LE Magazine September 2002
Page 4 of 4
Sports endurance
Health implications of creatine: can
oral creatine supplementation protect against neurological and
atherosclerotic disease?
Major achievements made over the last several years have
highlighted the important roles of creatine and the creatine
kinase reaction in health and disease. Inborn errors of
metabolism have been identified in the three main steps
involved in creatine metabolism: arginine: glycine
amidinotransferase (AGAT), S-adenosyl-L-methionine:
N-guanidinoacetate methyltransferase (GAMT) and the creatine
transporter. All these diseases are characterized by a lack of
creatine and phosphorylcreatine in the brain, and by (severe)
mental retardation. Similarly, knockout mice lacking the brain
cytosolic and mitochondrial isoenzymes of creatine kinase
displayed a slightly increased creatine concentration, but no
phosphorylcreatine in the brain. These mice revealed decreased
weight gain and reduced life expectancy, disturbed fat
metabolism, behavioral abnormalities and impaired learning
capacity. Oral creatine supplementation improved the clinical
symptoms in both AGAT and GAMT deficiency, but not in creatine
transporter deficiency. In addition, creatine supplementation
displayed neuroprotective effects in several animal models of
neurological disease, such as Huntington’s disease,
Parkinson’s disease or amyotrophic lateral sclerosis. All
these findings pinpoint to a close correlation between the
functional capacity of the creatine
kinase/phosphorylcreatine/creatine system and proper brain
function. They also offer a starting-point for novel means of
delaying neurodegenerative disease, and/or for strengthening
memory function and intellectual capabilities. Finally,
creatine biosynthesis has been postulated as a major effector
of homocysteine concentration in the plasma, which has been
identified as an independent graded risk factor for
atherosclerotic disease. By decreasing homocysteine
production, oral creatine supplementation may, thus, also
lower the risk for developing, e.g., coronary heart disease or
cerebrovascular disease. Although compelling, these results
require further confirmation in clinical studies in humans,
together with a thorough evaluation of the safety of oral
creatine supplementation.
Neuroscience 2002;112(2):243-60
Effects of creatine supplementation on
exercise performance and muscular strength in amyotrophic
lateral sclerosis: preliminary results.
Creatine supplementation in humans has been reported to
enhance power and strength both in normal subjects and in
patients with various neuromuscular diseases. The purpose of
this study was to examine the effects of supplementation on
exercise performance and maximal voluntary isometric muscular
contraction (MVIC) in amyotrophic lateral sclerosis (ALS)
patients. We report the results obtained in 28 patients with
probable/definite ALS. In each patient we acquired the
dynamometric measurement of MVIC in 10 muscle groups of upper
and lower limbs and a measure of fatigue by means of a
high-intensity intermittent protocol in elbow flexors and knee
extensors muscles. All patients completed the protocols at the
baseline and after supplementation of 20 g per day for seven
days and after supplementation of 3 g per day for three and
six months. MVIC increased after seven days of supplementation
in 20 patients (70%) in knee extensors and in 15 (53%) of them
also in elbow flexors. A statistically significant difference
between pre and post-treatment mean values of MVIC was found
both in elbow flexors (P<0.05) and knee extensors
(p<0.04). The analysis of the slopes of fatigue test showed
a statistically significant improvement after seven days of
supplementation in 11 patients (39%) in elbow flexors and in
nine patients (32%) also in knee extensors muscles. During the
six month follow-up period all the examined parameters showed
a linear progressive decline. In conclusion, our preliminary
results have demonstrated that supplementation temporarily
increases maximal isometric power in ALS patients so it may be
of potential benefit in situations such as high intensity
activity and it can be proposed as a symptomatic
treatment.
J Neurol Sci 2001 Oct
15;191(1-2):139-44
DHEA treatment reduces fat
accumulation and protects against insulin resistance in male
rats.
The purpose of this study was to determine whether
administration of dehydroepiandrosterone (DHEA) protects male
rats against the accumulation of body fat and the development
of insulin resistance with advancing age. We found that
supplementation of the diet with 0.3% DHEA between the ages of
five months and approximately 25 months resulted in a
significantly lower final body weight (DHEA, 593 +/- 18 g vs
control, 668 +/- 12 g, p < 0.02), despite no decrease in
food intake. Lean body mass was unaffected by the DHEA, and
the lower body weight was due to a approximately 25% reduction
in body fat. The rate of glucose disposal during a euglycemic,
hyperinsulinemic clamp was 30% higher in the DHEA group than
in the sedentary controls due to a greater insulin
responsiveness. The DHEA administration was as effective in
reducing body fat content and maintaining insulin
responsiveness as exercise in the form of voluntary wheel
running. The DHEA had no significant effect on muscle GLUT4
content. A preliminary experiment provided evidence suggesting
that muscle insulin signaling, as reflected in binding of
phosphatidylinositol 3-kinase to the insulin receptor
substrate-1, was enhanced in the DHEA-treated and wheel
running groups as compared to controls. These results provide
evidence that DHEA, like exercise, protects against excess fat
accumulation and development of insulin resistance in
rats.
J Gerontol A Biol Sci Med Sci 1998
Jan;53(1):B19-24
Herbal ephedra/caffeine for weight
loss: a six month randomized safety and efficacy trial.
OBJECTIVE: To examine long-term safety and efficacy for
weight loss of an herbal Ma Huang and Kola nut supplement
(90/192 mg/day ephedrine alkaloids/caffeine). DESIGN: Six
month randomized, double-blind placebo controlled trial.
SUBJECTS: A total of 167 subjects (body mass index (BMI)
31.8+/-4.1 kg/m(2)) randomized to placebo (n=84) or herbal
treatment (n=83) at two outpatient weight control research
units. MEASUREMENTS: Primary outcome measurements were changes
in blood pressure, heart function and body weight. Secondary
variables included body composition and metabolic changes.
RESULTS: By last observation carried forward analysis, herbal
vs placebo treatment decreased body weight (-5.3+/-5.0 vs
-2.6+/-3.2 kg, P<0.001), body fat (-4.3+/-3.3 vs -2.7+/-2.8
kg, P=0.020) and LDL-cholesterol (-8+/-20 vs 0+/-17 mg/dl,
P=0.013), and increased HDL-cholesterol (+2.7+/-5.7 vs
-0.3+/-6.7 mg/dl, P=0.004). Herbal treatment produced small
changes in blood pressure variables (+3 to -5 mmHg,
P</=0.05), and increased heart rate (4+/-9 vs -3+/-9 bpm,
P<0.001), but cardiac arrhythmias were not increased
(P>0.05). By self-report, dry mouth (P<0.01), heartburn
(P<0.05), and insomnia (P<0.01) were increased and
diarrhea decreased (P<0.05). Irritability, nausea, chest
pain and palpitations did not differ, nor did numbers of
subjects who withdrew. CONCLUSIONS: In this six month
placebo-controlled trial, herbal ephedra/caffeine (90/192
mg/day) promoted body weight and body fat reduction and
improved blood lipids without significant adverse events.
Int J Obes Relat Metab Disord 2002
May;26(5):593-604
Nutrition and dietary supplements.
Quality and number of subjects in blinded controlled
clinical trials about the nutrition and dietary supplements
discussed here is variable. Glucosamine sulfate and
chondroitin sulfate have sufficient controlled trials to
warrant their use in osteoarthritis, having less side effects
than currently used nonsteroidal anti-inflammatory drugs, and
are the only treatment shown to prevent progression of the
disease. Dietary supplements of ephedrine plus caffeine for
weight loss (weight loss being the current first line
recommendation of physicians for osteoporosis) show some
promise, but are not sufficient in number of study subjects.
Phenylpropanolamine is proven successful in weight loss. Both
ephedrine and phenylpropanolamine have resulted in deaths and
hence are worrisome as an over-the-counter dietary supplement.
Other commonly used weight loss supplements like Cola
acuminata, dwarf elder, yohimbine and garcinia camborgia are
either lacking controlled clinical trials, or in the case of
the last two supplements, have clinical trials showing lack of
effectiveness (although garcinia has been successful in trials
as part of a mixture with other substances, it is unclear if
it was a necessary part of the mixture). Safety of these
weight loss supplements is unknown. Chromium as a body
building supplement for athletes appears to have no efficacy.
Creatine may help more in weight lifting than sprinting, but
insufficient study subjects and safety information make more
studies necessary. Carbohydrate loading is used commonly
before endurance competitions, but may be underused as it may
be beneficial for other sport performances. Supplements for
muscle injury or cramps have had too few studies to determine
efficacy. Although proper rehydration with fluids and
electrolytes is necessary, a paucity of actual studies to
maximize prophylactic treatment for exercise induced cramping
still exists. Nutritional supplements for cardiovascular
disorders are generally geared to prevention. The United
States Department of Agriculture has good recommendations to
prevent atherosclerosis; a stricter version by Ornish was
shown to reverse coronary heart disease, and the low meat,
high fruit, and vegetable DASH diet has been found to decrease
hypertension. The epidemiologic studies of
hyperhomocysteinemia are impressive enough to give folic acid
(or vitamin B6 or B12) supplements to those with elevated
homocysteine levels and test patients who have a history of
atherosclerotic disease, but no controlled clinical trials
have been completed. Soluble fiber has several positive
studies in reduction of cholesterol levels and generally is
accepted. The data on vitamin E are the most confusing. This
vitamin was not helpful in cerebrovascular prevention in China
and not helpful at relatively small doses (50 mg) in the
United States or Finland against major coronary events. Levels
of 400 mg appeared to decrease cardiovascular disease in the
United States in studies based on reports by patients and in
one large clinical trial. Vitamin E also was successful in
prevention of restenosis after PTCA in one clinical trial.
Both of these clinical trials need to be repeated in other
developed country populations. Some nutritional and dietary
supplements are justifiably useful at this point in time.
Several meet the criteria of a late Phase 3 FDA clinical trial
(where it would be released for public use), but many dietary
supplements have insufficient numbers of studies. Some deaths
also have occurred with some supplements. If these supplements
were required to undergo clinical trials necessary for a new
drug by the FDA, they would not be released yet to the public.
Several nontoxic supplements appear promising, though need
further study. Because they have essentially no toxicity (such
as folic acid with B12, soluble fiber and vitamin E) and may
have efficacy, some of these supplementations may be useful
now, without randomized clinical trials.
Phys Med Rehabil Clin N Am 1999
Aug;10(3):673-703
Ephedrine, caffeine and aspirin:
safety and efficacy for treatment of human obesity.
The safety and efficacy of a mixture of ephedrine (75 to
150mg), caffeine (150mg) and aspirin (330mg), in divided
premeal doses, were investigated in 24 obese humans (mean BMI
37.0) in a randomized double blind placebo-controlled trial.
Energy intake was not restricted. Overall weight loss over
eight weeks was 2.2kg for ECA vs. 0.7 kg for placebo (p <
0.05). Eight of 13 placebo subjects returned five months later
and received ECA in an unblinded crossover. After eight weeks,
mean weight loss with ECA (ephedrine, caffeine and aspirin)
was 3.2 kg vs 1.3 kg for placebo (p = 0.036). Six subjects
continued on ECA for seven to 26 months. After five months on
ECA, average weight loss in five of these was 5.2 kg compared
to 0.03 kg gained during five months between studies with no
intervention (p = 0.03). The sixth subject lost 66 kg over 13
months by self-imposed caloric restriction. In all studies, no
significant changes in heart rate, blood pressure, blood
glucose, insulin, and cholesterol levels, and no differences
in the frequency of side effects were found. ECA in these
doses is thus well tolerated in otherwise healthy obese
subjects, and supports modest, sustained weight loss even
without prescribed caloric restriction, and may be more
effective in conjunction with restriction of energy
intake.
Int J Obes Relat Metab Disord 1993
Feb;17 Suppl 1:S73-8
Detection and determination of
anabolic steroids in nutritional supplements.
A method is described for the determination of anabolic
steroids including testosterone,
19-nor-4-androstene-3,17-dione, 4-androstene-3,17-dione and
nandrolone in food supplements. Initial clean-up is done by
HPLC followed by determination with GC/MS. A
‘contaminated’ food supplement was analyzed and
appeared to contain 19-nor-4-androstene-3,17-dione and
4-androstene-3,17-dione. One capsule of this nutritional
supplement was ingested by five male volunteers. Urine samples
were collected and analyzed by GC/MS and GC/MS-MS. Neither the
ratio testosterone/epitestosterone, nor the ratio
androstenedione/epitestosterone increased significantly.
Concentrations above 2 ng/ml for norandrosterone, the major
metabolite of nandrolone, were detected until 48-144 h after
ingestion of the food supplement.
J Pharm Biomed Anal 2001
Jul;25(5-6):843-52
Effect of oral androstenedione on
serum testosterone and adaptations to resistance training in
young men: a randomized controlled trial.
CONTEXT: Androstenedione, a precursor to testosterone, is
marketed to increase blood testosterone concentrations as a
natural alternative to anabolic steroid use. However, whether
androstenedione actually increases blood testosterone levels
or produces anabolic androgenic effects is not known.
OBJECTIVES: To determine if short- and long-term oral
androstenedione supplementation in men increases serum
testosterone levels and skeletal muscle fiber size and
strength and to examine its effect on blood lipids and markers
of liver function. DESIGN AND SETTING: Eight-week randomized
controlled trial conducted between February and June 1998.
PARTICIPANTS: Thirty healthy, normotestosterogenic men (aged
19 to 29 years) not taking any nutritional supplements or
androgenic-anabolic steroids or engaged in resistance
training. INTERVENTIONS: Twenty subjects performed eight weeks
of whole-body resistance training. During weeks 1, 2, 4, 5, 7
and 8, the men were randomized to either androstenedione, 300
mg/d (n = 10), or placebo (n = 10). The effect of a single
100-mg androstenedione dose on serum testosterone and estrogen
concentrations was determined in 10 men. MAIN OUTCOME
MEASURES: Changes in serum testosterone and estrogen
concentrations, muscle strength, muscle fiber cross-sectional
area, body composition, blood lipids, and liver transaminase
activities based on assessments before and after short- and
long-term androstenedione administration. RESULTS: Serum free
and total testosterone concentrations were not affected by
short- or long-term androstenedione administration. Serum
estradiol concentration (mean [SEM]) was higher (P<.05) in
the androstenedione group after two (310 [20] pmol/L), five
(300 [30] pmol/L) and eight (280 [20] pmol/L) weeks compared
with presupplementation values (220 [20] pmol/L). The serum
estrone concentration was significantly higher (P<.05)
after two (153 [12] pmol/L) and five (142 [15] pmol/L) weeks
of androstenedione supplementation compared with baseline (106
[11] pmol/L). Knee extension strength increased significantly
(P<.05) and similarly in the placebo (770 [55] N vs 1095
[52] N) and androstenedione (717 [46] N vs 1024 [57] N)
groups. The increase of the mean cross-sectional area of type
2 muscle fibers was also similar in androstenedione (4703
[471] vs 5307 [604] mm2; P<.05) and placebo (5271 [485] vs
5728 [451] mm2; P<.05) groups. The significant (P<.05)
increases in lean body mass and decreases in fat mass were
also not different in the androstenedione and placebo groups.
In the androstenedione group, the serum high-density
lipoprotein cholesterol concentration was reduced after two
weeks (1.09 [0.08] mmol/L [42 (3) mg/dL] vs 0.96 [0.08] mmol/L
[37 (3) mg/dL]; P<.05) and remained low after five and
eight weeks of training and supplementation. CONCLUSIONS:
Androstenedione supplementation does not increase serum
testosterone concentrations or enhance skeletal muscle
adaptations to resistance training in normotestosterogenic
young men and may result in adverse health consequences.
JAMA 1999 Jun 2;281(21):2020-8
Androgen use by athletes: a
reevaluation of the health risks.
It has been estimated that one to three million male and
female athletes in the United States have used androgens.
Androgen use has been associated with liver dysfunction,
altered blood lipids, infertility, musculotendinous injury and
psychological abnormalities. Although androgens have been
available to athletes for more than 50 years, there is little
evidence to show that their use will cause any long-term
detriment. Furthermore, the use of moderate doses of androgens
results in side effects that are largely benign and
reversible. It is our contention that the incidence of serious
health problems associated with the use of androgens by
athletes has been overstated.
Can J Appl Physiol 1996
Dec;21(6):421-40
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