Is Beta Alanine a Dangerous Neurotoxin? Or is the Latest Research Fearmongering Anti-Supplement Propaganda?

Could beta alanine "tingle down" your neuronal circuits? (img health.yahoo.com)

You wouldn't be taking a dietary supplement that does not have any studies about potential side effects, would you? ... I guess, most of you will answer this question with "No, never", or "no, I wouldn't" and will thus be pretty surprised to hear that their periworkout nutrition contains an "untested", brain-active compound with a highly familiar name: Beta-Alanine! Maybe some of you may be remembering an earlier post of mine about the hypothetical side effects the popular ergogenic could on your heart (see "Beta Alanine Suffocates Cardiomyocytes"; read more), but since I - or rather no scientists - has followed up on the notion that this widely used dietary supplement could turn out to be a wolf in sheep's clothing, even those of you who have read the respective post will probably have forgotten about it by now.

Even researchers still doubt the safety of creatine, why don't they care about beta alanine?

The absence of adequate data on its safety was also the main reason for Tanise Gemelli and her colleagues from the Universidade Federal do Rio Grande do Sul in Brazil to test whether the beta amino acid, of which the scientists emphasize that "studies about side-effects, especially brain effects in humans were not been performed" (Gemelli. 2013), is even save for human consumption.

Beta alanine, taurine and the liver - Or why the notion that chronic high dose beta alanine supplemenation may have side effects is not totally new: Taurine depletion in the liver (and other tissue) and subsequently increased susceptibility to oxidative damage by natural and exogenous pro-oxidant assaults are by no means a novel finding. In 1993, for example, Waterfield et al. were able to show that the depletion of the hepatic taurine stores due to the inhibitory effects of beta alanine on taurine uptake, increases the susceptibility of the liver to carbon tetrachloride toxicity (Waterfield. 1999; learn more about taurine).

As common practice dictates, studies into the potential side effects of drugs, supplements, herbs etc. always start with a rodent model. That may sound pathetic in the case of a substance that's being used by 100,000s of people on a daily basis, but would it would still be unethical to test a given substance, in this case beta alanine, on human subjects, if you assume that it may - in sufficiently high doses - induce similar neurological dysfunction as they've been observed in  patients with b-alaninemia, an inborn error of metabolism, in which high concentration of beta alanine accumulate, inhibit GABA uptake by competing for transporters GAT-3 and GAT-4 and cause clinical pathologies such as neurological abnormalities, even in the absence of an exogenous supply of the scarce amino acid (Gibson. 2001; Tiedje. 2010).

To elucidate whether similar neurological side effects would occur upon high dose supplementation in rodents, the Brazilian scientists administered three subsequent intraperitoneal injections (simulates oral ingestion; the injections are used solely to avoid that the animals regurgitate the substance) of 0.3 mg /g of body weight beta alanine on two different groups of Wistar rats in order to determin the oxidative stress parameters and kinase activities in their brains 60min after the amino acid made it into through their digestive tract (the use of two sets of rats was necessary, because "the buffer for brain  homogenization used for the determination of the oxidative stress parameters is different from that used for the determination of kinases activities"; Gemelli. 2013).

Figure 1: Markers of oxidative stress (DCF, sulfylhydryls, CAT, SOD; left) and levels of kinase activity (PK, AK, Cy-CK, Mi-CK; right) expressed relative to untreated control (Gemelli. 2013)

Despite the fact that a brief glimpse at the data in figure 1 will reveal that this loading protocol, which would be roughly equivalent to the ingestion of 3x3-4g of beta alanine in an average human being, will suffice to see that the increases in the serum and brain levels of the beta amino acid did yield the expected changes of all tested parameters the interpretations of these changes are not totally straight forward.

So what to the results tell us?

Creatine kinase (CK), pyruvate kinase (PK), and adenylate kinase (AK) are all thiol-containing enzymes that are involved in the phosphoryltransfer network, which is critical for an optimally functioning energy metabolism in almost all mammalian tissues. PK, in particular, is of paramount importance for optimal glucose metabolism and thus the provision of energy to the brain. It's under- and overexpression in the cerebral cortex, which plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness and the cerebellum, which is likewise involved in cognitive functions, regulates fear and pleasure responses and controls movement-related functions, respectively, could thus have significant negative effects on your physical and psychological health and behavior.

Does beta alanine hamper instead of improve your sprinting performance? The results are conflicting, but in a study from March 2013, the coingestion of BA and baking soda thwarted the ergogenic benefits of the latter (learn more)

"We observed that b-alanine administration inhibited the PK activity in cerebral cortex homogenates from rats. This same effect was observed in other amino acids administration, such as phenylalanine, where chronically induced hyperphenylalaninemia reduces PK activity in brain cortex of treated rats (Feksa. 2002). Pyruvate is an antioxidant (Das. 2005) and provides substrate for ATP synthesis in mitochondria (Yapicioglu. 2004). The diminution of PK activity is possibly caused by alteration of the crucial sulfhydryl groups of the enzyme, but it cannot be ruled out that may be caused by down-regulation of expression or damage to existing proteins." (Gemelli. 2013)

With the opposing effect in the cerebellum, the latter, i.e. the potential brain damage, remains yet just that - a potential consequence. In a similar vein, the dysregulation of CK and AK, which are likewise crucially involved in the brain energy metabolism and should actually act antagonistically, with the elevation of one of the two leading to a decrement in the other, does not necessary signal protein damage, but is an unquestionable sign that the administration of relatively high, but by no mean unrealistic dosages of beta alanine is able to disturb the normal enzymatic regulatory cycle of the brain - at least in rodents, I should add. It is nevertheless hard to debate that the..

"[i]mpairment of energy homeostasis and reduction of antioxidant defenses could [my empahsis] provoke oxidative stress with consequent apoptosis and brain cells death (Burlacu . 2001; Park. 2005). Considering that PK is also inhibited by b-alanine administration, the diminished activity of PK and AK, and possibly of other thiol-containing enzymes, might suggest a decreased ATP content with abnormal phosphoryltransfer network." (Gemelli. 2013) 

Moreover, the concomittant increase in Cy-CK activity corroborates the notion that the skewed energy supply leads to an increase in reactive oxygen species (ROS) in the cerebellum, with the differential reaction in the different parts of the brain being a result of the heterogeneous "sensitivity of [different brain] regions in response to exposures associated with oxidative stress" (Gemelli. 2013).

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On a side note: It is of paramount importance to distinguish between beta alanine and the histidine + beta alanine peptide carnosine. Higher concentrations of the latter have been shown to have protective effects against oxidative stress in the brain. The problem is thus "beta alanine specific" and could probably be reduced / maybe even be totally negligible if you stick to lower amounts of slow-release beta alanine which would avoid spikes of the potentially neuro-toxic amino acid and allow sufficient time for it to be bonded with histidine to form carnosine.

Bottom line: Despite the fact that the results are only preliminary and the differential accumulation of the potentially toxic chemicals and/or metabolite(s) in various regions of the brain that was accompaied by a modulation of metabolic and detoxification enzymes in the brains of the lab animals must not necessarily be accompanied by cellular damage. It could, as the scientists point out, impair the phosphoryltransfer network and reduce creatine and pyruvate content. This in turn could establish a vicious circle, in which "the diminution of antioxidant defenses increases kinases inhibition which decreases pyruvate and creatine content, and so on" (Gemelli. 2013) Needless to say that this would be hardly worth the highly exercise specific +2.85% increase in performance, Hobson et al. report in response to the chronic administration of beta alanine in a comprehensive meta analysis from 2012 that's too willingly hushed up by the majority of the supplement producer and the magazines that live off their advertisment money (Hobson. 2012).

Despite the fact that I never hid the fact that I am not a fan of beta alanine (also because I never noticed anything but tingles from using is), I would be hesitant to say that it would be wise to refrain from using respective supplements in the future altogether. What you may yet want to reconsider (at least until the whole issue is further investigated) is the use of large boluses of beta alanine on an empty stomach - according to previously conducted studies, that's nonsensical, anyway (Hobson. 2012; Stegens. 2013).


References:

• Feksa LR, Cornelio AR, Rech VC, Dutra-Filho CS, Wyse AT, Wajner M, Wannmacher CM. Alanine prevents the reduction of pyruvate kinase activity in brain cortex of rats subjected to chemically induced hyperphenylalaninemia. Neurochem Res. 2002 Sep;27(9):947-52.
• Burlacu A, Jinga V, Gafencu AV, Simionescu M. Severity of oxidative stress generates different mechanisms of endothelial cell death. Cell Tissue Res. 2001 Dec;306(3):409-16. 
• Das UN. Pyruvate is an endogenous anti-inflammatory and anti-oxidant molecule. Med Sci Monit. 2006 May;12(5):RA79-84.
• Gemelli T, de Andrade RB, Rojas DB, Bonorino NF, Mazzola PN, Tortorelli LS, Funchal C, Filho CS, Wannmacher CM. Effects of β-alanine administration on selected parameters of oxidative stress and phosphoryltransfer network in cerebral cortex and cerebellum of rats. Mol Cell Biochem. 2013 Apr 26.
• Gibson MK, Jakobs C. Disorders of b-and c-animo acids in free and peptide-linked forms. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds). The metabolic and molecular bases of inher-ited disease, 8th edn. McGraw Hill, New York,2001; pp 2079–2105.
• Hobson RM, Saunders B, Ball G, Harris RC, Sale C. Effects of β-alanine supplementation on exercise performance: a meta-analysis. Amino Acids. 2012 Jul;43(1):25-37. 
• Stegen S, Blancquaert L, Everaert I, Bex T, Taes Y, Calders P, Achten E, Derave W. Meal and Beta-Alanine Coingestion Enhances Muscle Carnosine Loading. Med Sci Sports Exerc. 2013 Mar 5.
• Tiedje KE, Stevens K, Barnes S, Weaver DF. b-Alanine as a small molecule neurotransmitter. Neurochem Intern. 2010; 57:177–188.
• Waterfield CJ, Turton JA, Scales MD, Timbrell JA. Reduction of liver taurine in rats by beta-alanine treatment increases carbon tetrachloride toxicity. Toxicology. 1993 Jan 29;77(1-2):7-20.

Science Round-Up Seconds: "Tomatorade(R)" or Why Tomato Juice is the Better Intra- & Postworkout Beverage. Up to 90% B12 Deficiency in Vegetarians & Vegans. Aluminum in Your Testes? Not With Vitamin E & Zinc.

Can't find "Tomatorade(R)", at your local supplement store, yet (surprising, right ;-)? The guys over @ SimplyRecipes have an easy and tweakable recipe describing how you can make your own "Tomatorade" or however you want to call it (photo by SimplyRecipes).

If you listened live to yesterday's installment of the SuppVersity Science Round-Up on Super Human Radio, you will probably have noticed that due to the technical problems and my teacherly tendency to talk for hours, Carl Lanore and I did not cover all the topics (click here do download the podcast if you haven't already done so)... but hey, that leaves more stuff for today, doesn't it?

I guess I will best package the newsitems into three servings, starting out with the one I like best, namely my Tomatorade(R) aka plain tomato juice news... but before I do so, I must thank Maxim Okhrimenko who corrected the statement I made about vodka in Russian babies' tea or other beverages. Normal Russians don't this. I actually did not intend to make that sound like "common practice" - sorry if it got across like that.

My sincere apologies for promoting prejudices like that. From a science perspective you could even argue that the Brits came up with the idea. In the 1850s William Woodward "invented" a concoction of dill seed oil, sodium bicarbonate and alcohol, called it "gripe water" and sold it as a soothing remedy for gastrointestinal troubles (Agarwal. 2000).

Tomatorade(R) - Tomato Juice turns out to be the ideal periworkout carb drink

What's LDH and CPK? While the former stands for lactate dehydrogenase and the latter is identical to CK, which is creatine kinase, both are considered markers of muscular exertion (LDH) and damage (CK) due to exercise. Very high levels of LDH occur for example in hemolytic situations, i.e. at times your red blood cells disintergrate or after a major trauma to a muscle (incl. a myocardial infarction), the same is true for CK, for which most laboratories will analyses tissue specific isoforms with CK-MB being the one that's indicating muscle damage from the minor DOMS after a leg workout to full rhabdomyolysis.

I know many of you will probably be shuddering, right now. "Carbohydrate drinks? I don't care if it's Tomato- or Gatorade, I don't want any of them." Still, what would you say, if I told you that "Tomatorade(R)", which consists of nothing else but 100% tomato juice could not just replenish your muscle glycogen levels, but would also reduce and even normalize LDH and CPK levels? Allow you to regenerate faster, train more frequently and eventually increase your performance and muscle gains- specifically if you are into weight lifting or other anaerobic activities? I see, now, I got you interested.

According to a paper that is going to be published in the next issue of Food Chemistry and Toxicology, the administration of tomato juice instead of a commercial exercise beverage to 9 out of 15 anaerobically trained athletes (11 men, 4 women) with elevated LDH (>300mg/dl) and CPK(>210mg/dl) baseline levels (as the scientists have it a clearcut sign of "endothelial dysfunction through oxidative stress" (Tsitsimpikou . 2013)) returned the LHD ad CPK levels back into the normal range in the course of the two months study period.

Figure 1: Effects of two month on an isocaloric amount tomato juice (here jovially called "Tomatorade(R)" ;-) vs. the regular carbohydrate workout drink the subjects usually consumed during and after their workouts (Tsitsimpikou. 2013)

Moreover, the consumption of vitamin, mineral and polyphenol-laden superdrink, in place of the athletes regular carbohydrate drink (the scientists made sure that the energy content was identical) also reduced the highly health relevant markers of whole body inflammation, homocysteine and C-reactive protein (CRP; see figure 1) - whether the mainly lycopene induced reductions in homocystein is actually protecting against endothelial damage or not, is yet still (or I should say, again) a matter of scientific debate (cf. Xaplanteris. 2012).

Brief update:  Just got a question from Sofeen on facebook about simply eating tomatoes. Now, you would have to eat plenty of them to see the effect, but in essence it should work. Nevertheless, when I contemplated the question I came up with an even better alternative: Tomato paste! When Tomatorade(R) is the carb beverage, then the paste would be one of those fancy carb gels - a gel, by the way, which has a 2.5x higher bioavailability for lycopene than you would get from regular tomatoes (Gärtner. 1997).

Vitamin B12 defieciency is rampant among vegetarians and (even more) vegans

I have previously pointed out that unless you are at least lacto-ovo-vegetarian, which means that you eat dairy products and eggs, you are going to have a very hard time building and maintaining the physique of your dreams. As a recent meta-analysis and review study by Pawlak et al. suggests, not being the leanest and most muscular on stage should yet actually be your least concern.

Suggested Read: "Want B12 But Hate Meat? Drink Milk!" Even some of the more advanced supplements cannot compete.

According to the data the researchers from different US institutions collected, the deficiency rates for "normal" vegetarians are

• 62% among  pregnant  women,
• between  25% and almost 86% among children,
• 21–41% among adolescents, and
• 11–90% among the elderly

Even higher rates, bordering the 90%+ range, when they were measured by holo-transcobalamin II essays were reported for vegans (adults). On top of that the scientists did not find any confounding factors,:

"The main finding of this review is that vegetarians  develop  B12 depletion or deficiency  regardless  of demographic  characteristics,  place of residency,  age, or type of vegetarian  diet. Vegetarians should thus take preventive measures to ensure adequate intake of this vitamin, including regular consumption of supplements containing B12." (Pawlak. 2013)

As preferable dietary sources the researchers suggest, the aforementioned dairy products and eggs:

• milk, which contains between 0.3 and 0.4 mg/100 g of B12, with an absorption rate of about 65%.
  
• the B12 content of cheese or cottage cheese ranges from 20 to 60% that of milk.
• the amount of B12 in a whole egg is between 0.9 and 1.4 mg/100g

Unfortunately, the amount of B12 is profoundly reduced during the heating process. For milk the B12 loss amounts to up to 30-50%, when you boil it and I bet you won't be much better off with hard boiled (yolks = hard) eggs.

If you avoid meat not for ethical reasons, but because you are afraid it's bad for you, read the "Meat-Ology" post

The scientists also point out that the vegan myth that your body a great ability to store B12 and it would take years if not decades for them to be depleted:

"Studies do not support the position that it takes up to 20 or 30 years to develop a deficiency.7 According to Donaldson, 47% of the sample developed a deficiency, and most of these individuals had adhered to a raw vegan diet for between 23 and 49 months or about 2–4 years. In a study conducted by Herrmann et al.66% of German participants who had adhered to a vegetarian diet for at least 2 years were found to be B12 deficient." (Pawlak. 2013)

Since the whole problem is further increased by the lack of hydrochloric acid (low-to-no intrinsic factor production, which is necessary for the absorption of B12), low iron induced damage to the gut mucosa and subsequent nutrient malabsorptions, I'd suggest that all of you who insist on following a vegetarian life-style go, have their levels checked and get some B12 injections if you are where Pawlak et al. believe you are: Rock bottom.

Protect your testes, rescue your sperm and testosterone production

A recently published paper has taken yet another look at ways to prevent testicular damage / toxicity subsequent to heavy metal exposure. Other than usual, the "suspect" is yet not lead, but rather aluminum, which was administered in toxic doses to male albino rodents.

Figure 2: Relative levels of testosterone, FSH, LH and prolactin in aluminum (50mg/kg) treated male albino rats after the administration of zinc, vitamin E or both; data expressed relative to healthy (non-Al intoxicated) control (Rawy. 2013)

As the data in figure 2 goes to show you, the Saudi-Arabian researchers were able to counter much of the detrimental effects on testicular morphology, spermatogenesis and hormone production by administering either zinc sulfate or vitamin E alone or in conjunction at human equivalent doses of 8mg/kg zinc sulfate (I may remind you that these were 8mg/kg of zinc sulfate, not of elemental zinc, so that we are talking about ~1.8mg/kg elemental zinc) and 2.4mg/kg vitamin E (~1,200-1,500IU), respectively.

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Now while that's it as far as today's Seconds are concerned, tomorrow is Saturday and in case you are into those shorter news items, you better make sure to come back for another installment of On Short Notice. And just in case you have not done so already, I would also suggest that you take a peek at the following recent Facebook news:

Older tomato news: The dehydrotomatine, α-tomatineand trigonelline from green tomatoes has fat burning effects (read more).

• Galactooligosaccharides increase bifido bacteria content in obese patients and result in positive effects on the immune response, and insulin, total cholesterol and triglyceride concentrations (read more). 
• Women with brittle bones cannot squat? False! They must squat, recent study says (read more)
• The fries a mother eats during pregnancy predispose her kids to become obese and develop metabolic syndrome syndrome - at least if the oil was (as it almost always is) oxidized during the heating process (read more).
• The Zinc equation: For every doubling in Zn intake, the difference in Zn serum or plasma concentration is 6% - this assumes zinc intakes in the normal range of <30mg/day (read more).

As usually there will be more for you to read in the course of the next 24 hours - so just "like" the SuppVersity Facebook page to make sure you are not missing out on anything important ;-)

References

• Agarwal KN, Gupta A, Pushkarna R, Bhargava SK, Faridi MM, Prabhu MK. The gripe water story.J R Soc Med.2000;93:172-174.
• Gärtner C, Stahl W, Sies H. Lycopene is more bioavailable from tomato paste than from fresh tomatoes. Am J Clin Nutr. 1997 Jul;66(1):116-22.
• Pawlak R, Parrott SJ, Raj S, Cullum-Dugan, D Lucus, D. How prevalent is vitamin B12 deficiency among vegetarians? Nutrition Reviews. 2 JAN 2013 [epub ahead of print]
• Rawy SM, Seif Al Nassr FM. Zinc sulphate and vitamin E alleviate reproductive toxicity caused by aluminium sulphate in male albino rats. Toxicol Ind Health. 2013 Jan 2.
• Tsitsimpikou C, Kioukia-Fougia N, Tsarouhas K, Stamatopoulos P, Rentoukas E, Koudounakos A, Papalexis P, Liesivuori J, Jamurtas A. Administration of tomato juice ameliorates lactate dehydrogenase and creatinine kinase responses to anaerobic training. Food Chem Toxicol. 2013 Jan 3.
• Xaplanteris P, Vlachopoulos C, Pietri P, Terentes-Printzios D, Kardara D, Alexopoulos N, Aznaouridis K, Miliou A, Stefanadis C. Tomato paste supplementation improves endothelial dynamics and reduces plasma total oxidative status in healthy subjects. Nutr Res. 2012 May;32(5):390-4.

Sip Casein(-ate) NOT Whey for Maximal Net Protein Retention? Not Despite, but Due to Less Leucine?

Image 1: Cows must be stupid animals, right? I mean everybody knows that whey is better than casein, so why would they "spike" their milk with this allegedly inferior protein source, instead of providing us and their calves with the "most anabolic", leucine-loaden whey protein? Or do cows know better than us?

Question: "Whey or Casein to maximize protein synthesis?" The answer appears to be easy: Whey, of course! Faster absorption, higher rates of hyperaminoacidemia (higher than normal amino acid levels in the blood), more leucine, more mTOR, more insulin, more, more ... and did I say more? Well, other than maybe Dr. Scott Connelly, who just came out with his new total milk protein based meal supplement product Physique 2.0, you will in fact be hard pressed to find anyone, let alone a renowned expert arguing in favor of casein. Yet still, Marielle P.K.J. Engelen and her colleagues from the University of Arkansas for Medical Science, Maastricht University, the Nutrition and Toxicology Research Institute Maastricht (NUTRIM),and the Federal University of Rio de Janeiro (UFRJ) dared conducting a trial which investigated just that (Engelen. 2012): "Which dairy protein is able to positively influence the protein metabolic response to exercise" - unfortunately in COPD patients.

COPD vs. control - different yet the same

Luckily the combined exercise and supplementation protocol in the course of which the 8 COPD patients and their age-matched (68.3y) healthy controls had reported to the lab fasted, where they - after the usual procedure of setting up a catheder, infusing a tracer, etc. - started consuming one of the following enteral protein meals

• 29.5 g sodium caseinate* and 68.5g of maltodextrin, or
• 29.5 g whey protein and 68.5g of maltodextrin
  *please make sure you read the info on caseinate vs. casein in the red box below

both dissolved in ultrapure water (1L) at 20 min intervals beginning at T = -2h; in plain English "two hours before the actual trial begun. In the course of the latter the healthy subjects (on which we are going to focus our attention here) pedaled on braked cycle ergometer at 50% of the COPD patients pre-determined maximal workload (this was a concession to the bad conditioning of the actual study subjects, the COPD patients) in the first and 50% of their own maximal workload in the second trial at T = 0 and T = 1h 20min, respectively.

Image 2: Don't be fooled micellar casein and caseinate are not the same (img. University of Guelph)

Caseinate is not casein! I have not discussed the actual study in isolation, here at the SuppVersity before, but I have broached on the issue in previous posts: There is more than a "three-letter difference" between "casein" and "caseinate", while the former actually (often things get "mislabeled" these days ;-) refers to intact casein micelles, which clot and form complex novel (and partially biologically functional) complexes in the course of the digestion process, the sodium bound "broken" micelles from the sodium caseinate don't, so that - as Stuart Phillips put it quite aptly in a comment on a similar study by Reitelseder et al. - the "digestion rates of this form of casein are not likely to be overtly different from those of whey" (Phillips. 2011). What we are comparing here are thusly proteins with "identical", or I should say, very similar digestion rates, yet slightly different amino acid compositions - this renders the study not less valuable, should yet be kept in mind as far as its practical implications (see my conclusion further down) are concerned.

Right before, as well as right after, and in the course of the 60min recovery period that followed each workout the subjects consumed a bolus of 0.67 mL/kg BW of the respective protein supplement which contained 18 mg protein/kg body weight (whey or caseinate) and 46 mg maltodextrin/ kg BW every 20 min. Afte 10 ingestions and a 75kg subject would thusly have consumed 13.5g of protein, total.

Figure 1: Total body net protein synthesis (synthesis - breakdown) and protein synthesis of the healthy subjects during (0-20min and 80-100min) and after the two exercise trials (data adapted from Engelen. 2012)

And even in view of the fact that we are not dealing with regular slow digesting casein micelles, the results, in terms of net protein retention and protein synthesis (cf. figure 1) were quite surprising:

The present study shows that net whole body protein anabolism was higher during casein than during whey protein feeding in both the COPD and control group which remained during and following exercise. The proteins were provided via sip feeding to evaluate the effects of the quality of the amino acid composition between casein and whey protein. [...] This difference in anabolism might be related to differences in BCAA distribution as LEU level is higher in whey than in casein protein, whereas the concentrations of ILE and VAL are lower

And though I am not quite sure, whether the researchers were aware that "their" caseinate is in fact not significantly slower digested than regular whey protein, this does not change the likeliness of their hypothesis (= hypothetical ;-) that the different amino acid make-up in general and maybe even the lower (!) leucine to isoleucine and valine ratio could be responsible for the statistically significant superiority of caseinate in

• whole body net protein synthesis during exercise and recovery
• whole body protein breakdown during recovery from the second, higher intensity exercise bout, and
• net whole body protein synthesis (=difference between synthesis and breakdown) during the whole study period, with the exception of recovery from 2nd exercise trial

Whether or  not this was a (direct) effect of the different ratios of the three BCAAs to each other, the minimally higher BCAA and EAA content (btw. why not the proline? I mean 11.23 in caseinate vs. 3.31 is a huge difference, cf. table 1) of the caseinate or maybe, despite similar digestion rates, still an effect that came about as a result of different digestion kinematics of whey and caseinate would require further studies.

Is whey no longer the whey to go?

Table 1: Amino acid composition (per 100g) of the sodium caseinate and whey used in the study (Engelen. 2012)

In view of what you should have learned yesterday about the influence of age, training status, experimental protocol, etc. on the effect-size of studies investigating strength gains in response to different exercise regimen (cf. Strength Gains Depend on Training Status, Age, Workout Frequency, Rest Intervals & More), it should also be clear that these results require further verification in different study populations and exercise contexts. It is yet still intriguing that - assuming that the scientists hypothesis holds, two of the generally accepted paradigms of intra- and peri-workout supplemenation, namely

1. the general superiority of whey proteins over every other form of dairy (let alone meat or whatever else) protein during or in the immediate vicinity of a workout
2. the importance of leucine as the single-most important dietary trigger for protein synthesis and against the breakdown of protein

If these paradigms were revised, the currently available 4:1:1 or even 8:1:1 BCAA supplements, as well as the whey-protein based intra-workout supplements, should (you know science is only part of the equation, when it comes to the production and sales ranks of dietary supplements ;-) disappear from the market.

Comparing apples to oranges and juices to whole fruits

Before the latter is going to happen, though, there is still a lot of scientific work to be done. After all, we are not only comparing apples with oranges here (as far as the trainees are concerned), but also juices with whole fruits, or put more simply: While the current study looked at whole body protein synthesis / breakdown, sports scientists usually focus on muscular (in many cases even either myofibrillar or sarcoplasmic) protein synthesis, the study at hand evaluated the protein turnover rates of the whole body. And while this is probably a "shortcoming" as far as the immediate muscle-building effects of the individual protein sources are concerned, the ever-increasing awareness of the far-reaching metabolic consequences of the integrity of our gut lining, which becomes a protein donor for the skeletal muscle tissue during strenuous exercise (after a workout you have a "leaky gut"), may make it worthwhile to look at protein synthesis in places other than your muscle as well. After your workout, at the latest, your gut and the other organs in the splachnic bed are going to (re-)claim their share of protein, anyway.

Short-Term Supplementation with Bovine Colostrum Does Not Improve Immune Variables in Well-Trained Athletes. Localized Effect on Intestinal Health Yet Possible.

Just in case you wonder that there were no news yesterday. Blogger was down, so it took me some time to be able to tell all of you, who followed my advice and tuned in to yesterday's episode of Carl Lenore's Super Human Radio: "Amino Acids for Super Humans" and heard Carl and me talk about his use of bovine colostrums as part of his peri-workout supplementation regimen that my concerns over the digestibility of the (mostly) immunomodulating long-chain peptides in colostrum (the milk mammals produce in the last days / first days after pregnancy), appear to be legit. At least the results of a recents study (Carol. 2011), which failed to produce any (systemic) immunomodulatory effects in well-trained athletes, would confirm my assumption that these longer amino acid chains are not able to overcome the tight gut junctions, which are genetically designed to "close" (the further tightening of the junctions is also known as "closure") within the first days after a mammal is born.

Figure 1: Two samples of human breast milk, which has a very different immunoglobulin composition than cows milk and colostrum, cf. Hurley. 2011 (image taken by Wikipedia user Azoreg)

That being said, the results of the aforementioned study that has been published in International Journal of Sports Nutrition and Exercise Metabolism do not come as a surprise for me: After 10 days of supplementation with either colostrums or skim milk powder, the 9 professional male athletes did show absolutely identical immune reactions to high intensity endurance exercise in a carbohydrate depleted state (the glycogen-depletion would augment the immunosuppressive effect of intense exercise beyond what would be seen under normal = glycogen-sufficient circumstances):

Plasma cortisol levels increased over time, reaching the highest level directly after exercise, and were still elevated ~22 hr after exercise compared with baseline values (p < .001). Neutrophil cell count was increased after exercise and dropped below starting values 22 hr after exercise (time effect p < .001). Circulating immunoglobulins did not change over time. A significant time effect was seen for interleukin (IL)-6, IL-10, IL-1-receptor agonist, and C-reactive protein, with levels being higher directly after exercise (p < .05). Other cytokines (interferon-γ, IL-1a, IL-8, tumor necrosis factor-a) did not show a time effect. No differences were seen between colostrum and skim-milk powder in any of the investigated variables.

The lack of systemic effects, i.e. effects on the body as a whole, due to the inability of the long chain peptides to cross the intestinal wall, on the other hand, does not preclude beneficial "side effects" within the gut, itself. Recent studies such as Moller et al. (Moller. 2011), for example showed direct beneficial effects of the "synergistic action of various milk bioactives" on dendritic cell (messengers between the innate and adaptive immunity) cytokine response within the gut. Further evidence for the localized effect of colostrum comes from a 2010 study by Marchbank (Marchbank. 2010) found that colostrum supplementation actually decreased or rather maintained gut permeability, which was otherwise reduced after exhaustive exercise:

Intestinal permeability in the placebo arm increased 2.5-fold following exercise (0.38 ± 0.012 baseline, to 0.92 ± 0.014, P < 0.01), whereas colostrum truncated rise by 80% (0.38 ± 0.012 baseline to 0.49 ± 0.017) following exercise.

These colostrum-specific results corroborate various studies on the effects of hydrolyzed milk peptides on insulin sensitivity, blood pressure and much more, indicate that there is much more to milk and milk products than the sum of their proteins, carbohydrates, fats, minerals and vitamins would suggest. Whether it always has to be colostrum, which is expensive and hard to come by, or raw, unpasteurized milk from the grass-fed cows of your local farmer would not suffice remains to be seen, though.