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Influence of the time of day in the effect of caffeine on maximal fat oxidation during exercise in women: a randomized, crossover, double-blind, and placebo-controlled study.
Muñoz, A, Aguilar-Navarro, M, Ruiz-Moreno, C, Varillas-Delgado, D, Amaro-Gahete, FJ, Gutiérrez-Hellín, J, Del Coso, J, López-Samanes, Á
European journal of applied physiology. 2024;(3):849-859
Abstract
PURPOSE Caffeine is a stimulant with well-recognized performance and metabolic benefits, however, there is a lack of studies investigating the time-of-day influence in the properties of caffeine to enhance fat oxidation in women. Thus, the aim of the present study was to evaluate the influence of the time of the day on the effect of caffeine on the maximal rate of fat oxidation during aerobic exercise in trained women. METHODS Fourteen female athletes (25.5 ± 7.1 years) took part in a randomized, crossover, double-blind study. All participants undertook four different experimental trials combining the ingestion of 3 mg/kg caffeine and a placebo either in the morning (8.00-10.00 h) and in the evening (17.00-19.00 h) realizing an incremental test on a cycle ergometer with 3 min stages at workloads from 30 to 70% of maximal oxygen uptake (VO2max). Substrate oxidation rates were measured by indirect calorimetry. In each trial, the maximum rate of fat oxidation (MFO) and the intensity that elicited MFO (Fatmax) were measured. RESULTS In comparison to placebo, MFO was significantly higher with caffeine both in the morning (0.24 ± 0.13 vs 0.30 ± 0.14 g/min; p < 0.001; ES = 0.79) and in the evening (0.21 ± 0.08 vs 0.28 ± 0.10 g/min; p = 0.002; ES = 0.72). No time-of-day effect on the capacity of caffeine to increase MFO was found (all p = 0.336) CONCLUSION The intake of 3 mg/kg of caffeine increased the use of fat as a fuel during exercise independently of the time-of-day in trained women. TRIAL REGISTRATION The study was registered in ClinicalTrials.gov with the following ID: NCT05880186 by 15 May 2023.
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Effect of 3 and 6 mg/kg of caffeine on fat oxidation during exercise in healthy active females.
Varillas-Delgado, D, Aguilar-Navarro, M, Muñoz, A, López-Samanés, Á, Ruiz-Moreno, C, Posada-Ayala, M, Amaro-Gahete, FJ, Del Coso, J, Gutiérrez-Hellín, J
Biology of sport. 2023;(3):827-834
Abstract
The aim of this study was to investigate the effect of 3 and 6 mg of caffeine per kg of body mass (mg/kg) on whole-body substrate oxidation during an incremental cycling exercise test in healthy active women. Using a double-blind placebo-controlled counterbalanced experimental design, 14 subjects performed three identical exercise trials after the ingestion of 3 or 6 mg/kg of caffeine or placebo. The exercise trials consisted of an incremental test on a cycle ergometer with 3-min stages at workloads from 30 to 70% of maximal oxygen uptake (VO2max). Substrate oxidation rates were measured by indirect calorimetry. During exercise, there was a significant effect of substance (F = 5.221; p = 0.016) on fat oxidation rate. In comparison to the placebo, 3 mg/kg of caffeine increased fat oxidation rates at 30 to 60% of VO2max (all p < 0.050) and 6 mg/kg at 30 to 50% of VO2max (all p < 0.050). There was also a significant effect of substance (F = 5.221; p = 0.016) on carbohydrate oxidation rate (F = 9.632; p < 0.001). In comparison to placebo, both caffeine doses decreased carbohydrate oxidation rates at 40 to 60% VO2max (all p < 0.050). The maximal rate of fat oxidation with placebo was 0.24 ± 0.03 g/min, which increased with 3 mg/kg to 0.29 ± 0.04 g/min (p = 0.032) and to 0.29 ± 0.03 with 6 mg/kg of caffeine (p = 0.042). Acute intake of caffeine improves the utilization of fat as a fuel during submaximal aerobic exercise in healthy active women with an effect of similar magnitude after the intake of 3 and 6 mg of caffeine per kg of body mass. Thus, the use of 3 mg/kg of caffeine would be more recommended than 6 mg/kg for women seeking increased fat utilization during submaximal exercise.
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Beetroot juice ingestion does not improve neuromuscular performance and match-play demands in elite female hockey players: a randomized, double-blind, placebo-controlled study.
López-Samanes, Á, Pérez-Lopez, A, Morencos, E, Muñoz, A, Kühn, A, Sánchez-Migallón, V, Moreno-Pérez, V, González-Frutos, P, Bach-Faig, A, Roberts, J, et al
European journal of nutrition. 2023;(3):1123-1130
Abstract
PURPOSE Beetroot juice is a dietary supplement that contains high levels of inorganic nitrate (NO3-) and that its intake has proven effective at increasing blood nitric oxide (NO) concentrations improving endurance performance. However, the effect of this supplement in team sport performance, especially in female athletes, has been barely studied. This study aimed to compare the acute effects of beetroot juice supplementation on neuromuscular performance and match-play demands in elite female field hockey players. METHODS Eleven elite female hockey players (22.8 ± 5.1 years) belonging to a bronze team medal in Eurohockey Club Champions Cup participated in this study. Participants were randomly divided into two groups undergoing a test battery with beetroot juice (70 mL, 6.4 mmol NO3-) or placebo (70 mL, 0.04 mmol NO3-) in two different days with one week between protocols. The neuromuscular test battery consisted of a countermovement jump, isometric handgrip strength (i.e., dominant hand), 20 m-sprint and repeated sprint ability test (RSA). Afterward, a simulated hockey match play (2 × 12.5 min) was performed and recorded by Global Positioning System (GPS). RESULTS No statistically significant improvements were observed in any physical parameters analysed comparing beetroot juice compared to placebo ingestion, countermovement jump (p = 0.776, ES = 0.16), isometric handgrip strength (p = 0.829; ES = - 0.08), 20 m sprint test (p = 0.227; ES = - 0.23), mean repeated sprint ability (p = 0.955, ES = 0.03) and in any physical match demands measured by GPS (p = 0.243-1.000; ES = 0.02-0.47). CONCLUSION Acute beetroot juice supplementation did not produce any statistically significant improvement in neuromuscular performance or match-play demands in elite female field hockey players. TRIAL REGISTRATION The study was registered in ClinicalTrials.gov with the following ID: NCT05209139. The study was retrospectively registered by 26 January 2022.
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Effect of caffeine intake on fat oxidation rate during exercise: is there a dose-response effect?
Gutiérrez-Hellín, J, Aguilar-Navarro, M, Ruiz-Moreno, C, Muñoz, A, Varillas-Delgado, D, Amaro-Gahete, FJ, Del Coso, J
European journal of nutrition. 2023;(1):311-319
Abstract
PURPOSE The effect of caffeine to enhance fat utilisation as fuel for submaximal aerobic exercise is well established. However, it is unknown whether this effect is dose dependent. The aim of this study was to investigate the effect of 3 and 6 mg of caffeine per kg of body mass (mg/kg) on whole-body substrate oxidation during an incremental cycling exercise test. METHODS In a double-blind, randomised, and counterbalanced experiment, 18 recreationally active males (maximal oxygen uptake [VO2max] = 56.7 ± 8.2 mL/kg/min) performed three experimental trials after ingesting either 3 mg/kg of caffeine, 6 mg/kg of caffeine or a placebo (cellulose). The trials consisted of an incremental exercise test on a cycle ergometer with 3-min stages at workloads from 30 to 80% of VO2max. Energy expenditure, fat oxidation rate, and carbohydrate oxidation rate were continuously measured by indirect calorimetry. RESULTS During exercise, there was significant effect of substance (F = 7.969; P = 0.004) on fat oxidation rate. In comparison to the placebo, the rate of fat oxidation was higher with 3 mg/kg of caffeine at 30, 40, 50 and 70% of VO2max [all P < 0.050, effect sizes (ES) from 0.38 to 0.50] and with 6 mg/kg of caffeine at 30, 40, 50, 60 and 70% of VO2max (all P < 0.050, ES from 0.28 to 0.76). Both 3 mg/kg (0.40 ± 0.21 g/min, P = 0.021, ES = 0.57) and 6 mg/kg of caffeine (0.40 ± 0.17 g/min P = 0.001, ES = 0.60) increased the maximal rate of fat oxidation during exercise over the placebo (0.31 ± 0.15 g/min). None of the caffeine doses produced any significant effect on energy expenditure or heart rate during exercise, while both caffeine doses reduced perceived fatigue at 80% of VO2max (all P < 0.050, ES from 0.71 to 1.48). CONCLUSION The effect of caffeine to enhance fat oxidation during submaximal aerobic exercise is of similar magnitude with 3 and 6 mg of caffeine per kg of body mass. Thus, a dose of 3 mg of caffeine per kg of body mass would be sufficient to enhance fat utilisation as fuel during submaximal exercise.
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Short-term complications and post-acute sequelae in hospitalized paediatric patients with COVID-19 and obesity: A multicenter cohort study.
Valenzuela, G, Alarcón-Andrade, G, Schulze-Schiapacasse, C, Rodríguez, R, García-Salum, T, Pardo-Roa, C, Levican, J, Serrano, E, Avendaño, MJ, Gutiérrez, M, et al
Pediatric obesity. 2023;(2):e12980
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Abstract
BACKGROUND Obesity increases the severity of coronavirus disease 2019 illness in adults. The role of obesity in short-term complications and post-acute sequelae in children is not well defined. OBJECTIVE To evaluate the relationship between obesity and short-term complications and post-acute sequelae of SARS-CoV-2 infection in hospitalized paediatric patients. METHODS An observational study was conducted in three tertiary hospitals, including paediatric hospitalized patients with a confirmatory SARS-CoV-2 RT-PCR from March 2020 to December 2021. Obesity was defined according to WHO 2006 (0-2 years) and CDC 2000 (2-20 years) growth references. Short-term outcomes were intensive care unit admission, ventilatory support, superinfections, acute kidney injury, and mortality. Neurological, respiratory, and cardiological symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms were considered as post-acute sequalae. Adjusted linear, logistic regression and generalized estimating equations models were performed. RESULTS A total of 216 individuals were included, and 67 (31.02%) of them had obesity. Obesity was associated with intensive care unit admission (aOR = 5.63, CI95% 2.90-10.94), oxygen requirement (aOR = 2.77, CI95% 1.36-5.63), non-invasive ventilatory support (aOR = 6.81, CI95% 2.11-22.04), overall superinfections (aOR = 3.02 CI95% 1.45-6.31), and suspected bacterial pneumonia (aOR = 3.00 CI95% 1.44-6.23). For post-acute sequalae, obesity was associated with dyspnea (aOR = 9.91 CI95% 1.92-51.10) and muscle weakness (aOR = 20.04 CI95% 2.50-160.65). CONCLUSIONS In paediatric hospitalized patients with COVID-19, severe short-term outcomes and post-acute sequelae are associated with obesity. Recognizing obesity as a key comorbidity is essential to develop targeted strategies for prevention of COVID-19 complications in children.
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Does the Time of Day Play a Role in the Acute Effect of p-Synephrine on Fat Oxidation Rate during Exercise in Women? A Randomized, Crossover and Double-Blind Study.
Gutiérrez-Hellín, J, Del Coso, J, Aguilar-Navarro, M, Varillas-Delgado, D, Ruiz-Moreno, C, López-Samanés, Á, Amaro-Gahete, FJ, Muñoz, A
Nutrients. 2022;(23)
Abstract
p-Synephrine is deemed a safe and effective substance to increase fat utilization during exercise of low-to-moderate intensity in men but not in women. Additionally, the existence of a diurnal variation in substrate utilization has been documented during exercise with enhanced fat oxidation in the evening compared with early morning. However, it remains unknown whether there is an interaction between the effect of p-synephrine and the time of the day on fat oxidation during exercise. This study aimed to evaluate the effect of the acute ingestion of 3 milligram of p-synephrine per kilogram of body mass (mg/kg) on fat oxidation during exercise of increasing intensity when the exercise is performed in the morning vs. the evening. Using a randomized, double-blind, placebo-controlled experimental design, 16 healthy and active women performed four identical exercise trials after the ingestion of 3 mg/kg of p-synephrine and 3 mg/kg of a placebo (cellulose) both in the morning (8-10 am) and in the evening (5-7 pm). In the exercise trials, the substances were ingested 60 min before an incremental test on a cycle ergometer with 3 min stages at workloads from 30 to 80% of maximal oxygen uptake (VO2max). Substrate oxidation rates were measured by indirect calorimetry. In each trial, the maximum rate of fat oxidation (MFO) and the intensity that elicited MFO (Fatmax) were measured. A two-way analysis of variance (time-of-the day × substance) was used to detect differences among the trials. With the placebo, MFO was 0.25 ± 0.11 g/min in the morning and 0.24 ± 0.07 g/min in the evening. With p-synephrine, MFO was 0.26 ± 0.09 g/min in the morning and 0.21 ± 0.07 g/min in the evening. There was no main effect of substance (p = 0.349), time of day (p = 0.186) and the substance × time of day (p = 0.365) on MFO. Additionally, Fatmax was reached at a similar exercise intensity with the placebo (41.33 ± 8.34% VO2max in the morning and 44.38 ± 7.37% VO2max in the evening) and with p-synephrine (43.33 ± 7.24% VO2max in the morning and 45.00 ± 7.43% VO2max in the evening), irrespective of the time of day with no main effect of substance (p = 0.633), time of day (p = 0.191), or interaction (p = 0.580). In summary, the acute intake of 3 mg/kg of p-synephrine before exercise did not increase MFO and Fatmax, independently of the time of day, in female athletes. This indicates that the time of day is not a factor explaining the lack of effectiveness of this substance to enhance fat oxidation during aerobic exercise in women.
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Preoperative Omega-6/Omega-3 Fatty Acid Ratio Could Predict Postoperative Outcomes in Patients with Surgically Resected Non-Small-Cell Lung Cancer.
Déniz, C, Raba-Parodi, C, García-Raimundo, E, Macía, I, Rivas, F, Ureña, A, Muñoz, A, Moreno, C, Serratosa, I, Masuet-Aumatell, C, et al
Current oncology (Toronto, Ont.). 2022;(10):7086-7098
Abstract
Introduction: The aim of this study was to determine whether preoperative nutritional status and inflammatory status, specifically polyunsaturated acids and the omega 6/3 ratio, would affect postoperative outcomes and complications in patients with lung cancer undergoing lung resection. Methods: This prospective observational study included 68 patients with early-stage non-small-cell lung cancer who were candidates for radical surgery. A complete nutritional assessment was performed. The primary study variable was postoperative complications and mortality in the first 30 days. Descriptive, bivariate, and logistic regression analyses were carried out. Results: A total of 50 men (73.53%) and 18 women (26.47%) underwent surgery, with a median age of 64.2 (±9.74) years. The mean omega 6/3 ratio was 17.39 (±9.45). A complication occurred in 39.7% of the study sample (n = 27), the most common being persistent air leak in 23.53% (n = 16). After performing the bivariate analysis, the only variable that remained significant was the omega 6/3 ratio; we observed that it had a prognostic value for persistent air leak (p = 0.001) independent of age, sex, comorbidity, preoperative respiratory function, and approach or type of surgery. The remaining nutritional and inflammatory markers did not have a statistically significant association (p > 0.05) with postoperative complications. However, this significance was not maintained in the multivariate analysis by a small margin (p = 0.052; 95% CI: 0.77-1.41). Conclusions: Omega 6/3 ratio may be a prognostic factor for air leak, independent of the patient's clinical and pathological characteristics.
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Mechanisms Leading to Gut Dysbiosis in COVID-19: Current Evidence and Uncertainties Based on Adverse Outcome Pathways.
Clerbaux, LA, Fillipovska, J, Muñoz, A, Petrillo, M, Coecke, S, Amorim, MJ, Grenga, L
Journal of clinical medicine. 2022;(18)
Abstract
Alteration in gut microbiota has been associated with COVID-19. However, the underlying mechanisms remain poorly understood. Here, we outlined three potential interconnected mechanistic pathways leading to gut dysbiosis as an adverse outcome following SARS-CoV-2 presence in the gastrointestinal tract. Evidence from the literature and current uncertainties are reported for each step of the different pathways. One pathway investigates evidence that intestinal infection by SARS-CoV-2 inducing intestinal inflammation alters the gut microbiota. Another pathway links the binding of viral S protein to angiotensin-converting enzyme 2 (ACE2) to the dysregulation of this receptor, essential in intestinal homeostasis-notably for amino acid metabolism-leading to gut dysbiosis. Additionally, SARS-CoV-2 could induce gut dysbiosis by infecting intestinal bacteria. Assessing current evidence within the Adverse Outcome Pathway framework justifies confidence in the proposed mechanisms to support disease management and permits the identification of inconsistencies and knowledge gaps to orient further research.
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Effect of p-Synephrine on Fat Oxidation Rate during Exercise of Increasing Intensity in Healthy Active Women.
Gutiérrez-Hellín, J, Aguilar-Navarro, M, Ruiz-Moreno, C, Muñoz, A, Amaro-Gahete, FJ, Posada-Ayala, M, López-Samanes, Á, Del Coso, J, Varillas-Delgado, D
Nutrients. 2022;(20)
Abstract
p-Synephrine is the principal alkaloid of bitter orange (Citrus aurantium). Several recent investigations have found that the intake of 2-3 mg/kg of p-synephrine raises fat oxidation rate during exercise of low-to-moderate intensity. However, these investigations have been carried out only with samples of male participants or mixed men/women samples. Therefore, the aim of this investigation was to study the effect of p-synephrine intake on fat oxidation during exercise of increasing intensity in healthy women. Using a double-blind, randomized experiment, 18 healthy recreationally active women performed two identical exercise trials after the ingestion of (a) 3 mg/kg of p-synephrine and (b) 3 mg/kg of a placebo (cellulose). The exercise trials consisted of a ramp test (from 30 to 80% of maximal oxygen uptake; VO2max) on a cycle ergometer while substrate oxidation rates were measured at each workload by indirect calorimetry. In comparison to the placebo, the intake of p-synephrine increased resting tympanic temperature (36.1 ± 0.5 vs. 36.4 ± 0.4 °C p = 0.033, d = 0.87) with no effect on resting heart rate (p = 0.111) and systolic (p = 0.994) and diastolic blood pressure (p = 0.751). During exercise, there was no significant effect of p-synephrine on fat oxidation rate (F = 0.517; p = 0.484), carbohydrate oxidation rate (F = 0.730; p = 0.795), energy expenditure rate (F = 0.480; p = 0.833), heart rate (F = 4.269; p = 0.068) and participant's perceived exertion (F = 0.337; p = 0.580). The maximal rate of fat oxidation with placebo was 0.26 ± 0.10 g/min and it was similar with p-synephrine (0.28 ± 0.08 g/min, p = 0.449, d = 0.21). An acute intake of 3 mg/kg of p-synephrine before exercise did not modify energy expenditure and substrate oxidation during submaximal aerobic exercise in healthy active women. It is likely that the increase in resting tympanic temperature induced by p-synephrine hindered the effect of this substance on fat utilization during exercise in healthy active women.
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An update on vitamin D signaling and cancer.
Carlberg, C, Muñoz, A
Seminars in cancer biology. 2022;:217-230
Abstract
A low vitamin D status is associated with an increased risk of various cancers, such as of colon, breast, prostate and hematological cells. The biologically most active vitamin D metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) is a high affinity ligand of the transcription factor vitamin D receptor (VDR). 1,25(OH)2D3 induces via VDR changes to the epigenome of healthy and neoplastic cells and in this way influences their transcriptome. Ligand-activated VDR binds to more than 10,000 loci within the human genome and affects the transcription of some 1000 target genes in a large proportion of human tissues and cell types. From the evolutionary perspective, the prime role of vitamin D was probably the control of energy metabolism later shifting to modulate innate and adaptive immunity as well as to regulate calcium and bone homeostasis. Since rapidly growing immune and cancer cells both use the same pathways and genes for controlling their proliferation, differentiation and apoptosis, not surprisingly, vitamin D signaling changes these processes also in neoplastic cells. Thus, anti-cancer effects of vitamin D may derive from managing growth and differentiation in immunity. This review provides an update on the molecular basis of vitamin D signaling, i.e., the effects of 1,25(OH)2D3 on the epigenome and transcriptome, and its relationship to cancer prevention and therapy.