Creatine Part I
Creatine is one of the most well-known and researched
supplements on the market. I believe it was around 1997 when the product first
arrived in Finland, and I quickly ended up trying it myself. Creatine can be
used in cycles or continuously, and everyone can find a method of use that
suits them if they experience benefits from it.
From my personal experience, I’ve found that using it
for 3-4 months at a time, twice a year, works best for me. As a
vegetarian/vegan, this may partly explain why creatine supplementation has had
a noticeably positive impact on my training results. Research has shown that
vegetarians tend to have lower creatine levels in their muscles and seem to
respond better to creatine supplementation (Burke, 2003). This makes sense
since dietary creatine comes exclusively from animal products.
Interestingly, recent discussions have included
observations about creatine's effects on cognitive function. However, I
personally haven’t noticed any effects in that regard—though I certainly
wouldn’t have minded! 😆 In
research studies, not all participants have shown increased brain creatine
levels, even when dosage, administration method, product type, and timing were
standardized. Perhaps for me, creatine only works below the brain level?
In recent years, researchers have also started
exploring creatine’s potential effects on brain function. In these writings, my
primary focus will be on creatine’s impact on muscle growth, strength, and
cognitive factors, but I’ll also cover general observations about its use.
Finally, I will outline the researched dosage protocols and recommendations for
creatine supplementation. However, in this first section, I will focus on
general aspects and cognitive findings related to creatine.
Creatine has traditionally been associated with energy
supply, particularly in short-duration, high-intensity efforts. This assumption
is based on the use of aerobic and anaerobic energy during performance. ATP
(adenosine triphosphate) is the molecule in which energy is stored. It is
present in all cells, including muscle cells. In order to initiate and sustain
muscle contraction, ATP must be continuously regenerated. This process occurs
in three ways: through creatine phosphate (CP), anaerobic glycolysis, and
aerobic glycolysis (oxidative system).
Every cell contains a small amount of CP, and when it
donates a phosphate group to ADP (adenosine diphosphate), ATP is formed. The
immediate energy source for muscle activity is ATP, which lasts only a few
seconds. CP can provide energy for about 10 seconds (ACSM’s Resources for the
Exercise Physiologist, Komi, 2003). Additionally, creatine plays a role in
energy transport from mitochondria (the cell’s "powerhouse," where
ATP is produced) to the cytoplasm, helping maintain ATP balance during high
energy demand. This prevents muscle fatigue by keeping ADP levels low and
reducing calcium leakage (Ca²⁺) from the sarcoplasmic reticulum (Sahlin, 2011;
Wallimann, 1977 & 1992).
If the performance continues beyond this point,
anaerobic glycolysis is utilized as an energy source. This process requires
carbohydrates—glucose and glycogen stored in muscles—which are broken down to
form ATP through phosphorylation (attachment of a phosphate group, PO₄³⁻, to a
molecule). This energy supply lasts for approximately 90 seconds. Longer
efforts require energy through the oxidative system, which involves two
pathways: the Krebs cycle and the electron transport chain. Here, energy is
derived from fats, carbohydrates, and to a limited extent, proteins. During
exercise, anaerobic and aerobic systems work together to generate ATP for
energy (ACSM’s Resources for the Exercise Physiologist, Komi, 2003). This means
that CP supplementation could be particularly beneficial for short bursts of
activity lasting under 10 seconds. Research has also been conducted on creatine
use in endurance sports, which I will discuss later.
Creatine is generally well tolerated, with minimal
known side effects. The most commonly reported side effect is water retention.
This also ties into concerns about kidney function in relation to creatine use.
But first, let’s address water retention…
Creatine is an osmotically active substance, meaning
that an increase in body creatine levels can theoretically lead to water
retention. Creatine is transported into muscles from the bloodstream via a
sodium-dependent creatine transporter (Wyss, 2000). This process occurs
alongside sodium, and water moves into the muscles to maintain intracellular
osmolality (solute concentration). However, significant changes in
intracellular sodium concentration due to creatine supplementation are
unlikely, given the function of sodium-potassium pumps (Francaux, 2006).
It appears that the most common side effect of
creatine supplementation is water retention, particularly in the initial phase
of use. Studies have shown an increase in total body water and extracellular
fluid after three days of creatine supplementation (Rosene, 2015).
Intracellular water content also increases in the early phase (Ziegenfuss,
1998).
When creatine was given to men and women at a dose of
0.03 g/kg/day for six weeks, no significant increase in total body water was
observed (Rawson, 2011). From my own experience, I always retain about 2-4 kg
of water during the first week of creatine use, but this stabilizes over time.
However, whenever I stop using creatine, my weight drops again—despite what
these studies suggest.
On the other hand, Ribeiro et al. (2020) examined the
combined effects of creatine supplementation and resistance training over an
eight-week period and found a significant increase in total body water (+7.0%)
and intracellular fluid (+9.2%) compared to the placebo group. In both groups,
extracellular fluid increased similarly (creatine group: 1.2% vs. placebo
group: 0.6%). However, the ratio of skeletal muscle mass to intracellular fluid
remained the same in both groups. Intracellular fluid plays an important role
as an intracellular signal for protein synthesis, which in turn promotes muscle
growth over time (Safdar, 2008). This has often been cited as evidence that
while creatine increases fluid levels, it also activates muscle hypertrophy.
Now, onto the kidneys... In skeletal muscle, both
creatine and phosphocreatine (PCr) degrade non-enzymatically into creatinine,
which enters the bloodstream and is eventually excreted in urine (Wyss, 2000).
Healthy kidneys filter creatinine from the blood into the urine; otherwise,
creatinine would accumulate in the bloodstream. Therefore, blood creatinine
levels can be used as a marker of kidney function. However, blood creatinine
levels are also linked to muscle mass as well as dietary intake of creatine and
creatinine itself. For example, men typically have higher blood creatinine
levels than women due to their greater muscle mass (Hultman, 1996). When taking
creatine supplements or consuming creatine-rich foods like meat, both blood and
urinary creatinine levels may temporarily rise. During creatine
supplementation, urinary creatine levels can become extremely high (>10
g/day), even though creatine is typically absent from urine (Rawson, 2002).
Although more than 95% of the body's creatine is
stored in skeletal muscle, the brain is also a highly metabolic tissue,
accounting for up to 20% of the body's total energy consumption (Gualano, 2009;
Turner, 2015). As such, creatine may serve as an important energy source for
the central nervous system (Sahlin, 2011; Wallimann, 1977 & 1992). However,
creatine is synthesized outside of muscle tissue, primarily in the liver,
pancreas, and kidneys. From these sources, as well as from dietary intake, creatine
enters the bloodstream and is transported to muscles via a transporter protein.
While skeletal muscles cannot synthesize creatine themselves, the brain does
have this ability (Andres, 2008; Braissant, 2017). This has led to the
assumption that the brain may be more resistant to external creatine
absorption. Instead, the brain likely relies on endogenous creatine synthesis
until a disturbance affects its creatine balance. Such disturbances may include
intense exercise or sleep deprivation, while chronic disruptions include
traumatic brain injury, aging, Alzheimer's disease, and depression.
Creatine may reduce the formation of reactive oxygen
species (e.g., free radicals) either by transporting ATP to the mitochondria or
by directly scavenging free radicals in the extracellular environment (Sestili,
2011). These direct and indirect antioxidant effects may provide benefits in
the treatment of neurodegenerative diseases (Beal, 2011). Creatine deficiency
syndromes, where brain creatine levels are low, manifest as cognitive and
developmental disorders (e.g., intellectual disability, learning difficulties,
autism, and epileptic seizures), which may be alleviated, at least partially,
with creatine supplementation (Kaldis, 1996; Salomons, 2003; Stockler, 1994
& 2007).
Creatine metabolism may also influence cognitive
processes by supporting ATP balance in situations where brain ATP production is
accelerated or disrupted. Such situations include complex cognitive tasks,
hypoxia (oxygen deprivation), sleep deprivation, and certain neurological
conditions (Dolan, 2019; Benton, 2010; McMorris, 2007). Creatine
supplementation may also be beneficial in recovery from mild traumatic brain
injury by supporting the brain’s energy needs. Several literature reviews have
examined the effects of creatine on brain creatine levels, cognitive function,
and mild traumatic brain injury (Dolan, 2019; Rae, 2015; Avgerinos, 2018).
Sleep deprivation is known to affect brain energy
production, and evidence suggests that creatine supplementation may enhance
cognitive performance under sleep-deprived conditions compared to a placebo.
However, only two studies have specifically investigated cognitive performance
following sleep deprivation, both of which included mild to moderate physical
activity (Hammett, 2010; Ling, 2009). For instance, after 24 hours of sleep
deprivation, creatine supplementation reduced performance deterioration in tasks
involving random movement generation, choice reaction time, balance, and mood
(Ling, 2009). Additionally, in a similar study conducted by the same research
group, creatine supplementation mitigated sleep deprivation-induced impairments
in complex cognitive functions (Hammett, 2010).
As is often the case, not all studies have found
cognitive benefits from creatine supplementation (Nemets, 2013; Alves, 2013;
Rawson, 2008; Merege-Filho, 2017). Studies on Huntington's disease, multiple
sclerosis (MS), amyotrophic lateral sclerosis (ALS), Parkinson’s disease, and
Duchenne muscular dystrophy have generally not shown significant effects from
creatine supplementation.
Creatine supplementation may be beneficial in the
treatment of various forms of depression (Hellem, 2015; Kious, 2019; Kondo,
2009; Lyoo, 2012; Roitman, 2007; Toniolo, 2017; Toniolo, 2018). Additionally,
some evidence suggests benefits in managing and protecting against concussions
and traumatic brain injuries (Forbes et al., 2022).
A systematic review by Prokopidis et al. (2023)
summarized findings indicating that creatine supplementation improved memory
performance in healthy individuals, particularly in older adults (66–76 years
old). The studies included in the review were of moderate quality, despite
being carefully selected. This pattern seems to apply to many studies in the
field.
Overall, there is some evidence suggesting that creatine supplementation may enhance cognitive function. These effects appear to be more pronounced under conditions of increased brain energy demand, such as sleep deprivation (Forbes et al., 2022). However, variability among studies makes direct comparisons challenging. Study populations differ, supplementation protocols vary (ranging from 2–20 g/day), and different brain regions have been examined using various methods. Additionally, brain phosphocreatine levels have been measured using different techniques, and different methods have been used to assess memory function. As a result, the optimal dosage for maximizing brain creatine absorption remains unclear and warrants further investigation. Current evidence suggests that creatine monohydrate supplementation increases brain creatine levels, but to a lesser extent than in skeletal muscle under similar supplementation protocols.
Photo 1 by Milad Fakurian on Unsplash
https://unsplash.com/photos/blue-and-green-peacock-feather-58Z17lnVS4U
Photo 2 by Aleksander Saks on Unsplash
https://unsplash.com/photos/a-bottle-of-creatine-next-to-a-spoon-on-a-table-lVZGEyL_j40
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