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Research Nut: Walnuts

Dietary walnut as food factor to rescue from NSAID-induced gastrointestinal mucosal damages.

An, J.M., E.H., Kim, H. Le, H.J. Lee, K.B. Hahm, 2020. Dietary walnut as food factor to rescue from NSAID-induced gastrointestinal mucosal damages. Arch Biochem Biophys. 689:108466. doi:10.1016/j.abb.2020.108466.

Nuclear factor erythroid-derived 2-like 2 (Nrf-2) is transcription factor implicated in the antioxidant response element-mediated induction of endogenous antioxidant enzyme such as heme oxygenase-1 (HO-1), glutamatecysteine ligase, and NAD(P)H quinone dehydrogenase 1, among which HO-1 is an enzyme catalyzing the degradation of heme.producing biliverdin, ferrous iron, and carbon monoxide. In the stomach, as much as regulating gastric acid secretions, well-coordinated establishment of defense system stands for maintaining gastric integrity. In previous study, author et al. for the first time discovered HO-1 induction was critical in affording faithful gastric defense against various irritants including Helicobacter pylori infection, stress, alcohol, nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, and toxic bile acids. In this review article, we can add the novel evidence that dietary walnut intake can be reliable way to rescue from NSAIDs-induced gastrointestinal damages via the induction of HO-1 transcribed with Nrf-2 through specific inactivation of Keap-1. From molecular exploration to translational animal model of indomethacin-induced gastrointestinal damages, significant induction of HO-1 contributed to rescuing from damages. In addition to HO-1 induction action relevant to walnut, we added the description the general actions of walnut extracts or dietary intake of walnut regarding cytoprotection and why we have focused on to NSAID damages.

Association of nut intake with risk factors, cardiovascular disease, and mortality in 16 countries from 5 continents: analysis from the Prospective Urban and Rural Epidemiology (PURE) study.

de Souza, R.J., M. Dehghan, A. Mente, S.I. Bangdiwala, S.H. Ahmed, K.F. Alhabib, Y. Altuntas, A. Basiak-Rasała, G-R Dagenais, R. Diaz, L.I. Amma, R. Kelishadi, R. Khatib, S.A. Lear, P. Lopez-Jaramillo, V. Mohan, P. Poirier, S. Rangarajan, A. Rosengren, R. Ismail, S. Swaminathan, E. Wentzel-Viljoen, K. Yeates, R. Yusuf, K.K. Teo, S.S. Anand, S. Yusuf, for the PURE study investigators, 2020. Association of nut intake with risk factors, cardiovascular disease, and mortality in 16 countries from 5 continents: analysis from the Prospective Urban and Rural Epidemiology (PURE) study. The American Journal of Clinical Nutrition, nqaa108, https://doi.org/10.1093/ajcn/nqaa108

Background: The association of nuts with cardiovascular disease and deaths has been investigated mostly in Europe, the USA, and East Asia, with few data available from other regions of the world or from low- and middle-income countries. Objective: To assess the association of nuts with mortality and cardiovascular disease (CVD). Methods: The Prospective Urban Rural Epidemiology study is a large multinational prospective cohort study of adults aged 35–70 y from 16 low-, middle-, and high-income countries on 5 continents. Nut intake (tree nuts and ground nuts) was measured at the baseline visit, using country-specific validated FFQs. The primary outcome was a composite of mortality or major cardiovascular event [nonfatal myocardial infarction (MI), stroke, or heart failure]. Results: We followed 124,329 participants (age = 50.7 y, SD = 10.2; 41.5% male) for a median of 9.5 y. We recorded 10,928 composite events [deaths (n = 8,662) or major cardiovascular events (n = 5,979)]. Higher nut intake (>120 g per wk compared with <30 g per mo) was associated with a lower risk of the primary composite outcome of mortality or major cardiovascular event [multivariate HR (mvHR): 0.88; 95% CI: 0.80, 0.96; P-trend = 0.0048]. Significant reductions in total (mvHR: 0.77; 95% CI: 0.69, 0.87; P-trend <0.0001), cardiovascular (mvHR: 0.72; 95% CI: 0.56, 0.92; P-trend = 0.048), and noncardiovascular mortality (mvHR: 0.82; 95% CI: 0.70, 0.96; P-trend = 0.0046) with a trend to reduced cancer mortality (mvHR: 0.81; 95% CI: 0.65, 1.00; P-trend = 0.081) were observed. No significant associations of nuts were seen with major CVD (mvHR: 0.91; 95% CI: 0.81, 1.02; P-trend = 0.14), stroke (mvHR: 0.98; 95% CI: 0.84, 1.14; P-trend = 0.76), or MI (mvHR: 0.86; 95% CI: 0.72, 1.04; P-trend = 0.29). Conclusions: Higher nut intake was associated with lower mortality risk from both cardiovascular and noncardiovascular causes in low-, middle-, and high-income countries.

The beneficial effects of nutraceuticals and natural products on small dense LDL levels, LDL particle number and LDL particle size: a clinical review.

Talebi, S., M. Bagherniya, S.L. Atkin, G. Askari, H.M. Orafai, A. Sahebkar, 2020. The beneficial effects of nutraceuticals and natural products on small dense LDL levels, LDL particle number and LDL particle size: a clinical review. Lipids in Health and Disease. 19:66
https://doi.org/10.1186/s12944-020-01250-6.

Cardiovascular diseases (CVDs) are globally the major causes of morbidity and mortality. Evidence shows that smaller and denser low-dense lipoprotein (sdLDL) particles are independent atherogenic risk factors for CVD due to their greater susceptibility to oxidation, and permeability in the endothelium of arterial walls. sdLDL levels are an independent risk factor and of more predictive value than total LDL-C for the assessment of coronary artery disease and metabolic syndrome. Functional food ingredients have attracted significant attention for the management of dyslipidemia and subsequently increase cardio-metabolic health. However, to date there is no study that has investigated the effect of these bioactive natural compounds on sdLDL levels. Therefore, the aim of the present review is to summarize the evidence accrued on the effect of special dietary ingredients such as omega-3 polyunsaturated fatty acids, nutraceuticals and herbal medicines on the levels of sdLDL, LDL particle number, and LDL particle size. Based on the results of the existing clinical trials this review suggests that natural products such as medicinal plants, nutraceuticals and omega-3 fatty acids can be used as adjunct or complementary therapeutic agents to reduce sdLDL levels, LDL particle numbers or increase LDL particle size and subsequently may prevent and treat CVD, with the advantage that these natural agents are generally safe, accessible, and inexpensive.

Tree nut snack consumption is associated with better diet quality and CVD risk in the UK adult population: National Diet and Nutrition Survey (NDNS) 2008-2014.

Dikariyanto, V., S.E. Berry, G.K. Pot, L. Francis, L. Smith, W.L. Hall, 2020. Tree nut snack consumption is associated with better diet quality and CVD risk in the UK adult population: National Diet and Nutrition Survey (NDNS) 2008-2014. Public Health Nutr. doi: 10.1017/S1368980019003914. [Epub ahead of print]

Objectives: To examine associations of tree nut snack (TNS) consumption with diet quality and cardiovascular disease (CVD) risk in UK adults from National Diet and Nutrition Survey (NDNS) 2008-2014. Design: Cross-sectional analysis using data from 4-d food diaries, blood samples and physical measurements for CVD risk markers. To estimate diet quality, modified Mediterranean Diet Score (MDS) and modified Healthy Diet Score (HDS) were applied. Associations of TNS consumption with diet quality and markers of CVD risk were investigated using survey-adjusted multivariable linear regression adjusted for sex, age, ethnicity, socio-economic and smoking status, region of residency and total energy and alcohol intake. Setting: UK free-living population. Subjects: 4738 adults (≥19 years). Results: TNS consumers had higher modified MDS and HDS relative to non-consumers. TNS consumers also had lower BMI, WC, SBP and DBP and higher HDL compared to non-consumers, although a dose-related fully adjusted significant association between increasing nut intake (g per 4184 kJ/1000 kcal energy intake) and lower marker of CVD risk was only observed for SBP. TNS consumption was also associated with higher intake of total fat, mono-, n-3 and n-6 polyunsaturated fatty acids, fibre, vitamin A, thiamin, folate, vitamin C, vitamin E, potassium, magnesium, phosphorus, selenium and iron; and lower intake of saturated fatty acids, trans fatty acids, total carbohydrate, starch, free sugar, sodium and chloride. Conclusions: TNS consumers report better dietary quality and consumption was associated with lower CVD risk factors. Encouraging replacement of less healthy snacks with TNS should be encouraged as part of general dietary guidelines.

Replacing saturated fats with unsaturated fats from walnuts or vegetable oils lowers atherogenic lipoprotein classes without increasing lipoprotein(a).

Tindall, A.M., P.M. Kris-Etherton, K.S. Petersen, 2020. Replacing saturated fats with unsaturated fats from walnuts or vegetable oils lowers atherogenic lipoprotein classes without increasing lipoprotein(a). J Nutr. pii: nxz313. doi: 10.1093/jn/nxz313. [Epub ahead of print]

Bachground: Walnuts have established lipid-/lipoprotein-lowering properties; however, their effect on lipoprotein subclasses has not been investigated. Furthermore, the mechanisms by which walnuts improve lipid/lipoprotein concentrations are incompletely understood. Objectives: We aimed to examine, as exploratory outcomes of this trial, the effect of replacing SFAs with unsaturated fats from walnuts or vegetable oils on lipoprotein subclasses, cholesterol efflux, and proprotein convertase subtilisin/kexin type 9 (PCSK9). Methods: A randomized, crossover, controlled-feeding study was conducted in individuals at risk of cardiovascular disease (CVD) (n = 34; 62% men; mean ± SD age 44 ± 10 y; BMI: 30.1 ± 4.9 kg/m2). After a 2-wk run-in diet (12% SFAs, 7% PUFAs, 12% MUFAs), subjects consumed the following diets, in randomized order, for 6 wk: 1) walnut diet (WD) [57-99 g/d walnuts, 7% SFAs, 16% PUFAs [2.7% α-linolenic acid (ALA)], 9% MUFAs]; 2) walnut fatty acid-matched diet [7% SFAs, 16% PUFAs (2.6% ALA), 9% MUFAs]; and 3) oleic acid replaces ALA diet (ORAD) [7% SFAs, 14% PUFAs (0.4% ALA); 12% MUFAs] (all percentages listed are of total kilocalories ). Serum collected after the run-in (baseline) and each diet period was analyzed for lipoprotein classes and subclasses (vertical auto profile), cholesterol efflux, and PCSK9. Linear mixed models were used for data analysis. Results: Compared with the ORAD, total cholesterol (mean ± SEM -8.9± 2.3 mg/dL; -5.1%; P < 0.001), non-HDL cholesterol (-7.4 ± 2.0 mg/dL; -5.4%; P = 0.001), and LDL cholesterol (-6.9 ± 1.9 mg/dL; -6.5%; P = 0.001) were lower after the WD; no other pairwise differences existed. There were no between-diet differences for HDL-cholesterol or LDL-cholesterol subclasses. Lipoprotein(a) [Lp(a)], cholesterol efflux, and PCSK9 were unchanged after the diets. Conclusions: In individuals at risk of CVD, replacement of SFAs with unsaturated fats from walnuts or vegetable oils improved lipid/lipoprotein classes, including LDL-cholesterol, non-HDL cholesterol, and total cholesterol, without an increase in Lp(a). These improvements were not explained by changes in cholesterol efflux capacity or PCSK9.

Angiopoietin-1 protects 3T3-L1 preadipocytes from saturated fatty acid-induced cell death.

Son, Y., J.M. Cox, J.L. Stevenson, J.A. Cooper, C.M. Paton, 2020. Angiopoietin-1 protects 3T3-L1 preadipocytes from saturated fatty acid-induced cell death. Nutr Res. 76:20-28.

Cross talk between endothelial cells and adipocytes is vital to adipocyte functions, but little is known about the mechanisms or factors controlling the process. Angiogenesis is a critical component linking the endothelium to healthy adipogenesis, yet it is not known if or how it is involved in adipocyte physiology. Therefore, the purpose of this study was to determine the effect of angiopoietin-1 (Ang-1) and -2 (Ang-2) as well as their receptor, Tie-2, on adipocyte physiology. 3T3-L1 pre- and mature adipocytes were found to express Ang-1, Ang-2, and Tie-2, which decrease upon polyunsaturated fatty acid treatment. Furthermore, 3T3-L1 cells treated with recombinant Ang-1 or Ang-2 increased expression of the antiapoptotic gene Bcl-x and decreased expression of the proapoptotic gene Casp-8. Next, preadipocytes were treated with saturated fatty acids (SFAs) to induce cell stress. SFA-mediated splicing of X-box-binding protein-1 was reduced by co-treatment with Ang-1, and cell viability was improved in the presence of SFAs + Ang-1. Taken together, these results indicate that Ang-1 may protect preadipocytes from SFA-induced apoptosis and endoplasmic reticulum stress.

Effect of a 2-year diet intervention with walnuts on cognitive decline. The Walnuts and Healthy Aging (WAHA) study: a randomized controlled trial.

Sala-Vila, A., C. Valls-Pedret, S. Rajaram, N. Coll-Padrós, M. Cofán, M. Serra-Mir, A.M. Pérez-Heras, I. Roth, T.M. Freitas-Simoes, M. Doménech, C. Calvo, A. López-Illamola, E. Bitok, N.K. Buxton, L. Huey, A. Arechiga, K. Oda, G.J. Lee, D. Corella, L. Vaqué-Alcázar, R. Sala-Llonch, D. Bartrés-Faz, J. Sabaté, E. Ro, 2020. Effect of a 2-year diet intervention with walnuts on cognitive decline. The Walnuts and Healthy Aging (WAHA) study: a randomized controlled trial. Am J Clin Nutr. pii: nqz328. doi: 10.1093/ajcn/nqz328. [Epub ahead of print]

Background: Walnut consumption counteracts oxidative stress and inflammation, 2 drivers of cognitive decline. Clinical data concerning effects on cognition are lacking. Objectives: The Walnuts and Healthy Aging study is a 2-center (Barcelona, Spain; Loma Linda, CA) randomized controlled trial examining the cognitive effects of a 2-y walnut intervention in cognitively healthy elders. Methods: We randomly allocated 708 free-living elders (63-79 y, 68% women) to a diet enriched with walnuts at ∼15% energy (30-60 g/d) or a control diet (abstention from walnuts). We administered a comprehensive neurocognitive test battery at baseline and 2 y. Change in the global cognition composite was the primary outcome. We performed repeated structural and functional brain MRI in 108 Barcelona participants. Results: A total of 636 participants completed the intervention. Besides differences in nutrient intake, participants from Barcelona smoked more, were less educated, and had lower baseline neuropsychological test scores than those from Loma Linda. Walnuts were well tolerated and compliance was good. Modified intention-to-treat analyses (n = 657) uncovered no between-group differences in the global cognitive composite, with mean changes of -0.072 (95% CI: -0.100, -0.043) in the walnut diet group and -0.086 (95% CI: -0.115, -0.057) in the control diet group (P = 0.491). Post hoc analyses revealed significant differences in the Barcelona cohort, with unadjusted changes of -0.037 (95% CI: -0.077, 0.002) in the walnut group and -0.097 (95% CI: -0.137, -0.057) in controls (P = 0.040). Results of brain fMRI in a subset of Barcelona participants indicated greater functional network recruitment in a working memory task in controls. Conclusions: Walnut supplementation for 2 y had no effect on cognition in healthy elders. However, brain fMRI and post hoc analyses by site suggest that walnuts might delay cognitive decline in subgroups at higher risk. These encouraging but inconclusive results warrant further investigation, particularly targeting disadvantaged populations, in whom greatest benefit could be expected.

Changes in nut consumption and subsequent cardiovascular disease risk among US men and women: 3 large prospective cohort studies.

Liu, X., M. Guasch-Ferré, J.P. Drouin-Chartier, D.K. Tobias, S.N. Bhupathiraju, K.M. Rexrode, W.C. Willett, Q. Sun, Y. Li, 2020. Changes in nut consumption and subsequent cardiovascular disease risk among US men and women: 3 large prospective cohort studies.
J Am Heart Assoc. 9(7):e013877. doi: 10.1161/JAHA.119.013877. Epub 2020 Apr 1.

Background: we aim to evaluate the association of within-individual changes in consumption of total and specific types of nuts and the subsequent risk of incident cardiovascular disease (CVD) in US men and women. Methods and Results: We included 34 103 men from the HPFS (Health Professionals Follow-Up Study) (1986-2012), 77 815 women from the NHS (Nurses’ Health Study) (1986-2012), and 80 737 women from the NHS II (1991-2013). We assessed nut consumption every 4 years using validated food frequency questionnaires. We used multivariable Cox proportional hazards regression models to examine the association between 4-year changes in nut consumption and risk of confirmed CVD end points in the subsequent 4 years. Per 0.5 serving/day increase in total nut consumption was associated with lower risk of CVD (relative risk [RR], 0.92; 95% CI, 0.86-0.98), coronary heart disease (RR, 0.94; 95% CI, 0.89-0.99), and stroke (RR, 0.89; 95% CI, 0.83-0.95). Compared with individuals who remained nonconsumers in a 4-year interval, those who had higher consumption of total nuts (≥0.5 servings/day) had a lower risk of CVD (RR, 0.75; 95% CI, 0.67-0.84), coronary heart disease (RR, 0.80; 95% CI, 0.69-0.93), and stroke (RR, 0.68; 95% CI, 0.57-0.82) in next 4 years. Individuals who decreased nut consumption by ≥0.50 servings/day had a higher risk of developing CVD (RR, 1.14; 95% CI, 0.99-1.32), coronary heart disease (RR, 1.06; 95% CI, 0.88-1.28), and stroke (RR, 1.28; 95% CI, 1.02-1.60) when compared with those who maintained their nut consumption. Conclusions: Increasing total consumption of nuts and intake of individual types of nuts (eg, walnuts, other tree nuts, and peanuts) was associated with a subsequent lower risk of CVD. These data support the role of nut intake in the primary prevention of CVD.

Consumption of Nuts at Midlife and Healthy Aging in Women.

Freitas-Simoes, T.M., M. Wagner, C. Samieri, A. Sala-Vila, F. Grodstein, 2020. Consumption of Nuts at Midlife and Healthy Aging in Women. J Aging Res. https://doi.org/10.1155/2020/5651737.

Background: Nut consumption may reduce age-related diseases and lead to better health and well-being in aging. Many conditions of aging develop over decades, and thus earlier lifestyle factors may particularly influence later health. Methods: In 1998 and 2002, we administered food frequency questionnaires to assess nut consumption (peanuts, walnuts, and other nuts and peanut butter) in women in the Nurses’ Health Study in their 50 s/early 60 s. In 2012, those who survived beyond 65 years with no chronic diseases, no reported memory impairment, no physical disabilities, and intact mental health were considered “healthy agers.” We used multivariable logistic regression to estimate odds ratios for healthy versus usual aging, controlled for sociodemographic, behavioral, dietary, and other potential confounding factors. Results: Of 33,931 participants at midlife, 16% became “healthy agers.” After age adjustment, we observed a significant association between total nut consumption at midlife and higher odds of healthy aging, with strongest associations observed excluding peanut butter (odds ratio (OR) = 1.46, 95% confidence interval (CI) 1.32–1.62, ≥3 servings/week versus none). Findings were attenuated after further control for covariates, including overall diet quality (OR = 1.14, 95% CI 1.02–1.28, P trend = 0.05). For nut types, we found statistically significantly higher odds of healthy aging across peanuts, walnuts, and other nuts after age adjustment. After full control for confounders, only walnut consumption remained associated with healthy aging (P trend = 0.0001); for example, the OR was 1.20 (95% CI 1.00–1.44) for ≥2 servings/week versus none. Conclusions: Women consuming nuts at midlife have a greater likelihood of overall health and well-being at older ages. Nut consumption may represent a simple intervention to explore and promote healthy aging.

Colon cancer prevention with walnuts: a longitudinal study in mice from the perspective of a gut enterotype-like cluster.

Chen Y., M. Nakanishi, E.J. Bautista, V. Qendro, E. Sodergren, D.W. Rosenberg, G.M. Weinstock, 2020. Colon cancer prevention with walnuts: a longitudinal study in mice from the perspective of a gut enterotype-like cluster. Cancer Prev Res (Phila). 13(1):15-24.

There is limited understanding of how walnut consumption inhibits the development of colorectal cancer. A possible mechanism may involve alterations to the gut microbiota. In this study, the effects of walnut on gut microbiota were tested in a mouse tumor bioassay using the colonotropic carcinogen, azoxymethane (AOM) added to the total Western diet (TWD). 16S rRNA pyrosequencing identified three enterotype-like clusters (E1, E2, and E3) in this murine model. E1, E2, and E3 are associated with AOM exposure, walnut consumption, and TWD diet, respectively. E2 and E3 showed distinct taxonomic and functional characteristics, while E1 represented an intermediate state. At the family level, E1 and E3 were both enriched with Bacteroidaceae, but driven by two different operational taxonomic units (OTU; OTU-2 for E1, OTU-4 for E3). E2 was overrepresented with Porphyromonadaceae and Lachnospiraceae, with OTU-3 (family Porphyromonadaceae) as the “driver” OTU for this cluster. Functionally, E3 is overrepresented with genes of glycan biosynthesis and metabolism, xenobiotic metabolism, and lipid metabolism. E2 is enriched with genes associated with cell motility, replication and repair, and amino acid metabolism. Longitudinally, E2 represents the gut microbial status of early life in these mice. In comparison with E1 and E3, E2 is associated with a moderate lower tumor burden (P = 0.12). Our results suggest that walnuts may reduce the risk of colorectal cancer within a Western diet by altering the gut microbiota. Our findings provide further evidence that colorectal cancer risk is potentially modifiable by diet via alterations to the microbiota.