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ART Home Creatine. Show the heart some love! Give Today. Help us advance cardiovascular medicine. Studies have consistently shown that creatine supplementation increases intramuscular creatine concentrations which may help explain the observed improvements in high intensity exercise performance leading to greater training adaptations.

Additionally, a number of clinical applications of creatine supplementation have been studied involving neurodegenerative diseases e.

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Additionally, researchers have identified a number of potentially beneficial clinical uses of creatine supplementation. Moreover, significant health benefits may be provided by ensuring habitual low dietary creatine ingestion e.

The purpose of this review is to provide an update to the current literature regarding the role and safety of creatine supplementation in exercise, sport, and medicine and to update the position stand of International Society of Sports Nutrition ISSN. Provided robust research on creatine monohydrate, I would identify creatine as the Swiss army knife of ergogenic aids!

I work with both high school male and female athletes that use creatine post-training. Here are five things to know about creatine and that may dispel any common misconceptions. Creatine is a naturally occurring compound formed by three amino acids, making it a tripeptide of the amino acids L-glycine, L-arginine, and L-methionine.

Creatine is assembled in a two-step process that occurs in the kidneys and liver. Ninety-five percent of creatine is found in skeletal muscle and the human body needs g per day. Antonio et al. Creatine can be safely supplemented with g daily post-training.

Contrary to popular belief, creatine does not cause cramping or dehydration. In fact, creatine reduces the risk of dehydration and muscular cramping. Creatine actually promotes hydration, reducing thermal stress during exercise in the heat, and even reduces injury risk. A study published in the Journal of Athletic Training carried out by Greenwood et al.

The creatine group experienced less incidence of cramping, heat illness, dehydration, muscle tightness, muscle strains, non-contact injuries, and fewer missed practices than those not taking creatine.

Creatine supplementation results in less cramping, fewer muscle injuries, faster recovery following injury, and greater tolerance to stress in hot conditions and extreme temps. Studies have demonstrated that creatine supplementation increases intramuscular creatine concentrations which lead to the following but not limited to:.

Creatine is safe, beneficial, and well-tolerated among youth athletes as evidenced by the available data. Some studies in youth athletes have shown:. Please read a previous blog that further explains the benefits of creatine for youth athletes.

The brain is one of the highest-cost muscles in the body. Creatine can protect the brain from ischemic cell damage due to a lack of oxygen by inhibiting ATP energy depletion and mitigating structural damage to the affected brain cells.

Concussions are not planned but what this incredible research tells us is that creatine can offer protective mechanisms by increasing energy production in the part of the brain responsible for generating ATP, cells energy currency , which is the mitochondria.

The addition of creatine to high-intensity interval training had no effect on body composition in recreationally active females [ 89 ]. In addition, the effects of creatine supplementation during resistance training overreaching had no effect on fat mass [ 70 ].

In other short-terms studies lasting weeks, there were no changes in fat mass from creatine supplementation. Becque et al.

In another 6-week investigation, no significant differences in fat mass or percentage body fat were observed after creatine supplementation [ 42 ].

Furthermore, creatine supplementation during an 8-week rugby union football season also had no effect on fat mass [ 92 ]. Nonetheless, there are several investigations that have used much longer treatment periods.

For example, healthy resistance-trained males were randomly assigned in a double-blind fashion to supplement with creatine i. Lean body mass and muscle fiber size increased; percent body fat and fat mass were unaffected over the week training period [ 93 ].

In older males ~70 yrs , 12 weeks of creatine supplementation during resistance training had no effect compared to placebo on fat mass [ 94 ].

Furthermore, Gualano et al. assessed the effects of creatine supplementation 24 weeks , with and without resistance training, in older females.

Results showed no effect from creatine on fat mass [ 95 ]. Candow et al. Study participants were randomized to supplement with creatine or placebo before or after resistance training 3 days per week. There was an increase over time for lean tissue and strength with a decrease in fat mass.

From a clinical perspective, children with acute lymphoblastic leukemia who supplemented with creatine 0.

In contrast, the children who did not consume creatine gained fat mass [ 97 ]. In two studies involving postmenopausal women, Lobo et al. Furthermore, two years of creatine supplementation also had no effect on fat mass [ 99 ]. Recently, Forbes et al. Nineteen studies with a total of participants were included.

Participants supplementing with creatine had a greater reduction in body fat percentage. There was no significant difference in absolute fat mass loss; however, the creatine group lost ~0. In summary, creatine supplementation does not increase fat mass across a variety of populations. Decades later, Harris et al.

This research sparked incredible interest in studying creatine supplementation strategies that would increase intramuscular creatine content, helping shape current recommendations. In addition to the seminal work of Harris et al. However, lower daily creatine supplementation dosing strategies i.

While effective, these non-loading creatine supplementation dosing strategies Figure 1 , side B delay maximum intramuscular creatine storage. Determination of which creatine supplementation strategy is preferred may depend on the goal of the individual.

Athletes who are carrying out a creatine loading phase i. less than or equal to 10 gram servings throughout the day, as dosages of greater than 10 grams may potentially lead to gastrointestinal distress i. Lower, daily dosages of creatine supplementation i. There has been an increasing number of studies showing that creatine supplementation plays a therapeutic role in a variety of clinical conditions see Gualano et al.

Perhaps one of the most promising conditions that could benefit from creatine supplementation is age-related sarcopenia. Sarcopenia is defined as a progressive and generalized skeletal muscle condition i. decrease in muscle mass, strength, and functionality that is associated with increased likelihood of adverse outcomes including falls, fractures, physical disability and mortality [ ].

While resistance training is considered cornerstone in the treatment of sarcopenia [ ], accumulating evidence indicates that creatine supplementation may enhance the anabolic environment produced by resistance training, subsequently mitigating indices of sarcopenia [ 9 , 10 , 19 , 27 ].

Creatine supplementation can increase functionality e. However, the literature indicates that creatine alone that is, without a concomitant resistance training program is unlikely to result in substantial gains in muscle strength and functional performance [ 95 , , , ], although it does improve some parameters of muscle fatigue [ , , ].

It is likely that increases in lean mass occasionally attributed to creatine supplementation in short-term studies e. Conversely, substantial evidence indicates that creatine supplementation is capable of augmenting the hypertrophic response to resistance training in young adults [ ], which is extended to older adults, as confirmed by three systematic reviews and meta-analyses [ 19 , , ].

Regarding aging bone, emerging research over the past decade has shown some benefits from creatine supplementation. More recently, Chilibeck et al.

However, a 2 year creatine supplementation protocol was infective for improving bone mass or bone geometry in post-menopausal women, again suggesting that creatine should be combined with resistance-type exercise to produce beneficial bone adaptations [ 99 ].

From a clinical and healthy aging perspective, it is recommended that creatine supplementation be combined with resistance training to produce the greatest adaptations in older adults. Future clinical trials involving frail populations with long-term follow-up s and larger samples are needed. In summary, there is growing body of evidence showing that creatine supplementation, particularly when combined with exercise, provides musculoskeletal and performance benefits in older adults.

For example, creatine supplementation with carbohydrate [ ] or carbohydrate and protein [ ] has been reported to promote greater muscle glycogen storage than carbohydrate supplementation alone. For example, Cooke and colleagues [ ] reported that creatine supplementation during recovery from exercise-induced muscle damage promoted less muscle enzyme efflux and better maintenance of isokinetic muscle performance.

Moreover, there is evidence that individuals supplementing their diet with creatine experienced less muscle damage, inflammation, and muscle soreness in response to running km [ ] as well as during 4-weeks of intensified training [ 70 ].

Third, there is evidence that athletes who supplement with creatine during training experience fewer musculoskeletal injuries, accelerated recovery time from injury [ 78 , ] and less muscle atrophy after immobilization [ , ].

Fourth, creatine supplementation with or without glycerol has been reported to help athletes hyper-hydrate and thereby enhance tolerance to exercise in the heat [ 28 , 37 , , , , , , , , , , , , , , , ].

Thus, there are a number of reasons beyond the ergogenic benefit that all types of athletes may benefit. Creatine kinetics may vary between healthy males and females [ ]. Females may have higher intramuscular creatine concentrations [ ] possibly due to lower skeletal muscle mass [ ].

As a result of hormone-driven changes in endogenous creatine synthesis, creatine transport, and creatine kinase CK kinetics, creatine bioavailability throughout various stages of female reproduction is altered, highlighting the potential positive implications for creatine supplementation in females [ 29 ].

The implications of hormone-related changes in creatine kinetics has been largely overlooked in performance-based studies [ 29 ].

Specifically, creatine supplementation may be of particular importance during menses, pregnancy, post-partum, perimenopause and postmenopause.

Creatine kinase, as well as enzymes associated with creatine synthesis, are influenced by estrogen and progesterone [ 1 ]. Creatine kinase levels are significantly elevated during menstruation [ ], with CK levels decreasing throughout the menstrual cycle, pregnancy, and with age. The lowest range of CK values have been reported during early pregnancy 20 weeks or less , equating to about half the concentration found at peak levels teenage girls [ , ].

Maternal creatine supplementation during pregnancy in pre-clinical animal studies have demonstrated a protective effect against fetal death and organ damage associated with intrapartum hypoxia [ , ]. Reduced creatine levels in late pregnancy have also been associated with low fetal growth [ ].

There is additional data that metabolic demand from the placenta during gestation further lowers the creatine pool of the mother [ ], which may be associated with low birth weight and pre-term birth. Creatine supplementation during pregnancy has been shown to enhance neuronal cell uptake of creatine and support mitochondrial integrity in animal offspring, thereby reducing brain injury induced by intrapartum asphyxia [ , ].

Although there are no human studies evaluating the effects of creatine supplementation during pregnancy, creatine could provide a safe, low-cost nutritional interventional for reducing intra- and post-partum complications associated with cellular energy depletion [ ].

This may be more important if the female is vegetarian, or unable to consume meat due to nausea or taste preferences i. meat contains about 0. Females have been reported to have lower levels of creatine in the brain frontal lobe [ ].

Increasing creatine concentrations in the brain as a result of supplementation, particularly in females, may support the reported benefits of reducing symptoms of depression [ , ] and ameliorating the effects of traumatic brain injury [ 12 , 22 ].

Depression is about 2 times higher among females throughout the reproductive years [ ] and accelerates around pubertal hormonal changes [ ]. Altered brain bioenergetics and mitochondrial dysfunction have been linked with depression, particularly as it relates to CK, ATP, and inorganic phosphate P i.

Creatine supplementation has been shown to significantly augment cerebral PCr and P i [ ], particularly in females. There is a small body of research that has investigated the effects of creatine supplementation in younger females. For example, Vandenberghe et al.

Hamilton et al. Furthermore, in college-aged females 20 yrs , creatine supplementation 0. In contrast, not all data show improved performance in females [ 89 , , ].

Additionally, Smith-Ryan et al. It is important to evaluate the benefit to risk ratio; as noted elsewhere in this document, there are minimal risks associated with creatine supplementation, particularly when it is evaluated against the potential benefits in females.

Accumulating research over the past decade in postmenopausal females demonstrates that creatine supplementation during a resistance training program can improve muscle mass, upper- and lower-body strength, and tasks of functionality s chair stand, lying prone-to-stand test, arm curl test for detailed review see Candow et al.

Creatine supplementation appears to be a viable option for post-menopausal females to improve muscle quality and performance. In addition to its beneficial effects on aging muscle, creatine supplementation may also have favorable effects on bone in postmenopausal females, if combined with resistance training.

For example, postmenopausal females who supplemented daily with 0. However, even without the stimulus of resistance training, there is some evidence that creatine supplementation can still be beneficial.

In summary, there is accumulating evidence that creatine supplementation has the potential to be a multifactorial therapeutic intervention across the lifespan in females, with little to no side effects. Creatine monohydrate powder has been the most extensively studied and commonly used form of creatine in dietary supplements since the early s [ 2 , ].

Creatine monohydrate was used in early studies to assess bioavailability, determine proper dosages, and assess the impact of oral ingestion of creatine on blood creatine and intramuscular creatine stores [ 35 , 60 , ]. These studies indicated that orally ingested creatine monohydrate e.

Short-term loading with creatine monohydrate e. Creatine monohydrate supplementation during training e. Despite the known efficacy, safety, and low cost of creatine monohydrate; a number of different forms of creatine have been marketed as more effective with fewer anecdotally reported adverse effects [ ].

These marketing efforts have fueled speculation that creatine monohydrate is not the most effective or safest form of creatine to consume. This notion is clearly refuted by understanding the well-known physio-chemical properties of creatine monohydrate, as well as current creatine supplementation literature.

A number of different forms of creatine e. have been marketed as more effective sources of creatine than creatine monohydrate [ ]. However, there are no peer-reviewed published papers showing that the ingestion of equal amounts of creatine salts [ , , , ] or other forms of creatine like effervescent creatine [ ], creatine ethyl ester [ 43 , , ], buffered creatine [ 41 ], creatine nitrate [ , ], creatine dipeptides, or the micro amounts of creatine contained in creatine serum [ ] and beverages e.

Creatine monohydrate crystallizes from water as monoclinic prisms that hold one molecule of water of crystallization per molecule of creatine [ ]. Creatine is considered a weak base pKb Creatine can also serve as a complexing agent with other compounds via ionic binding.

Creatine monohydrate powder contains the highest percentage of creatine Creatine monohydrate manufactured in Germany involves adding acetic acid to sodium sarconsinate, heating, adding cyanamide, cooling to promote crystallization, separation and filtration, and drying has been reported to produce Meanwhile, other sources of creatine monohydrate that have different starting materials e.

While the effects of ingesting these compounds on health are unknown, contamination with dihydrotriazine has been suggested to be of greatest concern since it is structurally related to carcinogenic compounds [ ]. For this reason, German sourced creatine monohydrate has been primarily used in research to establish safety and efficacy and is therefore the recommended source of creatine monohydrate to use in dietary supplements [ 2 , ].

Creatine monohydrate powder is very stable showing no signs of degradation into creatinine over years, even at elevated storage temperatures [ ]. However, creatine is not stable in solution due to intramolecular cyclization that converts creatine to creatinine especially at higher temperatures and lower pH [ , , , ].

The degradation of creatine can be reduced or halted by lowering the pH under 2. Moreover, since creatine is an ampholytic amino acid, it is not very soluble in water e. Mixing creatine in higher temperature solution increase solubility, which is the reason why initial studies administered creatine in hot tea [ 35 , 60 , , , , ] but the solubility has no influence on tissue uptake [ ].

The lack of solubility and stability of creatine in solution is the reason that creatine is primarily marketed in powder form and efforts to develop stable beverages containing physiologically effective doses of creatine e.

In summary, while some forms of creatine may be more soluble than creatine monohydrate when mixed in fluid, evidence-based research clearly shows creatine monohydrate to be the optimal choice.

Creatine supplementation appears to be generally safe and potentially beneficial for children and adolescents. Smaller, daily dosages of creatine supplementation g or 0.

Creatine supplementation and resistance training produces the vast majority of musculoskeletal and performance benefits in older adults. Creatine supplementation alone can provide some muscle and performance benefits for older adults.

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