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Walnut-associated fatty acids inhibit LPS-induced activation of BV-2 microglia.

Carey, A.N., D.R. Fisher, D.F. Bielinski, D.S. Cahoon, B. Shukitt-Hale, 2020. Walnut-associated fatty acids inhibit LPS-induced activation of BV-2 microglia. Inflammation. 43(1):241-250.

Walnuts have high levels of the omega-3 fatty acid alpha-linolenic acid (C18:3n-3, ALA) and the omega-6 fatty acid linoleic acid (C18:2n-6, LA). Previous research has demonstrated that pre-treatment of BV-2 microglia with walnut extract inhibited lipopolysaccharide (LPS)-induced activation of microglia. As an extension of that study, the effects of walnut-associated fatty acids on BV-2 microglia were assessed. BV-2 murine microglia cells were treated with LA, ALA, or a combination of LA+ALA prior to or after exposure to LPS. Nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) were measured in cell-conditioned media. Cyclooxeganse-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression were assessed in BV-2 microglia. Both LA and ALA protected against LPS-induced increases in NO, iNOS, COX-2, and TNF-alpha when used before LPS exposure. When BV-2 microglia were treated with fatty acids after LPS, only COX-2 and TNF-alpha were significantly attenuated by the fatty acids. There was no synergism of LA+ALA, as the LA+ALA combination was no more effective than LA or ALA alone. Fatty acids, like those found in walnuts, may protect against production of cytotoxic intermediates and cell-signaling molecules from microglia and may prove beneficial for preventing age- or disease-related neurodegeneration.

Effects of supplementing the usual diet with a daily dose of walnuts for two years on metabolic syndrome and its components in an elderly cohort.

Al Abdrabalnabi, A., S. Rajaram, E. Bitok, K. Oda, W.L. Beeson, A. Kaur, M. Cofán, M. Serra-Mir, I. Roth, E. Ros, J. Sabaté, 2020. Effects of supplementing the usual diet with a daily dose of walnuts for two years on metabolic syndrome and its components in an elderly cohort. Nutrients. 11;12(2). pii: E451. doi: 10.3390/nu12020451.

Accumulating evidence links nut consumption with an improved risk of metabolic syndrome (MetS); however, long-term trials are lacking. We examined the effects of a daily dose of walnuts for two years on MetS in a large elderly cohort. A total of 698 healthy elderly participants were randomly assigned to either a walnut supplemented or a control diet. The participants in the walnut group were provided with packaged walnuts (1, 1.5, or 2 oz. or ~15% of energy) and asked to incorporate them into their daily habitual diet. The participants in the control group were asked to continue with their habitual diet and abstain from eating walnuts and other tree nuts. Intake of n-3 fatty acid supplements was not permitted in either group. Fasting blood chemistries, blood pressure, and anthropometric measurements were obtained at baseline and at the end of intervention. A total of 625 participants (67% women, mean age 69.1 y) completed this two-year study (90% retention rate). Triglycerides decreased in both walnut (-.94 mg/dl) and control (-0.96 mg/dl) groups, with no significant between-group differences. There was a non-significant decrease in systolic and diastolic blood pressure in the walnut group (-1.30 and -0.71 mm Hg, respectively) and no change in the control group. Fasting blood glucose decreased by ~1 point in both the walnut and control groups. There were no significant between-group differences in the development or reversion of MetS. In conclusion, supplementing the diet of older adults with a daily dose of walnuts had no effect on MetS status or any of its components, although the walnut group tended to have lower blood pressure.

Effect of tree nuts consumption on serum lipid profile in hyperlipidemic individuals: A systematic review.

Altamimi, M., S. Zidan, M. Badrasawi, 2020. Effect of tree nuts consumption on serum lipid profile in hyperlipidemic individuals: A systematic review. Nutrition and Metabolic Insights.  13: 1–10.

Many epidemiological studies have regularly connected nuts intake with decreased risk for coronary heart disease. The primary mechanism by which nuts protect against cardiovascular disease is through the improvement of lipid and apolipoprotein profile. Therefore, numerous dietary intervention studies investigated the impact of nut consumption on blood lipid levels. Many studies have shown that nut intake can enhance the lipid profile in a dose-response way among individuals with increased serum lipids. This systematic review examines the effectiveness of nuts on the lipid profile among patients with dyslipidemia from different age groups. A total of 29 interventional studies from 5 databases met the inclusion criteria. In all, 20 studies were randomized controlled clinical trials, whereas 9 were crossover-controlled clinical trials. Participants included in the studies were different in terms of age, sex and, serum lipid profile. The studies were inconsistent in the type of tree nuts, duration, dose, and the nut forms. All studies indicated changes in the lipid profile after the intervention particularly on the total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, total cholesterol/high-density lipoprotein. Interventional periods ranged from 3 weeks up to 12 months with doses ranged from 15 to 126gm. In conclusion, this review provides an evidence of favorable effect of nuts consumption of serum lipid profile.

Comparative effects of different types of tree nut consumption on blood lipids: a network meta-analysis of clinical trials.

Liu, K., S. Hui, B. Wang, K. Kaliannan, X. Guo, L. Liang, 2020. Comparative effects of different types of tree nut consumption on blood lipids: a network meta-analysis of clinical trials. Am J Clin Nutr. 111(1):219-227.

BackgroundRecent evidence has confirmed that nuts are one of the best food groups at reducing LDL cholesterol and total cholesterol (TC). However, the comparative effects of different types of nuts on blood lipids are unclear. Objectives: This network meta-analysis of randomized clinical trials aimed to assess the comparative effects of walnuts, pistachios, hazelnuts, cashews, and almonds on typical lipid profiles. Methods: We conducted literature searches to identify studies comparing ≥2 of the following diets-walnut-enriched, pistachio-enriched, hazelnut-enriched, cashew-enriched, almond-enriched, and control diets-for the management of triglycerides (TGs), LDL cholesterol, TC, and HDL cholesterol. Random-effects network meta-analyses, ranking analyses based on the surface under the cumulative ranking (SUCRA) curves, and sensitivity analyses according to the potential sources of heterogeneity across the included studies were performed for each outcome. Results: Thirty-four trials enrolling 1677 participants were included in this study. The pistachio-enriched diet was ranked best for TG (SUCRA: 85%), LDL cholesterol (SUCRA: 87%), and TC (SUCRA: 96%) reductions. For TG and TC reductions, the walnut-enriched diet was ranked as the second-best diet. Regarding LDL cholesterol reduction, the almond-enriched diet was ranked second best. The pistachio-enriched and walnut-enriched diets were more effective at lowering TG, LDL cholesterol, and TC compared with the control diet. Regarding TG and TC reductions, the pistachio-enriched diet was also more effective than the hazelnut-enriched diet. For TG reduction, the walnut-enriched diet was better than the hazelnut-enriched diet. However, these findings are limited by the low quality of evidence ratings. In addition, the quality of this network meta-analysis was limited by the small number and generally poor reporting of available studies. Conclusions: The pistachio-enriched and walnut-enriched diet could be better alternatives for lowering TGs, LDL cholesterol, and TC compared with other nut-enriched diets included in this study. The findings warrant further evaluation by more high-quality studies. This network meta-analysis was registered at www.crd.york.ac.uk/PROSPERO as CRD42019131128.

Edible nuts for memory.

Arslan, J., A.-U.-H. Gilani, H. Jamshed, S.F. Khan, M.A. Kamal, 2020. Edible nuts for memory. Curr Pharm Des. 26(37):4712-4720.

Nuts hold prime significance throughout the world as they offer multiple health benefits owing to their highly nutritious profile. A number of scientific studies have demonstrated their actions against inflammation, oxidative damage, the aging process, as well as dementia or memory loss. However, only walnuts, followed by almonds, hazelnuts and pistachios, have shown promising results in empirical studies for memory improvements. So, the current review focuses on presenting hypotheses regarding anti-dementia property of nine different nuts: almond, walnut, pistachio, Brazil nut, peanut, pecans, cashew, hazelnut, and chestnut. The nutritious profile of nuts contains essential fats (mostly mono- and poly-unsaturated fatty acids), proteins (source for arginine, lysine and tryptophan), vitamins (riboflavin, folate, and various tocopherols), fibers, minerals (calcium, sodium, magnesium, phosphorus and potassium) and trace elements (copper, zinc, and selenium). Interestingly, the constituents of natural products, nuts being an excellent example, work synergistically and/or in a side-effect neutralizing manner. These latter properties can make nuts an alternate therapy for humankind to fight against memory loss.

Clinical and molecular characterization of walnut and pecan allergy (NUT CRACKER Study).

Elizur, A., M.Y. Appel, L. Nachshon, M.B. Levy, N. Epstein-Rigbi, B. Pontoppidan, J. Lidholm, M.R. Goldberg, 2020. Clinical and molecular characterization of walnut and pecan allergy (NUT CRACKER Study). J Allergy Clin Immunol: In Practice. 8(1):157-165.e2

Background: Diagnostic methods for distinguishing walnut-allergic patients from walnut-sensitized but walnut-tolerant individuals are limited. Furthermore, characteristics of single walnut versus dual walnut-pecan allergy are lacking. Objective: To provide clinical and molecular characteristics of walnut- and pecan-allergic patients. Methods: A prospective cohort study of 76 walnut-sensitized patients was performed. Walnut skin prick test and serum measurements of specific IgE to walnut and its components were performed. Patients were challenged to walnut and pecan unless they regularly consumed walnut and pecan. Results: Of the 76 patients studied, 61 were diagnosed as walnut-allergic and 15 as walnut-tolerant. IgE levels greater than or equal to 0.35 kUA/L to Jug r 1 or 4 provided the best diagnostic method for identifying walnut-allergic patients (accuracy, 0.93). Of the 61 walnut-allergic patients, 49 were pecan-allergic whereas 12 were pecan-tolerant. None of the walnut-tolerant patients was allergic to pecan. Dual allergic patients had significantly lower walnut reaction dose (median, 100 mg vs 1230 mg; P < .001). IgE levels greater than or equal to 0.35 kUA/L to Jug r 4, low-molecular-weight vicilins, or high-molecular-weight vicilins best segregated dual walnut-pecan–allergic patients from single walnut-allergic patients. Inhibition studies demonstrated that walnut pretreatment completely blocked IgE binding to pecan, whereas in some patients, pecan incubation only partially blocked IgE binding to walnut. Conclusions: Walnut components are helpful in diagnosing walnut allergy and in identifying patients with pecan coallergy. Competitive ELISA indicates that pecan comprises a subset of the allergenic determinants of walnut.

The effect of green Mediterranean diet on cardiometabolic risk; a randomised controlled trial.

Tsaban, G., A. Yaskolka Meir, E. Rinott, H. Zelicha, A. Kaplan, A. Shalev, A. Katz, A. Rudich, A. Tirosh, I. Shelef, I. Youngster, S. Lebovitz,  N. Israeli, M. Shabat, D. Brikner, E. Pupkin, M. Stumvoll, J. Thiery, U. Ceglarek, J.T. Heiker, A. Körner, K. Landgraf, M. von Bergen, M. Blüher, M.J. Stampfer, I. Shai, 2020. The effect of green Mediterranean diet on cardiometabolic risk; a randomised controlled trial. Heart. heartjnl-2020-317802.  doi: 10.1136/heartjnl-2020-317802.

Background: A Mediterranean diet is favourable for cardiometabolic risk. Objective To examine the residual effect of a green Mediterranean diet, further enriched with green plant-based foods and lower meat intake, on cardiometabolic risk. Methods:  For the DIRECT-PLUS parallel, randomised clinical trial we assigned individuals with abdominal obesity/dyslipidaemia 1:1:1 into three diet groups: healthy dietary guidance (HDG), Mediterranean and green Mediterranean diet, all combined with physical activity. The Mediterranean diets were equally energy restricted and included 28 g/day walnuts. The green Mediterranean diet further included green tea (3–4 cups/day) and a Wolffia globosa (Mankai strain; 100 g/day frozen cubes) plant-based protein shake, which partially substituted animal protein. We examined the effect of the 6-month dietary induction weight loss phase on cardiometabolic state. Results Participants (n=294; age 51 years; body mass index 31.3 kg/m2; waist circumference 109.7 cm; 88% men; 10-year Framingham risk score 4.7%) had a 6-month retention rate of 98.3%. Both Mediterranean diets achieved similar weight loss ((green Mediterranean −6.2 kg; Mediterranean −5.4 kg) vs the HDG group −1.5 kg; p<0.001), but the green Mediterranean group had a greater reduction in waist circumference (−8.6 cm) than the Mediterranean (−6.8 cm; p=0.033) and HDG (−4.3 cm; p<0.001) groups. Stratification by gender showed that these differences were significant only among men. Within 6 months the green Mediterranean group achieved greater decrease in low-density lipoprotein cholesterol (LDL-C; green Mediterranean −6.1 mg/dL (−3.7%), −2.3 (-0.8%), HDG −0.2 mg/dL (+1.8%); p=0.012 between extreme groups), diastolic blood pressure (green Mediterranean −7.2 mm Hg, Mediterranean −5.2 mm Hg, HDG −3.4 mm Hg; p=0.005 between extreme groups), and homeostatic model assessment for insulin resistance (green Mediterranean −0.77, Mediterranean −0.46, HDG −0.27; p=0.020 between extreme groups). The LDL-C/high-density lipoprotein cholesterol (HDL-C) ratio decline was greater in the green Mediterranean group (−0.38) than in the Mediterranean (−0.21; p=0.021) and HDG (−0.14; p<0.001) groups. High-sensitivity C-reactive protein reduction was greater in the green Mediterranean group (−0.52 mg/L) than in the Mediterranean (−0.24 mg/L; p=0.023) and HDG (−0.15 mg/L; p=0.044) groups. The green Mediterranean group achieved a better improvement (−3.7% absolute risk reduction) in the 10-year Framingham Risk Score (Mediterranean−2.3%; p=0.073, HDG−1.4%; p<0.001). Conclusions: The green MED diet, supplemented with walnuts, green tea and Mankai and lower in meat/poultry, may amplify the beneficial cardiometabolic effects of Mediterranean diet.

Walnuts and vegetable oils containing oleic acid differentially affect the gut microbiota and associations with cardiovascular risk factors: Follow-up of a randomized, controlled, feeding trial in adults at risk for cardiovascular disease.

Tindall, A.M., C.J. McLimans, K.S. Petersen, P.M. Kris-Etherton, R. Lamendella, 2020.  Walnuts and vegetable oils containing oleic acid differentially affect the gut microbiota and associations with cardiovascular risk factors: Follow-up of a randomized, controlled, feeding trial in adults at risk for cardiovascular disease. J Nutr. 150(4):806-817.

Background: It is unclear whether the favorable effects of walnuts on the gut microbiota are attributable to the fatty acids, including α-linolenic acid (ALA), and/or the bioactive compounds and fiber. Objective: This study examined between-diet gut bacterial differences in individuals at increased cardiovascular risk following diets that replace SFAs with walnuts or vegetable oils. Methods: Forty-two adults at cardiovascular risk were included in a randomized, crossover, controlled-feeding trial that provided a 2-wk standard Western diet (SWD) run-in and three 6-wk isocaloric study diets: a diet containing whole walnuts (WD; 57-99 g/d walnuts; 2.7% ALA), a fatty acid-matched diet devoid of walnuts (walnut fatty acid-matched diet; WFMD; 2.6% ALA), and a diet replacing ALA with oleic acid without walnuts (oleic acid replaces ALA diet; ORAD; 0.4% ALA). Fecal samples were collected following the run-in and study diets to assess gut microbiota with 16S rRNA sequencing and Qiime2 for amplicon sequence variant picking. RESULTS: Subjects had elevated BMI (30 ± 1 kg/m2), blood pressure (121 ± 2/77 ± 1 mmHg), and LDL cholesterol (120 ± 5 mg/dL). Following the WD, Roseburia [relative abundance (RA) = 4.2%, linear discriminant analysis (LDA) = 4], Eubacterium eligensgroup (RA = 1.4%, LDA = 4), LachnospiraceaeUCG001 (RA = 1.2%, LDA = 3.2), Lachnospiraceae UCG004 (RA = 1.0%, LDA = 3), and Leuconostocaceae (RA = 0.03%, LDA = 2.8) were most abundant relative to taxa in the SWD (P ≤ 0.05 for all). The WD was also enriched in Gordonibacter relative to the WFMD. Roseburia (3.6%, LDA = 4) and Eubacterium eligensgroup (RA = 1.5%, LDA = 3.4) were abundant following the WFMD, and Clostridialesvadin BB60group (RA = 0.3%, LDA = 2) and gutmetagenome (RA = 0.2%, LDA = 2) were most abundant following the ORAD relative to the SWD (P ≤ 0.05 for all). Lachnospiraceae were inversely correlated with blood pressure and lipid/lipoprotein measurements following the WD. Conclusions: The results indicate similar enrichment of Roseburia following the WD and WFMD, which could be explained by the fatty acid composition. Gordonibacter enrichment and the inverse association between Lachnospiraceae and cardiovascular risk factors following the WD suggest that the gut microbiota may contribute to the health benefits of walnut consumption in adults at cardiovascular risk. This trial was registered at clinicaltrials.gov as NCT02210767.

Walnut consumption and cardiac phenotypes: The Coronary Artery Risk Development in Young Adults (CARDIA) study.

Steffen, L.M., S.Y. Yi, D. Duprez, X. Zhou, J.M. Shikany, D.R. Jacobs Jr., 2020. Walnut consumption and cardiac phenotypes: The Coronary Artery Risk Development in Young Adults (CARDIA) study. Nutr Metab Cardiovasc Dis. 31(1):95-101.

Background and Aims: Observational studies and clinical trials have shown cardiovascular benefits of nut consumption, including walnuts. However, the relations of walnut consumption with systolic and diastolic function, risk factors for heart failure, are unknown.  We examined the associations of walnut consumption with cardiac structure and function parameters in black and white adults enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Methods and Results: After exclusions, the study population included 3,341 participants. Dietary intake was assessed using the CARDIA Diet History questionnaire at baseline, year 7 and year 20 exams.  Cardiac structure and function were measured by echocardiography at year 25. Multivariable linear regression evaluated the associations of walnut consumption with blood pressure (BP), heart rate, and cardiac phenotypes, adjusting for age, sex, race, lifestyle habits, and clinical characteristics. We found the majority of walnut consumers compared to non-consumers were females, whites, and more highly educated, and had lower waist circumference, diastolic BP, and heart rate, and higher diet quality score. Even though cardiac structure and function measures were generally within normal ranges among participants, walnut consumers had significantly better values for diastolic function parameters A wave, E/A ratio, septal and lateral e’ than non-consumers. Further adjustment for body mass index and diabetes status did not materially change the significance between walnut consumer groups. Systolic function parameters did not differ by walnut group.  Conclusion: Compared to non-consumers, walnut consumption is associated with better diastolic dysfunction in young to middle-aged adults.

Wolffia globosa–Mankai Plant-Based Protein Contains Bioactive Vitamin B12 and Is Well Absorbed in Humans.

Sela, I.,  A.Y. Meir, A. Brandis, R. Krajmalnik-Brown, L. Zeibich, D. Chang, B. Dirks, G. Tsaban, A. Kaplan, E. Rinott, H. Zelicha, 2020. Wolffia globosa–Mankai Plant-Based Protein Contains Bioactive Vitamin B12 and Is Well Absorbed in Humans. Nutrients. 12, 3067. doi: 10.3390/nu12103067

Abstract: Background: Rare plants that contain corrinoid compounds mostly comprise cobalamin analogues, which may compete with cobalamin (vitamin B12 (B12)) metabolism. We examined the presence of B12 in a cultivated strain of an aquatic plant: Wolffia globosa (Mankai), and predicted functional pathways using gut-bioreactor, and the effects of long-term Mankai consumption as a partial meat substitute, on serum B12 concentrations. Methods: We used microbiological assay, liquid-chromatography/electrospray-ionization-tandem-mass-spectrometry (LC-MS/MS), and anoxic bioreactors for the B12 experiments. We explored the effect of a green Mediterranean/low-meat diet, containing 100 g of frozen Mankai shake/day, on serum B12 levels during the 18-month DIRECT-PLUS (ID:NCT03020186) weight-loss trial, compared with control and Mediterranean diet groups. Results: The B12 content of Mankai was consistent at different seasons (p = 0.76). Several cobalamin congeners (Hydroxocobalamin(OH-B12); 5-deoxyadenosylcobalamin(Ado-B12); methylcobalamin(Me-B12); cyanocobalamin(CN-B12)) were identified in Mankai extracts, whereas no pseudo B12 was detected. A higher abundance of 16S-rRNA gene amplicon sequences associated with a genome containing a KEGG ortholog involved in microbial B12 metabolism were observed, compared with control bioreactors that lacked Mankai. Following the DIRECT-PLUS intervention (n = 294 participants; retention-rate = 89%; baseline B12 = 420.5 ± 187.8 pg/mL), serum B12 increased by 5.2% in control, 9.9% in Mediterranean, and 15.4% in Mankai-containing green Mediterranean/low-meat diets (p = 0.025 between extreme groups). Conclusions: Mankai plant contains bioactive B12 compounds and could serve as a B12 plant-based food source.