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Research Nut: Walnuts

Effects of diet composition on weight loss, metabolic factors and biomarkers in a 1-year weight loss intervention in obese women examined by baseline insulin resistance status.

Rock, C.L., S.W. Flatt, B. Pakiz, E.L.Quintana, D.D. Heath, B.K. Rana, L. Natarajan, 2016. Effects of diet composition on weight loss, metabolic factors and biomarkers in a 1-year weight loss intervention in obese women examined by baseline insulin resistance status. Metabolism. 65(11):1605-1613.

Background: Obesity is a risk factor for postmenopausal breast cancer incidence and pre- and postmenopausal breast cancer mortality, which may be explained by several metabolic and hormonal factors (sex hormones, insulin resistance, and inflammation) that are biologically related. Differential effects of dietary composition on weight loss and these metabolic factors may occur in insulin-sensitive vs. insulin-resistant obese women. Objective. To examine the effect of diet composition on weight loss and metabolic, hormonal and inflammatory factors in overweight/obese women stratified by insulin resistance status in a 1-year weight loss intervention. Methods and Results. Nondiabetic women who were overweight/obese (n = 245) were randomly assigned to a lower fat (20% energy), higher carbohydrate (65% energy) diet; a lower carbohydrate (45% energy), higher fat (35% energy) diet; or a walnut-rich (18% energy), higher fat (35% energy), lower carbohydrate (45% energy) diet. All groups lost weight at follow-up (P < 0.0001), with mean (SEM) percent loss of 9.2 (1.1)% in lower fat, 6.5 (0.9)% in lower carbohydrate, and 8.2 (1.0)% in walnut-rich groups at 12 months. The diet x time x insulin resistance status interaction was not statistically significant in the model for overall weight loss, although insulin sensitive women at 12 months lost more weight in the lower fat vs. lower carbohydrate group (7.5 kg vs 4.3 kg, P = 0.06), and in the walnut-rich vs. lower carbohydrate group (8.1 kg vs 4.3 kg, P = 0.04). Sex hormone binding globulin increased within each group except in the lower carbohydrate group at 12 months (P < 0.01). C-reactive protein and interleukin-6 decreased at follow-up in all groups (P < 0.01). Conclusions. Findings provide some support for differential effects of diet composition on weight loss depending on insulin resistance status. Prescribing walnuts is associated with weight loss comparable to a standard lower fat diet in a behavioral weight loss intervention. Weight loss itself may be the most critical factor for reducing the chronic inflammation associated with increased breast cancer risk and progression.

 

Inclusion of walnut in the diets of adults at risk for type 2 diabetes and their dietary pattern changes: a randomized, controlled, cross-over trial.

Njike VY, Yarandi N, Petraro P, Ayettey RG, Treu JA, Katz DL, 2016. Inclusion of walnut in the diets of adults at risk for type 2 diabetes and their dietary pattern changes: a randomized, controlled, cross-over trial. BMJ Open Diabetes Res Care. 4(1):e000293.

Abstract: Background: In our recently published study, including walnuts in the diets of adults with prediabetes led to overall improvement in diet quality. This report adds to those study findings by examining the food groups displaced during walnut inclusion in the diets of those adults with prediabetes. Methods: Randomized, controlled, modified Latin square parallel design with 2 treatment arms. The 112 participants (31 men, 81 women) were randomly assigned to a diet with or without dietary counseling to regulate calorie intake in a 1:1 ratio. Within each treatment arm, participants were further randomized to 1 of 2 sequence permutations to receive a walnut included diet with 56 g (366 kcal) of walnuts per day and a walnut-excluded diet. Participants in the calorie regulated arm received advice from a dietitian to preserve an isocaloric condition while including walnuts. We analyzed the 12 components of the 2010 Healthy Eating Index to examine dietary pattern changes of study participants. Results: Seafood and plant protein foods intake significantly increased with walnut inclusion, compared with their exclusion (2.14±2.06 vs −0.49±2.33; p=0.003). The ingestion of healthful fatty acids also significantly increased with walnut inclusion, compared with their exclusion (1.43±4.53 vs −1.76±4.80; p=0.02). Dairy ingestion increased with walnut inclusion in the calorie-regulated phase, compared with walnut inclusion without calorie regulation (1.06±4.42 vs −2.15±3.64; p=0.02). Conclusions: Our data suggest that walnut inclusion in the diets of adults at risk for diabetes led to an increase in intake of other healthful foods.

Effects of walnut consumption on colon carcinogenesis and microbial community structure.

Nakanishi, M., Y. Chen, V. Qendro, S. Miyamoto, E. Weinstock, G.M. Weinstock, D.W. Rosenberg, 2016. Effects of walnut consumption on colon carcinogenesis and microbial community structure.Cancer Prev Res. 9(8):692-703.

Walnuts are comprised of a complex array of biologically active constituents with individual cancer-protective properties. Here, we assessed the potential benefit of whole walnut consumption in a mouse tumor bioassay using azoxymethane (AOM). In study 1, a modest reduction (1.3-fold) in tumor numbers was observed in mice fed a standard diet (AIN-76A) containing 9.4% walnuts (15% of total fat). In Study 2, the effects of walnut supplementation were tested in the Total Western Diet (TWD). There was a significant reduction (2.3-fold; p<0.02) in tumor numbers in male mice fed TWD containing 7% walnuts (10.5% of total fat). Higher concentrations of walnuts lacked inhibitory effects, particularly in female mice, indicating there may be optimal levels of dietary walnut intake for cancer prevention. Since components of the Mediterranean diet have been shown to affect the gut microbiome, the effects of walnuts were therefore tested in fecal samples using 16S rRNA gene sequencing. Carcinogen treatment reduced the diversity and richness of the gut microbiome, especially in male mice, which exhibited lower variability and greater sensitivity to environmental changes. Analysis of individual operational taxonomic units (OTUs) identified specific groups of bacteria associated with carcinogen exposure, walnut consumption and/or both variables. Correlation analysis also identified specific OTU-clades that were strongly associated with the presence and number of tumors. Taken together, our results indicate that walnuts afford partial protection to the colon against a potent carcinogenic insult, and this may be due in part to walnut-induced changes to the gut microbiome.

Consumption of walnuts in combination with other whole foods produces physiologic, metabolic, and gene expression changes in obese C57BL/6J high-fat–fed male mice.

Luo, T., O. Miranda-Garcia, A. Adamson, J. Hamilton-Reeve, D.K. Sullivan, J.M. Kinchen, N.F. Shay, 2016.  Consumption of walnuts in combination with other whole foods produces physiologic, metabolic, and gene expression changes in obese C57BL/6J high-fat–fed male mice. J Nutr. 146(9):1641-50.

Background: Although a reductionist approach has sought to understand the roles of individual nutrients and biochemicals in foods, it has become apparent that there can be differences when studying food components in isolation or within the natural matrix of a whole food. Objective: The objective of this study was to determine the ability of whole-food intake to modulate the development of obesity and other metabolic dysfunction in mice fed a high-fat, Western-style obesogenic diet. To test the hypothesis that an n–3 (ω-3) polyunsaturated fatty acid-rich food could synergize with other, largely polyphenol-rich foods by producing greater reductions in metabolic disease conditions, the intake of English walnuts was evaluated in combination with 9 other whole foods. Methods: Eight-week-old male C57Bl/6J mice were fed low-fat (LF; 10% fat) and high-fat (HF) control diets, along with an HF diet with 8.6% (wt:wt) added walnuts for 9 wk. The HF control diet contained 46% fat with added sucrose (10.9%, wt:wt) and cholesterol (1%, wt:wt); the added sucrose and cholesterol were not present in the LF diet. Other groups were provided the walnut diet with a second whole food—raspberries, apples, cranberries, tart cherries, broccoli sprouts, olive oil, soy protein, or green tea. All of the energy-containing whole foods were added at an energy level equivalent to 1.5 servings/d. Body weights, food intake, and glucose tolerance were determined. Postmortem, serum lipids and inflammatory markers, hepatic fat, gene expression, and the relative concentrations of 594 biochemicals were measured. Results: The addition of walnuts with either raspberries, apples, or green tea reduced glucose area under the curve compared with the HF diet alone (−93%, −64%, and −54%, respectively, P < 0.05). Compared with HF-fed mice, mice fed walnuts with either broccoli sprouts or green tea (−49% and −61%, respectively, P < 0.05) had reduced hepatic fat concentrations. There were differences in global gene expression patterns related to whole-food content, with many examples of differences in LF- and HF-fed mice, HF- and walnut-fed mice, and mice fed walnuts and walnuts plus other foods. The mean ± SEM increase in relative hepatic concentrations of the n–3 fatty acids α-linolenic acid, eicosapentanoic acid, and docosapentanoic acid in all walnut-fed groups was 124% ± 13%, 159% ± 11%, and 114% ± 10%, respectively (P < 0.0001), compared with LF- and HF-fed mice not consuming walnuts. Conclusions: In obese male mice, walnut consumption with a high-fat Western-style diet caused changes in hepatic fat concentrations, gene expression patterns, and fatty acid concentrations. The addition of a second whole food in combination with walnuts produced other changes in metabolite concentrations and gene expression patterns and other physiologic markers. Importantly, these substantial changes occurred in mice fed typical amounts of intake, representing only 1.5 servings each food/d.

Greater adherence to the Alternative Healthy Eating Index is associated with lower incidence of physical function impairment in the Nurses’ Health Study.

Hagan, K.A., S.E. Chiuve, M.J. Stampfer, J.N. Katz, F. Grodstein, 2016. Greater adherence to the Alternative Healthy Eating Index is associated with lower incidence of physical function impairment in the Nurses’ Health Study. J Nutr. 146:1341-7.

Background: Physical function is integral to healthy aging, in particular as a core component of mobility and independent living in older adults, and is a strong predictor of mortality. Limited research has examined the role of diet, which may be an important strategy to prevent or delay a decline in physical function with aging. Objective: We prospectively examined the association between the Alternative Healthy Eating Index-2010 (AHEI-2010), a measure of diet quality, with incident impairment in physical function among 54,762 women from the Nurses’ Health Study. Methods: Physical function was measured by the Medical Outcomes Short Form-36 (SF-36) physical function scale and was administered every 4 y from 1992 to 2008. Cumulative average diet was assessed using food frequency questionnaires, administered approximately every 4 y. We used multivariable Cox proportional hazards models to estimate the HRs of incident impairment of physical function. Results: Participants in higher quintiles of the AHEI-2010, indicating a healthier diet, were less likely to have incident physical impairment than were participants in lower quintiles (P-trend < 0.001). The multivariable-adjusted HR of physical impairment for those in the top compared with those in the bottom quintile of the AHEI-2010 was 0.87 (95% CI: 0.84, 0.90). For individual AHEI-2010 components, higher intake of vegetables (P-trend = 0.003) and fruits (P-trend = 0.02); lower intake of sugar-sweetened beverages (P-trend < 0.001), trans fats (P-trend = 0.03), and sodium (P-trend < 0.001); and moderate alcohol intake (P-trend < 0.001) were each significantly associated with reduced rates of incident physical impairment. Among top contributors to the food components of the AHEI-2010, the strongest relations were found for increased intake of oranges, orange juice, apples and pears, romaine or leaf lettuce, and walnuts. However, associations with each component and with specific foods were generally weaker than the overall score, indicating that overall diet pattern is more important than individual parts. Conclusions: In this large cohort of older women, a healthier diet was associated with a lower risk of developing impairments in physical function.

Walnut phenolic extract and its bioactive compounds suppress colon cancer cell growth by regulating colon cancer stemness.

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.

 

Compositional analysis of walnut lipid extracts and properties as an anti-cancer stem cell regulator via suppression of the self-renewal capacity.

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.

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.

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.

Impact of providing walnut samples in a lifestyle intervention for weight loss: a secondary analysis of the HealthTrack trial.

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.

Urolithin A causes p21 up-regulation in prostate cancer cells.

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.