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 Well, the previously mentioned, as of yet unpublished data from a study by Ralf Jäger, Martin Purpura, and Roger C Harris did not just confirm the results of previous studies, which indicate that glucose (75g) and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.

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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.

Polarized Concomitant Training - Will it Help You Make Max. Gains & Improvements in Body Comp. W/ Strength+Cardio?

Polarized Concomitant Training - Will it Help You Make Max. Gains & Improvements in Body Comp. W/ Strength+Cardio?

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Polarized training? Find out more...

Does concurrent / concomitant training intensity distribution matter? Unless you're a first timer at the SuppVersity you will have read at least two or three previous articles of mine about studies investigating the effects of concurrent training, i.e. the combination of strength and cardio training, (i.e. concomitant training) here.

If you recall the results, you will know that previous research has demonstrated the influence of intensity distribution on strength endurance training adaptations.

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You may also remember that no previous study has addressed the influence of "intensity distribution", i.e. the way intensity and volume are distributed across the training sessions, on the effectiveness of concurrent training (CT | see Figure 1). The goal was to prevent interference of the two types of training:

Figure 1: Training design of the experimental groups during the 8-week training period. Continuous-line and dotted-line circles represent the different training session modalities for the PT and TT groups, respectively. PT: polarized training group; TT: Traditional-based training group; BW: brisk walking; RM: repetition maximum; RNG: running; IST: intermittent sprint training (Varela-Sanz. 2016).

"Another problem which must be solved is the comparison of external training loads. Thus, our independent variable and focus was training intensity distribution with an equivalent total external load [...] of both training programs. A training group performed a combination of strength and endurance training aligned with the current ACSM recommendations of intensity distribution, while another group performed the same amount of external workload but with a polarized intensity distribution. Both ex. groups were evaluated before and after an 8-week training period (weekly training frequency of 3 days), and compared to a control group. To examine the effectiveness of the [...] training regimes, [...] physical (jump capacity, upper- and lower-body strength, running performance, and body composition), physiological (heart rate variability), and perceptual variables (rate of perceived exertion, training impulse, and feeling scale) were examined as dependent variables" (Varela-Sanz. 2016)

Thirty-one healthy sport science students (30 men, 5 women; all moderately active, but training less than 2 days per week apart from their academic activities which included a variable amount of PA on a daily basis) volunteered and were, after a 2-week familiarization phase (training thrice a week for two weeks), evaluated for resting heart rate variability (HRV), countermovement jump, bench press, half squat, and maximum aerobic speed (MAS).

I don't get it. How exactly did this "polarized training" work? Yes, the protocol was different from the one you may remember from Seiler et al. (2006) who tried to quantify training intensity distribution in elite endurance athletes. More specifically, subjects trained thrice a week (i.e. Monday, Wednesday, and Friday) for ~120 min each on Monday and Friday, and ~60 min on Wednesday. The training sessions on Mondays and Fridays consisted of cardiorespiratory exercise training (i.e. brisk walking or running) followed by resistance exercise training; meanwhile on Wednesdays participants only performed cardiorespiratory exercise training.

Each training session started with a standardized warm-up that consisted of 5 min of calisthenics followed by 5 min of brisk walking at 30% of the MAS. Before resistance exercises, participants also performed a specific warm-up that consisted of 2 sets of 8 repetitions of the resistance circuit they performed during the familiarization period with a OMNI-Scale perception of effort of 2-3. Cooling down exercises consisted of 2-3 sets of 15 s of stretching exercises of the muscle groups involved during the session. The exercises during the actual workout were bench press and half squat. Based on the conclusions of Simão et al., whose study had revealed that you will see greater gains on those exercises you do first in your workout, the order of resistance exercises was alternated each week. In that, the TT group performed 3-5 sets of 10-12 RM with 3 min of rest between sets. The PT group performed 3-5 sets of 5 RM on Mondays, and 2-4 sets of 15 RM on Fridays. The rest between sets was always 3 min. Resistance exercise workloads were equated.

All were then randomly distributed into either a traditional-based training group (TT; n=11; 65-75% of MAS, combined with 10-12RM), polarized training group (PT; n=10; 35-40% and 120% of MAS, combined with 5RM and 15RM), or control group (CG; n=10).

Figure 2: Relative changes in heart rate, jump height, peak power, bench press (1RM) and half squat (1RM) after 8 weeks of traditional (TT), polarized (PT) training or control (Varela-Sanz. 2016).

After 8 weeks of training (3 days.week-1), TT and PT exhibited similar improvements in MAS, bench press and half squat performances. No differences were observed between TT and PT groups for perceived loads. There were no changes in heart rate variability (HRV) for any group although TT exhibited a reduction in resting HR.

Figure 3: Effect sizes corresponding to the relative values in Figure 1 (Varela-Sanz. 2016).

What is worth mentioning, though, is that, compared to other groups, the PT group maintained jump capacity with an increment in body weight and BMI without changes in body fatness, in other words: they gained muscle, but also fat (see Figure in Bottom Line | body fat measured by skinfold "only").

There's one thing we didn't discuss yet: Was the polarized training maybe less taxing or more fun? The findings of the study at hand suggest that this was the case: TT and PT reported similar perceptions of effort, sensations, and internal load levels over the 8-week training period. Briefly, RPE and TRIMPS increased progressively along the 8-week training period. These perceptual levels demonstrated an increase in external load during the 3rd microcycle compared to the 1st and 2nd microcycles of each mesocycle. Thus, "the current findings suggest that different concurrent training regimes of equated loads could be similarly perceived by participants" (Varela-Sanz. 2016).

Effects on body composition; effect sizes and rel. (%) changes (Varela-Sanz. 2016).

Bottom line: The previously outlined observations lead the scientists to conclude that their funky polarization approach to concurrent training "induced similar improvements in physical fitness of physically-active individuals", but that "PT produced a lower interference for jumping capacity despite an increment in body weight, whereas TT induced greater bradycardia" (Varela-Sanz. 2016).

The fact that there were further benefits in terms of peak power, squat and bench press performance, but that those were not statistically significant (see Figure 2), however, is something the scientists don't mention in the abstract, even though these differences could become significant in the longer (>8 weeks) term.

A mistake? No, in view of the conflicting evidence from the calculated effect sizes (see Figure 3), it is absolutely correct to say that there were no meaningful inter-group differences in the most important parameters for most trainees, i.e. the bench press, half squat and the effects on body comp (see Figure on the right) | Comment!

References:

• Seiler, K. Stephen, and Glenn Øvrevik Kjerland. "Quantifying training intensity distribution in elite endurance athletes: is there evidence for an “optimal” distribution?." Scandinavian journal of medicine & science in sports 16.1 (2006): 49-56.
• Simao, Roberto, et al. "Exercise order in resistance training." Sports Medicine 42.3 (2012): 251-265.
• Varela-Sanz, Adrián; Tuimil, José L.; Abreu, Laurinda; Boullosa, Daniel A. "Does concurrent training intensity distribution matter?" Journal of Strength & Conditioning Research: Post Acceptance: May 09, 2016 doi: 10.1519/JSC.0000000000001474.