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 Well, the previously mentioned, as of yet unpublished data from a study by Ralf Jäger, Martin Purpura, and Roger C Harris did not just confirm the results of previous studies, which indicate that glucose (75g)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

Protein Supps + Synthesis After 'Cardio': Milk (Natural 2:8 Whey:Casein) Protein is Best! Plus: 40g May Be Ideal Dose

Protein Supps + Synthesis After 'Cardio': Milk (Natural 2:8 Whey:Casein) Protein is Best! Plus: 40g May Be Ideal Dose

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Even though the study at hand has been conducted in an endurance training scenario, there's no reason to believe that the superiority of milk protein, the natural mix of whey and casein would be a "cardio-specific" thing. In fact, evidence to the contrary has been discussed previously, here and here.

Whey, casein, soy or the rarely used alternative, milk protein, what's best to kickstart the protein synthetic machinery even after endurance workouts? The absorption kinetics of the different proteins, the effects of which a group of scientists from Japan recently re-assessed would suggest that the answer is clear: whey protein, it's the fastest of the four proteins, contains the highest amount of BCAAs (esp. the mTOR- and MPS promoter leucine) content and has been repeatedly shown to rapidly cause significant hyperamonoacidemia (=extremely elevated amino acid levels in the blood | Boirie. 1997; Dangin. 2001; Norton. 2009).

In spite of the fact that whey is also the most insulinogenic of these proteins, it is yet also the one that has been shown to "maximize" amino acid oxidation, thereby contributing to a reduction in nitrogen retention (Boirie. 1997; Dangin. 2001). On the other hand, ingestion of CA causes slower but prolonged aminoacidemia and it has the best leucine net balance during the postprandial period (Boirie. 1997; Dangin. 2001), I've discussed in previous articles, such as "Protein Wheysting".

This is not an anti-high-protein article. It is one arguing in favor of "treating your protein right"

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This is where micellar casein (not sodium or calcium caseinate which are fast-, but slower-than-whey-absorbing "damaged" forms of casein, though) comes in. While casein does not produce the same rapid increase in serum amino acid levels it has been shown to cause moderate but prolonged muscle protein synthesis - the exact opposite of whey protein.

Figure 1: Fractional myofibrillar protein synthesis (A), plasma leucine (B) and plasma insulin (C) levels in young men after ingesting 0.3g/kg whey, casein or a protein-free control drink (Reitelseder. 2011)

The data from Reitelseder et al. (2011) illustrates the link between the time course of the myofibrilliar protein synthesis and a protein's digestion speed, the rate of appearance of leucine (Figure 1, B) in the blood and the protein's insulinogenic (Figure 2, C) effects quite nicely. It is thus only logical to assume and has in fact been shown that the co-ingestion of whey and casein, either mixed or as milk protein is superior to soy protein (SP) [22,23], but also to whey alone, even if the latter is "enhanced" with extra BCAAs and glutamine (learn more!)

Figure 2: As a SuppVersity reader you will rememeber that a previous study showed that whey + casein is profoundly more anabolic than whey that is combined with extra BCAAs and glutamine (Kerksick. 2006)

As the Japanese authors of the study at hand point out, these benefits are likely due to casein's ability to "contributes amino acids that have a prolonged protein-synthetic effect across the leg" - or, put more simply: whey pumps up the AA levels fast, so fast that your body gets wasteful; casein, on the other hand, provides them at a rate that's much more suitable for direct incorporation into the muscle.

Whey (open triangles) increases leucine +protein oxidation vs. casein (closed circles) in man (Boirie. 1997).

Thinking about the perfect mix: Wouldn't it make more sense to have more whey right after a workout and reduce the amount of casein? If that's what you are thinking right now, I have to warn you: As previously pointed out, there's a point of diminishing returns, when excess amino acids as you would increase them by increasing the amount of whey are oxidized and end up as "waste", namely ammonia (and after recycling urate) in your system. The increased leucine oxidation with whey (open triangles) vs. casein (filled circles), as it was observed by Boirie et al. 19 years ago in healthy subjects even though the subjects consumed 43g of casein and only 30g of whey to standardize the leucine content, attests to that. Needless to say, testing a 50:50 or even 60:40 ratio would be something for follow-up studies.

Table 1: Amino acids in milk (MP), caseinate (CA), whey (WP) and soy (SP) protein (Kanda. 2016).

What exactly the ideal ratio of whey to casein protein may be will still have to be determined (probably it'll depend on when you take your protein shake), but the 2:8 ratio, meaning 20% whey protein and 80% casein that was used in the study at hand is "nature's standard formula" and thus what your average milk protein will have. A protein, by the way, of which Kanda et al. wanted to confirm in their latest experiment that it "causes a prolonged increase in muscle protein synthesis compared to WP [whey protein]or CA [casein] alone" (Kanda. 2016).

In contrast to "the average" study, the Kanda et al. did so in the presence of an endurance, not a strength or no training stimulus at all and used both, the milk-derived proteins caseinate (CA | faster absorbing, non-micellar form of casein), whey (WP) & milk protein (MP) to soy (SP). You can review the individual amino acid composition of all four in Table 1 on the right and will notice that "technically speaking", i.e. judged based on its BCAA content, soy is the "worst muscle builder", whey the "best".

Time for the convenient, but annoying truth(s)!

Truth #1: It's a rodent study! That's convenient for the scientists, because using rodents is cheap and easy, but annoying for us, because rodents are a good model for humans, but only that - a model - and by no means the best one. Since we cannot switch the subjects, though, we have to live with the fact that the subjects in the study at hand were Sprague-Dawley rats with a bodyweight of approximately 150 g (at least there were many | n = 237) who were subjected to a swimming exercise protocol during which they swam for a whopping 2h.

You should care about postworkout protein synthesis! While previous studies had suggested that the FSR / MPS response to training and supplementation would not, a more recent study I discussed in detail, last week, clearly demonstrates that FSR / MPS does matter. Read it!

Now, where there's shadow, there's also light: The good thing about rodent studies (bad for the rats, though) is, after all, that, much in contrast to humans, rats can be sacrificed after an experiment like that and will thus allow researches to assess the effects of exercise and supplementation with the aforementioned proteins much more accurately than a single or even multiple muscle biopsies.

Table 2: Macronutrient profile of test proteins; milk (MP), caseinate (CA), whey (WP) and soy protein (SP | Kanda. 2016)

That does not fully compensate for truth #2, though, which is that the scientists made the mistake of using caseinate (Fonterra Co-operative Group, Ltd., Auckland, New Zealand), instead of the more expensive and slower/-est digesting (due to its micelle structure, which gels during the digestion process) molecularly intact micellar casein, of which one could expect that it may have postponed the peak in fractional protein synthesis (FSR) that occurred after 120 minutes with the caseinate even more (Figure 3, left).

Figure 3: Time course of the fractional protein synthesis after endurance exercise with all four proteins (left) and corresponding AUC values (~net protein influx, right | Kanda. 2016).

The previous hypothesis is obviously merely speculative and eventually irrelevant. I mean, micellar casein, or not, it is very unlikely that the overall AUC, i.e. the incremental area under the FSR curve and thus the net influx of protein into the muscle, would have been increased to a level that would top that of milk protein (black bar in Figure 3, right), which had a measurable, but not statistically significantly more pronounced effect on the protein influx than any other of the four proteins.

Bottom line: Yes, it's rodents, but eventually the study at hand simply extends previous studies (A, B) in humans, where the combination of whey + casein likewise outperformed the competition...

FSR during dose escalation study; the human equivalent dose (HED) of 3.09g/kg, the 100% dose, in rats is ~0.5g/kg in man and thus ca. 30-50g milk protein, depending on your body weight. (Kanda. 2015)

And when we are talking about "extending the existent research", it may be worth mentioning that the researchers also provide new evidence in regards to the "ceiling" or "muscle full"-effect that occurs when ingesting more protein won't yield any extra increases in protein synthesis. In the study at hand, this effect was reached at a human equivalent dosage of ca. 0.5g per kg body weight (that's the 100% dose in Figure 4) or ~ 40g which is - initially surprisingly - more than the often touted 20-30g (depending on the human study you cite). In view of the 20:80 mix of whey and casein, the lower leucine content and slower absorption of the latter, it is yet actually logical to need more milk protein vs. whey to "reach the ceiling" | Comment!

References:

• Boirie, Yves, et al. "Slow and fast dietary proteins differently modulate postprandial protein accretion." Proceedings of the National Academy of Sciences 94.26 (1997): 14930-14935.
• Dangin, Martial, et al. "The digestion rate of protein is an independent regulating factor of postprandial protein retention." American Journal of Physiology-Endocrinology And Metabolism 280.2 (2001): E340-E348.
• Kanda, Atsushi, et al. "Effects Of Whey, Casein, Or Milk Protein Ingestion On Muscle Protein Synthesis After Endurance Exercise." MEDICINE AND SCIENCE IN SPORTS AND EXERCISE. Vol. 46. No. 5. 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA: LIPPINCOTT WILLIAMS & WILKINS, 2014.
• Kerksick, Chad M., et al. "The effects of protein and amino acid supplementation on performance and training adaptations during ten weeks of resistance training." The Journal of Strength & Conditioning Research 20.3 (2006): 643-653.
• Norton, Layne E., et al. "The leucine content of a complete meal directs peak activation but not duration of skeletal muscle protein synthesis and mammalian target of rapamycin signaling in rats." The Journal of nutrition 139.6 (2009): 1103-1109.
• Reitelseder, Søren, et al. "Whey and casein labeled with L-[1-13C] leucine and muscle protein synthesis: effect of resistance exercise and protein ingestion." American Journal of Physiology-Endocrinology and Metabolism 300.1 (2011): E231-E242.

Peri-Workout BCAA + Glutamine + Citrulline Consumption Blunts Muscle & Fat Loss Compared to Powerade Placebo

Peri-Workout BCAA + Glutamine + Citrulline Consumption Blunts Muscle & Fat Loss Compared to Powerade Placebo

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"Shed the fat, keep the muscle!" That's a promise you will find not literally, but analogously in every ad for BCAAs, but do they actually do that? Help you shed fat and retain muscle? Scientific prove to support this claim is, as of yet, missing.

With BCAAs it is just as it is with 99.9% of the supplements: Ads and product labels are full of scientifically unproven claims. One of these unproven claims is that the consumption of branched-chain amino acids would protect you from losing muscle while you're dieting ... the problem with this notion is - as sound as it may seem in view of the mTOR promoting effects of leucine, there's no study which would prove that guzzling BCAAs all day will in promote fat and blunt lean mass losses when you're cutting.... or I should say "as of now, there was no study...", right? After all, there's this new study by Dudgeon et al.'s the abstract of which tells us that "BCAA supplementation in trained individuals performing resistance training while on a hypocaloric diet can maintain lean mass and preserve skeletal muscle performance while losing fat mass" (Dudgeon. 2015).

Learn more about amino acid and BCAA supplements at the SuppVersity

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As we are going to see after taking a look at the design and results of Dudgeon's single-blind study in seventeen resistance-trained males (21–28 years of age) on hypocaloric diets, this is yet a potentially misleading conclusion. Not because it was wrong, but rather because it omits an observation that could be of paramount importance to dieters who have the free choice between the two treatments, the subjects of the study were randomly assigned to, namely...

• 14g of Xtend (BCAA) before after workouts or
• 14 g Powerade (CHO) before and after workouts

The supplements were consumed for a total study time of 8 weeks during which all subjects trained four times per week according to a standardized workout program and consumed a diet that was programmed (but not controlled) to contain roughly 35% less energy than the subjects required on workout days and approximately 10% less energy than required on off-days.

In the strict sense, this is actually no "BCAA study": Some of you may already have realized that the "BCAA supplement" the scientists used, i.e. Scivation XTend, is not really a "BCAA only" supplement. Next to only 7 grams of BCAAs per 14g of powder the subjects ingested before and after the workout, it also contains 1 g citrulline and 2.5 g glutamine and obviously a hell lot of flavorings, fillers and what not. Now, while the latter are not of any importance, both of the former have been heralded as muscle protectors, as well, with citrulline probably having the more convincing scientific data to back it up (it appears to act similar to leucine, by the way | Moinard. 2007; Faure. 2012; Ventura. 2013) outside of scenarios with extremely high glucocorticoid levels where glutamine unquestionably helps (Hickson. 1995 & 1997; Salehian. 2006). It is thus in my humble opinion at least highly imprecise to conclude that the provision of 2x7g of BCAA ameliorated the the fat to muscle loss ratio during the 8-week study.

Now you may be rightly asking yourselves why I am so vague with respect to the energy deficit. Well, everything we learn from the full text of the study is that all subjects were "provided an individualized caloric restricted diet based on individual data (body mass, body composition, resting metabolic rate, etc.)" (Dudgeon. 2015) - a diet the scientists describe as follows:

Table 1: W/ the Harris-Benedict equation you calculate the basal metabolic rate and multiply it with a factor (multiplier) that describes your activity level best to arrive at the "real" estimated energy requirements.

"The caloric-restricted diet was designed as an 8 week “cut diet” for reducing body fat, and used a modified carbohydrate-restricted diet approach (percent of total calories for workout days were 30 % carbohydrates, 35 % protein and 35 % fat and for off days were 25 % carbohydrates, 40 % protein and 35 % fat). Each individual’s daily caloric and macronutrient intake was determined using the Harris Benedict formula with an activity factor of 1.35 (lightly active individual engaging in light exercise 1–3 days/week) for workout days and 1.125 (sedentary individual) for off days" (Dudgeon. 2015).

Since the Harris-Benedict formula is only a really rough estimate of how much energy you actually need, my previous estimations of the energy deficit are as "accurate" as I can possibly be. The 1604kcal that are printed in red bold letters on top of the exemplary meal plan in Figure 2, however, suggest that the deficit on the off days was significantly larger. After all, the subjects' mean weight was >80kg and their daily energy requirements should thus be at least 2,000kcal - even on off days (and the table in which the macronutrient composition is listed actually says that the mean intake was 2046 and 2264kcal/day for the BCAA and CHO group respectively).

Table 2: Sample dietary card for a subject during an off, non-workout, day (Dudgeon. 2015).

In view of the fact that the response I got from the authors to an email in which I asked about the exact kcal deficit only referred me to the previously cited passage about the activity factors, I guess it is futile to further speculate about the energy deficit, of which I would still like to add that it was probably higher in the heavier and taller BCAA group. Why? Well, the BCAA group had plans with 2456 and 2046 kcal on workout and off days, the CHO group on the other hand were fed 2717 and 2264 kcal... Whatever, let's get to the more relevant, but not less confusing changes in body weight, lean mass and fat mass the researchers report for the BCAA and CHO groups:

Figure 1: Pre and post absolute mean body weight, body fat and lean body mass values before and after the 8-week intervention; * p < 0.05 for the difference within groups (no difference between groups | Dudgeon. 2015)

-0.1 kg and -2.3 kg of body weight, +0.4 kg and -0.9 kg of lean mass and 0.6 kg and 1.4 kg fat mass in the BCAA and CHO groups respectively - that's in line with the previously cited conclusion. The BCAA supplement blunted the small loss of lean mass in the CHO group, but if we look at the complete dataset, a somewhat different image emerges; one in which the two classic markers of body composition, namely the relative amount of body fat (aka "body fat percentage") and the lean mass as percentage of the total mass changed in a way that favors CHO over BCAA supplements:

Figure 2: Pre vs. post values for body fat % and lean mass %, the two parameters you would classically use to assess body composition (instead of absolute lean and fat mass); pre-to-post change on top of the post-bars (Dudgeon. 2015).

Now, I am not saying that the consumption of the BCAA (+citrulline + glutamine) supplement did not blunt the loss of lean mass - it obviously did. What I want you to keep in mind, though, is the fact that the consumption of 14g of BCAAs before and after workouts appears to suffocated any dieting efforts - after all, the subjects lost a practically irrelevant (and for whatever reason allegedly statistical significant) amount of 600g body fat; that's in contrast to the 1.4 kg of fat mass the subjects in the control group lost; and that's a practically relevant insight, even if this fat loss was allegedly statistically non-significant, because  it implies that BCAAs practically blunt fat loss.

Whey + Casein - A Superior Post-Workout Shake that Kicks Every Amino Acid Product's Ass | read more

So what do we make of this study? Well, first of all, I would like to come back to something fundamental: This is yet another BCCA study that did not make the practically most relevant comparison of BCAAs and cheap (whey) protein protein supplements, in which BCAAs have hitherto always failed. In my humble opinion that's a problem, after all having a carbohydrate supplement as control in a dieting study is nice, but eventually not relevant for the average trainee who is probably not really considering extra-carbs when he's dieting.  What a real trainee would have been interested in, is whether BCAAs can prevent muscle catabolism to a significantly greater degree than the cheap whey protein he's using anyway...

... and maybe, whether the latter has a similar negative effect on fat loss as the BCAAs in the study at hand - which leads me to the actual take home message of the study, which is, as usually, not as straight forward as the conclusion of the abstract suggested. When all is said and done, the study at hand does after all suggest that someone who is approaching the single-digit body-fat zone, where every gram of muscle that is not lost counts, could benefit from the apparent lean mass protective effects of BCAA the scientists observed in the study at hand. It does yet also indicate that someone who's "making weight" for a competition should take a second look at the data in Figure 1 + 2 and acknowledge that taking a BCAA supplement may be the reason he will fail to achieve his weight loss goal. You don't believe that? Well, let's do some scientifically not exactly kosher extrapolations: If you manage to lose 10 kg in 10 weeks without BCAAs, for example, the data from the study at hand suggests that your weight loss "on BCAAs" over the course of those 10 weeks would be as meager as 434 grams ... whether that's in fact the case (I doubt it ;-) will have to be studied in future studies, just like the effect of BCAAs, citrulline and glutamine, alone and whether using your regular whey protein before and after the workout wouldn't have the exact same, or even better effects | Comment on Facebook!

References:

• Dudgeon, WD; Page Kelly, E; Scheett TP. "In a single-blind, matched group design: branched-chain amino acid supplementation and resistance training maintains lean body mass during a caloric restricted diet." Journal of the International Society of Sports Nutrition  (2016) 13:1.
• Faure, Cécile, et al. "Leucine and citrulline modulate muscle function in malnourished aged rats." Amino acids 42.4 (2012): 1425-1433.
• Moinard, Christophe, and Luc Cynober. "Citrulline: a new player in the control of nitrogen homeostasis." The Journal of nutrition 137.6 (2007): 1621S-1625S.
• Hickson, R. C., S. M. Czerwinski, and L. E. Wegrzyn. "Glutamine prevents downregulation of myosin heavy chain synthesis and muscle atrophy from glucocorticoids." American Journal of Physiology-Endocrinology and Metabolism 268.4 (1995): E730-E734.
• Hickson, Robert C., et al. "Protective effect of glutamine from glucocorticoid-induced muscle atrophy occurs without alterations in circulating insulin-like growth factor (IGF)-I and IGF-binding protein levels." Experimental Biology and Medicine 216.1 (1997): 65-71.
• Salehian, Behrouz, et al. "The effect of glutamine on prevention of glucocorticoid-induced skeletal muscle atrophy is associated with myostatin suppression." Metabolism 55.9 (2006): 1239-1247.
• Ventura, G., et al. "Effect of citrulline on muscle functions during moderate dietary restriction in healthy adult rats." Amino acids 45.5 (2013): 1123-1131.

Ashwagandha Boosts Size & Strength Increases, Augments Fat Loss & Recovery in 8-Week Resistance Training Study

Ashwagandha Boosts Size & Strength Increases, Augments Fat Loss & Recovery in 8-Week Resistance Training Study

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Ashwaghanda may be for gymrats, too.

Ashwaganda is one of the supplements that has been around forever. While this would suggest that it works, the relatively low number of people who actually use it suggests otherwise and scientific evidence in form of peer-reviewed, non-sponsored studies that would allow us to draw a reliable conclusion with regard to its usefulness for athletes is rare... Well, actually there are only four studies on Withania somnifera, which is also known as Indian Ginseng or Winter Cherry, of which you could say that they are at least relevant to the topic - even though none of them was conducted in resistance trained / training individuals.

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Body Pump, Cardio & Exercise Expenditure

Study Indicates Cut the Volume Make the Gains!

There's a study by Raut, et al. that evaluated the "tolerability, safety, and activity of Ashwagandha (Withania Somnifera) in healthy volunteers" from 2012; a study by Sandhu, et al. in which the researchers probed the "effects of Withania somnifera (Ashwagandha) and Terminalia arjuna (Arjuna) on physical performance and cardiorespiratory endurance in healthy young adults" and found an increase in velocity [+3%], relative power [+9%] and VO2 max [+7%] in response to 500mg/day for 8 weeks; a study by Choudhary et al. (2015) which found both, increases in VO2max and quality of life of 50 "athletic" individuals in response to a commercial Ashwaghanda product that goes by the cryptic acronym KSM-66 Ashwagandha; as well as a study by Shenoy, et al. (2012) which found 11%, 16% 16% and 2% increases in time to exhaustion, VO2, metabolic equivalents (METs) and respiratory exchange ratio (RER), respectively (note: the benefits were sign. lower in female study participants, see Table 1), in response to the same amount, i.e. 500 mg/day, of an aqueous root extract of Ashwagandha that has been used by Sandhu et al. two years before.

Table 1: Mean percentage (%) difference of pre-post readings of forty male and female elite (elite here refers to the participation of the athlete in at least state-level events) Indian cyclists in response to 8 weeks on 500 mg of standardized aqueous root extract, which was obtained in the form of capsules from Dabur India Limited (Sandhu. 2012).

With that being I should mention that several studies suggest that your source of Ashwaghanda may well determine its effects. So, any current and future contradictions in the literature may be related to the level of desirable and undesirable "active ingredients" in the tested extracts. Patel, et al., for example, report that 50% of the samples they analyzed in 2015 contained mercury (Hg) at levels "above the permissible limit". Reason enough for the researchers to conclude that the "consumption of drug (Ashwagandha) obtained from polluted areas may cause accumulated side effect as well as the toxic effect of the heavy metals, respectively" (Patel. 2015). In view of the fact that I assume that Wankhede et al. used an (a) heavy-metal free and (b) truly standardized extract with actual steroidal lactones (withanolides, withaferins), saponins and alkaloids like isopelletierine and anaferine in it, in their recent

"prospective, double-blind, placebo-controlled parallel group study to measure the possible effects of ashwagandha extract on muscle strength/size, muscle recovery, testosterone level and body fat percentage" (Wankhede. 2015)

in young men who participated in a standardized resistance training regimen, it is thus not totally impossible that the next best Ashwaghanda product from the internet will produce significantly different results. I guess you should keep that in mind if you plan to go shopping after reading this article. The product Wankhede, et al. used, by the way, was provided by Shri Kartikeya Pharma and Ixoreal BioMed and happened to be the same KSM-66 high-concentration root extract Choudhary et al. used in their likewise very recent study.

Figure 1: Overview of the study design as it is visualized in Wankhede et al. (2015)

I don't want to waste your precious time with speculations, though. Let's talk about Wankhede's recent study, on 57 men (18-50 years), who were randomly allocated to either the treatment group, in which the subjects consumed 300 mg of ashwagandha root extract twice daily, or the control group, which received identically looking starch placebo capsules.

BIA and CK - not the best ways to measure body fat and recovery: What should be noted about these measurements, though, is the fact that body fat levels were measured via bio impedance (BIA) and the recovery was judged based on creatine kinase (CK) values. With BIA being susceptible to variations in hydration status and other sources interference (Kyle. 2004) and the CK-values showing extreme inter-individual variability (learn more), the validity of these outcomes remains somewhat questionable.

Both, the subjects who received the active treatment in form of 2x300 mg/day Ashwagandha, as well as those who received the placebo treatment, underwent identical 8-week resistance training programs; programs, the scientists describe as follows:

"The resistance training program consisted of sets of exercises over major muscle groups in both the upper body and the lower body. [...] Each subject in both groups was asked to come to a training session every other day, with one rest day pe week, for three days per week. Every session began with a warm up consisting of five minutes of low-intensity aerobic exercise. The subjects were instructed to perform, for each set as many repetitions as they could until failure. The subjects were asked to go through the full range of motion and were demonstrated the proper technique for safe and effective weight lifting" (Wankhede. 2015).

The workouts were periodized with increasing number of sets from 1-2 to 3. More specifically, the subjects performed barbell squats, the leg extensions, seated leg curls, machine chest presses, barbell chest presses, seated machine rows, one-arm dumbbel rows, machine biceps curls, dumbbel biceps curls, cable triceps press-downs, dumbbell shoulder presses, and the straight-arm pull-downs in the first two weeks and barbell squat (3 sets) the leg extension (3 sets), the leg curl (2 sets), one chest exercise (flat, incline or decline press or fly, cable cross over, 3 sets), one back exercise (rows, pull up, pull down or seated cable row, 3 sets), another chest exercise (3 sets) another back exercise (3 sets), one biceps exercise or one triceps exercise (curls or extensions, 3 sets), and one shoulder exercise (raises or presses, 3 sets) for the rest of the 8-week study.

Figure 2: Absolute increases in thigh, arm and chest size and reduction in body fat (%) over the course of the 8-week study; the figures above the bars denote the inter-group difference in %, * denotes significant differences (Wankhede. 2015).

Significant inter-group differences were found for almost all of the measured variables: the size increases in the arms and chest, the change in body fat (remember, those are only BIA values), serum testosterone, and CK (remember, this is not a very reliable marker of exercise recovery), as well as the strength increase on the bench press and leg extension machine (1RM, each) differed significantly not just from pre- to post, but also from the supplement to the placebo group (see Figure 2, Figure 3).

Figure 3: Changes in 1RM (kg) strength and testosterone (ng/dL) over the course of the 8-week study; the figures above the bars denote the inter-group difference in %, * denotes significant differences (Wankhede. 2015).

Against that background it seems certainly warranted that Wankhede et al. postulate that their study "confirms previous data regarding the adaptogenic properties of ashwagandha" and it also clearly "suggests it [Ashwaghanda supplementation] might be a useful adjunct to strength training" (Wankhede. 2015). The authors are yet also right, when they point out that their study has...

"[...] the following limitations which should lead us to interpret the findings with some caution: the subjects are untrained and moderately young, the sample size of 50 is not large and the study period is of duration only 8 weeks" (Wankhede. 2015)

Accordingly, Wankhede et al. rightly demand that further "[r]esearch studying the possible beneficial effects of ashwagandha needs to be conducted", research that spans "longer periods of time" and includes "different populations including females and older adults of both genders" (Wankhede. 2015). In this regard, I would like to remind you that the previously discussed results Shenoy et al. published three years ago, in which the sex of the participants had a major impact on the study outcome, make studies comparing male to female resistance trainees particularly appealing - from a science perspective, obviously ;-)

Sometimes lab values are deceiving - specifically if allegedly pathological elevations of kidney, liver and (heart) muscle enzymes (CK) are nothing but a perfectly physiological reaction to exercise | learn more!

So, what's the verdict, then? Yes, this is definitely the most exciting 'Ashwaghanda study', I've seen so far. Next to the limitations Wankhede et al. already discuss in the conclusion of their recently published paper in the Journal of the International Society of Sports Nutrition one should not forget, though, that the methods they chose to determine the body composition and state of recovery of their subjects were appropriate, but not optimal. While the former would have been more reliable if they had used a DXA scan, the latter would actually have to be tested via several post-workout strength tests and auxiliary tests and questionnaires as it was done, for example, by Kraemer et al. (2010).

Enough of the complaints, though. Let's be greatful we even have a study investigating the effects of Ashwagandha on resistance training. Plus, the increases in strength, muscle size (which would be similarly thwarted by cell swelling in both groups when it was tested 'only' two days after the last workout) and testosterone, alone, warrant the authors' already carefully worded conclusion that "ashwagandha supplementation may be useful in conjunction with a resistance training program" (Wankhede. 2015) - even if the underlying mechanism is still unknown and the hypotheses the authors list in the discussion, i.e. (a) increase in testosterone (too low to have significant effects | learn why), (b) decrease in the levels of cortisol (not measured + acute cortisol elevations are associated w/ lean mass gains in strength training individuals | West. 2012), (c) beneficial effects on mitochondrial health and reduced ATP breakdown (observed only in rodents that were exposed to toxins vs. exercise), and (d) antianxiety effects and promotion of focus and concentration that "may translate to better coordination and recruitment of muscles" (Wankhede. 2015), are as the word "hypothesis" implies only hypothetical, i.e. conjectural | Comment on Facebook!

References:

• Choudhary, Bakhtiar, A. Shetty, and Deepak G. Langade. "Efficacy of Ashwagandha (Withania somnifera [L.] Dunal) in improving cardiorespiratory endurance in healthy athletic adults." AYU (An international quarterly journal of research in Ayurveda) 36.1 (2015): 63.
• Kyle, Ursula G., et al. "Bioelectrical impedance analysis—part II: utilization in clinical practice." Clinical nutrition 23.6 (2004): 1430-1453.
• Patel, Dhaval, Harisha C. Rudrappa, and Proshanta Majumder. "A comparative pharmacognostical, physicochemical, and heavy metal analysis on Ashwagandha root obtained from natural and polluted sources." International Journal of Green Pharmacy 9.1 (2015): 14.
• Raut, Ashwinikumar A., et al. "Exploratory study to evaluate tolerability, safety, and activity of Ashwagandha (Withania Somnifera) in healthy volunteers." Journal of Ayurveda and Integrative Medicine 3.3 (2012): 111.
• Sandhu, Jaspal Singh, et al. "Effects of Withania somnifera (Ashwagandha) and Terminalia arjuna (Arjuna) on physical performance and cardiorespiratory endurance in healthy young adults." International journal of Ayurveda research 1.3 (2010): 144.
• Shenoy, Shweta, et al. "Effects of eight-week supplementation of Ashwagandha on cardiorespiratory endurance in elite Indian cyclists." Journal of Ayurveda and integrative medicine 3.4 (2012): 209.
• Wankhede, Sachin, et al. "Examining the effect of Withania somnifera supplementation on muscle strength and recovery: a randomized controlled trial." Journal of the International Society of Sports Nutrition 12.1 (2015): 43.
• West, Daniel WD, and Stuart M. Phillips. "Associations of exercise-induced hormone profiles and gains in strength and hypertrophy in a large cohort after weight training." European journal of applied physiology 112.7 (2012): 2693-2702.