Archive

Research Nut: Walnuts

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.

Walnut oral immunotherapy for desensitisation of walnut and additional tree nut allergies (Nut CRACKER): a single-centre, prospective cohort study.

Elizur, A., M.Y. Appel, L. Nachshon, M.B. Levy, N. Epstein-Rigbi, B. Pontoppidan, J. Lidholm, M.R. Goldberg, 2019. Walnut oral immunotherapy for desensitisation of walnut and additional tree nut allergies (Nut CRACKER): a single-centre, prospective cohort study. Lancet Child Adolesc Health. 3(5):312-321.

Background: The safety and efficacy of oral immunotherapy for tree nut allergy has not been demonstrated to date, and its effectiveness is complicated by the high prevalence of co-allergies to several nuts. This study aimed to investigate the use of walnut oral immunotherapy in the desensitisation of walnut and additional tree nuts in patients who are co-allergic to several nuts. Methods: In a single-centre, prospective cohort study (the Nut Co-Reactivity ACquiring Knowledge for Elimination Recommendations study) at the Institute of Allergy, Immunology, and Paediatric Pulmonology at the Yitzhak Shamir Medical Centre, we recruited patients aged 4 years or older who were allergic to walnut, with or without co-allergy to pecan, hazelnut, and cashew. The diagnosis of each food allergy was based on a positive skin prick test or specific serum IgE (≥0·35 kUA/L) to the corresponding nut together with a positive oral food challenge, unless an immediate (within 2 h of exposure) reaction in the past year had been documented. Patients with uncontrolled asthma or a medical contraindication to receive adrenaline were excluded. Patients were assigned to walnut oral immunotherapy or the control group (observation and strict dietary exclusion) on the basis of the order of presentation to the clinic. Oral immunotherapy began with a 4-day dose-escalation phase to establish the single highest tolerated dose, which was consumed daily at home for 24 days; subsequent monthly dose escalations were repeated until 4000 mg walnut protein was achieved. Patients who were desensitised to walnut continued to consume 1200 mg walnut protein daily for 6 months as maintenance. The primary outcome was walnut desensitisation (passing an oral food challenge with 4000 mg of walnut protein) at the end of the study, analysed by intention to treat. In patients who were co-allergic to pecan, hazelnut, and cashew, the proportion who achieved cross-desensitisation to these nuts in addition to walnut desensitisation was examined. Findings: 73 patients with a walnut allergy were enrolled between May 15, 2016, and Jan 14, 2018. 49 (89%) of 55 patients in the oral immunotherapy group were desensitised to walnut compared with none of 18 patients in the control group (odds ratio 9·2, 95% CI 4·3-19·5; p<0·0001). Following walnut desensitisation, all patients who were co-allergic to pecan (n=46) were also desensitised to pecan. Additionally, 18 (60%) of 30 patients who were co-allergic to hazelnut or cashew, and 14 (93%) of 15 patients who were co-allergic to hazelnut alone, were either fully desensitised or responded to treatment. 47 (85%) of 55 patients had an adverse reaction (mostly grade 1 or 2) during up-dosing in the clinic; eight patients required intramuscular epinephrine in response to a dose at home. Of 45 patients who had follow-up data for the maintenance phase, all maintained walnut desensitisation and one patient required epinephrine during this period.  Interpretation: Walnut oral immunotherapy can induce desensitisation to walnut as well as cross-desensitisation to pecan and hazelnut in patients who have tree nut co-allergies, with a reasonable safety profile. A low daily dose of the allergen maintains desensitization.

Nut consumption in relation to cardiovascular disease incidence and mortality among patients with diabetes mellitus.

Liu, G., M. Guasch-Ferre, Y. Hu, Y. Li, F.B. Hu, E.B. Rimm, J.E. Manson, K. Rexrode, Q. Sun, 2019. Nut consumption in relation to cardiovascular disease incidence and mortality among patients with diabetes mellitus. Circulation Research. doi.org/10.1161/CIRCRESAHA.118.314316

Rationale: The evidence regarding the potential health benefits of nut consumption among individuals with type 2 diabetes is limited. Objective: To examine intake of total and specific types of nuts, including tree nuts and peanuts, in relation to subsequent risk of cardiovascular disease (CVD), including coronary heart disease (CHD) and stroke, and all-cause and cause-specific mortality among individuals with diabetes. Methods and Results: This prospective analysis included 16,217 men and women with diabetes at baseline or diagnosed during follow-up (Nurses’ Health Study: 1980-2014, Health Professionals Follow-Up Study: 1986-2014). Nut consumption was assessed using a validated food frequency questionnaire and updated every 2-4 years. During 223,682 and 254,923 person-years of follow-up, there were 3,336 incident CVD cases and 5,682 deaths. Higher total nut consumption was associated with a lower risk of CVD incidence and mortality. The multivariate-adjusted hazard ratios (95% confidence intervals) for participants who consumed 5 or more servings of total nuts per week (1 serving=28g), compared with those who consumed less than 1 serving per month, were 0.83 (0.71-0.98; P trend=0.01) for total CVD incidence, 0.80 (0.67-0.96; P trend=0.005) for CHD incidence, 0.66 (0.52-0.84; P trend<0.001) for CVD mortality, and 0.69 (0.61-0.77; P trend<0.001) for all-cause mortality. Total nut consumption was not significantly associated with risk of stroke incidence or cancer mortality. For specific types of nuts, higher tree nut consumption was associated with lower risk of total CVD, CHD incidence, and mortality due to CVD, cancer, and all causes, while peanut consumption was associated with lower all-cause mortality only (all P trend<0.001). In addition, compared with participants who did not change the consumption of total nuts from pre- to post-diabetes diagnosis, participants who increased consumption of total nuts after diabetes diagnosis had an 11% lower risk of CVD, a 15% lower CHD risk, a 25% lower CVD mortality, and a 27% lower all-cause mortality. The associations persisted in subgroup analyses stratified by sex/cohort, body mass index at diabetes diagnosis, smoking status, diabetes duration, nut consumption before diabetes diagnosis, or diet quality. Conclusions: Higher consumption of nuts, especially tree nuts, is associated with lower CVD incidence and mortality among participants with diabetes. These data provide novel evidence that supports the recommendation of incorporating nuts into healthy dietary patterns for the prevention of CVD complications and premature deaths among individuals with diabetes.

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

Al Wattar, B.H., J. Dodds, A. Placzek, L. Beresford, E. Spyreli, A. Moore, A. Moore, F.J. Gonzalez Carreras, F. Austin, N. Murugesu, T.J. Roseboom, M. Bes-Rastrollo, G.A. Hitman, R. Hooper, K.S. Khan, S. Thangaratinam, for the ESTEEM study group, 2019. Mediterranean-style diet in pregnant women with metabolic risk factors (ESTEEM): A pragmatic multicentre randomised trial. PLoS Med 16(7): e1002857. https://doi.org/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 highrisk 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, nonrefined 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 effect of nuts on markers of glycemic control: a systematic review and meta-analysis of randomized controlled trials.

Tindall, A.M., E.A. Johnston, P.M. Kris-Etherton, K.S. Petersen, 2019. The effect of nuts on markers of glycemic control: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr. 109:297–314.

Background: Observational evidence suggests higher nut consumption is associated with better glycemic control; however, it is unclear if this association is causal. Objectives: We aimed to conduct a systematic review and meta-analysis of randomized controlled trials to examine the effect of tree nuts and peanuts on markers of glycemic control in adults. Methods: A systematic review and meta-analysis of randomized controlled trials was conducted. A total of 1063 potentially eligible articles were screened in duplicate. From these articles, 40 were eligible for inclusion and data from these articles were extracted in duplicate. The weighted mean difference (WMD) between the nut intervention and control arms was determined for fasting glucose, fasting insulin, glycated hemoglobin (HbA1c), and homeostasis model assessment of insulin resistance (HOMA-IR) using the DerSimonian and Laird random-effects method. For outcomes where a limited number of studies were published, a qualitative synthesis was presented. Results: A total of 40 randomized controlled trials including 2832 unique participants, with a median duration of 3 mo (range: 1–12 mo), were included. Overall consumption of tree nuts or peanuts had a favorable effect on HOMA-IR (WMD: −0.23; 95% CI: −0.40, −0.06; I2=51.7%) and fasting insulin (WMD: −0.40μIU/mL;95% CI: −0.73, −0.07μ IU/mL; I2 = 49.4%). There was no significant effect of nut consumption on fasting blood glucose (WMD: −0.52 mg/dL;95% CI: −1.43,0.38mg/dL; I2 =53.4%) o rHbA1c (WMD: 0.02%; 95% CI: −0.01%, 0.04%; I2 =51.0%). Conclusions: Consumption of peanuts or tree nuts significantly decreased HOMA-IR and fasting insulin; there was no effect of nut consumption on HbA1c or fasting glucose. The results suggest that nut consumption may improve insulin sensitivity. In the future, well-designed clinical trials are required to elucidate the mechanisms that account for these observed effects.

Nut and peanut butter consumption and the risk of lung cancer and its subtypes: A prospective cohort study.

Nieuwenhuis, I., P.A. van den Brandt, 2019. Nut and peanut butter consumption and the risk of lung cancer and its subtypes: A prospective cohort study. Lung Cancer. 128:57-66.
Objectives: Nut consumption has been associated with reduced cancer-related mortality, but evidence for a relation between nut intake and lung cancer risk is limited. We investigated the association between total nut, tree nut, peanut, and peanut butter intake and the risk of lung cancer and its subtypes in the Netherlands Cohort Study. Materials and Methods: In 1986, dietary and lifestyle habits of 120,852 participants, aged 55–69 years, were measured with a questionnaire. After 20.3 years of follow-up, 3720 subcohort members and 2861 lung cancer cases were included in multivariable case-cohort analyses. Results: Total nut intake was not significantly associated with total lung cancer risk in men or women. For small cell carcinoma, a significant inverse association with total nut intake was observed in men after controlling for detailed smoking habits (HR (95%CI) for 10+ g/day vs. non-consumers: 0.62 (0.43-0.89), p-trend: 0.024). Inverse relations with small cell carcinoma were also found for tree nut and peanut intake in men in continuous analyses (HR (95%CI) per 5g/day increment: 0.70 (0.53-0.93) and 0.93 (0.88-0.98), respectively). For the other lung cancer subtypes, no significant associations were seen in men. Nut intake was not related to the risk of lung cancer subtypes in women, and no associations were found for peanut butter in both sexes. Conclusion: Increased nut intake might contribute to the prevention of small cell carcinoma in men. No significant associations were found in men for the other subtypes or total lung cancer, in women, or for peanut butter intake.

Identification and quantification of phytosterols in black walnut kernels.

Vu, D.C., Z. Leic, L.W. Sumner, M.V. Coggeshall, C.-H. Lin, 2019. Identification and quantification of phytosterols in black walnut kernels. J Food Compos Anal. 75:61-69.

This study aimed to identify and quantify phytosterols of six black walnut (Juglans nigra L.) varieties, and compare the levels of these phytosterols between black walnuts and English walnut (JuglansregiaL.). Totally, 13 phytosterols were identified in the black walnut kernels, with β-sitosterol predominating over the other sterols. The analysis also revealed the presence of 3 phytosterols, Δ5,23-stigmastadienol, cycloeucalenol and 28-methylobtusifoliol, which have never been reported in black walnuts. The average levels of total sterols ranged from 1236.0mg/kg to 1542.3 mg/kg. No significant differences were noted in total sterol levels between the studied black walnut varieties and English walnut. Through untargeted metabolomics analysis, five additional glycosylates and hydroxy cinnamates of phytosterols were putatively identified in the black walnuts. The findings from this research suggest black walnuts are rich in phytosterols most of which have been demonstrated to exert bioactivities. Future studies should be focused on seasonal and geographic variations in phytosterol content of black walnuts, and bioassay-guided purification to assess potential health-promoting properties of these phytosterols.

A 7-day high-PUFA diet reduces angiopoietin-like protein 3 and 8 responses and postprandial triglyceride levels in healthy females but not males: a randomized control trial.

Kaviani, S., C.M. Taylor, J.L. Stevenson, J.A. Cooper, C.M. Paton, 2019. A 7-day high-PUFA diet reduces angiopoietin-like protein 3 and 8 responses and postprandial triglyceride levels in healthy females but not males: a randomized control trial. BMC Nutrition. 5:1 doi.org/10.1186/s40795-018-0262-7.

Polyunsaturated fatty acids (PUFAs) have beneficial effects on hypertriglyceridemia although their effect on angiopoietin-like proteins (ANGPTLs), specifically ANGPTL3, ANGPTL4 and ANGPTL8 is unknown. Objective: To determine whether a high-PUFA diet improves postprandial triglyceride (TG) levels through reducing ANGPTL responses following high saturated fat (SFA) meals. Methods: Twenty-six adults were randomized into a PUFA diet (n = 16) or a control diet group (n = 10). Participants completed a pre-diet visit (v1) where they were given two SFA-rich, high-fat meals. Blood draws were taken at fasting and every 2 h postprandially for a total of 8 h. After v1, participants completed a 7d diet of the same macronutrient proportions (50% carbohydrate, 35% fat, 15% protein) but with different fatty acid (FA) compositions (PUFA = 21% of total energy from PUFAs vs. Control = 7% of total energy from PUFA). All participants then completed the post-diet visit (v2) identical to v1. Results: In the PUFA group, females, but not males, reduced TG concentrations (Area under the curve (AUC): 141.2 ± 18.7 vs. 80.7 ± 6.5 mg/dL/h, p = 0.01, for v1 vs. v2, respectively). Fasting and postprandial AUC levels of ANGPTL3 and 8, but not ANGPTL4, also decreased from v1 to v2 in PUFA females, but not males. No changes from v1 to v2 were seen in either sex in the control group. Conclusions: A PUFA-rich diet improves TG levels in response to high-SFA meals with reductions in ANGPTL3 and ANGPTL8. PUFAs may be more protective against hypertriglyceridemia in females, compared to males since no diet effect was observed in males.

Lower depression scores among walnut consumers in NHANES.

Arab, L., R. Guo, D. Elashoff, 2019. Lower depression scores among walnut consumers in NHANES. Nutrients. 11, 275; doi:10.3390/nu11020275.

Background: Multiple studies have shown a Mediterranean diet, characterized by their olive oil and nut consumption, to be correlated with lower depression risk. Objective: To examine whether part of this reduced risk in the United States is attributable to walnut consumption, we analyzed data on walnut consumption and depression scores from the National Health and Nutrition Examination Survey (NHANES). Methods: NHANES survey data for 2005 through 2014 was pooled for adults with 24 h recall dietary data. Depression scores were based on PHQ-9 self-report responses. A total of 26,656 participants were characterized as reporting the consumption of walnuts with high certainty, walnuts with other nuts, other nuts, or no nuts. Results: After an adjustment for covariates, walnut consumers showed lower depression scores compared to non-nut consumers. The least square mean for total depression score was 26% lower for walnut with high certainty consumers than for non-nut consumers (p < 0.0001), and the association was stronger among women (32%, p < 0.0001) than men (21%, p = 0.05). The significant contributors to this difference were due to walnut consumers reporting greater interest in doing things (p = 0.003), less hopelessness (p = 0.02), and feeling more energetic (p = 0.05) than non-nut consumers. Non-nut consumers were more likely to have trouble concentrating (p = 0.02), to feel they were moving or speaking abnormally (p = 0.03), and to have thought they were better off dead (p = 0.002). Conclusions: Depression scores were significantly lower among nut consumers and particularly walnut consumers as compared to non-nut consumers. After controlling for potential covariates, walnut users had scores significantly lower than other nut consumers. The difference was strongest among women, who are more likely than men to report higher depression scores.