Archive

Research Nut: Hazelnuts

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.

Nut Consumption and Survival in Patients With Stage III Colon Cancer: Results From CALGB 89803 (Alliance).

Fadelu, T., S. Zhang, D. Niedzwiecki, X. Ye, L.B. Saltz, R.J. Mayer, R.B. Mowat, R. Whittom, A. Hantel, A.B. Benson, D.M. Atienza, M. Messino, H.L. Kindler, A. Venook, S. Ogino, K. Ng, K. Wu, W. Willett, E. Giovannucci, J. Meyerhardt, Y. Bao, C.S. Fuchs, 2018. Nut Consumption and Survival in Patients With Stage III Colon Cancer: Results From CALGB 89803 (Alliance). J Clin Oncol. 36(11):1112-1120.

Purpose: Observational studies have reported increased colon cancer recurrence and mortality in patients with states of hyperinsulinemia, including type 2 diabetes, obesity, sedentary lifestyle, and high glycemic load diet. Nut intake has been associated with a lower risk of type 2 diabetes, metabolic syndrome, and insulin resistance. However, the effect of nut intake on colon cancer recurrence and survival is not known. Patients and Methods: We conducted a prospective, observational study of 826 eligible patients with stage III colon cancer who reported dietary intake on food frequency questionnaires while enrolled onto a randomized adjuvant chemotherapy trial. Using Cox proportional hazards regression, we assessed associations of nut intake with cancer recurrence and mortality. Results: After a median follow-up of 6.5 years, compared with patients who abstained from nuts, individuals who consumed two or more servings of nuts per week experienced an adjusted hazard ratio (HR) for disease-free survival of 0.58 (95% CI, 0.37 to 0.92; Ptrend = .03) and an HR for overall survival of 0.43 (95% CI, 0.25 to 0.74; Ptrend = .01). In subgroup analysis, the apparent benefit was confined to tree nut intake (HR for disease-free survival, 0.54; 95% CI, 0.34 to 0.85; Ptrend = .04; and HR for overall survival, 0.47; 95% CI, 0.27 to 0.82; Ptrend = .04). The association of total nut intake with improved outcomes was maintained across other known or suspected risk factors for cancer recurrence and mortality. Conclusion: Diets with a higher consumption of nuts may be associated with a significantly reduced incidence of cancer recurrence and death in patients with stage III colon cancer.

Almond, hazelnut and walnut, three nuts for neuroprotection in Alzheimer’s disease: A neuropharmacological review of their bioactive constituents.

Gorji, N., R. Moeini, Z. Memariani, 2018. Almond, hazelnut and walnut, three nuts for neuroprotection in Alzheimer’s disease: A neuropharmacological review of their bioactive constituents. Pharmacol Res. 129:115-127.

An increase in the prevalence of Alzheimer’s disease (AD) as a multifactorial neurodegenerative disorder is an almost obvious issue in the world. Research on natural products for finding effective drugs to prevent the disease are in progress. There is special attention to the three types of nuts including almond, hazelnut and walnut in manuscripts of traditional Persian medicine (PM) as the preventive agents against brain atrophy and memory loss. The purpose of this study is a pharmacological review of their bioactive constituents and introducing the value of these nuts as the effective supplements and natural medicinal foods in AD patients. Databases including PubMed and ScienceDirect were searched in title, abstract and keywords from year 2000 to present for AD-related research on these tree nuts, their major phytochemicals and their mechanisms of action. As result, almond, hazelnut and walnut provide macronutrients, micronutrients, and phytochemicals which affect several pathways in AD pathogenesis such as amyloidogenesis, tau phosphorylation, oxidative stress, cholinergic pathways, and some non-target mechanisms including cholesterol lowering and anti-inflammatory properties, as well as effect on neurogenesis. These nuts are recommended in PM for their brain-protective activity and particularly reversing brain atrophy in case of hazelnut. The therapeutical statements of PM scholars mentioned in their books are based on their clinical observations with support of a long history of experiences. Beyond the molecular activities attributed to the phytochemicals, the use of these tree nuts could be more considered in scientific research as the effective nutrients for prevention or even management of AD.

Effects of hazelnuts and cocoa on vascular reactivity in healthy subjects: a randomised study.

Adamo, M., A.M. Labate, A. Ferrulli, C. Macrì, I. Terruzzi, L. Luzi, 2018. Effects of hazelnuts and cocoa on vascular reactivity in healthy subjects: a randomised study. Int J Food Sci Nutr. 69(2):223-234.

Cocoa helps maintain endothelium-dependent vasodilation; consumption of hazelnuts has been associated with reduced cardiovascular disease risk. This study assesses the effects of hazelnuts and cocoa on vascular reactivity and metabolic profile. Sixty-one healthy volunteers, examined in a randomised, controlled, two-week intervention, received one of six breakfast integrations containing either hazelnuts, cocoa, both or none. Consumption of unpeeled hazelnuts improved HDL-cholesterol (+7.3%, p = .01 vs. baseline, p = .02 vs. control). Brachial artery peak systolic velocities (PSV) at rest increased with hazelnut integrations by 43.4% (p = .04 vs. control) and hazelnut-cocoa integrations by 26.4% (p = .01 vs. control). PSV after 3-min cuff occlusion increased by 60.7% (p = .002 vs. control) with a peeled hazelnut snack and by 64.7% with a hazelnut-cocoa integration (p = .04 vs. control). The combination hazelnut-cocoa may act in a synergic and protective way on cardiovascular system.

Daily consumption of Oregon hazelnuts affects α-tocopherol status in healthy older adults: A pre-post intervention study.

Michels A.J., S.W. Leonard, S.L. Uesugi, G. Bobe, B. Frei, M.G. Traber, 2018. Daily consumption of Oregon hazelnuts affects α-tocopherol status in healthy older adults: A pre-post intervention study. J Nutr. 2018;148:1924–1930.

Background: Inadequate vitamin E and magnesium intakes are of concern for older adults owing to the associated incidence of age-related diseases. Objective: This study was designed to determine the extent to which a 16-wk intervention with hazelnuts alters vitamin E and magnesium status in a group of older men and women, and used a pre-post intervention design without a control group to adjust for temporal changes. Methods: Participants (n = 32 including 22 women; mean ± SD age: 63 ± 6 y) consumed hazelnuts (∼57 g/d) for 16 wk. Blood and urine samples and anthropomorphic measures were taken at the start and end of the intervention to determine plasma concentrations of α-tocopherol and serum concentrations of magnesium, lipids, glucose, insulin, and high-sensitivity C-reactive protein along with urinary vitamin E metabolites; several other micronutrients were measured by a lymphocyte proliferation assay. There were 3 primary endpoints, calculated as the mean changes in measurements between baseline and the end of the 16-wk intervention for 1) plasma α-tocopherol, 2) urinary α-carboxyethyl hydroxychromanol (α-CEHC; an α-tocopherol metabolite), and 3) serum magnesium. Results: Hazelnut consumption increased concentrations of the urinary α-tocopherol metabolite α-CEHC (mean ± SD: 0.84 ± 0.45 to 1.14 ± 0.50 µmol/g creatinine; P = 0.0006). In addition, hazelnut consumption increased serum concentrations of magnesium (+2.1%, P= 0.05), decreased concentrations of fasting glucose (−3.4%, P = 0.03) and LDL cholesterol (−6.0%, P = 0.02), and decreased total: HDL cholesterol ratios (−4.5%, P = 0.009). No significant changes were observed in blood pressure, lymphocyte proliferation assays, and serum concentrations of insulin, high sensitivity C-reactive protein, triglyceride, α-tocopherol, or HDL cholesterol. Conclusions: Consuming hazelnuts improves a biomarker of vitamin E status in older adults. Vitamin E is a shortfall micronutrient, as identified by the Dietary Guidelines for Americans 2015–2020, which frequently is consumed at levels less than the Estimated Average Requirement of 12 mg/d; thus, hazelnuts should be considered as part of a healthy dietary pattern. This trial was registered at clinicaltrials.gov as NCT03485989.

Effect of nut consumption on semen quality and functionality in healthy men consuming a Western-style diet: a randomized controlled trial.

Salas-Huetos, A., R. Moraleda, S. Giardina, E. Anton, J. Blanco, J. Salas-Salvadó, M. Bulló, 2018. Effect of nut consumption on semen quality and functionality in healthy men consuming a Western-style diet: a randomized controlled trial. Am J Clin Nutr. 108:953–962.

Background: Human semen quality has declined in industrialized countries. Pollution, smoking, and the consumption of a Western style diet are all hypothesized as potential causes. Objective: We evaluated the effect of chronic consumption of nuts on changes in conventional semen parameters and the potential mechanisms implicated. Design: The FERTINUTS study was a 14-wk randomized, controlled, parallel trial. A total of 119 healthy men, aged 18–35 y, were allocated to 1 of 2 intervention groups: one group was fed the usual Western-style diet enriched with 60 g of a mixture of nuts/d (nut group), and the other was fed the usual Western-style diet avoiding nuts (control group). Semen and blood samples were collected at baseline and at the end of the intervention. Dietary information was recorded throughout the trial. Changes in conventional semen parameters (pH, volume, sperm count and concentration, motility, and morphology) were determined as primary outcomes. The effect of nut consumption on sperm DNA fragmentation (SDF), reactive oxygen species (ROS) production, chromosome anomalies (X, Y, and 18), total DNA methylation, and microRNA expression were measured in sperm samples as potential causes of the changes in the seminogram. Results: Compared with the control group, improvements in total sperm count (P = 0.002) and vitality (P = 0.003), total motility (P = 0.006), progressive motility (P = 0.036), and morphology of sperm (P = 0.008) were observed in the nut group. Participants in the nut group showed an increase in the consumption of total fat, monounsaturated fatty acids, polyunsaturated fatty acids, magnesium, vitamin E, α-linolenic acid, total omega-3 (n–3) and ω-3: ω-6 ratio intake during the intervention. Participants in the nut group showed a significant reduction in SDF (P < 0.001) and in the expression of hsa-miR-34b-3p (P = 0.036). No significant changes in ROS, sperm chromosome anomalies, or DNA methylation were observed between groups. Conclusions: The inclusion of nuts in a Western-style diet significantly improves the total sperm count and the vitality, motility, and morphology of the sperm. These findings could be partly explained by a reduction in the sperm DNA fragmentation. This trial was registered at ISRCTN as ISRCTN12857940.

Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts.

Estruch, R., E. Ros, J. Salas-Salvadó, M.-I. Covas, D. Corella, F. Arós, E. Gómez-Gracia, V. Ruiz-Gutiérrez, M. Fiol, J. Lapetra, R.M. Lamuela-Raventos, L. Serra-Majem, X. Pintó, J. Basora, M.A. Muñoz, J.V. Sorlí, J.A. Martínez, M. Fitó, A. Gea, M.A. Hernán, M.A. Martínez-González, PREDIMED Study Investigators, 2018. Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts. N Engl J Med.  378(25):e34. doi: 10.1056/NEJMoa1800389. Epub 2018 Jun 13.

Background: Observational cohort studies and a secondary prevention trial have shown inverse associations between adherence to the Mediterranean diet and cardiovascular risk. Methods: In a multicenter trial in Spain, we assigned 7447 participants (55 to 80 years of age, 57% women) who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was a major cardiovascular event (myocardial infarction, stroke, or death from cardiovascular causes). After a median follow-up of 4.8 years, the trial was stopped on the basis of a prespecified interim analysis. In 2013, we reported the results for the primary end point in the Journal. We subsequently identified protocol deviations, including enrollment of household members without randomization, assignment to a study group without randomization of some participants at 1 of 11 study sites, and apparent inconsistent use of randomization tables at another site. We have withdrawn our previously published report and now report revised effect estimates based on analyses that do not rely exclusively on the assumption that all the participants were randomly assigned. Results: A primary end-point event occurred in 288 participants; there were 96 events in the group assigned to a Mediterranean diet with extra-virgin olive oil (3.8%), 83 in the group assigned to a Mediterranean diet with nuts (3.4%), and 109 in the control group (4.4%). In the intention-to-treat analysis including all the participants and adjusting for baseline characteristics and propensity scores, the hazard ratio was 0.69 (95% confidence interval [CI], 0.53 to 0.91) for a Mediterranean diet with extra-virgin olive oil and 0.72 (95% CI, 0.54 to 0.95) for a Mediterranean diet with nuts, as compared with the control diet. Results were similar after the omission of 1588 participants whose study-group assignments were known or suspected to have departed from the protocol. Conclusions: In this study involving persons at high cardiovascular risk, the incidence of major cardiovascular events was lower among those assigned to a Mediterranean diet supplemented with extra-virgin olive oil or nuts than among those assigned to a reduced-fat diet. (Funded by Instituto de Salud Carlos III, Spanish Ministry of Health, and others; Current Controlled Trials number, ISRCTN35739639 .).