Beyond muscle: the effects of creatine supplementation on brain creatine, cognitive processing, and traumatic brain injury

The ergogenic and therapeutic effects of increasing muscle creatine by supplementation are well-recognized. It appears that similar benefits to brain function and cognitive processing may also be achieved with creatine supplementation, however research in this area is more limited, and important knowledge gaps remain. The purpose of this review is to provide a comprehensive overview of the current state of knowledge about the influence of creatine supplementation on brain function in healthy individuals. It appears that brain creatine is responsive to supplementation, however higher, or more prolonged dosing strategies than those typically used to increase muscle creatine, may be required to elicit an increase in brain creatine. The optimal dosing strategy to induce this response, is currently unknown, and there is an urgent need for studies investigating this. When considering the influence of supplementation strategies on cognitive processes, it appears that creatine is most likely to exert an influence in situations whereby cognitive processes are stressed, e.g. during sleep deprivation, experimental hypoxia, or during the performance of more complex, and thus more cognitively demanding tasks. Evidence exists indicating that increased brain creatine may be effective at reducing the severity of, or enhancing recovery from mild traumatic brain injury, however, only limited data in humans are available to verify this hypothesis, thus representing an exciting area for further research

Immunological implications of physical inactivity among older adults during the COVID-19 pandemic

Social distancing has been adopted worldwide to control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Social isolation is likely to lead to a decline in physical activity, which could result in immune system dysfunction, thereby increasing infection susceptibility and exacerbating the pathophysiology of conditions that are common among older adults, including cardiovascular disease, cancer, and inflammatory disorders. Older adults and people living with these comorbidities are at a greater risk for complications during coronavirus disease 2019 (COVID-19). In this review, we discuss the negative impact of physical inactivity on immune function and showcase evidence that regular physical activity may be an effective strategy to counter some of the deleterious effects of social isolation. Furthermore, we briefly highlight key research questions in exercise immunology, with a focus on older adults in the context of COVID-19. Although it is worth emphasizing that there is no direct evidence that physical activity can prevent or treat-COVID-19, promoting an active lifestyle is a key intervention to counteract the effects of social isolation, especially in older adults and other at-risk individuals, such as those living with chronic diseases associated with ageing and lifestyle.</p

Does creatine supplementation harm renal function?

Enquanto o consumo de creatina por atletas e praticantes de atividade física tem crescido vertiginosamente, os efeitos adversos desse suplemento continuam sendo alvos de calorosos debates científicos, sobretudo no que se refere à função renal. O objetivo dessa revisão é descrever as falhas metodológicas e lacunas na literatura, que contribuem para a divergência do tema. Relatos de caso sugerem que a creatina é um potencial agente nefrotóxico. Em contrapartida, estudos longitudinais, embora possuam diversas limitações, indicam o oposto. Pesquisas com humanos não demonstram efeitos deletérios da suplementação de creatina à função renal, porém a falta de controle experimental e o caráter retrospectivo da maioria delas comprometem as conclusões dos autores. Já os estudos experimentais com ratos empregam bons marcadores de função renal e possuem controle de variáveis satisfatório. Contudo, os resultados destes são contraditórios. Estudos futuros devem investigar os efeitos da suplementação de creatina em diversas patologias renais, assim como em idosos, diabéticos do tipo 2 e hipertensos, cuja propensão a nefropatia é bem descrita. Não há evidências de que a suplementação de creatina prejudique a função renal em sujeitos saudáveis, quando consumida na dosagem preconizada. Diante disso, questiona-se a legitimidade científica da proibição do comércio de creatina no Brasil.While creatine consumption has been greatly increasing among athletes and physical activity practitioners, the adverse effects of this supplement remain scientifically controversial, especially concerning renal function. The aim of this review is to describe the methodological limitations and gaps in the literature which contribute to the topic’s divergence. Case reports suggest that creatine is a nephrotoxic agent. On the other hand, despite having several limitations, longitudinal studies have indicated the opposite. Research with humans does not demonstrate any deleterious effects as a consequence of creatine supplementation; however, the absence of experimental control as well as their retrospective characteristics compromise the authors’ conclusion. Experimental studies with animal models though, use both gold standard for renal function and have satisfactory variable control. However, the results remain controversial. Future studies should investigate the effects of creatine supplementation in several kidneys diseases as well as in the elderly, type 2 diabetis and hypertensive individuals, whose tendency to renal dysfunction is well-described. There is not evidence that creatine supplementation causes renal deterioration in healthy subjects when it is ingested in the recommended dosage. Thus, we have some concerns about the sale prohibition of creatine supplementation in Brazil

Effect of a Single High-Dose Vitamin D3 on the Length of Hospital Stay of Severely 25-Hydroxyvitamin D-Deficient Patients with COVID-19

OBJECTIVES: In this ancillary analysis of a multicenter, double-blinded, randomized, placebo-controlled trial, we investigated the effect of a single high dose of vitamin D3&nbsp;on the length of hospital stay of patients with severe 25-hydroxyvitamin D deficiency and COVID-19. METHODS: The primary outcome was length of hospital stay, defined as the total number of days that patients remained hospitalized from the date of randomization until the date of hospital discharge. Secondary outcomes included serum levels of 25-hydroxyvitamin D, mortality during hospitalization, number of patients admitted to the intensive care unit, and number of patients who required mechanical ventilation. ClinicalTrials.gov: NCT04449718. RESULTS: Thirty-two patients were included in the study. The mean (SD) age was 58.5 (15.6) years, body mass index was 30.8 (8.6) kg/m2, and 25-hydroxyvitamin D level was 7.8 (1.6) ng/mL. No significant difference was observed in the median interquartile range of length of hospital stay between the vitamin D3&nbsp;group (6.0 [4.0-18.0] days)&nbsp;versus&nbsp;placebo (9.5 [6.3-15.5] days) (log-rank&nbsp;p=0.74; hazard ratio, 1.13 [95% confidence interval (CI), 0.53-2.40];&nbsp;p=0.76). Vitamin D3&nbsp;significantly increased serum 25-hydroxyvitamin D levels in the vitamin D3&nbsp;group compared with that in the placebo group (between-group difference, 23.9 ng/mL [95% CI, 17.7-30.1];&nbsp;p&lt;0.001). CONCLUSIONS: A dose of 200.000 IU of vitamin D3&nbsp;did not significantly reduce the length of hospital stay of patients with severe 25-hydroxyvitamin D deficiency and COVID-19

Nonplacebo controls to determine the magnitude of ergogenic interventions: a systematic review and meta-analysis.

Introduction: Placebos are used as a control treatment that is meant to be indistinguishable from the active intervention. However, where substantive placebo effects may occur, studies that do not include a non-placebo control arm may underestimate the overall effect of the intervention (active plus placebo components). This study aimed to determine the relative magnitude of the placebo effect associated with nutritional supplements (caffeine and extracellular buffers) by meta-analysing data from studies containing both placebo and non-placebo control sessions. Methods: Bayesian multilevel meta-analysis models were used to estimate pooled effects and express the placebo effect as a percentage of the overall intervention effect. Results: Thirty-four studies were included, with the median pooled effect size (ES0.5) indicating a very small (ES0.5=0.09 [95%CrI:0.01 to 0.17]) improvement in performance of placebo compared to control. There was no moderating effect of exercise type (capacity or performance), exercise duration or training status. The comparison between active intervention and control indicated a small to medium effect (ES0.5=0.37 [95%CrI:0.20 to 0.56]). Expressed in relative terms, the placebo effect was equivalent to 25% [75%CrI:16 to 35%] and 59% [75%CrI:34 to 94%] of the total intervention effect for buffers and caffeine. Conclusion: These results demonstrate a very small, but potentially important placebo effect with nutritional supplementation studies. A substantive proportion of supplement effects may be due to placebo effects, with the relative proportion influenced by the magnitude of the overall ergogenic effect. Where feasible, intervention studies should employ non-placebo control-arm comparators to identify the proportion of the effect estimated to come from placebo effects and avoid underestimating the overall benefits that the physiological plus psychobiological aspects associated with an intervention provide in the real world

Individual participant data meta-analysis provides no evidence of individual response variation in individuals supplementing with beta-alanine.

Currently, little is known about the extent of inter-individual variability in response to beta-alanine (BA) supplementation, nor what proportion of said variability can be attributed to external factors, or to the intervention itself (intervention response). To investigate this, individual participant data on the effect of BA supplementation on a high intensity cycling capacity test (CCT110%) were meta-analysed. Changes in time to exhaustion (TTE) and muscle carnosine (MCarn) were the primary and secondary outcomes. Multi-level distributional Bayesian models were used to estimate the mean and standard deviation of BA and placebo (PLA) group change scores. The relative sizes of group standard deviations were used to infer whether observed variation in change scores were due to intervention or non-intervention related effects. Six eligible studies were identified, and individual data were obtained from four of these. Analyses showed a group effect of BA supplementation on TTE (7.7[95%CrI:1.3 to 14.3 s]) and MCarn (18.1[95%CrI:14.5 to 21.9 mmol·kgDM-1]). A large intervention response variation was identified for MCarn (σ_IR= 5.8 [95%CrI: 4.2 to 7.4 mmol·kgDM-1]); however, equivalent change score standard deviations were shown for PLA (16.1[95%CrI:13.0 to 21.3 s]) and BA (15.9[95%CrI:13.0 to 20.0 s] conditions, with the probability that standard deviation was greater in PLA being 0.64. In conclusion, the similarity in observed change score standard deviations between groups for TTE indicates the source of variation is common and therefore unrelated to BA supplementation, likely originating instead from external factors, which may include, for example, nutritional intake, sleep patterns or training status

Redução na força muscular e capacidade funcional em pacientes fisicamente inativos com lúpus eritematoso sistêmico de início juvenil, apesar de doença muito leve

ResumoObjetivoComparar a força muscular (ou seja, a força muscular dos membros superiores e inferiores) e a capacidade funcional de pacientes fisicamente inativos com lúpus eritematoso sistêmico de início juvenil (LESJ) com controles saudáveis (CTRL).MétodosEstudo transversal cuja amostra foi composta por 19 pacientes com LESJ (entre 9 e 18 anos) e 15 CTRL pareados por idade, sexo, índice de massa corporal (IMC) e nível de atividade física (avaliada através do uso de acelerômetros). A força dos membros superiores e inferiores foi avaliada pelo teste de uma repetição máxima (1‐RM). A força isométrica foi avaliada através do uso de um dinamômetro. A capacidade funcional foi avaliada pelo Timed‐stands test (TST) e Timed‐up‐and‐go test (TUG).ResultadosQuando comparados com os CTRL, os pacientes com LESJ apresentaram menor força em 1‐RM no Leg press e supino (p=0,026 e p=0,008, respectivamente) e uma tendência a menor força de preensão manual (p=0,052). Os pacientes com LESJ apresentaram menores escores no TST (p=0,036) e uma tendência a maior pontuação no TUG (p=0,070), quando comparados com o grupo CTRL.ConclusãoPacientes com LESJ, fisicamente inativos, com doença muito leve mostraram redução na força muscular e capacidade funcional quando comparados com controles saudáveis pareados por níveis de atividade física. Esses achados sugerem que pacientes com LESJ podem apresentar mais efeitos deletérios por manter um estilo de vida fisicamente inativo do que controles saudáveis. Além disso, alguns efeitos “residuais” subclínicos da doença ou do tratamento farmacológico parecem afetar pacientes com LESJ, mesmo com uma doença bem controlada.AbstractObjectiveTo compare muscle strength (i.e. lower‐ and upper‐body strength) and function between physically inactive childhood‐onset systemic lupus erythematosus patients (C‐SLE) and healthy controls (CTRL).MethodsThis was a cross‐sectional study and the sample consisted of 19 C‐SLE (age between 9 to 18 years) and 15 CTRL matched by age, sex, body mass index (BMI), and physical activity levels (assessed by accelerometry). Lower‐ and upper‐body strength was assess by the one‐repetition‐maximum (1‐RM) test. Isometric strength was assessed through a handgrip dynamometer. Muscle function was evaluated by the timed‐stands test (TST) and the timed‐up‐and‐go test (TUG).ResultsWhen compared with CTRL, C‐SLE showed lower leg‐press and bench‐press 1‐RM (p=0.026 and p=0.008, respectively), and a tendency towards lower handgrip strength (p=0.052). C‐SLE showed lower TST scores (p=0.036) and a tendency towards higher TUG scores (p=0.070) when compared with CTRL.ConclusionPhysically inactive C‐SLE patients with very mild disease showed reduced muscle strength and functionality when compared with healthy controls matched by physical activity levels. These findings suggest C‐SLE patients may greatly suffer from a physically inactive lifestyle than healthy controls do. Moreover, some sub‐clinical “residual” effect of the disease or its pharmacological treatment seems to affect C‐SLE patients even with a well‐controlled disease

Effect of age, diet and tissue type on PCr response to creatine supplementation

Creatine/phosphorylcreatine (PCr) responses to creatine supplementation may be modulated by age, diet, and tissue, but studies assessing this possibility are lacking. Therefore we aimed to determine whether PCr responses vary as a function of age, diet, and tissue. Fifteen children, 17 omnivorous and 14 vegetarian adults, and 18 elderly individuals (“elderly”) participated in this study. Participants were given placebo and subsequently creatine (0.3 g·kg−1·day−1) for 7 days in a single-blind fashion. PCr was measured through phosphorus magnetic resonance spectroscopy (31P-MRS) in muscle and brain. Creatine supplementation increased muscle PCr in children (P < 0.0003) and elderly (P < 0.001), whereas the increase in omnivores did not reach statistically significant difference (P = 0.3348). Elderly had greater PCr increases than children and omnivores (P < 0.0001 for both), whereas children experienced greater PCr increases than omnivores (P = 0.0022). In relation to diet, vegetarians (P < 0.0001), but not omnivores, had significant increases in muscle PCr content. Brain PCr content was not affected by creatine supplementation in any group, and delta changes in brain PCr (−0.7 to +3.9%) were inferior to those in muscle PCr content (+10.3 to +27.6%; P < 0.0001 for all comparisons). PCr responses to a standardized creatine protocol (0.3 g·kg−1·day−1 for 7 days) may be affected by age, diet, and tissue. Whereas creatine supplementation was able to increase muscle PCr in all groups, although to different extents, brain PCr was shown to be unresponsive overall. These findings demonstrate the need to tailor creatine protocols to optimize creatine/PCr accumulation both in muscle and in brain, enabling a better appreciation of the pleiotropic properties of creatine

The ergogenic effect of beta-alanine combined with sodium bicarbonate on high-intensity swimming performance

We investigated the effect of beta-alanine (BA) alone (study A) and in combination with sodium bicarbonate (SB) (study B) on 100- and 200-m swimming performance. In study A, 16 swimmers were assigned to receive either BA (3.2 g·day−1 for 1 week and 6.4 g·day−1 for 4 weeks) or placebo (PL; dextrose). At baseline and after 5 weeks of supplementation, 100- and 200-m races were completed. In study B, 14 were assigned to receive either BA (3.2 g·day−1 for 1 week and 6.4 g·day−1 for 3 weeks) or PL. Time trials were performed once before and twice after supplementation (with PL and SB), in a crossover fashion, providing 4 conditions: PL-PL, PL-SB, BA-PL, and BA-SB. In study A, BA supplementation improved 100- and 200-m time-trial performance by 2.1% (p = 0.029) and 2.0% (p = 0.0008), respectively. In study B, 200-m time-trial performance improved in all conditions, compared with presupplementation, except the PL-PL condition (PL-SB, +2.3%; BA-PL, +1.5%; BA-SB, +2.13% (p < 0.05)). BA-SB was not different from BA-PL (p = 0.21), but the probability of a positive effect was 78.5%. In the 100-m time-trial, only a within-group effect for SB was observed in the PL-SB (p = 0.022) and BA-SB (p = 0.051) conditions. However, 6 of 7 athletes swam faster after BA supplementation. The probability of BA having a positive effect was 65.2%; when SB was added to BA, the probability was 71.8%. BA and SB supplementation improved 100- and 200-m swimming performance. The coingestion of BA and SB induced a further nonsignificant improvement in performance

Metabolismo de carnosina, suplementação de β-alanina e desempenho físico: uma atualização – PARTE I

Os papéis fisiológicos da carnosina tem despertado interesse recente, apesar de já ser uma substância estudada há anos. É formada através de aminoácidos (β-alanil e L-histidina) e juntamente com seus análogos metilados (anserina e ofidina- balenina) fazem parte da classe dos dipeptídeos contendo histidina (HCDs, do inglês Histidine-Containing Dipeptides), os quais são abundantemente encontrados em uma ampla gama de animais terrestres e aquáticos. Maiores concentrações estão no musculo esquelético e bulbo olfatório, estando em menor quantidade em regiões do sistema nervoso central, fluido cerebroespinhal, rins e baço. Dentre os papéis fisiológicos atribuídos a ela estão: função tamponante especialmente nas fibras tipo II; ação antioxidante e melhora da liberação do cálcio do retículo sarcoplasmático, e na sensibilidade do aparato contrátil ao cálcio. A suplementação de β-alanina é a forma mais eficiente de aumentar a carnosina muscular, e vem recebendo demasiado destaque na área de nutrição esportiva em anos recentes. Esta estratégia nutricional apresenta um efeito “dose-resposta†com a ingestão aguda, além da parestesia como efeito colateral. Até hoje permanece incerto o tempo exato de washout da carnosina no músculo esquelético após a interrupção da suplementação de β-alanina. Estudos futuros devem ser realizados para avaliar outros possíveis mecanismos de ação da carnosina, e confirmar os já existentes. ABSTRACTCarnosine metabolism, β-alanine supplementation and performance: an update - Part IThe physiological role of carnosine has attracted recent interest, even though it is a substance studied for years. It is formed by amino acids (β-alanyl and L-histidine) and together with their methylated analogues (anserine and balenine) are part of the class of histidine-containing dipeptides (HCDs, English Histidine-containing dipeptides), which are abundantly found in a wide range of terrestrial and aquatic animals. Higher concentrations are in the olfactory bulb and skeletal muscle being a lesser extent in regions of the central nervous system, cerebrospinal fluid, kidney and spleen. The physiological roles attributed to it are: buffering function especially in type II fibers; antioxidant and improves the release of calcium from the sarcoplasmic reticulum, and the sensitivity of the contractile apparatus to calcium. Supplementation of β-alanine is the most efficient way to increase muscle carnosine, and has been receiving substantial highlight in the sports nutrition area in recent years. This nutritional strategy presents a "dose -response" effect from acute ingestion, as well as paresthesia as a side effect. Until these days the exactly washout period of carnosine in the skeletal muscle remains uncertain after β-alanine supplementation interruption. Future studies should be conducted to evaluate other possible mechanisms of action of carnosine and confirm existing ones