Hardman, W.E., 2014. Diet components can suppress inflammation and reduce cancer risk. Nutr Res Pract. 8(3):233-40.
Epidemiology studies indicate that diet or specific dietary components can reduce the risk for cancer, cardiovascular disease and diabetes. An underlying cause of these diseases is chronic inflammation. Dietary components that are beneficial against disease seem to have multiple mechanisms of action and many also have a common mechanism of reducing inflammation, often via the NFκB pathway. Thus, a plant based diet can contain many components that reduce inflammation and can reduce the risk for developing all three of these chronic diseases. We summarize dietary components that have been shown to reduce cancer risk and two studies that show that dietary walnut can reduce cancer growth and development. Part of the mechanism for the anticancer benefit of walnut was by suppressing the activation of NFκB. In this brief review, we focus on reduction of cancer risk by dietary components and the relationship to suppression of inflammation. However, it should be remembered that most dietary components have multiple beneficial mechanisms of action that can be additive and that suppression of chronic inflammation should reduce the risk for all three chronic diseases.
Grace, M.H., Warlick, C.W., Neff, S.A., Lila, M.A. 2014. Efficient preparative isolation and identification of walnut bioactive components using high-speed counter-current chromatography and LC-ESI-IT-TOF-MS. Food Chem. 158:229-38.
Preparative isolation of complex mixtures of compounds from walnut polar extracts was established by a combination of high-speed counter-current chromatography (HSCCC) and electrospray ionization-ion trap-time of flight mass spectrometry (ESI-IT-TOF-MS). Compounds were isolated after a solvent optimization selection based on solute distribution in a biphasic solvent system. Isolation was achieved through one or two successive HSCCC runs, and final purification on Sephadex LH-20. Isolated compounds included ellagitannins, gallic acid, dicarboxylic acid glucosides, hydrojuglone glucoside, catechin, procyanidin B2, and megasterone glucosides. Praecoxin D was isolated for the first time from walnut, while praecoxin A methyl ester (5) and glansreginin A n-butyl ester (14) are newly identified compounds. The purity and identity of isolated compounds were confirmed by NMR and HPLC-ESI-MS/MS. These results provided a foundation for in depth characterization of walnut compounds and offered an efficient strategy for isolation of potentially health-relevant phytochemicals from walnuts.
Fisher, D.R., Poulose, S.M., Bielinski, D.F., Shukitt-Hale, B., 2014. Serum metabolites from walnut-fed aged rats attenuate stress-induced neurotoxicity in BV-2 microglial cells. Nutr Neurosci. Aug 25. [Epub ahead of print]
The shift in equilibrium towards excess reactive oxygen or nitrogen species production from innate antioxidant defenses in brain is a critical factor in the declining neural function and cognitive deficit accompanying age. Previous studies from our laboratory have reported that walnuts, rich in polyphenols, antioxidants, and omega fatty acids such as alpha-linolenic acid and linoleic acid, improve the age-associated declines in cognition and neural function in rats. Possible mechanisms of action of these effects include enhancing protective signaling, altering membrane microstructures, decreasing inflammation, and preventing accumulation of polyubiquitinated protein aggregates in critical regions of the brain. In the current study, we investigated whether the serum collected from aged animals fed with walnut diets (0, 6, and 9%, w/w) would enhance protection on stressed BV-2 microglia in vitro. In the growth medium, fetal bovine serum was substituted with the serum collected from 22-month-old rats fed per protocol for 12 weeks. Walnut diet serum (6 and 9%) significantly attenuated lipopolysaccharide-induced nitrite release compared to untreated control cells and those treated with serum from rats fed 0% walnut diets. The results also indicated a significant reduction in pro-inflammatory tumor necrosis factor-alpha, cyclooxygenase-2, and inducible nitric oxide synthase. These results suggest antioxidant and anti-inflammatory protection or enhancement of membrane-associated functions in brain cells by walnut serum metabolites.
Li, G., Y. Zhu, Y. Zhang, J. Lang, Y. Chen, W. Ling, 2013. Estimated daily flavonoid and stilbene intake from fruits, vegetables, and nuts and associations with lipid profiles in Chinese adults. J Acad Nutr Diet. 113:786-794.
Background: The scientific evidence for the association of daily flavonoid and stilbene intakes with cardiovascular risk factors in Chinese adults has not been reported previously. Objective: The aim of the study was to assess daily flavonoid and stilbene intakes and evaluate these compounds’ association with cardiovascular risk factors such as serum lipids and carotid intima–media thickness in Chinese adults. Design: A total of 1,393 subjects participated in this cross-sectional study from July 2008 to January 2010 in China. Dietary flavonoid and stilbene intakes as well as overall dietary intakes from foods and beverages were assessed with a quantitative food frequency questionnaire. Anthropometric measurements and cardiovascular risk factors including serum lipids, uric acid, and carotid intima–media thickness were examined. The relationship between flavonoids and stilbene intakes and these cardiovascular risk factors was examined using either partial correlation coefficients or analysis of covariance. Results: The richest sources of flavonoids and stilbenes were the fruit group including apple, plum, pear, and peach, followed by the vegetable group containing lotus root and taro. The daily intake of total flavonoids, anthocyanidins, flavonols, flavones, isoflavones, and stilbene were 165.6 mg/day, 27.6 mg/day, 123.7 mg/day, 10.7 mg/day, 3.7 mg/day, and 0.3 mg/day, respectively. Higher daily consumption of anthocyanidins was associated with elevated serum high-density lipoprotein cholesterol (HDL-C) concentrations (P trend=0.001), and higher total flavonoid and flavonol intakes were associated with lower serum triglycerides (TG) concentrations (P trend=0.020 and P trend=0.035, respectively) and TG/HDL-C ratios (P trend=0.040 and P trend=0.045, respectively) in female subjects. These significant relationships were not found in male subjects. Conclusions: The daily intakes of flavonoid and stilbene were estimated in the present study, and higher dietary flavonoid intake was associated with improving lipid profile in Chinese women. The results indicate that dietary flavonoids may have beneficial effect on preventing cardiovascular diseases.
Kornsteiner-Krenn, M., K.-H. Wagner, I. Elmadfa, 2013. Phytosterol content and fatty acid pattern of ten different nut types. International Journal for Vitamin and Nutrition Research. 83:263-270.
Ten different nut kinds (almonds, Brazil nuts, cashews, hazelnuts, macadamias, peanuts, pecans, pine nuts, pistachios, and walnuts) were evaluated for their total oil and phytosterol content as well as their fatty acid composition. The total oil content was the predominant component; mean values oscillated between 45.2 % (cashews) and 74.7 % (macadamias). Mean total phytosterol content ranged from 71.7 mg (Brazil nuts) to 271.9 mg (pistachios) per 100 g oil. ß-sitosterol was the major sterol (mean >71.7 mg/100 g oil) followed by minor contents of campesterol, ergosterol, and stigmasterol. Almonds, cashews, hazelnuts, macadamias, and pistachios were high in monounsaturated fatty acids (MUFA; > 55 %). MUFA- and polyunsaturated fatty acid (PUFA)-rich nuts were peanuts and pecans, whereas Brazil nuts, pine nuts, and walnuts had the highest PUFA content (> 50 %); the high unsaturated/saturated fatty acid ratio ranged from 4.5 to 11.8. However, the fatty acid pattern of every nut is unique.
Mandalari, G., C. Bisignano, A. Filocamo, S. Chessa, M. Saró, G. Torre, R.M. Faulks, P. Dugo, 2013. Bioaccessibility of pistachio polyphenols, xanthophylls, and tocopherols during simulated human digestion. Nutrition. 29:338–344.
Objective: The bioaccessibility of bioactives from pistachios has not been previously evaluated. In the present study we quantified the release of polyphenols, xanthophylls (lutein), and tocopherols from pistachios (raw pistachios, roasted salted pistachios, and muffins made with raw pistachios) during simulated human digestion. Methods: A dynamic gastric model of digestion that provides a realistic and predictive simulation of the physical and chemical processing and accurately mimics the residence time and the luminal environment within the human stomach was used for the digestion studies. Results: More than 90% of the polyphenols were released in the gastric compartment, with virtually total release in the duodenal phase. No significant differences were observed between raw shelled and roasted salted pistachio. The presence of a food matrix (muffin) decreased the bioaccessibility of protocatechuic acid (78%) and luteolin (36%). Almost 100% bioaccessibility of lutein and tocopherols was found after duodenal digestion, with no difference among the three samples. Conclusion: The rapid release of the assayed bioactives in the stomach maximizes the potential for absorption in the duodenum and contributes to the beneficial relation between pistachio consumption and health-related outcomes.
Valls-Pedret, C., R.M. Lamuela-Raventos, R.M., A. Medina-Remon, M. Quintana, D. Corella, X. Pinto, M.A. Martınez-Gonzalez, R. Estruch, E. Ros, 2012. Polyphenol-rich foods in the Mediterranean diet are associated with better cognitive function in elderly subjects at high cardiovascular risk. Journal of Alzheimer’s Disease. 29:773–782.
Brain oxidative processes play a major role in age-related cognitive decline, thus consumption of antioxidant-rich foods might help preserve cognition. Our aim was to assess whether consumption of antioxidant-rich foods in the Mediterranean diet relates to cognitive function in the elderly. In asymptomatic subjects at high cardiovascular risk (n = 447; 52% women; age 55–80 y) enrolled in the PREDIMED study, a primary prevention dietary-intervention trial, we assessed food intake and cardiovascular risk profile, determined apolipoprotein E genotype, and used neuropsychological tests to evaluate cognitive function. We also measured urinary polyphenols as an objective biomarker of intake. Associations between energy-adjusted food consumption, urinary polyphenols, and cognitive scores were assessed by multiple linear regression models adjusted for potential confounders. Consumption of some foods was independently related to better cognitive function. The specific associations [regression coefficients (95% confidence intervals)] were: total olive oil with immediate verbal memory [0.755 (0.151–1.358)]; virgin olive oil and coffee with delayed verbal memory [0.163 (0.010–0.316) and 0.294 (0.055–0.534), respectively];walnuts with working memory [1.191 (0.061–2.322)]; and wine with Mini-Mental State Examination scores [0.252 (0.006–0.496)]. Urinary polyphenols were associated with better scores in immediate verbal memory [1.208 (0.236–2.180)]. Increased consumption of antioxidant-rich foods in general and of polyphenols in particular is associated with better cognitive performance in elderly subjects at high cardiovascular risk. The results reinforce the notion that Mediterranean diet components might counteract age-related cognitive decline.
Li, N., X. Jia, C.-Y.O. Chen, J.B. Blumberg, Y. Song, W. Zhang, X. Zhang, G. Ma, J. Chen, 2007. Almond consumption reduces oxidative DNA damage and lipid peroxidation in male smokers. J. Nutr. 137:2717 -2722.
Smoking increases the risk of several chronic diseases associated with elevated oxidative stress status. Almonds are a good source of antioxidant nutrients and may diminish smoking-related biomarkers of oxidative stress. This study investigated whether almond consumption decreases biomarkers of oxidative stress in young male Chinese smokers. The Chinese CDC researchers conducted a randomized, crossover clinical trial with 60 healthy male soldiers (18-25 y) who were habitual smokers (5-20 cigarettes/d) and supplemented their diet with 84 g almonds or 120 g pork (to control for calories) daily for 4 wk with a 4-wk washout period between treatment periods. In addition, 30 healthy nonsmoking men were provided the same daily serving of pork as reference comparison. Blood and urine were collected and assessed for biomarkers of oxidative stress. Baseline values of urinary 8-hydroxy-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) and peripheral lymphocyte DNA strand breaks were significantly higher by 185, 64, and 97% in smokers than nonsmokers, whereas activities of plasma superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase were significantly lower by 15, 10, and 9%, respectively. After the almond intervention, serum a-tocopherol, SOD, and GPX increased significantly in smokers by 10, 35, and 16%, respectively and 8-OHdG, MDA, and DNA strand breaks decreased significantly by 28, 34, and 23%. No significant changes were found in smokers or nonsmokers after pork treatment. In smokers, after almond supplementation, the concentration of 8-OHdG remained significantly greater than in nonsmokers by 98%. These results suggest almond intake can enhance antioxidant defenses and diminish biomarkers of oxidative stress in smokers.
Tulipani, S., M. Urpi-Sarda, R. Garcıá -Villalba, M. Rabassa, P. López-Uriarte, M. Bulló, O. Jáuregui, F. Tomás-Barberán, J. Salas-Salvado,́ J. Carlos Espıń, C. Andrés-Lacueva, 2012. Urolithins are the main urinary microbial-derived phenolic metabolites discriminating a moderate consumption of nuts in free-living subjects with diagnosed metabolic syndrome. J. Agric. Food Chem. doi.org/10.1021/jf301509w.
Walnuts (Juglans regia L.), hazelnuts (Corylus avellana L.), and almonds (Prunus dulcis Mill.) are rich sources of ellagitannins and proanthocyanidins. Gut microbiota plays a crucial role in modulating the bioavailability of these high molecular weight polyphenols. However, to date there are no studies evaluating the capacity to produce nut phenolic metabolites in subjects with metabolic syndrome (MetS), a pathology associated with an altered gut bacterial diversity. This study applied a LC-MS targeted approach to analyze the urinary excretion of nut phenolic metabolites in MetS subjects following 12 weeks of nut consumption, compared to sex- and age-matched individuals given a nut-free control diet. Metabolites were targeted in both hydrolyzed and nonhydrolyzed urine by LC-PDA-QqQ-MS/MS analysis, and identification of metabolites lacking available standards was confirmed by LC-ESI-ITD-FT-MS. Ellagitannin-derived urolithins A and B significantly increased after the nutenriched-diet, urolithins C and D were also detected, and a complex combination of urolithin-conjugated forms was observed in nonhydrolyzed urine, confirming an extensive phase II metabolism after absorption. In contrast, no significant increases in proanthocyanidin microbial metabolites were observed in urine following nut consumption. Because the intestinal microbiota of the subjects in this study could catabolize ellagitannins into a wide range of urolithins, further research is strongly warranted on the in vivo potential of these microbial metabolites in reducing cardiometabolic risk.
Gentile, C., M. Allegra, F. Angileri, A.M. Pintaudi, M.A. Livrea, L. Tesoriere, 2012. Polymeric proanthocyanidins from Sicilian pistachio (Pistacia vera L.) nut extract inhibit lipopolysaccharide-induced inflammatory response in RAW 264.7 cells. Eur J Nutr. 51(3):353-63.
Background: Positive effects of pistachio nut consumption on plasma inflammatory biomarkers have been described; however, little is known about molecular events associated with these effects. Purpose: We studied the anti-inflammatory activity of a hydrophilic extract from Sicilian Pistacia L. (HPE) in a macrophage model and investigated bioactive components relevant to the observed effects. Methods: HPE oligomer/polymer proanthocyanidin fractions were isolated by adsorbance chromatography, and components quantified as anthocyanidins after acidic hydrolysis. Isoflavones were measured by gradient elution HPLC analysis. RAW 264.7 murine macrophages were pre-incubated with either HPE (1- to 20-mg fresh nut equivalents) or its isolated components for 1 h, then washed before stimulating with lipopolysaccharide (LPS) for 24 h. Cell viability and parameters associated with Nuclear Factor-κB (NF-κB) activation were assayed according to established methods including ELISA, Western blot, or cytofluorimetric analysis. Results: HPE suppressed nitric oxide (NO) and tumor necrosis factor-α (TNF-α) production and inducible NO-synthase levels dose dependently, whereas inhibited prostaglandin E2 (PGE2) release and decreased cyclooxygenase-2 content, the lower the HPE amount the higher the effect. Cytotoxic effects were not observed. HPE also caused a dose-dependent decrease in intracellular reactive oxygen species and interfered with the NF-κB activation. Polymeric proanthocyanidins, but not isoflavones, at a concentration comparable with their content in HPE, inhibited NO, PGE2, and TNF-α formation, as well as activation of IκB-α. Oligomeric proanthocyanidins showed only minor effects. Conclusions: Our results provide molecular evidence of anti-inflammatory activity of pistachio nut and indicate polymeric proanthocyanidins as the bioactive components. The mechanism may involve the redox-sensitive transcription factor NF-κB. Potential effects associated with pistachio nut consumption are discussed in terms of the proanthocyanidin bioavailability.
