Morning Versus Evening Intake of Creatine in Elite Female Handball Players

A great deal of evidence has been gathered on the use of creatine as an ergogenic supplement. Recent studies show greater benefits when creatine ingestion is performed close in time to training, but few studies tackle the way that circadian rhythms could influence creatine consumption. The aim of this study was therefore to observe the influence circadian rhythms exert on sports performance after creatine supplementation. Our method involved randomly assigning fourteen women players of a handball team into two groups in a single-blind study: one that consumed the supplement in the morning and one that consumed it in the evening, with both groups following a specific training program. After twelve weeks, the participants exhibited a decreased fat percentage, increased body weight and body water, and improved performance, with these results being very similar in the two groups. It is therefore concluded that, although circadian rhythms may influence performance, these appear not to affect creatine supplementation, as creatine is stored intramuscularly and is available for those moments of high energy demand, regardless of the time of day.

TAMI-25. UPREGULATION OF CREATINE METABOLISM BY MYELOID CELLS RESULTS IN GLIOBLASTOMA PROGRESSION

Malignant brain tumors are uniquely immunosuppressive, with a predominant infiltration of immunosuppressive tumor-associated myeloid cells (TAMCs) and a deficit in T-cells unrivaled to any other tumor. This unique tumor microenvironment (TME) promotes resistance to both conventional and immune therapies for this disease. The underlying mechanisms by which TAMCs promote glioblastoma (GBM) progression are not fully understood. We found that TAMCs specifically upregulate de-novo creatine metabolism within GBM using unbiased genetic and metabolic screening. This metabolic phenotype was confirmed in human GBM patients by comparing peripheral versus tumor-infiltrating myeloid cells. Examination of de-novo creatine generation using Carbon13 arginine flux revealed that TAMCs, but not tumor-infiltrating CD8+ T-cells, can produce creatine. Furthermore, we demonstrate that TAMCs actively secrete de-novo generated creatine into cell cultures. Examination of the single-cell microenvironment of GBM revealed that malignant cells preferentially express the creatine transporter, indicating that TAMC-derived creatine is taken up by GBM. Notably, SLC6A8 is directly upregulated in the context of hypoxia and suggests that creatine uptake is a mechanism to promote survival under hypoxic stress. Indeed, exogenous creatine supplementation promoted both the migration and survival of multiple glioblastoma cell lines in-vitro. Utilizing an established inhibitor of creatine metabolism, β-Guanidinopropionic acid (β -GPA), we found that β -GPA blocks both the migration and survival of glioma cells under hypoxic stress. Lastly, β -GPA also inhibited creatine secretion by TAMCs, showing that creatine blockade can also influence TAMC metabolic phenotype. In the future, we will examine the importance of creatine metabolism on both immune suppression and tumor progression in-vivo. This work provides novel insights into the role of creatine metabolism in GBM and identifies a unique therapeutic avenue for this devastating disease.

THE BIDIRECTIONAL EFFECT OF CREATINE SUPPORTS THE MAINTENANCE OF OXIDANT-ANTIOXIDANT HOMEOSTASIS DURING EXERCISE

The importance of supplements used with exercise is increasing day by day. In this study, it was aimed to evaluate the effects of creatine monohydrate (CrM) supplementation with different intensities of exercise on oxidative stress through dynamic thiol disulfide homeostasis. Fourty two BALB/c mice were used and randomly divided into 6 groups; control (C), low-intensity exercise (LIE), high-intensity exercise (HIE), C+CrM (4% of daily diet), LIE+CrM, and HIE+CrM groups. Exercise groups were performed low-intensity (8m/min/30min/day) and high-intensity (24m/min/30min/day) exercise on a mouse treadmill for 8 weeks. At the end of the experimental period, the thiol disulfide homeostasis levels analyzed by using a new automated measurement technique. When the native thiol and total thiol values were examined the difference between the groups was statistically significant (respectively, p=0.029, p=0,035). Creatine intake with exercise decreased native thiol and total thiol levels. However, serum disulfide levels were lower in LIE+CrM compared to other study groups, but there was no statistically significant difference. It is thought that creatine supplementation with exercise reduces the thiol-disulfide homeostasis burden of the organism, and that after the depletion of creatine stores, the sustainability of oxidant-antioxidant homeostasis can be extended, thus prolonging the duration of antioxidant resistance.

Assessing Creatine Supplementation for Neuroprotection against Perinatal Hypoxic-Ischaemic Encephalopathy: A Systematic Review of Perinatal and Adult Pre-Clinical Studies

There is an important unmet need to develop interventions that improve outcomes of hypoxic-ischaemic encephalopathy (HIE). Creatine has emerged as a promising neuroprotective agent. Our objective was to systematically evaluate the preclinical animal studies that used creatine for perinatal neuroprotection, and to identify knowledge gaps that need to be addressed before creatine can be considered for pragmatic clinical trials for HIE. Methods: We reviewed preclinical studies up to 20 September 2021 using PubMed, EMBASE and OVID MEDLINE databases. The SYRCLE risk of bias assessment tool was utilized. Results: Seventeen studies were identified. Dietary creatine was the most common administration route. Cerebral creatine loading was age-dependent with near term/term-equivalent studies reporting higher increases in creatine/phosphocreatine compared to adolescent-adult equivalent studies. Most studies did not control for sex, study long-term histological and functional outcomes, or test creatine post-HI. None of the perinatal studies that suggested benefit directly controlled core body temperature (a known confounder) and many did not clearly state controlling for potential study bias. Conclusion: Creatine is a promising neuroprotective intervention for HIE. However, this systematic review reveals key knowledge gaps and improvements to preclinical studies that must be addressed before creatine can be trailed for neuroprotection of the human fetus/neonate.

Efficacy of Creatine Supplementation Combined with Resistance Training on Muscle Strength and Muscle Mass in Older Females: A Systematic Review and Meta-Analysis

Sarcopenia refers to the age-related loss of muscle strength and muscle mass, which is associated with a reduced quality of life, particularly in older females. Resistance training (RT) is well established to be an effective intervention to counter indices of sarcopenia. Accumulating research indicates that the addition of creatine supplementation (Cr) to RT augments gains in muscle strength and muscle mass, compared to RT alone. However, some evidence indicates that sex differences may alter the effectiveness of Cr. Therefore, we systematically reviewed randomized controlled trials (RCTs) investigating the efficacy of Cr + RT on measures of upper- and lower-body strength and muscle mass in older females. A systematic literature search was performed in nine electronic databases. Ten RCTs (N = 211 participants) were included the review. Overall, Cr significantly increased measures of upper-body strength (7 studies, n = 142, p = 0.04), with no effect on lower-body strength or measures of muscle mass. Sub-analyses revealed that both upper-body (4 studies, n = 97, p = 0.05) and lower-body strength (4 studies, n = 100, p = 0.03) were increased by Cr, compared to placebo in studies ≥ 24 weeks in duration. In conclusion, older females supplementing with Cr experience significant gains in muscle strength, especially when RT lasts for at least 24 weeks in duration. However, given the level of evidence, future high-quality studies are needed to confirm these findings.

Creatine deficiency and heart failure

Impaired cardiac energy metabolism has been proposed as a mechanism common to different heart failure aetiologies. The energy-depletion hypothesis was pursued by several researchers, and is still a topic of considerable interest. Unlike most organs, in the heart, the creatine kinase system represents a major component of the metabolic machinery, as it functions as an energy shuttle between mitochondria and cytosol. In heart failure, the decrease in creatine level anticipates the reduction in adenosine triphosphate, and the degree of myocardial phosphocreatine/adenosine triphosphate ratio reduction correlates with disease severity, contractile dysfunction, and myocardial structural remodelling. However, it remains to be elucidated whether an impairment of phosphocreatine buffer activity contributes to the pathophysiology of heart failure and whether correcting this energy deficit might prove beneficial. The effects of creatine deficiency and the potential utility of creatine supplementation have been investigated in experimental and clinical models, showing controversial findings. The goal of this article is to provide a comprehensive overview on the role of creatine in cardiac energy metabolism, the assessment and clinical value of creatine deficiency in heart failure, and the possible options for the specific metabolic therapy.