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. Wyss M, Kaddurah-Daouk R.

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filter your search All Content All Journals Nephron. Advanced Search. Skip Nav Destination Close navigation menu Article navigation. Volume 55, Issue 2. Article Navigation. Letters December 10 Muscle Cramps: A Cause of Elevated Creatine Kinase Levels in Hemodialysis Patients Subject Area: Nephrology.

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Nutrition Evidence Based Creatine Side Effects: Is It Safe? FAQs You Should Know. Medically reviewed by Jared Meacham, Ph. Side effects How it works Dehydration and cramps Weight gain Kidneys and liver Digestion Acne Drug interaction Other effects Bottom line.

What is creatine? Is it bad for you? Purported side effects of creatine. How does creatine work biologically? Does it cause dehydration or cramps? Does creatine cause weight gain?

How does it affect your kidneys and liver? Does it cause digestive concerns? Does creatine give you acne? How does creatine interact with other drugs? Other potential side effects. The bottom line. How we reviewed this article: History.

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