Creatine Supplementation

By: Jeremy Partl, Registered Dietitian

While most people who pick up lifting weights, strength sports, and physique sports may think that the most common sports supplement is protein powder, if you encompass the years of literature and expand the discussion to athletic performance, creatine is one of the most (if not the most) popular nutritional ergogenic aids.^[1]

Despite over 500 peer-reviewed publications involving creatine supplementation, questions regarding the efficacy and safety of creatine still continue to pop up.

A while back, I wrote a short article titled “Simple Supplementation.” In that article, I briefly touched on creatine supplementation. But in this article, I want to go deeper into creatine and answer some of the most frequently asked questions.

The Basics of Creatine

Creatine is a naturally occurring non-protein amino acid compound that can be produced from reactions involving the amino acids arginine, glycine, and methionine in the kidneys and liver.^[2] However, we can also obtain creatine from meat (primarily red meat and seafood) and/or as a dietary supplement.

The majority of creatine is found in skeletal muscle (~95%), with the remaining small amounts also found in the brain and testes (~5%).^[3] Depending on muscle mass, the body needs to replenish about 1–3 grams of creatine per day to maintain normal (unsupplemented) creatine stores.^[4]

The main role of creatine in the body is in aiding energy production, especially under conditions of high energy demand such as intense physical or mental activity. The phosphocreatine stores donate high-energy phosphate groups to ADP, regenerating it to ATP, the primary energy carrier in the body.^[5]

A normal diet that contains 1–2 grams per day of creatine (the amount found in roughly a pound of uncooked beef or seafood) saturates muscle creatine stores to about 60–80% of full capacity. While the body can fill the rest endogenously, dietary supplementation of creatine may help saturate that remaining 20–40%.^[6] In the case of vegetarians and vegans, supplementation is especially important.

Benefits of Creatine Supplementation

With increased muscle availability of phosphocreatine stores, supplementation with creatine has been shown repeatedly to enhance acute exercise capacity and training adaptations.^[7] Most often, this would be expressed by allowing an individual to do more work over a series of sets or sprints, leading to greater gains in strength, muscle mass, and/or performance. For instance, if you have been able to lift a certain weight for ten reps, research suggests that creatine supplementation could increase that to 11-12 reps, which adds up over time (a 10-20% increase on average). ^[8]

In addition to the ergogenic benefits, recent research has highlighted a number of other applications of creatine supplementation, which may help individuals involved in intense training or anyone who just wants to enhance training adaptations. Some of those benefits include the following:

Closing out this section, I wanted to highlight research findings that have clearly shown several potential health and/or therapeutic benefits as we age and in clinical populations. Although additional research is needed to explore further the health and potential therapeutic benefits of creatine supplementation beyond performance, strength, and sport/training, creatine seems to be one of the most efficacious and multifaceted tools to support holistic health. Based on the available evidence, the following additional benefits may be reasonably on the table:^[12]

• “Creatine supplementation during energy-restriction-induced weight loss may be an effective way to preserve muscle while dieting and thereby help manage adult-onset obesity.”
• “Creatine supplementation may support cognitive function, particularly as one ages.”
• “Creatine supplementation may support healthy glucose management.”
• “Creatine supplementation may support heart metabolism and health, particularly during ischemic challenges.”
• “Long-term, high-dose creatine supplementation in individuals with creatine synthesis deficiencies can increase brain creatine and PCr levels and may reduce the severity of deficits associated with these disorders.”
• “The efficacy of long-term, high-dose creatine supplementation in individuals with neurodegenerative diseases is equivocal, while promising, in patients with muscular dystrophy.”
• “Creatine supplementation during pregnancy may help support the mother and child’s nutritional needs and health; however, due to the limited studies in pregnant humans, caution should be exercised when recommending use during human pregnancy.”
• “Creatine supplementation may have anti-inflammatory and immunomodulating effects.”
• “Creatine is an important energy source for immune cells, can help support a healthy immune system, and may have some anticancer properties.”
• “Creatine and/or GAA may improve functional capacity in patients with chronic fatigue-related syndromes such as post-viral fatigue syndrome (PFS) and myalgic encephalomyelitis (ME).”
• “Creatine may support mental health.”
• “Creatine may support reproductive health.”
• “Creatine may support skin health.”

One more thing. Compared to other supplements out there on the market (protein powders, fat burners, etc.), creatine is a dirt-cheap supplement.

Recommended Creatine Supplementation

With all those benefits, I hope you are at least open to (if not sold on) taking creatine. It is not my intention to sell it, but with such a robust number of benefits that impact all areas of life, to me, it is a no-brainer.

Tangent aside, if you do decide to supplement with creatine, here are the standard recommendations when it comes to getting efficacious doses:^[13]

• The most effective way to rapidly increase muscle creatine stores is to ingest 5 g of creatine monohydrate (or approximately 0.3 g/kg body weight) four times daily for 5–7 days. This is known as a rapid loading protocol.
• “An alternative supplementation protocol is to ingest 3 g/day of creatine monohydrate for 28 days.” (Kreider) However, this slow loading protocol would only result in a gradual increase in muscle creatine content and may have less of an immediate impact on exercise performance and/or training adaptations until creatine stores are fully saturated.
• “Once muscle creatine stores are fully saturated, creatine stores can generally be maintained by ingesting 3–5 g/day[.]” (Kreider) Some studies indicate that larger individuals may need to ingest as much as 5–10 g/day in order to maintain creatine stores.

The most common form of creatine widely used on the market and studied in the literature is creatine monohydrate.

While some forms of creatine may be more soluble than creatine monohydrate when mixed in fluid, evidence-based research and the recommendations of the International Society of Sports Nutrition state that “clinical evidence has not demonstrated that different forms of creatine such as creatine citrate, creatine serum, creatine ethyl ester, buffered forms of creatine, or creatine nitrate promote greater creatine retention than creatine monohydrate” and that creatine monohydrate is the optimal choice.^[14],^[15]

Creatine FAQ

Part of the rationale for writing this article was the abundance of questions and misconceptions involving creatine supplementation that still exist. Below, I will cover some of the most common questions that come up.

Does creatine cause water retention?

Creatine is taken up into muscles from circulation by a sodium-dependent creatine transporter that also involves the uptake of water into muscle to help maintain intracellular osmolality.

“[W]hile there is some evidence to suggest that creatine supplementation increases water retention, primarily attributed to increases in intracellular volume over the short term, there are several other studies suggesting it does not alter total body water (intra- or extracellular) relative to muscle mass over longer periods of time.”^[16]

Will creatine dehydrate you or cause muscle cramping?

In theory, the osmotic activity mentioned above seems to be detrimental to thermoregulation and may lead to extracellular dehydration, electrolyte imbalance, and muscle cramping or other heat-related musculoskeletal issues.

While some anecdotal evidence indicates that creatine users perceive supplementation to result in some adverse effects, most of the experimental and clinical evidence suggests that creatine users actually have lower rates of cramping, heat illnesses, dehydration, muscle tightness, muscle strains, and total injuries compared to non-users.^[17],^[18],^[19]

Will creatine supplementation hurt my kidneys?

Along with the common myth that high protein intakes will damage your kidneys, it’s commonly thought that creatine may also cause renal damage/dysfunction due to a very few cases in which individuals, purportedly taking creatine with or without other supplements, presented with high creatinine levels and/or renal dysfunction.

However, a much larger base of data suggests that when ingested at recommended dosages, creatine supplementation does not result in kidney damage and/or renal dysfunction in healthy individuals.^[20]

Furthermore, even for those who have pre-existing renal disease, studies have concluded that “there is no compelling evidence that creatine supplementation negatively affects renal function in healthy or clinical populations.”^[21] In these cases, though, it’s always recommended to keep your physician aware if you do decide to take creatine.

Does creatine cause you to go bald or lose hair faster?

The theory that creatine supplementation leads to hair loss/baldness gained some momentum after a study involving creatine supplementation in rugby players that resulted in an increase in serum dihydrotestosterone (DHT) concentrations over time.^[22] This is a common myth based on a loose causal link between DHT and hair loss.^[23] Another study notes that the rugby study’s results have not been replicated, and “intense resistance exercise itself can cause increases in these androgenic hormones.”^[24]

While it is possible that creatine supplementation upregulated androgenic hormones, the majority of available evidence does not support a link, and no study has reported specifically observed hair loss/baldness in humans.^[25]

Is creatine something my child/adolescent may take?

Very similar to the questioning of whether or not children should be lifting weights, the prevalence of questioning whether children and adolescence should take creatine still exists.

An emerging, yet still limited, body of literature in adolescent athletes using creatine has suggested that creatine use in adolescent athletes appears to be well-tolerated with no reported adverse events. Furthermore, creatine use even in infants, toddlers, and adolescents can be beneficial in both performance and clinical scenarios.^[26],^[27], ^[28]

For this reason, the ISSN recommends creatine supplementation as an acceptable nutrition strategy for younger individuals who: a.) are involved in serious/competitive supervised training; b.) are consuming a well-balanced and performance-enhancing diet; c.) are knowledgeable about appropriate use of creatine; and d.) do not exceed recommended dosages.^[29]

Is it necessary to load creatine rapidly?

As I mentioned earlier, there are two main strategies to achieving saturation of creatine in muscles: (1) a rapid loading phase or (2) a smaller, more consistent loading period. Lower daily doses for a longer amount of time (3-5 g or 0.1 g/kg of body mass) are just as effective for overall saturation levels.

There are a few situations where it may be advantageous to choose to do a faster loading period:

• You are hoping to maximize the ergogenic potential of creatine supplementation in a very short period of time (< 30 days).
• You want to avoid potential acute weight gain due to rapid fluid shifts that can sometimes occur during creatine loading.

A rapid loading protocol is a bit riskier, with some adverse effects (weight gain, GI distress, etc.). Thus, it’s highly emphasized that smaller dosing strategies (e.g., less than or equal to 10-gram servings) throughout the day are safer than dosages of greater than 10 grams at a time.^[30]

Would older adults benefit from creatine supplementation?

When it comes to the topic of creatine supplementation for older adults, the main consideration beyond the aforementioned benefits that cover all timeframes during the lifespan is its potential effect on sarcopenia—the age-related decrease in muscle mass, strength, and functionality.

There is a growing body of evidence indicating that creatine alone is unlikely to produce substantial gains in muscle strength and functional performance, although it does improve some parameters of muscle fatigue.^[31],^[32]

Emerging research over the past decade has also shown some benefits from creatine supplementation in increasing bone mineral content and reducing bone resorption. Although, just as with the aforementioned benefits on functionality and muscle mass, these benefits may be confounded with the combination of strength and resistance training versus supplementation alone in a lot of the literature.^[33],^[34]

While creatine supplementation alone can provide some muscle and performance benefits for older adults, the combination of creatine supplementation and resistance training may produce the vast majority of musculoskeletal and performance benefits observed in older adults.

Furthermore, a growing collection of evidence supports that creatine supplementation may “help lower cholesterol and triglyceride levels; reduce fat accumulation in the liver; reduce homocysteine levels; serve as an antioxidant; enhance glycemic control; slow tumor growth in some types of cancers; increase strength and/or muscle mass; minimize bone loss; improve functional capacity in patients with knee osteoarthritis and fibromyalgia; positively influence cognitive function; and in some instances, serve as an antidepressant.”^[35] In essence, if you want something that tackles nearly every area of health, creatine seems to be an effective tool.

Is creatine only useful for resistance/power type activities?

There are a number of reasons beyond the ergogenic benefits from which nearly everyone would see positive uses.

Whether it is the additional applications to sport and training (enhanced glycogen storage, decreased muscle damage/improved recovery, etc.) or clinical and health-related benefits (neuroprotection, functionality, antidepressant, etc.), this supplement’s benefits extend way beyond just the power athlete.

Is creatine only effective for males?

Physiologically, females may have higher intramuscular creatine concentrations (typically due to lower skeletal muscle mass) and also lower levels of creatine in the frontal lobe in the brain.^[36],^[37] In addition, as a result of hormone-driven changes during the various stages of female reproduction, creatine bioavailability is altered.^[38]

However, despite these differences physiologically, there does not appear to be significant responsiveness and/or performance effects on females to creatine supplementation (although the effects seem to be slightly diminished).^[39] Studies still suggest that creatine supplementation has the potential to be a multifactorial therapeutic intervention (increased muscle mass, performance benefits, neuroprotective benefits, reduction in pregnancy complications, etc.) across the lifespan in females, with little to no side effects.^[40]

Wrapping Up

I want to make it clear that I come from a food-first approach to nutrition that considers supplements as just something extra, playing only a small role in health enhancement. Typically, eating a varied diet of micronutrient-rich foods will provide nearly every nutrient needed for optimal health outcomes.

But if there was one supplement that I would recommend, even if you are getting enough in your diet, it may be creatine. Beyond extreme amounts in very short periods of time, keeping muscle levels of creatine saturated seems to have benefits that go way beyond the gym or field. It seems to be something actually advantageous, possibly from the crib to the cane.

References

^[1] Kreider, R. B., Kalman, D. S., Antonio, J., Ziegenfuss, T. N., Wildman, R., Collins, R., … & Lopez, H. L. (2017). International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. Journal of the International Society of Sports Nutrition, 14(1), 1-18.

^[2] Wyss, M., & Kaddurah-Daouk, R. (2000). Creatine and creatinine metabolism. Physiological reviews, 80(3), 1107-1213.

^[3] Buford, T. W., Kreider, R. B., Stout, J. R., Greenwood, M., Campbell, B., Spano, M., … & Antonio, J. (2007). International Society of Sports Nutrition position stand: creatine supplementation and exercise. Journal of the International Society of Sports Nutrition, 4(1), 1-8.

^[4] Brosnan, M. E., & Brosnan, J. T. (2016). The role of dietary creatine. Amino Acids, 48(8), 1785-1791.

^[5] https://examine.com/supplements/creatine/

^[6] Kreider, R. B., Kalman, D. S., Antonio, J., Ziegenfuss, T. N., Wildman, R., Collins, R., … & Lopez, H. L. (2017). International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. Journal of the International Society of Sports Nutrition, 14(1), 1-18.

^[7] Kreider, R. B., Kalman, D. S., Antonio, J., Ziegenfuss, T. N., Wildman, R., Collins, R., … & Lopez, H. L. (2017). International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. Journal of the International Society of Sports Nutrition, 14(1), 1-18.

^[8] Kreider, R. B. (2003). Effects of creatine supplementation on performance and training adaptations. Molecular and cellular biochemistry, 244(1), 89-94.

^[9] Kreider, R. B., & Jung, Y. P. (2011). Invite review: creatine supplementation in exercise, sport, and medicine. JENB (Journal of Exercise Nutrition & Biochemistry), 15(2), 53-69.

^[10] Kreider, R. B., Kalman, D. S., Antonio, J., Ziegenfuss, T. N., Wildman, R., Collins, R., … & Lopez, H. L. (2017). International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. Journal of the International Society of Sports Nutrition, 14(1), 1-18.

^[11] Kreider, R. B., Kalman, D. S., Antonio, J., Ziegenfuss, T. N., Wildman, R., Collins, R., … & Lopez, H. L. (2017). International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. Journal of the International Society of Sports Nutrition, 14(1), 1-18.

^[12] Kreider, R. B., & Stout, J. R. (2021). Creatine in Health and Disease. Nutrients, 13(2), 447.

^[13] Kreider, R. B., Kalman, D. S., Antonio, J., Ziegenfuss, T. N., Wildman, R., Collins, R., … & Lopez, H. L. (2017). International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. Journal of the International Society of Sports Nutrition, 14(1), 1-18.

^[14] Kreider, R. B., Kalman, D. S., Antonio, J., Ziegenfuss, T. N., Wildman, R., Collins, R., … & Lopez, H. L. (2017). International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. Journal of the International Society of Sports Nutrition, 14(1), 1-18.

^[15] Antonio, J., Candow, D. G., Forbes, S. C., Gualano, B., Jagim, A. R., Kreider, R. B., … & Ziegenfuss, T. N. (2021). Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show?. Journal of the International Society of Sports Nutrition, 18(1), 1-17.

^[16] Antonio, J., Candow, D. G., Forbes, S. C., Gualano, B., Jagim, A. R., Kreider, R. B., … & Ziegenfuss, T. N. (2021). Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show?. Journal of the International Society of Sports Nutrition, 18(1), 1-17.

^[17] Antonio, J., Candow, D. G., Forbes, S. C., Gualano, B., Jagim, A. R., Kreider, R. B., … & Ziegenfuss, T. N. (2021). Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show?. Journal of the International Society of Sports Nutrition, 18(1), 1-17.

^[18] Greenwood, M., Farris, J., Kreider, R., Greenwood, L., & Byars, A. (2000). Creatine supplementation patterns and perceived effects in select division I collegiate athletes. Clinical Journal of Sport Medicine, 10(3), 191-194.

^[19] Greenwood, M., Kreider, R. B., Melton, C., Rasmussen, C., Lancaster, S., Cantler, E., … & Almada, A. (2003). Creatine supplementation during college football training does not increase the incidence of cramping or injury. Molecular and cellular biochemistry, 244(1), 83-88.

^[20] Antonio, J., Candow, D. G., Forbes, S. C., Gualano, B., Jagim, A. R., Kreider, R. B., … & Ziegenfuss, T. N. (2021). Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show?. Journal of the International Society of Sports Nutrition, 18(1), 1-17.

^[21] Kreider, R. B., Kalman, D. S., Antonio, J., Ziegenfuss, T. N., Wildman, R., Collins, R., … & Lopez, H. L. (2017). International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. Journal of the International Society of Sports Nutrition, 14(1), 1-18.

^[22] Van der Merwe, J., Brooks, N. E., & Myburgh, K. H. (2009). Three weeks of creatine monohydrate supplementation affects dihydrotestosterone to testosterone ratio in college-aged rugby players. Clinical Journal of Sport Medicine, 19(5), 399-404.

^[23] Ustuner, E. T. (2013). Cause of androgenic alopecia: Crux of the matter. Plastic and Reconstructive Surgery Global Open, 1(7).

^[24] Common questions and misconceptions about creatine …. https://jissn.biomedcentral.com/articles/10.1186/s12970-021-00412-w

^[25] Antonio, J., Candow, D. G., Forbes, S. C., Gualano, B., Jagim, A. R., Kreider, R. B., … & Ziegenfuss, T. N. (2021). Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show?. Journal of the International Society of Sports Nutrition, 18(1), 1-17.

^[26] Jagim, A. R., Stecker, R. A., Harty, P. S., Erickson, J. L., & Kerksick, C. M. (2018). Safety of creatine supplementation in active adolescents and youth: A brief review. Frontiers in nutrition, 5, 115.

^[27] Antonio, J., Candow, D. G., Forbes, S. C., Gualano, B., Jagim, A. R., Kreider, R. B., … & Ziegenfuss, T. N. (2021). Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show?. Journal of the International Society of Sports Nutrition, 18(1), 1-17.

^[28] Kreider, R. B., Kalman, D. S., Antonio, J., Ziegenfuss, T. N., Wildman, R., Collins, R., … & Lopez, H. L. (2017). International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. Journal of the International Society of Sports Nutrition, 14(1), 1-18.

^[29] Kreider, R. B., Kalman, D. S., Antonio, J., Ziegenfuss, T. N., Wildman, R., Collins, R., … & Lopez, H. L. (2017). International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. Journal of the International Society of Sports Nutrition, 14(1), 1-18.

^[30] Antonio, J., Candow, D. G., Forbes, S. C., Gualano, B., Jagim, A. R., Kreider, R. B., … & Ziegenfuss, T. N. (2021). Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show?. Journal of the International Society of Sports Nutrition, 18(1), 1-17.

^[31] Gualano, B., Macedo, A. R., Alves, C. R. R., Roschel, H., Benatti, F. B., Takayama, L., … & Pereira, R. M. R. (2014). Creatine supplementation and resistance training in vulnerable older women: a randomized double-blind placebo-controlled clinical trial. Experimental gerontology, 53, 7-15.

^[32] Rawson, E. S., & Clarkson, P. M. (2000). Acute creatine supplementation in older men. International journal of sports medicine, 21(01), 71-75.

^[33] Chilibeck, P. D., Chrusch, M. J., Chad, K. E., Davison, K. S., & Burke, D. G. (2005). Creatine monohydrate and resistance training increase bone mineral content and density in older men. Journal of Nutrition Health and Aging, 9(5), 352.

^[34] Candow, D. G., Little, J. P., Chilibeck, P. D., Abeysekara, S., Zello, G. A., Kazachkov, M., … & Yu, P. H. (2008). Low-dose creatine combined with protein during resistance training in older men. Medicine & Science in Sports & Exercise, 40(9), 1645-1652.

^[35] Kreider, R. B., Kalman, D. S., Antonio, J., Ziegenfuss, T. N., Wildman, R., Collins, R., … & Lopez, H. L. (2017). International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. Journal of the International Society of Sports Nutrition, 14(1), 1-18.

^[36] Riehemann, S., Volz, H. P., Wenda, B., Hübner, G., Rößger, G., Rzanny, R., & Sauer, H. (1999). Frontal lobe in vivo 31P‐MRS reveals gender differences in healthy controls, not in schizophrenics. NMR in Biomedicine: An International Journal Devoted to the Development and Application of Magnetic Resonance In Vivo, 12(8), 483-489.

^[37] Kalhan, S. C., Gruca, L., Marczewski, S., & Bennett, C. (2016). Whole body creatine and protein kinetics in healthy men and women: effects of creatine and amino acid supplementation. Amino acids, 48(3), 677-687.

^[38] Ellery, S. J., Walker, D. W., & Dickinson, H. (2016). Creatine for women: a review of the relationship between creatine and the reproductive cycle and female-specific benefits of creatine therapy. Amino Acids, 48(8), 1807-1817.

^[39] Mihic, S., MacDonald, J. R., McKenzie, S., & Tarnopolsky, M. A. (2000). Acute creatine loading increases fat-free mass, but does not affect blood pressure, plasma creatinine, or CK activity in men and women. Medicine and science in sports and exercise, 32(2), 291-296.

^[40] Antonio, J., Candow, D. G., Forbes, S. C., Gualano, B., Jagim, A. R., Kreider, R. B., … & Ziegenfuss, T. N. (2021). Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show?. Journal of the International Society of Sports Nutrition, 18(1), 1-17.