Archive

Research Nut: Walnuts

The effect of a high-polyphenol Mediterranean diet (Green-MED) combined with physical activity on age-related brain atrophy: the Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT PLUS).

Kaplan, A., H. Zelicha, A. Yaskolka Meir, E. Rinott, G. Tsaban, G. Levakov, O. Prager, M. Salti, Y. Yovell, J. Ofer, S. Huhn, F. Beyer, V. Witte, A. Villringer, N. Meiran, T.B. Emesh, P. Kovacs, M. von Bergen, U. Ceglarek, M. Blüher, M. Stumvall, F.B. Hu, M.J. Stampfer, A. Friedman, I. Shelef, G. Avidan, I. Shai, 2022. The effect of a high-polyphenol Mediterranean diet (Green-MED) combined with physical activity on age-related brain atrophy: the Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT PLUS). Am. J. Clin. Nutr. 115(5):1270–1281. https://doi.org/10.1093/ajcn/nqac001

Background: The effect of diet on age-related brain atrophy is largely unproven. Objective: To explore the effect of a Mediterranean diet higher in polyphenols and lower in red/processed meat (Green-MED diet) on age-related brain atrophy. Methods: This 18-month clinical trial longitudinally measured brain structure volumes by magnetic-resonance-imaging using hippocampal-occupancy (HOC) and lateral-ventricle-volume (LVV) expansion scores as neurodegeneration markers. Abdominally obese/dyslipidemic participants were randomly assigned to (1)-healthy dietary guidelines (HDG), (2)-Mediterranean (MED) diet, or (3)-Green-MED diet (MED diet higher in polyphenols and lower in red/processed meat). All subjects received free gym memberships and physical activity guidance. Both MED groups consumed 28g/day walnuts (+440 mg/d polyphenols). The Green-MED group consumed green-tea (3-4 cups/day) and Mankai (Wolffia-globosa strain, 100g frozen-cubes/day) green shake (+800mg/day polyphenols). Results: Among 284 participants (age = 51years; 88% men; BMI = 31.2kg/m2; apolipoprotein E-ε4 genotype = 15.7%), 224 (79%) completed the trial with eligible whole-brain MRIs. The pallidum (-4.2%), third ventricle (+3.9%), and LVV (+2.2%) disclosed the largest volume changes. Compared to younger participants, atrophy was accelerated among those ≥ 50 years [HOC change = -1.0±1.4% vs. -0.06±1.1%; 95% confidence-interval (CI):0.6, 1.3; p<0.001; LVV change = 3.2±4.5% vs. 1.3±4.1%; 95%CI:-3.1, -0.8;p = 0.001]. In subjects ≥50years, HOC decline and LVV expansion were attenuated in both MED groups, with the best outcomes among Green-MED diet participants, as compared to HDG (HOC: -0.8±1.6% vs. -1.3±1.4%;95%CI: -1.5, -0.02;p = 0.042, LVV: 2.3±4.7% vs. 4.3±4.5;95%CI;0.3, 5.2;p = 0.021). Similar patterns were observed among younger subjects. Improved insulin sensitivity over the trial was the strongest parameter associated with brain atrophy attenuation (p<0.05). Greater Mankai, green-tea and walnuts intake and less red and processed meat were significantly and independently associated with reduced HOC decline (p<0.05). Elevated urinary levels of the Mankai-derived polyphenols: urolithin-A (r = 0.24;p = 0.013) and tyrosol (r = 0.26;p = 0.007) were significantly associated with lower HOC decline. Conclusions: A Green-MED, high-polyphenol diet, rich in Mankai, green tea and walnuts and low in red/processed meat is potentially neuroprotective for age-related brain atrophy.

The effects of a Mediterranean diet intervention on cancer-related fatigue for patients undergoing chemotherapy: a pilot randomized controlled trial.

Kleckner, A. S., J.E. Reschke, I.R. Kleckner, A. Magnuson, A.M. Amitrano, E. Culakova, M. Shayne, C.S. Netherby-Winslow, S. Czap, M.C. Janelsins, K.M. Mustian, L.J. Peppone, 2022. The effects of a Mediterranean diet intervention on cancer-related fatigue for patients undergoing chemotherapy: a pilot randomized controlled trial. Cancers. 14(17):4202. https://doi.org/10.3390/cancers14174202

Cancer-related fatigue is a common, burdensome symptom of cancer and a side-effect of chemotherapy. While a Mediterranean Diet (MedDiet) promotes energy metabolism and overall health, its effects on cancer-related fatigue remain unknown. In a randomized controlled trial, we evaluated a rigorous MedDiet intervention for feasibility and safety as well as preliminary effects on cancer-related fatigue and metabolism compared to usual care. Participants had stage I–III cancer and at least six weeks of chemotherapy scheduled. After baseline assessments, randomization occurred 2:1, MedDiet:usual care. Measures were collected at baseline, week 4, and week 8 including MedDiet adherence (score 0–14), dietary intake, and blood-based metabolic measures. Mitochondrial respiration from freshly isolated T cells was measured at baseline and four weeks. Participants (n = 33) were 51.0 ± 14.6 years old, 94% were female, and 91% were being treated for breast cancer. The study was feasible, with 100% completing the study and >70% increasing their MedDiet adherence at four and eight weeks compared to baseline. Overall, the MedDiet intervention vs. usual care had a small-moderate effect on change in fatigue at weeks 4 and 8 (ES = 0.31, 0.25, respectively). For those with a baseline MedDiet score <5 (n = 21), the MedDiet intervention had a moderate-large effect of 0.67 and 0.48 at weeks 4 and 8, respectively. The MedDiet did not affect blood-based lipids, though it had a beneficial effect on fructosamine (ES = −0.55). Fatigue was associated with mitochondrial dysfunction including lower basal respiration, maximal respiration, and spare capacity (p < 0.05 for FACIT-F fatigue subscale and BFI, usual fatigue). In conclusion, the MedDiet was feasible and attenuated cancer-related fatigue among patients undergoing chemotherapy, especially those with lower MedDiet scores at baseline.

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.

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.

The effect of high-polyphenol Mediterranean diet on visceral adiposity: the DIRECT PLUS randomized controlled trial.

Zelicha, H., N. Kloting, A. Kaplan, A. Yaskolka Meir, E. Rinott, G. Tsaban, Y. Chassidim,  M. Bluher, U. Ceglarek, B. Isermann, M. Stumvoll, R.N. Quayson, M. von Bergen, B. Engelmann, U.E. Rolle-Kampczyk, S.B. Haange, K.M. Tuohy, C. Diotallevi, I. Shelef, F.B. Hu, M.J. Stampfer, I. Shai, 2022. The effect of high-polyphenol Mediterranean diet on visceral adiposity: the DIRECT PLUS randomized controlled trial. BMC Medicine. 20(1):327. https://doi.org/10.1186/s12916-022-02525-8

Background: Mediterranean (MED) diet is a rich source of polyphenols, which benefit adiposity by several mechanisms. We explored the effect of the green-MED diet, twice fortified in dietary polyphenols and lower in red/processed meat, on visceral adipose tissue (VAT). Methods: In the 18-month Dietary Intervention Randomized Controlled Trial PoLyphenols UnproceSsed (DIRECT-PLUS) weight-loss trial, 294 participants were randomized to (A) healthy dietary guidelines (HDG), (B) MED, or (C) green-MED diets, all combined with physical activity. Both isocaloric MED groups consumed 28 g/day of walnuts (+ 440 mg/day polyphenols). The green-MED group further consumed green tea (3–4 cups/day) and Wolffia globosa (duckweed strain) plant green shake (100 g frozen cubes/day) (+ 800mg/day polyphenols) and reduced red meat intake. We used magnetic resonance imaging (MRI) to quantify the abdominal adipose tissues. Results: Participants (age = 51 years; 88% men; body mass index = 31.2 kg/m2; 29% VAT) had an 89.8% retention rate and 79.3% completed eligible MRIs. While both MED diets reached similar moderate weight (MED: − 2.7%, green-MED: − 3.9%) and waist circumference (MED: − 4.7%, green-MED: − 5.7%) loss, the green-MED dieters doubled the VAT loss (HDG: − 4.2%, MED: − 6.0%, green-MED: − 14.1%; p < 0.05, independent of age, sex, waist circumference, or weight loss). Higher dietary consumption of green tea, walnuts, and Wolffia globosa; lower red meat intake; higher total plasma polyphenols (mainly hippuric acid), and elevated urine urolithin A polyphenol were significantly related to greater VAT loss (p < 0.05, multivariate models). Conclusions: A green-MED diet, enriched with plant-based polyphenols and lower in red/processed meat, may be a potent intervention to promote visceral adiposity regression.

Effect of walnut predinner snack on mealtime hunger and nutrient intake among university students. 

Wilson, T., L.S. DeVaan, M.E. LaCasse, E.M. Gile, M.J. Weis, M.D. Ahmann, G.I. Schnellman, M.T. Lenz, T.L. Hooks, 2022. Effect of walnut predinner snack on mealtime hunger and nutrient intake among university students. J Medicinal Food. 25(1):89–96. https://doi.org/10.1089/jmf.2021.0092

Freshman-15 is a phenomenon of first-year university students resulting in weight gain partly due to new cafeteria eating patterns and stress. This study determined if a premeal walnut snack alters planned eating behavior and mealtime nutrient intake during a subsequent buffet-model meal. Healthy university students (n = 36; 18.1 ± 0.5 years; body mass index: 23.6 ± 3.9) received three treatments (90 min premeal) in randomized order on 3 consecutive days: (1) snack of 190 Cal (1 oz) of walnuts (WS), (2) snack of 190 Cal of gummy candy (GS), or (3) no snack (NS; control) before a standard cafeteria dinner (1760 Cal). Visual analog scale (VAS) surveys were administered before and after dinner, and caloric intake was determined. Premeal VAS desire to eat was lower after WS and GS than NS, whereas the sense of hunger and sense of fullness were higher after WS and GS compared with NS. Postmeal VAS was not different between treatments. Mealtime calories, total fat, saturated fat, cholesterol, protein, sodium, fiber, and sugar consumed after WS were significantly less than NS. Total fat and sodium consumed after GS did not significantly differ from NS. Mealtime total fat, sodium, and fiber for WS were significantly less than GC, and a trend was observed for total calories. Differences in calorie intake were not observed between treatments when snack calories were included as part of the mealtime caloric intake. These findings could be helpful for promoting WS and to a lesser degree GS for increased satiety before meals possibly leading to reduced food intake during dinner by university students.