Creatine

Creatine is a nitrogenous organic acid that occurs naturally in vertebrates. Approximately 95% of the body's creatine is stored in skeletal muscle, with smaller amounts in the brain, heart, and testes. The body synthesizes about 1-2 grams of creatine per day in the liver, kidneys, and pancreas from the amino acids glycine, arginine, and methionine. Additional creatine is obtained through diet, primarily from meat and fish.

Creatine's primary function is to facilitate the rapid regeneration of adenosine triphosphate (ATP), the body's energy currency. During high-intensity exercise, ATP is broken down to release energy, forming adenosine diphosphate (ADP). Creatine phosphate (phosphocreatine) donates a phosphate group to ADP, rapidly regenerating ATP and allowing continued high-intensity effort. This phosphocreatine system is particularly important for activities lasting up to 10 seconds, such as sprinting, weightlifting, and jumping.

As a dietary supplement, creatine monohydrate has been extensively studied since the early 1990s. Hundreds of clinical trials have consistently demonstrated that creatine supplementation increases intramuscular phosphocreatine stores by 10-40%, leading to improved performance in repeated high-intensity exercise bouts. It also promotes muscle cell hydration and may stimulate muscle protein synthesis, contributing to increased lean body mass over time.

Beyond athletic performance, creatine has gained attention for potential cognitive benefits. The brain requires substantial ATP for optimal function, and like muscle, brain phosphocreatine stores can be increased through supplementation. Studies suggest creatine may improve cognitive performance during sleep deprivation, mental fatigue, and in older adults.

Creatine monohydrate is the most studied and cost-effective form. Despite marketing claims for various "advanced" forms (ethyl ester, HCl, buffered), research consistently shows that creatine monohydrate is at least as effective, if not superior, to these alternatives. It has an exceptional safety profile, with no serious adverse effects reported in healthy individuals even with long-term use.

Creatine's primary mechanism involves its role in the phosphocreatine (PCr) energy system. When supplemented, creatine accumulates in muscle cells as both free creatine and phosphocreatine, increasing the total creatine pool by 10-40% depending on baseline levels and dosing protocol.

During high-intensity exercise, ATP is hydrolyzed to ADP + inorganic phosphate (Pi), releasing energy. To maintain ATP levels, the enzyme creatine kinase catalyzes the transfer of a phosphate group from phosphocreatine to ADP, rapidly regenerating ATP. This reaction is reversible: when ATP is abundant (during rest), creatine kinase phosphorylates creatine using ATP, recharging the phosphocreatine reservoir.

By increasing phosphocreatine stores, supplementation extends the capacity for rapid ATP regeneration during intense exercise. This delays fatigue, allowing more repetitions, greater training volume, and improved performance in activities like sprinting, weightlifting, and high-intensity interval training. The performance enhancement is most pronounced in repeated bouts with short rest periods, as phosphocreatine resynthesis between bouts is also improved.

Beyond the immediate energy system effects, creatine increases muscle cell hydration through osmotic mechanisms. This cell volumization may trigger anabolic signaling pathways, including increased protein synthesis and reduced protein breakdown. It may also stimulate satellite cell proliferation and differentiation, contributing to muscle growth over time.

For cognitive function, the mechanism is similar to that in muscle. The brain consumes approximately 20% of the body's energy while comprising only 2% of body weight, making it highly dependent on efficient ATP production. Brain phosphocreatine levels increase with supplementation, potentially supporting ATP regeneration during periods of high demand or compromised energy metabolism, such as sleep deprivation, mental fatigue, or aging.

Creatine is transported into cells by the creatine transporter (CreaT), a sodium-dependent transporter protein. Insulin and exercise can enhance CreaT activity and creatine uptake, which is why creatine is often taken with carbohydrates or protein. Once inside cells, creatine remains until used or slowly degraded to creatinine and excreted by the kidneys.

Creatine is found naturally in animal products, particularly meat and fish. However, obtaining therapeutic doses through diet alone would require consuming very large amounts of meat, making supplementation practical for most users.

Vegetarians and vegans have lower muscle creatine stores than meat-eaters. While not a true deficiency syndrome, low creatine levels limit high-intensity exercise capacity and may affect cognitive performance under stress.

No established RDA. Typical supplementation protocols include a loading phase (20 g/day for 5-7 days) followed by maintenance (3-5 g/day), or simply 3-5 g/day without loading. Higher doses may be used by larger athletes.

Creatine monohydrate is the gold standard - most researched, effective, and economical. Other forms marketed with claims of superior absorption but lack evidence to justify higher cost.