Creatine overview

Creatine is a naturally occurring, vital substance in the body. An average adult contains 80 to 130 grams. Creatine plays a central role in supplying energy to cells – in skeletal muscles, the heart, the brain, and other organs. Besides its role as an energy transporter, creatine very likely has a variety of other functions that have not yet been fully explored scientifically. Many researchers assume that creatine is important for organ function and the brain, as well as for overall health. For almost 200 years, scientists have been studying creatine, which they describe as a "nitrogenous organic acid" with the formula C4H9N3O2. Biologically speaking, creatine is a small and relatively simple molecule. Most people meet about half of their daily creatine requirements by eating meat and fish – the only significant dietary sources of creatine. The human body can synthesize another portion.An unbalanced diet, such as that of vegetarians and vegans, usually leads to below-average creatine levels.It is scientifically proven that creatine as a dietary supplement can improve physical performance. In this capacity, creatine is recognized by health and sports authorities worldwide. It is easily absorbed by the body and—when properly manufactured and taken in the recommended dose—has no harmful effects.

Approximately 90 percent of the body's creatine stores are located in skeletal muscle. All living cells need energy – and muscle cells, in particular, require large amounts of energy when they are active. Creatine helps to make this energy available. Energy is supplied in various ways within muscle cells. During prolonged exertion, such as long-distance running, the body first produces energy by using its glycogen stores (a carbohydrate), and then by burning fat. Because these processes depend on atmospheric oxygen, they are called aerobic. In contrast, during short, intense bursts of activity – such as sprinting – the muscles require a great deal of energy in a very short time. At the beginning of such anaerobic exertion, the muscles must therefore rely on energy sources that are immediately available. They exist in the form of the chemical substances adenosine triphosphate (ATP) and phosphocreatine (PCr). ATP and PCr complement each other and thus bridge the time until the breakdown of glucose (glycolysis), glycogen (glycogenolysis), and fat (lipolysis and fatty acid oxidation) can release further energy.

Adenosine triphosphate (ATP) is the energy currency for all biological processes and is supported by creatine. One molecule of ATP contains three so-called phosphate groups, which are chemically linked by a central backbone. When ATP cleaves off a phosphate group, energy is released for muscle work. What remains is adenosine diphosphate (ADP), which the body converts back into ATP using energy from our food. However, this process takes some time, and sufficient ATP is only available for a few seconds. Therefore, the body has an additional mechanism to quickly regenerate ATP during prolonged muscle activity. This is where creatine comes into play: In resting muscle, approximately two-thirds of creatine exists in the form of the more energy-rich phosphocreatine (PCr), which contains an additional phosphate group. Even before the hard-working muscles run out of ATP, the enzyme creatine kinase (CK) transfers this phosphate group to ADP, converting it back into ATP – but only as long as sufficient phosphocreatine is present. Since CK is one of the fastest naturally occurring enzymes, this ATP regeneration process is very efficient and keeps ATP availability high for several seconds. Only when approximately 80 percent of the PCr supply is depleted do ATP levels begin to decline. This allows the muscles to continue working anaerobically until the PCr supply becomes scarce. During the next rest phase, the produced creatine is reconstructed into phosphocreatine by adding a phosphate group. Once the PCr supply has returned to its baseline level, it is able to provide ATP during the next intense exertion.

Creatine is slowly broken down in the body (see section on creatine metabolism). To compensate for this natural loss, an average adult needs to replenish about two to three grams of creatine per day.
Just like human muscle, meat and fish also contain creatine. A balanced diet provides about half of one's creatine needs directly from these food sources; the body can produce the rest itself (see section on creatine production).
The following table shows the average amount of creatine in various raw foods:

• Meat 3-7
• Fish 3-7
• Milk 0.1
• Vegetables, grains, and legumes 0

Cooking destroys some of the creatine content in fish and meat.
Anyone who doesn't have a balanced diet and eats little fish and meat is likely to have lower creatine levels in their body. This is especially true for vegetarians and vegans, who consume little or no creatine through their diet, but also for athletes who need additional creatine for muscle growth and faster recovery after strenuous workouts. These groups, in particular, can benefit from taking additional creatine as a dietary supplement.

The body obtains the amino acids glycine, arginine, and methionine from ingested food and uses them to synthesize creatine. The first step of this synthesis takes place in the kidneys and pancreas. The enzyme AGAT combines the two amino acids arginine and glycine to form guanidinoacetate (GA). The liver absorbs the GA and, with the help of the enzyme GAMT and a derivative of the amino acid methionine, converts it into creatine. The creatine is then transported to the target organs—for example, skeletal muscle, heart, and brain. The creatine transporter (CrT) carries the creatine into the cells. An average man between the ages of 20 and 40 synthesizes about one gram of creatine per day. This value decreases with age. In women, the value is slightly lower than in men. Of the three important amino acids that the body needs to produce creatine, glycine is usually abundant. Arginine and especially methionine, however, are only available to a limited extent. To synthesize one gram of creatine, the body uses almost 40 percent of the daily methionine intake. Consequently, people whose diets contain few sources of methionine are likely to have lower creatine levels.

The body of an average adult contains approximately 80 to 130 grams of creatine and phosphocreatine, primarily stored in the muscles. When this phosphocreatine is used in the cells for energy storage and transport, it is constantly converted to creatine and back again to phosphocreatine. However, two to three grams of creatine are broken down into creatinine every day and thus lost from the bloodstream. The body compensates for this loss through the intake of creatine from food (about one to two grams per day for non-vegetarians) and its own creatine synthesis (about one gram per day). Creatine has high bioavailability: measurements have shown that when creatine monohydrate is taken as a dietary supplement, more than 95 percent – ​​depending on the dosage – enters the bloodstream. The maximum creatine level in the blood is usually reached one to two hours after ingestion. Studies have shown that individuals whose diets contain low amounts of creatine also tend to have lower creatine levels in their bodies. In contrast, individuals who supplement with creatine have higher levels on average. Creatine supplementation causes tissue creatine levels to reach a maximum that cannot be exceeded. Therefore, it is not beneficial to take higher doses of creatine over a prolonged period. The actual creatine stores in the body reflect the balance between the natural rate of creatine breakdown and the amounts of creatine synthesized in the body and ingested through food. Because the body's creatine stores are large compared to average daily intake and excretion rates, they adapt only slowly to changes in creatine intake: When creatine is taken as a dietary supplement at the recommended dose of three to five grams per day, creatine levels only reach their maximum after three to four weeks.

A small amount of creatine is constantly broken down into creatinine in the body. Creatinine travels from the cells into the bloodstream and is then excreted by the kidneys in the urine. Scientists have determined that an average adult loses about one to two percent of their creatine stores daily through this pathway. This loss is replenished by creatine ingested through food or produced by the body. If more creatine is ingested than the body needs, most of the excess is excreted in the urine. However, higher levels of creatine in the body also mean that more creatine is broken down into creatinine. This can slightly increase the creatinine concentration in the blood and urine. For the same reason, individuals with greater muscle mass may have higher creatinine levels compared to those with less muscle mass. This is no cause for concern, as the elevated creatinine levels are within normal limits and creatinine has never been proven harmful. Since doctors routinely measure blood creatinine levels to detect kidney disease, anyone undergoing a kidney function test should inform their doctor about their creatine supplementation. Elevated creatinine levels caused simply by creatine supplementation are usually harmless. To be on the safe side, individuals with existing kidney disease or those at increased risk (e.g., due to diabetes or high blood pressure) should consult their doctor before taking creatine.

Creatine, due to its role in supporting energy transport within cells in the form of phosphocreatine, is an ideal dietary supplement for athletes. Additional creatine intake can increase the phosphocreatine stores in the muscles. This, in turn, improves performance and supports recovery during both training and competition. Creatine is popular in the gym because it allows athletes to train more intensely and thus build muscle mass faster. However, creatine does not achieve this effect without training. This distinguishes it from the effects of banned substances such as steroids. Since the 1990s, many athletes and scientists have valued creatine as the most effective dietary supplement for improving exercise tolerance, muscle strength, and lean body mass. In strength training, creatine supplementation has consistently shown an increase in strength and the number of repetitions. These training benefits are transferable to all sports that require explosive, intense muscle power. Athletes in many disciplines—such as... Athletes in sports such as track cycling, sprinting, swimming, and football have used creatine for many years with excellent results. Creatine in its naturally occurring form, creatine monohydrate, has established itself as effective, safe, and legal. The European Food Safety Authority (EFSA), for example, confirms that creatine increases physical performance during short-term, high-intensity exercise. This is also enshrined in Article 13.1 of the EU Regulation on "Nutrition and health claims made on foods." Furthermore, there is evidence that creatine supports recovery after intense training.

Creatine is not only important as an energy storage and transporter in muscles. Over the past two decades, researchers have discovered that creatine performs other important functions in muscles as well as in other tissue and cell types. For example, creatine is thought to control the ADP-to-ATP ratio, preventing ADP levels in the interstitial fluid from rising too high and, conversely, from dropping too low in the mitochondria. This is particularly important for oxidative energy production in the mitochondria—the "powerhouses" of cells—and could represent one of creatine's most important roles in cellular energy metabolism. Creatine is also responsible for the transfer of energy from the mitochondria into the intracellular fluid—a complex process that depends on several different enzyme forms of creatine kinase. Creatine has been shown to act as an antioxidant, reducing cell damage caused by free radicals. Furthermore, creatine helps stabilize the cellular pH level (acidity). This is particularly important during intense exercise, when the intracellular fluid tends to become acidic. Creatine also plays a crucial role in balancing the various aerobic and anaerobic energy sources (e.g., glycolysis) available to cells. Many renowned researchers believe that creatine is important for maintaining overall health in muscles, bones, the brain, and the rest of the nervous system—especially in older adults. Creatine is indeed essential for health. Children whose bodies cannot produce or utilize creatine exhibit significant mental and physical disabilities. Creatine has also proven effective in treating a number of muscle diseases. While it does not offer a cure, it can, as a supportive therapy, delay the onset and progression of diseases such as muscular dystrophy. Creatine is currently being tested in long-term clinical trials for the treatment of Parkinson's and Alzheimer's diseases, multiple sclerosis (MS), ALS, and other diseases.

As a dietary supplement, creatine is available in various chemical forms. The underlying creatine molecule is always the same, but the chemical groups attached to it can vary.
The naturally occurring form of creatine in the body is creatine monohydrate. It is primarily used in dietary supplements and is by far the most thoroughly researched form of creatine.
Creatine monohydrate is stable, effective, safe, and easily absorbed by the body. This is the form of creatine that is generally recognized by food safety authorities worldwide. For example, the European Food Safety Authority (EFSA) explicitly refers to creatine monohydrate in its assessment of creatine.
To date, no more effective form of creatine has been found in recognized research compared to creatine monohydrate.
Since creatine monohydrate dissolves slowly in water or other beverages, some users prefer more readily soluble forms of creatine, e.g., creatine sulfate. B. Creatine citrate.
However, at the same total weight, these other soluble forms of creatine contain less creatine than creatine monohydrate. While creatine monohydrate contains approximately 88 percent creatine, other forms of creatine may contain less than 40 percent.
Alkaline creatine is another form of creatine that is advertised as having improved stability in stomach acid. However, recent studies have shown that alkaline creatine is no more effective than creatine monohydrate.

Aside from creatine monohydrate and related salts with improved solubility, there are other forms of creatine. However, these are far less researched and not approved in many countries. They are also usually more expensive than monohydrate. There is no scientific evidence that new creatine compounds are in any way more effective than creatine monohydrate. In some cases, the effect has worsened because the core structure of the creatine molecule has been altered in such a way that the newly formed compound behaves differently and sometimes unpredictably in the body. An example of this is creatine ethyl ester (CEE) with covalent chemical bonds. Unlike soluble creatine salts, this compound is not broken down into creatine and the salt component when ingested. While creatine monohydrate is almost completely absorbed by the body, scientific studies show that CEE is rapidly broken down into ineffective creatinine in the gastrointestinal tract.Different forms of creatineStability of creatine monohydrateAs a dry powder, creatine monohydrate can be stored for years. However, when creatine monohydrate is stirred into liquids, it slowly converts to creatinine, which is physiologically ineffective but not harmful.In slightly acidic drinks like orange juice, less than five percent of creatine monohydrate is broken down within eight hours. Therefore, creatine monohydrate can be safely mixed into drinks as long as they are consumed on the same day. In alkaline milk or yogurt drinks, creatine monohydrate can even be stored in the refrigerator for several weeks without undergoing significant transformation. The common claim that stomach acid quickly breaks down creatine monohydrate is false. In fact, most of the ingested creatine monohydrate passes through the stomach intact, is absorbed, and more than 95 percent enters the bloodstream. From there, as creatine molecules, it reaches target organs such as muscles, heart, and brain.

Creatine monohydrate has an excellent safety profile as a dietary supplement. Compared to approved drugs, dietary supplements are subject to a more stringent safety assessment. The positive assessment by the European Food Safety Authority reflects the overwhelming scientific consensus that chemically pure creatine monohydrate is safe when taken at the correct dosage.The only proven side effect is a slight weight gain. This is initially due to increased water retention in the muscles and subsequently to an increase in muscle mass – a desired effect for many athletes.There is no scientific evidence for the occasional claim that creatine damages the kidneys. As explained in the section on metabolism, an increase in creatinine levels is not necessarily a sign of kidney dysfunction, but can indicate that the body is excreting excess creatine.Some online comments link creatine supplementation to stomach upset or cramps. Controlled scientific studies have not been able to confirm these side effects, provided that pure creatine is taken in the recommended dosage with sufficient fluids. The vast majority of scientific studies, however, refer to creatine monohydrate. Other forms of creatine have so far only been studied to a lesser extent. As with any dietary supplement, purity is particularly important with creatine. Therefore, only use creatine from reputable sources of known origin.

Although creatine is essential for life, researchers have yet to determine exactly how much the body needs to stay healthy. Each person likely has their own individual requirements. Someone who trains extensively and eats little meat probably needs more creatine than someone whose physical activity is moderate and whose meat consumption is high. Taking creatine monohydrate as a dietary supplement increases creatine levels in the body. Creatine in moderate amounts has proven benefits. The European Food Safety Authority considers creatine intake at a dose of three grams per day to be safe. An expert panel in the USA has deemed an intake of five grams per day safe for consumers. Alzchem AG recommends a daily intake of three to five grams of pure creatine monohydrate. Articles on the internet suggest higher dosages than the recommended three to five grams of creatine per day. Instead, one could also start with a high dose before reducing it after a few days.However, high-dose strategies are unnecessary. Studies show that creatine levels in the body are just as high after three to four weeks of daily intake of three to five grams as after a high initial dose.