Effects of Creatine Supplementation on Brain Function and Health

While the vast majority of research involving creatine supplementation has focused on skeletal muscle, there is a small body of accumulating research that has focused on creatine and the brain. Preliminary studies indicate that creatine supplementation (and guanidinoacetic acid; GAA) has the ability to increase brain creatine content in humans. Furthermore, creatine has shown some promise for attenuating symptoms of concussion, mild traumatic brain injury and depression but its effect on neurodegenerative diseases appears to be lacking. The purpose of this narrative review is to summarize the current body of research pertaining to creatine supplementation on total creatine and phophorylcreatine (PCr) content, explore GAA as an alternative or adjunct to creatine supplementation on brain creatine uptake, assess the impact of creatine on cognition with a focus on sleep deprivation, discuss the effects of creatine supplementation on a variety of neurological and mental health conditions, and outline recent advances on creatine supplementation as a neuroprotective supplement following traumatic brain injury or concussion.     

Creatine Supplementation in Women’s Health: A Lifespan Perspective

Despite extensive research on creatine, evidence for use among females is understudied. Creatine characteristics vary between males and females, with females exhibiting 70–80% lower endogenous creatine stores compared to males. Understanding creatine metabolism pre- and post-menopause yields important implications for creatine supplementation for performance and health among females. Due to the hormone-related changes to creatine kinetics and phosphocreatine resynthesis, supplementation may be particularly important during menses, pregnancy, post-partum, during and post-menopause. Creatine supplementation among pre-menopausal females appears to be effective for improving strength and exercise performance. Post-menopausal females may also experience benefits in skeletal muscle size and function when consuming high doses of creatine (0.3 g·kg⁻¹·d⁻¹); and favorable effects on bone when combined with resistance training. Pre-clinical and clinical evidence indicates positive effects from creatine supplementation on mood and cognition, possibly by restoring brain energy levels and homeostasis. Creatine supplementation may be even more effective for females by supporting a pro-energetic environment in the brain. The purpose of this review was to highlight the use of creatine in females across the lifespan with particular emphasis on performance, body composition, mood, and dosing strategies.     

Media Use,Cognitive Performance,and Life Satisfaction of the Chinese Elderly

Media use and aging is an important interdisciplinary topic pertaining to communication, gerontology, and psychology, among others. Integrating research on media-induced recovery and life satisfaction, the present study examined media uses and effects in the context of health and aging. Specifically, data from a large random sample were analyzed to investigate the relationships between media use, cognitive performance, and life satisfaction among the Chinese elderly. Results, in general, lent support to the slightly modified structural model. Specifically, media-induced recovery outcomes can be categorized into proximate (e.g., cognitive performance), intermediate (e.g., health satisfaction), and distal levels (e.g., life satisfaction). Also, situational factors (e.g., disease history) had statistically significant effects on media-induced recovery outcomes. Theoretical and practical implications of the research findings were discussed, and future research directions were suggested.     

Prevention Neuroscience: A new frontier for preventive medicine

Prevention neuroscience may be defined as follows: an interdisciplinary field concerned with the neurobiological factors that influence susceptibility to preventable disease, disability or mortality. It includes, but is not limited to: examination of brain health as an outcome, brain activity as a predictor of health outcomes, brain structures/systems as causal determinants of health outcomes (e.g., health behaviours), and the brain as a mediator of other causal influences (e.g., social conditions) on health outcomes. This commentary describes concepts, theory and research illustrating each of these scenarios using exercise, smoking cessation, dietary behaviour, and health disparities as examples. It is argued that neuroscience may provide both concepts and methods that may be possible (even fruitful) to incorporate into preventive medicine research and health promotion practise. Although public health practitioners and cognitive neuroscientists have not traditionally crossed paths outside of the context of neurodegenerative diseases such as Alzheimer's and other dementias, it is easy to envision a future where many common disease prevention activities involve collaboration between the two disciplines, and the cache of tools available to the preventive medicine expert includes neuroimaging and neuromodulation techniques.     

Effects of beta-alanine on muscle carnosine and exercise performance: a review of the current literature

Muscle carnosine has been reported to serve as a physiological buffer, possess antioxidant properties, influence enzyme regulation, and affect sarcoplasmic reticulum calcium regulation. Beta-alanine (β-ALA) is a non-essential amino acid. β-ALA supplementation (e.g., 2-6 grams/day) has been shown to increase carnosine concentrations in skeletal muscle by 20-80%. Several studies have reported that β-ALA supplementation can increase high-intensity intermittent exercise performance and/or training adaptations. Although the specific mechanism remains to be determined, the ergogenicity of β-ALA has been most commonly attributed to an increased muscle buffering capacity. More recently, researchers have investigated the effects of co-ingesting β-ALA with creatine monohydrate to determine whether there may be synergistic and/or additive benefits. This paper overviews the theoretical rationale and potential ergogenic value of β-ALA supplementation with or without creatine as well as provides future research recommendations.     

The influence of creatine supplementation on the cognitive functioning of vegetarians and omnivores

Creatine when combined with P forms phosphocreatine that acts as a reserve of high-energy phosphate. Creatine is found mostly in meat, fish and other animal products, and the levels of muscle creatine are known to be lower in vegetarians. Creatine supplementation influences brain functioning as indicated by imaging studies and the measurement of oxygenated Hb. Given the key role played by creatine in the provision of energy, the influence of its supplementation on cognitive functioning was examined, contrasting the effect in omnivores and vegetarians. Young adult females (n 128) were separated into those who were and were not vegetarian. Randomly and under a double-blind procedure, subjects consumed either a placebo or 20?g of creatine supplement for 5?d. Creatine supplementation did not influence measures of verbal fluency and vigilance. However, in vegetarians rather than in those who consume meat, creatine supplementation resulted in better memory. Irrespective of dietary style, the supplementation of creatine decreased the variability in the responses to a choice reaction-time task.     

Benefits and drawbacks of guanidinoacetic acid as a possible treatment to replenish cerebral creatine in AGAT deficiency

Arginine–glycine amidinotransferase (AGAT) deficiency is a rare inherited metabolic disorder that severely affects brain bioenergetics. Characterized by mental retardation, language impairment, and behavioral disorders, AGAT deficiency is a treatable condition, where long-term creatine supplementation usually restores brain creatine levels and improves its clinical features. In some cases of AGAT deficiency, creatine treatment might be somewhat limited due to possible shortcomings in performance and transport of creatine to the brain. Guanidinoacetic acid (GAA), a direct metabolic precursor of creatine, has recently been suggested as a possible alternative to creatine to tackle brain creatine levels in experimental medicine. AGAT patients might benefit from oral GAA due to upgraded bioavailability and convenient utilization of the compound, while possible drawbacks (e.g. brain methylation issues, neurotoxicity, and hyperhomocysteinemia) should be accounted as well.     

The Application of Creatine Supplementation in Medical Rehabilitation

Numerous health conditions affecting the musculoskeletal, cardiopulmonary, and nervous systems can result in physical dysfunction, impaired performance, muscle weakness, and disuse-induced atrophy. Due to its well-documented anabolic potential, creatine monohydrate has been investigated as a supplemental agent to mitigate the loss of muscle mass and function in a variety of acute and chronic conditions. A review of the literature was conducted to assess the current state of knowledge regarding the effects of creatine supplementation on rehabilitation from immobilization and injury, neurodegenerative diseases, cardiopulmonary disease, and other muscular disorders. Several of the findings are encouraging, showcasing creatine’s potential efficacy as a supplemental agent via preservation of muscle mass, strength, and physical function; however, the results are not consistent. For multiple diseases, only a few creatine studies with small sample sizes have been published, making it difficult to draw definitive conclusions. Rationale for discordant findings is further complicated by differences in disease pathologies, intervention protocols, creatine dosing and duration, and patient population. While creatine supplementation demonstrates promise as a therapeutic aid, more research is needed to fill gaps in knowledge within medical rehabilitation.     

Physical activity and brain structure,brain function,and cognition in children and youth: A systematic review of randomized controlled trials

BackgroundPrevious reviews show a favourable relationship between physical activity (PA) and brain health in children and youth. The purpose of this systematic review was to extend the generalizability of previous findings using only studies that employed randomized controlled designs in a wider age range.MethodsAfter registration in PROSPERO, PRISMA guidelines were followed. Studies must have used a randomized controlled design; manipulated PA once (i.e., acute) or more (i.e., chronic) in apparently healthy children (1 month-17.99 years); and examined cognitive function, brain function, or brain structure as outcomes. Articles were reviewed for inclusion and data extraction were performed in duplicate.ResultsOverall, 84 studies from 83 papers with 12,600 unique participants were included (n_range = 10–1,224, M_range = 0.77–17 years). Studies were mostly rated as low risk of bias. The majority of studies (n = 52) reported at least one favourable cognitive function outcome associated with a PA intervention. Few studies (n = 6) reported an unfavourable outcome. Examining the multiple cognitive function outcomes within each study, PA had mostly no effect (n_acute = 29, n_chronic = 47) or a mix of favourable and no effects (n_acute = 20, n_chronic = 27). For brain function, acute PA was associated with no change (n = 2) whereas chronic PA was associated with a mix of increases, decreases, or no change (n = 3). For brain structure, two overlapping studies found either favourable or no effects of chronic PA.DiscussionPA is unlikely to harm brain health in children and youth and may confer some benefits. More research is needed to examine the relationship between PA and brain structure and function.     

The role of gangliosides in brain development and the potential benefits of perinatal supplementation

The maternal diet provides critical nutrients that can influence fetal and infant brain development and function. This review highlights the potential benefits of maternal dietary ganglioside supplementation on fetal and infant brain development. English-language systematic reviews, preclinical studies, and clinical studies were obtained through searches on PubMed. Reports were selected if they included benefits and harms of maternal ganglioside supplementation during pregnancy or ganglioside-supplemented formula after pregnancy. The potential benefits of ganglioside supplementation were explored by investigating the following: (1) their role in neural development, (2) their therapeutic use in neural injury and disease, (3) their presence in human breast milk, and (4) their use as a dietary supplement during or after pregnancy. Preclinical studies indicate that ganglioside supplementation at high doses (1% of total dietary intake) can significantly increase cognitive development and body weight when given prenatally. However, lower ganglioside supplementation doses have no beneficial cognitive effects, even when given throughout pregnancy and lactation. In human clinical trials, infants given formula supplemented with gangliosides showed increased cognitive development and an increase in ganglioside content. Ganglioside supplementation may promote brain development and function in offspring when administered at the optimum dosage. We propose that prenatal maternal dietary supplementation with gangliosides throughout pregnancy may promote greater long-term effects on brain development and function. Before this concept can be encouraged in preconception clinics, future research and clinical trials are needed to confirm the ability of dietary gangliosides to improve cognitive development, but available results already encourage this area of research.     

Anti-Inflammatory and Anti-Catabolic Effects of Creatine Supplementation: A Brief Review

It is well established that creatine supplementation, primarily when combined with resistance training, significantly increases measures of muscle mass and performance (primarily strength). Emerging research also indicates that creatine supplementation may have favorable effects on measures of bone biology. These anabolic adaptations may be related to creatine influencing cellular hydration status, high-energy phosphate metabolism, growth factors, muscle protein kinetics, and the bone remodeling process. Accumulating research also suggests that creatine supplementation has anti-inflammatory and anti-catabolic properties, which may help create a favorable environment for muscle and bone accretion and recovery from exercise. Creatine supplementation has the ability to decrease markers of inflammation and possibly attenuate cancerous tumor growth progression. From a musculoskeletal perspective, there is some evidence to show that creatine supplementation reduces measures of muscle protein catabolism (primarily in males) and bone resorption when combined with resistance training. The purpose of this brief review is to summarize the current body of literature examining the potential anti-inflammatory and anti-catabolic effects of creatine supplementation across various research populations.     

Role of Vitamin D in Cognitive Dysfunction: New Molecular Concepts and Discrepancies between Animal and Human Findings

Purpose of review: increasing evidence suggests that besides the several metabolic, endocrine, and immune functions of 1alpha,25-dihydroxyvitamin D (1,25(OH)2D), the neuronal effects of 1,25(OH)2D should also be considered an essential contributor to the development of cognition in the early years and its maintenance in aging. The developmental disabilities induced by vitamin D deficiency (VDD) include neurological disorders (e.g., attention deficit hyperactivity disorder, autism spectrum disorder, schizophrenia) characterized by cognitive dysfunction. On the other hand, VDD has frequently been associated with dementia of aging and neurodegenerative diseases (e.g., Alzheimer’s, Parkinson’s disease). Recent findings: various cells (i.e., neurons, astrocytes, and microglia) within the central nervous system (CNS) express vitamin D receptors (VDR). Moreover, some of them are capable of synthesizing and catabolizing 1,25(OH)2D via 25-hydroxyvitamin D 1alpha-hydroxylase (CYP27B1) and 25-hydroxyvitamin D 24-hydroxylase (CYP24A1) enzymes, respectively. Both 1,25(OH)2D and 25-hydroxyvitamin D were determined from different areas of the brain and their uneven distribution suggests that vitamin D signaling might have a paracrine or autocrine nature in the CNS. Although both cholecalciferol and 25-hydroxyvitamin D pass the blood–brain barrier, the influence of supplementation has not yet demonstrated to have a direct impact on neuronal functions. So, this review summarizes the existing evidence for the action of vitamin D on cognitive function in animal models and humans and discusses the possible pitfalls of therapeutic clinical translation.     

Wahrnehmung von gesundheitlichen Risiken

This article reviews central findings and current developments of psychological and sociological research on the perception of health risks. Risk perception is influenced by numerous psychological, social, political, and cultural factors. These factors can be categorized into (a) risk characteristics, (b) characteristics of the risk perceiving person and his/her situation, and (c) characteristics of risk communication. Thus, besides individual cognitive and affective processing of risk information, social processes of risk amplification (e.g., media effects) are also involved in the construction of individual risk perceptions. We discuss the recommendations for health risk communication that follow from these findings with regard to different communication goals.     

Potential of Creatine in Glucose Management and Diabetes

Creatine is one of the most popular supplements worldwide, and it is frequently used by both athletic and non-athletic populations to improve power, strength, muscle mass and performance. A growing body of evidence has been identified potential therapeutic effects of creatine in a wide variety of clinical conditions, such as cancer, muscle dystrophy and neurodegenerative disorders. Evidence has suggested that creatine supplementation alone, and mainly in combination with exercise training, may improve glucose metabolism in health individuals and insulin-resistant individuals, such as in those with type 2 diabetes mellitus. Creatine itself may stimulate insulin secretion in vitro, improve muscle glycogen stores and ameliorate hyperglycemia in animals. In addition, exercise induces numerous metabolic benefits, including increases in insulin-independent muscle glucose uptake and insulin sensitivity. It has been speculated that creatine supplementation combined with exercise training could result in additional improvements in glucose metabolism when compared with each intervention separately. The possible mechanism underlying the effects of combined exercise and creatine supplementation is an enhanced glucose transport into muscle cell by type 4 glucose transporter (GLUT-4) translocation to sarcolemma. Although preliminary findings from small-scale trials involving patients with type 2 diabetes mellitus are promising, the efficacy of creatine for improving glycemic control is yet to be confirmed. In this review, we aim to explore the possible therapeutic role of creatine supplementation on glucose management and as a potential anti-diabetic intervention, summarizing the current knowledge and highlighting the research gaps.     

Supplementation with NAD+ and Its Precursors to Prevent Cognitive Decline across Disease Contexts

The preservation of cognitive ability by increasing nicotinamide adenine dinucleotide (NAD⁺) levels through supplementation with NAD⁺ precursors has been identified as a promising treatment strategy for a number of conditions; principally, age-related cognitive decline (including Alzheimer’s disease and vascular dementia), but also diabetes, stroke, and traumatic brain injury. Candidate factors have included NAD⁺ itself, its reduced form NADH, nicotinamide (NAM), nicotinamide mononucleotide (NMN), nicotinamide riboside (NR), and niacin (or nicotinic acid). This review summarises the research findings for each source of cognitive impairment for which NAD⁺ precursor supplementation has been investigated as a therapy. The findings are mostly positive but have been made primarily in animal models, with some reports of null or adverse effects. Given the increasing popularity and availability of these factors as nutritional supplements, further properly controlled clinical research is needed to provide definitive answers regarding this strategy’s likely impact on human cognitive health when used to address different sources of impairment.     

Meta-Analysis Examining the Importance of Creatine Ingestion Strategies on Lean Tissue Mass and Strength in Older Adults

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.     

ω-3 Fatty Acids in the Prevention of Cognitive Decline in Humans

The brain is a lipid-rich organ where docosahexaenoic acid (DHA) is enriched and where eicosapentaenoic acid (EPA) may have anti-inflammatory effects. The potential role for n–3 (ω-3) fatty acids such as DHA and EPA in the prevention of cognitive decline, including Alzheimer’s disease (AD) has attracted major interest for the past 20 y. This review presents our understanding of recent observational, interventional, and experimental studies, with the aim of providing some answers to the following question: Can n–3 FA intake modulate cognitive function during aging? In longitudinal observation studies we mainly observe inverse relations between fish intake or serum concentrations of DHA and cognitive impairment. Intervention studies of EPA and DHA supplementation in healthy old individuals have been negative so far (i.e., after up to 2 years of treatment, no differences in cognitive decline between treated and nontreated participants have been observed). In studies that provided EPA and DHA to adults with mild cognitive impairment or age-related cognitive impairment the data seem to be positive. However, when patients with established AD were supplemented with EPA and DHA it appears no benefit was gained. For studies on healthy individuals, a major concern is that the treatment periods may have been too short. There might also be subgroup effects because of the carriage of apolipoprotein Eε4 alleles or risk factor burden. Experimental studies appear to be consistently positive (i.e., n–3 FA supplementation in rodents over a substantial portion of their lives reduces amyloid-β deposition and hippocampal neuron loss and improves cognitive functioning). We are getting closer to providing evidence-based recommendations on fish and fish oil intake to facilitate memory function during old age. In the meantime it is advised to follow the general CDC dietary recommendations of 2–3 fish meals per week or the equivalent intake of long chain n–3 fatty acids, particularly DHA.     

Examining the protective effects of brand equity in the keepin' it REAL substance use prevention curriculum

While branding appears to be an effective health prevention strategy, it is less clear how successful brands have protective effects. To better understand the role of branding in health prevention and promotion, it is necessary to examine how the persuasive mechanisms of branding function in health campaigns (e.g., modeling socially desirable behaviors). Using cross-sectional data (n?=?709), the current study uncovered the mechanisms explaining branding's effects on adolescent substance use in a school-based substance use intervention, the keepin' it REAL (kiR) curriculum. Consistent with our predictions, a confirmatory factor analysis suggested that kiR brand equity had a higher order, multidimensional factor structure. In addition, a path analysis revealed that brand equity affected adolescent substance use directly and through the predicted social cognitive processes, including refusal efficacy and resistance skills. Thus, it is concluded that kiR brand equity serves as a protective factor for adolescent substance use. Practical implications, research limitations, and future directions are discussed.     

Mediation of cognitive function by high fat diet following stress and inflammation

In addition to commonly advertised hazards of obesity contributed by excess dietary fat, evidence of alterations in brain chemistry and structure are well documented. This brief review examines the role of nutrients, minerals and certain lipids, primarily the essential fatty acids (FA), that are beneficial to the maintenance of good health and that may offer therapeutic options by dietary supplementation. The review also considers the damaging effects of stress, especially in pre-existing conditions of obesity and diabetes, as studied in both animals and humans. The main focus of this brief review is to examine the effects of a high fat diet on stress and the immune system with particular emphasis on brain and cognitive function.     

Creatine Supplementation,Physical Exercise and Oxidative Stress Markers: A Review of the Mechanisms and Effectiveness

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.