The greatest of all gifts is the power to estimate things at their true worth.

–François de La Rochefoucauld, French Author

here’s a part of human nature that seems to be hopelessly enthralled by the promise of bigger and better things. From cars with superfluous luxury features, to the newest electronic gadgets, it seems that we’re often willing to risk our hard–earned money for even the flimsiest promise of an improvement in our existing state of affairs.

Of course, psychologists and product–marketers alike know full–well the power of this promise in driving our actions and purchasing decisions. New product launches are the lifeblood of any business, and no company which wants to keep up with its competition can afford to appear stagnant in the eyes of a buying public with an insatiable appetite for novelty. As a result, we’ve come to see the words “New and Improved” plastered on nearly every consumer product – so much so, in fact, that there’s an implicit tendency to believe that “new” automatically means “improved.”

The nutritional supplement industry is far from exempt from this immutable law of consumer psychology, but the market pressures which drive the constant development of new products and new ingredients make for some interesting conundrums unique to the realm of nutrition. Many novel ingredients now being sold as nutritional supplements bear only a passing resemblance to substances which are found in food, and many of these substances have almost no safety or efficacy data to support their use.

Even subtle variations of existing, time–tested nutrients can have remarkably different effects than the original substances from which they were spawned – but this fact is often conveniently ignored by greedy product marketers who know that we’ll often throw caution to the wind when faced with the slightest opportunity to improve our physique or physical performance.

As the quintessential example of this phenomenon, in recent years many “new” versions of the dietary supplement, creatine, have been introduced into the marketplace – the two most notable types being buffered creatine and creatine esters.

Of course, the marketers of these products know that it will take some doing to unseat creatine monohydrate from its well–deserved status as the most extensively studied and most effective sports supplement which has ever been available. For this reason, their game plan seems to be a two–pronged attack, both to slander creatine monohydrate as inefficient (and even toxic), and to shamelessly tout their products as superior in the absence of even a shred of legitimate scientific evidence.

As we’ll see as we continue our Creatine Q & A in this issue of the Integrated Supplements Newsletter, “New” doesn’t always mean “Improved” – and this fact has never been truer than with the current crop of “new” creatines.

Q. Some sellers of nutritional supplements claim that creatine monohydrate is unstable and converts into the toxic compound, creatinine, rapidly when mixed with liquids. They also claim that creatine monohydrate degrades to creatinine rapidly when exposed to the acidic environment of the stomach, and that buffered versions of creatine are the most stable, effective forms. Are these claims true?

A. In a word: No. Not only has buffered creatine not been shown to be, in any way, superior to creatine monohydrate, but the very premise upon which buffered creatine is promoted – that creatine monohydrate degrades rapidly into creatinine – is faulty. Anybody who has actually followed the research on creatine monohydrate will realize immediately that the scientific–sounding claims made by the sellers of buffered creatine amount to little more than scare tactics and propaganda concocted in order to sell their product. The reality is that the conversion of creatine monohydrate to creatinine is almost a complete non–issue for all practical purposes.

But, at the very least, the exaggerated claims of the sellers of buffered creatines give us the opportunity to learn the truth about creatinine – a natural byproduct of creatine metabolism within our bodies.

Within the muscle cell, approximately 60 – 70% of total creatine is stored as phosphocreatine – the substance which donates a phosphate and regenerates the energy molecule, ATP. Both creatine and phosphocreatine are polar, electrically charged molecules which don’t freely pass out of the cell. We know that creatine can enter the cell, of course, but the hard time it has getting out of the cell once phosphocreatine is formed is why creatine supplementation is able to cause such dramatic increases in muscle creatine and phosphocreatine concentrations.

Within the cell, a small percentage of creatine and phosphocreatine are converted into the electrically inert substance, creatinine. Because creatinine lacks the polar nature and electrical charge of its predecessors, it is able to freely exit the cell, and is subsequently excreted by the kidneys. This slow and steady conversion of creatine and phosphocreatine to creatinine is why muscle creatine levels take several weeks to return to pre–supplementation level when creatine supplementation is ceased.

Now, the makers of buffered creatine don’t deny that creatinine is a natural byproduct of creatine metabolism. But they do make the explicit claim that much if not all of the creatine from creatine monohydrate supplements converts to creatinine when mixed with liquids, or in the acidic environment of the gastrointestinal tract. They also go on to claim that the side effects associated with creatine are due to the formation of creatinine before creatine even reaches the muscle.

But these claims are utter nonsense, as can be easily demonstrated by a look at the extensive scientific literature on the subject.

First of all, it’s been shown by many researchers that the conversion of creatine into creatinine in solution actually occurs relatively slowly – not in seconds or minutes, but rather, in hours or even days. To give a frame of reference, creatine conversion to creatinine after a full day in aqueous solution (mixed with water) at room temperature has been shown to occur at a rate of around 1– 2% at the most – a far cry from the 100% conversion in minutes or seconds as explicitly stated by the sellers of buffered creatine.

As evidence, researchers attempting to create creatine–fortified food products have extensively studied the stability of creatine over a wide range of pH values and storage temperatures. Their research clearly indicates that the conversion of creatine to creatinine is likely to be a complete non–issue for all practical usages of creatine monohydrate powder.

For example, patent research for creatine–fortified foods conducted by a respected group of creatine researchers found the following:

• Creatine in aqueous solution is completely stable for 8 hours at 25 ° C (77 ° F) at a pH of 7.5 (room–temperature water).

• Creatinine formation from creatine after 3 days at pH 5.5, 4.5, and 3.5 was 4%, 12%, and 21% respectively.

This data is from:

Patent Link – Compositions containing creatine.

See also: Harris, R C (2001) Effects and safety of dietary and supplementary creatine. In: Creatine. From basic science to clinical application. Paoletti R, Poli A and Jackson A S (eds) Kluwer Academic Publishers, Dordrecht, Netherlands. pp 33–39.

And, in addition to this research, the work of other researchers confirms the remarkable stability of creatine monohydrate:

Study Link – A simple LC method with UV detection for the analysis of creatine and creatinine and its application to several creatine formulations.

Quote from the above study:

The first–order degradation constant for creatine [was] calculated from the slope of the line and was 0.0263 per day at 25 ° C.

So, by all scientific accounts, it’s clear that the conversion of creatine to creatinine simply doesn’t take place in solution very quickly at all (even in acidic mediums like citrus juices or stomach acid).

Q. So creatine, for all practical purposes, doesn’t convert to creatinine when we prepare our creatine mixtures, but what about the claim that creatine converts to creatinine before it reaches our muscles? Does “un–buffered” creatine convert to creatinine inside our body to any meaningful extent?

A. No, not to any meaningful extent.

In the above graph, we see that creatine remained reasonably stable for at least four hours in a solution with a pH of 3.5. After taking a dose of creatine, serum levels of creatine reach their peak 2–3 hours after ingestion (depending upon the dose taken). So, even stomach acid is unlikely to cause creatinine formation to any significant extent.

And more directly, various studies have looked at the pharmacokinetics of creatine (pharmacokinetics is, basically, the study of how ingested compounds “move” around the body, what they’re converted into, and how they’re excreted). These studies simply show no evidence that creatine is massively degraded into creatinine before it reaches our muscles – quite the contrary, in fact.

The following study looked at serum creatine and serum creatinine levels in subjects who consumed a single 20 gram dose of creatine. Creatine and creatinine levels were measured over a six hour time–period.

While the researchers found that serum creatine levels increased greatly (50–fold, or 5000% at peak levels), serum creatinine increased by only a modest, biologically insignificant amount (13% at peak levels).

Study Link – Acute creatine ingestion in human: Consequences on serum creatine and creatinine concentrations.

Quote from the above study:

These results suggest that when acute doses of [creatine] are ingested in humans, the degree of conversion of exogenous [creatine] to [creatinine] in the stomach and the gut can be considered as negligible following the first 6 h of ingestion.

So, even a large dose of creatine (20 grams) did not lead to a meaningful increase in serum creatinine levels. Considering the fact that creatine reaches peak levels in serum after 2–3 hours, and returns to baseline levels after approximately 6 hours without any appreciable increase in serum creatinine, it’s simply unfounded to say that creatine converts to creatinine before it reaches our muscles.

Some studies show that creatine supplementation can lead to slight elevations in urinary creatinine concentrations, but many studies show creatine supplementation to have no such effect. In the following study, when subjects consumed creatine monohydrate in doses of 20 grams per day for five days followed by a dose of 5 grams per day for five days, researchers reported that this creatine intake had no effect on urinary creatinine levels.

Study Link – Effect of oral creatine supplementation on random urine creatinine, pH, and specific gravity measurements.

Quote from the above study:

This short–term study investigated the effects of oral creatine supplementation on urinary creatinine, pH, and specific gravity values. Individual plots of all discrete urine specimen values did not reveal any apparent effect of creatine administration on these measurements.

Note: Exercise itself has been shown to increase creatinine excretion, and many creatine studies involve intense exercise. It’s possible that some of the increases in creatinine excretion seen in the published literature may have more to do with the effects of exercise rather than creatine consumption.

Studies consistently show that the vast majority of excess creatine consumed is excreted unchanged as creatine – not creatinine. As evidence, the following study supplied a loading dose of creatine monohydrate (20 grams per day for 5 days) to an individual, followed by a 30–day washout period, followed by another loading period.

The researchers found that once tissue creatine stores were full, the excess creatine consumed was excreted as creatine – while creatinine level remained within normal limits:

Study Link – Effects of Repeated Creatine Supplementation on Muscle, Plasma, and Urine Creatine Levels.

Quote from the above study:

Urine creatine increased profoundly during both bouts of supplementation, with no obvious differences between supplementation bouts. Creatine retained by the body (total creatine ingested minus total creatine recovered in the urine) was 36.8 g during bout 1 and 36.6 g during bout 2. The man excreted 63.2% and 63.4% of supplemented creatine during bouts 1 and 2, respectively. Urine creatinine values were within normal limits during both bouts 1 and 2 of supplementation on all but one testing day, and day–to–day fluctuations were typical of a healthy, nonvegetarian adult.

These studies, taken together, are clear evidence that creatine does not convert to creatinine in any meaningful amount before we consume it; and also that creatine does not convert to creatinine in any meaningful amount after we consume it – either before, it reaches our muscles, or when an excess is being excreted in the urine. The simple fact is that the overwhelming amount of creatine research as a whole directly refutes the explicit claims of those selling buffered creatine.

And, in strictly logical sense, if creatine monohydrate did convert to creatinine at the rates the buffered creatine–sellers state, taking creatine wouldn’t elevate muscle creatine or phosphocreatine stores, improve performance, or aid in muscle building at all – yet it clearly does all of these things quite well.

So, in essence, the sellers of buffered creatine have set up a biological straw man. They’ve posited their product as a solution to a phenomenon – creatine to creatinine conversion – which the scientific literature indicates simply doesn’t exist in any practical, meaningful sense.

The only time the creatine to creatinine conversion achieves practical significance is when trying to stabilize creatine in liquids for long periods of time. This is why so many liquid creatine products have continually failed to deliver the benefits of powdered creatine monohydrate. These products may be many months old by the time they’re consumed, and in these products, the conversion of creatine to creatinine has proven to be a serious problem. As we referenced in last month’s newsletter, when independently tested, certain liquid creatine products have been found to contain almost no creatine whatsoever, while containing relatively high amounts of creatinine.

Q. Why do some people notice fewer side effects with buffered creatine (or esters, or chelates) than with creatine monohydrate?

A. As we mentioned in the previous Integrated Supplements Newsletter, most, if not all, creatine monohydrate–related side effects can be rectified simply by consuming less creatine – or smaller doses of creatine spaced out over the course of the day. If we do this, possible side–effects like stomach upset and water–retention will be largely eliminated.

Now of course, when we compare apples to apples, we see that the recommended dose of buffered creatine (and similarly, creatine esters and chelates et al.) will supply the body with just that – low doses of creatine.

On a molecular level, creatine monohydrate, which is simply creatine bound to a water molecule, will contain approximately 88% creatine by weight. Buffered creatine is simply creatine monohydrate with alkaline substances added to it – so, logically, it will contain less creatine than an equal weight of pure creatine monohydrate. Many other types of creatine salts, esters, and chelates will also contain far less creatine by weight relative to creatine monohydrate. For instance, creatine–magnesium chelate, will contain 45% creatine – roughly half that of creatine monohydrate.

So, the reason people sometimes notice fewer side–effects with the “newer” creatine products is simply because, in one way or another, they’re consuming less creatine – plain and simple. It isn’t because one creatine is “buffered,” or more soluble, or “stronger,” or more bioavailable, or absorbed better, or anything like that – although this is exactly what the marketing behind these products would have us believe.

And speaking of the side effects associated with creatine monohydrate, it’s worth noting, too, that some low–cost creatine monohydrate powders may cause gastrointestinal side effects if they are not pure creatine. In years past, more than a few sources of creatine monohydrate were found to contain fairly significant levels of creatinine and other contaminants as the result of an inefficient production process. It’s conceivable that cheaply produced creatine products may cause side effects because they are not, in fact, pure creatine monohydrate.

The lesson is: those who have experienced side effects with creatine monohydrate need not resort to over–priced and untested alternatives – they should merely make an effort to seek out creatine monohydrate of the highest purity, and find a dose that’s right for them. The long–term health benefits which are likely to result from creatine consumption are sure to make such simple experimentation more than worthwhile in the long–run.

Q. What about creatine esters like creatine ethyl ester?

A. The rampant promotion of creatine esters in recent years is yet another example of how greed and scientific speculation have served to tarnish the reputation of the entire sports nutrition industry. In the nearly complete absence of efficacy and safety research, creatine esters have been introduced into the nutritional supplement marketplace on the mere assumption that they would act as highly soluble, and highly absorbable forms of creatine.

But what limited research exists on these compounds indicates that this is not the case. With creatine esters, we simply find that, yet again, the claims of many supplement marketers are completely unsubstantiated. Unfortunately, if the history of the sports supplement industry is any indication, some customers will keep falling for the creatine–ester hype, the baseless claims will be repeated ad nauseam, and the products will continue to be sold, even after their worthlessness has become well–documented.

It’s actually hard to keep up with all of the outrageous claims which are made for creatine esters, but there are a few proposed mechanisms (ranging from the highly unlikely, to the scientifically impossible) by which creatine ethyl esters are often claimed to provide benefits above and beyond creatine monohydrate. But as the research stands now, the outlook is simply not good for creatine ethyl ester as a viable source of supplemental creatine.

As a bit of background, creatine esters are forms of creatine with an alcohol attached (at the caboxylic group of the molecule) whereas creatine monohydrate contains a water molecule attached at this same functional group. The most common creatine ester, creatine ethyl ester (CEE), is creatine bound to the alcohol, ethanol (more specifically, the ingredient commonly used in supplements is known as creatine ethyl ester hydrochloride). This compound will have a greater solubility in water than creatine monohydrate, and the presence of the lipophilic (fat–loving) esters on the creatine molecule is said by many to (somehow) allow greater creatine uptake by the cells.

But, let’s take a closer look at a few of the more common claims made for creatine esters:

Faulty Claim #1 – Creatine Ethyl Ester is more fat–soluble than creatine monohydrate, and will therefore cross (fat–containing) cell membranes, and enter cells more efficiently. This could lead to greater creatine concentrations within the cell.

The Truth: This claim is without any substantiation, and doesn’t even make sense from a theoretical standpoint. The presence of esterase enzymes in intestinal cells and the blood will break down CEE into creatine and ethanol quite rapidly. By the time CEE reaches the muscle cell, the vast majority of ester will already be dissociated from the molecule, and what’s left (if we’re lucky) will be plain old creatine. There’s simply no reason to believe that a substantial amount of CEE will remain intact by the time it reaches the target cell. Similarly, there’s no legitimate reason to believe that CEE will bypass creatine transporters, or be able to “force” the cell to hold more creatine or phosphocreatine.

In fairness, the researchers who are the patent–holders of creatine esters never anticipated that creatine esters would enter the target cell intact. The above nonsensical claim seems to have derived exclusively from the clueless marketers of creatine ethyl esters, and some ill–informed authors within the nutritional supplement industry.

The patent holders of creatine esters assumed that the ester forms would simply deliver more creatine into the bloodstream than creatine monohydrate. Although this doesn’t appear to be true in any practical sense either, this hypothesis is certainly more reasonable than assuming that the esters will be absorbed intact by the muscle cells.

We can see, in the following quote from the patent holders of creatine esters, that their proposed mechanism of action involved the possibility that creatine esters would simply be absorbed from the gastrointestinal tract more efficiently than creatine monohydrate:

Patent Link – Creatine ester pronutrient compounds and formulations.

Quote from the above patent:

An additional advantage of creatine esters is that, as the creatine ester compound moves from the intestinal tissue into the bloodstream, the creatine ester compounds themselves are biologically inactive, but esterase enzymes present in both the intestinal cells and the blood break the ester bonds of creatine ester, converting it to biologically active creatine. In other words, the advantages of the creatine ester are preserved during transport, such as increased solubility and permeability, but when needed, the creatine is available to be converted into its biologically active form.

It’s worth noting that if a small amount of creatine esters are absorbed into the target cell intact, this could potentially be a very bad thing. We simply have no evidence that these esters can safely increase phosphocreatine levels the way creatine monohydrate can. It’s entirely possible, that if these esters enter the target cell intact, they may actually inhibit phosphocreatine synthesis by interfering with the enzyme, creatine kinase (remember, CEE, in its intact form is completely foreign to human metabolism. Unlike free creatine there’s a chance that such a foreign molecule will inhibit the enzyme systems designed to utilize creatine). As a frame of reference, inhibitors of creatine kinase include known neurotoxins such as ethylene oxide and acrylamide, which are implicated in degeneration of the nervous system.

Study Link – Effects of neurotoxins on brain creatine kinase activity.

Quote from the above study:

The inhibition of [creatine kinase] may play a role in the pathogenesis of distal axonal degeneration in the central and peripheral nervous systems.

It’s unknown if this fact will have any practical significance as related to the consumption of creatine ethyl ester, (as the position of the ethyl ester indicates that it may not directly interfere with creatine binding to creatine kinase) but it’s certainly not a stretch to say that creatine ethyl esters could have negative effects on these same enzyme systems by indirect means (ethanol itself inhibits many enzyme systems even without being bound to creatine). The point is that scientific investigation into these possibilities is simply non–existent. Those consuming creatine esters should be aware that they are doing so in the complete absence of long–term safety data on the compound. As it stands now, creatine ethyl esters seem to offer all risk and no benefit.

Faulty Claim #2 – Creatine monohydrate is poorly absorbed and inefficient. Large doses of creatine monohydrate are needed in order to saturate the tissues, and these doses can cause bloating.

The Truth: Those who say that creatine monohydrate is poorly absorbed are engaging in some very sloppy thinking, to say the least. Scores of existing research make it clear that creatine monohydrate is very well–absorbed – both from the gastrointestinal tract into the bloodstream, and from the bloodstream into the target cells.

As evidence of efficient gastrointestinal absorption, studies have repeatedly shown that excess creatine is almost completely excreted in the urine (if an ingested compound ends up in the urine, it means, by definition, that it has been absorbed from the gastrointestinal tract – substances which are unabsorbed will be excreted in feces, and this just doesn’t happen with creatine consumption):

Study Link – Creatine Metabolism in Men: Urinary Creatine and Creatinine Excretions with Creatine Feeding.

Quote from the above study:

There was no significant increase in fecal nitrogen during the creatine–feeding period. Other investigators have reported the lack of significant amounts of isotope in the feces or other urine compounds after oral administration of [15N]creatine indicating that normally, urine is the only major excretory route of creatine and creatinine.

What people misconstrue as evidence of creatine monohydrate’s “poor absorption,” is that large doses of creatine monohydrate can draw water into the gastrointestinal tract if not consumed with sufficient liquid. Therefore, large doses of creatine can potentially cause stomach upset. This simply means that creatine should always be consumed with sufficient liquid (approximately 16 oz of water for every 5 grams of creatine). But, equally as important, as we saw in the previous Integrated Supplements Newsletter, large doses of creatine simply aren’t necessary in order to reap the full benefits of creatine.

As far as creatine absorption by the muscle (or other target) cell goes, we find, as well, that creatine, taken in the form of creatine monohydrate is very well absorbed. In fact, numerous studies have shown that creatine monohydrate is consistently able to elevate phosphocreatine stores to their maximal level. This point is an important one to consider – no matter what type of creatine is taken, there is simply a finite limit to the amount of creatine and phosphocreatine a cell will hold.

If excess creatine is excreted, this doesn’t mean that creatine is poorly absorbed by the cell, but that the cells have already been saturated with creatine. If creatine monohydrate were poorly (or inefficiently) absorbed by the target cell, we would see excretion rates remain constant throughout the supplementation period – but we don’t see this at all. What we do see is creatine excretion rates increasing as the cells become fully saturated with the maximum level of creatine they can hold:

Study Link – Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation.

Quote from the above study:

Uptake into muscle was greatest during the first 2 days of supplementation accounting for 32% of the dose administered in three subjects receiving 6 x 5g of creatine monohydrate/day. In these subjects renal excretion was 40, 61 and 68% of the creatine dose over the first 3 days. Approximately 20% or more of the creatine taken up was measured as phosphocreatine.

Where creatine monohydrate has repeatedly been shown to increase muscle creatine stores to their maximum level, it’s hard to fathom how anyone could say that creatine monohydrate is poorly absorbed – especially considering that no other type of creatine has been shown to increase muscle creatine/phosphocreatine stores at all, never mind more efficiently than creatine monohydrate.

Faulty Claim #3 – Creatine Ethyl Ester is more stable than creatine monohydrate, and will be absorbed and utilized more efficiently.

The Truth: Despite the many marketing claims which are made for creatine esters, this, in a nutshell, is the stated claim of the researchers who actually hold the patent on creatine esters. But, when discussing buffered creatines, we already showed that creatine monohydrate is, in fact, remarkably stable for all practical purposes – it simply doesn’t degrade into creatinine as the patent–holding researchers assumed.

It’s important to note that patents are not scientific studies. Patent applicants are free to speculate on how their inventions may be improvements upon existing inventions, but they are not required to prove this before patenting something. Often, the theories of patent holders (even if the patent holders happen to be scientists) turn out to be incorrect; and the invention offers no benefit over existing ones. For example, in the case of creatine esters, there are now several lines of evidence showing that creatine esters may very well convert to creatinine at an accelerated rate versus creatine monohydrate.

So, we may have a case of the pot calling the kettle black, so to speak. What little research is available on creatine esters seems to indicate strongly that they, and not creatine monohydrate, convert into creatinine very rapidly, both in solution, and in the body once consumed.

The first piece of evidence along these lines actually came from the creatine ethyl ester marketers themselves.

In the United States, companies seeking to introduce novel dietary ingredients into the food supply, or into the realm of dietary supplements are required to notify the Food and Drug Administration, and provide evidence that the substance is “reasonably expected to be safe.”

But the evidence submitted to the FDA supposedly supporting the safety of creatine ethyl ester was anything but convincing. First off, the vast majority of scientific references supplied by the marketers of CEE actually referenced the safety of creatine monohydrate, not creatine ethyl ester.

Noting that the submission for new dietary ingredient status suffered from a nearly complete lack of safety data on creatine ethyl ester per se, the FDA wrote in their reply:

FDA has carefully evaluated the information in your submission and the agency has significant concerns about the evidence upon which you rely to support your conclusion that “Creatine Ethyl Ester HCL” when used under the conditions recommended or suggested in the labeling of your product, will reasonably be expected to be safe.

In subsequent submissions to the FDA, the marketers of creatine ethyl ester argued that because creatine ethyl ester rapidly breaks down into creatine and ethanol, the safety of the compound could be logically deduced from the safety and widespread use of creatine (in monohydrate form) and ethanol (the alcohol found in alcoholic beverages).

But this strange sort of logic is riddled with flawed thinking.

We mentioned previously that if some creatine ethyl ester is absorbed intact by the target cell, the compound could be at least mildly toxic. This toxicity would be completely unique to creatine esters, and would be a complete non–issue with creatine monohydrate which lacks the ester linkage of creatine ethyl ester. In light of the possibility for harm, more thorough testing of the actual compound being introduced into the marketplace doesn’t seem like too much to ask for.

But beyond merely speculative differences between creatine monohydrate and creatine ethyl ester, there appear to be documented differences in how each compound is metabolized. The first piece of evidence for this is in the documents submitted to the FDA by the creatine ethyl ester marketers themselves.

In one of the studies submitted to the FDA by the marketers of CEE, radioactively labeled creatine ethyl ester was given to rats allowing the researchers to see exactly how the substance is metabolized.

But, although the marketers of creatine ethyl ester use the findings from this study as evidence to support their contention that creatine ethyl ester is metabolized similarly to creatine monohydrate, their own statements about the study show clearly that this is not the case.

To quote the CEE marketers in their submission to the FDA:

…following oral administration the [4– 14C] Creatine Ethyl Ester is rapidly absorbed from the gastro–intestinal tract, with radioactivity being detected in plasma within three minutes following administration. The peak concentration of the associated form (ester) occurred at five minutes following administration, and accounted for less than 15% of the total radioactivity present in the plasma.

So, we can see that, although the majority of creatine ethyl ester is broken down before it enters the bloodstream, 15% of it is absorbed intact. It’s likely that most of this CEE is degraded in plasma, but as of now, we don’t know how much, if any is taken up by the cells intact. The quote continues:

This indicates that its dissociation into creatine and ethanol is rapid and nearly complete within this initial five–minute period. At ten minutes following administration, approximately 2% of the total radioactivity present in plasma was in the associated ester form, with none detected after the ten–minute time point. The rapid dissociation of the ethyl ester in the plasma was accompanied by a concurrent rapid increase in creatine and creatinine levels as suggested in the earlier study (see Attachment 24). The peak level of creatine in plasma was equivalent to about 12% of the total radiocarbon present, and occurred at approximately thirty minutes following administration. The concentration gradually declined, and gave rise to creatinine levels that increased to approximately 80–90%, where they remained throughout the duration of this study period. This pharmacokinetic profile is expected, since creatinine is the known major metabolite of creatine.

But we know from the previous studies in this newsletter that creatine monohydrate doesn’t lead to a “rapid increase in …creatinine levels” as, apparently, creatine ethyl ester does. So, despite the contention of the CEE–marketers, this “pharmacokinetic profile” is absolutely NOT to be expected from any compound which is said to be metabolized similarly to creatine monohydrate.

In fact, in this creatine ethyl ester study, 80–90% of the radioactivity was measured as creatinine – indicating that, quite unlike creatine monohydrate, the majority of creatine ethyl ester rapidly degrades into creatinine upon ingestion.

And subsequent studies have confirmed that indeed, that there are some major differences between the stability of creatine monohydrate and creatine ethyl ester. These other studies also show that creatine ethyl ester may be particularly prone to rapidly convert to creatinine upon ingestion.

A study presented at the 4th International Society of Sports Nutrition (ISSN) annual meeting in 2007 tested the stability of creatine monohydrate and creatine ethyl ester in acidic solutions (pH of 1).

The study found:

• After 30 minutes in solution, greater than 99% of creatine remained available from the creatine monohydrate.

• After 30 minutes in solution, only 73% of creatine from creatine ethyl ester remained available from one sample, and 62% remained available from another sample.

• After 120 minutes in solution, more than 99% of creatine remained available from creatine monohydrate (further evidence of the remarkable stability of creatine monohydrate, by the way).

• After 120 minutes in solution, the two CEE samples tested showed 72% and 11% creatine available.

• Substantial creatinine formation (and not simply the dissociation of creatine from its ester) was noted in the CEE solutions.

Article Link – Creatine Efficacy Headlines At Sports Nutrition Meeting.

Admittedly, the research on the stability of CEE is preliminary, but it’s clear that, at the very least, there are major differences between creatine ethyl ester and creatine monohydrate – differences that do not bode well for the stability, safety, or effectiveness of creatine esters. The marketers of CEE seem to want to have their cake and eat it too. They want us to believe that CEE is different than creatine monohydrate when they tout its supposed benefits, but the same as creatine monohydrate when they attempt to assure us of its safety. Unfortunately for them, science simply doesn’t work this way.

So, it should be recognized explicitly that, at this point in time, every known piece of scientific literature on creatine ethyl ester (including the literature submitted to the FDA by the products’ marketers – to garner approval for CEE to be used in dietary supplements) showed that creatine ethyl ester degrades into creatinine at a markedly higher rate than creatine monohydrate – in both in vitro and in vivo studies.

And to boot, zero studies at this point have been conducted to show that creatine ethyl ester is in any way effective for increasing creatine or phosphocreatine levels. Nor have any studies been conducted to show that creatine ethyl ester improves any marker of health, or mental/physical function.

Considering that there is no evidence to support the contention that creatine ethyl ester is in any way superior to creatine monohydrate, the only reasonable conclusion we can draw at this point is that those consuming creatine esters have been deceived. They are not only not reaping the full benefits of creatine, but they are, instead, likely to be consuming a mildly toxic substance.

One of the most frustrating things about debunking the fraudulent and unsubstantiated claims of the sports nutrition industry is that there seems to be a limitless amount of them. Every day, it seems, we’re bombarded with one baseless claim after another; and, if we’re not careful, we could spend all of our time deconstructing assertions so ridiculous, that they’re not even open to legitimate scientific consideration in the first place.

To focus on the few (yet remarkably vocal) bad apples in the nutritional supplement industry, however, would ultimately be a disservice to the honest and hard–working researchers who are exploring the novel health–promoting actions of nutritional substances. At Integrated Supplements, we’d much rather spend our time bringing their research to your attention than exposing the snake–oil salesmen.

So, in the next issue of the Integrated Supplements Newsletter, we’ll explore some of the many health–promoting and anti–aging properties of creatine monohydrate. As we’ve mentioned previously, creatine monohydrate is shedding its reputation as a mere sports supplement, and is beginning to gain its rightful place in the upper echelon of health–supporting nutritional substances. No matter how much the shady marketers try to cloud the issue, when we look at the research, the far–reaching benefits of creatine monohydrate will be as clear as day.