Three Weeks of Creatine Monohydrate Supplementation Affects Dihydrotestosterone to Testosterone Ratio in College-Aged Rugby Players

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DOI: 10.1097/JSM.0b013e3181b8b52f · Source: PubMed
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Abstract
This study investigated resting concentrations of selected androgens after 3 weeks of creatine supplementation in male rugby players. It was hypothesized that the ratio of dihydrotestosterone (DHT, a biologically more active androgen) to testosterone (T) would change with creatine supplementation. Double-blind placebo-controlled crossover study with a 6-week washout period. Rugby Institute in South Africa. College-aged rugby players (n = 20) volunteered for the study, which took place during the competitive season. Subjects loaded with creatine (25 g/day creatine with 25 g/day glucose) or placebo (50 g/day glucose) for 7 days followed by 14 days of maintenance (5 g/day creatine with 25 g/day glucose or 30 g/day glucose placebo). Serum T and DHT were measured and ratio calculated at baseline and after 7 days and 21 days of creatine supplementation (or placebo). Body composition measurements were taken at each time point. After 7 days of creatine loading, or a further 14 days of creatine maintenance dose, serum T levels did not change. However, levels of DHT increased by 56% after 7 days of creatine loading and remained 40% above baseline after 14 days maintenance (P < 0.001). The ratio of DHT:T also increased by 36% after 7 days creatine supplementation and remained elevated by 22% after the maintenance dose (P < 0.01). Creatine supplementation may, in part, act through an increased rate of conversion of T to DHT. Further investigation is warranted as a result of the high frequency of individuals using creatine supplementation and the long-term safety of alterations in circulating androgen composition. STATEMENT OF CLINICAL RELEVANCE: Although creatine is a widely used ergogenic aid, the mechanisms of action are incompletely understood, particularly in relation to dihydrotestosterone, and therefore the long-term clinical safety cannot be guaranteed.
ORIGINAL RESEARCH
Three Weeks of Creatine Monohydrate Supplementation
Affects Dihydrotestosterone to Testosterone Ratio in
College-Aged Rugby Players
Johann van der Merwe, MBChB, Naomi E. Brooks, PhD, and Kathryn H. Myburgh, PhD
Objective: This study investigated resting concentrations of selected
androgens after 3 weeks of creatine supplementation in male rugby
players. It was hypothesized that the ratio of dihydrotestosterone (DHT,
a biologically more active androgen) to testosterone (T) would change
with creatine supplementation.
Design: Double-blind placebo-controlled crossover study with a
6-week washout period.
Setting: Rugby Institute in South Africa.
Participants: College-aged rugby players (n = 20) volunteered for
the study, which took place during the competitive season.
Interventions: Subjects loaded with creatine (25 g/day creatine
with 25 g/day glucose) or placebo (50 g/day glucose) for 7 days
followed by 14 days of maintenance (5 g/day creatine with 25 g/day
glucose or 30 g/day glucose placebo).
Main Outcome Measures: Serum T and DHT were measured and
ratio calculated at baseline and after 7 days and 21 days of creatine
supplementation (or placebo). Body composition measurements were
taken at each time point.
Results: After 7 days of creatine loading, or a further 14 days of
creatine maintenance dose, serum T levels did not change. However,
levels of DHT increased by 56% after 7 days of creatine loading and
remained 40% above baseline after 14 days maintenance (P,0.001).
The ratio of DHT:T also increased by 36% after 7 days creatine
supplementation and remained elevated by 22% after the maintenance
dose (P,0.01).
Conclusions: Creatine supplementation may, in part, act through an
increased rate of conversion of T to DHT. Further investigation is
warranted as a result of the high frequency of individuals using
creatine supplementation and the long-term safety of alterations in
circulating androgen composition.
Statement of Clinical Relevance: Although creatine is a widely
used ergogenic aid, the mechanisms of action are incompletely
understood, particularly in relation to dihydrotestosterone, and
therefore the long-term clinical safety cannot be guaranteed.
Key Words: creatine supplementation, rugby player, athlete, clinical
safety, DHT:T ratio
(Clin J Sport Med 2009;19:399–404)
INTRODUCTION
Creatine supplementation is a popular ergogenic aid. It
has been extensively researched in various athletic popula-
tions
1
and diseased populations.
2
Loading doses of creatine
taken for 5 to 7 days improves some types of exercise
performance
3–5
and, in some studies, also increased muscle
strength despite the short duration of supplementation.
6,7
Creatine supplementation alone or as part of a multicomponent
putative ergogenic aid may increase muscle mass, particularly
if taken for a longer time period and in conjunction with
increased volume of resistance training.
8
However, although
creatine is a popular ergogenic and androgenic aid used by
professional and recreational athletes, the mechanisms un-
derlying the enhancement of performance and muscle building
by creatine supplementation remain to be clearly elucidated. In
addition, very few studies have investigated the clinical safety
of creatine supplementation. Most studies investigating possi-
ble side effects have focused on renal function and hepatic
markers
9
and, although they have not shown any serious side
effects of creatine supplementation, the studies have been of
short duration
10
and long-term safety is not guaranteed.
11
Two main approaches have been followed to investigate
mechanisms by which creatine may influence skeletal muscle.
One involves the investigation of skeletal muscle biopsies
and the other main approach involves investigating possible
effects of creatine supplementation on the humoral endocrine
response to exercise. Testosterone can stimulate muscle
growth by increasing protein synthesis and potentially reusing
amino acids from muscle protein breakdown.
12
Testosterone,
growth hormone, and insulin growth factor-1 have been shown
to increase as an acute effect of resistance exercise,
13
an effect
that was enhanced by 7 days prior ingestion of a supplement
containing creatine (Muscle Fuel: Advocare, Carollton, Texas).
However, a similar study found no enhancement of the
growth hormone response to a 60-minute bout of resistance
training in subjects who had ingested creatine for 5 days, and
the testosterone response to exercise was not significant, with
Submitted for publication February 1, 2009; accepted July 22, 2009.
From the Department of Physiological Sciences, Stellenbosch University,
Stellenbosch, South Africa.
Reprints: Kathryn H. Myburgh, PhD, Department of Physiological Sciences,
Stellenbosch University, Private Bag XI, Matieland 7602, Stellenbosch,
South Africa (e-mail: khm@sun.ac.za).
Copyright Ó2009 by Lippincott Williams & Wilkins
Clin J Sport Med Volume 19, Number 5, September 2009 www.cjsportmed.com |399
or without the creatine supplementation.
14
In extreme,
overreaching training involving resistance training, it has
even been shown that total testosterone levels decrease after 4
weeks despite creatine supplementation.
15
These studies sug-
gest that the possible role for testosterone as a mediator of the
observed effects of creatine on muscle mass is controversial.
Testosterone can be converted into a more bioactive
metabolite, dihydrotestosterone (DHT), by 5-alpha reductase.
The role of 5-alpha-reductase in testosterone conversion is
well known in the literature focusing on alopecia
16
and prostate
hypertrophy,
17
even in young males with male pattern baldness.
8
In addition, biochemical studies of androgen receptor affinity
indicates that DHT is 4 times more biologically potent than T.
19
Therefore, to further explore this as a potential
mechanism for the effect of creatine supplementation on
muscle, we chose to investigate the ratio of DHT:testosterone
in young male athletes participating in team sports requiring
substantial strength (rugby). Previous studies have mainly
focused on the effects of training combined with creatine
supplementation during the strength improvement phase in
American football players.
20
We chose to investigate the rugby
players during the competitive season to minimize the
potential compounding effect of changing training at the
same time as providing the supplement.
The study design was a double-blind, placebo-controlled
crossover study with a 6-week washout period. We measured
serum testosterone (T) and DHT and calculated the ratio after
21 days of creatine supplementation. We hypothesized that we
would observe a change in the ratio of DHT:T.
METHODS
Subjects
Twenty white males (aged 18–19 years) from a Rugby
Institute situated near Stellenbosch University in South Africa
took part in the study. The study was approved by the
Stellenbosch University Ethics Committee and informed
consent was provided by each subject. None of the subjects
had taken any supplements with their normal diet for 6 weeks
before the study. Subjects were randomized into 2 groups for
a double-blind, placebo-controlled crossover study design with
a 6-week washout period (Figure 1). The randomization was
done as follows: when subjects were handed informed consent
forms, they were assigned a number based on arrival. The even
numbers were assigned to one group and the odd numbers the
other group. There were 4 subjects who dropped out, 2 from
each group. Two subjects left town, 1 subject went overseas
and 1 subject broke a leg. The data from the dropout subjects
were not included in the analysis.
Procedures
Subjects underwent a 7-day loading period with creatine
supplementation or placebo followed by a 14-day maintenance
dose (creatine or placebo). Creatine monohydrate was given
with glucose (25 g/day creatine and 25 g/day glucose) for
a loading dose and 5 g/day creatine and 25 g/day glucose for
a maintenance dose. The placebo group received glucose only
(50 g/day glucose) for a loading dose and 30 g/day glucose for
a maintenance dose. To maintain the double-blind status, the
FIGURE 1. Flow chart of double-blind
crossover study design of participa-
tion of subjects in the study is shown.
400 |www.cjsportmed.com q2009 Lippincott Williams & Wilkins
Merwe et al Clin J Sport Med Volume 19, Number 5, September 2009
supplement and placebo were given as capsules. Both groups
received the same number of capsules during the loading and
maintenance doses.
Training and Dietary Intake
Subjects were part of the Rugby Institute and underwent
standardized training, albeit for different player positions,
during the study. All subjects were residents at the Institute and
the same diet was given to all subjects. During part of the
washout period, all subjects had a short winter break and did
only maintenance training. Therefore, at the beginning of the
second phase of the study, subjects were in similar condition as
the start of the study and not fatigued from consecutive weeks
of match play.
Outcome Measures
Anthropometry measurements were taken on Day 0,
Day 7, and Day 21 in each leg of the study. Six skin fold
measurements were taken (triceps, subscapula, suprailiac,
abdominal, thigh, and midcalf). The average of 2 measure-
ments was calculated and the sum of 6 measurements was used
for calculation of body density and percent body fat.
21
Blood samples were taken at Day 0, Day 7, and Day 21
with athletes in the fully rested condition pretraining. Samples
were taken from the antecubital vein (SST; Vacutainer, BD,
South Africa), left to clot, and placed on ice. Serum was
separated by centrifuging at 3000 rpm at 4°C and samples
were stored at –70°C. All samples were taken at the same time
of day (4:00 PM to 5:00 PM). Serum was separated and frozen
within 1 hour of collection. Testosterone and DHT were
measured using DSL Testosterone and Dihydrotestosterone
radio immunoassay kits (DSL 4000 and DSL 9600; Diagnostic
Systems Laboratories, Inc, Webster, Texas). Analysis was
conducted according to the radioimmunoassay kit instructions.
Mean values for T levels were calculated and compared with
standards of known quantity representing 0 to 86.75 nmol/L
and compared against control values. Study values fall within
the expected range of 10.06 to 34.35 nmol/L for young adult
males. DHT analysis first included an extraction procedure
to remove T and therefore preventing crossreactivity and
rendering the kit 100% specific to DHT. Mean values of DHT
were calculated and compared with standards ranging from
0 to 8.6 nmol/L and controls ranging from 0.433 to 2.012
nmol/L. The laboratory upper limit for coefficient of variation
for both assays was less than 5% for individual subjects’
samples analyzed in triplicate.
Statistical Analysis
Subjects were assigned a number to maintain confiden-
tiality of results. Subjects were randomized into 2 groups at
baseline and baseline characteristics were compared using
Student unpaired ttest. Data collected over the 2 legs of the
study were pooled so that each subject served as their own
control and analyzed using repeated measures analysis of
variance. Differences at each time interval were analyzed post
hoc by Tukey test with significance set at P,0.01.
RESULTS
Baseline Characteristics and Anthropometry
Subjects were aged 18.7 60.53 years and their height
was 1.81 60.05 m. Body mass ranged from 74.4 to 107 kg.
There were no significant differences in any measurements at
baseline between the subjects randomized to placebo first
compared with those randomized to creatine first. As a result
of the crossover nature of the study design, each subject had 2
baseline time points. Baseline 1 was before any supplemen-
tation or placebo and baseline 2 after the 6-week washout
period. After washout, subjects had a similar baseline for
percent body fat and fat-free mass. Therefore, data are
presented as creatine or placebo with results pooled regardless
of which supplement was taken first. The pooled baseline data
is called Day 0.
Anthropometry measurements did not differ between the
two groups on Day 0 (Table 1), and neither creatine loading or
placebo affected body mass, percentage body fat, or fat-free
mass after 7 days or after 21 days.
Blood Measurements
Testosterone levels did not change significantly over
time in either group (P= 0.19; Table 2). With creatine, no
statistically significant increases in T concentrations were seen
after 7 days or after 21 days, but there was more variation in the
means over time (Table 2). Dihydrotestosterone did not change
with placebo; however, in the creatine group, there were sig-
nificant increases in DHT concentrations over time resulting in
a time 3group interaction (time 3group P,0.00001). After
7 days of loading, the increase in DHT was 56%, and after 14
more days on the maintenance dose, the elevation was still
40% above baseline.
After calculating the ratio of DHT to T, it was found that
there was a significantly higher ratio in the creatine group
(group 3time P,0.00001). This change in ratio amounted to
a 36% increase in conversion of T to DHT after 7 days of
TABLE 1. Body Composition Before Supplementation
(Day 0), After Loading (Day 7), and After Maintenance
Doses (Day 21) of Creatine with Carbohydrate or
Placebo with Carbohydrate
Day 0 Day 7 Day 21
Body mass, kg
Placebo 86.80 69.90 87.30 610.1 87.26 69.96
Creatine 87.04 610.66 87.80 610.88 87.80 610.82
Sum of 6 skin
folds, mm
Placebo 274 658 274 655 272 656
Creatine 272 654 269 649 269 643
Percent body fat
Placebo 13.53 63.95 13.54 63.94 13.47 63.97
Creatine 13.43 63.92 13.36 64.02 13.30 63.95
Fat-free mass, kg
Placebo 75.0 65.7 75.0 65.8 75.0 65.8
Creatine 75.0 66.7 75.8 66.8 75.8 66.5
Values are mean 6standard deviation; n = 20 subjects completing each of the arms
of the crossover design.
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Clin J Sport Med Volume 19, Number 5, September 2009 Creatine Supplementation and DHT:T Ratio in Male Rugby Players
creatine supplementation (post hoc test: P,0.001). The
conversion was still elevated by 22% at 21 days after 14 days
on maintenance (post hoc test: P,0.01).
DISCUSSION
Important features of this study were that all athletes
were in peak competitive condition at baseline and were
involved in the same training and competition structures.
Similar to Ziegenfuss et al,
22
the current study had a relatively
long washout period of 6 weeks as opposed to more commonly
used 4-week washout.
23–25
The main finding that is discussed
subsequently is that this is the first study to report an increase
in the DHT to T ratio in response to creatine loading, a
response that was also maintained during the maintenance
phase for at least another 2 weeks in young trained athletes. In
addition, this study used creatine monohydrate with carbohy-
drate as opposed to a multicomponent supplement so that all
findings can be attributed to creatine only.
Several other studies have investigated the possibility
that changes in androgens may underlie the positive effects of
creatine supplementation on muscle mass with creatine taken
alone or with other components. These studies investigated
mainly the growth hormone and insulin-like growth factor-1
axis or testosterone and sex hormone-binding globulin, or all,
but not DHT.
13,15
In 2 studies, increased growth hormone
and T responses were seen immediately after exercise in
supplemented subjects, who were supplemented with creatine
combined with branch-chain amino acids, taurine, caffeine,
and glucouronolactone.
26,27
In the first study, the supple-
mented subjects completed a loading dose phase. Although
subjects taking placebo also experienced a postexercise
increase in growth hormone, this increase was significantly
greater in the supplemented group than the control group.
29
In
the second study, the same research group found increases in
T and growth hormone after exercise in both groups when
supplementation was acute.
27
In these studies, the duration of
supplementation was 1 week
26
or 1 dose,
27
which raises the
question of whether or not a longer exposure would have
resulted in different results. Indeed, increased levels of T were
found in resting blood samples after 10 weeks of resistance
training with creatine supplementation compared with placebo
and with creatine and beta-alanine supplementation.
28
Similar
to Op’t Eijnde and Hespel, we did not find an effect of sup-
plementation with only creatine on resting testosterone levels
in trained subjects
14
despite the loading phase of 7 days and
a maintenance phase of another 14 days. Also, no changes in
plasma T were found after 6 weeks of supplementation with
beta-hydroxy beta-methylbutarate or the combination of crea-
tine and hydroxy beta-methylbutarate.
29
Therefore, our results
agree with these studies as well as Kraemer et al.
13
However,
the latter study did find a greater T response to a resistance
exercise training bout after a multicomponent supplement
containing 3 g creatine.
On the other hand, Volek et al
15
even found declines in
resting T despite creatine supplementation in subjects who
were becoming overreached. The players in our study did not
become overreached despite the long duration of the study and
competitive season, because there was a 2-week midseason
break, which coincided with the first 2 weeks of washout. Both
of these studies used creatine monohydrate as a single putative
ergogenic substance. In our study, creatine was taken in con-
junction with carbohydrate to enhance muscle uptake of
creatine but was not taken in combination with any other
putative anabolic supplements such as those that may be
hypothesized to work synergistically.
With no effect on resting T levels, the effect of creatine
supplementation on DHT becomes an even more important
finding. This effect was a large increase in DHT rather than
a marginal (possibly physiologically insignificant) effect.
As mentioned earlier, 5-alpha-reductase converts tes-
tosterone to DHT. There is low
30
or no
31
5-alpha-reductase in
muscle or bone suggesting that any potential effect on muscle
is mediated by conversion at other sites. Comparing the
androgen receptor physiology of T and DHT, studies have
indicated that DHT has higher affinity as well as longer recep-
tor occupancy than T, rendering it a more potent androgen.
19,32
In the face of T deficiency, DHT alone or DHTand T have been
used to prevent muscle weakness and atrophy.
33
However,
mechanistic studies do not clearly indicate its effect on muscle
tissue; DHT treatment in orchidectomized rats did not activate
the Akt anabolic signaling pathway involved in muscle
hypertrophy.
34
Nevertheless, in tissue culture addition of DHT
to the culture media, stimulate C2C12 cells (a satellite cell
line), proliferated
35
and promoted the commitment of a
pluripotent cell line to myogenic differentiation.
36
The second major finding of the current study was
a higher DHT:T ratio after 7 days of creatine loading, which
was maintained with another 2 weeks of maintenance dose.
Clinically, an increased ratio of DHT:T has been linked to
higher male pattern baldness.
16
Therefore, it is important to
also investigate the effects of this ratio on target tissues.
Litman et al
37
found racial/ethnical differences in the
ratio of DHT:T. They purported that prostate cancer, body
composition, and bone mass differences between the ethnic/
racial groups may be explained by differences in this ratio. In
this context, it is also pertinent to discuss the physiology of
TABLE 2. Testosterone, Dihydrotestosterone, and
Dihydrotestosterone to Testosterone Ratio Before, After
Loading, and After Maintenance Doses of Creatine with
Carbohydrate or Placebo with Carbohydrate
Day 0 Day 7 Day 21
Testosterone
(T; nmol/L)
Placebo 17.09 63.42 17.02 64.11 17.04 65.25
Creatine 14.44 62.95 16.08 62.86 16.69 64.61
Dihydrotestosterone
(DHT; nmol/L)
Placebo 1.26 60.52 1.09 60.40 1.06 60.43
Creatine 0.98 60.37 1.53 60.50* 1.38 60.45*
DHT:T ratio
Placebo 0.074 60.027 0.066 60.022 0.064 60.023
Creatine 0.069 60.023 0.096 60.031* 0.086 60.032
Values are mean 6standard deviation; n = 20 subjects completing each of the arms
of the crossover design.
*P,0.001.
P,0.01.
402 |www.cjsportmed.com q2009 Lippincott Williams & Wilkins
Merwe et al Clin J Sport Med Volume 19, Number 5, September 2009
DHT and DHT:T ratio without reference to possible ergogenic
mechanisms, but rather focusing on clinical safety. Previous
studies addressing safety issues indicated that creatine
supplementation does not seem to have short-term negative
effects on renal or hepatic function.
9
Nonetheless, more
comprehensive studies of long-term safety are still required.
11
The prostate is the best known tissue that is highly responsive
to androgens, including DHT.
33
DHT may be associated with
benign prostate hypertrophy,
39
but the association with
prostate cancer remains controversial.
40,41
Given this discussion, it would seem that DHT or the
DHT:T ratio may well be possible mechanisms for positive
effects of creatine on muscle mass. The increase in DHT and
DHT:T ratio after 7 days of creatine loading was not seen at
Day 21. There may be a dose–response to the amount of
creatine ingested and the maintenance dose may not be high
enough to maintain the increased ratio. However, in the current
study, we did not see changes in body mass or percent body
fat. Our study recruited rugby players during their competitive
season, after their initial preseason strength orientated training
was completed. On the one hand, this enabled us to determine
the effects of creatine supplementation on already trained
individuals without major additional training changes.
However, this may explain why body composition did not
change. One could speculate that a supplementation period of
longer than 21 days may have altered body composition even
in these subjects whose training did not change appreciably
during the course of the study.
In conclusion, creatine supplementation may act, at least
in part, through the increased rate of conversion of T to DHT.
Because of the potential clinical relevance of the endocrine
results of this study and the high frequency of individuals
using creatine supplementation without monitoring, further
investigation is warranted. Clearly, future studies on the
putative anabolic effects of creatine supplementation should be
more comprehensive in terms of potential humoral and
intramuscular effects.
ACKNOWLEDGMENTS
We thank the rugby players for their cooperation
throughout the duration of the study. We also thank the staff
involved with the rugby players and the Institute for
accommodating the study. Thanks to Mrs. Gail Nell (Chemical
Pathology, Grootte Schuur Hospital), Anneke Le Roux
(Biokineticist, private practice), and Jacolene Kroff, PhD
(Sport Science, Stellenbosch University) for technical support.
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  • ... O uso de recursos ergogênicos pelos atletas tem sido bastante utilizado para melhorar o desempenho. Nos últimos 10 anos, suplementação no rugby tem sido investigada em estudos com a creatina (2)(3)(4) , creatina associada com β-hidroxi-βmetilburato (HMB) (5)(6)(7) , álcool (8) , β-alanina (9) , bicarbonato de sódio (10) ; cafeína (11)(12)(13) , cafeína associada a carnitina (14) e cafeína associada ao carboidrato (15) . ...
    ... Na tentativa de elucidar mecanismos envolvidos nas melhoras do desempenho (resistência de força e potência) e da composição corporal (aumento na massa corporal e massa corporal magra), Van Der Merwe et al. (4) observaram incremento de 56% na concentração de diidrotestosterona e 36% na razão diidrotestosterona: testosterona após carga de creatina (25 g/dia + 25 g/dia de glicose por sete dias) e 22% após 14 dias de manutenção (5 g/dia + 25 g/dia de glicose). ...
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    Ergogênicos nutricionais e desempenho no rugby: revisão sistemática Nutritional ergogenics aids and rugby performance: systematic review R e s u m o _______________________________________________________________________________________ Objetivo: Apresentar ergogênicos nutricionais investigados cientificamente envolvendo jogadores de rugby e suas respostas no desempenho em treinos e jogos. Métodos: Foi conduzida revisão sistemática na base PubMed em Janeiro de 2013, utilizando-se as palavras-chave no campo resumo: rugby, suplementation, carbohydrate, protein, amino acid e caffeine de forma isolada e/ou combinada. Para análise, foram considerados estudos originais publicados nos últimos 10 anos. Resultados: Na busca inicial foram encontrados 53 artigos. Após leitura dos títulos e resumos foram excluídos 35 artigos. Cafeína e creatina foram os suplementos mais testados e representam 50% dos artigos analisados com jogadores de rugby. Outros suplementos como β-alanina, bicarbonato, carboidrato, HMB e Tribulus terrestris também foram testados e representam os outros 50% dos trabalhos analisados. Apenas cafeína e creatina apresentaram respostas positivas em medidas de desempenho. Conclusão: Cafeína e creatina podem adicionar respostas ao desempenho de jogadores de rugby submetidos a cargas intensas de trabalho. Por outro lado, consumo de álcool apresentou efeito ergolítico. P a l a v r as-c h a v e : Rugby. Suplementação. Desempenho. A b s t r a c t _______________________________________________________________________________________ Objective: To present nutritional ergogenic aids investigated by scientific research involving rugby players and their performance in trainings and matches. Methods: A systematic review was carried out through Pubmed database in January 2013 with the following keywords: rugby, supplementation, carbohydrate, protein, amino acid and caffeine isolated and/or combined. In the analyses, only original studies published in the last 10 years were considered. Results: Fifty-three articles were found in the initial search. After screening the title and abstract, 35 papers were excluded. Caffeine and creatine were the most tested supplements and they represented 50% of the papers analyzed. Others supplements, like β-alanine, bicarbonate, carbohydrate, HMB and Tribulus terrestris also were experimented and comprised the others 50% of the analyzed works. Only caffeine and creatine showed positive effects on performance measurements. Conclusion: Both caffeine and creatine can improve performance in rugby players under severe word load. On the other hand, alcohol consumption has ergolytic effect. K e y w o r d s : Rugby. Supplementation. Performance.
  • ... As long as formation of DHT is minimal or non-existent (Pathways 1, 3) then blocking IGFBP-3 formation or even blocking its ability to bind IGF-1 (Pathway 2) would allow for the possibility of cellular IGF-1 to produce growth uninhibited in the cytokines [36,[41][42][43]. ...
    ... A study showed that after 7 days (1 week) of creatine loading, or a further 2 weeks of creatine maintenance dose, there was no change in serum T levels. However, DHT levels increased by 56% after a week of creatine loading and remained 40% above baseline after two weeks of maintenance [42]. The effect of IGF-I was about 100x that of androgen [48]. ...
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    Today’s society recognizes how supplementation affects the body physiologically; conversely society does not understand the hidden side effects supplementation has on hair. This paper investigates and explains how hair loss is affected by various supplements. This paper was written in order to provide current and future hair loss professionals with an understanding of the numerous biochemical pathways that cause hair loss, and a method to evaluate, educate, and correct patients, resulting in hair loss prevention, growth, and/or faster regrowth. Supplements previously studied were included in this paper and explored further with relativity to the hair. These supplements include: anabolic steroids, creatine, growth hormone, androstenedione/similar pro-hormones, whey protein isolate(WPI), arginine, orthinine, DHEA (dehydroepiandrosterone), HCG (human chorionic gonadotropin), carnivores vs. vegetarians, soy, iodine, egg whites, and caffeine. In finding, particular supplements have a negative effect on hair loss (as illuminated through various metabolic pathways presented in this research). Specifically, whey protein isolate, growth hormones (GH), and anabolic precursors result in the highest amount of hair loss. Review of the patient’s supplements allows the medical practitioner to develop a plan towards hair loss prevention.
  • ... Because of the intermetabolic involvement of methionine and homocysteine, methyl donor balance is also affected. Morover creatine action through the increase rate of testosterone to the biologically active metabolite dihydrotestosterone is also arised [58]. Normal human doses are around 3 g/day, supraphysiological doses start from 5g/d, therapeutic dose in order to maintain muscle levels is 0.029 g/kgBW [59]. ...
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  • ... Further, another study reported that 50 or 100 mg/kg of Cr may help to alleviate decrements in skill performance in situations of sleep deprivation, such as trans-meridian travel [26]. Although Cr is a widely used ergogenic aid, it is recommended to keep in mind that the mechanisms of action after competition are not completely understood [27]. Level of Evidence: Low Timing: before training/competition ...
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    In the sport of rugby, athletes need a multitude of sport-specific skills along with endurance, power, and speed in order to optimize performance. Further, it is not unusual for athletes to play several competitive matches with insufficient recovery time. Rugby requires repeated bouts of high-intensity actions intermixed with brief periods of low to moderate active recovery or passive rest. Specifically, a match is characterized by repeated explosive activities, such as: jumps, shuffles, and rapid changes of direction. To facilitate adequate recovery, it is necessary to understand the type of fatigue induced and, if possible, its underlying mechanisms. Common approaches to recovery may include nutritional strategies as well as active (active recovery) and passive recovery (water immersions, stretching, and massage) methods. However, limited research exists to support the effectiveness of each strategy as it related to recovery from the sport of rugby. Therefore, the main aim of the current brief review is to present the relevant literature that pertains to recovery strategies in rugby.
  • ... With the depletion of PCr stores during intense exercise, the availability of energy decreases due to the impossibility of resynthesizing ATP; consequently, the ability to maintain a constant level of effort is reduced and this explains the use of creatine as a supplement. Research has shown that creatine monohydrate generates a significant increase in dihydrotestosterone (56-40%) during training periods 25 . Other studies have stressed the role of the amino acid arginine in directly affecting DHT without increasing testosterone levels, probably by increasing the activity of 5-alpha reductase. ...
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    OBJECTIVE: Androgenetic alopecia is the most common type of hair loss, affecting women (50% of menopausal women and a large number of women of childbearing age) as well as males (over 70% of adult men). Since the condition is of an evolutionary nature, it is important to intervene early in order to prevent the progression of the clinical picture. It is equally important to identify all the factors that may hinder the effectiveness of the therapy. MATERIALS AND METHODS: A literature search was conducted using, as electronic bibliographic database, Medline and the Cochrane library from 1995 until present. RESULTS: Patients who make use of certain supplements can be less responsive to medical treatments. CONCLUSIONS: The therapeutic approach to the patient with androgenetic alopecia should be global as the effectiveness of valid therapies may be affected by the patient overlooking the information received from the specialist.
  • ... The dietary supplements mainly tested in the 98 papers were: Creatine involved in 25.5% of the studies [17][18][19][23][24][25][26][27][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45]; Amino acids in 23.5% [15,20,22,28,40,[46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63] and Carbohydrates in 13.2% [20][21][22]29,38,[64][65][66][67][68][69][70][71]. ...
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  • ... As we used saliva measures we cannot rule out some local oral cavity artefact effect of creatine. Free testosterone levels have, however, been linked to intra-individual variance in short timeframe muscular power [35], and long-term creatine supplementation has been reported as influencing testosterone metabolite pathways [36], so the observation is perhaps worthy of some follow-up. ...
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    We investigated the effects of sleep deprivation with or without acute supplementation of caffeine or creatine on the execution of a repeated rugby passing skill. Ten elite rugby players completed 10 trials on a simple rugby passing skill test (20 repeats per trial), following a period of familiarisation. The players had between 7-9 h sleep on 5 of these trials and between 3-5 h sleep (deprivation) on the other 5. At a time of 1.5 h before each trial, they undertook administration of either: placebo tablets, 50 or 100 mg/kg creatine, 1 or 5 mg/kg caffeine. Saliva was collected before each trial and assayed for salivary free cortisol and testosterone. Sleep deprivation with placebo application resulted in a significant fall in skill performance accuracy on both the dominant and non-dominant passing sides (p < 0.001). No fall in skill performance was seen with caffeine doses of 1 or 5 mg/kg, and the two doses were not significantly different in effect. Similarly, no deficit was seen with creatine administration at 50 or 100 mg/kg and the performance effects were not significantly different. Salivary testosterone was not affected by sleep deprivation, but trended higher with the 100 mg/kg creatine dose, compared to the placebo treatment (p = 0.067). Salivary cortisol was elevated (p = 0.001) with the 5 mg/kg dose of caffeine (vs. placebo). Acute sleep deprivation affects performance of a simple repeat skill in elite athletes and this was ameliorated by a single dose of either caffeine or creatine. Acute creatine use may help to alleviate decrements in skill performance in situations of sleep deprivation, such as transmeridian travel, and caffeine at low doses appears as efficacious as higher doses, at alleviating sleep deprivation deficits in athletes with a history of low caffeine use. Both options are without the side effects of higher dose caffeine use.
  • ... One of the studies monitored effect of a 3-week diet enhanced with creatine in rugby players versus placebo. Creatine increased DHT levels but T level remained unchanged (Van der Merwe et al. 2009). Above mentioned studies show, that some food stimuli, stress or physical activity may change androgen levels and ratios which explain geographical differences among the androgens. ...
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    Dihydrotestosterone (DHT) originates via irreversible reduction of testosterone by catalytic activity of 5alpha-reductase enzyme and it is demonstratively the most effective androgen. Androgens influence adipose tissue in men either directly by stimulation of the androgen receptor or indirectly, after aromatization, by acting at the estrogen receptor. DHT as a non-aromatizable androgen could be responsible for a male type fat distribution. The theory of non-aromatizable androgens as a potential cause of a male type obesity development has been studied intensively. However, physiological levels of DHT inhibit growth of mature adipocytes. In animal models, substitution of DHT in males after gonadectomy has a positive effect on body composition as a testosterone therapy. Thus, DHT within physiological range positively influences body composition. However, there are pathological conditions with an abundance of DHT, e.g. androgenic alopecia and benign prostatic hyperplasia. These diseases are considered as risk factors for development of metabolic syndrome or atherosclerosis. In obese people, DHT metabolism in adipose tissue is altered. Local abundance of non-aromatizable androgen has a negative effect on adipose tissue and it could be involved in pathogenesis of metabolic and cardiovascular diseases. Increased DHT levels, compared to physiological levels, have negative effect on development of cardiovascular diseases. Difference between the effect of physiological and increased level brings about certain paradox.
  • Chapter
    Today’s society recognizes how supplementation affects the body physiologically; conversely, society does not understand the hidden side effects supplementation has on hair. This scientific paper investigates and explains how hair loss is affected by various supplements. This paper was written in order to provide current and future hair loss professionals with an understanding of the numerous biochemical pathways that cause hair loss and a method to evaluate, educate, and correct patients, resulting in hair loss prevention, growth, and/or faster regrowth. Supplements previously studied were included in this paper and explored further with relativity to the hair. These supplements include anabolic steroids, creatine, growth hormone, androstenedione/similar prohormones, whey protein isolate, arginine, ornithine, DHEA (dehydroepiandrosterone), HCG (human chorionic gonadotropin), carnivores versus vegetarians, soy, iodine, egg whites, and caffeine. In finding, particular supplements have a negative effect on hair loss (as illuminated through various metabolic pathways presented in this research). Specifically, whey protein isolate, growth hormones, and anabolic precursors result in the highest amount of hair loss. Supplemental hormonal modulation of hair regrowth (HMH) is the next step in hair loss prevention.
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    This review is focused on creatine (CR) (methyl guanidine acetic acid) and its application in the form of a dietary supplement. It has been especially utilized by athletes, but its pronounced therapeutic potential is also discussed in the present article. It is supposed that human body uses CR for the formation of creatine phosphate (PCr), which is necessary for muscular work as a source of energy. The effects of supplemented CR on dynamics of methionine cycle and other related metabolic pathways have not been fully explained yet. The review is focused on the description of affects caused by its application on human body and metabolism. Already the application of small amounts of CR rapidly increases levels of thiodiglycolic acid (TDGA) in urine after its supplementation, which phenomenon can serve as a sensitive marker of disturbance in metabolic pathways of 2C units and of thiolic compounds. Strong differences between initial and terminal TDGA levels in urine indicate that CR disturbed the equilibria of redox processes, catalyzed by folates and vitamin B12. Some theories for explanation of these effects are described in this manuscript. Nevertheless, similarly as in other metabolic studies, the results are significantly affected by the probands' individual responses, which reflect their individual genetic makeup. The various methods such as voltammetric (generally electrochemical), chromatographic, mass spectrometric, enzymatic etc., which have been most frequently utilized for determination of discussed compounds in common laboratories, have been reported.
  • Article
    Purpose: The purpose of this study was to examine the effect of creatine supplementation in conjunction with resistance training on physiological adaptations including muscle fiber hypertrophy and muscle creatine accumulation. Methods: Nineteen healthy resistance-trained men were matched and then randomly assigned in a double-blind fashion to either a creatine (N = 10) or placebo (N = 9) group. Periodized heavy resistance training was performed for 12 wk. Creatine or placebo capsules were consumed (25 g x d(-1)) for 1 wk followed by a maintenance dose (5 g x d(-1)) for the remainder of the training. Results: After 12 wk, significant (P < or = 0.05) increases in body mass and fat-free mass were greater in creatine (6.3% and 6.3%, respectively) than placebo (3.6% and 3.1%, respectively) subjects. After 12 wk, increases in bench press and squat were greater in creatine (24% and 32%, respectively) than placebo (16% and 24%, respectively) subjects. Compared with placebo subjects, creatine subjects demonstrated significantly greater increases in Type I (35% vs 11%), IIA (36% vs 15%), and IIAB (35% vs 6%) muscle fiber cross-sectional areas. Muscle total creatine concentrations were unchanged in placebo subjects. Muscle creatine was significantly elevated after 1 wk in creatine subjects (22%), and values remained significantly greater than placebo subjects after 12 wk. Average volume lifted in the bench press during training was significantly greater in creatine subjects during weeks 5-8. No negative side effects to the supplementation were reported. Conclusion: Creatine supplementation enhanced fat-free mass, physical performance, and muscle morphology in response to heavy resistance training, presumably mediated via higher quality training sessions.
  • Article
    Epidemiological studies strongly support the contention that surgical castration prior to age forty prevents both benign prostatic hypertrophy (BHP) and prostate cancer. 5α-Reductase deficiency in humans, an experiment of nature, is an uncommon genetically transmitted disorder in which prostate size remains very small throughout adult life. A 5α-reductase inhibitor, finasteride, has recently been shown in double-blind, placebo-controlled trails in patients with BPH to statistically decrease prostate size and improve clinical symptoms in comparison to placebo controls. In the untreated BPH prostate, tissue levels of dihydrotestosterone (DHT) and testosterone (T) averaged 4.2 and 0.2 ng/g, respectively. Following one week of finasteride therapy, T levels rose to a mean of 1.32 ng/g while DHT levels decreased to 0.62 ng/g. These values contrast with values in prostate tissue form surgical castrates in which DHT and T values average 1.14 ng/g and 0.1 ng/g, respectively. If we use the relative binding affinity of T and DHT to the androgen receptor as a criterion of biological androgen potency, T would appear to be one-fourth as potent as DHT. Using this 1:4 ratio to convert prostatic T to a biologically equivalent amount of prostatic DHT, the total biologically active DHT equivalent in the prostate following one week of finasteride averages 0.95 ng/g compared to a mean of 1.14 ng/g in surgical castrates. If the acute effects of finasteride on tissue T and DHT persist during chronic therapy, prostatic hormone concentrations could be said to closely resemble those found following surgical castration; such changes might prevent the occurrence of prostate cancer, similar to the effects noted after surgical castration in younger males. © 1992 Wiley-Liss, Inc.
  • Article
    Testosterone (T), 5α-androstan-17β-ol-3-one (dihydrotestosterone, DHT) and 5α-androstane-3α,17β-diol (3α-diol) were measured by radioimmunoassay (RIA) in the tissue homogenates, cytosols and nuclear fractions of the prostate (PR), bulbocavernosus/levator ani muscle (BCLA), skeletal muscle (musculus quadriceps femoris, SM) and heart muscle (HM) of adult male rats. The main results were: (a) In all three of the PR preparations the main metabolite found was DHT. T could not be detected in the cytosol and 3α-diol was absent in the nuclei, (b) The muscles contained predominantly T. Besides the homogenates DHT was found only in the nuclear fractions. 3α-diol could only be detected in the homogenates and HM-cytosol but not in the nuclei, (c) Comparing the various organs, a clear ranking, PR > BCLA > SM > HM, was found for DHT in the homogenates and similarly but less pronounced in the nuclear fractions, whereas T was generally higher in the muscle homogenates, cytosols and nuclear fractions than in the PR.These data are discussed with respect to the present knowledge of specific androgen accumulation and metabolism in the different organs.
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    The literature on creatine supplementation supporting its efficacy has grown rapidly and has included studies in both healthy volunteers and patient populations. However, the first rule in the development of therapeutic agents is safety. Creatine is well-tolerated in most individuals in short-term studies. However, isolated reports suggest creatine may be associated with various side effects affecting several organ systems including skeletal muscle, the kidney and the gastrointestinal tract. The majority of clinical studies fail to find an increased incidence of side effects with creatine supplementation. To date, studies have not found clinically significant deviations from normal values in renal, hepatic, cardiac or muscle function. Few data are available on the long-term consequences of creatine supplementation.
  • Article
    Many of the neuromuscular (e.g., muscular dystrophy) and neurometabolic (e.g., mitochondrial cytopathies) disorders share similar final common pathways of cellular dysfunction that may be favorably influenced by creatine monohydrate (CrM) supplementation. Studies using the mdx model of Duchenne muscular dystrophy have found evidence of enhanced mitochondrial function, reduced intra-cellular calcium and improved performance with CrM supplementation. Clinical trials in patients with Duchenne and Becker's muscular dystrophy have shown improved function, fat-free mass, and some evidence of improved bone health with CrM supplementation. In contrast, the improvements in function in myotonic dystrophy and inherited neuropathies (e.g., Charcot-Marie-Tooth) have not been significant. Some studies in patients with mitochondrial cytopathies have shown improved muscle endurance and body composition, yet other studies did not find significant improvements in patients with mitochondrial cytopathy. Lower-dose CrM supplementation in patients with McArdle's disease (myophosphorylase deficiency) improved exercise capacity, yet higher doses actually showed some indication of worsened function. Based upon known cellular pathologies, there are potential benefits from CrM supplementation in patients with steroid myopathy, inflammatory myopathy, myoadenylate deaminase deficiency, and fatty acid oxidation defects. Larger randomized control trials (RCT) using homogeneous patient groups and objective and clinically relevant outcome variables are needed to determine whether creatine supplementation will be of therapeutic benefit to patients with neuromuscular or neurometabolic disorders. Given the relatively low prevalence of some of the neuromuscular and neurometabolic disorders, it will be necessary to use surrogate markers of potential clinical efficacy including markers of oxidative stress, cellular energy charge, and gene expression patterns.
  • Article
    The aim of the present study was to examine the effect of creatine supplementation (CrS) on sprint exercise performance and skeletal muscle anaerobic metabolism during and after sprint exercise. Eight active, untrained men performed a 20-s maximal sprint on an air-braked cycle ergometer after 5 days of CrS [30 g creatine (Cr) + 30 g dextrose per day] or placebo (30 g dextrose per day). The trials were separated by 4 wk, and a double-blind crossover design was used. Muscle and blood samples were obtained at rest, immediately after exercise, and after 2 min of passive recovery. CrS increased the muscle total Cr content (9.5 +/- 2.0%, P < 0.05, mean +/- SE); however, 20-s sprint performance was not improved by CrS. Similarly, the magnitude of the degradation or accumulation of muscle (e.g., adenine nucleotides, phosphocreatine, inosine 5'-monophosphate, lactate, and glycogen) and plasma metabolites (e.g. , lactate, hypoxanthine, and ammonia/ammonium) were also unaffected by CrS during exercise or recovery. These data demonstrated that CrS increased muscle total Cr content, but the increase did not induce an improved sprint exercise performance or alterations in anaerobic muscle metabolism.
  • Article
    We analysed the effect of physiological doses of androgens following orchidectomy on skeletal muscle and bone of male rats, as well as the relationships between muscle performance, hypertrophy and the Akt/mammalian target of rapamycin (mTOR) signalling pathway involved in the control of anabolic and catabolic muscle metabolism. We studied the soleus muscle and tibia from intact rats (SHAM), orchidectomized rats treated for 3 months with vehicle (ORX), nandrolone decanoate (NAN) or dihydrotestosterone (DHT). Orchidectomy had very little effect on the soleus muscle. However, maximal force production by soleus muscle (+69%) and fatigue resistance (+35%) in NAN rats were both increased when compared with ORX rats. In contrast, DHT treatment did not improve muscle function. The relative number of muscle fibres expressing slow myosin heavy chain and citrate synthase activity were not different in NAN and ORX rats. Moreover, NAN and DHT treatments did not modify muscle weights and cross-sectional area of muscle fibres. Furthermore, phosphorylation levels of downstream targets of the Akt/mTOR signalling pathway, Akt, ribosomal protein S6 and eukaryotic initiation factor 4E-binding protein 1 were similar in muscles of NAN, DHT and ORX rats. In addition, trabecular tibia from NAN and DHT rats displayed higher bone mineral density and bone volume when compared with ORX rats. Only in NAN rats was this associated with increased bone resistance to fracture. Physiological doses of androgens are beneficial to muscle performance in orchidectomized rats without relationship to muscle and fibre hypertrophy and activation of the Akt/mTOR signalling pathway. Taken together our data clearly indicate that the activity of androgens on muscle and bone could participate in the global improvement of musculoskeletal status in the context of androgen deprivation induced by ageing.
  • Article
    To study the effects of 8-week creatine monohydrate (CrM) supplementation on blood and urinary clinical health markers in football players. 14 football players were randomly assigned in a double-blinded fashion to Cre (n = 7) or Pla (n = 7) group. The Cre group ingested 15 g/day of CrM for 7 days and 3 g/day for the remaining 49 days, whereas the Pla group ingested maltodextrin following the same protocol. Football-specific training was performed during the study. Total body mass was determined and blood and urine samples were analysed for metabolic, hepatic, renal and muscular function markers, before and after supplementation. A gain of total body mass was observed after CrM intake, but not with placebo. Blood and urinary markers remained within normal reference values. There were no significant changes in renal and hepatic markers after CrM intake. However, total creatine kinase (CK) activity significantly increased, and uric acid level tended to decrease after CrM use. Likewise, serum glucose decreased in the Cre group following supplementation. No significant differences in urine parameters were found in either group after supplementation. 8 weeks of CrM supplementation had no negative effects on blood and urinary clinical health markers in football players. Properties of CrM may, however, be associated with an increase in CK activity, improving the efficiency for ATP resynthesis, a phenomenon indirectly confirmed by the decreasing tendency in uric acid concentration. Furthermore, CrM seems to slightly influence glucoregulation in trained subjects.