The effect of conjugated linoleic acids on inflammation, oxidative stress, body composition and physical performance: a comprehensive review of putative molecular mechanisms.

Conjugated linoleic acids (CLAs) are polyunsaturated fatty acids primarily found in dairy products and ruminant animal products such as beef, lamb, and butter. Supplementation of CLAs has recently become popular among athletes due to the variety of health-promoting effects, including improvements in physical performance. Preclinical and some clinical studies have shown that CLAs can reduce inflammation and oxidative stress and favorably modulate body composition and physical performance; however, the results of previously published clinical trials are mixed. Here, we performed a comprehensive review of previously published clinical trials that assessed the role of CLAs in modulating inflammation, oxidative stress, body composition, and select indices of physical performance, emphasizing the molecular mechanisms governing these changes. The findings of our review demonstrate that the effect of supplementation with CLAs on inflammation and oxidative stress is controversial, but this supplement can decrease body fat mass and increase physical performance. Future well-designed randomized clinical trials are warranted to determine the effectiveness of (1) specific doses of CLAs; (2) different dosing durations of CLAs; (3) various CLA isomers, and the exact molecular mechanisms by which CLAs positively influence oxidative stress, inflammation, body composition, and physical performance.

Effect of enteral immunomodulatory nutrition formula on mortality and critical care parameters in critically ill patients: A systematic review with meta-analysis.

BACKGROUND: Enteral immunomodulatory nutrition is recommended as an adjuvant therapy for patients in intensive care units (ICU), but its effectiveness is incompletely understood. AIM: The aim of this review was to examine the effect of a commonly used immunomodulatory formula-omega-3 fatty acids, γ-linolenic acid, and antioxidants-on clinical outcomes and mortality risk in critically ill patients. DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). METHOD: PubMed, Scopus, and Institute for Scientific Information (ISI) Web of Knowledge databases were searched until 18 February 2021. RCTs that used the immunomodulatory formula in the ICU were included. RESULTS: Ten RCTs (1166 participants) were included in the meta-analysis. The immunomodulatory formula reduced the duration of ICU stay weighted mean difference [(WMD): -2.97 days; 95%CI: -5.59, -0.35)], mechanical ventilation (WMD = -2.20 days, 95%CI: -4.29, -0.10), sequential organ failure assessment and multiple organ dysfunction scores (Hedge's g: -0.42 U/L; 95% CI: -0.74, -0.11), decreased 8-day overall mortality risk (RR = 0.74, 95% CI: 0.58, 0.91), and extended the ICU-free days (WMD: 4.06 days, 95% CI: 0.02, 8.09). The improvement in respiratory function and reduction in mortality risk was more in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Furthermore, the reduction in mechanical ventilation and mortality risk was more evident in older (>60 years) vs young adults. CONCLUSION AND RELEVANCE TO CLINICAL PRACTICE: Taken together, the immunomodulatory formula may enhance clinical practice for critical care nurses, such that the prevalence and/or susceptibility to secondary conditions commonly encountered in the ICU (ie, ALI and ARDS) could be attenuated, ultimately allowing critical care nurses to focus their care on the primary reason for which a patient is in the ICU. The study protocol was registered in PROSPERO.

Doxorubicin-Induced Oxidative Stress and Endothelial Dysfunction in Conduit Arteries Is Prevented by Mitochondrial-Specific Antioxidant Treatment.

BACKGROUND: Doxorubicin (DOXO) chemotherapy increases risk for cardiovascular disease in part by inducing endothelial dysfunction in conduit arteries. However, the mechanisms mediating DOXO-associated endothelial dysfunction in (intact) arteries and treatment strategies are not established. OBJECTIVES: We tested the hypothesis that DOXO impairs endothelial function in conduit arteries via excessive mitochondrial reactive oxygen species (ROS) and that these effects could be prevented by treatment with a mitochondrial-targeted antioxidant (MitoQ). METHODS: Endothelial function (endothelium-dependent dilation [EDD] to acetylcholine) and vascular mitochondrial ROS were assessed 4 weeks following administration (10 mg/kg intraperitoneal injection) of DOXO. A separate cohort of mice received chronic (4 weeks) oral supplementation with MitoQ (drinking water) for 4 weeks following DOXO. RESULTS: EDD in isolated pressurized carotid arteries was 55% lower 4 weeks following DOXO (peak EDD, DOXO: 42 ± 7% vs. sham: 94 ± 3%; p = 0.006). Vascular mitochondrial ROS was 52% higher and manganese (mitochondrial) superoxide dismutase was 70% lower after DOXO versus sham (p = 0.0008). Endothelial function was rescued by administration of the mitochondrial-targeted antioxidant, MitoQ, to the perfusate. Exposure to plasma from DOXO-treated mice increased mitochondrial ROS in cultured endothelial cells. Analyses of plasma showed differences in oxidative stress-related metabolites and a marked reduction in vascular endothelial growth factor A in DOXO mice, and restoring vascular endothelial growth factor A to sham levels normalized mitochondrial ROS in endothelial cells incubated with plasma from DOXO mice. Oral MitoQ supplementation following DOXO prevented the reduction in EDD (97 ± 1%; p = 0.002 vs. DOXO alone) by ameliorating mitochondrial ROS suppression of EDD. CONCLUSIONS: DOXO-induced endothelial dysfunction in conduit arteries is mediated by excessive mitochondrial ROS and ameliorated by mitochondrial-specific antioxidant treatment. Mitochondrial ROS is a viable therapeutic target for mitigating arterial dysfunction with DOXO. (J Am Coll Cardiol CardioOnc 2020;2:475-88) © 2020 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

Biochemical, Anthropometric, and Physiological Responses to Carbohydrate-Restricted Diets Versus a Low-Fat Diet in Obese Adults: A Randomized Crossover Trial.

Some research supports high-fat carbohydrate (CHO)-restricted diets for weight and fat loss and improvement of cardiovascular disease risk factors. To test this, a randomized crossover study was designed. Subjects (17 obese men and women [BMI: 30-38 kg/m2]) were fed three diets (supplying 1600 and 2200 kilocalories (kcal)/day for women and men, respectively) for 4 weeks, with each trial separated by 4-week washout periods. One CHO-restricted diet (10% CHO, 50% fat, and 40% protein content) was rich in plant foods and mushrooms, while the other CHO-restricted diet included more animal foods (10% CHO, 60% fat, and 30% protein content). The third diet was lower in fat and protein content (LF) and higher in CHOs (61% CHO, 21% fat, and 18% protein content). Body composition was assessed through hydrostatic weighing before and after each diet trial. Fasting blood samples were collected weekly for analysis of hormones and lipids. Data were analyzed through repeated measures analysis of variance with post hoc paired comparison t-tests. Weight and fat loss were similar (P > .05) among trials. Subjects lost lean mass (P < .05) during CHO-restricted trials, but not in the LF trial. Insulin concentrations decreased (P < .05) during the CHO-restricted trial and tended (P = .05) to decrease during the LF trial. Total cholesterol decreased (P < .05) for all trials; however, high-density lipoprotein cholesterol decreased (P < .05) and triacylglycerols were higher (P < .05) following the LF trial. Taken together, energy restriction regardless of diet composition promoted similar weight loss; however, CHO-restricted diets based on either plants/mushrooms or animal foods elicited a more beneficial lipid-altering effect in comparison with the LF diet.

A diet containing high- versus low-daidzein does not affect bone density and osteogenic gene expression in the obese Zucker rat model.

Phytoestrogens are nonsteroidal plant compounds with similar chemical structures to mammalian estrogen capable of mimicking the effect of estrogen in selective tissues. A diet rich in phytoestrogens is associated with a variety of health benefits including decreased risks for heart disease, breast cancer, and osteoporosis. Obesity has long thought to be associated with improved bone density due to increased mechanical loading, but recent literature suggests obesity may actually decrease bone health. Daidzein, a soy-derived phytoestrogen, has been shown to improve parameters of bone health in lean animal models of osteoporosis but has not been tested in obese animals. Following a one-week acclimation to a standard AIN-93G diet, 19 five-week-old female obese Zucker rats (OZR) were randomly assigned to a modified AIN-93G diet containing either high daidzein (HD, 0.121 g kg-1 feed) or low daidzein (LD, 0.01 g kg-1 feed). After 8 weeks, tibias and femurs were removed to assess true density (Archimedes principal), mechanical strength (three-point bending test), and femoral osteogenic gene expression. Serum was collected to assess osteocalcin and deoxypyridinoline. Our results indicated that there were no significant differences between the measures for tibial or femoral true density or mechanical strength for the rats in the HD and LD diet groups. Similarly, there were no significant differences in gene expressions related to osteogenic pathways, or serum biomarkers of bone formation and resorption. Overall, an increased dose of daidzein from soy protein supplementation does not elicit an improvement in markers of bone health in obese Zucker rats.

Heat therapy improves glucose tolerance and adipose tissue insulin signaling in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is associated with high rates of obesity and metabolic dysfunction. Repeated passive heat exposure (termed heat therapy) is a novel lifestyle intervention for improving health in obese women with PCOS. The purpose of this study was to examine changes in metabolic function in obese women with PCOS following heat therapy. Eighteen age- and BMI-matched obese women with PCOS (age: 27 ± 1 yr, BMI: 41.3 ± 1.1 kg/m-2) were assigned to heat therapy (HT) or time control (CON). HT participants underwent 30 one-hour hot tub sessions over 8-10 wk, while CON participants completed all testing but did not undergo heat therapy. Before (Pre), at the mid-point (Mid), and following (Post) 8-10 wk of heat therapy, metabolic health was assessed using a 2-h oral glucose tolerance test, a subcutaneous abdominal fat biopsy (Pre-Post only), and other blood markers relating to metabolic function. HT participants exhibited improved fasting glucose (Pre: 105 ± 3, Post: 89 ± 5mg/dl; P = 0.001), glucose area under the curve (AUC) (Pre: 18,698 ± 1,045, Post: 16,987 ± 1,017 mg·dl-1·min-1; P = 0.028) and insulin AUC (Pre: 126,924 ± 11,730, Post: 91,233 ± 14,429 IU l-1·min-1; P = 0.012). Adipocyte insulin signaling (p-AKT at Ser-473 with 1.2 nM insulin) increased in HT (Pre: 0.29 ± 0.14, Post: 0.93 ± 0.29 AU; P = 0.021). Additionally, serum testosterone declined in HT participants (Pre: 51 ± 7, Post: 34 ± 4 ng/dl; P = 0.033). No parameters changed over time in CON, and no change in BMI was observed in either group. HT substantially improved metabolic risk profile in obese women with PCOS. HT also reduced androgen excess and may improve PCOS symptomology.

Snack selection influences glucose metabolism, antioxidant capacity and cholesterol in healthy overweight adults: A randomized parallel arm trial.

Including carbohydrate/fructose-rich foods (predominantly fruit) in the diets of overweight individuals can improve chronic disease risk factors. We hypothesized dried plums (DP) would improve nutrient consumption, total antioxidant capacity (TAC), lipid and adipokine profiles, and would decrease adiposity and inflammation. To test this, we studied the effects of 8-weeks of twice-daily snacking of macronutrient-matched 100kcal servings of DP or refined carbohydrate-rich snack (low-fat muffins: LFM) on daily energy and nutrient consumption, and chronic disease risk factors in overweight adults. Body weight/composition, waist circumference, blood pressure, plasma glucose, insulin, c-peptide, lipids, TAC, adipokines and inflammation were measured at baseline and throughout the study. Postprandial glucose and insulin were assessed following assigned test foods at baseline and 8-weeks. Repeated measures ANOVAs were undertaken to examine group and time differences. Post-hoc independent and paired samples t-tests were conducted where necessary. DP increased (P<.05) overall intake of dietary fiber and potassium, and TAC, from baseline to 8-weeks. Baseline postprandial glycemia tended (P=.09) to be lower with DP versus LFM, while both groups had a decreased response after 8-weeks. Postprandial insulinemia was lower (P<.05) for DP at both time-points. No differences in body weight/composition, blood pressure, or fasting glucose, insulin, triglycerides, total cholesterol, HDL-C, inflammation or adipokines were detected. Low-density lipoprotein cholesterol (LDL-C) increased (P<.05) throughout the trial following LFM. Overall, DP lessened postprandial insulinemia, improved nutrient consumption and plasma TAC, and maintained plasma LDL-C compared to a macronutrient-matched refined carbohydrate snack, which could decrease chronic disease risk.

Meta-inflammation and cardiometabolic disease in obesity: Can heat therapy help?

Obesity and associated metabolic dysfunction have reached epidemic proportions worldwide. The current theory linking metabolic disease and obesity involves ischemic adipose tissue initiating an inflammatory cascade that results in systemic insulin resistance and may eventually lead to type II diabetes mellitus. Diabetes and associated metabolic dysfunction increase the risk of developing cardiovascular disease and fatal cardiovascular events. By targeting key steps in this process, ischemia and inflammation, this cascade may be prevented or reversed and thus metabolic and cardiovascular health may be preserved in obesity. Regular heat exposure (termed 'heat therapy') offers potential to improve cardiometabolic health in obese individuals through a variety of mechanisms that include but are not limited to heat shock proteins, hypoxia-inducible factor 1α, and hemodynamic effects. The purpose of this review is to highlight the cardiometabolic decline in obese individuals stemming from adipose tissue dysfunction, and examine the ways in which heat therapy and associated cellular and systemic adaptations can intersect with this decline in function to improve or restore cardiovascular and metabolic health.