MIHIC, S., J. R. MACDONALD, S. MCKENZIE, and M. A. TARNOPOLSKY. Acute creatine loading increases fat-free mass but does not affect blood pressure, plasma creatinine, or CK activity in men and women. Med. Sci. Sports Exerc., Vol. 32, No. 2, pp. 291-296, 2000. Creatine monohydrate (CrM) administration may enhance high intensity exercise performance and increase body mass, yet few studies have examined for potential adverse effects, and no studies have directly considered potential gender differences.
Purpose: The purpose of this study was to examine the effect of acute creatine supplementation upon total and lean mass and to determine potential side effects in both men and women.
Methods: The effect of acute CrM (20 g·d-1 × 5 d) administration upon systolic, diastolic, and mean BP, plasma creatinine, plasma CK activity, and body composition was examined in 15 men and 15 women in a randomized, double-blind experiment. Additionally, ischemic isometric handgrip strength was measured before and after CrM or placebo (PL).
Results: CrM did not affect blood pressure, plasma creatinine, estimated creatinine clearance, plasma CK activity, or handgrip strength (P > 0.05). In contrast, CrM significantly increased fat-free mass (FFM) and total body mass (P < 0.05) as compared with PL, with no changes in body fat. The observed mass changes were greater for men versus women.
Conclusions: These findings suggest that acute CrM administration does not affect blood pressure, renal function, or plasma CK activity, but increases FFM. The effect of CrM upon FFM may be greater in men as compared with that in women.
The use of creatine monohydrate (CrM) as a potential ergogenic agent has been examined extensively (1-3,7-9,12,13,20,23,25). Studies have demonstrated an increase in intra-muscular total creatine (TCr) and phosphocreatine (PCr) (13,14,16), while others have found enhanced athletic performance (2,3,8,12,20). In addition to functioning as a temporal energy buffer (14,35), acute CrM administration may also increase total body mass (TBM) (1,2,8,13,22). These factors may contribute to the potential utility of CrM as an ergogenic agent in sporting events requiring a high energy output and/or a high body mass. These properties also predict that CrM could be used as an adjunctive treatment in patients with muscle wasting (i.e., neuromuscular disease, AIDS, postsurgery).
If CrM is to be useful as an ergogenic or therapeutic strategy, it is important to determine whether there are gender specific differences in the response to its administration. There is evidence that intra-muscular TCr concentration relative to fat-free tissue is higher in women than men (10). If TCr is higher in women, there may be an attenuated ability to derive therapeutic benefit from CrM administration (14). The mechanism(s) behind the increase in body mass in response to CrM are unclear; however, it is probable that in the early phase this is caused by an increase in intra-cellular water retention (14,16,35). A confounding variable in many studies is the super-imposition of exercise during the acute CrM loading phase which makes it difficult to factor out a potential interaction between CrM and exercise. For this reason, we chose to study the effects of acute CrM administration per se upon body mass accretion without the co-intervention of exercise training.
In spite of the extensive use of CrM supplementation for performance enhancement, there have been few studies examining or reporting potential side effects. Several anecdotal reports of elevated blood pressure and plasma creatine kinase (CK) activity have appeared on the internet and in lay publications. Some anecdotes have suggested that three recent hyperthermia/dehydration related deaths in college athletes were linked to the simultaneous use of CrM; however, a review by the U.S. Center for Disease Control concluded that CrM ingestion was not a contributing factor (17). A recent case report suggested that CrM administration was responsible for reversible renal deterioration in a young male with pre-existing focal segmental glomerulosclerosis (28). In contrast to these anecdotal reports, there have been few side effects reported in both acute/short-term (5-28 d) (1-3,7,8,12,14,16,20,23,25) and long-term protocols (>1 yr) (34). Given the extensive use of CrM among athletes and the potential for important therapeutic uses in patients, it is important that studies examine the potential side effects in randomized double-blind trials.
An ergogenic effect of CrM administration has been demonstrated in short duration high-intensity exercise (2,3,8,12). These effects have been related to increased PCr availability and/or the rate of PCr re-synthesis during prolonged repeated muscle contractions (13). In the current study an ischemic exercise protocol was used to eliminate the possibility of PCr re-synthesis during the intermittent recovery phase. This technique allowed the separation of the aforementioned mechanistic possibilities.
This study was designed to address two principal questions with respect to acute CrM administration: 1) Are there effects upon blood pressure, renal function (as assessed by plasma creatinine and estimated creatinine clearance), and plasma CK activity?; and 2) Do men and women have similar increases in TBM and what is the compositional increase? A secondary objective was to examine whether an ergogenic effect of CrM administration would be apparent under ischemic conditions. It was hypothesized that 20 g·d-1 of CrM over 5 d would not have an effect upon blood pressure, estimated creatinine clearance, or plasma CK activity but would increase FFM and TBM in both men and women.