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The beneficial effects of tree nuts on the aging brain.

Carey, A.N., S.M. Poulose, B. Shukitt-Hale, 2012. The beneficial effects of tree nuts on the aging brain. Nutrition and Aging. 1:55–67.

Dietary patterns may play an important role in protecting the brain from the cellular and cognitive dysfunction associated with the aging process and neurodegenerative diseases. Tree nuts are showing promise as possible dietary interventions for age-related brain dysfunction. Tree nuts are an important source of essential nutrients, like vitamin E, folate, and fiber. Tree nuts also contain a variety of components, such as phytochemicals like flavonoids, proanthocyanidins, and phenolic acids, as well as monounsaturated and omega-3 and omega-6 polyunsaturated fatty acids that have the potential to combat age-related brain dysfunction. Evidence is accumulating that suggests that tree nuts and their bioactive constituents have the potential to reduce oxidative stress and inflammation, as indicated by decreased lipid peroxidation in vivo and reduced production of the free radical nitric oxide and the pro-inflammatory cytokine tumor necrosis factor-alpha in vitro. Also, tree nut consumption might have the ability to mitigate some of the cognitive decline associated with aging. Here we review the current knowledge of how the consumption of nuts may improve brain health, specifically focusing on walnuts, almonds, pistachios, and pecans.

Dietary walnuts inhibit colorectal cancer growth in mice by suppressing angiogenesis.

Nagel, J.M., M. Brinkoetter, F. Magkos, X. Liu, J.P. Chamberland, S. Shah, J. Zhou, G. Blackburn, C.S. Mantzoros, 2012. Dietary walnuts inhibit colorectal cancer growth in mice by suppressing angiogenesis. Nutrition. 28(1):67-75.

OBJECTIVE: Animal studies have demonstrated that dietary supplementation with flaxseed oil inhibits colorectal cancer growth. Recent data indicate that walnuts have strong antiproliferative properties against colon cancer cells in vitro but no previous study has assessed the effects of walnuts in vivo or performed a joint evaluation of flaxseed oil and walnuts. The aim of the present study was to examine the effect of dietary walnuts on colorectal cancer in vivo and to comparatively evaluate their efficacy in relation to flaxseed oil. METHODS: HT-29 human colon cancer cells were injected in 6-wk-old female nude mice. After a 1-wk acclimation period, mice (n = 48) were randomized to diets containing ∼19% of total energy from walnuts, flaxseed oil, or corn oil (control) and were subsequently studied for 25 d. RESULTS: Tumor growth rate was significantly slower in walnut-fed and flaxseed-fed mice compared with corn oil-fed animals (P < 0.05) by 27% and 43%, respectively. Accordingly, final tumor weight was reduced by 33% and 44%, respectively (P < 0.05 versus control); the differences between walnut and flaxseed diets did not reach significance. We found no differences among groups in metabolic and hormonal profile, serum antioxidant capacity, or inflammation (P > 0.05). However, walnuts and flaxseed oil significantly reduced serum expression levels of angiogenesis factors, including vascular endothelial growth factor (by 30% and 80%, respectively), and approximately doubled total necrotic areas despite smaller tumor sizes (P < 0.05 versus control). Dietary walnuts significantly decreased angiogenesis (CD34 staining; P = 0.017 versus control), whereas this effect did not reach significance in the flaxseed oil group (P = 0.454 versus control). CONCLUSION: We conclude that walnuts in the diet inhibit colorectal cancer growth by suppressing angiogenesis. Further studies are needed to confirm our findings in humans and explore underlying mechanisms.

Out-of-hand nut consumption is associated with improved nutrient intake and health risk markers in US children and adults: National Health and Nutrition Examination Survey 1999-2004.

O’Neil, C.E., D.R. Keast, T.A. Nicklas, V.L. Fulgoni, 2012. Out-of-hand nut consumption is associated with improved nutrient intake and health risk markers in US children and adults: National Health and Nutrition Examination Survey 1999-2004. Nutrition Research. 32:185-194.

The purpose of this study was to determine the association of out-of-hand nut (OOHN) consumption with nutrient intake, diet quality, and the prevalence of risk factors for cardiovascular disease and metabolic syndrome. Data from 24-hour recalls from individuals aged 2+ years (n = 24,385) participating in the 1999-2004 National Health and Nutrition Examination Survey were used. The population was divided into children aged 2 to 11, 12 to 18, and adults 19+ years, and each group was dichotomized into OOHN consumers and nonconsumers. Out-of-hand nut consumers were defined as those individuals consuming ¼ oz of nuts or more per d. Means, standard errors, and covariate-adjusted analyses of variance were determined using appropriate sample weights. Diet quality was determined using the Healthy Eating Index-2005. Significance was set at P < .05. The percent of OOHN consumers increased with age: 2.1% ± 0.3%, 2.6% ± 0.3%, 6.5% ± 0.5%, and 9.6% ± 0.5% those aged 2 to 11, 12 to 18, 19 to 50, and 51+ years, respectively. The 2 latter groups were combined into a single group of consumers aged 19+ years for subsequent analyses. Consumers of OOHN from all age groups had higher intakes of energy, monounsaturated and polyunsaturated fatty acids, dietary fiber, copper, and magnesium and lower intakes of carbohydrates, cholesterol, and sodium than did nonconsumers. Diet quality was higher in OOHN consumers of all age groups. In children aged 2 to 11 years, consumers had a higher prevalence of overweight/obesity. In those aged 12 to 18 years, weight and percent overweight were lower in consumers. Adult consumers had higher high-density lipoprotein cholesterol, red blood cell folate, and serum folate levels and lower insulin, glycohemoglobin, and C-reactive protein levels than did nonconsumers. Adult consumers also had a 19% decreased risk of hypertension and a 21% decreased risk of low high-density lipoprotein cholesterol levels. Data suggested that OOHN consumption was associated with improved nutrient intake, diet quality, and, in adults, a lower prevalence of 2 risk factors for metabolic syndrome. Consumption of OOHN, as part of a healthy diet, should be encouraged by health professionals.

The ability of walnut extract and fatty acids to protect against the deleterious effects of oxidative stress and inflammation in hippocampal cells.

Carey, A.N., D.R. Fisher, J.A. Joseph, B. Shukitt-Hale, 2012. The ability of walnut extract and fatty acids to protect against the deleterious effects of oxidative stress and inflammation in hippocampal cells. Nutr. Neurosci. doi: 10.1179/1476830512Y.0000000023.

Previous research from our lab has demonstrated that dietary walnut supplementation protects against agerelated cognitive declines in rats; however, the cellular mechanisms by which walnuts and polyunsaturated fatty acids (PUFAs) may affect neuronal health and functioning in aging are undetermined. Objectives: We assessed if pretreatment of primary hippocampal neurons with walnut extract or PUFAs would protect cells against dopamine- and lipopolysaccharide-mediated cell death and calcium dysregulation. Methods: Rat primary hippocampal neurons were pretreated with varying concentrations of walnut extract, linoleic acid, alpha-linolenic acid, eicosapentaenoic acid, or docosahexaenoic acid prior to exposure to either dopamine or lipopolysaccharide. Viability was assessed using the Live/Dead Cellular Viability/Cytotoxicity Kit. Also, the ability of the cells to return to baseline calcium levels after depolarization was measured with fluorescent imaging. Results: Results indicated that walnut extract, alpha-linolenic acid, and docosahexaenoic acid provided significant protection against cell death and calcium dysregulation; the effects were pretreatment concentration dependent and stressor dependent. Linoleic acid and eicosapentaenoic acid were not as effective at protecting hippocampal cells from these insults. Discussion: Walnut extract and omega-3 fatty acids may protect against age-related cellular dysfunction, but not all PUFAs are equivalent in their beneficial effects.

Nut consumption is associated with decreased health risk factors for cardiovascular disease and metabolic syndrome in U.S. adults: NHANES 1999–2004.

O’Neil, C.E., D.R. Keast, T.A. Nicklas, V.L. Fulgoni, 2011. Nut consumption is associated with decreased health risk factors for cardiovascular disease and metabolic syndrome in U.S. adults: NHANES 1999–2004. Journal of the American College of Nutrition. 30(6):502–510.

Background: Few recent epidemiologic studies have assessed the effect that nut consumption (including tree nuts and peanuts) has on health risks, including metabolic syndrome (MetS). Objective: This study compared the health risk for cardiovascular disease, type 2 diabetes, and MetS of nut consumers with that of nonconsumers. Design: Adults 19+ years (n = 13,292) participating in the 1999–2004 National Health and Nutrition Examination Survey were used. Intake from 24-hour recalls was used to determine intake. Nut/tree nut consumers consumed ≥¼ ounce per day. Covariate-adjusted means, standard errors, and prevalence rates were determined for the nut consumption groups. Results: The prevalence of nut consumers was 18.6% ± 0.7% and 21.0% ± 0.9% in those 19–50 years and 51 years and older, respectively. Nut consumption was associated with a decreased body mass index (27.7 kg/m2 ± 0.2 vs 28.1 ± 0.1 kg/m2, p<0.05), waist circumference (95.6 ± 0.4 cm vs 96.4 ± 0.3 cm, p < 0.05), and systolic blood pressure (121.9 ± 0.4 mmHg vs 123.20 ± 0.3 mmHg, p < 0.01) compared with nonconsumers. Tree nut consumers also had a lower weight (78.8 ± 0.7 kg vs 80.7 ± 0.3 kg, p < 0.05). Nut consumers had a lower percentage of two risk factors for MetS: hypertension (31.5% ± 1.0% vs 34.2% ± 0.8%, p < 0.05) and low high density lipoprotein-cholesterol (HDL-C) (29.6% ± 1.0% vs 34.8% ± 0.8%, p < 0.01). Tree nut consumers had a lower prevalence of four risk factors for MetS: abdominal obesity (43.6% ± 1.6% vs 49.5% ± 0.8%, p < 0.05), hypertension (31.4% ± 1.2% vs 33.9% ± 0.8%, p < 0.05), low HDL-C (27.9% ± 1.7% vs 34.5% ± 0.8%, p < 0.01), high fasting glucose (11.4% ± 1.4% vs 15.0% ± 0.7%, p < 0.05), and a lower prevalence of MetS (21.2% ± 2.1% vs 26.6% ± 0.7%, p < 0.05). Conclusion: Nut/tree nut consumption was associated with a decreased prevalence of selected risk factors for cardiovascular disease, type 2 diabetes, and MetS.

Adherence to the mediterranean diet in patients with type 2 diabetes mellitus and HbA1c Level.

Díez-Espino, J., P. Buil-Cosiales, M. Serrano-Martínez, E. Toledo, J. Salas-Salvadó, M.Á. Martínez-González, 2011. Adherence to the mediterranean diet in patients with type 2 diabetes mellitus and HbA1c Level. Ann Nutr Metab. 58:74–78.

Rationale and Objective: The Mediterranean diet (MeDiet) has beneficial effects on cardiovascular risk factors. We analyzed the association between adherence of a MeDiet in patients with type 2 diabetes mellitus (T2DM) and levels of HbA1c. Patients and Methods: This was a cross-sectional study in individuals with T2DM participating in the PREDIMED trial at the centre of Pamplona. Information on diet was collected with a validated 14 point scale of adherence to the MeDiet and blood samples were obtained to assess HbA1c levels. Results: We studied 383 participants with T2DM, 53.4% women (mean age 69 ± 6 years). HbA1c data were available in 262 cases (mean 6.9 ± 1.5%). Although there was a potential inverse non-significant association between adherence to MeDiet and HbA1c levels after adjusting for age and sex, it was not statistically significant. Multivariate analysis additionally adjusted for physical activity, smoking, time of evolution of the T2DM, body mass index and insulin treatment found similar findings (OR = 0.69, 95% CI 0.17–2.83). Conclusions: Although we found not enough evidence to support that a MeDiet is associated with lower levels of HbA1c in patients with T2DM, our results suggested an inverse trend. Future studies with larger sample size are necessary.

The effect of the Mediterranean diet on plasma brain-derived neurotrophic factor (BDNF) levels: The PREDIMED-NAVARRA randomized trial. Nutritional Neuroscience.

Sánchez-Villegas, A., C. Galbete, M.Á. Martinez-González, J.A. Martinez, C. Razquin, J. Salas-Salvadó, R. Estruch, P. Buil-Cosiales, A. Martí, 2011. The effect of the Mediterranean diet on plasma brain-derived neurotrophic factor (BDNF) levels: The PREDIMED-NAVARRA randomized trial. Nutritional Neuroscience.  14(5):195-201.

Objectives: There are no human studies assessing the effect of nutritional interventions on plasma brainderived neurotrophic factor (BDNF) concentrations. The aim of this study was to assess the role of a nutritional intervention based on a Mediterranean diet (MeDiet) on plasma BDNF levels. Methods: PREvención con Dieta MEDiterránea (PREDIMED) is a randomized clinical trial designed to assess the effect of a Mediterranean diet (MeDiet) on the primary prevention of cardiovascular disease. For this analysis, 243 participants from the Navarra centre were randomly selected. Participants were assigned to one of three dietary interventions: control (low-fat) diet, MeDiet supplemented with virgin olive oil (MeDiet + VOO), or MeDiet supplemented with nuts (MeDiet + Nuts). Plasma BDNF levels were measured after 3 years of intervention. Multivariate-adjusted means of BDNF for each intervention were compared using generalized linear models. Logistic regression models were fit to assess the association between the dietary intervention and the likelihood to have low plasma BDNF values (<13 μg/ml, 10th percentile). Analyses were repeated after stratifying the sample according to baseline prevalence of different diseases. Results: Higher but non-significant plasma BDNF levels were observed for participants assigned to both MeDiets. Participants assigned to MeDiet + Nuts showed a significant lower risk (odds ratios (OR) = 0.22; 95% confidence intervals (CI) = 0.05–0.90) of low plasma BDNF values (<13 μg/ml) as compared to the control group. Among participants with prevalent depression at baseline, significantly higher BDNF levels were found for those assigned to the MeDiet+ Nuts. Discussion: Adherence to a MeDiet was associated to an improvement in plasma BDNF concentrations in individuals with depression.

Metabolomics unveils urinary changes in subjects with metabolic syndrome following 12-week nut consumption.

Tulipani, S., R. Llorach, O. Jáuregui, P. López-Uriarte, M. Garcia-Aloy, M. Bullo, J. Salas-Salvadó,  C. Andrés-Lacueva, 2011. Metabolomics unveils urinary changes in subjects with metabolic syndrome following 12-week nut consumption. J. Proteome Res. 10:5047–5058.

Through an HPLC-Q-TOF-MS-driven nontargeted metabolomics approach, we aimed to discriminate changes in the urinary metabolome of subjects with metabolic syndrome (MetS), following 12 weeks of mixed nuts consumption (30 g/day), compared to sex and age-matched individuals given a control diet. The urinary metabolome corresponding to the nut-enriched diet clearly clustered in a distinct group, and the multivariate data analysis discriminated relevant mass features in this separation. Metabolites corresponding to the discriminating ions (MS features) were then subjected to multiple tandem mass spectrometry experiments using LC-ITD-FT-MS, to confirm their putative identification. The metabolomics approach revealed 20 potential markers of nut intake, including fatty acid conjugated metabolites, phase II and microbial-derived phenolic metabolites, and serotonin metabolites. An increased excretion of serotonin metabolites was associated for the first time with nut consumption. Additionally, the detection of urinary markers of gut microbial and phase II metabolism of nut polyphenols confirmed the understanding of their bioavailability and bioactivity as a priority area of research in the determination of the health effects derived from nut consumption. The results confirmed how a non-targeted metabolomics strategy may help to access unexplored metabolic pathways impacted by diet, thereby raising prospects for new intervention targets.

Mediterranean nuts: origins, ancient medicinal benefits and symbolism.

Casas-Agustench, P., A. Salas-Huetos, J. Salas-Salvado´, 2011. Mediterranean nuts: origins, ancient medicinal benefits and symbolism. Public Health Nutrition: 14(12A): 2296–2301.

Objective: To consider historical aspects of nuts in relation to origin and distribution, attributed medicinal benefits, symbolism, legends and superstitions. Design: Review of historical aspects of nuts. Setting: Mediterranean region. Subjects: The varieties reviewed include almonds, walnuts, hazelnuts, pine nuts and pistachios. Results and conclusions: Like other foods, nuts have a wide variety of cultural connections to the areas where they grow and to the people who live there or eat them. History, symbolism and legends reveal the ancient tradition of nuts and how they are related to the lives of our ancestors. Archaeological excavations in eastern Turkey have uncovered the existence of a non-migratory society whose economy centered on harvesting nuts. This shows that nuts have been a staple in the human diet since the beginnings of history. Moreover, since ancient times nuts have been used for their medicinal properties. They also play a role in many old legends and traditions.

Tree nut phytochemicals: composition, antioxidant capacity, bioactivity, impact factors. A systematic review of almonds, Brazils, cashews, hazelnuts, macadamias, pecans, pine nuts, pistachios and walnuts.

Bolling, B.W., C.-Y. O. Chen, D.L. McKay, J.B. Blumberg, 2011. Tree nut phytochemicals: composition, antioxidant capacity, bioactivity, impact factors. A systematic review of almonds, Brazils, cashews, hazelnuts, macadamias, pecans, pine nuts, pistachios and walnuts. Nutrition Research Reviews 24:244–275

Tree nuts contain an array of phytochemicals including carotenoids, phenolic acids, phytosterols and polyphenolic compounds such as flavonoids, proanthocyanidins (PAC) and stilbenes, all of which are included in nutrient databases, as well as phytates, sphingolipids, alkylphenols and lignans, which are not. The phytochemical content of tree nuts can vary considerably by nut type, genotype, pre- and post-harvest conditions, as well as storage conditions. Genotype affects phenolic acids, flavonoids, stilbenes and phytosterols, but data are lacking for many other phytochemical classes. During the roasting process, tree nut isoflavones, flavanols and flavonols were found to be more resistant to heat than the anthocyanins, PAC and trans-resveratrol. The choice of solvents used for extracting polyphenols and phytosterols significantly affects their quantification, and studies validating these methods for tree nut phytochemicals are lacking. The phytochemicals found in tree nuts have been associated with antioxidant, anti-inflammatory, anti-proliferative, antiviral, chemopreventive and hypocholesterolaemic actions, all of which are known to affect the initiation and progression of several pathogenic processes. While tree nut phytochemicals are bioaccessible and bioavailable in humans, the number of intervention trials conducted to date is limited. The objectives of the present review are to summarize tree nut: (1) phytochemicals; (2) phytochemical content included in nutrient databases and current publications; (3) phytochemicals affected by pre- and post-harvest conditions and analytical methodology; and (4) bioactivity and health benefits in humans.