Creatine Side Effects - FAQ

❓Common questions and misconceptions about creatine:

There have been over 500 scientific papers examining the side effects of creatine, including a deep dive in 2017 by the International Society of Sports Nutrition (ISSN) that looked at creatine effects on performance, recovery, and a complete safety profile. However, despite abundant and clear research, a number of questions and misconceptions about the topic still remain - even among highly educated specialists. In this article I address some of the main conclusions from these studies.

👨🏽‍⚕️Does creatine cause kidney damage?

When ingested at recommended dosages, creatine does not result in kidney damage and/or renal dysfunction.

The connection between creatine supplementation and kidney damage/renal dysfunction can be traced back to two things: a poor understanding of creatine-creatinine metabolism and a case study published in 1998.

Creatinine metabolism: About 1-3% of creatine in the body is naturally degraded to creatinine. This occurs whether creatine is endogenously produced or ingested in the form of food/supplements. It just so happens that creatinine has also been traditionally used by physicians as a biomarker for kidney health and hence, physicians are conditioned to associate increases in creatinine with kidney damage. When people first started ingesting creatine supplements - and therefore artificially inflating their creatinine levels as a consequence, this caused some concern among unaware doctors. However, we now know that despite creatinine levels being artificially high among people who use creatine supplements, these numbers do not reflect kidney damage.

The case study from 1998: In this study, a young man with existing kidney disease who had been taking creatine in addition to a number of medications seemed to get worse. Unfortunately, the investigators at the time didn't account for his pre-existing condition, ignored prior studies showcasing the safety profile of creatine, and disregarded the fact that the dose of creatine this patient took was only marginally higher than what you'd get from a regular diet (15 g/day for 7 days; followed by 2 g/day for 7 weeks).

Shortly after this case study was published, two separate teams of experts in creatine metabolism wrote letters to the editor of Lancet in protest. However, the notion that creatine supplementation led to kidney damage and/or renal dysfunction had unfortunately already gained traction and momentum.

Since then, the interest and number of experimental and controlled research trials investigating the effects of creatine supplementation on kidney/renal function dramatically increased, and these follow up studies unequivocally showed that creatine is safe and does not result in kidney damage. Here are some of those studies:

Safety of creatine supplementation - Subcell Biochem . 2007;46:275-89. doi: 10.1007/978-1-4020-6486-9_14.
Effects of Creatine Supplementation on Renal Function: A Systematic Review and Meta-Analysis - J Ren Nutr. 2019 Nov;29(6):480-489. doi: 10.1053/j.jrn.2019.05.004
In sickness and in health: the widespread application of creatine supplementation - Amino Acids . 2012 Aug;43(2):519-29. doi: 10.1007/s00726-011-1132-7

👴🏽👵🏽Is creatine beneficial for older adults?

Creatine supplementation - particularly when combined with exercise, is not only safe, but provides remarkable musculoskeletal and performance benefits in older adults. These benefits, in turn, have a compounding effect on wellness and longevity.

Supplementing with creatine can enhance functional abilities such as strength, daily activities, and fatigue resistance, as well as promote muscle mass among older adults. Nonetheless, existing literature suggests that relying solely on creatine intake, without concurrent participation in a resistance training regimen, is improbable to yield significant increases in muscle strength and overall functional performance. Interestingly, even without exercise, creatine does seems to show improvement in certain aspects of muscle fatigue. Regardless, from a clinical and healthy aging perspective, it is universally advised to couple creatine supplementation with resistance training to obtain the most significant benefits.

In addition to functional benefits, creatine supplementation coupled with resistance training has been shown to enhance mineral content in aging bones and mitigate the effects of age-related sarcopenia. Bone loss and sarcopenia - both natural processes associated with aging, can significantly impact your health: Fractures resulting from weakened bones can lead to prolonged recovery periods, reduced mobility, and even long-term disability. Sarcopenia, on the other hand, can result in diminished strength and endurance, hindering the ability to perform routine tasks or engage in physical activities. These combined effects increase the risk of falls, fractures, and loss of independence. Furthermore, bone loss and muscle deterioration can contribute to decreased metabolic rate and insulin resistance - potentially heightening the risk of chronic conditions such as osteoporosis, diabetes, and cardiovascular disease.

Lastly - and this is my favorite part, creatine has neuroprotective properties that have recently garnered some attention. Creatine helps shield brain cells from oxidative stress and inflammation, and in this way, it offers a protective effect against neurodegenerative conditions like Alzheimer's and Parkinson's disease. While more research is needed, creatine's neuroprotective properties hold promise for promoting long-term brain health. More info here: Effects of Creatine Supplementation on Brain Function and Health

💉💪🏽Is creatine an anabolic steroid?

Nope. Creatine is an amino acid.

🧑🏽‍🦲Does creatine cause hair loss/baldness?

Evidence indicates that creatine supplementation does not cause hair loss/baldness.

Most of the speculation about the potential link between using creatine supplements and hair loss or baldness originates from a lone study conducted by van der Merwe and colleagues (Its always lone studies). In this study, college-aged male rugby players who took creatine supplements (25 g/day for 7 days, followed by 5 g/day for 14 additional days) observed a rise in serum dihydrotestosterone (DHT) levels over the course of the study.

Since DHT has been linked to some (but not all) occurrences of hair loss/baldness the myth that creatine supplementation leads to hair loss / baldness was then born and gained popularity. However, this study did not measure baldness directly, did not follow the subjects long-term, and had a number of limitations in the experimental design including confounding variables. Additionally, other research groups have been unable to replicate the results in this study - this is generally a dead giveaway of invalid or flawed studies.

Subsequently, a total of 12 additional studies have examined the impact of creatine supplementation on testosterone levels. Among these studies, two indicated minimal and practically insignificant rises in total testosterone after six and seven days of supplementation, and the other ten studies did not observe any significant alterations in testosterone concentrations. It's worth noting that out of these ten studies, five also measured free testosterone, a precursor to DHT, and found no notable increases. Here are some of those studies:

The effects of creatine supplementation on performance and hormonal response in amateur swimmers. Science and Sports. 2011;26:272–277. doi: 10.1016/j.scispo.2011.07.003.
Effects of short term creatine supplementation and resistance exercises on resting hormonal and cardiovascular responses. Science and Sports. 2015;30:105–109. doi: 10.1016/j.scispo.2014.03.006.
Effect of creatine and beta-alanine supplementation on performance and endocrine responses in strength/power athletes. Int. J. Sport Nutr. Exerc. Metab. 2006;16:430–446.

💧Does creatine lead to water retention?

In the short term: yes - primarily due to increases in intracellular volume. Over the long term and particularly relative to muscle mass: no.

Creatine is an osmotically active substance, and hence, it is widely known that the most commonly observed side effect of creatine supplementation is an increase in water retention during the first few days of supplementation. For example, research studies have shown that a three-day period of creatine supplementation led to higher levels of total body water (TBW), extracellular body water (ECW), and intracellular water (ICW).

Interestingly, the notion that these findings extend over the long-term are equally widely accepted. However, under mostly incorrect assumptions. It turns out that more refined studies have shown that although creatine intake is associated with an increase in body mass and TBW in the sort term, it does not alter ICW or ECW volumes over the long term. Pretty crazy, huh? Here are some examples:

In this study by Andre, et. al., male subjects engaged in resistance training, who were provided with creatine at a dosage equivalent to 0.3 g/kg of lean body mass per day for a week (around 20 g/day), followed by four weeks at 0.075 g/kg of lean body mass per day (approximately 5 g/day), did not show any notable alterations in intracellular body water, extracellular body water, or total body water.
In this study by Jagim, et. al., resistance-trained men who ingested creatine supplements (20 g/day for a week, followed by 5 g/day for 21 days) did not experience a substantial rise in intracellular water, extracellular body water, or total body water.
In this study by Raqwson, et. al., , researches showed that males and females ingesting creatine (0.03 g/kg/day for six weeks) experienced no significant increase in total body of water.
And this study by Spillane, et. al., investigators showed that over the span of six weeks, non-resistance-trained males who were administered creatine supplementation at a rate of 0.3 g/kg lean body mass for five days, followed by 0.075 g/kg lean body mass for 42 days, did not exhibit noteworthy alterations in total body water.

⚡Does creatine lead to dehydration and muscle cramping?

There is no scientific support from experimental and/or clinical research to substantiate the claim that creatine supplementation leads to dehydration and muscle cramping.

The idea suggesting that creatine supplementation could result in dehydration and muscle cramping relies on the concept that creatine might impact the distribution of bodily fluids due to its osmotic properties. In scenarios involving loss of body water, such as intense exercise-induced sweating or exposure to higher temperatures, the potential accumulation of intracellular fluid could hypothetically interfere with thermal regulation. In theory, this could lead to extracellular dehydration, disruptions in electrolyte balance, and the emergence of muscle cramps or other heat-related musculoskeletal issues.

In practice, however, creatine supplementation has been shown to reduce the frequency of muscle cramps and other closely-related pathologies. A study by ********Greenwood et al. that monitored injury rates in Division IA NCAA collegiate football players showed that within the test subjects, creatine users had significantly less cramping (p = 0.021), heat illnesses and dehydration (p = 0.043), muscle tightness (p = 0.020), muscle strains (p = 0.021), and total injuries (p < 0.001) compared to non-users. And in a study performed in patients undergoing hemodialysis, creatine supplementation was shown to decrease the occurrence of muscle cramps by 60%: **Creatine monohydrate treatment alleviates muscle cramps associated with hemodialysis. Nephrol Dial Transplant . 2002 Nov;17(11):1978-81. doi: 0.1093/ndt/17.11.1978. And a separate

✅Are other forms of creatine similar or superior to monohydrate?

Although certain variations of creatine might exhibit higher solubility than creatine monohydrate when dissolved in liquids, extensive research consistently indicates that creatine monohydrate remains the preferred and most effective option.

Research indicates that the consumption of alternate formulations of creatine have a lower physiological effect on intramuscular creatine reserves and/or performance when compared to creatine monohydrate. Any discernible disparities in performance appear to be more closely associated with the presence of other nutrients to which creatine is connected or consumed alongside in supplement compositions. Save your money by buying high quality creatine monohydrate instead of gimmicky stuff with additional components.

🏃🏽‍♀️Is creatine effective for females?

Creatine supplementation holds promise as a multifaceted therapeutic approach for females throughout their lives, with minimal to negligible adverse effects.

Accumulating research over the past decade shows that although the kinetics of creatine can differ between healthy males and females, creatine nonetheless offers a great number of benefits to females across their lifespan:

Although there are no human studies evaluating the effects of creatine supplementation during pregnancy, this study by Guingand et. al., suggests that creatine could provide a safe, low-cost nutritional interventional for reducing intra- and post-partum complications associated with cellular energy depletion.
Studies by Kondo et. al. and Hellem et. al., indicate that increasing creatine concentrations in the brain as a result of supplementation may reduce symptoms of depression in females.
Vandenberghe et al. showed that creatine supplementation in younger females (20 g/day for 4 days followed by 5 g/day thereafter) during 10 weeks of resistance training significantly increased intramuscular concentrations, muscle mass and strength compared to placebo in females (19-22 yrs)
Lastly, accumulating research over the past decade reviewed here shows that creatine supplementation in post-menopausal women during a resistance training program can improve muscle mass, upper- and lower-body strength, and tasks of functionality

🐼Does creatine increase fat mass?

Creatine supplementation does not increase fat mass

The concern that creatine supplementation might lead to an increase in fat mass is widespread - particularly due to increases in overall body mass after using creatine supplements. However, a range of randomized controlled trials spanning from one week to two years in duration refute this notion:

A study by Silva, et. al., focusing on different scenarios such as three weeks of creatine supplementation in swimmers or its combination with high-intensity interval training for recreationally active females, showed no alteration in body composition.
A study by Volek, et. al., in this study, when administered during resistance training overreaching, creatine supplementation demonstrated no effect on fat mass [70].
A separate study involving healthy male bodybuilders found that a daily intake of 5 g of creatine either before or after training had no impact on fat mass [90].
Becque et al. observed no changes in fat mass after six weeks of supplementation combined with resistance training.
Another 6-week study reported no significant alterations in fat mass or percentage of body fat.
Lastly, a recent systematic review and meta-analysis conducted by Forbes et al., a thorough review of randomized controlled trials involving older adults (aged 50 years and above) who combined creatine supplements with resistance training revealed intriguing findings. The analysis covered nineteen studies involving 609 participants, showing that those who took creatine had a bigger decrease in body fat percentage. Although there was no major difference in the overall loss of fat mass, the creatine group had around 0.5 kg more reduction in fat mass compared to those not taking creatine.

🚸Is creatine harmful for children and adolescents?

Based on the limited evidence, creatine supplementation appears safe and potentially beneficial for children and adolescents.

A considerable portion of dietary supplement surveys highlights a relatively high prevalence of creatine supplementation among youth and adolescent athletes. Concerns regarding the safety of creatine supplementation in individuals aged < 19 years remain prominent. While ample evidence in adult populations supports the safety and tolerability of creatine supplementation over both short and extended periods, the applicability of these findings to children and adolescents remains less conclusive.

From a clinical viewpoint, creatine supplementation emerges as a potential avenue for health improvements with minimal adverse outcomes in younger individuals. For example, research by Hayashi et al. showcased enhancements in pediatric patients with systemic lupus erythematosus, Tarnopolsky et al. demonstrated significant enhancements in fat-free mass and hand grip strength in 30 pediatric patients with Duchenne muscular dystrophy, and Sakellaris et al. reported noteworthy improvements in traumatic brain injury-related outcomes among children and adolescents receiving oral creatine supplementation (0.4 g/kg/day) for six months.

These findings lend support to the notion that creatine supplementation is likely safe for children and adolescents. Reinforcing this belief is the recent classification of creatine as generally recognized as safe (GRAS) by the United States Food and Drug Administration (FDA) in late 2020 (https://www.fda.gov/media/143525/download**). This classification signifies that existing scientific data on creatine's safety is robust and has been endorsed by a consensus of qualified experts, affirming its safety under intended usage conditions (https://www.fda.gov/media/143525/download**). Although GRAS excludes infants and young children, it still encompasses older children and adolescents.

Disclaimer: This content is provided for educational purposes only and should not be construed as medical advice. Always consult with your primary care physician (PCP) or a qualified healthcare professional before making any changes to your lifestyle, diet, or exercise routine. The information presented in this article is not intended to diagnose, treat, cure, or prevent any disease. Individual results may vary. The author and publisher of this article are not responsible for any adverse effects or consequences resulting from the use or application of the information provided. Please use your own discretion and judgment when implementing any suggestions or recommendations.