Creatine is a popular nutritional supplement that has been discussed extensively elsewhere in this website. Animal studies indicate that creatine supplementation exerts a neuroprotective effect after traumatic brain and spinal cord injury and with amyotrophic lateral sclerosis (i.e., Lou Gerhig’s Disease). The following are abstracts from several professional publications that discuss this effect:

SPINAL CORD INJURY:

Protective effects of oral creatine supplementation on spinal cord injury in rats.
Spinal Cord. 2002 Sept;40(9):449-56.
Hausmann ON, Fouad K, Wallimann T, Schwab ME., Brain Research Institute, University of Zurich and Department of Biology, Swiss Federal Institute of Technology, Zurich, Switzerland.

STUDY DESIGN: To evaluate a potential protective effect of increased creatine levels in spinal cord injury (SCI) in an animal model. OBJECTIVES: Acute SCI initiates a series of cellular and molecular events in the injured tissue leading to further damage in the surrounding area. This secondary damage is partly due to ischemia and a fatal intracellular loss of energy. Phospho-creatine in conjunction with the creatine kinase isoenzyme system acts as a potent intracellular energy buffer. Oral creatine supplementation has been shown to elevate the phospho-creatine content in brain and muscle tissue, leading to neuroprotective effects and increased muscle performance. SETTING: Zurich, Switzerland. METHODS: Twenty adult rats were fed for 4 weeks with or without creatine supplemented nutrition before undergoing a moderate spinal cord contusion. RESULTS: Following an initial complete hindlimb paralysis, rats of both groups substantially recovered within 1 week. However, creatine fed animals scored 2.8 points better than the controls in the BBB open field locomotor score (11.9 and 9.1 points respectively after 1 week; P=0.035, and 13 points compared to 11.4 after 2 weeks). The histological examination 2 weeks after SCI revealed that in all rats a cavity had developed which was comparable in size between the groups. In creatine fed rats, however, a significantly smaller amount of scar tissue surrounding the cavity was found. CONCLUSIONS: Thus creatine treatment seems to reduce the spread of secondary injury. Our results favour a pretreatment of patients with creatine for neuroprotection in cases of elective intramedullary spinal surgery. Further studies are needed to evaluate the benefit of immediate creatine administration in case of acute spinal cord or brain injury.

Creatine diet supplement for spinal cord injury: influences on functional recovery and tissue sparing in rats.
J Neurotrauma. 2003 July;20(7):659-69.

Rabchevsky AG, Sullivan PG, Fugaccia I, Scheff SW., Sanders-Brown Center on Aging, Department of Physiology, University of Kentucky, 236 Health Sciences Research Building, Lexington, Kentucky 40536-0305, USA.

Creatine-supplemented diet significantly attenuates cortical damage after traumatic brain injury in rodents. The protective mechanism likely involves maintenance of mitochondrial homeostasis. In the present study, we used two separate contusion spinal cord injury (SCI) instruments--the NYU device and the PSI Infinite Horizon (IH) impactor--to assess the efficacy of creatine-supplemented diets on hind limb functional recovery and tissue sparing in adult rats. Rats were fed control versus 2% creatine-supplemented chow for 4-5 weeks prior to SCI (pre-fed), after which most resumed a control diet while some remained on a 2% creatine diet (pre & post-fed). Following long-term behavioral analysis (BBB), the amount of spared spinal cord tissue among the dietary regimen groups was assessed using stereology. Comparatively, both instruments caused similar amounts of gray matter damage while the NYU device rendered a greater loss of white matter, reflected in more severe hind limb functional deficits than with the IH impactor. Relative to the control fed groups injured with either instrument, none of the creatine fed animals showed improvements in hind limb function or white matter tissue sparing. Although creatine did not attenuate gray matter loss in the NYU cohort, it significantly spared gray matter in the IH cohort with pre-fed and pre & post-fed regimens. Such selective sparing of injured spinal cord gray matter with a dietary supplement yields a promising strategy to promote neuroprotection after SCI. The relationship between the efficacy of creatine and the magnitude of the insults is discussed.

HEAD INJURY:

Dietary supplement creatine protects against traumatic brain injury.
Ann Neurol. 2000 Nov;48(5):723-9.
Sullivan PG, Geiger JD, Mattson MP, Scheff SW., Sanders-Brown Center on Aging, University of Kentucky, Lexington 40536-0230, USA.

Creatine, one of the most common food supplements used by individuals at almost every level of athleticism, promote gains in performance, strength, and fat-free mass. Recent experimental findings have demonstrated that creatine affords significant neuroprotection against ischemic and oxidative insults. The present experiments investigated the possible effect of creatine dietary supplementation on brain tissue damage after experimental traumatic brain injury. Results demonstrate that chronic administration of creatine ameliorated the extent of cortical damage by as much as 36% in mice and 50% in rats. Protection seems to be related to creatine-induced maintenance of mitochondrial bioenergetics. Mitochondrial membrane potential was significantly increased, intramitochondrial levels of reactive oxygen species and calcium were significantly decreased, and adenosine triphosphate levels were maintained. Induction of mitochondrial permeability transition was significantly inhibited in animals fed creatine. This food supplement may provide clues to the mechanisms responsible for neuronal loss after traumatic brain injury and may find use as a neuroprotective agent against acute and delayed neurodegenerative processes.

AMYOTROPHIC LATERAL SCLEROSIS:

Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis.
Nat Med. 1999 March;5(3):347-50.
Klivenyi P, Ferrante RJ, Matthews RT, Bogdanov MB, Klein AM, Andreassen OA, Mueller G, Wermer M, Kaddurah-Daouk R, Beal MF., Neurochemistry Laboratory, Neurology Service, Massachusetts General Hospital and Harvard Medical School, Boston 02118, USA.

Mitochondria are particularly vulnerable to oxidative stress, and mitochondrial swelling and vacuolization are among the earliest pathologic features found in two strains of transgenic amyotrophic lateral sclerosis (ALS) mice with SOD1 mutations. Mice with the G93A human SOD1 mutation have altered electron transport enzymes, and expression of the mutant enzyme in vitro results in a loss of mitochondrial membrane potential and elevated cytosolic calcium concentration. Mitochondrial dysfunction may lead to ATP depletion, which may contribute to cell death. If this is true, then buffering intracellular energy levels could exert neuroprotective effects. Creatine kinase and its substrates creatine and phosphocreatine constitute an intricate cellular energy buffering and transport system connecting sites of energy production (mitochondria) with sites of energy consumption, and creatine administration stabilizes the mitochondrial creatine kinase and inhibits opening of the mitochondrial transition pore. We found that oral administration of creatine produced a dose-dependent improvement in motor performance and extended survival in G93A transgenic mice, and it protected mice from loss of both motor neurons and substantia nigra neurons at 120 days of age. Creatine administration protected G93A transgenic mice from increases in biochemical indices of oxidative damage. Therefore, creatine administration may be a new therapeutic strategy for ALS.