 |
| Illustration
1: There is a bunch of things that could potentially go wrong with
creatine uptake: The creatine from dietary sources could be
mal-absorbed (1) in the small intestine, (2) not make it into the cell,
or (3) be excreted too readily either before or immediately after it was
transported into the muscle. |
Question from Lerner (via comments): Do Creatine Transporters behave the same as glucose transporters? (I.e.,
serum insulin binds to cellular insulin receptors, which causes
Transporters to migrate from inside the cell to the plasma membrane -
and the Transporters then pull in the external glucose.)
Answer Dr. Andro: As you may have noticed, I took the freedom to set Learner's question into a broader context. A context I broached in my
dissertations on Athletic Edge Nutrition's new creatine product Creatine RT
on Tuesday, Aug 16, 2011. Thus, the questions I will be trying to
answer (unfortunately, I have to rely on existing studies and do not
have my own lab, here ;-) are the following ones:
- How does creatine get into the blood?
- How does creatine get into the muscle? (cf. Part II)
- What can influence these processes?
In view of the fact that this is quite an extensive topic, I decided to tackle it in a
two part series, where
in part 1 (today) I will focus on the issue of creatine absorption into the bloodstream, a putative problem the clever researchers from the supplement industry pretend to have solved, already.
Creatine ethyl-ester, Creatine malate, Creatine citrate, Creatine HCL, Creatine whatever, and Krealkalyn(TM)...
are the names of the "solutions" to the purported inferiority of
creatine monohydrate, the shelves of your local supplement story have to
offer.
How does Creatine Get into Your Blood?
In
essence all these esters, acids, chlorides and other "creatine +
X"-combinations have been designed to mug you... ah, I mean to increase
the amount of creatine that makes it into your bloodstream, or in other
words, to
increase bioavailability. Now, as Wesley Mc Call and Adam Persky state in chapter 13 of
Creatine and Creatine Kinase in Health and Disease, there are four potential reasons why creatine bioavailability could be less than 100%, in the first place:
- Degradation (to creatinine) in the stomach
- Insufficient dissolution, i.e. passing the intestines "unsolved"
- Problems with creatine uptake by the epithelial cells
- Degradation by gut bacteria
1. Creatine could degrade when it reaches your stomach:
We know for certain that
creatine degradation is maximal at pH 3 (
Cannon. 1927,
cf. figure 1). Now, a healthy stomach should have a pH of 1 and for
about 84 years everybody (supplement producers included) would have been
able to take a look at the data of the 1927 study by Cannon and Shore,
who found that
after 25 h in a solution with a pH of 1 only ~2% of the creatine would have "degraded" into its dehydration product creatinine
and that the often cited "breakdown" of creatine monohydrate in the
acidic milieu of your stomach is not really an issue, after all.
 |
| Figure 1: Percent creatinine in solution of previously pure creatine after 25, 50, 125 and 1903h at a certain pH (data adapted from Cannon. 1927). |
Moreover, the data in figure 1 clearly shows that
you
would have to have the creatine sit in your stomach for more than 2h
before it would make a statistically significant difference (25h:
pH1=2%, pH6=2%; 125h ph1=9%, pH6=3%) whether your stomach had a pH 1
or a pH that is greater 6. Now, that certainly sounds ridiculously
long, still in conjunction with food (
Mc Call. 2008) and outside of the petri dish these effects are, as we are about to see further down, still physiological relevant.
 |
| Image 2: You
probably expected that it ain't advisable to take your creatine with a
Big Mac, but would you have guessed that juices are counter-indicated,
as well? |
Did you know that the ingestion of a meal will
increase the PH of your stomach drastically? Dressman, et al. report an
increase to pH ~6 after consuming a hamburger and a glass of milk (
Dressman. 1990).
After no more than 30 minutes, however, gastric secretion had reduced the pH to 4-3 and after
roughly 90 minutes, the stomach of the subjects was the same "acid pit"
(pH 1.3) as it was before the ingestion of the meal. This goes to tell
you that
taking creatine with a meal or even worse right after a meal could be counter-indicated.
Tip: You better
wait at least 90 minutes after your last meal, before you flush down your creatine
with water,
as even the presence of carbohydrates from juices has been shown to
"delay the time to peak concentration", which usually is less than 2h
and to decrease the maximal concentration at peak concentration (
Mc Call. 2008).
What you certainly want to avoid, though, is a pH somewhere between 3-4. However, even in this
"worst"
case scenario less than 10% of the creatine would undergo the (at
higher pH partly reversible!) reaction from creatine to creatinine. So, as Mc Call and Persky point out, the "relatively short time the creatine actually spends in the stomach means
that very little of the oral dose of creatine should be lost" (
Mc Call. 2008) - at least, if you take it on an empty (and healthy, i.e. highly acidic) stomach.
2. Creatine (Monohydrate) could not dissolve and thus be not absorbed
 |
| Illustration 2: Creatine is taken up by enterocytes in the jejunum and the illeum. |
The issue of
undissolved creatine monohydrate crystals,
has been discussed on bulletin-boards and in the ads of several
supplement companies ever since the first "advanced" creatine products
hit the market. Yet, while it is beyond debate that the enterocytes of
your small intestines (in rats creatine has been found to be absorbed in
the ileum (
Peral. 2005) and the jejenum (
Tosco. 2004), cf. image 2) cannot absorb bulky creatine crystals,
the solubility of creatine monohydrate in water at 20°C is 14 g/L at a neutral pH of 7.
Now, with lower pHs and higher temperatures (as mentioned before your
stomach should have a pH of about 1-2 and your body temperature
obviously is ~37°C) it is absolutely unlikely that the creatine would
not dissolve. Using creatine citrate, which, due to its lower pH
(solution has pH 3.5), has a 1.5x higher solubility, or other highly
soluble forms of creatine is thus not necessary, if your stomach is the
warm acid pit it is supposed to be.
Interestingly, a
study by Harris et al. suggests that the creatine from meat such as the
paddies of the burger in image 2 (I am assuming here that there is still
some meat in McDonalds burgers / here in Germany they have recently
begun
advertising their meat quality
;-) is more readily absorbed (this refers to absolute amounts, not to
the time-course) than either creatine suspended (=more creatine in water
than can be solved) in water or creatine tablets / lozenges (
Harris. 2002). A probable explanation for this phenomenon could be that the
creatine is safely contained in the meat,
until the latter is broken down by enzymes that are activated as the
pH of the stomach is decreasing. Thus only very limited amounts of free
creatine will be exposed to pH levels in the detrimental3-4 range.
3. Creatine could simply not be taken up by the enterocytes in the small intestine
Obviously,
any general digestive problem related to nutrient transport across the
epithelial barrier in the intestines could compromise creatine uptake,
as well. As mentioned earlier
the presence of large (180g) amounts of carbohydrates have been shown to slow gastric emptying and consequently creatine absorption,
considerably
(
Vist. 1995). In addition several other meal-constituents could also increase the pH temporarily and thus
initially decrease solubility
(when pH is still very high) and
consequently increase creatine to
creatinine breakdown (when the pH passes the critical 3-4 range, see
above).
4. Creatine could be degraded by bacteria in the gut
 |
| Image 2: Biridobacterium tongum is a probiotic and a natural enemy of putrefective bacteria, who "suffocate" from the lactic acid, acetic acid and bacteriocins (image from dophilus.com) |
Even if the creatine survives passage through the
stomach, is dissolved and the enerocytes are ready to absorb it, it
could still be
taken up by putrefective bacteria (bacteria that break
down organic material) of which William C. Rose in a paper in the
Annual Review of Biochem. writes
that they transform creatine into methylhydantoin, which previously
had been shown to yield sarcosine under the influence of
micro-organisms" (
Rose. 1933) Unless you want Patrick Arnolds
sarcosine as an adjunct to
d-aspartic acid (as in
TestForce 2), I would say this is another good reason to keep your gut clean and tidy ;-)
Conclusion: Absorption should not be an issue
If
your gut is healthy, acidic and free of pathogenic amounts of
putrefective bacteria there is absolutely no reason you could have
problems absorbing creatine - especially if you stick to my
recommendations and
- do not escalate single dosages beyond 5g,
- take your creatine on an empty stomach (or at least 90 min after your last meal)*
(taking creatine with carbs + protein will increase breakdown to creatinine, and decrease the maximal serum levels, but, on the other hand, it will increase muscular creatine retention, cf. Part II)
- do not take creatine with a meal or protein or large amounts of carbohydrates**
(read more on the carb issue in the 2nd part of this installment of "Ask Dr. Andro", tomorrow)
A tweak to this general guideline resolves around the
"mysterious" issue of alkaline creatine. The results from the Cannon
study show that you have the choice:
- increase your stomach pH beyond 6, or
- decrease your stomach pH below 2
if you want to avoid the breakdown of creatine to creatinine.
 |
| Figure 2: Relative increase in creatine in dry muscle mass of horses, after supplementation with creatine monohydrate, kre-alkalyn or Gastner's patented creatine + sodium carbonate +sodium hydrogen carbonate formula (Gastner. 2010) |
Timing creatine away from meals would be option #2,
option
#1, on the other hand, would entail supplementing with some strong
alkalizing agent such as sodium or potassium bicarbonate, and in
fact, this is exactly what KreAlkalyn, the purported "super-creatine" is
- a ph-buffered creatine-monohydrate product. Thomas Gastner holds the
patent to a formula
of which had a higher stability than KreAlkalyn and consists of nothing
else but 2.98g creatine monohydrate + 150mg sodium carbonate + 118mg
sodium hydrogen carbonate. According to self-conducted animal
experiments (horses= the increased stability entailed a statistically
significant improvement in muscular creatine retention after 4 weeks on
creatine enriched feed pellets (+7% over creatine monohydrate and +10%
over KreAlkalyn).
 |
Image 3: Kre-Alkalyn - expensive, but probably
useless - at least when taken with food. |
The results of Gastner's experiment should obviously
be taken with some skepticism. Nevertheless, the picture we are seeing
here is conclusive, because
either you rely on the acidity of your stomach (using plain creatine monohydrate)
or you put enough alkaline buffers into your product
so that the acidity of the stomach remains greater than pH 6 for a long
enough amount of time. With Kre-Alkalyn (and horse stomachs) it appears
that
Jeffrey Gollini who holds the patent for KreAlkalyn managed to hit exactly that most unfavorable pH range,
where the overall pH of the food + KreAlkalyn solution in the
(horse-)stomach falls back into the 3-4 range very quickly and the
creatine uptake is reduced due to the increased breakdown of creatine
to creatinine.
In summary, this is
a clear points win for
creatine monohydrate taken on an empty stomach (or, alternatively with a
significant amount of buffers + food). Fidgeting with citrates,
malates, and esters which will eventually be cleaved (if you are unlucky
at the very same moment your gastric pH has returned to the "danger
zone" of 3-4), may be promotional, but either is not likely to be
superior (citrate, malate & co) or has been shown (creatine ethyl
ester, cf.
Spillane. 2009) to be inferior to the undefeated 'top dog'
creatine monohydrate.
