Written by Victor R. Prisk, M.D.
11 August 2017


Creatine: What is the Best Form?

All You Need To Know For Spectacular Gains


As you can see by the ads in MD and online, the supplement industry is in constant flux. There are new products and formulations introduced to the market every day. However, it is very rare for a product or especially an ingredient to create noteworthy evolution in supplement performance. Arguably, the greatest leap up this axiomatic evolutionary ladder occurred with the advent of creatine supplements in the 1990s. Creatine has proven over and over to be “the real deal” in clinical research and bro-science. It’s a muscle-building, performance-enhancing supplement that nearly all athletes should use.

Many innovative forms of creatine have hit the market since the introduction of creatine monohydrate (CM) in the early 1990s. Companies bank on the fact that creatine, at least in monohydrate form, is a reliably effective supplement. Athletes and even average consumers are familiar with the name “creatine,” whether they think it is a performance-enhancing drug or a healthy supplement. In order to create new buzz about creatine, many different angles have been used.

First, creatine can come in various physical forms. These could be liquids, powders, gels, chews or pills. These products may mix creatine with other supplements in the hope to increase absorption or effectiveness. Second, creatine comes in different chemical forms (i.e., salts and esters). Also, because creatine is technically an amino acid, it can be combined with other amino acids to make a peptide chain (di- and tri- peptides). We will go into more detail about this in the content that follows. Third, it has been suggested that these various forms of creatine act physiologically different than CM. Claims of better absorption, greater strength gains, or less side effects are used in marketing to differentiate products from CM. With all of this variety, has any form been shown to outperform or even match the performance of original CM?

Structure and Function

For those who aren’t as familiar with creatine structure and function, I will provide a brief review. Creatine is made in the body from the amino acids arginine, glycine and methionine. Creatine is not an essential nutrient, but methionine is an essential amino acid that must be obtained in the diet. Otherwise, fish, meats and supplements act as an excellent source of creatine. Vegetarians (especially vegans) can be relatively deficient in their creatine intake.

Creatine is involved in energy production in many tissues. In muscle and brain cells, creatine is converted to creatine phosphate to act as a phosphate donor to recreate needed ATP (adenosine triphosphate) from ADP (adenosine diphosphate). Creatine phosphate makes sure that ATP is immediately available for short bursts of energy; a couple of examples would be a 30-second sprint or one set of lifts in the gym. Deficiency of creatine in a vegetarian diet results in poorer results on tests of cognitive function, with improvements in memory upon supplementation.1 Levels in muscle can be increased by up to 40 percent with dietary supplementation.2

It can be said that creatine is one of the most studied supplements on the planet. It has also been said that CM is the most effective, safe and well-studied performance-enhancing supplement.2 Studies show that using creatine enhances strength, speed and even endurance. It was initially thought that based on creatine’s mechanism of action, it would only be useful in buffering short bursts of energy. Research has demonstrated how increasing creatine stores through supplementation can improve endurance performance by increasing blood volume, glycogen storage and respiratory efficiency.3

More Lean Muscle Mass

More important for the bodybuilding community is creatine’s ability to improve lean muscle mass and muscle hypertrophy. Supplementation with creatine, protein and carbohydrate seem to be ideal for muscle growth. Creatine, when combined with exercise, induces an anabolic environment whereby changes in gene expression occur. This correlates well with notable rises in muscle IGF-1 production by muscle. In one study, creatine induced greater than 20 percent increases in IGF-1 and two times greater increases in lean body mass. More recent studies demonstrated the added antioxidant and DNA-protective effect of creatine supplementation, which presumably improves recovery.3

With this information in hand, it is clear to see why CM has become such a popular supplement. So why change it? In order to keep customers interested in the latest and greatest supplements, manufacturers have made many forms of creatine. Creatine is a weak base that can combine with acids to form a “salt.” Creatine salts like creatine malate, creatine citrate and creatine tartrate have all been marketed as sports supplements. These salts have unaltered creatine that breaks off their acid moiety in the body, releasing creatine to form creatine phosphate. Other derivatives such as creatine esters (creatine ethyl ester; CEE) or creatine alcohols (creatinol-O-phosphate) have also been marketed. However, these derivatives are chemically altered and it can’t be presumed that they become creatine in the body.2

Creatine Salts

Interestingly, some companies suggest that some of these salts have better absorption characteristics than CM, and therefore you can take less. However, compared to CM many of the salts actually have less creatine per gram than CM. For instance, the salts creatine malate, citrate, and pyruvate have ~25 percent to 30 percent less creatine per gram than CM. Even if absorption is better than CM (i.e., creatine pyruvate is ~15% better absorbed) the amount absorbed is still 10 percent less than CM. Further, just because creatine is absorbed faster this doesn’t mean that it will work better. You should load your creatine at 20 grams per day (five grams, four times per day) for up to a week anyway.

On the other hand, co-consumption of carbohydrate, low-dose D-Pinitol and protein can improve creatine retention.2, 4 Whether these boost the performance benefits of the CM is unproven. It had also been previously suggested that co-ingestion with Russian tarragon (Artemisia dracunculus), an extract that has insulin-like activity, could improve creatine loading.2 However, recent data shows that this fails to improve sprint performance over CM alone.5

Research has even explored supplementation with the creatine precursor guanidinoacetic acid (GAA). Much like beta-alanine is a precursor for carnosine, GAA is methylated to become creatine. Supplementation with GAA is well absorbed and capable of increasing creatine levels.6 However, supplementation results in elevations in homocysteine levels, which has been associated with vascular disease. GAA’s ability to boost performance is yet to be determined.

Liquid and ‘Alkalinized’ Creatine

Some companies have suggested that their form of creatine might be more stable in liquid form. The problem with creatine in solution is that it is non-enzymatically converted to inactive creatinine unless the pH is very low (very acidic) or very high (alkaline). Creatine salts such as creatine citrate do not improve creatine stability in solution. Studies also show that CEE is also less stable in solution than CM.2 In fact, CEE is so unstable that it is more likely to become creatinine in stomach acid. Studies confirm that CEE has lower bioavailability than CM, and may even be toxic by increasing creatinine levels in the blood.7 Other companies have used combinations of creatine with an amino acid like leucine or glutamine (leucyl-creatine). They have been able to demonstrate greater stability in acidic solutions like ready-to-drink formulations, but the data is limited to their patent (#US8445466).

The other product that hasn’t necessarily been proven to work is the patented “alkalinized” creatine. In fact, because the pH of the stomach is so low (acidic), creatine is actually stable and absorbed well (under pH of 2.5) without being converted to creatinine. It takes very high (alkaline) pH’s to make creatine stable at the other end of the spectrum. However, the addition of alkalinizing agents can potentially bring up the stomach pH, but not enough to make it alkaline. Therefore, alkalinized creatine may actually increase the breakdown of creatine to creatinine in the stomach.8 Studies show that CM is nearly 99 percent absorbed intact without alkalization and without significant side effects. Direct comparison of alkalinized creatine and CM demonstrated inferior performance of the alkalinized creatine in body composition and strength.9

Improved Performance

With regard to performance improvement, creatine salts such as creatine pyruvate and creatine citrate improved endurance in one study, but the study didn’t have a CM group to compare.10 It is thought that some of the improvement in performance could be contributed by the salt of pyruvate. As already mentioned, CEE did not increase muscle creatine levels or improve performance, and alkalinized creatine was inferior to CM. Creatine alcohols have very little data to support any effect after oral supplementation.

A recently published study in the Journal of Strength and Conditioning Research examined the effects of polyethylene glycosylated creatine (PEG-creatine) supplementation on anaerobic performance measures, muscular strength and endurance (bench press and leg extension), and body composition.11 This study involved a randomized, double-blind, placebo-controlled design of 77 adult men supplemented with 1.25 or 2.5 grams of PEG-creatine per day and then tested for improvements at 28 days. Compared to placebo, both doses showed significant improvements in lower-body vertical power, agility, change-of-direction ability, upper-body muscular endurance, and body mass. Additionally, the PEG-creatine treatments showed very little weight gain. As I have suggested in previous articles, this form of creatine may be of benefit to those in sports with weight classes. This data confirmed previous studies that lower doses of PEG-creatine could be as effective as five grams of CM.12

Be a Smart Consumer

A review article by Jäger et al. in 2011 suggested that some of the various creatine salts and modified creatines may be on the market without approval from the U.S. Food and Drug Administration (FDA) or even illegally. The FDA requires filing of a new dietary ingredient notification in the case of the chemical modification of creatine. Without evidence of safety, the FDA feels companies may be putting Americans at increased risk of illness or injury. At this point, it is very important that we all become smart consumers of nutritional supplements and perform our own “due diligence” before putting ourselves at risk with any supplement. Consider the source of the supplement and the possibilities of misrepresentation by the manufacturer. Read this column for updates on bogus or harmful products.

In summary, creatine has revolutionized the supplement industry. The combination of creatine, carbohydrate and protein is an essential component of any mass-building routine. Creatine monohydrate is the gold standard, but other forms of creatine have their place in the market. Perhaps more importantly, creatine monohydrate supplementation is the most scientifically researched form of creatine, is safe and very effective for bodybuilding and sports performance.


Dr. Victor Prisk is a board certified orthopaedic surgeon and IFBB professional bodybuilder in Pittsburgh, PA. Dr. Prisk is an active member of the GNC Medical Advisory Board and creator of the “G.A.I.N. Plan.” He is an NCAA All-American gymnast, champion swing dancer and NPC Welterweight National Champion.