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Hyperoxia and Antioxidants for Myocardial Injury in Noncardiac Surgery: A 2 × 2 Factorial, Blinded, Randomized Clinical Trial.
Holse, C, Aasvang, EK, Vester-Andersen, M, Rasmussen, LS, Wetterslev, J, Christensen, R, Jorgensen, LN, Pedersen, SS, Loft, FC, Troensegaard, H, et al
Anesthesiology. 2022;(3):408-419
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Abstract
BACKGROUND Hyperoxia and oxidative stress may be associated with increased risk of myocardial injury. The authors hypothesized that a perioperative inspiratory oxygen fraction of 0.80 versus 0.30 would increase the degree of myocardial injury within the first 3 days of surgery, and that an antioxidant intervention would reduce degree of myocardial injury versus placebo. METHODS A 2 × 2 factorial, randomized, blinded, multicenter trial enrolled patients older than 45 yr who had cardiovascular risk factors undergoing major noncardiac surgery. Factorial randomization allocated patients to one of two oxygen interventions from intubation and at 2 h after surgery, as well as antioxidant intervention or matching placebo. Antioxidants were 3 g IV vitamin C and 100 mg/kg N-acetylcysteine. The primary outcome was the degree of myocardial injury assessed by the area under the curve for high-sensitive troponin within the first 3 postoperative days. RESULTS The authors randomized 600 participants from April 2018 to January 2020 and analyzed 576 patients for the primary outcome. Baseline and intraoperative characteristics did not differ between groups. The primary outcome was 35 ng · day/l (19 to 58) in the 80% oxygen group; 35 ng · day/l (17 to 56) in the 30% oxygen group; 35 ng · day/l (19 to 54) in the antioxidants group; and 33 ng · day/l (18 to 57) in the placebo group. The median difference between oxygen groups was 1.5 ng · day/l (95% CI, -2.5 to 5.3; P = 0.202) and -0.5 ng · day/l (95% CI, -4.5 to 3.0; P = 0.228) between antioxidant groups. Mortality at 30 days occurred in 9 of 576 patients (1.6%; odds ratio, 2.01 [95% CI, 0.50 to 8.1]; P = 0.329 for the 80% vs. 30% oxygen groups; and odds ratio, 0.79 [95% CI, 0.214 to 2.99]; P = 0.732 for the antioxidants vs. placebo groups). CONCLUSIONS Perioperative interventions with high inspiratory oxygen fraction and antioxidants did not change the degree of myocardial injury within the first 3 days of surgery. This implies safety with 80% oxygen and no cardiovascular benefits of vitamin C and N-acetylcysteine in major noncardiac surgery.
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Prospective randomized multicentre comparison on sibling oocytes comparing G-Series media system with antioxidants versus standard G-Series media system.
Gardner, DK, Kuramoto, T, Tanaka, M, Mitzumoto, S, Montag, M, Yoshida, A
Reproductive biomedicine online. 2020;(5):637-644
Abstract
RESEARCH QUESTION Does the inclusion of three antioxidants (A3), acetyl-l-carnitine (ALC), N-acetyl-l-cysteine (NAC) and alpha-lipoic acid (ALA) improve human embryo development and pregnancy potential? DESIGN Prospective randomized multicentre comparison of sibling oocytes. A total of 1563 metaphase II oocytes from 133 patients in two IVF centres. Day 3 embryo and day 5/6 blastocyst quality were assessed. Good embryo quality on day 3 was defined as 8 to 10 cells with even cells and low fragmentation; good quality blastocysts as 3BB or greater. Clinical outcome was assessed on transfers of fresh or vitrified-warmed blastocyst on day 5. RESULTS Of the two-pronuclei, 40.7% (G-Series) and 50.2% (G-Series with A3 group) resulted in good quality embryos on day 3 (P < 0.05). The implantation rate by fetal sac was 39.2% and 50.6%, and by fetal heartbeat was 37.8% and 47.1% for the G-Series and G-Series with A3 group, respectively. When stratified by female patient age, patients 35-40 years had an implantation rate by fetal sac and heart of 23.5% in the G-Series compared with 57.5% (P < 0.05) and 50.0% (P < 0.05) in the A3 group. The ongoing pregnancies in patients 35-40 years were significantly higher in the A3 group (50%) compared with the control (25.8%) (P < 0.05). CONCLUSIONS The presence of antioxidants during IVF and embryo culture for patients 35-40 years resulted in a significant increase in implantation and pregnancy rate. Supplementation of antioxidants to IVF and culture media may therefore improve the viability of human embryos in assisted reproductive technologies, plausibly through the reduction of oxidative stress.
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Hyperoxia and antioxidants during major non-cardiac surgery and risk of cardiovascular events: Protocol for a 2 × 2 factorial randomised clinical trial.
Petersen, C, Loft, FC, Aasvang, EK, Vester-Andersen, M, Rasmussen, LS, Wetterslev, J, Jorgensen, LN, Christensen, R, Meyhoff, CS
Acta anaesthesiologica Scandinavica. 2020;(3):400-409
Abstract
BACKGROUND Myocardial injury after non-cardiac surgery occurs in a high number of patients, resulting in increased mortality in the post-operative period. The use of high inspiratory oxygen concentrations may cause hyperoxia, which is associated with impairment of coronary blood flow. Furthermore, the surgical stress response increases reactive oxygen species, which is involved in several perioperative complications including myocardial injury and death. Avoidance of hyperoxia and substitution of reactive oxygen species scavengers may be beneficial. Our primary objective is to examine the effect of oxygen and added antioxidants for prevention of myocardial injury assessed by area under the curve for troponin measurements during the first three post-operative days. METHODS The VIXIE trial (VitamIn and oXygen Interventions and cardiovascular Events) is an investigator-initiated, blinded, 2 × 2 factorial multicentre clinical trial. We include 600 patients with cardiovascular risk factors undergoing major non-cardiac surgery. Participants are randomised to an inspiratory oxygen fraction of 0.80 or 0.30 during and for 2 hours after surgery and either an intravenous bolus of vitamin C and an infusion of N-acetylcysteine or matching placebo of both. The primary outcome is the area under the curve for high-sensitive cardiac troponin release during the first three post-operative days as a marker of the extent of myocardial injury. Secondary outcomes are mortality, non-fatal myocardial infarction and non-fatal serious adverse events within 30 days. PERSPECTIVE The current trial will provide further evidence for clinicians on optimal administration of perioperative oxygen in surgical patients with cardiovascular risks and the clinical effects of two common antioxidants.
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A longitudinal study of pre-pregnancy antioxidant levels and subsequent perinatal outcomes in black and white women: The CARDIA Study.
Harville, EW, Lewis, CE, Catov, JM, Jacobs, DR, Gross, MD, Gunderson, EP
PloS one. 2020;(2):e0229002
Abstract
BACKGROUND Although protective associations between dietary antioxidants and pregnancy outcomes have been reported, randomized controlled trials of supplementation have been almost uniformly negative. A possible explanation is that supplementation during pregnancy may be too late to have a beneficial effect. Therefore, we examined the relationship between antioxidant levels prior to pregnancy and birth outcomes. METHODS AND FINDINGS Serum carotenoids and tocopherols were assayed in fasting specimens at 1985-86 (baseline) and 1992-1993 (year 7) from 1,215 participants in Coronary Artery Risk Development in Young Adults (CARDIA) study. An interviewer-administered quantitative food-frequency questionnaire assessed dietary intake of antioxidants. Pregnancy outcome was self-reported at exams every 2 to 5 years. Linear and logistic regression modeling was used to assess relationships of low birthweight (LBW; <2,500 g), continuous infant birthweight, preterm birth (PTB; <37 weeks) and length of gestation with antioxidant levels adjusted for confounders, as well as interactions with age and race. RESULTS In adjusted models, lycopene was associated with higher odds of LBW (adjusted odds ratio for top quartile, 2.15, 95% confidence interval 1.14, 3.92) and shorter gestational age (adjusted beta coefficient -0.50 weeks). Dietary intake of antioxidants was associated with lower birthweight, while supplement use of vitamin C was associated with higher gestational age (0.41 weeks, 0.01, 0.81). CONCLUSIONS Higher preconception antioxidant levels are not associated with better birth outcomes.
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Patient-reported outcomes in Friedreich's ataxia after withdrawal from idebenone.
Cook, A, Boesch, S, Heck, S, Brunt, E, Klockgether, T, Schöls, L, Schulz, A, Giunti, P
Acta neurologica Scandinavica. 2019;(6):533-539
Abstract
OBJECTIVES Friedreich's ataxia is the most common inherited ataxia, and pathogenesis is known to involve mitochondrial oxidative stress. Idebenone is a potent antioxidant which has already been evaluated in several clinical trials in FRDA, with reports of symptomatic benefit but inconclusive objective results. Following patient consultation on design, we have completed a treatment-withdrawal study to establish whether patients could correctly determine their treatment allocation to placebo or idebenone. Our aim was to capture subjective experiences of symptoms such as fatigue, which can be difficult to measure with questionnaires or semi-quantitative scales, particularly in chronic, slowly progressive conditions. MATERIALS AND METHODS Patients taking idebenone for at least 12 months as part of the open-label MICONOS Extension Study were randomized to receive either placebo or idebenone continuation for 2-month treatment cycles. The primary endpoint was patient assessment of treatment assignment. RESULTS A total of 29 patients were randomized, forming the idebenone group (n = 16) and the placebo group (n = 13). No significant differences were detected between the idebenone and placebo groups on assessment of treatment assignment or early study withdrawal. A small but significant difference in ataxia rating scale scores was detected between treatment groups when considering ambulatory patients only. CONCLUSIONS This study provides no data to suggest that FRDA patients could correctly determine their treatment assignment over a 2-month period. We hope that this study design will help inform future trials so that patients' experiences of symptoms are more reliably measured.
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Bio-optimized Curcuma longa extract is efficient on knee osteoarthritis pain: a double-blind multicenter randomized placebo controlled three-arm study.
Henrotin, Y, Malaise, M, Wittoek, R, de Vlam, K, Brasseur, JP, Luyten, FP, Jiangang, Q, Van den Berghe, M, Uhoda, R, Bentin, J, et al
Arthritis research & therapy. 2019;(1):179
Abstract
OBJECTIVES Comparison of two doses of bio-optimized Curcuma longa extract (BCL) in the management of symptomatic knee osteoarthritis (OA). METHODS A prospective, randomized, 3-month, double-blind, multicenter, three-group, placebo-controlled trial assessing Patient Global Assessment of Disease Activity (PGADA) and serum sColl2-1, a biomarker of cartilage degradation, as co-primary endpoints. Pain on visual analog scale (VAS), Knee injury and Osteoarthritis Outcome Score (KOOS), and paracetamol/non-steroidal anti-inflammatory drug (NSAID) consumption were used as secondary endpoints. RESULTS One hundred fifty patients with knee OA were followed for 90 days. Low and high doses of BCL showed a greater decrease of PGADA than placebo. Analysis of sColl2-1 showed in the placebo and BCL low-dose groups, but not in the BCL high-dose group, a transient but non-significant increase of sColl2-1 between T0 and T1. Thereafter, in all groups, sColl2-1 decreased between T1 and T3 (all p < 0.01), but no difference between the groups was found. Pain reduction at day 90 in the low- and high-dose BCL groups (- 29.5 mm and - 36.5 mm) was higher than that in the placebo (- 8 mm; p = 0.018). The global KOOS significantly decreased overtime, but changes were comparable across treatment arms. The ratio of patients with adverse events (AE) related to the product was similar in the placebo and treatment groups, but the number of AE linked to the product was higher in the high-dose BCL group compared to the placebo (p = 0.012). CONCLUSIONS BCL appeared safe and well-tolerated with no evidence of severe adverse effects. Efficacy analysis suggested positive trends for measurements of PGADA and serum levels of an OA biomarker and showed a rapid and significant decrease of pain in knee OA (Trial registration: ISRCTN, ISRCTN12345678. Registered 21 September 2016-retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02909621?term=osteoarthritis+curcumin&rank=5-Evaluation of FLEXOFYTOL® Versus PLACEBO (COPRA) NCT02909621).
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Antioxidants linked with physical, cognitive and psychological frailty: Analysis of candidate biomarkers and markers derived from the MARK-AGE study.
Rietman, ML, Spijkerman, AMW, Wong, A, van Steeg, H, Bürkle, A, Moreno-Villanueva, M, Sindlinger, T, Franceschi, C, Grubeck-Loebenstein, B, Bernhardt, J, et al
Mechanisms of ageing and development. 2019;:135-143
Abstract
Frailty among elderly people leads to an increased risk for negative health outcomes. To prevent frailty, we need a better understanding of the underlying mechanisms and early detection of individuals at risk. Both may be served by identifying candidate (bio)markers, i.e. biomarkers and markers, for the physical, cognitive, and psychological frailty domains. We used univariate (Rank-ANOVA) and multivariate (elastic net) approaches on the RASIG study population (age range: 35-74 years, n = 2220) of the MARK-AGE study to study up to 331 (bio)markers between individuals with and without frailty for each domain. Biomarkers and markers identified by both approaches were studied further regarding their association with frailty using logistic regression. Univariately, we found lower levels of antioxidants, including β-cryptoxanthin and zeaxanthin, in those who were physically, cognitively or psychologically frail. Additionally, self-reported health was worse in these three frail groups. Multivariately, we observed lower levels of β-cryptoxanthin and zeaxanthin in the cognitively frail. Levels of these carotenoids were inversely associated with the risk of being cognitively frail after adjusting for confounders. Antioxidants and self-reported health are potential (bio)markers to detect persons at risk of becoming frail. The biomarkers identified may indicate the involvement of inflammation in frailty, especially for physical and cognitive frailty.
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Tomato Phytonutrients Balance UV Response: Results from a Double-Blind, Randomized, Placebo-Controlled Study.
Groten, K, Marini, A, Grether-Beck, S, Jaenicke, T, Ibbotson, SH, Moseley, H, Ferguson, J, Krutmann, J
Skin pharmacology and physiology. 2019;(2):101-108
Abstract
BACKGROUND Our previous double-blinded, placebo-controlled cross-over study indicated that a nutritional supplement named lycopene-rich tomato nutrient complex (TNC) can protect from UVA1-induced (340-400 nm) and UVA- (320-400 nm)/UVB-induced (280-320 nm) upregulation of molecular markers associated with oxidative stress, inflammation, and ageing. OBJECTIVES in the current double-blind, randomized, placebo-controlled multicenter study, we analyze whether a similar, synergistic carotenoid-rich TNC can protect from broadband UVB-induced threshold erythema formation assessed as increase in minimal erythemal dose (MED) reading, the intensity of erythema formation, and the upregulation of molecular markers associated with inflammation and immunosuppression, and whether this correlates with carotenoid blood levels. METHODS One hundred and forty-nine healthy volunteers were randomized to two groups and subjected to a 5-week washout phase, followed by a 12-week treatment phase receiving either 15 mg lycopene, 5.8 mg phytoene and phytofluene, 0.8 mg β-carotene, 5.6 mg tocopherols from tomato extract, and 4 mg carnosic acid from rosemary extract per day or placebo made from medium-chain triglycerides. At the end of each phase, MED determination, UVB irradiation, chromametry, biopsies, and blood samples were undertaken. RESULTS The active supplement was well tolerated. Interestingly, no significant difference was seen in the MED between the active-supplement and placebo groups, as determined by visual grading by expert assessors. Of note, the carotenoid-containing supplement significantly protected against UVB-induced erythema formation measured as Δa* after the intervention minus Δa* after the washout phase as compared to the placebo. Moreover, intake of the active supplement significantly protected against UVB-induced upregulation of IL6 and TNFα as compared with the intake of placebo. Lastly, carotenoid plasma levels were significantly increased. CONCLUSION This well-tolerated carotenoid-containing supplement significantly protected against UVB-induced erythema formation and upregulation of proinflammatory cytokines in healthy volunteers.
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Role of Antioxidants in Minor Salivary Glands Cancer in the Elderly.
Oteri, G, Lentini, M, Cicciù, M, Peditto, M, Rey, EO, Carrión, AB, Marciano, A
The Journal of craniofacial surgery. 2019;(3):823-828
Abstract
BACKGROUND Minor salivary gland tumors (MSGTs) are infrequent, representing 10% to 15% of all salivary neoplasms. Despite this low frequency, a significant increase in the incidence of these tumors has been reported in the lasts 30 years. While tumors of the salivary glands can appear at any age, different authors consider the peak of incidence to be associated with old age (60+). The etiopathogenesis of MSGTs remains unclear. In this context, the aim of this study was to explore the hypothesis that age-related changes in salivary antioxidant capacity are involved in the pathogenesis of minor salivary glands tumors to identify possible preventive measures.Furthermore the study aimed to describe the clinico-pathological features of a multi-institutional case series of MSGTs which results are consistent with data in the literature. METHODS An electronic search of the English language literature was performed using PubMed and Google scholar (). Databases were screened for papers using a number of search strings constructed using relevant terms (minor salivary glands tumors, elderly, diet, antioxidant, saliva, salivary glands). RESULTS According to the world literature, the peak of incidence of MSGTs is between the fifth and seventh decades of life. To date, the only confirmed risk factor for salivary gland tumors is the exposure to ionizing radiation. The significantly reduced salivary antioxidant capacity in old people may explain the higher prevalence of these tumors in the elderly population. CONCLUSIONS Further investigation is required to determine the real etiopathogenesis of MSGTs and why these tumors result more frequent in elderly patients.
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Effects of Tualang Honey on Cancer Related Fatigue: A Multicenter Open-label Trial of H&N Cancer Patients.
Ramasamy, V, Binti Mat Lazim, N, Abdullah, B, Singh, A
The Gulf journal of oncology. 2019;(30):43-51
Abstract
INTRODUCTION Cancer related fatigue (CRF) is a problem experienced by head and neck cancer patients, especially those who undergo chemoradiation therapy. CRF may persist for years post chemoradiation therapy and significantly impair their quality of life (QOL). Tualang honey is rich in amino acids, vitamins, minerals and enzymes. It is proven to have anti-inflammatory, antioxidant and anti-tumour properties. As CRF is related to inflammatory mediators, the effects of Tualang Honey may improve CRF. The aim of this study is to determine if Tualang honey has a role in improving CRF and quality of life among head and neck cancer patients post chemoradiation. METHODOLOGY In this open labelled randomized clinical trial, 40 participants aged between 18 and 65 with head and neck cancer who completed chemotherapy and/or radiotherapy in Hospital USM, Kelantan Malaysia or Hospital Taiping were recruited and randomized into two groups: Tualang honey (experimental) group or Vitamin C (control) group. They were prescribed with either daily oral Tualang honey 20mg or vitamin C tablet 100 mg for 8 weeks. Level of fatigue and quality of life were measured using FACIT-Fatigue and FACT H&N questionnaires at baseline, 4 weeks and 8 weeks. The white cell count and C-reactive protein level were also measured at baseline, 4 weeks and 8 weeks. RESULTS After four and eight weeks of treatment with Tualang honey or Vitamin C, the fatigue level for experimental group was better than in the control group, and the differences were statistically significant (p<0.05). Statistically significant improvements were seen on quality of life (p<0.05) for the experimental group at week 8, however, no significant improvements were seen in white cell count and C-reactive protein level between control and experimental group. CONCLUSION Our research provided support for the use of Tualang honey to improve CRF and QOL in head and neck cancer patients post chemotherapy or radiotherapy.