Creatine is a naturally occurring compound stored primarily in skeletal muscle, where it plays a critical role in regenerating adenosine triphosphate (ATP), the primary energy currency of cells, during high-intensity, short-duration activities. Synthesized in the liver, kidneys, and pancreas from arginine and glycine, creatine is transported into cells via the Na+/Cl– dependent creatine transporter (CRT) and converted to phosphocreatine (PCr), a high-energy compound that rapidly replenishes ATP during periods of intense energy demand. This tightly regulated system ensures energy homeostasis, supporting both physical performance and neurological function. Recognized as one of the most thoroughly researched ergogenic aids, creatine also has a well established safety profile when consumed within recommended dosages. While traditionally valued for its performance enhancing benefits, emerging research suggests that creatine’s applications may extend beyond athletic performance to include neuroprotection, metabolic regulation and healthy aging. This article builds upon these well established ergogenic benefits of creatine while exploring its broader physiological, metabolic and neurological implications for health and disease prevention.

   When considering the addition of any new supplement to a health regimen, the first and most important question should always be: “Is it safe?” In scientific research, one of the key factors in determining the reliability of a study’s findings is its statistical power. Essentially, whether the study included a sufficient number of participants to detect meaningful effects. Studies that are underpowered, or too small in scale, are often considered preliminary and require further investigation to confirm their conclusions. Fortunately, creatine is one of the most extensively researched supplements available, and the consensus in the scientific literature is clear: it is safe for healthy individuals. Furthermore, its safety profile has been confirmed across a wide range of populations, dosages, and durations. With a strength of evidence (SOE) score of 2, creatine is widely considered among the safest supplements available. This is particularly significant as emerging research continues to reveal additional benefits of creatine beyond athletic performance, including the previously mentioned promising effects on cognitive function, neuroprotection and overall cellular health, especially with long term use and higher dosages.

   When creatine monohydrate is ingested, it is absorbed through the small intestine into the bloodstream and transported to tissues with high energy demands, primarily skeletal muscle and the brain. This transport is mediated by the CRT, which facilitates the uptake of creatine into cells. Once inside the cell, creatine is phosphorylated by the enzyme creatine kinase (CK) to form PCr, a high-energy compound. Phosphocreatine then serves as a rapid energy reserve, donating a phosphate group to regenerate ATP during short bursts of high-intensity activity. This PCr/CK system functions as a critical energy buffer, helping to maintain cellular energy balance, particularly during periods of intense physical exertion or cognitive stress.

   To realize the full benefits of creatine supplementation, it's essential to begin with a clearly defined strategy tailored to individual goals. A personalized approach enables evidence-based decision making regarding the most effective protocols. An initial consideration is designing a regimen that supports sufficient tissue saturation, especially when higher cumulative doses may be needed to elicit cognitive or neuroprotective effects. A commonly recommended approach is “microdosing,” which involves administering smaller amounts of creatine multiple times throughout the day. This method can reduce the risk of GI discomfort while allowing higher dosages to be consumed. Additionally, consuming creatine alongside meals or snacks has been shown to further minimize GI side effects. These minimal effort strategies allow the primary goal of optimal creatine saturation within the target tissue to be reached, while simultaneously avoiding the potential side effects associated with higher dosages. While current evidence suggests that timing (e.g., pre- or post-exercise) has little effect on musculoskeletal benefits, emerging research indicates that timing may be relevant in other contexts. For example, creatine appears to buffer against the cognitive and physiological effects of sleep deprivation when consumed following poor or insufficient sleep, suggesting that timing considerations should align with the intended therapeutic goal.

   Although creatine is naturally found in commonly consumed animal-based foods, individuals following a strictly plant-based diet typically have limited dietary access to it. Because the creatine content in whole foods is relatively low, supplementation is often necessary to achieve optimal levels, especially for those with performance or health goals. The most popular form, bulk creatine monohydrate powder, is widely used due to its affordability and ease of dosing. For more precise or convenient intake, alternative delivery options such as single-use packets or chewable edibles offer a reliable way to maintain consistent and individualized dosing. The products shown above undergo rigorous third-party testing and are available in various convenient forms, such as bulk powder, 1.5g chewable edibles, and 5g single-serve packets. Starting with as little as 1.5g per day provides a flexible foundation to incrementally reach a target daily intake of 8–10 grams, a range that research suggests may offer additional physiological and cognitive advantages.

   Creatine plays a critical role in brain energy metabolism by functioning as both an energy buffer and transport system. It stores energy as phosphocreatine and facilitates the delivery of mitochondrial energy to areas of high demand, including neural tissue. Importantly, creatine crosses the blood-brain barrier, supporting brain energy homeostasis and potentially enhancing bioenergetic capacity. By promoting rapid ATP regeneration and improving mitochondrial efficiency, creatine may help reduce oxidative stress and support neuronal resilience, particularly during periods of cognitive stress, sleep deprivation or neurological injury. Emerging evidence also links creatine supplementation to improvements in working memory, reaction time and mental fatigue, especially in individuals with lower baseline creatine levels or elevated cognitive demands.

   For general brain health, daily creatine monohydrate supplementation at a dose of 5-10 grams is supported by a growing body of evidence as a prophylactic. Additionally, research findings suggest that creatine may serve as a safe and effective long term strategy to support cognitive function in otherwise healthy individuals with sustained daily intake proving sufficient to maintain elevated brain creatine levels over time. Creatine has also emerged as a promising adjunct in the management of traumatic brain injuries (TBIs), offering potential benefits across prevention, mitigation, and treatment. Studies suggest it may reduce the risk and severity of second impact syndrome, a key concern given the established link between low brain creatine levels and the progression of recurrent symptoms. Short term, high dose protocols (≥20 grams/day for 7–10 days) have been proposed to rapidly elevate brain creatine stores, supporting energy metabolism and potentially improving TBI-related outcomes.

   In summary, creatine supplementation offers both acute and long term cognitive benefits. During periods of high mental demand or sleep deprivation, doses of 5-10 grams have been shown to enhance performance, likely due to creatine’s ability to buffer ATP depletion and reduce mental fatigue. Additionally, emerging research suggests that creatine may benefit older adults and individuals with neurodegenerative conditions. A daily dose of 10 grams, typically divided into two servings, has been linked to improvements in memory, processing speed and mood, positioning creatine as a potential adjunct for cognitive aging and early stage neurodegenerative disorders. Its sound safety profile and encouraging data support the need for further scientific research to fully explore its therapeutic potential in neurological health.

 

 

Myth: Long term creatine use has negative kidney health implications. 

Fact: Extensive research indicates that creatine supplementation does not adversely affect kidney function in healthy individuals. However, those with pre-existing kidney conditions should consult a healthcare provider before use. Current evidence supports the safety of creatine supplementation for kidney health in healthy individuals. However, individuals with kidney disease or other health concerns should seek medical advice before starting supplementation.

Myth: Creatine causes premature hair loss in adult men. 

Fact: Concerns have also been raised about potential hair loss in men, often attributed to increased dihydrotestosterone (DHT) levels; however, current research indicates that creatine does not significantly alter androgen levels. The original research study, with only 20 participants, showed a nonsignificant increase in levels at DHT, however hair loss was not directly measured. Additionally, no study has been able to replicate these preliminary findings, further supporting that creatine has no direct impact on hair loss. More recent research has directly assessed follicular health (below), providing strong evidence against this longstanding myth. 

Myth: To gain the maximum benefits of creatine, it must be cycled. 

Fact: Exogenous creatine intake can suppress the body’s natural (endogenous) creatine production. Over time, receptor sensitivity may also diminish, which may have, in part, contributed as to why some experts recommend cycling creatine. Intramuscular creatine levels remain elevated during continuous supplementation, but if intake is paused, these levels typically return to baseline within a month. Due to the lack of reported side effects, in addition to the clear data supporting optimal saturation levels required, creatine is not needed to be cycled. 

Myth: Creatine leads to unwanted water retention.

Fact: Research collectively supports the idea that creatine supplementation causes water retention primarily in muscle tissue (70% water), enhancing energy metabolism and performance. However, there is no evidence to suggest that it causes bloating or unwanted water retention in other parts of the body. The increase in body weight due to creatine is typically attributed to muscle water retention, not general systemic bloating. By adhering to recommended dosing protocols and allowing the body time to adjust, individuals can safely enjoy the benefits of creatine without experiencing adverse effects related to water retention.

Myth: To be effective, creatine must be taken immediately pre- or post-workout. 

Fact: Current scientific evidence supports the notion that creatine supplementation is effective regardless of whether it is taken before or after exercise. The key factor is consistent daily intake to maintain elevated muscle creatine levels, rather than the specific timing relative to workouts. However, while the timing of creatine supplementation may not significantly impact its benefits for muscle performance, it appears to play a more crucial role in supporting cognitive and brain health, especially during periods of sleep deprivation. 

 

   As scientific interest in creatine continues to expand, several critical areas are emerging as key focuses for future research. These include its potential role in preventing, managing, and treating traumatic brain injuries (TBIs); its use as an adjunct therapy for mental health conditions such as depression; and its possible protective effects against neurodegenerative diseases like Parkinson’s, Huntington’s, and Alzheimer’s. As Dr. Andy Galpin states, “there are no free lunches in physiology, only trade-offs.” Yet, considering the strength of evidence (SOE) and the extensive volume of existing research, creatine stands out as a compound associated with minimal and low-risk trade-offs. This favorable safety profile supports a strong and expanding foundation for ongoing research into creatine’s full therapeutic potential.

 

A list of referenced studies below: