1- Featured Article: Is serum a hoax?
This Month’s Featured Article:
Is Serum a Hoax?
by Alfredo Franco, PhD
Last month we discussed a recent study comparing the effects of a commercially available liquid formulation of creatine (Creatine SerumTM) with that of traditional creatine powder. This study found that “when taken according to the manufacturers’ recommendations”, Creatine SerumTM was less effective than ordinary creatine monohydrate powder at assisting in the performance of brief bouts of intense exercise. One possible explanation for the apparent lack of effect of the serum would be a substantially smaller quantity of creatine monohydrate in a single serving of the serum.
According to the manufacturer (Muscle Marketing USA) a single dose (5 milliliters) of Creatine SerumTM contains the equivalent of 2.5 grams of creatine monohydrate powder. This is a surprising claim, especially since it surpasses the previously experimentally measured solubility of creatine monohydrate in water. A main objective of today’s study, therefore, was to undeniably determine the amount of active creatine contained in a single dose of Creatine SerumTM.
Study Title: The creatine content of Creatine SerumTM and the change in the plasma concentration with ingestion of a single dose.
As boldly stated in the title, the goals of this study were two-fold. First, the study wanted to clearly establish once and for all the amount of creatine monohydrate that is actually present in a recommended serving of Creatine SerumTM. The next objective was to follow the appearance of creatine in the blood stream of a person ingesting a single dose of serum. This response was then to be compared to the response obtained from the same amount of pure creatine monohydrate powder as reputed to be contained in a single dose of serum.
Product Creatine Content
To say that the authors of this study were careful would be an understatement. Four different bottles of Creatine SerumTM were purchased on separate dates and sent to five different laboratories for various forms of analyses. Their experimental approach to the study of the serum was unusually deliberate, even for a peer-reviewed scientific study. The most obvious result was that a recommended dose of serum contains only 10 milligrams of creatine, or 250-times less than that stated on the label (2.5 grams). Four of four labs agreed unanimously on this point. On the other hand, a typical dose of serum was found to contain nearly 90 milligrams of creatinine, the natural degradation product of creatine. Therefore, it appears that, at best, a single dose of serum might have contained at one time only 100 milligrams of creatine monohydrate (instead of the claimed 2.5 grams). It would also appear that most of the creatine had converted to creatinine during packing and subsequent storage. Not surprising, since the conversion of creatine to creatinine is favored in water and by acidic pHs, two conditions that the serum has working against it. The serum is a water-based formulation and has a pH of 4.0, relatively acidic when compared to the body’s neutral pH of 7.4. Yet, despite these probable drawbacks, the product literature claims stability for up to two years. The low level of creatine in the serum was also indicated by a previous study that appeared a few years earlier (Dash and Sawhney, 2002).
Changes in Plasma Creatine Levels
The authors next gave six experimental subjects one of three supplementing conditions in random order: a single dose of serum, 2.5 grams of creatine monohydrate powder dissolved in water, or just plain water. Each subject then had his blood drawn and analyzed for the presence of creatine using high-performance liquid chromatography (HPLC). HPLC is a sensitive biochemical technique used to separate and identify individual components present in a solution. The following week each subject was then given one of the other remaining supplementing conditions and the process repeated. In this manner, after three weeks all six subjects had consumed all three supplementing conditions with one week’s rest between trials. One week should be sufficient time for the 2.5 grams of ingested creatine to be washed out of the body and hence to avoid cross-contamination of the results. Furthermore, none of the subjects had taken creatine-containing supplements for at least 6 months prior to participating in the study.
Changes in plasma creatine concentration following the ingestion of creatine monohydrate powder (blue circles), Creatine SerumTM (red circles), or water (black triangles). The error bars present in the original scientific article have been removed to better observe the trend in serum creatine concentration. Adapted from Harris et al., (2004).
Immediately after consuming one of the creatine supplements (or water), the amount of creatine that then showed up their blood streams was followed by HPLC. Not surprisingly, creatine monohydrate powder dissolved in water gave the greatest response. Following a single 2.5 gram bolus of creatine monohydrate powder serum creatine levels rose from a baseline of ~60 micromolar/liter to nearly 250 micromolar/liter, over four-fold (see figure-blue circles). The response to ingesting the powder was prompt and transient; a significant rise in serum creatine content was evident after only 30 minutes and reached maximal levels after one hour.
Serum creatine levels then steadily declined over the subsequent eight hours, eventually returning to pre-supplemented plasma levels. This drop in serum creatine levels is a reflection of the amount of creatine that is actively being absorbed by muscles as well as of the removal of excess creatine from the blood stream by the kidneys. Measuring the amount of creatine excreted from the body in the urine over 8 hours suggested that the body (presumably musculature) retained a little less than one (1) gram of the ingested creatine monohydrate. This is the reason that ingesting too much creatine only really benefits the manufacturer and is potentially damaging to the kidneys. All this is explained in greater detail in my creatine guide.
By contrast, a 5 milliliter (~one fifth fluid ounce) shot of Creatine SerumTM didn’t produce a significant rise in serum creatine levels over baseline (red circles). In fact, the response to the serum was nearly identical to that observed after drinking plain water (black triangles). This analysis agrees with the previous finding of this study that a single dose of the serum actually contains very little creatine monohydrate.
Non-detected Forms of Creatine
The authors of the study also wanted to examine the possibility that other forms, or precursors, of creatine might have escaped detection using the before mentioned biochemical methodologies. Creatine is an amino acid and, by definition, is a nitrogen-containing molecule. In fact, there are three nitrogen atoms per molecule of creatine, or creatinine. Therefore, determining the total amount of nitrogen contained within the serum should be indicative of the total amount of creatine precursors originally present in the formula. That is, of course, excluding other nitrogen containing molecules (not related to creatine) also present in the formulation. Unfortunately, measuring the total amount of nitrogen accounted for 85% of the creatine and creatinine already measured using the previous biochemical methods. In other words, quantifying total nitrogen exposed no previously hidden pool of creatine.
Supporting literature from Muscle Marketing USA, Inc. (MMUSA) implies that a unique creatine-phosphate complex is an essential part of the formulation of Creatine SerumTM. Given this impetus, the researchers next searched for the presence of phosphocreatine in the serum. Phospho-creatine (creatine coupled to a phosphate group) is the activated form of creatine naturally stored within most cells of the body. The cell, by adding a phosphate group to creatine (via the actions of an enzyme known as creatine kinase), endows it with the capacity to produce energy (ATP) on demand. Consequently, most of the physical benefits typically rendered by creatine supplementation are the direct result of elevated phosphocreatine levels within the muscle cell. Phosphocreatine, however, was not detected in the serum, which is really not that surprising, given that phosphocreatine is even less stable than creatine in aqueous solutions and at acidic pHs. In other words, if phosphocreatine had been present at one time, it probably would have been spontaneously converted to phosphocreatinine and subsequently to creatinine early on. In fact, only trace amounts of phosphorus were found at all, ruling out the existence of any other phosphorus-containing derivative of creatine. The available evidence thus seems to suggest that there are no other hidden forms of creatine present in Creatine SerumTM.
Finally, two experimental subjects were asked to take the serum sublingually, as recommended by the manufacturer. According to MMUSA’s literature, the creatine within the serum is best absorbed directly through the mucous membranes of the mouth, thereby bypassing the stomach’s destructive digestive juices. Under instructions from the investigators, each subject held two doses of the serum under their tongue for 2-4 minutes. The amount of creatine appearing in their bloodstreams was then determined as outlined previously. No change in plasma creatine concentration was observed in response to sublingual administration.
Indeed, the outlook looks bleak for Creatine SerumTM. The authors of this study estimated that given the very small amount of creatine (at most 100 milligrams per dose) in fact available in a serving of the serum one would need to consume 15 liters (3,000 doses, or 100 bottles) of the product to retain as much creatine (30 grams) as during a typical loading phase using traditional powder. That is, of course, assuming that all the creatine available in the serum is retained by the body and not excreted in the urine, which would be unlikely even for the powder.The trace amount of creatine in a single dose of serum would be insufficient to raise muscle creatine levels to a significant degree and accounts for the apparent lack of effect of Creatine SerumTM over explosive bouts of exercise as discussed last month’s newsletter.
I will not go as far as to say that Creatine SerumTM is a hoax, since I do not have access to its original formulation. What I can say, however, is that the burden of proof now stands with Muscle Marketing USA, Inc. (MMUSA).
This study was published in 2004. Since then changes in the formulation of Creatine SerumTM, or in the claims made by MMUSA may have occurred, which will have a bearing on the relevance of the study.
I would like to invite a response to these criticisms from Dr. Amir Zeibak, founder and CEO of MMUSA. Perhaps he may be able to enlighten us to any important aspects of the serum these studies may have missed.
Roger C. Harris, Anthony L. Almada, D. Beorn Harris, Mark Dunnett and Peter Hespel (2004) The creatine content of Creatine SerumTM and the change in the plasma concentration with ingestion of a single dose. Journal of Sports Sciences Volume 22, pages 851–857.
Dash, A. K. and Sawhney, A. (2002) A simple LC method with UV detection for the analysis of creatine and creatinine and its application to several creatine formulations. Journal of Pharmaceutical and Biomedical Analysis Volume 29, pages 939-945.
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