Circulating Antioxidant Levels Research Articles

Association between the composite dietary antioxidant index and risk of infertility: Evidence from NHANES 2013-2020 and a Mendelian randomization study.

The Composite Dietary Antioxidant Index (CDAI) measures the antioxidant capacity of the diet, which is believed to provide protection against various diseases, including depression, osteoporosis, and papillomavirus infection, by neutralizing harmful oxidative stress. However, the relationship between CDAI and infertility is not well understood. This research aims to explore the potential correlations between CDAI and the risk of infertility. This research harnessed data from the National Health and Nutrition Examination Survey (NHANES) to execute a cross-sectional analysis involving 8263 US women aged 20-45. Each participant was subjected to two distinct 24-h dietary recall interviews. We calculated the CDAI using average daily antioxidant intake. Infertility was assessed using a standardized questionnaire. The association between CDAI and infertility was examined using weighted multiple logistic regression models, while nonlinear correlations were explored through restricted cubic splines. To affirm the robustness of our findings, sensitivity and subgroup analyses were performed using unweighted logistic regression. Additionally, to ascertain the causal influence of circulating antioxidant levels on infertility, a two-sample univariable Mendelian randomization (MR) analysis was conducted, using the inverse variance weighted (IVW) method as the primary analytic approach. Participants who were infertile exhibited lower CDAI levels compared to their fertile counterparts. When confounding variables were accounted for in the multivariate weighted logistic regression model, an inverse relationship was observed between CDAI and infertility, with the odds ratio for the highest versus lowest quartile being 0.55 (0.33-0.90, P = 0.02). However, the IVW method indicated that genetically predicted elevated levels of CDAI did not significantly correlate with infertility. Cross-sectional observational studies indicate that antioxidants from diets might diminish infertility risks. However, findings from MR studies do not confirm a causal connection. Additional prospective research is required to elucidate this association further.

Abstract 3440: Etiology of prostate cancer with the TMPRSS2:ERG fusion: A systematic review of risk factors

Abstract Background: The TMPRSS2:ERG gene fusion is the most common somatic alteration in primary prostate cancer and an early event in carcinogenesis. There are emerging data highlighting etiologic differences in prostate cancer by TMPRSS2:ERG status. This systematic review synthesized evidence from epidemiologic studies on prostate cancer risk factors for tumors with and without the TMPRSS2:ERG fusion. Methods: A systematic literature search was performed in Ovid MEDLINE, EMBASE, and Web of Science without language restriction for studies published by September 27, 2022. Studies that assessed associations between epidemiologic and genetic factors and prostate cancer risk by tumor TMPRSS2:ERG (ERG) fusion status in human populations were included. Results: Of 3,071 records identified, 20 publications comprising prospective cohort and case-control studies from five study populations (published 2009-2022) were included. Risk factors included germline genetic variants, circulating hormones, diet, lifestyle factors, and medications. The included studies suggested that taller height and higher total and free circulating testosterone levels tended to be associated with higher risk of ERG-positive, but not ERG-negative prostate cancer. CAG repeat length in the androgen receptor (AR) gene, related inversely to transcriptional activity, appeared to be associated with a lower risk of ERG-positive, but not ERG-negative prostate cancer. There was statistical evidence for etiologic differences for several germline single nucleotide polymorphisms (SNPs) by ERG status. Excess body weight, greater vigorous physical activity, greater lycopene intake, and calcium channel blocker use appeared to specifically be associated with a lower risk of ERG-positive tumors. Associations of other potential etiologic factors, including diabetes mellitus, baldness, aspirin use, circulating antioxidant levels, and sex hormones other than testosterone, with ERG-positive prostate cancer were null or inconclusive. Most associations had low precision, and the results were based on few distinct study populations, highlighting a need for replication. Conclusions: Prostate cancer with the TMPRSS2:ERG fusion may be an etiologically distinct subtype impacted by certain modifiable and hormonally-acting risk factors that align with the established mechanistic role of this gene fusion in androgen, insulin, and growth factor pathways. The findings suggest a potentially distinct genetic predisposition to prostate cancer with or without the TMPRSS2:ERG fusion. More broadly, these findings suggest that considering molecular subtypes of prostate cancer, beyond TMPRSS2:ERG, may strengthen etiologic understanding of prostate cancer and evidence for prevention. Citation Format: Colleen B. McGrath, Alaina H. Shreves, Megan R. Shanahan, Hannah E. Guard, Manelisi V. Nhliziyo, Kathryn L. Penney, Tamara L. Lotan, Michelangelo Fiorentino, Konrad H. Stopsack, Lorelei A. Mucci. Etiology of prostate cancer with the TMPRSS2:ERG fusion: A systematic review of risk factors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3440.

Association between circulating antioxidants and sleep disorders: comprehensive results from NHANES 2017-2018.

Background: Oxidative stress plays an important role in the occurrence and pathological process of numerous human diseases. A bidirectional relationship was found between sleep disorders and oxidative stress. However, the association between circulating antioxidant levels and the risk of sleep disorders at the population-scale has yet to be determined. Methods: We used the dataset from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 data release cycle and included 3062 adult participants aged 25-75 years. The circulating antioxidants levels in serum were measured, and the sleep status was assessed by self-reported sleep disorder questionnaire tests. We investigated the association and exposure-response relationship between the 12 main circulating antioxidants and sleep disorders using a generalized additive model (GAM), multiple linear, binary logistic, and restricted cubic spline (RCS) regression models. Multiple sensitivity analyses were conducted to validate the results of our study. Results: Significantly lower serum concentrations of ten antioxidants were observed in the group which had trouble sleeping symptoms compared to the control group. After adjusting for all the covariates, the binary logistic regression models indicated that six of the circulating antioxidants including alpha-carotene, alpha-cryptoxanthin, trans-beta-carotene, beta-cryptoxanthin, lutein and zeaxanthin, and vitamin C, showed a significant association with the risk of overall trouble sleeping symptoms, with odds ratios corresponding to 0.88 (95% CI: 0.80-0.96), 0.74 (95% CI: 0.62-0.87), 0.87 (95% CI: 0.79-0.97), 0.85 (95% CI: 0.75-0.95), 0.72 (95% CI: 0.61-0.84), and 0.83 (95% CI: 0.74-0.93), respectively. The GAM and multiple linear regression revealed similar associations whereas the RCS regression models further confirmed their significant negative exposure-response relationship. Conclusions: The circulating carotenoids and vitamin C levels were negatively correlated with the risk of sleep disorders. Higher circulating antioxidant levels were significantly associated with a lower risk of sleep disorders. The potential health risk of low circulating antioxidants levels was higher in the female population than in the male population.

Interplay between oxidative damage, the redox status, and metabolic biomarkers during long-term fasting

Obesity and its related metabolic disorders, as well as infectious diseases like covid-19, are important health risks nowadays. It was recently documented that long-term fasting improves metabolic health and enhanced the total antioxidant capacity. The present study investigated the influence of a 10-day fasting on markers of the redox status in 109 subjects. Reducing power, 2,2’-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt radical cation(ABTS) radical scavenging capacity, and hydroxyl radical scavenging capacity increased significantly, and indicated an increase of circulating antioxidant levels. No differences were detected in superoxide scavenging capacity, protein carbonyls, and superoxide dismutase when measured at baseline and after 10 days of fasting. These findings were concomitant to a decrease in blood glucose, insulin, glycated hemoglobin (HbA1c), total cholesterol, low-density lipoprotein (LDL) and triglycerides as well as an increase in total cholesterol/high-density lipoprotein (HDL) ratio. In addition, the well-being index as well as the subjective energy levels increased, documenting a good tolerability. There was an interplay between redox and metabolic parameters since lipid peroxidation baseline levels (thiobarbituric acid reactive substances [TBARS]) affected the ability of long-term fasting to normalize lipid levels. A machine learning model showed that a combination of antioxidant parameters measured at baseline predicted the efficiency of the fasting regimen to decrease LDL levels. In conclusion, it was demonstrated that long-term fasting enhanced the endogenous production of antioxidant molecules, that act protectively against free radicals, and in parallel improved the metabolic health status. Our results suggest that the outcome of long-term fasting strategies could be depending on the baseline values of the antioxidative and metabolic status of subjects.

Acute exposure to traffic-related air pollution alters antioxidant status in healthy adults

BackgroundExposure to traffic-related air pollution is associated with an increased risk of cardiovascular and respiratory disease. Evidence suggests that inhaled pollutants precipitate these effects via multiple pathways involving oxidative stress. ObjectivePostulating that a decrease in circulating antioxidant levels reflect an oxidative response, we investigated the effect of inhaled diesel exhaust (DE) on the ratio of reduced to oxidized glutathione (GSH/GSSG) in healthy adults, and whether pre-exposure antioxidant supplementation blunted this response. We also examined exposure-related changes in antioxidant/stress response leukocyte gene expression (GCLc, HMOX-1, IL-6, TGFβ) and plasma IL-6 levels. MethodsNineteen nonsmoking adults participated in a double-blind, randomized, four-way crossover study. Each subject completed 120-min exposures to filtered air and DE (200 μg/m3), with and without antioxidant pretreatment. Antioxidant comprised 1000 mg ascorbate for 7 days and 1200 mg N-acetylcysteine 1 day prior to exposure, with 1000 mg and 600 mg, respectively, administered 2 h prior to exposure. Whole blood glutathione was measured pre- and post-exposure; plasma IL-6 and mRNA expression were quantified pre, during and post exposure. ResultsDiesel exhaust exposure was associated with significantly decreased GSH/GSSG (p = 0.001) and a 4-fold increase in IL-6 mRNA (p = 0.01) post exposure. Antioxidant pretreatment did not significantly mediate the effect of DE exposure on GSH/GSSG, though appeared to decrease the effect of exposure on IL-6 mRNA expression. ConclusionsAcute DE inhalation induced detectable oxidative effects in healthy adults, which were not significantly attenuated by the selected antioxidant pre-treatment. This finding supports the premise that oxidative stress is one mechanism underlying the adverse effects of traffic-related air pollution.

Chitosan Oligosaccharides Show Protective Effects in Coronary Heart Disease by Improving Antioxidant Capacity via the Increase in Intestinal Probiotics.

We explored the effects of chitosan oligosaccharides (COS) on coronary heart disease (CHD) patients. The component of COS was measured by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). CHD patients were evenly assigned into the COS group (COG) and the placebo group (CG). The duration of treatment was 6 months and therapeutic results were explored by measuring left ventricular ejection fraction (LVEF) value, Lee scores, quality of life (QOL), blood urea nitrogen, and serum creatinine. The intestinal flora were determined by 16s rDNA sequencing. The circulating antioxidant levels and lipid profiles were compared between two groups. There were 7 different degrees of polymerization (DP4-10) in COS. Lee scores, QOL scores, and LVEF values in the COG group were higher than those in the CG group (P < 0.05). COS treatment improved blood urea nitrogen and serum creatinine when compared with controls (P < 0.05). Circulating antioxidant levels were higher in the COG group than in the CG group. COS consumption increased the serum levels of SOD and GSH and reduced the levels of ALT and AST (P < 0.05). Meanwhile, lipid profiles were improved in the COG group. COS consumption increased the abundance of Faecalibacterium, Alistipes, and Escherichia and decreased the abundance of Bacteroides, Megasphaera, Roseburia, Prevotella, and Bifidobacterium (P < 0.05). On the other hand, COS consumption increased the probiotic species Lactobacillus, Lactococcus, and Phascolarctobacterium. The increased species have been reported to be associated with antioxidant properties or lipid improvement. COS had similar effects with chitohexaose on the growth rate of these species. Therefore, COS ameliorate the symptoms of CHD patients by improving antioxidant capacities and lipid profiles via the increase of probiotics in the intestinal flora.

Black Garlic Improves Heart Function in Patients With Coronary Heart Disease by Improving Circulating Antioxidant Levels.

Background: Black garlic (BG) has many health-promoting properties.Objectives: We aimed to explore the clinical effects of BG on chronic heart failure (CHF) in patients with coronary heart disease (CHD).Design: The main components of BG were measured by gas chromatography–mass spectrometry (GC–MS) and its antioxidant properties were determined by the clearance rate of free radicals. One hundred twenty CHF patients caused by CHD were randomly and evenly assigned into BG group and placebo group (CG). The duration of treatment was 6 months. Cardiac function was measured according to the New York Heart Association (NYHA) functional classification system. The following parameters were measured, including walking distance, BNP precursor N-terminal (Nt-proBNP), left-ventricular ejection fraction (LVEF) value, and the scores of quality of life (QOL). The circulating antioxidant levels were compared between two groups.Results: There are 27 main compounds in BG with strong antioxidant properties. BG treatment improved cardiac function when compared with controls (P < 0.05). The QOL scores and LVEF values were higher in the BG group than in the CG group while the concentration of Nt-proBNP was lower in the BG group than in the CG group (P < 0.05). Circulating antioxidant levels were higher in the BG group than in the CG group. Antioxidant levels had positive relation with QOL and LVEF values, and negative relation with Nt-proBNP values.Conclusion: BG improves the QOL, Nt-proBNP, and LVEF in CHF patient with CHD by increasing antioxidant levels.

Abstract 664: Regulation of Angiogenesis and Associated Inflammation by Antioxidant Glutathione in Smooth Muscle Cells

Peripheral artery blockage due to formation of atherosclerotic plaques in PVD (Peripheral Vascular Diseases) causes loss of blood flow to peripheral limbs leading to pathogenic consequences, necrosis and in severe cases amputation of the limb. Angiogenesis, the development of new collateral blood vessels is necessary to compensate for this loss of blood flow and prevent pathogenesis resulting from blockage. However, PVD patients, to their detriment, often see decreased angiogenesis and lack of adequate compensatory neo-vascularization along with decreased circulating antioxidant levels. Angiogenesis requires a specific balance of Reactive Oxygen Species(ROS) and neutralizing antioxidants including Glutathione (GSH). Interestingly, our mouse models of PVD with femoral artery ligation (FAL) show a contradictory increase in angiogenesis with a slight decrease in GSH (~80% GSH, Gclm HET mice) compared to WT (100% GSH), not seen with severely decreased GSH in Gclm KO mice (~20% GSH). This suggests that the balance of ROS and antioxidants can be adjusted to a favorable outcome. This led us to hypothesize that a slight decrease in GSH is beneficial and provides “necessary” inflammation to kick-start angiogenesis. To investigate this hypothesis, we performed mRNA-seq analysis on Smooth Muscle Cells (SMCs), an important component of blood vessels known to promote angiogenesis. SMCs were isolated from Gclm WT/HET/KO mice and subjected to hypoxia/re-oxygenation (HR) to mimic blood flow blockage and reperfusion in-vivo . Our hypothesis was confirmed with an increased inflammatory gene expression profile in HET SMCs compared to WT and KO. Results show that slight decrease in antioxidant GSH leads to significant increases in the IL-8, NF-kB, fMLP, MAPK kinase and Notch related signaling pathways, all of which positively influence inflammation associated angiogenesis. Our study suggests that a slight increase in oxidative stress leads to an “appropriate” increase in inflammation and provides adequate environment for accelerated angiogenesis and subsequent tissue perfusion.

Effects of Lead Exposure on Sperm Quality and Reproductive Success in an Avian Model.

Lead (Pb) poisoning via ingestion of shot pellets is a frequent cause of death in wild birds and also has a wide range of subclinical effects. Here we report on the sublethal effects Pb exposure has on the breeding performance of red-legged partridges (Alectoris rufa). We studied the effects of Pb exposure on sperm quality, reproductive success, egg properties, laying performance, antioxidant levels, and carotenoid-based coloration. Birds were exposed by oral gavage to one or three No. 6 Pb shot pellets (2.8 mm in diameter, mean mass ± SD: 109 ± 7.97 mg). We show that exposure to three pellets (330 mg) reduced the hatching rate of females and decreased the acrosome integrity and sperm motility of males. In addition, females exposed to 1 pellet (110 mg) produced heavier eggs and chicks, whereas males exposed to 1 pellet presented an increase in sperm vigor. Sperm viability, concentration, progressiveness or fecundation rate were not affected by Pb treatment. Pb exposure increased circulating antioxidant levels in males, whereas the percentage of carotenoid-pigmented eye-ring area decreased in exposed females. Several sperm parameters showed positive relationships with coloration and antioxidant levels, suggesting that males displaying redder ornaments may be more capable of protecting sperm from oxidative stress in the event of sublethal Pb exposure.

In vivo changes in plasma coenzyme Q10, carotenoid, tocopherol, and retinol levels in children after computer tomography

BackgroundLow dose X-irradiation (IR) from computer tomography (CT) can generate free radicals, which can damage biologically relevant molecules and ultimately lead to cancer. These effects are especially concerning for children owing to their higher radiosensitivity and longer life expectancy than adults. The lipid phase micronutrients (LPM) coenzyme Q10, carotenoids, E vitamers, and vitamin A are potent radical scavengers that can act as intracellular antioxidants. MethodsWe investigated changes in circulating levels of these LPM in 17 children (0.25–6y) undergoing medically indicated CT scans involving relatively low IR doses. Blood was drawn before and 1h after CT scans and analyzed using HPLC with electrochemical and UV/VIS detection. ResultsWe found significant decreases (p<0.05) in post-CT plasma levels in several LPM which suggests that these LPM can serve as biodosimeters and may protect against damage from IR during clinical procedures such as CT. The strongest predictors for pre- to post-CT changes for many LPM were their baseline levels. ConclusionFuture larger studies are warranted to confirm our findings and to test whether high circulating antioxidant levels protect against IR damage in vivo with an ultimate goal of establishing prophylactic modalities for CT-induced IR damage.

Inverse association of serum carotenoids with prevalence of metabolic syndrome among Japanese

Several epidemiological studies have shown that circulating antioxidant levels are inversely associated with metabolic syndrome status. The purpose of this study was to examine the association of serum carotenoid levels, which have potent antioxidant effects, with metabolic syndrome and metabolic syndrome components in Japanese subjects. We conducted a cross-sectional study of 931 subjects (318 men and 613 women), aged 39-70 years, who attended a health examination. Metabolic syndrome was defined according to the diagnostic definition from the Japanese Examination Committee of Criteria for Metabolic Syndrome, which was released in 2005. Serum carotenoids were measured by high-performance liquid chromatography. A significantly lower odds ratio (OR) for metabolic syndrome was observed in the highest tertile of serum β-cryptoxanthin (OR:0.45; 95% CI:0.22-0.93 in men and 0.41; 0.17-0.93 in women) and β-carotene (OR:0.45; 95% CI:0.21-0.95 in men and 0.37; 0.15-0.83 in women) compared to the lowest tertiles, in both sexes, but no significant association was found in male smokers. In women, moreover, OR for metabolic syndrome in the highest tertile of serum zeaxanthin/lutein (OR:0.37; 95% CI:0.16-0.84) was significantly lower than in the lowest tertile. Serum levels of β-cryptoxanthin, α-carotene, and β-carotene were significantly decreased with an increasing number of metabolic syndrome components in both sexes. These findings indicate that carotenoids may be important factors in the prevention of metabolic syndrome in nonsmokers, but further studies are required in smokers.

Honest sexual signalling mediated by parasite and testosterone effects on oxidative balance.

Extravagant ornaments evolved to advertise their bearers' quality, the honesty of the signal being ensured by the cost paid to produce or maintain it. The oxidation handicap hypothesis (OHH) proposes that a main cost of testosterone-dependent ornamentation is oxidative stress, a condition whereby the production of reactive oxygen and nitrogen species (ROS/RNS) overwhelms the capacity of antioxidant defences. ROS/RNS are unstable, very reactive by-products of normal metabolic processes that can cause extensive damage to key biomolecules (cellular proteins, lipids and DNA). Oxidative stress has been implicated in the aetiology of many diseases and could link ornamentation and genetic variation in fitness-related traits. We tested the OHH in a free-living bird, the red grouse. We show that elevated testosterone enhanced ornamentation and increased circulating antioxidant levels, but caused oxidative damage. Males with smaller ornaments suffered more oxidative damage than those with larger ornaments when forced to increase testosterone levels, consistent with a handicap mechanism. Parasites depleted antioxidant defences, caused oxidative damage and reduced ornament expression. Oxidative damage extent and the ability of males to increase antioxidant defences also explained the impacts of testosterone and parasites on ornamentation within treatment groups. Because oxidative stress is intimately linked to immune function, parasite resistance and fitness, it provides a reliable currency in the trade-off between individual health and ornamentation. The costs induced by oxidative stress can apply to a wide range of signals, which are testosterone-dependent or coloured by pigments with antioxidant properties.