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

Even though the study at hand has been conducted in an endurance training scenario, there's no reason to believe that the superiority of milk protein, the natural mix of whey and casein would be a "cardio-specific" thing. In fact, evidence to the contrary has been discussed previously, here and here.
Whey, casein, soy or the rarely used alternative, milk protein, what's best to kickstart the protein synthetic machinery even after endurance workouts? The absorption kinetics of the different proteins, the effects of which a group of scientists from Japan recently re-assessed would suggest that the answer is clear: whey protein, it's the fastest of the four proteins, contains the highest amount of BCAAs (esp. the mTOR- and MPS promoter leucine) content and has been repeatedly shown to rapidly cause significant hyperamonoacidemia (=extremely elevated amino acid levels in the blood | Boirie. 1997; Dangin. 2001; Norton. 2009).

In spite of the fact that whey is also the most insulinogenic of these proteins, it is yet also the one that has been shown to "maximize" amino acid oxidation, thereby contributing to a reduction in nitrogen retention (Boirie. 1997; Dangin. 2001). On the other hand, ingestion of CA causes slower but prolonged aminoacidemia and it has the best leucine net balance during the postprandial period (Boirie. 1997; Dangin. 2001), I've discussed in previous articles, such as "Protein Wheysting".
This is not an anti-high-protein article. It is one arguing in favor of "treating your protein right"

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This is where micellar casein (not sodium or calcium caseinate which are fast-, but slower-than-whey-absorbing "damaged" forms of casein, though) comes in. While casein does not produce the same rapid increase in serum amino acid levels it has been shown to cause moderate but prolonged muscle protein synthesis - the exact opposite of whey protein.
Figure 1: Fractional myofibrillar protein synthesis (A), plasma leucine (B) and plasma insulin (C) levels in young men after ingesting 0.3g/kg whey, casein or a protein-free control drink (Reitelseder. 2011)
The data from Reitelseder et al. (2011) illustrates the link between the time course of the myofibrilliar protein synthesis and a protein's digestion speed, the rate of appearance of leucine (Figure 1, B) in the blood and the protein's insulinogenic (Figure 2, C) effects quite nicely. It is thus only logical to assume and has in fact been shown that the co-ingestion of whey and casein, either mixed or as milk protein is superior to soy protein (SP) [22,23], but also to whey alone, even if the latter is "enhanced" with extra BCAAs and glutamine (learn more!)
Figure 2: As a SuppVersity reader you will rememeber that a previous study showed that whey + casein is profoundly more anabolic than whey that is combined with extra BCAAs and glutamine (Kerksick. 2006)
As the Japanese authors of the study at hand point out, these benefits are likely due to casein's ability to "contributes amino acids that have a prolonged protein-synthetic effect across the leg" - or, put more simply: whey pumps up the AA levels fast, so fast that your body gets wasteful; casein, on the other hand, provides them at a rate that's much more suitable for direct incorporation into the muscle.
Whey (open triangles) increases leucine +protein oxidation vs. casein (closed circles) in man (Boirie. 1997).
Thinking about the perfect mix: Wouldn't it make more sense to have more whey right after a workout and reduce the amount of casein? If that's what you are thinking right now, I have to warn you: As previously pointed out, there's a point of diminishing returns, when excess amino acids as you would increase them by increasing the amount of whey are oxidized and end up as "waste", namely ammonia (and after recycling urate) in your system. The increased leucine oxidation with whey (open triangles) vs. casein (filled circles), as it was observed by Boirie et al. 19 years ago in healthy subjects even though the subjects consumed 43g of casein and only 30g of whey to standardize the leucine content, attests to that. Needless to say, testing a 50:50 or even 60:40 ratio would be something for follow-up studies.
Table 1: Amino acids in milk (MP), caseinate (CA), whey (WP) and soy (SP) protein (Kanda. 2016).
What exactly the ideal ratio of whey to casein protein may be will still have to be determined (probably it'll depend on when you take your protein shake), but the 2:8 ratio, meaning 20% whey protein and 80% casein that was used in the study at hand is "nature's standard formula" and thus what your average milk protein will have. A protein, by the way, of which Kanda et al. wanted to confirm in their latest experiment that it "causes a prolonged increase in muscle protein synthesis compared to WP [whey protein]or CA [casein] alone" (Kanda. 2016).

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

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

Truth #1: It's a rodent study! That's convenient for the scientists, because using rodents is cheap and easy, but annoying for us, because rodents are a good model for humans, but only that - a model - and by no means the best one. Since we cannot switch the subjects, though, we have to live with the fact that the subjects in the study at hand were Sprague-Dawley rats with a bodyweight of approximately 150 g (at least there were many | n = 237) who were subjected to a swimming exercise protocol during which they swam for a whopping 2h.
You should care about postworkout protein synthesis! While previous studies had suggested that the FSR / MPS response to training and supplementation would not, a more recent study I discussed in detail, last week, clearly demonstrates that FSR / MPS does matter. Read it!
Now, where there's shadow, there's also light: The good thing about rodent studies (bad for the rats, though) is, after all, that, much in contrast to humans, rats can be sacrificed after an experiment like that and will thus allow researches to assess the effects of exercise and supplementation with the aforementioned proteins much more accurately than a single or even multiple muscle biopsies.
Table 2: Macronutrient profile of test proteins; milk (MP), caseinate (CA), whey (WP) and soy protein (SP | Kanda. 2016)
That does not fully compensate for truth #2, though, which is that the scientists made the mistake of using caseinate (Fonterra Co-operative Group, Ltd., Auckland, New Zealand), instead of the more expensive and slower/-est digesting (due to its micelle structure, which gels during the digestion process) molecularly intact micellar casein, of which one could expect that it may have postponed the peak in fractional protein synthesis (FSR) that occurred after 120 minutes with the caseinate even more (Figure 3, left).
Figure 3: Time course of the fractional protein synthesis after endurance exercise with all four proteins (left) and corresponding AUC values (~net protein influx, right | Kanda. 2016).
The previous hypothesis is obviously merely speculative and eventually irrelevant. I mean, micellar casein, or not, it is very unlikely that the overall AUC, i.e. the incremental area under the FSR curve and thus the net influx of protein into the muscle, would have been increased to a level that would top that of milk protein (black bar in Figure 3, right), which had a measurable, but not statistically significantly more pronounced effect on the protein influx than any other of the four proteins.
Bottom line: Yes, it's rodents, but eventually the study at hand simply extends previous studies (A, B) in humans, where the combination of whey + casein likewise outperformed the competition...

FSR during dose escalation study; the human equivalent dose (HED) of 3.09g/kg, the 100% dose, in rats is ~0.5g/kg in man and thus ca. 30-50g milk protein, depending on your body weight. (Kanda. 2015)
And when we are talking about "extending the existent research", it may be worth mentioning that the researchers also provide new evidence in regards to the "ceiling" or "muscle full"-effect that occurs when ingesting more protein won't yield any extra increases in protein synthesis. In the study at hand, this effect was reached at a human equivalent dosage of ca. 0.5g per kg body weight (that's the 100% dose in Figure 4) or ~ 40g which is - initially surprisingly - more than the often touted 20-30g (depending on the human study you cite). In view of the 20:80 mix of whey and casein, the lower leucine content and slower absorption of the latter, it is yet actually logical to need more milk protein vs. whey to "reach the ceiling" | Comment!
  • Boirie, Yves, et al. "Slow and fast dietary proteins differently modulate postprandial protein accretion." Proceedings of the National Academy of Sciences 94.26 (1997): 14930-14935.
  • Dangin, Martial, et al. "The digestion rate of protein is an independent regulating factor of postprandial protein retention." American Journal of Physiology-Endocrinology And Metabolism 280.2 (2001): E340-E348.
  • Kanda, Atsushi, et al. "Effects Of Whey, Casein, Or Milk Protein Ingestion On Muscle Protein Synthesis After Endurance Exercise." MEDICINE AND SCIENCE IN SPORTS AND EXERCISE. Vol. 46. No. 5. 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA: LIPPINCOTT WILLIAMS & WILKINS, 2014.
  • Kerksick, Chad M., et al. "The effects of protein and amino acid supplementation on performance and training adaptations during ten weeks of resistance training." The Journal of Strength & Conditioning Research 20.3 (2006): 643-653.
  • Norton, Layne E., et al. "The leucine content of a complete meal directs peak activation but not duration of skeletal muscle protein synthesis and mammalian target of rapamycin signaling in rats." The Journal of nutrition 139.6 (2009): 1103-1109.
  • Reitelseder, Søren, et al. "Whey and casein labeled with L-[1-13C] leucine and muscle protein synthesis: effect of resistance exercise and protein ingestion." American Journal of Physiology-Endocrinology and Metabolism 300.1 (2011): E231-E242.
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