesity. The mineral selenium (Se), of which one of the main food sources is the Brazil nut, has important antioxidant and anti-inflammatory functions through the action of selenoproteins. Thus, the evaluation of the influence of this micronutrient in this context is of great relevance. The aim of this study was to evaluate the effects of Brazil nut intake with high Se concentrations on inflammatory biomarkers and its relation to Se status in obese women. Methods:A randomized controlled clinical trial was carried out with 55 women recruited at Clinical Hospital in São Paulo, Brazil. Patients were randomly assigned to either the Brazil nut group (BN) or the control group (CO) and followed up for 2 mo. The BN group consumed 1 unit/d of Brazil nuts (∼ 1261 μg/Se); the CO group did not receive any intervention. At baseline and after 2 mo, analysis of biochemical parameters related to Se status, oxidative stress, and inflammatory biomarkers were performed. Results:At baseline, both groups did not present Se deficiency. In the BN group, a significant increase (P < 0.05) in all Se biomarkers and in gene expression of several proinflammatory parameters (interleukin-6, tumor necrosis factor-α, and Toll-like receptors 2 and 4) were observed after the intervention period. No changes were observed for the CO group. Conclusion:Although there were no changes in plasma inflammatory biomarkers levels, a significant increase in gene expression may be an indication of a proinflammatory stimulus in obesity, induced by the consumption of Brazil nuts with high Se levels.