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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.
Meta-Analysis Examining the Importance of Creatine Ingestion Strategies on Lean Tissue Mass and Strength in Older Adults.
Forbes, SC, Candow, DG, Ostojic, SM, Roberts, MD, Chilibeck, PD
Nutrients. 2021;(6)
Abstract
Creatine supplementation in conjunction with resistance training (RT) augments gains in lean tissue mass and strength in aging adults; however, there is a large amount of heterogeneity between individual studies that may be related to creatine ingestion strategies. Therefore, the purpose of this review was to (1) perform updated meta-analyses comparing creatine vs. placebo (independent of dosage and frequency of ingestion) during a resistance training program on measures of lean tissue mass and strength, (2) perform meta-analyses examining the effects of different creatine dosing strategies (lower: ≤5 g/day and higher: >5 g/day), with and without a creatine-loading phase (≥20 g/day for 5-7 days), and (3) perform meta-analyses determining whether creatine supplementation only on resistance training days influences measures of lean tissue mass and strength. Overall, creatine (independent of dosing strategy) augments lean tissue mass and strength increase from RT vs. placebo. Subanalyses showed that creatine-loading followed by lower-dose creatine (≤5 g/day) increased chest press strength vs. placebo. Higher-dose creatine (>5 g/day), with and without a creatine-loading phase, produced significant gains in leg press strength vs. placebo. However, when studies involving a creatine-loading phase were excluded from the analyses, creatine had no greater effect on chest press or leg press strength vs. placebo. Finally, creatine supplementation only on resistance training days significantly increased measures of lean tissue mass and strength vs. placebo.
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3.
The Potential Role of Creatine in Vascular Health.
Clarke, H, Hickner, RC, Ormsbee, MJ
Nutrients. 2021;(3)
Abstract
Creatine is an organic compound, consumed exogenously in the diet and synthesized endogenously via an intricate inter-organ process. Functioning in conjunction with creatine kinase, creatine has long been known for its pivotal role in cellular energy provision and energy shuttling. In addition to the abundance of evidence supporting the ergogenic benefits of creatine supplementation, recent evidence suggests a far broader application for creatine within various myopathies, neurodegenerative diseases, and other pathologies. Furthermore, creatine has been found to exhibit non-energy related properties, contributing as a possible direct and in-direct antioxidant and eliciting anti-inflammatory effects. In spite of the new clinical success of supplemental creatine, there is little scientific insight into the potential effects of creatine on cardiovascular disease (CVD), the leading cause of mortality. Taking into consideration the non-energy related actions of creatine, highlighted in this review, it can be speculated that creatine supplementation may serve as an adjuvant therapy for the management of vascular health in at-risk populations. This review, therefore, not only aims to summarize the current literature surrounding creatine and vascular health, but to also shed light onto the potential mechanisms in which creatine may be able to serve as a beneficial supplement capable of imparting vascular-protective properties and promoting vascular health.
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4.
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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5.
Creatine Supplementation, Physical Exercise and Oxidative Stress Markers: A Review of the Mechanisms and Effectiveness.
Arazi, H, Eghbali, E, Suzuki, K
Nutrients. 2021;(3)
Abstract
Oxidative stress is the result of an imbalance between the generation of reactive oxygen species (ROS) and their elimination by antioxidant mechanisms. ROS degrade biogenic substances such as deoxyribonucleic acid, lipids, and proteins, which in turn may lead to oxidative tissue damage. One of the physiological conditions currently associated with enhanced oxidative stress is exercise. Although a period of intense training may cause oxidative damage to muscle fibers, regular exercise helps increase the cells' ability to reduce the ROS over-accumulation. Regular moderate-intensity exercise has been shown to increase antioxidant defense. Endogenous antioxidants cannot completely prevent oxidative damage under the physiological and pathological conditions (intense exercise and exercise at altitude). These conditions may disturb the endogenous antioxidant balance and increase oxidative stress. In this case, the use of antioxidant supplements such as creatine can have positive effects on the antioxidant system. Creatine is made up of two essential amino acids, arginine and methionine, and one non-essential amino acid, glycine. The exact action mechanism of creatine as an antioxidant is not known. However, it has been shown to increase the activity of antioxidant enzymes and the capability to eliminate ROS and reactive nitrogen species (RNS). It seems that the antioxidant effects of creatine may be due to various mechanisms such as its indirect (i.e., increased or normalized cell energy status) and direct (i.e., maintaining mitochondrial integrity) mechanisms. Creatine supplement consumption may have a synergistic effect with training, but the intensity and duration of training can play an important role in the antioxidant activity. In this study, the researchers attempted to review the literature on the effects of creatine supplementation and physical exercise on oxidative stress.
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6.
Short-Term Creatine Loading Improves Total Work and Repetitions to Failure but Not Load-Velocity Characteristics in Strength-Trained Men.
Feuerbacher, JF, von Schöning, V, Melcher, J, Notbohm, HL, Freitag, N, Schumann, M
Nutrients. 2021;(3)
Abstract
This study assessed the effects of a 7-day creatine (CRE) supplementation on the load-velocity profile and repeated sub-maximal bouts in the deep squat using mean propulsive velocity (MPV) and mean propulsive power (MPP). Eleven strength-trained men (31.4 ± 5.4 years) supplemented 0.3 g·kg-1·d-1 CRE or a placebo (PLA, maltodextrin) for seven days in a randomized order, separated by a 30-day washout period. Prior to and after the supplementation, the subjects performed an incremental maximal strength (1RM) test, as well as 3 × 10 repetitions and a repetitions-to-failure test (RFT), all at 70% 1RM. Maximal strength remained statistically unaltered in CRE (p = 0.107) and PLA (p = 0.568). No statistical main effect for time (p = 0.780) or interaction (p = 0.737) was observed for the load-velocity profile. The number of repetitions during RFT remained statistically unaltered in both conditions (CRE: +16.8 ± 32.8%, p = 0.112; PLA: +8.2 ± 47.2%, p = 0.370), but the effect size was larger in creatine compared to placebo (g = 0.51 vs. g = 0.01). The total work during RFT increased following creatine supplementation (+23.1 ± 35.9%, p = 0.043, g = 0.70) but remained statistically unaltered in the placebo condition (+15.0 ± 60.8%, p = 0.801, g = 0.08; between conditions: p = 0.410, g = 0.25). We showed that CRE loading over seven days did not affect load-velocity characteristics but may have increased total work and power output during submaximal deep squat protocols, as was indicated by moderate effect sizes.
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7.
Guanidinoacetic acid loading for improved location-specific brain creatine.
Ostojic, SM
Clinical nutrition (Edinburgh, Scotland). 2021;(1):324-326
Abstract
BACKGROUND We conducted here a secondary analysis of previously completed guanidinoacetic acid (GAA) loading trials categorizing participants into responders and non-responders using cut-off points for an increase in the location-specific levels of brain creatine (e.g. thalamus, cerebellum, white and grey matter). METHODS A total of 19 healthy men (mean age = 24.8 years) who were supplemented with 3 g/d of GAA for 4 weeks, with total brain creatine evaluated using 1.5 T magnetic resonance spectroscopy (MRS) were included in this report. RESULTS An average elevation in total creatine content after 28-day GAA loading was 17.3% in the cerebellum (95% confidence interval [CI] from 9.7 to 24.9), 12.1% in the white matter (95% CI from 5.1 to 19.1), and 8.9% in the grey matter (95% CI from 5.2 to 12.6), while total creatine actually dropped in the thalamus at a follow-up for 9.1% (95% CI from 6.8 to 11.4). The prevalence of responders was the highest for the cerebellum (73.6%), followed by the white matter (47.3%) and the grey matter (42.1%), while only two individuals (10.5%) experienced a relevant rise in the thalamus creatine content at 28-day follow-up (P < 0.001). CONCLUSION This aftermath evaluation of previously published data suggests a relatively favorable (and location-specific) response rate to short-term GAA loading in healthy young men. A somewhat contrasting location-dependent pattern for GAA and creatine to positively affect brain creatine may be of great interest to the scientific community by dispensing different interventions to tackle poor bioenergetics in distinct brain regions.
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8.
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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9.
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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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.