Scientific Research

The Potential Medicinal Uses of Creatine
Jeffrey R. Stout, PhD, FACSM, CSCS*DIntroduction
In skeletal muscle, creatine (Cr) is primarily stored as free Cr and phosphocreatine (PCr), and is found naturally in foods such as meat. Phosphocreatine is the primary fuel reserve for the resynthesis of adenosine triphosphate (ATP) during anaerobic exercise. Therefore, rapid depletion of muscle PCr is believed to be a limiting factor when performing maximal anaerobic work. In healthy subjects, several studies have demonstrated ergogenic benefits from acute Cr supplementation on strength, running, cycling, and jumping. Furthermore, recent studies have also demonstrated that Cr supplementation during resistance training resulted in greater increases in fat-free mass (FFM), muscular strength, and training volume load when compared to resistance training alone. Possible mechanisms responsible for the effects of Cr supplementation on body composition and strength include: 1) a significant increase in PCr content, which would allow for greater total training volume and consequently, a greater training stimulus, and/or 2) a Cr driven increase in protein synthesis.

Neuromuscular Disorders
Within the last several years, Cr supplementation has been explored as a potential therapeutic intervention for various neuromuscular and neurodegenerative disorders because skeletal muscle PCr concentrations are compromised in many of these conditions. Recently, Canadian scientists demonstrated that short-term (10 days) Cr supplementation significantly increased strength and total body mass in patients with a variety of neuromuscular diseases, including mitochondrial cytopathies, dystrophies/congenital myopathies, and polymyositis. Also, 8 weeks of creatine supplementation in patients with various neuromuscular dystrophies (e.g., facioscapulohumeral dystrophy, Becker dystrophy, Duchenne dystrophy, sarcoglycan-deficient limb girdle muscular dystrophy) produced a moderate but significant improvement in muscle strength and daily-life activities. More recently, researchers in the United States conducted a 15-week resistance exercise and Cr supplementation investigation using a subject with myasthenia gravis (MG). Patients with MG typically exhibit skeletal muscle wasting, neuromuscular fatigue, and weakness. These symptoms may be caused by a functional blocking or loss of postsynaptic acetylcholine receptors at the neuromuscular junction, as well as a decreased PCr content in skeletal muscle. Following Cr supplementation (5 grams/day) and resistance training, the MG patient increased his body weight (7 %), FFM (4%), total body training volume (26%), and leg strength (25%).

Myocardial Disease
Cr supplementation has also been demonstrated to have a positive effect on exercise tolerance in chronic heart failure (CHF) patients. Reduced Cr availability has been implicated in the metabolic abnormalities of failing myocardial tissue. Cr supplementation has been shown to attenuate pharmacologically-induced metabolic stress in rat myocardium, despite the fact that the contribution of PCr to energy delivery in myocardial tissue is normally negligible. Recently, scientists in Sweden and the United Kingdom examined the effects of Cr supplementation for one week in patients with CHF. Patients with CHF typically exhibit depressed cardiac and skeletal muscle Cr levels, with symptoms of limited physical endurance and skeletal muscle strength. The results in both studies demonstrated significant increases in skeletal muscle endurance, strength, Cr (17%) and PCr (12%) levels. However, in this instance, the Cr supplementation did not improve heart function.

Traumatic Brain Injury and Neurologic Disease
There has been an enormous amount of research conducted on the treatment of traumatic brain injury (TBI), which affects approximately 7 million people annually in North America. This includes athletes participating in sports such as football, boxing, hockey, and soccer, where participants may be exposed to repeated concussions. While little can be done medicinally to prevent such an injury, it is the secondary effects of the trauma following TBI that are often devastating. These effects include cellular damage that results in mitochondrial dysfunction associated with disruption in cellular calcium homeostasis, which is critically related to ATP use and synthesis. Together, normal operation of these processes carry paramount importance for proper brain function.

Since creatine has been shown in numerous instances to support levels of ATP, research is underway to determine its potential supportive role following TBI. While studies utilizing creatine following brain injury are limited, they are nevertheless promising. For instance, Canadian scientists discovered that chronic administration of creatine prevented cortical damage by as much as 36% in mice and 50% in rats following brain tissue damage. The researchers concluded that prevention was related to creatine-induced maintenance of mitochondrial bioenergetics.

In a related study involving the effects of creatine on neurological disorders, rats with a chemically induced condition that mimicked Huntington’s disease were administered creatine for a two week period. Following supplementation, the rats demonstrated significant neuroprotection, preservation of ATP and PCr, and reduced oxidative stress. As a result, research is underway to investigate the effects of creatine on patients with Lou Gehrig’s disease, Parkinson’s disease, and Alzheimer’s. Because all of these conditions involve impaired energy production in the brain that leads to cellular damage, creatine provides encouragement towards an improved and prolonged life for patients stricken with such diseases.

Diabetes
Creatine has also been shown to reduce circulating blood sugar concentrations 60 to 120 minutes after a single 3 gram oral dose in insulin-dependent (Type I) diabetics. These changes were observed without alterations in serum insulin or changes in blood sugar in age-matched, non-diabetic controls. This suggest that creatine may enhance glucose disposal and/or reduce liver glucose production in hyperglycemic Type I diabetics.

Summary
While creatine has definitely left its mark on the athletic and fitness worlds, the coming years may find creatine launching itself into arenas far more important than those that reward strength and speed. Whether it’s the training table or hospital bed, creatine is rapidly becoming a safe, effective supplement for an incredible array of applications. Without question, athletes will continue to use creatine to improve advanced function; however, it is now possible to visualize creatine as instrumental in simply promoting function in those with delicate health. Weakness and poor endurance are hallmarks of many disease processes, and to date there exist few medicinal choices for improving these conditions. Since creatine has already proven itself superior in these areas athletically, it will only be fitting to find it as a preeminent topic of future medical research.