Tuesday, April 24, 2012

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.


ProudDaddy said...

Holy Cow!

Bernardo - BR said...

Finally, we just just consume milk as the best source of protein.

Lerner said...

Greetings! Long time no see. I kind of like seeing this study because it fits with my theory that when everybody knows that some idea is true, then that idea has peaked - as far as its popularity goes. Lots of people want to be part of new trends, and companies need new 'revolutionary' products to drive sales.

So it looks like casein powder is on deck to rocket up in popularity. Next might be meat powders. Then whey will be ready for a comeback - how about liposomal and pegylated whey for before bedtime? :)

Interesting... I never knew that molecules could form micelles without a lipid component. It seems that the bound calcium atoms at one end form attraction to each other and that makes them organize into micelle like structures.

Maybe we'll also one day be seeing super hi-speed blenders getting sold, for taking ordinary milk and making some of it into hi-speed casein by breaking up the structure.

Time marches on :) Probably the first supplement I ever bought was dessicated liver, maybe that'll make a comeback, too, this time as a PWO.

Prof. Dr. Andro said...

finally - "Lerner the Resurrection" ;-)

The most intriguing thing about the micelles, which are in fact held together by calcium phosphate bonds is that they are the magic behind milks ability to deliver those minerals effectively.

that being said, there is evidence that the intact micelles (vs. the ones in the caseinate) have, in fact due to their ability to clump and form larger structures, other (beneficial) biological properties, esp. wrt to their ability to trigger / induce the release of gut / satiety hormones of which I believe that they will soon emerge as the novel go-to for weight loss and improvements in body composition

Prof. Dr. Andro said...

with regular milk you do obviously get tons of carbs, as well. That being said, it is not for nothing that study after study showed that chocolate milk is an effective post-workout drink... so, if you are not following the total low-carb hype, milk is good, but even better if you "spike" it with some protein powder, I believe...

Lerner said...

LOL!!!! And Ellen Ripley says 'hi', too! :)

Can you say a quick sentence or two on why cow's milk has a greater % casein than human, roughly 2-to-1? (I also generally add some whey to milk PWO on large-muscle-group days, it seems natural.)

Børge Fagerli said...

My go-to protein powder for years has been a 50:50 combination of whey and casein (which I believe is pretty close to the ratio in human breast milk), I might only use some PeptoPro/BCAA/EAA immediately pre-workout if I haven't eaten for a while and because a solid meal with e.g. casein or whole foods is uncomfortable to train on.

As with many other things in this field, it's like a pendulum swinging. It used to be way over on the left field with super-fast amino acids spiked every few hours, then it was in the right field with only 2-3 meals as per the IF lore...now it seems to center itself somewhere in the middle.

People are attracted to extremes, though...

Prof. Dr. Andro said...

"Human and Bovine milk differ substantially in the ratio of Whey to Casein protein (approximately 60:40 in human milk and approximately 20:80 in Bovine milk) and in the proportions of specific proteins."

it should be said though that the casein content of human milk (and I suppose of cows milk) changes as the baby / calf ages. The addition of whey PWO by the way is certainly no bad idea. Also, the caseinate in the study at hand does in fact "perform" very similar to whey... I am intrigued if this could be due to the differences in proline after all, it figures in tissue repair (part of the arginine metabolism), cf. http://www.ncbi.nlm.nih.gov/pubmed/18806115

Prof. Dr. Andro said...

not a bad decision. And in the end, I suppose that overthinking all those supplementation issue is probably more catabolic than not hitting the optimal ratio *rofl*

steve said...

Any particular brands of protein powder recommended? Thoughts on grass fed whey?

Prof. Dr. Andro said...

aside from "damage" to the protein structure due to processing issues the best among the standard whey isolates are cross-flow microfiltrates; but even those are associated with losses and the isolation increases the pro-insulinogenic effect; I also have NOT noticed any benefits from isolates vs. concentrates (I am yet also not lactose intolerant) and like the latter better because they are less processed and taste better (I like my protein thick). I also have a cheap micellar casein and mix them in a 2:1 or 1:2 ratio pre-workout and at other timepoints, respectively.

the "grass-fed whey" is if you asked me a waste of money... even the difference in fatty acid composition of grass fed vs. "normal fed" is largely overestimated (not that it is not important, but the differences are less extreme than the paleo crowd would makke it appear, its not that "normal meat" is all n-6 and grass fed is all n-3 + tons of CLA < that's hilarious) and I have not seen any study that would show differences in amino acid composition or something like "gluten residues" in those ultra-processed protein powders.

steve said...

Thank you! After a workout I have be eating Fage 2% yogurt with some fruit which contains 20G of protein. Probably not as good as whey, but less costly and satisfying.
Generally, I like to exercise on an empty stomach, particularly if i do cardio LISS which more often than not I will do first thing in the am.
I agree with you regarding the grass fed vs non with respect to 03 vs o6 benefits, but believe that the grass fed not being factory farmed might have certain humane advantages,but not quite sure. I actually like the taste better of grass fed beef when i have vs non.

Lerner said...

quoting myself: "how about... pegylated whey for before bedtime?"

I was half joking, but should have guessed that something similar already exists - e.g., "Nutrateric®... a revolutionary, pharmaceutically-developed coating system... the resulting digestion can take more than twice as long as other forms of non-coated protein, further enhancing the extended release capacity..."

I ran across that yesterday. C'est la vie.

Prof. Dr. Andro said...

that is somewhat illogical. I mean, THIS casein = caseinate digest as fast as whey - so if anything the pegylated whey would make the "sipping" obselete, but why not use plain casein, then?

if I am missing something here, let me know

Anonymous said...

what about sodium caseinate?

Anonymous said...

sry mixed up what kind of caseinate it was... I meant calcium caseinate