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The metabolic interplay between dietary carbohydrate and exercise and its role in acute appetite regulation in males: a randomized controlled study.
Frampton, J, Serrano-Contreras, JI, Garcia-Perez, I, Franco-Becker, G, Penhaligan, J, Tan, ASY, de Oliveira, ACC, Milner, AJ, Murphy, KG, Frost, G, et al
The Journal of physiology. 2023;(16):3461-3480
Abstract
An understanding of the metabolic determinants of postexercise appetite regulation would facilitate development of adjunctive therapeutics to suppress compensatory eating behaviours and improve the efficacy of exercise as a weight-loss treatment. Metabolic responses to acute exercise are, however, dependent on pre-exercise nutritional practices, including carbohydrate intake. We therefore aimed to determine the interactive effects of dietary carbohydrate and exercise on plasma hormonal and metabolite responses and explore mediators of exercise-induced changes in appetite regulation across nutritional states. In this randomized crossover study, participants completed four 120 min visits: (i) control (water) followed by rest; (ii) control followed by exercise (30 min at ∼75% of maximal oxygen uptake); (iii) carbohydrate (75 g maltodextrin) followed by rest; and (iv) carbohydrate followed by exercise. An ad libitum meal was provided at the end of each 120 min visit, with blood sample collection and appetite assessment performed at predefined intervals. We found that dietary carbohydrate and exercise exerted independent effects on the hormones glucagon-like peptide 1 (carbohydrate, 16.8 pmol/L; exercise, 7.4 pmol/L), ghrelin (carbohydrate, -48.8 pmol/L; exercise: -22.7 pmol/L) and glucagon (carbohydrate, 9.8 ng/L; exercise, 8.2 ng/L) that were linked to the generation of distinct plasma 1 H nuclear magnetic resonance metabolic phenotypes. These metabolic responses were associated with changes in appetite and energy intake, and plasma acetate and succinate were subsequently identified as potential novel mediators of exercise-induced appetite and energy intake responses. In summary, dietary carbohydrate and exercise independently influence gastrointestinal hormones associated with appetite regulation. Future work is warranted to probe the mechanistic importance of plasma acetate and succinate in postexercise appetite regulation. KEY POINTS Carbohydrate and exercise independently influence key appetite-regulating hormones. Temporal changes in postexercise appetite are linked to acetate, lactate and peptide YY. Postexercise energy intake is associated with glucagon-like peptide 1 and succinate levels.
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The effects of SCFAs on glycemic control in humans: a systematic review and meta-analysis.
Cherta-Murillo, A, Pugh, JE, Alaraj-Alshehhi, S, Hajjar, D, Chambers, ES, Frost, GS
The American journal of clinical nutrition. 2022;(2):335-361
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BACKGROUND Noncommunicable disease development is related to impairments in glycemic and insulinemic responses, which can be modulated by fiber intake. Fiber's beneficial effects upon metabolic health can be partially attributed to the production of SCFAs via microbial fermentation of fiber in the gastrointestinal tract. OBJECTIVES We aimed to determine the effects of SCFAs, acetate, propionate, and butyrate on glycemic control in humans. METHODS The CENTRAL, Embase, PubMed, Scopus, and Web of Science databases were searched from inception to 7 December 2021. Papers were included if they reported a randomized controlled trial measuring glucose and/or insulin compared to a placebo in adults. Studies were categorized by the type of SCFA and intervention duration. Random-effects meta-analyses were performed for glucose and insulin for those subject categories with ≥3 studies, or a narrative review was performed. RESULTS We identified 43 eligible papers, with 46 studies within those records (n = 913), and 44 studies were included in the meta-analysis. Vinegar intake decreased the acute glucose response [standard mean difference (SMD), -0.53; 95% CI, -0.92 to -0.14; n = 67] in individuals with impaired glucose tolerance or type 2 diabetes and in healthy volunteers (SMD, -0.27; 95% CI, -0.54 to 0.00; n = 186). The meta-analyses for acute acetate, as well as acute and chronic propionate studies, showed no significant effect. CONCLUSIONS Vinegar decreased the glucose response acutely in healthy and metabolically unhealthy individuals. Acetate, propionate, butyrate, and mixed SCFAs had no effect on blood glucose and insulin in humans. Significant heterogeneity, risks of bias, and publication biases were identified in several study categories, including the acute vinegar glucose response. As evidence was very uncertain, caution is urged when interpreting these results. Further high-quality research is required to determine the effects of SCFAs on glycemic control.
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Characterization of diet-dependent temporal changes in circulating short-chain fatty acid concentrations: A randomized crossover dietary trial.
Brignardello, J, Fountana, S, Posma, JM, Chambers, ES, Nicholson, JK, Wist, J, Frost, G, Garcia-Perez, I, Holmes, E
The American journal of clinical nutrition. 2022;(5):1368-1378
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BACKGROUND Production of SCFAs from food is a complex and dynamic saccharolytic fermentation process mediated by both human and gut microbial factors. Knowledge of SCFA production and of the relation between SCFA profiles and dietary patterns is lacking. OBJECTIVES Temporal changes in SCFA concentrations in response to 2 contrasting diets were investigated using a novel GC-MS method. METHODS Samples were obtained from a randomized, controlled, crossover trial designed to characterize the metabolic response to 4 diets. Participants (n = 19) undertook these diets during an inpatient stay (of 72 h). Serum samples were collected 2 h after breakfast (AB), after lunch (AL), and after dinner (AD) on day 3, and a fasting sample (FA) was obtained on day 4. The 24-h urine samples were collected on day 3. In this substudy, samples from the 2 extreme diets representing a diet with high adherence to WHO healthy eating recommendations and a typical Western diet were analyzed using a bespoke GC-MS method developed to detect and quantify 10 SCFAs and precursors in serum and urine samples. RESULTS Considerable interindividual variation in serum SCFA concentrations was observed across all time points, and temporal fluctuations were observed for both diets. Although the sample collection timing exerted a greater magnitude of effect on circulating SCFA concentrations, the unhealthy diet was associated with a lower concentration of acetic acid (FA: coefficient: -17.0; SE: 5.8; P-trend = 0.00615), 2-methylbutyric acid (AL: coefficient: -0.1; SE: 0.028; P-trend = 4.13 × 10-4 and AD: coefficient: -0.1; SE: 0.028; P-trend = 2.28 × 10-3), and 2-hydroxybutyric acid (FA: coefficient: -15.8; SE: 5.11; P-trend: 4.09 × 10-3). In contrast, lactic acid was significantly higher in the unhealthy diet (AL: coefficient: 750.2; SE: 315.2; P-trend = 0.024 and AD: coefficient: 1219.3; SE: 322.6; P-trend: 8.28 × 10-4). CONCLUSIONS The GC-MS method allowed robust mapping of diurnal patterns in SCFA concentrations, which were affected by diet, and highlighted the importance of standardizing the timing of SCFA measurements in dietary studies. This trial was registered on the NIHR UK clinical trial gateway and with ISRCTN as ISRCTN43087333.
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The acute effect of glucagon on components of energy balance and glucose homoeostasis in adults without diabetes: a systematic review and meta-analysis.
Frampton, J, Izzi-Engbeaya, C, Salem, V, Murphy, KG, Tan, TM, Chambers, ES
International journal of obesity (2005). 2022;(11):1948-1959
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OBJECTIVE Using a systematic review and meta-analysis, we aimed to estimate the mean effect of acute glucagon administration on components of energy balance and glucose homoeostasis in adults without diabetes. METHODS CENTRAL, CINAHL, Embase, MEDLINE, PubMed, and Scopus databases were searched from inception to May 2021. To be included, papers had to be a randomised, crossover, single- or double-blind study, measuring ad libitum meal energy intake, energy expenditure, subjective appetite, glucose, and/or insulin following acute administration of glucagon and an appropriate comparator in adults without diabetes. Risk of bias was assessed using the Revised Cochrane Risk of Bias Tool for Randomized trials with additional considerations for cross-over trials. Certainty of evidence was assessed using the GRADE approach. Random-effect meta-analyses were performed for outcomes with at least five studies. This study is registered on PROSPERO (CRD42021269623). RESULTS In total, 13 papers (15 studies) were considered eligible: energy intake (5 studies, 77 participants); energy expenditure (5 studies, 59 participants); subjective appetite (3 studies, 39 participants); glucose (13 studies, 159 participants); insulin (12 studies, 147 participants). All studies had some concerns with regards to risk of bias. Mean intervention effect of acute glucagon administration on energy intake was small (standardised mean difference [SMD]: -0.19; 95% CI, -0.59 to 0.21; P = 0.345). Mean intervention effect of acute glucagon administration on energy expenditure (SMD: 0.72; 95% CI, 0.37-1.08; P < 0.001), glucose (SMD: 1.11; 95% CI, 0.60-1.62; P < 0.001), and insulin (SMD: 1.33; 95% CI, 0.88-1.77; P < 0.001) was moderate to large. CONCLUSIONS Acute glucagon administration produces substantial increases in energy expenditure, and in circulating insulin and glucose concentrations. However, the effect of acute glucagon administration on energy intake is unclear. Insufficient evidence was available to evaluate the acute effect of glucagon on subjective appetite.
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Vitamin D Supplementation Does Not Influence SARS-CoV-2 Vaccine Efficacy or Immunogenicity: Sub-Studies Nested within the CORONAVIT Randomised Controlled Trial.
Jolliffe, DA, Vivaldi, G, Chambers, ES, Cai, W, Li, W, Faustini, SE, Gibbons, JM, Pade, C, Coussens, AK, Richter, AG, et al
Nutrients. 2022;(18)
Abstract
Vitamin D deficiency has been reported to associate with the impaired development of antigen-specific responses following vaccination. We aimed to determine whether vitamin D supplements might boost the immunogenicity and efficacy of SARS-CoV-2 vaccination by conducting three sub-studies nested within the CORONAVIT randomised controlled trial, which investigated the effects of offering vitamin D supplements at a dose of 800 IU/day or 3200 IU/day vs. no offer on risk of acute respiratory infections in UK adults with circulating 25-hydroxyvitamin D concentrations <75 nmol/L. Sub-study 1 (n = 2808) investigated the effects of vitamin D supplementation on the risk of breakthrough SARS-CoV-2 infection following two doses of SARS-CoV-2 vaccine. Sub-study 2 (n = 1853) investigated the effects of vitamin D supplementation on titres of combined IgG, IgA and IgM (IgGAM) anti-Spike antibodies in eluates of dried blood spots collected after SARS-CoV-2 vaccination. Sub-study 3 (n = 100) investigated the effects of vitamin D supplementation on neutralising antibody and cellular responses in venous blood samples collected after SARS-CoV-2 vaccination. In total, 1945/2808 (69.3%) sub-study 1 participants received two doses of ChAdOx1 nCoV-19 (Oxford−AstraZeneca); the remainder received two doses of BNT162b2 (Pfizer). Mean follow-up 25(OH)D concentrations were significantly elevated in the 800 IU/day vs. no-offer group (82.5 vs. 53.6 nmol/L; mean difference 28.8 nmol/L, 95% CI 22.8−34.8) and in the 3200 IU/day vs. no offer group (105.4 vs. 53.6 nmol/L; mean difference 51.7 nmol/L, 45.1−58.4). Vitamin D supplementation did not influence the risk of breakthrough SARS-CoV-2 infection in vaccinated participants (800 IU/day vs. no offer: adjusted hazard ratio 1.28, 95% CI 0.89 to 1.84; 3200 IU/day vs. no offer: 1.17, 0.81 to 1.70). Neither did it influence IgGAM anti-Spike titres, neutralising antibody titres or IFN-γ concentrations in the supernatants of S peptide-stimulated whole blood. In conclusion, vitamin D replacement at a dose of 800 or 3200 IU/day effectively elevated 25(OH)D concentrations, but it did not influence the protective efficacy or immunogenicity of SARS-CoV-2 vaccination when given to adults who had a sub-optimal vitamin D status at baseline.
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Gut-muscle crosstalk. A perspective on influence of microbes on muscle function.
Chew, W, Lim, YP, Lim, WS, Chambers, ES, Frost, G, Wong, SH, Ali, Y
Frontiers in medicine. 2022;:1065365
Abstract
Our gastrointestinal system functions to digest and absorb ingested food, but it is also home to trillions of microbes that change across time, nutrition, lifestyle, and disease conditions. Largely commensals, these microbes are gaining prominence with regards to how they collectively affect the function of important metabolic organs, from the adipose tissues to the endocrine pancreas to the skeletal muscle. Muscle, as the biggest utilizer of ingested glucose and an important reservoir of body proteins, is intricately linked with homeostasis, and with important anabolic and catabolic functions, respectively. Herein, we provide a brief overview of how gut microbiota may influence muscle health and how various microbes may in turn be altered during certain muscle disease states. Specifically, we discuss recent experimental and clinical evidence in support for a role of gut-muscle crosstalk and include suggested underpinning molecular mechanisms that facilitate this crosstalk in health and diseased conditions. We end with a brief perspective on how exercise and pharmacological interventions may interface with the gut-muscle axis to improve muscle mass and function.
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The acute effect of fasted exercise on energy intake, energy expenditure, subjective hunger and gastrointestinal hormone release compared to fed exercise in healthy individuals: a systematic review and network meta-analysis.
Frampton, J, Edinburgh, RM, Ogden, HB, Gonzalez, JT, Chambers, ES
International journal of obesity (2005). 2022;(2):255-268
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OBJECTIVE To determine the acute effect of fasted and fed exercise on energy intake, energy expenditure, subjective hunger and gastrointestinal hormone release. METHODS CENTRAL, Embase, MEDLINE, PsycInfo, PubMed, Scopus and Web of Science databases were searched to identify randomised, crossover studies in healthy individuals that compared the following interventions: (i) fasted exercise with a standardised post-exercise meal [FastEx + Meal], (ii) fasted exercise without a standardised post-exercise meal [FastEx + NoMeal], (iii) fed exercise with a standardised post-exercise meal [FedEx + Meal], (iv) fed exercise without a standardised post-exercise meal [FedEx + NoMeal]. Studies must have measured ad libitum meal energy intake, within-lab energy intake, 24-h energy intake, energy expenditure, subjective hunger, acyl-ghrelin, peptide YY, and/or glucagon-like peptide 1. Random-effect network meta-analyses were performed for outcomes containing ≥5 studies. RESULTS 17 published articles (23 studies) were identified. Ad libitum meal energy intake was significantly lower during FedEx + Meal compared to FedEx + NoMeal (MD: -489 kJ; 95% CI, -898 to -80 kJ; P = 0.019). Within-lab energy intake was significantly lower during FastEx + NoMeal compared to FedEx + NoMeal (MD: -1326 kJ; 95% CI, -2102 to -550 kJ; P = 0.001). Similarly, 24-h energy intake following FastEx + NoMeal was significantly lower than FedEx + NoMeal (MD: -2095 kJ; 95% CI, -3910 kJ to -280 kJ; P = 0.024). Energy expenditure was however significantly lower during FastEx + NoMeal compared to FedEx+NoMeal (MD: -0.67 kJ/min; 95% CI, -1.10 to -0.23 kJ/min; P = 0.003). Subjective hunger was significantly higher during FastEx + Meal (MD: 13 mm; 95% CI, 5-21 mm; P = 0.001) and FastEx + NoMeal (MD: 23 mm; 95% CI, 16-30 mm; P < 0.001) compared to FedEx + NoMeal. CONCLUSION FastEx + NoMeal appears to be the most effective strategy to produce a short-term decrease in energy intake, but also results in increased hunger and lowered energy expenditure. Concerns regarding experimental design however lower the confidence in these findings, necessitating future research to rectify these issues when investigating exercise meal timing and energy balance. PROSPERO REGISTRATION NUMBER CRD42020208041. KEY POINTS Fed exercise with a standardised post-exercise meal resulted in the lowest energy intake at the ad libitum meal served following exercise completion. Fasted exercise without a standardised post-exercise meal resulted in the lowest within-lab and 24-h energy intake, but also produced the lowest energy expenditure and highest hunger. Methodological issues lower the confidence in these findings and necessitate future work to address identified problems.
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The Effect of a Single Bout of Continuous Aerobic Exercise on Glucose, Insulin and Glucagon Concentrations Compared to Resting Conditions in Healthy Adults: A Systematic Review, Meta-Analysis and Meta-Regression.
Frampton, J, Cobbold, B, Nozdrin, M, Oo, HTH, Wilson, H, Murphy, KG, Frost, G, Chambers, ES
Sports medicine (Auckland, N.Z.). 2021;(9):1949-1966
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BACKGROUND Elevated glucose and insulin levels are major risk factors in the development of cardiometabolic disease. Aerobic exercise is widely recommended to improve glycaemic control, yet its acute effect on glycaemia and glucoregulatory hormones has not been systematically reviewed and analysed in healthy adults. OBJECTIVE To determine the effect of a single bout of continuous aerobic exercise on circulating glucose, insulin, and glucagon concentrations in healthy adults. METHODS CENTRAL, CINAHL, Embase, Global Health, HMIC, Medline, PubMed, PsycINFO, ScienceDirect, Scopus and Web of Science databases were searched from inception to May 2020. Papers were included if they reported a randomised, crossover study measuring glucose and/or insulin and/or glucagon concentrations before and immediately after a single bout of continuous aerobic exercise (≥ 30 min) compared to a time-matched, resting control arm in healthy adults. The risk of bias and quality of evidence were assessed using the Cochrane Risk of Bias Tool and GRADE approach, respectively. Random-effects meta-analyses were performed for glucose, insulin, and glucagon. Sub-group meta-analyses and meta-regression were performed for categorical (metabolic state [postprandial or fasted], exercise mode [cycle ergometer or treadmill]) and continuous (age, body mass index, % males, maximal aerobic capacity, exercise duration, exercise intensity) covariates, respectively. RESULTS 42 papers (51 studies) were considered eligible: glucose (45 studies, 391 participants), insulin (38 studies, 377 participants) and glucagon (5 studies, 47 participants). Acute aerobic exercise had no significant effect on glucose concentrations (mean difference: - 0.05 mmol/L; 95% CI, - 0.22 to 0.13 mmol/L; P = 0.589; I2: 91.08%, large heterogeneity; moderate-quality evidence). Acute aerobic exercise significantly decreased insulin concentrations (mean difference: - 18.07 pmol/L; 95% CI, - 30.47 to - 5.66 pmol/L; P = 0.004; I2: 95.39%, large heterogeneity; moderate-quality evidence) and significantly increased glucagon concentrations (mean difference: 24.60 ng/L; 95% CI, 16.25 to 32.95 ng/L; P < 0.001; I2: 79.36%, large heterogeneity; moderate-quality evidence). Sub-group meta-analyses identified that metabolic state modified glucose and insulin responses, in which aerobic exercise significantly decreased glucose (mean difference: - 0.27 mmol/L; 95% CI, - 0.55 to - 0.00 mmol/L; P = 0.049; I2: 89.72%, large heterogeneity) and insulin (mean difference: - 42.63 pmol/L; 95% CI, - 66.18 to - 19.09 pmol/L; P < 0.001; I2: 81.29%, large heterogeneity) concentrations in the postprandial but not fasted state. Meta-regression revealed that the glucose concentrations were also moderated by exercise duration and maximal aerobic capacity. CONCLUSIONS Acute aerobic exercise performed in the postprandial state decreases glucose and insulin concentrations in healthy adults. Acute aerobic exercise also increases glucagon concentrations irrespective of metabolic state. Therefore, aerobic exercise undertaken in the postprandial state is an effective strategy to improve acute glycaemic control in healthy adults, supporting the role of aerobic exercise in reducing cardiometabolic disease incidence. PROSPERO REGISTRATION NUMBER CRD42020191345.
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Exploring the Evidence for an Immunomodulatory Role of Vitamin D in Juvenile and Adult Rheumatic Disease.
Zou, J, Thornton, C, Chambers, ES, Rosser, EC, Ciurtin, C
Frontiers in immunology. 2020;:616483
Abstract
Vitamin D is synthesized in the skin following exposure to UVB radiation or is directly absorbed from the diet. Following hydroxylation in the liver and kidneys, vitamin D becomes its bioactive form, 1,25(OH)2D, which has been described to have potent immunomodulatory capacity. This review will focus on the effect of vitamin D in modulating the dysregulated immune system of autoimmune rheumatic diseases (ARD) patients across age, in particular in arthritis (rheumatoid arthritis and juvenile idiopathic arthritis), and systemic lupus erythematosus (with adult and juvenile onset). As well as delineating the impact of vitamin D on the innate and adaptive immune functions associated with each disease pathology, this review will also summarize and evaluate studies that link vitamin D status with disease prevalence, and supplementation studies that examine the potential benefits of vitamin D on disease outcomes. Exploring this evidence reveals that better designed randomized controlled studies are required to clarify the impact of vitamin D supplementation on ARD outcomes and general health. Considering the accessibility and affordability of vitamin D as a therapeutic option, there is a major unmet need for evidence-based treatment recommendations for the use of vitamin D in this patient population.
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Moderate intensity exercise training combined with inulin-propionate ester supplementation increases whole body resting fat oxidation in overweight women.
Malkova, D, Polyviou, T, Rizou, E, Gerasimidis, K, Chambers, ES, Preston, T, Tedford, MC, Frost, G, Morrison, DJ
Metabolism: clinical and experimental. 2020;:154043
Abstract
BACKGROUND Our previous work has shown that oral supplementation with inulin propionate ester (IPE) reduces intra-abdominal fat and prevents weight gain and that oral propionate intake enhances resting fat oxidation. The effects of IPE combined with exercise training on energy substrate utilisation are unknown. The aim of this study was to investigate the impact of 4-weeks IPE supplementation, in combination with a moderate intensity exercise training programme, on whole body fat oxidation and on plasma GLP-1 and PYY. METHODS Twenty overweight healthy women participated in randomised parallel study and underwent 4 weeks of supervised exercise training either with IPE (EX/IPE group) or Placebo (EX/Placebo group) supplementation. Before and after the intervention participants conducted an experimental trial, which involved collection of expired gas and blood samples in the fasted state and during 7 h of the postprandial state. RESULTS Within groups, the EX/IPE group significantly enhanced the amount of fat (Pre, 24.1 ± 1.2 g; Post, 35.9 ± 4.0 g, P < 0.05) oxidised and reduced CHO (Pre, 77.8 ± 6.0 g; Post, 57.8 ± 7.7 g, P < 0.05) oxidised, reduced body weight (Pre, 77.3 ± 4.2 kg; Post, 76.6 ± 4.1 kg, P < 0.05) and body fat mass (Pre, 37.7 ± 1.9%; Post, 36.9 ± 1.9%, P < 0.05). In EX/Placebo group, changes in amount of fat (Pre, 36.8 ± 3.9 g; Post, 37.0 ± 4.0 g) and CHO (Pre, 62.7 ± 6.5 g; Post, 61.5 ± 7.4 g) oxidised, body weight (Pre, 84.2 ± 4.3 kg; Post, 83.6 ± 4.3 kg) and body fat mass (Pre, 40.1 ± 1.9%; Post, 38.7 ± 1.5%) were not significant (P > 0.05). Comparing between groups, changes in the amount of fat oxidised were significantly (P < 0.05) different and a trend for difference was observed for amount of CHO oxidised (P = 0.06) and RER (P = 0.06). The interventions had no impact on fasting or postprandial plasma concentrations of GLP-1 and PYY. CONCLUSION Moderate intensity exercise training programmes when combined with daily oral IPE supplementation may help overweight women to achieve increase in fat oxidation. The study was registered at clinicaltrials.gov as NCT04016350.