Does Creatine Really Effect Your Kidneys?

Questions and concerns involving creatine supplementation and kidney damage/renal dysfunction are common. In terms of pervasive misinformation in the sport nutrition arena, the notion that creatine supplementation leads to kidney damage/renal dysfunction is perhaps second only to the myth that protein supplementation and high habitual protein intake causes kidney damage.

Today, after more than 20 years of research which demonstrates no adverse effects from recommended dosages of creatine supplements on kidney health, unfortunately, this concern still persists.

While the origin is unknown, the connection between creatine supplementation and kidney damage/renal dysfunction could be traced back to two things: a poor understanding of creatine and creatinine metabolism and a case study published in 1998.

Creatine Metabolism

Both creatine and phosphocreatine are degraded non-enzymatically to creatinine in skeletal muscle tissue.  Creatinine is exported to the blood, filtered through the kidney and excreted in the urine. Since the kidney filters creatinine, blood creatinine levels can be used as a proxy marker of kidney function.

One important point to keep in mind is that the amount of creatinine in the blood is related to muscle mass (i.e males have higher blood creatinine than females) and both dietary creatine and creatinine intake⁽¹⁾.

Creatine supplementation and creatine containing foods such as red meat increase both blood and urinary creatinine levels.

Although creatine isn’t normally present in urine, it can reach very high levels (>10g/day) during creatine supplementation⁽²⁾.

Interestingly, there appears to be an unsubstantiated perspective that if the kidneys are “forced” to excrete higher than normal levels of creatine or creatinine, then some sort of kidney “overload” will occur, causing kidney damage or dysfunction.

In reality, transient increases in blood or urinary creatine or creatinine due to creatine supplementation are unlikely to reflect a decrease in kidney function.

One important caveat is to remember to use caution when using blood creatinine and estimated creatinine clearance/glomerular filtration rate in people consuming a lot of meat or supplementing with creatine. 

A review investigating the safety of creatine supplementation found no increase in serum creatinine in 12 studies, 8 studies showed an increase that stayed within the normal range, and only 2 studies showed an increase above normal limits (although not different from the control group in one study)⁽³⁾.

The infamous case study of 1998

A young male who had kidney disease for 8 years had recently begun creatine supplementation (15 g/day for 7 days; followed by 2 g/day for 7 weeks). Based on enhanced blood levels of creatinine and subsequent estimate of calculated creatine clearance, his kidney health was presumed to be deteriorating, although he was otherwise in good health. He was encouraged to stop creatine supplementation⁽⁴⁾.

The authors of this case study ignored the fact that evidence already proven that blood and urine creatine levels can increase following ingestion of creatine containing food products, including creatine supplements.

They also ignored the inclusion of two investigations indicating that creatine supplementation did not negatively impact kidney function^(5,6).

In addition, they also failed to mention that the dosage utilized during the maintenance phase was only slightly higher than the daily creatine intake of a typical omnivore’s dietary intake.

For example, a large hamburger or steak per day contains about 0.7 g of creatine / 6 oz serving⁽⁷⁾.

In response to this case study, two separate teams of experts in creatine metabolism wrote letters to the editor of Lancet (the journal that published the case study)^(6,8), but unfortunately, the idea that creatine supplementation leads to kidney damage and/or dysfunction perpetuated and gained momentum throughout the coming years.

Relevant & Recent Evidence

There have been many experimental and controlled research trials investigating the effects of creatine supplementation on kidney function since this case study was reported in 1998^(9,10). 

Overall, the research indicates no adverse effects from consuming recommended doses of creatine supplements on kidney function.

Upon reviewing a small number of case studies which reported renal dysfunction in individuals supplementing with creatine, there are some crucial points to keep in mind.  Similar to the case report in 1998, there were many confounding variables (variables that influence other factors) in these other case reports.  

Such confounding variables found were:

• Medications
• Pre-existing kidney disease
• Concomitant supplement ingestion
• Inappropriate creatine dosages (e.g., 100x recommended dose)
• Anabolic androgenic steroid use

Survey data indicates that creatine supplementation usage ranges between 8-74% in athletes and other exercising individuals⁽¹¹⁾.

Even if we stay really the conservating, the low end of 8% of exercising individuals using creatine supplements represents thousands of exposures across several decades. If there was any link between creatine supplementation and kidney health, there would be a big increase in kidney damage/dysfunction in young, physically fit healthy individuals. 

Of course, no such evidence has been demonstrated since 1992 after seminal work was published on the benefits of creatine supplementation. In fact, after nearly 30 years of post-marketing surveillance, thousands of exposures, and multiple clinical trials, no such evidence exists.

Summary

In summary, experimental and controlled research indicates that creatine supplementation, when ingested at recommended dosages, does not result in kidney damage and/or renal dysfunction in healthy individuals.

References:
1.    Hultman, E., et al., Muscle creatine loading in men. J Appl Physiol (1985), 1996. 81(1): p. 232-7.
2.    Rawson, E.S., et al., Differential response of muscle phosphocreatine to creatine supplementation in young and old subjects. Acta Physiol Scand, 2002. 174(1): p. 57-65.
3.    Persky, A.M. and E.S. Rawson, Safety of creatine supplementation. Subcell Biochem, 2007. 46: p. 275-89.
4.    Pritchard, N.R. and P.A. Kalra, Renal dysfunction accompanying oral creatine supplements. Lancet, 1998. 351(9111): p. 1252-3.
5.    Poortmans, J.R., et al., Effect of short-term creatine supplementation on renal responses in men. Eur J Appl Physiol Occup Physiol, 1997. 76(6): p. 566-7.
6.    Greenhaff, P., Renal dysfunction accompanying oral creatine supplements. Lancet, 1998. 352(9123): p. 233-4.
7.    ES., R., The safety and efficacy of creatine monohydrate supplementation: What we have learned from the past 25 years of research. Gatorade Sports Science Exchange., 2018. 9: p. 1-6.
8.    Poortmans, J.R. and M. Francaux, Renal dysfunction accompanying oral creatine supplements. Lancet, 1998. 352(9123): p. 234.
9.    de Souza E Silva A; Pertille, A.R.B., C. G.; Aparecida de Oliveira Silva, J; de Jesus, D. V.; Ribeiro, A G S V; Baganha, R. J.; de Oliveira, J. J., Effects of Creatine Supplementation on Renal Function: A Systematic Review and Meta-Analysis. J. Ren. Nutr., 2019. 29: p. 480-489.
10.    Gualano, B., et al., In sickness and in health: the widespread application of creatine supplementation. Amino Acids, 2012. 43(2): p. 519-29.
11.    Rawson, E.S., P.M. Clarkson, and M.A. Tarnopolsky, Perspectives on Exertional Rhabdomyolysis. Sports Med, 2017. 47(Suppl 1): p. 33-49.