Lee, J., Y.S. Kim, J. Lee, S.C. Heo, K.L. Lee, S.W. Choi, Y. Kim, 2016. Walnut phenolic extract and its bioactive compounds suppress colon cancer cell growth by regulating colon cancer stemness.Nutrients. 8, 439; doi:10.3390/nu8070439.
Abstract: Walnut has been known for its health benefits, including anti-cardiovascular disease and anti-oxidative properties. However, there is limited evidence elucidating its effects on cancer stem cells (CSCs) which represent a small subset of cancer cells that provide resistance against chemotherapy. This study aimed to evaluate the anti-CSCs potential of walnut phenolic extract (WPE) and its bioactive compounds, including (+)-catechin, chlorogenic acid, ellagic acid, and gallic acid. In the present study, CD133+CD44+ cells were isolated from HCT116 cells using fluorescence-activated cell sorting (FACS) and then treated with WPE. As a result, survival of the CD133+CD44+ HCT116 cells was inhibited and cell differentiation was induced by WPE. In addition, WPE down-regulated the CSC markers, CD133, CD44, DLK1, and Notch1, as well as the β-catenin/p-GSK3β signaling pathway. WPE suppressed the self-renewal capacity of CSCs. Furthermore, the WPE exhibited stronger anti-CSC effects than its individual bioactive compounds. Finally, the WPE inhibited specific CSC markers in primary colon cancer cells isolated from primary colon tumor. These results suggest that WPE can suppress colon cancer by regulating the characteristics of colon CSCs.
Chung J, Kim YS, Lee J, Le JH, Choi SW, Kim Y., 2016. Compositional analysis of walnut lipid extracts and properties as an anti-cancer stem cell regulator via suppression of the self-renewal capacity.Food Sci. Biotechnol. 25(2): 623-629.
Colon cancer is a leading cause of cancer-related deaths worldwide. Effects of walnut (Juglans regia L.) lipid extracts (WLEs) on the self-renewal capacity of cancer stem cells (CSCs) in colon cancer were investigated. The dominant component of WLEs was α-linoleic acid (64.6%), followed by α-linolenic acid (14.6%), and oleic acid (12.6%). A higher concentration of γ-tocopherol (37.1%) was also present than of α-tocopherol (0.6%). CD133+CD44+CSCs treated with WLEs showed inhibition of colony formation and sphere formation, indicating a decrease in the self-renewal capacity. Treatment with WLEs also resulted in down-regulation of protein levels, including Notch1, phospho-GSK3β (p- GSK3β), and β-catenin, which are associated with CSCs and the self-renewing capacity. WLEs rich in essential fatty acids and γ-tocopherol can exert therapeutic actions on colon cancer via targeting of CSCs.
Al Wattar, B.H., J. Dodds, A. Placzek, E. Spyreli, A. Moore, R. Hooper, L. Beresford, T.J. Roseboom, M. Bes-Rastrollo, G. Hitman, K.S. Khan, S. Thangaratinam; ESTEEM study group, 2016. Effect of simple, targeted diet in pregnant women with metabolic risk factors on maternal and fetal outcomes (ESTEEM): study protocol for a pragmatic multicentre randomised trial. BMJ Open. 2016;6:e013495. doi:10.1136/bmjopen-2016013495.
Introduction: Women with metabolic risk factors are at higher risk of adverse pregnancy outcomes. Mediterranean-based dietary interventions have the potential to minimise these risks. We aim to evaluate the effectiveness of a simple, targeted intervention modelled on Mediterranean diet in preventing maternal and fetal complications in pregnant women with metabolic risk factors. Methods and Analysis: Pregnant women with a singleton pregnancy <18 weeks gestation, and without pre-existing diabetes, chronic renal disease and autoimmune diseases will be recruited. Women with metabolic risk factors will be randomised to receive a dietary intervention based on a Mediterranean pattern, supplemented with extra virgin olive oil and mixed nuts until delivery. The intervention will be delivered through a series of one to one and group sessions. The primary outcome is a composite maternal outcome of pre-eclampsia or gestational diabetes and a composite fetal outcome of stillbirth, small for gestational age fetus or admission to the neonatal intensive care unit. Secondary outcomes include maternal, fetal, dietary and laboratory outcomes. We aim to randomise 1230 eligible women with metabolic risk factors. We will also compare the outcomes in women with and without these risk factors. The sample size will provide us with 80% power at 5% significance, assuming a 20% loss to follow-up to detect a 30% reduction in maternal and fetal complications. Ethics and Dissemination: The ESTEEM trial is designed to provide a definitive estimate of the effects of Mediterranean dietary pattern in pregnancy on maternal and fetal outcomes. The pragmatic nature of ESTEEM ensures the applicability of its findings into clinical practice. The findings of the study will be published in peer-reviewed journals and presented at national and international scientific meetings and congresses.
Neale, E.P., L.C. Tapsell, A. Martin, M.J. Batterham, C. Wibisono, Y.C. Probst, 2016. Impact of providing walnut samples in a lifestyle intervention for weight loss: a secondary analysis of the HealthTrack trial. Food and Nutrition Research. 61:1, 1344522. doi:1080/16546628.2017.1344522.
Background: Being more specific about individual food choices may be advantageous for weight loss. Including a healthy food (e.g. walnuts) may help to expose effects. Objective: To examine the impact of including walnuts in diets for weight loss. Design: Secondary analysis of the HealthTrack lifestyle intervention trial. Overweight and obese participants were randomized to: usual care (C), interdisciplinary intervention including individualized dietary advice (I), or interdisciplinary intervention including 30 g walnuts/day (IW). Changes in body weight, energy intake, intake of key foods, physical activity, and mental health over three and 12 months were explored. Results: A total of 293 participants completed the intensive three-month study period, and 175 had data available at 12 months. The IW group achieved the greatest weight loss at three months. IW reported significant improvements in healthy food choices, and decreased intakes of discretionary foods/beverages, compared to C. Weight loss remained greatest in IW at 12 months. Discussion: Significant effects were seen after three months, with the IW group achieving greater weight loss and more favorable changes in food choices. Conclusions: Including 30 grams walnuts/day in an individualized diet produced weight loss and positive changes in food choice.
Sánchez-González, C., C.J. Ciudad, M. Izquierdo-Pulido, V. Noé V., 2016. Urolithin A causes p21 up-regulation in prostate cancer cells. Eur J Nutr. 55(3):1099-112.
Purpose: Walnuts contain several bioactive compounds, including pedunculagin, a polyphenol metabolized by microbiota to form urolithins, namely urolithin A (UA). The aim of this study was to determine gene expression changes in prostate cancer cells after incubation with UA. Methods: We performed a genomic analysis to study the effect of UA on LNCaP prostate cells. Cells were incubated with 40 µM UA for 24 h, and RNA was extracted and hybridized to Affymetrix Human Genome U219 array. Microarray results were analyzed using GeneSpring v13 software. Differentially expressed genes (p < 0.05, fold change > 2) were used to perform biological association networks. Cell cycle was analyzed by flow cytometry and apoptosis measured by the rhodamine method and by caspases 3 and 7 activation. Cell viability was determined by MTT assay. Results: We identified two nodes, FN-1 and CDKN1A, among the differentially expressed genes upon UA treatment. CDKN1A was validated, its mRNA and protein levels were significantly up-regulated, and the promoter activation measured by luciferase. Cell cycle analysis showed an increase in G1-phase, and we also observed an induction of apoptosis and caspases 3 and 7 activation upon UA treatment. Conclusion: Our results indicate a potential role of UA as a chemopreventive agent for prostate cancer.
Baer, D., S. Gebauer, J. Novotny, 2016. Walnuts consumed by healthy adults provide less available energy than predicted by the Atwater Factors. J Nutr. 146:1–5.
Background: Previous studies have shown that the metabolizable energy (ME) content (energy available to the body) of certain nuts is less than predicted by the Atwater factors. However, very few nuts have been investigated to date, and no information is available regarding the ME of walnuts. Objective: A study was conducted to determine the ME of walnuts when consumed as part of a typical American diet. Methods: Healthy adults (n = 18; mean age = 53.1 y; body mass index = 28.8 kg/m2) participated in a randomized crossover study with 2 treatment periods (3 wk each). The study was a fully controlled dietary feeding intervention in which the same base diet was consumed during each treatment period; the base diet was unsupplemented during one feeding period and supplemented with 42 g/d walnuts during the other feeding period. Base diet foods were reduced in equal proportions during the walnut period to achieve isocaloric food intake during the 2 periods. After a 9 d diet acclimation period, subjects collected all urine and feces for ;1 wk (as marked by a Brilliant Blue fecal collection marker) for analysis of energy content. Administered diets, walnuts, and fecal and urine samples were subjected to bomb calorimetry, and the resulting data were used to calculate the ME of the walnuts. Results: One 28-g serving of walnuts contained 146 kcal (5.22 kcal/g), 39 kcal/serving less than the value of 185 kcal/ serving (6.61 kcal/g) currently used for food labeling. The ME of the walnuts was 21% less than that predicted by the Atwater factors (P < 0.0001). Conclusion: Consistent with other tree nuts, Atwater factors overestimate the metabolizable energy value of walnuts. These results could help explain the observations that consumers of nuts do not gain excessive weight, and improve the accuracy for food labeling.
Sala-Vila, A., M. Guasch-Ferré, F.B. Hu, A. Sánchez-Tainta, M. Bulló, M. Serra-Mir, C. López-Sabater, J.V. Sorlí, F. Arós, M. Fiol, M.A. Muñoz, L. Serra-Majem, J.A. Martínez, D. Corella, M. Fitó, J. Salas-Salvadó, M.A. Martínez-González, R. Estruch, E. Ros; and PREDIMED Investigators, 2016. Dietary α-linolenic acid, marine ω-3 fatty acids, and mortality in a population with high fish consumption: findings from the PREvención con DIeta MEDiterránea (PREDIMED) study. J Am Heart Assoc. 26:5(1).
Background: Epidemiological evidence suggests a cardioprotective role of α-linolenic acid (ALA), a plant-derived ω-3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω-3 fatty acids (long-chain n-3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all-cause and cardiovascular disease mortality. We also examined the effect of meeting the society’s recommendation for long-chain n-3 polyunsaturated fatty acids (≥500 mg/day). Methods and Results: We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable-adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9-y follow-up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56-0.92) for all-cause mortality and 0.95 (95% CI 0.58-1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for long-chain n-3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67-1.05) for all-cause mortality, 0.61 (95% CI 0.39-0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29-0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22-1.01) for sudden cardiac death. The highest reduction in all-cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45-0.87]). Conclusions: In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all-cause mortality, whereas protection from cardiac mortality is limited to fish-derived long-chain n-3 polyunsaturated fatty acids.
Le, T., S.W. Flatt, L. Natarajan, B. Pakiz, E.L. Quintana, D.D. Heath, B.K. Rana, C.L. Rock, 2016. Effects of diet composition and insulin resistance status on plasma lipid levels in a weight loss intervention in women. J Am Heart Assoc. 5(1). doi: 10.1161/JAHA.115.002771.
Background: Optimal macronutrient distribution of weight loss diets has not been established. The distribution of energy from carbohydrate and fat has been observed to promote differential plasma lipid responses in previous weight loss studies, and insulin resistance status may interact with diet composition and affect weight loss and lipid responses. Methods and Results: Overweight and obese women (n=245) were enrolled in a 1‐year behavioral weight loss intervention and randomly assigned to 1 of 3 study groups: a lower fat (20% energy), higher carbohydrate (65% energy) diet; a lower carbohydrate (45% energy), higher fat (35% energy) diet; or a walnut‐rich, higher fat (35% energy), lower carbohydrate (45% energy) diet. Blood samples and data available from 213 women at baseline and at 6 months were the focus of this analysis. Triglycerides, total cholesterol, and high‐ and low‐density lipoprotein cholesterol were quantified and compared between and within groups. Triglycerides decreased in all study arms at 6 months (P<0.05). The walnut‐rich diet increased high‐density lipoprotein cholesterol more than either the lower fat or lower carbohydrate diet (P<0.05). The walnut‐rich diet also reduced low‐density lipoprotein cholesterol in insulin‐sensitive women, whereas the lower fat diet reduced both total cholesterol and high‐density lipoprotein cholesterol in insulin‐sensitive women (P<0.05). Insulin sensitivity and C‐reactive protein levels also improved. Conclusions: Weight loss was similar across the diet groups, although insulin‐sensitive women lost more weight with a lower fat, higher carbohydrate diet versus a higher fat, lower carbohydrate diet. The walnut‐rich, higher fat diet resulted in the most favorable changes in lipid levels.
Key area: insulin resistance, lipids, walnuts/ weight management/weight, satiety,
Djoussé, L., B. Lu, M.J. Gaziano, 2016. Effects of walnut consumption on endothelial function in people with type 2 diabetes: a randomized pilot trial. Curr Nutr Rep. 5(1):1-8.
The aim of this study was to obtain preliminary data to test the hypothesis that (1) a 12-week intervention with 28 g/day of walnuts improves endothelial function in people with type 2 diabetes mellitus (DM) and (2) intake of walnuts improves plasma adipokines after 12 weeks of intervention. In this pilot randomized, single-blinded, controlled trial of 26 adult subjects with prevalent DM, each subject was randomized to a usual diet with 28 g of walnuts per day or usual diet without walnuts (control group). Reactive hyperemia index (RHI), a measure of endothelial function, was measured non-invasively at baseline and after 12 weeks using Endo-PAT2000. We used linear regression to examine the effects of the intervention on RHI. The mean age at baseline was 64.8 ± 11.6 years; 61.5 % of participants were female, and 15.4 % had coronary artery disease. The standard error of RHI was 0.19. The difference in change in RHI during the intervention between the two groups was −0.029 (95 % confidence interval (CI) −0.52, 0.46, p = 0.23). Walnut intervention led to a suggestive increase in adiponectin, albeit non-statistically significant (difference 0.50 μg/ml (95 % CI −0.10, 1.09), p = 0.65). We demonstrated the feasibility of the proposed randomized trial and obtained needed standard deviations to calculate the required sample size to test proposed hypotheses in an efficacy trial.
Yu, Z., V.S. Malik, N. Keum, F.B. Hu, E.L. Giovannucci, M.J. Stampfer, W.C. Willett, C.S. Fuchs, Y. Bao, 2016. Associations between nut consumption and inflammatory biomarkers. AJCN. First published ahead of print July 27, 2016 as doi: 10.3945/ajcn.116.134205.
Background: Increased nut consumption has been associated with reduced risk of cardiovascular disease and type 2 diabetes, as well as a healthy lipid profile. However, the associations between nut consumption and inflammatory biomarkers are unclear. Objective: We investigated habitual nut consumption in relation to inflammatory biomarkers in 2 large cohorts of US men and women. Design: We analyzed cross-sectional data from 5013 participants in the Nurses’ Health Study (NHS) and Health Professionals Follow-Up Study (HPFS) who were free of diabetes. Nut intake, defined as intake of peanuts and other nuts, was estimated from food frequency questionnaires, and cumulative averages from 1986 and 1990 in the NHS and from 1990 and 1994 in the HPFS were used. Plasma biomarkers were collected in 1989–1990 in the NHS and 1993–1995 in the HPFS. Multivariate linear regression was used to assess the associations of nut consumption with fasting plasma C-reactive protein (CRP, n = 4941), interleukin 6 (IL-6, n = 2859), and tumor necrosis factor receptor 2 (TNFR2, n = 2905). Results: A greater intake of nuts was associated with lower amounts of a subset of inflammatory biomarkers, after adjusting for demographic, medical, dietary, and lifestyle variables. The relative concentrations (ratios) and 95% CIs comparing subjects with nut intake of $5 times/wk and those in the categories of never or almost never were as follows: CRP: 0.80 (0.69, 0.90), P-trend = 0.0003; and IL-6: 0.86 (0.77, 0.97), P-trend = 0.006. These associations remained significant after further adjustment for body mass index. No significant association was observed with TNFR2. Substituting 3 servings of nuts/wk for 3 servings of red meat, processed meat, eggs, or refined grains/wk was associated with significantly lower CRP (all P , 0.0001) and IL-6 (P ranges from 0.001 to 0.017). Conclusion: Frequent nut consumption was associated with a healthy profile of inflammatory biomarkers.
