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Research Nut: Walnuts

Reduction in serum LDL cholesterol using a nutrient compendium in hyperlipidemic adults unable or unwilling to use statin therapy: a double-blind randomized crossover clinical trial.

Kopecky, S.L., S. Alias, E. Klodas, P.J.H. Jones, 2022. Reduction in serum LDL cholesterol using a nutrient compendium in hyperlipidemic adults unable or unwilling to use statin therapy: a double-blind randomized crossover clinical trial. J. Nutr. 152(2), 458–465. https://doi.org/10.1093/jn/nxab375

Background: Many hyperlipidemic patients prescribed β-hydroxy-β-methylglutaryl coenzyme A reductase inhibitors (statins) are unable or unwilling to take them. A hedonically acceptable snack-based solution formulated from cholesterol-lowering food ingredients could represent a therapeutic alternative but has not been tested in this population. Objectives: To evaluate the effect of snacks containing a compendium of functional bioactives on fasting LDL cholesterol in statin candidates unwilling to use or intolerant to ≥1 statin drug. Secondary outcomes included changes in circulating total cholesterol (TC), triglycerides, HDL cholesterol, fasting glucose, insulin, and high-sensitivity C-reactive protein concentrations, as well as effects of single-nucleotide polymorphisms (SNPs) on outcome. Methods: This multicenter, randomized, double-blind, free-living crossover study was composed of 2 regimented phases of 4 wk each, separated by a 4-wk washout. Eighteen men and 36 women, with a mean ± SD age of 49 ± 12 y and mean ± SD LDL cholesterol of 131 ± 32.1 mg/dL, were instructed to ingest a variety of ready-to-eat snacks twice daily as a substitute for something they were consuming already. Other behavior changes were actively discouraged. Treatment products provided ≥5 g fiber, 1000 mg ω-3 (n-3) fatty acids, 1000 mg phytosterols, and 1800 μmol antioxidants per serving. Control products were calorie-matched like-items drawn from the general grocery marketplace. Serum lipids were measured at baseline and the end of each phase and compared using the ANOVA model. Compliance to study foods was confirmed by serum 18:3n-3 concentration assessment. Results: Comparing intervention phase endpoints, LDL cholesterol was reduced a mean ± SD of 8.80 ± 1.69% (P < 0.0001), and TC was reduced a mean ± SD of 5.08 ± 1.12% (P < 0.0001) by treatment foods compared with control foods, whereas effects on other analytes did not differ between treatments. SNPs were not significantly related to outcomes (P ≥ 0.230). Compliance with study foods was 95%. Conclusions: Consumption of hedonically acceptable snacks containing a compendium of cholesterol-lowering bioactive compounds can rapidly and meaningfully reduce LDL cholesterol in adult patients unable or unwilling to take statin drugs.

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

The effects of the Green-Mediterranean diet on cardiometabolic health are linked to gut microbiome modifications: a randomized controlled trial. 

Rinott, E., A.Y. Meir, G. Tsaban, H. Zelicha, A. Kaplan, D. Knights, K. Tuohy, M.U. Scholz, O. Koren, M.J. Stampfer, D.D. Wang, I. Shai, I. Youngster, 2022. The effects of the Green-Mediterranean diet on cardiometabolic health are linked to gut microbiome modifications: a randomized controlled trial. Genome Med. 14(1):29. https://doi.org/10.1186/s13073-022-01015-z

Background: Previous studies have linked the Mediterranean diet (MED) with improved cardiometabolic health, showing preliminary evidence for a mediating role of the gut microbiome. We recently suggested the Green-Mediterranean (Green-MED) diet as an improved version of the healthy MED diet, with increased consumption of plant-based foods and reduced meat intake. Here, we investigated the effects of MED interventions on the gut microbiota and cardiometabolic markers, and the interplay between the two, during the initial weight loss phase of the DIRECT-PLUS trial. Methods: In the DIRECT-PLUS study, 294 participants with abdominal obesity/dyslipidemia were prospectively randomized to one of three intervention groups: healthy dietary guidelines (standard science-based nutritional counseling), MED, and Green-MED. Both isocaloric MED and Green-MED groups were supplemented with 28g/day walnuts. The Green-MED group was further provided with daily polyphenol-rich green tea and Mankai aquatic plant (new plant introduced to a western population). Gut microbiota was profiled by 16S rRNA for all stool samples and shotgun sequencing for a select subset of samples. Results: Both MED diets induced substantial changes in the community structure of the gut microbiome, with the Green-MED diet leading to more prominent compositional changes, largely driven by the low abundant, “non-core,” microorganisms. The Green-MED diet was associated with specific microbial changes, including enrichments in the genus Prevotella and enzymatic functions involved in branched-chain amino acid degradation, and reductions in the genus Bifidobacterium and enzymatic functions responsible for branched-chain amino acid biosynthesis. The MED and Green-MED diets were also associated with stepwise beneficial changes in body weight and cardiometabolic biomarkers, concomitantly with the increased plant intake and reduced meat intake. Furthermore, while the level of adherence to the Green-MED diet and its specific green dietary components was associated with the magnitude of changes in microbiome composition, changes in gut microbial features appeared to mediate the association between adherence to the Green-MED and body weight and cardiometabolic risk reduction. Conclusions: Our findings support a mediating role of the gut microbiome in the beneficial effects of the Green-MED diet enriched with Mankai and green tea on cardiometabolic risk factors.