Posted by Larry Hoover on October 15, 2004, at 12:11:16
In reply to brain fog and creatine/methylation, posted by raybakes on October 14, 2004, at 9:12:36
> Hi everyone, went to an interesting conference at the weekend, ed mitchell, the astronaut was there, and skip atwater from the monroe institute was there talking about hemi sync.
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> I took a few supplements along as I didn't want to get brain fog and miss most of what they were saying - serrapeptase worked really well at keeping the blood going to my brain, but I was amazed at how well betaine worked at keeping me alert. Methylation was obviously helping with my brain energy, but why? I bought a biochemistry book in one of the breaks and it said that 70% of all methylation reactions in the body are used to form creatine - previously I've done really badly on creatine, but now I can take a small amount as long as I've taken plenty of folinic acid (not folate) sublingual B12, and betaine (and sometimes some methionine). Now if I take a little creatine, I stay alert. The book also mentioned that creatine can work to maintain correct acid/alkaline balance in cells too.I'm glad you're helping to push my brain back into a good zone, Ray. Here are a few abstracts about creatine. I don't know if I own some, or not. But it's certainly going to be something I keep on my shelf.
Neurosci Res. 2002 Apr;42(4):279-85.
Effects of creatine on mental fatigue and cerebral hemoglobin oxygenation.
Watanabe A, Kato N, Kato T.
Department of Neuropsychiatry, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, 113-8655, Tokyo, Japan.
While the role of creatine in preventing muscle (peripheral) fatigue for high performance athletes is well understood, its biochemical role in prevention of mental (central) fatigue is not. Creatine is abundant in muscles and the brain and after phosphorylation used as an energy source for adenosine triphosphate synthesis. Using double-blind placebo-controlled
paradigm, we demonstrated that dietary supplement of creatine (8 g/day for 5 days) reduces mental fatigue when subjects repeatedly perform a simple mathematical calculation. After taking the creatine supplement, task-evoked increase of cerebral oxygenated hemoglobin in the brains of subjects measured by near infrared spectroscopy was significantly reduced, which is
compatible with increased oxygen utilization in the brain.
Brain Res. 1999 Jan 16;816(1):124-30.Exogenous creatine delays anoxic depolarization and protects from hypoxic damage: dose-effect relationship.
Balestrino M, Rebaudo R, Lunardi G.
Department of Neurological Sciences, University of Genova, Via De Toni 5, 16132, Genoa, Italy.
Incubation of hippocampal slices with different concentrations of creatine (0.5, 1, 10, 25 mM) results in a dose-dependent increase in intracellular phosphocreatine (PCr). Electrophysiological evidence suggests that this effect can protect neurons from anoxic damage by delaying the depletion of ATP during oxygen deprivation. In this paper we show that incubation of
brain slices with varying doses of creatine increases intracellular phosphocreatine and delays anoxic depolarization (AD) in a dose-dependent way. Specifically, addition to the incubation medium of 1 mM creatine significantly increased AD latency during hypoxia and prevented irreversible neuronal damage. Adding 0.5 mM creatine had no significant effect. Higher concentrations of creatine (up to 25 mM) did not provide any better protection. Our data also suggest a linear correlation between intracellular PCr and AD latency. These data report neural protection by exogenous creatine at concentrations lower than those usually reported in the literature. Copyright 1999 Elsevier Science B.V.
Amino Acids. 2002;23(1-3):221-9.Role of creatine and phosphocreatine in neuronal protection from anoxic and ischemic damage.
Balestrino M, Lensman M, Parodi M, Perasso L, Rebaudo R, Melani R, Polenov S, Cupello A.
Department of Neurological and Vision Sciences, University of Genova, Italy.
Phosphocreatine can to some extent compensate for the lack of ATP synthesis that is caused in the brain by deprivation of oxygen or glucose. Treatment of in vitro rat hippocampal slices with creatine increases the neuronal store of phosphocreatine. In this way it increases the resistance of the tissue to anoxic or ischemic damage. In in vitro brain slices pretreatment with creatine delays anoxic depolarization (AD) and prevents the irreversible loss of evoked potentials that is caused by transient anoxia, although it seems so far not to be active against milder, not AD-mediated, damage. Although creatine crosses poorly the blood-brain barrier, its administration in vivo at high doses through the intracerebroventricular or the intraperitoneal way causes an increase of cerebral phosphocreatine that has been shown to be of therapeutic value in vitro. Accordingly, preliminary data show that creatine pretreatment decreases ischemic damage in vivo.
J Neurochem. 2001 Jan;76(2):425-34.On the mechanisms of neuroprotection by creatine and phosphocreatine.
Brustovetsky N, Brustovetsky T, Dubinsky JM.
Department of Neuroscience, University of Minnesota, Minneapolis 55455, USA.
Creatine and phosphocreatine were evaluated for their ability to prevent death of cultured striatal and hippocampal neurons exposed to either glutamate or 3-nitropropionic acid (3NP) and to inhibit the mitochondrial permeability transition in CNS mitochondria. Phosphocreatine (PCr), and to a lesser extent creatine (Cr), but not (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK801), dose-dependently ameliorated 3NP toxicity when applied simultaneously with the 3NP in Mg2+-free media. Pre-treatment of PCr for 2 or 5 days and Cr for 5 days protected against glutamate excitotoxicity equivalent to that achieved by MK801 post-treatment. The combination of PCr or Cr pre-treatment and MK801 post-treatment did not provide additional protection, indicating that both prevented the toxicity attributable to secondary glutamate release. To determine if Cr or PCr directly inhibited the permeability transition, mitochondrial swelling and depolarization were assayed in isolated, purified brain mitochondria. PCr reduced the amount of swelling induced by calcium by 20%. Cr decreased mitochondrial swelling when inhibitors of creatine kinase octamer-dimer transition were present. However, in brain mitochondria prepared from rats fed a diet supplemented with 2% creatine for 2 weeks, the extent of calcium-induced mitochondrial swelling was not altered. Thus, the neuroprotective properties of PCr and Cr may reflect enhancement of cytoplasmic high-energy phosphates but not permeability transition inhibition.
J Neurochem. 2000 May;74(5):1968-78.Protective effect of the energy precursor creatine against toxicity of glutamate and beta-amyloid in rat hippocampal neurons.
Brewer GJ, Wallimann TW.
Department of Medical Microbiology/Immunology, Southern Illinois University School of Medicine, Springfield, Illinois 62794-9626, USA. gbrewer@siumed.edu
The loss of ATP, which is needed for ionic homeostasis, is an early event in the neurotoxicity of glutamate and beta-amyloid (A(beta)). We hypothesize that cells supplemented with the precursor creatine make more phosphocreatine (PCr) and create larger energy reserves with consequent neuroprotection against stressors. In serum-free cultures, glutamate at 0.5-1 mM was toxic to embryonic hippocampal neurons. Creatine at >0.1 mM greatly reduced glutamate toxicity. Creatine (1 mM) could be added as late as 2 h after glutamate to achieve protection at 24 h. In association with neurotoxic protection by creatine during the first 4 h, PCr levels remained constant, and PCr/ATP ratios increased. Morphologically, creatine protected against glutamate-induced dendritic pruning. Toxicity in embryonic neurons exposed to A(beta) (25-35) for 48 h was partially prevented by creatine as well. During the first 6 h of treatment with A(beta) plus creatine, the molar ratio of PCr/ATP in neurons increased from 15 to 60. Neurons from adult rats were also partially protected from a 24-h exposure to A(beta)
(25-35) by creatine, but protection was reduced in neurons from old animals. These results suggest that fortified energy reserves are able to protect neurons against important cytotoxic agents. The oral availability of creatine may benefit patients with neurodegenerative diseases.
Brain Res. 2000 Mar 31;860(1-2):195-8.Neuroprotective effects of creatine administration against NMDA and malonate toxicity.
Malcon C, Kaddurah-Daouk R, Beal MF.
Neurochemistry Laboratory, Neurology Service, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
We examined whether creatine administration could exert neuroprotective effects against excitotoxicity mediated by N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainic acid. Oral administration of 1% creatine significantly attenuated striatal excitotoxic lesions produced by NMDA, but had no effect on lesions produced by AMPA or kainic acid. Both creatine and nicotinamide can exert significant protective effects against malonate-induced striatal lesions. We, therefore, examined whether nicotinamide could exert additive neuroprotective effects with creatine against malonate-induced lesions. Nicotinamide with creatine produced significantly better neuroprotection than creatine alone against malonate-induced lesions. Creatine can, therefore, produce significant neuroprotective effects against NMDA mediated excitotoxic lesions in vivo and the combination of nicotinamide with creatine exerts additive neuroprotective effects.
Exp Gerontol. 2000 Dec;35(9-10):1165-83.Neuronal plasticity and stressor toxicity during aging.
Brewer GJ.
Department of Neurology, School of Medicine, Southern Illinois University, Springfield, IL, 62794-9626, USA. gbrewer@siumed.edu
Brain aging, Alzheimer disease and stroke share common elements of deficits in calcium regulation, declines in mitochondrial function, increases in generation of reactive oxygen species (ROS), accumulated damage from ROS and immune system dysfunction. The problem is to distinguish less significant side reactions, such as gray hair, from aspects of aging that contribute to disease. Toward establishing cause and effect relationships, a neuron cell culture system is described that allows comparisons with age under uniform environmental conditions. This neuron culture model indicates that susceptibility to death by apoptosis and consequences of the inflammatory response from beta-amyloid are age-related and an inherent characteristic of the neurons. Further mechanistic investigations are possible. New therapeutic approaches are suggested that combine inhibition of calcium overloads (calcium channel blockers), reduced ROS damage (melatonin, N-acetyl-cysteine), and bolstered mitochondrial function and energy generation (creatine). Together with newly demonstrated capabilities for adult and aged neuron regeneration and multiplication, i.e. plasticity, these approaches offer new hope toward reversing age-related decrements and damage from neurodegenerative disease.
> I've always wondered why methylation and SAMe are helpful in depression - is it because the brain is starving of energy? It's also interesting that creatine can reduce antibodies and raise glutathione, as glutathione needs a lot of energy to keep it activated.
Yes. But also, methylation is a required component of DNA transcription, something you need to do every single day. If the rate of protein synthesis falls, everything bogs down.
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> http://hdlighthouse.org/see/diet/supplements/creatine/creatine14.htm
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> Ray
>Lar
poster:Larry Hoover
thread:402926
URL: http://www.dr-bob.org/babble/alter/20040928/msgs/403368.html