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
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.
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
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.