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Effects of the Dietary Approaches to Stop Hypertension Diet on Change in Cardiac Biomarkers Over Time: Results From the DASH-Sodium Trial.
Belanger, MJ, Kovell, LC, Turkson-Ocran, RA, Mukamal, KJ, Liu, X, Appel, LJ, Miller, ER, Sacks, FM, Christenson, RH, Rebuck, H, et al
Journal of the American Heart Association. 2023;12(2):e026684
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Most deaths from cardiovascular disease (CVD) can be attributed to specific modifiable risk factors. The Dietary Approaches to Stop Hypertension (DASH) diet, rich in fruits, vegetables, low-fat dairy and reduced in saturated fat and cholesterol, is associated with a lower risk of CVD events over time. The aim of this study was to examine the time course of change in biomarkers of cardiac injury, strain, and inflammation from consuming the DASH diet in comparison with a typical American diet. This study is a secondary analysis of the DASH-Sodium randomised clinical trial which recruited adult men and women, aged ≥22years. The participants were randomly assigned in a parallel-arm design to the DASH diet or a typical American diet (control) in a 1:1 ratio. Results show that in comparison with a typical American diet, the DASH diet reduced two of the investigated biomarkers progressively over a 12-week period. Authors conclude that their findings highlight the need for public health policies and interventions that support sustained adherence to a healthy eating pattern for cardiovascular health.
Abstract
Background The Dietary Approaches to Stop Hypertension (DASH) diet has been shown to reduce biomarkers of cardiovascular disease. We aimed to characterize the time course of change in biomarkers of cardiac injury (high-sensitivity cardiac troponin I), cardiac strain (NT-proBNP [N-terminal pro-B-type natriuretic peptide]), and inflammation (hs-CRP [high-sensitivity C-reactive protein]) while consuming the DASH diet. Methods and Results The DASH-Sodium trial was a randomized controlled trial of 412 adults with elevated blood pressure or hypertension. Participants were randomly assigned to 12 weeks of the DASH diet or a typical American diet. Energy intake was adjusted to maintain body weight. Measurements of high-sensitivity cardiac troponin I, NT-proBNP, and hs-CRP were performed in stored serum specimens, collected at baseline and ≈4, 8, and 12 weeks after randomization. In both the control diet and DASH diet, levels of NT-proBNP decreased; however, there was no difference between diets (P-trend compared with control=0.22). On the DASH diet versus control, levels of high-sensitivity cardiac troponin I decreased progressively during follow-up (P-trend compared with control=0.025), but a statistically significant between-diet difference in change from baseline levels was not observed until week 12 (% difference, 17.78% [95% CI, -29.51% to -4.09%]). A similar pattern was evident for hs-CRP (P-trend compared with control=0.01; % difference at week 12, 19.97% [95% CI, -31.94% to -5.89%]). Conclusions In comparison with a typical American diet, the DASH diet reduced high-sensitivity cardiac troponin I and hs-CRP progressively over 12 weeks. These results suggest that the DASH diet has cumulative benefits over time on biomarkers of subclinical cardiac injury and inflammation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00000608.
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Metabolomic Profiles Associated With Blood Pressure Reduction in Response to the DASH and DASH-Sodium Dietary Interventions.
Kim, H, Appel, LJ, Lichtenstein, AH, Wong, KE, Chatterjee, N, Rhee, EP, Rebholz, CM
Hypertension (Dallas, Tex. : 1979). 2023;80(7):1494-1506
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DASH (Dietary Approaches to Stop Hypertension) diet is recommended for reducing blood pressure (BP) and the risk of cardiovascular disease (CVD). The DASH diet emphasises the intake of fruits, vegetables, and low-fat dairy, includes a variety of protein sources and it is low in red and processed meats and sugar-sweetened beverages. The aim of this study was to identify metabolites associated with differences in systolic blood pressure (SBP) or diastolic blood pressure (DBP) in response to the diet interventions. This study used data from 2 randomised controlled feeding trials (DASH trial and DASH-Sodium trial). Results show the identification of 42 unique metabolites (9 serum and 33 urine) which were significantly associated with changes in SBP or DBP DASH diet versus control diet interventions. Furthermore, pathway overrepresentation analysis revealed metabolite pathways that were relevant for the association between DASH diet and BP. Authors conclude that their findings provide insights on formulating intervention strategies to reduce BP.
Abstract
BACKGROUND The DASH (Dietary Approaches to Stop Hypertension) diets reduced blood pressure (BP) in the DASH and DASH-Sodium trials, but the underlying mechanisms are unclear. We identified metabolites associated with systolic BP or diastolic BP (DBP) changes induced by dietary interventions (DASH versus control arms) in 2 randomized controlled feeding studies-the DASH and DASH-Sodium trials. METHODS Metabolomic profiling was conducted in serum and urine samples collected at the end of diet interventions: DASH (n=219) and DASH-Sodium (n=395). Using multivariable linear regression models, associations were examined between metabolites and change in systolic BP and DBP. Tested for interactions between diet interventions and metabolites were the following comparisons: (1) DASH versus control diets in the DASH trial (serum), (2) DASH high-sodium versus control high-sodium diets in the DASH-Sodium trial (urine), and (3) DASH low-sodium versus control high-sodium diets in the DASH-Sodium trial (urine). RESULTS Sixty-five significant interactions were identified (DASH trial [serum], 12; DASH high sodium [urine], 35; DASH low sodium [urine], 18) between metabolites and systolic BP or DBP. In the DASH trial, serum tryptophan betaine was associated with reductions in DBP in participants consuming the DASH diets but not control diets (P interaction, 0.023). In the DASH-Sodium trial, urine levels of N-methylglutamate and proline derivatives (eg, stachydrine, 3-hydroxystachydrine, N-methylproline, and N-methylhydroxyproline) were associated with reductions in systolic BP or DBP in participants consuming the DASH diets but not control diets (P interaction, <0.05 for all tests). CONCLUSIONS We identified metabolites that were associated with BP lowering in response to dietary interventions. REGISTRATION URL: https://www. CLINICALTRIALS gov/ct2/show/NCT03403166; Unique identifier: NCT03403166 (DASH trial). URL: https://www. CLINICALTRIALS gov/ct2/show/NCT00000608; Unique identifier: NCT00000608 (DASH-Sodium trial).
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Moderate alcohol consumption and lipoprotein subfractions: a systematic review of intervention and observational studies.
Wilkens, TL, Tranæs, K, Eriksen, JN, Dragsted, LO
Nutrition reviews. 2022;80(5):1311-1339
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Moderate consumption of alcohol has been considered as cardioprotective as it may reduce the risk of cardiovascular diseases by improving the lipid profile. This systematic review investigated the effects of regular moderate alcohol consumption of up to 60 g/day on lipoprotein subfraction changes and underlying mechanisms. A total of one hundred and fourteen studies were included in this review. The results showed that up to 60 g/day of alcohol intake increased the high-density lipoprotein (HDL) subfractions. Alcohol also increased the cardioprotective effect by increasing the cholesterol efflux capacity and paraoxonase activity in moderate drinkers. Moderate intake may also positively affect the low-density lipoprotein size. Further robust studies are required to investigate the effects of alcohol consumption on LDL subfractions and apoB lipoproteins in people with chronic diseases. Healthcare professionals can use the results of this research to understand the impact of moderate alcohol intake on HDL subfractions and its association with cardiovascular disease.
Abstract
CONTEXT Moderate alcohol consumption is associated with decreased risk of cardiovascular disease (CVD) and improvement in cardiovascular risk markers, including lipoproteins and lipoprotein subfractions. OBJECTIVE To systematically review the relationship between moderate alcohol intake, lipoprotein subfractions, and related mechanisms. DATA SOURCES Following PRISMA, all human and ex vivo studies with an alcohol intake up to 60 g/d were included from 8 databases. DATA EXTRACTION A total of 17 478 studies were screened, and data were extracted from 37 intervention and 77 observational studies. RESULTS Alcohol intake was positively associated with all HDL subfractions. A few studies found lower levels of small LDLs, increased average LDL particle size, and nonlinear relationships to apolipoprotein B-containing lipoproteins. Cholesterol efflux capacity and paraoxonase activity were consistently increased. Several studies had unclear or high risk of bias, and heterogeneous laboratory methods restricted comparability between studies. CONCLUSIONS Up to 60 g/d alcohol can cause changes in lipoprotein subfractions and related mechanisms that could influence cardiovascular health. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. 98955.
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Oxidative Stress and Inflammation Are Associated With Age-Related Endothelial Dysfunction in Men With Low Testosterone.
Babcock, MC, DuBose, LE, Witten, TL, Stauffer, BL, Hildreth, KL, Schwartz, RS, Kohrt, WM, Moreau, KL
The Journal of clinical endocrinology and metabolism. 2022;107(2):e500-e514
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Serum testosterone declines gradually with age at a rate of ~1% per year after the third decade. Vascular aging, featuring endothelial dysfunction mediated by oxidative stress and inflammation, is a major risk factor for the development of age-associated cardiovascular disease (CVD). The aim of this study was to examine the effects of low testosterone on cardiovascular aging in men. This study is a cross-sectional study which recruited 58 healthy men of all races/ethnic backgrounds aged 50-75 years (middle-aged/older) and 18-40 years (young). Results show that middle-aged/older men with lower testosterone have evidence of “accelerated” vascular aging, as indicated by a greater age-associated endothelial dysfunction of large arteries compared with their age-matched peers. The greater macrovascular endothelial dysfunction in middle-aged/older men with chronically low testosterone was independent of CVD risk factors or symptoms of androgen deficiency. Furthermore, increased systemic oxidative stress and inflammation are mechanistically linked to the greater age-associated endothelial dysfunction in middle-aged/older men with lower testosterone. Authors conclude that normal physiological levels of testosterone may be beneficial to cardiovascular health by attenuating the age-related decline in endothelial function.
Abstract
CONTEXT Vascular aging, including endothelial dysfunction secondary to oxidative stress and inflammation, increases the risk for age-associated cardiovascular disease (CVD). Low testosterone in middle-aged/older men is associated with increased CVD risk. OBJECTIVE We hypothesized that low testosterone contributes to age-associated endothelial dysfunction, related in part to greater oxidative stress and inflammation. METHODS This cross-sectional study included 58 healthy, nonsmoking men categorized as young (N = 20; age 29 ± 4 years; testosterone 500 ± 58 ng/dL), middle-aged/older with higher testosterone (N = 20; age 60 ± 6 years; testosterone 512 ± 115 ng/dL), and middle-aged/older lower testosterone (N = 18; age 59 ± 8 years; testosterone 269 ± 48 ng/dL). Brachial artery flow-mediated dilation (FMDBA) was measured during acute infusion of saline (control) and vitamin C (antioxidant). Markers of oxidative stress (total antioxidant status and oxidized low-density lipoprotein cholesterol), inflammation (interleukin [IL]-6 and C-reactive protein [CRP]), and androgen deficiency symptoms were also examined. RESULTS During saline, FMDBA was reduced in middle-aged/older compared with young, regardless of testosterone status (P < 0.001). FMDBA was reduced in middle-aged/older lower testosterone (3.7% ± 2.0%) compared with middle-aged/older higher testosterone (5.7% ± 2.2%; P = 0.021), independent of symptoms. Vitamin C increased FMDBA (to 5.3% ± 1.6%; P = 0.022) in middle-aged/older lower testosterone but had no effect in young (P = 0.992) or middle-aged/older higher testosterone (P = 0.250). FMDBA correlated with serum testosterone (r = 0.45; P < 0.001), IL-6 (r = -0.41; P = 0.002), and CRP (r = -0.28; P = 0.041). CONCLUSION Healthy middle-aged/older men with low testosterone appear to have greater age-associated endothelial dysfunction, related in part to greater oxidative stress and inflammation. These data suggest that low testosterone concentrations may contribute to accelerated vascular aging in men.
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Cardiometabolic Risk Factors and Incident Cardiovascular Disease Events in Women vs Men With Type 1 Diabetes.
Braffett, BH, Bebu, I, El Ghormli, L, Cowie, CC, Sivitz, WI, Pop-Busui, R, Larkin, ME, Gubitosi-Klug, RA, Nathan, DM, Lachin, JM, et al
JAMA network open. 2022;5(9):e2230710
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In the general population, women have a lower absolute risk of cardiovascular disease (CVD) compared with men. However, among individuals with type 1 or type 2 diabetes, the relative risk of CVD is similar or higher in women compared with men. The aim of this study was to assess sex differences in achieving recommended CVD risk management targets and associations with CVD events. This is a cohort study which included a total of 1441 (men n= 736) participants with type 1 diabetes. Results show that the prevalence and mean levels of most cardiometabolic risk factors (except for pulse rate and haemoglobin A1c) were consistent with a less atherogenic profile among women compared with men. Furthermore, achieving treatment targets for blood pressure, lipids, and glucose was associated with significantly decreased risk of CVD in both women and men. Authors conclude that their findings argue for a recalibration of CVD risk factor stratification in revised clinical care guidelines and therapeutic recommendations by sex for individuals with type 1 diabetes.
Abstract
IMPORTANCE The lower risk of cardiovascular disease (CVD) among women compared with men in the general population may be diminished among those with diabetes. OBJECTIVE To evaluate cardiometabolic risk factors and their management in association with CVD events in women vs men with type 1 diabetes enrolled in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. DESIGN, SETTING, AND PARTICIPANTS This cohort study used data obtained during the combined DCCT (randomized clinical trial, conducted 1983-1993) and EDIC (observational study, conducted 1994 to present) studies through April 30, 2018 (mean [SD] follow-up, 28.8 [5.8] years), at 27 clinical centers in the US and Canada. Data analyses were performed between July 2021 and April 2022. EXPOSURE During the DCCT phase, patients were randomized to intensive vs conventional diabetes therapy. MAIN OUTCOMES AND MEASURES Cardiometabolic risk factors and CVD events were assessed via detailed medical history and focused physical examinations. Blood and urine samples were assayed centrally. CVD events were adjudicated by a review committee. Linear mixed models and Cox proportional hazards models evaluated sex differences in cardiometabolic risk factors and CVD risk over follow-up. RESULTS A total of 1441 participants with type 1 diabetes (mean [SD] age at DCCT baseline, 26.8 [7.1] years; 761 [52.8%] men; 1390 [96.5%] non-Hispanic White) were included. Over the duration of the study, compared with men, women had significantly lower body mass index (BMI, calculated as weight in kilograms divided by height in meters squared; β = -0.43 [SE, 0.16]; P = .006), waist circumference (β = -10.56 cm [SE, 0.52 cm]; P < .001), blood pressure (systolic: β = -5.77 mm Hg [SE, 0.35 mm Hg]; P < .001; diastolic: β = -3.23 mm Hg [SE, 0.26 mm Hg]; P < .001), and triglyceride levels (β = -10.10 mg/dL [SE, 1.98 mg/dL]; P < .001); higher HDL cholesterol levels (β = 9.36 mg/dL [SE, 0.57 mg/dL]; P < .001); and similar LDL cholesterol levels (β = -0.76 mg/dL [SE, 1.22 mg/dL]; P = .53). Women, compared with men, achieved recommended targets more frequently for blood pressure (ie, <130/80 mm Hg: 90.0% vs 77.4%; P < .001) and triglycerides (ie, <150 mg/dL: 97.3% vs 90.5%; P < .001). However, sex-specific HDL cholesterol targets (ie, ≥50 mg/dL for women, ≥40 mg/dL for men) were achieved less often (74.3% vs 86.6%; P < .001) and cardioprotective medications were used less frequently in women than men (ie, angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker: 29.6% [95% CI, 25.7%-33.9%] vs 40.0% [95% CI, 36.1%-44.0%]; P = .001; lipid-lowering medication: 25.3% [95% CI, 22.1%-28.7%] vs 39.6% [95% CI, 36.1%-43.2%]; P < .001). Women also had significantly higher pulse rates (mean [SD], 75.2 [6.8] beats per minute vs 71.8 [6.9] beats per minute; P < .001) and hemoglobin A1c levels (mean [SD], 8.3% [1.0%] vs 8.1% [1.0%]; P = .01) and achieved targets for tighter glycemic control less often than men (ie, hemoglobin A1c <7%: 11.2% [95% CI, 9.3%-13.3%] vs 14.0% [95% CI, 12.0%-16.3%]; P = .03). CONCLUSIONS AND RELEVANCE These findings suggest that despite a more favorable cardiometabolic risk factor profile, women with type 1 diabetes did not have a significantly lower CVD event burden than men, suggesting a greater clinical impact of cardiometabolic risk factors in women vs men with diabetes. These findings call for conscientious optimization of the control of CVD risk factors in women with type 1 diabetes.
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The Weight Optimization Revamping Lifestyle using the Dietary Guidelines (WORLD) Study: Sustained Weight Loss Over 12 Months.
Psota, TL, Tindall, AM, Lohse, B, Miller, PE, Petersen, KS, Kris-Etherton, PM
Obesity (Silver Spring, Md.). 2020;28(7):1235-1244
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Effective long-term weight loss strategies to reduce the risk of death and diseases associated with being obese or overweight are required, as restrictive programmes are difficult to sustain, and weight loss may be heavily influenced by behavioural factors. This randomised control trial of 101 premenopausal women with obesity or overweight aimed to compare a lower-fat and moderate-fat diets, both with nutrition education for 12 months. The results showed that both treatment groups lost weight. Both groups consumed the same amount of fat but increased their diet quality. Diet quality and greater attendance at nutritional education sessions were associated with greater weight loss. Cholesterol was significantly lower in both groups, but blood pressure remained unchanged. Interestingly there were a large number of women who did not complete the trial. It was concluded that irrespective of the amount of fat consumed, nutrition education can help to achieve sustained weight loss, improve diet quality and decrease heart disease risk for at least 12 months. This study could be used by healthcare professionals to understand that recommending fat-based targets for weight loss may be ineffective and the importance of emotional and behavioural support for individuals on a weight loss regime to improve their risk for heart disease.
Abstract
OBJECTIVE This study aimed to compare two energy-restricted, nutrient-dense diets at the upper or lower ends of the dietary fat recommendation range (lower fat [20% energy from fat] versus moderate fat [35%]) on weight loss using behavioral theory-based nutrition education. METHODS A total of 101 premenopausal women with overweight or obesity were randomized to an energy-restricted lower-fat or moderate-fat diet for 1 year. Interventions included 28 behavioral theory-based nutrition education sessions plus weekly exercise sessions. RESULTS Both treatment groups experienced weight loss (-5.0 kg for lower fat and -4.3 kg for moderate fat; P < 0.0001), but there was no difference in weight loss or fat intake between groups. Total and low-density lipoprotein cholesterol decreased (-3. 4 mg/dL and -3.8 mg/dL; P < 0.05), and high-density lipoprotein cholesterol increased (1.9 mg/dL; P < 0.05) in both groups at 12 months. Diet quality, assessed by the Healthy Eating Index, increased significantly at 4 months versus baseline (70.8 [0.9] vs. 77.8 [1.0]) and was maintained through 12 months. Higher Healthy Eating Index scores were associated with greater weight loss at 4 months (r = -0.2; P < 0.05). CONCLUSIONS In the context of a well-resourced, free-living weight-loss intervention, total fat intake did not change; however, theory-based nutrition education underpinned by food-based recommendations resulted in caloric deficits, improvements in diet quality, and weight loss that was sustained for 1 year.
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Effect of a Comprehensive Cardiovascular Risk Reduction Intervention in Persons With Serious Mental Illness: A Randomized Clinical Trial.
Daumit, GL, Dalcin, AT, Dickerson, FB, Miller, ER, Evins, AE, Cather, C, Jerome, GJ, Young, DR, Charleston, JB, Gennusa, JV, et al
JAMA network open. 2020;3(6):e207247
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Heart disease death rates in individuals with serious mental illness are double that of the general population, indicating a concerted effort is needed to help this group of people. However, previous studies on interventions have failed to show improvements indicating a requirement to identify effective solutions. This randomised control trial of 269 individuals with mental illness aimed to determine the effectiveness of an 18-month management plan to reduce heart disease risk. The results showed that heart disease risk was significantly decreased when individuals with mental illness were in a closely monitored management programme. This programme consisted of behavioural counselling and care coordination. It was concluded that a multi-faceted care management plan can significantly reduce the risk of heart disease in individuals with serious mental illness. This study could be used by health care professionals to understand that individuals with mental illness are at a higher risk of death from heart disease and that they need to consider enrolling them into a closely monitored management plan.
Abstract
Importance: Persons with serious mental illness have a cardiovascular disease mortality rate more than twice that of the overall population. Meaningful cardiovascular risk reduction requires targeted efforts in this population, who often have psychiatric symptoms and cognitive impairment. Objective: To determine the effectiveness of an 18-month multifaceted intervention incorporating behavioral counseling, care coordination, and care management for overall cardiovascular risk reduction in adults with serious mental illness. Design, Setting, and Participants: This randomized clinical trial was conducted from December 2013 to November 2018 at 4 community mental health outpatient programs in Maryland. The study recruited adults with at least 1 cardiovascular disease risk factor (hypertension, diabetes, dyslipidemia, current tobacco smoking, and/or overweight or obesity) attending the mental health programs. Of 398 participants screened, 269 were randomized to intervention (132 participants) or control (137 participants). Data collection staff were blinded to group assignment. Data were analyzed on the principle of intention to treat, and data analysis was performed from November 2018 to March 2019. Interventions: A health coach and nurse provided individually tailored cardiovascular disease risk reduction behavioral counseling, collaborated with physicians to implement appropriate risk factor management, and coordinated with mental health staff to encourage attainment of health goals. Programs offered physical activity classes and received consultation on serving healthier meals; intervention and control participants were exposed to these environmental changes. Main Outcomes and Measures: The primary outcome was the change in the risk of cardiovascular disease from the global Framingham Risk Score (FRS), which estimates the 10-year probability of a cardiovascular disease event, from baseline to 18 months, expressed as percentage change for intervention compared with control. Results: Of 269 participants randomized (mean [SD] age, 48.8 [11.9] years; 128 men [47.6%]), 159 (59.1%) had a diagnosis of schizophrenia or schizoaffective disorder, 67 (24.9%) had bipolar disorder, and 38 (14.1%) had major depressive disorder. At 18 months, the primary outcome, FRS, was obtained for 256 participants (95.2%). The mean (SD) baseline FRS was 11.5% (11.5%) (median, 8.6%; interquartile range, 3.9%-16.0%) in the intervention group and 12.7% (12.7%) (median, 9.1%; interquartile range, 4.0%-16.7%) in the control group. At 18 months, the mean (SD) FRS was 9.9% (10.2%) (median, 7.7%; interquartile range, 3.1%-12.0%) in the intervention group and 12.3% (12.0%) (median, 9.7%; interquartile range, 4.0%-15.9%) in the control group. Compared with the control group, the intervention group experienced a 12.7% (95% CI, 2.5%-22.9%; P = .02) relative reduction in FRS at 18 months. Conclusions and Relevance: An 18-month behavioral counseling, care coordination, and care management intervention statistically significantly reduced overall cardiovascular disease risk in adults with serious mental illness. This intervention provides the means to substantially reduce health disparities in this high-risk population. Trial Registration: ClinicalTrials.gov Identifier: NCT02127671.
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Dietary flavanols improve cerebral cortical oxygenation and cognition in healthy adults.
Gratton, G, Weaver, SR, Burley, CV, Low, KA, Maclin, EL, Johns, PW, Pham, QS, Lucas, SJE, Fabiani, M, Rendeiro, C
Scientific reports. 2020;10(1):19409
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Fruits and vegetables contain flavonoids that can protect against vascular diseases and cognitive ageing. Studies have shown that cocoa flavonoids can enhance the function of endothelial cells and blood vessels in peripheral arteries. This randomised, double-blinded, placebo-controlled crossover study assessed the effects of cocoa flavanols on cerebral and peripheral vascular and cognitive function. The healthy young subjects showed greater tissue oxygenation and cerebrovascular reactivity in the frontal parts of the brain during the carbon dioxide challenge after high cocoa flavonoid intervention. Furthermore, the cocoa flavonoid intervention improved cognitive and peripheral endothelial functions in healthy young subjects. Even though the mechanistic link behind the beneficial effects of flavonoids is not understood completely, the positive effects could be due to the ability of flavanols to enhance the bioavailability of circulation Nitric Oxide (NO). The study also found that flavonoids improved cognitive function in healthy individuals only when there was a high cognitive demand. Further robust studies are required to evaluate the mechanisms behind the benefits associated with acute flavonoid intake. Healthcare professionals can utilise the findings from this study to gain insight into the advantages of consuming a flavonoid-rich diet. Additionally, they can learn about the differing responses to flavanol intake between individuals.
Abstract
Cocoa flavanols protect humans against vascular disease, as evidenced by improvements in peripheral endothelial function, likely through nitric oxide signalling. Emerging evidence also suggests that flavanol-rich diets protect against cognitive aging, but mechanisms remain elusive. In a randomized double-blind within-subject acute study in healthy young adults, we link these two lines of research by showing, for the first time, that flavanol intake leads to faster and greater brain oxygenation responses to hypercapnia, as well as higher performance only when cognitive demand is high. Individual difference analyses further show that participants who benefit from flavanols intake during hypercapnia are also those who do so in the cognitive challenge. These data support the hypothesis that similar vascular mechanisms underlie both the peripheral and cerebral effects of flavanols. They further show the importance of studies combining physiological and graded cognitive challenges in young adults to investigate the actions of dietary flavanols on brain function.
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Treatment With a Marine Oil Supplement Alters Lipid Mediators and Leukocyte Phenotype in Healthy Patients and Those With Peripheral Artery Disease.
Schaller, MS, Chen, M, Colas, RA, Sorrentino, TA, Lazar, AA, Grenon, SM, Dalli, J, Conte, MS
Journal of the American Heart Association. 2020;9(15):e016113
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Peripheral artery disease (PAD) is one of the most advanced forms of atherosclerosis. This disease state begins from an inflammatory lesion. The aim of this study was to investigate the impact of a short-course, oral, enriched marine oil supplement on circulating leukocytes and biochemical mediators in patients with symptomatic PAD and healthy controls. This study is a prospective, open-label, nonblinded study. Twenty participants completed the study: ten with PAD and 10 healthy individuals. Results show: - a shift in the leukocyte profiling towards a less inflammatory and more pro-resolving phenotype, most notably within the PAD cohort. - that supplementation led to an increase in phagocytic [a type of immune cell] activity of peripheral blood monocytes and neutrophils. - that circulating monocyte phenotyping demonstrated reduced expression of multiple proinflammatory markers. - that gene expression patterns in mono-derived macrophage from patients with PAD displayed a less inflammatory (type 1 macrophage) and greater reparative (type 2 macrophage) phenotype after supplementation. Authors conclude that their findings provide a foundation for characterising biochemical and cellular biomarkers of inflammation and resolution in PAD.
Abstract
Background Peripheral artery disease (PAD) is an advanced form of atherosclerosis characterized by chronic inflammation. Resolution of inflammation is a highly coordinated process driven by specialized pro-resolving lipid mediators endogenously derived from omega-3 fatty acids. We investigated the impact of a short-course, oral, enriched marine oil supplement on leukocyte phenotype and biochemical mediators in patients with symptomatic PAD and healthy volunteers. Methods and Results This was a prospective, open-label study of 5-day oral administration of an enriched marine oil supplement, assessing 3 escalating doses in 10 healthy volunteers and 10 patients with PAD. Over the course of the study, there was a significant increase in the plasma level of several lipid mediator families, total specialized pro-resolving lipid mediators, and specialized pro-resolving lipid mediator:prostaglandin ratio. Supplementation was associated with an increase in phagocytic activity of peripheral blood monocytes and neutrophils. Circulating monocyte phenotyping demonstrated reduced expression of multiple proinflammatory markers (cluster of differentiation 18, 163, 54, and 36, and chemokine receptor 2). Similarly, transcriptional profiling of monocyte-derived macrophages displayed polarization toward a reparative phenotype postsupplementation. The most notable cellular and biochemical changes over the study occurred in patients with PAD. There were strong correlations between integrated biochemical measures of lipid mediators (specialized pro-resolving lipid mediators:prostaglandin ratio) and phenotypic changes in circulating leukocytes in both healthy individuals and patients with PAD. Conclusions These data suggest that short-term enriched marine oil supplementation dramatically remodels downstream lipid mediator pathways and induces a less inflammatory and more pro-resolution phenotype in circulating leukocytes and monocyte-derived macrophages. Further studies are required to determine the potential clinical relevance of these findings in patients with PAD. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02719665.
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A clinically meaningful metric of immune age derived from high-dimensional longitudinal monitoring.
Alpert, A, Pickman, Y, Leipold, M, Rosenberg-Hasson, Y, Ji, X, Gaujoux, R, Rabani, H, Starosvetsky, E, Kveler, K, Schaffert, S, et al
Nature medicine. 2019;25(3):487-495
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The human immune system changes with age, ultimately leading to a clinically evident, profound deterioration resulting in high morbidity and mortality rates attributed to infectious and chronic diseases. The aim of this study was to assess at high resolution the dynamics of older adults’ immune systems. The study uses multiple ‘omics’ technologies in a cohort of 135 adults (63 young adults and 72 older adults) of different ages who were sampled longitudinally over the course of 9 years to comprehensively capture population- and individual-level changes in the immune system over time. Results indicate that immune-cell frequencies changed at substantially different rates; some cell subsets show no directionality of change yet differ between young and old individuals, whereas other cell subsets continued changing (either increasing or decreasing) throughout the course of the study. Authors postulate that an individual’s immune age is a function of life history, namely environmental exposure coupled with genetic background. Thus, immune modulators may one day be identified that affect the position of an individual’s immune system along the immunological landscape.
Abstract
Immune responses generally decline with age. However, the dynamics of this process at the individual level have not been characterized, hindering quantification of an individual's immune age. Here, we use multiple 'omics' technologies to capture population- and individual-level changes in the human immune system of 135 healthy adult individuals of different ages sampled longitudinally over a nine-year period. We observed high inter-individual variability in the rates of change of cellular frequencies that was dictated by their baseline values, allowing identification of steady-state levels toward which a cell subset converged and the ordered convergence of multiple cell subsets toward an older adult homeostasis. These data form a high-dimensional trajectory of immune aging (IMM-AGE) that describes a person's immune status better than chronological age. We show that the IMM-AGE score predicted all-cause mortality beyond well-established risk factors in the Framingham Heart Study, establishing its potential use in clinics for identification of patients at risk.