Creatine is a derivative of the amino acids glycine, arginine, and methionine that is made in the body and obtained through food. Creatine is used as part of a reserve energy system which helps cells meet their real-time energy needs, and stave off fatigue when working at maximum capacity. Muscles have the largest creatine stores. Creatine supplementation is used in combination with strength training to boost muscle gains and is generally safe. Creatine stores in the brain may allow for more flexible energy utilization. However, the ability of creatine supplementation to influence cognition appears limited.
Observational studies suggest that adequate dietary intake of creatine promotes cognitive performance, while clinical studies suggest that the potential impact of additional creatine supplementation depends on baseline brain metabolic status and cognitive task complexity. Trials to date have not shown a protective effect for neurodegenerative disease. Our search identified:
Higher dietary intake of creatine, 1 gram or more per day, has been associated with better performance on cognitive tests in people over age 60 [1; 2]. This level of intake is in line with the level needed to maintain creatine stores in muscle. However, the level of creatine in the brain is tightly regulated, such that brain creatine stores are less likely to change in response to fluctuations in dietary levels compared to muscle stores [3; 4]. For example, vegetarians tend to have lower intramuscular levels, but normal brain creatine levels [4]. Since the loss of muscle tissue in late life is itself a risk factor for dementia [5], observed associations between creatine levels and cognition could be a byproduct of better preservation of muscle, though this has not been tested directly. High dose creatine loading has been used as a reliable way of boosting up muscle creatine stores [6]. The impact of similar creatine loading paradigms on brain stores has been less consistent, only modestly boosting brain levels in those with low baseline creatine [3]. Consistent with this, the impact of creatine supplementation on cognition has been mixed in clinical trials [7]. Creatine has been more likely to show benefit when baseline levels are lower and energy demand is increased, such as in older adults, following sleep deprivation, and when performing complex cognitive tasks at a high rate of speed [8; 9]. Similar to how it is used in muscle, higher levels of creatine may delay the onset of fatigue in brain cells.
Due to its potential role in promoting more efficient energy utilization in the brain, creatine was expected to help maintain cognitive function in patients with neurodegenerative disease [10]. However, no clear benefits have been observed in clinical trials conducted to date in patients with Parkinson’s disease, Huntington’s disease, or amyotrophic lateral sclerosis (ALS) [11; 12; 13]. A study testing creatine supplementation in Alzheimer’s disease patients is ongoing [10].
Creatine has shown good safety in hundreds of clinical studies, the vast majority of which tested creatine for muscle-related outcomes. The most reported side effect is a small weight gain, primarily in men, during a high dose loading phase that is related to increased water retention in the muscle [14]. Gastrointestinal effects such as nausea or bloating have been reported, but incidence rates in clinical studies are similar to control groups [15]. Rare case reports of liver or kidney injury in young men appear to be related to the use of creatine in conjunction with cocktails of multiple other supplements and/or at extremely high doses [16]. Observational studies suggest that consumption of ≥ 2 grams of creatine per day is not associated with elevated risk for liver or kidney problems [16; 17]. However, caution is still warranted in individuals with reduced kidney function.
NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.
Creatine can be obtained through food, with typical consumption around 1-2 grams per day. Enriched dietary sources include red meat, poultry, and seafood. There is currently no clinically established dose of creatine for optimizing brain stores or use in neurological disorders. The most widely used and tested form of creatine supplement for muscles is creatine monohydrate, typically taken in the form of an oral powder [14]. Traditional doses for creatine monohydrate to build muscle creatine stores include a loading phase of 20 grams per day for 5-7 days followed by a maintenance phase of 5 grams per day. Studies suggest that brain creatine stores are less responsive to supplementation and may require higher doses (i.e. 20 grams per day), but this has not been clinically verified. Excessive use of creatine supplements may decrease the body’s endogenous production of creatine, such that supplementation becomes less effective over time [8].
Full scientific report (PDF) on Cognitive Vitality Reports
For more information on the history, use, and safety see Drugs.com