Walk down any supplement aisle and you will find creatine sold as hydrochloride, buffered powder, liquid, gummies, nitrate, and molecules with names that sound more like patents than nutrients. Every one of them is marketed as an improvement on plain creatine monohydrate, the white powder that has been studied since the early 1990s. Dr. Ralf Jäger, a chemist who spent the early part of his career trying to build a better creatine and who later co authored two major scientific reviews on the subject, has a blunt answer to whether any of them succeeded. According to Jäger, creatine monohydrate is still what he calls the king of the castle, and the newer forms have not caught up on safety data, efficacy data, or direct comparisons.
This article works through his argument, checks it against the published research, and explains why solubility, plasma levels, and marketing claims are not the same thing as evidence that creatine actually reaches your muscles.
Why Monohydrate Is the Benchmark
Jäger opens by noting that creatine is the most researched and, in his view, the most effective ingredient in sports nutrition after protein, and that creatine monohydrate has been on the market for more than 30 years. The published record supports the first part of that claim. The International Society of Sports Nutrition’s 2017 position stand (Kreider et al., 2017) concludes that creatine monohydrate is the most effective ergogenic nutritional supplement available to athletes for increasing high intensity exercise capacity and lean body mass during training, and that supplementation at up to 30 g per day for five years has been safe and well tolerated in healthy people. Ranking creatine “second to protein” is Jäger’s own framing rather than a formal scientific finding, and reasonable people could argue about that ordering.
What monohydrate does inside the body is well documented. Jäger’s 2011 review with Kreider and colleagues (Jäger et al., 2011) summarised decades of muscle biopsy work showing that monohydrate raises muscle creatine and phosphocreatine by roughly 15 to 40 percent, improves anaerobic exercise capacity, and allows more training volume, which over time translates into gains in strength, power, and muscle mass. The same review reported that monohydrate is not broken down during digestion, and that nearly 99 percent of what you swallow is either taken up by muscle or excreted in urine. In plain terms, almost none of it is wasted.
That is the standard any new form has to beat. Jäger explains that his group first assessed the alternatives in 2011, asking three questions of each: is it safe, has it been clinically validated, and how does it compare to monohydrate. They found nothing better. In preparation for the talk, they repeated the exercise, and the updated review (Kreider, Jäger, and Purpura, 2022) reached the same conclusion: monohydrate remains the only source of creatine with substantial evidence for bioavailability, efficacy, and safety, and the only one explicitly recommended by professional societies.
A note on independence is warranted here. Jäger is an author on both reviews, previously worked for the company that manufactures the Creapure brand of monohydrate, and ran several of the creatine salt studies discussed below through his own consultancy. None of that makes the data wrong, and the underlying trials are published and peer reviewed, but readers should know that the person making the case has spent his career close to the product.
The Chemist Who Tried to Beat It
Jäger’s credibility on this topic comes partly from having failed at it himself. He describes training as an organic chemist in Germany and at Caltech, then taking his first industry job as head of a laboratory at SKW, the company that became Degussa and is now AlzChem. He was given three annual goals: stabilise creatine in water, find a form of creatine better than monohydrate, and find new health applications. Looking back, he says that had he known then what he knows now, he is not sure he would have taken the job, because the first two tasks turned out to be extremely difficult, if not impossible.
That framing matters because it sets up the rest of the talk. The problems with monohydrate that motivate new forms are real, but they are physical and practical problems, not biological ones. Solving them chemically tends to change the molecule in ways that make it worse at the one thing that matters, which is getting creatine into muscle.
What People Dislike About Monohydrate
Jäger lists the legitimate complaints, and it is worth taking each seriously, because they are the reason the alternative market exists.
The first is that there is no acute effect. Creatine works by raising the creatine content of muscle, so you either take a larger amount for a short loading period or a smaller amount for several weeks. Nothing happens after a single dose. The published loading data bears this out: the 2022 review summarises classic work showing that 20 g per day for six days raised muscle creatine by about a third, while 3 g per day took roughly five weeks to produce a smaller but meaningful rise.
The second is weight gain. Jäger explains the mechanism: when creatine is transported into muscle, sodium is dragged in with it, and sodium pulls water. The result is a rise in cellular hydration and therefore in body weight. He notes that this cell swelling may actually be part of how creatine works, because it appears to stimulate muscle protein synthesis, but that many people, and in his experience women in particular, avoid creatine because of it. The research here is more nuanced than the talk suggests. A 2021 expert review of common creatine questions (Antonio et al., 2021) confirms early water retention during loading but finds no evidence of disproportionate long term water gain. Abbie Smith-Ryan, whose group published a lifespan review of creatine in women (Smith-Ryan et al., 2021), has since said publicly that the weight gain evidence comes mainly from men on loading doses and that women in her studies generally do not gain weight. So the reluctance Jäger describes is real, but the fear behind it is only partly justified.
The third is nonresponse. Jäger states that a certain share of people do not raise their muscle creatine as much as others. Syrotuik and Bell (2004) documented this directly with muscle biopsies, finding responders, partial responders, and nonresponders within a group of eleven men after a five day load. Responders tended to start with lower muscle creatine, more type II muscle fibres, and more lean mass; nonresponders started with already high creatine stores and showed no strength improvement.
The fourth and fifth are practical: monohydrate has limited solubility, so it settles at the bottom of a glass, and it is unstable in liquid over time. The sixth is dose size. A standard serving is about 5 g, which Jäger points out is hard to fit into a capsule, a gummy, or any of the convenient formats consumers increasingly prefer.
Put together, that is a genuine list of shortcomings. What follows is Jäger’s account of how the industry tried to address them, and why the fixes have not proven themselves.
What Happens to Creatine in Liquid and in Your Stomach
The stability question underlies several of the alternative forms, so Jäger spends time on the chemistry. Creatine in solution slowly converts to creatinine, a waste product, through a reaction in which the molecule folds and bonds to itself. How fast this happens depends on pH and temperature: the lower the pH and the higher the temperature, the faster the loss. He cites data showing significant degradation within 72 hours at pH 3.5.
The published figures match. Work by Harris and colleagues, summarised in the 2022 review, found creatine stable for about three days at neutral pH, but at room temperature losing around 4 percent at pH 5.5, 12 percent at pH 4.5, and 21 percent at pH 3.5 over the same period. Monohydrate powder, by contrast, is remarkably stable: the review reports no detectable creatinine after more than three years of storage at 40 degrees Celsius.
This raises an obvious worry. The stomach is highly acidic, so does creatine survive digestion? Jäger’s answer is that chemistry rescues us. Below about pH 2.5 the creatine molecule becomes protonated, which blocks the folding reaction, so degradation stops. The same thing happens at very high pH through the opposite process, deprotonation. Because stomach acid sits below 2.5, creatine is effectively stable during digestion. The review confirms this, estimating that less than 1 percent of monohydrate is lost to creatinine in the gut.
Jäger describes how strict his own definition of a stable creatine liquid was during his industry years: no detectable creatinine at all. Under that standard, every approach failed. He notes that some products on the market use a looser definition and accept meaningful creatinine content alongside the creatine. He also describes a clever workaround that worked for cosmetics but not for supplements: because the creatine to creatinine reaction is an equilibrium, adding creatinine to a cream stops further creatine loss, which is why creatine appears in skincare products. That trick is unusable in an oral product, he says, because you cannot feed a person that much creatinine. The only reliable way to sell a stable creatine drink, in his account, is to keep the creatine physically separated from the liquid, for example in a cap that releases it when opened.
Why There Are So Many Forms
Jäger reports that a database search turned up 88 creatine related compounds. The 2022 review specifies that this count came from PubChem rather than PubMed, but the number stands, and the review adds that some marketed “creatine” molecules are not in the database at all because their structure has been altered enough that they no longer contain creatine.
The reviewers laid out a simple three step test for any claimed new form, and it is a useful lens for the rest of this article. First, does the compound actually contain an intact creatine molecule that can be released during digestion? Second, does swallowing it raise creatine in the blood to physiologically meaningful levels? Third, does it raise creatine in muscle, measured by biopsy or spectroscopy, by an amount comparable to monohydrate? A form that fails the first test is not creatine. A form that passes the second but has never been tested on the third has not been shown to work. And a form that passes all three but does not exceed monohydrate has no reason to cost more.
Liquid Creatine and Creatine Serum
The first case study Jäger offers is the most cautionary. He recalls that companies have periodically claimed to have found the “holy grail” of stable liquid creatine, and that the best known example was Muscle Marketing USA’s creatine serum, marketed as safer and more effective than monohydrate powder. According to Jäger, a study by Richard Kreider found no meaningful uptake of creatine into the blood after taking it, and no increase in muscle creatine after chronic use, for the straightforward reason that the product did not contain enough creatine to do anything.
The published record is consistent. Kreider and colleagues (2003) gave forty men either the serum at its label dose, the serum at eight times the label dose, a liquid placebo, or 20 g per day of monohydrate for five days. Monohydrate raised muscle creatine by about 28 percent; neither serum dose had any effect on muscle creatine or ATP. The authors concluded that claims of superiority over monohydrate appeared to be false. A separate chemical analysis cited in the 2022 review found less than 10 mg of creatine and around 90 mg of creatinine in a serum sample, meaning the product had largely degraded into its waste product. Readers should note that the 2003 trial was funded by Degussa, Jäger’s former employer and a monohydrate manufacturer, which was also in litigation with the serum company at the time. The result has never been contradicted.
Buffered Creatine
Kre-Alkalyn takes the opposite approach to stability, using very high pH to prevent conversion to creatinine, and Jäger notes it too was marketed as superior to monohydrate. He describes what he calls a very impressive study that compared the two directly and found that on muscle creatine content, lean mass, and performance, the buffered form did not outperform monohydrate.
That study is Jagim et al. (2012), a double blind trial in 36 resistance trained participants. One group took monohydrate at standard loading and maintenance doses, one took Kre-Alkalyn at its manufacturer’s recommended 1.5 g per day, and one took Kre-Alkalyn at monohydrate equivalent doses. All groups improved, but the authors found no evidence that the buffered product produced greater changes in muscle creatine, body composition, or training adaptations, and no evidence of fewer side effects. Their stated conclusion was that the findings do not support claims that buffered creatine is more effective or safer than monohydrate. This is exactly the kind of head to head, biopsy backed comparison the three step test calls for, and it went against the newer product.
Molecules That Are Not Creatine
Jäger’s sharpest criticism is reserved for what was sold as “super creatine,” which is creatine covalently bonded to the amino acid leucine. His point is chemical rather than clinical: once you form a covalent bond across the creatine structure, the result is a different molecule. It might release creatine during digestion, or it might not, and the burden is on the seller to show it does. He notes that the same company markets a related creatine and glutamine molecule, and that the company’s own data showed it does not fully dissociate, which he says raises serious doubt about the leucine version too. He also cites a published animal study in which monohydrate far outperformed the compound at raising muscle creatine.
That animal study exists. da Silva (2022) fed rats a creatine free diet for two weeks, then gave them either a control diet, monohydrate, or an equal molar dose of creatyl-L-leucine for a week. The creatyl-L-leucine group showed no accumulation of either the compound itself or of creatine in muscle, brain, or plasma, while the monohydrate group did. The author concluded it is not a significant bioavailable source of creatine. No human trial appears to exist. The 2022 review places creatyl-L-leucine in its “no evidence” category alongside creatine serum.
Although Jäger did not discuss it in this talk, the same review covers creatine ethyl ester, another chemically altered form, and reports a human trial (Spillane et al., 2009) in which the ester raised serum creatinine to more than double placebo levels while raising muscle creatine less than monohydrate. It is another example of the same principle: modify the molecule and you usually make it worse.
Creatine Salts: Better Solubility, Unproven Uptake
The salts are where Jäger is most sympathetic, because the chemistry is sound. He explains that creatine is a weak base, so it forms salts with strong acids. Drop a creatine salt into water and you have creatine plus an acid, which lowers the pH of the glass and, because creatine dissolves better at low pH, improves solubility. He notes wryly that the old advice to mix creatine into orange juice or hot tea was really just an intuitive use of the same two levers, acidity and heat. The 2022 review gives the numbers: monohydrate solubility rises from about 6 g per litre at 4 degrees to 45 g per litre at 60 degrees, and creatine pyruvate in water produces a pH of 2.6 and dissolves at 54 g per litre.
Salts also dissociate in the stomach, releasing ordinary creatine. Jäger points to plasma studies of creatine citrate and creatine pyruvate at doses matched for creatine content, which show significant rises in blood creatine, with peak values that were actually higher than monohydrate. He is careful to add the limitation: there is no muscle biopsy study for either salt, so nobody knows whether higher blood levels translate into more creatine in muscle, better retention, or any performance advantage.
That plasma study is Jäger’s own (Jäger, Harris, Purpura, and Francaux, 2007). Six people took 4.4 g of creatine as monohydrate, tri creatine citrate, or creatine pyruvate in a crossover design. Pyruvate produced peak plasma creatine about 17 percent higher and total exposure about 14 percent higher than monohydrate; citrate did not differ from monohydrate. The authors themselves concluded that because monohydrate absorption is already close to 100 percent, differences in bioavailability were unlikely and the small kinetic differences were unlikely to affect muscle creatine during loading. Six participants is a very small sample, and the 2022 review confirms that no study since has measured muscle creatine after citrate or pyruvate.
There is a further point the talk does not make but the review does. Because the acid takes up part of the molecule’s weight, salts contain less creatine gram for gram: monohydrate is about 88 percent creatine, creatine HCl about 78 percent, creatine pyruvate about 60 percent, and creatine citrate about 41 percent. A 5 g scoop of a salt is not a 5 g dose of creatine. Marketing that promises a “smaller effective dose” runs directly against this arithmetic.
Why Blood Levels Do Not Prove Anything
This is the most useful idea in the talk for anyone reading supplement marketing. Jäger warns that many companies run a quick absorption study, show more creatine in the blood than monohydrate, and claim a better product. He states plainly that such a study only shows the product is different, not that it is better or worse, because you would need to look inside the muscle to know.
His illustration is elegant. It is well established that taking creatine with a large amount of carbohydrate produces an insulin spike, which drives more creatine into muscle and improves retention. Green and colleagues (1996) showed this in the classic study: creatine taken with roughly 90 g of simple sugars raised muscle creatine by more than 25 percent, about 60 percent more than creatine alone, and produced a meaningful rise in every subject, whereas only half the subjects taking creatine alone reached that threshold. Yet when you measure plasma creatine in that scenario, it is lower, not higher, because the creatine is leaving the blood faster. In this case, lower plasma creatine is the sign of better absorption. A company could, in principle, run a plasma study against carbohydrate loaded monohydrate, “win” it, and be selling the worse product. The 2022 review makes the same point in formal language: higher blood creatine could mean tissue uptake is slower, and lower could mean it is faster, so plasma data alone cannot settle bioavailability.
Creatine Nitrate and Creatine HCl
Creatine nitrate is the one salt with muscle data, and Jäger says it did not go the salt’s way. A study from Kreider’s lab measured muscle creatine and found monohydrate produced the greater increase. Galvan et al. (2016) ran an acute crossover in 13 people and a 28 day randomised, double blind trial in 48, comparing 1.5 g and 3 g of creatine nitrate with 5 g and 3 g of monohydrate. The nitrate raised plasma nitrate as expected and was not associated with safety concerns, but the 2022 review’s summary of the muscle data shows monohydrate ahead, and it lists creatine nitrate among forms for which clinical evidence has not shown greater creatine retention than monohydrate.
Jäger mentions creatine HCl only in passing, grouping it with pyruvate and citrate as salts that have independent studies showing they work. The research since the talk reinforces that reading without changing the verdict. A 2024 trial in resistance trained men found that creatine HCl and creatine monohydrate both improved strength and body composition relative to placebo, with no reported advantage for HCl. A 2025 triple blind trial in elite handball and softball players compared 5 g per day of each against placebo over eight weeks; the trial was designed specifically to test HCl’s claims of superiority at low doses, and nothing published from it changes the reviewers’ categorisation of HCl as having only limited evidence.
The practical summary Jäger offers is fair to the salts: as long as a salt contains bioavailable creatine and is dosed to deliver enough of it, you will see a performance benefit. He cites his own group’s work on pyruvate and citrate, in which 5 g per day for four weeks significantly improved mean power and contraction velocity during intermittent maximal handgrip exercise compared with placebo (Jäger et al., 2008), and a study in Finnish Olympic canoeists in which creatine pyruvate improved performance. He acknowledges that neither study included a monohydrate arm and says he would expect monohydrate to perform identically. The 2022 review describes the canoeing study as improving paddle rate and lowering blood lactate rather than race times specifically; the primary paper could not be accessed for this article. Salts work because they contain creatine. That is also why they have not been shown to work better.
The Regulatory Picture
Jäger closes his survey with regulation, which he argues tells a similar story. Creatine monohydrate was on the market before October 1994, making it an “old dietary ingredient” under US law, and the Creapure brand has FDA GRAS status, which allows its use in foods rather than only supplements. He notes that a magnesium creatine form has self affirmed GRAS, a company led process that does not go through the FDA. For new dietary ingredient notifications, he says the public database shows positive outcomes for creatine pyruvate at 5 to 10 g per day and for creatine nitrate at a low daily dose, with most other creatine forms that applied having been objected to.
The nitrate history is more tangled than the talk implies. Trade press coverage records that the FDA issued an objection letter to creatine nitrate’s NDI notification in 2011 on the grounds of insufficient safety evidence, and that the company only learned about six years later that the agency no longer objected. The specific 750 mg figure Jäger quotes could not be verified from an independent source and is reported here on his authority alone. Jäger also makes a reasonable chemist’s argument that a true salt should not need a notification at all, since it dissociates completely into two old ingredients, and FDA draft guidance does contemplate such an exemption. Even so, his broader point stands: the regulatory record favours monohydrate, and most alternatives have not cleared the bar.
Who Is Actually Taking Creatine
Jäger frames all of this against a market that has changed considerably. He cites industry figures showing that 22 percent of US gyms closed during the pandemic and that more than 30 billion dollars in revenue was lost, with gym numbers since recovering to around 2019 levels. IHRSA’s own tally supports the closure rate and puts the revenue loss at 29.2 billion dollars between March 2020 and June 2021. Brands that sold mainly through gyms suffered alongside them.
He also cites survey data suggesting that more people now believe exercise improves health (60 percent, up from 53 percent in 2006), that average training frequency has risen from 2.7 to 3.4 days per week, and that motivations have shifted from appearance toward general health. His most striking figure is that only 21 percent of people who train five or more times a week use creatine, and that among people training three or four times a week creatine does not even appear on the list of supplements used. He calls this shocking given what creatine can do. These survey figures could not be traced to a public source and should be read as industry estimates rather than established facts. Even so, the pattern they describe is plausible and consistent with the underuse the ISSN has long complained about, and it makes the point that arguments over exotic forms are a sideshow compared with simply getting more people to take the basic one.
The Verdict
Jäger’s conclusion, and the conclusion of the 2022 review, is that nothing has changed since 2011. Creatine monohydrate is highly effective and safe. Some innovations make technical sense: salts genuinely improve solubility, and separating creatine from liquid genuinely solves stability. But improved solubility does not automatically mean improved absorption, more creatine in muscle, or better performance, and the data to make that leap do not exist. Salts such as pyruvate, citrate, and HCl have independent studies showing they work, because they contain creatine. What the reviewers could not find was a single double blind, placebo controlled, randomised trial in which any new form beat monohydrate. Where direct comparisons have been run, for creatine serum, buffered creatine, creatine ethyl ester, creatine nitrate, and creatyl-L-leucine, the newer product has either matched or lost.
For a reader deciding what to buy, the practical translation is simple. Choose creatine monohydrate from a manufacturer with good purity data, take 3 to 5 g daily or use a short loading phase if you want faster saturation, take it with food or carbohydrate if you want to maximise retention, and mix it fresh rather than letting it sit in liquid. If you prefer a salt for taste or mixing, expect the same results, check that the dose delivers enough actual creatine, and do not pay extra for claims of superiority that no trial has demonstrated. The problems with monohydrate are real but mostly cosmetic. The thing it does well, it does better than anything invented to replace it.