Creatine Supplements

Harmful or Possibly Beneficial?

Why Creatine?

• Creatine is being used more and more by all types of athletes all over the world.

• One question that always comes up is whether or not supplemental creatine has any negative effect on organ systems (especially the kidneys.)

• Many studies have been done and we will analyze some of the results

What does creatine do?• Creatine undergoes

phosphorylation by CPK to become phosphocreatine.

• Once this happens phosphocreatine (PCr) donates a phosphate group to ADP to create ATP.

• Phsophocreatine is a battery that can restore ATP when needed

• PCr hydrolysis provides energy for short bursts of explosive energy production

• This quick transition is recorded in the studies as “explosive energy” or “short-duration, high intensity energy”

• Creatine supplements are recorded to maximize PCr content in muscles by 20% which converts to about 85-105 mmol/kg dry weight (Febbraio, M.A., T.R. Flanagan).

• They have also been shown to increase water weight of the user, but according to table 1 this is mostly due to the fact that as new muscle is built their cells are made up of about 60-70% water.

Variable Placebo Placebo Creatine Creatine

Day 0 63 0 63

Body Mass (kg) 71.9 ± 7.3 72.6 ± 6.7 69.8 ± 8.9 71.8 ± 9.0*Total Body Water (kg) 39.6 ± 2.5 40.1 ± 2.2 38.0 ± 3.9 39.1 ± 4.1*Extracellular water (%) 25.9 ± 1.3 26.1 ± 2.0 25.4 ± 1.3 25.5 ± 1.3Intracellular water (%) 29.5 ± 1.2 29.3 ± 1.3 29.2 ± 1.2 29.3 ± 0.9

* Significantly different (p< 0.05) between placebo group and creatine supplementation when comparing the changes between 0 and 63 days.

Table 1. Effect of 9 weeks of creatine supplementation on body composition estimated by bio-impedance in trained volunteers. Values are means ± SD. (Poortmans, J.R., Francaux M.)

Effects on the Kidneys

• Because the end product of creatine breakdown is creatinine, the serum creatinine levels increase with supplementation.

• In a study done by Crim et al. healthy young men were given .23 g/day for 9 days which they were training on a treadmill then 10 g/day for ten days which they rested.

• Creatinine clearance increased by 10-30%.

• There was no change in urea clearance to indicate changes in renal function

Dosage (g/day)

Duration (weeks)

Urea Excretion (g/24h)

Urea Excretion (g/24h)

Authors

baseline creatine

5 10 18.82 ± 2.27 19.94 ± 2.10 Vandenberghe et al.

20 1 12.6 ± 2.84 10.33 ± 2.09 Poortmans & Francaux

3 9 12.6 ± 2.84 10.83 ± 6.27 Poortmans & Francaux

<10 8-260 12.3 ± 4.6 Poortmans & Francaux

Table 2. Effect of creatine supplementation on urea excretion in urine

• Due to the fact that there is no significant data that shows a decreased urea production in the urine, creatine seems to not have any inhibitory effect on the liver.

• Many of the studies I mentioned earlier all point to the safety of creatine as a supplement. Further studies include the testing of creatine over long, medium, and short amounts of time.

Short term Creatine trialPoortmans JR, Auquier H, Renaut V, et al. • One trial measured various renal markers over a short term

creatine supplementation. • Five men in good health (age 25.1 ± 2.7 years) received 20 g/day for

5 days (this is the dose that the back of the supplement bottles suggest).

• After two weeks of no supplements, the men were given a placebo in the same dosage regimen.

• There were no changes in serum creatinine, urine creatinine, and clearance creatinine (measured by a 24 hour urine collection).

• There was no statistical significance in the amount of total protein or albumin in the urine between the creatine users and the placebo users.

• From this trial and others which show no increase in urine creatinine it seems to show that short term creatine loading does not affect the kidneys in an inhibitory regard.

Medium term Creatine trial Poortmans JR, Francaux M

• 20 healthy men (21 ± 1.7 years) were randomized to receive a placebo or a 21 g/day loading dose for five days followed by a maintenance dose of 3 g/day for 58 days (this is the dosage suggested for long term supplementation on the back of the bottles).

• Once again there were no significant differences found in creatinine clearance, urea clearance, or albumin excretion rate between the placebo and creatine group.

• This trial shows that maintenance doses of 3 g/day (which are recommended by the manufacturers) taken for no longer than two months will not affect renal function adversely.

Long term Creatine trialPoortmans JR, Francaux M

• A longer trial involved doses of maintenance creatine supplementation over varied amounts of time from 10 months to 5 years.

• The doses ranged from 2 to 30 g/day.• The data on this trial is a bit scattered because of the

duration of the test but overall the authors found that long term use of creatine did not alter renal markers suck as urine output, urea clearance, urine albumin, and creatinine clearance.

• This trial, in comparison with others, has a major flaw in that many variables, including time and dose of creatine supplementation, were not standardized.

Mean values (± SEM) of plasma and urine contents of the control and creatine groups. From: POORTMANS: Med Sci Sports Exerc, Volume 31(8).August 1999.1108-1110 (http://www.ncbi.nlm.nih.gov/pubmed/10449011)

Major flaws with these studies• The patients in these trials were given amounts of

creatine that had been accurately measured and accurately supplemented.

• Because it is a supplement, the FDA does not have to approve or verify the dosage amounts on the back of the manufacturers bottles. These amounts could be grossly underestimated causing a potential overdose.

• Furthermore, most athletes that are looking for an extra edge will abuse these drugs profusely and there are no studies (and none can be done ethically) that show the side effects of purposely abusing and overdosing on creatine supplements.

The two case studies that break all of the rules.

• Case 1 : A 20 year old man presents himself at the hospital with interstitial nephritis and focal tubular injury.

• He had been taking creatine 20 grams daily. – After a month he developed nausea, vomiting, bilateral

flank pain, dehydration, proteinuria, hematuria

– Creatinine on admission was 1.4 which increased to 2.3 mg/dL

– In the hospital, off creatine, his health improved

Koshy KM, Griswold E, Schneeberger EE.

• Case 2: 25 year old man with a history of FSGS with frequently relapsing steroid responsive nephrotic syndrome. Maintained for five years on cyclosporine– He started creatine supplements 20 g/day for one

week and 2 g/day after that – Serum creatinine of 1.1 – 1.2 mg/dL, CrCl of 91-141

mL/min– Serum creatinine increased to 1.8 mg/dL– One month later the creatinine was 2.0 (CrCl 54

ml/min)

• One month after stopping the supplement, the CrCl returned to 115 mL/min.

Pritchard NR, Kalra PA

Possible benefits of creatine supplementation

• Peter Klivenyi, Robert Ferrante, Russell T. Matthews et al. have shown potential uses of creatine in patients with ALS.

• Trials included G93A mice which are genetically mutated to acquire ALS. – 1% creatine survival extended by 13 days– 2% creatine survival extended by 26 days

• Mice fed these supplements were much more active in their exercise trials. Creatine seemed to have neuroprotective effects on the mice

Overall Message• Although the media loves to make a villain out of all

performance enhancing drugs, creatine has not been shown to cause any significant renal damage except in rare occasions where the patients illness could have been ignited from some other source. This is the moral for those with pre-existing renal disease : do not take creatine. There has been enough evidence to show that people with damaged kidneys will not be able to control the increased serum creatinine and they will likely fall into acute renal failure. Creatine is a safe and effective drug as long as it is used appropriately and it not abused.