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Research Area: Cardiovascular Health

Walnut consumption and health outcomes with public health relevance-a systematic review of cohort studies and randomized controlled trials published from 2017 to present. 

Lockyer, S., A.E. de la Hunty, S. Steenson, A. Spiro, S.A. Stanner, 2022. Walnut consumption and health outcomes with public health relevance-a systematic review of cohort studies and randomized controlled trials published from 2017 to present. Nutr. Rev. 81(1):26–54. https://doi.org/10.1093/nutrit/nuac040

Context: Considering the accumulation of recent studies investigating the health effects of walnut consumption, both including and beyond cardiovascular health effects, a systematic review of this literature to investigate the strength of the evidence is warranted. Objective: To investigate associations between walnut consumption and outcomes with public health relevance (specifically all-cause mortality, type 2 diabetes, CVD, metabolic syndrome, obesity, cancer, neurological and mental health, musculoskeletal, gastrointestinal, and maternal disorders) and the effect on associated disease risk markers, reported in studies published from 2017 to present. Data sources: MEDLINE, FSTA, CENTRAL, and Scopus were searched from 1 January 2017 to 5 May 2021. Data extraction: Human studies (cohort studies and RCTs) ≥3 weeks in duration comparing consumption of walnuts (whole, pieces, or 100% butter) to a control and measuring associations with relevant public health outcomes and disease risk markers were assessed. Key study characteristics were extracted independently by 2 investigators using a standardized table. The quality of the studies was assessed using the Cochrane Risk-of-Bias tool 2.0 and the Newcastle-Ottawa Scale. Data analysis: Only 1 RCT was considered to be at low risk of bias for any of its outcomes. The cohort studies were considered to be of moderate or high quality. The results were synthesized using vote counting, based on the direction of effect. Thirty-three articles, 23 describing RCTs (walnut dose ∼10-99 g/day, 1,948 subjects) and 10 describing cohort studies (∼675,928 subjects), were included. Vote counting could be performed for the blood lipids, cardiovascular function, inflammation- and hemostatic-related factors, markers of glucose metabolism, and body weight and composition outcome groupings. The results are presented in effect direction plots. With respect to blood lipids, results from 8/8 RCTs favoured walnuts, in accordance with associations with a reduced risk of CVD suggested by cohort studies; results from 6/6 RCTs favoured control with respect to body weight and composition, although most of these effects were small. This was contrary to cohort study results suggesting small benefits of walnut consumption on body weight. There was no overall consistent direction of effect for cardiovascular function, markers of glucose metabolism, or inflammation- and hemostatic-related factors. Conclusions: Evidence published since 2017 is consistent with previous research suggesting that walnut consumption improves lipid profiles and is associated with reduced CVD risk. Evidence is accumulating in other areas, such as cognitive health, although more research is needed to draw firm conclusions.

Circulating linoleic acid at the time of myocardial infarction and risk of primary ventricular fibrillation.

Oliveras, T., I. Lázaro, F. Rueda, G. Cediel, D.L. Bhatt, M. Fitó, F. Madrid-Gambin, O.J. Pozo, W.S. Harris, C. García-García, A. Sala-Vila, A. Bayés-Genís, 2022. Circulating linoleic acid at the time of myocardial infarction and risk of primary ventricular fibrillation. Sci. Rep. 12(1):4377. https://doi.org/10.1038/s41598-022-08453-0

Primary ventricular fibrillation (PVF) is a major driver of cardiac arrest in the acute phase of ST-segment elevation myocardial infarction (STEMI). Enrichment of cardiomyocyte plasma membranes with dietary polyunsaturated fatty acids (PUFA) reduces vulnerability to PVF experimentally, but clinical data are scarce. PUFA status in serum phospholipids is a valid surrogate biomarker of PUFA status in cardiomyocytes within a wide range of dietary PUFA. In this nested case-control study (n = 58 cases of STEMI-driven PVF, n = 116 control non-PVF STEMI patients matched for age, sex, smoking status, dyslipidemia, diabetes mellitus and hypertension) we determined fatty acids in serum phospholipids by gas-chromatography, and assessed differences between cases and controls, applying the Benjamini-Hochberg procedure on nominal P-values to control the false discovery rate (FDR). Significant differences between cases and controls were restricted to linoleic acid (LA), with PVF patients showing a lower level (nominal P = 0.002; FDR-corrected P = 0.027). In a conditional logistic regression model, each one standard deviation increase in the proportion of LA was related to a 42% lower prevalence of PVF (odds ratio = 0.58; 95% confidence interval, 0.37, 0.90; P = 0.02). The association lasted after the inclusion of confounders. Thus, regular consumption of LA-rich foods (nuts, oils from seeds) may protect against ischemia-driven malignant arrhythmias.

Key Area: Heart Health

Impact of α-linolenic acid, the vegetable ω-3 fatty acid, on cardiovascular disease and cognition.

Sala-Vila, A., J. Fleming, P. Kris-Etherton, E. Ros, 2022. Impact of α-linolenic acid, the vegetable ω-3 fatty acid, on cardiovascular disease and cognition. Adv. Nutr. 13(5):1584–1602. https://doi.org/10.1093/advances/nmac016

Given the evidence of the health benefits of plant-based diets and long-chain n-3 fatty acids, there is keen interest in better understanding the role of alpha-linolenic acid (ALA), a plant-derived n-3 fatty acid, on cardiometabolic diseases and cognition. There is increasing evidence for ALA largely based on its major food sources (i.e., walnuts and flaxseed); however, this lags behind our understanding of long-chain n-3 fatty acids. Meta-analyses of observational studies have shown that increasing dietary ALA is associated with a 10% lower risk of total cardiovascular disease and a 20% reduced risk of fatal coronary heart disease. Three randomized controlled trials (Alpha Omega trial, Prevención con Dieta Mediterránea [PREDIMED] trial, and Lyon Diet Heart Study) all showed benefits of diets high in ALA on cardiovascular-related outcomes, but the Alpha Omega trial, designed to specifically evaluate ALA effects, only showed a trend for benefit. Randomized controlled trials have shown that dietary ALA reduced total cholesterol, low-density-lipoprotein cholesterol, triglycerides, and blood pressure, and epidemiological studies and some trials also have shown an anti-inflammatory effect of ALA; which collectively account for, in part, the cardiovascular benefits of ALA. A meta-analysis reported a trend toward diabetes risk reduction with both dietary and biomarker ALA. For metabolic syndrome and obesity, the evidence for ALA benefits is inconclusive. The role of ALA in cognition is in the early stages but shows promising evidence of counteracting cognitive impairment. Much has been learned about the health benefits of ALA and with additional research we will be better positioned to make strong evidence-based dietary recommendations for the reduction of many chronic diseases.

Association of nut consumption with CVD risk factors in young to middle-aged adults: The Coronary Artery Risk Development in Young Adults (CARDIA) study. 

Yi, S.Y., L.M. Steffen, X. Zhou, J.M. Shikany, D.R., Jr. Jacobs, 2022. Association of nut consumption with CVD risk factors in young to middle-aged adults: The Coronary Artery Risk Development in Young Adults (CARDIA) study. Nutr Metab Cardiovasc Dis. 32(10):2321–2329. https://doi.org/10.1016/j.numecd.2022.07.013

Background and Aims: Few studies have examined long-term associations of walnut, other nut, and no nut consumption with cardiovascular disease (CVD) risk factors. Results from prospective studies with long-term follow-up can provide further evidence for dietary guideline messaging to consume nuts. Therefore, we examined the associations of walnut, other nut, and no nut consumption with diet quality and CVD risk factors over 30 years of follow-up. Methods and Results: Data were analyzed from 3,092 young adults enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Dietary intake, including walnuts and other nuts, was assessed 3 times over 20 years. CVD risk factors were measured at multiple exams. General linear regression evaluated the associations of walnut, other nut, and no nut consumption with CVD risk factors over 30 years (Y30) of follow-up. The 20-year cumulative mean intake of walnuts (0.74 oz/d), other nuts (1.6 oz/d), or no nut consumption was differentially associated with HEI-2015 and CVD risk factors by Y30. Generally, walnut consumers had significantly higher HEI-2015, lower body mass index, waist circumference, blood pressure, and triglyceride concentration, and gained less weight since baseline than other nut consumers (p ≤0.05 for all). Further, walnut consumers had lower fasting blood glucose than no nut consumers (p ≤0.05). Conclusion: Study findings that walnut and other nut consumption was associated with better CVD risk factors and diet quality aligns with the 2020-2025 U.S. Dietary Guidelines for Americans recommendation to consume nuts, such as walnuts, within the context of a healthy diet.

Cumulative average nut consumption in relation to lower incidence of hypertension: a prospective cohort study of 10,347 adults.

Jung, S., H.W. Woo, J. Shin, Y.-M. Kim, M.-H. Shin, S.-B. Koh, H.C. Kim, M.K. Kim, 2022. Cumulative average nut consumption in relation to lower incidence of hypertension: a prospective cohort study of 10,347 adults. Eur J Nutr. doi.org/10.1007/s00394-021-02743-5.

Purpose: Maintaining optimal blood pressure (BP) levels can be an effective preventive strategy for reducing disease burden. Nut consumption may play a preventive role against hypertension, which is a lifelong condition. We aimed to prospectively examine the association between cumulative average nut consumption and the incidence of hypertension in Korean adults aged 40 years and older. Methods: A total of 10,347 participants who were free of hypertension at baseline, were included. Hypertension was defined as having a physician diagnosis and taking antihypertensive medications or having abnormal BP (systolic ≥ 140 mmHg or diastolic ≥ 90 mmHg). As an exposure, cumulative average nut consumption was calculated using repeated food-frequency questionnaires (mean: 2.1). We used a modified Poisson regression model with a robust error estimator to estimate the incidence rate ratios (IRRs) with 95% confidence intervals (CIs) for hypertension. Results: We identified 2047 incident cases of hypertension during 44,614 person-years of follow-up. Among both men and women, an average nut consumption of ≥ 1 serving/week (15 g/week]) was inversely associated with hypertension incidence (IRR = 0.74, 95% CI = 0.58–0.96, p for trend = 0.013 for men; IRR = 0.72, 95% CI = 0.59–0.88, p for trend = 0.002 for women) and these significant associations were consistently observed across the strata of potential confounders. Conclusion: An average consumption of at least one serving (15 g) per week of peanuts, almonds, and/or pine nuts may be inversely associated with the risk of hypertension among Korean adults aged 40 years and older, in a dose–response manner.

Effects of walnut consumption for 2 years on lipoprotein subclasses among healthy elders: findings from the WAHA Randomized Controlled Trial.

Rajaram, S., M. Cofán, A. Sala-Vila, E. Haddad, M. Serra-Mir, E. Bitok, I. Roth, T.M. Freitas-Simoes, A. Kaur, C. Valls-Pedret, M. Doménech, K. Oda, D. Corella, J. Sabaté, E. Ros, 2021. Effects of walnut consumption for 2 years on lipoprotein subclasses among healthy elders: findings from the WAHA Randomized Controlled Trial. Circulation. 144(13):1083–1085.

Background: Frequent consumption of nuts, an important component of plant-based diets, is associated with 15% lower total cardiovascular disease (CVD) and 23% lower CVD mortality rates. Small, short-term randomized controlled trials (RCTs) indicate that diets supplemented with nuts have a consistent cholesterol-lowering effect; however, no trials of nut-enriched diets for lipid changes focused on elderly individuals, recruited participants from diverse geographical locations, or lasted 2 years. Also, there is little information concerning effects of nuts on lipoprotein subclasses. Objective: We hypothesized that incorporating walnuts into the usual diet would improve the lipid profile irrespective of differences in geographical and dietary background. Methods: The Walnuts and Healthy Aging (WAHA) study is a two-center (Barcelona, Spain and California, USA), 2-year, parallel-group RCT testing the effects of walnut supplemented diets in healthy elders. Lipoprotein changes were a pre-specified secondary outcome. Eligible candidates were cognitively healthy elders (63-79 years-old) without major comorbidities. Participants (n=708) were allocated to either a walnut-free (control) or walnut-supplemented diet (≈15% of energy, 30-60g/day). In 2-monthly visits, compliance, tolerance, medication changes, and body weight were recorded. At each visit, 8–week allotments of raw, pieced walnuts were delivered to the corresponding group. Results: 636 participants completed the study (90% retention rate) and 628 had full data for lipoprotein analyses (mean age 69 years, 67% women, 32% treated with statins). Mean baseline LDL-C and triglycerides were 117 and 105 mg/dL, respectively. The walnut diet significantly decreased (mg/dL) total cholesterol (mean -8.5 [95% CI, -11.2, -5.4]), LDL-C (mean -4.3 [-6.6, -1.6]), and intermediate-density lipoprotein (IDL)-C (-1.3 [-1.5, -1.0]), corresponding to reductions of 4.4%, 3.6%, and 16.8%, respectively, while triglycerides and HDL-C were unaffected (Figures-B, C). Total LDL particles and small LDL particle number decreased by 4.3% and 6.1%, respectively (Figure-D). Results were not different by study site. Lipid responses to the walnut diet differed by sex: LDL-C was reduced by 7.9% in men and by 2.6% in women (P-interaction=0.007). Conclusions: The results demonstrate that incorporating daily doses of walnuts (≈15% of energy) to the habitual diet of free-living elders with an essentially normal lipid profile resulted in a mean 4.3 mg/dL LDL-C reduction, which is modest, although greater responses have been observed among individuals with hypercholesterolemia. Our data also support a beneficial effect of the walnut diet on NMR-assessed lipoprotein subfractions, with reductions of IDL-C (a sizable contributor to remnant-C) and total LDL particles. Prospective studies have reported that LDL particle number consistently outperforms LDL-C in CVD risk prediction and that remnant-C causally relates to CVD independent of LDL-C. That lipid responses were not different in two cohorts consuming diverse diets strengthens the generalization of our results. WAHA is the largest and longest nut trial to date, overcoming the limitations of prior smaller and shorter nut studies. The novel finding of sexual dimorphism in LDL-C response to walnut supplementation needs confirmation. WAHA was conducted in free-living individuals, who chose their daily foods, which may be viewed as desirable since it is closer to real life than the situation in controlled feeding studies. On the basis of associations ascertained in cohort studies, the observed shift of the lipoprotein subclass phenotype suggests a reduction of lipoprotein-related CVD risk by long-term consumption of walnuts, which provides novel mechanistic insight for their potential cardiovascular benefit beyond effects on the standard lipid panel. Our data reinforce the notion that regular walnut consumption may be a useful part of a multi-component dietary intervention or dietary pattern to lower atherogenic lipids and improve CVD risk.

Association of walnut consumption with total and cause-specific mortality and life expectancy in U.S. adults.

Liu, X., M. Guasch-Ferré, D.K. Tobias, Y. Li, 2021. Association of walnut consumption with total and cause-specific mortality and life expectancy in U.S. adults. Nutrients. 13(8), 2699. https://doi.org/10.3390/nu13082699

Walnut consumption is associated with health benefits. We aimed to (1) examine the association between walnut consumption and mortality and (2) estimate life expectancy in relation to walnut consumption in U.S. adults. We included 67,014 women of the Nurses’ Health Study (1998–2018) and 26,326 men of the Health Professionals Follow-up Study (1998–2018) who were free of cancer, heart disease, and stroke at baseline. We used Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During up to 20 years of follow-up, we documented 30,263 deaths. The hazard ratios for total mortality across categories of walnut intake (servings/week), as compared to non-consumers, were 0.95 (95% confidence interval (CI), 0.91, 0.98) for <1 serving/week, 0.94 (95% CI, 0.89, 0.99) for 1 serving/week, 0.87 (95% CI, 0.82, 0.93) for 2–4 servings/week, and 0.86 (95% CI, 0.79, 0.93) for >=5 servings/week (p for trend <0.0001). A greater life expectancy at age 60 (1.30 years in women and 1.26 years in men) was observed among those who consumed walnuts more than 5 servings/week compared to non-consumers. Higher walnut consumption was associated with a lower risk of total and CVD mortality and a greater gained life expectancy among U.S. elder adults.

Dietary recommendations for prevention of atherosclerosis

Riccardi, G., A. Giosuè, I. Calabrese, O. Vaccaro, 2021.Dietary recommendations for prevention of atherosclerosis. Cardiovasc Res. doi: 10.1093/cvr/cvab173. Online ahead of print.

This review aims at summarizing updated evidence on cardiovascular disease (CVD) risk associated with consumption of specific food items to substantiate dietary strategies for atherosclerosis prevention. A systematic search on PubMed was performed to identify meta-analyses of cohort studies and RCTs with CVD outcomes. The evidence is highly concordant in showing that, for the healthy adult population, low consumption of salt and foods of animal origin, and increased intake of plant-based foods-whole grains, fruits, vegetables, legumes, and nuts-are linked with reduced atherosclerosis risk. The same applies for the replacement of butter and other animal/tropical fats with olive oil and other unsaturated-fat-rich oil. Although the literature reviewed overall endorses scientific society dietary recommendations, some relevant novelties emerge. With regard to meat, new evidence differentiates processed and red meat-both associated with increased CVD risk-from poultry, showing a neutral relationship with CVD for moderate intakes. Moreover, the preferential use of low-fat dairies in the healthy population is not supported by recent data, since both full-fat and low-fat dairies, in moderate amounts and in the context of a balanced diet, are not associated with increased CVD risk; furthermore, small quantities of cheese and regular yogurt consumption are even linked with a protective effect. Among other animal protein sources, moderate fish consumption is also supported by the latest evidence, although there might be sustainability concerns. New data endorse the replacement of most high glycemic index (GI) foods with both whole grain and low GI cereal foods. As for beverages, low consumption not only of alcohol, but also of coffee and tea is associated with a reduced atherosclerosis risk while soft drinks show a direct relationship with CVD risk. This review provides evidence-based support for promoting appropriate food choices for atherosclerosis prevention in the general population.

Effects of extra virgin olive oil and pecans on plasma fatty acids in patients with stable coronary artery disease.

de Araújo, A.R., G.R. Sampaio, L.R. da Silva, V.L. Portal, M.M. Markoski, A.S. de Quadros, M.M. Rogero, E.A.F. da Silva Torres, A. Marcadenti, 2021. Effects of extra virgin olive oil and pecans on plasma fatty acids in patients with stable coronary artery disease. Nutrition. 91-92:111411. https://doi.org/10.1016/j.nut.2021.111411

Objective: The aim of this study was to determine the effects of a healthy diet supplemented with extra virgin olive oil or pecans on plasma fatty acids (PFAs) in patients with stable coronary artery disease (CAD). Methods: Patients 40 to 80 y of age were randomized to one of three dietary interventions (allocation ratio 1: 1: 1): healthy diet based on guidelines (control group [CG]), healthy diet supplemented with 30 g/d of pecans (PNG), or a healthy diet supplemented with 30 mL/d of extra virgin olive oil (OOG). PFAs were identified at baseline and at the end of follow-up (12 wk), and correlations between dietary fatty acids intake, PFAs, and clinical biomarkers of the lipid profile were also assessed before and after the interventions. Results: Among 149 participants included in the analysis (43 CG; 51 PNG; and 55 OOG), correlations were observed between food intake, PFAs, and lipid profile before and after interventions independent of statins used, but all were considered weak. At the end of the study, the OOG showed increased concentrations of oleic fatty acid independently of the type of statin in use (1.49%; 95% confidence interval, 0.08-2.89; P = 0.029); however, there were no significant differences between the groups regarding the final mean values of oleic fatty acid or in the other PFAs. Conclusions: In patients with stable CAD, there were no significant differences in PFAs after 12 wk according to dietary interventions evaluated.

Acute consumption of pecans decreases angiopoietin-like protein-3 in healthy males: a secondary analysis of randomized controlled trials.

Guarneiri, L.L., M.O. Spaulding, A.R. Marquardt, J.A. Cooper, C.M. Paton, 2021. Acute consumption of pecans decreases angiopoietin-like protein-3 in healthy males: a secondary analysis of randomized controlled trials. Nutr Res. 92:62-71. https://doi.org/10.1016/j.nutres.2021.06.001

Angiopoietin-like proteins (ANGPTL)-3 and -4 regulate lipid metabolism, but the effect of tree nuts of varying fatty acid composition on post-meal responses is unknown. The purpose of the study was to conduct a secondary analysis of two studies on ANGPTL3 and -4 responses to meals containing different tree nuts. We hypothesized that the pecan-containing meal would mitigate postprandial rises in ANGPTL3 compared to the traditional meal without nuts in males, but not females. In addition, we hypothesized that there would be no other differences between any other treatments in ANGPTL3 or -4 responses. The two studies were double-blind, randomized crossover trials. Twenty-two adults (10=male, 12=female) completed study 1, which compared meals containing pecans vs. no nuts (control), and thirty adults (14=male, 16=female) completed study 2, which compared meals containing black walnuts, English walnuts (EW), or no nuts (control). Blood was collected at fasting, 30, 60, 120, and 180min postprandially. In study 1, ANGPTL3 was suppressed more in pecan vs. control in males (iAUC: -579.4±219.4 vs. -128.4±87.1pg/mL/3h, P<.05). In study 2, there was no difference in ANGPTL3 between black walnuts vs. EW, but ANGPTL3 was suppressed more in control vs. black walnuts in females only (iAUC: -196.4±138.4 vs. 102.1±90.1pg/mL/3h, P<.05). There were no differences in ANGPTL4 between treatments. In conclusion, adding pecans to a meal decreased ANGPTL3 in males, but not females. These data highlight the importance of investigating the impact of nutrients and sex on postprandial ANGPTL3 ad -4 responses to better understand their ability to reduce cardiovascular disease risk.