creatine research

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Ann Pharmacother. 2005 Jun;39(6):1093-6. Epub 2005 May 10.

The effect of creatine intake on renal function.

OBJECTIVE: To examine the effect of creatine supplementation on renal function and estimates of creatinine clearance. DATA SOURCES: A MEDLINE search was conducted (1966-September 2004) using the key terms creatine, creatinine, kidney function tests, drug toxicity, and exercise. Relevant articles were cross-referenced to screen for additional information. DATA SYNTHESIS: Supplementation with creatine, an unregulated dietary substance, is increasingly common in young athletes. To date, few studies have evaluated the impact of creatine on renal function and estimates of creatinine clearance. Because creatine is converted to creatinine in the body, supplementation with large doses of creatine may falsely elevate creatinine concentrations. Five studies have reported measures of renal function after acute creatine ingestion and 4 after chronic ingestion. All of these studies were completed in young healthy populations. Following acute ingestion (4-5 days) of large amounts of creatine, creatinine concentrations increased slightly, but not to a clinically significant concentration. Creatinine is also only minimally affected by longer creatine supplementation (up to 5.6 y).

CONCLUSIONS: Creatine supplementation minimally impacts creatinine concentrations and renal function in young healthy adults. Although creatinine concentrations may increase after long periods of creatine supplementation, the increase is extremely limited and unlikely to affect estimates of creatinine clearance and subsequent dosage adjustments. Further studies are required in the elderly and patients with renal insufficiency.
 
Nutrition. 2004 Jul-Aug;20(7-8):609-14.

Scientific basis and practical aspects of creatine supplementation for athletes.

Volek JS, Rawson ES.

Department of Kinesiology, University of Connecticut, Storrs, Connecticut 06269, USA. jeff.volek@uconn.edu

A large number of studies have been published on creatine supplementation over the last decade. Many studies show that creatine supplementation in conjunction with resistance training augments gains in muscle strength and size. The underlying physiological mechanism(s) to explain this ergogenic effect remain unclear. Increases in muscle fiber hypertrophy and myosin heavy chain expression have been observed with creatine supplementation. Creatine supplementation increases acute weightlifting performance and training volume, which may allow for greater overload and adaptations to training. Creatine supplementation may also induce a cellular swelling in muscle cells, which in turn may affect carbohydrate and protein metabolism. Several studies point to the conclusion that elevated intramuscular creatine can enhance glycogen levels but an effect on protein synthesis/degradation has not been consistently detected. As expected there is a distribution of responses to creatine supplementation that can be largely explained by the degree of creatine uptake into muscle. Thus, there is wide interest in methods to maximize muscle creatine levels. A carbohydrate or carbohydrate/protein-induced insulin response appears to benefit creatine uptake.

In summary, the predominance of research indicates that creatine supplementation represents a safe, effective, and legal method to enhance muscle size and strength responses to resistance training.
 
J Sports Sci. 2004 Sep;22(9):851-7.

The creatine content of Creatine Serum and the change in the plasma concentration with ingestion of a single dose.

Harris RC, Almada AL, Harris DB, Dunnett M, Hespel P.

School of Sports, Exercise and Health Sciences, University College Chichester, College Lane, Chichester PO19 6PE, UK. rharris@ucc.ac.uk

Three samples of Creatine Serum ATP Advantage from Muscle Marketing USA, Inc. were assayed for creatine by two different techniques by four independent laboratories, and for creatinine by two different techniques by two laboratories. A further sample was assayed for phosphorylcreatine. Dry weight and total nitrogen were also analysed. Six male volunteers ingested in random order, over 3 weeks: (A) water; (B) 2.5 g creatine monohydrate (Cr.H2O) in solution; and (C) 5 ml Creatine Serum (reportedly containing an equivalent amount of Cr.H2O). Blood samples were collected before and up to 8 h after each treatment and plasma was analysed for creatine and creatinine. Eight-hour urine samples were analysed for creatine. Ingestion of 2.5 g creatine monohydrate in solution resulted in a significant increase in plasma creatine (from 59.1+/-11.8 micromol.l(-1) to 245.3+/-74.6 microM micromol.l(-1); mean+/-s) and urinary creatine excretion. No increase in plasma or urinary creatine or creatinine was found on ingestion of Creatine Serum or water. Analysis showed 5 ml of Creatine Serum to contain <10 mg Cr.H2O and approximately 90 mg creatinine. Phosphorylcreatine was not detectable and only a trace amount of phosphorous was present. Total nitrogen analysis ruled out significant amounts of other forms of creatine.

We conclude that the trace amounts of creatine in the product would be too little to affect the muscle content even with multiple dosing.
 
J Appl Physiol. 1996 Jul;81(1):232-7.

Muscle creatine loading in men.

Hultman E, Soderlund K, Timmons JA, Cederblad G, Greenhaff PL.

Department of Physiology and Pharmacology, University Medical School, Queen's Medical Centre, Nottingham, United Kingdom.

The effect of dietary creatine and supplementation on skeletal muscle creatine accumulation and subsequent degradation and on urinary creatinine excretion was investigated in 31 male subjects who ingested creatine in different quantities over varying time periods. Muscle total creatine concentration increased by approximately 20% after 6 days of creatine supplementation at a rate of 20 g/day. This elevated concentration was maintained when supplementation was continued at a rate of 2 g/day for a further 30 days. In the absence of 2 g/day supplementation, total creatine concentration gradually declined, such that 30 days after the cessation of supplementation the concentration was no different from the presupplementation value. During this period, urinary creatinine excretion was correspondingly increased. A similar, but more gradual, 20% increase in muscle total creatine concentration was observed over a period of 28 days when supplementation was undertaken at a rate of 3 g/day.

In conclusion, a rapid way to "creatine load" human skeletal muscle is to ingest 20 g of creatine for 6 days. This elevated tissue concentration can then be maintained by ingestion of 2 g/day thereafter. The ingestion of 3 g creatine/day is in the long term likely to be as effective at raising tissue levels as this higher dose.
 
J Appl Physiol Vol. 89, Issue 3, 1165-1171, September 2000

Protein- and carbohydrate-induced augmentation of whole body creatine retention in humans

This study investigated the effect of creatine supplementation in conjunction with protein and/or carbohydrate (CHO) ingestion on plasma creatine and serum insulin concentrations and whole body creatine retention. Twelve men consumed 4 × 5 g of creatine on four occasions in combination with 1) 5 g of CHO, 2) 50 g of protein and 47 g of CHO, 3) 96 g of CHO, or 4) 50 g of CHO. The increase in serum insulin was no different when the protein-CHO and high-CHO treatments were compared, but both were greater than the response recorded for the low-CHO treatment (both P < 0.05). As a consequence, body creatine retention was augmented by ~25% for protein-CHO and high-CHO treatments compared with placebo treatment. The areas under creatine- and insulin-time curves were related during the first oral challenge (r = 0.920, P < 0.05) but not after the fourth (r = 0.342).

It is concluded, first, that the ingestion of creatine in conjunction with ~50 g of protein and CHO is as effective at potentiating insulin release and creatine retention as ingesting creatine in combination with almost 100 g of CHO. Second, the stimulatory effect of insulin on creatine disposal was diminished within the initial 24 h of supplementation.
 
J Herb Pharmacother. 2004;4(1):1-7.

Effects of creatine supplementation on renal function.

Creatine is a popular supplement used by athletes in an effort to increase muscle performance. The purpose of this review was to assess the literature evaluating the effects of creatine supplementation on renal function. A PubMed search was conducted to identify relevant articles using the keywords, creatine, supplementation, supplements, renal dysfunction, ergogenic aid and renal function. Twelve pertinent articles and case reports were identified. According to the existing literature, creatine supplementation appears safe when used by healthy adults at the recommended loading (20 gm/day for five days) and maintenance doses (</=3 gm/day). In people with a history of renal disease or those taking nephrotoxic medications, creatine may be associated with an increased risk of renal dysfunction. One case report of acute renal failure was reported in a 20-year-old man taking 20 gm/day of creatine for a period of four weeks. There are few trials investigating the long-term use of creatine supplementation in doses exceeding 10 gm/day. Furthermore, the safety of creatine in children and adolescents has not been established. Since creatine supplementation may increase creatinine levels, it may act as a false indicator of renal dysfunction. Future studies should include renal function markers other than serum creatinine and creatinine clearance.
 
Curr Sports Med Rep. 2002 Apr;1(2):103-6.

Effects of creatine use on the athlete's kidney.

With regard to athletes attempting to improve their performance, at the present time creatine monohydrate is clearly the most widely used dietary supplement or ergogenic aid. Loading doses as high as 20 g/d are typical among athletes. The majority (> 90%) of the creatine ingested is removed from the plasma by the kidney and excreted in the urine. Despite relatively few isolated reports of renal dysfunction in persons taking creatine, the studies completed to date suggest that in normal healthy individuals the kidneys are able to excrete creatine, and its end product creatinine, in a manner that does not adversely alter renal function. This situation would be predicted to be different in persons with impaired glomerular filtration or inherent renal disease. The question of whether long-term creatine supplementation (ie, months to years) has any deleterious affects on renal structure or function can not be answered at this time. The limited number of studies that have addressed the issue of the chronic use of creatine have not seen remarkable changes in renal function. However, physicians should be aware that the safety of long-term creatine supplementation, in regard to the effects on the kidneys, cannot be guaranteed. More information is needed on possible changes in blood pressure, protein/albumin excretion, and glomerular filtration in athletes who are habitual users of this compound.
 
Med Sci Sports Exerc. 1999 Aug;31(8):1108-10.

Long-term oral creatine supplementation does not impair renal function in healthy athletes.

PURPOSE: Oral creatine supplementation is widely used in sportsmen and women. Side effects have been postulated, but no thorough investigations have been conducted to support these assertions. It is important to know whether long-term oral creatine supplementation has any detrimental effects on kidney function in healthy population. METHODS: Creatinine, urea, and plasma albumin clearances have been determined in oral creatine consumers (10 months to 5 yr) and in a control group. RESULTS: There were no statistical differences between the control group and the creatine consumer group for plasma contents and urine excretion rates for creatinine, urea, and albumin. Clearance of these compounds did not differ between the two groups. Thus, glomerular filtration rate, tubular reabsorption, and glomerular membrane permeability were normal in both groups.

CONCLUSIONS: Neither short-term, medium-term, nor long-term oral creatine supplements induce detrimental effects on the kidney of healthy individuals.
 
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