Discussion
The results of the current meta-analysis, performed on 25 treatment
arms, showed advantageous effects of creatine consumption in reduction
of CK and LDH concentration after different follow-ups after exercise.
Muscle Damage is a phenomenon that may happen because of several
reasons, like cell necrosis or rupture, including about 10 to 55 percent
of total muscular injuries (43). The
muscle damage can be determined as the plasma membrane disruption,
accompanied by the muscle proteins loss (i.e. CK, LDH and myoglobin),
increased inflammatory cells crowd in the muscle fibers (i.e.
neutrophils and macrophages), influx of serum proteins, DOMS, functional
impairment (week performance and loss of strength), and some structural
disorders like sarcomere Z lines disarrangement
(7, 44).
The present meta analysis evaluated indirect muscle damage indices,
including CK and LDH among trained and untrained both sexes individuals,
looking at reported articles. Proteins like CK and LDH have been
extensively applied as markers of muscle micro-damages
(45) and usually has been evaluated to be
an indirect biomarkers of post exercise muscle damage due to their
easiness of identification and the relatively low cost of tests to
quantify it (46,
47). In spite of CK and LDH rising post
exercise being much variable and affected by exercise variable and
individual factors, the assessment of CK and LDH pre- and post-exercise
may provide a diagnostic tool for the detection of post-exercise muscle
damage, with much less invasiveness than needed in a muscle biopsy
(48).
Wide assays has assessed the creatine consumption effects on performance
in exercise (12). However, a few surveys
have assessed the effect of creatine consumption on muscle recovery post
exercise damage (49,
50). Willoughby and Rosene
(51) have indicated that by ongoing
creatine consumption post exercise, creatine may operate as a gene
transcription co-regulator of amino acid pools, therefore increasing
synthesis of myofibrillar protein during recovery after exersice
(52).
Almost 95 percent of creatine is accumulated in skeletal muscles while
the remained 5 percent is stored the brain, testes and heart
(53, 54).
Of this, about 60 percent of creatine is accumulated as phosphocreatine
with the remaining creatine containing the free creatine pool
(55). Creatine consumption (e.g. 20 g/day
for 5 days) has been reported to enhance phosphocreatine and muscle free
creatine usually by 15 to 40 percent
(56). It is indicated that creatine, can
bind to the plasma membrane due to amphipathic nature, therewith
increasing membrane stability and decrease CK and LDH loss
(57).
In the current meta-analysis the positive effects of creatine could
cause decrease in CK concentration overall, regardless of subgroup
analysis, while being non-significant in LDH. Subgroup analysis showed
the creatine supplementation effect on lowering serum CK is significant
in 48, 72 and 96 hours follow-ups after exercise. But due to high
heterogeneity of the data to our knowledge these results should not be
considered reliable. Also, creatine consumption reduce LDH significantly
in 48 hours follow-ups after exercise and there was no considerable
heterogeneity between trials. CK and LDH responses might depend on when
the initial muscle damage happened, the training status of the
individuals and the orientation with the physical activity applied
(58), and thus the limit of myocellular
specific proteins release. In this regard, trials with untrained
participants had a significant decrease in CK concentrations with
creatine supplementation.
According to expectations, dose of >20 g/day creatine had
significant effect on lowering CK. But contrary to expectations trials
with creatine supplementation duration of less than one week had
significant lower CK concentration. It can be speculated that
participant in all 8 trials (2 studies) that used >20 g/day
creatine, conducted with duration of less than one week
(31, 39).
Above-mentioned subgroup analysis indicated that dose of creatine
supplementation is more important than duration of supplementation for
decreased CK concentration.
Weight gain is the only side effect that has been suggested which may be
a desirable effect for many patient populations and athletes
(59-61). Contrary to this safety, worries
have been increased in scientific community and media related to the
creatine consumption (62-64). In this
case worries have been increased that consumption of creatine may
elevate chronically creatine synthesis suppression, promote muscle,
liver and renal damage, alter electrolyte situation and lead to
long-term side effects (63,
65, 66).
Moreover, creatine has been reported to cause dehydration, diarrhea,
promote cramping and increase gastrointestinal upset
(67-69).
The present meta-analysis had several limitations. No included studies
in this meta-analysis blinded the providers/ assessors and only one
study blinded the participants. Due to the nature of physical activity
interventions, blinding in such studies may be challenging. Moreover,
evidence was downgraded due to the lack of homogeneity among included
articles and subgroup hypothesis were not sufficient for founding the
source of heterogeneity. However, follow-ups after exercise explained
potential between-study heterogeneity, especially for LDH concentration.
Lack of information about data on intensity and frequency of exercise,
genetic background, lifestyle factors and lack of complete baseline CK
and LDH data for subgroup analysis make overall interpretation of the
results difficult. Further, a significant gender affect was suggested in
activity of serum CK concentration in other investigations
(70). Many factors can influence the high
heterogeneity stated.
The main strengths of the current meta-analysis are evaluation of
<24, 24, 48, 72 and 96 hours follow-ups measurement of muscle
damage indices after exercise and subgroup analysis based on follow-ups,
the dose of supplementation, trial duration and train status of
individuals on the overall effect sizes. The second one, we endeavored
to minimize any biases in this meta-analysis procedure by conducting a
comprehensive search of the databases as well as performing and
describing the results using the PRISMA guidelines.