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Research Area: Cardiovascular Health

Chronic almond nut snacking alleviates perceived muscle soreness following downhill running but does not improve indices of cardiometabolic health in mildly overweight, middle-aged, adults.

Siegel, L., J. Rooney, L. Marjoram, L. Mason, E. Bowles, T.V. van Keulen, C. Helander, V. Rayo, M.Y. Hong, C. Liu, S. Hooshmand, M. Kern, O.C. Witard, 2024. Chronic almond nut snacking alleviates perceived muscle soreness following downhill running but does not improve indices of cardiometabolic health in mildly overweight, middle-aged, adults. Front. Nutr. 10:1298868. https://doi.org/10.3389/fnut.2023.1298868

Introduction: As a popular food snack rich in protein, fiber, unsaturated fatty acids, antioxidants and phytonutrients, almond nut consumption is widely associated with improvements in cardiometabolic health. However, limited data exists regarding the role of almond consumption in improving exercise recovery. Accordingly, we aimed to investigate the impact of chronic almond snacking on muscle damage and cardiometabolic health outcomes during acute eccentric exercise recovery in mildly overweight, middle-aged, adults. Methods: Using a randomized cross-over design, 25 mildly overweight (BMI: 25.8 ± 3.6 kg/m2), middle-aged (35.1 ± 4.7 y) males (n = 11) and females (n = 14) performed a 30-min downhill treadmill run after 8-weeks of consuming either 57 g/day of whole almonds (ALMOND) or an isocaloric amount (86 g/day) of unsalted pretzels (CONTROL). Muscle soreness (visual analogue scale), muscle function (vertical jump and maximal isokinetic torque) and blood markers of muscle damage (creatine kinase (CK) concentration) and inflammation (c-reactive protein concentration) were measured pre and post (24, 48, and 72 h) exercise. Blood biomarkers of cardiometabolic health (total cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol), body composition and psycho-social assessments of mood (POMS-2 inventory), appetite and well-being were measured pre and post intervention. Results: Downhill running successfully elicited muscle damage, as evidenced by a significant increase in plasma CK concentration, increased perception of muscle soreness, and impaired vertical jump performance (all p < 0.05) during acute recovery. No effect of trial order was observed for any outcome measurement. However, expressed as AUC over the cumulative 72 h recovery period, muscle soreness measured during a physical task (vertical jump) was reduced by ~24% in ALMOND vs. CONTROL (p < 0.05) and translated to an improved maintenance of vertical jump performance (p < 0.05). However, ALMOND did not ameliorate the CK response to exercise or isokinetic torque during leg extension and leg flexion (p > 0.05). No pre-post intervention changes in assessments of cardiometabolic health, body composition, mood state or appetite were observed in ALMOND or CONTROL (all p > 0.05). Conclusion: Chronic almond supplementation alleviates task-specific perceived feelings of muscle soreness during acute recovery from muscle damaging exercise, resulting in the better maintenance of muscle functional capacity. These data suggest that almonds represent a functional food snack to improve exercise tolerance in mildly overweight, middle-aged adults.

Association of tree nut consumption with cardiovascular disease and cardiometabolic risk factors and health outcomes in US adults: NHANES 2011-2018.

Lopez-Neyman, S. M., N. Zohoori, K.S. Broughton, D.C. Miketinas, 2023. Association of tree nut consumption with cardiovascular disease and cardiometabolic risk factors and health outcomes in US adults: NHANES 2011-2018. Curr. Dev. Nutr. 7(10):102007. https://doi.org/10.1016/j.cdnut.2023.102007

Background: Tree nuts are nutrient dense, and their consumption has been associated with improvements in health outcomes. Objective: To estimate the usual tree nut intake and examine the association between tree nut consumption and cardiometabolic (CM) health outcomes in a nationally representative sample of US adults. Methods: Cross-sectional data were analyzed from a sample of 18,150 adults aged ≥ 20y who provided at least one reliable 24-h dietary recall and had complete data for the variables of interest in the NHANES 2011-2018. Tree nut consumers were defined as those consuming ≥ ¼ ounce/d (7.09 g). The National Cancer Institute Method was used to estimate the usual tree nut intake among consumers. Measurement error calibrated regression models were used to assess the association between tree nut consumption and each health outcome of interest. Results: Approximately 8% of all participants (n = 1238) consumed tree nuts and had a mean ± SE usual intake of 39.5 ± 1.8 g/d. Tree nut consumers were less likely to have obesity (31% vs. 40%, P < 0.001) and low high-density lipoprotein cholesterol (22% vs. 30%, P < 0.001) compared with nonconsumers. Moreover, tree nut consumers had a lower mean waist circumference (WC) (97.1 ± 0.7 vs. 100.5 ± 0.3 cm, P < 0.001) and apolipoprotein B (87.5 ± 1.2 vs. 91.8 ± 0.5 mg/dL, P = 0.004) than nonconsumers. After adjusting models for demographics and lifestyle covariates, the difference in WC between average intake (33.7 g/d) and low threshold intake (7.09/g) of tree nuts was -1.42 ± 0.58 cm (P = 0.005). Conclusions: Most US adults do not consume tree nuts, yet modest consumption was associated with decreased prevalence of cardiovascular disease and CM risk factors and improvement for some health outcome measures.

Effect of almond consumption on insulin sensitivity and serum lipids among Asian Indian adults with overweight and obesity- A randomized controlled trial.

Gayathri, R., K. Abirami, N. Kalpana, V.S. Manasa, V. Sudha, S. Shobana, R.G. Jeevan, V. Kavitha, K. Parkavi, R.M. Anjana, R. Unnikrishnan, K. Gokulakrishnan, D.A. Beatrice, K. Krishnaswamy, R. Pradeepa, R.D. Mattes, J. Salas-Salvadó, W. Willett, V. Mohan, 2023. Effect of almond consumption on insulin sensitivity and serum lipids among Asian Indian adults with overweight and obesity- A randomized controlled trial. Front. Nutr. 9: 1055923. https://doi.org/10.3389/fnut.2022.1055923

Background: Asian Indians have an increased susceptibility to type 2 diabetes and premature coronary artery disease. Nuts, like almonds, are rich in unsaturated fat and micronutrients with known health benefits. Objectives: This study aimed to assess the efficacy of almonds for reduction of insulin resistance and improving lipid profile in overweight Asian Indian adults. Methods: This parallel-arm, randomized, controlled trial was conducted in Chennai, India on 400 participants aged 25-65 years with a body mass index ≥ 23 kg/m2. The intervention group received 43 g of almonds/day for 12 weeks, while the control group was advised to consume a customary diet but to avoid nuts. Anthropometric, clinical, and dietary data were assessed at periodic intervals. Glucose tolerance, serum insulin, glycated hemoglobin, C-peptide and lipid profile were assessed at baseline and end of the study. Insulin resistance (homeostasis assessment model-HOMA IR) and oral insulin disposition index (DIo) were calculated. Results: A total of 352 participants completed the study. Significant improvement was seen in DIo [mean (95% CI) = + 0.7 mmol/L (0.1, 1.3); p = 0.03], HOMA IR (-0.4 (-0.7, -0.04; p = 0.03) and total cholesterol (-5.4 mg/dl (-10.2, -0.6); p = 0.03) in the intervention group compared to the control group. Incremental area under the curve (IAUC) and mean amplitude of glycemic excursion (MAGE) assessed using continuous glucose monitoring systems were also significantly lower in the intervention group. Dietary 24-h recalls showed a higher significant reduction in carbohydrate and increase in mono unsaturated fatty acid (MUFA) and polyunsaturated fatty acids (PUFA) intake in the intervention group compared to the control group. Conclusion: Daily consumption of almonds increased the intake of MUFA with decrease in carbohydrate calories and decreases insulin resistance, improves insulin sensitivity and lowers serum cholesterol in Asian Indians with overweight/obesity. These effects in the long run could aid in reducing the risk of diabetes and other cardiometabolic disease.

Walnut inclusion in a palm oil-based atherogenic diet promotes traits predicting stable atheroma plaque in Apoe-deficient mice.

Lázaro, I., J. Bobi, M. Cofán, G. Kapravelou, A.J. Amor, J. Surra, C. Gómez-Guerrero, E. Ortega, J. Osada, A.P. Dantas, A. Sala-Vila, 2023. Walnut inclusion in a palm oil-based atherogenic diet promotes traits predicting stable atheroma plaque in Apoe-deficient mice. Front. Nutr. 10:1079407. https://doi.org/10.3389/fnut.2023.1079407

Introduction: The lower rates of cardiovascular disease in Southern Europe could be partially explained by the low prevalence of lipid-rich atheroma plaques. Consumption of certain foods affects the progression and severity of atherosclerosis. We investigated whether the isocaloric inclusion of walnuts within an atherogenic diet prevents phenotypes predicting unstable atheroma plaque in a mouse model of accelerated atherosclerosis. Methods: Apolipoprotein E-deficient male mice (10-week-old) were randomized to receive a control diet (9.6% of energy as fat, n = 14), a palm oil-based high-fat diet (43% of energy as fat, n = 15), or an isocaloric diet in which part of palm oil was replaced by walnuts in a dose equivalent to 30 g/day in humans (n = 14). All diets contained 0.2% cholesterol. Results: After 15 weeks of intervention, there were no differences in size and extension in aortic atherosclerosis among groups. Compared to control diet, palm oil-diet induced features predicting unstable atheroma plaque (higher lipid content, necrosis, and calcification), and more advanced lesions (Stary score). Walnut inclusion attenuated these features. Palm oil-based diet also boosted inflammatory aortic storm (increased expression of chemokines, cytokines, inflammasome components, and M1 macrophage phenotype markers) and promoted defective efferocytosis. Such response was not observed in the walnut group. The walnut group’s differential activation of nuclear factor kappa B (NF-kappaB; downregulated) and Nrf2 (upregulated) in the atherosclerotic lesion could explain these findings. Conclusion: The isocaloric inclusion of walnuts in an unhealthy high-fat diet promotes traits predicting stable advanced atheroma plaque in mid-life mice. This contributes novel evidence for the benefits of walnuts, even in an unhealthy dietary environment.

Walnut inclusion in a palm oil-based atherogenic diet promotes traits predicting stable atheroma plaque in Apoe-deficient mice.

Lázaro. I., J. Bobi, M. Cofán, G. Kapravelou, A.J. Amor, J. Surra, C. Gómez-Guerrero, E. Ortega, J. Osada, A.P. Dantas, A. Sala-Vila, 2023. Walnut inclusion in a palm oil-based atherogenic diet promotes traits predicting stable atheroma plaque in Apoe-deficient mice. Front. Nutr. 10:1079407. https://doi.org/10.3389/fnut.2023.1079407

INTRODUCTION: The lower rates of cardiovascular disease in Southern Europe could be partially explained by the low prevalence of lipid-rich atheroma plaques. Consumption of certain foods affects the progression and severity of atherosclerosis. We investigated whether the isocaloric inclusion of walnuts within an atherogenic diet prevents phenotypes predicting unstable atheroma plaque in a mouse model of accelerated atherosclerosis. METHODS: Apolipoprotein E-deficient male mice (10-week-old) were randomized to receive a control diet (9.6% of energy as fat, n = 14), a palm oil-based high-fat diet (43% of energy as fat, n = 15), or an isocaloric diet in which part of palm oil was replaced by walnuts in a dose equivalent to 30 g/day in humans (n = 14). All diets contained 0.2% cholesterol. RESULTS: After 15 weeks of intervention, there were no differences in size and extension in aortic atherosclerosis among groups. Compared to control diet, palm oil-diet induced features predicting unstable atheroma plaque (higher lipid content, necrosis, and calcification), and more advanced lesions (Stary score). Walnut inclusion attenuated these features. Palm oil-based diet also boosted inflammatory aortic storm (increased expression of chemokines, cytokines, inflammasome components, and M1 macrophage phenotype markers) and promoted defective efferocytosis. Such response was not observed in the walnut group. The walnut group’s differential activation of nuclear factor kappa B (NF-KB; downregulated) and Nrf2 (upregulated) in the atherosclerotic lesion could explain these findings. CONCLUSION: The isocaloric inclusion of walnuts in an unhealthy high-fat diet promotes traits predicting stable advanced atheroma plaque in mid-life mice. This contributes novel evidence for the benefits of walnuts, even in an unhealthy dietary environment.

Key Area: Heart Health

A walnut-enriched diet for 2 years changes the serum oxylipin profile in healthy older persons.

Cofán, M., A. Checa, M. Serra-Mir, I. Roth, C. Valls-Pedret, A. Lopez-Illamola, M. Doménech, S. Rajaram, I. Lázaro, J. Sabaté, E. Ros, C.E. Wheelock, A. Sala-Vila, 2023. A walnut-enriched diet for 2 years changes the serum oxylipin profile in healthy older persons. J Nutr. S0022-3166(23)72794-6. https://doi.org/10.1016/j.tjnut.2023.12.007.

Background: Oxylipins are products derived from polyunsaturated fatty acids (PUFAs) that play a role in cardiovascular disease and aging. Fish oil-derived n-3 PUFAs promote the formation of anti-inflammatory and vasodilatory oxylipins; however, there are little data on oxylipins derived from α-linolenic acid (C18:3n-3), the primary plant-derived n-3 PUFA. Walnuts are a source of C18:3n-3.Objectives: To investigate the effect on serum oxylipins of a diet enriched with walnuts at 15% energy (30-60 g/d; 2.6-5.2 g C18:3n-3/d) for 2 y compared to a control diet (abstention from walnuts) in healthy older males and females (63-79 y). Methods: The red blood cell proportion of α-linolenic acid was determined by gas chromatography as a measure of compliance. Ultra-performance liquid chromatography-tandem mass spectrometry was used to measure serum concentrations of 53 oxylipins in participants randomly assigned to receive the walnut diet (n = 64) or the control diet (n = 51). Two-year concentration changes (final minus baseline) were log-transformed (base log-10) and standardized (mean-centered and divided by the standard deviation of each variable). Volcano plots were then generated (fold change ≥1.5; false discovery rate ≤0.1). For each oxylipin delta surviving multiple testing, we further assessed between-intervention group differences by analysis of covariance adjusting for age, sex, BMI, and the baseline concentration of the oxylipin. Results: The 2-y change in red blood cell C18:3n-3 in the walnut group was significantly higher than that in the control group (P < 0.001). Compared to the control diet, the walnut diet resulted in statistically significantly greater increases in 3 C18:3n-3-derived oxylipins (9-HOTrE, 13-HOTrE, and 12,13-EpODE) and in the C20:5n-3 derived 14,15-diHETE, and greater reductions of the C20:4n-6-derived 5-HETE, 19-HETE, and 5,6-diHETrE. Conclusions: Long-term walnut consumption changes the serum oxylipin profile in healthy older persons. Our results add novel mechanistic evidence on the cardioprotective effects of walnuts.

Key Area: Heart Health

Almonds vs. carbohydrate snacks in an energy-restricted diet: Weight and cardiometabolic outcomes from a randomized trial.

Carter, S., A.M. Hill, L.C. Mead, H.Y. Wong, C. Yandell, J.D. Buckley, S.Y. Tan, G.B. Rogers, F. Fraysse, A.M. Coates, 2023. Almonds vs. carbohydrate snacks in an energy-restricted diet: Weight and cardiometabolic outcomes from a randomized trial. Obesity (Silver Spring). 31(10):2467-2481. https://doi.org/10.1002/oby.23860

Objective: This study evaluated weight and cardiometabolic outcomes after a 3-month energy-restricted diet (−30%) containing almonds (almond-enriched diet [AED]) or containing carbohydrate-rich snacks (nut-free control diet [NFD]) (Phase 1), followed by 6 months of weight maintenance (Phase 2). Methods: Participants (25–65 years old) with overweight or obesity (BMI 27.5–34.9 kg/m2) were randomly allocated to AED (n = 68) or NFD (n = 72). Results: Both groups lost weight during Phase 1 (p < 0.001) (mean [SE], −7.0 [0.5] kg AED vs. −7.0 [0.5] kg NFD, p = 0.858) and Phase 2 (p = 0.009) (−1.1 [0.5] kg AED vs. −1.3 [0.6] NFD, p = 0.756), with improvements in percentage lean mass after Phase 2 (4.8% [0.3%], p < 0.001). Reductions occurred in fasting glucose (−0.2 [0.07] mmol/L, p = 0.003), insulin (−8.1 [4.0] pmol/L, p = 0.036), blood pressure (−4.9 [0.8] mm Hg systolic, −5.0 [0.5] mm Hg diastolic, p < 0.001), total cholesterol (−0.3 [0.1] mmol/L), low-density lipoprotein (LDL) (−0.2 [0.1] mmol/L), very low density lipoprotein (−0.1 [0.03] mmol/L), and triglycerides (−0.3 [0.06] mmol/L) (all p < 0.001), and high-density lipoprotein increased (0.1 [0.02] mmol/L, p = 0.011) by the end of Phase 2 in both groups. There were group by time interactions for lipoprotein particle concentrations: very small triglyceride-rich (−31.0 [7.7] nmol/L AED vs. −4.8 [7.9] nmol/L NFD, p = 0.007), small LDL (−109.3 [40.5] nmol/L AED vs. −20.7 [41.6] nmol/L NFD, p = 0.017), and medium LDL (−24.4 [43.4] nmol/L AED vs. −130.5 [44.4] nmol/L NFD, p = 0.045). Conclusions: An energy-restricted AED resulted in weight loss and weight loss maintenance comparable to an energy-restricted NFD, and both diets supported cardiometabolic health. The AED resulted in greater improvements in some lipoprotein subfractions, which may enhance reductions in cardiovascular risk.

Mixed nuts as healthy snacks: effect on tryptophan metabolism and cardiovascular risk factors.

Yang, J., R. Lee, Z. Schulz, A. Hsu, J. Pai, S. Yang, S.M. Henning, J. Huang, J.P. Jacobs, D. Heber, Z. Li., 2023. Mixed nuts as healthy snacks: effect on tryptophan metabolism and cardiovascular risk factors. Nutrients. 15, 569; https://doi.org/10.3390/nu15030569.

We recently demonstrated that the consumption of mixed tree nuts (MTNs) during caloric restriction decreased cardiovascular risk factors and increased satiety. Tryptophan (Trp) metabolism has been indicated as a factor in cardiovascular disease. Here, we investigated the effect of MTNs on Trp metabolism and the link to cardiovascular risk markers. Plasma and stool were collected from 95 overweight individuals who consumed either MTNs (or pretzels) daily as part of a hypocaloric weight loss diet for 12 weeks followed by an isocaloric weight maintenance program for an additional 12 weeks. Plasma and fecal samples were evaluated for Trp metabolites by LC–MS and for gut microbiota by 16S rRNA sequencing. Trp–kynurenine metabolism was reduced only in the MTNs group during weight loss (baseline vs. week 12). Changes in Trp–serotonin (week 24) and Trp–indole (week 12) metabolism from baseline were increased in the MTNs group compared to the pretzel group. Intergroup analysis between MTN and pretzel groups does not identify significant microbial changes as indicated by alpha diversity and beta diversity. Changes in the relative abundance of genus Paludicola during intervention are statistically different between the MTNs and pretzel group with p < 0.001 (q = 0.07). Our findings suggest that consumption of MTNs affects Trp host and microbial metabolism in overweight and obese subjects.

Interplay of walnut consumption, changes in circulating miRNAs and reduction in LDL-cholesterol in elders.

Gil-Zamorano, J., M. Cofán, M.C. López de Las Hazas, T. García-Blanco, A. García-Ruiz, M. Doménech, M. Serra-Mir, I. Roth, C. Valls-Pedret, S. Rajaram, J. Sabaté, E. Ros, A. Dávalos, A. Sala-Vila, 2022. Interplay of walnut consumption, changes in circulating miRNAs and reduction in LDL-cholesterol in elders. Nutrients. 14(7):1473. https://doi.org/10.3390/nu14071473

The mechanisms underlying the lipid-lowering effect of nuts remain elusive. This study explores whether one-year supplementation with walnuts decreases LDL-cholesterol (LDL-C) by affecting the expression of circulating microRNAs (c-miRNA). In this sub-study of the Walnuts and Healthy Aging (WAHA) trial, we obtained fasting serum at baseline and at 1 year from 330 free-living participants (63–79 year, 68% women), allocated into a control group (CG, abstinence from walnuts, n = 164) and a walnut group (WG, 15% of daily energy as walnuts, ~30–60 g/day, n = 166). Participants in the WG showed a 1 year decrease in LDL-C (−9.07, (95% confidence interval: −12.87; −5.73) mg/dL; p = 0.010 versus changes in the CG). We conducted a miRNA array in eight randomly selected participants in the WG who decreased in LDL-C. This yielded 53 c-miRNAs with statistically significant changes, 27 of which survived the correction for multiple testing. When validating them in the full population, statistical significance lasted for hsa-miR-551a, being upregulated in the WG. In mediation analysis, the change in hsa-miR-551a was unrelated to LDL-C decrease. Long-term supplementation with walnuts decreased LDL-C independently of the changes in c-miRNA. The hsa-miR-551a upregulation, which has been linked to a reduced cell migration and invasion in several carcinomas, suggests a novel mechanism of walnuts in cancer risk.

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.