What is creatine? What is the role of supplementation?
Figure 1. Photo of creatine supplement from Optimum Nutrition
Creatine is a chemical substrate that can be found within the cells of our body. The role of creatine is to provide a short burst of energy that allow us to generate movement and strength. However, given that it has a short-lived nature, creatine is quickly broken down into creatinine and to be excreted into the urine. Creatinine, unlike creatine, is a toxic metabolite and it is often measured by medical doctors to determine kidney injury in the clinical setting. Muscular damage increases the level of creatinine and causes a condition call rhabdomyolysis, which can be fatal to our kidney function. Figure 2 below shows the synthetic and breakdown of creatine in a more detail and scientific fashion. As you can see, creatine can be phosphorylated (meaning adding on an ATP) in order for it to be stored as phosphocreatine within the skeletal muscle. Note that phosphocreatine is the only form of storage in our body and there are approximately 150 grams of PC at one point in time. Therefore, the goal of creatine supplementation is to allow our body to have optimal substrates to generate phosphocreatine to allow for optimal muscle strength.
Figure 3. Phosphocreatine, or creatine phosphate metabolism compare to other modes of metabolism. Note that creatine phosphate can be used in a short amount of time to create the maximal energy and power.
Is it worth it?
There is a meta-analysis and review published by Dr. Cooper and Dr. Jimenez from the University of Greenwich and Victoria University in the UK that sums up the recent scientific evidence of creatine supplementation. What they have found is that creatine has demonstrated neuromuscular performance enhancing properties on short duration, predominately in anaerobic and intermittent exercises, such as bodybilding and HIIT training. This is not surprising as we already know that creatine is the substrate for the generation of creatine phosphate, which can be stored within the body to create a short burst of energy. It appears that creatine supplementation facilitates the reuptake of calcium ions into the sacroplasmic reticulum to enhance musclar contraction, which resulted in a 20% increase in muscle contraction and effect size in one study. It also increases the maximum amount of weight lifted in those individuals by 13% with the use of creatine supplementation in a prolonged period of time. Regarding muscle hypertrophy, Cribb et al in 2007 demonstrated that by consuming 0.1g/kg/d of creatine, they have observed significant increase in lean body mass, fiber cross sectional area, and the amount of contractile protein in young athletes. This is signficant as there are no other enhancement products in the market except for anabolic steriod that has demonstrated similar efficacy. In addition, another group Burke et al also shows a significant increase in IGF1 level in young athletes who consumes approximately 60 days of creatine. IGF-1 level is associated with insulin signaling in our body, which is an anabolic hormone signaling pathway that can lead to muscle growth. However, there are many cancer that is associated with increase IGF1 level but there is no evidence linking the increase IGF1 level in potential causes of cancer in those population who takes creatine on a regular basis. In short, what we learn from these data is that creatine supplementation can be helpful in regards to gaining strength, muscle size, and increase lean body mass. However, we do not know the potential pitfall of using creatine daily as there are no sufficient data suggesting its harm.
From an economics perspective, the cost of creatine ranges from $17 USD to $50 USD for a month worth of supply. The market of supplementation remains approximately 32 billion USD. Unfortunately, it is not tightly regulated by the FDA. A lot of the current supplements have demonstrated toxic heavy metal and other contaminants that may potentially cause harm to our body, though this is not clearly investigated.
Benefits of creatine other than bodybuilding/ performance enhancement?
Interestingly, a case report in the Journal of American Gastroenterology, one of the most renown peer-reviewed journal in the field of GI, was published in December of 2016 which showed that dietary creatine hydrochloride may be a possible novel treatment for Crohn’s disease induced ileitis. Dr. David Lee and Dr. Abik Roy from Columbia University wrote a case study on a gentleman with marked reduction in ileal ulceration with creatine supplementation in 2016. In summary, this patient is a 33 year old male with medical history notable for CD presented to the hospital for a 2 year history of bloody vomiting and anal pain after the diagnosis of Crohn’s disease. A colonoscopy at that time showed progressive ileitis with >30% ulceration at his ileum. Due to his severe ileitis, the patient decided to initiate creatine hydrochloride supplementation for 6 months prior to starting his mesalmine regimen. The result suggests that there is a significant reduction in the ulceration of his ileum and a decrease in his inflammatory markers in the body at the end of his supplementation. This case report suggested that there might be a role of dietary creatine supplementation in patients with CD, however, it merely shows a correlation with dietary creatine as a potential cause of his improvement in symptoms. At this time, GI doctors do not recommend the initiation of creatine supplementation in patient without consulting their physicians.
Figure 4. Colonoscopy image demonstrating the effect of creatine supplementation in CD ileitis after 6 months of supplementation. Left: ulcer. Right: same segment without ulcer.
Potential harm from creatine supplementation?
There are numerous case reports that have demonstrated in selected individuals who have genetic kidney disease who progresses to renal failure secondary to creatine supplementation. However, in those studies that have demonstrated potential harm in the setting of creatine use, the authors cannot distinguish other confounding variables that potentially causes renal failure, leaving their conclusion not able to be adequately supported scientifically.
Interestingly, a few studies that have been performed in the past few year suggests that creatine supplementation does not impair kidney function in type 2 diabetic patients. Another paper published in 2013 by Lugaresi et al from University of Sao Paulo demonstrated that 12 week continuous use of creatine supplementation appears to be safe in healthy subjects. However, there are lack of evidence on long term use of creatine at this time.
Figure 5. Data demonstrating no difference in kidney function in both placebo vs creatine use groups.
- There are shown benefits of creatine supplementation in strength and performance enhancement.
- There is insufficient data regarding kidney impairment from creatine use. However, that does not exclude any harm from contaminant in creatine products.
- There are no strict regulation of creatine supplementation within the United States.
- One should be mindful that the supplementation market is a multi-billion dollar business.
Jeffrey Lei MSIV
University of Utah School of Medicine