The Effect of Vitamin D Consumption on Pro-Inflammatory Cytokines in Athletes: A Systematic Review of Randomized Controlled Trials.

Vitamin D is essential for the optimal health of the skeletal system. However, this vitamin also plays a role in other functions of the human body, such as muscle, immune, and inflammatory functions. Some studies have reported that adequate levels of vitamin D improve immune system function by reducing the levels of certain pro-inflammatory cytokines, which can protect against the risk of post-exercise illness. This systematic review aims to investigate the effects of vitamin D supplementation on pro-inflammatory cytokines in athletes. This study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature search was conducted in SPORTDiscus, PubMed, ScienceDirect, and Google Scholar up to 1 October 2023. The quality of the articles was evaluated using the Risk of Bias 2 Tool. After searching the databases, a total of 7417 studies were identified, 6 of which met the eligibility criteria, and their outcomes were presented. The six studies included 176 participants. All six studies are randomized control trials, including a total of 176 subjects, primarily men (81%). Regarding the types of athletes, most participants were endurance athletes. Our investigation in this systematic review demonstrated that out of the six studies, only two of them reported significant changes in IL-6 and TNF-α levels after taking high-dose vitamin D. Other studies did not present any significant changes after vitamin D supplementation in athletes with respect to IL-6 and TNF-α levels. Further studies are needed to determine the effectiveness of vitamin D supplementation for athletes as a disease-prone community.

Pre-exercise meal on oxidation of energy substrates during maximal exercise test in non-trained individuals.

Objective: This study aimed to compare the influence of a high carbohydrate meal versus high-fat meal on the oxidation of substrates during an exercise incremental test. Materials and methods: Ten untrained male subjects underwent two days of the protocol. Randomly, they received a high carbohydrate meal or a high-fat meal, receiving the other one in the next protocol. On both days, they performed an incremental treadmill test, with heart rate and maximal oxygen consumption to estimate the oxidation of substrates. Results: The high-fat meal showed an increase in the absolute amount of oxidized fat along with the incremental test (P < 0.05; effect size = 0.9528), and a reduction in the respiratory exchange ratio at low intensities (P < 0.05; effect size = 0.7765). Conclusion: The meals presented no difference when compared to maximum oxidation point of substrates, the oxidation rate of substrates over time, and heart rate. A pre-test high-fat meal in untrained individuals was shown to be a modulating factor of total oxidized fats throughout the exercise, although it did not exert a significant effect on the rate of this oxidation over time.

Pre-exercise meal on oxidation of energy substrates during maximal exercise test in non-trained individuals

ABSTRACT Objective: This study aimed to compare the influence of a high carbohydrate meal versus high-fat meal on the oxidation of substrates during an exercise incremental test. Materials and methods: Ten untrained male subjects underwent two days of the protocol. Randomly, they received a high carbohydrate meal or a high-fat meal, receiving the other one in the next protocol. On both days, they performed an incremental treadmill test, with heart rate and maximal oxygen consumption to estimate the oxidation of substrates. Results: The high-fat meal showed an increase in the absolute amount of oxidized fat along with the incremental test (P < 0.05; effect size = 0.9528), and a reduction in the respiratory exchange ratio at low intensities (P < 0.05; effect size = 0.7765). Conclusions: The meals presented no difference when compared to maximum oxidation point of substrates, the oxidation rate of substrates over time, and heart rate. A pre-test high-fat meal in untrained individuals was shown to be a modulating factor of total oxidized fats throughout the exercise, although it did not exert a significant effect on the rate of this oxidation over time.

Effects of aerobic and resistance exercise training associated with carnosine precursor supplementation on maximal strength and V̇O2max in rats with heart failure.

BACKGROUND: Combined exercise training (CET) has been associated with positive responses in the clinical status of patients with heart failure (HF). Other nonpharmacological tools, such as amino acid supplementation, may further enhance its adaptation. The aim was to test whether CET associated with supplementing carnosine precursors could present better responses in the functional capacity and biochemical variables of rats with HF. METHODS: Twenty-one male Wistar rats were subjected to myocardial infarction and allocated to three groups: sedentary (SED, n = 7), CET supplemented with placebo (CETP, n = 7), and CET with HF supplemented with ß-alanine and L-histidine (CETS, n = 7). The trained animals were submitted to a strength protocol three times per week. Aerobic training was conducted twice per week. The supplemented group received ß-alanine and L-histidine orally (250 mg/kg per day). RESULTS: Maximum oxygen uptake, running distance, time to exhaustion and maximum strength were higher in the CET-P group than that in the SED group and even higher in the CET-S group than that in the CET-P group (P < 0.01). CET-S showed lower oxidative stress and inflammation markers and higher heat shock protein 72 kDa content and mRNA expression for calcium transporters in the skeletal muscle compared to SED. CONCLUSION: CET together with ß-alanine and L-histidine supplementation in rats with HF can elicit adaptations in both maximum oxygen uptake, running distance, time to exhaustion, maximum strength, oxidative stress, inflammation and mRNA expression. Carnosine may influence beneficial adjustments in the cell stress response in the skeletal muscle and upregulate the mRNA expression of calcium transporters.

Biochemical analysis of ectonucleotidases on primary rat vascular smooth muscle cells and in silico investigation of their role in vascular diseases.

Vascular smooth muscle cells (VSMCs) exhibit a high degree of plasticity when they undergo the progression from a normal to a disease condition, which makes them a potential target for evaluating early markers and for the development of new therapies. Purinergic signalling plays a key role in vascular tonus control, ATP being an inductor of vasoconstriction, whereas adenosine mediates a vasodilation effect antagonising the ATP actions. The control of extracellular ATP and adenosine levels is done by ectonucleotidases, which represent a potential target to be evaluated in the progression of cardiovascular diseases. In this study, we analysed the basal activity and expression of the ectonucleotidases in aortic rat VSMCs, and we further performed in silico analysis to determine the expression of those enzymes in conditions that mimicked vascular diseases. Cultured in vitro VSMCs showed a prominent expression of Entpd1 followed by Entpd2 and Nt5e (CD73) and very low levels of Entpd3. Slightly faster AMP hydrolysis was observed when compared to ATP and ADP nucleotides. In silico analysis showed that the ectonucleotidases were modulated after induction of conditions that can lead to vascular diseases such as, hypertensive and hypotensive mice models (Nt5e); exposition to high-fat (Entpd1 and Entpd2) or high-phosphate (Nt5e) diet; mechanical stretch (Entpd1, Entpd2 and Nt5e); and myocardial infarction (Entpd1). Our data show that VSMCs are able to efficiently metabolise the extracellular nucleotides generating adenosine. The modulation of Entpd1, Entdp2 and Nt5e in vascular diseases suggests these ectoenzymes as potential targets or markers to be investigated in future studies.

Quantification of DNA Damage in Different Tissues in Rats with Heart Failure.

BACKGROUND: Chronic heart failure (CHF) is a complex syndrome which comprises structural and functional alterations in the heart in maintaining the adequate blood demand to all tissues. Few investigations sought to evaluate oxidative DNA damage in CHF. OBJECTIVE: To quantify the DNA damage using the comet assay in left ventricle (LV), lungs, diaphragm, gastrocnemius and soleus in rats with CHF. METHODS: Twelve male Wistar rats (300 to 330 g) were selected for the study: Sham (n = 6) and CHF (n = 6). The animals underwent myocardial infarction by the ligation of the left coronary artery. After six weeks, the animals were euthanized. It was performed a cell suspension of the tissues. The comet assay was performed to evaluate single and double strand breaks in DNA. Significance level (p) considered < 0.05. RESULTS: The CHF group showed higher values of left ventricle end-diastolic pressure (LVEDP), pulmonary congestion, cardiac hypertrophy and lower values of maximal positive and negative derivatives of LV pressure, LV systolic pressure (p < 0.05). CHF group showed higher DNA damage (% tail DNA, tail moment and Olive tail moment) compared to Sham (p < 0.001). The tissue with the highest damage was the soleus, compared to LV and gastrocnemius in CHF group (p < 0.05). CONCLUSION: Our results indicates that the CHF affects all tissues, both centrally and peripherically, being more affected in skeletal muscle (soleus) and is positively correlated with LV dysfunction.

ß-Alanine and l-histidine supplementation associated with combined training increased functional capacity and maximum strength in heart failure rats.

NEW FINDINGS: What is the central question of the study? Does ß-alanine with l-histidine supplementation associated with endurance and strength training improve echocardiographic parameters, functional capacity, and maximum strength in rats with chronic heart failure? What is the main finding and its importance? ß-Alanine with l-histidine supplementation associated with endurance and strength training increased functional capacity and maximum strength through increasing exercise capacity peripherally but did not affect echocardiographic parameters in rats with chronic heart failure. Combined training (CT) has been associated with positive responses in the clinical status of patients with chronic heart failure (CHF). Other non-pharmacological tools, such as amino acid supplementation, may further enhance its adaptation. However, the effects of ß-alanine and l-histidine supplementation in CHF remain unclear. In the present study, the aim was to test whether supplementing carnosine precursors with CT could give improved responses in the functional capacity and echocardiographic variables of rats with CHF. Twenty-four Wistar rats, were submitted to myocardial infarction and allocated to three groups: animals with CHF kept in sedentary conditions (SED, n = 8), animals with CHF submitted to CT in strength and aerobic exercise supplemented with placebo (CT-P, n = 8) and animals with CHF submitted to CT in strength and aerobic exercise supplemented with ß-alanine and l-histidine (CT-S, n = 8). The trained animals were submitted to a strength protocol three times per week with intensity of 65-75% of one repetition maximum test. Aerobic training was conducted two times per week (50 min, 15 m min-1 ). The supplemented group received ß-alanine and l-histidine orally (each 250 mg kg-1  day-1 ). No changes in echocardiographic and morphological parameters were found among the groups (P > 0.05). Functional capacity, Δ V̇O2max and maximum strength were higher in CT-P than in SED and even higher in CT-S than in CT-P (P < 0.01). The CT was able to improve functional capacity, but the supplementation was shown to enhance these parameters even further in the CHF rats. We conclude that the increase in functional capacity and strength gained through CT and supplementation were associated with the improvement in peripheral parameters with no changes in cardiac variables.

Quantification of DNA Damage in Different Tissues in Rats with Heart Failure / Quantificação de Dano em DNA em Diferentes Tecidos em Ratos com Insuficiência Cardíaca

Abstract Background: Chronic heart failure (CHF) is a complex syndrome which comprises structural and functional alterations in the heart in maintaining the adequate blood demand to all tissues. Few investigations sought to evaluate oxidative DNA damage in CHF. Objective: To quantify the DNA damage using the comet assay in left ventricle (LV), lungs, diaphragm, gastrocnemius and soleus in rats with CHF. Methods: Twelve male Wistar rats (300 to 330 g) were selected for the study: Sham (n = 6) and CHF (n = 6). The animals underwent myocardial infarction by the ligation of the left coronary artery. After six weeks, the animals were euthanized. It was performed a cell suspension of the tissues. The comet assay was performed to evaluate single and double strand breaks in DNA. Significance level (p) considered < 0.05. Results: The CHF group showed higher values of left ventricle end-diastolic pressure (LVEDP), pulmonary congestion, cardiac hypertrophy and lower values of maximal positive and negative derivatives of LV pressure, LV systolic pressure (p < 0.05). CHF group showed higher DNA damage (% tail DNA, tail moment and Olive tail moment) compared to Sham (p < 0.001). The tissue with the highest damage was the soleus, compared to LV and gastrocnemius in CHF group (p < 0.05). Conclusion: Our results indicates that the CHF affects all tissues, both centrally and peripherically, being more affected in skeletal muscle (soleus) and is positively correlated with LV dysfunction.

Resumo Fundamento: A insuficiência cardíaca crônica (ICC) é uma síndrome complexa que compreende alterações estruturais e funcionais no coração, mantendo demanda sanguínea adequada a todos os tecidos. Poucas investigações procuraram avaliar o dano oxidativo ao DNA na ICC. Objetivo: Quantificar o dano ao DNA utilizando o ensaio cometa no ventrículo esquerdo (VE), pulmões, diafragma, gastrocnêmio e sóleo em ratos com ICC. Métodos: Doze ratos Wistar machos (300 a 330 g) foram selecionados para o estudo: placebo (n = 6) e ICC (n = 6). Os animais foram submetidos a infarto do miocárdio através de ligadura da artéria coronária esquerda. Após seis semanas, os animais foram sacrificados. Foi realizada uma suspensão celular dos tecidos. O ensaio cometa foi realizado para avaliar as quebras de fita simples e dupla no DNA. Nível de significância (p) < 0,05. Resultados: O grupo ICC apresentou maiores valores de pressão diastólica final do ventrículo esquerdo (PDFVE), congestão pulmonar, hipertrofia cardíaca e menores valores de derivados máximos positivos e negativos da pressão do VE, pressão sistólica do VE (p < 0,05). O grupo ICC apresentou maior dano ao DNA (% de DNA da cauda, momento da cauda e momento da cauda de Olive) em comparação ao placebo (p < 0,001). O tecido com maior dano foi o sóleo, comparado ao VE e ao gastrocnêmio no grupo ICC (p < 0,05). Conclusão: Nossos resultados indicam que a ICC afeta todos os tecidos, de maneira central e periférica, sendo mais afetada no músculo esquelético (sóleo) e está positivamente correlacionada com a disfunção do VE.

Resistance training and L-arginine supplementation are determinant in genomic stability, cardiac contractility and muscle mass development in rats.

L-arginine supplementation has been related to increased maximum strength and improvement of hemodynamic parameters in several diseases. The aim of our study was to evaluate the effect of L-arginine supplementation and resistance training on muscle mass, hemodynamic function and DNA damage in healthy rats subjected to a low-arginine concentration diet. Twenty three Wistar rats (290-320g) were divided into 4 groups: Sedentary (SED-Arg, n = 6), Sedentary+Arg (SED+Arg, n = 6), Resistance Training (RT-Arg, n = 5), Resistance Training+Arg (RT+Arg, n = 6). Trained animals performed resistance training protocol in a squat apparatus adapted for rats (4 sets of 10-12 repetitions, 90s of interval, 4x/week, 65-75% of One Maximum Repetition, for 8 weeks). Comet assay was performed to measure DNA damage in leukocytes. The resistance training induced higher muscle mass in trained groups. The L-arginine supplementation increased both gastrocnemius and left ventricle to body mass ratio and increased left ventricle contractility without changing hemodynamic variables. The SED+Arg group showed higher concentration of extracellular heat shock protein 72 (eHSP72) and total testosterone, as well as lower uric acid concentration in blood versus SED-Arg group. The administration of isolated L-arginine supplementation and its association with resistance training promoted less damage in leukocytes DNA. In conclusion, the L-arginine supplementation showed synergistic effect with resistance training regarding leukocyte genomic stability in a low-L-arginine diet scenario.

Functional capacity in a rat model of heart failure: impact of myocardial infarct size.

NEW FINDINGS: What is the central question of this study? To the best of our knowledge, no studies have evaluated oxygen uptake, carbon dioxide production and exercise tolerance in rats that have undergone myocardial infarction classified by myocardial infarct (MI) size. What is the main finding and its importance? Oxygen uptake and exercise intolerance are MI size dependent, and classification based on MI size can distinguish rats with functional capacity impairment. Rats with a large MI (>40% of the left ventricle) might provide a good model for the testing of new therapies that have the potential to modify the variables of functional capacity. Oxygen uptake (V̇O2) and exercise tolerance in rats classified by myocardial infarct (MI) size are underexplored. The aim of this study was to evaluate V̇O2, carbon dioxide production (V̇CO2) and exercise tolerance in rats that had undergone myocardial infarction. Fourteen weeks after myocardial infarction or sham surgery, rats underwent an integrated approach to evaluation of left ventricular function and V̇O2/V̇O2V̇CO2V̇CO2, exercise tolerance and skeletal muscle weight. Based on determination of MI size, rats were assigned to sham-operated controls (Sham, n = 12), small myocardial infarction (SMI, n = 8) and large myocardial infarction (LMI, n = 5) groups. The LMI rats showed lower systolic (ejection fraction and fractional shortening) and diastolic (E/A ratio) left ventricular function compared with SMI. Maximal V̇O2 (∼24%, P < 0.05), V̇O2 reserve (∼30%, P < 0.05), time to exhaustion (∼36%, P < 0.05) and maximal velocity (∼30%, P < 0.05) were lower in LMI compared with sham-operated control animals, with no difference between SMI rats and sham-operated controls. Maximal V̇CO2 and respiratory exchange ratio showed no significant difference between MI rats and sham-operated control rats. The LMI rats demonstrated lower gastrocnemius weight (∼12%, P < 0.05) and soleus weight (∼19%, P = 0.07) compared with sham-operated control rats. Significant correlations between MI size, left ventricular end-diastolic pressure, right ventricle hypertrophy, pulmonary congestion, ejection fraction and fractional shortening with maximal V̇O2 and distance run were observed. Oxygen uptake and exercise intolerance are MI size dependent.

High-intensity resistance training alone or combined with aerobic training improves strength, heart function and collagen in rats with heart failure.

BACKGROUND: Resistance training (RT) has been associated with positive responses in patients with cardiovascular disease, and when it is combined with continuous aerobic training (CAT), favorable adaptations appear to be even more pronounced. However, the effects of high-intensity RT alone or in combined with CAT in the case of heart failure (HF) is not completely elucidated. METHODS: 28 male Wistar rats with HF (90 days old) were allocated to 4 groups: high-intensity RT (RT, n=7), CAT (CAT, n=7), RT and CAT (RT+CAT, n=7) and sedentary (Sed, n=7). Trained animals were subjected to a RT protocol in an adapted squat apparatus for rats (4 bouts, 6-8 reps, 90 s interval, 3×/week, 75% to 85% of one maximum repetition (1RM) for 8 weeks). The animals subjected to CAT performed it 3×/week during 50 min/session at 16 m/min. The animals of the combined exercise regimen performed both the RT and CAT exercise protocols. RESULTS: The left ventricular end-diastolic pressure (LVEDP), collagen volume fraction and right ventricular hypertrophy were lower in RT, CAT and RT+CAT groups when compared to Sed group (P<0.05) for all outcomes. Regarding the inflammatory profile, only the CAT group showed greater IL-10 concentrations. CONCLUSION: We concluded that RT combined with CAT was able to improve the strength in animals with HF, which was associated to improvement in ventricular structure and function.

Maximal oxygen uptake and exercise tolerance are improved in rats with heart failure subjected to low-level laser therapy associated with resistance training.

Exercise tolerance and maximal oxygen uptake (VO2max) are reduced in heart failure (HF). The influence of combined resistance training (RT) and low-level laser therapy (LLLT) on exercise tolerance and VO2max in HF has not yet been explored. The aim of this study was to evaluate the influence of combined RT and LLLT on VO2max and exercise tolerance in rats with HF induced by myocardial infarction (MI). Rats were allocated to sedentary sham (Sed-Sham, n = 12), sedentary heart failure (Sed-HF, n = 9), RT heart failure (RT-HF, n = 7) and RT associated with LLLT heart failure (RT + LLLT-HF, n = 7) groups. After MI or sham surgery, rats underwent a RT and LLLT protocol (applied immediately after RT) for 8 weeks. VO2max and exercise tolerance were evaluated at the end of protocol. HF rats subjected to LLLT combined with RT showed higher VO2basal (41 %), VO2max (40 %), VO2reserve (39 %), run distance (46 %), time to exhaustion (30 %) and maximal velocity (22 %) compared with HF rats that underwent RT alone. LLLT associated with RT improved oxygen uptake and exercise tolerance compared with RT alone in HF rats.

Effects of creatine supplementation associated with resistance training on oxidative stress in different tissues of rats.

BACKGROUND: Creatine supplementation is known to exert an effect by increasing strength in high intensity and short duration exercises. There is a hypothesis which suggests that creatine supplementation may provide antioxidant activity by scavenging Reactive Oxygen Species. However, the antioxidant effect of creatine supplementation associated with resistance training has not yet been described in the literature. Therefore, we investigated the effect of creatine monohydrate supplementation associated with resistance training over maximum strength gain and oxidative stress in rats. METHODS: Forty male Wistar rats (250-300 g, 90 days old) were randomly allocated into 4 groups: Sedentary (SED, n = 10), Sedentary + Creatine (SED-Cr, n = 10), Resistance Training (RT, n = 10) and Resistance Training + Creatine (RT-Cr, n = 10). Trained animals were submitted to the RT protocol (4 series of 10-12 repetitions, 90 second interval, 4 times per week, 65% to 75% of 1MR, for 8 weeks). RESULTS: In this study, greater strength gain was observed in the SED-Cr, RT and RT-Cr groups compared to the SED group (P < 0.001). The RT-Cr group showed a higher maximum strength gain when compared to other groups (P < 0.001). Creatine supplementation associated with resistance training was able to reduce lipoperoxidation in the plasma (P < 0.05), the heart (P < 0.05), the liver (P < 0.05) and the gastrocnemius (P < 0.05) when compared to control groups. However, the supplementation had no influence on catalase activity (CAT) in the analyzed organs. Only in the heart was the CAT activity higher in the RT-Cr group (P < 0.05). The activity of superoxide dismutase (SOD) was lower in all of the analyzed organs in the SED-Cr group (P < 0.05), while SOD activity was lower in the trained group and sedentary supplemented group (P < 0.05). CONCLUSIONS: Creatine was shown to be an effective non-enzymatic antioxidant with supplementation alone and also when it was associated with resistance training in rats.