No Advantage of Bolus Ingestion of EAAs in Young Men!? Cereal Bread Not Better for Weight Control. Saturated Fat & the Heart. Plus: Serine for Your Weekend Alcohol Binge!

The "muscle full effect" indicates you don't have to consume 4 scoops at once.

With the publication of the latest issue of The Journal of Nutrition came a handful of interesting scientific papers I will briefly introduce in today's SuppVersity Nutrition Science Update.

The corresponding studies deal with the link of saturated fat to heart disease (Puaschitz. 2014), the effects of proteinogenic amino acid serine (one of the non-essential amino acids) on homocysteine metabolism in a rodent model of alcoholic fatty liver disease (Sim. 2014).

And when we're through with those, we will take a closer look at the effects of cereal enriched breads on the appetite ratings and postprandial glucose, insulin, and gastrointestinal hormone responses related to hunger and satiety in healthy men and women (Gonzalez-Anton. 2014), and the "muscle full effect", or rather limits to maximal protein synthesis in man (Mitchell. 2014).

Read more short news here at the SuppVersity

Obesity Research Upd. Nov. '14

Exercise Res. Upd. Nov '12(1)

Exercise Res. Upd. Nov '12(2)

Nutrition Res. Update Nov. '14

Weight Loss Tricks & More

Reductive Stress, Iron & the Military

• Saturated fat and your heart - Right from the Haukeland University Hospital in Norway comes a new study that investigated the associations between self-reported dietary SFA intake and risk of subsequent coronary events and mortality in patients with coronary artery disease (CAD).
  
  The study included patients who participated in the Western Norway B-Vitamin Intervention Trial and completed a 169-item semiquantitative food-frequency questionnaire after coronary angiography - 2412 patients, total, 81% men, 19% women with a mean age of 61.7 y.
  After a median follow-up of 4.8 y, a total of 292 (12%) patients experienced at least one major coronary event during follow-up.  And while a gigh intake of SFAs was associated with a number of risk factors at baseline, "there were no significant associations between SFA intake and risk of coronary events [age- and sex-adjusted HR (95% CI) was 0.85 (0.61, 1.18) for the upper vs. lower SFA quartile] or any secondary endpoint. Estimates were not appreciably changed after multivariate adjustments" (Puaschitz. 2014).
  

  

  Figure 1: Hazard ratios according to % saturated fat intake of total energy intake compared to minimal saturated fat intake (HR = 100%) in 2412 subjects (Puaschitz. 2014).

  In other words, if you ask researchers from Northern Europe, their answer to the question, whether our high intake of saturated fats is the reason we are dying prematurely from heart disease is "no". This stand in line with a recent review of the current evidence by O'Keffee et al. who point highlight that the different results (which often depend on the country, where the studies are conducted) may be attributable to the fact that "not all SFA are created equal and the food sources of SFA". Accordingly the researchers from the King's College in London, the Luke’s/Roosevelt Hospital, the New York Nutrition Obesity Research Centre and the Columbia University in New York recommend that "individual characteristics of the SFA, such as chain length, should be considered in dietary recommendations" (O’Keeffe. 2014)... and I would like to add: In every future study, as well.
  
  I mean, this and the foods from which the subjects in the study at hand got the majority of their saturated fat intake may well be the reason that there was a statistically significant correlation between high fat intakes and the occurernce of coronary artery disease (remember: all participants had CAD, already) in the cohort Western Norway B-Vitamin Intervention Trial.
• L-Serine as super-supplement for binge drinkers? At least in rodents the provision of 200mg/kg body weight (for humans this would be ~1.2-1.5g/day) serine in the diet led to an attenuation of alcohol-induced increases in serum homocysteine and hepatic triglyceride (TG) concentrations (>5-fold in the control mice) by 60.0% and 47.5%, respectively.
  

  

  Figure 2: Liver triglyceride levels, serum ALT and serum homocysteine levels in control mice (C) and "binge drinking mice" (EV) with and without 20mg/kg (ES20) and 200mg/kg (ES200) serine in their diets (Sim. 2014)

  Moreover, in the chronic ethanol study, l-serine also decreased hepatic neutral lipid accumulation by 63.3% compared with the ethanol group and ramped up the glutathione and S-adenosylmethionine content of the liver by 94.0% and 30.6%, respectively.
  
  If we assume that serine is only half as powerful, when it is given to humans, I would recommend you drink your Vodka Red Bull with serine in the future ;-)
• Super-satiating cereal enriched breads - I guess "super-satuating" is an exaggeration, but there is no doubt that the addition of variety of cereal flours (wheat, oat, and spelt) and 22% dried fruits (figs, apricots, raisins, and prunes) to regular bread lead to a significant improvement of appetite control by reducing hunger and enhancing satiety in 30 healthy adults (17 men and 13 women) aged 19–32 y with body mass index of 19.2–28.5 who participated in an experiment that was conducted at the University of Granada in Spain (Gonzalez-Anton. 2014).
  

  

  Figure 3: The hormonal changes would indicate increased satiety, the subjects reported increased satiety, but their 4h energy intake was identical in both condition (Gonzalez-Anton. 2014)

  Whether the decrease in prospective consumption and increased satiety is enough to have long-term benefits on weight control is yet questionable, because the subsequent ad libitum energy intake in a 4 h period after the ingestion of the "enriched" bread did not differ from that in the control condition, even though the postprandial blood glucose, insulin, ghrelin, were lower and the pancreatic polypeptide AUC (an indicator of satiety) was higher than with the control bread.
  
  Speaking of insulin: In view of the fact that the latter actually is a satiety hormone and its release is closely related to glucagon-like peptide (GLP) 1 and gastric inhibitory polypeptide (GIP) where the AUC (areas under the curve) were lowered as well, it's eventually maybe not too surprising that the "enriched" bread was not better than the regular one.
• Muscle full? What's limiting protein Synthesis? Scientists from the Clinical, Metabolic, and Molecular Physiology, MRC–Arthritis Research UK Centre of Excellence for Musculoskeletal Ageing Research at the University of Nottingham and the Royal Derby Hospital in the United Kingdom recently determined the effect of Bolus (=all the aminos at once) vs. Spread EAA feeding in young men, hypothesizing that muscle-full is regulated by a dose-, not delivery profile–, dependent mechanism; and what they found was surprising for us - not for the researchers, though:

  

  Figure 4: Even though the study was conducted in young men, the overall dosage of 15g may potentially have had an effect on the outcome. On the other hand: If you "overdose" it would actually be more likely for spread protein ingestion to have superior effects. Against that background the "low" dose of "only" 15g of pure EAAs is not an argument that would falsify the results of the study at hand (Mitchell. 2014)

  "Despite distinct plasma and muscle profiles, Bolus feeding provided no anabolic advantage over Spread feeding (or vice versa); these findings are in keeping with our hypothesis of there being an intrinsic muscle-full state in young men at rest.
  
  Bolus feeding led to rapid aminoacidemia with a brisk upstroke and high peak plasma EAA and leucine concentrations. Spread feeding, by comparison, resulted in lower, later peak concentrations. Despite this, identical MPS responses were observed, even with the same latency (of ~90 min) and amplitude.
  
  Furthermore, with both feeding strategies, basal MPS was observed 180 min after consumption of either Bolus or the initial Spread doses. This preceded the peak Spread plasma EAAs, in keeping with the onset of a muscle-full state.

  As the scientists point out, their results do thus "suggest that, in healthy young men, it is dose dependent mechanisms that regulate the size of the anabolic response to feeding and that this response" and that this dose-dependent anabolic response "is not perturbed by later arriving, lower-amplitude aminoacidemia." The researchers also highlight hat it would seem "vital to have such a mechanism in place"; because of the "stability of muscle mass from year to year in healthy younger populations" (Mitchell. 2014). Eventually, the differences may well be explained by the existence of three distinct phases in the postprandial period, the scientists argue:
  

  

  Figure 5: Absolute changes in FSR from fasted (2120 to 0 min) to fed (0 to 240 min) (A), actual FSRs (B) and plasma EAA and insulin concentrations, phospho- 4EBP1 Thr65/70 and muscle protein synthetic rates, normalized to their own data spans shown on the same axis (C and D) in young men after consumption of 15 g of mixed-EAA meals by Bolus or Spread treatment. The black arrows represent ingestion of 15 g EAAs once, and the gray arrows represent ingestion of 3.75 g EAAs 4 times (Mitchell. 2014)

  "After the onset of essential aminoacidemia, a latent period exists when a significant negative arteriovenous EAA balance is detectable (Mitchell. 2013) but incorporation of EAAs into newly synthesized myofibrillar proteins is not. The existence of a similar latent period in response to Bolus and Spread EAA ingestion suggests that providing time for adequate intracellular EAA accumulation, even with rapid aminoacidemia with Bolus, is crucial before MPS can be ‘‘switched on.’’ After this latent period, a transient stimulation in MPS, lasting ;90 min (Bohé. 2001), occurs before the onset of the muscle-full state restores basal MPS despite sustained, near-peak postprandial EAA availability" (Mitchell. 2014).

  Put simply, it takes long enough for the muscle protein synthesis to gain full speed to incorporate all the amino acids the healthy subjects received in 4x45min boluses.
  
  Practically speaking this does not necessarily mean that you should give up your previous protein feeding strategies. With intact proteins, of which you know that they are more than the sum of their EAA parts (see "Whey Beyond Brawn"), studies by Moore et al. (2012 | learn more) and Burke et al. (2012 | learn more) yielded different results... albeit with less frequent biopsies that were taken across the postprandial period and thus a lower temporal resolution that does not exclude that said studies simply overlooked the dose-dependency of the muscle-full effect Mitchell et al. demonstrate in the study at hand.

10+ Things You Probably Didn't Know Whey Protein | more

So what are the take home messages from today's research update? I guess the one you will be most interested in, is the related to the Mitchell study which indicates that protein timing and / or the importance of bolus ingestions may previously have been overrated - at least in the short run. We should not forget, after all, that this is a result that would stand in line with Alan Aragon's & Brad Schoenfeld's recent review (Aragon. 2014  on nutrient timing which found a significant effect for the amount of protein people consume, but no evidence of the purported importance of protein timing.

This is yet not the only myth that is tumbling. The idea of heart disease triggering saturated fats and the notion that you could make bread a superfood by adding cereals and dried fruits did not get away unscathed either. With the impressive effects of serine in the rodent study by Sim et al. (2014), we do have another myth to bother with - one of which I would like to remind you that it has to remain a myth until the results have been confirmed in human beings | Comment on Facebook!

References:

• Aragon, Alan Albert, and Brad Jon Schoenfeld. "Nutrient timing revisited: is there a post-exercise anabolic window." J Int Soc Sports Nutr 10.1 (2013): 5.
• Bohé, Julien, et al. "Latency and duration of stimulation of human muscle protein synthesis during continuous infusion of amino acids." The Journal of physiology 532.2 (2001): 575-579.
• Burke LM, Hawley JA, Ross ML, Moore DR, Phillips SM, Slater GR, Stellingwerff T, Tipton KD, Garnham AP, Coffey VG. Preexercise aminoacidemia and muscle protein synthesis after resistance exercise. Med Sci Sports Exerc. 2012 Oct;44(10):1968-77.
• O’Keeffe, Majella, and Marie-Pierre St-Onge. "Saturated Fat and Cardiovascular Disease: A Review of Current Evidence." Current Cardiovascular Risk Reports 7.2 (2013): 154-162. 
• Mitchell, William Kyle, et al. "Development of a new Sonovue™ contrast‐enhanced ultrasound approach reveals temporal and age‐related features of muscle microvascular responses to feeding." Physiological reports 1.5 (2013). 
• Mitchell, William Kyle et al. "A Dose- rather than Delivery Profile–Dependent Mechanism Regulates the ‘‘Muscle-Full’’ Effect in Response to Oral Essential Amino Acid Intake in Young Men."J. Nutr. February 1, 2015
• Moore DR, Areta J, Coffey VG, Stellingwerff T, Phillips SM, Burke LM, Cléroux M, Godin JP, Hawley JA. Daytime pattern of post-exercise protein intake affects whole-body protein turnover in resistance-trained males. Nutr Metab (Lond). 2012 Oct 16;9(1):91.
• Puaschitz et al. "Dietary Intake of Saturated Fat Is Not Associated with Risk of Coronary Events or Mortality in Patients with Established Coronary Artery Disease." J. Nutr. February 1, 2015 jn.114.203505
• Sim, et al. "l-Serine Supplementation Attenuates Alcoholic Fatty Liver by Enhancing Homocysteine Metabolism in Mice and Rats." J. Nutr. February 1, 2015 jn.114.199711.

Whey Protein Alone Won't Cover the EAA Requirements of Hard Working Athletes, Study Says. Plus: US Whey More Digestible & 88% Higher in Leucine than Brazilian Whey

Not all protein supplements are created equal. And this goes for whey supplements from different countries, too.

In their accepted manuscript for LWT - Food Science and Technology, Cristine Couto Almeida and her colleagues write: "When the calculated AAS and PDCAAS based on the suggestion for adult athletes were considered, both [US & Brazilian whey protein] supplements exhibited suboptimal score values for several EAA [... and] were unable to supply the suggested adult athlete EAA requirement" (Almeida. 2014).

Shocked? I'd hope not. I mean, you don't even know what the scientists base their conclusion on - right? So before we even try to put things into perspective, it would be wise to take a look a the design of this in vitro study.

You can learn more about protein intake at the SuppVersity

Are You Protein Wheysting?

5x More Than the FDA Allows!

Protein requ. of athletes

High EAA protein for fat loss

Protein Timing DOES Matter!

Less Fat, More Muscle!

While the researchers from the Universidade Federal de Rio de Jaieiro acknowledge that whey protein, in general, is an effective adjunct to the diet of strength and even endurance athletes, they insist that there is too little "information regarding the WP supplement protein quality" and thus set out to "to investigate the protein quality of commercial WP supplements produced by U.S. and Brazilian companies based on in vitro digestibility (IVPD) assay, EAA, AAS and [protein digestibility-corrected amino acid] PDCAAS." (Almeida. 2014)

To this ends, the researchers acquired fifteen samples of whey protein (WP), soy protein, and caseinate isolate powder from a commercial retailer specialized on nutritional supplements. The supplements had been manufactured at different countries - eight from USA companies (WP-USA), and seven from Brazilian companies (WP-BRA). The supplements manufactured with soy protein and caseinate isolate powder were used as references in a study that yielded quite surprising results.

Figure 1: Essential amino acid composition of two commercial whey protein supplements (Almeida. 2014).

As you can see in Figure 1 the amino acid composition of the whey proteins from Brazil and the US varied significantly. The US whey, for example had significantly higher amounts of leucine, while the Brazilian whey was loaded with the essential amino acid lysine. While it is possible that the variations in the other amino acids are a result differences that were present in the milk, already, I would guess that the US whey was either openly (the scientists don't disclose the brands, otherwise I'd check) or secretly spiked with leucine to promote muscle anabolism.

Figure 2: Relative loss (%) of amino acids during simulated (in vitro) digestion in US and Brazilian whey (Almeida. 2014).

What are the numbers based on: Whether the amount of aminos is sufficient or not was calculated based on the WHO recommendation (WHO. 2007), assuming a normal (=comparatively low) protein intake.

If you consume twice the WHO suggestions for athletes, you are thus not at a risk of being deficient in any of the EAAs, but could maybe optimize the ratio of the individual amino acids by not covering your protein needs from a single protein source.

Even if we assume the latter was the case and the producer added free form amino acids to the whey, though, this does not explain the other differences, because if you add say 20g of leucine to 100g of EAA and measure the amino acid content of the 100g of your new mix, the content of all other amino acids would be lower.

 As you can easily see in Figure 1, though, this was not the case in the study at hand. Plus: There were also significant differences in the protein digestibility-corrected amino acid composition, i.e. the marker of whether or not the content of a certain essential amino acid per gram of protein was sufficient or not. In that, values <1.0 indicate there is too little of this amino acid in the mix.

Figure 3: Amino acid score and protein digestibility-corrected amino acid composition for the commercial
US and Brazilian whey supplements (Almeida. 2014).

As you can see in Figure 3, the latter was the case for threonine and valine in the US whey and for isoleucine and leucine in the whey protein from Brazil.

Figure 4: According to the standardized in vitro digestion assay (AOAC. 2012) the scientists used soy protein has by far the lowest digestibility and will thus be effectively delivering the lowest percentage of the amino acids it contains into your circulation (Almeida. 2014).

What does this mean? I must admit this sounds awful, but in practice it means only that you would end up getting your EAAs at an allegedly suboptimal ratio (I doubt we know what this ratio is, though) if you covered your complete protein needs with whey protein. In that, it is interesting that you would get too little threonine and valine form US wheys and too little leucine and isoleucine from Brazilian wheys.

Actual deficiency symptoms as you may have expected them, when you've read the statement that whey protein supplements were "unable to supply the suggested adult athlete EAA requirement" (Almeida. 2014), however are unlikely, because (a) I assume most of you won't live off whey protein as their only protein source and (b) even if you did, you would probably consume more than the WHO recommendation for athletes (WHO. 2014) that's at the heart of Almeida et al.'s calculation suggests | Comment of Facebook!

References:

• Almeida, Cristine Couto, et al. "In vitro digestibility of commercial whey protein supplements." LWT-Food Science and Technology (2014). 
• AOAC International, and George W. Latimer. Official Methods of analysis of AOAC International. AOAC International, 2012.
• Hsu, H. W., et al. "A multienzyme technique for estimating protein digestibility." Journal of Food Science 42.5 (1977): 1269-1273.
• WHO. "Protein and amino acid requirements in human nutrition." World Health Organization technical report series 935 (2007):

Alanyl-Glutamine or Alanine + Glutamine? Dipeptide or Free Form Aminos? What Offer Maximal Muscle Protection?

"Wouldn't have happened if she'd used alanyl-glutamine instead of regular that cheap alanine + glutamine combo!" - True or False? Recent study says: False!

If you combine your liver's favorite gluconeogenic amino acids, i.e. alanine and glutamine, into a single peptide the result is called alanyl-glutamine and marketed as the ueber-potent alternative to regular l-glutamine supplements. It goes without saying that a comparison like this is about as stupid as comparing french fries with mayo to regular french fries and saying that the former are worse because they contain more fat, or whatever. Even if we didn't care about the physiological significance of the effects of alanyl-glutamine, we would obviously have to compare the purported cryogenic effects of this "innovative" dipeptide to those of a simple combination of free form amino acids to deserve the bragging rights for having created an advanced form of glutamine.

Alanine + glutamine vs. alanyl-glutamine - fight!

By now you are probably asking yourselves why I am bothering you with things like this. Right? Well, the reason is that Éder Ricardo Petry and his colleagues from the University of Sao Paulo must recently have been pondering the same question. To answer it, they conducted an experiment that would allow them to verify if the oral supplementation with l-glutamine and l-alanine as dipeptide has more pronounced muscle protective effects than a simple mixture of l-glutamine and l-alanine (GLN+ALA, both in their free forms) in a group of Wistar rats that are subjected to intense aerobic training (treadmill).

I know what you are thinking now: "Not another rodent study...", but think about it: How many people are willing to pay $50 and more on supplements without any in vivo evidence of their efficacy let alone long-term safety? Against that background Petry's rodent is a major advancement - isn't it?

True or False: You can (ab-)use glutamine to replenish your glycogen stores!? True! It sounds strange, but according to a study from the late 20th century glutamine is a pretty effective glycogen replenisher, even in the absence of your bodies favorite nitrous glucose precursor alanine | learn more

Don't get me wrong, there are a few alanyl-glutamine studies in humans, but there is not a single one that would compare the dipeptide to a reasonable placebo in an exercise scenario. I mean, who tells me that the basketball players in the 2012 study by Hoffman et al. wouldn't have experience the same beneficial effects on basketball skill performance and visual reaction time if their rehydration solution had contained alanine and glutamine or even glutamine alone? Yes, I know... the increased absorption: Well, let's just look at a fair comparison, i.e. the study at hand, and see what happens when the dreams of supplement formulators and reality meet ;-)

Ok, back to the facts - the exercise & supplementation protocol

The male Wistar rats, the researchers used in their experiment were exercised 5x per week - at increasing intensities: Starting with 30 and 45 min of treadmill running (incline 3°) at 20 and 22.5 m/min in the first three weeks, the speed and duration of their treadmill runs increased to 60 min at a speed of 25 m/min in week four and remained like that for the rest of the 8-week study period.

The supplements were administered via oral gavage in the course of the last 3 weeks, only. The daily doses for the animals in the dipeptide (DIP) and free form amino acid groups (GLN+ALA) were...

• 1.5g/kg alanyl-glutamine in the DIP group,
• 0.67g/kg l-alanine + 1.0g/kg l-glutamine in the GLN+ALA group, and
• plain water in the control group

The amount of of alanyl-glutamine the scientists used was calculated in such a way that the total amount of l-glutamine was the same as that of l-glutamine administered in its free form.

Changes? YES! Dipeptide benefits? Not really...

The gavage was provided 1 h after the end of each session of exercise, after which the animals had with free access to water and chow. To make sure that the results of the examinations on the last day of exercise would not reflect the acute effects of a single dose of the supplements, the animals were killed 10 h after the last exercise session.

Figure 1: Plasma glutamine, glutamate, ammonium, malondialdehyde, myoglobin, and creatine kinase activity in Wistar rats supplemented with alanyl-glutamine (DIP) or regular glutamine + alanine; data expressed rel. to control (Petry. 2013)

The virtually identical increases in l-glutamine and l-glutamate, you see in Figure 1 should thus represent the baseline and not the 'immediately post supplementation level' of these amino acids. For the exercise-induced accumulation of ammonium, malondialdehyde (MDA; indicates lower lipid oxidation), myoglobin and creatine kinase (both indicate lower muscle damage) the timing is not that important, anyway. What is important, however, is the fact that there were no physiologically relevant advantages for the "super glutamine".

DHEA & estrogen are alternative muscle protectors. Despite the fact that estrogen has repeatedly been shown to have muscle protective-effects, I would not suggest you steel your granny's HRT medication. DHEA on the other hand, may be something to consider - specifically if you are about to overreach, like the male subjects in a 2012 study by Liao et al. (learn more)

If we take a closer look at the p-values and the statistical significance of these changes, it turns out that, the minor increase in glutamate aside, all of the difference to the placebo group were statistically significant. The DIP vs. GLN+ALA differences, on the other hand, were marginal and reached statistical significance only in the case of the marker of myoglobin. Where the dipeptide has a physiologically probably irrelevant edge of 9% over the GLN + ALA combination.

Figure 2: Glutathione (GSH) and glutathione disulfide (GSSG = used glutathione) levels in soleus and gastrocnemius skeletal muscles of the rodents; data expressed relaitve to control (Petry. 2013)

For the muscular GSH levels, it does not look much different. In this case, there is however not even a statistical difference between alanyl-glutamine and the simple l-alanine + l-glutamine mix - neither for the universal anti-oxidant glutathione (GSH), nor for its "used form" glutathione disulfide (GSSG).

Does that mean that alanyl-glutamine is another supplemental rip-off?I would say that it's too early to use such harsh words. There was after all one statistically, and maybe even physiologically relevant difference between the two groups I didn't mention, yet: The dipeptide group presented with a different heat-shock protein response: They had higher HSP-70 and lower HSF-1 levels in the soleus and lower HSP-70 and lower HSF-1 levels in the gastrocnemius.

"Will training your biceps, heal your heart & protect your brain!?" - a study on the effects of exercise induced HSP increases suggests so | more

In view of the fact that the subsequent "deficit in HSP70 expression" is supposed to "impair recovery from these injuries" Petry et al. are probably right to point out that

"one cannot discard the possibility that part of the beneficial effects of high-intensity exercise training may be due to the enhancement of HSP70 expression which is exacerbated by glutamine supplementation."

In view of the fact that the total amount of proteins from the HSP70 and HSF1 family was increased in both groups, and the differences appear random, it is impossible to tell, whether the slight differences in HSP expression actually matter and whether this is an advantage for alanyl-glutamine or rather for the cheap free form amino acids.

Before future studies provide additional data based on which we can decide whether these differences are relevant and why they differ between slow- (soleus) and fast-twitch (gastrocnemius) skeletal muscle fibers, I'd say that the study at hand would suggest that alanine and glutamine have muscle protective effects irrespective of whether they are bound or not, when you ingest them.

References:

• Cruzat VF, Rogero MM, Tirapegui J. Effects of supplementation with free glutamine and the dipeptide alanyl-glutamine on parameters of muscle damage and inflammation in rats submitted to prolonged exercise. Cell Biochem Funct. 2010 Jan;28(1):24-30. 
• Cruzat VF, Tirapegui J. Effects of oral supplementation with glutamine and alanyl-glutamine on glutamine, glutamate, and glutathione status in trained rats and subjected to long-duration exercise. Nutrition. 2009 Apr;25(4):428-35.
• Hoffman JR, Williams DR, Emerson NS, Hoffman MW, Wells AJ, McVeigh DM, McCormack WP, Mangine GT, Gonzalez AM, Fragala MS. L-alanyl-L-glutamine ingestion maintains performance during a competitive basketball game. J Int Soc Sports Nutr. 2012 Mar 7;9(1):4.
• Petry ER, Cruzat VF, Heck TG, et al. Alanyl-glutamine and glutamine plus alanine supplements improve skeletal redox status in trained rats: Involvement of heat shock protein pathways. Life Sciences. 20 November 2013 [ahead of print]
• Rogero MM, Tirapegui J, Pedrosa RG, Castro IA, Pires IS. Effect of alanyl-glutamine supplementation on plasma and tissue glutamine concentrations in rats submitted to exhaustive exercise. Nutrition. 2006 May;22(5):564-71.

Science Round-Up Seconds - GABA & Exercise: Both Can Improve and Mess With Your Sleep. Plus: Natural GABA Alternatives and Sleep As An Overtraining-Gauge

Don't forget that and prioritize proper sleep hygiene over pills and powders.

Let me make get this straight, yesterday's episode (please note that at the minute I post this article, the download is not yet working, should go up within the next hour, though) of the Science Round-Up on Super Human Radio was not only ultra-long (120min+), it was also largely speculative. If you already listened to the show, you will know that Carl and I took up on a discussion Dan Rollins triggered on his, Carl's and my Facebook page(s). Contrary to what you would expects Dan felt that gamma-Aminobutyric acid aka GABA would not help him calm down and let him sleep. For him GABA turned out to have stimulative rather than sedative effects.

I am not going to repeat all the potential explanations I went through in the first ~40min of the show here. Instead, I'd suggest you simply download the podcast and listen to the various hypothesis which range from (a) the general issue of whether or not GABA even crosses the blood-brain-barrier, over (b) the possibility that the GH spike, the sedative (low blood glucose) and the agitating effect (catecholamine + cortisol release with very low blood glucose) could all be brought about by a GABA induced increase in insulin production and a corresponding reduction in blood glucose levels to (c) potential confounding factors such as caffeine consumption (Roca. 1988; Desaulles. 1991; Mukhopadhyay. 1995), interactions with beta alanine, taurine or glycine (Tiedje. 2010; El Idrissi. 2013; Kletke. 2013), (d) genetic differences as with the tingling for beta alanine (Macphee. 2013) or (e) the influence of exercise on the density of GABA receptors in the brain (Dishman. 1990).

Enough of the speculations: What are proven alternatives

Against the background that we still don't really know why Dan and others don't seem to benefit from GABA supplementation the way Carl and Alisa do, we do know that there are other natural alternatives:

• Valerian [dosage: 400-900mg] - inhibits breakdown of GABA in the brain; assuming that GABA makes it across the blood-brain-barrier, valerian would thus work synergistically with oral GABA 

• 

  Due to its anti-PPAR-gamma effect ginseng also made it into the list of "agents that may help you to stay lean" I posted earlier this year. Want to know about the other "20 Anti-Obesity Agents Have the Potential to Inhibit Fat Gain Right at the Cellular Level"? Here you go!

  Ginseng [1-2g crude root extract or 200-600mg of extract] - ginsenoids compete with GABA on both the GABA-A & GABA-B receptor and are thus thought to exert their calming (only in low! doses) effects on the CNS via direct GABA-ergic effects; sedative effects have been observed for Panax ginseng (Korean or Asian ginseng), Panax quinquefolius (American ginseng), and Panax vietnamensis (Vietnamese ginseng); if you feel agitated, reduce the dosage
• Kava kava [180-210mg of kava lactones] - the active agents in Kava kava belong to a group of resinous compounds known as kava lactones or kava pyrones, they bind to the benzodiazepine binding site of the GABA receptor, which could reduce the risk of unwanted excitatory effects
• Passion flower (Passiflora incarnata) [4-8g as a tea] - has been used as a sleeping aid for centuries; chrysin, a mild anti-estrogen appears to be the active ingredient (GABA-A binding; cf. Zhai. 2008); warning: must not be consumed by pregnant women (!) PI can initiate uterine contractions

• 

  I know you don't want to hear that, but(!) don't forget that it could also be your BCAA product that keeps you you from falling asleep and makes you wake up several times during the night by blocking the uptake of tryptophan and thus depleting your brain of the raw material for serotonin (read more).

  Hops (Humulus lupus) [0.5g of dried herb] - has binding affinities to both the melatonin and serotonine receptor (Abourashed. 2004) and can increase GABA in the brain (Franco. 2012); warning: must not be consumed by women with a (family) history of breast cancer (!) hobs has mild, but distinct pro-estrogenic activity (Hajirahimkhan. 2013)
• L-tryptophan [1g] / 5-HTP [100mg] - both will increase serotonin and could thus be stacked with agents that act on GABA; incidentally, there is paucity of research on the efficacy of either of the two as sleep aid
• Melatonin [1-10mg] - as both Carl and I pointed out on the show, melatonin is not an acute sedative, but a signal that it's time to "shut down", don't expect it to actively "send you into sleep", like a sleeping pill

Aside from these agents, Carl and I talked about accupuncture and low energy emission therapy (LEET), as well. While the mechanisms of the former are still not fully understood (e.g. Kwok. 2013), the amplitude modulated high frequency fields the LEET mouthpiece emits right into your brain have been shown to modify the release of GABA and the concentration of benzodiazepine receptors in the rat brain. In addition, low level electromagnetic fields can directly induce the release of melatonin in mammals (Reiter. 1993).

If you are sprinting because of the increase in EPOC, you are a fool.

Read more about exercise and energy expenditure tomorrow! With the info on energy expenditure also crammed into this article it would have been too packed. Therefore you will have to live with a 24h deleay until you learn about the energetic costs of bench pressing, the laughable EPOC effects of HIIT and the evidence that exercise does not just make you hungry. If you feel that's not tolerable, you can already learn about the pathetic EPOC effects of HIIT and exercise & hunger in previous articles.

I already hinted at the physiological (side?) effects of chronic endurance training on the expression of the GABA receptors in rodent brains early in the show (and this article). It should thus not surprise you that exercise can have major impacts on the onset, quality and duration of your sleep - both positive and negative ones, obviously [based on data from Youngstedt (1997; published online 2003)]:

• 

  "90 Min Sleep Restriction Changes in Insulin Resistance Last For One Week"

  Timing of your workouts: While working out 4-8h before bed will have you fall asleep easily, you may experience problems if you have to ignore the onset of tiredness, because you have been exercising more than 8h before you go to bed or to close to hitting the hay. Incidentally, working out 4-8h before bed another advantage: It will help you to sleep through.
• Working out outdoors: The light exposure, the fresh air all that makes working out outdoors so healthy for you (as long as you are not living in Beijing ;-) will energize you and could keep you from falling asleep.
• Duration of your workout: There is a U-shaped dose-response curve for the negative effects of working out on your REM sleep. As Carl rightly pointed out during the show the negative effects of short exercise durations (<1h) is probably in as much a question of intensity / exhaustion (you train intense, when you train short) as the cumulative effects of "exercising" for more than 2h straight (which is by the way more than twice as detrimental for your sleep quality than the <1h exercise)
  
  Aside from its effect on the workout duration will also affect your overall sleep needs with both exercises in the 1-2h and exercises in the >2h range having a major impact on the amount of time you got to spend in bed to recover.
• Exercise intensity*: With a high propensity of low intensity exercise to help you sleep through, a walk on a treadmill in the evening is not going to compromise a good nights sleep, the HIIT workout that would improve your postprandial triglyceride response on the next day (I used this SuppVersity Facebook News as a discussion starter in the live-show), on the other hand may have you wake up several times during the night (*note: I used the studies on the post-exercise heat load in Youngstedt et al. as a proxy for intensity).

If you wanted to distill some practical advice on how you can / should exercise to avoid that your workouts will interfere with your sleep, you should (a) leave at least 4h between any intense workout and hitting the hay (HIIT, weight lifting, etc.) and (b) make use of the beneficial effects of moderate duration (20-40min) light intensity workouts (walking on an incline treadmill, cycling etc.) on sleep onset and quality.

Did you know that...

there are other agents that can "spike" GH temporarily?

• intravenous (iv) insulin 0.2 IU/kg - 50x increase
• intramuscular (im) glucagon 1 mg - 21x incr.
• iv. arginine 20 g/m² as an infusion over 30 minutes - 11x incr.

All observed in a human study involving 18 perfectly healthy young men(Rahim. 1996).

In view of the effect GABA has on the release of insulin from the pancreas, it is not unlikely that my previously voiced hypothesis that the "relaxation" and the "agitation" are responses to low and very low glucose levels would also explain the increase in GH as a response to the hypoglycemic effects of insulin.

What can you take away from the first part of this installment of the Science Round-Up Seconds?

• GABA does not work for everyone
• esp. in higher doses GABA can have excitatory, instead of calming effects
• the exact reasons that this happens is not clear; temporary hypogylcemia is albeit not the least likely candidate
• the hypoglycemia would also explain the GH release which is yet very unlikely to have beneficial effects on muscle growth (GH & gains don't correlate) or fat loss
• among the GABA alternatives, those with a specificity for the benzo docking site on the GABA receptor could work for people for whom GABA itself is excitatory
• working out too late / too intense can compromise sleep
• being "tired but wired" indicates sympathetic overtraining (too much intensity)
• constant fatigue + an increased sleep demand, but light and ineffective sleep is more indicative  parasympathetic overtraining (too much volume)

References:

• Abourashed EA, Koetter U, Brattström A. In vitro binding experiments with a Valerian, hops and their fixed combination extract (Ze91019) to selected central nervous system receptors. Phytomedicine. 2004 Nov;11(7-8):633-8.
• Desaulles E, Boux O, Feltz P. Caffeine-induced Ca2+ release inhibits GABAA responsiveness in rat identified native primary afferents. Eur J Pharmacol. 1991 Oct 2;203(1):137-40. 
• Dishman RK, Dunn AL, Youngstedt SD, Davis JM, Burgess ML, Wilson SP, Wilson MA. Increased open field locomotion and decreased striatal GABAA binding after activity wheel running. Physiol Behav. 1996 Sep;60(3):699-705.
• El Idrissi A, Shen CH, L'amoreaux WJ. Neuroprotective role of taurine during aging. Amino Acids. 2013 Oct;45(4):735-50. doi: 10.1007/s00726-013-1544-7. Epub 2013 Aug 21.
• Kletke O, Gisselmann G, May A, Hatt H, A Sergeeva O. Partial agonism of taurine at gamma-containing native and recombinant GABAA receptors. PLoS One. 2013 Apr 30;8(4):e61733.
• Kwok T, Leung PC, Wing YK, Ip I, Wong B, Ho DW, Wong WM, Ho F. The effectiveness of acupuncture on the sleep quality of elderly with dementia: a within-subjects trial. Clin Interv Aging. 2013;8:923-9.
• Macphee S, Weaver IN, Weaver DF. An Evaluation of Interindividual Responses to the Orally Administered Neurotransmitter β -Alanine. J Amino Acids. 2013;2013:429847.
• Mukhopadhyay S, Poddar MK. Caffeine-induced locomotor activity: possible involvement of GABAergic-dopaminergic-adenosinergic interaction. Neurochem Res. 1995 Jan;20(1):39-44.
• Rahim A, Toogood AA, Shalet SM. The assessment of growth hormone status in normal young adult males using a variety of provocative agents. Clin Endocrinol (Oxf). 1996 Nov;45(5):557-62.
• Reiter RJ. Electromagnetic fields and melatonin production. Biomed Pharmacother. 1993;47(10):439-44.
• Roca DJ, Schiller GD, Farb DH. Chronic caffeine or theophylline exposure reduces gamma-aminobutyric acid/benzodiazepine receptor site interactions. Mol Pharmacol. 1988 May;33(5):481-5.
• Tiedje KE, Stevens K, Barnes S, Weaver DF. Beta-alanine as a small molecule neurotransmitter. Neurochem Int. 2010 Oct;57(3):177-88.
• Youngstedt SD, O'Connor PJ, Dishman RK. The effects of acute exercise on sleep: a quantitative synthesis. Sleep. 1997 Mar;20(3):203-14.
• Zhai K, Hu L, Chen J, Fu CY, Chen Q. Chrysin induces hyperalgesia via the GABAA receptor in mice. Planta Med. 2008 Aug;74(10):1229-34.

L-Ornithine an Anti-Stress Agent: Lower Cortisol, Higher DHEA, Better Sleep W/ Only 400mg of Ornithine Pre-Bed. Plus: Mini-Review of Add. Benefits - Burns, Gut Health, etc.

Stressed? Maybe ornithine can help. Or is this study just a hoax!?

Sounds like marketing shenanigan, right? "Lower Cortisol, Higher DHEA, Better Sleep W/ Only 400mg of Ornithine Pre-Bed." Ok, if it was marketing it would probably say "with only 5g of ornithine." I mean, 400mg that's not enough to generate significant revenues - is it?

But before we get to the marketing side of things, let's first look at the science, researchers from the Research Laboratories for Health Science & Food Technologies present in a recent paper in the Nutrition Journal, an open-access journal which charges scientists a certain fee for processing their papers.

You can learn more about sleep and the circadian rhythm at the SuppVersity

Sunlight, Bluelight, Backlight and Your Clock

Sunlight a La Carte: "Hack" Your Rhythm

Breaking the Fast to Synchronize the Clock

Fasting (Re-)Sets the Peripheral Clock

Vitamin A & Caffeine Set the Clock

Pre-Workout Supps Could Ruin Your Sleep

In their 8 week study, Mika Miyake et al. provided fifty-two apparently healthy Japanese adults who had previously felt slightly stressed and fatigue with either L-ornithine (400 mg/day) or placebo capsules.

The participants were advised to take one (400mg) capsule everyday before going to bed for eight weeks. At the end of the study period, all participants arrived at the laboratory fasted for blood sampling and a handful of other tests.

Figure 1: Effect of L-ornithine supplementation on serum stress markers.Means of the change from 0 weeks of each stress marker level (A, DHEA-S; B, cortisol; C, cortisol/DHEA-S) to 2, 4, and 8 weeks: mean ± SE. White circles (○) indicate the placebo and black circles (●) indicate L-ornithine. (Miyake. 2014)

The blood was analyzed for serum cortisol and DHEAS levels. In addition, the perceived mood and quality of sleep were measured by the Profile of Mood States (POMS) tests, the Athens Insomnia Scale (AIS), and Ogri-Shirakawa-Azumi sleep inventory MA version (OSA-MA).

Figure 2: Effect of L-ornithine supplementation on OSA.Means of the change from 0 weeks of each OSA score (A, sleepiness on rising; B, initiation and maintenance of sleep; C, frequent dreaming; D, refreshing; E, sleep length) to 1, 2, 3, 4, 5, 6, 7 and 8 weeks: mean ± SE. White circles (○) indicate the placebo and black circles (●) indicate L-ornithine

Significant changes were observed for serum cortisol levels and the cortisol/DHEA-S ratio. Both were significantly decreased in the L-ornithine group in comparison with the placebo group. The POMS and OSA-MA tests (not shown in Figure 1) revealed that similar beneficial effects occurred for anger (sign. reduced) and perceived sleep quality, which were both improved in the L-ornithine group compared to the placebo group.

Is there anything else ornithine is good for? Sugino et al. report that l-ornithine supplementation (2-6g/day) attenuates physical fatigue in healthy volunteers by modulating lipid and amino acid metabolism (2008). It enhances wound healing in mice and man (Shi. 2002; Coudray-Lucas. 2000). It improves muscle protein synthesis after surgery (Wernerman. 1987). Just like arginine, it holds the potential to improve gut health (Cynober. 1994; de Oca. 1997; Raul. 1995). But it is, unlike arginine, is no insulin secretagogue (=won't trigger an insulin release; Bucci. 1992) - Bottom line: Lots of potential, but nothing that would make it a "must have" supplement.

Quite impressive results, considering the fact that we are talking about a minimal amount of an amino acids fitness enthusiasts know mainly as an ineffective growth hormone booster (Lambert. 1993). What did you say? "Bias"? Well, the product used in the study is produced by the Kyowa Hakko Bio Company a company that is an affiliate of Kirin Company Limited, to which the authors belong, but that does not mean that the results are inaccurate.

Nevertheless, I would advise you to keep it in mind before you buy a 5kg bag of ornithine as an anti-stress treatment for the next 10 years - maybe 25g for an 8-week test-run are a better idea. Not necessarily because of a potential bisa, but rather in view of the small number of study participants  and the fact that we don't know exactly the mechanism that triggers the increase in DHEA, decrease in cortisol and overall anti-stress effect.

Even in animal models, where similar effects on the HPTA have been observed (Kurata. 2012), it is not clear, whether all this may in fact be a result of the  influence L-ornithine has on the urea cycle (converts ammonia to urea in the liver), as some scientists apparently believe. Overall, we are thus dealing with an interesting finding, but one that needs independent confirmation from a larger trials, and one I would have significantly more faith in if I know exactly how it came about (mechanistically) | Comment on Facebook!

References:

• Bucci, L. R., et al. "Ornithine supplementation and insulin release in bodybuilders." International journal of sport nutrition 2.3 (1992): 287-291. 
• Coudray-Lucas, Colette, et al. "Ornithine [alpha]-ketoglutarate improves wound healing in severe burn patients: A prospective randomized double-blind trial versus isonitrogenous controls." Critical care medicine 28.6 (2000): 1772-1776.
• Cynober, L. "Can arginine and ornithine support gut functions?." Gut 35.1 Suppl (1994): S42-S45.
• de Oca, Javier, et al. "Effect Of Oral Supplementation Of Ornithine-[Alpha]-Ketoglutarate On The Intestinal Barrier After Orthotopic Small Bowel Transplantation." Transplantation 63.5 (1997): 636-639.
• Kurata, Koji, et al. "Orally administered l-ornithine reduces restraint stress-induced activation of the hypothalamic-pituitary-adrenal axis in mice." Neuroscience letters 506.2 (2012): 287-291.
• Lambert, M. I., et al. "Failure of commercial oral amino acid supplements to increase serum growth hormone concentrations in male body-builders." International Journal of Sport Nutrition 3.3 (1993): 298-305.
• Miyake, Mika, et al. "Randomised controlled trial of the effects of L-ornithine on stress markers and sleep quality in healthy workers." Nutrition Journal 13.1 (2014): 53.
• Raul, Francis, et al. "Functional and metabolic changes in intestinal mucosa of rats after enteral administration of ornithine α-ketoglutarate salt." Journal of Parenteral and Enteral Nutrition 19.2 (1995): 145-150.
• Shi, Han Ping, et al. "Effect of supplemental ornithine on wound healing." Journal of Surgical Research 106.2 (2002): 299-302.
• Sugino, Tomohiro, et al. "L-ornithine supplementation attenuates physical fatigue in healthy volunteers by modulating lipid and amino acid metabolism." Nutrition research 28.11 (2008): 738-743.
• Wernerman, J., et al. "Ornithine-alpha-ketoglutarate improves skeletal muscle protein synthesis as assessed by ribosome analysis and nitrogen use after surgery." Annals of surgery 206.5 (1987): 674.

The Satiating Secret of Arginine, Lysine and Glutamic Acid. Plus: Things You May Not Know About These Aminos

No, no and no. No amino acids = no satiety = no weight loss.

Personally, I have never been interested in products that would increase satiety. Being a born masochist, at least, when it comes to cutting body fat, I always liked being hungry... well, at least until I had to learn that there is an intricate hormonal connection between "being hungry" and the diet-induced reduction in metabolic rate, hormonal production etc. That changed my whole perspective on agents that increase satiety completely, and I started to read read papers like the one Jordi et al. are about to publish in one of the upcoming issues of the Journal of Physiology (Jordi. 2013).

The satiety shoot-out

According to the researchers from the University of Zurich, the top-dogs, or rather the most satiating among the so-called proteogenic amino acids, which are ...

• L-Leucine (Leu / L)
• L-Lysine (Lys / K)
• L-Methionine (Met / M)
• L-Phenylalanine (Phe / F)
• L-Proline (Pro / P)
• L-Serine (Ser / S)
• L-Threonine (Thr / T)
• L-Tryptophan (Trp / W)
• L-Tyrosine (Tyr / Y)
• L-Valine (Val / V)

• L-Alanine (Ala / A)
• L-Arginine (Arg / R)
• L-Asparagine (Asn / N)
• L-Aspartic acid (Asp / D)
• L-Cysteine (Cys / C)
• L-Glutamic acid (Glu / E)
• L-Glutamine (Gln / Q)
• Glycine (Gly / G)
• L-Histidine (His / H)
• L-Isoleucine (Ile / I)

... are L-arginine (Arg), L-lysine (Lys) and L-glutamic acid (Glu). The Swiss scientists were able to demonstrate that these three amino acids induced neuronal activity in the area postrema and the nucleus of the solitary tract. That sounds funky, but non-significant, right? Well, it wouldn't be, as long as you did not take into consideration that we know from previous studies that these brain regions are responsible for the regulation of energy intake - specifically our appetite for more.

Additional info: Just to complete the list, I want to add a non-proteogenic amino acid (an amino acid that is not used by the body to "build" proteins) with profound satiety effects. One you actually have heard about several times in the past weeks: Taurine! In 2012 Solon et al. published a study that shows quite conclusively that taurine, once it crosses the blood brain barrier, will reduces food intake, but also locomotor activity in rodents (Solon. 2012). As the scientists point out, These effects are accompanied by the modulation of expression of the "satiety hormone" NPY.

L-arginine has research to support its use as anti-diabetic weight-loss adjuvants (learn more); and the results of the study at hand suggest that its benefits may be mediated by its effects on the brain & gut.

From a "what are the downstream effects on my metabolism"-perspective, however, it may in fact be even more important that the amino acids also provoked an increase in gastric distension by differentially altering gastric secretion and/or emptying. After all, ...

"[...] these peripheral mechanical vagal stimuli were dissociated from the amino acids' effect on food intake. [So that it is prudent to assume that] Arg, Lys and Glu had a selective impact on food processing and intake suggesting them as direct sensory input to assess dietary protein content and quality in vivo. " (Jordi. 2013; my emphasis)

In other words: L-arginine, L-lysine and L-glutamic acid are not simply going to reduce your cravings they will also tell your body: Hey there's some good quality protein coming in.

---

Hold on! Where are the proven benefits? I have to admit all that sounds as if it would be of questionable relevance but any SuppVersity reader for whom this is not the first visit to this webpage will probably have read about the surprisingly profound weight loss benefits of L-arginine, which have only recently been tracked down to its interactions with the GLP-1 one of the so-called satiety proteins with far-reaching downstream effects on glucose and fatty acid metabolism (learn more about the fat burning prowess of L-arginine).

As far as glutamic acid is concerned, it may be worth mentioning that Freiberg et al. reported more than 20 years ago that certain glutamic acid derivates can act directly on the cholecystokinin receptor, which is - along the the PYY receptor one of the major "You are full! Now stop eating"-switches of the mammalian body (Freiberg. 1990).

Figure 1: AUC in response to ingestion of 25g of glucose or water w/ or w/out 150mg/kg lysine (Kalogeropoulou. 2009)

Similarly unknown as the involvement of glutamic acid in the concert of satiety hormones is the effect lysine (150mg/kg) had on the glucose, insulin and glucagon resonse of healthy volunteers, when Kalogeropoulou et al. administered it either alone or in conjunction with 25g of glucose to thirteen healthy volunteers, where it triggered an increase in glucagon and insulin, when it was administered alone and significant reduction in the blood sugar response, when it was administered in conjunction with the 25g of glucose (Kalogeropoulou. 2009). Interestingly the increased glucsose disposal did not depend on an increase in insulin, so that it must be related to downstream improvements in insulin sensitivity and the efficacy of glucose uptake.


References:

• Freidinger RM, Whitter WL, Gould NP, Holloway MK, Chang RS, Lotti VJ. Novel glutamic acid derived cholecystokinin receptor ligands. J Med Chem. 1990 Feb;33(2):591-5.
• Kalogeropoulou D, LaFave L, Schweim K, Gannon MC, Nuttall FQ. Lysine ingestion
  markedly attenuates the glucose response to ingested glucose without a change in
  insulin response. Am J Clin Nutr. 2009 Aug;90(2):314-20.
• Jordi J, Herzog B, Camargo SM, Boyle CN, Lutz TA, Verrey F. Specific Amino Acids Inhibit Food Intake via the Area Postrema or Vagal Afferents. J Physiol. 2013 Jul 29. [Epub ahead of print] 
• Solon CS, Franci D, Ignacio-Souza LM, Romanatto T, Roman EA, Arruda AP, Morari J, Torsoni AS, Carneiro EM, Velloso LA. Taurine enhances the anorexigenic effects of insulin in the hypothalamus of rats. Amino Acids. 2012 Jun;42(6):2403-10.

High and Low Dose BCAA Supplementation Have Minimal, Non-Significant Effects on Markers of Muscle Damage 24h and 48h Post Heavy Resistance Training

Image 1: Cover of the September issue of the International Journal of Wrestling Science - don't tell me you don't have a subscription, yet!

I don't know about you, but I feel that it's quite interesting to look at the highly heterogeneous dosage suggestions on the labels of the ever-increasing number of BCAA supplements on the market. Interestingly, almost every producer claims in his "non FDA-approved" statements that his supplement contains "scientifically supported" or "clinically validated" amounts of branch-chained amino acids in the "optimal" (whatever that may be) ratio of 2:1:1, 3:1:1, 4:1:1, 8:1:1, ... and all the other variations that appear to be limited only by the patent applications and lawyers of the financially more potent players in the business. From a scientific perspective, however, this "optimal" amount has still to be elucidated - at least to my knowledge, no respectable scientist has yet claimed to have found the "optimal" amount and composition of free form amino acids for a given subgroup of athletes, let alone strength athletes, bodybuilders or figure competitors, in general.

At this point I would like to add that no respectable scientist would ever dare to make the claim that he or she has found the "optimal free form amino acid supplement" for all, or even a significantly large group of athletes, unless he or she would be interested in losing his reputation as a "respectable scientist" ;-)

In a recently published study scientists from the Department of Physical education and Sports Science University of Tabriz in Tabriz, Iran, set out to establish whether there is at least a significant difference between the effects of ~15g (210mg/kg) or 33g (450mg/kg) of branched chain-amino acids taken before and after the completion of an intense resistance training regimen comprised of 7 exercises à 3 sets of 10 repetitions (Amirsasan. 2011). Yet, despite the fact, that even the "low dose" of 15g of BCAAs (in the customary 2:1:1 ratio, i.e. 7.5g of leucine + 3.75g of iso-leucine + 3.7g of valine) was about 1.5x higher than what I have seen as "suggested dosing" or "serving size" on very high-dosed commercial supplements, the effects of this amino acid overkill were "sobering", to say the least.

Figure 1: Effects of "low" (210mg/kg) and "high" (450mg/kg) dose BCAA supplement on enzymatic markers of muscle damage relative to pre-values in the placebo group (data calculated based on Amirsasan. 2011)

As the data in figure 1 goes to show both the "low" as well as the "high" (or should I say "overkill" ;-) dose of pre- and post-workout BCAAs had only marginal, and certainly statistically non-significant effects on creatine kinase (overall - CK; muscle specific - CK MB) and lactate dehydrogenase activity, both established indicators of (exercise-induced) muscle damage.

Comparison of results between groups in mean and amplitude changes of serum indexes of cell damage (CK-LDH-CKMB), 24 and 48 hours after the exercise performance showed no significant difference between the 3 groups. In other words, different amounts of BCAA did not significantly affect the serum cell injury indexes (CK-LDH-CKMB), 24 and 48 hours after the heavy resistance activity.

These results are interesting, because they contradict previous findings by Sharp et al. who reported "significantly reduced" creatine kinase levels with BCAA supplementation in likewise previously strength-trained athletes on a similarly intense (8 exercises; 3x 6-8 repetitions) resistance training protocol (Sharp. 2010), as well as the results of studies in endurance athletes and previously untrained subjects, where the provision of BCAAs decreased creatine kinase and lactate dehydrogenase enzyme expression, across-the-board (Greer. 2007; Koba. 2007; Matsumoto. 2009).

"To supplement or not?" This question may arise if you have a look at the data from this study. Thor, in a comment to this posts poses the question whether his "personal experience" that "having the fast digesting aminos seemed to increase [his] ability to have a more successful work out" is, after all "only in [his] head" and while I cannot say for sure how much of it may be the result a placebo-effect in his case, I can provide you with the results of a 2011 study by Greer et al. who found no increases in exercise performance despite reduced perceived rates of exertion with BCAA supplementation after a 90-minute cycling bout (Greer. 2011). These results seem to confirm the "central fatigue hypothesis" according to which BCAAs exert their beneficial effects agains (perceived) fatigue via modulation of the availability of the serotonin precursor tryptophan. In a 2007 review of the literature, Meeusen and Watson do yet conclude that the "nutritional manipulation of these systems [neurotransmitter] through the provision of amino acids has proven largely unsuccessful" (Meeusen. 2007)... All that does not take away from the established beneficial effects of chronic low-dose BCAA (in particular, leucine) supplementation on endurance performance and strength adaptations to exercise (e.g. Crowe. 2006; Matsumoto. 2009). In the respective studies, dosages in the 1.5-3.0g/day range have yet been sufficient, to elicit these beneficial effects - and that in subject groups that are not particularly well-known for their exorbitantly high protein intakes ;-)

Image 2: When bought in bulk and without the addition of a ton of fancy extras BCAAs have become reasonably priced - whether they are a "necessary" part of your supplement regimen may yet depend on your dietary protein intake.

Probably - this would at least be my first guess - the outcome of these studies was not so much affected by the actual study protocol, but rather by the habitual dietary protein intake of their subjects. With endurance athletes (Koba. 2007; Matsumoto. 2009),  recreationally active (Sharp. 2010) and untrained (Greer. 2007) we usually see much lower dietary protein intake than with professional wrestlers, which prompts me to repeat my previously stated skepticism towards the usefulness of large boluses of additional free form amino acids in a group of athletes whose habitual dietary protein intake is way beyond the 1.5g/kg level, anyway... but hey, that's just the opinion of a brainy physicist; so if your brawny guru says you need those 150g of BCAAs on top of your 5x50g whey protein shakes and your 3 pound of lean meat - go for it!