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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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The Impact of Coconut Oil and Epigallocatechin Gallate on the Levels of IL-6, Anxiety and Disability in Multiple Sclerosis Patients.
Platero, JL, Cuerda-Ballester, M, Ibáñez, V, Sancho, D, Lopez-Rodríguez, MM, Drehmer, E, Ortí, JER
Nutrients. 2020;12(2)
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Multiple Sclerosis (MS) is associated with high levels of inflammation, especially the inflammatory molecule interleukin 6 (IL-6). Anxiety has been reported to be linked to inflammation and IL-6. Epigallocatechin gallate (EGCG) is a naturally occurring chemical, which has anti-inflammatory properties and has been related to improvements in anxiety. This pilot study of 51 individuals with MS aimed to assess the impact of EGCG and coconut oil on IL-6 and anxiety over 4 months. The results showed that individuals receiving EGCG and coconut oil had decreased IL-6 and anxiety. However, the individuals who did not also showed decreased IL-6 but not anxiety. It was concluded that anxiety was decreased in individuals with MS when taking EGCG and coconut oil, but this does not appear to be as a direct result of decreased IL-6 levels. It may be due to the Mediterranean diet all participants were asked to follow during the intervention. This study could be used by healthcare professionals to understand the relationship between IL-6 and anxiety in patients with MS.
Abstract
BACKGROUND Due to the inflammatory nature of multiple sclerosis (MS), interleukin 6 (IL-6) is high in blood levels, and it also increases the levels of anxiety related to functional disability. Epigallocatechin gallate (EGCG) decreases IL-6, which could be enhanced by the anti-inflammatory effect of high ketone bodies after administering coconut oil (both of which are an anxiolytic). Therefore, the aim of this study was to assess the impact of coconut oil and EGCG on the levels of IL-6, anxiety and functional disability in patients with MS. METHODS A pilot study was conducted for four months with 51 MS patients who were randomly divided into an intervention group and a control group. The intervention group received 800 mg of EGCG and 60 mL of coconut oil, and the control group was prescribed a placebo. Both groups followed the same isocaloric Mediterranean diet. State and trait anxiety were determined before and after the study by means of the State-Trait Anxiety Inventory (STAI). In addition, IL-6 in serum was measured using the ELISA technique and functional capacity was determined with the Expanded Disability Status Scale (EDSS) and the body mass index (BMI). RESULTS State anxiety and functional capacity decreased in the intervention group and IL-6 decreased in both groups. CONCLUSIONS EGCG and coconut oil improve state anxiety and functional capacity. In addition, a decrease in IL-6 is observed in patients with MS, possibly due to the antioxidant capacity of the Mediterranean diet and its impact on improving BMI.
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Rhodiola/Cordyceps-Based Herbal Supplement Promotes Endurance Training-Improved Body Composition But Not Oxidative Stress and Metabolic Biomarkers: A Preliminary Randomized Controlled Study.
Liao, YH, Chao, YC, Sim, BY, Lin, HM, Chen, MT, Chen, CY
Nutrients. 2019;11(10)
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Physical inactivity has negative health consequences. Such consequences include muscle loss, weight gain, low-grade inflammation, oxidative stress and increased disease risk for metabolic disorders such as type 2 diabetes and cardiovascular diseases. The development of such chronic metabolic disorders often starts at a much younger age, long before it manifests as clinical disease decades later. Endurance exercise is one way to reduce the development and progression of metabolic disease. In addition, the herb Rhodiola crenulata (RC) and fungus Cordyceps sinensis (CS) have shown to bear benefits on metabolic disease parameters. Both have long been used in Chinese medicine for their health-promoting, antioxidant and anti-inflammatory effects. This study sought to assess whether the benefits of regular endurance training can be futher enhanced with the supplementation of RC and CS. This randomized, double-blind, placebo-controlled trial enrolled 14 young sedentary adults who received an 8-week endurance training program. They also received either supplements or a placebo. Measurements and markers of body composition, oxidative stress and metabolic function were obtained before and after the intervention. The results found no difference in blood fats and oxidative stress markers between groups. In fact endurance training alone improved endurance capacity and glycemic control, but again with no particular difference between control and intervention. However, the supplementation group showed improvement in body composition with reduced body fat and increased muscle mass compared to the control group. Larger studies are needed to strengthen the results.
Abstract
Rhodiola crenulata (R) and Cordyceps sinensis (C) are commonly used herbs that promote health in traditional Chinese medicine. These two herbs have also been shown to exhibit anti-inflammation and antioxidant functions. Regular endurance training reveals potent endurance capacity, body composition improvement, and metabolic-related biomarker benefits. However, it is not known whether the combination of Rhodiola crenulata and Cordyceps sinensis (RC) supplementation during endurance training provides additive health benefits. The purpose of this study was to investigate the effects of 8-week endurance training plus RC supplementation on body composition, oxidative stress, and metabolic biomarkers in young sedentary adults. METHODS Fourteen young sedentary adults (8M/6F) participated in this double-blind randomized controlled study. Participants were assigned to exercise training with placebo groups (PLA, n = 7, 4M/3F; age: 21.4 ± 0.4 years) and exercise training with the RC group (RC, 20 mg/kg/day; n = 7, 4M/3F; age: 21.7 ± 0.4 years). Both groups received identical exercise training for eight weeks. The body composition, circulating oxidative stress, and blood metabolic biomarkers were measured before and after the 8-week intervention. RESULTS Improvement in body composition profiles were significantly greater in the RC group (body weight: p = 0.044, BMI: p = 0.003, upper extremity fat mass: p = 0.032, lower extremity muscle mass: p = 0.029, trunk fat mass: p = 0.011) compared to the PLA group after training. The blood lipid profile and systemic oxidative stress makers (thiobarbituric reactive substanceand total antioxidant capacity) did not differ between groups. Although endurance training markedly improved endurance capacity and glycemic control ability (i.e., fast blood glucose, insulin, and HOMA index), there were no differences in these variables between treatments. CONCLUSIONS In this preliminary investigation, we demonstrated that an 8-week RC supplementation (20 mg/kg/day) faintly enhanced endurance training-induced positive adaptations in body composition in young sedentary individuals, whereas the blood lipid profile and systemic oxidative stress states were not altered after such intervention.