Creatine as a booster for human brain function. How might it work?

Rae, Caroline; Bröer, Stefan

doi:10.1016/j.neuint.2015.08.010

Cited by 85 publications

(76 citation statements)

References 122 publications

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“…Interestingly, studies on aging WM in rhesus monkeys (Bowley et al, 2010; Sandell and Peters, 2003) reported that cellular aging in WM are correlated with a number of microstructural changes, such as reduction in the number of myelinated nerve fibers, increased occurrence of degenerating axons with less compact myelin sheaths showing segmental demyelination followed by ongoing, albeit inadequate, reparative processes. Therefore, our observations of increased [Cho], indicating altered cellular membrane turn-over, and increased [mI], indicating altered gliosis, in WM suggest that similar cellular aging with microstructural alterations also exist in humans, while the observed increase of [tCr] in white matter may indicate a compensatory alteration of the energy supply and neuroprotection (Rae and Broer, 2015). It is worth noting that except for NAA the correlations with age found for Cho, tCr, Glx and mI were mainly weak (with most correlation coefficients, R, around 0.3), which means that factors related to age might account for a statistically significant but relatively small contribution to the variance in these metabolites.…”

Section: Discussionmentioning

confidence: 78%

Physiological neuronal decline in healthy aging human brain — An in vivo study with MRI and short echo-time whole-brain 1H MR spectroscopic imaging

et al. 2016

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Knowledge of physiological aging in healthy human brain is increasingly important for neuroscientific research and clinical diagnosis. To investigate neuronal decline in normal aging brain eighty-one healthy subjects aged between 20 to 70 years were studied with MRI and whole-brain 1H-MR spectroscopic imaging. Concentrations of brain metabolites N-acetyl-aspartate (NAA), choline (Cho), total creatine (tCr), myo-inositol (mI), and glutamine+glutamate (Glx) in ratios to internal water, and the fractional volumes of brain tissue were estimated simultaneously in eight cerebral lobes and in cerebellum. Results demonstrated that an age-related decrease in gray matter volume was the largest contribution to changes in brain volume. Both lobar NAA and the fractional volume of gray matter (FVGM) decreased with age in all cerebral lobes, indicating that the decreased NAA was predominantly associated with decreased gray matter volume and neuronal density or metabolic activity. In cerebral white matter Cho, tCr, and mI increased with age in association with increased fractional volume, showing altered cellular membrane turn-over, energy metabolism, and glial activity in human aging white matter. In cerebellum tCr increased while brain tissue volume decreased with age, showing difference to cerebral aging. The observed age-related metabolic and microstructural variations suggest that physiological neuronal decline in aging human brain is associated with a reduction of gray matter volume and neuronal density, in combination with cellular aging in white matter indicated by microstructural alterations and altered energy metabolism in the cerebellum.

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Section: Discussionmentioning

confidence: 78%

Physiological neuronal decline in healthy aging human brain — An in vivo study with MRI and short echo-time whole-brain 1H MR spectroscopic imaging

et al. 2016

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“…For example, genetic mutations of the SLC6A8 gene encoding the Cr transporter are associated with intellectual disability (van de Kamp et al 2013) that is refractory to oral Cr (Salomons et al 2001;van de Kamp et al 2012). In contrast, deficiency syndromes associated with genetic mutations affecting Cr-synthesizing enzymes arginine-glycine amidinotransferase and guanidinoacetate methyltransferase also result in the absence or severe downregulation of brain Cr levels and significant cognitive deficits but are responsive to dietary Cr supplementation (Rae and Bröer 2015). Conversely, memory training can alter metabolite levels in the hippocampi of elderly subjects, including increases in Cr and choline levels (Valenzuela et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Chronic dietary creatine enhances hippocampal-dependent spatial memory, bioenergetics, and levels of plasticity-related proteins associated with NF-κB

et al. 2018

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The brain has a high demand for energy, of which creatine (Cr) is an important regulator. Studies document neurocognitive benefits of oral Cr in mammals, yet little is known regarding their physiological basis. This study investigated the effects of Cr supplementation (3%, w/w) on hippocampal function in male C57BL/6 mice, including spatial learning and memory in the Morris water maze and oxygen consumption rates from isolated mitochondria in real time. Levels of transcription factors and related proteins (CREB, Egr1, and IκB to indicate NF-κB activity), proteins implicated in cognition (CaMKII, PSD-95, and Egr2), and mitochondrial proteins (electron transport chain Complex I, mitochondrial fission protein Drp1) were probed with Western blotting. Dietary Cr decreased escape latency/time to locate the platform ( < 0.05) and increased the time spent in the target quadrant ( < 0.01) in the Morris water maze. This was accompanied by increased coupled respiration ( < 0.05) in isolated hippocampal mitochondria. Protein levels of CaMKII, PSD-95, and Complex 1 were increased in Cr-fed mice, whereas IκB was decreased. These data demonstrate that dietary supplementation with Cr can improve learning, memory, and mitochondrial function and have important implications for the treatment of diseases affecting memory and energy homeostasis.

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“…Increased dietary intake of creatine can elevate brain creatine levels which can sustain cognitive function under oxidative and nitrosative stress. Several in vitro or even preclinical studies showed that creatine directly preserves mitochondrial function in adult neurodegenerative conditions [64,65]. Clearly, mitochondrial impairment contributes directly and/or indirectly to the pathogenesis of numerous neurodegenerative disorders [66].…”

Section: Neuro-nutraceuticals: Definition Examples and Mechanisms Ofmentioning

confidence: 99%

Role of Nutraceuticals in Modulation of Gut-Brain Axis in Elderly Persons

Enciu¹,

Codrici²,

Mihai³

et al. 2018

Gerontology

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A rather new and somewhat unusual concept connects brain functions to gut microbiota. It is called "gut-brain axis" (or "microbiota-gut-brain axis") and states that probiotics consumption and a healthy gut microbiota positively influence brain functions related to behavior and cognition. Synergistic with a low chronic grade peripheral inflammation, this faulty barrier exposes the aged brain to negative extra-cerebral signals. Given the quasi-constant failure of pharmacological treatments in neurodegenerative diseases, increased interest is directed toward allopathic medicine, including dietary supplements. Interplay between gut microbiota and central nervous system by immune, neural and metabolic pathways is being explored as a possible modulator of cognitive impairment and behavior disorders. In elderly persons, this axis has been reported to be altered, contributing to systemic inflammation and was also indicated as a possible marker for early frailty in younger population. Currently, there are several clinical trials addressing the relationship between gut microbiota and central nervous system psychiatric disorders and at least one directly investigating whether there is a correlation between composition of gut microbiome, permeability of intestinal barrier and systemic inflammation in patients with dementia. This chapter discusses evidence-based data on positive modulation of gut-brain axis to alleviate behavior and cognition alterations in the elderly.

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Creatine as a booster for human brain function. How might it work?

Cited by 85 publications

References 122 publications

Physiological neuronal decline in healthy aging human brain — An in vivo study with MRI and short echo-time whole-brain 1H MR spectroscopic imaging

Physiological neuronal decline in healthy aging human brain — An in vivo study with MRI and short echo-time whole-brain 1H MR spectroscopic imaging

Chronic dietary creatine enhances hippocampal-dependent spatial memory, bioenergetics, and levels of plasticity-related proteins associated with NF-κB

Role of Nutraceuticals in Modulation of Gut-Brain Axis in Elderly Persons

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