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1.
Characterization of seizures and EEG findings in creatine transporter deficiency due to SLC6A8 mutation.
Abdennadher, M, Inati, SK, Rahhal, S, Khan, O, Bartolini, L, Thurm, A, Theodore, W, Miller, JS, Porter, FD, Bianconi, S
American journal of medical genetics. Part A. 2024;(2):337-345
Abstract
Seizures occur in up to 59% of boys with creatine transporter deficiency (CTD). While seizure phenotypes have been previously described, electroencephalogram (EEG) findings have only been reported in several case reports. In this prospective observational study, we report seizure characteristics and EEG findings in combination with neurobehavioral and SLC6A8 pathogenic variants in twenty males with CTD. Eighteen study participants (SP) underwent video-EEG, and seven had follow-up EEG recordings. Seizures typically occurred by age of 2 years. Thirteen (65%) had non-febrile seizures, requiring anti-seizure medications in nine. Four had febrile seizures. Seizures were bilateral tonic-clonic in 7 SP and focal impaired awareness in 5 SP; often responding to 1 to 2 antiseizure medications. EEG showed slowing in 5 SP, beta activity in 6 SP, and focal/multifocal, and/or generalized epileptiform activity in 9 SP. Follow-up EEGs in 7 SP showed emergence of epileptiform activity in 1 SP, and increased activity in 2 SP. In conclusion, seizures were frequent in our cohort but tended to respond to antiseizure medications. Longitudinal follow up provided further insight into emergence of seizures and EEG abnormalities soliciting future studies with long term follow up. Biomarkers of epileptogenicity in CTD are needed to predict seizures in this population.
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2.
Creatine in Health and Disease.
Kreider, RB, Stout, JR
Nutrients. 2021;(2)
Abstract
Although creatine has been mostly studied as an ergogenic aid for exercise, training, and sport, several health and potential therapeutic benefits have been reported. This is because creatine plays a critical role in cellular metabolism, particularly during metabolically stressed states, and limitations in the ability to transport and/or store creatine can impair metabolism. Moreover, increasing availability of creatine in tissue may enhance cellular metabolism and thereby lessen the severity of injury and/or disease conditions, particularly when oxygen availability is compromised. This systematic review assesses the peer-reviewed scientific and medical evidence related to creatine's role in promoting general health as we age and how creatine supplementation has been used as a nutritional strategy to help individuals recover from injury and/or manage chronic disease. Additionally, it provides reasonable conclusions about the role of creatine on health and disease based on current scientific evidence. Based on this analysis, it can be concluded that creatine supplementation has several health and therapeutic benefits throughout the lifespan.
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3.
The Role of Creatine in the Development and Activation of Immune Responses.
Bredahl, EC, Eckerson, JM, Tracy, SM, McDonald, TL, Drescher, KM
Nutrients. 2021;(3)
Abstract
The use of dietary supplements has become increasingly common over the past 20 years. Whereas supplements were formerly used mainly by elite athletes, age and fitness status no longer dictates who uses these substances. Indeed, many nutritional supplements are recommended by health care professionals to their patients. Creatine (CR) is a widely used dietary supplement that has been well-studied for its effects on performance and health. CR also aids in recovery from strenuous bouts of exercise by reducing inflammation. Although CR is considered to be very safe in recommended doses, a caveat is that a preponderance of the studies have focused upon young athletic individuals; thus there is limited knowledge regarding the effects of CR on children or the elderly. In this review, we examine the potential of CR to impact the host outside of the musculoskeletal system, specifically, the immune system, and discuss the available data demonstrating that CR can impact both innate and adaptive immune responses, together with how the effects on the immune system might be exploited to enhance human health.
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4.
Chronic Dialysis Patients Are Depleted of Creatine: Review and Rationale for Intradialytic Creatine Supplementation.
van der Veen, Y, Post, A, Kremer, D, Koops, CA, Marsman, E, Appeldoorn, TYJ, Touw, DJ, Westerhuis, R, Heiner-Fokkema, MR, Franssen, CFM, et al
Nutrients. 2021;(8)
Abstract
There is great need for the identification of new, potentially modifiable risk factors for the poor health-related quality of life (HRQoL) and of the excess risk of mortality in dialysis-dependent chronic kidney disease patients. Creatine is an essential contributor to cellular energy homeostasis, yet, on a daily basis, 1.6-1.7% of the total creatine pool is non-enzymatically degraded to creatinine and subsequently lost via urinary excretion, thereby necessitating a continuous supply of new creatine in order to remain in steady-state. Because of an insufficient ability to synthesize creatine, unopposed losses to the dialysis fluid, and insufficient intake due to dietary recommendations that are increasingly steered towards more plant-based diets, hemodialysis patients are prone to creatine deficiency, and may benefit from creatine supplementation. To avoid problems with compliance and fluid balance, and, furthermore, to prevent intradialytic losses of creatine to the dialysate, we aim to investigate the potential of intradialytic creatine supplementation in improving outcomes. Given the known physiological effects of creatine, intradialytic creatine supplementation may help to maintain creatine homeostasis among dialysis-dependent chronic kidney disease patients, and consequently improve muscle status, nutritional status, neurocognitive status, HRQoL. Additionally, we describe the rationale and design for a block-randomized, double-blind, placebo-controlled pilot study. The aim of the pilot study is to explore the creatine uptake in the circulation and tissues following different creatine supplementation dosages.
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5.
Efficacy of Creatine Supplementation and Resistance Training on Area and Density of Bone and Muscle in Older Adults.
Candow, DG, Chilibeck, PD, Gordon, JJ, Kontulainen, S
Medicine and science in sports and exercise. 2021;(11):2388-2395
Abstract
PURPOSE To examine the efficacy of creatine (Cr) supplementation and any sex differences during supervised whole-body resistance training (RT) on properties of bone and muscle in older adults. METHODS Seventy participants (39 men, 31 women; mean age ± standard deviation: 58 ± 6 yr) were randomized to supplement with Cr (0.1 g·kg-1·d-1) or placebo (Pl) during RT (3 d·wk-1 for 1 yr). Bone geometry (radius and tibia) and muscle area and density (forearm and lower leg) were assessed using peripheral quantitative computed tomography. RESULTS Compared with Pl, Cr increased or maintained total bone area in the distal tibia (Cr, Δ +17 ± 27 mm2; Pl, Δ -1 ± 22 mm2; P = 0.031) and tibial shaft (Cr, Δ 0 ± 9 mm2; Pl, Δ -5 ± 7 mm2; P = 0.032). Men on Cr increased trabecular (Δ +28 ± 31 mm2; P < 0.001) and cortical bone areas in the tibia (Δ +4 ± 4 mm2; P < 0.05), whereas men on Pl increased trabecular bone density (Δ +2 ± 2 mg·cm-3; P < 0.01). There were no bone changes in the radius (P > 0.05). Cr increased lower leg muscle density (Δ +0.83 ± 1.15 mg·cm-3; P = 0.016) compared with Pl (Δ -0.16 ± 1.56 mg·cm-3), with no changes in the forearm muscle. CONCLUSIONS One year of Cr supplementation and RT had some favorable effects on measures of bone area and muscle density in older adults.
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6.
Efficacy of Creatine Supplementation Combined with Resistance Training on Muscle Strength and Muscle Mass in Older Females: A Systematic Review and Meta-Analysis.
Dos Santos, EEP, de Araújo, RC, Candow, DG, Forbes, SC, Guijo, JA, de Almeida Santana, CC, Prado, WLD, Botero, JP
Nutrients. 2021;(11)
Abstract
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.
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7.
Creatine for Exercise and Sports Performance, with Recovery Considerations for Healthy Populations.
Wax, B, Kerksick, CM, Jagim, AR, Mayo, JJ, Lyons, BC, Kreider, RB
Nutrients. 2021;(6)
Abstract
Creatine is one of the most studied and popular ergogenic aids for athletes and recreational weightlifters seeking to improve sport and exercise performance, augment exercise training adaptations, and mitigate recovery time. Studies consistently reveal that creatine supplementation exerts positive ergogenic effects on single and multiple bouts of short-duration, high-intensity exercise activities, in addition to potentiating exercise training adaptations. In this respect, supplementation consistently demonstrates the ability to enlarge the pool of intracellular creatine, leading to an amplification of the cell's ability to resynthesize adenosine triphosphate. This intracellular expansion is associated with several performance outcomes, including increases in maximal strength (low-speed strength), maximal work output, power production (high-speed strength), sprint performance, and fat-free mass. Additionally, creatine supplementation may speed up recovery time between bouts of intense exercise by mitigating muscle damage and promoting the faster recovery of lost force-production potential. Conversely, contradictory findings exist in the literature regarding the potential ergogenic benefits of creatine during intermittent and continuous endurance-type exercise, as well as in those athletic tasks where an increase in body mass may hinder enhanced performance. The purpose of this review was to summarize the existing literature surrounding the efficacy of creatine supplementation on exercise and sports performance, along with recovery factors in healthy populations.
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8.
The effect of multi-ingredient intra- versus extra-cellular buffering supplementation combined with branched-chain amino acids and creatine on exercise-induced ammonia blood concentration and aerobic capacity in taekwondo athletes.
Durkalec-Michalski, K, Kusy, K, Główka, N, Zieliński, J
Journal of the International Society of Sports Nutrition. 2021;(1):48
Abstract
BACKGROUND This study aimed to investigate the effect of multi-ingredient intra- (BA) versus extra- (ALK) cellular buffering factor supplementation, combined with the customary intake of branched-chain amino acids (BCAA) and creatine malate (TCM), on body composition, exercise variables, and biochemical and hematological parameters in 9 elite taekwondo athletes. METHODS Eight-week randomized double-blind crossover BA (5.0 g·day-1 of β-alanine) versus ALK (0.07 g·kgFFM-1·day-1 of sodium bicarbonate) supplementation combined with BCAA (0.2 g·kgFFM-1·day-1) and TCM (0.05 g·kgFFM-1·day-1) during a standard 8-week taekwondo training period was implemented. In the course of the experiment, body composition (dual X-ray absorptiometry), aerobic capacity (ergospirometric measurements during an incremental treadmill test until exhaustion), and exercise blood biomarkers concentrations were measured. Data were analyzed using repeated measures within-between interaction analysis of variance with the inclusion of experimental supplementation order. RESULTS The maximum post-exercise blood ammonia concentration decreased in both groups after supplementation (from 80.3 ± 10.6 to 72.4 ± 10.2 µmol∙L-1, p = 0.013 in BA; from 81.4 ± 8.7 to 74.2 ± 8.9 µmol∙L-1, p = 0.027 in ALK), indicating reduced exercise-related adenosine triphosphate degradation. However, no differences were found in body composition, aerobic capacity, blood lactate concentration, and hematological parameters after neither BA (combined with BCAA and TCM) nor ALK (combined with BCAA and TCM) supplementation. CONCLUSIONS In highly trained taekwondo athletes, neither extra- nor intracellular buffering enhancement resulting from BA and ALK supplementation, combined with BCAA and TCM treatment, affects body mass and composition, maximum oxygen uptake, and hematological indices, even though certain advantageous metabolic adaptations can be observed.
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9.
Creatine and Nicotinamide Prevent Oxidant-Induced Senescence in Human Fibroblasts.
Mahajan, AS, Arikatla, VS, Thyagarajan, A, Zhelay, T, Sahu, RP, Kemp, MG, Spandau, DF, Travers, JB
Nutrients. 2021;(11)
Abstract
Dermal fibroblasts provide structural support by producing collagen and other structural/support proteins beneath the epidermis. Fibroblasts also produce insulin-like growth factor-1 (IGF-1), which binds to the IGF-1 receptors (IGF-1Rs) on keratinocytes to activate signaling pathways that regulate cell proliferation and cellular responses to genotoxic stressors like ultraviolet B radiation. Our group has determined that the lack of IGF-1 expression due to fibroblast senescence in the dermis of geriatric individuals is correlated with an increased incidence of skin cancer. The present studies tested the hypothesis that pro-energetics creatine monohydrate (Cr) and nicotinamide (NAM) can protect normal dermal human fibroblasts (DHF) against experimentally induced senescence. To that end, we used an experimental model of senescence in which primary DHF are treated with hydrogen peroxide (H2O2) in vitro, with senescence measured by staining for beta-galactosidase activity, p21 protein expression, and senescence associated secretory phenotype cytokine mRNA levels. We also determined the effect of H2O2 on IGF-1 mRNA and protein expression. Our studies indicate that pretreatment with Cr or NAM protects DHF from the H2O2-induced cell senescence. Treatment with pro-energetics post-H2O2 had no effect. Moreover, these agents also inhibited reactive oxygen species generation from H2O2 treatment. These studies suggest a potential strategy for protecting fibroblasts in geriatric skin from undergoing stress-induced senescence, which may maintain IGF-1 levels and therefore limit carcinogenesis in epidermal keratinocytes.
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10.
Creatine Enhances the Effects of Cluster-Set Resistance Training on Lower-Limb Body Composition and Strength in Resistance-Trained Men: A Pilot Study.
Bonilla, DA, Kreider, RB, Petro, JL, Romance, R, García-Sillero, M, Benítez-Porres, J, Vargas-Molina, S
Nutrients. 2021;(7)
Abstract
Creatine monohydrate (CrM) supplementation has been shown to improve body composition and muscle strength when combined with resistance training (RT); however, no study has evaluated the combination of this nutritional strategy with cluster-set resistance training (CS-RT). The purpose of this pilot study was to evaluate the effects of CrM supplementation during a high-protein diet and a CS-RT program on lower-limb fat-free mass (LL-FFM) and muscular strength. Twenty-three resistance-trained men (>2 years of training experience, 26.6 ± 8.1 years, 176.3 ± 6.8 cm, 75.6 ± 8.9 kg) participated in this study. Subjects were randomly allocated to a CS-RT+CrM (n = 8), a CS-RT (n = 8), or a control group (n = 7). The CS-RT+CrM group followed a CrM supplementation protocol with 0.1 g·kg-1·day-1 over eight weeks. Two sessions per week of lower-limb CS-RT were performed. LL-FFM corrected for fat-free adipose tissue (dual-energy X-ray absorptiometry) and muscle strength (back squat 1 repetition maximum (SQ-1RM) and countermovement jump (CMJ)) were measured pre- and post-intervention. Significant improvements were found in whole-body fat mass, fat percentage, LL-fat mass, LL-FFM, and SQ-1RM in the CS-RT+CrM and CS-RT groups; however, larger effect sizes were obtained in the CS-RT+CrM group regarding whole body FFM (0.64 versus 0.16), lower-limb FFM (0.62 versus 0.18), and SQ-1RM (1.23 versus 0.75) when compared to the CS-RT group. CMJ showed a significant improvement in the CS-RT+CrM group with no significant changes in CS-RT or control groups. No significant differences were found between groups. Eight weeks of CrM supplementation plus a high-protein diet during a CS-RT program has a higher clinical meaningfulness on lower-limb body composition and strength-related variables in trained males than CS-RT alone. Further research might study the potential health and therapeutic effects of this nutrition and exercise strategy.