From Microcosm to Macrocosm: The -Omics, Multiomics, and Sportomics Approaches in Exercise and Sports.

This article explores the progressive integration of -omics methods, including genomics, metabolomics, and proteomics, into sports research, highlighting the development of the concept of "sportomics." We discuss how sportomics can be used to comprehend the multilevel metabolism during exercise in real-life conditions faced by athletes, enabling potential personalized interventions to improve performance and recovery and reduce injuries, all with a minimally invasive approach and reduced time. Sportomics may also support highly personalized investigations, including the implementation of n-of-1 clinical trials and the curation of extensive datasets through long-term follow-up of athletes, enabling tailored interventions for athletes based on their unique physiological responses to different conditions. Beyond its immediate sport-related applications, we delve into the potential of utilizing the sportomics approach to translate Big Data regarding top-level athletes into studying different human diseases, especially with nontargeted analysis. Furthermore, we present how the amalgamation of bioinformatics, artificial intelligence, and integrative computational analysis aids in investigating biochemical pathways, and facilitates the search for various biomarkers. We also highlight how sportomics can offer relevant information about doping control analysis. Overall, sportomics offers a comprehensive approach providing novel insights into human metabolism during metabolic stress, leveraging cutting-edge systems science techniques and technologies.

Lipid oxidation dysregulation: an emerging player in the pathophysiology of sepsis.

Sepsis is a life-threatening organ dysfunction caused by abnormal host response to infection. Millions of people are affected annually worldwide. Derangement of the inflammatory response is crucial in sepsis pathogenesis. However, metabolic, coagulation, and thermoregulatory alterations also occur in patients with sepsis. Fatty acid mobilization and oxidation changes may assume the role of a protagonist in sepsis pathogenesis. Lipid oxidation and free fatty acids (FFAs) are potentially valuable markers for sepsis diagnosis and prognosis. Herein, we discuss inflammatory and metabolic dysfunction during sepsis, focusing on fatty acid oxidation (FAO) alterations in the liver and muscle (skeletal and cardiac) and their implications in sepsis development.

Investigations into Annona fruit consumption as a potential source of dietary higenamine intake in the context of sports drug testing.

Higenamine is prohibited in sports as a ß2 -agonist by the World Anti-Doping Agency. As a key component of a great variety of plants, including the Annonaceae family, one aim of this research project was to evaluate whether the ingestion of Annona fruit could lead to higenamine adverse analytical findings. Single-dose administration studies including three Annona species (i.e., Annona muricata, Annona cherimola, and Annona squamosa) were conducted, leading to higenamine findings below the established minimum reporting level (MRL) of 10 ng/mL in urine. In consideration of cmax values (7.8 ng/mL) observed for higenamine up to 24 h, a multidose administration study was also conducted, indicating cumulative effects, which can increase the risk of exceeding the applicable MRL doping after Annona fruit ingestion. In this study, however, the MRL was not exceeded at any time point. Further, the major urinary excretion of higenamine in its sulfo-conjugated form was corroborated, its stability in urine was assessed, and in the absence of reference material, higenamine sulfo-conjugates were synthesized and comprehensively characterized, suggesting the predominant presence of higenamine 7-sulfate. In addition, the option to include complementary biomarkers of diet-related higenamine intake into routine doping controls was investigated. A characteristic urinary pattern attributed to isococlaurine, reticuline, and a yet not fully characterized bismethylated higenamine glucuronide was observed after Annona ingestion but not after supplement use, providing a promising dataset of urinary biomarkers, which supports the discrimination between different sources of urinary higenamine detected in sports drug testing programs.

A sportomics soccer investigation unveils an exercise-induced shift in tyrosine metabolism leading to hawkinsinuria.

Tyrosine metabolism has an intense role in the synthesis of neurotransmitters. Our study used an untargeted, sportomics-based analysis of urine samples to investigate changes in metabolism during a soccer match in 30 male junior professional soccer players. Samples were collected before and after the match and analyzed using liquid chromatography and mass spectrometry. Results showed significant changes in tyrosine metabolism. Exercise caused a downregulation of the homogentisate metabolites 4-maleylacetoacetate and succinylacetone to 20% (p = 4.69E-5) and 16% (p = 4.25E-14), respectively. 4-Hydroxyphenylpyruvate, a homogentisate precursor, was found to be upregulated by 26% (p = 7.20E-3). The concentration of hawkinsin and its metabolite 4-hydroxycyclohexyl acetate increased ~six-fold (p = 1.49E-6 and p = 9.81E-6, respectively). Different DOPA metabolism pathways were also affected by exercise. DOPA and dopaquinone increased four-to six-fold (p = 5.62E-14 and p = 4.98E-13, respectively). 3-Methoxytyrosine, indole-5,6-quinone, and melanin were downregulated from 1 to 25%, as were dopamine and tyramine (decreasing to up to 5% or 80%; p= 5.62E-14 and p = 2.47E-2, respectively). Blood TCO2 decreased as well as urinary glutathione and glutamate (40% and 10% respectively) associated with a two-fold increase in pyroglutamate. Our study found unexpected similarities between exercise-induced changes in metabolism and the inherited disorder Hawkinsinuria, suggesting a possible transient condition called exercise-induced hawkinsinuria (EIh). Additionally, our research suggests changes in DOPA pathways may be involved. Our findings suggest that soccer exercise could be used as a model to search for potential countermeasures in Hawkinsinuria and other tyrosine metabolism disorders.

A burst of fenoterol excretion during the recovery of a weight loss protocol.

Fenoterol is a sympathomimetic ß2 receptor agonist primarily used as a bronchodilator. Due to its sympathomimetic actions, the World Anti-Doping Agency (WADA) has banned it. Multiple acute weight loss protocols (WLP) are used by Olympic athletes for sports that segregate athletes by weight; these generally involve caloric and water deprivation combined with heat exposure. Athletes use WLP before weigh-in, then transition to different body acute weight regain protocols (WRP) before competitions. Here, we studied the pharmacokinetics of fenoterol under WLP conditions: energetic dietary restriction, decreased water intake, and exposure to a dry sauna (80 ± 2 °C), followed by a WRP. Five elite-level female judo athletes participated in the study. Four received fenoterol (200 µg; n = 2 or 400 µg; n = 2), while one was a control receiving placebo under identical conditions. We measured excretion of the fenoterol parent molecule and presented qualitative data of its sulfated metabolite using QqQ tandem quadrupole mass spectrometry for 118 h. The fenoterol parent appeared earlier in urine than did its conjugated metabolite; excretion profiles were similar among all subjects. The centers of mass for fenoterol parent curves were (time, fenoterol): athlete A (10.9, 7.3); athlete B (9.2, 27.3); athlete C (8.5, 6.9); athlete D (9.7, 5.0). After initiating WRP, we observed a burst in urinary fenoterol excretion once in complete decay. This trend was observed for all four athletes who received fenoterol. Our results suggest that during hypohydration, some of the unmetabolized fenoterol accumulates in tissues, then is released during rehydration. These findings can be important for detecting fenoterol use in athletes.

Dietary higenamine from Annonaceae family fruits as a possible source of unintentional doping.

Members of the genus Aconitum have been used for millennia, both as poisons and medicines, in Eastern culture. Higenamine has non-selective beta-agonist effects, activating both ß1 and ß2 adrenoreceptors, and is present in a variety of plants. The World Anti-Doping Agency has banned Higenamine both in competition and out of competition. Due to the common uses of higenamine in Brazilian culture, both as medicine and food, we studied the urinary concentrations of higenamine after the consumption of fruits of the Annona genus. We evaluated whether the ingestion of these fruits has the potential to cause anti-doping code violations. We measured higenamine concentrations for a 72 h period in the urine of ten healthy, physically active males (age 20-30; weight 70-80 kg; not consuming supplements or medications) after eating a unique meal containing fruits. Fruit consumption ranges were: Carica papaya (control) 348 ± 98 g; A. muricata 450 ± 282 g; and A. squamosa 314 ± 60 g. (all mean± SD). Higenamine was measured using ultra-performance liquid chromatography coupled with electrospray-tandem mass spectrometry. The appearance of urinary higenamine occurred within the first 12 h after eating A. muricata (n = 3), and the maximum concentration found was 1.9 ng/mL. The ingestion of A. squamosa has also been shown to cause higenamine urinary excretion. The elimination kinetics of the subjects who ingested A. squamosa (n = 4) were different from each other. After ingestion of the control fruit, C. papaya, we detected no higenamine in the urine of any participants (n = 3). Although the kinetics varied by individuals and fruits, A. muricata ingestion produced higher higenamine excretion; however, the A. squamosa portion weighed ∼66 % of the A. muricata portion. We conclude that eating Annonaceae family fruits cause detectable higenamine excretion. Conversely, single ingestion did not reach the WADA's threshold to cause adverse analytical findings.

Sportomics suggests that albuminuria is a sensitive biomarker of hydration in cross combat.

We have been using sportomics to understand hypermetabolic stress. Cross Combat (CCombat) has recently been initiated as a high-intensity functional training method inspired by CrossFit. We used a CCombat session to induce metabolic stress and evaluated its effects on hydration and kidney function. Blood samples were collected from 16 elite-level professional male athletes engaged in training sessions over a 96-h protocol. Blood myoglobin increased by ~ 3.5-fold (119 ± 21 to 369 ± 62 nmol/L; p = .001) in response to the protocol, returning to the pre-exercise level within 48 h. Furthermore, D-dimer levels increased from 6.5 ± 0.6 to 79.4 ± 21.3 µmol/L (p < .001) in response to exercise decreasing during recovery with high variability among the studied athletes. Albuminemia and creatininemia increased ~ 10% and cystatin C increased ~ 240% (1.7 ± 0.1 to 5.7 ± 0.5 mg/L; p < .001; effect size = 2.4) in response to the protocol. We measured albuminuria (HuA) to assess kidney permeability to albumin caused by exercise. HuA increased ~ 16-fold (0.16 ± 0.03 to 2.47 ± 0.41 µmol/L; p < .001; effect size = 1.4) in response to exercise, dropping and reaching basal levels during 48 h. Here, we suggest that microalbuminuria can be used as an early, sensitive, easy, and inexpensive biomarker to evaluate hydration status changes during intensive exercise, decreasing chronic impairment in renal function.

Sports and performance in the transgender population: a systematic review and meta-analysis / Deporte y rendimiento en la población transgénero: revisión sistemática y metanálisis / Esportes e desempenho na população transgênero: uma revisão sistemática e metanálise

ABSTRACT Introduction: The debate surrounding the regulations on the participation of transgender individuals in sports is not recent, but it is still ongoing. Some sports organizations are more flexible in this regard, while others are more conservative. Objective: Through a systematic review and meta-analysis, this study summarizes the scientific evidence of the effects of cross-sex hormone therapy on muscle strength, hematocrit, and hemoglobin measurements, parameters that seem to be linked to sports performance. Methods: We conducted electronic searches for manuscripts published before November 20th, 2020. Studies published in three different databases (PubMed, SciELO, and Lilacs) were included, without any time or language restriction, and using keywords such as "transgender", "gender dysphoria", "strength", "hematocrit", and "hemoglobin". The PRISMA systematization was used for the elaboration of this review, while a meta-analysis was conducted to mathematically evidence the results. The meta-analysis was performed using the random effect model, to find the pooled estimate effect of cross-sex hormone therapy on the parameters analyzed. Results: The electronic search retrieved 21 articles that were eligible for inclusion. Cross-sex hormone therapy influenced the three parameters analyzed in almost all the studies. Overall, there was a significant increase in muscle strength in female-to-males (FtMs), per muscle group analyzed: +17.7% (95% confidence interval [CI]14.9;20.6). In male-to-females (MtFs) the results of the muscle strength analysis were more controversial, but the pooled estimate effect showed a decrease: −3.6% (95% confidence interval [CI] −6.6; −0.6). Conclusion: Muscle strength, hematocrit, and hemoglobin were altered as a result of cross-sex hormone therapy in both FtMs and MtFs. However, there was a lack of studies comparing the transgender individuals to the population of the same desired gender. Such studies are needed, to better infer rules for the participation of transgender athletes in Olympic sports. Level of Evidence I; Systematic Review and Meta-analysis.

RESUMEN Introducción: El debate sobre las regulaciones relativas a la participación de las personas transgénero en el deporte no es reciente. Algunas organizaciones deportivas son más flexibles, mientras que otras, más conservadoras. Objetivo: Este estudio tuvo como objetivo resumir la evidencia científica sobre los efectos de la terapia hormonal cruzada en la fuerza muscular, hematocrito, y hemoglobina, parámetros que parecen estar vinculados al rendimiento deportivo, mediante revisión sistemática y metanálisis. Métodos: Realizamos búsquedas electrónicas de manuscritos publicados antes del 20 de noviembre de 2020. Se incluyeron estudios publicados en tres bases de datos (PubMed, SciELO y Lilacs) sin restricción de tiempo o lenguaje. Se utilizaron palabras clave como "transgénero", "disforia de género", "fuerza", "hematocrito" y "hemoglobina". Para la elaboración de esta revisión se utilizó la sistematización PRISMA, mientras que se realizó un metanálisis para evidenciar matemáticamente los resultados. El metanálisis se realizó utilizando el modelo de efecto aleatorio, para encontrar el efecto de estimación agrupado de la terapia hormonal cruzada en los parámetros analizados. Resultados: La búsqueda electrónica incluyó 21 artículos. La terapia hormonal cruzada influyó en los tres parámetros analizados en casi todos los estudios. En general, hubo un aumento significativo en la fuerza muscular en hombres trans (FtMs), por grupo muscular analizado: +17.7% (95% intervalo de confianza [CI]14.9;20.6). En mujeres trans (MTFs) los resultados en el análisis de fuerza muscular fueron más controvertidos, pero el efecto de estimación agrupado mostró una disminución: −3.6% (95% intervalo de confianza [CI] −6.6; −0.6). Conclusión: Fuerza muscular, hematocrito, y hemoglobina han cambiado sus niveles en respuesta a la terapia hormonal cruzada en hombres trans y mujeres trans. Sin embargo, encontramos una falta de estudios que compararan a las personas transgénero con la población del mismo género deseado, lo que sería necesario para inferir mejor las reglas sobre la participación de los transexuales en los deportes olímpicos. Nivel de Evidencia I; Revisión sistemática y Metanálisis.

RESUMO Introdução: O debate sobre as regulamentações relativas à participação de transgêneros no esporte não é recente, mais ainda está em progresso. Algumas organizações esportivas são mais flexíveis nesse aspecto, enquanto outras são mais conservadoras. Objetivo: Mediante revisão sistemática e metanálise, este estudo resume as evidências científicas dos efeitos do tratamento hormonal de redesignação sexual nas medidas de força muscular, hematócritos e hemoglobina, parâmetros que parecem estar ligados ao desempenho esportivo. Métodos: Foram realizadas buscas eletrônicas de artigos publicados antes de 20 de novembro de 2020 incluídos em três bancos de dados (PubMed, SciELO e Lilacs), sem restrição de tempo ou idioma, sendo usados os descritores "transgender", "gender dysphoria", "strength", "hematocrit" e "hemoglobin". A sistematização PRISMA foi usada para a elaboração desta revisão, enquanto a metanálise foi realizada para evidenciar matematicamente os resultados. A metanálise foi realizada com o modelo de efeito aleatório para encontrar o efeito combinado estimado do tratamento hormonal de redesignação sexual sobre os parâmetros analisados. Resultados: A busca eletrônica recuperou 21 artigos elegíveis. O tratamento hormonal de redesignação sexual influenciou os três parâmetros analisados em quase todos os estudos. No geral, houve um aumento significativo da força muscular nos homens trans (FtMs) no grupo de músculos analisado: +17,7% (intervalo de confiança [IC] de 95% 14,9; 20,6). Nas mulheres trans (MtFs) os resultados da análise da força muscular foram mais controversos, mas o efeito de estimativa agrupado mostrou uma diminuição: −3,6% (intervalo de confiança [IC] de 95% 6,6; −0,6). Conclusão: Força muscular, hematócritos e hemoglobina tiveram níveis alterados em resposta ao tratamento hormonal de redesignação sexual tanto em FtMs quanto em MtFs. No entanto, há escassez de estudos que comparem os indivíduos transgênero com a população do mesmo gênero desejado. Esses estudos são necessários para melhor definir as regras da participação de transgêneros nos esportes olímpicos. Nível de Evidência I; Revisão Sistemática e Metanálise.