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Creatine guide. Part 1: Background Questions

Source: www.creatinemonohydrate.net
1. What is creatine?

Creatine is, and always has been, a natural component of skeletal muscle. The only reason that creatine may seem like something new is a recent boom in scientific research in the area since the early 1990s. In a sense, creatine was rediscovered when world-class athletes became wise to the option of utilizing it to enhance their physical performance.

In truth, however, creatine was identified as an indispensable part of skeletal muscle some time ago. Nearly two centuries ago (1835) a French scientist and philosopher named Michel-Eugene Chevreul isolated a component from skeletal muscle that he gave the name Creatine after the Greek word for flesh, or Kreas. A few years later (1847) a German scientist named Justus von Liebig proposed that creatine is necessary to support muscular activity when he observed that wild (active) foxes contain more intramuscular creatine than foxes kept in captivity. Liebig later went as far as lending his name to a commercial extract of meat that he asserted would help the body perform extra "work". Indeed, Liebig's "Fleisch Extrakt" could reasonably be considered the original creatine supplement - complete with marketing strategy.

In fact, meat and fish are the richest natural sources of creatine. Carnivores therefore, receive their creatine directly via dietary channels. Conversely, herbivores (and strict vegetarians), since they abstain from consuming these sources of creatine, are solely reliant on their body's natural ability to synthesis creatine from basic components. Omnivores, on the other hand, have at their disposal both avenues from which to fulfill their daily creatine requirement.

When dietary creatine intake is restricted (or entirely absent) the body can produce creatine from amino acids made available during the digestion of foods. Therefore, in one way or another, creatine is acquired from our diets. The production of new creatine (synthesis) principally takes place in the liver and kidneys, although the pancreas also contributes some to the body's new synthesis of creatine. Creatine is produced in a chemical reaction involving three amino acids, arginine, glycine and methionine. Of these three, the requirement for dietary methionine is most critical, since the body does not readily produce it from starting materials.

Although creatine is present in most cell types to varying degrees, the greater part of the body's entire creatine reserve (95%) is found within skeletal muscle. The remainder (~5%) is principally found within the heart, brain and testes. These are all tissues with extremely high energy expenditures. Following ingestion (or synthesis) creatine is transported to our muscles where it serves to increase muscle energy levels. Creatine achieves this by increasing the availability of ATP, the cell's energy molecule.

To become physiologically active creatine must first be enzymatically transformed into another molecule known as phosphocreatine (PCr). PCr is nothing more than a molecule of creatine that has been modified with the covalent attachment of a phosphate group. On average the body goes through about 2 grams of creatine (creatine and PCr) each day through a process of spontaneous degradation. This entails the spontaneous conversion of creatine and PCr into an energetically inert molecule known as creatinine. We typically notice an improvement in exercise performance when our muscle creatine levels increase by at least 20% as a result of creatine supplementation.

Recently it has become popular to supplement one's diet with synthetically produced creatine in hopes of enhancing athletic performance. Synthetic creatine is sold as citrate, phosphate or monohydrate salts. Creatine monohydrate is the most commonly used form in athletics and is nothing more than a molecule of creatine accompanied by a molecule of water. A gram of creatine monohydrate also contains more creatine than a gram of either creatine citrate or a gram of creatine phosphate. You therefore consume less creatine monohydrate powder to get the same amount of active creatine.

2. How does creatine work?

Simply speaking, creatine (phosphocreatine) increases muscle energy availability. The cells of our body store their energy in the form of a molecule known as Adenosine TriPhohsphate, or ATP. The amount of work our muscles can perform is a direct consequence of the amount of ATP they have stored as well as the ease with which ATP is regenerated with the help of PCr during strenuous exercise. Think of ATP as the cell's energy currency and phosphocreatine as a credit card with an adjustable balance - the balance being set by creatine intake.

First and foremost creatine enhances physical performance by increasing the number of times that ATP can be recycled during physical exertion without increasing the absolute amount of ATP stored within our muscles. In the short-term this means that creatine supplementation should improve our ability to sustain near maximal force generation during repetitive bouts of intense exercise without actually increasing the amount of peak force we can produce. Later on, however, given that the appropriate metabolic circumstances had been correctly established, this improvement in exercise output should then translate into an increase in maximal force generation through the production of new muscle tissue.

Creatine also supports a variety of other anabolic pathways simply by enhancing the body's methylation status. Creatine supplementation, since it alleviates the need to synthesize creatine from amino acids (particularly methionine), spars much of the body's methyl reserves. These available methyl groups can then be used to activate several key growth factors and metabolic pathways. Moreover, the recycling of our methyl reserves is assured by certain B-vitamins, namely folic acid, vitamin B12 and vitamin B6. Therefore, combining this methyl-sparring capacity of creatine with the methyl-recycling capacity of certain B vitamins will multiply the benefits rendered by creatine supplementation. An athlete simply can not afford to compromise his methlyation status!

3. What are natural sources of creatine?

In one form or another, creatine is obtained from the foods we eat.

DIETARY CREATINE: Creatine is directly obtained from sources of skeletal muscle, ie meat and fish. During the digestive process the creatine contained within these foods is directly released into the blood stream where it is transported to skeletal muscle for absorption.

For example, 2-3 pounds of raw meat or fish contain the equivalent of 5 grams of pure creatine monohydrate powder. Since heat degrades creatine, however, cooking reduces the creatine content of these foods and increases the amount you'll need to eat to obtain a given amount of creatine.

CREATINE SYNTHESIS: When dietary creatine intake doesn't meet the body's needs, new creatine can also be synthesized from the three amino acids; arginine, glycine and methionine, made available during the digestion of foods. Importantly, methionine availability sets an upper limit on creatine synthesis, since the body can not produce it on its own. Methionine is thus classified as an essential amino acid and, in this capacity, provides us with our principal source of exogenous methyl groups to support growth and development. In essence, methylation maintains life! It is thus imperative that methionine be present in our diets to assure that these indispensable cellular processes continue unabated.

Interestingly, methionine is also one of the amino acids used in the synthesis of creatine. Therefore, creatine supplementation, by alleviating the need to synthesize creatine from methionine, spars the body's methyl reserves. These available methyl groups can then be used to activate key anabolic pathways. Previously, it was largely unexplained why creatine supplementation under certain circumstances stimulates anabolic hormone release, reduced blood cholesterol levels, reduced protein degradation following intense exercise (an anti-catabolic effect) and so on. In all likelihood, these "unexplained attributes" of creatine supplementation are surely a consequence of its beneficial effect over cellular methylation status.

To paraphrase, creatine promotes muscle anabolism via two principal pathways: (1) creatine supplementation increases muscle's immediate energy reserves (ATP and PCr), thereby increasing exercise output; (2) creatine supplementation augments cellular methylation capacity, thereby creating a more favorable metabolic environment to support muscle anabolism. It is my opinion that taking full advantage of creatine's ability to enhance cellular methylation will be the next big wave in creatine optimization.

Interestingly, the ability to synthesize creatine appears to have evolved later on in the animal kingdom. Primitive organisms, such as invertebrates, do not possess the enzymes needed to synthesize creatine from amino acids, despite containing creatine in their tissues. These organisms must therefore take up creatine from their surroundings. In other words, creatine supplementation was the original strategy of life on this earth.

Natural Creatine Champion: Since fish is one of the richest natural sources of methionine, eating fish provides both a direct source of creatine as well as an adequate supply of dietary methionine for new creatine synthesis.

In particular, sushi and sashimi (raw seafood) are excellent natural sources of creatine since they will retain much more of their original creatine content. Remember, heat (cooking) degrades creatine. I personally recommend maguro (tuna), sake (salmon) and saba (mackerel), since they are also exceptional sources of omega 3 fatty acids. Omega 3s are essential fats that are turning out to be invaluable for overall good health.

Heart-Smart Properties of Fish
- The omega 3 fatty acids have also been shown to reduce bad cholesterol (low density lipoproteins) and thus exert a protective influence over the development of coronary heart disease.
- Fish is also lower in saturated fats than either beef or pork. The incidence of coronary heart disease is well correlated with the presence of saturated fats in the diet. In light of this threat most doctors are now advising that we watch our dietary intake of saturated fats.
- The abundance of methionine and creatine in fish will also improve your methylation status, which is important for overall health and longevity (see above).
- Dietary creatine intake also reduces the levels of homocysteine in the blood stream. Homocysteine is produced from imbalances in cellular methylation capacity and has very dangerous repercussions for mental and physical health. Homocysteine is a major culprit responsible for several neurodegenerative disorders, including Down’s syndrome, Parkinson’s disease, Alzheimer's disease, stroke and dementia. Elevated serum homocysteine has also been shown to increase the risk of cardiovascular disease (see next), renal disease, hepatic disease, and anemias. Without a doubt, blood homocysteine levels need to be kept in check and increasing creatine intake (supplementation) appears to be a good place to start.
- Finally, creatine has been shown to lower total plasma cholesterol as well as reduce low density lipoproteins (LDLs) levels in the blood stream and, given that fish is one of the best sources of creatine... Well, you get the picture.
- It thus appears that for a variety of reasons that tuna and salmon are heart smart.


Vegetarians: Anyone with sub-average intake of meat and fish will express lower than "normal" creatine levels. The same is true for lacto-vegetarians, which limit their animal protein consumption to milk and eggs. Creatine might therefore be advisable for athletes who purposefully restrict their animal protein intake.

Interestingly, vegetarians and vegans also typically express higher than average plasma homocysteine levels, since they must solely rely on their body's capacity to synthesize creatine from arginine, glycine and methionine (see above CREATINE SYNTHESIS). Further accentuating the already elevated levels of homocysteine in vegetarians (and vegans) is the fact that animal proteins are the richest natural sources of the B-vitamins (folic acid, B 12 and B6) used to clear homocysteine from the blood stream and to restore the body's methyl reserves. Creatine and vitamin B supplementation may prove particularly beneficial in these cases.

4. How does creatine get into muscle?

From the blood creatine is transported into skeletal muscle by special transporter molecules expressed on the muscle surface. In essence, these transporters harness the energy of sodium entering the cell to transport creatine inward. Furthermore, given that in a living cell sodium levels are much higher outside than inside, creatine transport is unidirectional - inward.

Transporter function is regulated by other physiological processes. For example, creatine transporter activity is enhanced by co-ingestion of highly glycemic foods, an effect mediated by insulin release. Insulin stimulates the extrusion of sodium from the cell, thereby creating a ionic environment conducive for creatine transport (see previous paragraph). Therefore, taking measures to improve one's insulin sensitivity should enhance creatine uptake into skeletal muscle.

The activity of these creatine transporters is also influenced by the presence of creatine itself in the following manners: (1) elevated plasma creatine interrupts creatine uptake into skeletal muscle via these transporters; (2) the synthesis of creatine from amino acids is also stopped by elevated plasma creatine. These are nothing more than examples of normal regulatory feedback processes that are common in cell biology. However, how exogenous creatine supplementation influences these processes in humans is still an open issue. This is why it is often recommended to periodically stop taking creatine to let the body recuperate. Omitting the load phase from supplementation will also mitigate this drawback of creatine supplementation.

5. Do all muscles respond the same to creatine?

Not all muscle types respond equally to creatine supplementation. Muscles can be loosely described as either fast or slow. As the name implies, fast muscle fibers mediate abrupt movements. Fast muscle fibers are also those that predominantly use creatine energy production. Hence, explosive movements respond best to creatine supplementation.

Slow muscle fibers, on the other hand, do not rely that heavily on creatine energy production. Slow muscle fibers are also those that play an important role during endurance exercise. It follows that endurance tasks are influenced less by creatine supplementation. In addition, many endurance sports may be adversely effected by the increase in weight associated with creatine supplementation.

6. Does everyone respond to creatine?

Not everyone responds to creatine supplementation. It is estimated that between 20-30% of the population will not respond to creatine supplementation. This isn't to say that many "nonresponders" wouldn't convert to full-fledged "responders" given the right information. For example, taking creatine with highly glycemic sugars is sufficient in many cases to convert nonresponders into "super" responders. Furthermore, adding essential B-vitamins to your supplementing regimen will greatly accentuate the anabolic potential of creatine supplementation.

I would warn against, however, pounding your systems with highly glycemic carbohydrates in hopes of maximizing creatine absorption. When and how these sugars are taken is a very important consideration. The chronic consumption of highly glycemic sugars can eventually lead to a condition of insulin-resistance, which would be an anabolic dead end. In fact, insulin-resistance is currently one of America's greatest health problems. Insulin is one of your most important anabolic hormones (next to growth hormone and testosterone) and you wouldn't want to attenuate its effects.

Another important consideration is your existing muscle creatine levels. Persons with naturally high creatine levels typically benefit less from creatine supplementation. This is the reason that vegetarians typically respond so robustly to creatine supplementation. Furthermore, the benefits you perceive from creatine use depend on the exercise task being used to measure its effectiveness. There is also some indication that creatine may be less effective in children and the elderly. Finally your simple, every day dietary habits, such as alcohol and caffeine consumption, can profoundly influence creatine's effectiveness.

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