Glutamine or BCAA, Which is the Better Fatique Buffer? 18g GLU Suprisingly Effective, 9.5g BCAAs (Un-)Surprisingly Useless as Blood Fatigue Factors & Cytokine Buffers

Rowing is an excellent cardio exercise for wanna be bodyuilders, by the way!

I am not really a fan of glutamine, but unlike BCAAs that are still hyped all over the Internet, the conditionally essential amino acid which is the most abundant of all amino acids in human blood is at least not falsely heralded as a potent catabolic, anabolic, weight loss adjuvant and what not, any longer.

Against that background I have to admit that I am not exactly unhappy to tell you that Ga Hee Koo, Jin Hee Woo, Sung Whun Kang, and Ki Ok Sjin who work at the Dong-A University and the Republic of Korea Airforce Academy, have recently observed that BCAAs have absolutely no, glutamine at least a minimal impact on the blood fatigue factor response of juvenile athletes in response to a 2,000 m all out rowing challenge w/ placebo, BCAA or glutamine supps.

Learn more about glutamine and BCAAs at the SuppVersity

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In the corresponding experiment, the scientists from the College of Sports Science at the Dong-A University had five male juvenile elite rowing athletes perform the same 2,000m rowing test at maximal intensity after having received a placebo, BCAA, or glutamine for 7 days before
the test. The specific supplementation regimen included:

• BCAA (Spomax, Seoul, Republic of Korea) was given three times a day (25% valine, 50% leucine, 25% isoleucine, 3.15 g/day).
• L-glutamine (Optimum Nutrition, Aurora, IL, USA, 6 g/day) was given three times a day.

Blood samples were collected from the antecubital vein on the day of testing while resting before the test, immediately at the end of test, and 30 min after the test. All tests were conducted with a 1-week interval to eliminate the potential effects from potentially longer-lasting effects of the previously administered supplement.

Which parameters did the researchers test and why? Koo et al. tested lactate, the accumulation of which will eventually impair ATP synthesis and lead to muscular fatigue. They tested the accumulation and clearance of ammonia, which can trigger central fatigue, when the levels increase rapidly during high intensity exercise. And they tested creatine kinase (CK) which is a classic marker of muscle damage and IL-8 and IL-15, two cytokines that will be elevated, when the activity of the immune system is not sufficient to deal with exercise induced stressors.

The actual test was conducted with an indoor rowing machine (Concept², Morrisville, VT, USA) two times each for supplementation with the placebo, BCAA, and glutamine. All the subjects performed a 2,000 m (Olympic single scull race) race at their own individual maximum paces (42–45 pace for 0m~250m, 40 pace for 250m~500m, 36–38 pace for 500m~1,500 m, and over 42 pace for 1,500 m~2,000 m)

Figure 1: Serum markers of fatigue and muscle damage, expressed relative to placebo (Koo. 2014)

There were no significant differences in lactate levels; a significant phopshorus-sparing effect from BCAAs (small effect size) and glutamine (large effect size) of which the scientists believe that it was mediated by the use of the amino acids to maintain adequate muscular ATP levels; and there was a non-significantly elevated level of ammonia in the glutamine group (some arginine could help clear those | learn more) that returned to normal 30 min after the test.

The dosages are not the same! That's unfair! No, it's not necessarily unfair, but it would still have been better to test 18g of glutamine vs. 18g of BCAAs. There is after all one thing both have in common: They both can be used as workout fuel in the muscle, so the advantage of glutamine may have become smaller (maybe even non-significant), if both had been administered at the same amounts.

The creatine kinase levels (a marker of muscle damage) and the levels of interleukin-8 and interleukin-15, however, were significantly lower in the glutamine than they were in either the BCAA or placebo group. This is a result of which the authors of the study believe that, it may...

"[...]represent the effects of energy supplementation from glutamine supply, which activated as a fuel in the muscle and as a nitrogen precursor for nucleotide synthesis" (Koo. 2014). 

An alternative explanation would be that glutamine (probably via its connection to glutathione; see Roth. 2002) had a direct protive effect on the skeletal muscle tissue during the workouts.

Figure 2: Serum levels of inflammatory cytokines expressed relative to placebo (Koo. 2014)

This hypothesis would also be supported by the changes in interleukin expression. i.e. the blunted increase of interleukin-8. IL-8 is an inflammatory cytokine that serves as a chemical signal which attracts neutrophils at the site of inflammation. The corresponding increase in IL-15, which was likewise reduced in response to sub-chronic glutamine supplementation, on the other hand, indicates a reduced production (not activity!) of natural killer cells.

Table 1: Intense exercise is not the only condition / disease that's associated  with low blood glutamine levels (Roth. 2002)

In that, it is crucial to understand that the authors (imho reasonably) believe that the increase in IL-8 & IL-15 is a compensatory mechanism which is initiated to counter the reduced immune function that occurs, when the amount of glutamine in the blood and skeletal tissue drops. We do after all know for sure that the this will result in a significant decrease in the cell proliferation rate of lymphocytes, the amount of antioxidants, peptides, amino sugars related to cell resistance against apoptotic processes, purines, as well as the synthesis of key molecules such as pyrimidines which are all involved in redox reactions (Roth. 2002).

Whether supplementation is warranted with low(er) intensity exercise, as well, is however questionable. Previous research by Ostrowski et al. (2001), who had their subjects exercise at significantly lower intensities, did not find comparable increases in IL-8. This difference is probably due to a comparably lower amount of exercise induced stress that corresponds to the reduced intensity. In this context it's also worth mentioning that Fischer et al. (2006) report that the blood chemokine concentrations would increase little or remain stagnant unless a sufficient muscle mass is mobilized and maintained at a certain level of intensity sufficiently... now, everyone who has ever done an all-out rowing time trial will confirm: This is (a) intense and will (b) involve almost every muscle in your body.

If maximal muscle hypertrophy, not performance increases in all-out (aerobic) exercise and protecting your immune function is your goal, buy some whey + casein and stay away from glutamine & BCAAs unless you insist on wasting money on hitherto unproven promises of strength & size gains | learn more

Bottom line: In contrast to BCAAs which will "only" blunt the increase in debilitating phosphorus in the blood,  "glutamine supplementation could be helpful for enhancement of immune function and the defensive inflammatory reaction after exercise." (Koo. 2014)

The results of the study at hand do thus confirm an older piece of broscience, i.e. the importance and efficiency of adequate amounts of glutamine (15g or more per day!) for recovery and immune function. They do yet also put another question mark behind the ergogenic potential of brach-chained amino acids about which I have written repeatedly in previous articles here at the SuppVersity (in other contexts, BCAAs may well be superior to glutamine, but long-term studies to prove any of the claimed benefits are missing, as well).

Whether the results from the study at hand warrant the consumption of 18g of glutamine per day for all of us, is still questionable. If you are in a phase of your training that requires a lot of all-out exercise and already feel that your immune defenses are dwindling, it probably won't hurt to buy a cheap 500g bag of glutamine from the bulk supplier you trust. Don't expect instant results of illusive tingles as you'll get them with certain other supplements. If there are benefits they will only be visible over time and will include faster / more complete recovery, reduced rates of infection and overall fatigue. Eventually, these would help you to make faster gains in strength and size, though | Comment on Facebook.

References:

• Fischer, Christian P. "Interleukin-6 in acute exercise and training: what is the biological relevance." Exerc Immunol Rev 12.6-33 (2006): 41.
• Koo, Ga Hee, et al. "Effects of Supplementation with BCAA and L-glutamine on Blood Fatigue Factors and Cytokines in Juvenile Athletes Submitted to Maximal Intensity Rowing Performance." Journal of Physical Therapy Science 26.8 (2014): 1241-1246.
• Ostrowski, Kenneth, et al. "Chemokines are elevated in plasma after strenuous exercise in humans." European journal of applied physiology 84.3 (2001): 244-245.
• Roth, Erich, et al. "Regulative potential of glutamine—relation to glutathione metabolism." Nutrition 18.3 (2002): 217-221.

Easy Whey to Prevent LPS Induced Inflammation? Whey Protein Prevents LPS Binding to TRL-4 and IL-8 Production. Surprise: Pressurized Denatured Whey Works Best!

Unlikely that this or whatever whey protein you have bought as of late was pressurized with an Avure High Pressure Processing System at more than 500mPa in order to denature it (yeah you're reading right) and produce a bunch of fancy new peptides which appear to have even more potent anti-LPS effects than those in regular whey protein (hydrolysate).

Saturday's post on saturated fatty acids and their negative effects on post-prandial endotoxemia has turned out to be (un-)surprisingly popular. I am still not sure if this will be same for the post at hand; and that despite the fact that it revolves around the exact same topic, namely the inflammatory reaction to lipopolysaccharides (LPS). In the case of endotoxins such as LPS, the inflammation, which is, as you all should by now be aware of, an endogenous "alert, defense and repair" reaction of our bodies, is actually triggered by their interaction with the so-called toll-like-receptor. Now scientists from the McGill University in Montreal have found that there is a substance all of you are familiar with and some of you may even be consuming on daily or at least regular basis that can block this interaction, as well as the ensuing overproduction of cytokines and/or other well-meant, but in the end potentially hazardous immune responses.

There is al-wheys something new about whey ;-)

As the researchers point out the beneficial effects of whey proteins don't just go way beyond their muscle building effects and are mediated by several and not just one of it's amino acid, protein and peptide ingredients:

"Whey proteins (WP), a by-product of the cheese-making industry, possess nutritional benefits as a source of protein of high biological value. Whey products and whey-derived peptides have demonstrated a number of anti-inflammatory effects. These anti-inflammatory effects include decreased cytokine release in rodent models of ischaemia– reperfusion and exposure to LPS. In addition, individual whey constituents, such as lactoferrin or glycomacropeptide, and peptides released from these by pepsin– pancreatin hydrolysis exhibit anti-inflammatory effects, such as suppression of tissue neutrophilia or inhibition of inflammatory cytokine release." (Iskandar. 2013)

In that, whey proteins have been shown to be particularly useful for the treatment and/or management of chronic inflammatory diseases such as cystic fibrosis, a disease passed down through families that causes thick, sticky mucus to build up in the lungs, digestive tract, and other areas of the body and a disease that will probably make you - just like me - think about the high cysteine content of whey, immediately.

"Under pressure..."

For the study at hand the researchers used two different epithelial cell types and added lipopsaccharides (LPS), as well as

• regular whey (Inpro 90 Whey Protein Isolate from Vitalus Nutrition) that had been enzymatically hydrolysated (=predigested) to yield a product that would be similar to what many supplement are now selling you as either intra- or post-workout "super whey" (their not my claim ;-), or
• pressurized whey, which was based on the same raw material, but was pressurized before being hydrolysated

to their petri dishes and observed the effect the additional whey proteins had on the LPS-induced interleukin-8 (IL-8) production and the binding of the Escherichia coli LPS to the TRL4s (toll-like receptor 4) on the surface of the epithelial cells.

Figure 1: Differential effects of different doses (in µg/ml) regular and pressurized whey protein hydrolysate on LPS-induced IL-8 secretion in 1HAEo- cells (left) and corresponding LPS-binding to toll-like receptors on the surface of the cells (right); data expressed relative to LPS only (Iskandar. 2013)

As the data in figure 1 clearly shows, both whey protein hydrolysate, the regular, as well as the pressurized one had similar effects on the binding of LPS. The ensuing decrease in cytokine production (IL-8) was yet statistically significant only in the dish with the pressurized whey protein hydrolysate. Moreover at the highest dosage of the normal whey protein hydrolysate, there is what you could call a "rebound effect", if this reached statistical significance - which it obviously didn't.

Figure 2: Effect of 500 or 1000mg/ml of pressurized whey protein and native whey protein hydrolysates on 1HAEo- cell culture medium ferric-reducing antioxidant power  (FRAP); data expressed relative to basal levels (Iskandar. 2013)

That said, the overall effect size dependent not just on the type of whey protein hydrolysate, but also on the cell type: While the 1HAEOo- cells (shown in figure 1) needed the highest tested dose to show statistically significant reductions in IL-8 production, the effect reached significance at 500 µg/ml for the CFTE29o- cells using the pressurized whey protein hydrolysate and at 1,000µg/ml for the regular WPH (obviously no rebound here).

A similar difference was observed in the results FRAP essay (FRAB stands for ferric reducing ability of plasma and the results provide information about the general antioxidant defenses of the cells). While the CFTE29o- cells (shown in figure 2) were happy with both whey protein hydrolysate, the pressurized WPH had a minimal, but statistically non-significant edge in the 1HAEOo- cells.

Is there anything special about pressurized hydrolysates?

In previous studies the researchers had already established that pressurization of WP improves its
in vitro digestibility, promotes the release of novel peptides by gastrointestinal digestive enzymes and enhances the antiinflammatory effect (Vilela. 2006).

"These in vitro findings were also confirmed in clinical studies. Thus, a 2-week supplementation with pressurised whey increased the levels of glutathione, a crucial low-molecular anantioxidant, in peripheral blood mononuclear cel. Further, we have reported that a 1-month dietary supplementation with pressurised whey improved nutritional status and markers of systemic inflammation in patients with CF [cystic fibrosis]." (Iskandar. 2012)

In the study at hand, the research team from Canada did now want to (a) investigate the potential anti-inflammatory and antioxidant effects of pressurized and regular whey protein hydrolysates in the context of cystic fibrosis and non- CF respiratory epithelial cells and (b) explore the mechanisms by which pressurised and native whey exert their beneficial anti-inflammatory effects. Their research hypothesis was that it is the difference in peptide (=complex bond of amino acids that has different effects from the same amino acids in isolation) availability that is enhanced by the pressurisation of whey that's responsible for it's superiority compared to regular whey proteins.

Establishing the (leaky) gut, bacteria, non-alcoholic fatty liver disease connection

With the researchers focus being on cystic fibrosis, the results of this in-vitro trial are still highly meaningful for all of us. In particular the more potent increase in overall anti-oxidant capacity upon exposure of the epithelial cell lines would suggest that the ingestion of pressurized whey proteins could exert similar benficial effects in other parts of the body, specifically the digestive tract, as well.

Suggested read: "Plus: 20+ Things to Protect and Restore the Integrity of Your Intestinal Wall" (read more)

On the other hand, the more important blockage of the toll-like receptors, was virtually identical with both the regular and the pressurized whey protein and the general implications of these findings are actually pretty far-reaching. After all, TRL4 has only recently been implicated in the development of fibrosis in non-alcoholic fatty liver disease subsequent to alteration of gut microbiota, increased intestinal permeability and the ensuing increase in exposure of the liver to gut-derived bacterial products (Frainarius. 2012). The exact same horror-scenario many of you will probably have had on mind, when they read about the effects the high saturated fat content had in the study by Mani et al. from Saturday.

Bottom line: So will just having your daily whey protect your gut from all assaults? Probably not, but is may be just another one of the many small things which may not render your intestinal wall and overall immune system bullet-proof but will at least help them to come with the omnipresent and 24/7 assault they are exposed to. Whether it's really got to be pressurized whey, on the other hand, remains questionable. Personally, I don't think so - if you take a look at the dose-dependently reduced expression of IL-8 in response to LPS exposure upon co-administration with pressurized and normal whey, it seems as if the pressurized variety did not only have the edge, but was also lacking the rebound effect that occurred at very high doses in the 1HAEo-cells.

If you want to live out your OCD tendencies on your whey intake, start with rule #1 "Never Sip Your Whey" (read why).

Since, previous have shown that pressurization does impart significant changes not just to the digestibility of whey protein hydrolysates, but also to their peptide structure (Vilela. 2006), it could thus well be that the observed differences are of real world importance, as well, and cannot be compensated for by just taking more of the "regular" whey protein hydrolysates.  I hope there will soon be comparative studies in human subjects available, until then I would not worry too much about not getting the "optimal" whey protein to combat TRL-4 binding of LPS and increase anti-oxidant defenses. As a regular SuppVersity reader, you are probably apart of the privileged part of the Western society which has to care least about LPS and overall (bad) inflammation, anyways. Plus, as the study goes to show "regular" whey has similar, albeit not "optimal" effects in this regard.

References:

• Iskandar MM, Dauletbaev N, Kubow S, Mawji N, Lands LC. Whey protein hydrolysates decrease IL-8 secretion in lipopolysaccharide (LPS)-stimulated respiratory epithelial cells by affecting LPS binding to Toll-like receptor 4. Br J Nutr. 2013 Jan 3:1-11.
• Frasinariu OE, Ceccarelli S, Alisi A, Moraru E, Nobili V. Gut-liver axis and fibrosis in nonalcoholic fatty liver disease: An input for novel therapies. Dig Liver Dis. 2012 Dec 29.
• Vilela RM, Lands LC, Chan HM, Azadi B, Kubow S. High hydrostatic pressure enhances whey protein digestibility to generate whey peptides that improve glutathione status in CFTR-deficient lung epithelial cells. Mol Nutr Food Res. 2006 Nov;50(11):1013-29.