CREATINE and the BRAIN
CONCUSSION – TBI
Turner CE1, Byblow WD2, Gant N3.
– Impairment or interruption of O2 compromises brain function and plays a role in neurological and neurodegenerative conditions
– Creatine is a naturally occurring compound involved in the buffering, transport, and regulation of cellular energy
– It has the potential to replenish cellular adenosine triphosphate without oxygen.
– Creatine is also neuroprotective in vitro against anoxic/hypoxic damage.
– Creatine has been associated with improved symptoms in neurological disorders defined by impaired neural energy provision
– Here we investigate, for the first time in humans, the utility of creatine as a dietary supplement to protect against energetic insult.
– Assess Creatine’s effect on neurophysiological and neuropsychological function of healthy young adults during acute O2 deprivation
– 15 healthy adults were supplemented with creatine and placebo treatments for 7 d, which increased brain creatine on average by 9.2%.
– A hypoxic gas mixture (10% O2) was given for 90 min, causing global O2 deficit and impairing a range of neuropsychological processes
(1) Hypoxia-induced decrements in attentional capacity were restored and corticomotor excitability increased
(2) A neuromodulatory effect of creatine via increased energy availability is presumed to be a contributing factor of the restoration
(1) Creatine increases corticomotor excitability, and prevents decline in attention that occurs during severe O2 deficit
(2) This is the first demonstration of creatine’s utility as a neuroprotective supplement when cellular energy provision is compromised
Jooyoung Kim,1 Joohyung Lee,1 Seungho Kim,2 Daeyoung Yoon,2 Jieun Kim,1 Dong Jun Sung3,*
(1) Creatine is a widely used dietary supplement to improve exercise performance by reducing exercise-induced muscle damage.
(2) It has been suggested that Creatine reduces muscle damage by decreasing inflammatory response and oxidative stress, regulating calcium homeostasis, and activating satellite cells
(3) This review discusses regulatory effects of creatine on muscle damage
Smith RN1, Agharkar AS1, Gonzales EB2.
(1) Creatine is an endogenous compound synthesized from arginine, glycine and methionine
(2) This dietary supplement can be acquired from food sources such as meat and fish, along with athlete supplement powders
(1) Creatine may be important in preventing or delaying onset of neurodegenerative diseases associated with aging
(2) On average, 30% of muscle mass is lost by age 80, while muscular weakness remains a vital cause for loss of independence
(3) Creatine has been studied in treating congestive heart failure, gyrate atrophy, insulin insensitivity, cancer, and high cholesterol
AGING & THE BRAIN
(1) antioxidant properties
(2) reduces mental fatigue
(3) protects the brain from neurotoxicity
(4) improves facets/components of neurological disorders like depression and bipolar disorder
(5) Fight PD, HD, ALS, long-term memory impairments associated with the progression of Alzheimer’s disease, and stroke
Christiano Robles Rodrigues Alves, and Bruno Gualano
– To assess effects of creatine, associated or not with strength training, upon emotional and cognitive measures in older woman
– 24-wks; individuals were allocated into one of the following groups (n=14 each):
2) creatine supplementation
3) placebo associated with strength training
4) creatine supplementation associated with strength training.
– given creatine (4 x 5 g/d for 5 days followed by 5 g/d) or placebo (dextrose at the same dosage) and were strength trained or not
(1) Both training groups had significant reductions on the Depression Scale when compared with non-trained placebo and creatine
(2) No significant differences between the non-trained placebo and creatine groups, or between the trained placebo and creatine groups
(3) Both trained groups, irrespective of creatine supplementation, had better muscle strength performance than the non-trained groups
(4) Neither strength training nor creatine supplementation altered any parameter of cognitive performance. Food intake remained unchanged.
(1) Creatine did not promote any significant change in cognitive function and emotional parameters in healthy older individuals
(2) Strength training per se improved emotional state and muscle strength, but not cognition, with no additive effects of creatine
– Our main findings are as follows:
(i) creatine per se or additively to strength training does not promote any benefit on selected aspects of cognitive function and emotional state
(ii) strength training per se is able to improve emotional measures, but not cognitive function.
– A high turnover of ATP is necessary to match the fluctuating energetic demand in the brain.
– In this respect, the phosphorylcreatine system has been thought to have a pivotal role to normal cerebral metabolism
– Changes in brain energy metabolism, neuronal plasticity, and cellular resiliency are associated with the pathogenesis of depressive disorders
– Brain bioenergetics and cell survival pathways are potential therapeutic targets for long-term clinical relief and symptom remission
– Creatine has emerged as being potentially capable of buffering metabolic processes, preventing energy exhaustion and neuronal death
– There is a large body of literature showing that alterations in brain creatine and phosphorylcreatine levels are associated with depression
– Preliminary findings suggested that creatine supplementation improves depressive symptoms in humans
– Patients with treatment-resistant depression or post-traumatic stress disorders associated or not with comorbid depression supplemented with creatine monohydrate for 4 weeks reported elevated mood on the Hamilton Depression Rating Scale.
– Conversely, in the current study, creatine, combined or not with strength training, failed to improve emotional measures
– The possible explanation for these conflicting findings may lie in differences among studied populations
– Whilst creatine has been shown to be effective in ameliorating symptoms in patients with severe psychiatric disorders, it is possible that this dietary supplement has limited (if any) effect in apparently mentally healthy elderly individuals.
– We also hypothesized that this dietary supplement could promote beneficial effects upon cognitive function
– Previous studies showed supplementation can improve selected aspects of cognitive performance in young individuals as well as in elderly
– Creatine also alleviates mental fatigue induced by stressor stimulus, such as mathematical calculus and sleep deprivation
– A recent study demonstrated that in vegetarians, but not in omnivors, creatine supplementation improved memory
– Both vegetarians and meat eaters experienced decreased variability in the responses to a choice reaction-time task
– However, in the current study, creatine was unable to promote any significant improvement in several aspects of cognitive function.
– Although it is difficult to reconcile these conflicting findings, a few explanations do exist
– Overall, the most important effects of creatine supplementation on cognitive function have been seen either under:
i) stressing conditions, such as sleep deprivation, exhausting exercise and mental fatigue
ii) vegetarian diet, which might lead to partial depletion in brain creatine content
– Therefore, we speculate that creatine does not benefit cognitive function in healthy individuals not subjected to stressing conditions
– An overview of the literature points to other factors that may be responsible for divergent results with respect to creatine effects on cognition, including:
1) the variation in the follow-up period of supplementation (i.e., 7 d to 24 weeks)
2) the age of the participants (i.e., adults versus elderly)
3) the different types of cognitive tests applied (i.e., memory, time-to-reaction, intelligence, attention, verbal fluency tests)
4) the experimental design (i.e., nonrandomized versus randomized controlled trials)
Ellen Cristini de Freitas
– Evaluate the effects of creatine (Cr) on oxidative stress and inflammation markers after acute repeated-sprint exercise in humans
– 25 players under age 20 y were randomly assigned to two groups:
(1) Cr supplemented (2) placebo.
– Double-blind controlled supplementation was performed using Cr (0.3 g/kg) or placebo tablets for 7 d.
– Before and after 7 d of supplementation, the athletes performed two consecutive Running-based Anaerobic Sprint Tests (RAST).
– RAST consisted of six 35-m sprint runs at maximum speed with 10 sec rest between them.
– Blood samples were collected just prior to start of test (pre), just after the completion (0 h), and 1 h after completion.
(1) Average, maximum, and minimum power values were greater in the Cr-supplemented group compared with placebo
(2) Significant increases in plasma tumor necrosis factor alpha (TNF-α) and C-reactive protein (CRP) up to 1 h after acute sprint exercise in the placebo-supplemented group
(3) Malondialdehyde, lactate dehydrogenase (LDH), catalase, and superoxide dismutase enzymes increased after exercise in both groups.
(4) Red blood cell glutathione was lower after exercise in both groups.
(5) Cr supplementation reversed the increase in TNF-α and CRP as well as LDH induced by acute exercise.
(6) Controversially, Cr supplementation did not inhibit the rise in oxidative stress markers.
(7) Also, antioxidant enzyme activity was not different between placebo and Cr-supplemented groups.
– Cr supplementation inhibited the increase of inflammation markers TNF-α and CRP, but not oxidative stress markers, due to acute exercise
(1) There is a substantial body of literature, which has demonstrated that creatine has neuroprotective effects both in vitro and in vivo
(2) We carried out studies examining the efficacy of creatine as a neuroprotective agent in vivo.
(3) Creatine can protect against excitotoxic lesions produced by N-methyl-D: -aspartate.
(4) Creatine is neuroprotective against lesions produced by the toxins malonate and 3-nitropropionic acid (3-NP)
(5) Creatine produced dose-dependent neuroprotective effects against MPTP toxicity
– Creatine produced an extension of survival, improved motor performance, and reduction in loss of motor neurons in a mouse model
PARKINSON’S & HUNTINGTON’S
(1) Creatine increases the brain levels of creatine and phosphocreatine
(2) Due to its neuroprotective effects, creatine is now in clinical trials for the treatment of PD and HD
(3) Creatine produced an extension of survival, improved motor function, and a reduction in striatal atrophy in mouse models of HD
(1) We recently examined the neuroprotective effects of a combination of CoQ10 with creatine against both MPTP and 3-NP toxicity
(2) CoQ + Creatine produced additive neuroprotective effects in a chronic MPTP model
(3) In the 3-NP model of HD, CoQ and creatine produced additive neuroprotective effects against the size of the striatal lesions
(4) In the R6/2 transgenic mouse model of HD, the combination of CoQ and creatine produced additive effects on improving survival
(1) Creatine may stabilize mitochondrial creatine kinase, and prevent activation of the mitochondrial permeability transition
(2) Creatine, however, was still neuroprotective in mice, which were deficient in mitochondrial creatine kinase
– Creatine, therefore, shows great promise in the treatment of a variety of neurodegenerative diseases
(1) Creatine (Cr) can be either ingested from fish or meat, produced by the body, primarily in the liver or supplemented
(2) It is used as an ergogenic aid to improve muscle mass, strength, and endurance.
(3) Creatine has positive therapeutic benefits in various oxidative stress-associated diseases
(4) Creatine has also been shown to exert direct antioxidant effects.
(5) Aim: Investigate effects of resistance exercise (RE) on oxidative stress response and oxidative DNA damage in male athletes and whether supplementation with Cr could negate any observed differences
– For 7 days 27 resistance-trained men were divided into:
(1) Cr group: 21.6 ± 3.6 yrs, taking 4 × 5 g Cr monohydrate per day
(2) Placebo (PL) group: 21.2 ± 3.2 years, taking 4 × 5 g maltodextrin per day
– Before and after the 7th day supplementation subjects performed an RE protocol; 7 sets of 4 exercises using 60-90 1 repetition maximum
– The Cr supplementation induces a significant increase in athletics performance
– Cr supplementation reduced oxidative DNA damage and lipid peroxidation induced by a single bout of RE
Combination Therapy with Coenzyme Q10 and Creatine Produces Additive Neuroprotective Effects in Models of Parkinson’s and Huntington’s Diseases – 2009
Lichuan Yang,1 and M. Flint Beal
– Coenzyme Q10 (CoQ10) and Creatine are promising agents for neuroprotection in neurodegenerative diseases via their effects on improving mitochondrial function and cellular bioenergetics and their properties as antioxidants
– We examined whether a combination of CoQ10 with creatine can exert additive neuroprotective effects in a MPTP mouse model of Parkinson’s disease (PD), a 3-NP rat model of Huntington’s disease (HD) and the R6/2 transgenic mouse model of HD.
(1) Additive neuroprotective effects against dopamine depletion in the striatum and loss of tyrosine hydroxylase neurons in the substantia nigra pars compacta (SNpc) following chronic subcutaneous administration of MPTP.
(2) Significant reduction in lipid peroxidation and pathologic α-synuclein accumulation in the SNpc neurons of the MPTP-treated mice.
(3) Additive neuroprotective effects in reducing striatal lesion volumes produced by chronic subcutaneous administration of 3-NP to rats.
(4) Significant effects on blocking 3-NP-induced impairment of glutathione homeostasis and reducing lipid peroxidation and DNA oxidative damage in the striatum.
(5) Lastly, the combination of CoQ10 and creatine produced additive neuroprotective effects on improving motor performance and extending survival in the transgenic R6/2 HD mice.
– Combination therapy using CoQ10 and creatine may be useful in treatment of neurodegenerative diseases such as PD and HD