Creatine Uptake, Bioavailability, and Efficacy - We've Gotten it all Wrong and Low Serum Creatine Levels are Better!?

Creatine Uptake, Bioavailability, and Efficacy - We've Gotten it all Wrong and Low Serum Creatine Levels are Better!?

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If you put some faith into the marketing campaigns of supp producers, there's a creatine for everyone: one to get lean, one to get strong and one to get big and buffed... bullocks!

It has been a while since I've discussed the bioavailability of different forms of creatine. On various supplement sites, the notion that there was one form of creatine that was significantly more bioavailable and would thus allow you to 'load' muscle phosphocreatine (PCr) faster and more efficiently is obviously still a matter of constant debate... a debate of which the latest study by Ralf Jäger et al. (2016) indicates that it may argue based on a fundamentally flawed premise, i.e. that higher serum levels of creatine after the ingestion of a given product would signify an increased efficacy in terms of performance / strength / size gains.

How come? Well, the previously mentioned, as of yet unpublished data from a study by Ralf Jäger, Martin Purpura, and Roger C Harris did not just confirm the results of previous studies, which indicate that glucose (75g) and alpha lipoic acid (ALA | 200mg) will increase the bioavailability of creatine, i.e. "the proportion of a drug or other substance [in this case creatine] that enters the circulation when introduced into the body" (Merriam-Webster.com), it also indicates that the practically relevant predictor of creatine's efficacy is - assuming equal dosing and complete absorption - not a high, but rather a low level of creatine in the blood.

You can learn more about creatine at the SuppVersity

Creatine Doubles 'Ur GainZ!

Creatine Loading = Unnecessary

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Build 'Ur Own Buffered Creatine

What? Let me explain: Initially, it may be worth pointing out that we are talking about a small scale study the results of which have not yet been published in the peer-reviewed journal. In that study, Jäger et al. aimed to compare the effects of ingesting tricreatine citrate (5g, TCrC),

• in combination with 75g of glucose and 200mg of alpha-lipoic acid, or
• without the former bioavailability enhancers.

on only six subjects. These three men and three women (35.5+/-14.5 yrs, 172.5+/-12.2 cm, 75.3+/-9.0 kg), who were all healthy, normal-weight and non-vegetarian and thus not, with creatine being a deficiency nutrient in vegetarians, extraordinarily susceptible to creatine supplementation (Burke. 2003), participated in two testing sessions during which they received the previously explained two treatments (the powdered supplements were simply dissolved in 450 ml of water).

Adding carbohydrates or cinnamon to creatine may well increase its uptake to the muscle. What it does not do, however, is to enhance creatine's efficacy - at least not in a 2015 3-week creatine loading study Islam et al. conducted in 25 recreational gymrats.

What's the increased absorption worth? If we rely on a a recent study by Islam, et al. (2015) the answer is (unfortunately) nothing. In their 2015 study, the scientists from the Wilfrid Laurier University and the University of Lethbridge in Canada found no (=zero) significant differences in anaerobic power, strength, and endurance when creatine was administered solo, with the same 70 g carbohydrate (CHO) that were used in Jäger et al. (2016), or 500 mg cinnamon extract (CIN), of which the authors believed that its proven ability to improve insulin sensitivity and up-regulate glucose transport in skeletal muscle would likewise enhance the uptake of creatine in the muscle and thus make it more effective.

With their cross-over after the initial test and a 7 day break between the tests, the scientists would have been able to compare the effect of adding glucose and alpha lipoic acid to the tricreatine citrate (Creapure™ Citrate, AlzChem, Trostberg, Germany | 65% w/w creatine) on an individual level. Corresponding data, however, is not (yet?) available. Instead, we get the likewise interesting statistical averages (see Figure 1):

Figure 1: Mean plasma creatine concentration over 8 hours following ingestion of 5g tricreatine citrate (TCrC) and 5g tricreatine citrate + 75g glucose + 200mg alpha-lipoic acid (TCrC+Glu+ALA | Jäger. 2016).

And these data present a quite intriguing result. More specifically, they indicate that the increase in peak concentration and the area under the curve (indicative of the total amount of creatine that appeared in the blood of the subjects) were significantly lower in the TCrC+Glu+ALA group in comparison to TCrC (75.3%, p<0.05, and 82.2% respectively).

Less creatine in the blood with sugar + ALA? That's bad, right? No that's good!

Just as the likewise lower 0.5 and 1h plasma concentrations of creatine, in the TCrC+Glu+ALA group (in comparison to TCrC), these reductions do not indicate a reduced efficacy of the supplement. On the contrary! The significantly elevated mean 8h urinary creatine elimination in the control group (TCrC | 26.5 ± 13.9% of the dose administered  vs. 17.2 ± 13.0% for TCrC+Glu+Ala) rather indicates that the addition of glucose and ALA "enhanced rate of creatine uptake into the muscle" - as previous studies indicate probably due to the presence of raised insulin (by glucose) and / or an increased insulin sensitivity (by ALA / Koszalka. 1972; Steenge. 1998; Pittas. 2010).

Figure 2: The study on creatine + glucose and creatine + cinammon by Islam et al. (red box) is not the only one that shows that the increased deposition of creatine in the muscle doesn't give you athletic advantages. The exact same results have been observed in an 8-week study comparing 70 g of a dextrose placebo (PL), 5 g creatine/70 g of dextrose (CRD) or 3.5 g creatine/900 mg fenugreek extract (CRF) by Taylor et al. (2011)

Why's this study relevant? Well, the answer should be obvious. The few allegedly 'advanced creatine products' on the market that actually have scientific back-up of their efficacy often refer to studies showing increases in plasma creatine of which the study at hand shows that they are no valid predictor of the actual efficacy of the supplement. The latter obviously depends on muscle creatine uptake, not serum peak levels or AUC. Don't be a fool, though: This does not mean that lower serum levels after ingestion were automatically better. After all, those lower levels of creatine in the blood may well be a mere result of an impaired / incomplete absorption in the gut.

Confusing? Well, let's summarize: By measuring the creatine level in the blood and the excretion of creatine in urine, Jäger et al. were able to refute the (ostensibly) logical assumption that higher serum creatine levels would indicate an improved efficacy. What they did not prove conclusively, however, is that the creatine levels in the muscle were in fact significantly higher (no biopsies) and, most importantly, that this makes a performance difference. The latter has after all been refuted in previous studies, such as Islam et al. (2015 | see red box and Figure 2). The hunt for the "best form" of creatine will thus probably go on, albeit with different experimental means, i.e. either the measurement of serum and urinary creatine as it was done in the study at hand or (even better) the direct assessment of muscle creatine stores and the actual performance benefits | Comment!

References:

• Burke, Darren G., et al. "Effect of creatine and weight training on muscle creatine and performance in vegetarians." Medicine and science in sports and exercise 35.11 (2003): 1946-1955.
• Jäger, Ralf, Martin Purpura and Roger C Harris. "Reduction of Plasma Creatine Concentrations as an Indicator of Improved Bioavailability." Upublished data from privatt conversation (2016).
• Koszalka, Thomas R., and Carole L. Andrew. "Effect of insulin on the uptake of creatine-1-14C by skeletal muscle in normal and X-irradiated rats." Experimental Biology and Medicine 139.4 (1972): 1265-1271.
• Pittas, G., et al. "Optimization of insulin-mediated creatine retention during creatine feeding in humans." Journal of sports sciences 28.1 (2010): 67-74.
• Steenge, G. R., et al. "Stimulatory effect of insulin on creatine accumulation in human skeletal muscle." American Journal of Physiology-Endocrinology And Metabolism 275.6 (1998): E974-E979.
• Taylor, Lem, et al. "Effects of combined creatine plus fenugreek extract vs. creatine plus carbohydrate supplementation on resistance training adaptations." Journal of sports science & medicine 10.2 (2011): 254.

Creatine: 17-20g for Loading is Bogus, 5-7g May be More Than Necessary to Maintain, Study in Gymrats Suggests

Creatine: 17-20g for Loading is Bogus, 5-7g May be More Than Necessary to Maintain, Study in Gymrats Suggests

build muscle build strength creatine gain muscle too much of a good thing

Yes, this study suggests that my previous statement that 3g of creatine per day are probably enough.... still direct comparisons of diff. doses are warranted.

You may remember that I wrote about the uselessness and possible negative effects of creatine loading on your body composition in October 2015. In the respective study, the scientists did yet not measure if there wasn't still a benefit in terms of increased skeletal muscle creatine and / or whether the creatine was excreted in the urine as creatine monohydrate (OK) or creatinine (not so good).

In a new study from the Baylor University, Andre, et al. did just that: They tested the effects of five weeks of resistance training in conjunction with a typical relative Cr dosing protocol followed by four weeks of resistance training after ceasing Cr supplementation on: 1) body composition and muscle strength, 2) whole-body Cr metabolism.

You can learn more about creatine at the SuppVersity

Creatine Doubles 'Ur GainZ!

Creatine, DHT & Broscience

Creatine Pre or After Workouts?

1st Benefits of Creatine-HCL

Creatine Blunts Fat Loss?

Build 'Ur Own Buffered Creatine

The scientists recruited nineteen apparently healthy, resistance-trained [regular, consistent resistance training (i.e., thrice weekly) for at least one year prior to the study], males between the ages of 18-23 completed the study. Participants were required to perform a leg press 1-RM of at least 2.5 times their body weight followed by at least 10 repetitions at 70% of their 1-RM during a familiarization session to be considered trained to participate (Coburn and Malek, 2012). Afterwards, the subjects were randomly assigned to groups using a random number generator. Supplementation involved orally ingesting packets containing

• powdered dextrose placebo [PL (AST Sports Science; Golden, CO, USA)] or 
• Cr monohydrate [CR (AST Sports Science; Golden, CO, USA)]. 

After baseline testing procedures and lean body mass determination via DEXA, participants in the CR and PL group ingested their respective supplement at a relative daily dose of 0.3 g/kg lean body mass (17-20 g/day) for one week in the loading phase and immediately following the loading phase, a relative daily dose of 0.075 g/kg lean body mass (5-7 g/day), during the four-week maintenance phase. All groups ceased supplementation on Day 36 following the four-week maintenance phase, which was then followed by a four-week washout phase without supplementation.

Table 1: Overview of the training program the subjects followed (Andre. 2016).

"Participants performed four one-repetition maximum (1-RM) tests on the angled leg press sled (Nebula, Columbus, OH, USA) at Day 0, 8, 36, 64. Participants warmed-up by completing two sets of 8-10 repetitions at approximately 50% of the estimated 1-RM, with two minutes rest in between all sets. Participants completed three to five repetitions at approximately 75% of the estimated 1-RM. The weight was increased conservatively, and the participant attempted to lift the weight for one repetition. If successful, the participant rested for two minutes before attempting the next weight increment. This was continued until the participant failed to complete the lift (Schwarz. 2015). For the 70% 1-RM evaluation during the familiarization session, participants were allowed to rest five minutes following the determination of their 1-RM" (Andre. 2016).

Participants followed a periodized 4-day/week resistance-training program split into two upper-body and two lower body workouts/week, for nine weeks (Table 1). As the authors further point out, the subjects performed "three sets of 10 repetitions with as much weight as they could lift per set (~70 – 80% of 1RM). If they could lift fewer than 10 repetitions, they were instructed to reduce the weight, and if they could lift more than 10 repetitions at a given weight, they were instructed to increase the weight" (Andre. 2016). The subjects were also instructed to rest "no longer than three minutes between exercises and no longer than two minutes between sets" (Andre. 2016); verbal confirmation of how to properly perform each exercise was given only during the familiarization session, though - still, resistance training compliance for CR and PL were 95.23 ±9.36 % and 93.74 ±8.82 %.

Figure 1: Relative changes (difference to day 1) in lean mass and leg press strength  (Andre. 2016)

That's topped only by the adherence to the supplementation protocol, which was 96.21 ±4.87 % and 94.69 ±3.98 % for CR and PL, respectively. Other relevant results not related to the creatine excretion / storage were:

• a group x time interaction for increases in total body mass Day 1 and 64 (p = 0.03) and exclusive lean mass at Day 1 and 64 (p = 0.01) favoring, as expected, the creatine group,
• significant leg strength increases in both groups without inter-group differences, even though the absolute strength gains on the leg press were almost 6kg higher (31.16 ± 26.90 vs. 25.68 ± 17.77 kg) for the creatine group,
• no significant effects on body water (in neither of the groups, by the way)
• no significant differences in food intake and / or the macronutrient composition of the diet, of which you will probably be intrigued to hear that it was between 1.1 and 1.3 g/kg, only

While selected rel. differences of the former, auxiliary findings are illustrated in Figure 1, Figure 2 is about selected aspects of the main research interest of Andre: the increases in muscle creatine and serum creatine. What I did not plot was the amount of creatine and creatinine the subjects pissed out.

Figure 2: Levels of muscle and serum creatine in the subjects over the course of the study (Andre. 2016).

The urinary creatine levels increased over 1000-fold from baseline levels (250 to 25000 µM in the first week) upon loading, and remained similarly elevated (4500 to 8200 from day 15-36) after one week of supplementation (Figure 2). As a result, a significant increase in urinary Cr was observed; however, there was no significant increase in creatinine, which is a good thing, because this is the agent that's supposed to be harsh on the kidneys. As the scientists point out...

"[t]hese findings are consistent with previous studies showing increases in urinary Cr but not in urinary Crn (Powers et al., 2003; Syrotuik and Bell, 2004). This suggests the supplementation dose of Cr was higher than the functional capacity to be metabolized, and was wasted via urinary excretion. Despite the supplementation dose based on lean mass measures to attempt to reduce this occurrence, considerable amounts of Cr were still essentially wasted" (Andre. 2016).

The increases in serum Cr concentrations, which were significant after three and seven days of Cr supplementation, and at the end of the maintenance phase, are likewise no and the lack of increase of serum creatinine good news. As the scientists point out, the increases in serum and urinary creatine in combination with the intramuscular total Cr data allow us to postulate that "the exogenous Cr supplementation apparently saturated intramuscular Cr stores given the high levels of serum and urinary Cr" (Andre. 2016).

If you haven't read it, yet I suggest you read up on my previous article about a study in Elite Footballers, where high doses of creatine actually resulted in inferior effects on body composition than lower doses. Quite an interesting result in view of the "more helps more"-mentality that's prevalent in the fitness community.

So, what's the overall verdict? Well, that should be obvious: "the overall Cr supplementation dose could be lowered given the high levels of urinary Cr" (Andre. 2016). Unfortunately, an investigation at lower relative supplementation doses of Cr in resistance-trained males, as the scientists demand it, has still to be conducted to "further clarify the dose response to elicit elevated intramuscular Cr stores with minimal excretion of Cr" (Andre. 2016).

Ah... and before I forget it: The study also observed that only one of the 11 subjects in the creatine group would be classified as nonresponder (Greenhaff et al., 1994). That individual observed an increase of only 18 mmol/kg dry weight - that's only 60% of the average 30 mmol/kg increase, and would qualify the subjects as quasi-, not non-responder, a result that could be explained by differences in the fiber comp. of his muscle (Lemon. 2002) | Comment!

References:

• Andre, Thomas L., et al. "Effects of Five Weeks of Resistance Training and Relatively-Dosed Creatine Monohydrate Supplementation on Body Composition and Muscle Strength, and Whole-Body Creatine Metabolism in Resistance-Trained Males." International Journal of Kinesiology and Sports Science 4.2 (2016): 27-35.
• Lemon, Peter WR. "Dietary creatine supplementation and exercise performance: why inconsistent results?." Canadian journal of applied physiology 27.6 (2002): 663-680.
• Powers, Michael E., et al. "Creatine supplementation increases total body water without altering fluid distribution." Journal of athletic training 38.1 (2003): 44.
• Schwarz, Neil A., et al. "Acute Myosin Heavy Chain Isoform mRNA Expression in Response to Two Resistance Exercise Intensities With Equal Volume Load in Resistance-Trained Men." The Journal of Strength & Conditioning Research 29.8 (2015): 2326-2332. 
• Syrotuik, Daniel G., and Gordon J. Bell. "Acute Creatine Monohydrate Supplementation: Adescriptive Physiological Profile of Responders Vs. Nonresponders." The Journal of Strength & Conditioning Research 18.3 (2004): 610-617.

First Study to Provide Evidence Creatine HCL Could Beat Monohydrate as a Muscle Builder and Fat Shredder, BUT...

First Study to Provide Evidence Creatine HCL Could Beat Monohydrate as a Muscle Builder and Fat Shredder, BUT...

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"Dude, that better be creatine HCL in dat drink of yours, because..." - bullshit, no?

I have to admit that I still have my doubts about the reproducibility and practical significance of the results, but since the authors declare that they have no competing interests, I think it is worth taking a look at what is the first (and only) study to suggest that any of the bazillion allegedly "superior" forms of creatine are actually an improvement over good old plain creatine monohydrate.

You will probably have heard the yadiyada about how creatine doesn't dissolve properly and creatine HCL was 41 times more soluble in water than creatine monohydrate, would permeate the intestinal tract easier and would thus yield significantly better results than plain monohydrate... right?

Obviously you've heard that bullshit. "Bullshit"? Yes, it's bullshit, because as of now there has been ZERO experimental evidence that the last and most important claim that the increased solubility of the product would improve its effect is more than yet another marketing gag.

You can learn more about creatine at the SuppVersity

Creatine Doubles 'Ur GainZ!

Creatine, DHT & Broscience

Creatine Pre or After Workouts?

ALA + Creatine = Max Uptake?

Creatine Blunts Fat Loss?

Build 'Ur Own Buffered Creatine

With a recent study from Brazil, this evidence appears to be finally there. In the corresponding experiment, Elias de Franca et al. compared the effects of two different doses of creatine HCl (1.5 g and 5 g) with creatine monohydrate (or "monohidrate" as the scientists like to spell it ;-) on the strength (std. 1-RM testing) and body composition (skinfold method) of recreational weightlifters.

As the scientists point out, all subjects had their diet homogenized by the research team nutritionist. In addition, subjects who hadn't been "creatine free" for at least 2 months were excluded. Whey protein, ad other amino acid supplements were - that's my understanding of the full text - allowed, but "managed to fit in the protein amount of the diet" (Franca. 2015). How much of a standardization in terms supplementation existed, is yet by no means clear. What I can tell you is that all subjects received either placebo (CG | capsules with resistant starch), 5 g creatine monohydrate (CMG), 5g creatine HCL (HCl-1) or 1.5 g creatine HCL (HCl-2) for 28 days. In that, the dosage for the creatine monohydrate group was selected based on a study by Hultman et al. that shows that 5 g of CrM during 28 days, is enough to promote the ergogenic effects of the supplement. By choosing the same and a lower dose of creatine HCL of which the the manufacturer obviously claims that it has the same effect as 5 g of the real deal, Franca et al. were able to (a) verify / falsify the claim and (b) check whether increasing the dosage beyond those 1.5g that are supposedly equal to 5 g of creatine monohydrate would yield significant advantages..

Figure 1: Pre / post (and rel. change in % above post-bar) strength data (de Franca. 2015).

As you would expect it, the training alone produced some changes in the male and female subjects' strength parameters. Figure 1 displays how the 1RM strength on the leg and bench press developed over the course of the 28 days and 8 workouts that were completed in an AB, CD, AB, CD fashion, i.a. as a basic 2-way split with different exercises in weeks 1, 3 vs. 2, 4. All programs (full text lacks detailed information) were composed of four exercises of chest and back muscles, three to shoulder muscles, four to legs muscles, three to biceps and triceps, and two abdominal exercises, though; and subjects performed four sets of 10 to 12 reps (80% to 90% of 1 MR) of each exercise and with every set being executed until momentary exhaustion.

No significant inter-group differences = no true benefit! In contrast to what you will probably read elsewhere the study at hand did not really show that creatine HCL is superior to creatine monohydrate. It did, not even as the scientists rightly say "induce changes on body composition in recreational weightlifters" (de Franca. 2015) while creatine monohydrate did not. Why's that? Well, de Franca et al. have (deliberately or not) left out two words that are of utmost importance: statistically significant. These two words must go before the word "changes" and they tell you that the body composition changes in the creatine HCL group with their laughable N = 7 and N = 6 subjects were significant, while those in the monohydrate group (N = 8) were not. On average, however, both groups gained almost the same amount of muscle and lost almost the same amount of fat. Accordingly, there is no wonder that there is no significant inter-group difference... not even for the placebo group, by the way. To say that one, i.e. PLA, CreM or CreHCL has been shown to yield superior results would thus be simply lying (most likely to increase one's sale).

Interestingly, enough, the scientist analysis of the data shows that none of the (in absolute terms high) increases in bench press performance reached statistical significance. Similarly, the only 1-RM increase for the leg press was the one in the 5g creatine HCL group, where the probability p that the increase we see was coincidental is smaller than 5% (p < 0.05)

Figure 2: Pre / post (and rel. change in % above post-bar) body composition data (de Franca. 2015).

If we continue to look at statistical significant results, only, the data in Figure 2 is what will make snake oil vendors love and abuse this study: according to the researchers' statistics software, only the 8% reduction in body fat of the two creatine HCL groups and the 15% increase in lean mass in the 5g creatine HCL groups were statistically significant.

Now, malicious gossip has it that this wouldn't prove anything, because there is (a) no significant inter-group difference, and because (b) the absolute increase in lean mass in the creatine monohydrate group was greater than in any HCL group and that the subjects in the 8 subjects in the monohydrate group were much fatter (yes, not significantly, though) than the 13 men and women in the other two groups. Speaking of men and women,... I wonder why the authors don't disclose the number of each in the groups. They only say that there were 60-70% men, 30-40% women in both groups. Well, that's nice, but since de Franca et al. "lost" 13 of their 40 subjects along the way (the abstract says they had 40 subjects, but there are 6, 7, 6, and 8 subjects in the four groups), this only adds to the already existing doubts about the reliability, reproducibility and the foreseeable mainstream interpretation of this study.

Want to "Advance" Your Creatine? Add Bicarbonate | read more

Bottom line: You may be asking yourselves why I am not all excited now. Well, I tell you what: The scientists write that they "hypothesized that, CrHCl im proves performance similarly to CrM, but promotes different results in body composition" (de Franca. 2015) - why on earth would they do that. If there was a science-based hypothesis to be made, it would be that creatine HCL would yield the same effects as creatine at lower dosages, because it dissolves better and is taken up faster (Gufford. 2010), so that less is necessary to saturate the muscle. To speculate that it would produce of all things what people are willing to pay for the most is... to say the least, a bit suspicious, don't you agree?

The same goes for the surprising "coincidence" that the researchers, who obviously couldn't afford reliable DXA scans (Pietrobelli. 1998) *cough*, were able to conclude, without reference to the conclusion being (a) based on the lack of statistical significance and (b) made in view of identical changes in body mass (within standard deviations), that their caliper data tells them "that CrHCl and CrM improve performance but only CrHCl induces changes on the body composition in recreational weightlifters" (de Franca. 2015).

Thus, I personally would suggest we all wait for independent, adequately powered research to (a) confirm the findings and (b) show that there is a significant inter-group difference with an advantage for creatine HCL. Until that study is done, peer-reviewed and published, I refuse to get all excited about yet another form of allegedly "superior creatine" companies use for the sole purpose of increasing the margins on products that would otherwise hardly have margin | Comment!

References:

• de França, Elias, et al. "Creatine HCl and Creatine Monohydrate Improve Strength but Only Creatine HCl Induced Changes on Body Composition in Recreational Weightlifters." Food and Nutrition Sciences 6.17 (2015): 1624.
• Gufford, Brandon T., et al. "Physicochemical characterization of creatine N-methylguanidinium salts." Journal of dietary supplements 7.3 (2010): 240-252.
• Pietrobelli, Angelo, et al. "Dual-energy X-ray absorptiometry: fat estimation errors due to variation in soft tissue hydration." American Journal of Physiology-Endocrinology And Metabolism 274.5 (1998): E808-E816.
• Wells, J. C. K., and M. S. Fewtrell. "Measuring body composition." Archives of Disease in Childhood 91.7 (2006): 612-617.

Creatine and Bicarbonate - A Worthwhile Combination: Supplements Exert Great Individual and Small Combined Effects on HIIT Performance Test in Nine Well-Trained Men

Creatine and Bicarbonate - A Worthwhile Combination: Supplements Exert Great Individual and Small Combined Effects on HIIT Performance Test in Nine Well-Trained Men

baking soda bicarbonate creatine high volume mean power peak power performance sodium bicarbonate total volume total work volume

The results of a Wingate test cannot be translated 1:1 to any sports.

You will probably remember my article about the combination of creatine and bicarbonate. Mixing both is basically what the producers of "buffered creatine" supplements do. Albeit with amounts of bicarbonate that may affect the uptake of the latter and offer benefits if you have to load as fast as possible, but won't have individual performance effects (learn more).

Other studies I've likewise covered in the SuppVersity News in the past showed both significant as well as borderline significant and non-significant beneficial effects of combining creatine and bicarbonate for a performance enhancing double-whammy in trained individuals.

You can learn more about bicarbonate and pH-buffers at the SuppVersity

The Hazards of Acidosis

Build Bigger Legs W/ Bicarbonate

HIIT it Hard W/ NaCHO3

Creatine + BA = Perfect Match

Bicarb Buffers Creatine

Bicarbonate Works for Most(!) Athletes

Against that background it is not surprising that a recent study by Griffen et al. (2015) found similarly ambiguous results. The study investigated the effects of creatine and sodium bicarbonate coingestion on mechanical power during repeated sprints. To this ends, nine well-trained men (age = 21.6 ± 0.9 yr, stature = 1.82 ± 0.05 m, body mass = 80.1 ± 12.8 kg) participated in a double-blind, placebo-controlled, counterbalanced, crossover study using six 10-s repeated Wingate tests.

Before each of the performance tests, the participants ingested either a placebo (0.5 g/kg of maltodextrin), 20 g/d of creatine monohydrate + placebo (Cre), 0.3 g/kg of sodium bicarbonate + placebo (Bi), or coingestion  (Cre + Bi) for 7 days, with a 7-day washout between conditions. Participants were randomized into two groups with a differential counterbalanced order. Creatine conditions were ordered first and last. The participants individual mechanical power output (W), total work (J) and fatigue index (W/s) were measured during each test and analyzed using the magnitude of differences between groups in relation to the smallest worthwhile change in performance.

Figure 1: Subject allocation.

Yes, the washout period could be a problem: With only nine participants you have to do crossover study, but in view of the results of previous studies (McKenna. 1999), which report washout times of 4 weeks, the scientists would have been on the safer side if they had planned for a washout of 28, not just 7 days. Now you may argue that not all subjects started "on" creatine, so that the residual effect could average out. The problem, however, is that the significance of the results of a study with only nine participants gets impaired with every subject who was in a creatine group before being randomly assigned to one of the placebo + X groups, so that the researchers would have had to order all the creatine conditions last, not one first and the other last, as it is depicted in Figure 1 and described in the full text of the study.

As the data in Figure 2 tells you, both, the creatine (effect size (ES) = 0.37–0.83) and sodium bicarbonate (ES = 0.22–0.46) supplementation, resulted in meaningful improvements of all three indices of mechanical power output compared to placebo. Now what we are really interested in, though, is what the combination of the two did...

• In general, the coingestion provided "small meaningful improvements on indices of mechanical power output (W)" (Griffen. 2015) 
• The previously mentioned advantage was yet only seen when comparing sodium bicarbonate (ES = 0.28–0.41) with the combination treatment; a similar beneficial effect was not seen compared to creatine alone

This does obviously mean that the addition of bicarbonate to creatine did not result in meaningful increases in power output in this particular exercise test.

Figure 2: The only relevant advantage of combining both creatine and bicarbonate was seen for the total work done (orange bars, see orange arrow); this however is also among the most relevant measures for real athletes (Griffin. 2015).

What it did do and that's what we actually take bicarbonate for is to "provided a small meaningful improvement in total work (J; ES = 0.24) compared with creatine" (Griffin. 2015) - or, in other words, anyone who does not just one, but several all-out sprints (and that's almost every athlete) will see a small but meaningful performance increase, one that may make the difference between victory and defeat (see Figure 1, orange bars).

The increase in PGC-1a expression you get if you do HIIT w/ sodium bicarbonate and the correspondingly increased stimulus for mitochondrial biogenenesis is a hitherto often overlooked benefit of "baking soda" supplementation | learn more

Disappointing? I would not say so, which significant improvements in response to both supplements and a potential "game changing" increase in the total work the subjects were able to perform on the cycle ergometer during the repeated Wingate tests, both supplements have proven their efficacy and the potential benefits of combining them. Benefits the Griffin et al rightly call "small", but "meaningful" in the conclusion to their recently published paper.

The fact that these benefits may not be as exorbitant as some of you may have hoped for does not imply that the combination of creatine and bicarbonate supplements is useless. In view of the overall small study size (low number of subjects even for a crossover study), the problem with the washout and the specificity of the exercise - who knows what the results in the gym or on a football field would have looked like, thus, future studies are warranted | Comment!

References:

• Barber, James J., et al. "Effects of combined creatine and sodium bicarbonate supplementation on repeated sprint performance in trained men." The Journal of Strength & Conditioning Research 27.1 (2013): 252-258.
• Griffen, C., et al. "Effects of Creatine and Sodium Bicarbonate Co-Ingestion on Multiple Indices of Mechanical Power Output During Repeated Wingate Tests in Trained Men." International Journal of Sport Nutrition and Exercise Metabolism, 2015, 25, 298-306.
• McKenna, Michael J., et al. "Creatine supplementation increases muscle total creatine but not maximal intermittent exercise performance." Journal of Applied Physiology 87.6 (1999): 2244-2252.

Creatine Loading - Unnecessary or Counterproductive? No Significant Difference, but Slight Advantage for Low Dose, No-Loading Protocol in 10-Week Study W/ Elite Footballers

Creatine Loading - Unnecessary or Counterproductive? No Significant Difference, but Slight Advantage for Low Dose, No-Loading Protocol in 10-Week Study W/ Elite Footballers

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Not just for women who are always afraid of an increase in water retention, loading protocols may not exactly be the best way of taking creatine monohydrate.

Let's be clear, here: I do not doubt that using 20g of creatine per day for 1-2 weeks aka "creatine loading" is the fastest way to supercompensate one's intra-muscular phosphocreatine and thus short-term energy stores.

What I seriously doubt, though, is that more than 0.1% of the SuppVersity readers have a good reason to make sure that they achieve maximal creatine levels in the shortest period of time. Rather than that, most of you are probably interested in augmenting their size and strength gains in the long(er) run and that's exactly where an older 10-week study shows that increased creatine dosages and / or loading are neither necessary nor beneficial for well-trained athletes.

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The study was designed to compare the effects of low doses of creatine (3g/day) and creatine loading (20g/day for 7 days + 5g/day thereafter) on strength, urinary creatinine concentration, and percentage of body fat. To this ends, Wilder et al. recruited 25 "highly trained" division IA collegiate football players who took creatine monohydrate for 10 weeks during a sport-specific, periodized, off-season strength and conditioning program. Onerepetition maximum (1-RM) squat, urinary creatinine concentrations, and %-age of body fat were analyzed. As previously pointed out, the subjects were

"randomly placed 25 subjects into 1 of 3 groups: (1) creatine supplementation of 3 g·d21; (2) creatine supplemen tation of 20 g·d21 for 7 days, followed by creatine supplementation of 5 g·d21 for the remainder of the study; or (3) a placebo group" (Wilder. 2001).

Creatine supplementation took place in a single-blind fashion, with each subject receiving a high or low dose of creatine or the placebo. Each creatine tablet (Createam Chewables, NutraSense Co, Shawnee Mission, KS) contained 1 g of creatine and 1.4 g of dextrose. The placebo tablet (Nutrasense) contained 2.4 g of dextrose.

"For the first week (loading phase), ingestion occurred 4 times per day. High-dose creatine (5 cre atine tablets), low-dose creatine (3 creatine tablets and 2 placebo tablets), or placebo (5 placebo tablets) was taken when the subjects awoke, before and after the workout session, and in the evening before bed. For the subsequent 9 weeks, the high or low dose of creatine or the placebo dose was ingested once per day after workouts and at the same time on off days" (Wilder. 2001).

During the 10-week supplementation period, all subjects participated only in the University’s off-season conditioning program, which consisted of periodized resistance and agility workouts. More specifically, the program consisted of 4 h/week of heavy resistance training and 4 h/week of conditioning. Weight training and conditioning were performed on Monday, Tuesday, Thursday, and Friday.

• Strength program: The primary exercises in the strength program were the front squat, back squat, hang clean, power clean, overhead press, bench press, single-arm dumbbell press, 1-arm rows, straight-leg dead lift, power shrugs, upright rows, chin-ups, dips, medicine ball plyometrics, and bumper-plate push-ups. 
• Periodization scheme: The periodization protocol was a 5-week base hypertrophy phase (4 to 6 sets at 50% to 80% 1-RM), followed by a 2-week power phase (3 to 5 sets at 80% to 88%). After this 7- week period, a 2-week strength phase (1 to 3 sets at 90% to 95%) was implemented, followed by a 1-week peak strength phase (1 to 3 sets at 95% to 100%). 

All sessions (strength and conditioning) were supervised by the strength and conditioning staff, athletic trainers, and football coaches.

Figure 1: Changes in strength and lean mass gains over the course of the 10-week study (Wilder. 2001).

If you look exclusively at the statistically significant study outcomes that are based on blood analyses as well as the results of the standardized performance tests, there are two surprising and one obvious results:

• Creatine loading + high dose supplementation did not produce significantly different effects on strength, urinary creatinine, or percentage of body fat than training, alone.
• There were no significant inter-group differences for loading + high dose vs. low dose supplementation over the course of the 10-week study.
• Significant side effects weren't observed in any of the three study groups.

Now, I could probably stop right here and cite the authors' conclusion that their data suggest "that creatine monohydrate in any amount does not have any beneficial ergogenic effects in highly trained collegiate football players," (Wilder. 2001), but that's not what I am going to do.

Let's talk safety - briefly! It should be obvious that the increased dose of creatine during the loading phase poses a greater risk of side effects. Aside from diarrhea and anecdotal reports of muscle cramps, however, there is little evidence that creatine supplementation in general and creatine loading in particular would produce side effects such as changes in live enzymes, urea or and kidneys health (glomerular filtration urea and albumin excretion rates) in healthy subjects supplemented with creatine, even during several months, in both young and older populations (Kim. 2011). In addition, the potential increase in urinary methylamine and formaldehyde after a heavy load of creatine (20 g/day | levels will still be in the normal range) will have no effect on kidney function and the claim that they may trigger carcinogenesis appears far-fetched (read more). Still, Kim et al. advise that "high-dose ([3–5 g/day) creatine supplementation should not be used by individuals with pre-existing renal disease or those with a potential risk for renal dysfunction (diabetes, hypertension, reduced glomerular filtration rate)" (Kim. 2011). For everyone else, health should thus not be an argument to stick to lower dosages of creatine.

Figure 2: Pre- / post changes in body fat (%) - Note: The differences didn't reach statistical significance due to inter-individual differences (Wilder. 2001)

If we discard the criteria of statistical significance (which was low, because of large inter-individual variations), there are inter-group differences that may even matter.

If you review the data in Figures 1+2, you can easily see that the low dose supplementation group saw (on average) the greatest improvements in strength and lean mass; and that in the absence of the albeit non-significant, but still measurable unwanted fat gain of 0.96% in the loading and 0.78% in the placebo group (vs. -0.39% body fat loss in the low dose group).

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Bottom line: I am not saying that the study at hand can prove the superiority of low vs. high dose (+loading) supplementation for creatine monohydrate. All that I am saying is that the still commonly used loading scheme for creatine, as well as the often practiced "more helps more" approach to creatine supplementation lack scientific backup - unless, obviously, it is used specifically to maximize the phosphocreatine stores in your muscles in the shortest amount of time (in this case loading may be the way to go).

Eventually, it would obviously be nice if we had more studies that investigate the differential effects of loading and/or high vs. low dosing. In view of the number of creatine studies, it is pretty surprising that Wilder's study practically the only one dealing with this issue, right? Comment!

References:

• Kim, Hyo Jeong, et al. "Studies on the safety of creatine supplementation." Amino Acids 40.5 (2011): 1409-1418.
• Wilder, Nathan, et al. "The effects of low-dose creatine supplementation versus creatine loading in collegiate football players." Journal of athletic training 36.2 (2001): 124.