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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 influence of macronutrient intake, stress and prostaglandin levels (pgf2α) of urine with the incidence of dysmenorrhea in adolescents.
Tahir, A, Sinrang, AW, Jusuf, EC, Syamsuddin, S, Stang, Arsyad, A
Gaceta sanitaria. 2021;35 Suppl 2:S298-S301
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Dysmenorrhea is a health problem that has a negative impact on the physical and emotional aspects of health. It also causes absenteeism in school that affects academic performance. The aim of this study was to analyse the influence of macronutrient intake, stress, and prostaglandin levels (pgf2α) on adolescent dysmenorrhea incidence. This study is an observational cohort study of 16 years old adolescents with a menstrual cycle every 21–35 days and a menstrual period of about 5–7 days. Results show that: - levels of pgf2α affect the incidence of dysmenorrhea i.e., prostaglandins can reduce or temporarily inhibit blood supply to the uterus, causing the uterus to lack oxygen and cause myometrium contraction which in turn causes pain. - stress is very influential with dysmenorrhea as it can interfere with the work of the endocrine system. - an insufficient intake of nutrients may increase the risk of dysmenorrhoea. Thus, adolescents should ensure adequate intake of macronutrients especially during menstruation. Authors conclude that stress and prostaglandin levels significantly affect the occurrence of dysmenorrhea in adolescents.
Abstract
OBJECTIVES This study aimed to analyze the influence of macronutrient intake, stress, and prostaglandin levels (pgf2α) on adolescent dysmenorrhea incidence. METHOD This type of study is observational analytic with a cohort study draft done in January-March 2020 at High junior school 21 Makassar. Respondents in this study were grade X and XI students divided into 64 teenagers who had dysmenorrhea and 64 adolescents who did not experience Dysmenrhea. The criteria of the respondent in this study were the reproductive age, already experiencing menstruation, knowing the time and date of menstruation, menstrual cycles were regular, and willing to be respondents. The study used Menstrual Symptoms Questionnaire (MSQ) and used an ultrasonography (ultrasound) examination to perform the sample cervical. Food recall 24 hours to assess the intake of macronutrients, Depression Anxiety Stress Scales (DASS 42) to measure stress levels, and an examination of urine prostaglandin levels using the method Enzyme-Linked Immunosorbent Assay (ELISA). Urine intake is carried out on the second day as much as 2-5cc. Data were analyzed by the Chi-square test and logistics regression backward. RESULT A multivariate analysis showed a variable that strongly affects dysmenorrhea is stress with the value p=0.000 and the level of prostaglandins with p-value=0.003 compared to other variables. CONCLUSION Stress and prostaglandin levels significantly affect the occurrence of dysmenorrhea in adolescents.
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Stress matters: Randomized controlled trial on the effect of probiotics on neurocognition.
Papalini, S, Michels, F, Kohn, N, Wegman, J, van Hemert, S, Roelofs, K, Arias-Vasquez, A, Aarts, E
Neurobiology of stress. 2019;10:100141
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Increasing animal studies indicate the role of probiotics in regulating mood and cognition through the gut-brain axis, however in human studies evidence of this causal association is lacking. The aim of this double-blind, randomised, placebo-controlled intervention was to investigate the effects of probiotics on neurocognitive measures in 58 healthy participants. Participants were randomly assigned to either probiotic or placebo group and were tested once before and after the 28-day intervention. The neurocognitive outcomes measured included emotion reactivity, emotion regulation, cognitive control and the effects of acute stress on working memory. These were assessed through functional MRI (fMRI) and questionnaires. This study found when stress was induced, probiotic supplementation led to a significant improvement in working memory performance. Without stress, there was no causal association between neurocognitive outcomes and probiotic intake. Based on these results, the authors conclude that during challenging situations, probiotics can aid in buffering the detrimental effects of stress on cognition.
Abstract
Probiotics are microorganisms that provide health benefits when consumed. In animals, probiotics reverse gut microbiome-related alterations in depression-like symptoms, in cognition, and in hormonal stress response. However, in humans, a causal understanding of the gut-brain link in emotion and cognition is lacking. Additionally, whether the effects of probiotics on neurocognition are visible only in presence of stress, remains unclear. We investigated the effects of a multispecies probiotic (Ecologic®Barrier) on specific neurocognitive measures of emotion reactivity, emotion regulation, and cognitive control using fMRI. Critically, we also tested whether probiotics can buffer against the detrimental effects of acute stress on working memory. In a double blind, randomized, placebo-controlled, between-subjects intervention study, 58 healthy participants were tested once before and once after a 28-day intervention. Without stress induction, probiotics did not affect brain, behavioral, or related self-report measures. However, relative to placebo, the probiotics group did show a significant stress-related increase in working memory performance after supplementation. This change was associated with intervention-related neural changes in frontal cortex during cognitive control exclusively in the probiotics group. Overall, our results show neurocognitive effects of a multispecies probiotic in healthy women only under challenging situations, buffering against the detrimental effects of stress on cognition.
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Reversal of cognitive decline: a novel therapeutic program.
Bredesen, DE
Aging. 2014;6(9):707-17
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Alzheimer’s Disease (AD) is estimated to affect 30 million individuals globally, with projections as high as 150 million by 2050 if no effective treatment is found. This report describes a personalised, multi-modal, therapeutic programme used with 10 individuals with various degrees of cognitive decline. The goal was to optimise metabolic parameters and lifestyle factors and was personalised based on laboratory test results. 9 out of 10 of the case study patients experienced improvement in cognitive abilities, beginning within 3-6 months of starting the programme. These effects were sustained at 2.5 year follow up. The 1 patient who did not benefit had advanced AD, in comparison to the other patients with subjective or mild cognitive decline. The authors call for a more extensive trial of the therapeutic programme.
Abstract
This report describes a novel, comprehensive, and personalized therapeutic program that is based on the underlying pathogenesis of Alzheimer's disease, and which involves multiple modalities designed to achieve metabolic enhancement for neurodegeneration (MEND). The first 10 patients who have utilized this program include patients with memory loss associated with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI). Nine of the 10 displayed subjective or objective improvement in cognition beginning within 3-6 months, with the one failure being a patient with very late stage AD. Six of the patients had had to discontinue working or were struggling with their jobs at the time of presentation, and all were able to return to work or continue working with improved performance. Improvements have been sustained, and at this time the longest patient follow-up is two and one-half years from initial treatment, with sustained and marked improvement. These results suggest that a larger, more extensive trial of this therapeutic program is warranted. The results also suggest that, at least early in the course, cognitive decline may be driven in large part by metabolic processes. Furthermore, given the failure of monotherapeutics in AD to date, the results raise the possibility that such a therapeutic system may be useful as a platform on which drugs that would fail as monotherapeutics may succeed as key components of a therapeutic system.