EFFECTS
OF CREATINE SUPPLEMENTATION DURING TRAINING ON THE INCIDENCE
OF MUSCLE CRAMPING, INJURIES, AND GI DISTRESS
R.B. Kreider, C. Rasmussen, J. Ransom, and A.L. Almada.
Exercise and Sport Nutrition Laboratory, Department of HMSE,
The University of Memphis, Memphis, TN 38152.
Anecdotal reports have suggested that creatine supplementation
during training may increase the incidence of cramping,
muscle strains/pulls, and/or gastrointestinal (GI) distress.
This study evaluated the incidence of side effects reported
in subjects who participated in one of five placebo, double-blind,
and randomized studies which investigated the effects of
ingesting creatine or creatine-containing supplements during
training. One hundred sixty-four post-study questionnaires
were evaluated in which 84 subjects ingested placebos and
80 subjects ingested supplements containing creatine during
training. Training and supplementation protocols included:
1.) 9 d of ingesting a carbohydrate placebo (n=9) or 21
g/d of creatine (n=9) in male and female elite junior swimmers
during training (20.5 ± 2 hr/wk); 2.) 14 d of ingesting
a carbohydrate placebo (n=7), 16.5 g/d of creatine (n=8),
or Phosphagen HP® containing 15.75 g/d of creatine (n=9)
in untrained and competitively trained male and female endurance
athletes; 3.) 28 d of ingesting a carbohydrate placebo (n=11),
Gainers Fuel 1000® (n=10), or Phosphagain® containing
20 g/d of creatine (n=7) during resistance-training (7.6
± 2 hr/wk); 4.) 28 d of ingesting a carbohydrate
placebo (n=22) or Phoshagen HP containing 15.75 g/d of creatine
(n=23) in college football players undergoing resistance/agility
training (8 hr/wk); or, 5.) 84 d of ingesting a carbohydrate
placebo (n=13), MetRx® (n=12), Phosphagain® containing
20 g/d of creatine (n=11), or Phosphagain II® containing
25 g/d of creatine (n=13) in college football players undergoing
resistance/agility training and spring football practice.
Results revealed no reports of muscle cramping or injury
in subjects taking placebos or creatine-containing supplements
during training. Further, a significantly greater incidence
(p<0.05) of GI distress was reported in subjects ingesting
placebos compared to creatine-containing supplements. These
findings indicate that creatine supplementation during various
exercise training conditions does not increase the incidence
of muscle cramping, muscle strains/pulls, or GI distress.
Presented at the National Strength and Conditioning Association
Convention, Nashville, TN, June 24-28, 1998.
Creatine Monohydrate May Improve Blood Lipid Profiles
C.P. Earnest, A.L. Almada, and T.L. Mitchell, "High-Performance
Capillary Electrophoresis-Pure Creatine Monohydrate Reduces
Blood Lipids in Men and Women,"Clin. Sci. 91 (1996):
113-118.
Just when you thought the news about creatine monohydrate
couldn't get any better, we're finding that creatine may,
in addition to its well-documented positive effects on body
composition and athletic performance, reduce blood lipids.
A team of researchers in Dallas, Texas, including EAS researcher
Anthony Almada, B.Sc., M.Sc., examined the effects of creatine
monohydrate (5 grams) combined with glucose (1 gram) on
the blood chemistry of 34 male and female subjects, ages
32-70 years. Scientists measured creatine's effects against
those of a placebo containing 6 grams of glucose for a total
of 56 days, with dosages of both creatine and the placebo
given orally 4 times a day for 5 days, then twice a day
for 51 days.
Results indicated significant reductions in plasma total
cholesterol, triglycerides, and very low-density lipoproteins
(VLDL) in the creatine monohydrate group. High levels of
these substances in the blood can lead to heart disease,
a problem that killed over 740,000 Americans in 1993 alone.
Researchers also noted a trend towards a reduction in blood
glucose for subjects ingesting creatine monohydrate.
Additionally, the trend for lower blood glucose in subjects
receiving creatine monohydrate indicates the possibility
that creatine enhances insulin sensitivity, which could
prove helpful for some diabetics. This result could also
mean that glucose moves from the bloodstream into muscle
cells more quickly with creatine use. Again, further research
is necessary to determine whether or not these results can
be repeated and strengthened, but there is a strong possibility
that creatine monohydrate can actually lower blood lipids
and improve glucose metabolism.
Safety Report on Creatine
T. Mitchell, A. Almada, and C. Earnest, "Creatine
Reduces Blood Lipid Concentrations in Men and Women,"
"Influence of Chronic Creatine Supplementation on Hepatorenal
Function," "Impact of Chronic Creatine Supplementation
on Serum Enzyme Concentrations," FASEB J.
10.3 (1996): A251, A791, A790.
A group of scientists from Texas Woman's University and
the Cooper Clinic in Dallas, Texas, presented results of
the longest creatine supplementation study to date. These
studies were designed to assess the influence of eight weeks
of creatine ingestion on various markers of metabolism and
organ function. Although a large number of creatine supplementation
studies have been conducted, virtually all of them focused
on muscular performance and muscle metabolism after short-term
supplementation.
Thirty-four men and women (ages 32-70) participated in
this double-blind, placebo-controlled study. Twenty subjects
received creatine (20 grams per day for 5 days, then 10
grams a day for 51 days, followed by a 4-week "washout"
/non-supplemented period), while the remaining 14 received
a glucose placebo. Few changes in the blood profiles were
noted in the creatine group: a slight increase in blood
urea nitrogen (BUN) in only the women at week eight was
seen (BUN is a marker of liver and kidney function and protein
metabolism), and among the men, at week three, a mild elevation
in creatine phosphokinase (CPK) was seen. Both returned
to baseline after week 12. CPK is an enzyme critical to
creatine and energy metabolism. It's continuously released
from various cells including skeletal muscle and is a crude
marker of muscle cell membrane integrity.
Interestingly, recent university studies with creatine
HP noted similar effects in a group of young, resistance-trained
males, with CPK going up in the HP group but not in the
placebo group. Increases in CPK suggest either an increase
in muscular force or tension production, consequent decreases
in the stability of muscle-cell membranes (leading to increased
CPK "leak"), decreases in muscle-cell membrane
integrity (more "holes"), and/or an increase in
the activity/concentration of this enzyme due to increased
concentrations of one of the substrates for this enzyme,
which may induce creatine-loaded cells to synthesize more
CPK. Why women didn't show an increase in CPK may be due
to the protective effect of estrogens on cell membranes.
(The majority of the women had moderate circulating concentrations
of estrogens, either naturally or from oral estrogens.)
Liver enzymes didn't increase nor did blood creatinine,
the irreversible breakdown product of creatine, commonly
mistaken for creatine and incorrectly believed to be toxic
to the kidneys.
Comments: The most fascinating observation from these studies
was a drop in blood triglycerides, total cholesterol, and
VLDL cholesterol, a blood lipoprotein enriched in triglycerides,
in the creatine group (these findings were published in
full, peer-review form in the July 1996 issue of Clinical
Science). As all of the subjects began with moderately elevated
blood cholesterol and triglycerides, these findings suggest
creatine may prove to be a useful nutritional supplement
in the management of high blood lipids. The mechanism of
creatine's action is suggested by the reduction of blood
glucose in the males who received creatine. As insulin regulates
both carbohydrate and triglyceride/VLDL metabolism, and
creatine and fourth-generation diabetes drugs (like metformin)
are classified as guanidine-containing compounds with glucoregulatory
actions, this raises the likelihood that, at least in this
group of individuals, creatine may be capable of potentiating
the action of insulin. Similar to the persistence of vanadyl
sulfate's effects in diabetic individuals, four weeks after
going off Phosphagen, triglycerides and VLDL remained reduced.
The fact that EAS funded these studies underscores the company's
commitment to extending the science of creatine supplementation
by continuing to examine the safety and biological effects
of this fascinating nutrient.
Creatine and its application as an ergogenic aid.
Greenhaff PL. Department of Physiology and Pharmacology,
University
Medical School, Queens Medical Centre, Nottingham, U.K.
Int J Sport Nutr, 5 Suppl():S100-10 1995 Jun
Phosphocreatine (PCr) availability is likely to limit performance
in brief, high-power exercise because the depletion of PCr
results in an inability to maintain adenosine triphosphate
(ATP) resynthesis at the rate required. It is now known
that the daily ingestion of four 5-g doses of creatine for
5 days will significantly increase intramuscular creatine
and PCr concentrations prior to exercise and will facilitate
PCr resynthesis during recovery from exercise, particularly
in those individuals with relatively low creatine concentrations
prior to feeding. As a consequence of creatine ingestion,
work output during repeated bouts of high-power exercise
has been increased under a variety of experimental conditions.
The reduced accumulation of ammonia and hypoxanthine in
plasma and the attenuation of muscle ATP degradation after
creatine feeding suggest that the ergogenic effect of creatine
is achieved by better maintaining ATP turnover during contraction.
Creatine depletion elicits structural, biochemical, and
physiological adaptations in rat costal diaphragm.
Levine S; Tikunov B; Henson D; LaManca J; Sweeney HL Pulmonary
and Critical Care Section, Veterans Affairs Medical Center,
Philadelphia, Pennsylvania, USA. Am J Physiol, 271(5 Pt
1):C1480-6 1996 Nov
To elucidate adaptations elicited by creatine (Cr) depletion
in the costal diaphragm (Dia), 16 12-wk-old male Fisher
344 rats had 2% beta-guanidinopropionic acid (beta-GPA),
a competitive inhibitor of Cr transport into muscle, added
to their food; a control group (Con) of 16 rats ate normal
rat chow. After 18 wk, beta-GPA and Con Dia did not differ
histochemically with respect to fiber-type distribution;
however, the cross-sectional area of type II(b + x) fibers
was 33% less in beta-GPA than Con Dia. Biochemically, the
proportion of myosin heavy chain IIb in beta-GPA Dia was
decreased 42% from Con Dia, whereas the proportions of myosin
heavy chains I and IIa were increased. Physiologically,
both peak twitch tension and tetanic tension in beta-GPA
Dia were decreased 40% from Con. To assess fatigability,
we used the protocol of Kelsen and Nochomovitz (J. Appl.
Physiol. 53; 440-447, 1982) for 2-6 min duration; the percentage
of initial force exhibited by beta-GPA Dia was approximately
twice that of Con Dia. We conclude that these structural,
biochemical, and physiological adaptations elicited by Cr
depletion can all be explained by selective atrophy of IIb
muscle fibers in the Dia.
Creatine kinase of rat heart mitochondria. The demonstration
of functional coupling to oxidative phosphorylation in an
inner membrane-matrix preparation.
Saks VA; Kuznetsov AV; Kupriyanov VV; Miceli MV; Jacobus
WE J Biol Chem, 260(12): 7757-64 1985 Jun 25
To define more clearly the interactions between mitochondrial
creatine kinase and the adenine nucleotide translocase,
the outer membrane of rat heart mitochondria was removed
by digitonin, producing an inner membrane-matrix (mitoplast)
preparation. This mitoplast fracton was well-coupled and
contained a high specific activity of mitochondrial creatine
kinase. Outer membrane permeabilization was documented by
the loss of adenylate kinase, a soluble intermembrane enzyme,
and by direct antibody inhibition of mitochondrial creatine
kinase activity. With this preparation, we documented four
important aspects of functional coupling. Kinetic studies
showed that oxidative phosphorylation decreased the value
of the ternary enzyme-substrate complex dissociation constant
for MgATP from 140 to 16 microM. Two approaches were used
to document the adenine nucleotide translocase specificity
for ADP generated by mitochondrial creatine kinase. Exogenous
pyruvate kinase (20 IU/ml) could not readily phosphorylate
ADP produced by creatine kinase, since added pyruvate kinase
did not markedly inhibit creatine + ATP-stimulated respiration.
Additionally, when ADP was produced by mitochondrial creatine
kinase, the inhibition of the translocase required 2 nmol
of atractyloside/mg of mitoplast protein, while only 1 nmol/mg
was necessary when exogenous ADP was added. Finally, the
mass action ratio of the mitochondrial creatine kinase reaction
exceeded the apparent equilibrium constant when ATP was
supplied to the creatine kinase reaction by oxidative phosphorylation.
Overall, these results are consistent with much data from
intact rat heart mitochondria, and suggest that the outer
membrane plays a minor role in the compartmentation of adenine
nucleotides. Furthermore, since the removal of the outer
membrane does not alter the unique coupling between oxidative
phosphorylation and mitochondrial creatine kinase, we suggest
that this cooperation is the result of protein-protein proximity
at the inner membrane surface
