What exactly is creatine and how is it produced?

Contrary to popular belief, creatine is not an amino acid, a steroid, or a synthetic compound. It is a nitrogenous organic molecule found naturally in all mammals. Our bodies synthesize it in a two-step process that primarily involves the kidneys and liver.

The process begins with two amino acids: arginine and glycine . In the kidneys, these two amino acids combine to form an intermediate compound called guanidinoacetate (GAA). Once produced, GAA travels through the bloodstream to the liver. There, a specific enzyme, guanidinoacetate methyltransferase (GAMT), adds a methyl group, transforming GAA into creatine.

Once synthesized, creatine is released into the bloodstream and distributed throughout the body to be used by tissues with high energy demands. For creatine to enter cells, it needs the help of a specialized protein known as the creatine transporter (CreaT1) , encoded by a gene linked to the X chromosome. This protein acts as a gateway, capturing creatine from the blood and transporting it into the cell.

While nearly all tissues contain some creatine, its distribution is not uniform. Approximately 95% of the body's creatine is stored in skeletal muscle . The remaining 5% is distributed among other vital tissues such as the brain, spinal cord, heart, and even reproductive cells. This distribution gives us a clear clue about its function: it is present where energy is needed quickly and intensely.

The Central Role of Creatine: How It Nourishes Your Cells

The primary function of creatine is intrinsically linked to cellular energy metabolism, specifically the phosphocreatine system. To understand this, we must first discuss adenosine triphosphate (ATP) , the universal "energy currency" of the cell. Any process that requires energy, from a muscle contraction to a thought, uses ATP. When "used up," ATP loses a phosphate group and becomes adenosine diphosphate (ADP).

The Energy Damping System

Our cells only store a very limited amount of ATP, enough for a few seconds of maximum effort. This is where creatine comes in. Inside the cell, creatine is "loaded" with a phosphate group to become phosphocreatine (PCr) . This molecule acts as an immediate energy reserve.

When you perform high-intensity activity, such as weightlifting or sprinting, ATP is rapidly consumed and converted into ADP. Phosphocreatine immediately steps in, donating its phosphate group to ADP to regenerate ATP at an astonishing rate. This reaction, catalyzed by the enzyme creatine kinase (CK), allows energy production to continue at a very high rate before other metabolic systems, such as anaerobic glycolysis (which produces lactic acid), can fully activate. Essentially, phosphocreatine acts as an energy buffer , recycling ADP back into ATP.

The Creatine-Phosphocreatine Cycle and Mitochondrial Function

Further research has revealed an even more sophisticated mechanism known as the "creatine-phosphocreatine cycle or shuttle." This system directly connects the mitochondria (the cell's "powerhouses" where most ATP is produced) to the areas of the cell where energy is used.

Inside the mitochondria, newly produced ATP donates its phosphate to creatine, forming phosphocreatine. This phosphocreatine, being a smaller molecule, travels efficiently through the cytoplasm to where energy is needed (for example, the contractile fibers of muscle). There, it donates its phosphate to regenerate ATP locally, and the "unloaded" creatine returns to the mitochondria to repeat the cycle. This system not only transports energy, but the high concentration of creatine within the cell also acts as a signal for the mitochondria to produce more ATP, optimizing the entire energy production chain.

Other Mechanisms of Action

Beyond its energy role, creatine has other beneficial effects:

• Antioxidant Potential: Studies have shown that creatine possesses antioxidant properties, helping to protect tissues, including the brain and muscles, from damage caused by oxidative stress.
• Reduced Protein Breakdown: As creatine concentration increases in the muscle cell, water is drawn in, causing slight cell swelling (volumization). This state of cellular hydration is an anabolic signal that reduces protein breakdown (catabolism). Less catabolism, combined with the stimulus of training, leads to a more positive net protein balance, facilitating greater long-term muscle mass gains.

Natural Sources and Effective Supplementation Protocols

The body obtains creatine in two ways: through endogenous production (which it manufactures itself in the kidneys and liver) and through diet. The richest dietary sources of creatine are red meat and fish , since it is stored in the skeletal muscle of animals.

Considerations for Vegetarian and Vegan Diets

Because the main sources of creatine are animal-based, people who follow strict vegetarian or vegan diets typically have significantly lower muscle creatine levels than omnivores. Lacto-ovo-vegetarians have intermediate levels. This relative deficiency makes creatine supplementation particularly beneficial for this population. In fact, some studies have shown that supplementation in vegans not only improves physical performance but also complex cognitive functions, likely due to the restoration of creatine levels in the brain.

Creatine Monohydrate Supplementation Protocols

The most studied, economical, and effective form of creatine is creatine monohydrate . There are two main protocols for saturating muscles with creatine:

1. Rapid Loading Phase: This is the classic method used in many of the initial studies. It consists of taking a high dose, typically 20 grams per day (divided into four 5-gram doses), for 4 to 5 days . This protocol quickly saturates muscle stores. After the loading phase, a maintenance dose is used.
2. Slow Loading Phase (or Direct Maintenance): A more practical and better-tolerated approach for most people. It consists of taking a lower daily dose, 3 to 5 grams per day , continuously. With this method, muscle stores are fully saturated in approximately one month, achieving the same end result as rapid loading but more gradually.

Once the muscles are saturated, a maintenance dose of 2 to 3 grams per day is sufficient to maintain elevated levels. For most healthy individuals, the slow-loading protocol (3-5 grams daily) is the recommended option due to its simplicity and excellent tolerability. Starting with low doses and taking creatine with a meal can help minimize any potential gastrointestinal discomfort.

Proven Impact on Physical Performance and Strength

The scientific evidence supporting the benefits of creatine on athletic performance is overwhelming and consistent. Its effects are primarily observed in activities that rely on the rapid energy of the phosphocreatine system.

Performance Improvement in High-Intensity Exercises

The most documented benefit is improved performance during repetitive sets of short-duration, high-intensity exercise. This includes:

• Weightlifting: Allows you to perform one or two more repetitions per set or lift a slightly heavier load.
• Sprints: Improves the ability to maintain maximum speed in repeated sprints.
• Team sports: It is highly beneficial in intermittent sports such as football, basketball or hockey, which involve constant starts, stops and bursts of speed.

Increased Muscle Mass and Strength

When combined with a resistance training (weightlifting) program, creatine supplementation consistently leads to greater gains in both muscle mass and strength compared to training alone. This effect has been demonstrated in a wide range of populations, including young adults, women, and, very significantly, older adults . The increase in lean mass is due both to the ability to train at higher intensity and to the direct effects of creatine on muscle cells, such as the reduction of protein breakdown.

Effects on Aerobic Endurance

The impact of creatine on endurance performance is a more controversial and context-dependent topic. The main potential drawback is a slight initial weight gain (1-2 kg) due to water retention in the muscles. In bodyweight activities, such as running a marathon or hill sprint, this extra weight could be detrimental to performance. However, in weight-bearing activities, such as cycling on flat terrain or rowing, there could be a benefit by improving the ability to sustain higher-intensity efforts during the event (e.g., a final sprint).

Beyond Sport: Clinical Applications and Therapeutic Potential

Interest in creatine has transcended the sports arena and entered the field of medicine. Since cellular energy dysfunction and oxidative stress are underlying factors in many diseases, creatine has been studied as a potential therapeutic agent in various conditions, especially neuromuscular and neurometabolic disorders.

Research in patients with these conditions often reveals low levels of creatine and phosphocreatine in muscle and brain tissue, suggesting a chronic energy deficiency.

Mitochondrial Diseases

In patients with primary mitochondrial diseases, where ATP production is compromised, creatine supplementation has been shown to improve performance in high-intensity exercise. Furthermore, it has been used successfully as part of a supplement "cocktail" that includes antioxidants such as coenzyme Q10, alpha-lipoic acid, and vitamin E, demonstrating improvements in overall mitochondrial function and a reduction in oxidative stress.

Muscular Dystrophy

Research into muscular dystrophies has yielded very positive results. In a double-blind clinical trial in patients with Duchenne Muscular Dystrophy , creatine supplementation not only increased strength in the dominant hand but also slowed strength loss over time and increased lean muscle mass. A systematic review of the global literature (Cochrane review) confirmed these findings, concluding that creatine increases strength by an average of 8.5% in patients with different types of muscular dystrophy.

However, it is crucial to note that the response may vary depending on the type of dystrophy. For example, in myotonic dystrophy, the benefits were not clear in sedentary patients, suggesting that combining it with exercise might be necessary to observe improvements.

McArdle's disease

McArdle's disease is a metabolic disorder where patients cannot break down muscle glycogen for energy. This makes them heavily reliant on the phosphocreatine system for high-intensity exertion. In this case, dosage is critical. Low doses of creatine (approximately 60 mg/kg) have shown benefits by increasing phosphocreatine stores. Surprisingly, high doses (equivalent to 20 g/day in an adult) proved detrimental. The theory is that excess creatine may inhibit a key enzyme (phosphofructokinase) in the glycolytic pathway, worsening the metabolic bottleneck these patients already experience. This is a clear example of "more is not always better" and underscores the importance of proper dosage in clinical settings.

Frequently Asked Questions About Creatine

Is creatine safe? Does it damage the kidneys?

Creatine is one of the safest and most studied supplements on the market. Decades of research in healthy populations have found no evidence that creatine supplementation at recommended doses causes kidney damage. The misconception stems from the fact that creatine is broken down into creatinine, a marker used to assess kidney function. Supplementation does increase blood creatinine levels, but this is an expected byproduct and not a sign of kidney damage in a healthy individual.

Do I need to do a charging phase?

No, the loading phase isn't strictly necessary. Taking 3 to 5 grams daily will saturate your muscles in approximately 3-4 weeks. The loading phase (20g/day for 5 days) simply accelerates this process, but the end result is the same. Slow loading is more practical and causes less gastrointestinal discomfort.

Should I take creatine before or after training?

The exact timing doesn't seem to be as crucial as consistency. The most important thing is to take it every day to keep your muscles saturated. Some evidence suggests that taking it after training along with carbohydrates and protein might slightly improve absorption, but the difference is minimal. Choose a time of day that's easiest for you to remember and stick to.

Does creatine cause water retention?

Yes, creatine attracts water into muscle cells (intracellular water retention). This is part of its mechanism of action and is beneficial for cellular hydration and anabolism. It should not be confused with subcutaneous water retention (bloating), which is not a typical effect of high-quality creatine monohydrate.

Conclusion: A Key Molecule for Energy and Health

Creatine is emerging not as a simple supplement for athletes, but as a fundamental bioenergetic molecule with profound implications for human health. Its central role in ATP regeneration makes it an exceptionally effective tool for improving strength, power, and muscle mass when combined with training. However, its benefits extend far beyond the gym, showing significant potential as a therapeutic agent in a variety of clinical conditions characterized by energy deficiency.

From optimizing performance in elite athletes to helping preserve muscle mass in older adults and offering metabolic support in neuromuscular diseases, creatine is establishing itself as a safe, accessible compound backed by a solid scientific foundation. Understanding its true nature allows us to use it in an informed way, harnessing its power to boost cellular vitality and improve quality of life.