Dr. Dwayne Jackson

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Supplement in Focus: Creatine

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Supplement in Focus: Creatine




Creatine biochemistry and physiology 101


With about a quarter century of clinical testing in the lab and field-testing in gyms around the world, creatine has stood the test of time and the rigor of science better than any other muscle-building supplement. Synthesized in the liver from arginine, methionine, and glycine and found in high concentrations in meat and fish, creatine is the ideal supplement for strength and power athletes. When supplemented, creatine is rapidly taken up and stored in skeletal muscle where it provides much needed high energy creatine phosphate to supply muscles with the substrates that form ATP (energy for contraction). In the end, having elevated creatine stores in muscle promotes dramatic increases in strength and power during explosive and extended performances with less time needed for rest.

Increased creatine phosphate levels also buffer (reduce) muscle acidity that occurs when you perform high repetition exercises or sports where you go all out for extended periods. Under these conditions your body gets its ATP from anaerobic glycolosis—leading to lactic acid build up and a loss of muscle power. This loss of power is primarily due to lactic acid’s inhibitory effects on phosphofructokinase (which is the rate limiting enzyme for glycolysis), which results in decreased ATP (energy) output. Lucky for you, the acidity lowering effect of creatine supplementation allows ATP production to go at top speed even when you are going all out, thus and enabling you to perform longer at max intensity.

Creatine as an anabolic agent


Beyond its dramatic effects on strength and athletic performance through increased energy production, there is an uncontested body of research illustrating creatine’s direct and indirect effects on protein synthesis and skeletal muscle growth. One proposed mechanism for creatine’s muscle-building effect is based on its ability to create an osmotic gradient in muscle cells, which promotes cell volumization by driving water into muscle cells. This not only makes creatine-loaded muscles appear larger, but the “stretching” of cells also turns on anabolism and protein synthesis—resulting in muscle growth. Support for creatine as an anabolic agent is highlighted by a study published in the International Journal of Sport Nutrition and Exercise Metabolism showing that creatine supplementation increases growth-promoting insulin-like growth factor 1 (IGF-1) content in resistance-trained skeletal muscle. In a more recent placebo controlled study published in Molecular and Cellular Endocrinology, it was reported that subjects who weight-trained while using creatine had twice the reduction in myostatin compared to those training with the placebo! (What is myostatin? It is a potent catabolic regulator of muscle mass, and consequently acts as a growth inhibitor in skeletal muscle). In the same study it was found that subjects using creatine had greater increases upper and lower body strength and lean body mass than resistance training with placebo.


Creating the best creatine


As with most products, supplement companies are constantly trying to improve the digestibility, bioavailability and potency of creatine. This focus has led to the development of several forms of this great supplement. In this article you will learn about the innovative compounds and products that have been developed over the past few years in the quest to make this super supplement better.


Creatine Monohydrate

Creatine monohydrate is so named because it contains one molecule of water bound to each molecule of creatine. This was the first form to start all the hype about creatine’s muscle- and strength-building properties and, as a result, it’s the most studied and scientifically supported form of creatine today. Creatine monohydrate provides great benefits for most and is generally well tolerated as a micro-ionized powder. Early versions of creatine were not micro-ionized, which caused some users to feel bloated and develop cramps, and even gave some individuals diarrhea.

Creatine monohydrate is likely the most affordable form of creatine on the market, but be aware that there are substandard products out there. That said, buy from reputable and well-established companies for assurance that you’re getting uncontaminated pharmaceutical-grade micro-ionized creatine monohydrate.

Creatine HCL

This relatively new player is simply a compound of creatine and hydrochloric acid and is patented under the name Con-Cret. Presently there hasn’t been an abundance of research using this form of creatine, but ProMera Health (who owns Con-Cret) recently had two major Universities conduct a double blind, placebo-controlled, balanced cross-over trial to compare the absorption of Con-Cret vs. creatine monohydrate and other forms of creatine. The researchers reported Con-Cret was absorbed over 60% better than creatine monohydrate, which means you can take much less creatine HCL and get the same (or better) effects as creatine monohydrate. Many claim this form of creatine is better tolerated and results in less bloating compared to other forms.

Creatine AKG

Creatine AKG is creatine bound to alpha-ketoglutarate (AKG). This form is supposed to be better absorbed into the blood than other forms of creatine. This is because it is digested high in the digestive tract. Users who commonly get cramps and diarrhea from creatine monohydrate claim that creatine AKG is easier on their system.

Creatine Nitrate

This nitrate salt form of creatine was developed to increase creatine bioavailability. Although data is limited, studies presented at the Presentations at FIP Pharmaceutical Sciences World Congress 2010 in New Orleans suggest that this form of creatine is more soluble (dissolvable in water) and stays in solution better than other forms of creatine. Although increased solubility may help with taste, it is not known if creatine nitrate increases strength and/or performance.

Creatine Anhydrous

This is the same as creatine monohydrate, except that it has been dehydrated. Thus, you get a little more creatine per gram when you buy the anhydrous form (about 5-6%) and its effects are comparable to creatine monohydrate.

Di- and Tri-Creatine Malate

This is a compound that’s formed by bonding two (Di) or three (Tri) creatine molecules to malic acid. Malic acid is an organic substance that serves as an important intermediate in the citric acid (Krebs) energy cycle. This form of creatine was developed based on the hypotheses that it would boost ATP (energy) production greater than creatine monohydrate and that it would be more tolerable in the body because it’s highly dissolvable in water. There is little to no research to support creatine malate as a superior form of creatine, but anecdotal evidence suggests that it’s well tolerated in those who cannot take creatine monohydrate because of gastrointestinal problems.

Creatine Citrate

Creatine citrate is a compound made by binding creatine to the important Krebs cycle intermediate, citric acid. Based on the importance of citric acid in the production of ATP, the rationale behind formulating this compound was that creatine citrate might provide greater muscular energy compared to creatine taken on its own. As well, this compound readily dissolves in water, making it easier to digest. At present there have been no peer-reviewed articles to substantiate creatine citrate as superior to creatine on its own. Also, it should be noted that because this is formed by binding a single creatine molecule to a single citric acid molecule, there is less total creatine provided per gram (about 40-50% less) when compared to creatine monohydrate or anhydrous.

Creatine Pyruvate

This is what you get when you bind creatine to pyruvate. Pyruvate supplies energy to the body during aerobic exercise. Data published in the Journal of the International Society of Sports Nutrition suggests that this form of creatine might increase exercise endurance due to enhanced activity of aerobic metabolism. Other studies suggest that creatine pyruvate also helps buffer lactic acid during high intensity exercise, which would enable you to push harder for longer during training sessions.

Creatine Orotate

This is another compound that shows promise in theory but is yet to be studied extensively. Creatine orotate is a compound formed by binding creatine with orotic acid and is patented under the name CreaTate. The purported benefits of this supplement over creatine monohydrate include increased muscle phosphocreatine and free creatine levels (via augmented uridine concentration) and increased muscle carnosine levels. In theory, this supplement should increase muscular strength and endurance. In support, there are numerous studies illustrating orotic acid’s ability to increase muscle carnosine leading to increased muscular endurance.

Creatine Kre-Alkalyn

This is another patented form of creatine. It’s reported to be “buffered creatine” that’s produced at a higher pH, which apparently blunts the conversion of creatine to inactive creatinine, leaving more creatine to be absorbed. In addition, this form apparently doesn’t convert to creatine until it enters muscle cells, albeit there have been no clinical trials conducted to prove this. Thus, the founders claim it can be taken in much smaller doses with the same benefits as creatine monohydrate and, because doses are smaller, it’s taken in capsule form. Although there are no studies published on this supplement, numerous anecdotal reports support this form of creatine.

Creatine Phosphate

As the name implies, this is creatine bound to phosphate, an essential step usually carried out in the body to make creatine active. This form of creatine was released soon after creatine monohydrate and quickly became popular; however, it was made obsolete when it was shown to be less effective than creatine monohydrate.

Creatine Serum

Also known as liquid creatine, this form is precisely what the name implies. The idea behind creating creatine serum was to increase digestibility and bypass the stomach’s acidic environment (known to degrade creatine). The problem is that creatine is very unstable in liquid and thus should be taken immediately after dissolving in water. Because of the unstable nature of creatine in liquid, early versions of this supplement were completely useless. However several companies have been working on versions of liquid creatine that they claim are stable for up to years. There are still no published data to substantiate these claims.

Creatine Tatrate

This form is the result of binding a creatine molecule with a molecule of tartaric acid. You rarely see this form used as a stand-alone supplement, however because of its stability when formed in a solid, it’s usually included in products like energy bars, capsules, tablets or chewables. An interesting and disconcerting fact is that tartaric acid is a known muscle toxin at high doses.

Creatine Titrate

This is a pH-shifted form of creatine that increases the solubility of creatine in water. The theory is that more dissolved creatine makes for easier digestion and greater bioavailability. Users report less bloating and great outcomes, although evidence is purely anecdotal at present.

Magnesium Creatine Chelate

Chelating creatine and magnesium together forms this compound. The rationale behind the development of this compound was based on the fact that magnesium is essential for the conversion of creatine phosphate to ATP for energy. In addition, chelation increases the stability of the compound.  Scientific evidence proves that this form of creatine works better than taking a creatine and magnesium supplement separately. Researchers have reported greater increases in leg strength and cell volumization in those who took magnesium creatine compared to those who took the creatine and magnesium separately.


This form comes from binding the amino acids taurine and glutamine with creatine. The basis for developing this supplement was to enhance muscle cell volumization. This is a reasonable postulate because all three of these are cell volumizers when supplemented on their own. Furthermore, the amino acids in this combination may enhance recovery and strength gains, however there have been no peer-reviewed studies published on this compound.

Creatine HMB

This is what you get when beta-hydroxy beta methylbutyrate (HMB) is bound to creatine. It’s well documented that HMB speeds recovery, is anti-catabolic and aids in fat loss, especially in those who have just started heavy weight training. By binding HMB with creatine the compound is more soluble and apparently less prone to degradation in the stomach. As a result creatine HMB is speculated to be a more bioavailable form that gives you all of the benefits of creatine and HMB supplementation. Studies that have used this compound are lacking but users generally report good results.

Creatine Ethyl Ester (CEE)

Also known as creatine ester or CEE, this is one of the newest creatine forms and is made by adding an alcohol and an acid to form creatine ester ethyl hydrochloride. The patent on CEE is in the hands of UNeMed at the University of Nebraska Medical Center. The motivation for developing CEE was in an effort to provide a more bioavailable form of creatine. The addition of an ester to creatine theoretically increases the lipophilicity (fat dissolvability) of creatine, making it very easy for it to cross cell membranes driving more creatine into muscle cells. Unfortunately, recent scientific evidence has shown that the addition of an ethyl group to creatine reduces its acid stability and is inactivated to creatinine in the physiological environment.

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